Addressing Combative Behaviour in Spanish Bulls by Measuring Hormonal Indicators.

The fighting bull is characterised by its natural aggressiveness, but the physiological mechanisms that underlie its aggressive behaviour are poorly studied. This study determines the hormonal component of aggressiveness in fighting bulls by analysing their behaviour during a fight and correlating it to their serotonin, dopamine and testosterone levels. We also determine whether aggressive behaviour can be estimated in calves. Using 195 animals, samples were obtained when the animals were calves and after 5 years. Aggressiveness scores were obtained by an observational method during bullfights, and serotonin, dopamine and testosterone levels were determined in all animals using validated enzyme immunoassay kits. The results revealed a strong correlation of serotonin and dopamine levels with aggressiveness scores in bulls during fights, but no correlation was found with respect to testosterone. These correlations led to established cut-off point and linear regression curves to obtain expected aggressiveness scores for calves at shoeing. There were no significant differences between the expected scores obtained in calves and the observed scores in bulls. Therefore, this study demonstrates that hormone determination in calves may be a great indicator of combativeness in bulls and can reliably be used in the selection of fighting bulls.

A new species of terrestrial toad of the Rhinellafestae group (Anura, Bufonidae) from the highlands of the Central Cordillera of the Andes of Colombia.

The genus Rhinella (Bufonidae) comprises 92 species of Neotropical toads. In Colombia, Rhinella is represented by 22 recognized species, of which nine belong to the Rhinellafestae group. Over the past decade, there has been increasing evidence of cryptic diversity within this group, particularly in the context of Andean forms. Specimens of Rhinella collected in high Andean forests on both slopes of the Central Cordillera in Colombia belong to an undescribed species, Rhinellakumandaysp. nov. Genetic analyses using the mitochondrial 16S rRNA gene indicated that the individuals belong to the festae species group. However, they can be distinguished from other closely related species such as Rhinellaparaguas and Rhinellatenrec by a combination of morphological traits including the presence of tarsal fold, a moderate body size, and substantial genetic divergence in the 16S rRNA gene (> 5%). Through this integrative approach, the specimens from the Central Cordillera of Colombia are considered an evolutionary divergent lineage that is sister to R.paraguas, and described as a new species. Rhinellakumandaysp. nov. is restricted to the Central Cordillera of Colombia inhabiting both slopes in the departments of Caldas and Tolima, in an elevational range between 2420 and 3758 m. With the recognition of this new species, the genus Rhinella now comprises 93 species with 23 of them found in Colombia, and ten species endemic to the country.

Challenges in the surgical treatment and management of the patient with super super obesity.

Obesity is defined by the Body Mass Index (BMI) which is derived by the weight and height of a person (BMI > 30). Furthermore, obesity is classified as super-obesity (BMI >50 kg/m2) and super-super obesity (BMI >60 kg/m2) by the International Bariatric Surgery Registry (Renquist K. Obesity classification. Obes Surg 1997;7:523). Patients with super-super obesity have a greater incidence of comorbid diseases and are at greater risk of postoperative morbidity and mortality and longer length of hospital stay (LOS). Soong et al. described short-term outcomes after weight loss surgery comparing a group of patients with super-obesity with another group of patients with super-super obesity. The authors concluded that experienced surgeons could achieve comparable outcomes in both groups. However, higher BMI is associated with longer operative time, longer LOS, and delayed discharge to chronic care facilities (Soong TC, Lee MH, Lee WJ, et al. Long-term efficacy of bariatric surgery for the treatment of super-obesity: comparison of SG, RYGB, and OAGB. Obes Surg. 2021;31:3391-99. https://doi.org/10.1007/s11695-021-05464-0). The following paradigmatic case report aims at showing the complex management of a patient with super-super obesity, with BMI of 141.2 kg/m2 and associated multiple comorbidities.

Trastorno eréctil ¿Qué factores pueden afectar a su gravedad? Un estudio descriptivo-correlacional / Erectile dysfunction: what factors affect its severity? A descriptive correlate story

Una de las disfunciones sexuales más comunes es el trastorno eréctil (TE). Pretendemos identificar factores asociados a la gravedad del TE. Treinta y seis hombres, entre 18 y 70 años, que presentan un diagnóstico de TE, basado en los criterios DSM-V, han sido evaluados a través de una entrevista clínica y de una batería de 7 cuestionarios (IIEF, SCL-90, PDQ-4, PSWQ, STAI, SSES, SSEI). La metodología se centró en un estudio cuantitativo, de tipo descriptivo-correlacional de diseño ex post facto con muestreo por conveniencia. Los resultados del modelo de regresión final muestran que la autoeficacia sexual, determinadas tendencias de personalidad y la sintomatología de depresión, somatización, obsesión-compulsión y ansiedad son factores asociados a la gravedad del TE, explicando el 51,3% de la varianza. Poder identificar aquellos factores asociados a la gravedad del TE, puede tener una relevante importancia para poder trabajar en su prevención y mejorar la orientación de las intervenciones psicológicas.(AU)

One of the most common sexual dysfunctions is erectile disorder (ED). Therefore, this research aims to identify factors associated with the severity of ED. Thirty-six men, aged 18 to 70 years, with a diagnosis of ED, based on DSM-V criteria, were assessed by means of a clinical interview and a battery of 7 questionnaires (IIEF, SCL-90, PDQ-4, PSWQ, STAI, SSES, SSEI). The methodology focused on a quantitative, descriptive-correlational study of ex post facto design with convenience sampling. The results of the final regression model shows that sexual self-efficacy, certain personality tendencies and the symptomatology of depression, somatization, obsession-compulsion and anxiety are factors associated with the severity of TE, explaining 51.3% of the variance. Being able to identify those factors associated with the severity of TE may be of relevant importance in order to work on its prevention and improve the orientation of psychological interventions.(AU)

Maternal outcomes using delayed pushing versus immediate pushing in the second stage of labour: An umbrella review.

INTRODUCTION: Different systematic reviews have been developed in the last decades about maternal risks of immediate pushing and delayed pushing, depending on the duration of the second stage of labour, but they do not provide conclusive evidence. AIM: The main aim of this overview of systematic reviews was to assess the maternal outcomes using delayed pushing and immediate pushing in the second stage of labour in women receiving epidural analgesia. METHODS: We searched systematically in PubMed (Medline), EMBASE, CINAHL, and Scopus (October 26th, 2023). Methodological quality was analysed using AMSTAR and ROBIS scales, and the strength of evidence was established according to the guidelines advisory committee grading criteria. The outcome measures were the duration of the second stage of labour, duration of active pushing, caesarean section, instrumental vaginal birth, spontaneous vaginal birth, fatigue score, perineal lacerations, postpartum haemorrhage, and rate of episiotomy. Seven systematic reviews with and without meta-analysis were included. RESULTS: Results showed that delayed pushing increases the total time of the second stage of labour, although delayed pushing decreases the duration of active pushing with moderate quality of evidence. Mixed results were found with respect to the variables instrumental vaginal birth, spontaneous vaginal birth, and fatigue score although the results favour delayed pushing or show no statistically significant differences with respect to immediate pushing. No favourable results were ever found for immediate pushing with respect to delayed pushing, with a limited quality of evidence. Even so, delayed pushing seems to be associated with a significant increase in spontaneous vaginal birth rates. The results found no significant differences between the immediate pushing and delayed pushing groups in the caesarean section rates, perineal lacerations, postpartum haemorrhage, and episiotomy ratio, with a limited quality of evidence. CONCLUSIONS: This study shows that delayed pushing during the second stage of labour produces at least the same maternal outcomes as immediate pushing, although we note that delayed pushing produces an increase of the duration of the second stage of labour, a shorter duration of the active pushing and a tendency to increase spontaneous vaginal birth and to reduce the instrumental vaginal birth rates and fatigue scores. This should be considered clinically. This review was registered in the International Prospective Register of Systematic Reviews PROSPERO (CRD42023397616).

Dysregulation of micro-RNA 143-3p as a Biomarker of Carotid Atherosclerosis and the Associated Immune Reactions During Disease Progression.

Atherosclerosis commonly remains undiagnosed until disease manifestations occur. The disease is associated with dysregulated micro(mi)RNAs, but how this is linked to atherosclerosis-related immune reactions is largely unknown. A mouse model of carotid atherosclerosis, human APOB100-transgenic Ldlr-/- (HuBL), was used to study the spatiotemporal dysregulation of a set of miRNAs. Middle-aged HuBL mice with established atherosclerosis had decreased levels of miR-143-3p in their carotid arteries. In young HuBL mice, early atherosclerosis was observed in the carotid bifurcation, which had lower levels of miR-15a-5p, miR-143-3p, and miR-199a-3p, and higher levels of miR-155-5p. The dysregulation of these miRNAs was reflected by specific immune responses during atheroprogression. Finally, levels of miR-143-3p were 70.6% lower in extracellular vesicles isolated from the plasma of patients with carotid stenosis compared to healthy controls. Since miR-143-3p levels progressively decrease when transitioning between early and late experimental carotid atherosclerosis, we propose it as a biomarker for atherosclerosis.

Culicoides-Specific Fitness Increase of Vesicular Stomatitis Virus in Insect-to-Insect Infections.

Vesicular stomatitis virus (VSV) is an arthropod-borne virus affecting livestock. In the United States, sporadic outbreaks result in significant economic losses. During epizootics, Culicoides biting midges are biological vectors and key to the geographic expansion of outbreaks. Additionally, Culicoides may play a role in VSV overwintering because females and males are capable of highly efficient venereal transmission, despite their relatively low virus titers. We hypothesized that VSV propagated within a midge has increased fitness for subsequent midge infections. To evaluate the potential host-specific fitness increase, we propagated three viral isolates of VSV in porcine skin fibroblasts and Culicoides cell lines. We then evaluated the viral infection dynamics of the different cell-source groups in Culicoides sonorensis. Our results indicate that both mammalian- and insect-derived VSV replicate well in midges inoculated via intrathoracic injection, thereby bypassing the midgut barriers. However, when the virus was required to infect and escape the midgut barrier to disseminate after oral acquisition, the insect-derived viruses had significantly higher titers, infection, and dissemination rates than mammalian-derived viruses. Our research suggests that VSV replication in Culicoides cells increases viral fitness, facilitating midge-to-midge transmission and subsequent replication, and further highlights the significance of Culicoides midges in VSV maintenance and transmission dynamics.

Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers.

Gene therapy presents an innovative approach to the treatment of previously incurable diseases. The advancement of research in the field of nanotechnology has the potential to overcome the current limitations and challenges of conventional therapy methods, and therefore to unlocking the full potential of dendrimers for use in the gene therapy of neurodegenerative disorders. The blood-brain barrier (BBB) poses a significant challenge when delivering therapeutic agents to the central nervous system. In this study, we investigated the biophysical properties of dendrimers and their complexes with siRNA directed against the apolipoprotein E (APOE) gene to identify an appropriate nanocarrier capable of safely delivering the cargo across the BBB. Our study yielded valuable insights into the complexation process, stability over time, the mechanisms of interaction, the influence of dendrimers on the oligonucleotide's spatial structure, and the potential cytotoxic effects on human cerebral microvascular endothelium cells. Based on our findings, we identified that the dendrimer G3Si PEG6000 was an optimal candidate for further research, potentially serving as a nanocarrier capable of safely delivering therapeutic agents across the BBB for the treatment of neurodegenerative disorders.

Shifting targets: typhoid's transformation from an environmental to a vaccine-preventable disease, 1940-2019.

160 years after the discovery of its waterborne transmission and 120 years after the development of the first-generation of vaccines, typhoid fever remains a major health threat globally. In this Historical Review, we use WHO's Institutional Repository for Information Sharing to examine changes in typhoid control policy from January, 1940, to December, 2019. We used a mixed-methods approach in the analysis of infection control priorities, combining semi-inductive thematic coding with historical analysis to show major thematic shifts in typhoid control policy, away from water, sanitation, and hygiene (WASH)-based control towards vaccine-based interventions concurrent with declining attention to the disease. Documentary analysis shows that, although international planners never officially disavowed WASH and low-income countries persistently lobbied for WASH, vaccines emerged as a permanent stopgap while meaningful support of sustained WASH strengthening lost momentum-with serious, long-term ramifications for typhoid control.

Adenylate kinase 9 is essential for sperm function and male fertility in mammals.

Despite passing routine laboratory tests for semen quality, bulls used in artificial insemination exhibit significant variation in fertility. Routine analysis of fertility data identified a dairy bull with extreme subfertility (10% pregnancy rate). To characterize the subfertility phenotype, a range of in vitro, in vivo, and molecular assays were carried out. Sperm from the subfertile bull exhibited reduced motility and severely reduced caffeine-induced hyperactivation compared to controls. Ability to penetrate the zona pellucida, cleavage rate, cleavage kinetics, and blastocyst yield after IVF or AI were significantly lower than in control bulls. Whole-genome sequencing from semen and RNA sequencing of testis tissue revealed a critical mutation in adenylate kinase 9 (AK9) that impaired splicing, leading to a premature termination codon and a severely truncated protein. Mice deficient in AK9 were generated to further investigate the function of the gene; knockout males were phenotypically indistinguishable from their wild-type littermates but produced immotile sperm that were incapable of normal fertilization. These sperm exhibited numerous abnormalities, including a low ATP concentration and reduced motility. RNA-seq analysis of their testis revealed differential gene expression of components of the axoneme and sperm flagellum as well as steroid metabolic processes. Sperm ultrastructural analysis showed a high percentage of sperm with abnormal flagella. Combined bovine and murine data indicate the essential metabolic role of AK9 in sperm motility and/or hyperactivation, which in turn affects sperm binding and penetration of the zona pellucida. Thus, AK9 has been found to be directly implicated in impaired male fertility in mammals.

Untangling an insect's virome from its endogenous viral elements.

BACKGROUND: Insects are an important reservoir of viral biodiversity, but the vast majority of viruses associated with insects have not been discovered. Recent studies have employed high-throughput RNA sequencing, which has led to rapid advances in our understanding of insect viral diversity. However, insect genomes frequently contain transcribed endogenous viral elements (EVEs) with significant homology to exogenous viruses, complicating the use of RNAseq for viral discovery. METHODS: In this study, we used a multi-pronged sequencing approach to study the virome of an important agricultural pest and prolific vector of plant pathogens, the potato aphid Macrosiphum euphorbiae. We first used rRNA-depleted RNAseq to characterize the microbes found in individual insects. We then used PCR screening to measure the frequency of two heritable viruses in a local aphid population. Lastly, we generated a quality draft genome assembly for M. euphorbiae using Illumina-corrected Nanopore sequencing to identify transcriptionally active EVEs in the host genome. RESULTS: We found reads from two insect-specific viruses (a Flavivirus and an Ambidensovirus) in our RNAseq data, as well as a parasitoid virus (Bracovirus), a plant pathogenic virus (Tombusvirus), and two phages (Acinetobacter and APSE). However, our genome assembly showed that part of the 'virome' of this insect can be attributed to EVEs in the host genome. CONCLUSION: Our work shows that EVEs have led to the misidentification of aphid viruses from RNAseq data, and we argue that this is a widespread challenge for the study of viral diversity in insects.

Role of miR-15a-5p and miR-199a-3p in the inflammatory pathway regulated by NF-κB in experimental and human atherosclerosis.

BACKGROUND: Cardiovascular diseases (CVDs) prevalence has significantly increased in the last decade and atherosclerosis development is the main trigger. MicroRNAs (miRNAs) are non-coding RNAs that negatively regulate gene expression of their target and their levels are frequently altered in CVDs. METHODS: By RT-qPCR, we analysed miR-9-5p, miR-15a-5p, miR-16-5p and miR-199a-3p levels in aorta from apolipoprotein knockout (ApoE-/- ) mice, an experimental model of hyperlipidemia-induced atherosclerosis, and in human aortic and carotid atherosclerotic samples. By in silico studies, Western blot analysis and immunofluorescence studies, we detected the targets of the altered miRNAs. RESULTS: Our results show that miR-15a-5p and miR-199a-3p are significantly decreased in carotid and aortic samples from patients and mice with atherosclerosis. In addition, we found an increased expression in targets of both miRNAs that participate in the inflammatory pathway of nuclear factor kappa B (NF-κB), such as IKKα, IKKß and p65. In human vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs), the overexpression of miR-15a-5p or miR-199a-3p decreased IKKα, IKKß and p65 protein levels as well as NF-κB activation. On the other hand, miR-15a-5p and miR-199a-3p overexpression reduced ox-LDL uptake and the inflammation regulated by NF-κB in VSMCs. Moreover, although miR-15a-5p and miR-199a-3p were significantly increased in exosomes from patients with advanced carotid atherosclerosis, only in the ROC analyses for miR-15a-5p, the area under the curve was 0.8951 with a p value of .0028. CONCLUSIONS: Our results suggest that the decrease of miR-199a-3p and miR-15a-5p in vascular samples from human and experimental atherosclerosis could be involved in the NF-κB activation pathway, as well as in ox-LDL uptake by VSMCs, contributing to inflammation and progression atherosclerosis. Finally, miR-15a-5p could be used as a novel diagnostic biomarker for advanced atherosclerosis.

Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors.

Karyopherins mediate the movement between the nucleus and cytoplasm of specific proteins in diverse cellular processes. Through a loss-of-function approach, we here examine the role of Karyopherin Subunit Alpha 2 (Kpna2) in spermatogenesis. Knockout male mice exhibited reduced body size and sperm motility, increased sperm abnormalities, and led to the dysregulation of testis gene expression and ultimately to infertility. Impaired mRNA expression mainly affected clusters of genes expressed in spermatids and spermatocytes. Downregulated genes included a set of genes that participate in cell adhesion and extracellular matrix (ECM) organization. We detected both the enrichment of some transcription factors that bind to regions around transcription start sites of downregulated genes and the impaired transport of specific factors to the nucleus of spermatid cells. We propose that Kpna2 is essential in the seminiferous tubules for promoting the translocation of testis-specific transcription factors that control the expression of genes related to ECM organization.

microRNA Expression Dynamics in Culicoides sonorensis Biting Midges Following Blood-Feeding.

Culicoides sonorensis midges vector multiple livestock arboviruses, resulting in significant economic losses worldwide. Due to the tight association between virus transmission, blood feeding, and egg development, understanding midge physiology is paramount to limiting pathogen transmission. Previous studies have demonstrated the importance of small non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), in multiple aspects of vector physiology. These small ncRNAs regulate gene expression at the post-transcriptional level and display differential expression during pathogen infection. Due to the lack of annotated miRNAs in the biting midge and associated expression profiles, we used small RNA-Seq and miRDeep2 analyses to determine the Culicoides miRNAs in whole females and midgut tissues in response to blood feeding. Our analyses revealed 76 miRNAs within C. sonorensis composed of 73 orthologous and three candidate novel miRNAs, as well as conserved miRNA clusters. miRNA conservation suggests an interesting evolutionary relationship between miRNA expression and hematophagy in the infraorder Culicomorpha. We also identified multiple blood meal-regulated and tissue-enriched miRNAs. Lastly, we further identified miRNAs with expression patterns potentially associated with virus infection by probing publicly available datasets. Together, our data provide a foundation for future ncRNA work to untangle the dynamics of gene regulation associated with midge physiology.

[The impact of SARS-CoV-2 pandemic on patients who attend a pediatric emergency department for mental health issues]. / Impacto de la pandemia por SARS-CoV-2 en los pacientes que acuden a urgencias de pediatría por problemas de salud mental.

The lockdown during the SARS-CoV-2 pandemic and the effect of the virus on the population could be a precipitating factor for mental health disorders in the pediatric population. OBJECTIVE: To compare the reasons for consultation, diagnoses at discharge, and admission and re-consultation rates of pediatric patients attending the Emergency Department due to mental health disorders before and after the SARS-CoV-2 pandemic lockdown. PATIENTS AND METHOD: Retrospective, descriptive study. Patients under 16 years of age consulting due to mental health-related disorders during the pre- (07/01/2018-07/01/2019) and post-lockdown (07/01/2020-07/01/2021) periods were included. The frequency of mental health diagnoses, need for drug administration, hospitalization, and reconsultations were compared. RESULTS: 760 patients were included, 399 pre-lockdown and 361 postlockdown. After the lockdown, there was a 45.7% increase in the frequency of mental health-related consultations with respect to the total number of emergency consultations. Behavioral alterations were the most frequent reason for consultation in both groups (34.3% vs. 36.6%, p = 0.54). In the post-lockdown period, consultations related to self-harm attempts (16.3% vs. 24.4%, p < 0.01) and the diagnosis of depression (7.5% vs. 18.5%, p < 0.01) increased significantly. There was an increase of 58.8% in patients who were hospitalized with respect to the total number of ED patients (0.17% vs. 0.27%, p = 0.003) and in the number of re-consultations (12% vs. 17.8%, p = 0.026). No differences were observed in days of hospitalization (7 days [IQR 4-13] vs. 9 days [IQR 9-14], p0.45). CONCLUSION: In the post-lockdown period, the proportion of pediatric patients presenting to the ED with mental health disturbances increased.

Estudio y manejo de casos y contactos en el ámbito escolar, análisis del impacto de las medidas aplicadas al alumnado / Study and management of cases and contacts in the school environment, analysis of the impact of measures applied to students

Fundamento: Desde septiembre de 2020, los centros escolares permanecieron abiertos bajomedidas de prevención de la infección por COVID-19 y una estrecha vigilancia y control porparte de Salud Pública. Métodos: Se describió la organización y el procedimiento de rastreo escolar durante la pande-mia de COVID-19 en Navarra. Se estudió el alumnado rastreado, cuarentenas escolares, trans-misión en el aula, e impacto en la actividad educativa. Resultados: El rastreo fue desarrollado por el Departamento de Salud en coordinación con elDepartamento de Educación. Durante el curso 2020/21, la incidencia en escolares fue similar oinferior a la población general y las ondas epidémicas no mostraron relación con los periodoslectivos. El 26% del alumnado, mayormente de educación infantil y primaria, estuvo en cuaren-tena. La tasa de ataque secundaria (TAS) en las aulas fue inferior al 5%. En el curso 2021/22, laincidencia aumentó con la entrada de la variante Ómicron. Se indicó cuarentena en el 17% delalumnado de infantil y primaria durante el primer trimestre, y en el 11% durante el segundo. LaTAS ascendió al 18% en el primer trimestre, y la transmisión alcanzó niveles muy altos en el se-gundo, con grandes brotes. Las cuarentenas tuvieron un gran impacto en la actividad lectiva. Conclusiones: La gestión de casos y contactos en el ámbito escolar resultó de suma importan-cia para mantener un balance equilibrado entre la seguridad y el control de la pandemia en lasaulas, y asegurar las garantías pedagógicas y el bienestar de la infancia.(AU)

Why do viruses make aphids winged?

Aphids are hosts to diverse viruses and are important vectors of plant pathogens. The spread of viruses is heavily influenced by aphid movement and behaviour. Consequently, wing plasticity (where individuals can be winged or wingless depending on environmental conditions) is an important factor in the spread of aphid-associated viruses. We review several fascinating systems where aphid-vectored plant viruses interact with aphid wing plasticity, both indirectly by manipulating plant physiology and directly through molecular interactions with plasticity pathways. We also cover recent examples where aphid-specific viruses and endogenous viral elements within aphid genomes influence wing formation. We discuss why unrelated viruses with different transmission modes have convergently evolved to manipulate wing formation in aphids and whether this is advantageous for both host and virus. We argue that interactions with viruses are likely shaping the evolution of wing plasticity within and across aphid species, and we discuss the potential importance of these findings for aphid biocontrol.

Los áfidos albergan diversos virus y son vectores de importantes patógenos de plantas. La propagación de virus está fuertemente influenciada por el movimiento y el comportamiento de los áfidos. En consecuencia, la plasticidad de las alas (en la cual algunos individuos desarrollan alas dependiendo de las condiciones ambientales) es un factor importante en la propagación viral asociada a los áfidos. En este documento revisamos varios ejemplos fascinantes en los que virus de plantas transmitidos por áfidos interactúan con la plasticidad fenotípica de las alas, indirectamente manipulando la fisiología de la planta y directamente a través de interacciones moleculares con los mecanismos de plasticidad fenotípica del áfido. También describimos ejemplos recientes que demuestran como algunos virus específicos de áfidos y elementos virales endógenos localizados en los genomas de áfidos influyen en la formación de alas. Últimamente, discutimos por qué virus no relacionados con diferentes modos de transmisión han evolucionado convergentemente para manipular la formación de alas en áfidos y si este fenómeno es beneficioso para el insecto y el virus. Nosotros objetamos que las interacciones con virus están probablemente influenciando la evolución intra- e interespecífica de la plasticidad de las alas en áfidos, y discutimos el potencial de estos hallazgos para el control biológico de los áfidos.

Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis.

BACKGROUND AND AIMS: The molecular mechanisms driving non-alcoholic fatty liver disease (NAFLD) are poorly understood; however, microRNAs might play a key role in these processes. We hypothesize that let-7d-5p could contribute to the pathophysiology of NAFLD and serve as a potential diagnostic biomarker. METHODS: We evaluated let-7d-5p levels and its targets in liver biopsies from a cross-sectional study including patients with NAFLD and healthy donors, and from a mouse model of NAFLD. Moreover, the induction of let-7d-5p expression by fatty acids was evaluated in vitro. Further, we overexpressed let-7d-5p in vitro to corroborate the results observed in vivo. Circulating let-7d-5p and its potential as a NAFLD biomarker was determined in isolated extracellular vesicles from human plasma by RT-qPCR. RESULTS: Our results demonstrate that hepatic let-7d-5p was significantly up-regulated in patients with steatosis, and this increase correlated with obesity and a decreased expression of AKT serine/threonine kinase (AKT), insulin-like growth factor 1 (IGF1), IGF-I receptor (IGF1R) and insulin receptor (INSR). These alterations were corroborated in a NAFLD mouse model. In vitro, fatty acids increased let-7d-5p expression, and its overexpression decreased AKT, IGF-IR and IR protein expression. Furthermore, let-7d-5p hindered AKT phosphorylation in vitro after insulin stimulation. Finally, circulating let-7d-5p significantly decreased in steatosis patients and receiver operating characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker. CONCLUSIONS: Our results highlight the emerging role of let-7d-5p as a potential therapeutic target for NAFLD since its overexpression impairs hepatic insulin signalling, and also, as a novel non-invasive biomarker for NAFLD diagnosis.

An ancient testis-specific IQ motif-containing H gene regulates specific transcript isoform expression during spermatogenesis.

Spermatogenic cells express more alternatively spliced RNAs than most whole tissues; however, the regulation of these events remains unclear. Here, we have characterized the function of a testis-specific IQ motif-containing H gene (Iqch) using a mutant mouse model. We found that Iqch is essential for the specific expression of RNA isoforms during spermatogenesis. Using immunohistochemistry of the testis, we noted that Iqch was expressed mainly in the nucleus of spermatocyte and spermatid, where IQCH appeared juxtaposed with SRRM2 and ERSP1 in the nuclear speckles, suggesting that interactions among these proteins regulate alternative splicing (AS). Using RNA-seq, we found that mutant Iqch produces alterations in gene expression, including the clear downregulation of testis-specific lncRNAs and protein-coding genes at the spermatid stage, and AS modifications - principally increased intron retention - resulting in complete male infertility. Interestingly, we identified previously unreported spliced transcripts in the wild-type testis, while mutant Iqch modified the expression and use of hundreds of RNA isoforms, favouring the expression of the canonical form. This suggests that Iqch is part of a splicing control mechanism, which is essential in germ cell biology.

Auto-brewery syndrome A diagnostic challenge

Auto-brewery syndrome is defined as intestinal distillation syndrome and is probably caused by an overgrowth of microorganisms which metabolize carbohydrates to ethanol. In this report, we describe the case of a patient with classical symptoms of auto-brewery syndrome, with no prior alcohol ingestion and clinical improvement after medical treatment was instituted. It is a very rare case and, due to its inadequate description in the medical literature, we attempt to describe the essentials of the disease and the diagnostic challenge it represents. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2565).