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There is a growing development of immunochromatographic tests for the detection of specific Plasmodium spp. antigens. These tests rely on capturing antigens from peripheral blood using monoclonal or polyclonal antibodies against specific targets. We present the case of a 28-year-old male patient with a history of two previous episodes of Plasmodium falciparum malaria, treated appropriately seven months and three years ago. He was referred to our institution with a six-day history of fever, epigastric pain, hematuria, and vomiting. Serial thick and thin blood smears were negative for hemoparasites, but a Bioline™ Malaria Ag P.f/Pan rapid test was positive for the Pan (pLDH) band. Given the clinical context and inability to visualize Plasmodium in blood smears, the positive pLDH band on the rapid malaria test was considered a possible false positive. Subsequent tests concluded that the patient was experiencing a cytomegalovirus (CMV) infection, which improved with supportive management, and he was discharged symptom-free. Malaria remains a major public health issue in tropical and subtropical regions. While rapid diagnostic tests are crucial for timely diagnosis, false positives due to cross-reactivity with other infections and conditions are reported. Our case highlights the potential for cross-reactivity with CMV infections, although direct evidence of active viral replication was not obtained. This phenomenon can lead to the overestimation of malaria cases and inappropriate treatment, underscoring the need for careful interpretation of rapid test results.
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Mitophagy is the degradation of mitochondria via the autophagy-lysosome system, disruption of which has been linked to multiple neurodegenerative diseases. As a flux process involving the identification, tagging, and degradation of subcellular components, the analysis of mitophagy benefits from the microscopy analysis of fluorescent reporters. Studying the pathogenic mechanisms of disease also benefits from analysis in animal models in order to capture the complex interplay of molecular and cell biological phenomena. Here, we describe protocols to analyze mitophagy reporters in Drosophila by light microscopy.
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Mitocondrias , Mitofagia , Animales , Mitocondrias/metabolismo , Genes Reporteros , Drosophila/metabolismo , Microscopía Fluorescente/métodos , Drosophila melanogaster/metabolismo , Lisosomas/metabolismo , Autofagia/fisiología , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genéticaRESUMEN
Background: The purpose of this study was to explore the usage patterns and profiles of social media (SM) platforms among Radiation Oncologists (RO) and Physicists in the scope of the Catalan-Occitan Oncology Group (GOCO). Materials and methods: From November 2022 to March 2023, a comprehensive survey was sent to Radiation Oncology professionals within the GOCO group, comprising 31 questions that covered demographics (4) and general inquiries (9), user behavior on social media (7), profile of SM activity (7), and participants' opinions (4) regarding professional use of SM. The survey reached professionals from 12 centers, encompassing 10 in Catalonia and 2 in French Occitania. Results: The survey achieved a 61.37% response rate (178/290 professionals) with an average age of 41.9 years. 120 (67%) were ROs, and 58 (33%) were Physicists. Instagram led in usage (n = 116), followed by Facebook (n = 107) and Twitter (n = 77). Age correlated inversely with the number of platforms used (Spearman's rank correlation coefficient -0.238, p = 0.001). 28% (n = 42) changed clinical practices based on SM information. A 78.5% (n = 117) didn't counter inappropriate content. Most (71.7%, n = 109) spent < 1 hour daily on professional SM use, however more Physicians exceeded 2 hours compared to Physicists (Cohen's kappa 2 = 0.07). 41.8% (n = 64) weren't emotionally concerned while 22.9% (n = 35) felt overwhelmed by SM overload. Conclusions: The study offers valuable insights into the usage patterns, preferences, and attitudes of Radiation Oncology professionals towards SM platforms. This understanding is crucial for optimizing content quality and delivering relevant information, thereby enabling more effective marketing strategies and enhancing emotional management among these professionals.
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Intramuscular fat (IMF) content is important for meat production and human health, where the host genetics and its microbiome greatly contribute to its variation. The aim of this study is to describe the consequences of the genetic modification of IMF by selecting the taxonomic composition of the microbiome, using rabbits from the 10th generation of a divergent selection experiment for IMF (high (H) and low (L) lines differ by 3.8 standard deviations). The selection altered the composition of the gut microbiota. Correlated responses were better distinguished at the genus level (51 genera) than at the phylum level (10 phyla). The H-line was enriched in Hungateiclostridium, Limosilactobacillus, Legionella, Lysinibacillus, Phorphyromonas, Methanosphaera, Desulfovibrio, and Akkermansia, while the L-line was enriched in Escherichia, Methanobrevibacter, Fonticella, Candidatus Amulumruptor, Methanobrevibacter, Exiguobacterium, Flintibacter, and Coprococcus, among other genera with smaller line differences. A microbial biomarker generated from the abundance of four of these genera classified the lines with 78% accuracy in a logit regression. Our results demonstrate different gut microbiome compositions in hosts with divergent IMF genotypes. Furthermore, we provide a microbial biomarker to be used as an indicator of hosts genetically predisposed to accumulate muscle lipids, which opens up the opportunity for research to develop probiotics or microbiome-based breeding strategies targeting IMF.
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Mitochondrial dysfunction is a common feature of C9orf72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD); however, it remains unclear whether this is a cause or consequence of the pathogenic process. Analysing multiple aspects of mitochondrial biology across several Drosophila models of C9orf72-ALS/FTD, we found morphology, oxidative stress, and mitophagy are commonly affected, which correlated with progressive loss of locomotor performance. Notably, only genetic manipulations that reversed the oxidative stress levels were also able to rescue C9orf72 locomotor deficits, supporting a causative link between mitochondrial dysfunction, oxidative stress, and behavioural phenotypes. Targeting the key antioxidant Keap1/Nrf2 pathway, we found that genetic reduction of Keap1 or pharmacological inhibition by dimethyl fumarate significantly rescued the C9orf72-related oxidative stress and motor deficits. Finally, mitochondrial ROS levels were also elevated in C9orf72 patient-derived iNeurons and were effectively suppressed by dimethyl fumarate treatment. These results indicate that mitochondrial oxidative stress is an important mechanistic contributor to C9orf72 pathogenesis, affecting multiple aspects of mitochondrial function and turnover. Targeting the Keap1/Nrf2 signalling pathway to combat oxidative stress represents a therapeutic strategy for C9orf72-related ALS/FTD.
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Esclerosis Amiotrófica Lateral , Proteína C9orf72 , Modelos Animales de Enfermedad , Demencia Frontotemporal , Proteína 1 Asociada A ECH Tipo Kelch , Mitocondrias , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Fenotipo , Transducción de Señal , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Mitocondrias/metabolismo , Animales , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Humanos , Demencia Frontotemporal/genética , Demencia Frontotemporal/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Especies Reactivas de Oxígeno/metabolismo , Mitofagia/genética , Dimetilfumarato/farmacología , MasculinoRESUMEN
The brain has computational capabilities that surpass those of modern systems, being able to solve complex problems efficiently in a simple way. Neuromorphic engineering aims to mimic biology in order to develop new systems capable of incorporating such capabilities. Bio-inspired learning systems continue to be a challenge that must be solved, and much work needs to be done in this regard. Among all brain regions, the hippocampus stands out as an autoassociative short-term memory with the capacity to learn and recall memories from any fragment of them. These characteristics make the hippocampus an ideal candidate for developing bio-inspired learning systems that, in addition, resemble content-addressable memories. Therefore, in this work we propose a bio-inspired spiking content-addressable memory model based on the CA3 region of the hippocampus with the ability to learn, forget and recall memories, both orthogonal and non-orthogonal, from any fragment of them. The model was implemented on the SpiNNaker hardware platform using Spiking Neural Networks. A set of experiments based on functional, stress and applicability tests were performed to demonstrate its correct functioning. This work presents the first hardware implementation of a fully-functional bio-inspired spiking hippocampal content-addressable memory model, paving the way for the development of future more complex neuromorphic systems.
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Potenciales de Acción , Hipocampo , Modelos Neurológicos , Redes Neurales de la Computación , Potenciales de Acción/fisiología , Hipocampo/fisiología , Humanos , Memoria/fisiología , Neuronas/fisiología , Animales , Simulación por Computador , Aprendizaje/fisiología , Región CA3 Hipocampal/fisiologíaRESUMEN
INTRODUCTION: Ulcerative colitis (UC) and Crohn's disease (CD) are diseases that cause a significant impact on patients' quality of life. The aim of this study is to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQoL). MATERIAL AND METHODS: Observational, descriptive, cross-sectional study, carried out at Torrecárdenas Hospital (Almería). Patients over 14 years of age diagnosed with CD or UC were included. For the assessment of HRQoL, the reduced 9-item IBDQ-9 questionnaire was used. RESULTS: 106 patients with a mean age of 44 years were included, with a female predominance. Forty-five percent of the patients in the sample had UC compared to 55% with CD. Of the patients, 69.8% were in clinical remission. The median questionnaire score was 60.8 points out of 100. Statistically significant differences were observed between sexes, with worse HRQoL for females. No differences were observed between patients with UC and CD. Differences were also detected between patients who underwent surgery and those who did not. A negative association was observed between the number of flares and the questionnaire score. CONCLUSIONS: In our study population, there is an acceptable HRQoL, with no differences observed between CD and UC. Female sex, absence of clinical remission, number of previous outbreaks, and surgery have a negative association with HRQoL.
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INTRODUCTION: Understanding the intricate dynamics between different waves of the COVID-19 pandemic and the corresponding variations in clinical outcomes is essential for informed public health decision-making. Comprehensive insights into these fluctuations can guide resource allocation, healthcare policies, and the development of effective interventions. This study aimed to compare the characteristics and clinical outcomes of COVID-19 at peak transmission points by including all patients attended during the first four pandemic waves in a referral center in Colombia. MATERIAL AND METHODS: In a prospective observational study of 2733 patients, clinical and demographic data were extracted from the Fundacion Valle de Lili's COVID-19 Registry, focusing on ICU admission, Invasive Mechanical Ventilation (IMV), length of hospital stay, and mortality. RESULTS: Our analysis unveiled substantial shifts in patient care patterns. Notably, the proportion of patients receiving glucocorticoid therapy and experiencing secondary infections exhibited a pronounced decrease across waves (p < 0.001). Remarkably, there was a significant reduction in ICU admissions (62.83% vs. 51.23% vs. 58.23% vs. 46.70 %, p < 0.001), Invasive Mechanical Ventilation (IMV) usage (39.25% vs. 32.22% vs. 31.22% vs. 21.55 %, p < 0.001), and Length of Hospital Stay (LOS) (9 vs. 8 vs. 8 vs. 8 days, p < 0.001) over the successive waves. Surprisingly, hospital mortality remained stable at approximately 18â20 % (p > 0.05). Notably, vaccination coverage with one or more doses surged from 0 % during the initial waves to 66.71 % in the fourth wave. CONCLUSIONS: Our findings emphasize the critical importance of adapting healthcare strategies to the evolving dynamics of the pandemic. The reduction in ICU admissions, IMV utilization, and LOS, coupled with the rise in vaccination rates, underscores the adaptability of healthcare systems. Hospital mortality's persistence may warrant further exploration of treatment strategies. These insights can inform public health responses, helping policymakers allocate resources effectively and tailor interventions to specific phases of the pandemic.
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COVID-19 , Unidades de Cuidados Intensivos , Tiempo de Internación , Respiración Artificial , Humanos , COVID-19/epidemiología , Colombia/epidemiología , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Respiración Artificial/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Pandemias , Hospitalización/estadística & datos numéricos , Anciano , Adulto , Mortalidad Hospitalaria , SARS-CoV-2 , Estudios de CohortesRESUMEN
Meniere disease is a complex inner ear disorder with significant familial aggregation. A differential prevalence of familial MD (FMD) has been reported, being 9-10% in Europeans compared to 6% in East Asians. A broad genetic heterogeneity in FMD has been described, OTOG being the most common mutated gene, with a compound heterozygous recessive inheritance. We hypothesize that an OTOG-related founder effect may explain the higher prevalence of FMD in the European population. Therefore, the present study aimed to compare the allele frequency (AF) and distribution of OTOG rare variants across different populations. For this purpose, the coding regions with high constraint (low density of rare variants) were retrieved in the OTOG coding sequence in Non-Finnish European (NFE).. Missense variants (AF < 0.01) were selected from a 100 FMD patient cohort, and their population AF was annotated using gnomAD v2.1. A linkage analysis was performed, and odds ratios were calculated to compare AF between NFE and other populations. Thirteen rare missense variants were observed in 13 FMD patients, with 2 variants (rs61978648 and rs61736002) shared by 5 individuals and another variant (rs117315845) shared by two individuals. The results confirm the observed enrichment of OTOG rare missense variants in FMD. Furthermore, eight variants were enriched in the NFE population, and six of them were in constrained regions. Structural modeling predicts five missense variants that could alter the otogelin stability. We conclude that several variants reported in FMD are in constraint regions, and they may have a founder effect and explain the burden of FMD in the European population.
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Frecuencia de los Genes , Enfermedad de Meniere , Mutación Missense , Población Blanca , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Europa (Continente)/epidemiología , Efecto Fundador , Ligamiento Genético , Predisposición Genética a la Enfermedad , Enfermedad de Meniere/genética , Enfermedad de Meniere/epidemiología , Prevalencia , Población Blanca/genética , Pueblo EuropeoRESUMEN
INTRODUCTION: Bats are a diverse group of mammals that have unique features allowing them to act as reservoir hosts for several zoonotic pathogens such as Leptospira. Leptospires have been classified into pathogenic, intermediate, and saprophytic groups and more recently into clades P1, P2, S1, and S2, being all the most important pathogenic species related to leptospirosis included within the P1/pathogenic clade. Leptospira has been detected from bats in several regions worldwide; however, the diversity of leptospires harboured by bats is still unknown. AIM: The aim of the present study was to determine the genetic diversity of Leptospira spp. harboured by bats worldwide. METHODS: A systematic review was conducted on four databases to retrieve studies in which Leptospira was detected from bats. All studies were screened to retrieve all available Leptospira spp. 16S rRNA sequences from the GenBank database and data regarding their origin. Sequences obtained were compared with each other and reference sequences of Leptospira species and analysed through phylogenetic analysis. RESULTS: A total of 418 Leptospira spp. 16S rRNA sequences isolated from 55 bat species from 14 countries were retrieved from 15 selected manuscripts. From these, 417 sequences clustered within the P1/pathogenic group, and only one sequence clustered within the P2/intermediate group. Six major clades of P1/pathogenic Leptospira spp. were identified, three of them composed exclusively of sequences obtained from bats. CONCLUSION: We identified that bats harbour a great genetic diversity of Leptospira spp. that form part of the P1/pathogenic clade, some of which are closely related to leptospirosis-associated species. This finding contributes to the knowledge of the diversity of leptospires hosted by bats worldwide and reinforces the role of bats as reservoirs of P1/pathogenic Leptospira spp.
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Quirópteros , Variación Genética , Leptospira , Leptospirosis , Filogenia , Animales , Quirópteros/microbiología , Leptospira/genética , Leptospira/clasificación , Leptospira/aislamiento & purificación , Leptospirosis/veterinaria , Leptospirosis/microbiología , Leptospirosis/epidemiología , Reservorios de Enfermedades/veterinaria , Reservorios de Enfermedades/microbiología , ARN Ribosómico 16S/genética , ZoonosisRESUMEN
Wood density is a fundamental property related to tree biomechanics and hydraulic function while playing a crucial role in assessing vegetation carbon stocks by linking volumetric retrieval and a mass estimate. This study provides a high-resolution map of the global distribution of tree wood density at the 0.01° (~1 km) spatial resolution, derived from four decision trees machine learning models using a global database of 28,822 tree-level wood density measurements. An ensemble of four top-performing models combined with eight cross-validation strategies shows great consistency, providing wood density patterns with pronounced spatial heterogeneity. The global pattern shows lower wood density values in northern and northwestern Europe, Canadian forest regions and slightly higher values in Siberia forests, western United States, and southern China. In contrast, tropical regions, especially wet tropical areas, exhibit high wood density. Climatic predictors explain 49%-63% of spatial variations, followed by vegetation characteristics (25%-31%) and edaphic properties (11%-16%). Notably, leaf type (evergreen vs. deciduous) and leaf habit type (broadleaved vs. needleleaved) are the most dominant individual features among all selected predictive covariates. Wood density tends to be higher for angiosperm broadleaf trees compared to gymnosperm needleleaf trees, particularly for evergreen species. The distributions of wood density categorized by leaf types and leaf habit types have good agreement with the features observed in wood density measurements. This global map quantifying wood density distribution can help improve accurate predictions of forest carbon stocks, providing deeper insights into ecosystem functioning and carbon cycling such as forest vulnerability to hydraulic and thermal stresses in the context of future climate change.
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Ecosistema , Madera , Canadá , Bosques , Hojas de la Planta , CarbonoRESUMEN
BACKGROUND: Growth rate is an important component of feed conversion efficiency in cattle and varies across the different stages of the finishing period. The metabolic effect of the rumen microbiome is essential for cattle growth, and investigating the genomic and microbial factors that underlie this temporal variation can help maximize feed conversion efficiency at each growth stage. RESULTS: By analysing longitudinal body weights during the finishing period and genomic and metagenomic data from 359 beef cattle, our study demonstrates that the influence of the host genome on the functional rumen microbiome contributes to the temporal variation in average daily gain (ADG) in different months (ADG1, ADG2, ADG3, ADG4). Five hundred and thirty-three additive log-ratio transformed microbial genes (alr-MG) had non-zero genomic correlations (rg) with at least one ADG-trait (ranging from |0.21| to |0.42|). Only a few alr-MG correlated with more than one ADG-trait, which suggests that a differential host-microbiome determinism underlies ADG at different stages. These alr-MG were involved in ribosomal biosynthesis, energy processes, sulphur and aminoacid metabolism and transport, or lipopolysaccharide signalling, among others. We selected two alternative subsets of 32 alr-MG that had a non-uniform or a uniform rg sign with all the ADG-traits, regardless of the rg magnitude, and used them to develop a microbiome-driven breeding strategy based on alr-MG only, or combined with ADG-traits, which was aimed at shaping the rumen microbiome towards increased ADG at all finishing stages. Combining alr-MG information with ADG records increased prediction accuracy of genomic estimated breeding values (GEBV) by 11 to 22% relative to the direct breeding strategy (using ADG-traits only), whereas using microbiome information, only, achieved lower accuracies (from 7 to 41%). Predicted selection responses varied consistently with accuracies. Restricting alr-MG based on their rg sign (uniform subset) did not yield a gain in the predicted response compared to the non-uniform subset, which is explained by the absence of alr-MG showing non-zero rg at least with more than one of the ADG-traits. CONCLUSIONS: Our work sheds light on the role of the microbial metabolism in the growth trajectory of beef cattle at the genomic level and provides insights into the potential benefits of using microbiome information in future genomic breeding programs to accurately estimate GEBV and increase ADG at each finishing stage in beef cattle.
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Genómica , Microbiota , Bovinos/genética , Animales , Fenotipo , Peso Corporal , Metagenoma , Alimentación AnimalRESUMEN
Meniere Disease (MD) is a chronic inner ear disorder characterized by vertigo attacks, sensorineural hearing loss, tinnitus, and aural fullness. Extensive evidence supporting the inflammatory etiology of MD has been found, therefore, by using transcriptome analysis, we aim to describe the inflammatory variants of MD. We performed Bulk RNAseq on 45 patients with definite MD and 15 healthy controls. MD patients were classified according to their basal levels of IL-1ß into 2 groups: high and low. Differentially expression analysis was performed using the ExpHunter Suite, and cell type proportion was evaluated using the estimation algorithms xCell, ABIS, and CIBERSORTx. MD patients showed 15 differentially expressed genes (DEG) compared to controls. The top DEGs include IGHG1 (p = 1.64 × 10-6) and IGLV3-21 (p = 6.28 × 10-3), supporting a role in the adaptative immune response. Cytokine profiling defines a subgroup of patients with high levels of IL-1ß with up-regulation of IL6 (p = 7.65 × 10-8) and INHBA (p = 3.39 × 10-7) genes. Transcriptomic data from peripheral blood mononuclear cells support a proinflammatory subgroup of MD patients with high levels of IL6 and an increase in naïve B-cells, and memory CD8+ T cells.
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Enfermedad de Meniere , Humanos , Enfermedad de Meniere/metabolismo , Leucocitos Mononucleares/metabolismo , Interleucina-6/metabolismo , Linfocitos T CD8-positivos/metabolismo , Perfilación de la Expresión GénicaRESUMEN
PURPOSE: To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus. METHODS: After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development. RESULTS: The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes. CONCLUSIONS: The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.
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Pérdida Auditiva Sensorineural , Acúfeno , Humanos , Acúfeno/epidemiología , Acúfeno/genética , Estudio de Asociación del Genoma Completo , Audición , HiperacusiaRESUMEN
A multi-method approach integrating data from four independent sources was used to describe some key features of the epidemiology and estimate the herd and within-herd incidence of fractured humeri in New Zealand dairy cattle for the period 2007-2015. The first dataset was from a national case series where cases of humeral fractures in dairy cattle were identified by veterinarians across New Zealand between the 2007/2008 and 2011/2012 lactation seasons. The second dataset was from a pet food company based in the Waikato region, which collated the number of casualty first- and second-lactation cows found to have a fractured humerus post-slaughter in the 2014/2015 lactation season, and the third dataset was a case series conducted by veterinarians employed in a Waikato veterinary business, also from the 2014/2015 lactation season. For the final dataset, 505 randomly selected New Zealand dairy farmers completed a phone survey on the incidence of non-responsive, non-weight-bearing forelimb lameness in first- and second-lactation cows in the 2014/2015 lactation season. Using the telephone survey results, the within-herd and herd-level incidence of cases for first- and second-lactation dairy animals was calculated. The national case series reported 149 cases of humeral fractures in 22 dairy herds; the pet food case series identified 61 cases from 41 farms; and the practice-based case series found 14 cases from 10 farms. Humeral fractures exclusively affected first- and second-lactation dairy cows and had a peak incidence between calving and early mating. The national telephone survey found that non-weight-bearing forelimb lameness requiring euthanasia of first- or second-lactation cows occurred in 11.7% of herds, with a mean within-herd incidence of 2.6% for first lactation cows and 2.8% for second-lactation cows for affected herds. These combined datasets demonstrate that humeral fractures in young, lactating dairy cattle are more common than previously suspected and that they occur nationally and over multiple years on some farms. Further work on this condition is urgently required in New Zealand to establish cost-effective management practices that will reduce unnecessary animal suffering and waste.