Treatment adherence rates across different psychiatric disorders and settings: findings from a large patient cohort.

Approximately 50% of patients with psychiatric disorders do not fully adhere to the prescribed psychopharmacological therapy, significantly impacting the progression of the disorder and the patient's quality of life. The present study aimed to assess potential differences in terms of rates and clinical features of treatment adherence in a large cohort of psychiatric patients with different diagnoses attending various psychiatric services. The study included 307 psychiatric patients diagnosed with a primary major depressive disorder, bipolar disorder, anxiety disorder, schizophrenic spectrum disorder, or personality disorder. Patient's adherence to treatment was evaluated using the Clinician Rating Scale, with a cutoff of at least five defining adherence subgroups. One-third of the sample reported poor medication adherence. A lower rate of adherence emerged among patients with schizophrenic spectrum disorder and bipolar disorder. Subjects with poor adherence were more frequently inpatients and showed higher current substance use, a greater number of previous hospitalizations, and more severe scores at psychopathological assessment compared with patients with positive adherence. Poor adherence was associated with symptom severity and increased rates of relapses and rehospitalizations. In addition, substance use appears to be an unfavorable transdiagnostic factor for treatment adherence.

Historical account of clinical observations on leprosy and related manifestations in the Comacchio area, Italy, in the XIX century.

Known before Christ and in ancient Egypt, leprosy was believed to be a mysterious disease of supernatural origin. It covered the body with lumps and sores, dulled the senses, produced altered facial features and mutilation of the limbs. By the 6th century AD, the disease had certainly made its appearance in Western Europe and continued to occur in the following centuries. It was also thought to be attributable to poverty and poor sanitation. Leprosy was not considered an infectious disease until 1873, when physician G. H. A. Hansen first identified Mycobacterium leprae, calling it Hansen's bacillus, and the disease was named Hansen's disease. This paper analyses clinical reports on leprosy observed in Northern Italy, in the Comacchio area near Ferrara (Po Delta), in the 19th century, taking into consideration documents and manuscripts of the time. The scholars who made the greatest contribution to the description of the disease in and around Comacchio area were Antonio Campana, Andrea Verga, Alessandro Colla, Clodoveo Biagi, Ottone Schrön, Giacomo Sangalli, Raffaele Cavalieri, and local physicians Cristoforo Belloli, and Francesco Ballotta. Observations on the manifestations of the disease and attempts to cure it, including milk diet, are reported. In particular, this morbid form, which was not found in neighboring territories, was called "Mal di formica" because of its benignity at onset, its slowness and its slow progress. Tubercular Leprosy or Mal di fegato, a form of incurable leprosy was nothing more than the leprosy or elephantiasis described by the Greeks and Hebrews. The people most affected were women, who accounted for two-thirds of the sick. According to some authors, the causes of leprosy could be attributed to overuse of certain rotten or salted fish. Campana was the first to think that a lazaret should be erected for the sick.

The role of endoplasmic reticulum aminopeptidases in type 1 diabetes mellitus.

Type-I diabetes mellitus (T1DM) is generally considered as a chronic, T-cell mediated autoimmune disease. This notwithstanding, both the endogenous characteristics of ß-cells, and their response to environmental factors and exogenous inflammatory stimuli are key events in disease progression and exacerbation. As such, T1DM is now recognized as a multifactorial condition, with its onset being influenced by both genetic predisposition and environmental factors, among which, viral infections represent major triggers. In this frame, endoplasmic reticulum aminopeptidase 1 (ERAP1) and 2 (ERAP2) hold center stage. ERAPs represent the main hydrolytic enzymes specialized in trimming of N-terminal antigen peptides to be bound by MHC class I molecules and presented to CD8+ T cells. Thus, abnormalities in ERAPs expression alter the peptide-MHC-I repertoire both quantitatively and qualitatively, fostering both autoimmune and infectious diseases. Although only a few studies succeeded in determining direct associations between ERAPs variants and T1DM susceptibility/outbreak, alterations of ERAPs do impinge on a plethora of biological events which might indeed contribute to the disease development/exacerbation. Beyond abnormal self-antigen peptide trimming, these include preproinsulin processing, nitric oxide (NO) production, ER stress, cytokine responsiveness, and immune cell recruitment/activity. The present review brings together direct and indirect evidence focused on the immunobiological role of ERAPs in T1DM onset and progression, covering both genetic and environmental aspects.

The Italian lazarets of the Adriatic Sea: from their institution to the fight against the economic and demographic collapse caused by epidemics.

Since antiquity, with the growth of the human population and the expansion of nuclei of people (aggregations), infectious diseases have been a constant presence which decisively changed the course of history. The word "lazaret", meaning hospital for the hospitalization and treatment of plague victims and later, also leprosy, is Venetian. It was coined in the 14th century, and was exported to the world; it is still in use although it has slightly modified its meaning: "hospital in general, and shelter for infectious diseases". Lazarets perhaps arose from the overlapping and crossing of the name Nazareth associated with Lazarus, protector of leprosy patients and from other contagious diseases in general. The island of "Lazzaretto Vecchio", overlooking the Lido di Venezia, was named Isola di Santa Maria di Nazareth before the 15th century. However, the first city to take an official step in this direction was the Republic of Ragusa (Croatia), a city-state and flourishing Maritime Republic which was a trading pivot between the Ottoman Empire and the West. In 1377, for the first time in history, the city established a thirty-day quarantine on the three uninhabited islands of Mrkan, Bobara and Supetar for people arriving from infected places. The Republic of San Marco (Venezia) devised one of the oldest and most far-sighted sanitary solutions to contain the spread of the plague: a lazaret, or sanitary model of isolation and treatment that spread, with the name radiating from Venice, around the world. Venetian lazarets were the site of the Republic's innovative strategy to prevent and combat the plague, not only by isolating people for quarantine and goods from infected countries, but also by implementing complex procedures of 'contumacy and purgation' that required a constant investment of economic resources and slowed down traffic. Venice's governors quickly realized that spending money to prevent and fight the plague in lazarets was the only way to counter the economic and demographic collapse caused by epidemics. In the wake of the Venetian and Ragusian lazarets, Trieste also established its first lazaretto in 1717. This was because ships laden with goods from the Near East began to arrive in the city, and this new situation necessitated the adoption of a regulation of contumacy and the construction of a lazaret. This study aims to bring light to the main lazarets over the centuries, particularly those in the Ferrara district and those located in the upper Adriatic Sea, such as Trieste and other neighbouring cities built to fights pandemics.

A Historical Collection of Termites in Ferrara: Recovery, Cataloguing and Geographical Analyses.

Termites are an insect group relevant for recycling of organic matter, but they are also biodeteriogenic and may cause serious damages to wooden structures (including historical buildings and ancient libraries) in anthropogenic environments. The collection of Italian and foreign termites gathered over the years by Antonio Springhetti, Professor of Zoology at the University of Ferrara (Ferrara, Italy) and internationally renowned entomologist, contains over 44,000 specimens, collected by Springhetti during his field campaigns or donated by other entomologists from all over the world. The collection is currently preserved at the Department of Life Sciences and Biotechnology of the University of Ferrara. Unfortunately, all documents, publications and notes concerning the Springhetti Collection were lost; thus, in 2020, the collection was completely re-catalogued within the University Museum System and analyzed in detail. The collection contains specimens dating back to 1878 and represents not only a valuable scientific tool for studies on these ecologically relevant insects that may cause damages to historical buildings, ancient books and artworks but also an important cultural asset for the University Museum System.

Analysis of Insect Pests in an 18th-Century Historical Pharmacy: A Case Study in Ferrara.

Historical pharmacies are valuable artistic, cultural, and scientific assets. In Italy, 482 historical pharmacies have been catalogued thus far, among which is the Navarra-Bragliani Pharmacy in Ferrara, whose wood furniture dates back to the 18th century. A study on insects causing biodeterioration was carried out for the first time on this valuable asset in order to monitor and preserve it. Insect samples were collected during surveys and examined by stereomicroscopy and scanning electron microscopy, using taxonomical keys for identification. The results revealed the presence of three species of Coleoptera-the first one specialised to attack wood materials, the second one polyphagous, and the third one feeding on materials of animal origin. The data obtained in this investigation may be useful for the preservation of the precious furnishing of the historical Navarra-Bragliani Pharmacy for performing similar studies on other ancient pharmacies aimed to protect these valuable cultural and scientific assets.

Antigen presentation in SARS-CoV-2 infection: the role of class I HLA and ERAP polymorphisms.

Given the highly polymorphic nature of Human Leukocyte Antigen (HLA) molecules, it is not surprising that they function as key regulators of the host immune response to almost all invading pathogens, including SARS-CoV-2, the etiological agent responsible for the recent COVID-19 pandemic. Several correlations have already been established between the expression of a specific HLA allele/haplotype and susceptibility/progression of SARS-CoV-2 infection and new ones are continuously emerging. Protective and harmful HLA variants have been described in both mild and severe forms of the disease, but considering the huge amount of existing variants, the data gathered in such a brief span of time are to some extent confusing and contradictory. The aim of this mini-review is to provide a snap-shot of the main findings so far collected on the HLA-SARS-CoV-2 interaction, so as to partially untangle this intricate yarn. As key factors in the generation of antigenic peptides to be presented by HLA molecules, ERAP1 and ERAP2 role in SARS-CoV-2 infection will be revised as well.

Cutaneous myiasis in cats and dogs: Cases, predisposing conditions and risk factors.

Two cases of cutaneous myiasis diagnosed in 2018 in Emilia-Romagna region (northern Italy) were reported. The first one, described in a domestic cat Felis silvestris catus L. (Carnivora: Felidae) and caused by Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae), was the first one of this type ever reported in Italy in cats. The second one was described in a domestic dog Canis lupus familiaris L. (Carnivora: Canidae) and caused by Lucilia sericata (Meigen) (Diptera: Calliphoridae) and was unusual because it occurred in absence of lesions. An extensive literature search on cutaneous myiasis in these two domestic animal species was performed in order to draw attention to predisposing conditions and risk factors.

Epidemiological and clinical features of Spanish flu in the city of Ferrara and in Italy. Containment rules and health measures adopted in the past to fight the pandemic.

The "Spanish" flu has often been described as the "Greatest Medical Holocaust in History" and most victims were young and healthy. In Italy, as elsewhere, this pandemic influenza struck in three successive and close waves with incredible speed in a very short time. The virus first arrived in a few Italian regions and gripped the country in an epidemic clamp. When the flu hit Ferrara, the health authorities began to claim that it was no more or less like the same disease that Ferrara had also experienced in the 19th century, although the population was not very willing to believe them. Moreover, the control measures were considered by all to be extremely mild, varying only the opening hours of cinemas and pharmacies and forbidding spitting on the ground; there was no disinfection of stores and streets and the dead were left at home for three days, unlike in larger cities. In 1918-19, Ferrara did much to contain the devastating effects of the war, especially in terms of saving lives. The largest Red Cross unit in Italy, later called Ospedale Nuovo, was built. Moreover, since Ferrara was the first hospital evacuation zone, it was necessary to build other hospitals in the city's schools in addition to the already existing ones, including the famous Ospedale Militare Neurologico di Villa Seminario, which was the first Italian neurological hospital of the Great War for veterans of the front line, intended for the specialised treatment of nervous disorders and psychosis caused by the war or by bombs. We have extracted the cases of death from the Register of Deaths of the Municipality of Ferrara. During the period January 1918 - June 1919, in addition to the number of deaths due to influenza, grippe or Spanish flu we also considered influenza-related complications affecting mortality and identified seven main groups of diseases by grouping them according to morbid forms and anatomical location. According to these criteria, 1,059 deaths were attributable to influenza or related causes during January-December 1918. This partly reflects the excess of deaths in the year 1918 of 1,279 over the average for the years 1916-1919, and 1920. The largest number of deaths was attributable to bronchopneumonia and pneumonia. However, an increase in mortality from other infectious diseases such as typhoid ileus, tuberculosis, malaria and smallpox was observed during the same period until January 2019, making up the shortfall in the total number of deaths recorded.

Control measures of a 400-year-old plague epidemic: an example of past efficiency at controlling disease and similarities with current epidemics.

The plague caused by the bacterium Yersinia pestis, provides one of the best historical examples of pandemic infection. It can therefore be considered the first "globalized" disease, thanks also to the crowds that favoured the rebalancing of infectious agents between Europe and the Middle East. In this paper we analyse all the official documents of the time, highlighting the most effective prevention measures implemented in the city of Ferrara during the Italian plague. Historical mortality data for the 1630 Italian plague in northern Italy are first analysed. In contrast to the high rates recorded throughout the area from Milan to Florence, the mortality rate in Ferrara remained normal over the period. From the city's documents it emerged that the authorities, from the 16th century onwards, had already understood that the spread of the contagion could also occur through domestic animals, although rats are never mentioned. The strength of Ferrara's response to the "plague emergency" stems from an efficient and emergency-ready health control system, financed and supported by the "permanent surveillance team of the city and the Pontifical Legation of Ferrara - Azienda Sanitaria Pubblica" even in times of great economic difficulty for the State. Among the various measures that the city of Ferrara adopted to deal with the plague the following should be mentioned: guards at the city gates, lazarettos, safety of doctors, self-isolation and treatment of every suspicious case as if it were a real case of plague, measures to support the poorer classes of the population, veterinary and hygiene standards for the city and for housing, management of Catholic religious functions and the precepts of the Legation of Ferrara, which was under papal control, closure of churches to avoid mass gatherings, and limitations of all kinds of social and economic relations within and outside the population. The broad regimen, laid down in the 16th century, contains extremely modern health rules which are very much in line with those recommended by the WHO and the health authorities of each individual state in the current COVID-19 pandemic, even starting with hand-washing. The fight against epidemics of the past, especially the history of the plague in the 17th century, anticipates very important and valid concepts, and represents a wake-up call for the recent epidemics of emerging pathogens.

A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection?

Following influenza infection, rs2248374-G ERAP2 expressing cells may transcribe an alternative spliced isoform: ERAP2/Iso3. This variant, unlike ERAP2-wt, is unable to trim peptides to be loaded on MHC class I molecules, but it can still dimerize with both ERAP2-wt and ERAP1-wt, thus contributing to profiling an alternative cellular immune-peptidome. In order to verify if the expression of ERAP2/Iso3 may be induced by other pathogens, PBMCs and MDMs isolated from 20 healthy subjects were stimulated with flu, LPS, CMV, HIV-AT-2, SARS-CoV-2 antigens to analyze its mRNA and protein expression. In parallel, Calu3 cell lines and PBMCs were in vitro infected with growing doses of SARS-CoV-2 (0.5, 5, 1000 MOI) and HIV-1BAL (0.1, 1, and 10 ng p24 HIV-1Bal/1 × 106 PBMCs) viruses, respectively. Results showed that: (1) ERAP2/Iso3 mRNA expression can be prompted by many pathogens and it is coupled with the modulation of several determinants (cytokines, interferon-stimulated genes, activation/inhibition markers, antigen-presentation elements) orchestrating the anti-microbial immune response (Quantigene); (2) ERAP2/Iso3 mRNA is translated into a protein (western blot); (3) ERAP2/Iso3 mRNA expression is sensitive to SARS-CoV-2 and HIV-1 concentration. Considering the key role played by ERAPs in antigen processing and presentation, it is conceivable that these enzymes may be potential targets and modulators of the pathogenicity of infectious diseases and further analyses are needed to define the role played by the different isoforms.

Comparative Study of SPA Mud from "Bacino Idrominerario Omogeneo dei Colli Euganei (B.I.O.C.E.)-Italy" and Industrially Optimized Mud for Skin Applications.

The term "Salus per aquam (SPA) therapies" refers to therapeutic pathways that includes mud therapy. The therapeutic efficacy of a peloid depends on its chemical and mineralogical composition, as well as its technological properties. Considering the increasing use of clay-based products, it becomes essential to characterize peloids from a qualitative and quantitative point of view. Therefore, this research project aimed to develop a protocol that allows characterization of the chemical-physical composition of sludges collected from different areas of the Homogeneous Euganean Hills Hydromineral Basin (B.I.O.C.E.). The study established a comparative study both between different matrices and between the same matrices at different maturation times, including also a comparison with an industrialized product, that can be used at home, which maintains the characteristics of a natural mud. This research was developed studying the pH, grain size distribution, and chemical and mineralogical composition. Peloids are characterized by a neutral/basic pH and are divided into two categories from a granulometric point of view: The chemical composition allowed observation of numerous correlations between oxides present in the samples and to quantify the presence of heavy metals. Mineralogical analysis made it possible to identify and compare the composition of each sample, also according to the maturation time. Thanks to the methods adopted, important correlations were achieved.

An Overview on ERAP Roles in Infectious Diseases.

Endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 (ERAPs) are crucial enzymes shaping the major histocompatibility complex I (MHC I) immunopeptidome. In the ER, these enzymes cooperate in trimming the N-terminal residues from precursors peptides, so as to generate optimal-length antigens to fit into the MHC class I groove. Alteration or loss of ERAPs function significantly modify the repertoire of antigens presented by MHC I molecules, severely affecting the activation of both NK and CD8+ T cells. It is, therefore, conceivable that variations affecting the presentation of pathogen-derived antigens might result in an inadequate immune response and onset of disease. After the first evidence showing that ERAP1-deficient mice are not able to control Toxoplasma gondii infection, a number of studies have demonstrated that ERAPs are control factors for several infectious organisms. In this review we describe how susceptibility, development, and progression of some infectious diseases may be affected by different ERAPs variants, whose mechanism of action could be exploited for the setting of specific therapeutic approaches.

Empirical "integrated disease management" in Ferrara during the Italian plague (1629-1631).

Plague, a highly infective disease caused by Yersinia pestis (Proteobacteria: Enterobacteriales), ravaged Europe from 1347 over the course of more than 450 years. During the Italian Plague (1629-1631), the disease was rampaging in the entire Northern Italy down to Tuscany, but the city of Ferrara was relatively spared, in spite that the economic activities were maintained with highly affected cities, such as Milan, through the relevant salt commerce. The aim of the study is to evaluate the hygiene rules that were effective in preventing the spread of the plague in Ferrara in 1630, by examining historical documents and reports. According to these documents, a kind of empirical "integrated disease management" was carried out, using remedies including compounds with bactericidal, anti-parasite and repellent activity, and by technical strategies including avoidance of possible plague carriers. The anti-plague remedies and technical strategies used in ancient Ferrara are critically analysed using a multidisciplinary approach (pharmaceutic, medical, epidemiologic and entomological) and compared to current prevention protocols.

Gonorrhea, a current disease with ancient roots: from the remedies of the past to future perspectives.

Gonorrhea can be traced back to the earliest records of the human race even if Albert Neisser first described gonococcus in 1879. The Romans, Jews and Arabs all have documents referring to gonorrhea and each society had their own description of symptoms and treatment. The Roman physician Galen in 130 AD described the disease as an "involuntary escape of semen". The word itself derives from the Greek, meaning "the flow of seed". Gonorrhea is currently the second most commonly notifiable sexually transmitted infection (STI) reported to Centers for Disease Control and Prevention (CDC), second only to chlamydial infection. Gonorrhea notifications have been on the rise all over the world and in several European countries since the early 2000s, particularly in populations with higher frequency of spread of STIs, such as men who have sex with men and young heterosexual individuals of both sexes. Having been recognized at least 3500 years ago, the fight against the disease began infinitely before the antibiotic era, using healing compounds. In the absence of an ideal vaccine, the most important challenge today is the emergence of the multidrug-resistant gonorrhea, which is currently the main reason for public concern responsible for the evolution of N. gonorrheae into a superbug. N. gonorrheae strains resistant to extended spectrum cephalosporin (ESC) form a threat to effective control of gonorrhea for which there are currently ongoing clinical trials to evaluate the efficacy and safety profile of old and new antimicrobial molecules for monotherapy and as dual therapy of gonorrhea. In this paper we investigated the remedies and treatments employed against gonorrhea during the 19th century in Ferrara, referring to Campana's Pharmacopoeia and unpublished manuscripts concerning the treatment of this disease in medical practice. The remedies for gonorrhea adopted in the city were in line with those utilized in other countries. Among these, copaiba oleoresins have been demonstrated to have been efficacious in the past against gonococcal disease in popular medical use and, recently, against a large number of bacteria, fungi and protozoa, which will call for more in vitro and clinical studies to evaluate their real effectiveness on the N. gonorrheae bacterium.

Ancient treatment for lice: a source of suggestions for carriers of other infectious diseases?

Louse infestation is one of the oldest contagious pestilential diseases of humankind, which has recently re-emerged in several developing countries as well as in homeless individuals and migrants. The present work provides the first phase of an historical excursus of louse remedies based on the classics of pharmaceutical literature, codes, pharmacopoeia and treatises. The second phase involves a literature search, based on the principal medical databases (SciFinder, Pubmed, Google Scholar, ISI-Web of Science and Scopus), to match ancient raw materials and active principles for the treatment of pediculosis and their possible applications, with other current infectious pathologies transmitted by different carriers. In this regard, Rhododendron tomentosum has revealed repellent insect activity, particularly against Aedes aegypti, responsible for Dengue fever, Chikungunya, Zika fever, Mayaro, yellow fever and other infectious diseases. Petroselinum crispum is an insecticide employed for resistant strains of A. aegypti. In the case of Delphinium staphisagria, the phytochemical profile was further investigated with the identification of further molecules in addition to delphinine. The latter shows interesting activities against Trypanosoma cruzi and Leishmania. Anthemis pyrethrum, now renamed as Anacyclus pyrethrum, although not containing pyrethrins present in several plants of the genus Chrysanthemum, revealed pediculicidal activity but did not produce satisfactory results in antiprotozoal activity.

Essential oil extraction, chemical analysis and anti-Candida activity of Foeniculum vulgare Miller - new approaches.

A comprehensive study on essential oil samples of Foeniculum vulgare Miller from Tarquinia (Italy) is reported. A 24-h systematic steam distillation was performed on different harvested samples applying different extraction times. The GC-MS analysis of the residue outcome showed o-cymene, α-phellandrene, α-pinene and estragole as the major constituents. The predominance and continued presence of o-cymene makes this fennel oil a rather unique chemotype. An evident correlation between the antifungal activity and phenological stage is demonstrated. The most active fractions were particularly rich in estragole, as well as a significant amount of fenchone that possibly exerts some additive effect in the expression of overall antifungal potency. Pre-fruiting material produced oil particularly rich in o-cymene. With reference to the duration of the extraction, the maximum amount of oil was released within the first 3 h, whereas the reproductive phase material needed at least 6 h for the extraction.

Antidermatophytic Action of Resorcinol Derivatives: Ultrastructural Evidence of the Activity of Phenylethyl Resorcinol against Microsporum gypseum.

In this work, we evaluated the antidermatophytic activities of three resorcinol derivatives that have a history of use in dermo-cosmetic applications to discover molecules with multiple dermatological activities (i.e., multi-target drugs), thereby reducing the cost and time necessary for new drug development. The antidermatophytic activities of the three skin lighteners were evaluated relative to the known antifungal drug fluconazole on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum, Microsporum canis, Trichophyton violaceum, Arthroderma cajetani, Trichophyton mentagrophytes, Epidermophyton floccosum, Nannizzia gypsea, Trichophyton rubrum and Trichophyton tonsurans. Among the three tested resorcinols, only two showed promising properties, with the ability to inhibit the growth of all tested dermatophytes; additionally, the IC50 values of these two resorcinols against the nine dermatophytes confirmed their good antifungal activity, particularly for phenylethyl resorcinol against M. gypseum. Ultrastructural alterations exhibited by the fungus were observed using scanning electron microscopy and transmission electron microscopy and reflected a dose-dependent response to treatment with the activation of defence and self-preservation strategies.

[The nineteenth-century epidemic waves of influenza]. / L'influenza nelle ondate epidemiche del XIX secolo.

The retrospective analysis undertaken by our working group in the sphere of infectious diseases, with particular emphasis on nineteenth-century epidemics, regards influenza, which according to the scholar W.I. Beveridge, was defined as "one of the greatest enemies of man". The work is divided into three parts: influenza, its historical names and the characteristics of the recurrent epidemics from the sixteenth to the nineteenth century among the world's population. This part is followed by treatment and remedial action in the nineteenth century. The third, deals with death attributed to influenza and its complications observed in the city of Ferrara in the years when outbreaks occurred, affecting the majority of the populations: 1830-1833, 1836-1837, 1847-1848, 1857-1858, 1873-1875, 1889-1892, the latter known as the great pandemic.