Evaluating the spike in the symptomatic proportion of SARS-CoV-2 in China in 2022 with variolation effects: a modeling analysis.

Despite most COVID-19 infections being asymptomatic, mainland China had a high increase in symptomatic cases at the end of 2022. In this study, we examine China's sudden COVID-19 symptomatic surge using a conceptual SIR-based model. Our model considers the epidemiological characteristics of SARS-CoV-2, particularly variolation, from non-pharmaceutical intervention (facial masking and social distance), demography, and disease mortality in mainland China. The increase in symptomatic proportions in China may be attributable to (1) higher sensitivity and vulnerability during winter and (2) enhanced viral inhalation due to spikes in SARS-CoV-2 infections (high transmissibility). These two reasons could explain China's high symptomatic proportion of COVID-19 in December 2022. Our study, therefore, can serve as a decision-support tool to enhance SARS-CoV-2 prevention and control efforts. Thus, we highlight that facemask-induced variolation could potentially reduces transmissibility rather than severity in infected individuals. However, further investigation is required to understand the variolation effect on disease severity.

The Art of Stem Cell-Based Therapy.

Potency assays represent crucial experiments at the hub of the comprehensive complexity surrounding cell therapy. Moreover, numerous factors beyond biological and scientific considerations are involved in achieving successful potency assays that fulfil regulatory authority approval for a new advanced therapy medicinal product. Though this can mean a frustratingly long period of discovery and development, progress in cell therapy is nowadays proceeding remarkably quickly, assisted by the potency assay rigorously placing emphasis on the need to critically analyse the key factor/s responsible for the therapeutic mechanism of action. History has shown that it can take many decades for there to be an improved understanding of a mechanism of action. Yet the chasing of precise targets has revolutionised medicine, with no clearer example than approaches to viral pandemics. The centuries involved in the eradication of smallpox have paved the way for an unprecedented pace of vaccine development for the Covid-19 pandemic. Such extraordinary accomplishments foster encouragement that similarly for stem cell-based therapy, our scientific knowledge will continue to improve apace. This chapter focuses on the art of experimentation and discovery, introducing potency assay requisites and numerous factors that can influence potency assay outcomes. A comprehensive understanding of potency assays and their development can hasten the provision of new cell therapies to help resolve burdensome diseases of unmet medical need.

Nathanael Mathaeus von Wolf and Johanna Henrietta Trosiener (Schopenhauer). Variolation in the 18th century on the Polish lands according to the guidelines of a doctor and the memoirs of his patient.

Variolation became a popular method in Europe in the eighteenth century. Sources from Gdansk not only illustrate the guidelines that were used for these procedures, but also make it possible to compare that with the memories of the person on whom it was performed. In this case, the primary sources are: a 1772 work by physician Nathanael Mathaeus von Wolf, and the diaries of Johanna Henrietta Trosiener, mother of Arthur Schopenhauer. As the comparative analysis shows, the theoretical assumptions were sometimes changed during the practical implementation of variolation.

Face masking and COVID-19: potential effects of variolation on transmission dynamics.

Face masks do not completely prevent transmission of respiratory infections, but masked individuals are likely to inhale fewer infectious particles. If smaller infectious doses tend to yield milder infections, yet ultimately induce similar levels of immunity, then masking could reduce the prevalence of severe disease even if the total number of infections is unaffected. It has been suggested that this effect of masking is analogous to the pre-vaccination practice of variolation for smallpox, whereby susceptible individuals were intentionally infected with small doses of live virus (and often acquired immunity without severe disease). We present a simple epidemiological model in which mask-induced variolation causes milder infections, potentially with lower transmission rate and/or different duration. We derive relationships between the effectiveness of mask-induced variolation and important epidemiological metrics (the basic reproduction number and initial epidemic growth rate, and the peak prevalence, attack rate and equilibrium prevalence of severe infections). We illustrate our results using parameter estimates for the original SARS-CoV-2 wild-type virus, as well as the Alpha, Delta and Omicron variants. Our results suggest that if variolation is a genuine side-effect of masking, then the importance of face masks as a tool for reducing healthcare burdens from COVID-19 may be under-appreciated.

Life and death of smallpox.

Smallpox is an ancient scourge known since the Antiquity. It is caused by a highly contagious airborne poxvirus. This strictly human disease exists in two forms: variola major (Asian smallpox) with mortality of 20-45%, and an attenuated form called variola minor or alatrim with mortality of 1-2%, which only recently appeared in Europe and America towards the end of the 19th century. The first smallpox pandemic was the "Antonine plague", which swept through the Roman Empire in the 2nd century AD, after which smallpox became endemic in the Old World, causing seasonal and regional epidemics in Europe, affecting mostly young children until the 19th century. The discovery of the New World in 1492 and the opening of the African slave trade favored in 1518 the contamination by smallpox of the native Amerindian populations, who were massively decimated during the following centuries. In the absence of any effective treatment, preventive methods were developed from the 18th century. First, variolation was used, a dangerous procedure that consists in inoculating intradermally a small quantity of virus from convalescent patients. In the early 19th century, Edward Jenner popularized the practice of inoculating cowpox, a mild cow disease. This procedure proved to be very effective and relatively safe, leading to the decline of smallpox during the 19th century. In the 20th century, a ten-year WHO vaccination campaign led to the total eradication of smallpox in 1977. During that century, smallpox caused an estimated 300-500 million deaths worldwide. Using molecular approach, it has been discovered that the smallpox virus emerged 3000-4000 years ago in East Africa and is closely related to the taterapox virus from African gerbils and to the camelpox virus, which causes variola in camelids. Today, smallpox virus strains are stored in freezers at the CDC in Atlanta and at the Vector Center in Koltsovo, Siberia. That is why smallpox remains a potential threat to the highly susceptible human species, as a result of an accident or malicious use of the virus as a biological weapon.

Mandating immunity in the Ottoman Empire: A history of public health education and compulsory vaccination.

Histories of medicine and vaccinology routinely reference the Ottoman Empire with regard to Lady Mary Wortley Montagu, her children's variolation, and the transmission of this knowledge throughout Britain and thereafter Europe. Few, however, follow the empire's ongoing relationship with vaccination after the Montagu family's departure. This article examines this aspect of Ottoman medical history by noting how Jenner's advances diffused back into the empire and then presenting and analyzing how imperial, medical, and even community leaders began to both educationally condition the population and gradually enact legislation that mandated vaccination. Owing to severe infrastructural, personnel, and financial deficits, instability, and popular fears and trepidation, the empire's aspirations to achieve universal vaccination were far from realized by the time of its early 1920s demise-especially throughout largely rural Anatolia. Ottoman institutional, educational, and legislative advances, however, collectively prepared the ground for the succeeding Turkish republic and its public health agenda. Given the republic's promotion of its efforts to modernize Turkey amid its mutual initiatives of nation-building, the empire's histories of providing this foundation are also sometimes overlooked.

Smallpox Vaccine and Resident Responses in Modern Shanghai: Focusing on Regional and Cultural Comparison.

In modern Shanghai, smallpox was one of the most threatening diseases with its mortality rate going up to 30 percent. In response to the disease, Dr. William Lockhart, a medical missionary of the London Missionary Society, introduced vaccination to the Chinese people in Shanghai. He built the first western style hospital in Shanghai, Renji Hospital, in 1843. At this time, native doctors also played a very important role. For example, Huang Chun-pu was in charge of the dispensary in the Chinese City in Shanghai, and he was the one who introduced vaccination under Dr. Lockhart's direction. In 1868, the Health Office of Shanghai Municipal Council began to implement a vaccination program. Around the turn of the 20th century, the Health Office of Shanghai Municipal Council managed several sub-district offices, hospitals, dispensaries, gaol, and even the traditional place like simiao for the free vaccinations. Urban residents benefited from a sanitary system, such as wide and free vaccination, compared to people who lived in rural areas. Moreover, Shanghai possessed the advantage of having the vaccine as a staple product of the Municipal Laboratory. The number of units of the vaccine issued from the Laboratory in sequence of years from 1898 to 1920 has been 115,351 on average. Unlike the International Settlement, where systematic inoculation was conducted under the leadership of the Municipal Council, the Chinese City was still reliant on charity organizations in the early 1900s. The foreign residence in the International Settlement had a strong influence from the foreign governments, and foreign doctors were well-aware of the need for the vaccination. However, the Chinese City was a Chinese enclave that was still under the traditional rule of the Qing Dynasty. In addition, the people of Shanghai had different perceptions of the smallpox vaccination, and this became an obstacle to the establishment of urban sanitation systems. Some Chinese people still relied on the traditional Chinese variolation and Chinese custom. For example, Chinese people still applied for inoculation in the spring and avoided summer and fall following traditional Chinese variolation, even though the best time to get vaccinated was in early winter before the spread of smallpox. In addition, foreigners were often more problematic than Chinese because they often overlooked the importance of vaccines and relied on drugs instead. The municipal authority, therefore, provided a wide range of free vaccinations for the poor and needy people regardless of their nationalities, and with such measures, sought to establish a stable urban sanitation system. This had been the key to the success of hygiene policies.

The geography of smallpox in England before vaccination: A conundrum resolved.

Smallpox is regarded as an ancient and lethal disease of humans, however very little is known about the prevalence and impact of smallpox before the advent of vaccination (c.1800). Here we use evidence from English burial records covering the period 1650-1799 to confirm a striking geography to smallpox patterns. Smallpox apparently circulated as a childhood disease in northern England and Sweden, even where population densities were low and settlement patterns dispersed. However, smallpox was a relatively rare epidemic disease in southern England outside the largest cities, despite its commercialised economy and the growing spatial interconnectedness of its settlements. We investigated a number of factors hypothesised to influence the regional circulation of smallpox, including exposure to naturally occurring orthopox viruses, settlement patterns, and deliberate preventative measures. We concluded that transmission was controlled in southern England by local practices of avoidance and mass inoculation that arose in the seventeenth and eighteenth centuries. Avoidance measures included isolation of victims in pest houses and private homes, as well as cancellation of markets and other public gatherings, and pre-dated the widespread use of inoculation. The historical pattern of smallpox in England supports phylogenetic evidence for a relatively recent origin of the variola strains that circulated in the twentieth century, and provides evidence for the efficacy of preventative strategies complementary to immunisation.

The prevention and eradication of smallpox: a commentary on Sloane (1755) 'An account of inoculation'.

Sir Hans Sloane's account of inoculation as a means to protect against smallpox followed several earlier articles published in Philosophical Transactions on this procedure. Inoculation (also called 'variolation') involved the introduction of small amounts of infectious material from smallpox vesicles into the skin of healthy subjects, with the goal of inducing mild symptoms that would result in protection against the more severe naturally acquired disease. It began to be practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu who influenced Sloane to promote its use, including the inoculation of the royal family's children. When Edward Jenner's inoculation with the cow pox ('vaccination') followed 75 years later as a safer yet equally effective procedure, the scene was set for the eventual control of smallpox epidemics culminating in the worldwide eradication of smallpox in 1977, officially proclaimed by WHO in 1980. Here, we discuss the significance of variolation and vaccination with respect to scientific, public health and ethical controversies concerning these 'weapons of mass protection'. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

Science and society: vaccines and public health.

Most public health research is devoted to the measurement of disease burdens and of the costs and effectiveness of control measures. The history of immunization provides many colourful examples of various ways in which such measurements are made, of how they have influenced policies, and of the importance of public perception of the magnitudes of the various burdens, benefits and risks. Improving the public's ability to evaluate evidence is itself an important aspect of public health.

Trends in Research on the History of Medicine in Korea before the Modern Era / 의사학

Research on the history of medicine in Korea in the form of modern scholarship began with the publication in 1930 of Yi Neunghwa's "A History of the Development of Medicine in Korea." The purpose of the present study lies in surveying studies on the history of medicine in Korea in the past 80 years since the publication of Yi's paper. In terms of periodization, research on the history of medicine in Korea is bifurcated by the publication of two comprehensive histories.i. e., Miki Sakae's A History of Medicine and Disease in Korea (1963) and Kim Du-jong's The Complete History of Medicine in Korea (1966). Indeed, all earlier studies converged in these two books. Because Miki and Kim both had majored in Western medicine and conducted research based on similar perspectives, data, and methods, the two works overlap considerably, and Kim's book, as the later of the two, unfortunately lost the initiative to the former to a considerable extent. As a result of these two scholars' research, it became possible to trace the overall flow of the history of medicine in Korea. Following the publication of works by Miki and Kim and with the advent of the 1980's, research on the history of medicine in premodern Korea was renovated with the emergence of no fewer than some dozen new doctoral degree holders in the field. In fact, these young scholars went beyond surveying trends in each era to expand the scope of specific discussions and topics per era, to delve into the actual contents, and to elucidate the function of medicine in society. The fruits of studies conducted in the past 80 years on the history of medicine in premodern Korea can be summarized as follows. 1) before the 5th century AD: the existence of a comprehensive medical practice in regions inhabited by those considered to be the ancestors of the Korean people; and information on medication including ginseng. 2) 5th-10th centuries: the existence of professional medical posts; the management of medicine by the royal household; institutions for medical education; the import and use of Chinese medical texts; the compilation of independent medical texts; the transmission of medical knowledge to Japan; and the import and export of medicinal ingredients. 3) 10th-14th centuries: public medical organs; medicine focusing on domestic medication; the invitation of medical doctors and the transmission of new medicine from Song China; the inclusion of medicine in the civil service examinations; the compilation of diverse types of Korean medical texts including those on native medicinal ingredients; disaster relief organs; regional medical organs; regional medicinal ingredient tribute system; and the state's measures against infectious diseases. 4) 14th-17th centuries: the consolidation of traditional East Asian medicine; the consolidation of Korean medicine including native medicinal ingredients; the emergence of a medical tradition that stresses the Daoist preservation of health ; and the publication of dozens of types of Chinese and Korean medical texts led by the entral and regional governments. Also noteworthy is the emergence of simple medical texts on emergency relief, pregnancy and childbirth, smallpox, and epidemics ( as well as the dissemination of their vernacular editions. In addition, there were phenomena such as the increasing occupation of the posts of medical officials by the non-aristocratic middling jung'in class; the existence of Confucian scholar-physicians and women physicians; and the compilation of texts on independent external medicine. 5) 17th-19th centuries: the formation of medicinal ingredient markets; the spread of pharmacies throughout the provinces; a vogue for Ming Chinese medical texts; veneration for the Treasured Mirror of Eastern Medicine; the emergence of a positivistic stance toward medical research; a vogue for experiential remedies; interest in Western medicine; compilation of several medical texts on measles; criticism of Chinese traditional medicine and/or Korean traditional medicine; the spread of variolation; attempts to introduce smallpox vaccination ; Korean-Japanese medical exchange through the dispatch of Korean goodwill missions to Japan; a great vogue for the Treasured Mirror of Eastern Medicine in both China and Japan; the emergence of independent medical texts on acupuncture; the successful cultivation and massive export of ginseng; and the birth of the Sasang (4-type) constitutional typology, a native medical tradition.