Tuesday, November 1, 2022

Survey the effect of drug treatment on modulation of cytokines gene expression in Allergic Rhinitis

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Abstract

Allergic rhinitis as common airway disease has high prevalence in all peoples worldwide. In allergic diseases, Th2 cells release type 2 cytokines which support the inflammation in airways. All the drugs used for allergic rhinitis, do not cure completely, and the choice of drugs according to cost and efficacy is very important in all groups of atopic patients. Therefore, in this study, the effect of commercial drugs on cytokine gene expression has been studied. Male Balb/c mice were divided into six groups. Allergic rhinitis was induced in five of the six groups with ovalbumin, and four of these five groups were treated with salbutamol, budesonide, theophylline and montelukast. The 5th group was used as positive control group and the 6th group as negative control group. For the survey, RNA was extracted, cDNA was synthesized, and quantitative real time PCR was done for 21 genes. The four drugs had different effect on mRNA expression of cytokines (IL-1b, 2, 4, 5, 7, 8, 9, 11, 12, 13 , 17, 18, 22, 25, 31, 33, 37, IFN-γ, TNF-α, TGF-β1 and Eotaxin) in the allergic rhinitis groups. Salbutamol can be used during pregnancy and breastfeeding, but it has some side effects. Budesonide in the inhaled form is generally safe in pregnancy. Theophylline cannot control allergic attack in the long run. Montelukast is not useful in the treatment of acute. Immunomodulatory and anti-inflammatory effects of drugs in control of allergic rhinitis via Th2 cytokines can be new approaches in molecular medicine.
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Association of preoperative low skeletal muscle mass with postoperative complications after selective neck dissection

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Skeletal muscle mass (SMM) is an emerging predictive and prognostic factor in head and neck cancer patients. The aim of this study was to investigate the predictive value of low SMM for postoperative complications in clinically T1 –2 oral cavity cancer patients undergoing selective neck dissection. A retrospective study in clinically T1–2 oral cavity cancer patients who underwent selective neck dissection between 2011 and 2017 was performed. The predictive value of low SMM for the occurrence of postoperative complications and prolonged hospital stay was evaluated. (Source: International Journal of Oral and Maxillofacial Surgery)
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COVID-19 Vaccination and the Timing of Surgery Following COVID-19 Infection

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imageObjective: To evaluate whether COVID-19 vaccination status or mode of anesthesia modified the temporal harms associated with surgery following coronavirus disease-2019 (COVID-19) infection. Background: Surgery shortly after COVID-19 infection is associated with higher rates of complications, leading to recommendations to delay surgery following COVID-19 infection when possible. However, prior studies were based on populations with low or no prevalence of vaccination. Methods: A retrospective cohort study of patients who underwent scheduled surgery in a health system from January 1, 2018 to February 28, 2022 (N=228,913) was performed. Patients were grouped by time of surgery relative to COVID-19 test positivity: 0 to 4 weeks after COVID-19 ("early post-COVID-19"), 4 to 8 weeks after COVID-19 ("mid post-COVID-19"), >8 weeks after COVID-19 ("late post-COVID-19"), surgery at least 30 days before subsequent COVID-19 ("pre-COVID-19"), and surgery with no prior or subsequent test positivity for COVID-19. Results: Among patients who were not fully vaccinated at the time of COVID-19 infection, the adjusted rate of perioperative complications for the early post-COVID-19 group was significantly higher than for the pre-COVID-19 group (relative risk: 1.55; P=0.05). No significantly higher risk was identified between these groups for patients who were fully vaccinated (0.66; P=1.00), or for patients who were not fully vaccinated and underwent surgery without general anesthesia (0.52; P=0.83). Conclusions: Surgery shortly following COVID-19 infection was not associated with higher risks among fully vaccinated patients or among patients who underwent surgery without general anesthesia. Further research will be valuable to understand additional factors that modify perioperative risks associated with prior COVID-19 infection.
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A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation

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imageObjective: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). Background: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. In addition, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. Methods: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 years follow up, 32% beyond Milan criteria). The resulting 4 gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. Results: HepatoPredict identifies 99% disease-free patients (>5 year) from a retrospective cohort, including many outside clinical criteria (16%–24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88.5%–94.4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. Conclusions: HepatoPredict outperforms conventional clinical-pathologic selection criteria (Milan, UCSF), providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs.
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Sirtuin 1 deletion increases inflammation and mortality in sepsis

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imageBACKGROUND Sepsis is a hyperinflammatory response to infection that can lead to multiorgan failure and eventually death. Often, the onset of multiorgan failure is heralded by renal dysfunction. Sirtuin 1 (SIRT1) promotes cellular stress resilience by inhibiting inflammation and promoting mitochondrial function. We hypothesize that SIRT1 plays an important role in limiting the inflammatory responses that drive organ failure in sepsis, predominantly via expression in myeloid cells. METHODS We performed cecal ligation and puncture (CLP) on whole body SIRT1 knockout (S1KO) and myeloid cell–specific S1KO (S1KO-LysMCre) mice on a C57BL/6J background. Serum interleukin (IL)-6 was quantified by enzyme-linked immunosorbent assay. Renal mitochondrial complex activity was measured using Oxygraph-2k (Oroboros Instruments, Innsbruck, Austria). Blood urea nitrogen (BUN) was measured from serum. Survival was monitored for up to 5 days. RESULTS Following CLP, S1KO mice had decreased renal mitochondrial complex I–dependent respiratory capacity (241.7 vs. 418.3 mmolO2/mg/min, p = 0.018) and renal mitochondrial complex II–dependent respiratory capacity (932.3 vs. 1,178.4, p = 0.027), as well as reduced rates of fatty acid oxidation (187.3 vs. 250.3, p = 0.022). Sirtuin 1 knockout mice also had increased BUN (48.0 mg/dL vs. 16.0 mg/dL, p = 0.049). Interleukin-6 levels were elevated in S1KO mice (96.5 ng/mL vs. 45.6 ng/mL, p = 0.028) and S1KO-LysMCre mice (35.8 ng/mL vs. 24.5 ng/mL, p = 0.033) compared with controls 12 hours after surgery. Five-day survival in S1KO (33.3% vs. 83.3%, p = 0.025) and S1KO-LysMCre (60% vs. 100%, p = 0.049) mice was decreased compared with controls. CONCLUSION Sirtuin 1 deletion increases systemic inflammation in sepsis. Renal mitochondrial dysfunction, kidney injury, and mortality following CLP were all exacerbated by SIRT1 deletion. Similar effects on inflammation and survival were seen following myeloid cell–specific SIRT1 deletion, indicating that SIRT1 activity in myeloid cells may be a significant contributor for the protective effects of SIRT1 in sepsis.
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Accessibility of Level III trauma centers for underserved populations: A cross-sectional study

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imageBACKGROUND By providing definitive care for many, and rapid assessment, resuscitation, stabilization, and transfer to Level I/II centers when needed, Level III trauma centers can augment capacity in high resource regions and extend the geographic reach to lower resource regions. We sought to (1) characterize populations served principally by Level III trauma centers, (2) estimate differences in time to care by trauma center level, and (3) update national estimates of trauma center access. METHODS In a cross-sectional study (United States, 2019), we estimated travel time from census block groups to the nearest Level I/II trauma center and nearest Level III trauma center. Block groups were categorized based on the level of care accessible within 60 minutes, then distributions of population characteristics and differences in time to care were estimated. RESULTS An estimated 22.8% of the US population (N = 76,119,228) lacked access to any level of trauma center care within 60 minutes, and 8.8% (N = 29,422,523) were principally served by Level III centers. Black and American Indian/Alaska Native (AIAN) populations were disproportionately represented among those principally served by Level III centers (39.1% and 12.2%, respectively). White and AIAN populations were disproportionately represented among those without access to any trauma center care (26.2% and 40.8%, respectively). Time to Level III care was shorter than Level I/II for 27.9% of the population, with a mean reduction in time to care of 28.9 minutes (SD = 31.4). CONCLUSION Level III trauma centers are a potential source of trauma care for underserved populations. While Black and AIAN disproportionately rely on Level III centers for care, most with access to Level III centers also have access to Level I/II centers. The proportion of the US population with timely access to trauma care has not improved since 2010. LEVEL OF EVIDENCE Prognostic/Epidemiological; Level IV.
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Integrating traffic safety data with area deprivation index: A method to better understand the causes of pediatric pedestrian versus automobile collisions

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imageBACKGROUND The purpose of this study was to identify clinical and traffic factors that influence pediatric pedestrian versus automobile collisions (P-ACs) with an emphasis on health care disparities. METHODS A retrospective review was performed of pediatric (18 years or younger) P-ACs treated at a Level I pediatric trauma center from 2008 to 2018. Demographic, clinical, and traffic scene data were analyzed. Area deprivation index (ADI) was used to measure neighborhood socioeconomic disadvantage (NSD) based on home addresses. Traffic scene data from the California Statewide Integrated Traffic Records System were matched to clinical records. Traffic safety was assessed by the streetlight coverage, the proximity of the collision to home addresses, and sidewalk coverage. Descriptive statistics and univariate analysis for key variables and outcomes were calculated using Kruskal-Wallis, Wilcoxon, χ2, or Fisher's exact tests. Statistical significance was attributed to p values of
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Transcriptome reveals the dysfunction of pancreatic islets after wound healing in severely burned mice

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imageBACKGROUND Severely burned patients have a higher risk of diabetes mellitus after healing, but its mechanism remains unclear. Therefore, the purpose of the study was to explore the influence of burns on pancreatic islets of mice after wound healing. METHODS Forty-two male C57BL/6 mice were randomized into a sham group and a burn group and subjected to sham treatment or a third-degree burn model of 30% total body surface area. Fasting blood glucose was detected weekly for 8 weeks after severe burns. Glucose-stimulated insulin secretion was measured 8 weeks post severe burns. Islets of the two groups were isolated and mRNA libraries were sequenced by the Illumina sequencing platform. The expressions of differentially expressed genes (DEGs) related to the cell cycle and the amounts of mitochondrial DNA were detected by quantitative real-time polymerase chain reaction after gene ontology, gene set enrichment analysis, and protein-protein network analysis. Hematoxylin-eosin staining of pancreatic tail tissue and adenosine triphosphate (ATP) assay of islets were performed. RESULTS The levels of fasting blood glucose were significantly higher within 8 weeks post severe burns. Glucose-stimulated insulin secretion was impaired at the eighth week post severe burns. Totally 128 DEGs were selected. Gene ontology and gene set enrichment analysis indicated that the pathways related to the cell cycle, protein processing, and oxidative phosphorylation were downregulated. The expressions of DEGs related to the cell cycle showed a consistent trend with mRNA sequencing data, and most of them were downregulated post severe burns. The cell mass of the burn group was less than that of the sham group. Also, the concentration of ATP and the amount of mitochondrial DNA were lower in the burn group. CONCLUSION In the model of severe-burned mice, disorders in glucose metabolism persist for 8 weeks after burns, which may be related to low islet cell proliferation, downregulation of protein processing, and less ATP production.
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Reading the signs in penetrating cervical vascular injuries: Analysis of hard/soft signs and initial management from a nationwide vascular trauma database

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imageBACKGROUND Algorithms for management of penetrating cervical vascular injuries (PCVIs) commonly call for immediate surgery with "hard signs" and imaging before intervention with "soft signs." We sought to analyze the association between initial examination and subsequent evaluation and management approaches. METHODS Analysis of PCVIs from the American Association for the Surgery of Trauma Prospective Observational Vascular Injury Treatment vascular injury registry from 25 US trauma centers was performed. Patients were categorized by initial examination findings of hard signs or soft signs, and subsequent imaging and surgical exploration/repair rates were compared. RESULTS Of 232 PCVI patients, 110 (47%) had hard signs (hemorrhage, expanding hematoma, or ischemia) and 122 (53%) had soft signs. With hard signs, 61 (56%) had immediate operative exploration and 44% underwent computed tomography (CT) imaging. After CT, 20 (18%) required open surgical repair, and 7% had endovascular intervention. Of note, 21 (19%) required no operative intervention. A total of 122 patients (53%) had soft signs on initial examination; 37 (30%) had immediate surgery, and 85 (70%) underwent CT imaging. After CT, 9% had endovascular repair, 7% had open surgery, and 65 (53%) were observed. No difference in mortality was observed for hard signs patients undergoing operative management versus observation alone (23% vs. 17%, p = 0.6). Those with hemorrhage as the primary hard signs most often required surgery (76%), but no interventions were required in 19% of hemorrhage, 20% of ischemia, and 24% of expanding hematoma. CONCLUSION Although hard signs in PCVIs are associated with the need for operative intervention, initial CT imaging can facilitate endovascular options or nonoperative management in a significant subgroup. Hard signs should not be considered an absolute indication for immediate surgical exploration. LEVEL OF EVIDENCE Prognostic/Epidemiological; Level IV.
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Early expression of IL-10, IL-12, ARG1, and NOS2 genes in peripheral blood mononuclear cells synergistically correlate with patient outcome after burn injury

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imageBACKGROUND No methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, noninvasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients. METHODS This prospective observational study enrolled two patient cohorts within a single burn center into an institutionally approved institutional review board study. Blood draws were performed
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