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O lupus eritematoso e uma doenca autoimune que pode ocorrer de forma sistemica ou cutânea. O lupus eritematoso cutâneo cronico (LECC) e a apresentacao cronica da doenca e clinicamente apresenta-se como maculas ou papulas eritematosas e posteriormente como placas discoides que cicatrizam e pigmentam na pele. E subdividido em LE discoide (LED), LE profundo/paniculite (LEP) e LE chilblain (LECH). O LED e o mais comum e pode se subdividir em localizado, no qual as lesoes ocorrem em face, orelhas e couro cabeludo e na forma disseminada em que as lesoes se encontram acima e abaixo do pescoco. Essa doenca pode exibir manifestacoes orais, sendo importante sua identificacao e tratamento. Esse relato tem como objetivo apresentar um caso clinico de paciente com multiplas manifestacoes orais de lupus eritematoso cutâneo, sem manifestacoes em pele simultâneas. Ao exame clinico foi observada uma lesao liquenoide no labio inferior, em palato duro observou-se uma area extensa, eritematosa e assintomatica, com linhas brancas reticulares e gengivite descamativa em maxila e mandibula. Em mucosa jugal havia areas liquenoides e pigmentadas. Uma biopsia incisional foi realizada no palato duro e a analise histopatologica revelou fragmento da mucosa bucal exibindo hiperqueratose e degeneracao focal da camada basal. Foram solicitados exames complementares os quais descartaram envolvimento sistemico. Por fim destaca-se a diversidade de manifestacoes orais em paciente com lupus e a importância do exame de mucosa, mesmo na ausencia de lesoes cutâneas.

The main role of vitamin D is to control mineral homeostasis. However, recent studies suggested the existence of a number of extraskeletal effects. Among the latter, preclinical studies provided consistent data on the involvement of vitamin D in innate and adaptive immunity and autoimmunity. Molecular biology studies showed that both vitamin D receptor and vitamin D enzymatic complexes are expressed in a large number of cells and tissues unrelated to mineral homeostasis. In contrast, only a few randomized clinical trials in humans investigated the possible role of vitamin D in the prevention or treatment of immunological disorders. In this regard, low serum vitamin D levels have been reported in observational trials in human autoimmune disorders. The aim of the present paper was to review the potential implications of vitamin D in immune modulation, with special focus on thyroid autoimmune disorders.

Whether differentiated thyroid cancer (DTC) occurring concomitantly with Graves’ disease (GD) is more aggressive and bound to a less favorable outcome is controversial. Aim of this multicenter retrospective study was to compare baseline features and outcome of DTC patients with GD (DTC/GD+) or without GD (DTC/GD−). Enrolled in this study were 579 patients referred to five endocrine units (Cagliari, Pavia, Pisa, Siena, and Varese) between 2005 and 2014: 193 patients had DTC/GD+ , 386 DTC/GD−. Patients were matched for age, gender and tumor size. They underwent surgery because of malignancy, large goiter size, or relapse of hyperthyroidism in GD. Baseline DTC features (histology, lymph node metastases, extrathyroidal extension) did not differ in the two groups, except for multifocality which was significantly more frequent in DTC/GD+ (27.5% vs. 7.5%, p

Gomberg, Mikhail/0000-0002-1070-5229; Nicolaidou, Electra/0000-0002-8221-0217 WOS:000468972400005 PubMed ID: 30968980 Background Anogenital warts (AGW) can cause economic burden on healthcare systems and are associated with emotional, psychological and physical issues. Objective To provide guidance to physicians on the diagnosis and management of AGW. Methods Fourteen global experts on AGW developed guidance on the diagnosis and management of AGW in an effort to unify international recommendations. Guidance was developed based on published international and national AGW guidelines and an evaluation of relevant literature published up to August 2016. Authors provided expert opinion based on their clinical experiences. Results A checklist for a patient's initial consultation is provided to help physicians when diagnosing AGW to get the relevant information from the patient in order to manage and treat the AGW effectively. A number of frequently asked questions are also provided to aid physicians when communicating with patients about AGW. Treatment of AGW should be individualized and selected based on the number, size, morphology, location, and keratinization of warts, and whether they are new or recurrent. Different techniques can be used to treat AGW including ablation, immunotherapy and other topical therapies. Combinations of these techniques are thought to be more effective at reducing AGW recurrence than monotherapy. A simplified algorithm was created suggesting patients with 1-5 warts should be treated with ablation followed by immunotherapy. Patients with >5 warts should use immunotherapy for 2 months followed by ablation and a second 2-month course of immunotherapy. Guidance for daily practice situations and the subsequent action that can be taken, as well as an algorithm for treatment of large warts, were also created. Conclusion The guidance provided will help physicians with the diagnosis and management of AGW in order to improve the health and quality of life of patients with AGW. Meda Pharma S.p.A. a Mylan Company Medical writing support was funded by Meda Pharma S.p.A. a Mylan Company.

We present a fully reconfigurable single-photon camera, able to operate in both analog and digital modalities so to exploit the best performance out of the two features while solving usual issues that affect SPAD imagers. At first, one of the problems in SPAD arrays is the presence of hot pixels, with much higher dark count rate (DCR) compared to others, that impair system performance and are inevitable because of the presence of trapped charge or impurities in the semiconductor. Then, analog SiPMs provide photon-number resolved analog output, but they give no information about where photons hit the active area. Instead, digital SiPMs (dSiPMs) are position sensitive, can integrate also on-chip electronics (e.g., to count and to time-stamp single photons) and can enable/disable each single pixel, depending on their DCR or the user application. The latter feature can be mandatory in applications where the background is comparable to the dark-count rate of the SPAD microcell. Instead, applications such as Light Detection and Ranging (LiDAR) may not care about hot pixels because usually ambient light background is much higher (e.g., up to 100 klux). The novel camera employs a versatile dSiPM based on a 5 × 5 SPAD array imager, configured for photoncounting applications: each SPAD has both an individual digital output pulse and a common analog output with programmable pulse-width. Thus, it provides all advantages of SPAD arrays, since each SPAD can count the photons detected therein, by means of FPGA-based programmable counters with integration period ranging from 2 ms to 500 ms. Moreover, the chip also provides the advantages of analog SiPMs, since it detects coincidences in an analog way, by using current pulses generated by the triggered SPADs and summing them together to provide a common output analog current. The pulse widths are adjustable in amplitude and in time duration, from 1 ns to 10 ns, so to select the desired coincidence window. A comparator signals when more than a user-selectable number N of photons get concurrently detected. Such a feature has been profitably exploited in LiDAR and Quantum Imaging applications. Furthermore, the availability of the 25 digital outputs allows to extract also the position of the detected photons. The developed camera is also suitable for TOF measurements. Feeding both the output of the comparator and the sync signal coming from a laser illuminator to a Time-to-Digital Converter (TDC), single point distance measurement can be performed. The great advantage of using coincidences is the reduction of the pile-up effect and the unwelcome ambient light triggering, thus drastically improving background rejection in most applications.

BACKGROUND SARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world with several million victims in 213 countries. Switzerland was severely hit by the virus, with 43,000 confirmed cases as of 1 September 2020. AIM In cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19, in addition to their mandatory reporting system. METHODS Patients hospitalised for more than 24 hours with a positive polymerase chain-reaction test, from 20 Swiss hospitals, are included. Data were collected in a customised case report form based on World Health Organisation recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms was more than 5 days after the patient’s admission date. RESULTS As of 1 September 2020, 3645 patients were included. Most patients were male (2168, 59.5%), and aged between 50 and 89 years (2778, 76.2%), with a median age of 68 (interquartile range 54–79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported, with hypertension (1481, 61.7%), cardiovascular diseases (948, 39.5%) and diabetes (660, 27.5%) being the most frequent in adults; respiratory diseases and asthma (4, 21.1%), haematological and oncological diseases (3, 15.8%) were the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly respiratory diseases (2470, 93.2% in adults; 16, 55.2% in children), and renal (681, 25.7%) and cardiac (631, 23.8%) complications for adults. The second and third most frequent complications in children affected the digestive system and the liver (7, 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989, 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. A total of 527 (14.5%) deaths were registered, all among adults. CONCLUSION The surveillance system has been successfully initiated and provides a robust set of data for Switzerland by including about 80% (compared with official statistics) of SARS-CoV-2/COVID-19 hospitalised patients, with similar age and comorbidity distributions. It adds detailed information on the epidemiology, risk factors and clinical course of these cases and, therefore, is a valuable addition to the existing mandatory reporting.

Several tests based on chemiluminescence immunoassay techniques have become available to test for SARS-CoV-2 antibodies. There is currently insufficient data on serology assay performance beyond 35 days after symptoms onset. We aimed to evaluate SARS-CoV-2 antibody tests on three widely used platforms. A chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, USA), a luminescence immunoassay (LIA; Diasorin, Italy), and an electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics, Switzerland) were investigated. In a multigroup study, sensitivity was assessed in a group of participants with confirmed SARS-CoV-2 ( n = 145 ), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e., healthy blood donors, n = 191 , and healthcare workers, n = 1002 ). Receiver operating characteristic (ROC) curves, multilevel likelihood ratios (LR), and positive (PPV) and negative (NPV) predictive values were characterized. Finally, analytical specificity was characterized in samples with evidence of the Epstein–Barr virus (EBV) ( n = 9 ), cytomegalovirus (CMV) ( n = 7 ), and endemic common-cold coronavirus infections ( n = 12 ) taken prior to the current SARS-CoV-2 pandemic. The diagnostic accuracy was comparable in all three assays (AUC 0.98). Using the manufacturers’ cut-offs, the sensitivities were 90%, 95% confidence interval [84,94] (LIA), 93% [88,96] (CMIA), and 96% [91,98] (ECLIA). The specificities were 99.5% [98.9,99.8] (CMIA), 99.7% [99.3,99.9] (LIA), and 99.9% [99.5,99.98] (ECLIA). The LR at half of the manufacturers’ cut-offs were 60 (CMIA), 82 (LIA), and 575 (ECLIA) for positive and 0.043 (CMIA) and 0.035 (LIA, ECLIA) for negative results. ECLIA had higher PPV at low pretest probabilities than CMIA and LIA. No interference with EBV or CMV infection was observed, whereas endemic coronavirus in some cases provided signals in LIA and/or CMIA. Although the diagnostic accuracy of the three investigated assays is comparable, their performance in low-prevalence settings is different. Introducing gray zones at half of the manufacturers’ cut-offs is suggested, especially for orthogonal testing approaches that use a second assay for confirmation.

We present the development and the validation of two SPAD camera systems, based on two SPAD array chips (Figure 1), respectively with 8x8 and 128x1 high-performance CMOS SPAD pixels, able to acquire both photon-counting 2D “intensity” images and photon-timing 3D “time-resolved” (hence, also distance-resolved) maps. Each pixel integrates a 30 μm SPAD detector, an 8-bit in-pixel counter (to counts the number of photons detected during user-selectable timeslots in the nanoseconds and microsecond range), and a 12-bit Time-to-Digital Converter (to timestamp the arrival time of the first photon detected by each SPAD, with sub-nanosecond resolution). In addition, the two array chips have the capability of actively gating the SPADs, driving the SPAD bias voltage above or below breakdown, with subnanosecond transitions allowing efficient time-domain filtering of incoming light. Active gating can be enabling in applications such as non-line of sight 3D ranging and time-domain functional Near-Infrared Spectroscopy (fNIRS), since it allows hiding unwelcome reflections, stray rays, or luminescence/fluorescence excitation signals. In fact, this feature allows the user to selectively avoid “early” photons, for instance those reflected by the sample surface, while measuring only the useful “late” photons, for instance those which interacted with the deeper biological tissue’s layers, preventing the triggering due to the strong reflections, which would saturate the SPADs. For optimizing chip operation in many different applications, both systems are extremely versatile and allow the user to customize the cameras for various measurement setups. The cameras quantum sensitivity allows the reconstruction of faint optical signals through the Time-Correlated Single Photon Counting (1) (TCSPC) technique. In addition, they enable many quantum experiments where information on each photon arrival time is required for example to identify time-coincident events with entangled photons. The 128x1 linear array is perfectly suited for spectroscopy applications, particularly for advanced Raman techniques, thanks to on-chip time-gating and time-tagging capabilities.

Overweight and obesity are often associated with impaired thyroid function. Conversely, thyroid dysfunctions are associated with changes in body weight and basal metabolic rate.

We present the development and characterization of a camera system based on an improved version of a previously developed 32×32 SPADs and TDCs array, with extended duty cycle (80%) and enhanced single-shot precision (175ps rms).

Introduction In puerperium, the hypoestrogenic state induced by delivery and subsequently sustained by lactation may lead to vaginal dryness, burning, and itching sensation, contributing to the onset of sexual dysfunction. Material and methods This was a prospective, randomized, controlled, open-label study (NCT04560283) for evaluating the effects of application of a prolonged-release hyaluronic acid derivative vaginal gel in restoring sexual function during the postpartum period. Eighty-five patients were randomized to apply prolonged-release Hydeal-D 0.2% vaginal gel (Fidia Farmaceutici, Abano Terme, Italy; n = 43) every three days for 12 consecutive weeks or expectant management (n = 42). Results Women undergoing treatment had a more elevate increase in Female Sexual Function Index (FSFI) total score (+15.1 ± 11.9 vs +6.5 ± 8.9, p < 0.001) and a higher decrease in vaginal pH (−1.2 ± 0.7 vs −0.2 ± 1.1; p < 0.001). Moreover, the proportion of vaginal smears with maturation index (VMI) >65 was significantly higher in patients treated (80.6% vs 35.3%; p = 0.004). Edinburgh Postnatal Depression Scale (EPDS) decreased significantly in both groups with no inter-group difference (p = 0.459). Only two cases (4.8%) of moderate vaginal burning sensation were reported in patients undergoing local vaginal therapy. Conclusions The results of our study demonstrated that hyaluronic acid derivative vaginal gel (Hydeal-D) was able to improve sexual function of puerperal women in the short-term treatment.KEY MESSAGEIn the puerperium, the hypoestrogenic state induced by delivery and subsequently sustained by lactation may lead to vaginal dryness, burning, and itching sensation, contributing to the onset of sexual dysfunction.Hydeal-D is a prolonged-release hyaluronic acid derivative characterised by elevated resistance to enzymatic breakdown. During puerperium, its local application may improve the vaginal microenvironment by ensuring a better migration and proliferation of cells involved in local tissue repair.Among puerperal women, Hydeal-D vaginal gel causes a significant improvement of sexual function, including desire, arousal, and lubrification, compared to expectant management. Furthermore, it leads to a decrease in vaginal pH and an increase of the trophic status of vaginal epithelium.

Ucides cordatus (Linnaeus, 1763), the uçá crab, is a subsistence resource for the communities surrounding the mangroves of the RDS Municipal Piraquê-açú and Piraquê-mirim (ES, Brazil). In order to subsidize the management of this resource, population and commercial density (extractive potential), the average size of the crabs, the sex ratio, as well as the percentage of open and closed galleries in the post-closed period were estimated in 18 plots of 100m² along the Estuarine System. The population density found was 0.74 ± 0.24 ind./m² and the commercial 0.10 ± 0.05 ind./m², which may indicate continuous exploration of the species in the region. The sex ratio was 2: 3, with carapace width (LC) for males from 55.77 to 80.38 mm and mean of 67.12 ± 6.50 mm, and females from 25.34 to 74.94 mm and a mean of 61.60 ± 11.40 mm, values ​​close to those found in previous studies in the RDS. The similarities regarding the environmental conditions in which the uçá crab populations are found throughout SEPAPM demonstrate the potential for monitoring the species, so management strategies are proposed in order to assist the management of this fishing resource in the Municipal Reserve. Ucides cordatus (Linnaeus, 1763), el cangrejo uçá, es un recurso de subsistencia para las comunidades aledañas a los manglares de RDS Municipal Piraquê-açú y Piraquê-mirim (ES, Brasil). Para subsidiar el manejo de este recurso, se estimó la densidad poblacional y comercial (potencial extractivo) en 18 parcelas el tamaño promedio de los cangrejos, la proporción de sexos, así como el porcentaje de galerías abiertas y cerradas en el período post-cerrado. de 100m² a lo largo del Sistema Estuarino. La densidad poblacional encontrada fue de 0,74 ± 0,24 ind./ m² y la comercial de 0,10 ± 0,05 ind./m², lo que puede indicar exploración continua de la especie en la región. La proporción de sexos fue de 2: 3, con ancho de caparazón (LC) para machos de 55,77 a 80,38 mm y media de 67,12 ± 6,50 mm, y hembras de 25,34 a 74,94 mm y una media de 61,60 ± 11,40 mm, valores cercanos a los encontrados en estudios previos en RDS. Las similitudes en cuanto a las condiciones ambientales en las que se encuentran poblaciones de cangrejo uçá a lo largo de la SEPAPM demuestran el potencial de monitoreo de la especie, por lo que se proponen estrategias de manejo para ayudar al manejo de este recurso pesquero la Reserva Municipal. Ucides cordatus (Linnaeus, 1763), o caranguejo-uçá, é um recurso de subsistência as comunidades do entorno dos manguezais da RDS Municipal Piraquê-açú e Piraquê-mirim (ES, Brasil). Com o objetivo de subsidiar a gestão deste recurso foi estimada a densidade populacional e comercial (potencial extrativo), o tamanho médio dos caranguejos, a razão sexual, bem como a porcentagem de galerias abertas e fechadas, no período pós-defeso, em 18 parcelas de 100m² ao longo do Sistema Estuarino. A densidade populacional encontrada foi 0,74 ± 0,24 ind./ m² e a comercial 0,10 ± 0,05 ind./m² podendo indicar contínua exploração da espécie na região. A razão sexual foi de 2:3, com largura de carapaça (LC) para machos de 55,77 a 80,38 mm e média de 67,12 ± 6,50 mm, e fêmeas de 25,34 a 74,94 mm e média de 61,60 ± 11,40 mm, valores próximos aos encontrados em estudos anteriores na RDS. As similaridades quanto às condições ambientais em que as populações de caranguejo-uçá se encontram ao longo do SEPAPM demonstram o potencial existente para o monitoramento da espécie, por isso são propostas estratégias de manejo a fim de auxiliar a gestão deste recurso pesqueiro na RDS Municipal.

BackgroundSARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world causing several million victims in 213 countries. Switzerland was severely hit by the virus, with 43’000 confirmed cases as of September 1st, 2020.AimIn cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19 in addition to their mandatory reporting system.MethodsPatients hospitalised for more than 24 hours with a positive PCR test, from 20 Swiss hospitals, are included. Data collection follows a custom Case Report Form based on WHO recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms started more than 5 days after the patient’s admission date.ResultsAs of September 1st, 2020, 3645 patients were included. Most patients were male (2168 - 59.5%),and aged between 50 and 89 years (2778 - 76.2%), with a median age of 68 (IQR 54-79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported: hypertension (1481 - 61.7%), cardiovascular diseases (948 - 39.5%), and diabetes (660 - 27.5%) being the most frequent in adults; respiratory diseases and asthma (4 −21.1%), haematological and oncological diseases (3 – 15.8%) being the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly for respiratory diseases (2470 - 93.2% in adults, 16 – 55.2% in children), renal (681 – 25.7%) and cardiac (631 – 23.8%) complication for adults. The second and third most frequent complications in children affected the digestive system and the liver (7 - 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989 - 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. 527 (14.5%) deaths were registered, all among adults.ConclusionThe surveillance system has been successfully initiated and provides a very representative set of data for Switzerland. We therefore consider it to be a valuable addition to the existing mandatory reporting, providing more precise information on the epidemiology, risk factors, and clinical course of these cases.

BACKGROUND The principality of Liechtenstein had its first COVID-19 case at the beginning of March 2020. After exponential growth, the pandemic’s first wave was contained, with the last case being diagnosed 52 days after the initial occurrence. AIM To characterise the COVID-19 pandemic in Liechtenstein. METHODS All patients diagnosed in Liechtenstein were followed up until recovery and again 6–8 weeks after symptom onset. They were contacted every 2 days to record their clinical status until the resolution of their symptoms. The diagnosis of COVID-19 was based on clinical symptoms and molecular testing. Household and close workplace contacts were included in the follow-up, which also comprised antibody testing. In addition, public health measures installed during the pandemic in Liechtenstein are summarised. RESULTS During the first wave, 5% of the population obtained a reverse transcriptase polymerase chain reaction test. A total of 95 patients (median age 39 years) were diagnosed with COVID-19 (82 who resided in Liechtenstein), resulting in an incidence in Liechtenstein of 0.211%. One patient, aged 94, died (mortality rate 1%). Only 62% of patients could retrospectively identify a potential source of infection. Testing the patients’ household and close workplace contacts (n = 170) with antibody tests revealed that 25% of those tested were additional COVID-19 cases, a quarter of whom were asymptomatic. Those households which adhered to strict isolation measures had a significantly lower rate of affected household members than those who didn’t follow such measures. The national public health measures never restricted free movement of residents. Masks were only mandatory in healthcare settings. The use of home working for the general workforce was promoted. Gatherings were prohibited. Schools, universities, certain public spaces (like sports facilities and playgrounds), childcare facilities, nonessential shops, restaurants and bars were closed. Social distancing, hygienic measures, solidarity and supporting individuals who were at risk were the main pillars of the public health campaigns. CONCLUSION The close collaboration of all relevant stakeholders allowed for the complete workup of all COVID-19 patients nationwide. A multitude of factors (e.g., young age of the patients, low-threshold access to testing, close monitoring of cases, high alertness and adherence to public health measures by the population) led to the early containment of the first wave of the pandemic, with a very low rate of serious outcomes. Antibody testing for SARS-CoV-2 revealed a substantial proportion of undiagnosed COVID-19 cases among close contacts of the patients.

Knowledge of the sensitivities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests beyond 35 days after the clinical onset of COVID-19 is insufficient. We aimed to describe positivity rate of SARS-CoV-2 assays employing three different measurement principles over a prolonged period. Two hundred sixty-eight samples from 180 symptomatic patients with COVID-19 and a reverse transcription polymerase chain reaction (RT-PCR) test followed by serological investigation of SARS-CoV-2 antibodies were included. We conducted three chemiluminescence (including electrochemiluminescence assay (ECLIA)), four enzyme-linked immunosorbent assay (ELISA), and one lateral flow immunoassay (LFIA) test formats. Positivity rates, as well as positive (PPVs) and negative predictive values (NPVs), were calculated for each week after the first clinical presentation for COVID-19. Furthermore, combinations of tests were assessed within an orthogonal testing approach employing two independent assays and predictive values were calculated. Heat maps were constructed to graphically illustrate operational test characteristics. During a follow-up period of more than 9 weeks, chemiluminescence assays and one ELISA IgG test showed stable positivity rates after the third week. With the exception of ECLIA, the PPVs of the other chemiluminescence assays were ≥95% for COVID-19 only after the second week. ELISA and LFIA had somewhat lower PPVs. IgM exhibited insufficient predictive characteristics. An orthogonal testing approach provided PPVs ≥ 95 % for patients with a moderate pretest probability (e.g., symptomatic patients), even for tests with a low single test performance. After the second week, NPVs of all but IgM assays were ≥95% for patients with low to moderate pretest probability. The confirmation of negative results using an orthogonal algorithm with another assay provided lower NPVs than the single assays. When interpreting results from SARS-CoV-2 tests, the pretest probability, time of blood draw, and assay characteristics must be carefully considered. An orthogonal testing approach increases the accuracy of positive, but not negative, predictions.

Immune evasion and disease progression of Treponema pallidum subsp. pallidum are associated with sequence diversity in the hypervariable 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 seven variable regions, or were conducted on isolates passed through rabbits. As a consequence, a complete profile of tprK during infection in the human host is still lacking. Furthermore, prior studies examining how T. pallidum subsp. pallidum uses its repertoire of genomic donor sites to generate diversity within the variable regions of the tprK have 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 subsp. pallidum collected from early lesions of patients attending two sexually transmitted infection clinics in Italy. We demonstrate that strains collected from cases of secondary syphilis contain significantly more unique variable region sequences and full-length TprK sequences than those from cases of primary syphilis. Our data, combined with recent data available on Chinese T. pallidum subsp. pallidum specimens, show the near-complete absence of overlap in TprK sequences among the 41 specimens profiled to date. We further estimate that the potential antigenic variability carried by TprK rivals that of current estimates of the human adaptive immune system. These data underscore the immunoevasive ability of TprK that allows T. pallidum subsp. pallidum to establish lifelong infection. IMPORTANCE Syphilis continues to be a significant public health issue in both low- and high-income countries, including the United States where the rate of syphilis infection has increased over the past 5 years. Treponema pallidum subsp. pallidum, the causative agent of syphilis, carries the outer membrane protein TprK that undergoes segmental gene conversion to constantly create new sequences. We performed full-length deep sequencing of TprK to examine TprK diversity in clinical T. pallidum subsp. pallidum strains. We then combined our results with data from all samples for which TprK deep sequencing results were available. We found almost no overlap in TprK sequences between different patients. Moreover, our data allowed us to estimate the total number of TprK variants that T. pallidum subsp. pallidum can potentially generate. Our results support how the T. pallidum subsp. pallidum TprK antigenic variation system is an equal adversary of the human immune system leading to pathogen persistence in the host.

The outbreak of the COVID-19 pandemic (caused by SARS-CoV-2) is a public health emergency of magnitude.1 The rapid spread of the novel coronavirus in such a densely populated area as Lombardy threatened the capacity of the health system. All health facilities were reorganised to contain the spread of the virus. Unprecedented social isolation measures (lockdown) were adopted to control the epidemic.2 In relation to sexual health, one would assume that the lockdown should reduce the opportunity for sexual encounters and acquisition opportunities for STIs. In Milan, the main city of the Lombardy region, there are two main STI centres which account for about 80% of STI diagnosis. On 8 March, regional ordinance limited outpatient activity to acute cases only. The two STI centres remained open for ‘emergencies’. Patients …

BackgroundSyphilis incidence has exponentially increased in recent decades, particularly among men who have sex with men (MSM). Primary syphilis is characterised by a chancre appearing at the site of Treponema pallidum (TP) inoculation. Atypical morphological variants of syphilitic chancre are frequent. Clinical suspicion must be confirmed either by the demonstration of TP within the lesion through direct tests, such as dark field microscopy (DFM) or T. pallidum nucleic acid amplification technique (TP-NAAT), or by serological tests.ObjectivesTo analyse the clinical features, the sexual behaviour and the role of diagnostic tests in a cohort of men with primary syphilis in Milan.MethodsEpidemiological, clinical and laboratory data of male patients with primary syphilis seen at the STI Center of the University of Milan between 2015 and 2019 were retrospectively evaluated. Diagnosis was confirmed by at least one positive diagnostic test of either DFM, TP-NAAT or serology.ResultsAmong a total of 244 patients, 160 (65.6%) were MSM and 32 (13.1%) were living with HIV. One hundred twenty-four (50.8%) patients had a clinically atypical chancre. Chancres were exclusively extragenital in 30 (12.3%) patients, with MSM being more commonly affected (MSM vs heterosexuals: 16.3% vs 4.8%, respectively; p=0.012), and anal region the most frequently involved site. Chancres were multiple in 68/242 (28.1%) patients and morphologically atypical in 76/244 (31.1%). Diagnosis was obtained by (1) both serology and direct methods in 158/244 patients (64.7%), (2) serology solely in 47/244 (19.3%) and (3) direct methods solely in 39/244 (16%). DFM yielded positive results in 83/139 (59.7%) patients, while TP-NAAT gave positive results in 114/121 (94.2%) patients.ConclusionsPatients with primary syphilis frequently present with morphologically atypical chancres. Furthermore, MSM commonly exhibit extragenital involvement. A combined diagnostic approach including both direct and indirect tests is needed.