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We describe the peculiar facial morphology of a carved head dating to the end of the Roman Republican period (40 BCE) which displays evident unilateral asymmetry. A comprehensive discussion of the different etiologies is provided and a contextualization of this condition in the broader frame of Roman artistic verism is offered. This case study contributes to the knowledge of disease presentation in the ancient world, with a special focus on the anatomy of soft tissue pathology.

The term "microbiome" is said to have been coined in 2001 by the American Nobel laureate-microbiologist Joshua Ledeberg (1925-2008). However, the history of microbiome began earlier, and founds its birth on the work of some "giants of Medicine." Here, we report a brief history of the main stages that led to current knowledge and use of the microbiome.

Dear Editor,Recognized for centuries, cryptorchidism or undescended testis, is the most common problem in pediatric urology and it is estimated to affect 1–4% of full term and up to 30% of preterm ...

SUMMARYDiffuse midline glioma (DMG) is a uniformly fatal pediatric cancer driven by oncohistones that do not readily lend themselves to drug development. To identify druggable targets for DMG, we conducted a genome-wide CRISPR screen that reveals a DMG selective dependency on the de novo pathway for pyrimidine biosynthesis. This metabolic vulnerability reflects an elevated rate of uridine/uracil degradation that depletes DMG cells of substrates for the alternate salvage pathway for pyrimidine biosynthesis. A clinical stage inhibitor of DHODH (rate limiting enzyme in the de novo pathway) diminishes UMP pools, generates DNA damage, and induces apoptosis through suppression of replication forks--an “on target” effect, as shown by uridine rescue. MALDI mass spectroscopy imaging demonstrates that this DHODH inhibitor (BAY2402234) accumulates in brain at therapeutically relevant concentrations, suppresses de novo pyrimidine biosynthesis in vivo, and prolongs survival of mice bearing intracranial DMG xenografts, highlighting BAY2402234 as a promising therapy against DMGs.

The search for clinical signs suggestive of diseases and medical analysis in works of art and portraits (sculpture, painting, engraving, photography, etc.) is known as iconodiagnosis1 . This exercise is highly enjoyable, but limited by the own subjectivity of the spectators and their background. The lack of crosschecking by using additional sources of information can lead to misinterpretation. We review briefly the common methodological pitfalls to avoid.

Introduction: Visual narratives such as manga, comics and cartoons can play an important role in educating readers on various aspects of life including medicine and disabilities. Methods: We reviewed the animated series entitled "Captain Tsubasa", focusing our analysis on the episodes which introduced the character Jun Misugi, a football player suffering from an unspecified congenital heart disease (CHD). Discussion: For a child with a CHD, the practice of sports could be risky but also an opportunity to improve heart function and reach personal fulfillment. CHD have an important impact on children's quality of life, and sports participation has beneficial effects on quality of life, weight loss, and exercise capacity, in patients with CHD. Restricting sports could have a negative impact on quality of life, and on the disease acceptance in children with CHD. The story of Jan Misugi could be considered as an educational medical tool to sensitize children with CHD who face sport' restriction.

Background Intracranial meningiomas are brain tumors that have probably been known the longest, largely because of the occasional production of grotesque cranial deformities that have attracted the attention and interest of humankind. Because of the tendency of some intracranial meningiomas to cause skull deformation and thickening, these tumors have given rise to various speculations and theories related to their origin, starting in prehistoric times up to the present. Methods From the Steinheim skull and “pharaonic meningiomas” to the first meningioma monograph and the first explanations of Harvey Cushing regarding the mechanism of hyperostosis, this review aims to weave again the story of Arachne. We identify the main contributors who have tried to understand and explain the tendency of some of these tumors to cause hyperostosis or other skull bone involvements. Conclusions The contribution of neurosurgeons or pathologists over the centuries is of undeniable importance and is the basis for understanding future molecular mechanisms.

Beginning with the thirteenth century, the papacy has exerted an important role in the development of anatomy and medical sciences through the protection and support provided to anatomists, who were in most cases the personal physicians of the popes as well. The work is intended to be a lesson of anatomy of Papal tiara, presenting the most important contributing popes, the anatomists-physicians whom they supported and protected and the relations between papacy and medical sciences.

Many world-renowned scientists and artists had autism spectrum disorder (ASD). We suggest that the French mathematician and physicist Blaise Pascal (1623-1662) also had ASD. As a boy, he demonstrated his mastery of language, mathematics and science. He showed single-mindedness and obsessive interests in the pursuit of science in his younger years and later he pursued with religion with the same determination. Pascal neglected social interactions; he was cold and aloof and had an obsessive revulsion to any expression of emotional attachment. As shown by his funerary mask and the autopsy report Pascal had craniosynostosis (primary nonsyndromic oxycephaly) with atrophy of the right half of the face. Congenital facial asymmetry due to craniosynostosis has a genetic basis. This suggests that Pascal's facial deformity may betray his propensity to suffer from genetically determined diseases including ASD. Despite the intrinsic limitations of a diagnosis based only on biographical information, we surmise that Pascal had the three key symptoms (obsessive interests, difficulty in social relationship and problems in communicating) that characterize ASD individuals.

Surprisingly, Catholic hagiography can teach us a lot about medicine. As an example, we present here the history of Saint Roch who is considered, along with Saint Sebastian, one of the two main Saints who act as protectors against plagues and have often been invoked by Catholic people during the recent COVID-19 pandemic. Whereas Saint Sebastian is associated with plagues only symbolically, Catholic tradition considers Saint Roch to have had real contact with the bubonic plague. Indeed, during his pilgrimage to Rome, Saint Roch helped people suffering from the plague and was, subsequently, himself infected. He was then forced to retire in solitary confinement to avoid the plague’s spread and followed scrupulously the necessary restrictive measures. Saint Roch’s story provides useful lessons about the importance of social responsibility by respecting the restrictive rules during difficult times such as the COVID-19 epidemic.

Pietro Vannucci (ca. 1450 - 1523), better known as Pietro Perugino, was one of the most brilliant Italian Renaissance painter working in Rome, Florence, and Perugia. The sense of spaciousness and the compositional clarity of his painting anticipated the ideals of High Renaissance [1].

International audience; Background: In the absence of a treatment still considered universally effective, and of a vaccine validated by the health authorities, we wanted to know which Catholic saint the European Christian community turned to in the event of infection with Covid-19 to request a miraculous healing. Methodology: An online survey was carried out on a sample of 1158 adults using social media tools. Results: All results are presented in this research, with a few saints in the majority, and some dictated by the symptomatology of the Covid-19 infection or the personalities of certain « doctor guru ». Conclusion: This medico-anthropological study is revealing the psychology of Western patients vis-à-vis the magic-religious means used in the fight against diseases, particularly in the epidemic/pandemic context.

International audience; Brainstem is one of the most complex structures of the human body, and has the most complex intracranial anatomy, which makes surgery at this level the most difficult. Due to its hidden position, the brainstem became known later by anatomists, and moreover, brainstem surgery cannot be understood without knowing the evolution of ideas in neuroanatomy, neuropathology, and neuroscience. Starting from the first attempts at identifying brainstem anatomy in prehistory and antiquity, the history of brainstem discoveries and approach may be divided into four periods: macroscopic anatomy, microscopic anatomy and neurophysiology, posterior fossa surgery, and brainstem surgery. From the first trepanning of the posterior fossa and later finger surgery, to the occurrence of safe entry zones, this paper aims to review how neuroanatomy and brainstem surgery were understood historically, and how the surgical technique evolved from Galen of Pergamon up to the twenty-first century.

The provision of sedation and general anesthesia will inevitably result in situations when an emergent airway is required. Positive pressure ventilation (PPV), chin lift/jaw thrust, and adjunct airways will often suffice. On occasion, there will be a need to place an advanced airway. Familiarity with supraglottic airways, intubation, indirect video laryngoscopy, and direct laryngoscopy are critical. The anesthesia provider should also be familiar with a surgical airway such as cricothyroidotomy.

To celebrate the 250th anniversary of the birth of the great classical composer, Ludwig van Beethoven (1770-1827), we point out how his hearing loss affected him and how the primitive hearing aids at that time helped mitigate his hearing loss. From the age of 26, Beethoven began to suffer from a fluctuating, progressive hearing loss ("my hearing grew worse and worse"), This started in his left ear ("in my left ear, with which this illness of my ears had started"), where he had difficulty hearing higher pitched tones ("I don't hear the high notes of the instruments and voices") and words ("Sometimes, I cannot hear people who speak quietly, I can hear the sounds, but not the words") and associated with tinnitus ("my ears, they still keep buzzing and humming day and night") and loudness recruitment ("if someone yells, it is unbearable to me").However, in spite of his hearing loss, Beethoven never lost his love for music and continued composing music, at times using some of the acoustic hearing aids that were just being developed. We analyze and describe the ear trumpets, and the resonant plate that engineer Johan Nepomuk Maelzel and piano-maker Conrad Graf, respectively, constructed to try to improve Beethoven's hearing. Moreover, we discuss the possible use of a wooden drumstick Beethoven might have used to improve his perception of the piano's sound.

What is the place of medico-historical cases in the professional practice of the disciplinary field of medicine and biology? How can these patients from the past be used for teaching and continuing medical education? How to justify their place in biomedical publications? In this article, we explain all the legitimacy of paleomedicine, and the need to intensify such research in the form of a well-individualised branch of paleopathology and the history of medicine.

Sir Martin Frobisher (ca 1535-1594), the famous Elizabethan explorer and privateer, sustained a bullet to the outer plate of his ilium from a low-velocity bullet wound fired at close range from an arquebus, an early form of musket. The bullet was removed, but he subsequently died from gas gangrene. This paper looks at the management of this injury in Tudor times and compares it to current practice. The arrival of gunpowder and the seriousness of the resulting injuries spurred innovation in surgical practice, such that at the time of Frobisher's death, the Tudor military surgeon had considerable expertise and skill. The wound, treated properly, was not serious, but his first surgeon failed to remove the wadding that the bullet took with it. This was recognised as an error at the time. A Tudor surgeon today would note that the surgical management has not really changed since their time, even though they did not understand infection and bacterial contamination. Guidelines on managing gunshot wounds, and most research, is focussed on high-velocity injuries where removal of foreign material (clothing) is mentioned. Low-velocity injuries are treated as "outpatients" and the importance of removing foreign material, especially when the bullet is left in situ, is not mentioned. The inexperienced surgeon of today risks making the same error as Frobisher's surgeon.

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.

International audience

King of the Spanish Habsburg dynasty and sovereign of the overseas Spanish Empire, Charles II of Spain, was physically disabled, disfigured, mentally retarded, and he proved impotent. He is known in history as El Hechizado (the Bewitched) because both him and the people believed that his mental and physical incapacity were due to a “witchcraft act.” Although several authors speculated about different diseases, most of them genetic such as pituitary hormone deficiency, distal renal tubular acidosis, Klinefelter syndrome, fragile X syndrome, or male XX hermaphroditism, the hypothesis of hydrocephalus was not taken into account. We don’t have clear elements to hypothesize a certain etiology of Charles II’ hydrocephalus; however, we think the herpetic infection he suffered of after his birth should not be ignored.

Overweight, workaholic, and a caffeine abuser, Honoré de Balzac lived a life of excess. He prematurely died at the age of 51 owing to gangrene associated with congestive heart failure. Textual sources allow us to take a glimpse into his last 3 months of life. Because of ventricular hypertrophy, Balzac's respiratory conditions were appalling and he developed severe leg edemas and possibly stasis dermatitis. Here we report on Balzac's demise and provide first evidence of a pioneering medical treatment applied to save his life: the use of a trocar to drain leg edema. Based on the empirical observation of the benefits derived from an accidental leg drainage, Balzac's physicians anticipated the invention of the "Southey tube", whose use evolved in the following century to treat obstinate edema in heart failure patients. Unfortunately, following the daily maneuvers for trocar insertion and in the absence of adequate disinfection measures and antibiotics, bacteria infected the open wound and gave rise to the gangrene, which caused the writer to die within 24 hours of its onset.

We developed novel zwitterionic near infrared (NIR) fluorescent agents (ABZWCY-HPβCD and AAZWCY-HPβCD), which exhibit favorable hydrophilicity, low plasma protein binding, high stability and non-toxicity. These attractive characteristics ensure that they are excreted rapidly, without any skin accumulation or metabolism in vivo. More importantly, zwitterionic HPβCD based agents can be efficiently filtrated by the glomerulus and completely excreted through the kidneys into urine without reabsorption or secretion in the kidney proximal tubule. Relying on these novel zwitterionic NIR agents and a transcutaneous device, we demonstrate a rapid, robust and biocompatible approach for assessing kidney function in rat models of both healthy rats and those with kidney disease, without the need for time-consuming blood/urine sample preparation. Our work provides a promising tool for in vivo real-time non-invasive kidney function assessment in preclinical applications.

A1AT deficiency- a genetically inherited autosomal codominant disease with more than 120 identified alleles- was first identified by Laurell and Eriksson in 1963. The most common hereditary disorder in adults, A1AT causes an increased risk of developing pulmonary emphysema and liver disease. In A1AT patients, lung disease generally presents at a younger age than "usual" chronic obstructive pulmonary disease (COPD) and it may be misdiagnosed as asthma. Because A1AT deficiency patients can show the same clinical features as non-deficient COPD (including increased evidence of bronchiectasis, frequent exacerbations, impaired health status and a degree of reversibility of airflow obstruction), the World Health Organization recommend to test every patient with a diagnosis of COPD or adult-onset asthma for A1AT deficiency. Despite these recommendations, the epidemiology of A1AT deficiency remains uncertain. Although recently discovered A1AT deficiency has affected human populations since antiquity. By using scientific data and recently studied skeletons and historical cases, we show that it is now possible to reconstruct the natural history of pathological processes, whether due to genetic, infectious or environmental factors. We believe that the evolution of disease in patients and research to elucidate the relationship between social science and environmental are pertinent contemporaneous subjects.

Introduction Recent paleopathological cases have shown the usefulness of interdisciplinary odontological studies in the investigation of historical figures. Observation A macroscopic examination of the mandible of Saint-Louis (13th c. AD), conserved in the cathedral of Notre-Dame (Paris, France) was carried out, and compared with biographical data about the life and death of the King, and contemporaneous cases of infectious/inflammatory diseases. We found post-mortem tooth loss associated with moderate signs of infectious and inflammatory diseases, which precise diagnoses are discussed facing historical chronicles and sources: main diagnosis is scurvy, potentially associated with bacterial infection. Discussion Our results support the identification of the relics, and improve the knowledge about the saint's circumstances of death related to metabolic deficiencies and infections.

St. John of the Cross (1542–1591) died aged 49 years after 3 months of excruciating pain following a trivial lesion in his right foot. Erysipelas, a superficial bacterial infection of the skin, and subsequent sepsis were previously suggested as the cause of his death. Here, an alternative diagnosis is proposed. An accurate perusal of his biography allowed the symptomatology, the clinical evolution, the depth of the infection and the associated systemic manifestations displayed by Fray John to be reconstructed. St. John of the Cross developed cellulitis in the foot, which turned into a cutaneous abscess. To treat the toxaemia and inhibit further necrosis of the skin, excision of necrotic tissue and cauterization of the sores were performed to no avail. The infection burrowed through the fascial planes and reached the bones of the leg, leading to osteomyelitis. In the absence of antibiotic treatments and proper antiseptic procedures, the soft-tissue infection spread deeper to the bones. It is not unconceivable that the surgery might have further promoted the spread of the bacteria giving rise to the secondary sepsis that led to St. John’s premature death.