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1.
BMC Infect Dis ; 24(1): 222, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38374000

ABSTRACT

INTRODUCTION: The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis. METHODOLOGY: Retrospective, multicenter, descriptive study based on a 3-year follow-up of patients diagnosed with HIV infection due to MTCT in 2018 in 10 hospitals in 8 Latin American countries (Costa Rica, Ecuador, Mexico, Honduras, El Salvador, Panama, Guatemala and Venezuela). The hospitals belonged to the PLANTAIDS network, which is included in CYTED (Ibero-American Programme of Science and Technology for Development). RESULTS: The study population comprised 72 pediatric patients (38.9% male). The median age at diagnosis was 2.4 years (IQR: 0.8-5.4). There were 35 cases of opportunistic infections corresponding to 25 patients (34.7%), with tuberculosis being the most common. Adequate childhood vaccination coverage was achieved in 80.5%. There were 3 cases of acute SARS-CoV-2 infection, and these were asymptomatic or mildly symptomatic. According to the Centers for Disease Control and Prevention (CDC) classification, the most frequent clinical-immunological stage at all check-ups was C1. Three patients died from opportunistic infections and/or advanced HIV infection. CONCLUSIONS: It is important to diagnose HIV infection early in pediatrics, since early initiation of ART is associated with a decrease in mortality. Despite this, HIV infection has a poor prognosis in children, necessitating adequate follow-up to ensure adherence to health care and ART, although it can sometimes prove difficult in children.


Subject(s)
HIV Infections , Opportunistic Infections , Child , Humans , Male , Female , Infant , Child, Preschool , Latin America/epidemiology , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV , Retrospective Studies , Infectious Disease Transmission, Vertical/prevention & control , Follow-Up Studies
2.
Community Dent Oral Epidemiol ; 52(1): 84-92, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37668224

ABSTRACT

OBJECTIVE: This systematic review with meta-analysis was performed to assess whether motivational interviewing (MI) effectively prevents oral morbidities in adults. METHODS: Studies considered were randomized controlled trials, cluster-randomized controlled trials and community-based randomized trials assessing interventions based on MI or indicating that a counselling technique based on the principles developed by Miller and Rollnick was used. Controls were any type of oral health education or negative controls. Participants were 18-60 years old. The main outcome was any oral morbidity. From 602 studies identified in MEDLINE, Scopus, Web of Science and LILACS databases, seven studies were included in the synthesis. RESULTS: Studies included only evaluated periodontal outcomes, no studies were found for other oral morbidities. Patients' mean age was 43.7 years, and the follow-up time after MI or MI-based intervention varied between 1 month and 1 year. The total study population was 272 people with moderate-to-severe periodontitis; other groups analysed were pregnant women (n = 112) and patients with mental disorders and alcohol problems (n = 60). Meta-analysis for the plaque index (four studies, n = 267), bleeding on probing (two studies, n = 177) and gingival index (two studies, n = 166) were carried out. The summary effects for the random-effects model were estimated respectively as -3.59 percentage points (CI: [-11.44; 4.25] for plaque index, -6.41 percentage points (CI: [-12.18, -0.65]) for bleeding on probing and -0.70 (CI: [-1.87; 0.48]) for gingival index, marginally favouring the MI group. The reduced number of studies, the non-disclosure of some aspects of the data and the heterogeneity among them undermine the precision of the estimates. CONCLUSION: The current evidence available is limited to periodontal outcomes, and it is not possible to determine whether MI effectively prevents oral morbidities in adults.


Subject(s)
Motivational Interviewing , Periodontitis , Adolescent , Adult , Female , Humans , Middle Aged , Pregnancy , Young Adult , Motivational Interviewing/methods , Periodontitis/prevention & control
3.
Article in English | LILACS-Express | LILACS | ID: biblio-1535945

ABSTRACT

Aim: To describe the clinical picture, diagnosis, and treatment of a patient with encephalopathy as a manifestation of manganese-induced non-Wilsonian hepatolenticular degeneration (NWHD) in a high-complexity care center in a Latin American country. Case description: A 55-year-old male patient from the United States with a history of liver disease associated with alcohol consumption was admitted to the emergency department due to diarrhea, hematemesis, and psychomotor agitation. During his stay, his state of consciousness deteriorated, requiring orotracheal intubation. In his diagnostic study, cerebrospinal fluid tests were negative for infectious etiologies; the endoscopic examinations showed no marks of portal hypertension bleeding, while ammonium and tests for metabolic causes were normal. However, areas of hyperintensity in the basal ganglia were documented on brain MRI, with normal ceruloplasmin serum and urine copper levels, which ruled out Wilson's disease and determined the diagnosis of manganese-induced NWHD. Conclusion: NWHD is a rare cause of chronic encephalopathy with clinical manifestations of extrapyramidal symptoms secondary to basal ganglia dysfunction due to severe liver disease. Its diagnosis becomes a challenge, given that manganese deposits produce it, and no biomarkers can establish the level of exposure to this metal. Brain MRI is indispensable in reflecting these deposits in the basal ganglia.


Objetivo: Describir la presentación clínica, el diagnóstico y el tratamiento de un paciente con encefalopatía como manifestación de degeneración hepatolenticular no wilsoniana producida por manganeso, en un centro de alta complejidad de un país latinoamericano. Descripción del caso: Paciente masculino de 55 años, procedente de Estados Unidos, con antecedente de enfermedad hepática asociada con consumo de alcohol, quien ingresó al servicio de urgencias por un cuadro de diarrea, hematemesis y agitación psicomotora. Durante la estancia presentó deterioro en el estado de consciencia, por lo que requirió intubación orotraqueal. En su estudio diagnóstico, las pruebas de líquido cefalorraquídeo fueron negativas para etiologías infecciosas, en los estudios endoscópicos no tenía estigmas de sangrado portal hipertensivo y el amonio y los estudios para causas metabólicas fueron normales. Sin embargo, se documentaron áreas de hiperintensidad en los ganglios de la base en la resonancia magnética cerebral, con niveles de ceruloplasmina sérica y cobre urinario normales, lo que descartó enfermedad de Wilson y definió el diagnóstico de degeneración hepatolenticular no wilsoniana por depósitos de manganeso. Conclusión: La degeneración hepatolenticular no wilsoniana es una causa infrecuente de encefalopatía crónica con manifestaciones clínicas de extrapiramidalismo, secundaria a disfunción de los ganglios de la base por enfermedad hepática grave. Su diagnóstico se convierte en un reto, dado que se produce por depósitos de manganeso y no existen biomarcadores que puedan establecer el nivel de exposición a este metal. La resonancia magnética cerebral juega, por tanto, un papel indispensable al reflejar esos depósitos en los ganglios de la base.

4.
iScience ; 26(10): 107898, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37790273

ABSTRACT

An excessive production of lactate by cancer cells fosters tumor growth and metastasis. Therefore, targeting lactate metabolism and transport offers a new therapeutic strategy against cancer, based on dependency of some cancer cells for lactate as energy fuel or as oncogenic signal. Herein we present a family of anionophores based on the structure of click-tambjamines that have proved to be extremely active lactate carriers across phospholipid membranes. Compound 1, the most potent lactate transmembrane carrier, was studied in HeLa cells. The use of a monocarboxylate transporters (MCTs) inhibitor proved that 1 is an active lactate transporter in living cells, confirming the results obtained in phospholipid vesicles. Moreover, an additive effect of compound 1 with cisplatin was observed in HeLa cells. Identification of active lactate anionophores working in living cells opens up ways to exploit this class of compounds as molecular tools and drugs addressing dysregulated lactate metabolism.

5.
Org Biomol Chem ; 21(12): 2509-2515, 2023 03 22.
Article in English | MEDLINE | ID: mdl-36880402

ABSTRACT

A series of fluorescent coumarin bis-ureas 1-4 have been synthesised, and their anion transport properties studied. The compounds function as highly potent HCl co-transport agents in lipid bilayer membranes. Single crystal X-ray diffraction of compound 1 showed antiparallel stacking of the coumarin rings, stabilised by hydrogen bonds. Binding studies, using 1H-NMR titration, showed moderate chloride binding in DMSO-d6/0.5% with 1 : 1 binding mode (for transporter 1) and 1 : 2 binding mode (host: guest, for transporters 2-4). We examined the cytotoxicity of compounds 1-4 against three cancer cell lines, lung adenocarcinoma (A549), colon adenocarcinoma (SW620) and breast adenocarcinoma (MCF-7). The most lipophilic transporter, 4 showed a cytotoxic effect against all three cancer cell lines. Cellular fluorescence studies showed compound 4 crossed the plasma membrane and localised in the cytoplasm after a short time. Interestingly, compound 4, lacking any lysosome targeting groups, was co-localised with LysoTracker Red at 4 and 8 h in the lysosome. Cellular anion transport of compound 4 was assessed by measuring intracellular pH and showed a decrease in cellular pH, which may be due to the capacity of transporter 4 to co-transport HCl across biological membranes, as evidenced by the liposomal studies.


Subject(s)
Adenocarcinoma , Antineoplastic Agents , Colonic Neoplasms , Humans , Cell Line, Tumor , Cell Death , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Anions/chemistry , Coumarins/pharmacology , Hydrogen-Ion Concentration
6.
J Clin Exp Dent ; 15(2): e125-e134, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36911151

ABSTRACT

Background: The growth of ameloblastomas (odontogenic tumours) and odontogenic keratocyst (OKC) (developmental cyst) is associated with the expression of proteins related to cell survival and apoptosis. Bcl-2-associated protein X (Bax) and the tumour suppressor protein p53 collectively promote p53-mediated apoptosis. This study aimed to assess the immunohistochemical expression of p53, Bcl-2 and Bax in conventional ameloblastoma (CA), unicystic ameloblastoma (UA) types, and OKC sporadic (OKC-NS/S) and syndromic (OKC-NBSCC). Material and Methods: Paraffinized blocks of CA (n=18), UA (n=15), OKC-NS/S (n=18) and OKC-NBSCC (n=15) fixed in 10% formalin were used. After diagnosis, tissue specimens were stained by immunohistochemistry for p53, Bcl-2 and Bax marker. Stained cells were randomly counted in five high power fields. The data analysis was performed via Shapiro-Wilk test, ANOVA with Tukey's multiple comparisons or Kruskal-Wallis with Dunn's multiple comparisons. Statistical significance was defined as p<0.05. Results: We did not observe differences between p53 expression in CA, mural UA (MUA), intraluminal/luminal UA (I/LUA), OKC-NS/S, and OKC-NBSCC (19.69%, 18.74%, 16.76%, 12.35% and 9.04%, respectively). Similar results were recognized for Bax expression in CA, MUA, I/LUA, OKC-NS/S, and OKC-NBSCC (33.72%, 34.95%, 22.94, 21.58% and 20.76%, respectively). However, we recognized significant differences between Bcl-2 expression in OKC-NS/S vs MUA, OKC-NS/S vs I/LUA, OKC-NS/S vs CA, OKC-NBSCC vs MUA, OKC-NBSCC vs I/LUA, and I/LUA vs CA. P53, Bcl-2 and Bax levels were higher in mural morphological areas versus intraluminal and luminal morphological areas in UA. Conclusions: There is a tendency for an increased expression of p53, Bcl-2, and Bax proteins in CA, and mural proliferation of UA, compared to lesions with a cystic morphology, which could be associated with a local aggressive behaviour. Key words:p53, Bcl-2, Bax protein, apoptosis, odontogenic tumour, odontogenic cyst.

7.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 41(1): 36-39, Ene. 2023. graf, tab
Article in Spanish | IBECS | ID: ibc-214215

ABSTRACT

Introducción: Las enfermedades infecciosas pueden beneficiarse de la aplicación de la telemedicina (TM). Este estudio realiza una descripción de las enfermedades infecciosas atendidas por el Servicio de Telemedicina del Hospital Central de la Defensa Gómez Ulla (STM-HCDGU). Métodos: Análisis de las e-consultas realizadas por miembros de las Fuerzas Armadas de España desplazados a zona de operaciones en el periodo comprendido entre el 1 de enero del 2015 y el 31 de diciembre del 2018 que desarrollaron sintomatología infecciosa. Resultados: Se diagnosticaron 127 enfermedades infecciosas, siendo las más frecuentes las de etiología respiratoria y posteriormente la malaria. Geográficamente, África y los contingentes embarcados fueron los más significados. Fue necesario evacuar a 18 pacientes al HCDGU, siendo el diagnóstico de malaria el motivo de evacuación más frecuente, causa del único caso mortal. Conclusiones: Las enfermedades infecciosas se benefician de la aplicación de la TM, siendo una herramienta importante para el diagnóstico y tratamiento de estas, constituyendo una oportunidad para ampliar a otras poblaciones desplazadas o remotas.(AU)


Introduction: Infectious pathologies can benefit from the application of Telemedicine (TM). This study provides a description of the infectious pathology treated by the Telemedicine Service of the Hospital Central de la Defensa Gómez Ulla (STM-HCDGU). Methods: Analysis of the e-consultations made by members of the Armed Forces of Spain displaced to the area of operations in the period between 01/1/2015 and 31/12/2018 who developed symptoms of infectious diseases. Results: 127 infectious diseases were diagnosed, the most frequent being those of respiratory etiology and later malaria. Geographically Africa and embarked contingents were the most significant. It was necessary to evacuate 18 patients to the HCDGU, being the diagnosis of malaria the most frequent reason for evacuation, cause of the only fatal case. Conclusions: infectious diseases benefit from the application of TM, being an important tool for the diagnosis and treatment of these, constituting an opportunity to expand to other displaced or remote populations.(AU)


Subject(s)
Humans , Telemedicine , Communicable Diseases , Remote Consultation , 51708 , Epidemiology, Descriptive , Spain
9.
Article in English | MEDLINE | ID: mdl-35810142

ABSTRACT

INTRODUCTION: Infectious pathologies can benefit from the application of Telemedicine (TM). This study provides a description of the infectious pathology treated by the Telemedicine Service of the Hospital Central de la Defensa Gómez Ulla (STM-HCDGU). METHODS: Analysis of the e-consultations made by members of the Armed Forces (FA) of Spain displaced to the area of ​​operations (ZO) in the period between 01/1/2015 and 31/12/2018 who developed infectious symptoms. RESULTS: 127 infectious diseases were diagnosed, the most frequent being those of respiratory etiology and later malaria. Geographically Africa and embarked contingents were the most significant. It was necessary to evacuate 18 patients to the HCDGU, being the diagnosis of malaria the most frequent reason for evacuation, cause of the only fatal case. CONCLUSIONS: infectious diseases benefit from the application of TM, being an important tool for the diagnosis and treatment of these, constituting an opportunity to expand to other displaced or remote populations.


Subject(s)
Communicable Diseases , Malaria , Military Personnel , Telemedicine , Humans , Communicable Diseases/diagnosis , Communicable Diseases/therapy , Hospitals
10.
Andrology ; 11(1): 24-31, 2023 01.
Article in English | MEDLINE | ID: mdl-36375449

ABSTRACT

BACKGROUND: Ample evidence indicates a sex-related difference in severity of COVID-19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID-19 severity. OBJECTIVE: To test the association between the androgen receptor polyQ polymorphism and COVID-19 severity in a large cohort of COVID-19 male patients. MATERIALS AND METHODS: This study included 1136 male patients infected with SARS-CoV-2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short (<23 repeats) or long (≥23 repeats) allele carriers. The association between polyQ alleles (short or long) and COVID-19 severity was assessed by Chi-squared (Chi2 ) and logistic regression analysis. RESULTS: The mean number of polyQ CAG repeats was 22 (±3). Patients were classified as oligosymptomatic (15.5%), hospitalized (63.2%), and severe patients (21.3%) requiring substantial respiratory support. PolyQ alleles distribution did not show significant differences between severity classes in our cohort (Chi2 test p > 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis). DISCUSSION: Androgen sensitivity may be a critical factor in COVID-19 disease severity. However, we did not find an association between the polyQ polymorphism and the COVID-19 severity. Additional studies are needed to clarify the mechanism underlying the association between androgens and COVID-19 outcome. CONCLUSIONS: The results obtained in our study do not support the role of this polymorphism as biomarker of COVID-19 severity.


Subject(s)
COVID-19 , Receptors, Androgen , Humans , Male , Receptors, Androgen/genetics , Alleles , Trinucleotide Repeats/genetics , Retrospective Studies , COVID-19/genetics , SARS-CoV-2/genetics , Biomarkers
11.
Geroscience ; 45(1): 543-553, 2023 02.
Article in English | MEDLINE | ID: mdl-36184726

ABSTRACT

Clonal hematopoiesis, especially that of indeterminate potential (CHIP), has been associated with age-related diseases, such as those contributing to a more severe COVID-19. Four studies have attempted to associate CHIP with COVID-19 severity without conclusive findings. In the present work, we explore the association between CHIP and COVID-19 mortality. Genomic DNA extracted from peripheral blood of COVID-19 patients (n = 241 deceased, n = 239 survivors) was sequenced with the Myeloid Solutions™ panel of SOPHiA Genetics. The association between clonality and age and clonality and mortality was studied using logistic regression models adjusted for sex, ethnicity, and comorbidities. The association with mortality was performed with patients stratified into four groups of age according to the quartiles of the distribution: 60-74 years, 75-84 years, 85-91 years, and 92-101 years. Clonality was found in 38% of the cohort. The presence of CHIP variants, but not the number, significantly increased with age in the entire cohort of COVID-19 patients, as well as in the group of survivors (p < 0.001). When patients were stratified by age and the analysis adjusted, CHIP classified as pathogenic/likely pathogenic was significantly more represented in deceased patients compared with survivors in the group of 75-84 years (34.6% vs 13.7%, p = 0.020). We confirmed the well-established linear relationship between age and clonality in the cohort of COVID-19 patients and found a significant association between pathogenic/likely pathogenic CHIP and mortality in patients from 75 to 84 years that needs to be further validated.


Subject(s)
COVID-19 , Clonal Hematopoiesis , Humans , Aged , Hematopoiesis/genetics , Comorbidity
12.
Gac. méd. Méx ; 158(6): 380-386, nov.-dic. 2022. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1430367

ABSTRACT

Resumen Introducción: Las bioprótesis de válvulas cardiacas son el estándar de oro para el reemplazo quirúrgico de la válvula aórtica en pacientes seleccionados. Objetivo: Evaluar la seguridad y eficacia de la válvula cardiaca bioprotésica del Instituto Nacional de Cardiología (INC) en humanos. Métodos: Estudio unicéntrico que incluyó 341 pacientes que se sometieron a reemplazo valvular quirúrgico único de válvula aórtica con válvula INC. Resultados: Se realizaron 318 implantes de novo (93 %) y 23 como segunda cirugía (7 %); las puntuaciones STS fueron de 1.4 y 1.8 % y el seguimiento de 42 y 46 meses, respectivamente. No existieron diferencias en las complicaciones ni en la tasa de implantación de marcapasos. Ambos grupos mantuvieron una FEVI normal. Se observó mejoría global en la clase funcional con empeoramiento solo en dos pacientes del grupo de novo. La disfunción de la prótesis INC que ameritó reintervención quirúrgica se observó en ocho pacientes (4.65 %) del grupo de novo versus un paciente (7.69 %) con segunda cirugía. Conclusiones: La válvula cardiaca INC es eficaz y segura, se asocia a baja tasa de complicaciones y mejoría de la clase funcional durante el seguimiento a largo plazo. Se necesitan estudios prospectivos comparativos de esta válvula.


Abstract Introduction: Heart valve bioprostheses are the gold standard for aortic valve surgical replacement in selected patients. Objective: To evaluate the safety and efficacy of the of the National Institute of Cardiology (INC) bioprosthetic heart alve of the National Institute of Cardiology (INC) bioprosthetic heart valve in humans. Methods: Single-center study that ncluded 341 patients who underwent single surgical aortic valve replacement with INC heart valve. Results: 318 implants were performed de novo (93%) and 23 as redo surgery (7%); STS scores were 1.4 and 1.8%, and follow-up was for 42 and 46 months, respectively. There were no differences in clinical complications or pacemaker implantation rate. Both groups maintained a normal LVEF. Overall improvement in functional class was observed, with worsening only in two patients of the de novo group. INC prosthesis dysfunction requiring surgical reintervention was observed in eight patients (4.65%) of the de novo group vs. one patient in the redo group. Conclusions: The INC heart valve is efficacious and safe, and is associated with a The INC heart valve is efficacious and safe, and is associated with a low rate of complications and functional class improvement during long-term follow-up. Prospective, comparative studies of this valve are required.

13.
Case Rep Med ; 2022: 1559360, 2022.
Article in English | MEDLINE | ID: mdl-36092309

ABSTRACT

Alcaligenes faecalis (A. faecalis) is a Gram-negative rod rarely isolated as an infective bacterium worldwide. The first cases of infections caused by this microorganism, such as pneumonia, soft tissue infections, urinary tract infections, bacteremia, and meningitis, date back more than 40 years and are almost entirely in newborns and immunosuppressed hosts. Optimal antibiotic therapy for A. faecalis has not been well established in the literature. We report a case of an immunocompetent patient in Colombia who had meningitis due to A. faecalis after a dental procedure. It is important to know about this microorganism that nowadays could be considered a potentially emerging pathogen in immunocompetent adults.

14.
Open Heart ; 9(2)2022 08.
Article in English | MEDLINE | ID: mdl-35926961

ABSTRACT

BACKGROUND: The evaluation of long-term inflammatory response and function in postoperative patients with aortic valve replacement (AVR) deserves special analysis because it is important to try to prevent reoperation and improve durability and functionality of the prostheses. It is our objective METHODS: In this study, we included a cohort of patients with aortic valve damage treated by AVR with mechanical prosthesis, bio prosthesis and we included a control group. RESULTS: We found that IL-4 and osteopontin levels were higher in patients with mechanical vs biological prostheses (p=0.01 and p=0.04, respectively), osteoprotegerin (OPG) levels were decreased (p=0.01), women had lower levels of ET-1 and IL-6, (p=0.02) (p=0.04), respectively. Patients older than 60 years had decreased levels of IL-1ß p<0.001) and a higher concentration of IL-4 p<0.05). IL-1ß, OPG and TNFα were higher in patients with less than 5 years of evolution vs more than 10 years (p=0.004, p=0.02 and p=0.03, respectively). Factors such as age, gender, prosthetic and elevated IL-1B and ET-1 levels are associated with valve dysfunction prosthetic. These results indicate that the inflammatory involvement present prior to valve replacement may be perpetuated by various factors in the long term. CONCLUSIONS: The findings provide us with the opportunity to effectively treat patients with AVR in the postoperative period, which could prolong the functionality of the bio prostheses. TRIAL REGISTRATION NUMBER: NCT04557345.


Subject(s)
Bioprosthesis , Heart Valve Diseases , Heart Valve Prosthesis Implantation , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Bioprosthesis/adverse effects , Female , Heart Valve Diseases/diagnosis , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/methods , Humans , Interleukin-4 , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Retrospective Studies
15.
Cancers (Basel) ; 14(14)2022 Jul 12.
Article in English | MEDLINE | ID: mdl-35884450

ABSTRACT

Overcoming resistance is one of the most challenging features in current anticancer therapy. Autophagy is a cellular process that confers resistance in some advanced tumors, since it enables cancer cells to adapt to stressful situations, such as anticancer treatments. Hence, the inhibition of this cytoprotective autophagy leads to tumor cells sensitization and death. In this regard, we designed a novel potent anionophore compound that specifically targets lysosomes, called LAI-1 (late-stage autophagy inhibitor-1), and evaluated its role in blocking autophagy and its potential anticancer effects in three lung cancer cell lines from different histological subtypes. Compared to other autophagy inhibitors, such as chloroquine and 3-Methyladenine, the LAI-1 treatment induced more potent anticancer effects in all tested cancer cells. LAI-1 was able to efficiently target and deacidify lysosomes, while acidifying cytoplasmic pH. Consequently, LAI-1 efficiently blocked autophagy, indicated by the increased LC3-II/I ratio and p62/SQSTM1 levels. Moreover, no colocalization was observed between autophagosomes, marked with LC3 or p62/SQSTM1, and lysosomes, stained with LAMP-1, after the LAI-1 treatment, indicating the blockage of autophagolysosome formation. Furthermore, LAI-1 induced cell death by activating apoptosis (enhancing the cleavage of caspase-3 and PARP) or necrosis, depending on the cancer cell line. Finally, LAI-1 sensitized cancer cells to the first-line chemotherapeutic agent cisplatin. Altogether, LAI-1 is a new late-stage autophagy inhibitor that causes lysosomal dysfunction and the blockage of autophagolysosome formation, as well as potently induces cancer cell death and sensitization to conventional treatments at lower concentrations than other known autophagy inhibitors, appearing as a potential new therapeutic approach to overcome cancer resistance.

16.
Sci Rep ; 12(1): 10369, 2022 06 20.
Article in English | MEDLINE | ID: mdl-35725860

ABSTRACT

Rare variants affecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n = 44). To this end, different etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodeficiencies or blood coagulation were studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially influence COVID-19 outcome in our cohort of patients. Further studies are needed to confirm the ultimate role of the genetic variants described in the present study on COVID-19 severity.


Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Aged , COVID-19/genetics , Cohort Studies , Genetic Predisposition to Disease , Humans , Middle Aged , Exome Sequencing
17.
J Clin Med ; 11(9)2022 Apr 22.
Article in English | MEDLINE | ID: mdl-35566467

ABSTRACT

Sexuality is a component of great relevance in humans. Sexual disorders are a major public health problem representing a high prevalence in the general population. DSM-5 genito-pelvic pain/penetration disorder (GPPPD) includes dyspareunia and vaginismus (DSM-IV-TR). To assess the importance of research on these disorders in Spain, we evaluated the Spanish scientific publications of primary and community care. The objective was to quantify the magnitude of the publications of GPPPD in Spanish women in primary and community care. For this, we used the method of conducting a systematic review and meta-analysis of studies evaluating GPPPD. As main results, of the 551 items found, we selected 11 studies that met the inclusion criteria. In primary care in Spain, one in nine women has these disorders; the percentage of women with GPPPD in this study (raw data) was 11.23% (95% CI: 0-29%) (vaginismus 5%; penetration pain 8.33%; dyspareunia 16.45%). These percentages can differ of those from other countries, and they are at the top of the data of the European countries (9-11.9%). There is much variability in the studies found in the world with respect to the prevalence of these health problems.

18.
Trop Dis Travel Med Vaccines ; 8(1): 12, 2022 May 15.
Article in English | MEDLINE | ID: mdl-35568905

ABSTRACT

Since the COVID-19 outbreak, millions of people have been infected with SARS-CoV-2 around the world. An area of epidemiological relevance is Latin America, tropical regions, due to the distribution of endemic diseases such as chikungunya, dengue (DENV), malaria, Zika virus, where febrile disease abounds. The early signs and symptoms of DENV and COVID-19 could be similar, making it a risk that patients may be wrongly diagnosed early during the disease. The problem increases since COVID-19 infection can lead to false positives in DENV screening tests. We present two cases of acute undifferentiated febrile syndrome that were diagnosed with SARS-CoV-2 and DENV co-infection, confirmed by ELISA and RT-PCR for both viral pathogens. The occurrence of simultaneous or overlapped infections can alter the usual clinical course, severity, or outcome of each infection. Therefore, epidemiological surveillance and intensified preparation for those scenarios must be considered, as well as further studies should be done to address cases of co-infection promptly to avoid major complications and fatal outcomes during the current pandemic. Other endemic tropical diseases should not be neglected.

19.
Preprint in English | medRxiv | ID: ppmedrxiv-22271678

ABSTRACT

Ample evidence indicates a sex-related difference in severity of COVID-19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyQ polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID-19 severity. In this study, we analyzed this association in a large cohort of 1136 men classified into three groups according to their degree of COVID-19 severity, finding a similar distribution of polyQ alleles among severity groups. Therefore, our results do not support the role of this polymorphism as a biomarker of COVID-19 severity.

20.
Materials (Basel) ; 15(3)2022 Feb 02.
Article in English | MEDLINE | ID: mdl-35161108

ABSTRACT

Currently, a significant portion (~50%) of global warming emissions, such as CO2, are related to energy production and transportation. As most energy usage will be electrical (as well as transportation), the efficient management of electrical power is thus central to achieve the XXI century climatic goals. Ultra-wide bandgap (UWBG) semiconductors are at the very frontier of electronics for energy management or energy electronics. A new generation of UWBG semiconductors will open new territories for higher power rated power electronics and solar-blind deeper ultraviolet optoelectronics. Gallium oxide-Ga2O3 (4.5-4.9 eV), has recently emerged pushing the limits set by more conventional WBG (~3 eV) materials, such as SiC and GaN, as well as for transparent conducting oxides (TCO), such asIn2O3, ZnO and SnO2, to name a few. Indeed, Ga2O3 as the first oxide used as a semiconductor for power electronics, has sparked an interest in oxide semiconductors to be investigated (oxides represent the largest family of UWBG). Among these new power electronic materials, AlxGa1-xO3 may provide high-power heterostructure electronic and photonic devices at bandgaps far beyond all materials available today (~8 eV) or ZnGa2O4 (~5 eV), enabling spinel bipolar energy electronics for the first time ever. Here, we review the state-of-the-art and prospects of some ultra-wide bandgap oxide semiconductor arising technologies as promising innovative material solutions towards a sustainable zero emission society.

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