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Since COVID-19 began to spread, hypotheses about the possible causes of the disease and its treatment have increased worldwide, engenedering fears and concerns. This context of uncertainty, as well as the great changes that people were forced to accept in their daily lives, have challenged the general population, affecting public opinion and collective imagination inevitably, with also a negative impact on compliance with public health policies. This study explored the personal attitudes towards the COVID-19 pandemic and their association with denial stances in the Italian context. The aim was to address the relevance of these phenomena and in what guise they are present in relation to the grounds supporting them, as an avenue to be more effective in public health under different domains. An online questionnaires was set out to survey the general population over 18 throughout the Italian country, including students and health professionals, to offer geographic and professional diversity. General population was also stratified based on their direct or indirect experience of COVID-19, whilst health participants were recruited with regard to their involvement in a COVID centre. A total of 2110 questionnaire were filled out between December 2020 and April 2021. Of the participants, 85.45% completely disagree with the possibility that COVID-19 is not real and that the cultural, social and economic system wanted us to believe otherwise, whereas 69% had doubts about what has been claimed to date about the existence of COVID-19. Trust in institutions and types of COVID-19 experience affected these beliefs. The results also show that stress, anxiety, sadness, and vulnerability increased as compared to the pre-COVID- 19 pandemic timeframe. The fundings of this national survey revealed how much behaviors based on social responsibility and rational prudence are important for defensing human life.

The American Board of Oral and Maxillofacial Surgery (ABOMS) has been serving the specialty since 1946. The ABOMS frequently reviews its strategic plan, mission, and vision. The board administers 4 examinations (the Oral and Maxillofacial Surgery In-service Training Examination, the Qualifying Examination, the Oral Certifying Examination, and Certificates of Added Qualifications in Head and Neck Oncologic and Reconstructive Surgery and Pediatric Craniomaxillofacial Surgery) and also oversees the Certification Maintenance process for diplomates. The members of the Examination Committee and directors are volunteers who create, validate, and deliver examination content for the various examinations by the ABOMS.

Histone deacetylase inhibitors (HDACis) are part of a growing class of epigenetic therapies used for the treatment of cancer. While elevated levels of the efflux pump P-gp are associated within vitroresistance to romidepsin, this mechanism does not translate to the clinic. We developed a romidepsin-resistant cell line with a resistance mechanism independent of P-gp function that acts upstream of the deacetylation process. We found that expression of the methyltransferase METTL7A is necessary for resistance, and that expression of METTL7A in naïve cells can drive resistance to thiol-containing HDACis. We demonstrate that METTL7A can methylate romidesinin vitroand that the ability of METTL7A to drive resistance to thiol-containing HDACis can be blocked by the methyltransferase inhibitor DCMB. Our data supports a model whereby exposure of cells to romidepsin selects for upregulation of the methyltransferase METTL7A, which in turn modifies the zinc-binding thiol, inactivating the drug.

The preparation of homoallylic alcohols by addition of organometallic allyl compounds to carbonyls is an important strategy in organic chemistry. Allylating organometallic cobalt species can be generated employing stoichiometric quantities of Zn acting as reductant. To avoid the employment of stoichiometric amount of Zn, we have developed an allylation reaction of aromatic and aliphatic aldehydes promoted by photoredox catalysis in the presence of a cobalt complex, and we present herein a full account of our research. In the presence of the abundant CoBr2 (10 mol %), 4,4′-di-tert-butyl-2,2′-dipyridyl (dtbbpy, 10 mol %), allyl acetate (3 equiv.), [Ir(dtbbpy)(ppy)2]PF6 (ppy=2-phenylpyridine, 2 mol %), and N,N-diisopropylethylamine (4 equiv.), an allylation of aldehydes is taking place, in moderate to good yields. Substrates scope, limitations, and photophysical investigations of this new process are reported. (Figure presented.).

Directly targeting RAS is a desirable approach for treating RAS-mutated tumors because direct RAS inhibitors block all RAS effector pathways simultaneously. Recently, several groups have developed agents that directly target KRAS by covalently modifying KRASG12C. KRAS is commonly altered in adult malignancies such as lung, pancreatic, and colorectal adenocarcinoma, but is less commonly altered in pediatric cancer. However, rare pediatric tumors harboring K-, H-, or NRASG12C are observed. The efficacy of KRASG12C inhibitors in pediatric malignancies is currently unknown, and the ability of these drugs to modify H- and NRASG12C has been incompletely characterized. Here we show that the KRASG12C inhibitors AMG 510, MRTX849, and ARS-1620 slow the release of GDP from H-, N-, and KRASG12C in vitro. Using RASless MEFs, we show that the activity of AMG 510 is specific for H-, N- or KRASG12C, while MRTX849 has both G12C and RAS-independent effects on cell viability. The KRASG12C inhibitors decreased cell viability in KRAS-mutant cell lines derived from patients with the pediatric solid tumor neuroblastoma. MRTX849 was more potent than AMG 510 in neuroblastoma cell lines but was less efficacious and less G12C-specific. The KRASG12C inhibitors also decreased cell viability in an NRASG12C-mutant T-cell ALL cell line derived from an adolescent patient but only MTRX849 decreased cell viability in an HRASG12C-mutant rhabdomyosarcoma cell line. These results suggest that KRASG12C inhibitors may be a treatment option for pediatric patients with H-, N- or KRASG12C mutant solid tumors or leukemia. Future studies will be aimed at testing the efficacy of these inhibitors in xenograft models of pediatric cancer and identifying non-RAS targets of MRTX849. Citation Format: Hannah Price, Stacey Stauffer, Katie Powell, Andrew Baker, Andrew Perciaccante, Edjay Ralph Hernandez, Patience Odeniyide, Christine Pratilas, William Burgan, Lisa Jenkins, Kent L. Rossman, Marielle Yohe. Preclinical efficacy of KRASG12C inhibitors in models of pediatric cancer [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr B038.

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.

Dysregulation in glomerular hemodynamics favors hyperfiltration in diabetic kidney disease (DKD). Although carnosine supplementation ameliorates features of DKD, its effect on glomerular vasoregulation is not known. We assessed the influence of carnosine and carnosinase-1 (CN1) on afferent glomerular arteriole vasodilation and its association with glomerular size, hypertrophy, and nephrin expression in diabetic BTBRob/ob mice. Two cohorts of mice including appropriate controls were studied: i.e., diabetic mice that received oral carnosine supplementation (cohort 1) and human (h)CN1 transgenic (TG) diabetic mice (cohort 2). The lumen area ratio (LAR) of the afferent arterioles and glomerular parameters were measured by conventional histology. Three-dimensional analysis using a tissue clearing strategy was also used. In both cohorts, LAR was significantly larger in diabetic BTBRob/ob versus nondiabetic BTBRwt/ob mice (0.41?? 0.05 vs. 0.26 ?? 0.07, P < 0.0001 and 0.42 ?? 0.06 vs. 0.29 ?? 0.04, P < 0.0001) and associated with glomerular size (cohort 1: r = 0.55, P = 0.001 and cohort 2: r = 0.89, P < 0.0001). LAR was partially normalized by oral carnosine supplementation (0.34 ?? 0.05 vs. 0.41?? 0.05, P = 0.004) but did not differ between hCN1 TG and wild-type BTBRob/ob mice. In hCN1 TG mice, serum CN1 concentrations correlated with LAR (r = 0.90, P = 0.006). Diabetic mice displayed decreased nephrin expression and increased glomerular hypertrophy. This was not significantly different in hCN1 TG BTBRob/ob mice (P = 0.06 and P = 0.08, respectively). In conclusion, carnosine and CN1 may affect intraglomerular pressure in an opposing manner through the regulation of afferent arteriolar tone. This study corroborates previous findings on the role of carnosine in the progression of DKD. NEW & NOTEWORTHY Dysregulation in glomerular hemodynamics favors hyperfiltration in diabetic kidney disease (DKD). Although carnosine supplementation ameliorates features of DKD, its effect on glomerular vasoregulation is not known. We assessed the influence of carnosine and carnosinase-1 (CN1) on afferent glomerular arteriole vasodilation and its association with glomerular size, hypertrophy, and nephrin expression in diabetic BTBRob/ob mice. Our results provide evidence that carnosine feeding and CN1 overexpression likely affect intraglomerular pressure through vasoregulation of the afferent arteriole.

Since Antiquity, votive offerings were deposited in temples dedicated to deities in order to fulfil a special request of a supplicant. Later, in Orthodox churches, votive offerings entered in the form of anatomical ex-voto or tamata, metallic effigies that realistically represented the disease-affected portion of the body. In this paper, we show four tamata from eighteenth-nineteenth century identified in the museum of the Orthodox monastery of Floresti (Romania); votive offerings that represent ocular pathologies. Even if the supplicants did not have a medical background and often did not fully understand their diseases, the votive offerings demonstrate their ability to observe pathological changes, at the same time emphasising the importance of their faith in the healing process.

Here we report the application of dual nickel/photoredox catalysis to the allylation of aliphatic, aromatic and heteroaromatic aldehydes by using commercially available reagents. The process utilizes the combination of a Ni(ii) complex, [Ru(bpy)3]2+ as a photoredox catalyst, and allylacetate under blue LED irradiation, and allows the synthesis of a large variety of homoallylic alcohols.

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.

Although reprogramming of cellular metabolism is a hallmark of cancer, little is known about how metabolic reprogramming contributes to early stages of transformation. Here, we show that the histone deacetylase SIRT6 regulates tumor initiation during intestinal cancer by controlling glucose metabolism. Loss of SIRT6 results in an increase in the number of intestinal stem cells (ISCs), which translates into enhanced tumor initiating potential in APCmin mice. By tracking down the connection between glucose metabolism and tumor initiation, we find a metabolic compartmentalization within the intestinal epithelium and adenomas, where a rare population of cells exhibit features of Warburg-like metabolism characterized by high pyruvate dehydrogenase kinase (PDK) activity. Our results show that these cells are quiescent cells expressing +4 ISCs and enteroendocrine markers. Active glycolysis in these cells suppresses ROS accumulation and enhances their stem cell and tumorigenic potential. Our studies reveal that aerobic glycolysis represents a heterogeneous feature of cancer, and indicate that this metabolic adaptation can occur in non-dividing cells, suggesting a role for the Warburg effect beyond biomass production in tumors.

Graphical Abstract Application of small chiral organic molecules in catalysis has been dominated by formation of chiral enamines or iminium ions. Nucleophiles – electrophiles reactivity has been exploited in many papers. Now, the possibility to combine organocatalysis with photochemistry open new “exciting” possibilities and opportunities, in reactions that are mediated by radicals.

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.

Chronic kidney disease (CKD) affects 10% of the population worldwide. It often leads to poor quality of life, especially among people suffering from end-stage CKD. Detection and treatment of the renal disorders at an early stage can help in postponing of end-stage disease as well as its treatment options, such as renal transplant and dialysis. The current routine measurement of glomerular filtration rate (GFR) includes methods that are expensive, cumbersome, time-consuming, inaccurate, often inconvenient and invasive for the patients. Non-invasive diagnostic techniques can help to overcome many of these drawbacks. This paper reviews the progress made in the field of transcutaneous GFR measurement as a way for a simpler, non-invasive, cheaper, and patient-friendly assessment of renal function. We have discussed the various markers designed in combination with different measurement devices for the measurement of GFR. Also, we have compared the different kinetic models used to study the marker’s clearance from the plasma; which ultimately helps in calculating the GFR. Most of these techniques have been limited to pre-clinical studies until now, with promising results for their transition into clinical use in the near future.

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.

Introduction La sante des dirigeants mondiaux est une source legitime de preoccupation pour la population et pour les historiens. Les troubles cognitifs peuvent avoir un impact sur les decisions relatives a leur mandat, en particulier lorsqu’ils surviennent au debut de leur mandat. Le cancer et les maladies cardio-vasculaires peuvent entrainer une invalidite avec impossibilite d’exercer les fonctions prevues ou une mort inattendue avec vacance du pouvoir. L’histoire mondiale a montre a plusieurs reprises que les hommes politiques avaient tendance a cacher leur maladie au public bien avant qu’elle ne devienne evidente. Les affections cutanees sont plus difficiles a cacher, lorsqu’elles touchent le visage ou les mains, ou lorsque les traitements systemiques ont un impact sur l’apparence physique. Materiel et methodes Nous avons revu les affections cutanees typiques rencontrees chez les leaders mondiaux et les hommes politiques de l’apres-guerre. Cette selection des cas les plus connus est non exhaustive et se base sur les souvenirs des auteurs, ainsi que sur des sources librement accessibles sur Internet. Nous avons egalement cherche a classer ces affections. Nous avons exclu les caracteristiques cutanees associees au vieillissement (alopecie androgenique, rides), a l’origine ethnique et les traitements cosmetiques presumes. Resultats Les caracteristiques de 26 leaders mondiaux et hommes politiques du 20e siecle, tous de sexe masculin sauf une, ont ete revues. Le vitiligo etait l’affection la plus frequente (n = 5), suivie de la rosacee (n = 4). Discussion Nous avons considere 7 categories d’affections cutanees pouvant s’appliquer aux hommes politiques : – une lesion cutanee “marque de fabrique”, si caracteristique qu’elle permet une identification immediate de l’homme politique : Gorbatchev et sa tache lie de vin ; – une lesion cutanee maligne qui peut avoir un impact sur la carriere politique ou le mandat (Robert Bourassa) ; – des symptomes cutanes qui peuvent reveler une maladie systemique (la peau bronzee de Kennedy, attribuee a la maladie d’Addison ou le syndrome de Cushing iatrogene de Georges Pompidou) ; – les affections cutanees avec impact negatif sur l’image des hommes politiques (le visage rouge de Sir Edward Leigh, les cicatrices d’acne de Manuel Noriega, le vitiligo d’Edouard Philippe) ; – les dermatoses “defigurantes” peuvent avoir un impact positif en termes de perception publique ; – lesions cutanees pouvant etre liees a une agression ou un empoisonnement ; – les affections cutanees centres de couverture mediatique et d’une meilleure reconnaissance du public lorsqu’elles sont divulguees au public (pemphigoide, erysipele, dermatoporose, argyrie). Tout en reconnaissant les limites de notre etude, nous avons pu illustrer le spectre des manifestations cutanees chez les politiciens et leur impact possible, que ce soit pendant leur mandat ou en campagne.

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

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.