Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) ...attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications.
We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed.
Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19.
The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients.
National Institutes of Health. VIDEO ABSTRACT.
The Saccharomyces Genome Database (SGD, http://www.yeastgenome.org) is the community resource for the budding yeast Saccharomyces cerevisiae. The SGD project provides the highest-quality manually ...curated information from peer-reviewed literature. The experimental results reported in the literature are extracted and integrated within a well-developed database. These data are combined with quality high-throughput results and provided through Locus Summary pages, a powerful query engine and rich genome browser. The acquisition, integration and retrieval of these data allow SGD to facilitate experimental design and analysis by providing an encyclopedia of the yeast genome, its chromosomal features, their functions and interactions. Public access to these data is provided to researchers and educators via web pages designed for optimal ease of use.
Inflammasome activation is critical for host defenses against various microbial infections. Activation of the NLRC4 inflammasome requires detection of flagellin or type III secretion system (T3SS) ...components by NLR family apoptosis inhibitory proteins (NAIPs); yet how this pathway is regulated is unknown. Here, we found that interferon regulatory factor 8 (IRF8) is required for optimal activation of the NLRC4 inflammasome in bone-marrow-derived macrophages infected with Salmonella Typhimurium, Burkholderia thailandensis, or Pseudomonas aeruginosa but is dispensable for activation of the canonical and non-canonical NLRP3, AIM2, and Pyrin inflammasomes. IRF8 governs the transcription of Naips to allow detection of flagellin or T3SS proteins to mediate NLRC4 inflammasome activation. Furthermore, we found that IRF8 confers protection against bacterial infection in vivo, owing to its role in inflammasome-dependent cytokine production and pyroptosis. Altogether, our findings suggest that IRF8 is a critical regulator of NAIPs and NLRC4 inflammasome activation for defense against bacterial infection.
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•IRF8 is required for the optimal activation of NLRC4 inflammasome•The expression of Naip1, Naip2, Naip5, and Naip6 is dependent on IRF8•IRF8 is dispensable for the activation of NLRP3, AIM2, and Pyrin inflammasomes•Irf8–/– mice are susceptible to S. Typhimurium and B. thailandensis infection
Optimal activation of NLRC4 inflammasome in response to pathogenic bacteria is dependent on IRF8.
The Indian coastal waters are stressed due to a multitude of factors, such as the discharge of industrial effluents, urbanization (municipal sewage), agricultural runoff, and river discharge. The ...coastal waters along the eastern and western seaboard of India exhibit contrasting characteristics in terms of seasonality, the magnitude of river influx, circulation pattern, and degree of anthropogenic activity. Therefore, understanding these processes and forecasting their occurrence is highly necessary to secure the health of coastal waters, habitats, marine resources, and the safety of tourists. This article introduces an integrated buoy-satellite based Water Quality Nowcasting System (WQNS) to address the unique challenges of water quality monitoring in Indian coastal waters and to boost the regional blue economy. The Indian National Centre for Ocean Information Services (INCOIS) has launched a first-of-its-kind WQNS, and positioned the buoys at two important locations along the east (Visakhapatnam) and west (Kochi) coast of India, covering a range of environmental conditions and tourist-intensive zones. These buoys are equipped with different physical-biogeochemical sensors, data telemetry systems, and integration with satellite-based observations for real-time data transmission to land. The sensors onboard these buoys continuously measure 22 water quality parameters, including surface current (speed and direction), salinity, temperature, pH, dissolved oxygen, phycocyanin, phycoerythrin, Coloured Dissolved Organic Matter, chlorophyll-a, turbidity, dissolved methane, hydrocarbon (crude and refined), scattering, pCO2 (water and air), and inorganic macronutrients (nitrite, nitrate, ammonium, phosphate, silicate). This real-time data is transmitted to a central processing facility at INCOIS, and after necessary quality control, the data is disseminated through the INCOIS website. Preliminary results from the WQNS show promising outcomes, including the short-term changes in the water column oxic and hypoxic regimes within a day in coastal waters off Kochi during the monsoon period, whereas effluxing of high levels of CO2 into the atmosphere associated with the mixing of water, driven by local depression in the coastal waters off Visakhapatnam. The system has demonstrated its ability to detect changes in the water column properties due to episodic events and mesoscale processes. Additionally, it offers valuable data for research, management, and policy development related to coastal water quality.
•First-of-its-kind water quality nowcasting system for Indian coastal waters.•Combines real-time data from moored buoy-based observatories and satellites.•Provides continuous measurements of 22 key water quality parameters.•Potential contributor to India's “Clean Ocean” initiative addressing the Ocean Decade challenge.
We examined the impact of maternal use of different household cooking fuels in India on low birth weight (LBW<2500g), and neonatal mortality (death within 28 days of birth). Using cross-sectional ...data from India's National Family Health Survey (NFHS-3), we separately analyzed the prevalence of these two outcomes in households utilizing three types of high-pollution fuels for cooking – biomass, coal, and kerosene – using low-pollution fuels (gas and biogas) as the comparison “control” group. Taking socioeconomic and child-specific factors into account, we employed logistic regression to examine the impact of fuel use on fetal and infant health. The results indicate that household use of high-pollution fuels is significantly associated with increased odds of LBW and neonatal death. Compared to households using cleaner fuels (in which the mean birth weight is 2901g), the primary use of coal, kerosene, and biomass fuels is associated with significant decreases in mean birth weight (of −110g for coal, −107g for kerosene, and −78g for biomass). Kerosene and biomass fuel use are also associated with increased risk of LBW (p<0.05). Results suggest that increased risk of neonatal death is strongly associated with household use of coal (OR 18.54; 95% CI: 6.31–54.45), and perhaps with kerosene (OR 2.30; 95% CI: 0.95–5.55). Biomass is associated with increased risk of neonatal death among infants born to women with no more than primary education (OR 7.56; 95% CI: 2.40–23.80). These results are consistent with a growing literature showing health impacts of household air pollution from these fuels.
Hypoxia can occur after repair of transposition of great arteries. The most common cause of right to left shunt after arterial switch surgery is related to increased right ventricular pressures and ...persistent neonatal pulmonary arterial hypertension. We report a case of TGA repair causing right to left shunt with normal right ventricular pressures. Persistence of Eustachian valve with patent foramen ovale (PFO) is the unusual cause of hypoxia and desaturation. The patient was successfully managed by excision of Eustachian valve and closure of PFO.
The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) collects and organizes biological information about the chromosomal features and gene products of the budding yeast Saccharomyces ...cerevisiae. Although published data from traditional experimental methods are the primary sources of evidence supporting Gene Ontology (GO) annotations for a gene product, high-throughput experiments and computational predictions can also provide valuable insights in the absence of an extensive body of literature. Therefore, GO annotations available at SGD now include high-throughput data as well as computational predictions provided by the GO Annotation Project (GOA UniProt; http://www.ebi.ac.uk/GOA/). Because the annotation method used to assign GO annotations varies by data source, GO resources at SGD have been modified to distinguish data sources and annotation methods. In addition to providing information for genes that have not been experimentally characterized, GO annotations from independent sources can be compared to those made by SGD to help keep the literature-based GO annotations current.
End stage heart failure is a lethal disease with a dismal 5 year survival. Heart transplantation has proven to be a highly effective modality of treatment in appropriately selected group of such ...patients. This is a retrospective analysis of medium term outcomes of heart transplantation in the setting of a private health facility in India. The objective of this study was two fold.11To document the short term and medium term survival of patients undergoing a heart transplant procedure2To identify the risk factors for unfavorable outcomes with subgroup analysis.
The outcome of 257 heart transplants done at a single centre from October 2012 to October 2019 was analyzed. Patients with combined Heart and lung transplants and those whose complete medical records were unavailable were excluded from the study. Survival was tracked at 60 days, 90 days, one year and beyond for a maximum of 7 years. Preoperative patient risk profiles were characterized on the basis of INTERMACS category.
There were 176 male and 81 female patients. The age range was from 8 months to 78 years with a mean of 32.9 years. Survival at 2 months was 87%, at 90 days was 83%, at one year was 81%, 2 years was 75%, at 3 years was 72% and at 5 years and beyond was 62% for the whole series. Strong predictors of 90 day mortality included INTERMACS category (odd's ratio 0.289, p = 0.000) and creatinine more than 1.5 mg/dl (odd's ratio 2.48, p = 0.056). Recipient pulmonary vascular resistance and donor organ ischemic times were not found to be statistically significant factors affecting outcome. Medium term survival was influenced by INTERMACS category (Hazard ratio > 3 for INTERMACS category 1 compared to INTERMACS 4 or 5, p < 0.0001) and creatinine > 1.5 mg/dl (Hazard ratio 2.15, p = 0.003). This effect of creatinine was related to the age of the recipient. Hazard ratio 1.4, p = 0.524 if age <30 and Hazard ratio 4.78, p = 0.006, if age was >50.
Satisfactory medium term outcome is possible after heart transplantation even in resource constrained environment of a developing country.
Reactive oxygen species (ROS) like superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism. Overproduction or insufficient removal of ROS ...results in significant damage to cell structure and functions. Antioxidants applied directly and at relatively high concentrations to cellular systems are effective in protection against the damaging actions of ROS. Microorganisms including Gram-positive and negative bacteria, fungi, protozoa, algae, etc., can be disease causing microorganism. Antimicrobial agents have the capability to inhibitor destroy the microorganisms. The problems arising from the use of antioxidant and antimicrobial agents include poor solubility, instability during storage, low bioavailability, and difficulty to reach target organs with sufficient doses. Liposomal antimicrobial agent and liposomal antioxidants enhance the solubility, bioavailability, and stability of antimicrobial agent and antioxidants.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Mutations in
, the gene encoding pyrin in humans, are associated with the autoinflammatory disorder familial Mediterranean fever. Pyrin is an innate sensor that assembles into an inflammasome complex ...in response to Rho-modifying toxins, including
toxins A and B. Cell death pathways have been shown to intersect with and modulate inflammasome activation, thereby affecting host defense. Using bone marrow-derived macrophages and a murine model of peritonitis, we show in this study that receptor-interacting protein kinase (RIPK) 3 impacts pyrin inflammasome activation independent of its role in necroptosis. RIPK3 was instead required for transcriptional upregulation of
through negative control of the mechanistic target of rapamycin (mTOR) pathway and independent of alterations in MAPK and NF-κB signaling. RIPK3 did not affect pyrin dephosphorylation associated with inflammasome activation. We further demonstrate that inhibition of mTOR was sufficient to promote
expression and pyrin inflammasome activation, highlighting the cross-talk between the mTOR pathway and regulation of the pyrin inflammasome. Our study reveals a novel interaction between molecules involved in cell death and the mTOR pathway to regulate the pyrin inflammasome, which can be harnessed for therapeutic interventions.
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