1,640 research outputs found
Acute upper airway failure and mediastinal emphysema following a wire-guided percutaneous cricothyrotomy in a patient with severe maxillofacial trauma
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69538.pdf (publisher's version ) (Open Access)BACKGROUND: In the presence of severe maxillofacial trauma, management of the airway is important because this condition poses a significant threat to airway patency. That securing the airway is not always straightforward is described and illustrated in this paper. CASE: We present the case of a 23-year-old patient who sustained severe maxillofacial injury for which airway control was necessary. A wire-guided percutaneous dilation cricothyrotomy was performed, which was most probably the cause of an acute loss of airway patency. The literature regarding the role of percutaneous techniques in an elective and emergency setting is reviewed
4-Octyl itaconate reduces influenza A replication by targeting the nuclear export protein CRM1
In recent years, especially since the outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic, the cell-permeable itaconate derivative 4-octyl itaconate (4-OI) has gained traction as a potential antiviral agent. Here, we demonstrate that 4-OI inhibits replication of multiple influenza A viruses (IAV) by restricting nuclear export of viral ribonucleoproteins, a key step in the IAV replication cycle. This nuclear retention is achieved by deactivation and subsequent degradation of chromosomal maintenance 1 protein (CRM1), also known as exportin 1 (XPO1), a host cell protein exploited by IAV during replication. 4-OI-mediated deactivation of CRM1 resulted in the accumulation of the IAV nucleoprotein, the Rev protein of feline immunodeficiency virus, as well as the natural CRM1 cargos p53 and p65, in the nucleus of treated cells. Further mechanism of action studies revealed that, similar to known CRM1 inhibitors, 4-OI modifies a key cysteine in the cargo binding pocket of CRM1 at position 528 through an alkylation reaction called 2,3-dicarboxypropylation. Subsequent studies in a cell line in which the cysteine at position 528 in CRM1 protein was substituted by a serine confirmed that modification of this residue was indeed the cause for the observed inhibitory effect induced by 4-OI on CRM1 function. Overall, this study demonstrated a mechanism through which 4-OI directly interferes with the replication cycle of CRM1-dependent viruses, which contributes to the understanding of the antiviral and anti-inflammatory properties of this multifaceted immuno-metabolite. IMPORTANCE Itaconate derivates, as well as the naturally produced metabolite, have been proposed as antivirals against influenza virus. Here, the mechanism behind the antiviral effects of exogenous 4-octyl itaconate (4-OI), a derivative of itaconate, against the influenza A virus replication is demonstrated. The data indicate that 4-OI targets the cysteine at position 528 of the CRM1 protein, resulting in inhibition of the nuclear export of viral ribonucleoprotein complexes in a similar manner as previously described for other selective inhibitors of nuclear export. These results postulate a mechanism not observed before for this immuno-metabolite derivative. This knowledge is helpful for the development of derivatives of 4-OI as potential antiviral and anti-inflammatory therapeutics.</p
B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies.</p
B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies.</p
Respiratory Infections by HMPV and RSV Are Clinically Indistinguishable but Induce Different Host Response in Aged Individuals
Background: Human metapneumovirus and respiratory syncytial virus can cause severe respiratory diseases, especially in infants, young children, and the elderly. So far it remains unclear why infections in the elderly become life threatening despite the presence of neutralizing antibodies in the serum, and to which extent double infections worsen the clinical course. Methods: Young and aged BALB/c-mice were infected with RSV or/and HMPV. Appearance of the mice was observed during course of infection. On day 5 p.i. animals were dispatched by cervical dislocation and levels of TNF-a and NF-kB were determined. Results: The observation of activity, weight and appearance of the different mice showed no differences among the tested groups. Despite this, the immunologic response depends on the animals ’ age and the virus they were infected with. In young animals, NF-kB levels were elevated if infected with HMPV and HMPV/RSV but remained low in RSV infections, whereas in aged animals the opposite was observed: solely RSV-infected animals showed elevated levels of NF-kB. TNF-a was slightly elevated in HMPV-infected young and old animals, but only in young animals this elevation was significant. Conclusions: Contrary to other studies, no weight loss or change in activity despite productive lung infection with the different viruses were observed. This may be due to the weaker anaesthesia or the lesser volume of virus solution used
Relevance of human metapneumovirus in exacerbations of COPD
BACKGROUND AND METHODS: Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR. RESULTS: We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 Ă— 10(5 )viral copies/ml in nasal lavage and 1.88 Ă— 10(5 )viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD. CONCLUSION: HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely
Epidemiological analysis of respiratory viral etiology for influenza-like illness during 2010 in Zhuhai, China
Stereotyping of medical disability claimants' communication behaviour by physicians: towards more focused education for social insurance physicians
Background: Physicians who hold medical disability assessment interviews (social insurance physicians) are probably influenced by stereotypes of claimants, especially because they have limited time available and they have to make complicated decisions. Because little is known about the influences of stereotyping on assessment interviews, the objectives of this paper were to qualitatively investigate: (1) the content of stereotypes used to classify claimants with regard to the way in which they communicate; (2) the origins of such stereotypes; (3) the advantages and disadvantages of stereotyping in assessment interviews; and (4) how social insurance physicians minimise the undesirable influences of negative stereotyping. Methods: Data were collected during three focus group meetings with social insurance physicians who hold medical disability assessment interviews with sick-listed employees (i.e. claimants). The participants also completed a questionnaire about demographic characteristics. The data were qualitatively analysed in Atlas.ti in four steps, according to the grounded theory and the principle of constant comparison. Results: A total of 22 social insurance physicians participated. Based on their responses, a claimant's communication was classified with regard to the degree of respect and acceptance in the physician-claimant relationship, and the degree of dominance. Most of the social insurance physicians reported that they classify claimants in general groups, and use these classifications to adapt their own communication behaviour. Moreover, the social insurance physicians revealed that their stereotypes originate from information in the claimants' files and first impressions. The main advantages of stereotyping were that this provides a framework for the assessment interview, it can save time, and it is interesting to check whether the stereotype is correct. Disadvantages of stereotyping were that the stereotypes often prove incorrect, they do not give the complete picture, and the claimant's behaviour changes constantly. Social insurance physicians try to minimise the undesirable influences of stereotypes by being aware of counter transference, making formal assessments, staying neutral to the best of their ability, and being compassionate. Conclusions: We concluded that social insurance physicians adapt their communication style to the degree of respect and dominance of claimants in the physician-claimant relationship, but they try to minimise the undesirable influences of stereotypes in assessment interviews. It is recommended that this issue should be addressed in communication skills trainin
Case-finding of dementia in general practice and effects of subsequent collaborative care; design of a cluster RCT
<p>Abstract</p> <p>Background</p> <p>In the primary care setting, dementia is often diagnosed relatively late in the disease process. Case finding and proactive collaborative care may have beneficial effects on both patient and informal caregiver by clarifying the cause of cognitive decline and changed behaviour and by enabling support, care planning and access to services.</p> <p>We aim to improve the recognition and diagnosis of individuals with dementia in general practice. In addition to this diagnostic aim, the effects of case finding and subsequent care on the mental health of individuals with dementia and the mental health of their informal carers are explored.</p> <p>Methods and design</p> <p>Design: cluster randomised controlled trial with process evaluation.</p> <p>Participants: 162 individuals ≥ 65 years, in 15 primary care practices, in whom GPs suspect cognitive impairment, but without a dementia diagnosis.</p> <p>Intervention; case finding and collaborative care: 2 trained practice nurses (PNs) invite all patients with suspected cognitive impairment for a brief functional and cognitive screening. If the cognitive tests are supportive of cognitive impairment, individuals are referred to their GP for further evaluation. If dementia is diagnosed, a comprehensive geriatric assessment takes place to identify other relevant geriatric problems that need to be addressed. Furthermore, the team of GP and PN provide information and support.</p> <p>Control: GPs provide care and diagnosis as usual.</p> <p>Main study parameters: after 12 months both groups are compared on: 1) incident dementia (and MCI) diagnoses and 2) patient and caregiver quality of life (QoL-AD; EQ5D) and mental health (MH5; GHQ 12) and caregiver competence to care (SSCQ). The process evaluation concerns facilitating and impeding factors to the implementation of this intervention. These factors are assessed on the care provider level, the care recipient level and on the organisational level.</p> <p>Discussion</p> <p>This study will provide insight into the diagnostic yield and the clinical effects of case finding and collaborative care for individuals with suspected cognitive impairment, compared to usual care. A process evaluation will give insight into the feasibility of this intervention.</p> <p>The first results are expected in the course of 2013.</p> <p>Trial registration</p> <p>NTR3389</p
Extragalactic Globular Clusters and Galaxy Formation
Globular cluster (GC) systems have now been studied in galaxies ranging from
dwarfs to giants and spanning the full Hubble sequence of morphological types.
Imaging and spectroscopy with the Hubble Space Telescope and large ground-based
telescopes have together established that most galaxies have bimodal color
distributions that reflect two subpopulations of old GCs: metal-poor and
metal-rich. The characteristics of both subpopulations are correlated with
those of their parent galaxies. We argue that metal-poor GCs formed in low-mass
dark matter halos in the early universe and that their properties reflect
biased galaxy assembly. The metal-rich GCs were born in the subsequent
dissipational buildup of their parent galaxies and their ages and abundances
indicate that most massive early-type galaxies formed the bulk of their stars
at early times. Detailed studies of both subpopulations offer some of the
strongest constraints on hierarchical galaxy formation that can be obtained in
the near-field.Comment: 74 pages, including 14 figures. In press for Annual Reviews of
Astronomy and Astrophysic
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