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The role of human oncoviruses in melanoma has been poorly investigated. The aim of this study was to investigate the association between oncoviruses and melanomas searching for human papillomavirus (HPV), Epstein Barr virus (EBV), and human herpesvirus 8DNA in melanoma specimens. Formalin-fixed and paraffin-embedded tissue specimens of cutaneous, mucosal, and ocular melanomas (OM) were selected from the Pathology Departments of the Galliera Hospital (Genoa) and the University Hospitals of Turin and Cagliari. Cutaneous and mucosal nevi have been collected as controls. The oncoviruses search has been performed with different polymerase chain reaction reagent kits. Fifty-four melanomas (25 mucosal, 12 ocular, and 17 cutaneous) and 26 nevi (15 cutaneous and 11 mucosal) specimens were selected. The detection rate for one of the investigated oncoviruses was 17% in mucosal, 20% in ocular, and 0% in cutaneous melanomas (CMs). Despite the differences between groups seeming remarkable, there was no statistical significance (p 0.5). Our data do not support a primary role of oncoviruses in melanoma carcinogenesis; however, the finding of HPV and EBV DNA in a considerable fraction of mucosal and OMs suggests that these viruses may act as cofactors in the development of extra-CMs.

We analyze the economic consequences on firm profitability, performance, and investments of having another firm in the same market affiliated with a criminal organization. We do so by evaluating the spillover effects of a law providing the judicial administration of organized crime firms through the imposition of external managers in order to remove the connection to the criminal organization, and at the same time guarantee the continuity of production. By using detailed information on more than 180,000 companies, we exploit the firms’ yearly variation in the exposure to criminal firms’ judicial administration in their market (in the same province and industry). The empirical design allows us to control for confounding effects at the firm, market, and year levels. The results show that there is a large, positive spillover from the enforcement law, suggesting that the burden the organized crime firms impose on other firms is very large. Firms’ performance and turnover increases by 2.2 and 0.7%, respectively, in the first 4 years after an organized crime firm enters the status of judicial administration. Investments measured by tangible and intangible assets increase with the number of firms entering into judicial administration by 0.75%. These results suggest that intensifying confiscation measures against criminal organizations has a strong positive effect on the economy.

This paper studies the spread of compliance behavior in neighborhood networks involving over 500,000 households in Austria. We exploit random variation from a field experiment which varied the content of mailings sent to potential evaders of TV license fees. Our data reveal a strong treatment spillover: 'untreated' households, who were not part of the experimental sample, are more likely to switch from evasion to compliance in response to the mailings received by their network neighbors. We analyze the spillover within a model of communication in networks based on DeGroot (1974). Consistent with the model, we find that (i) the spillover increases with the treated households' eigenvector centrality and that (ii) local concentration of equally treated households produces a lower spillover. These findings carry important implications for enforcement policies.

Pityriasis rosea (PR), PR-like eruptions (PR-LE), and herpes zoster have been frequently reported during the COVID-19 pandemic and following COVID-19 vaccination. PR is a self-limiting exanthematous disease and herpes zoster is a treatable condition; therefore, their occurrence does not require discontinuation of the vaccination schedule. PR-LE is a hypersensitivity reaction and is, therefore, less predictable in its course. In the case of a booster dose, the clinical manifestation may not recur, may be different from PR-LE, or may present with systemic symptoms; however, in the case of PR-LE, the possibility of mild and predominantly cutaneous adverse events should not discourage all eligible candidates from receiving and completing the COVID-19 vaccination program, as such adverse reactions represent a small risk considering the possible severe and fatal outcome of COVID-19. We emphasize the relevance of looking for any viral reactivation in patients infected with SARS-CoV-2 who have skin eruptions. The search for viral reactivations could be useful not only for distinguishing between PR and PR-LE but also because viral reactivations may contribute to a patient's systemic inflammation and influence the course of the disease.

In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical challenges, including absence of an in vitro culture system until very recently, have hampered efforts to catalog the diversity of strains collected worldwide. Here, we provide near-complete genomes from 196 T. pallidum strains – including 191 T. pallidum subsp. pallidum – sequenced directly from patient samples collected from 8 countries and 6 continents. Maximum likelihood phylogeny revealed that samples from most sites were predominantly SS14 clade. However, 99% (84/85) of the samples from Madagascar formed two of the five distinct Nichols subclades. Although recombination was uncommon in the evolution of modern circulating strains, we found multiple putative recombination events between T. pallidum subsp. pallidum and subsp. endemicum, shaping the genomes of several subclades. Temporal analysis dated the most recent common ancestor of Nichols and SS14 clades to 1717 (95% HPD: 1543-1869), in agreement with other recent studies. Rates of SNP accumulation varied significantly among subclades, particularly among different Nichols subclades, and was associated in the Nichols A subclade with a C394F substitution in TP0380, a ERCC3-like DNA repair helicase. Our data highlight the role played by variation in genes encoding putative surface-exposed outer membrane proteins in defining separate lineages, and provide a critical resource for the design of broadly protective syphilis vaccines targeting surface antigens.Author SummaryEach year, millions of new cases of venereal and congenital syphilis, caused by the bacterium Treponema pallidum (T. pallidum) subsp. pallidum, are diagnosed worldwide, resulting in significant morbidity and mortality. Alongside endemic circulation of syphilis in low-income countries, disease resurgence in high-income nations has underscored the need for a vaccine. Due to prior technological limitations in culturing and sequencing the organism, the extent of the genetic diversity within modern strains of T. pallidum subsp. pallidum remains poorly understood, hampering development of a broadly protective vaccine. In this study, we obtained 196 near-complete T. pallidum genomes directly from clinical swabs from eight countries across six continents. Of these, 191 were identified as T. pallidum subsp. pallidum, including 90 Nichols clade genomes. Bayesian analysis revealed a high degree of variance in mutation rate among subclades. Interestingly, a Nichols subclade with a particularly high mutation rate harbors a non-synonymous mutation in a putative DNA repair helicase. Coupling sequencing data with protein structure prediction, we identified multiple novel amino acid variants in several proteins previously identified as potential vaccine candidates. Our data help inform current efforts to develop a broadly protective syphilis vaccine.

A clearer understanding of the structure of pest populations in newly invaded areas is a key step towards their effective management. Here, we use Drosophila suzukii as a model to highlight how populations from separate geographical regions differ in their genetic and phenotypic traits, including those associated with their invasiveness. New X-linked data indicate the presence of at most three D. suzukii genetic clusters in Europe, while North American populations are characterised by a larger genetic diversity. We found a likely new colonisation event from America to Italy and demonstrate that reference genomes from Italian and Californian populations lay in highly distant clusters. Comparative genomics indicate that these two genomes bear the traces of distinct evolutionary forces and are genetically distant, having diversified long ago in their native Asian range. Phenotypic studies further indicate that European and North American populations have differences in hatch rate, generation time, and parasitoid susceptibility. The observed genotypic and phenotypic differences likely represent a small fraction of the features unique to each of the two populations. The results provide some new insights towards both fundamental and management studies on invasive pests, particularly when findings are transferred across populations found in different geographical regions.

In response to the Covid-19 outbreak, among other previous ``non-pharmaceutical interventions99, on March 22, 2020 the Italian Government imposed an economic lockdown and ordered the closing of all non-essential economic activities. This paper estimates the causal effect of this measure on mortality by Covid-19 and on mobility patterns. The identification of the causal effect exploits the variation in the number of active workers across municipalities induced by the economic lockdown. The difference-in-difference empirical design compares outcomes in municipalities above and below the median variation in the share of active population before and after the lockdown within a province, also controlling for municipality-specific dynamics, daily-shocks at the provincial level and municipal unobserved characteristics. Our results show that the intensity of the economic lockdown is associated to a statistically significant reduction in mortality by Covid-19 and, in particular, for age groups between 40-64 and older. Back of the envelope calculations indicate that 4,793 deaths were avoided, in the 26 days between April 5 to April 30, in the 3,518 municipalities which experienced a more intense lockdown. Assuming linearity, a 1 percentage point reduction in the share of active population caused a 1.32 percentage points reduction in mortality by Covid-19. We also find that the economic lockdown, as expected, led to a reduction in human mobility. Several robustness checks corroborate our empirical findings.

Highlights • An enanthem is a mucosal eruption that precede, follow or occur simultaneously with an exanthem. • Enanthems may be triggered by an underlying infection or a drug received by the patient or both. • Patterns are: vesicular, macular, maculo-papular, maculo-papular-petechial, and petechial. • Erythemato-vesicular and petechial patterns are the most frequent in adults. • Some enanthems are pathognomonic for a disease as Koplik's spots for measles., Globalization entails several medical problems, along with economic and social complications. Migrations from the other continents, increasing numbers of tourists world-wide, importation of foreign parasites, Aedes albopictus for example, have made diseases so far unknown in Europe a reality. The rapid spread of the COVID-19 pandemic throughout the world is a warning that other epidemics are still possible. Most, if not all of these diseases, transmitted by viruses or bacteria, present with cutaneous symptoms and signs that are highly important for a speedy diagnosis, a fundamental concept for arresting the diseases and saving lives. Dermatologists play a significant role in delineating cutaneous and mucosal lesions that are often lumped together as a rash. We provide a review of many of these cutaneous and mucosal lesions that sometimes are forgotten or even ignored.

Data on the prevalence of sexually transmitted infections (STIs) and risk factors among incarcerated people are few and data about STIs awareness among inmates are even lacking. This study aimed to assess prevalence of STIs, risky behaviours and STIs level of knowledge in male inmates of the Casa Circondariale-Genova Marassi, the main penitentiary in Genoa, Italy. Between January and June 2019, 662 inmate medical records were retrospectively examined to obtain clinical and laboratory data about STIs. To investigate the inmate level of knowledge of STIs and their risky behaviours, 111consenting participants answered, anonymously, a written questionnaire. One hundred and twenty-two patients had at least one infectious disease when entered the prison: HIV (1.8%), HBV (2.7%), HCV (12.5%) and syphilis (1.3%). When asked to select from a list of diseases which ones they thought to be sexually transmitted, only 12% of the inmates answered correctly; most of them ignored which body fluids are at risk for HIV transmission, which STIs can induce tumors and if any vaccination exists to prevent STIs. Substance abuse was common among inmates that frequently exchanged needles for injecting drugs. To reduce the STIs incidence, it is necessary to target high-risk populations: everyone entering a prison should be offered a systematic screening of all STIs, including those currently neglected. Since STIs knowledge among inmates is poor and risky behaviours are diffuse, informative interventions in prison may provide an opportunity to educate such a high-risk population.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. In women with genital infection, the virus can be transmitted by sex to the oral cavity of their partners and then to their own oral cavity. The aim of the present study was to establish the prevalence of cervical/anal/oral HPV infection in women attending the Dermatology Unit of the Policlinico San Martino of Genoa, the regional reference hospital in Liguria, Italy.Between January 2016 and December 2018, the female patients attending the STI center (cases) and those requiring a full body skin examination for skin cancer screening ("supposed" healthy population: controls) were recruited. Cervical/anal/oral samples were collected with ThinPrep liquid based cytology preparation system: polymerase chain reaction for HPV and cytological evaluation were performed. Overall, 85 cases and 31 controls were recruited.Cervical HPV infection was detected in 60% of the cases and 48% of the controls; anal HPV infection in 44% of the cases and 26% of the controls. Cervical and anal HPV infection resulted associated, especially in the control group. Moreover, 32% of the cases and 29% of the controls proved HPV positive in the oral cavity. In the cases of our series, prevalence of cervical, anal and oral HPV infection was higher compared with the controls.The high prevalence of anal-oral infections and the frequent association between anal and cervical infections, provide reason to suggest HPV screening also in the anal and oral regions, which may represent HPV reservoirs and grounds for cancer development.

A new type of coronavirus family (SARS-CoV-2), which can be found in humans and animals, with many varieties and clinical symptoms, was first seen in Wuhan, China in late 2019, under the name novel Coronavirus Disease 2019 (COVID-19). In the literature, cutaneous symptoms related to the disease are generally emphasized. However, it is not yet known whether this new SARS-CoV-2 virus, which has entered our lives, plays a role in the etiopathogenesis of dermatological diseases. The patients who were admitted to the dermatology outpatient clinic between 1 April and 15 May 2019, and on 1 April and 15 May 2020 were retrospectively analyzed by searching the hospital automation system and patient files. The reason for the same months to be included in the study was to exclude seasonal effects on the diseases. After pandemic, the number of patients with Pityriasis rosea and Kawasaki disease increased significantly in patients who applied to the dermatology outpatient clinic. Our study is the first study showing Pityriasis rosea increase during the pandemic period. We think that this increase is related to HHV-6 reactivation. Herein, we wanted to draw attention to two diseases in which Human Herpes 6 (HHV-6) was accused in etiopathogenesis: Kawasaki disease and Pityriasis rosea.

Treponema pallidum subsp. pallidum DNA and RNA were detected in a semen specimen of a syphilis patient with no genital or anal sores and no clinically evident orchitis. No nucleic acids were found in a urine sample of the same patient collected immediately before the semen sample. Exposure to the syphilis agent through semen could account for transmission episodes in the absence of direct contact with a syphilitic sore.

Immune evasion and disease progression of Treponema pallidum subspecies pallidum are associated with sequence diversity in the hypervariable, putative outer membrane protein TprK. Previous attempts to study variation within TprK have sequenced at depths insufficient to fully appreciate the hypervariable nature of the protein, failed to establish linkage between the protein’s 7 variable regions, or were conducted on strains passed through rabbits. As a consequence, a complete profiling of tprK during infection in the human host is still lacking. Furthermore, prior studies examining how T. pallidum uses its repertoire of genomic donor sites to generate diversity within the V regions of the tprK also yielded a partial understanding of this process, due to the limited number of tprK alleles examined. In this study, we used short- and long-read deep sequencing to directly characterize full-length tprK alleles from T. pallidum collected from early lesions of patients attending two STD clinics in Italy. Our data, combined with recent data available on Chinese T. pallidum strains, show the near complete absence of overlap in TprK sequences among the 41 strains profiled to date. Moreover, our data allowed us to redefine the boundaries of tprK V regions, identify 55 donor sites, and estimate the total number of TprK variants that T. pallidum can potentially generate. Altogether, our results support how T. pallidum TprK antigenic variation system is an unsurmountable obstacle for the human immune system to naturally achieve infection eradication, and reiterate the importance of this mechanism for pathogen persistence in the host.ImportanceSyphilis continues to be a significant public health issue in both low- and high-income nations, including the United States, where the number of infectious syphilis cases has increased dramatically over the past five years. T. pallidum, the causative agent of syphilis, encodes an outer membrane protein TprK that undergoes segmental gene conversion to constantly create new sequences. We performed deep TprK profiling to understand full-length TprK diversity in T. pallidum-positive clinical specimens and compared these to all samples for which TprK deep sequencing is available. We found almost no overlap in TprK sequences between different patients. We further estimate that the total baseline junctional diversity of full-length TprK rivals that of current estimates of the human adaptive immune system. These data underscore the immunoevasive ability of TprK that allows T. pallidum to establish lifelong infection.

In response to the Covid-19 outbreak, among other previous "non-pharmaceutical interventions'', on March 22, 2020 the Italian Government imposed an economic lockdown and ordered the closing of all non-essential economic activities. This paper estimates the causal effect of this measure on mortality by Covid-19 and on mobility patterns. The identification of the causal effect exploits the variation in the number of active workers across municipalities induced by the economic lockdown. The difference-in-difference empirical design compares outcomes in municipalities above and below the median variation in the share of active population before and after the lockdown within a province, also controlling for municipality-specific dynamics, daily-shocks at the provincial level and municipal unobserved characteristics. Our results show that the intensity of the economic lockdown is associated to a statistically significant reduction in mortality by Covid-19 and, in particular, for age groups between 30-64 and older. Back of the envelope calculations indicate that 4,793 deaths were avoided, in the 26 days between April 5 to April 30, in the 3,518 municipalities which experienced a more intense lockdown. Assuming linearity, a 1 percentage point reduction in the share of active population caused a 1.32 percentage points reduction in mortality by Covid-19. We also find that the economic lockdown, as expected, led to a reduction in human mobility. Several robustness checks corroborate our empirical findings.

Dear Editor, We agree with Shiva et al 1 about the relevance of assessing Treponema pallidum particle agglutination (TPPA) titres in the cerebrospinal fluid (CSF) samples of patients with suspected neurosyphilis. For many years, we have been using T. pallidum haemagglutination test (TPHA) both in diagnosing neurosyphilis and in the follow-up of our patients after treatment. It would have been interesting to know the trend of CSF-TPPA titres over time in Shiva’s …

This study analyzes voters’ response to criminal justice policies by exploiting a natural experiment. The 2006 Italian Collective Pardon Bill, designed and promoted by the incumbent center-left (CL) coalition, unexpectedly released about one-third of the prison population, creating idiosyncratic incentives to recidivate across pardoned individuals. Municipalities where resident pardoned individuals had a higher incentive to recidivate experienced a higher recidivism rate. We show that in those municipalities voters “punished” the CL coalition in the 2008 parliamentary elections. A one standard deviation increase in the incentive to recidivate—corresponding to an increase of recidivism of 15.9%—led to a 3.06% increase in the margin of victory of the center-right (CR) coalition in the post-pardon national elections (2008) relative to the last election before the pardon (2006). We also provide evidence of newspapers being more likely to report crime news involving pardoned individuals and of voters hardening their views on the incumbent national government’s ability to control crime. Our findings indicate that voters keep politicians accountable by conditioning their vote on the observed effects of public policies.