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1.
IJID Reg ; 13: 100432, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39308787

RESUMEN

Objectives: To describe the sociodemographic distribution of dermatomycosis and the visits burden over a 10-year period of care. Methods: An ecological study was conducted using data on visits and people treated in the Colombian Health System during 2010-2019 using the International Classification of Diseases, Tenth Revision codes (ICD-10). Departments and geopolitical regions were the units of analysis, and visit burden was reported as frequency, intensity (visits per person), and rate of dermatomycosis visits (per 10,000 visits; 95% confidence interval). Results: A total of 4,570,593 visits were analyzed. The most used ICD-10 codes were B369 (superficial mycosis, unspecified), B360 (pityriasis versicolor), B354 (Tinea corporis), B359 (dermatophytosis), and B351 (Tinea unguium) (56.5%), with visits primarily involving the adult population (27-59 years; 32.2%), women (43.4%), and urban populations (57.3%). Amazonas department had the highest rate of visits (2.36 per 10,000), while Nariño had the highest intensity of visits (1.94 visits per person). Caribbean region had the highest rate of visits (17.0 per 10,000 visits; 17.0-17.0), followed by the Amazon region (16.3 per 10,000 visits; 16.2-16.4). Conclusions: The annual visits burden of dermatomycosis in Colombia is high and concentrated in susceptible geographic areas, possibly due to socio-environmental factors. This health problem is overshadowed by chronic diseases and trauma but is often recurrent, and chronic, and induces out-of-pocket costs for treatment.

2.
Toxics ; 12(8)2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39195716

RESUMEN

Bioelectrochemical processes are emerging as one of the most efficient and sustainable technologies for wastewater treatment. Their application for industrial wastewater treatment is still low due to the high toxicity and difficulty of biological treatment for industrial effluents. This is especially relevant in pharmaceutical industries, where different solvents, active pharma ingredients (APIs), extreme pH, and salinity usually form a lethal cocktail for the bacterial community in bioreactors. This work evaluates the impact of the anode architecture on the detoxification performance and analyzes, for the first time, the profile of some key bioremediation enzymes (catalase and esterase) and reactive oxygen species (ROS) during the operation of microbial electrochemical cells treating real pharmaceutical wastewater. Our results show the existence of oxidative stress and loss of cell viability in planktonic cells, while the electrogenic bacteria that form the biofilm maintain their biochemical machinery intact, as observed in the bioelectrochemical response. Monitorization of electrical current flowing in the bioelectrochemical system showed how electroactive biofilm, after a short adaptation period, started to degrade the pharma effluent. The electroactive biofilms are responsible for the detoxification of this type of industrial wastewater.

3.
MicroPubl Biol ; 20242024.
Artículo en Inglés | MEDLINE | ID: mdl-39100195

RESUMEN

The Drosophila kikkawai feature with NCBI Gene ID 108084518 was determined to be an ortholog of Drosophila melanogaster Sox102F , a member of the FlyBase High Mobility Group Box Transcription Factors gene group (FBgg0000748). Five isoforms were constructed using the GEP F element annotation protocol, the longest being novel isoform Sox102F-PNE (identified using the XM_017180752 RefSeq prediction and RNA-seq data). Among the isoforms found in both D. melanogaster and D. kikkawai , Sox102F-PB is the longest and exhibits a 1.18x coding span expansion due to transposable element insertion into an intron. All D. kikkawai protein isoforms contain the conserved domain HMG_box_dom (IPR009071).

4.
Rev Med Inst Mex Seguro Soc ; 62(1): 1-10, 2024 Jan 08.
Artículo en Español | MEDLINE | ID: mdl-39106439

RESUMEN

Background: Non-pharmacological interventions (NFI) or preventive actions (PA) are the best alternatives to control future pandemics, especially in vulnerable populations, such as semi-urban areas. Objective: To describe the predominant health behavior groups (HBG) and associated factors during the third wave of COVID-19 in a semi-urban area. Material and methods: A survey which included characteristics, factors related to COVID-19, perceptions of health behavior and PA was applied in a probabilistic sample in a first-level hospital in the State of Mexico. People of both sexes over 18 years of age were included. Using a hierarchical cluster analysis, HBGs were obtained and characterized with a descriptive and multivariate statistical analysis. Results: In a probabilistic sample (n = 260), 4 HBGs were identified: 2 of high-risk (HRG) and 2 of low-risk (LRG), and the proportions were 43.5% y 56.5%, respectively. The sociodemographic characteristics of both groups were similar. Perceptions of severity and COVID-19-related barriers significantly influenced health behaviors in LRG. In HRG, low security played a significant role, highlighting the importance of comorbidities as a clinical factor. Conclusions: In a semi-urban area, 2 crucial health behaviors were identified: one associated with low risk and the other with high risk. In the HRG, the perception of insecurity was particularly relevant, emphasizing the importance of comorbidities as a clinical factor.


Introducción: las intervenciones no farmacológicas (INF) o acciones preventivas (AP) contra enfermedades son la mejor alternativa para controlar futuras pandemias, en especial en poblaciones vulnerables, como las zonas semiurbanas. Objetivo: describir los grupos predominantes de conductas de salud (GCS) y los factores asociados durante la tercera ola de la COVID-19 en una zona semiurbana. Material y métodos: se aplicó una encuesta que incluyó las características, los factores relacionados con COVID-19, las percepciones de conductas de salud y las AP, en una muestra probabilística en un hospital de primer nivel del Estado de México. Se incluyeron personas de ambos sexos, mayores de 18 años. Mediante un análisis de conglomerados se caracterizaron los GCS con un análisis estadístico descriptivo y multivariado. Resultados: en una muestra probabilistica (n = 260), se identificaron cuatro GCS: 2 de riesgo alto de contagio por la COVID-19 (GRA) y 2 de riesgo bajo (GRB) y las proporciones fueron 43.5% y 56.5%, respectivamente. Las características sociodemográficas de los grupos fueron similares. Para los GRB los factores significativos fueron las percepciones sobre la severidad y las barreras relacionadas con la COVID-19. En los GRA fue la seguridad baja y destacó la importancia de la comorbilidad como factor clínico. Conclusiones: en una zona semiurbana se identificaron 2 conductas de salud de importancia: una de bajo riesgo y otra de alto riesgo. En el GRA, la percepción de seguridad baja fue especialmente relevante, lo cual resalta la importancia de las comorbilidades como factor clínico.


Asunto(s)
COVID-19 , Conductas Relacionadas con la Salud , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Femenino , Masculino , México/epidemiología , Adulto , Persona de Mediana Edad , Estudios Transversales , Adulto Joven , Anciano , Población Suburbana , Adolescente , Encuestas y Cuestionarios
5.
Oncogenesis ; 13(1): 30, 2024 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-39097594

RESUMEN

Neratinib is a tyrosine kinase inhibitor that is used for the therapy of patients with HER2+ breast tumors. However, despite its clinical benefit, resistance to the drug may arise. Here we have created cellular models of neratinib resistance to investigate the mechanisms underlying such resistance. Chronic neratinib exposure of BT474 human HER2+ breast cancer cells resulted in the selection of several clones resistant to the antiproliferative action of the drug. The clones were characterized biochemically and biologically using a variety of techniques. These clones retained HER2 levels similar to parental cells. Knockdown experiments showed that the neratinib-resistant clones retained oncogenic dependence on HER2. Moreover, the tyrosine phosphorylation status of BT474 and the resistant clones was equally sensitive to neratinib. Transcriptomic and Western analyses showed that peptidylarginine deiminase 3 was overexpressed in the three neratinib-resistant clones studied but was undetectable in BT474 cells. Experiments performed in the neratinib-resistant clones showed that reduction of PADI3 or inhibition of its function restored sensitivity to the antiproliferative action of neratinib. Moreover, overexpression of FLAG-tagged PADI3 in BT474 cells provoked resistance to the antiproliferative action of neratinib. Together, these results uncover a role of PADI3 in the regulation of sensitivity to neratinib in breast cancer cells overexpressing HER2 and open the possibility of using PADI3 inhibitors to fight resistance to neratinib.

6.
Mol Cytogenet ; 17(1): 16, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39010086

RESUMEN

BACKGROUND: Differences in Sex Development (DSD) is a heterogeneous group of congenital alterations that affect inner and/or outer primary sex characters. Although these conditions do not represent a mortality risk, they can have a severe psycho-emotional impact if not appropriately managed. The genetic changes that can give rise to DSD are diverse, from chromosomal alterations to single base variants involved in the sexual development network. Epidemiological studies about DSD indicate a global frequency of 1:4500-5500, which can increase to 1:200-300, including isolated anatomical defects. To our knowledge, this study is the first to describe epidemiological and genetic features of DSD in a cohort of Mexican patients of a third-level care hospital. METHODS: Descriptive and retrospective cross-sectional study that analyzed DSD patients from 2015 to 2021 attended a Paediatric Hospital from Mexico City. RESULTS: One hundred one patients diagnosed with DSD were registered and grouped into different entities according to the Chicago consensus statement and the diagnosis defined by the multidisciplinary group. Of the total, 54% of them belong to the chromosomal DSD classification, 16% belongs to 46, XX and 30% of them belongs to the 46, XY classification. CONCLUSION: The frequency for chromosomal DSDs was consistent with the literature; however, we found that DSD 46, XY is more frequent in our cohort, which may be due to the age of the patients captured, the characteristics of our study population, or other causes that depend on the sample size.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38929036

RESUMEN

The WHO Dementia Global Action Plan states that rehabilitation services for dementia are required to promote health, reduce disability, and maintain quality of life for those living with dementia. Current services, however, are scarce, particularly for people with young-onset dementia (YOD). This article, written by an international group of multidisciplinary dementia specialists, offers a three-part overview to promote the development of rehabilitation services for YOD. Firstly, we provide a synthesis of knowledge on current evidence-based rehabilitative therapies for early-onset Alzheimer's disease (EOAD), behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and posterior cortical atrophy (PCA). Secondly, we discuss the characteristics of rehabilitation services for YOD, providing examples across three continents for how these services can be embedded in existing settings and the different roles of the rehabilitation multidisciplinary team. Lastly, we conclude by highlighting the potential of telehealth in making rehabilitation services more accessible for people with YOD. Overall, with this paper, we aim to encourage clinical leads to begin introducing at least some rehabilitation into their services, leveraging existing resources and finding support in the collective expertise of the broader multidisciplinary dementia professional community.


Asunto(s)
Demencia , Humanos , Demencia/rehabilitación , Demencia/terapia , Edad de Inicio , Países en Desarrollo , Países Desarrollados , Telemedicina
8.
J Mol Biol ; 436(15): 168631, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38821350

RESUMEN

Mitophagy is a specific type of autophagy responsible for the selective elimination of dysfunctional or superfluous mitochondria, ensuring the maintenance of mitochondrial quality control. The initiation of mitophagy is coordinated by the ULK1 kinase complex, which engages mitophagy receptors via its FIP200 subunit. Whether FIP200 performs additional functions in the subsequent later phases of mitophagy beyond this initial step and how its regulation occurs, remains unclear. Our findings reveal that multiple phosphorylation events on FIP200 differentially control the early and late stages of mitophagy. Furthermore, these phosphorylation events influence FIP200's interaction with ATG16L1. In summary, our results highlight the necessity for precise and dynamic regulation of FIP200, underscoring its importance in the progression of mitophagy.


Asunto(s)
Proteínas Relacionadas con la Autofagia , Mitocondrias , Mitofagia , Fosforilación , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Humanos , Mitocondrias/metabolismo , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Factores de Escisión y Poliadenilación de ARNm/genética , Células HeLa , Proteínas Portadoras/metabolismo
9.
Implement Sci Commun ; 5(1): 50, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702751

RESUMEN

BACKGROUND: Patient navigation is an individualized intervention to facilitate comprehensive care which has not yet been fully implemented in obstetric or postpartum care. METHODS: We aimed to develop and evaluate a mechanism to incorporate feedback regarding implementation of postpartum patient navigation for low-income birthing individuals at an urban academic medical center. This study analyzed the role of an Implementation Advisory Board (IAB) in supporting an ongoing randomized trial of postpartum navigation. Over the first 24 months of the trial, the IAB included 11 rotating obstetricians, one clinic resource coordinator, one administrative leader, two obstetric nurses, one primary care physician, one social worker, and one medical assistant. Members completed serial surveys regarding program implementation, effects on patient care, and areas for improvement. Quarterly IAB meetings offered opportunities for additional feedback. Survey responses and meeting notes were analyzed using the constant comparative method and further interpreted within the Exploration, Preparation, Implementation, Sustainment (EPIS) Framework. RESULTS: Members of the IAB returned 37 surveys and participated in five meetings over 24 months. Survey analysis revealed four themes among the inner context: reduced clinician burden, connection of care teams, communication strategies, and clinic workflow. Bridging factors included improved patient access to care, improved follow-up, and adding social context to care. Innovation factors included availability of navigators, importance of consistent communication, and adaptation over time. Meeting notes highlighted the importance of bidirectional feedback regarding implementation, and members expressed positive opinions regarding navigators' effects on patient care, integration into clinic workflow, and responsiveness to feedback. IAB members initially suggested changes to improve implementation; later survey responses demonstrated successful program adaptations. CONCLUSIONS: Members of an implementation advisory board provided key insights into the implementation of postpartum patient navigation that may be useful to promote dissemination of navigation and establish avenues for the engagement of implementing partners in other innovations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03922334 . Registered April 19, 2019. The results here do not present the results of the primary trial, which is ongoing.

10.
Nat Commun ; 15(1): 3059, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637500

RESUMEN

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.


Asunto(s)
Mpox , Orthopoxvirus , Poxviridae , Humanos , Monkeypox virus/genética , Genómica , Mpox/genética
11.
Health Sci Rep ; 7(3): e1965, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38524774

RESUMEN

Background and Aim: Until the May 2022 Monkeypox (MPXV) outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the MPXV outbreak in the South of Spain. Methods: Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak. Results: Whole genome sequencing of a total of 160 MPXV viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of MPXV viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating MPXV viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing before treatment.

12.
Health Equity ; 8(1): 132-137, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38435025

RESUMEN

Background: The current approach to increasing diversity in medical education fails to consider local community demographics when determining medical school matriculation. Purpose: We propose that medical schools better reflect their surrounding community, both because racially/ethnically concordant physicians have been shown to provide better care and to repair the historical and current racist impacts of these institutions that have criminalized, displaced, and excluded local Black and Brown communities. Methods and Results: In this study, we used geospatial analysis to determine that medical school enrollments generally fail to reflect their surrounding community, represented as their core-based statistical area, within which the individual medical schools reside.

13.
Environ Sci Pollut Res Int ; 31(13): 20461-20476, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38376785

RESUMEN

In the last few decades, there has been a growing interest in understanding the behavior of personal care products (PCPs) in the aquatic environment. In this regard, the aim of this study is to estimate the accumulation and effects of four PCPs within the clam Ruditapes philippinarum. The PCPs selected were triclosan, OTNE, benzophenone-3, and octocrylene. A progressive uptake was observed and maximum concentrations in tissues were reached at the end of the exposure phase, up to levels of 0.68 µg g-1, 24 µg g-1, 0.81 µg g-1, and 1.52 µg g-1 for OTNE, BP-3, OC, and TCS, respectively. After the PCP post-exposure period, the removal percentages were higher than 65%. The estimated logarithm bioconcentration factor ranged from 3.34 to 2.93, in concordance with the lipophobicity of each substance. No lethal effects were found although significant changes were observed for ethoxyresorufin O-demethylase activity, glutathione S-transferase activity, lipid peroxidation, and DNA damage.


Asunto(s)
Bivalvos , Cosméticos , Contaminantes Químicos del Agua , Animales , Peroxidación de Lípido , Daño del ADN , Alimentos Marinos , Contaminantes Químicos del Agua/análisis
14.
J Womens Health (Larchmt) ; 33(7): 975-985, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38265478

RESUMEN

Background: Although the postpartum period is an opportunity to address long-term health, fragmented care systems, inadequate attention to social needs, and a lack of structured transition to primary care threaten patient wellbeing, particularly for low-income individuals. Postpartum patient navigation is an emerging innovation to address these disparities. Methods: This mixed-methods analysis uses data from the first year of an ongoing randomized controlled trial to understand the needs of low-income postpartum individuals through 1 year of patient navigation. We designed standardized logs for navigators to record their services, tracking mode, content, intensity, and target of interactions. Navigators also completed semistructured interviews every 3 months regarding relationships with patients and care teams, care system gaps, and navigation process. Log data were categorized, quantified, and mapped temporally through 1 year postpartum. Qualitative data were analyzed using the constant comparative method. Results: Log data from 50 participants who received navigation revealed the most frequent needs related to health care access (45.4%), health and wellness (18.2%), patient-navigator relationship building (14.8%), parenting (13.6%), and social determinants of health (8.0%). Navigation activities included supporting physical and mental recovery, accomplishing health goals, connecting patients to primary and specialty care, preparing for health system utilization beyond navigation, and referring individuals to community resources. Participant needs fluctuated, yielding a dynamic timeline of the first postpartum year. Conclusion: Postpartum needs evolved throughout the year, requiring support from various teams. Navigation beyond the typical postpartum care window may be useful in mitigating health system barriers, and tracking patient needs may be useful in optimizing postpartum care. Clinical Trial Registration: Registered April 19, 2019, enrollment beginning January 21, 2020, NCT03922334, https://clinicaltrials.gov/ct2/show/NCT03922334.


Asunto(s)
Accesibilidad a los Servicios de Salud , Navegación de Pacientes , Periodo Posparto , Pobreza , Humanos , Femenino , Adulto , Embarazo , Atención Posnatal , Investigación Cualitativa
15.
EMBO Rep ; 25(1): 168-197, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38225354

RESUMEN

Cell commitment to tumourigenesis and the onset of uncontrolled growth are critical determinants in cancer development but the early events directing tumour initiating cell (TIC) fate remain unclear. We reveal a single-cell transcriptome profile of brain TICs transitioning into tumour growth using the brain tumour (brat) neural stem cell-based Drosophila model. Prominent changes in metabolic and proteostasis-associated processes including ribogenesis are identified. Increased ribogenesis is a known cell adaptation in established tumours. Here we propose that brain TICs boost ribogenesis prior to tumour growth. In brat-deficient TICs, we show that this dramatic change is mediated by upregulated HEAT-Repeat Containing 1 (HEATR1) to promote ribosomal RNA generation, TIC enlargement and onset of overgrowth. High HEATR1 expression correlates with poor glioma patient survival and patient-derived glioblastoma stem cells rely on HEATR1 for enhanced ribogenesis and tumourigenic potential. Finally, we show that HEATR1 binds the master growth regulator MYC, promotes its nucleolar localisation and appears required for MYC-driven ribogenesis, suggesting a mechanism co-opted in ribogenesis reprogramming during early brain TIC development.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Antígenos de Histocompatibilidad Menor , Proteínas Proto-Oncogénicas c-myc , Proteínas de Unión al ARN , Animales , Humanos , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Carcinogénesis/patología , Transformación Celular Neoplásica/patología , Proteínas de Unión al ADN/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Glioblastoma/metabolismo , Glioma/patología , Antígenos de Histocompatibilidad Menor/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo
16.
Pers Soc Psychol Bull ; : 1461672231219719, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38284645

RESUMEN

Using data from 15 countries, this article investigates whether descriptive and prescriptive gender norms concerning housework and child care (domestic work) changed after the onset of the COVID-19 pandemic. Results of a total of 8,343 participants (M = 19.95, SD = 1.68) from two comparable student samples suggest that descriptive norms about unpaid domestic work have been affected by the pandemic, with individuals seeing mothers' relative to fathers' share of housework and child care as even larger. Moderation analyses revealed that the effect of the pandemic on descriptive norms about child care decreased with countries' increasing levels of gender equality; countries with stronger gender inequality showed a larger difference between pre- and post-pandemic. This study documents a shift in descriptive norms and discusses implications for gender equality-emphasizing the importance of addressing the additional challenges that mothers face during health-related crises.

17.
Cureus ; 15(11): e48401, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38074021

RESUMEN

Objectives Stereotactic radiosurgery combined with pharmacological treatment is currently one of the most acceptable alternatives for the treatment of trigeminal neuralgia (TN). Our primary endpoint was to report the short-term response (one month) outcomes of 10 patients with refractory TN after CyberKnife® (CK) radiosurgery; secondary endpoints were to assess early side effects and complications. Methods Ten female patients with TN refractory to pharmacological and/or non-pharmacological treatment received a single dose of 90 Gy with CyberKnife® radiosurgery. Clinical and demographic characteristics were obtained from medical records. The visual analog scale (VAS) was used to assess facial pain before as well as seven, 15, and 30 days after treatment. Friedman test was performed to evaluate pain relief in treated patients. Results All patients responded well to the CK and experienced initial adequate pain relief during the first 30 days (p<0.001). No significant differences (p=0.661) were found between six patients who received CK radiosurgery as the first treatment option and those who underwent other non-pharmacological treatments. One patient was re-irradiated with 75 Gy. Transient facial paresthesia was observed in 3/10 patients without any other complications. Conclusion High-tech CK treatment is safe, non-invasive, fast, with minimal side effects, and effective in achieving short-term pain relief in patients with refractory TN, even in those with multiple previous interventions. Given these results, we recommend evaluating CK radiosurgery as the first-line treatment of choice for trigeminal neuralgia refractory to pharmacological treatment.

19.
J Clin Immunol ; 43(8): 2076-2089, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37740092

RESUMEN

Variants of uncertain significance (VUS) in CTLA4 are frequently identified in patients with antibody deficiency or immune dysregulation syndromes including, but not limited to, patients with multi-organ autoimmunity and autoinflammation. However, to ascertain the diagnosis of CTLA4 insufficiency, the functional relevance of each variant needs to be determined. Currently, various assays have been proposed to assess the functionality of CTLA4 VUS, including the analysis of transendocytosis, the biological function of CTLA4 to capture CD80 molecules from antigen presenting cells. Challenges of this assay include weak fluorescence intensity of the internalized ligand, poor reproducibility, and poor performance upon analyzing thawed cells. In addition, the distinction of pathogenic from non-pathogenic variants and from wild-type CTLA4, and the classification of the different VUS according to its level of CTLA4 dysfunction, would be desirable. We developed a novel CD80-expressing cell line for the evaluation of CD80-transendocytosis and compared it to the published transendocytosis assay. Our approach showed lower inter-assay variability and better robustness regardless the type of starting material (fresh or thawed peripheral mononuclear cells). In addition, receiver operating characteristic analysis showed 100% specificity, avoiding false positive results and allowing for a clear distinction between pathogenic and non-pathogenic variants in CTLA4-variant carriers. With our transendocytosis assay, we assessed the pathogenicity of 24 distinct CTLA4 variants from patients submitted to our diagnostic unit. Significantly impaired transendocytosis was demonstrated for 17 CTLA4 variants, whereas seven variants tested normal. In conclusion, our upgraded transendocytosis assay allows a reliable assessment of newly identified variants in CTLA4.


Asunto(s)
Células Presentadoras de Antígenos , Autoinmunidad , Humanos , Antígeno CTLA-4/genética , Citometría de Flujo , Reproducibilidad de los Resultados
20.
Int J Mol Sci ; 24(16)2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37628979

RESUMEN

Marine ecosystems are among the richest in terms of biodiversity, and at present, still remain largely unknown today. In the molecular biology era, several analyses have been conducted to unravel the biological processes in this ecosystem. These systems have provided biotechnological solutions to current problems, including the treatment of diseases, as well as for the development of new biotechnological tools with applications in biomedicine and/or agri-food. In addition, in the context of climate change and global warming, these studies become even more necessary for the development of molecular tools that allow a reliable follow-up of this situation to anticipate alterations and responses of bioindicator species and to create a database to prevent and predict the environmental and climatic changes before the damage is irreversible. Proteomics approaches have revealed their potential use to obtain the set of biological effectors that lead to the real biological station on a specific stage, the proteins. In addition, proteomics-based algorithms have allowed the discovery of proteins with new potential biotechnological applications from proteome data through "applied proteomics". In this project, the first proteome analysis of the sea anemone, Anemonia sulcata, and its symbiont has been developed. These organisms present a wide distribution sea ecosystem. In Spain, it is accepted as a fishing and aquaculture species. Moreover, Anemonia sulcate has a symbiotic relation with autotroph Dinoflagellates, Symbiodinium spp., that allows the study of its relation at the molecular level. For the first characterization of A. sulcata proteome, three independent biological replicates were used, and proteins were extracted and analyzed by LC-MS/MS, allowing the quantification of 325 proteins, 81 from Symbiodinium spp. proteins and 244 from A. sulcata proteins. These proteins were subjected to gene ontology categorization by Cellular Component, Molecular Function and Biological Process. These analyzes have allowed the identification of biomarkers of gene expression as potential powerful emerging diagnostic tools to identify and characterize the molecular drivers of climate change stresses and improve monitoring techniques. In addition, through the application of novel algorithms for the detection of bioactive compounds based on the analysis of molecules of marine origin, the proteome has allowed the identification of proteins with potential applications in the fields of biomedicine and agri-food.


Asunto(s)
Dinoflagelados , Anémonas de Mar , Animales , Proteómica , Ecosistema , Cambio Climático , Proteoma , Cromatografía Liquida , Espectrometría de Masas en Tándem , Biomarcadores
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