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1.
Commun Biol ; 7(1): 1253, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39362977

RESUMEN

Bioactive metabolites play a crucial role in shaping interactions among diverse organisms. In this study, we identified cyclo(Pro-Tyr), a metabolite produced by Bacillus velezensis, as a potent inhibitor of Botrytis cinerea and Caenorhabditis elegans, two potential cohabitant eukaryotic organisms. Based on our investigation, cyclo(Pro-Tyr) disrupts plasma membrane polarization, induces oxidative stress and increases membrane fluidity, which compromises fungal membrane integrity. These cytological and physiological changes induced by cyclo(Pro-Tyr) may be triggered by the destabilization of membrane microdomains containing the [H+]ATPase Pma1. In response to cyclo(Pro-Tyr) stress, fungal cells activate a transcriptomic and metabolomic response, which primarily involves lipid metabolism and Reactive Oxygen Species (ROS) detoxification, to mitigate membrane damage. This similar response occurs in the nematode C. elegans, indicating that cyclo(Pro-Tyr) targets eukaryotic cellular membranes.


Asunto(s)
Botrytis , Caenorhabditis elegans , Membrana Celular , ATPasas de Translocación de Protón , Caenorhabditis elegans/metabolismo , Animales , ATPasas de Translocación de Protón/metabolismo , ATPasas de Translocación de Protón/genética , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Antifúngicos/farmacología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Microdominios de Membrana/metabolismo , Microdominios de Membrana/efectos de los fármacos
2.
Eur J Hum Genet ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333429

RESUMEN

Establishing a molecular diagnosis remains challenging in half of individuals with childhood-onset neuromuscular diseases (NMDs) despite exome sequencing. This study evaluates the diagnostic utility of combining genomic approaches in undiagnosed NMD patients. We performed deep phenotyping of 58 individuals with unsolved childhood-onset NMDs that have previously undergone inconclusive exome studies. Genomic approaches included trio genome sequencing and RNASeq. Genetic diagnoses were reached in 23 out of 58 individuals (40%). Twenty-one individuals carried causal single nucleotide variants (SNVs) or small insertions and deletions, while 2 carried pathogenic structural variants (SVs). Genomic sequencing identified pathogenic variants in coding regions or at the splice site in 17 out of 21 resolved cases, while RNA sequencing was additionally required for the diagnosis of 4 cases. Reasons for previous diagnostic failures included low coverage in exonic regions harboring the second pathogenic variant and involvement of genes that were not yet linked to human diseases at the time of the first NGS analysis. In summary, our systematic genetic analysis, integrating deep phenotyping, trio genome sequencing and RNASeq, proved effective in diagnosing unsolved childhood-onset NMDs. This approach holds promise for similar cohorts, offering potential improvements in diagnostic rates and clinical management of individuals with NMDs.

3.
Womens Health (Lond) ; 20: 17455057241279039, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39320480

RESUMEN

BACKGROUND: Some studies have reported that homocysteine, vitamin B12, and folic acid levels are associated with polycystic ovary syndrome (PCOS), whereas other studies yielded controversial results. OBJECTIVES: This study aimed to systematize the available evidence of homocysteine, vitamin B12, and folate levels in women with and without PCOS. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND METHODS: A systematic search without language restrictions was performed on PubMed, Ovid/Medline, Scopus, Embase, and Web of Science. In addition, the reference lists of the selected studies were reviewed. The Newcastle-Ottawa Scale was employed to evaluate the quality of studies. The means and standard deviations of the outcomes were pooled as standardized mean differences (SMDs) with 95% confidence intervals (CI). Furthermore, the DerSimonian and Laird method was employed for the quantitative synthesis. RESULTS: A total of 75 studies met the eligibility criteria for at least one outcome. Patients with PCOS had higher circulating homocysteine levels than those without (SMD: 0.82; 95% CI: 0.62-1.02, n = 70 studies, p < 0.001). This trend remained in the sensitivity and subgroup analyses by world regions of studies, assay methods, and insulin resistance. No significant differences were observed in circulating vitamin B12 (SMD: -0.11; 95% CI: -0.25 to 0.03; n = 17 studies, p = 0.13) and folate levels (SMD: -0.2; 95% CI: -0.68 to 0.27; n = 17 studies, p = 0.41) between patients with and without PCOS. CONCLUSIONS: (i) Patients with PCOS exhibited significantly higher homocysteine levels than those without, and (ii) no significant differences were observed in both vitamin B12 and folate levels in women with and without PCOS. REGISTRATION: PROSPERO ID (CRD42023432883).


Asunto(s)
Ácido Fólico , Homocisteína , Síndrome del Ovario Poliquístico , Vitamina B 12 , Humanos , Síndrome del Ovario Poliquístico/sangre , Ácido Fólico/sangre , Femenino , Vitamina B 12/sangre , Homocisteína/sangre
5.
J Eye Mov Res ; 17(2)2024.
Artículo en Inglés | MEDLINE | ID: mdl-39246715

RESUMEN

This cross-sectional study examined eye movement performance in patients aged 4 to 16 years. Measurements of eye movements were obtained before and after performing therapy for inhibition of four primitive reflexes, asymmetric tonic neck reflex, symmetric tonic neck reflex, labyrinthine tonic reflex and Moro reflex. Subsequently the scores of the four primitive reflexes were compared with the results of five variables: fixation maintenance, % mean saccade size, motility excursions, fixations during excursions and mean duration of fixations. The comparisons showed a significant reduction in evidence of fixation maintenance as well as mean saccade size due to the inhibition of the four primitive reflexes. There was also a significant increase in ocular motility while fixations per saccade and average duration of fixations also decreased significantly. Visual balance between values of both eyes improved in all tests. A device called VisagraphTM III, which measures eye movements, was used for data collection. These results suggest that the oculomotor improvements reflect the involvement of other maturational processes such as the emergence and inhibition of primitive reflexes, the whole reorganization being key to future reading and attentional processes.

6.
Diabetes Metab Syndr ; 18(7): 103095, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39098208

RESUMEN

BACKGROUND & AIMS: Asprosin is a promising candidate for novel treatments for metabolic-endocrine disorders. The objective of this systematic review and meta-analysis was to consolidate the existing evidence regarding asprosin levels in patients diagnosed with type 2 diabetes (T2D), metabolic syndrome (MetS), and obesity. METHODS: Scopus, Embase, PubMed, Ovid/Medline, and Web of Science were systematically searched without restrictions. We only used the standardized mean differences (SMD) with their 95 % confidence intervals (95 % CI) as the effect measure. A random-effects model (DerSimonian and Laird method) was used for the meta-analysis. Risk of bias was assessed with the Newcastle-Ottawa Scale and Newcastle-Ottawa Scale for Cross-Sectional Studies. RESULTS: Twenty-six studies (n = 3,787) were included in the meta-analysis. Participants with T2D had higher asprosin values than those without T2D (SMD: 1.64; 95 % CI: 1.08-2.21; I2 = 97 %). Patients with MetS had higher asprosin levels compared to those without MetS (SMD: 0.99; 95 % CI: 0.34-1.64; I2 = 96 %). Patients with obesity had higher asprosin levels than participants without obesity (SMD: 1.49; 95 % CI: 0.23-2.76; I2 = 98 %). CONCLUSIONS: Asprosin is significantly higher in patients with either T2D, MetS, or obesity, compared with controls.


Asunto(s)
Diabetes Mellitus Tipo 2 , Fibrilina-1 , Síndrome Metabólico , Obesidad , Humanos , Síndrome Metabólico/sangre , Diabetes Mellitus Tipo 2/sangre , Obesidad/complicaciones , Obesidad/sangre , Biomarcadores/análisis , Biomarcadores/sangre , Pronóstico , Adipoquinas
7.
Food Res Int ; 192: 114743, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39147549

RESUMEN

Oil-in-water emulsions (EM) have been extensively used for the encapsulation of lipophilic bioactive compounds and posterior incorporation into food matrices to obtain functional foods. Conversely, novel excipient oil-in-water emulsions (EXC) present identical composition and structure as EM, albeit are not bioactive by themselves since no bioactive compound is encapsulated. Instead, EXC aims at improving the bioavailability of foods' natural bioactive compounds upon co-ingestion with nutrient-rich foods. In this work, EM and EXC were produced and their stability and functionality as delivery systems for α-tocopherol compared. Emulsions were formulated with corn oil and lecithin, and their composition was optimized using experimental designs. Formulations produced with 3 % lecithin and 5 % oil attained smallest particles sizes with the lowest polydispersity index of all tested formulations and remained stable up to 60 days. Encapsulation of α-tocopherol did not have a significative impact on the structural properties of the particles produced with the same composition. α-tocopherol stability during in vitro digestion was superior in EM regardless the processing methodology (EM stability < 50 %, EXC stability < 29 %), indicating that EM offered greater protection against the digestive environment. α-tocopherol's bioaccessibility was significantly increased when encapsulated or when digested with added excipient emulsions (82-92 % and 87-90 % for EM and EXC, respectively). In conclusion, EM were more efficient vehicles for the selected bioactive compound, however, the good results obtained with EXC imply that excipient emulsions have a great potential for applications on foods to improve their natural bioactive compounds' bioavailability without the need of further processing.


Asunto(s)
Disponibilidad Biológica , Digestión , Emulsiones , Excipientes , Tamaño de la Partícula , alfa-Tocoferol , Emulsiones/química , alfa-Tocoferol/química , Excipientes/química , Lecitinas/química , Aceite de Maíz/química , Sistemas de Liberación de Medicamentos
8.
Actas Dermosifiliogr ; 2024 Jul 18.
Artículo en Inglés, Español | MEDLINE | ID: mdl-39032775

RESUMEN

Atopic dermatitis (AD) is a chronic, inflammatory skin disease affecting all age groups, particularly children. This systematic review provides an overview of the humanistic and economic disease burden in the pediatric population with AD in Spain. The evidence, collected from 11 observational studies published over the past 10 years, exhibits the most common characteristics of the patients, disease burden, patient-reported outcomes, use of resources, and treatment patterns. The burden of AD extends beyond physical symptoms, with associated comorbidities such as asthma and impaired health-related quality of life and mental health disorders, particularly in severe cases. Traditional therapies, primarily topical corticosteroids, face adherence and efficacy challenges. Despite promising innovative treatments and available biological therapies, their use is still limited in the pediatric population. The findings of the present review highlight the scarce scientific evidence on the economic burden of pediatric AD, as well as the most updated humanistic evidence on this disease. At the same time, the need for individualized care and innovative therapeutic interventions to address the multifaceted challenges of pediatric AD in Spain is evident.

9.
Actas Dermosifiliogr ; 2024 Jul 18.
Artículo en Inglés, Español | MEDLINE | ID: mdl-39032773

RESUMEN

BACKGROUND: Functional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents. OBJECTIVE: To evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used. PATIENTS AND METHODS: The Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016-2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had two photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores - both before and after treatment - as well as the outcomes percent considered excellent (>9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents' assessments. RESULTS: The median follow-up was 3.1 years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; p<0.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; p>0.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever. CONCLUSION: This is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the three therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.

10.
Actas Dermosifiliogr ; 2024 Jul 18.
Artículo en Inglés, Español | MEDLINE | ID: mdl-39032783

RESUMEN

Justification and objectives: The Spanish Academy of Dermatology and Venereology (AEDV) Psoriasis and Pediatric Working Groups (PSW and PWG) have developed a set of recommendations for the management of pediatric psoriasis based on the best available evidence and experts' opinion. Methodology: The methodology of nominal groups was followed, with help from a scoping review. A coordinator was designated, and a group of experts was selected based on their experience and knowledge on the management of psoriasis. The coordinator defined both the objectives and the key points of the document. Then, with help from a documentalist, a systematic literature review was conducted across Medline, Embase and Cochrane Library until May 2023. Systematic literature reviews, meta-analyses, and observational studies were included. National and international clinical practice guidelines and consensus documents were reviewed. With this information, the coordinator proposed preliminary recommendations that were discussed and modified in a nominal group meeting with all experts. After several review processes, which included an external review, the final document was generated. Results: Practical recommendations on the evaluation and management of patients with pediatric psoriasis are presented in association with other AEDV documents. The evaluation of the pediatric patient, the definition of the therapeutic objectives, the criteria for indication and selection of treatment are addressed. Practical issues such as therapeutic failure, response maintenance, comorbidity and risk management are also included.

11.
J Diabetes Complications ; 38(9): 108810, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39042958

RESUMEN

AIM: To determine the association between atherogenic markers, such as total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL-C), triglycerides/HDL-C ratio (TG/HDL-C), and triglycerides-glucose index (TyG), and the risk of 1-year amputation in adults with diabetic foot in a tertiary level hospital. METHODS: Retrospective cohort study conducted in 162 adult patients with diabetic foot. The outcome was amputation, defined as "primary amputation in patients' clinical history after their first hospitalization due to foot ulcer.". The cutoff point was determined using Youden's J statistic. The relative risk (RR) was presented as an association measure. RESULTS: A TyG index of >9.4 [RR: 1.64 (1.10-2.45)] was associated with a high risk of amputation after 1-year in adults with diabetic foot. However, while a TC/HDL ratio of >4.69 [RR: 1.38 (0.94-2.03)] and a TG/HDL-C ratio > 3.57 [RR: 1.35 (0.89-2.06)] did not show associations with risk of amputation after 1-year. CONCLUSIONS: Only a TyG index of >9.4 was associated with an increased risk of 1-year amputation in adults with diabetic foot. Future studies with larger samples and a longitudinal design may provide more robust evidence and a better understanding of clinical implications.


Asunto(s)
Amputación Quirúrgica , Biomarcadores , Pie Diabético , Centros de Atención Terciaria , Humanos , Pie Diabético/cirugía , Pie Diabético/sangre , Pie Diabético/epidemiología , Amputación Quirúrgica/estadística & datos numéricos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Centros de Atención Terciaria/estadística & datos numéricos , Biomarcadores/sangre , Estudios de Cohortes , Aterosclerosis/sangre , Aterosclerosis/epidemiología , Aterosclerosis/cirugía , Aterosclerosis/complicaciones , Factores de Riesgo , Triglicéridos/sangre , HDL-Colesterol/sangre , Adulto , Glucemia/análisis , Glucemia/metabolismo
12.
Int J Mol Sci ; 25(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39063034

RESUMEN

Duchenne and Becker muscular dystrophies, caused by pathogenic variants in DMD, are the most common inherited neuromuscular conditions in childhood. These diseases follow an X-linked recessive inheritance pattern, and mainly males are affected. The most prevalent pathogenic variants in the DMD gene are copy number variants (CNVs), and most patients achieve their genetic diagnosis through Multiplex Ligation-dependent Probe Amplification (MLPA) or exome sequencing. Here, we investigated a female patient presenting with muscular dystrophy who remained genetically undiagnosed after MLPA and exome sequencing. RNA sequencing (RNAseq) from the patient's muscle biopsy identified an 85% reduction in DMD expression compared to 116 muscle samples included in the cohort. A de novo balanced translocation between chromosome 17 and the X chromosome (t(X;17)(p21.1;q23.2)) disrupting the DMD and BCAS3 genes was identified through trio whole genome sequencing (WGS). The combined analysis of RNAseq and WGS played a crucial role in the detection and characterisation of the disease-causing variant in this patient, who had been undiagnosed for over two decades. This case illustrates the diagnostic odyssey of female DMD patients with complex structural variants that are not detected by current panel or exome sequencing analysis.


Asunto(s)
Cromosomas Humanos X , Distrofina , Genómica , Distrofia Muscular de Duchenne , Translocación Genética , Humanos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/diagnóstico , Femenino , Distrofina/genética , Cromosomas Humanos X/genética , Genómica/métodos , Variaciones en el Número de Copia de ADN , Secuenciación del Exoma , Transcriptoma/genética , Cromosomas Humanos Par 17/genética
13.
Adv Appl Microbiol ; 128: 1-40, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39059841

RESUMEN

In Chile, as in the rest of the world, only a small fraction of the fungal diversity inhabiting the wide variety of its ecosystems is known. This diversity must hide an inestimable richness of species with interesting biotechnological potential, including fungal pigment producers. Recently, interest in filamentous fungi has increased significantly due to their importance as alternative sources of pigments and colorants that are environmentally and human health friendly. As a result, fungal pigments are gaining importance in various industrial applications, such as food, textiles, pharmaceuticals, cosmetics, etc. The increasing consumer demand for "green label" natural colorants requires the exploration of different ecosystems in search of new fungal species that are efficient producers of different pigment with a wide range of colors and ideally without the co-production of mycotoxins. However, advances are also needed in pigment production processes through fermentation, scale-up from laboratory to industrial scale, and final product formulation and marketing. In this respect, the journey is still full of challenges for scientists and entrepreneurs. This chapter describes studies on pigment-producing fungi collected in the forests of central-southern Chile. Aspects such as the exploration of potential candidates as sources of extracellular pigments, the optimization of pigment production by submerged fermentation, methods of pigment extraction and purification for subsequent chemical characterization, and formulation (by microencapsulation) for potential cosmetic applications are highlighted. This potential use is due to the outstanding bioactivity of most fungal pigments, making them interesting functional ingredients for many applications. Finally, the use of fungal pigments for textile and spalting applications is discussed.


Asunto(s)
Bosques , Hongos , Pigmentos Biológicos , Pigmentos Biológicos/biosíntesis , Pigmentos Biológicos/química , Chile , Hongos/metabolismo , Hongos/genética , Hongos/clasificación , Fermentación
14.
Actas Dermosifiliogr ; 115(9): T915-T916, 2024 Oct.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38925451
15.
Mol Genet Metab ; 142(3): 108511, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38878498

RESUMEN

The diagnosis of Mendelian disorders has notably advanced with integration of whole exome and genome sequencing (WES and WGS) in clinical practice. However, challenges in variant interpretation and uncovered variants by WES still leave a substantial percentage of patients undiagnosed. In this context, integrating RNA sequencing (RNA-seq) improves diagnostic workflows, particularly for WES inconclusive cases. Additionally, functional studies are often necessary to elucidate the impact of prioritized variants on gene expression and protein function. Our study focused on three unrelated male patients (P1-P3) with ATP6AP1-CDG (congenital disorder of glycosylation), presenting with intellectual disability and varying degrees of hepatopathy, glycosylation defects, and an initially inconclusive diagnosis through WES. Subsequent RNA-seq was pivotal in identifying the underlying genetic causes in P1 and P2, detecting ATP6AP1 underexpression and aberrant splicing. Molecular studies in fibroblasts confirmed these findings and identified the rare intronic variants c.289-233C > T and c.289-289G > A in P1 and P2, respectively. Trio-WGS also revealed the variant c.289-289G > A in P3, which was a de novo change in both patients. Functional assays expressing the mutant alleles in HAP1 cells demonstrated the pathogenic impact of these variants by reproducing the splicing alterations observed in patients. Our study underscores the role of RNA-seq and WGS in enhancing diagnostic rates for genetic diseases such as CDG, providing new insights into ATP6AP1-CDG molecular bases by identifying the first two deep intronic variants in this X-linked gene. Additionally, our study highlights the need to integrate RNA-seq and WGS, followed by functional validation, in routine diagnostics for a comprehensive evaluation of patients with an unidentified molecular etiology.


Asunto(s)
Intrones , ARN Mensajero , Humanos , Masculino , Intrones/genética , ARN Mensajero/genética , ATPasas de Translocación de Protón Vacuolares/genética , Trastornos Congénitos de Glicosilación/genética , Trastornos Congénitos de Glicosilación/diagnóstico , Trastornos Congénitos de Glicosilación/patología , Mutación , Secuenciación Completa del Genoma , Secuenciación del Exoma , Análisis de Secuencia de ARN , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/patología , Niño , Empalme del ARN/genética , Preescolar
16.
Int J Antimicrob Agents ; 64(2): 107248, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38908535

RESUMEN

INTRODUCTION: We systematically assessed benefits and harms of the use of ivermectin in non-hospitalized patients with early COVID-19. METHODS: Five databases were searched until October 17, 2023, for randomized controlled trials (RCTs) in adult patients with COVID-19 treated with ivermectin against standard of care (SoC), placebo, or active drug. Primary outcomes were hospitalization, all-cause mortality, and adverse events (AEs). Secondary outcomes included mechanical ventilation (MV), clinical improvement, clinical worsening, viral clearance, and severe adverse events (SAEs). Random effects meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. Pre-specified subgroup analyses (ivermectin dose, control type, risk of bias, follow-up, and country income) and trial sequential analysis (TSA) were performed. RESULTS: Twelve RCTs (n = 7,035) were included. The controls were placebo in nine RCTs, SoC in two RCTs, and placebo or active drug in one RCT. Ivermectin did not reduce hospitalization (relative risk [RR], 0.81, 95% confidence interval [95% CI] 0.64-1.03; 8 RCTs, low QoE), all-cause mortality (RR 0.98, 95% CI 0.73-1.33; 9 RCTs, low QoE), or AEs (RR 0.89, 95% CI 0.75-1.07; 9 RCTs, very low QoE) vs. controls. Ivermectin did not reduce MV, clinical worsening, or SAEs and did not increase clinical improvement and viral clearance vs. controls (very low QoE for secondary outcomes). Subgroup analyses were mostly consistent with main analyses, and TSA-adjusted risk for hospitalization was similar to main analysis. CONCLUSIONS: In non-hospitalized COVID-19 patients, ivermectin did not have effect on clinical, non-clinical or safety outcomes versus controls. Ivermectin should not be recommended as treatment in non-hospitalized COVID-19 patients.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Ivermectina , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2 , Ivermectina/uso terapéutico , Ivermectina/efectos adversos , Humanos , SARS-CoV-2/efectos de los fármacos , Hospitalización/estadística & datos numéricos , Resultado del Tratamiento , COVID-19/mortalidad , Antivirales/uso terapéutico , Antivirales/efectos adversos , Respiración Artificial/estadística & datos numéricos
17.
New Microbes New Infect ; 60-61: 101439, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911488

RESUMEN

Introduction: Avian influenza A H5N1 is a significant global public health threat. Although relevant, systematic reviews about its prevalence in animals are lacking. Methods: We performed a systematic literature review in bibliographic databases to assess the prevalence of H5N1 in animals. A meta-analysis with a random-effects model was performed to calculate the pooled prevalence and 95 % confidence intervals (95%CI). In addition, measures of heterogeneity (Cochran's Q statistic and I2 test) were reported. Results: The literature search yielded 1359 articles, of which 33 studies were fully valid for analysis, including 96,909 animals. The pooled prevalence for H5N1 in birds (n = 90,045, 24 studies) was 5.0 % (95%CI: 4.0-6.0 %; I2 = 99.21); in pigs (n = 3,178, 4 studies) was 1.0 % (95%CI: 0.0-1.0 %); in cats (n = 2,911, 4 studies) was 0.0 % (95%CI: 0.0-1.0 %); and in dogs (n = 479, 3 studies) was 0.0 % (95%CI: 0.0-2.0 %). Conclusions: While the occurrence of H5N1 in animals might be comparatively limited compared to other influenza viruses, its impact on public health can be substantial when it transmits to humans. This virus can potentially induce severe illness and has been linked to previous outbreaks. Therefore, it is essential to closely monitor and comprehend the factors influencing the prevalence of H5N1 in both avian and human populations to develop effective disease control and prevention strategies.

18.
PLoS One ; 19(6): e0305689, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38917093

RESUMEN

BACKGROUND: Dengue has emerged as an unprecedented epidemic in Peru, and it is anticipated that this issue will escalate further owing to climate change. This study aimed to determine the risk factors associated with death from dengue in patients treated at Hospital II in Pucallpa, Peru. METHODOLOGY: This retrospective cohort study collected information from the medical records of patients with a diagnosis of dengue treated at Hospital II Pucallpa-Peru between January 2019 and March 2023. The primary outcome was death, and the secondary outcome was death, development of severe dengue, or Intensive Care Unit (ICU) admission. Cox regression models were used to determine risk factors. FINDINGS: The clinical records of 152 patients were evaluated, with a median age of 27.5 years (interquartile range, 11-45). Among all patients, 29 (19.1%) developed severe dengue, 31 (20.4%) were admitted to the ICU, and 13 (8.6%) died during follow-up. In the survival analysis, bilirubin >1.2 mg/dL was associated with a higher risk of death aHR: 11.38 (95% CI: 1.2 106.8). Additionally, factors associated with poor prognosis included having 1 to 3 comorbidities aRR: 1.92 (1.2 to 3.2), AST ≥251 U/L aRR: 6.79 (2.2 to 21.4), history of previous dengue aRR: 1.84 (1.0 to 3.3), and fibrinogen ≥400 mg/dL aRR: 2.23 (1.2 to 4.1). SIGNIFICANCE: Elevated bilirubin was associated with death from dengue, whereas an increase in comorbidities and a history of previous dengue were related to a poor prognosis of the disease. Early identification of severe dengue would be more feasible with improved access to laboratory testing, particularly in tropical areas with a high dengue incidence.


Asunto(s)
Dengue , Humanos , Perú/epidemiología , Factores de Riesgo , Masculino , Adulto , Femenino , Persona de Mediana Edad , Dengue/epidemiología , Dengue/mortalidad , Estudios Retrospectivos , Adolescente , Adulto Joven , Niño , Unidades de Cuidados Intensivos , Dengue Grave/epidemiología , Dengue Grave/mortalidad , Pronóstico , Estudios de Cohortes
19.
FASEB J ; 38(11): e23716, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38847490

RESUMEN

Tumor hypoxia has been associated with cancer progression, angiogenesis, and metastasis via modifications in the release and cargo composition of extracellular vesicles secreted by tumor cells. Indeed, hypoxic extracellular vesicles are known to trigger a variety of angiogenic responses via different mechanisms. We recently showed that hypoxia promotes endosomal signaling in tumor cells via HIF-1α-dependent induction of the guanine exchange factor ALS2, which activates Rab5, leading to downstream events involved in cell migration and invasion. Since Rab5-dependent signaling is required for endothelial cell migration and angiogenesis, we explored the possibility that hypoxia promotes the release of small extracellular vesicles containing ALS2, which in turn activate Rab5 in recipient endothelial cells leading to pro-angiogenic properties. In doing so, we found that hypoxia promoted ALS2 expression and incorporation as cargo within small extracellular vesicles, leading to subsequent transfer to recipient endothelial cells and promoting cell migration, tube formation, and downstream Rab5 activation. Consequently, ALS2-containing small extracellular vesicles increased early endosome size and number in recipient endothelial cells, which was followed by subsequent sequestration of components of the ß-catenin destruction complex within endosomal compartments, leading to stabilization and nuclear localization of ß-catenin. These events converged in the expression of ß-catenin target genes involved in angiogenesis. Knockdown of ALS2 in donor tumor cells precluded its incorporation into small extracellular vesicles, preventing Rab5-downstream events and endothelial cell responses, which depended on Rab5 activity and guanine exchange factor activity of ALS2. These findings indicate that vesicular ALS2, secreted in hypoxia, promotes endothelial cell events leading to angiogenesis. Finally, these events might explain how tumor angiogenesis proceeds in hypoxic conditions.


Asunto(s)
Movimiento Celular , Vesículas Extracelulares , Factores de Intercambio de Guanina Nucleótido , Transducción de Señal , beta Catenina , Proteínas de Unión al GTP rab5 , Humanos , Proteínas de Unión al GTP rab5/metabolismo , Proteínas de Unión al GTP rab5/genética , beta Catenina/metabolismo , Vesículas Extracelulares/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Factores de Intercambio de Guanina Nucleótido/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Línea Celular Tumoral
20.
Infez Med ; 32(2): 183-201, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827825

RESUMEN

Introduction: Dengue is a vector-borne disease, especially important in tropical and subtropical areas. The first presentation of many arboviral diseases occurred mainly in animals, including multiple Alphaviruses and Flaviviruses, such as dengue. Objective: To determine the serological and molecular frequency of the dengue virus in animals. Methods: A systematic literature review was carried out in five databases for the proportion of animals infected with dengue, defined by molecular and serological tests. A meta-analysis was performed using a random-effects model to calculate the pooled prevalence and 95% confidence intervals (CI). Cochran?s Q test and the I2 statistic were used to assess the heterogeneity between the two studies. Results: The presence of dengue in bats, primates, birds, sheep, horses, cattle, pigs, rodents and buffaloes, according to serological methods, had a prevalence of 10%, 29%, 8%, 1%, 11%, 0%, 49%, 2%, 7%, respectively. According to molecular methods, the presence of dengue in bats had a seroprevalence of 6.0%. Conclusion: The present study confirms the presence of the Dengue virus in a large group of animal species, with potential implications as possible reservoirs of this virus, raising the possibility of zoonotic transmission.

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