183 research outputs found
Corticosteroids for severe sepsis: an evidence-based guide for physicians
Septic shock is characterized by uncontrolled systemic inflammation that contributes to the progression of organ failures and eventually death. There is now ample evidence that the inability of the host to mount an appropriate hypothalamic-pituitary and adrenal axis response plays a major in overwhelming systemic inflammation during infections. Proinflammatory mediators released in the inflamed sites oppose to the anti-inflammatory response, an effect that may be reversed by exogenous corticosteroids. With sepsis, via nongenomic and genomic effects, corticosteroids restore cardiovascular homeostasis, terminate systemic and tissue inflammation, restore organ function, and prevent death. These effects of corticosteroids have been consistently found in animal studies and in most recent frequentist and Bayesian meta-analyses. Corticosteroids should be initiated only in patients with sepsis who require 0.5 ÎŒg/kg per minute or more of norepinephrine and should be continued for 5 to 7 days except in patients with poor hemodynamic response after 2 days of corticosteroids and with a cortisol increment of more than 250 nmol/L after a standard adrenocorticotropin hormone (ACTH) test. Hydrocortisone should be given at a daily dose of 200 mg and preferably combined to enteral fludrocortisone at a dose of 50 ÎŒg. Blood glucose levels should be kept below 150 mg/dL
GATA2 Mediates Thyrotropin-Releasing Hormone-Induced Transcriptional Activation of the Thyrotropin ÎČ Gene
Thyrotropin-releasing hormone (TRH) activates not only the secretion of thyrotropin (TSH) but also the transcription of TSHÎČ and α-glycoprotein (αGSU) subunit genes. TSHÎČ expression is maintained by two transcription factors, Pit1 and GATA2, and is negatively regulated by thyroid hormone (T3). Our prior studies suggest that the main activator of the TSHÎČ gene is GATA2, not Pit1 or unliganded T3 receptor (TR). In previous studies on the mechanism of TRH-induced activation of the TSHÎČ gene, the involvements of Pit1 and TR have been investigated, but the role of GATA2 has not been clarified. Using kidney-derived CV1 cells and pituitary-derived GH3 and TαT1 cells, we demonstrate here that TRH signaling enhances GATA2-dependent activation of the TSHÎČ promoter and that TRH-induced activity is abolished by amino acid substitution in the GATA2-Zn finger domain or mutation of GATA-responsive element in the TSHÎČ gene. In CV1 cells transfected with TRH receptor expression plasmid, GATA2-dependent transactivation of αGSU and endothelin-1 promoters was enhanced by TRH. In the gel shift assay, TRH signal potentiated the DNA-binding capacity of GATA2. While inhibition by T3 is dominant over TRH-induced activation, unliganded TR or the putative negative T3-responsive element are not required for TRH-induced stimulation. Studies using GH3 cells showed that TRH-induced activity of the TSHÎČ promoter depends on protein kinase C but not the mitogen-activated protein kinase, suggesting that the signaling pathway is different from that in the prolactin gene. These results indicate that GATA2 is the principal mediator of the TRH signaling pathway in TSHÎČ expression
CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients
SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Spinal Cord Injury Causes Sustained Disruption of the Blood-Testis Barrier in the Rat
There is a high incidence of infertility in males following traumatic spinal cord injury (SCI). Quality of semen is frequently poor in these patients, but the pathophysiological mechanism(s) causing this are not known. Blood-testis barrier (BTB) integrity following SCI has not previously been examined. The objective of this study was to characterize the effects of spinal contusion injury on the BTB in the rat. 63 adult, male Sprague Dawley rats received SCI (nâ=â28), laminectomy only (nâ=â7) or served as uninjured, age-matched controls (nâ=â28). Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), BTB permeability to the vascular contrast agent gadopentate dimeglumine (Gd) was assessed at either 72 hours-, or 10 months post-SCI. DCE-MRI data revealed that BTB permeability to Gd was greater than controls at both 72 h and 10 mo post-SCI. Histological evaluation of testis tissue showed increased BTB permeability to immunoglobulin G at both 72 hours- and 10 months post-SCI, compared to age-matched sham-operated and uninjured controls. Tight junctional integrity within the seminiferous epithelium was assessed; at 72 hours post-SCI, decreased expression of the tight junction protein occludin was observed. Presence of inflammation in the testes was also examined. High expression of the proinflammatory cytokine interleukin-1 beta was detected in testis tissue. CD68+ immune cell infiltrate and mast cells were also detected within the seminiferous epithelium of both acute and chronic SCI groups but not in controls. In addition, extensive germ cell apoptosis was observed at 72 h post-SCI. Based on these results, we conclude that SCI is followed by compromised BTB integrity by as early as 72 hours post-injury in rats and is accompanied by a substantial immune response within the testis. Furthermore, our results indicate that the BTB remains compromised and testis immune cell infiltration persists for months after the initial injury
Systematic review of the evidence relating FEV1 decline to giving up smoking
<p>Abstract</p> <p>Background</p> <p>The rate of forced expiratory volume in 1 second (FEV<sub>1</sub>) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta.</p> <p>Methods</p> <p>Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors.</p> <p>Results</p> <p>Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex.</p> <p>Conclusion</p> <p>The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV<sub>1 </sub>decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.</p
Longâterm care facilities' response to the COVID â19 pandemic: An international, crossâsectional survey
Aims To (i) assess the adherence of longâterm care (LTC) facilities to the COVIDâ19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions. Design Crossâsectional survey. Methods Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVIDâ19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines. Results The adherence was significantly higher among facilities with more preâpandemic inâservice education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less workâlife imbalance. Conclusions Preâpandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks. Impact This is the first study to comprehensively examine the adherence of LTC facilities to COVIDâ19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to preâpandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks. Patient or public contribution No Patient or Public Contribution
Preoperative Percutaneous Transthoracic Needle Biopsy Increased the Risk of Pleural Recurrence in Pathological Stage I Lung Cancer Patients With Sub-pleural Pure Solid Nodules
A Note on the NP-hardness of the Topological Via Minimization Problem.
Suppose that we are given a two-layer routing area bounded by a closed continuous curve B, a set of terminals placed on B which are available on both layers, and a set of two terminal-nets. The topological via minimization problem is the problem of routing the nets by zero-width wires such that no two wires corresponding to different nets intersect on the same layer and the number of vies used is minimized. Very recently, it was reported that this problem is NP-hard but the proof contains a critical flaw. In this paper, we present a correct NP-hardness proof of the problem
- âŠ