Advances in experimental medicine and biology最新文献

While viruses are considered the most common infectious triggers for cytokine storm syndromes (CSS), a growing list of bacterial pathogens, particularly intracellular organisms, have been frequently reported to be associated with this syndrome. Both familial and sporadic cases of CSS are often precipitated by acute infections. It is also important to note that an underlying precipitating infection might not be clinically obvious as the CSS clinical picture can mimic an infectious process or an overwhelming septicemia. It is important to detect such an underlying treatable condition. In addition, infections can also be acquired during the course of CSS due to the concurrent immune suppression with treatment. Optimal CSS outcomes require treating bacterial infections when recognized.CSS should always be suspected in patients presenting with a sepsis-like or multi-organ dysfunction picture. There are many criteria proposed to diagnose CSS in general, with HLH-2004 being the most commonly used. Alternatively, criteria have been proposed for CSS occurring in specific underlying conditions such as systemic lupus erythematosus (SLE) or systemic juvenile idiopathic arthritis (sJIA). However, waiting for many of these criteria to be fulfilled could lead to significant delay in diagnosis, and the physician needs a high index of suspicion for CSS in critically ill febrile hospitalized patients in order to properly recognize the condition. Thus, there should be diagnostic equipoise between CSS and infections, including bacterial, in this population. In this chapter, we discuss the more common bacterial precipitants of CSS with many of the cases being discussed in the pediatric age group.

Lockdown restrictions and social distancing regulations enforced by governments worldwide to prevent COVID-19 transmission have caused momentous disruption to the global education sector. Educators and students across all institutions and levels had to suddenly adapt to a new reality where in-person teaching was replaced by hybrid or remote learning activities. This chapter aims to evaluate the impact of the pandemic on teaching, learning and assessment in higher education. It discusses the challenges presented by the shift to online teaching and the pedagogical strategies developed to foster student engagement and assess their progress in a remote learning setting. Moreover, this chapter explores the impact of the pandemic on wellbeing and mental health of students and academic staff. The last section draws on the lessons learned from the pandemic to identify areas of good practice that are likely to positively shape the post-pandemic higher education panorama.

Chronic conditions or diseases are defined as persistent conditions lasting ≥ 1 year requiring either ongoing medical attention or limiting daily living or both (Agency for Healthcare Research and Quality (AHRQ) in Programs: SHARE approach workshop, Agency for Healthcare Research and Quality (AHRQ) (2016) Programs: SHARE approach workshop 2016. https://www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/workshop/index.html . Accessed 20 Jan 2017). Physical chronic conditions, including diabetes, hypertension, heart disease, arthritis, and stroke, are prevalent, especially in the older population. Over 90% of older adults have at least 1 and 77% have ≥ 2 chronic conditions (American Diabetes Association (ADA) in Statistics about diabetes, American Diabetes Association (ADA) (2023) Statistics about diabetes. https://diabetes.org/about-us/statistics/about-diabetes . Accessed 20 Apr 2023). Chronic conditions account for $4.1 trillion of the nation's annual healthcare expenditure (Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion in Health and economic costs of chronic conditions, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion. Health and Economic Costs of Chronic Conditions (2022). https://www.cdc.gov/chronicdisease/about/costs/index.htm . Accessed 7 Jan 2023). There are marked disparities based on age, color, and income, with older people, people of color, and lower-income people having higher treatment costs or even lost wages in response to having chronic conditions. Chronic conditions are the on-the-top leading causes for death with diabetes being the top 7th in the USA in 2019 (Ferguson in Metabolic Syndrome Related Dis, Ferguson et al., Metab Syndr Relat Disord 21:177-187, 2023).

Ebstein anomaly is a rare congenital heart defect, accounting for less than 1% of cardiac malformations and occurring in approximately 1 out of 210,000 live births. It is characterized by an abnormality of the tricuspid valve, where the valve is positioned lower than normal in the right ventricle. Although primarily a tricuspid valve defect, the right ventricle itself is often structurally abnormal and weakened (myopathic).

Monkeypox virus (MPXV) of poxviridae family causes a zoonotic disease called monkeypox (Mpox). MPXV cases have a fatality ratio ranging from 0 to 11% globally and have been more prevalent in children. There are three generations of smallpox vaccines that protect against MPXV. First and second generation of the vaccinia virus (VACV) vaccine protects MPXV. However, various adverse side effects were associated with the first and second generations of vaccines. In contrast, the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) replication-incompetent vaccine shows fewer adverse effects and a significant amount of neutralizing antibodies in mammalian cells. A third-generation Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) was approved to prevent Mpox in 2019. Recently, MVA-BN-based Imvanex, Imvamune, and JYNNEOS vaccines have also been administered against MPXV. Globally, the World Health Organization (WHO) declared a global health emergency in May 2022 due to increased MPXV cases. Various computational studies have also designed a multi-epitope-based vaccine against the MPXV. In the multi-epitope-based vaccine, different epitopes like B-cell, Cytotoxic T Lymphocyte (CTL), CD8+, and CD4+ epitopes were derived from MPXV proteins. Further, these epitopes were linked with the help of various linkers to design a multi-epitope vaccine against MPXV. In summary, we have provided an overview of the current status of the vaccine against MPXV.

Monkeypox has been endemic in Congo and Nigeria for at least five decades. Since early May 2022, there have been numerous unprecedented outbreaks throughout the world in places without any previously reported cases. While a majority of the diagnosed cases have been within Europe and the Americas, several cases have occurred in non-endemic African countries. As of December 2022, 82,999 cases had been reported globally, prompting concern among the World Health Organization (WHO) members. While the WHO has not labeled this epidemic a Global Health Emergency, member states have begun to put forward plans to consolidate their emergency vaccine stockpiles and share the limited number of vaccines made by the single FDA-approved manufacturer, Bavarian Nordic. Many countries are concerned about how vaccines will be shared. Some of the larger donor States are positioned to be the biggest beneficiaries of vaccine sharing, while States from areas that have been suffering from the virus since the 1970s have not been allocated any. This pattern of vaccine distribution echoes that seen during the early part of the COVID-19 pandemic. Due to the similarities between Monkeypox and Smallpox, contact precautions and vaccination seem to be effective strategies to combat its rapid spread. We aim to evaluate how an eradication program model similar to that used for Smallpox can be applied to Monkeypox, and whether it can address vaccine inequity. To do this, we use a multi-pronged approach targeting disease surveillance, vaccine awareness, manufacturing, cost, and distribution strategies.

Molluscum contagiosum virus is a poxvirus belonging to the Poxviridae family, which includes Orthopoxvirus, Parapoxvirus, Yantapoxvirus, Molluscipoxvirus, Smallpox virus, Cowpox virus and Monkeypox virus. MCV belongs to the genus Molluscipoxvirus and has a tropism for skin tissue. MCV infects keratinocytes and, after an incubation period of 2 weeks to 6 weeks, causes a breakdown of the skin barrier with the development of papules of variable size depending on the proper functioning of the immune response (both adaptive and acquired). MCV only infects humans and does not cause viraemia. MCV encodes for several inhibitory proteins responsible to circumvent the immune response through different signalling pathways. Individuals who can be infected with MCV are children, immunocompromised individuals such as organ transplant recipients and Human Immunodeficiency Virus (HIV)-infected individuals. Current treatments to manage MCV-induced lesions are different and include the use of immunomodulators, which, however, do not provide an effective response.

Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral pneumonia (with or without bacterial superinfections). Historically variola virus has been the poxviridae most frequently associated with the development of pneumonia with many large outbreaks worldwide before its eradication in 1980. It is still considered a biological threat for its potential in biological warfare and bioterrorism. Smallpox pneumonia can be severe with the onset of acute respiratory distress syndrome (ARDS) and death. Vaccinia virus, used for vaccination against smallpox exceptionally, in immunocompromised patients, can induce generalized (with also lung involvement) severe disease after vaccination. MPXV virus occasionally can cause pneumonia particularly in immunocompromised patients. The pathophysiology of poxviridae pneumonia is still an area of active research; however, in animal models these viruses can cause both direct damage to the lower airways epithelium and a hyperinflammatory syndrome, like a cytokine storm. Multiple mechanisms of immune evasion have also been described. The treatment of poxviridae pneumonia is mainly based on careful supportive care. Despite the absence of randomized clinical trials in patients with poxviridae pneumonia there are antiviral drugs, such as tecovirimat, cidofovir and brincidofovir, FDA-approved for use in smallpox and also available under an expanded access protocol for treatment of MPXV. There are 2 (replication-deficient modified vaccinia Ankara and replication-competent vaccinia virus) smallpox vaccines FDA-approved with the first one also approved for prevention of MPXV in adults that are at high risk of infection.

Poxviruses target innate immunity mediators such as tumor necrosis factors, interleukins, interferons, complement, and chemokines. It also targets adaptive immunity such as CD4⁺ T cells, CD4⁺ T cells, and B cells. Emerging of the recent epidemic of monkeypox virus (MPXV), a zoonotic disease native to Central and Western Africa, besides the lack of permitted treatments for poxviruses infections, encouraged researchers to identify effective inhibitors to help in preventing and treating poxviruses infections. Natural bioactive components, particularly polyphenolics, are promising for creating powerful antioxidants, anti-inflammatory, immune-stimulating, and antiviral agents. As a result, they are potentially effective therapies for preventing and treating viral diseases, such as infections caused by poxviruses including the recent pandemic MPXV. Polyphenolics: rosmarinic acid, caffeic acid, resveratrol, quercitrin, myricitrin, gingerol, gallotannin, and propolis-benzofuran A, as well as isoquinoline alkaloids: galanthamine and thalimonine represent prospective antiviral agents against MPXV, they can inhibit MPXV and other poxviruses via targeting different viral elements including DNA Topoisomerase I (TOP1), Thymidine Kinase (TK), serine/threonine protein kinase (Ser/Thr kinase), and protein A48R. The bioactive extracts of different traditional plants including Guiera senegalensis, Larrea tridentata, Sarracenia purpurea, Kalanchoe pinnata (Lam.) Pers., Zingiber officinale Roscoe, Quercus infectoria, Rhus chinensis, Prunella vulgaris L., Salvia rosmarinus, and Origanum vulgare also can inhibit the growth of different poxviruses including MPXV, vaccinia virus (VACV), variola virus, buffalopox virus, fowlpox virus, and cowpox virus. There is an urgent need for additional molecular studies to identify and confirm the anti-poxviruses properties of various natural bioactive components, especially those that showed potent antiviral activity against other viruses.

Poxviruses belong to the family of double-stranded DNA viruses, and it is pathogenic for humans and spread worldwide. These viruses cause infections and various diseases in human. So, it is required to develop new drugs for the treatment of smallpox or other poxvirus infections. Very few potential compounds for the treatment of poxvirus such as smallpox, chickenpox, and monkeypox have been reported. Most of the compounds has used as vaccines. Cidofovir is most commonly used as a vaccine for the treatment of poxviruses. There are no phytochemicals reported for the treatment of poxviruses. Very few phytochemicals are under investigation for the treatment of poxviruses.