Coenzyme Q10 and vitamin D interventions could ameliorate COVID-19 related cellular bioenergetic dysfunction and cytokine storms

The immune response to SARS-CoV-2 varies from asymptomatic or mild symptoms of high temperature, muscle aches and coughs lasting 7 to 14 days to lower respiratory tract infections leading to pneumonia and serious respiratory distress as well as long COVID-19. Complications occur due to an abnormal immune response which involves upregulation of multiple cytokines leading to sustained inflammation which results in the spread of infection to vital organs. The double vaccine roll out has been rapid however vaccine mediated antibodies are not 100% effective against future coronavirus variants which may become increasingly more resistant and easily transmissible to overcome host immunity. Invariably supportive therapies will be needed. Research has shown that coenzyme Q10 and vitamin D deficiencies can have detrimental effects on immune cell defence, function and cytokine secretion promoting inflammation and sepsis especially against microbes. Early interventions including supplementation of these factors could mitigate cellular dysfunction especially in relation to mitochondria bioenergetics and help maintain cell immunity. This is particularly important as chronically ill COVID-19 patients seem to display abnormal immune cell phenotypes in infected organs indicating this could contribute to disease progression. The immune response and proposed roles of Vitamin D and Coenzyme Q10 in COVID-19 are discussed

Macrophage derived platelet activating factor implicated in the resolution phase of gouty inflammation

Human blood derived in vitro differentiated monocytes or macrophages are a population of cells which have been investigated over the years to determine the role these cells play in the resolution phase of gout. Macrophages are able to phagocytose monosodium urate monohydrate (MSU) crystals without releasing inflammatory factors. This study analysed macrophage platelet activating factor secretion and its possible role in the pathway of gout resolution. Analysis of sunatants from in vitro differentiated macrophages stimulated with MSU crystals revealed the secretion of platelet activating factor (PAF) mean ± SEM; ng/mL per 106 cells. This secretion was absent in immature monocytes treated similarly. When these monocytes were pretreated with recombinant human PAF-acetylhydrolase (rhuPAF-AH) and MSU crystals resulted in TNFα suppression. Addition of WEB2086, a platelet activating factor (PAF) antagonist, to differentiated macrophages with MSU crystals unmasked TNFα secretion mean ± SEM; ng/mL per 106 cells. This study identifies a role for PAF and the PAF receptor antagonist in the pathway by which macrophages ingest MSU crystals and resolve the concomitant inflammation

Rapunzel Syndrome: a rare cause of acute small bowel obstruction

The Rapunzel syndrome is a very rare condition where trichobezoar hasextended up to the small bowel. Here we are reporting a rare case of Rapunzel syndrome in an adolescent girl with history of trichophagia who presented with small bowel obstruction. Patient underwent exploratory laparotomy and bezoar was removed through gastrotomy. Post-operative course was unremarkable.KEY WORDS: Rapunzel syndrome; Trichobezoars; Psychotherapy; Gastrotom

Urate crystals induce macrophage PAF‑AH secretion which is differentially regulated by TGFβ1 and hydrocortisone

The aim of the present study was to establish the role of platelet‑activating factor acetyl hydrolase (PAF‑AH) in the resolution phase of gout using an established in vitro mononuclear cell model. The effects of signalling pathway inhibitors on PAF‑AH secretion, as well as the effects of the common treatments hydrocortisone and colchicine, an antibody against the anti‑inflammatory cytokine transforming growth factor β1 (TGFβ1), and the transcriptional inhibitor actinomycin D, were also investigated. The effect of recombinant PAF‑AH on cytokine secretion by these cells was also determined. Human peripheral blood‑derived monocytes were isolated and differentiated into macrophages. Monocytes and macrophages were stimulated with monosodium monohydrate urate (MSU) crystals or lipopolysaccharide in the presence or absence of AEG3482 [a c‑Jun N‑terminal kinase (JNK) inhibitor], MG132 (a proteasome inhibitor), hydrocortisone or colchicine. Cultures were then analysed for PAF‑AH secretion using ELISA. A 6‑fold upregulation of PAF‑AH secretion was observed following macrophage exposure to MSU crystals for 24 h (29.3±6 vs. 5.4±0.3 ng/ml unstimulated; P<0.05). Following 72 h, PAF‑AH levels decreased significantly (11.1±1.8; P<0.01). Secretion was further enhanced following pre‑treatment with the JNK protein kinase inhibitor AEG3482 prior to MSU crystal stimulation (P<0.05) and was abrogated when cells were preincubated with actinomycin D or the proteasome inhibitor MG132 (50, 100 and 200 µM). The addition of recombinant PAF‑AH (2.5‑10 ng/ml) to MSU crystal‑stimulated immature monocyte cultures significantly decreased pro‑inflammatory interleukin (IL)‑1β (unstimulated 687±124 vs. stimulated 113±30 pg/ml) and IL‑6 secretion (unstimulated 590±50 vs. stimulated 182±19 pg/ml). Treatment of MSU crystal‑stimulated macrophages with hydrocortisone (2 µM) also significantly decreased PAF‑AH release (P<0.05). Neutralising anti‑TGFβ1 addition decreased PAF‑AH dose‑dependently with the highest inhibition observed at 1 µg/ml (P<0.05). The results implicated that PAF‑AH may have an anti‑inflammatory role in the resolution phase of gout

Macrophage derived platelet activating factor implicated in the resolution phase of gouty inflammation

Human blood derived in vitro differentiated monocytes or macrophages are a population of cells which have been investigated over the years to determine the role these cells play in the resolution phase of gout. Macrophages are able to phagocytose monosodium urate monohydrate (MSU) crystals without releasing inflammatory factors. This study analysed macrophage platelet activating factor secretion and its possible role in the pathway of gout resolution. Analysis of sunatants from in vitro differentiated macrophages stimulated with MSU crystals revealed the secretion of platelet activating factor (PAF) mean ± SEM; ng/mL per 106 cells. This secretion was absent in immature monocytes treated similarly. When these monocytes were pretreated with recombinant human PAF-acetylhydrolase (rhuPAF-AH) and MSU crystals resulted in TNFα suppression. Addition of WEB2086, a platelet activating factor (PAF) antagonist, to differentiated macrophages with MSU crystals unmasked TNFα secretion mean ± SEM; ng/mL per 106 cells. This study identifies a role for PAF and the PAF receptor antagonist in the pathway by which macrophages ingest MSU crystals and resolve the concomitant inflammation

Decentralized Detection With Correlated Gaussian Observations: Parallel And Tandem Networks With Two Sensors

Signal detection in cognitive radio involves the determination of presence or absence of a primary user signal so that the secondary user may opportunistically gain access when the spectrum is unoccupied. In decentralized sensing scheme, two or more secondary users sense the spectrum, process individual observation and then pass the quantized data to a fusion center where a decision with regard to which hypothesis being true, that is, a signal being present or absent, is made. In the second part of the thesis, we study Bayes error performance of two-sensor tandem network designed to detect the presence or absence of deterministic signals in correlated Gaussian noise. Hence, the correlation coefficient remains identical under both hypotheses. Specifically, we address the question of which sensor ought to serve as the fusion center for optimal detection performance. In the process of this query, we draw some inference parallel to the “Good, Bad and Ugly’’ signal regions formulated originally for the two-sensor one-bit-per-sensor parallel fusion network by Willet,et.al. In the tandem “Good” region, numerical results conclusively show that the strategy of placing better sensor, i.e the sensor with higher signal to noise ratio, serving as the fusion center is preferred for better detection performance. In the first part of thesis, we study the error performance in a parallel network consisting of two sensors. In the parallel configuration, each sensor quantizes it\u27s own observation into a single-bit and transmits them to the fusion center. At the fusion center, the performance of AND and OR rules are examined by assuming the observations at the two sensors are jointly Gaussian, with specific means, variances and correlation coefficient, under hypothesis H1, whereas the observations under H0 are still Gaussian with specific means and variances but are statistically independent. The optimum quantizers at each sensor are found by minimizing the probability of error at the fusion center. We use a genetic algorithm (GA) to find a sub-optimal solution. It was observed that, when prior probabilities of hypotheses are equal, AND performs at least as well as OR

An access control and authorization model with Open stack cloud for Smart Grid

In compare to Authentication for identification and relationship of an identity of a user with its task and process within the system, authorization in access control is much anxious about confirming that user and its task in the form of system process, access to the assets of any particular domain is only approved when proven obedient to the identified policies. Access control and authorization is always an area of interest for researchers for enhancing security of critical assets from many decades. Our prime focus and interest is in the field of access control model based on Attribute base access control (ABAC) and with this paper we tried to integrate ABAC with openstack cloud for achieving finer level of granularity in access policies for domain like smart grid. Technical advancement of current era demands that critical infrastructure like traditional electrical grid open ups to the modern information and communication technology to get the benefit in terms of efficiency, scalability, accessibility and transparency for better adaptability in real world. Incorporation of ICT with electric grid makes it possible to do greater level of bi-directional interaction among stake holders like customer, generation units, distribution units and administrations and these leads international organization to contribute for standardization of smart grid concepts and technology so that the realization of smart grid becomes reality. Smart grid is a distributed system of very large scale by its nature and needs to integrate available legacy systems with its own security requirements. Cloud computing proven to be most efficient approach for said requirements and we have identified openstack as our cloud platform. We have integrated ABAC approach with default RBAC approach of openstack and provide a frame work that supports and integrate multiple access control polices in making authorization decisions. Smart grid domain in considered as case study which requires support of multiple access policies (RBAC, ABAC or DAC etc) with our model for access control and authorization