Aagesenkronborg4815

Insecticide resistance is challenging the effectiveness of insecticide-based control interventions to reduce malaria burden in Africa. Understanding the molecular basis of insecticides resistance and patterns of gene flow in major malaria vectors such as Anopheles funestus are important steps for designing effective resistance management strategies. Here, we investigated the association between patterns of genetic structure and expression profiles of genes involved in the pyrethroid resistance in An. funestus across Uganda and neighboring Kenya.

Blood-fed mosquitoes An. funestus were collected across the four localities in Uganda and neighboring Kenya. A Microarray-based genome-wide transcription analysis was performed to identify the set of genes associated with permethrin resistance. 17 microsatellites markers were genotyped and used to establish patterns of genetic differentiation.

Microarray-based genome-wide transcription profiling of pyrethroid resistance in four locations across Uganda (Arua, Bul) and revealed a barrier to gene flow between Arua and other areas, possibly associated with Rift Valley.

The correlation between patterns of genetic structure and variation in gene expression could be used to inform future interventions especially as new insecticides are gradually introduced.

The correlation between patterns of genetic structure and variation in gene expression could be used to inform future interventions especially as new insecticides are gradually introduced.The enzyme kynurenine 3-monooxygenase (KMO) operates at a critical branch-point in the kynurenine pathway (KP), the major route of tryptophan metabolism. As the KP has been implicated in the pathogenesis of several human diseases, KMO and other enzymes that control metabolic flux through the pathway are potential therapeutic targets for these disorders. While KMO is localized to the outer mitochondrial membrane in eukaryotic organisms, no mitochondrial role for KMO has been described. In this study, KMO deficient Drosophila melanogaster were investigated for mitochondrial phenotypes in vitro and in vivo. We find that a loss of function allele or RNAi knockdown of the Drosophila KMO ortholog (cinnabar) causes a range of morphological and functional alterations to mitochondria, which are independent of changes to levels of KP metabolites. Notably, cinnabar genetically interacts with the Parkinson's disease associated genes Pink1 and parkin, as well as the mitochondrial fission gene Drp1, implicating KMO in mitochondrial dynamics and mitophagy, mechanisms which govern the maintenance of a healthy mitochondrial network. Overexpression of human KMO in mammalian cells finds that KMO plays a role in the post-translational regulation of DRP1. These findings reveal a novel mitochondrial role for KMO, independent from its enzymatic role in the kynurenine pathway.Hypertension is the most important cause of death and disability in the elderly. In 9 out of 10 cases, the molecular cause, however, is unknown. One mechanistic hypothesis involves impaired endothelium-dependent vasodilation through reactive oxygen species (ROS) formation. Indeed, ROS forming NADPH oxidase (Nox) genes associate with hypertension, yet target validation has been negative. We re-investigate this association by molecular network analysis and identify NOX5, not present in rodents, as a sole neighbor to human vasodilatory endothelial nitric oxide (NO) signaling. In hypertensive patients, endothelial microparticles indeed contained higher levels of NOX5-but not NOX1, NOX2, or NOX4-with a bimodal distribution correlating with disease severity. Mechanistically, mice expressing human Nox5 in endothelial cells developed-upon aging-severe systolic hypertension and impaired endothelium-dependent vasodilation due to uncoupled NO synthase (NOS). We conclude that NOX5-induced uncoupling of endothelial NOS is a causal mechanism and theragnostic target of an age-related hypertension endotype. Nox5 knock-in (KI) mice represent the first mechanism-based animal model of hypertension.

Southeast Asian countries host signficant numbers of forcibly displaced people. This study was conducted to examine how health systems in Southeast Asia have responded to the health system challenges of forced migration and refugee-related health including the health needs of populations affected by forced displacement; the health systems-level barriers and facilitators in addressing these needs; and the implications of existing health policies relating to forcibly displaced and refugee populations. This study aims to fill in the gap in knowledge by analysing how health systems are organised in Southeast Asia to address the health needs of forcibly displaced people.

We conducted 30 semistructured interviews with health policy-makers, health service providers, and other experts working in the United Nations (n = 6), ministries and public health (n = 5), international (n = 9) and national civil society (n = 7), and academia (n = 3) based in Indonesia (n = 6), Malaysia (n = 10), Myanmar (n = 6), and Thailandoncerns and barriers to access among migrants experiencing forced displacement, particularly refugees and asylum seekers, in Southeast Asia. Findings provide practical new insights with implications for informing policy and practice. Overall, sociopolitical inclusion of forcibly displaced populations remains difficult in these four countries despite their significant contributions to host-country economies.

To our knowledge, this is one of the first qualitative studies to investigate the health concerns and barriers to access among migrants experiencing forced displacement, particularly refugees and asylum seekers, in Southeast Asia. Findings provide practical new insights with implications for informing policy and practice. Overall, sociopolitical inclusion of forcibly displaced populations remains difficult in these four countries despite their significant contributions to host-country economies.Echolocating bats rely upon spectral interference patterns in echoes to reconstruct fine details of a reflecting object's shape. However, the acoustic modulations required to do this are extremely brief, raising questions about how their auditory cortex encodes and processes such rapid and fine spectrotemporal details. Here, we tested the hypothesis that biosonar target shape representation in the primary auditory cortex (A1) is more reliably encoded by changes in spike timing (latency) than spike rates and that latency is sufficiently precise to support a synchronization-based ensemble representation of this critical auditory object feature space. To test this, we measured how the spatiotemporal activation patterns of A1 changed when naturalistic spectral notches were inserted into echo mimic stimuli. Neurons tuned to notch frequencies were predicted to exhibit longer latencies and lower mean firing rates due to lower signal amplitudes at their preferred frequencies, and both were found to occur. Comparative analyses confirmed that significantly more information was recoverable from changes in spike times relative to concurrent changes in spike rates. With this data, we reconstructed spatiotemporal activation maps of A1 and estimated the level of emerging neuronal spike synchrony between cortical neurons tuned to different frequencies. The results support existing computational models, indicating that spectral interference patterns may be efficiently encoded by a cascading tonotopic sequence of neural synchronization patterns within an ensemble of network activity that relates to the physical features of the reflecting object surface.BACKGROUND Cardioversion is a safe, commonly used procedure throughout the world. It is performed over 30 000 times per year in the United States, specifically for atrial fibrillation. Procedural risks from cardioversion include clot dislodgement, sedation effects, site pain, burns, hypotension, dysrhythmias, or heart failure. Generally, back pain is considered to be simple muscle soreness, and cardioversion consents therefore do not include discussion of back injuries. CASE REPORT A 46-year-old man with no prior back pain or injury history underwent a planned synchronized cardioversion for atrial fibrillation. He immediately reported new back pain following the procedure. No unusual event such as a fall occurred near the time of the procedure, but upon evaluation, he was found to have a new lumbar compression fracture that caused incapacitating pain for more than 6 weeks. CONCLUSIONS Cardioversion has been found to be a safe, effective treatment for atrial fibrillation. CWI12 Adverse effects are generally minor, and the frequency of adverse effects appear to be low overall. The case reported here represents a rare, but possibly underreported adverse effect, namely, lumbar compression fracture due to cardioversion. Patients should be counseled on the possibility of back injury, even compression fracture, as a result of cardioversion. It would also be prudent to broaden the differential diagnosis possibilities should a patient complain of back pain after cardioversion.BACKGROUND Sudden sensorineural hearing loss (SSNHL) is currently treated with a combination of drugs, predominantly with glucocorticoids (GCs). However, the mechanisms of action of GCs in SSNHL are unknown. This study aimed to analyze the role of endoplasmic reticulum stress (ERS) in SSNHL pathogenesis and prognosis. MATERIAL AND METHODS In this study, we evaluated the expression and activation status of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-C/EBP homologous protein (CHOP) pathway in peripheral blood mononuclear cells (PBMCs) from patients with SSNHL and compared them with those in healthy controls. We also compared differences in expression of activating transcription factor 4 (ATF4) and CHOP before and after glucocorticoid treatment in patients with improved and unimproved SSNHL. RESULTS Treatment with GCs significantly improved hearing in 55% of patients with SSNHL. Levels of phosphorylated PERK (p-PERK) and phosphorylated eukaryotic initiation factor 2alpha were increased in PBMCs from patients with SSNHL compared with healthy controls. ATF4 and CHOP expression were also significantly elevated. After treatment, the amount of ATF4 and CHOP proteins in PBMCs in the patients whose SSNHL improved was significantly reduced compared with the levels measured before treatment in all patients with SSNHL. The expression of the ATF4 and CHOP proteins in PBMCs in the unimproved group, however, was not significantly changed relative to pretreatment levels. CONCLUSIONS ERS may play a significant role in the pathogenesis of SSNHL, and the responsiveness of the condition to GC-mediated mitigation of ERS may be one of the key factors that affect patient prognosis.The epidemiology of maxillofacial fractures is variable in different geographic regions. Economic and social conditions, laws and types of behavior can be considered the most important factors influencing these differences.Mandibular fractures were first cited in 1650 BC in an Egyptian papyrus. Today, these fractures are one of the most prevalent facial skeletal injuries.A 4-year retrospective study was performed and the trauma - related data were collected from medical and radiological archives. The analysis comprised patients admitted for mandibular fracture at Sapienza University of Rome - Policlinico Umberto I between January 1, 2016 and December 31, 2019. The data include age, sex, etiology, anatomical sites of the fractures, eventual maxillofacial associated fractures and treatment.We collected 172 patients, 138 males (80.2%) and 34 females (19.8%) with 270 mandibular fractures. The average age was 35.4 years. The youngest and oldest patients were aged 6 and 90 years, respectively. The age group 20 to 29 years was the most represented with 52 patients (30.