Changes in the expression level of the genes involved in the innate and adaptive immunity of divers

From time immemorial, humans had engaged in breath-hold diving. Developing the scuba (self-contained underwater breathing apparatus) in the last century has made humans increase the capabilities and efficiency of diving. Shallow diving is usually without side effects, but there may be a series of side effects called Decompression Sickness (DCS), which can even lead to severe neurological damages and death in deep and long dives. Scuba diving and its complications alter the pattern of many genes expression involved in innate and adaptive immunity. Researchers have reported various types of these changes in both the genomes of healthy and sick divers. This study surveyed the ten gene expression levels imported into immune responses like apoptosis and inflammation by real-time PCR in Iranian professional fit divers in steady-state. These genes were: Interleukins (IL-6, IL-8, IL-10), Tumor Necrosis Factor (TNFα), complement C3 (C3α), Tumor Necrosis Factor Receptor Type 1 - Associated Death Domain (TRADD), bradykinin receptor B2 (BDKRB2), rennin (REN), arachidonate 5-lipoxygenase (ALOX5), and prostaglandin-endoperoxide synthase 2 (PTGS2). The results showed that the expression levels of TNFα, ALOX5, TRADD, and interleukin genes increased, but PTGS2, REN, and C3α genes' expression levels did not change much. BDKRB2 gene expression level also decreased

Changes in the expression level of the genes involved in the innate and adaptive immunity of divers

771-778From time immemorial, humans had engaged in breath-hold diving. Developing the scuba (self-contained underwater breathing apparatus) in the last century has made humans increase the capabilities and efficiency of diving. Shallow diving is usually without side effects, but there may be a series of side effects called Decompression Sickness (DCS), which can even lead to severe neurological damages and death in deep and long dives. Scuba diving and its complications alter the pattern of many genes expression involved in innate and adaptive immunity. Researchers have reported various types of these changes in both the genomes of healthy and sick divers. This study surveyed the ten gene expression levels imported into immune responses like apoptosis and inflammation by real-time PCR in Iranian professional fit divers in steady-state. These genes were: Interleukins (IL-6, IL-8, IL-10), Tumor Necrosis Factor (TNFα), complement C3 (C3α), Tumor Necrosis Factor Receptor Type 1 - Associated Death Domain (TRADD), bradykinin receptor B2 (BDKRB2), rennin (REN), arachidonate 5-lipoxygenase (ALOX5), and prostaglandin-endoperoxide synthase 2 (PTGS2). The results showed that the expression levels of TNFα, ALOX5, TRADD, and interleukin genes increased, but PTGS2, REN, and C3α genes' expression levels did not change much. BDKRB2 gene expression level also decreased

In vitro cytotoxicity against K562 tumor cell line, antibacterial, antioxidant, antifungal and catalytic activities of biosynthesized silver nanoparticles using Sophora pachycarpa extract

In the present study, we demonstrate the green synthesis of silver nanoparticles using Sophora pachycarpa extract (S. pachycarpa; SPE) as capping, reducing, and stabilizing agents. The biosynthesized silver nanoparticles (SPE-AgNPs) were tested for catalytic, antibacterial, antifungal, antioxidant, and anti-cancer activities. The affecting parameters (the concentration of silver nitrate, the temperature of the reaction, and time of reaction) on the synthesis process were optimized. The biosynthesized SPE-AgNPs were studied by X-Ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS) and Fourier-transform infrared spectroscopy (FT-IR). The FESEM and TEM results revealed spherical and oval-like morphology with sizes ranging from 30 to 40 nm. Photocatalytic performance experiments of SPE-AgNPs were determined by the rapid degradation of the eriochrome black T (EBT) and methylene blue (MB) under sunlight and UV irradiations. The results showed that SPE-AgNPs degraded more than 90% and 80% of both dyes under UV and sunlight irradiations, respectively. In addition, the SPE-AgNPs exhibited good antibacterial and antifungal properties against S. aureus, S. epidermidis, P. aeruginosa, E. coli, K. pneumoniae, E. faecalis, and C. albicans with MIC values of 6.25, 6.25, 0.78, 0.39, 0.78, 1.56 and 0.78 µg/ml. The green synthesized SPE-AgNPs were found to inhibit the activity of DPPH free radicals efficiently. Eventually, the SPE-AgNPs exhibited significant in vitro cytotoxicity against K562 tumor cell line (IC50 = 19.5 µg/ml). All these studies indicated that AgNPs synthesized using S. pachycarpa extract have applications in the environmental and biomedical fields

Imipenem resistance of Pseudomonas in pneumonia: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Pneumonia, and particularly nosocomial (NP) and ventilator-associated pneumonias (VAP), results in high morbidity and costs. NPs in particular are likely to be caused by <it>Pseudomonas aeruginosa </it>(PA), ~20% of which in observational studies are resistant to imipenem. We sought to identify the burden of PA imipenem resistance in pneumonia.</p> <p>Methods</p> <p>We conducted a systematic literature review of randomized controlled trials (RCT) of imipenem treatment for pneumonia published in English between 1993 and 2008. We extracted study, population and treatment characteristics, and proportions caused by PA. Endpoints of interest were: PA resistance to initial antimicrobial treatment, clinical success, microbiologic eradication and on-treatment emergence of resistance of PA.</p> <p>Results</p> <p>Of the 46 studies identified, 20 (N = 4,310) included patients with pneumonia (imipenem 1,667, PA 251; comparator 1,661, PA 270). Seven were double blind, and 7 included US data. Comparator arms included a β-lactam (17, [penicillin 6, carbapenem 4, cephalosporin 7, monobactam 1]), aminoglycoside 2, vancomycin 1, and a fluoroquinolone 5; 5 employed double coverage. Thirteen focused exclusively on pneumonia and 7 included pneumonia and other diagnoses. Initial resistance was present in 14.6% (range 4.2-24.0%) of PA isolates in imipenem and 2.5% (range 0.0-7.4%) in comparator groups. Pooled clinical success rates for PA were 45.2% (range 0.0-72.0%) for imipenem and 74.9% (range 0.0-100.0%) for comparator regimens. Microbiologic eradication was achieved in 47.6% (range 0.0%-100.0%) of isolates in the imipenem and 52.8% (range 0.0%-100.0%) in the comparator groups. Resistance emerged in 38.7% (range 5.6-77.8%) PA isolates in imipenem and 21.9% (range 4.8-56.5%) in comparator groups.</p> <p>Conclusions</p> <p>In the 15 years of RCTs of imipenem for pneumonia, PA imipenem resistance rates are high, and PA clinical success and microbiologic eradication rates are directionally lower for imipenem than for comparators. Conversely, initial and treatment-emergent resistance is more likely with the imipenem than the comparator regimens.</p

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Using research to prepare for outbreaks of severe acute respiratory infection

Severe acute respiratory infections (SARI) remain one of the leading causes of mortality around the world in all age groups. There is large global variation in epidemiology, clinical management and outcomes, including mortality. We performed a short period observational data collection in critical care units distributed globally during regional peak SARI seasons from 1 January 2016 until 31 August 2017, using standardised data collection tools. Data were collected for 1 week on all admitted patients who met the inclusion criteria for SARI, with follow-up to hospital discharge. Proportions of patients across regions were compared for microbiology, management strategies and outcomes. Regions were divided geographically and economically according to World Bank definitions. Data were collected for 682 patients from 95 hospitals and 23 countries. The overall mortality was 9.5%. Of the patients, 21.7% were children, with case fatality proportions of 1% for those less than 5 years. The highest mortality was in those above 60 years, at 18.6%. Case fatality varied by region: East Asia and Pacific 10.2% (21 of 206), Sub-Saharan Africa 4.3% (8 of 188), South Asia 0% (0 of 35), North America 13.6% (25 of 184), and Europe and Central Asia 14.3% (9 of 63). Mortality in low-income and low-middle-income countries combined was 4% as compared with 14% in high-income countries. Organ dysfunction scores calculated on presentation in 560 patients where full data were available revealed Sequential Organ Failure Assessment (SOFA) scores on presentation were significantly associated with mortality and hospital length of stay. Patients in East Asia and Pacific (48%) and North America (24%) had the highest SOFA scores of >12. Multivariable analysis demonstrated that initial SOFA score and age were independent predictors of hospital survival. There was variability across regions and income groupings for the critical care management and outcomes of SARI. Intensive care unit-specific factors, geography and management features were less reliable than baseline severity for predicting ultimate outcome. These findings may help in planning future outbreak severity assessments, but more globally representative data are required

Using research to prepare for outbreaks of severe acute respiratory infection

Severe acute respiratory infections (SARI) remain one of the leading causes of mortality around the world in all age groups. There is large global variation in epidemiology, clinical management and outcomes, including mortality. We performed a short period observational data collection in critical care units distributed globally during regional peak SARI seasons from 1 January 2016 until 31 August 2017, using standardised data collection tools. Data were collected for 1 week on all admitted patients who met the inclusion criteria for SARI, with follow-up to hospital discharge. Proportions of patients across regions were compared for microbiology, management strategies and outcomes. Regions were divided geographically and economically according to World Bank definitions. Data were collected for 682 patients from 95 hospitals and 23 countries. The overall mortality was 9.5%. Of the patients, 21.7% were children, with case fatality proportions of 1% for those less than 5 years. The highest mortality was in those above 60 years, at 18.6%. Case fatality varied by region: East Asia and Pacific 10.2% (21 of 206), Sub-Saharan Africa 4.3% (8 of 188), South Asia 0% (0 of 35), North America 13.6% (25 of 184), and Europe and Central Asia 14.3% (9 of 63). Mortality in low-income and low-middle-income countries combined was 4% as compared with 14% in high-income countries. Organ dysfunction scores calculated on presentation in 560 patients where full data were available revealed Sequential Organ Failure Assessment (SOFA) scores on presentation were significantly associated with mortality and hospital length of stay. Patients in East Asia and Pacific (48%) and North America (24%) had the highest SOFA scores of &gt;12. Multivariable analysis demonstrated that initial SOFA score and age were independent predictors of hospital survival. There was variability across regions and income groupings for the critical care management and outcomes of SARI. Intensive care unit-specific factors, geography and management features were less reliable than baseline severity for predicting ultimate outcome. These findings may help in planning future outbreak severity assessments, but more globally representative data are required