Noise-induced hearing loss in the pre-industrial era: early contributions in De Morbis Artificum by Bernardino Ramazzini (1633-1714).

OBJECTIVE: Noise-induced hearing loss is the most prevalent occupational disease worldwide and is historically associated with the Industrial Revolution. This study analyses early descriptions of this disorder during the pre-industrial period in the work of the Italian physician Bernardino Ramazzini (1633-1714). METHOD: Primary and secondary historical literature were reviewed. RESULTS: Ramazzini described hearing loss in corn millers and in coppersmiths and recognised that this disorder is irreversible and progressive when exposure to noise continues. He also seemed to describe tinnitus. He further suggested the use of earplugs as a preventive measure for these classes of workers. Ramazzini's anatomical and pathological knowledge appears to be based on ancient authors; he did not discuss contemporaneous medical authors' work on hearing function. CONCLUSION: Despite some limitations, Ramazzini's work appears pioneering for his time and represents an important milestone in the history of otolaryngology.

Exposure to chronic stress impairs the ability to cope with an acute challenge: Modulation by lurasidone treatment.

Chronic stress represents a major contributor for the development of mental illness. This study aimed to investigate how animals exposed to chronic mild stress (CMS) responded to an acute stress (AS), as a vulnerability's challenge, and to establish the potential effects of the antipsychotic drug lurasidone on such mechanisms. Adult male Wistar rats were exposed or not (controls) to a CMS paradigm for 7 weeks. Starting from the end of week 2, animals were randomized to receive vehicle or lurasidone for 5 weeks. Sucrose intake was used to measure anhedonia. At the end, half of the animals were exposed to an acute stress before sacrifice. Exposure to CMS produced a significant reduction in sucrose consumption, whereas lurasidone progressively normalized such alteration. We found that exposure to AS produced an upregulation of Brain derived neurotrophic factor (Bdnf) in the prefrontal cortex of controls animals. This response was impaired in CMS rats and restored by lurasidone treatment. While in control animals, AS-induced increase of Bdnf mRNA levels was specific for Parvalbumin cells, CMS rats treated with lurasidone show a significant upregulation of Bdnf in pyramidal cells. Furthermore, when investigating the activation of different brain regions, CMS rats showed an impairment in the global response to the acute stressor, that was largely restored by lurasidone treatment. Our results suggest that lurasidone treatment in CMS rats may regulate specific circuits and mechanisms, which will ultimately contribute to boost resilience under stressful challenges.

A damned soul with goiter. "The life of Christ" (c. 1480) by Giovanni Martino Spanzotti.

The church of San Bernardino in Ivrea (Piedmont) houses a cycle of frescoes of "The Life of Christ" by the Italian painter Giovanni Martino Spanzotti. In the painting, a damned soul of the Hell with a large bi-lobar goiter is represented, confirming the interest of Renaissance artists towards thyroid diseases.

The sponge-bearer suffers from goiter: "The Passion of Christ" (c. 1530) by Fermo Stella.

In the partition of the church of San Bernardino in Caravaggio (Lombardy), Fermo Stella (c. 1490-1562) depicted a cycle of frescoes of "The Passion of Christ". In the central panel, "The Crucifixion" one of the tortures of Christ, the sponge-bearer, shows a large goiter and other signs of hypothyroidism (macroglossia, expressionless face, and puffiness around the eyes), confirming that the Renaissance artists often represented sinful and wicked individuals as affected by thyroid diseases.

Association between seasonal flu vaccination and COVID-19 among healthcare workers.

BACKGROUND: In next fall and winter, SARS-CoV-2 could circulate in parallel with seasonal influenza. The dual epidemics will result in considerable morbidity and mortality; therefore, influenza vaccination may be essential. Recent studies found increased risk of coronavirus in individuals receiving influenza vaccination. AIMS: Our aim is to analyse the association between influenza vaccination and COVID-19 in a population of healthcare workers (HCWs). METHODS: IgG antibodies against SARS-CoV-2 were detected in 3520 HCWs at a large hospital in Northern Italy. For each participant, we collected data on flu immunization status for the last five flu seasons. Logistic regression was used to test associations between seasonal flu vaccination status and a positive serology tests for COVID-19. RESULTS: During the last five flu seasons, 2492 vaccinations were administered. Serology tests were negative for 3196 (91%) HCWs and residents and only 21 (1%) people had an equivocal test (12.0-15.0 AU/mL). Only 128 (4%) people received a diagnosis of COVID-19, with a positive swab test. No flu vaccinations for the last five flu seasons were specifically associated with diagnosis of COVID-19 or with positive results of serology tests. CONCLUSIONS: Flu vaccinations did not appear to be associated with SARS-CoV-2 infection. Influenza vaccination should continue to be recommended for HCWs and for individuals at increased risk for severe illness from respiratory infection.

At the origin of "Endocrinology and Art": Woman's Head (third century BCE).

In 1911, the Danish physician Hans Christian Gram (1853-1938) sustained to have found signs of hyperthyroidism in a marble head of a Roman woman that he observed in the Ny Carlsberg Glyptotek in Copenhagen. It could be one of the first examples of a clinical diagnosis of an endocrine disease in an ancient statue.

Self-reported prevalence of sleep disorders among medical and nursing students.

BACKGROUND: Sleep disorders are highly prevalent among university students. In particular, the symptoms of sleep disorders are more prevalent among healthcare students. AIMS: To assess the prevalence of risk factors of insomnia and sleep disorders and to examine the correlations between them among nursing and medical students. We also compared the effects of shift work during internship. METHODS: The sample was 417 healthcare students; 202 of them were nursing students, and the remaining 215 were medical students. We used a self-administered questionnaire to assess the risk factors for insomnia (i.e. age, BMI, tobacco consumption, physical activity and perceived stress, using the General Health Questionnaire-12). We also used the Sleep and Daytime Habits Questionnaire and Epworth Sleepiness Scale to assess the prevalence of sleep disorders and daytime sleepiness. RESULTS: A higher percentage of nursing students than medical students were aged 25 years or older, engaged in inadequate levels of physical activity and consumed tobacco. With the exception of tobacco consumption among nursing students, high scores on the GHQ-12 were the only risk factor associated with daytime and nighttime symptoms and poor sleep quality. There was no significant association between the symptoms of sleep disorders and shift work including night shifts. CONCLUSIONS: Since sleep disorders are highly prevalent among healthcare students, early detection and management is recommended. This will decrease the risk of harm to students and patients, due to medical mistakes.

"The giant Hans Kraus" (1553): a Renaissance acromegaly by anonymous painter.

The Wunderkammer of Schloss Ambras in Innsbruck was one of the first cabinets of curiosities, created in the sixteenth century. Among the many curiosities, the cabinet includes an anonymous Renaissance painting called "Der Riese Hans Kraus" (The giant Hans Kraus). The details suggest us that it could be a representation of an individual affected by acromegaly.

Maternal stress during pregnancy induces depressive-like behavior only in female offspring and correlates to their hippocampal Avp and Oxt receptor expression.

The majority of studies examining the consequences of prenatal stress in rodent models analyze pups having been raised by their biological mother, i.e. the female which experienced stress during her pregnancy. To test whether pregnancy stress changes maternal behavior and thereby - in addition to stress exposure in utero - influences behavior and brain function of offspring, we implemented a fostering model, in which mouse pups that were not stressed in utero, are raised by dams which were exposed to stress during their pregnancy. We found that dams, which were stressed during pregnancy (PS foster dams), unexpectedly displayed slightly more active and passive light time nursing compared to unstressed dams (CON foster dams). Adult male offspring which were raised by a PS foster dam showed significantly less anxiety-like behavior compared to males raised by a CON foster dam, whereas adult female offspring which were raised by PS foster dams displayed increased depressive-like behavior as a tendency. Since the arginine vasopressin receptor 1a (AvpR1a) and the structurally related oxytocin receptor (OxtR) are both closely related to stress-responsiveness, anxiety and depression, mRNA expression of these genes were assessed in the hippocampus of adult male and female offspring. No significant differences in mRNA expression of both receptor types were observed, however, in female offspring of PS foster dams maternal licking/grooming correlated positively with AvpR1a and negatively with OxtR mRNA expression. These findings indicate that stress during pregnancy does not reduce, but slightly increase maternal behavior, which might lead to sex-specific behavioral outcomes and changes in hippocampal AvpR1a and OxtR mRNA expression in adult offspring.

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets.

Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses and a major cause of morbidity worldwide. Currently available antidepressants are effective for most patients, although around 30% are considered treatment resistant (TRD), a condition that is associated with a significant impairment of cognitive function and poor quality of life. In this respect, the identification of the molecular mechanisms contributing to TRD represents an essential step for the design of novel and more efficacious drugs able to modify the clinical course of this disorder and increase remission rates in clinical practice. New insights into the neurobiology of TRD have shed light on the role of a number of different mechanisms, including the glutamatergic system, immune/inflammatory systems, neurotrophin function, and epigenetics. Advances in drug discovery processes in TRD have also influenced the classification of antidepressant drugs and novel classifications are available, such as the neuroscience-based nomenclature that can incorporate such advances in drug development for TRD. This review aims to provide an up-to-date description of key mechanisms in TRD and describe current therapeutic strategies for TRD before examining novel approaches that may ultimately address important neurobiological mechanisms not targeted by currently available antidepressants. All in all, we suggest that drug targeting different neurobiological systems should be able to restore normal function but must also promote resilience to reduce the long-term vulnerability to recurrent depressive episodes.

The "thirsty dropsy": Early descriptions in medical and non-medical authors of thirst as symptom of chronic heart failure.

BACKGROUND: Patients with chronic heart failure may suffer from severe thirst, even if mechanisms that cause thirst in subjects affected by this condition are not clear. Medical and non-medical authors may have already recognized this symptom during the classical age. METHODS: We analyzed association between thirst and dropsy (an ancient medical term used to indicate different conditions including chronic heart failure) in past medical and non-medical literature. RESULTS: Hippocrates and Celsus first recognized thirst as a symptom of dropsy in the classical age. Greco-Roman intellectuals (Polybius, Ovid, Horace) and theologians belonging to the first years of the Christian era (Augustine, Caesarius, Gregory I) showed to know that dropsy people were often thirsty. These authors also influenced medieval poets and writers, including Dante Alighieri. In the Renaissance, the physician and alchemist Paracelsus again evidenced this symptom and the iatrochemist Robert Fludd tried to explain pathophysiology of dropsy, basing on thirst. CONCLUSIONS: The relationship between thirst and dropsy was well known by physicians and intellectuals in the classical age and in the first years of the Christian era, so influencing the Renaissance physicians.

Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events.

Stressful life events occurring in adulthood have been found able to affect mood and behavior, thus increasing the vulnerability for several stress-related psychiatric disorders. However, although there is plenty of clinical data supporting an association between stressful life events in adulthood and an enhanced vulnerability for psychopathology, the underlying molecular mechanisms are still poorly investigated. Thus, in this study we performed peripheral/whole-genome transcriptomic analyses in blood samples obtained from 53 adult subjects characterized for recent stressful life events occurred within the previous 6 months. Transcriptomic data were analyzed using Partek Genomics Suite; pathway and network analyses were performed using Ingenuity Pathway Analysis and GeneMANIA Software. We found 207 genes significantly differentially expressed in adult subjects who reported recent stressful life experiences (n=21) compared with those without such experiences (n=32). Moreover, the same subjects exposed to such stressful experiences showed a reduction in leukocyte telomere length. A correlation analyses between telomere length and transcriptomic data indicated an association between the exposures to recent stressful life events and the modulation of several pathways, mainly involved in immune-inflammatory-related processes and oxidative stress, such as natural killer cell signaling, interleukin-1 (IL-1) signaling, MIF regulation of innate immunity and IL-6 signaling. Our data suggest an association between exposures to recent stressful life events in adulthood and alterations in the immune, inflammatory and oxidative stress pathways, which could be also involved in the negative effect of stressful life events on leukocyte telomere length. The modulation of these mechanisms may underlie the clinical association between the exposure to recent Stressful life events in adulthood and an enhanced vulnerability to develop psychiatric diseases in adulthood.