ABSTRACT
BACKGROUND: The da Vinci Single-Port Robot System (DVSP) allows three robotic instruments and an articulated scope to be inserted through a single small incision. It received FDA approval in 2014 and was first introduced in 2018. The aim of this new system was to overcome the limitations of single-incision laparoscopic and robotic surgery. Since then, it has been approved for use only for urologic and transoral surgeries in some countries. It has been used as part of experimental protocols in general surgery. OBJECTIVE: By obtaining the CE mark at the end of January 2024, DVSP will soon enter the European market. This review aims to comprehensively describe the applications of DVSP in general surgery. DESIGN: A search of PubMed, Embase, and Ebsco databases up to March 2024 was conducted, with registration in PROSPERO (CRD42024536430), following the preferred reporting items for Systematic reviews and Meta-analyses for scoping review (PRISMA-Scr) guidelines. All the studies about the use of DVSP in general surgery were included. RESULTS: Fifty-six studies were included. The following surgical areas of use were identified: transabdominal and transanal colorectal, cholecystectomy, abdominal wall repair, upper gastroesophageal tract, liver, pancreas, breast, and thyroid surgery. The reported surgical and short-term outcomes are promising; a wide range of procedures have been performed safely. Some groups have found advantages, such as faster discharge, shorter operative time, and less postoperative pain compared to multiport robotic surgery. CONCLUSION: Five years after its initial clinical applications, the use of the DVSP in general surgery procedures has demonstrated feasibility and safety. Hernia repair, cholecystectomy, and colorectal surgery emerge as the most frequently conducted interventions with this robotic system. Nevertheless, there is anticipation for further studies with larger sample sizes and extended follow-up periods to provide more comprehensive insights and data on the long-term outcomes, including the incidence of incisional hernia.
ABSTRACT
Hyperparasitism is defined as the interaction where one parasite is infected by another parasite. In bat flies (Streblidae and Nycteribiidae), both hyperparasites and microparasites (bacteria, viruses, fungi, and arthropods such as mites) have been documented. Fungi belonging to the order Laboulbeniales are microscopic parasites of a wide diversity of arthropod hosts. Three genera exclusively target bat flies: Arthrorhynchus, which parasitizes species within Nycteribiidae in the Eastern Hemisphere, while genus Gloeandromyces and Nycteromyces parasitize Streblidae in the Western Hemisphere. Among the hyperparasitic arthropods, mites of family Neothrombidiidae, particularly the monospecific genus Monunguis, are known to parasitize bat flies. Here we present the first records of the hyperparasites Monunguis streblida and Gloeandromyces pageanus f. polymorphus parasitizing Streblidae bat flies in Colombia and a summary of these hyperparasitic interactions in the Neotropics. We detected fungi and mites parasitizing bat flies that were collected in the Magdalena River Basin, Colombia, in field expeditions in 2018, 2022, and 2023. We identified 17 bat flies and two species of hyperparasites, specifically M. streblida and the fungi Gloeandromyces. Our search for reports of these interactions in the Neotropics revealed that seven species of Trichobius (Streblidae) are parasitized by M. streblida, whereas Paratrichobius longicrus (Streblidae) is parasitized by Gloeandromyces pageanus f. polymorphus. These interactions have been reported in 11 countries, but our records are the first of M. streblida and Laboulbeniales fungi parasitizing bat flies in Colombia. So far, a total of 14 species of fungi and one species of mite have been associated with 19 species of bat flies, which in turn, are linked to 15 species of Neotropical bats.
Subject(s)
Chiroptera , Diptera , Animals , Diptera/microbiology , Diptera/parasitology , Chiroptera/parasitology , Colombia , Mites/microbiology , Mites/physiology , Host-Parasite InteractionsABSTRACT
The hard tick clade (Ixodidae) currently comprises 762 species worldwide (266 Prostriata and 496 Metastriata). A quarter of hard ticks are found in the Neotropical region, and 42 species have been documented in Colombia. Ixodidae species are important vectors of pathogens such as bacteria, helminths, protozoa, and viruses. In tick-borne diseases, vertebrate hosts perform an important role in the transmission, maintenance, and spread of pathogens. Colombia ranks sixth among countries with the highest mammal biodiversity, with a total of 548 species, where some of these species may be involved in pathogen transmission cycles with ticks as vectors. This research evaluated the presence of two genera of bacteria (Borrelia and Rickettsia) and the protozoan (Babesia) in ticks and mammals in the Orinoquia region of Colombia, establishing interaction networks. The information comes from 734 mammals (655 wild and 79 domestic), belonging to 59 species. Tick infestation (n = 1,805) was found with 14.85 % (n = 109) of the examined mammals and corresponds to nine tick species confirmed morphologically and molecularly. To detect pathogens 272 ticks were collected while feeding on 96 mammals; samples from 93 mammals were analyzed. The presence of borreliae from the relapsing fever group (RFG) and the Lyme disease group (LDG) were detected. Rickettsia spp. was detected in ticks and mammals, while Babesia bigemina was only detected in ticks. This research is the first to address the prevalence of zoonotic pathogens in domestic and wild mammals infested with hard ticks in the Department of Arauca, Colombia. Considering that reporting cases of infections with Babesia, Borrelia, and Rickettsia in Colombia is not mandatory, their impact on public health cannot be estimated. This highlights the importance of continuously detecting, confirming, and identifying these and other important pathogens within the "One Health" framework, as they have a significant economic and medical-veterinary impact globally.
Subject(s)
Babesia , Borrelia , Host-Pathogen Interactions , Ixodidae , Mammals , Rickettsia , Animals , Colombia , Mammals/parasitology , Mammals/microbiology , Rickettsia/isolation & purification , Rickettsia/genetics , Ixodidae/microbiology , Ixodidae/parasitology , Babesia/isolation & purification , Borrelia/isolation & purification , Borrelia/pathogenicity , Tick Infestations/veterinary , Tick Infestations/epidemiology , Tick Infestations/parasitology , Tick-Borne Diseases/microbiology , Tick-Borne Diseases/epidemiology , Tick-Borne Diseases/transmission , Tick-Borne Diseases/parasitologyABSTRACT
The modulation of actin polymerization is a common theme among microbial pathogens. Even though microorganisms show a wide repertoire of strategies to subvert the activity of actin, most of them converge in the ones that activate nucleating factors, such as the Arp2/3 complex. Brucella spp. are intracellular pathogens capable of establishing chronic infections in their hosts. The ability to subvert the host cell response is dependent on the capacity of the bacterium to attach, invade, avoid degradation in the phagocytic compartment, replicate in an endoplasmic reticulum-derived compartment and egress. Even though a significant number of mechanisms deployed by Brucella in these different phases have been identified and characterized, none of them have been described to target actin as a cellular component. In this manuscript, we describe the identification of a novel virulence factor (NpeA) that promotes niche formation. NpeA harbors a short linear motif (SLiM) present within an amphipathic alpha helix that has been described to bind the GTPase-binding domain (GBD) of N-WASP and stabilizes the autoinhibited state. Our results show that NpeA is secreted in a Type IV secretion system-dependent manner and that deletion of the gene diminishes the intracellular replication capacity of the bacterium. In vitro and ex vivo experiments demonstrate that NpeA binds N-WASP and that the short linear motif is required for the biological activity of the protein.IMPORTANCEThe modulation of actin-binding effectors that regulate the activity of this fundamental cellular protein is a common theme among bacterial pathogens. The neural Wiskott-Aldrich syndrome protein (N-WASP) is a protein that several pathogens target to hijack actin dynamics. The highly adapted intracellular bacterium Brucella has evolved a wide repertoire of virulence factors that modulate many activities of the host cell to establish successful intracellular replication niches, but, to date, no effector proteins have been implicated in the modulation of actin dynamics. We present here the identification of a virulence factor that harbors a short linear motif (SLiM) present within an amphipathic alpha helix that has been described to bind the GTPase-binding domain (GBD) of N-WASP stabilizing its autoinhibited state. We demonstrate that this protein is a Type IV secretion effector that targets N-WASP-promoting intracellular survival and niche formation.
Subject(s)
Bacterial Proteins , Virulence Factors , Wiskott-Aldrich Syndrome Protein, Neuronal , Virulence Factors/metabolism , Virulence Factors/genetics , Wiskott-Aldrich Syndrome Protein, Neuronal/metabolism , Wiskott-Aldrich Syndrome Protein, Neuronal/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Humans , Type IV Secretion Systems/metabolism , Type IV Secretion Systems/genetics , Animals , Mice , Protein Binding , Brucella/metabolism , Brucella/genetics , Brucella/pathogenicity , Amino Acid Motifs , Actins/metabolism , Brucellosis/microbiology , Macrophages/microbiology , Host-Pathogen InteractionsABSTRACT
The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of the principal triggers. Therefore, there is an urgent need to decipher the underlying mechanisms involved in atherosclerosis progression. In this respect, microRNAs dysregulation is frequently involved in the progression of multiple diseases including CVDs. Our aim was to demonstrate that let-7d-5p unbalance could contribute to the pathophysiology of atherosclerosis and serve as a potential diagnostic biomarker. We evaluated let-7d-5p levels in vascular biopsies and exosome-enriched extracellular vesicles (EVs) from patients with carotid atherosclerosis and healthy donors. Moreover, we overexpressed let-7d-5p in vitro in vascular smooth muscle cells (VSMCs) to decipher the targets and the underlying mechanisms regulated by let-7d-5p in atherosclerosis. Our results demonstrate that let-7d-5p was significantly upregulated in carotid plaques from overweight patients with carotid atherosclerosis. Moreover, in EVs isolated from plasma, we found that let-7d-5p levels were increased in carotid atherosclerosis patients compared to control subjects specially in overweight patients. Receiver Operating Characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker for atherosclerosis. In VSMCs, we demonstrated that increased let-7d-5p levels impairs cell proliferation and could serve as a protective mechanism against inflammation by impairing NF-κB pathway without affecting insulin resistance. In summary, our results highlight the role of let-7d-5p as a potential therapeutic target for atherosclerosis since its overexpression induce a decrease in inflammation and VSMCs proliferation, and also, as a novel non-invasive diagnostic biomarker for atherosclerosis in overweight patients.
Subject(s)
Atherosclerosis , Cell Proliferation , MicroRNAs , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , NF-kappa B , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , NF-kappa B/metabolism , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Male , Female , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atherosclerosis/genetics , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Middle Aged , Aged , Inflammation/metabolism , Inflammation/pathology , Biomarkers/metabolism , Signal Transduction , Disease Progression , Carotid Artery Diseases/metabolism , Carotid Artery Diseases/pathology , Carotid Artery Diseases/genetics , Extracellular Vesicles/metabolism , Extracellular Vesicles/pathologyABSTRACT
Ticks are obligate hematophagous ectoparasites of vertebrates and are relevant worldwide due to the number of bacterial and other pathogens they can transmit. To date, the knowledge about the microorganisms that ticks harbor and transmit to their hosts is incipient. In this study, 24 samples of mammals belonging to four taxonomic orders and ticks of the genera Amblyomma and Rhipicephalus from the Orinoco region of Colombia were analyzed to described and compare the bacterial microbiome. Genetic extraction was performed, and the V3-V4 region of the 16S rRNA gene was amplified by PCR. Libraries were created, and those samples with adequate quality indices were sequenced using Illumina MiSeq technology. Bacterial taxonomic assignment analyses were conducted through Amplicon Sequence Variants (ASVs) and Operational Taxonomic Units (OTUs). The results correspond to 16 samples that passed the quality filters, with 3218 OTUs (415 families). Although a considerable number of unknown bacteria was found, Enterobacteriaceae, Beijerinckiaceae, Moraxellaceae, and Burkholderiaceae are the most prevalent families, and the presence of the genera Coxiella, Escherichia-Shigella, Enterobacter, which can harbor pathogenic species was confirmed. In individuals of Amblyomma mixtum found actively feeding on Hydrochoerus hydrochaeris, bacteria of the genera Escherichia-Shigella and Enterobacter were documented. Similarly, Rhipicephalus microplus found actively feeding on Odocoileus virginianus cariacou shared Escherichia-Shigella. Ralstonia was shared among the blood samples of H. hydrochaeris, while Anaplasma and Eubacterium were shared in blood and liver samples of O. v. cariacou. Shared bacteria between A. mixtum and R. microplus included Bacillus, Coxiella, and Escherichia-Shigella. The results highlight the need of additional studies in other natural regions of Colombia and other American countries where tick-borne diseases have been detected. Likewise, the recorded data are the first at the level of bacterial communities in ticks of the family Ixodidae and provide valuable knowledge for the understanding host-tick and pathogen interactions.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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)
Subject(s)
Humans , Male , Sexuality , Erectile Dysfunction , Sexual Dysfunctions, Psychological , Anxiety , Depression , Self Concept , Epidemiology, Descriptive , Psychosomatic Medicine , Psychiatry , Surveys and QuestionnairesABSTRACT
BACKGROUND: The transfer of information at the change of shift is a critical point for patient experience during the care process. The aim of this study was to evaluate caregivers' perceptions before and after the implementation of a multidisciplinary bedside handoff in a pediatric emergency department (PED). METHODS: This was a quality improvement pre-post intervention, single-center study. The authors included caregivers of patients allocated in the observation unit of a PED during health care provider shift change. The study was made up of the following phases: (1) preintervention survey distribution, (2) implementation of the bedside handoff, involving all health care professionals (including nurses, nursing assistants, and pediatricians) and caregivers, and (3) postintervention survey distribution. The survey explored the three dimensions of patient experience defined as main study outcomes: information received and communication with professionals, participation, and continuity of care. RESULTS: A total of 102 surveys were collected (51 each in the preintervention and postintervention phases). In the preintervention phase, 94.1% of caregivers would have wished to be actively involved in the change of shift. In the postintervention phase, more caregivers felt that professionals had proper introductions (49.0% vs. 84.3%; p < 0.01), had kept them informed of the plan to be followed (58.8% vs. 84.3%; p = 0.02), and encouraged questions (45.1% vs. 82.4%; p < 0.01). Caregivers of the postintervention phase perceived less disorganization during the change of shift (25.5% vs. 5.9%; p = 0.01) and a greater sense of continuity (64.7% vs. 86.3%; pâ¯=â¯0.02). CONCLUSION: The bedside handoff is a useful strategy to improve patient and family perceptions of communication with professionals, information received, and continuity of care at health care providers shift change. Future lines of research and improvement include ensuring equity in participation in the bedside handoff for all caregivers, monitoring the handoffs to determine how often patients/caregivers participate and correct mistakes in information transfer. and exploring professionals' perceptions.
Subject(s)
Communication , Continuity of Patient Care , Emergency Service, Hospital , Patient Handoff , Quality Improvement , Humans , Emergency Service, Hospital/organization & administration , Patient Handoff/standards , Patient Handoff/organization & administration , Quality Improvement/organization & administration , Continuity of Patient Care/organization & administration , Male , Caregivers , Female , ChildABSTRACT
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.
ABSTRACT
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).
Subject(s)
Lacerations , Postpartum Hemorrhage , Pregnancy , Female , Humans , Cesarean Section , Delivery, Obstetric/methods , Labor Stage, Second , Systematic Reviews as TopicABSTRACT
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.
ABSTRACT
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.
Subject(s)
Dendrimers , Neurodegenerative Diseases , Humans , RNA, Small Interfering/genetics , Dendrimers/chemistry , Silanes/chemistryABSTRACT
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.
Subject(s)
Typhoid Fever , Typhoid-Paratyphoid Vaccines , Vaccine-Preventable Diseases , Humans , Typhoid Fever/prevention & control , Typhoid Fever/epidemiology , Sanitation , Hygiene , Water SupplyABSTRACT
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.
Subject(s)
Plant Viruses , Virome , Animals , Insecta/genetics , Plant Viruses/genetics , Genome, Insect , High-Throughput Nucleotide SequencingABSTRACT
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.
Subject(s)
Adenylate Kinase , Infertility , Semen , Animals , Cattle , Female , Male , Mice , Pregnancy , Adenylate Kinase/genetics , Adenylate Kinase/metabolism , Fertility , Mammals , Semen/metabolism , Semen Analysis , Sperm Motility , Spermatozoa/metabolismABSTRACT
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.