•The observed allodynia relationship to neonatal anoxia requires better understanding to improve quality of life and pediatrics approaches in neonatal care.•Neonatal oxygen deprivation revealed ...significant reduction in the mechanical nociceptive threshold.•Equal and strong nociceptive damage was revealed in both sexes but, histological sex difference was seen at VPL.•The nociceptive damage chronically seen at suckling period increased in adolescence.•These results address further studies concerning the nature of the mechanisms the sexes deal with pain.
Chronic neuropathic pain resulting from damage to the central or peripheral nervous system is a prevalent and debilitating condition affecting 7–18% of the population. Symptoms include spontaneous pain, dysesthesia, paresthesia, allodynia and hyperalgesia. The reported sensory symptoms are comorbid with behavioral disabilities such as insomnia and depression. Neonatal anoxia, a worldwide clinical problem in both neonatal and pediatric care, causes long-term deficits similar to those mentioned. The effect of neonatal anoxia on the maturation of nociceptive pathways has been sparsely explored. To address this question and to determine whether the effects differ depending on sex, a neonatal anoxia model was used in which Wistar rat pups approximately 30 h old and of both sexes were placed in a chamber with 100% nitrogen flow at 3.5 L/min for 25 min at 36 °C ± 1 °C. After recovery, the animals (n = 16 in each group (anoxia and control; males and females)) were returned to their mothers. The control animals were subjected to the same conditions, but no gas exchange was performed. At postnatal day (PND) 18 and PND43, the animals were subjected to pain testing by stimulation of the hind paws with von Frey monofilaments. The results revealed a significant reduction (approximately 50%) in the pain threshold in the animals exposed to anoxia in comparison with their respective controls. The pain threshold increased between PND18 and PND43. A sex-based difference was observed in the male control group at PND18. Histological analysis revealed decreased cell numbers in the ventral posterolateral thalamic nucleus (VPL), with sex differences. These results demonstrate the long-lasting negative impact of neonatal anoxia and indicate the relevance of performing suitable approaches taking in consideration the possible sex differences.
Though influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work ...has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human
ocular tissues and corneal or conjunctival cell monolayers, leaving the determinants of ocular tropism unclear. Here, we evaluated the effect of several variables on tropism for ocular cells cultured
and examined the potential effect of the tear film on viral infectivity. All viruses tested were able to replicate in primary human corneal epithelial cell monolayers subject to aerosol inoculation. The temperature at which cells were cultured post-inoculation minimally affected infectivity. Replication efficiency, in contrast, was reduced at 33°C relative to 37°C and this effect was slightly greater for the conjunctivitis isolates than the respiratory ones. With the exception of a seasonal H3N2 virus, the subset of viruses studied in multi-layer corneal tissue constructs also replicated productively after either aerosol or liquid inoculation. Human tears significantly inhibited hemagglutination of both ocular and non-ocular isolates, but the effect on viral infectivity was more variable, with tears reducing the infectivity of non-ocular isolates more than ocular isolates. These data suggest that most influenza viruses may be capable of establishing infection if they reach the surface of ocular cells, but that this is more likely for ocular tropic viruses as they are better able to maintain their infectivity during passage through the tear film.
The potential spread of zoonotic influenza viruses to humans represents an important threat to public health. Unfortunately, despite the importance of cellular and tissue tropism to pathogenesis, determinants of influenza viral tropism have yet to be fully elucidated. Here, we sought to identify factors which limit the ability of most influenza viruses to cause ocular infection. Though ocular symptoms in humans caused by avian influenza viruses tend to be relatively mild, these infections are concerning due to the potential of the ocular surface to serve as a portal of entry for viruses that go on to establish respiratory infections. Furthermore, a better understanding of the factors which influence infection and replication in this non-canonical site may point toward novel determinants of tropism in the respiratory tract.
•AI implementation in medical imaging/radiotherapy is impeded by lack of training.•There is a distinct lack of knowledge of AI governance frameworks.•Different professionals identify different ...priorities for AI adoption.•Customised training and governance frameworks can accelerate AI implementation.
Medical Imaging and radiotherapy (MIRT) are at the forefront of artificial intelligence applications. The exponential increase of these applications has made governance frameworks necessary to uphold safe and effective clinical adoption. There is little information about how healthcare practitioners in MIRT in the UK use AI tools, their governance and associated challenges, opportunities and priorities for the future.
This cross-sectional survey was open from November to December 2022 to MIRT professionals who had knowledge or made use of AI tools, as an attempt to map out current policy and practice and to identify future needs. The survey was electronically distributed to the participants. Statistical analysis included descriptive statistics and inferential statistics on the SPSS statistical software. Content analysis was employed for the open-ended questions.
Among the 245 responses, the following were emphasised as central to AI adoption: governance frameworks, practitioner training, leadership, and teamwork within the AI ecosystem. Prior training was strongly correlated with increased knowledge about AI tools and frameworks. However, knowledge of related frameworks remained low, with different professionals showing different affinity to certain frameworks related to their respective roles. Common challenges and opportunities of AI adoption were also highlighted, with recommendations for future practice.
Color is a signature visual feature in nature; however, the ability to trigger color change in the presence of different environmental stimuli is unique to only a handful of species in the animal ...kingdom. We exploit the natural color-changing properties of the predominant pigment in arthropods and cephalopodsxanthommatin (Xa)and describe its utility as a new broad-spectrum electrochromic material. To accomplish this goal, we explored the spectroelectrochemical properties of Xa adsorbed to an indium-doped tin oxide-coated substrate chemically modified with poly(3,4-ethylene dioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS). We identified a synergistic role between PEDOT:PSS and Xa that contributed to its absorption profile, which could be modulated across multiple cycles. By varying the ratio of the two electroactive components, we also altered the perceived visible color of Xa-based devices, which cycled from different shades of red to yellow under reducing and oxidizing potentials, respectively. Together, our data illustrate the utility of Xa-based devices as new broad-spectrum electrochromic materials.
(MPXV) is a human pathogen that is a member of the
genus, which includes
and
(the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host ...factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. We validated the role of a set of vacuolar protein sorting (VPS) genes during infection, VPS51 to VPS54 (VPS51-54), which comprise the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex involved in retrograde transport of endosomes to the
-Golgi apparatus. Our data demonstrate that VPS52 and VPS54 were dispensable for mature virion (MV) production but were required for extracellular virus (EV) formation. For comparison, a known antiviral compound, ST-246, was used in our experiments, demonstrating that EV titers in VPS52 and VPS54 knockout (KO) cells were comparable to levels exhibited by ST-246-treated wild-type cells. Confocal microscopy was used to examine actin tail formation, one of the viral egress mechanisms for cell-to-cell dissemination, and revealed an absence of actin tails in VPS52KO- or VPS54KO-infected cells. Further evaluation of these cells by electron microscopy demonstrated a decrease in levels of wrapped viruses (WVs) compared to those seen with the wild-type control. Collectively, our data demonstrate the role of GARP complex genes in double-membrane wrapping of MVs necessary for EV formation, implicating the host endosomal trafficking pathway in orthopoxvirus infection.
Human monkeypox is an emerging zoonotic infectious disease caused by
(MPXV). Of the two MPXV clades, the Congo Basin strain is associated with severe disease, increased mortality, and increased human-to-human transmission relative to the West African strain. Monkeypox is endemic in regions of western and central Africa but was introduced into the United States in 2003 from the importation of infected animals. The threat of MPXV and other orthopoxviruses is increasing due to the absence of routine smallpox vaccination leading to a higher proportion of naive populations. In this study, we have identified and validated candidate genes that are required for MPXV infection, specifically, those associated with the Golgi-associated retrograde protein (GARP) complex. Identifying host targets required for infection that prevents extracellular virus formation such as the GARP complex or the retrograde pathway can provide a potential target for antiviral therapy.
A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently ...identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans.
Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage are known to be present during severe human infections, the role of pulmonary endothelial cells in the pathogenesis of avian influenza virus infections is largely unknown. By comparing human seasonal influenza strains to avian influenza viruses, we provide greater insight into the interaction of influenza virus with human pulmonary endothelial cells. We show that human influenza virus infection is blocked during the early stages of virus entry, which is likely due to the relatively high expression of the host antiviral factors IFITMs (interferon-induced transmembrane proteins) located in membrane-bound compartments inside cells. Overall, this study provides a mechanism by which human endothelial cells limit replication of human influenza virus strains, whereas avian influenza viruses overcome these restriction factors in this cell type.
Neonatal hypoxic‐ischemic encephalopathy (HIE) is one of the most important reasons for morbidity and mortality in term‐born infants. HIE impacts early somatic, neurological, and motor development ...including social. To illustrate the damages in the sensorimotor system, an adapted and validated model of neonatal anoxia is used. This study evaluated the sex differences in Wistar rats, neurological reflex, and motor development at the suckling period. Short‐ and long‐term impairments associated with sex differences were observed. In general, anoxic males were more affected in comparison to their control group and to anoxic females. Long‐lasting effects of the injury in adolescent rats predominately affected males. Similar to previous studies, we also found a decrease in the number of the substantia nigra cells in both sexes, compared to their control. So far, the results indicate that HIE caused neurobehavioral alterations and asymmetrical motor behavior with brain damage, possibly related to cognitive impairments previously observed at adolescence. These alterations may represent a useful endpoint for studying the efficacy of potential strategies that may improve the developmental consequences of a perinatal asphyxia insult in humans.
Activation of TLRs by bacterial products results in rapid activation of genes encoding products designed to protect the host from perturbing microbes. In the intestine, which is colonized by a large ...and diverse population of commensal bacteria, TLR signaling may not function in a simple on/off mode. Here, we show that the flagellin receptor TLR5 has an essential and nonredundant role in protecting the gut from enteric microbes. Mice lacking TLR5 (TLR5KO mice) developed spontaneous colitis, as assessed by well-defined clinical, serologic, and histopathologic indicators of this disorder. Compared with WT littermates, TLR5KO mice that had not yet developed robust colitis exhibited decreased intestinal expression of TLR5-regulated host defense genes despite having an increased bacterial burden in the colon. In contrast, such TLR5KO mice displayed markedly increased colonic expression of hematopoietic-derived proinflammatory cytokines, suggesting that elevated levels of bacterial products may result in activation of other TLRs that drive colitis in TLR5KO mice. In accordance, deletion of TLR4 rescued the colitis of TLR5KO mice in that mice lacking both TLR4 and TLR5 also had elevated bacterial loads in the colon but lacked immunological, histopathological, and clinical evidence of colitis. That an engineered innate immune deficiency ultimately results in spontaneous intestinal inflammation supports the notion that an innate immune deficiency might underlie some instances of inflammatory bowel disease.
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