In Dec 2019, a novel pathogen emerged, and within weeks, led to the emergence of the biggest global health crises seen to date. The virus called ‘SARS-CoV-2’, causes coronavirus disease which was ...named ‘COVID-19’ by the World Health Organization (WHO). The speedy spread of this infection globally became a source of public worry and several unknowns regarding this new pathogen created a state of panic. Mass media became the major source of information about the novel coronavirus. Much like the previous pandemics of SARS (2003), H1N1 (2009), and MERS (2012), the media significantly contributed to the COVID-19 infodemics. In this review, we analyze the role of mass media and public health communications from December 31, 2019 to July 15, 2020, and make scientific inferences. The COVID-19 pandemic highlights multiple social, cultural, and economic issues arising from the media’s arguable role. The racial prejudices linked to the origin of the virus prevented collaborations among scientists to find a solution. Media coverage of coronavirus news during geographical lockdowns, extended quarantines, and financial and social hardships induced fear and caused psychological stress. Domestic and elderly abuse upsurged. The unscientific cures and unverified medicines endorsed by the politicians and fake doctors proved harmful. The media played a worldwide role in coronavirus disease tracking and updates through live updates dashboard. The media allowed for timely interventions by the Center For Disease Control And Prevention (CDC) and the World Health Organization (WHO), enabling a rapid and widespread reach of public health communications. We saw an upward trend for the promotion of health and hygiene practices worldwide by adaption of safe health practices such as increased hand washing, use of face coverings, and social distancing. Media reinforced illness-preventing guidelines daily, and people were encouraged to use telehealth to meet their healthcare needs. Mass media has an imperative role in today’s world and it can provide a unified platform for all public health communications, comprehensive healthcare education guidelines, and robust social distancing strategies while still maintaining social connections. It can enable equal access to healthcare, end discrimination, and social stigmatization. The role of media and public health communications must be understood and explored further as they will be an essential tool for combating COVID-19 and future outbreaks.
Physician burnout is a universal dilemma that is seen in healthcare professionals, particularly physicians, and is characterized by emotional exhaustion, depersonalization, and a feeling of low ...personal accomplishment. In this review, we discuss the contributing factors leading to physician burnout and its consequences for the physician's health, patient outcomes, and the healthcare system. Physicians face daily challenges in providing care to their patients, and burnout may be from increased stress levels in overworked physicians. Additionally, the healthcare system mandates physicians to keep a meticulous record of their physician-patient encounters along with clerical responsibilities. Physicians are not well-trained in managing clerical duties, and this might shift their focus from solely caring for their patients. This can be addressed by the systematic application of evidence-based interventions, including but not limited to group interventions, mindfulness training, assertiveness training, facilitated discussion groups, and promoting a healthy work environment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hydantoins comprise an important class of compounds which have long attracted attention due to their remarkable biological and pharmacological properties including antitumor and antiviral activities. ...As a continuation of our studies on hydantoins derivatives we report the successful synthesis of hydantoins derivatives. These synthesized compounds were evaluated for their cytotoxic activity against Vero cells
L20B (African green monkey kidney cell line) and Human Rhabdomyosarcoma
RD cell lines using methotrexate drug (MTX) as a reference drug in cytotoxic activity studies. The percentage of the cell line viability was carried out by using Trypan blue dye exclusion method. The tested compounds showed equipotent cytotoxicity effect against Vero cells (L20B) and a moderate effect against Human Rhabdomyosarcoma (RD) cell lines. These results exhibited better activity for 4a-b compounds than the reference drug methotrexate (MTX). Molecular docking studies indicated that the synthesized compounds are suitable inhibitors of humain dihydrofolate reductase (DHFR) enzyme, which may explain the high antiproliferative activity.
Communicated by Ramaswamy H. Sarma
Summary
We have previously demonstrated that the activation of the spleen tyrosine kinase (Syk)/inhibitory‐κB (IκB)‐α/nuclear factor‐κB (NF‐κB) p65 signalling pathway contributes to hypotension and ...inflammatory response in a rat models of zymosan (ZYM)‐induced non‐septic shock. The purpose of this study was to further examine the possible mechanism underlying the effect of inhibition of Syk by BAY61‐3606 via NF‐κB activity at the level of nuclear translocation regarding the production of vasodilator and proinflammatory mediators in lipopolysaccharide (LPS) (septic)‐ and ZYM (non‐septic)‐induced shock. Administration of LPS (10 mg/kg, ip) or ZYM (500 mg/kg, ip) to male Wistar rats decreased mean arterial pressure and increased heart rate that was associated with an increase in the activities of cyclooxygenase and nitric oxide synthase, tumour necrosis factor‐α, and interleukin‐8 levels, and NF‐κB activation and nuclear translocation in sera and/or cardiovascular and renal tissues. BAY61‐3606 (3 mg/kg, ip), the selective Syk inhibitor, given 1 hour after LPS‐ or ZYM injection reversed all the above‐mentioned effects. These results suggest that Syk contributes to the LPS‐ or ZYM‐induced hypotension and inflammation associated with transactivation of NF‐κB in septic and non‐septic shock.
Neuroinflammation plays a critical role during sepsis triggered by microglial activation. Mammalian target of rapamycin (mTOR) has gained attraction in neuroinflammation, however, the mechanism ...remains unclear. Our goal was to assess the effects of mTOR inhibition by rapamycin on inflammation, microglial activation, oxidative stress, and apoptosis associated with the changes in the inhibitor-κB (IκB)-α/nuclear factor-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α) pathway activity following a systemic challenge with lipopolysaccharide (LPS). Rats received saline (10 mL/kg), LPS (10 mg/kg), and (or) rapamycin (1 mg/kg) intraperitoneally. Inhibition of mTOR by rapamycin blocked phosphorylated form of ribosomal protein S6, NF-κB p65 activity by increasing degradation of IκB-α in parallel with HIF-1α expression increased by LPS in the kidney, heart, lung, and brain tissues. Rapamycin attenuated the increment in the expression of tumor necrosis factor-α and interleukin-1β, the inducible nitric oxide synthase, gp91
phox
, and p47
phox
in addition to nitrite levels elicited by LPS in tissues or sera. Concomitantly, rapamycin treatment reduced microglial activation, brain expression of caspase-3, and Bcl-2-associated X protein while it increased expression of B cell lymphoma 2 induced by LPS. Overall, this study supports the hypothesis that mTOR contributes to the detrimental effect of LPS-induced systemic inflammatory response associated with neuroinflammation via IκB-α/NF-κB/HIF-1α signaling pathway.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Shock is classified based on the: Hypovolemic, cardiogenic, obstructive, and vasodilatory.•Vasodilatory (vasoplegic, vasogenic, or distributive) shock may be inflammatory, neurogenic, or ...anaphylactic.•Septic shock is the most common form of vasodilatory shock leading to multiple organ dysfunction syndrome.•Eicosanoids derived from CYP pathway of AA have been implicated in the pathogenesis of inflammatory shock states.•Targeting eicosanoids derived from CYP pathway of AA may provide a novel therapeutic approach to inflammatory shock.
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock, the most common form of vasodilatory shock, is a subset of sepsis in which circulatory and cellular/metabolic abnormalities are severe enough to increase mortality. Inflammatory shock constitutes the hallmark of sepsis, but also a final common pathway of any form of severe long-term tissue hypoperfusion. The pathogenesis of inflammatory shock seems to be due to circulating substances released by pathogens (e.g., bacterial endotoxins) and host immuno-inflammatory responses (e.g., changes in the production of histamine, bradykinin, serotonin, nitric oxide NO, reactive nitrogen and oxygen species, and arachidonic acid AA-derived eicosanoids mainly through NO synthase, cyclooxygenase, and cytochrome P450 CYP pathways, and proinflammatory cytokine formation). Therefore, refractory hypotension to vasoconstrictors with end-organ hypoperfusion is a life threatening feature of inflammatory shock. This review summarizes the current knowledge regarding the role of eicosanoids derived from CYP pathway of AA in animal models of inflammatory shock syndromes with an emphasis on septic shock in addition to potential therapeutic strategies targeting specific CYP isoforms responsible for proinflammatory/anti-inflammatory mediator production.
Purpose: We have previously demonstrated that activation of the mammalian target of rapamycin (mTOR)/inhibitory-κB-α/nuclear factor-κB p65 signaling pathway mediates organ injuries through increased ...oxidative/nitrosative stress and inflammatory response in rat models of hind limb ischemia/reperfusion (HL I/R). Following up our previous findings regarding I/R injury through mammalian target of rapamycin (mTOR), we aimed to focus on the possible interaction between mammalian target of rapamycin (mTOR and mitogen-activated protein kinase kinase (MEK)1/extracellular signal-regulated kinase (ERK) 1/2 pathway in hind limb ischemia/reperfusion (HL I/R) resulting in target and remote organ injuries in the present study.
Materials and Methods: Male Wistar rats were divided into four groups. HL I/R was induced by occluding with tourniquets of both hind limbs. Following 4 h, the tourniquets were removed following reperfusion for 4 h. After 4 h of reperfusion blood, kidney, and gastrocnemius muscle were collected.
Results: HL I/R caused an increase in phosphorylation and/or expression of rpS6, MEK1, ERK1/2, tumor necrosis factor-α, inducible nitric oxide synthase, gp91phox, p22phox, and nitrotyrosine as well as nitrite levels in gastrocnemius muscle, kidney, and/or serum. Additionally, nicotinamide adenine dinucleotide phosphate oxidase and myeloperoxidase levels were increased in the tissues of rats subjected to HL I/R. Rapamycin, the selective inhibitor of mTOR, abolished all the effects mentioned above caused by HL I/R in the rat’s muscle and kidney.
Conclusion: These data suggest that activation of the MEK1/ERK1/2 pathway contributes to mTOR-mediated HL I/R-induced target and remote organ injury.
Amaç: Arka bacak iskemisi/reperfüzyonun (İ/R) sıçan modellerinde, rapamisinin memelilerdeki hedefi (mTOR)/inhibitör-κB-α/nükleer faktör-κB p65 sinyal ileti yolu etkinliğinin, artan oksidatif/nitrozatif stres ve inflamatuvar yanıt yoluyla organ zedelenmelerine aracılık ettiğini daha önce göstermiştik. mTOR’un İ/R zedelenmesine katkıda bulunduğuna ilişkin önceki bulgularımızı referans alarak, bu çalışmada arka bacak İ/R'ye bağlı hedef ve uzak organ zedelenmelerinde mTOR ile MEK1/ERK1/2 yolu arasındaki olası etkileşime odaklanmayı amaçladık.
Gereç ve Yöntem: Erkek Wistar sıçanlar dört gruba ayrıldı. Arka bacak İ/R, her iki arka ekstremitelerine turnikeler uygulanarak iskemi oluşturuldu. İskemiden 4 saat sonra turnikeler açılarak 4 saat reperfüzyon uygulandı. 4 saatlik reperfüzyondan sonra kan, böbrek ve gastroknemius kası izole edildi.
Bulgular: Arka bacak İ/R uygulaması gastroknemius kasında, böbrekte ve/veya serumda rpS6, MEK1, ERK1/2, tümör nekroz faktörü-α, indüklenebilir nitrik oksit sentaz, gp91phox, p22phox ve nitrotirozinin fosforilasyonu ve/veya ekspresyonu ile birlikte nitrit düzeylerinde artışa neden oldu. Ayrıca, İ/R uygulanan sıçanların dokularında nikotinamit adenin dinükleotit fosfat oksidaz ve miyeloperoksidaz seviyeleri arttı. mTOR'un seçici inhibitörü olan rapamisin, sıçanlarda kas ve böbrek dokusunda İ/R'nin neden olduğu yukarıda bahsedilen tüm etkileri ortadan kaldırdı.
Sonuç: Bu veriler, MEK1/ERK1/2 yolunun etkinliğinin, mTOR’un aracılık ettiği arka bacak İ/R’nin neden olduğu hedef ve uzak organ zedelenmesine katkıda bulunduğunu göstermektedir.
The present study aimed to explore the contribution of mammalian target of rapamycin (mTOR) in deoxycorticosterone acetate (DOCA) salt-induced hypertension and related pathophysiological changes in ...cardiovascular and renal tissues. DOCA salt loading resulted in an increase in systolic blood pressure, diastolic blood pressure, and mean blood pressure along with the activity of ribosomal protein S6, the effector protein of mTOR. Treatment with rapamycin, the selective inhibitor of mTOR, initiated at the fourth week of DOCA- salt administration normalized the systolic blood pressure and attenuated ribosomal protein S6 activity in the heart, aorta, and kidney. Cardiac and vascular hypertrophy, oxidative stress, and infiltration of macrophages (CD68+), the marker of inflammation, were also reduced in rapamycin-treated, DOCA-salt, hypertensive rats. In addition, renal hypertrophy and dysfunction were also reduced with rapamycin-treated hypertensive rats. Moreover, these pathophysiological changes in DOCA-salt hypertensive rats were associated with increased NADPH oxidase (NOX) activity, gp91phox (formerly NOX2) expression, ERK1/2, and p38 MAPK activities in the heart, aorta, and kidney were minimized by rapamycin. These data indicate that mTOR plays an important role in regulating blood pressure and the development of cardiovascular and renal pathophysiological changes, most likely due to increased NOX expression/activity, ERK1/2, and p38 MAPK activity with macrophages infiltration in the heart, kidney, and aorta. Pharmacological inhibition of mTOR and related signaling pathways could serve as a novel target for the treatment of hypertension.
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