The plague which hit the city of Bologna in the year 1630.

In the year 1630, similarly to other cities of Northern Italy, Bologna was affected by a plague epidemic. It occurred after the arrival of Lansquenet troops, engaged by the Emperor Frederick II in the siege of Mantua city. The human losses have been calculated by the historian demographer Bellettini in the terms of around 15,000 people, so that the number of inhabitants in Bologna declined from 62,000 to 47,000 units in the time span of 7-8 months. Initially, during the winter and the early spring, although the plague epidemic had been known after that it involved many cities close to Bologna (i.e. Turin, Milan, Venice, Genoa and Verona), the population tried to keep the epidemic hidden, being afraid that commerce exchanges could be affected by this event. Later, starting from the month of May, under the guidance of cardinal Bernardino Spada, cooperating with the numerous religious orders and in particular with the one of the Camillians, the city reacted, launching an organization effort which significantly aided in the containment of the plague epidemic. A number of Lazarettos were organized outside of the city walls and relevant sums supported the clean operation of over 3,000 houses. The city Senate sustained the poor population with a sum of 700,000 lire and grain donations. Even if the loss of human lives was high, it resulted not so dramatic, compared with that paid by other Italian cities. From a cultural point of view, according to the belief of the scientific knowledge of that time, the miasmatic theories were still considered satisfactory, although in the common practice the people who could leave the city escaped from Bologna, in order to avoid the contagion. We can argue that the impact of the epidemic was reduced by means of the organizational approach with strict isolation measures for sick persons, the closing of the city walls in the urban areas more affected by the plague, and finally a sanctionatory and punitive approach for individuals, who disregarded the applied rules.

Figurative aspects suggestive of infectious diseases in the ceramic pots of the pre-Columbian Moche culture. Analysis of the ceramics collection in the Larco Museum of Lima, Peru.

The historical-medical and anthropological studies, regarding Mesoamerica and South America, have been mainly focused on the great empires (Inca, Atzec, Maya), while other civilizations have been less investigated and only recently are gaining interest. In general, the paleopathological research provides interesting data to know the type of nutrition and the general environmental conditions as well as to point out some ritual mutilation practices, which were relatively frequent in the pre-Columbian cultures. A lot of civilizations flourished in the South America before the arrival of the Spanish Conquistadores in the new world. In the last years it is progressively increasing the interest for the study of the Moche culture as well as for a deeper knowledge of pathocenosis of infectious diseases in the Moche society. Human infectious diseases are known to have a frequent animal origin, in particular from domesticated species, although the species domesticated in the pre-Columbian era were a small number. The purpose of our paper has been to examine the archeological findings suggestive of infectious diseases in artistic ceramic pots, dating back to the Moche period. We examined the iconography of ceramic pots belonging to the collection of the Larco Museum in Lima and reproducing body signs suggestive of infectious diseases. We identified 8 handworks with very interesting features by a medical point of view. In these handworks there are signs and lesions possibly associated with infectious diseases: risus sardonicus, orbital edema, facial nerve palsy, dorsal kyphosis, face and skin lesions. These features are compatible with some infectious diseases, including: syphilis, Bartonella bacilliformis, leishmaniasis, Pott's disease and Chagas disease. A wide discussion about these handworks is provided.

The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities.

In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy.

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.

The plague in Bologna in the year 1527.

In the year 1527, following the invasion of Italy by Landsknechts, who were headed by Georg von Frundsberg, the bubonic plague appeared in the country. These soldiers were part of an army that Charles V sent to invade Italy in order to subjugate the Italian states which had adhered to the League of Cognac. In Bologna during the year 1527 believers held a procession from the Sanctuary of the Madonna del Soccorso, through the city, as far as the Church of San Rocco. The reason for this practice was linked with the plague epidemic. After some cases of plague observed in the Borgo di San Pietro district the miracle of the interruption of the epidemics, thanks to the intervention of Our Lady, was narrated by the faithfuls. Later, after several decades, it was reported by several authors from Bologna, who were not witnesses to the facts, that the epidemic had involved 12,000 out of a total population of around 60,000 inhabitants at that time. We re-evaluated this situation starting from the demographic data concerning the citizens in Bologna during the 15th, 16th and 17th centuries. Furthermore, we performed a search in the State Archives in the city of Bologna in order to find any public notices from the city authorities in the year 1527 aiming to counteract a plague epidemic. Our investigation found no elements to support the outbreak of this disease. Throughout the 16th century, until 1590, the population grew significantly, and no public notices were issued or specific laws enacted to deal with the plague until the year 1557. However, it remains possible that in the area in question, some episodes of plague occurred, but it was fortunately a micro-epidemic, which involved a very poor area of the city. Then this disease was self-limited. However, in our opinion, this episode proved very important, since in this district of Bologna, and around a wooden image of the Madonna del Soccorso, a confraternity took place, and its activities continued until the year 1798. This group of citizens also played a major role in many charitable activities to aid the inhabitants of Bologna, during a difficult historical period, namely the Protestant Reformation, and contributed to strengthen the faith of Catholic believers.

The destiny of Italian prisoners in Austro-Hungarian POW camps during the First World War: remembering the defeat of Caporetto 100 years on.

The living conditions of Italian prisoners during the First World War were extremely difficult. At the end of the conflict, the treatment of Italian soldiers in Austro-Hungarian POW camps and in those of the German territories was recognized as particularly harsh in comparison with that of other prisoners. The reasons may be ascribed to three main factors. The Italian prisoners paid the price of being considered traitors, since Italy was allied with the Austro-Hungarian Empire and with Germany until 1914, subsequently switching to the side of France, the United Kingdom and Russia. The Italian government and the Italian High Command considered their soldiers poorly inclined to engage in a war which became over time increasingly costly in terms of human sacrifice. The strategy pursued by the General-in-Chief Luigi Cadorna was very aggressive and showed little care for the life conditions of his troops, who were frequently thrown into the fray and exposed to potential slaughter. Due to this negative judgement on their troops' willingness to fight, the government did not help, and even hindered, the despatch of packages of food and clothes to prisoners in the Austro-Hungarian and German camps via the Red Cross. The idea of a better life in the trenches compared with that expected in the camps as prisoners was widespread. Thirdly, the maritime blockade of the Adriatic Sea over time reduced to starvation the populations of Austria, Hungary and Germany, which obviously had grave repercussions on prisoners. It was estimated that around 100,000 Italians lost their lives in POW camps; after the defeat at Caporetto, when over 250,000 prisoners were captured, the number of deaths rose. The main causes of death were: tuberculosis, pneumonia, malnutrition and typhoid fever. At the end of the war, when coming back to Italy, former POWs were interned for months in camps (located predominantly in the Emilia region) and had to face interrogation and trials to demonstrate they were not deserters and were free to go back home. In the meantime, many lost their lives due to "Spanish" flu, pneumonia and other infectious diseases. Only the mobilization both of families and public opinion forced the Italian government to close the camps at the end of the year 1919.

The health of Italian troops and prisoners during World War I.

During the Great War, which involved Italy from May 1915 until November 1918, the Italian Army paid an extremely high price in terms of suffering; around 600,000 soldiers died. About 100,000 of these deaths were caused by diseases, mainly infectious ones. The casualties accounted for over one million cases. Epidemics of cholera and petechial typhus were recorded as well as an increase in morbidity due to tuberculosis and malaria, which had shown some minor epidemiological reduction in several regions of Italy during the years preceding the Great War. A large number of soldiers acquired respiratory tract and brain infections. Severe limb infections were due to war wounds, but also to a novel disorder called "trench foot", In a context of general hygienic decay, death and stress linked to massive bombing, severe psychiatric disorders were observed. They were called "shell shock" in English (and known in Italy as "the wind of the howitzer"). The patients suffering from the above psychiatric disorders were considered simulators by the great majority of psychiatrists, who largely believed such soldiers wanted to avoid active combat. They were subjected to electric shocks and later sent back to the war front or to a mental hospital in the most severe cases. In some dramatic occurrences, like at the time of the Caporetto defeat, a substantial number of soldiers were dealt rough justice in front of firing squads under the suspicion of desertion. Yet World War I, with its dramatic load of suffering, forced the medical environment to develop extremely innovative techniques and research applied to clinical practice. During the decades to follow, such efforts yielded major results in the field of pharmacology: studies which led to the discovery of the first antibiotics were set in motion.

Plagues and artistic votive expressions (ex voto) of popular piety.

In past centuries, epidemics, the scourge of humankind, caused pain, anger, uncertainty of the future, social as well as economic disorder and a significant impact on their victims, involving also their spiritual sphere. The latter effect led to undoubted effects on participation in the religious and social life of communities. The custom of preparing artistic votive expressions has been lost in the mists of time and evidence of ex voto gifts, offered by believers to pagan gods, has been found in prehistoric archaeological sites. Furthermore, several finds from the Ancient Greek and Roman worlds may be observed in our museums. These remains are generally ceramic and metal artifacts, reproducing limbs and other body parts which had been healed. These elements, according to the belief of those making the offerings, had benefited from the miraculous intervention of a thaumaturgical deity. With the advent of Christianity, some pre-existing religious practices were endorsed by the new religion. Believers continued to demonstrate their gratitude in different ways either to miracle-working saints or to the Virgin Mary, because they thought that, thanks to an act of faith, their own health or that of a family member would benefit from the direct intervention of the divine entities to whom they had prayed. In the Ancient Greek world, it was believed that the god Asclepius could directly influence human events, as testified by the popularity of shrines and temples to the god, especially at Epidaurus. In the Christian world as well, particular places have been detected, often solitary and secluded in the countryside or in the mountains, where, according to tradition, direct contact was established between the faithful and Saints or the Virgin Mary Herself. Manifestations occurred by means of miracles and apparitions, thereby creating a direct link between the supernatural world and believers. Religious communities, in these extraordinary places, responded to the call through the building of shrines and promotion of the cult. Over time, the faithful reached these places of mystery, performing pilgrimages with the aim of strengthening their religious faith, but also with the purpose of seeking intercession and grace. In this case, the request for clemency assumed spiritual characteristics and also became a profession of faith. Accordingly, the shrines in the Christian world are places where supernatural events may occur. In these environments the believer resorted to faith, when medicine showed its limits in a tangible way. For the above reasons, while epidemics were occurring, the requests for clemency were numerous and such petitions were both individual and collective. In particular, by means of votive offerings (ex voto) the believers, both individually and collectively, gave the evidence of the received grace to the thaumaturgical Saint. Through the votive act, a perpetual link between the believer and the Saints or Holy Virgin was forged and a strong request for communion was transmitted. The aim of the present study is to describe the role played by votive tablets (ex voto) in the last 500-600 years, as visible evidence of human suffering. From this perspective, these votive expressions may assume the role of markers because, in accordance with the expressions of popular faith, they allow us to follow the most important outbreaks that have caused distress to Christian communities.

Italian prisoners with tuberculosis in the early nineteenth century: the experience in the Pianosa prison hospital.

In the late nineteenth century, with industrial growth and the resulting mass urbanisation, tuberculosis represented a plague mainly among the poor social classes. The outdated and crowded Italian prisons (formerly old monasteries) during the early 1900s were insufficient to "host" the multitude of inmates condemned or waiting for judgment. Italian prisoners were beset by hunger and poor hygiene facilities. Clothes did not differ between winter and summer. The Criminal Sanatorium of Pianosa was officially inaugurated in 1907, but from the 1860s it had been set up to host an agricultural penal colony. Here we report the excellent results obtained between 1907 and 1909 in the management of tuberculosis among prisoners in Pianosa, where surgery was also available. In those times, climate therapy with an enriched and varied nutrition was the only effective treatment for tuberculosis. Overall, of the 913 prisoners housed in Pianosa in that period and according to the acknowledged scientific criteria, the following results were achieved: complete cure in 182, improvement in 416, mild amelioration in 94, worsening in 80, no change in 20. The number of prisoners who died or were transferred to another prison is unknown. The case series of the prison hospital in Pianosa may be reconstructed thanks to data published by the Director Roberto Passini. The better outcome of the prisoners in Pianosa, in comparison with inmates of other Italian institutions, was due both to treatment standards (climate, nutritional, hygienic, and surgical) and to the proportionally longer period of stay in Pianosa for prisoners with already confirmed detention periods.

[The treatment of wounds during World War I].

The First World War was a huge tragedy for mankind, but, paradoxically, it represented a source of significant progress in a broad series of human activities, including medicine, since it forced physicians to improve their knowledge in the treatment of a large number of wounded soldiers. The use of heavy artillery and machine guns, as well as chemical warfare, caused very serious and life-threatening lesions and wounds. The most frequent causes of death were not mainly related to gunshot wounds, but rather to fractures, tetanus and septic complications of infectious diseases. In the first part of this article, we describe the surgical procedures and medical therapies carried out by Italian physicians during the First World War, with the aim of treating wounded soldiers in this pre-antibiotic era. Antibacterial solutions, such as those of Dakin-Carrel and sodium hypochlorite and boric acid, the tincture of iodine as well as the surgical and dressing approaches and techniques used to remove pus from wounds, such as ignipuncture and thermocautery or lamellar drainage are reported in detail. In the second part of the paper, the organization of the Italian military hospitals network, the systems and tools useful to transport wounded soldiers both in the front lines and in the rear is amply discussed. In addition, the number of soldiers enrolling, and those dying, wounded or missing during the Great War on the Italian front is estimated.

Dental worm disease.

During human evolution, the period in which groups of humans stopped harvesting fruits and seeds growing wild and introduced the cultivation of cereals as well as the domestication of animals represents a very important event. This circumstance had a considerable impact on human pathocenosis, increasing the risk of infectious diseases of animal origin. The aim of this review was to summarise the archaeological and palaeo-pathological evidence in the literature concerning this topic. Starting from early prehistory (about 1.5 million years ago) up to the historical period, several authors have described the changes in human habits and the consequent changes in food supply, leading to the transition from a protein- to a carbohydrate-rich diet across a broad interval of time. This led to additional problems for human health. The increased accumulation of carbohydrate debris in the odonto-stomatological apparatus, without the appropriate use of hygiene in the oral cavity, increased the risk of infectious disease involving the mouth. Therefore, since the Neolithic period there has been a higher risk of tooth caries, abscesses, deep infection of the teeth roots, reaching also the mandibular and maxillary bone. Several hypotheses have been proposed by the distinct civilizations, which have alternated in the different ages, to explain the cause of these human health problems, including the idea that a "dental worm" could be involved in this process, such as in the Sumerian period. We describe and discuss further modifications of this theory, developed in Egypt, Assyria, Babylon, China, Greece, in Etruscan cities and in Rome in ancient times as well as in the Middle Ages, and the evolution of scientific thought on this topic in the past 300 years. In addition, the results of some palaeo-pathological studies, which were performed on human remains, such as the maxillary bone and teeth, mainly in different geographical areas in Italy, are examined and reported.

Pestilence, riots, lynchings and desecration of corpses. The sleep of reason produces monsters.

Vampirism has been a component of Central European and Balkan folklore since the Middle Ages and was often believed to be responsible for the transmission of serious infectious diseases such as plague and tuberculosis/consumption. Vampirism was believed to be spread within the same family or village and if the rite of the so-called second burial after death was not performed. The practice of "second burial" entailed exhumation of the body and the removal of the shroud from the mouth of the corpse, and a search for evidence if the corpse had chewed the cloth. If the shroud was chewed, a handful of earth or a brick was put into the body's mouth so that the vampire could no longer harm others. In some cases, the corpse was decapitated and an awl, made of ash, was thrust into its chest. Furthermore, the limbs were nailed down to prevent its movements. Remarkably, these beliefs were not restricted to the popular classes, but were also debated by theologians, political scientists at the height of the eighteenth century (Enlightenment). In the Habsburg Empire, this question attained such important political, social as well as health connotations as to force the Empress Maria Theresa to entrust an ad hoc study to her personal physician Gerard van Swieten with a view to determining what was true about the apparitions of vampires that occurred throughout central Europe and in the Balkans. The result of this investigation led to a ban on the "second burial" rites. Despite this prohibition, the practice of necrophilia on the bodies of suspected people continued, and both a cultured and popular literature on vampirism continued to flourish well into the nineteenth century.

MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma.

Aim of the present review is to summarize the current knowledge about the potential relationship between miRNAs and hepatitis B virus (HBV)-hepatitis C virus (HCV) related liver diseases. A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine miRNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma (HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "microRNAs", "miRNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma miRNAs, including miR-21, miR-122, mi-125a/b, miR-199a/b, miR-221, miR-222, miR-223, miR-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of miRNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of miRNAs for HCC early detection and prognosis.

Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review.

AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.

[Epidemics on the sea: migrants journeys in the nineteenth century]. / Le epidemie sul mare. Odissee di migranti nel XIX secolo.

In the nineteenth century travelling by ship became faster due to the introduction of the steam engine. Population growth, economic crises and food shortages forced millions of Italians to consider migration towards the Americas as a real opportunity. Travel conditions on ships and steamers were particularly difficult. People were crammed into dormitories where ventilation was poor, food was insufficient, hygiene was appalling and promiscuity was rife. Under such conditions, epidemics of cholera, typhus and measles were all too likely to develop, but mycobacterium tuberculosis also proliferated. The health authorities attempted to block the spread of epidemics by means of either health licenses - papers certifying good health of the crew and passengers, which had to be exhibited on arrival - or quarantine, involving the ship and all its contents, if infectious diseases were detected or suspicious deaths occurred during the ship's voyage. In this article the particularly unfortunate stories of Italian immigrants, who boarded ships and steamers, are reported. In the second half of the nineteenth century, but also in the first decades of the twentieth, millions of Italians whose aim was to reach the Americas paid a very high price. Italy did not provide acceptable living conditions for millions of farmers and town-dwellers, and migration in search of work was in many cases the only solution. Although many during their sea voyages became ill or died of starvation or infectious diseases, migration, supported by hope, continued.

[The experiments conducted by Japanese on human guinea pigs, and the use of biological weapons during the Sino-Japanese war (1937-1945)]. / Gli esperimenti su cavie umane effettuati dai giapponesi e l'utilizzo delle armi biologiche nel teatro di guerra cino-giapponese (1937-1945)

Starting from the end of the nineteenth century, and during the first four decades of the past century, Japan showed considerable military expansion, on the back of a pan-Asiatic and imperialistic ideology, comparable only to those expressed by Wilhelmian and Nazi Germany. This growth led to Japan playing an extremely important role in the Asia-Pacific continent, which unavoidably brought the country onto a collision course with the British Empire and the United States of America. The Japanese general Shiro Ishii, who had undoubted organisational abilities but also a propensity for crimes against mankind, starting from the end of the 1920s and during the subsequent decade, under the suggestion of a military physician, developed a research programme to obtain biological weapons, since he was aware of the lack of raw materials, technology and scientific background in nuclear weapons. This project was taken forward despite Japan's ratification of the Geneva protocol, undersigned by 70 nations, which posed strict limits to the use of both biological and chemical weapons. In actual fact, the protocol allowed these weapons for defensive purposes, and permitted their experimental development. The research programme, developed with the support of the high command of the Japanese army and certainly known by the Emperor (Tenno) Hirohito, had its operative basis from the year 1932 in the satellite state of Manchukuo, but later and paralleling the increased, aggressive behaviour towards China and the English and American colonies during World War II, spread towards other Asian provinces occupied by the Japanese armies, with other operative units. In these dedicated bases, which were true concentration camps, numerous experiments were carried out on human guinea pigs, frequently concluding with vivisection. Among others, experiments of freezing, thirst, hunger, loss of blood, wounding with firearms, and bone fractures, were performed, as well as the inoculation of microorganisms (including Yersinia pestis, Vibrio cholerae, Richettsia typhi, and Salmonella typhi), and spores of Bacillus anthracis. With regard to infectious diseases, the objective was to establish the most effective models for the use of biological weapons, taking into consideration the features of territories and populations to be placed under attack. It has been estimated that over 100,000 people suffered in such experiments, and according to the authors who studied these facts on the basis of original documentation, approximately 540,000 subjects lost their lives in China and Korea due to epidemics caused by the Japanese between 1937 and 1945.

The Bolognese surgeon Giuseppe Ruggi: how and why the aseptic surgery was introduced in Bologna in the middle half of the XIX century.

BACKGROUND: The first reliable statistic data about perioperatory mortality were published in 1841 by the French Joseph-Francois Malgaigne (1806-1863): he referred to a mean mortality of 60% for amputations and this bad result was to be attributed mainly to hospital acquired diseases. The idea of "hospital acquired disease" although vague, included five infective nosologic entities, which at that time were diagnosed more frequently: erysipelas, tetan, pyemia, septicemia, and gangrene. Nonetheless, the suppuration with pus production was considered from most of the surgeons and doctors of that time as a necessary and unavoidable step in the process of wound healing. During the end of the eighteenth century, hospitals of the main European cities were transforming into aggregations of several wards, where the high concentration of patients created poor sanitary conditions and a consistent increase of perioperatory mortality. In 1865, Lister applied his first antiseptic dressing on the surface of an exposed fracture. These experimental attempts lead to an effective reduction of wound infections respect to the dressing with strings used previously. DISCUSSION: Lister's innovations in the field of wound treatment were based on two brand new concepts: germs causing rot were ubiquitarious and the wound infection was not a normal step in the process of wound healing. The concept of antisepsis was hardly accepted in the European surgical world: "Of all countries, Italy is the most indifferent and uninterested in experimenting this method, which has been so favorably judged from the greatest surgical societies in Germany". This quotation from the young surgeon Giuseppe Ruggi (1844-1925) from Bologna comes from his article where he presented his first experiences on aseptic medications started the previous year in the Surgical Department of Maggiore Hospital in Bologna. In his report, Ruggi described the adopted technique and suggested that the medication should be extended to all the surgical patients of the hospital:"… this is needed to totally remove from the hospital all those elements of infection which grow in the wounds dressed with the old method". The experimentation of this new dressing for the few treated cases was rigorous and concerned both the sterilization of surgical tools with the fenic acid (5%) and the shaving of the skin. Ruggi also observed that there was no correlation between the seriousness of the wound and its extension or way of healing: when "simple" cases that "should heal without complication" showed fever he often realized that "it was often due to a medication performed without following the rules for an accurate disinfection and dressing". Ruggi thought that the fever was connected to "reabsorption of pyrogenic substances, which can be removed cleaning and disinfecting the wound" in cases of wounds not accurately dressed and rarely medicated. Frequent postoperative medications of the wound were able to eliminate the fever within 2 h. Ruggi's attitude toward the fine reasoning lead him to introduce the concept of immunodeficiency related to physical deterioration: "… patients treated for surgical disease may sometimes suffer from complications of medical conditions, which initially escape the most accurate investigations… The surgical operation could, in some cases, hold the balance of power". CONCLUSIONS: The obtained results, published in 1879, appear extremely interesting. As he wrote in 1898, for the presentation of his case record of more than 1000 laparotomies, he had started "… operating as a young surgeon without any tutor, helped only by his mind and what he could deduce from publications existing at the moment …".

[The re-introduction of malaria in the Pontine Marshes and the Cassino district during the end of World War II. Biological warfare or global war tactics?]. / La reintroduzione della malaria nell'Agro Pontino e a Cassino sul finire della II Guerra Mondiale. Guerra biologica o tattica di guerra totale?

After the fall of the Fascist regime on September 8, 1943, Italy was split into two parts: (i) the Southern regions where the King Victor Emanuel III and the military general staff escaped was under the control of English-American allied armies, and (ii) the northern regions comprising Lazio, Tuscany, Umbria, and Marche still under the control of the Germans. The German Wehrmacht, after suffering several defeats on Southern lines, established a new strengthened line of defence called the Gustav line, located south of Rome and crossing in the western portion the recently-drained Pontine Marshes. In his book published in 2006, Frank Snowden hypothesised that occupying German armies in 1943 had initiated a programme of re-flooding the Pontine plain as a biological warfare strategy to re-introduce malaria infection in the territories south of Rome, Such a plan was intended (i) to slow down the advance of English-American forces, and (ii) to punish Italians who abandoned their former allies. Other authors, including Annibale Folchi, Erhard Geissler, and Jeanne Guillemin, have disputed this hypothesis based on an analysis of recently-uncovered archive documents. What is not disputed is that the flooding of the Pontine and Roman plains in 1943 contributed to a severe malaria epidemic in 1944, which was associated with exceptionally high morbidity and mortality rates in the afflicted populations. Herein, we critically evaluate the evidence and arguments of whether the Wehrmacht specifically aimed to spread malaria as a novel biological warfare strategy in Italy during the Second World War. In our opinion, evidence for specific orders to deliberately spread malaria by the German army is lacking, although the strategy itself may have been considered by Nazis during the waning years of the war.

[The infectious diseases experiments conducted on human guinea pigs by Nazis in concentration camps]. / Gli esperimenti di infezioni su cavie umane compiuti dai nazisti nei campi di concentramento.

The author systematically examined all available publications and web documents, with regard to scientifically documented experiments carried out by Nazi physicians in their concentration camps during World War II. This research focused on human experiments dealing with: malaria, tuberculosis, petechial typhus, viral hepatitis, and those regarding sulphonamides as antimicrobial agents. The concentration camps involved by experimental programmes on human guinea pigs were: Natzweiler Struthof, Dachau, Mauthausen, Buchenwald, Neuengamme, Ravensbrück, Sachsenhausen and Auschwitz. Overall, around 7,200 deported prisoners went to their deaths during or because of these experiments (also considering human trials other than previously quoted ones). At the end of the war several physicians were charged with war crimes in two trials (Nuremberg and Dachau), and those found guilty were sentenced to death, or years of imprisonment. Some of them, including the notorious Josef Mengele, succeeded in escaping capture and being brought to justice. Thanks to these trials, partial light has been shed on these crimes, which not infrequently had children as designated victims, selected with excruciating cruelty in special segregation sections. The SS was the key structure which ensured maximum efficiency for these experimental programmes, from both logistic planning through to an operative control system carried out in concentration camps, and thanks to an autonomous, dedicated medical structure, which included a rigid hierarchy of physicians directly dependent on the head of SS forces (Reichsführer), i.e. Dr. Heinrich Himmler. Moreover, it is worth noting that also physicians who were not part of the SS corps collaborated in the above experiments on human guinea pigs: these included military personnel belonging to the Wehrmacht, academic physicians from German universities, and researchers who worked in some German pharmaceutical industries, such as IG Farben, Bayer and Boehring.