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[This corrects the article DOI: 10.3389/fmed.2023.1122529.].
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Atopic dermatitis is a chronic skin condition that has significant psychosocial and quality-of-life impact. The condition causes physical discomfort, emotional distress, embarrassment, social stigma, and daily activity limitation. In an effort to assess these aspects of disease burden, quality-of-life measurement tools were developed. Through use of these tools, we have expanded our knowledge of the psychosocial and quality-of-life burden of this condition. A variety of quality of assessment tools exist, yet there is no consensus on which tool is best suited to assess the quality-of-life impact of atopic dermatitis. Research studies assessing quality-of-life in atopic dermatitis patients utilize a variety of quality-of-life measurement tools; this complicates comparisons across research studies. Though comparison across studies is difficult, the data echoes tremendous overall burden of disease, especially pertaining to psychosocial status and life quality.
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Dermatitis Atópica , Calidad de Vida , Dermatitis Atópica/psicología , Humanos , Calidad de Vida/psicología , Costo de Enfermedad , Encuestas y Cuestionarios , Estigma SocialRESUMEN
Background: Microsurgical treatment of paraclinoid aneurysms is a complex task that generally requires anterior clinoid process (ACP) removal to obtain adequate surgical exposure. This procedure poses a considerable technical difficulty due to the association of the ACP to critical neurovascular structures. Furthermore, anatomical variations in the parasellar region, such as the caroticoclinoid foramen (CCF) or an interclinoid bridge (ICB), may impose additional challenges and increase surgical complications. The present study aims to briefly review some anatomic variations in the parasellar region and describe a step-by-step surgical technique for a hybrid anterior clinoidectomy based on the senior author's experience. Methods: We present two cases with bone variations on the parasellar region in patients with a paraclinoid aneurysm and another with a posterior communicating segment aneurysm treated by microsurgical clipping at our hospital. Results: We focused on safely dealing with these variations during surgery, without further complications, and with good postoperative results. Patients were discharged with no significant deficit. Postoperative control, computed tomography angiography showed complete exclusion of aneurysms. Conclusion: Although anatomical variations in the parasellar region can complicate surgical clipping of these aneurysms, it is essential to ensure the best possible surgical outcome to conduct thorough preoperative and radiological evaluations.
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Falcotentorial meningiomas are rare tumors, representing only 2-3% of all intracranial meningiomas. These tumors can grow rapidly, leading to severe neurological complications. They grow at the junction of the tentorium cerebelli and the falx cerebri, in close proximity to the great vein of Galen. The surgical approach depends on several factors, such as the tumor's size, the patency of the straight sinus, and its location, either above or below the tentorium. Complete removal of the tumor in this area is difficult due to its deep location near major neurovascular structures. Various surgical approaches can be employed to remove these tumors, and the decision on which approach to use should be based on its advantages and disadvantages.
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Mesoscopic carbon-based perovskite solar cells (CPSCs) are often cited as a potential frontrunner to perovskite commercialization. Infiltration, the extent to which perovskite fills the mesoporous scaffold, is critical for optimum performance and stability. However, infiltration data are usually presented as qualitative photographic comparisons of samples with extreme infiltration variation. This work examines how small infiltration defects impact performance using an optical microscopy examination of the base TiO2 layer to identify issues and develop targeted techniques for infiltration enhancement. Critically, the uninfiltrated area at the base of the stack was found to correlate well with PCE across multiple batches of varied print quality and ZrO2 thickness. Through reduction of mesh mark defects and improvement of print quality in the ZrO2 and carbon layers, a champion PCE of 15.01% is attained. It follows that this facile, multiscaled, nondestructive technique could enable targeted performance enhancement and quality control in future scale-up initiatives.
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BACKGROUND: Chronic pain management remains a challenging aspect of neurosurgical care, with facet arthrosis being a significant contributor to the global burden of low back pain. This study evaluates the effectiveness of cryotherapy as a minimally invasive treatment for patients with facet arthrosis. By focusing on reducing drug dependency and pain intensity, the research aims to contribute to the evolving field of pain management techniques, offering an alternative to traditional pain management strategies. METHODS: Through a retrospective longitudinal analysis of patients with facet osteoarthritis treated via cryotherapy between 2013 and 2023, we evaluated the impact on medication usage and pain levels, utilizing the Visual Analog Scale for pre- and posttreatment comparisons. RESULTS: The study encompassed 118 subjects, revealing significant pain alleviation, with Visual Analog Scale scores plummeting from 9.0 initially to 2.0 after treatment. Additionally, 67 patients (56.78%) reported decreased medication consumption. These outcomes underscore cryotherapy's potential as a pivotal tool in chronic pain management. CONCLUSIONS: The findings illuminate cryotherapy's efficacy in diminishing pain and curtailing medication dependency among patients with facet arthrosis. This study reaffirms cryotherapy's role in pain management and propels the discourse on nontraditional therapeutic avenues, highlighting the urgent need for personalized and innovative treatment frameworks.
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Crioterapia , Manejo del Dolor , Articulación Cigapofisaria , Humanos , Femenino , Masculino , Persona de Mediana Edad , Crioterapia/métodos , Estudios Retrospectivos , Anciano , Articulación Cigapofisaria/cirugía , Manejo del Dolor/métodos , Resultado del Tratamiento , Dimensión del Dolor , Estudios Longitudinales , Osteoartritis/terapia , Osteoartritis/complicaciones , Osteoartritis/cirugía , Adulto , Dolor de la Región Lumbar/terapia , Dolor de la Región Lumbar/etiología , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Dolor Crónico/terapia , Dolor Crónico/etiología , Osteoartritis de la Columna Vertebral/complicaciones , Osteoartritis de la Columna Vertebral/cirugíaRESUMEN
BACKGROUND: Vascular neurosurgical procedures require temporary or permanent surgical clips to treat cerebral aneurysms, arteriovenous malformations, or bypass surgery. In this scenario, surgical clips should have specific characteristics such as high-quality material, proper design, closing force, and biocompatibility. Due to these characteristics, the price of these clips does not allow their availability at the experimental surgery laboratory worldwide. METHODS: We describe here the technique for manufacturing handcrafted clips of low cost, using dental stainless steel or titanium wire of 0.18 mm, 0.20 mm, or 0.22 mm in diameter. We must complete six steps to obtain the clip using our hands and small electrician needle nose pliers for wire molding. RESULTS: These clips have a closing force of 30-60 gr/cm2 (depending on the wire diameter). They can be used in the experimental surgery laboratory to clip arteries or veins during vascular microsurgery procedures. Also, they can be used as temporary clips with confidence in low-flow bypass (v.gr. superficial temporal artery to middle cerebral artery or occipital artery to posterior inferior cerebellar artery anastomoses). CONCLUSIONS: Making practical low-cost clips for use in laboratory procedures or during low-flow anastomosis as temporary clips is possible. The main advantages are the low cost and the worldwide availability of the basic materials. The main disadvantage is the learning curve to get the ability to master the manufacturing of these clips.
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Aneurisma Intracraneal , Microcirugia , Humanos , Instrumentos Quirúrgicos , Procedimientos Neuroquirúrgicos/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Anastomosis QuirúrgicaRESUMEN
Diabetes and poor glycemic control are significant predictors of severity and death in the COVID-19 disease. The perception of this risk in individuals with type 2 diabetes (T2D) could modify coping styles, leading to behaviors associated with better self-care and metabolic control. Theoretically, active coping is associated with better glycemic control in patients with T2D. Nonetheless, information during extreme risk like the COVID-19 pandemic is still limited. Our objective was to evaluate the association between coping styles and risk perception in the COVID-19 pandemic and the change in metabolic parameters. This is a prospective study that included individuals with T2D treated in a tertiary care center during the COVID-19 outbreak who returned to follow-up one year later. We assessed coping styles and risk perception with the Extreme Risk Coping Scale and the risk perception questionnaire. Clinical characteristics and metabolic parameters were registered in both visits. Groups were compared using Kruskal Wallis tests, and changes in metabolic parameters were assessed with Wilcoxon rank sum tests. Our sample included 177 participants at baseline, and 118 concluded the study. Passive coping was more frequent in women. Low-risk perception was associated with higher age, lower psychiatric comorbidities, and lower frequency of psychiatric treatment compared with other risk perception groups. Patients with active coping plus high-risk perception did not have a change in metabolic parameters at follow-up, whereas patients with other coping styles and lower risk perception had an increase in total cholesterol, LDL-cholesterol, and triglycerides. There were no differences by coping group or by risk perception in glycemic control.
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Introducción. En las últimas décadas se han desarrollado diferentes scores y modelos para predecir el pronóstico en pacientes con enfermedad hepática crónica avanzada. Los más reconocidos y utilizados son el sistema de estadificación de Child-Pugh (CP) y el score de MELD, pero estos carecen de herramientas para evaluar objetivamente otros factores pronósticos. Por este motivo, se ha incorporado el concepto de fragilidad a la hepatología clínica. El objetivo de este artículo es examinar la aplicabilidad del índice de fragilidad hepática (IFH) en pacientes con cirrosis evaluados para trasplante hepático en Uruguay. Metodología. Estudio observacional, descriptivo y retrospectivo en el Servicio de Enfermedades Hepáticas del Hospital Central de las Fuerzas Armadas (HCFFAA) de enero de 2018 a diciembre de 2021. Resultados. Se evaluaron un total de 78 pacientes, excluyéndose 19 de estos, culminando con una muestra final de 59 pacientes. La edad media fue de 52 años, siendo el 66 % hombres. La principal etiología de la cirrosis fue la alcohólica, y la comorbilidad más frecuente fue el sobrepeso/obesidad (66 %). La media de IFH fue de 4,03 ± 0,45. El 90 % de los pacientes eran prefrágiles, el 10 % frágiles y ningún paciente fue clasificado como no frágil. El 76 % presentaba un estadio avanzado de la enfermedad al momento de la evaluación 42 % CP estadio B, 34 % CP C, 24 % CP A, con una media de MELD-Na de 17,8 ± 7,6. El 17 % tuvo complicaciones infecciosas. La mortalidad global (n=78) fue del 12 %, y la de los pacientes con IFH calculado fue del 22 %. Conclusiones. El cálculo del IFH es realizable en cirróticos como herramienta objetiva que brinda una mirada integral del paciente. A mayor severidad de la cirrosis, mayor es el IFH. Sin embargo, este índice no parece ser un predictor de la eventual realización del trasplante hepático, ni de muerte en lista de espera en nuestros pacientes.
Introduction. In recent decades, several scores and models have been proposed to predict prognosis in patients with advanced chronic liver disease. The most recognized and used are the Child-Pugh (CP) and the Model for End-stage Liver Disease (MELD) scores, but they lack tools to objectively evaluate other prognostic factors. For this reason, the concept of fragility has been incorporated into clinical hepatology. The objective of this study was to evaluate the applicability of the liver frailty index (LFI) in patients with cirrhosis evaluated for liver transplantation in Uruguay. Methodology. Observational, descriptive and retrospective study at the Hospital Central de las Fuerzas Armadas (HCFFAA) Liver Disease Service from January 2018 to December 2021. Results. A total of 78 patients were evaluated, 19 were excluded, culminating in a final sample of 59 patients. The mean age was 52 years, with 66% being men. The main etiology of cirrhosis was alcoholic and the most frequent comorbidity was overweight/obesity (66%). The mean LFI was 4.03 ± 0.45. 90% of patients were pre-fragile, 10% were fragile, and no patient was classified as non-fragile. 76% had an advanced stage of the disease at the time of evaluation: 42% CP stage B, 34% CP C, 24% CP A, with a mean MELD-Na of 17.8 ± 7.6. 17% had infectious complications. Overall mortality (n=78) was 12%, and that of patients with calculated LFI was 22%. Conclusions. The LFI can be calculated in cirrhotic patients, and it is an objective tool that provides a comprehensive view of the patient. LFI depends on the severity of the cirrhosis. However, this index is not a predictor of liver transplantation or death on the waiting list in our patients.
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OBJECTIVE: The use of intraoperative techniques to detect residual tumors has recently become increasingly important. Intraoperative MRI has long been considered the gold standard; however, it is not widely used because of high equipment costs and long acquisition times. Consequently, real-time intraoperative ultrasound (ioUS), which is much less expensive than MRI, has gained popularity. The aim of the present study was to evaluate the capacity of ioUS to accurately determine the primary tumor volume and detect residual tumors. METHODS: A prospective study of adult patients who underwent surgery for intra-axial brain tumors between November 2017 and October 2020 was performed. Navigated intraoperative ultrasound (nioUS) of the brain was used to guide tumor resection and to detect the presence of residual disease. Both convex (5-8 MHz) and linear array (6-13 MHz) probes were used. Tumor volume and residual disease were measured with nioUS and compared with MR images. A linear regression model based on a machine learning pipeline and a Bland-Altman analysis were used to assess the accuracy of nioUS versus MRI. RESULTS: Eighty patients (35 females and 45 males) were included. The mean age was 58 years (range 25-80 years). A total of 88 lesions were evaluated; there were 64 (73%) gliomas, 19 (21.6%) metastases, and 5 (5.7%) other tumors, mostly located in the frontal (41%) and temporal (27%) lobes. Most of the tumors (75%) were perfectly visible on ioUS (grade 3, Mair grading system), except for those located in the insular lobe (grade 2). The regression model showed a nearly perfect correlation (R2 = 0.97, p < 0.001) between preoperative tumor volumes from both MRI and nioUS. Ultrasonographic visibility significantly influenced this correlation, which was stronger for highly visible (grade 3) tumors (p = 0.01). For residual tumors, the correlation between postoperative MRI and nioUS was weaker (R2 = 0.78, p < 0.001) but statistically significant. The Bland-Altman analysis showed minimal bias between the two techniques for pre- and postoperative scenarios, with statistically significant results for the preoperative concordance. CONCLUSIONS: The authors' findings show that most brain tumors are well delineated by nioUS and almost perfectly correlated with MRI-based measurements both pre- and postoperatively. These data support the hypothesis that nioUS is a reliable intraoperative technique that can be used for real-time monitoring of brain tumor resections and to perform volumetric analysis of residual disease.
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Neoplasias Encefálicas , Imagen por Resonancia Magnética , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Adulto , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos , Anciano de 80 o más Años , Carga Tumoral , Neoplasia Residual/diagnóstico por imagen , Neuronavegación/métodos , Glioma/diagnóstico por imagen , Glioma/cirugía , Glioma/patología , Procedimientos Neuroquirúrgicos/métodos , Monitoreo Intraoperatorio/métodosRESUMEN
BACKGROUND: A trauma registry review of our trauma center's alcohol misuse screening compliance noted inconsistent screening and data collection methods, putting our American College of Surgeons trauma center reverification at risk for a deficiency. OBJECTIVE: The objective of this study was to evaluate an alcohol misuse screening improvement initiative on screening compliance in trauma patients. METHODS: This before and after analysis of a quality improvement initiative to improve alcohol misuse screening was conducted from 2019 to 2021 at a Southwestern U.S. Level II trauma center on admitted trauma patients aged 13 years and older. The multicomponent initiative included a change in the screening instrument and timing of application, implementing electronic medical record documentation screens, and educating staff. The primary outcome measure was screening adherence. RESULTS: A total of n = 4,734 patients were included in the study period. Alcohol misuse screening improved from 2.9% to 87.4% and remained sustained for over a year after the initiative's implementation. CONCLUSION: The performance improvement initiative improved the alcohol misuse screening process, resulting in consistent screenings exceeding the American College of Surgeons standards of 80% for verified trauma centers.
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Alcoholismo , Humanos , Alcoholismo/diagnóstico , Etanol , Documentación , Registros Electrónicos de Salud , HospitalizaciónRESUMEN
BACKGROUND AND OBJECTIVES: Cortical motor stimulation (CMS) is used to modulate neuropathic pain. The literature supports its use; however, short follow-up studies might overestimate its real effect. This study brings real-world evidence from two independent centers about CMS methodology and its long-term outcomes. METHODS: Patients with chronic refractory neuropathic pain were implanted with CMS. The International Classification of Headache Disorders 3rd Edition was used to classify craniofacial pain and the Douleur Neuropathique en 4 Questions Scale score to explore its neuropathic nature. Demographics and clinical and surgical data were collected. Pain intensity at 6, 12, and 24 months and last follow-up was registered. Numeric rating scale reduction of ≥50% was considered a good response. The Clinical Global Impression of Change scale was used to report patient satisfaction. RESULTS: Twelve males (38.7%) and 19 females (61.3%) with a mean age of 55.8 years (±11.9) were analyzed. Nineteen (61.5%) were diagnosed from painful trigeminal neuropathy (PTN), and seven (22.5%) from central poststroke pain. The mean follow-up was 51 months (±23). At 6 months, 42% (13/31) of the patients were responders, all of them being PTN (13/19; 68.4%). At last follow-up, only 35% (11/31) remained responders (11/19 PTN; 58%). At last follow-up, the global Numeric rating scale reduction was 34% ( P = .0001). The Clinical Global Impression of Change scale punctuated 2.39 (±0.94) after 3 months from the surgery and 2.95 (±1.32) at last follow-up ( P = .0079). Signs of suspicious placebo effect were appreciated in around 40% of the nonresponders. CONCLUSION: CMS might show long-term efficacy for neuropathic pain syndromes, with the effect on PTN being more robust in the long term. Multicentric clinical trials are needed to confirm the efficacy of this therapy for this and other conditions.
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Dolor Crónico , Neuralgia , Masculino , Femenino , Humanos , Persona de Mediana Edad , Neuralgia/diagnóstico , Neuralgia/terapia , Dolor Facial , Estudios de Seguimiento , Síndrome , Dolor Crónico/tratamiento farmacológicoRESUMEN
BACKGROUND: Prurigo nodularis (PN) is a chronic disease characterized by intense pruritus and nodular lesions associated with reduced quality of life. Until recently, no US Food and Drug Administration (FDA)-approved therapies have been available for the management of PN. Treatment regimens have been highly variable and clinical management guidelines are lacking overall; formal treatment guidelines do not exist within the US. In 2022, dupilumab became the first FDA-approved medication for PN. Multiple novel agents that target the neuroimmune underpinnings of the disease are currently in development and show promise for this challenging disorder. OBJECTIVE: To review current treatments and emerging therapies for effective management of patients with PN. METHODS: We reviewed publications on PN management identified from PubMed, Embase, Web of Science, and the Cochrane Library. We also included publicly available data on clinical trials for PN therapies reported on the US National Library of Medicine ClinicalTrials.gov, the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) Database, and the European Clinical Trials (EudraCT) Database. RESULTS: The recommended management of PN begins with an assessment of disease severity, including disease burden and pruritus intensity, and evaluation of comorbid medical disorders. Treatment goals include resolution of itch, improvement in nodules or cutaneous lesions, and improvement in quality of life. Therapies should be selected based on a patient’s clinical presentation and comorbidities. Treatment should simultaneously address the neural and immunologic components of PN. Combination therapy, particularly with conventional agents, may be beneficial. LIMITATIONS: Data on most conventional PN treatments are limited to anecdotal reports, small clinical trials, or expert consensus recommendations. No head-to-head comparative trials have evaluated the relative efficacy of conventional and/or emerging agents, or combination therapy. CONCLUSION: An effective treatment approach for patients with PN should reduce pruritus, allow nodular lesions to heal, and improve individual quality of life. The treatment landscape for PN is rapidly evolving with one FDA-approved agent and several new promising therapies on the horizon. J Drugs Dermatol. 2023;22:12(Suppl 2):s15-22.
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Prurigo , Humanos , Prurigo/diagnóstico , Prurigo/tratamiento farmacológico , Prurigo/complicaciones , Calidad de Vida , Prurito/diagnóstico , Prurito/tratamiento farmacológico , Prurito/etiología , Resultado del Tratamiento , ComorbilidadRESUMEN
Navigating robots with precision in complex environments remains a significant challenge. In this article, we present an innovative approach to enhance robot localization in dynamic and intricate spaces like homes and offices. We leverage Visual Question Answering (VQA) techniques to integrate semantic insights into traditional mapping methods, formulating a novel position hypothesis generation to assist localization methods, while also addressing challenges related to mapping accuracy and localization reliability. Our methodology combines a probabilistic approach with the latest advances in Monte Carlo Localization methods and Visual Language models. The integration of our hypothesis generation mechanism results in more robust robot localization compared to existing approaches. Experimental validation demonstrates the effectiveness of our approach, surpassing state-of-the-art multi-hypothesis algorithms in both position estimation and particle quality. This highlights the potential for accurate self-localization, even in symmetric environments with large corridor spaces. Furthermore, our approach exhibits a high recovery rate from deliberate position alterations, showcasing its robustness. By merging visual sensing, semantic mapping, and advanced localization techniques, we open new horizons for robot navigation. Our work bridges the gap between visual perception, semantic understanding, and traditional mapping, enabling robots to interact with their environment through questions and enrich their map with valuable insights. The code for this project is available on GitHub https://github.com/juandpenan/topology_nav_ros2.
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The lack of economic resources has a negative effect on the maternal role of younger mothers. In Chile, the majority of adolescent pregnancies occur in socially and economically vulnerable contexts. The current study aimed to examine the relationship between demographic variables within the family context and parenting behaviors among Chilean adolescent mothers (including affection, responsiveness, encouragement, and teaching). These factors were correlated with communication, problem-solving abilities, and personal-social development in typically developing infants. The study included a sample of 79 Chilean adolescent mother-child dyads with children aged 10 to 24 months. Communication, problem-solving, and personal-social development were assessed using the Ages and Stages Questionnaire-3, along with a demographic information questionnaire. The parenting behaviors mentioned above were observed using the Spanish version of Parenting Interactions with Children: Checklist of Observations Linked to Outcomes. The findings indicated that mothers in employment and those who had not dropped out of school had children with better problem-solving skills. Additionally, children residing with their fathers and female children performed better in communication, problem-solving, and personal-social development. Maternal responsiveness was associated with communication and problem-solving, while maternal encouragement was linked to improved problem-solving skills. Maternal teaching was connected to communication, problem-solving, and personal-social development. The study emphasized the significance of parenting and sociodemographic factors among adolescent mothers and their influence on their children's development.
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The gene dosage compensation hypothesis presents a mechanism through which the expression of certain genes is modulated to compensate for differences in the dose of genes when additional chromosomes are present. It is one of the means through which cancer cells actively cope with the potential damaging effects of aneuploidy, a hallmark of most cancers. Dosage compensation arises through several processes, including downregulation or overexpression of specific genes and the relocation of dosage-sensitive genes. In cancer, a majority of compensated genes are generally thought to be regulated at the translational or post-translational level, and include the basic components of a compensation loop, including sensors of gene dosage and modulators of gene expression. Post-translational regulation is mostly undertaken by a general degradation or aggregation of remaining protein subunits of macromolecular complexes. An increasingly important role has also been observed for transcriptional level regulation. This article reviews the process of targeted gene dosage compensation in cancer and other biological conditions, along with the mechanisms by which cells regulate specific genes to restore cellular homeostasis. These mechanisms represent potential targets for the inhibition of dosage compensation of specific genes in aneuploid cancers. This article critically examines the process of targeted gene dosage compensation in cancer and other biological contexts, alongside the criteria for identifying genes subject to dosage compensation and the intricate mechanisms by which cells orchestrate the regulation of specific genes to reinstate cellular homeostasis. Ultimately, our aim is to gain a comprehensive understanding of the intricate nature of a systems-level property. This property hinges upon the kinetic parameters of regulatory motifs, which we have termed "gene dosage sensor loops." These loops have the potential to operate at both the transcriptional and translational levels, thus emerging as promising candidates for the inhibition of dosage compensation in specific genes. Additionally, they represent novel and highly specific therapeutic targets in the context of aneuploid cancer.
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Compensación de Dosificación (Genética) , Neoplasias , Humanos , Dosificación de Gen , Regulación de la Expresión Génica , Aneuploidia , Regulación hacia Abajo , Neoplasias/genéticaRESUMEN
Tumor heterogeneity leads to drug resistance in cancer treatment with the crucial role of sphingolipids in cell fate and stress signaling. We analyzed sphingolipid metabolism and autophagic flux to study chemotherapeutic interactions on the A549 lung cancer model. Loaded cells with fluorescent sphingomyelin analog (BODIPY) and mCherry-EGFP-LC3B were used to track autophagic flux and assess cytotoxicity when cells are exposed to chemotherapy (epirubicin, cisplatin, and paclitaxel) together with sphingolipid pathway inhibitors and autophagy modulators. Our cell model approach employed fluorescent sphingolipid biosensors and a Gaussian Mixture Model of cell heterogeneity profiles to map the influence of chemotherapy on the sphingolipid pathway and infer potential synergistic interactions. Results showed significant synergy, especially when combining epirubicin with autophagy inducers (rapamycin and Torin), reducing cell viability. Cisplatin also synergized with a ceramidase inhibitor. However, paclitaxel often led to antagonistic effects. Our mapping model suggests that combining chemotherapies with autophagy inducers increases vesicle formation, possibly linked to ceramide accumulation, triggering cell death. However, the in silico model proposed ceramide accumulation in autophagosomes, and kinetic analysis provided evidence of sphingolipid colocalization in autophagosomes. Further research is needed to identify specific sphingolipids accumulating in autophagosomes. These findings offer insights into potential strategies for overcoming chemotherapy resistance by targeting the sphingolipid pathway.
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Neoplasias Pulmonares , Esfingolípidos , Humanos , Esfingolípidos/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Cisplatino/farmacología , Epirrubicina , Cinética , Ceramidas/farmacología , Ceramidas/metabolismo , Paclitaxel/farmacologíaRESUMEN
Background: Hemifacial spasm (HFS) is characterized by involuntary, progressive, and intermittent spasms in the upper and lower facial muscles. Due to the high success rate, microvascular decompression (MVD) is the treatment of choice, and intraoperative neuromonitoring (INM) is considered useful for achieving safe surgery. Still, most centers do not have this technology. Methods: We analyzed 294 patients with HFS treated with MVD without INM. We only included patients with a neurovascular etiology while excluding other causes, such as tumors. As part of the postoperative evaluation, we assessed preoperative magnetic resonance imaging and pure-tone audiometry. Results: The main complication was peripheral facial paralysis in 50 patients, followed by hypoacusis in 22 patients and deafness in 17 patients, associated with a failed surgical outcome (P = 0.0002). The anterior inferior cerebellar artery (AICA) was an offending vessel, and the involvement of more than one vessel was significantly associated with the development of facial nerve palsy (P = 0.01). AICA was also associated with hearing impairment (P = 0.04). Over 90% of immediate complications improve in the follow-up (6 months), and one patient did not show a cure for initial HFS. Conclusion: MVD is the method with the highest long-term cure rates for treating HFS; however, we must inquire into the multiple factors of the patient and the surgeon to predict surgical outcomes. INM is not a must during MVD for HFS. We recommend its use depending on the availability and mainly on the surgeon's skills, for surgeons.
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Climate change challenges modern agriculture to develop alternative and eco-friendly solutions to alleviate abiotic and/or biotic stresses. The use of soil microbiomes from extreme environments opens new avenues to discover novel microorganisms and microbial functions to protect plants. In this study we confirm the ability of a bioinoculant, generated by natural engineering, to promote host development under water stress. Microbiome engineering was mediated through three factors i) Antarctic soil donation, ii) water deficit and iii) multigenerational tomato host selection. We revealed that tomato plants growing in soils supplemented with Antarctic microbiota were tolerant to water deficit stress after 10 generations. A clear increase in tomato seedling tolerance against water deficit stress was observed in all soils over generations of Host Mediated Microbiome Engineering, being Fildes mixture the most representatives, which was evidenced by an increased survival time, plant stress index, biomass accumulation, and decreased leaf proline content. Microbial community analysis using 16s rRNA gene amplicon sequencing data suggested a microbiome restructuring that could be associated with increased tolerance of water deficit. Additionally, the results showed a significant increase in the relative abundance of Candidatus Nitrosocosmicus and Bacillus spp. which could be key taxa associated with the observed tolerance improvement. We proposed that in situ microbiota engineering through the evolution of three factors (long-standing extreme climate adaption and host and stress selection) could represent a promising strategy for novel generation of microbial inoculants.
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Incoercible or intractable pain is defined as pain that is refractory to pharmacological treatment to such an extent that opioid and analgesic adverse effects outweigh the therapeutic effects. The anterior cingulate cortex (ACC) is involved in the perception of pain, especially emotional pain, so it is logical that cingulotomy has an effective therapeutic effect. Therefore, we evaluated the effectiveness of cingulotomy for the treatment of incoercible pain. An observational, longitudinal, retrospective, and analytical study was carried out on a series of cases in which bilateral cingulotomy was performed for incoercible pain, and follow-up was performed 6 months after neurosurgery in the outpatient clinic at the Neurotraumatology Clinic. A positive correlation was observed between pain intensity and medication use, indicating that an increase in pain was associated with a greater requirement for analgesics. The result was a significant reduction in pain, as measured by the visual analog scale of pain, and decreased drug use after cingulotomy. We concluded that cingulotomy reduces incoercible pain and the need for medication.