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Background: Aging and binge alcohol abuse are both known as independent risk factors for both atrial and ventricular arrhythmias. With the COVID-19 pandemic, increased social isolation has significantly increased alcohol consumption worldwide. Older adults are a high-risk drinking group and alcohol significantly enhances the risk of arrhythmia onset. Yet, how alcohol (a secondary stressor) drives spontaneous atrial and ventricular arrhythmia onset in the aged heart (a primary stressor) remains unclear. Objective(s): We recently reported the stress-response kinase c-jun N-terminal kinase 2 (JNK2) underlies alcohol-enhanced atrial arrhythmia vulnerability (pacing-induced) in healthy young hearts. Here, we reveal a critical role of JNK2 in alcohol-driven arrhythmia onset in the aged heart in vivo. Method(s): Ambulatory ECGs were recorded using wireless telemeters in binge alcohol-exposed aged (24 months) and young mice (2 months). Spontaneous premature atrial and ventricular contractions (PACs, PVCs), atrial and ventricular tachycardia (AT, VT) were quantified as previously described. The role of JNK2 in triggered arrhythmic activities was assessed using a well-evaluated JNK2-specific inhibitor and our unique cardiac-specific MKK7D and MKK7D-JNK2dn mouse models with tamoxifen inducible overexpression of constitutively active MKK7 (a JNK upstream activator) or co-expression of MKK7D and inactive dominant negative JNK2 (JNK2dn). Result(s): We found that binge alcohol exposure in aged mice (n=14) led to spontaneous PACs/PVCs (75% of the mice), and AT/VT episodes (50%) along with a 21% mortality rate. However, alcohol-exposed young (n=5) and non-alcohol-exposed aged mice (n=11) were absent of any spontaneous arrhythmic activities or premature death. Intriguingly, JNK2-specific inhibition in vivo abolished those alcohol-associated triggered activities and mortality in aged mice. The causative role of JNK2 in triggered arrhythmias and premature death was further supported by the high frequency of spontaneous PACs/PVCs and nonsustained AT/VT episodes along with a 50% mortality rate in MKK7D mice (n=10), which was strikingly alleviated in MKK7D-JNK2dn mice (n=5) with cardiac-specific JNK2 competitive inhibition. Conclusion(s): Our findings are the first to reveal that stress kinase JNK2 underlies binge alcohol-evoked atrial and ventricular arrhythmia initiation in aged mice. Modulating JNK2 could be a novel therapeutic strategy to treat and/or prevent binge drinking-evoked cardiac arrhythmias.Copyright © 2023
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Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg.kg-1), and positive control sildenafil group (100 mg.kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% +/- 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF- kappaB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF- kappaB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-kappaB and signal transducer and activator of transcription 3 (STAT3) by DYY.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.
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Intro: Several rodents, including mice and the brown rat, are synanthropic animals usually found in rural and urban environments in contact with other animals and humans. Rodents are natural reservoirs of infectious agents and could harbour a plethora of zoonotic pathogens of public health importance. Taking advantage of a parallel study on presence and distribution of Hantaviruses, we aimed to investigate the occurrence in mice of other viruses with zoonotic or economic impact. Method(s): From May to July 2022, 41 mice (Mus domesticus) were captured and killed by using baited snap traps in 13 selected cattle, goat and poultry farms located in the Piedmont region. Gut and lung samples were homogenised and tested by PCR methods for pan-Coronavirus (CoV) and SARS-CoV-2, pan-Pestivirus, Mammalian orthoreoviruses, Canine Distemper virus (CDV), Flaviviruses, Influenza A (IAV) and D (IDV) viruses. Finding(s): All captured animals did not present at necropsy lesions related to infectious diseases. Virological investigations detected the presence of CoV in six mice. By sequencing Rodent CoVs was identified in two samples (four more pending). Mammalian orthoreovirus was detected in nine animals and typing and characterization are in progress. One mouse, captured in a bovine farm, tested slightly positive for IDV and confirmation of positivity is in progress by complete sequencing with NGS approach. All samples were negative for Flaviviruses, IAV, CDV, pan-Pestivirus and SARS-CoV-2. Conclusion(s): Rodents are well adapted to a wide range of habitats, including peri-urban and rural environments, where they benefit from human activities. These results, although preliminary, underline the importance of enhancing surveillance in rodents in anthropized areas to better assess the presence of zoonotic agents and the potential risk of transmission.Copyright © 2023
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The occurrence of Cryptosporidium species infection and its risk factors in neonatal goats is less explored. Also it is due to the fact that diseases like colibacillosis and neonatal viral enteritis complex caused by Group A rotaviruses and Bovine corona viruses can co-exist with Cryptosporidium and can lead to mixed infections and the latter is often overlooked. Therefore, in the current research we explored the cryptosporidial occurrence in neonatal goats of Mathura district of Uttar Pradesh, India. In this study, a total of 644 faecal samples were collected from neonatal goats at different villages and certain organized farms of Mathura district age-wise, season-wise and breed-wise, and were examined for Cryptosporidium based on modified Ziehl-Neelsen technique, conventional 18SSU rRNA nested PCR assay. The overall prevalence of Cryptosporidium infection in goats based on microscopy was 36.80% (237/644;p value <0.0001) and 18SSU rRNA nested PCR 52.95% (341/644;p value <0.0001) respectively. Cryptosporidium species typing was also done using 18SSU rRNA nested PCR-RFLP product using enzymes Mbo-II, Ssp-I and Vsp-I, which revealed species including C. parvum C. bovis, C. ryanae, C. hominis and C. andersoni. Also the infection was clinically associated based on age, gender and seasons to identify the causal relationships that precipitate the cryptosporidial infection in goat kids. Since mZN microscopy based screening requires expertise and may sometimes be confuse with other weak acid fast bodies and also due to low sensitivity, combination of diagnostic tests are used in this study to identify the best test combination that yields best statistical fit in terms of kappa-agreement and McNemar's test. Cryptosporidiosis is caused by an enteric protozoan parasite and the first report in sheep and goat was observed in early 1980s, with other important etiological agents for neonatal diarrhoea, mortality and morbidity in neonatal kids and lambs, responsible for economic losses.Copyright © 2023 Indian Veterinary Assocaition. All rights reserved.
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As important combat platforms, large warships have the characteristics of compact internal space and dense personnel. Once infectious diseases occur, they are very easy to spread. Therefore, it is very important to select suitable forecasting models for infectious diseases in this environment. This paper introduces 4 classic dynamics models of infectious diseases, summarizes various kinds of compartmental models and their key characteristics, and discusses several common practical simulation requirements, helping relevant health personnel to cope with the challenges in health and epidemic prevention such as the prevention and control of coronavirus disease 2019.Copyright © 2022, Second Military Medical University Press. All rights reserved.
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*Presenting author Emerging infectious diseases have been causing outbreaks in humans for centuries and most infectious diseases originate in animals. Re-emerging zoonotic pathogens are rapidly increasing in prevalence or geographic range and causing a significant and growing threat to global health. The present work provides an insight of zoonotic viruses risk at human-bat/rodent interfaces in Cambodia. We conducted studies to investigate the circulation of zoonotic viruses and the risk of exposure in human living at the interfaces with bats and rodents. Rodent's samples were collected in rural and urban areas of Cambodia. Organs were tested for Hantavirus, Orthohepevirus species C and Arenavirus. Bat's samples were collected in Steung Treng for Sarbecovirus and in Battambang and Kandal for Nipah virus detection. People working/living at the human-animal interfaces were screened for IgG antibodies. In rodents (750), hantavirus was detected in 3.3% rodents from urban areas only. Seoul orthohantavirus was the most predominant virus followed by Thottapalayam virus. HEV-C was detected only in rodents from urban settings (1.8%). Arenavirus was detected in both rural (6.8%) and urban (2.5%) areas. In humans (788), the seroprevalence of IgG antibodies against hantavirus, HEV-A and Arenavirus was 10.0%, 24% and 23.4% respectively. NiV was detected in flying fox's urines collected between 2013-2016 in Kandal (0.63%) and in Battambang (1.03%). Blood samples collected in both provinces were negative for NiV antibodies. SARS-CoV-2 related virus was detected in Rhinolphus shameli in Steung Treng in 2010, 2020 and 2021. Blood samples from people living at the vicinity of positive bats were positive for antibodies against CoV (7.7%), but no specific neutralizing SARS-CoV2 antibodies were detected. Our studies provided insight of the risk of zoonoses in Cambodia and highlighted the importance of zoonotic surveillance and further One Health effort to prevent, detect, and respond to future cross-species transmission.Copyright © 2023
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Intro: The burden of infectious diseases is influenced by the structure of the population at risk. Population ageing may have implications for the disease burden of future epidemics. Moreover, changing household structures induced by population ageing may influence the dynamics of disease transmission and burden of infections transmitted via close contact interactions. We aim to investigate the impact of demographic change on the disease transmission dynamics and future disease burden and illustrate this for COVID-19 and influenza-like illness (ILI). Method(s): We simulate the Belgian population between 2020 and 2050 using an individual-based model with census data. The simulated population structures were used as input for an infectious disease model that distinguishes between exposure to infection in the household versus exposure in the community at large. We mimicked outbreaks of COVID-19 and ILI of varying total final size. Finding(s): The simulated population ages between 2020 and 2050, which also affects household size and composition. As the proportion of elderly people in the population increases, the overall attack rate slightly decreases because older age groups have fewer contacts and are therefore less likely to incur and transmit infections. Despite the lower per-person attack rate, the estimated disease burden increases as morbidity and mortality increases with the age at infection. Conclusion(s): The demographic changes induced by population ageing have an impact on the burden of future outbreaks of COVID-19 and ILI in Belgium. The shifting age distribution implies that the elderly, a population group with increased morbidity and mortality in case of infection, make up an increasing proportion of the total population. Population ageing also leads to an increasing proportion of single-person households and collective households (e.g. nursing homes) in the population. Since the household attack rate varies by household size and composition, the living arrangements of the elderly population influences the disease burden of future epidemics to some extent.Copyright © 2023
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Background/Aims Traditionally viewed from the perspective of cartilage degeneration, osteoarthritis is increasingly seen as a disease of global joint dysfunction. Connective tissue extracellular matrix (ECM) is a crucial determinant of joint mechanobiology, providing cells with scaffolding, topographical cues, and a reservoir of soluble factors. While ECM dysregulation has been extensively studied in osteoarthritic cartilage, it remains poorly defined in other joint tissues. Here, we systematically review the composition, architecture, and remodelling of non-cartilage soft joint tissue ECM in human osteoarthritis and animal disease models. Methods A systematic search strategy was run through the MEDLINE, EMBASE and Scopus databases on 30 October 2020 and repeated on 1 October 2021. The search criteria included disease nomenclature, relevant tissues, as well as structural ECM components and architectural features. All papers were independently screened by two reviewers on the Covidence platform according to predefined eligibility criteria. Relevant clinical, demographic, and biological data were extracted from included studies, which were assessed for bias using the OHAT Risk of Bias Rating Tool for Human and Animal Studies. Results 148 of 8,156 identified studies met all eligibility criteria. 113 papers evaluated human osteoarthritis;of 35 animal studies, the most frequently used models involved surgical joint destabilisation in small mammals. ECM was best defined in menisci, ligaments, and synovium;fewer papers assessed skeletal muscles, tendons, and fat pads. Compared to the healthy joint, osteoarthritis is associated with qualitative and quantitative alterations in structural ECM components, most notably collagens and proteoglycans. In recent years, whole proteome sequencing has been employed to address these changes systematically. The mechanical properties of ECM change significantly in osteoarthritis in response to post-translational modifications, extensive calcification, and the marked loss of matrix organisation across the joint. Notably, some aspects of ECM remodelling in these tissues appear to precede discernible cartilage dysregulation. Similar ECM dysregulation is also observed in animal models, although intermodel variability in arthritogenic precipitant and the range of reported outcomes make comparisons difficult. Many studies are limited by significant bias, notably in the infrequent reporting of investigator blinding, and in the poor demographic matching of osteoarthritic and control patients. Encouragingly, the quality of methodology reporting and use of age-matched control populations have improved in recent years. Conclusion Current data provide compelling evidence of whole joint ECM changes in osteoarthritis and importantly suggest that these changes occur early in the disease process. How ECM dysfunction affects the behaviour of tissue-resident cells remains less well understood. Our work will support the design of disease-relevant biomaterials used to model osteoarthritis in vitro, helping to address this issue, by more accurately recreating the extracellular environment. Furthermore, the development of imaging modalities sensitive to connective tissue ECM changes warrants investigation from both diagnostic and prognostic perspectives.
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Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response and ultimate tissue scarring. Energy balance may be crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs Metformin (AMPk activator) and Baicalin (Cpt1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID19 patients that had been previously treated with Metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-beta-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two new indole derivatives IND6 and IND8 with AMPK activating capacity. Consistently, a reduced stay in the intensive care unit was observed in COVID-19 patients previously exposed to Metformin. Baicalin also reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19, while in vitro both drugs improved mitochondrial function and prevented TGF-beta-induced renal epithelial cell dedifferentiation. Our results support that strategies based on energy supply may prove useful in the prevention of COVID-19-induced lung and renal damage.Copyright © 2023
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Background/Aims Research has shown nurse-led gout clinics provide better outcomes compared to usual care. This District General Hospital set up a pilot nurse-led gout clinic in autumn 2019. This aimed to improve patients' understanding of their condition, achieve better control of serum uric acid levels (SUA), reduce flares and prevent Emergency Department attendances. Methods A modified clinic protocol, closely modelled on BSR guidance was agreed within the department. With consultant supervision, one nurse specialist provided a mix of in-person and telephone appointments. Targets were set aiming for SUA <360mumol/L for most patients and <300mumol/L for those with erosive change or tophi. All patients were offered prophylaxis. Patients required a rheumatologist's diagnosis of gout or crystal confirmation for enrolment. Exclusion criteria were significant renal or hepatic derangement. Within 3 months of the service starting SARS-CoV-2 impacted the operation of healthcare worldwide and led to the closure of routine outpatient clinics in Northern Ireland. A decision was made to switch the gout clinic to run entirely by telephone. Blood testing was facilitated through primary care and phlebotomy hubs. Results Over a 19-month period, 78 patients were treated and audited through this clinic: 69 men and 9 women. Average age was 57, mean SUA 509 mumol/L at referral and 322 mumol/L on discharge. 69 patients received allopurinol and 9 received febuxostat. No patients required uricosuric drugs. All patients were offered and agreed to take prophylaxis with a majority (85.8%) remaining on it for 3-6 months. Patients required a mean of 3.38 appointments prior to discharge from the clinic. The mean dose of urate lowering therapy on discharge was 315.9mg allopurinol and 93.3mg febuxostat. 95% experienced >=2 flares during their enrolment in the clinic with no patients requiring Emergency Department attendance due to gout flare. Conclusion The nurse-led gout clinic was well received by patients and was effective as a telephone service during the pandemic when so many services were stood down. The clinic was able to continue to provide education, deliver effective reductions in uric acid as well as reduce incidence of flares and Emergency Department attendances. Lower doses of urate lowering therapy than expected were needed to achieve target. A small number of patients were discharged prior to enrolment for initial non-engagement which may have been exacerbated by the lack of face-to-face appointments. Our COVID-19 model did struggle with those patients needing an interpreter. In-person initial appointments have since been restarted;however, a greater proportion of reviews will continue to be offered by telephone given the unexpected success of the model. This audit showed that a nurse-led gout clinic can run successfully, even during a pandemic with a significant reliance on telephone consultations.
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The COVID-19 pandemic is a global outbreak of coronavirus, an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One in five adults who have had COVID-19 in the past was still experiencing any one of the symptoms of long COVID like headache, brain fog, fatigue, and shortness of breath. Up to 30% of individuals with mild to severe infection show diverse neurological symptoms, including dementias. Hence, it is very much important to characterize the neurotropism and neurovirulence of the SARS-CoV-2 virus. This helps us understand the mechanisms involved in initiating inflammation in the brain, further leading to the development of earlyonset Alzheimer's disease and related dementias (ADRDs). In our brain gene expression analysis, we found that severe COVID-19 patients showed increased expression of innate immune response genes and genes that are implicated in AD pathogenesis. To study the infection-induced ADRDs, we used a mouse-adapted strain of the SARS-CoV-2 (MA10) virus to infect mice of different age groups (3, 6, and 20 Months). In this study, we found that aged mice showed evidence of viral neurotropism, prolonged viral infection, increased expression of tau aggregator FKBP51, interferoninducible gene Ifi204, and complement genes like C4 and C5AR1. Brain histopathology also showed the AD signature including tau-phosphorylation, tau-oligomerization, and alpha-synuclein expression in aged MA10-infected mice. The results from gene expression profiling of SARS-CoV-2 infected and AD brains and studies with MA10 aged mice show that COVID-19 infection increases the risk of AD in the aged population. Furthermore, this study helps us to understand the crucial molecular markers that are regulated during COVID infection that could act as major players in developing ADRDs. Future studies will be involved in understanding the molecular mechanisms of ADRD in response to COVID infection and developing novel therapies targeting AD.
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Background: Diarrhea was typical symptoms of the coronavirus disease 2019 (COVID-19). However, the underlying mechanism had not been fully understood. Aim(s): The study aimed to explore the mechanism of intestinal injury during COVID-19 in a coronavirus murine hepatitis virus strain 3 (MHV-3) induced acute mouse model. Method(s): MHV-3 induced acute infection Balb/cJ mice model was established. Intestine samples were collected at indicated time points as 0 h, 24 h, 48 h and 60 h post infection. The mRNA and protein expression of IL1b, TNFalpha, IL6, caspase 3 and cleaved caspase 3 were examined by real-time quantitative PCR (qPCR) and western blot respectively. The intestine injury and apoptosis were measured by HE staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Moreover, Z-DEVD-FMK (caspase 3 inhibitor) pre-treated MHV-3 infection mice model were established, in which the apoptosis of intestine was evaluated as well. Meanwhile, the murine intestinal cell MODE-K was infected by MHV-3 in vitro for evaluation of virus induced apoptosis. Result(s): Post MHV-3 infection, the histopathology of intestine tissue showed extraordinary injury with time dependence, as well as high level of TUNEL positivity. The mRNA levels of inflammatory cytokine IL1b, TNFalpha and IL6 were significantly increased. The protein expressions of caspase 3 and cleaved caspase 3 in the intestine was found significantly elevated from 24 to 48 h post MHV-3 infection. Z-DEVD-FMK pretreatment inhibited caspase 3 and cleaved caspase 3 expression and decreased TUNEL positivity. Meanwhile, alleviated gut injury and inhibited TNFalpha expression were observed. In vitro treated by MHV-3, intestinal cell line MODE-K showed nine-fold increase of apoptosis by comparison with saline treated ones. The expressions of apoptosis crucial protein caspase3 and cleaved caspase3 significantly elevated, as well as TNFalpha. Conclusion(s): Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis, which might shed light on the treatment of intestinal complications in COVID-19.
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The development of coronavirus infection outbreak into a pandemic, coupled with the lack of effective COVID-19 therapies, is a challenge for the entire pharmaceutical industry. This study aimed to assess the treatment and preventive efficacy of the amino acid-peptide complex (APC) in male Syrian hamsters infected with SARSCoV-2 (intranasal administration of 26 mul of the virus culture, titer of 4 x 104 TCD50/ml). In a modeled COVID-19 case, APC administered for treatment and preventive purposes reduced lung damage. Compared to the positive control group, test group had the lung weight factor 15.2% smaller (trend), which indicates a less pronounced edema. Microscopic examination revealed no alveolar edema, atypical hypertrophied forms of type II alveolocytes, pulmonary parenchyma fibrinization. The macrophage reaction intensified, which is probably a result of the APC-induced activation of regenerative processes in the lung tissues. Spleens of the animals that received APC for therapeutic and preventive purposes were less engorged and had fewer hemorrhages. The decrease of body weight of the test animals that received APC for treatment and prevention was insignificant (p < 0.05), which indicates a less severe course of COVID-19. Administered following a purely therapeutic protocol, APC proved ineffective against SARS-CoV-2 post-infection. Thus, APC-based drug used as a therapeutic and preventive agent reduces pulmonary edema and makes morphological signs of lung tissue damage less pronounced in male Syrian hamsters infected with SARS-CoV-2.Copyright © Extreme Medicine.All right reserved.
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Worldwide, up to 8.8 million excess deaths/year have been attributed to air pollution, mainly due to the exposure to fine particulate matter (PM). Traffic-related noise is an additional contributor to global mortality and morbidity. Both health risk factors substantially contribute to cardiovascular, metabolic and neuropsychiatric sequelae. Studies on the combined exposure are rare and urgently needed because of frequent co-occurrence of both risk factors in urban and industrial settings. To study the synergistic effects of PM and noise, we used an exposure system equipped with aerosol generator and loud-speakers, where C57BL/6 mice were acutely exposed for 3d to either ambient PM (NIST particles) and/or noise (aircraft landing and take-off events). The combination of both stressors caused endothelial dysfunction, increased blood pressure, oxidative stress and inflammation. An additive impairment of endothelial function was observed in isolated aortic rings and even more pronounced in cerebral and retinal arterioles. The increase in oxidative stress and inflammation markers together with RNA sequencing data indicate that noise particularly affects the brain and PM particularly affects the lungs. Noise also increased levels of circulating stress hormones adrenaline and noradrenaline, while PM increased levels of circulating cytokines CD68 and MCP-1. The combination of both stressors has additive adverse effects on the cardiovascular system that are based on PM-induced systemic inflammation and noise-triggered stress hormone signaling. We demonstrate an additive upregulation of ACE-2 in the lung, suggesting that there may be an increased vulnerability to COVID-19 infection. The data warrant further mechanistic studies to characterize the propagation of primary target tissue damage (lung, brain) to remote organs such as aorta and heart by combined noise and PM exposure.Copyright © 2023
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In the present COVID-19 situation, it poses a danger to a person's life because of organ infection and other health problems. It is mandatory to research work to find a better COVID-19 infection diagnosis method through scans and contact tracing through the AI method. In this, a novel AI structural model is intended to identify the infection features in the respective regions of human being availability, which makes the infection monitoring easier to identify an infected and non-infected human being from the population identified. The method used for monitoring the multiplicative nature of Coronavirus infections is through contact feature tracing and infection confirmation status and confirms the Coronavirus cases from scans and feature analysis to include real-time contact tracking from the same region and distant regions, providing an efficient method to track the infection spread. The anticipated model is used to forecast coronavirus transmission using feature forecasting data. The performance assessment is compared based on the outcomes of the suggested model and shows an enhanced COVID-19 diagnostic model.Copyright All © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research.
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Intro: Vaccinations have decreased the case fatality rate of COVID-19. Nonetheless, there appear to be differences in the duration of vaccine efficacy against death across populations.We aim to model the duration between vaccine type and time to death stratified by primary and booster series vaccination in Malaysia. Method(s): Data for all COVID-19 deaths between 1 February 2020 and 31 August 2022 were extracted from the Ministry of Health Malaysia data repository. Information was available on age, sex, nationality, region, vaccine status, vaccine type, and the duration from vaccination to death. The duration between primary or booster vaccination and death was modelled using Poisson regression. Finding(s): A total of 25,759 (77%), 7,421 (20%), and 1,036 (2.9%) unvaccinated, primary series vaccinated, and booster vaccinated COVID-19 deaths were respectively reported between 1 February 2020-31 August 2022 in Malaysia. The median duration between primary series vaccination and death, with AstraZeneca, Pfizer and Sinovac vaccines was respectively 150 (IQR: 73-211), 158 (IQR:88-229) and 105 (65-139) days. The median duration between booster vaccine and death with a Homologous or Heterologous vaccine was 86 (IQR: 59- 139) and 106 (66-139) days, respectively. Individuals with an AstraZeneca and Sinovac primary series had 19% (95% CI: 0.8-0.82) and 33% (95% CI: 66-0.68, p<0.01) shorter duration from vaccination to death than individuals with Pfizer vaccines. Individuals with a heterologous booster vaccination had an 8% (95% CI: 1.07-1.10, p<0.01) longer duration from vaccination to death than individuals receiving a homologous booster dose. Conclusion(s): There appear to be differences in the duration between vaccination and death by vaccine type. This must be considered alongside immune evasive variants and level of naturally acquired immunity when planning for vaccination programmes that are central to keeping COVID-19-associated mortalities low.Copyright © 2023
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The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 +/- 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 +/- 0.21 lg PFU/g) and ribavirin group (5.2 +/- 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (p < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (p < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (p > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.Copyright © Extreme Medicine.All right reserved.