Long-term effects of SARS-CoV-2 infection in patients with and without chemosensory disorders at disease onset: a psychophysical and magnetic resonance imaging exploratory study.

A preserved sense of smell and taste allows us to understand many environmental "messages" and results in meaningfully improvements to quality of life. With the COVID-19 pandemic, it became clear how important these senses are for social and nutritional status and catapulted this niche chemosensory research area towards widespread interest. In the current exploratory work, we assessed two groups of post-COVID-19 patients who reported having had (Group 1) or not (Group 2) a smell/taste impairment at the disease onset. The aim was to compare them using validated smell and taste tests as well as with brain magnetic resonance imaging volumetric analysis. Normative data were used for smell scores comparison and a pool of healthy subjects, recruited before the pandemic, served as controls for taste scores. The majority of patients in both groups showed an olfactory impairment, which was more severe in Group 1 (median UPSIT scores: 24.5 Group 1 vs 31.0 Group 2, p = 0.008), particularly among women (p = 0.014). No significant differences emerged comparing taste scores between Group 1 and Group 2, but dysgeusia was only present in Group 1 patients. However, for taste scores, a significant difference was found between Group 1 and controls (p = 0.005). No MRI anatomical abnormalities emerged in any patients while brain volumetric analysis suggested a significant difference among groups for the right caudate nucleus (p = 0.028), although this was not retained following Benjamini-Hochberg correction. This exploratory study could add new information in COVID-19 chemosensory long-lasting impairment and address future investigations on the post-COVID-19 patients' research.

Porcine oocyte preincubation in oviductal fluid flush before in vitro fertilization in the presence of oviductal epithelial cells improves monospermic zygote production.

The present study was designed to evaluate the effect of the combination of oviduct fluid flush (OFF) and oviduct epithelial cells (OEC) in modulating the incidence of polyspermy in pigs. Therefore, for in vitro fertilization (IVF), oocyte and sperm were co-cultured in Tris-buffered medium (TBM) either supplemented with 10% OFF (OFFD group), or in the presence of a bovine OEC monolayer (OEC group), or the oocytes were exposed to OFF for 30 min before IVF (OFFB group), or in the presence of an OEC monolayer (OFFB + OEC group). Regardless of sperm concentration used (0.5, 1.5, and 4.5 × 105 cells/ml), supplementation of IVF medium with 10% OFF led to an increased (P < 0.05) monospermy rate, without alteration (P > 0.05) of the penetration rate in comparison with the control and OEC groups. When the IVF medium was supplemented with heparin, an overall increase (P < 0.05) of the final output of the IVF system in terms of zygotes with two pronuclei (2PN) was observed in the OFFD group, compared with the control and OEC groups, at a sperm concentration of 4.5 × 105 cells/ml. At this concentration, OFFB improved the monospermy rate but decreased the penetration rate, resulting in low efficiency of monospermic zygotes production. Despite this, no major effect was observed in the developmental competence of the presumed zygotes up to the blastocyst stage. The combination of OFFB with OEC improved the penetration rate, while maintaining the high monospermic rate induced by OFFB. In conclusion, the combination of treatment of oocytes by diluted OFF 30 min before IVF, followed by IVF in the presence of OEC, improved monospermic zygote production without reducing the penetration rate, when the IVF medium was supplemented with heparin.

Validation of a Novel Wearable Multistream Data Acquisition and Analysis System for Ergonomic Studies.

Nowadays, the growing interest in gathering physiological data and human behavior in everyday life scenarios is paralleled by an increase in wireless devices recording brain and body signals. However, the technical issues that characterize these solutions often limit the full brain-related assessments in real-life scenarios. Here we introduce the Biohub platform, a hardware/software (HW/SW) integrated wearable system for multistream synchronized acquisitions. This system consists of off-the-shelf hardware and state-of-art open-source software components, which are highly integrated into a high-tech low-cost solution, complete, yet easy to use outside conventional labs. It flexibly cooperates with several devices, regardless of the manufacturer, and overcomes the possibly limited resources of recording devices. The Biohub was validated through the characterization of the quality of (i) multistream synchronization, (ii) in-lab electroencephalographic (EEG) recordings compared with a medical-grade high-density device, and (iii) a Brain-Computer-Interface (BCI) in a real driving condition. Results show that this system can reliably acquire multiple data streams with high time accuracy and record standard quality EEG signals, becoming a valid device to be used for advanced ergonomics studies such as driving, telerehabilitation, and occupational safety.

A review of outbreaks of cryptosporidiosis due to unpasteurized milk.

PURPOSE: This review analysed outbreaks of human cryptosporidiosis due to raw milk. The objective of our study was to highlight and identify underestimated and underreported aspects of transmission of the parasite as well as the added value of genotyping Cryptosporidium isolates. METHODS: We conducted a descriptive literature review using the digital archives Pubmed and Embase. All original papers and case reports referring to outbreaks of Cryptosporidium due to unpasteurized milk were reviewed. The cross-references from these publications were also included. RESULTS: Outbreaks have been described in the USA, Australia, and the UK. Laboratory evidence of Cryptosporidium from milk specimens was lacking in the majority of the investigations. However, in most recent reports molecular tests on stool specimens along with epidemiological data supported that the infection was acquired through the consumption of unpasteurized milk. As the incubation period for Cryptosporidium is relatively long (days to weeks) compared with many other foodborne pathogens (hours to days), these reports often lack microbiological confirmation because, by the time the outbreak was identified, the possibly contaminated milk was not available anymore. CONCLUSION: Cryptosporidiosis is generally considered a waterborne intestinal infection, but several reports on foodborne transmission (including through raw milk) have been reported in the literature. Calves are frequently infected with Cryptosporidium spp., which does not multiply in milk. However, Cryptosporidium oocysts can survive if pasteurization fails. Thus, pasteurization is essential to inactivate oocysts. Although cryptosporidiosis cases acquired from raw milk are seldom reported, the risk should not be underestimated and Cryptosporidium should be considered as a potential agent of contamination. Genotyping Cryptosporidium isolates might be a supportive tool to strengthen epidemiologic evidence as well as to estimate the burden of the disease.

Tropheryma whipplei Colonization in Adults and Children: A Prospective Study.

We conducted a prospective cohort study at the IRCCS Sacro Cuore Don Calabria Hospital in Negrar di Valpolicella from 2019 to 2021 to investigate the duration of T. whipplei colonization. In addition, the correlation between persistent colonization and the continent of origin, current treatment regimen, clinical manifestations, and parasite coinfection was evaluated. The cohort included subjects who were tested in a previous study (years 2014-2016) and found to be positive for T. whipplei DNA in fecal samples. Thirty-three subjects were enrolled in a prospective study between 2019 and 2021. Feces, saliva, urine, and blood were collected at baseline and after 12 months. Medical history, current treatment, and symptoms were recorded. Among them, 25% showed persistent intestinal or oral colonization, 50% had no colonization at both visits, and 25% had intermittent colonization. No association was found between persistent T. whipplei colonization and subjects' continent of origin, current treatment regimen, initial clinical manifestations, and parasite coinfection. The longest duration of persistent T. whipplei intestinal colonization exceeded six years, with 11 subjects presenting persistent positivity for more than three years, including 1 minor. Our research was limited by the lack of a strain-specific identification of T. whipplei that made it impossible to distinguish between persistence of the same T. whipplei strain, reinfection from household exposure, or infection by a new strain. Larger prospective studies are needed to further explore the implications of this persistence and determine the key factors influencing the duration of colonization and its potential health impacts.

Derivation of two human induced pluripotent stem cell lines carrying a missense mutation in FHL1 (c.377G > A, p.C126Y) linked to familial muscular dystrophy.

FHL1 gene locates in the Xq26 region and encodes for four and half LIM domain protein 1. It plays a crucial role in muscle cells and mutations in FHL1 are related to muscular dystrophy (MD). Peripheral blood mononuclear cells (PBMCs) were obtained from 2 family patients with MD that carry a pathogenic missense mutation in FHL1 (c.377G > A, p.C126Y). Induced pluripotent stem cells (iPSCs) were generated by PBMCs reprogramming using the lentiviral-hSTEMCCA-loxP vector, obtaining FHL1-T and FHL1-V iPSCs lines from patients. FHL1 genotype was maintained, and stemness and pluripotency were confirmed in both iPSCs lines.

The transcription factor OCT6 promotes the dissolution of the naïve pluripotent state by repressing Nanog and activating a formative state gene regulatory network.

In the mouse embryo, the transition from the preimplantation to the postimplantation epiblast is governed by changes in the gene regulatory network (GRN) that lead to transcriptional, epigenetic, and functional changes. This transition can be faithfully recapitulated in vitro by the differentiation of mouse embryonic stem cells (mESCs) to epiblast-like cells (EpiLCs), that reside in naïve and formative states of pluripotency, respectively. However, the GRN that drives this conversion is not fully elucidated. Here we demonstrate that the transcription factor OCT6 is a key driver of this process. Firstly, we show that Oct6 is not expressed in mESCs but is rapidly induced as cells exit the naïve pluripotent state. By deleting Oct6 in mESCs, we find that knockout cells fail to acquire the typical morphological changes associated with the formative state when induced to differentiate. Additionally, the key naïve pluripotency TFs Nanog, Klf2, Nr5a2, Prdm14, and Esrrb were expressed at higher levels than in wild-type cells, indicating an incomplete dismantling of the naïve pluripotency GRN. Conversely, premature expression of Oct6 in naïve cells triggered a rapid morphological transformation mirroring differentiation, that was accompanied by the upregulation of the endogenous Oct6 as well as the formative genes Sox3, Zic2/3, Foxp1, Dnmt3A and FGF5. Strikingly, we found that OCT6 represses Nanog in a bistable manner and that this regulation is at the transcriptional level. Moreover, our findings also reveal that Oct6 is repressed by NANOG. Collectively, our results establish OCT6 as a key TF in the dissolution of the naïve pluripotent state and support a model where Oct6 and Nanog form a double negative feedback loop which could act as an important toggle mediating the transition to the formative state.

Pituitary stem cells: past, present and future perspectives.

Pituitary cells that express the transcription factor SOX2 are stem cells because they can self-renew and differentiate into multiple pituitary hormone-producing cell types as organoids. Wounding and physiological challenges can activate pituitary stem cells, but cell numbers are not fully restored, and the ability to mobilize stem cells decreases with increasing age. The basis of these limitations is still unknown. The regulation of stem cell quiescence and activation involves many different signalling pathways, including those mediated by WNT, Hippo and several cytokines; more research is needed to understand the interactions between these pathways. Pituitary organoids can be formed from human or mouse embryonic stem cells, or from human induced pluripotent stem cells. Human pituitary organoid transplantation is sufficient to induce corticosterone release in hypophysectomized mice, raising the possibility of therapeutic applications. Today, pituitary organoids have the potential to assess the role of individual genes and genetic variants on hormone production ex vivo, providing an important tool for the advancement of exciting frontiers in pituitary stem cell biology and pituitary organogenesis. In this article, we provide an overview of notable discoveries in pituitary stem cell function and highlight important areas for future research.

Generation of two edited iPSCs lines by CRISPR/Cas9 with point mutations in PKP2 gene for arrhythmogenic cardiomyopathy in vitro modeling.

The arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease characterized by the progressive replacement of contractile myocardium by fibro-fatty adipose tissue, that generates ventricular arrhythmias and sudden death in patients. The ACM has a genetic origin with alterations in desmosomal genes with the most commonly mutated being the PKP2 gene. We generated two CRISPR/Cas9 edited iPSCs lines, one iPSC line with a point mutation in PKP2 reported in patients with ACM and another iPSC line with a premature stop codon to knock-out the same gene.

Leprosy in an Adopted Woman Diagnosed by Molecular Tools: A Case Report from a Non-Endemic Area.

Coupled with its rarity in non-endemic areas, the clinical heterogeneity of leprosy makes diagnosis very challenging. We report a diagnosis of multibacillary leprosy in a 22-year-old Indian woman, adopted at the age of 10 and living in Italy. The patient presented with painful skin lesions on the face, trunk, and lower and upper extremities, associated with dysesthesia and a motor deficit in her left leg following corticosteroid therapy interruption. Histopathology results from the skin lesions suggested leprosy, but no acid-fast bacilli were identified. Molecular biology in a center specializing in tropical diseases confirmed the diagnosis, allowing prompt and adequate treatment. Genotype analysis allowed the identification of a genotype 1D of M. leprae, facilitating the epidemiological investigation of the plausible infection origin. No resistances to rifampicin, dapsone, or ofloxacin were detected. Leprosy will continue to exist in high-income nations, and the incidence may rise over time due to increasing migration and globalization. CARE guidelines were followed.

Management of imported complicated urogenital schistosomiasis in Europe: a TropNet retrospective study.

BACKGROUND: Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma. Schistosoma haematobium causes urogenital schistosomiasis (UGS), a chronic disease characterized by pathology of the urogenital tract leading to potentially severe morbidity for which the treatment is poorly standardized. We conducted a survey in TropNet centres on the clinical presentations and management strategies of complicated urogenital schistosomiasis (cUGS). METHODS: We reviewed the clinical records of patients seen at TropNet centres over a 20-year timespan (January 2001-December 2020). Case definition for cUGS included the presence of urogenital cancer, obstructive uropathy, kidney insufficiency of all grades and female or male genital involvement leading to infertility. Collected data included demographic information, patient category (traveller or migrant), imaging data, microbiological data (serology results and presence/absence of eggs in urine), histological features and outcome at last visit recorded. RESULTS: Eight centres contributed with at least one case. Overall, 31 patients matched the inclusion criteria. Sub-Saharan Africa was the most likely place of infection for included patients. Median age was 30.6 years (range 21-46, interquartile ranges, IQR 27-33). Most patients (28/31, 90.3%) were males. Hydronephrosis was the most frequent complication, being present in 18 (58.1%) patients, followed by cancer, present in 5 patients (16.1%); 27 patients (87.1%) required surgical management of some sort. Use of praziquantel varied across centres, with six different regimens employed. DISCUSSION: Very few cases of cUGSs were found in our survey, possibly indicating underdiagnosis of this condition. Hydronephrosis was the most frequently observed urogenital complication, and most patients required invasive procedures. Infection by S. haematobium can result in considerable morbidity, resulting in clinically challenging presentations requiring a multidisciplinary approach. As such, development of common protocols for early diagnosis and treatment is urgently needed.

Impact, healthcare utilization and costs of travel-associated mosquito-borne diseases in international travellers: a prospective study.

BACKGROUND: International travellers frequently acquire infectious diseases whilst travelling, yet relatively little is known about the impact and economic burden of these illnesses on travellers. We conducted a prospective exploratory costing study on adult returning travellers with falciparum malaria, dengue, chikungunya or Zika virus. METHODS: Patients were recruited in eight Travel and Tropical Medicine clinics between June 2016 and March 2020 upon travellers' first contact with the health system in their country of residence. The patients were presented with a structured 52-question self-administered questionnaire after full recovery to collect information on patients' healthcare utilization and out-of-pocket costs both in the destination and home country, and about income and other financial losses due to the illness. RESULTS: A total of 134 patients participated in the study (malaria, 66; dengue, 51; chikungunya, 8; Zika virus, 9; all fully recovered; median age 40; range 18-72 years). Prior to travelling, 42% of patients reported procuring medical evacuation insurance. Across the four illnesses, only 7% of patients were hospitalized abroad compared with 61% at home. Similarly, 15% sought ambulatory services whilst abroad compared with 61% at home. The average direct out-of-pocket hospitalization cost in the destination country (USD $2236; range: $108-$5160) was higher than the direct out-of-pocket ambulatory cost in the destination country (USD $327; range: $0-$1560), the direct out-of-pocket hospitalization cost at home (USD $35; range: $0-$120) and the direct out-of-pocket ambulatory costs at home (US$45; range: $0-$192). Respondents with dengue or malaria lost a median of USD $570 (Interquartile range [IQR] 240-1140) and USD $240 (IQR 0-600), respectively, due to their illness, whilst those with chikungunya and Zika virus lost a median of USD $2400 (IQR 1200-3600) and USD $1500 (IQR 510-2625), respectively. CONCLUSION: Travellers often incur significant costs due to travel-acquired diseases. Further research into the economic impact of these diseases on travellers should be conducted.

Tropheryma whipplei, Helicobacter pylori, and Intestinal Protozoal Co-Infections in Italian and Immigrant Populations: A Cross-Sectional Study.

Tropheryma whipplei (TW), Helicobacter pylori (HP), and intestinal protozoa (IP) are widespread pathogens with similar routes of transmission and epidemiological risk factors. Epidemiological data on co-infection between TW, HP, and IP are scarce. We aim to more deeply investigate the co-infection rate for these pathogens, evaluating the risk factors and symptoms. Methods: This is a cross-sectional study conducted at the IRCCS Sacro Cuore Don Calabria Hospital in Northern Italy, a referral center for tropical and Whipple's disease (WD). Stored stool samples from 143 subjects previously tested for TW DNA by real-time PCR were explored for HP and IP DNA detection. The virulence factor cagA was investigated in HP-positive patients. Results: A history of migration was reported significantly more in TW-positive than in negative subjects (34.1% vs. 9.1%, p = 0.001) and in HP-infected than in those non-infected (59.1% vs. 9.1%, p < 0.001). The HP infection rate differed significantly between TW-infected and uninfected groups (31.8% vs. 8.1%, p = 0.001), while no difference was observed for IP infection. Significantly higher TW intestinal colonization was found in HP-infected patients than in non-infected (63.6% vs. 24.8%, p < 0.001). In addition, the proportion of Blastocysts positive finding was also significantly higher in HP-infected than in non-infected (40.9% vs. 17.4%, p = 0.018). Conclusions: The present study is the first to report a high TW and HP co-infection rate. To reduce the risk of morbidity from a chronic infection of either pathogen, clinicians may consider TW-HP molecular screening on the same stool sample for patients with suspected HP disease or WD, particularly in case of travel history.

Association Between Sex Hormone Levels and Clinical Outcomes in Patients With COVID-19 Admitted to Hospital: An Observational, Retrospective, Cohort Study.

Understanding the cause of sex disparities in COVID-19 outcomes is a major challenge. We investigate sex hormone levels and their association with outcomes in COVID-19 patients, stratified by sex and age. This observational, retrospective, cohort study included 138 patients aged 18 years or older with COVID-19, hospitalized in Italy between February 1 and May 30, 2020. The association between sex hormones (testosterone, estradiol, progesterone, dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19, in-hospital mortality) was explored in 120 patients aged 50 years and over. STROBE checklist was followed. The median age was 73.5 years [IQR 61, 82]; 55.8% were male. In older males, testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L, p =0.0378 and 3.7 vs. 8.5 nmol/L, p =0.0011, respectively). Deceased males had lower testosterone (2.4 vs. 4.8 nmol/L, p =0.0536) and higher estradiol than survivors (40 vs. 24 pg/mL, p = 0.0006). Testosterone was negatively associated with ARDS (OR 0.849 [95% CI 0.734, 0.982]), severe COVID-19 (OR 0.691 [95% CI 0.546, 0.874]), and in-hospital mortality (OR 0.742 [95% CI 0.566, 0.972]), regardless of potential confounders, though confirmed only in the regression model on males. Higher estradiol was associated with a higher probability of death (OR 1.051 [95% CI 1.018, 1.084]), confirmed in both sex models. In males, higher testosterone seems to be protective against any considered outcome. Higher estradiol was associated with a higher probability of death in both sexes.

Tropheryma whipplei intestinal colonization in immunocompromised children in Iran: a preliminary study.

Aim & method:Tropheryma whipplei causes Whipple's disease. Children are reservoirs of this bacterium. The aim of this study was to investigate the presence of T. whipplei in children with immunodeficiency in central Iran from July 2018 to February 2019. Stool samples were tested by SYBR Green and Taq-Man real-time PCR assays. For confirmation, the isolated DNA was sequenced. Results: One hundred and thirty children were enrolled. Acute lymphocytic leukemia was the most reported immunodeficient disease (77%), followed by non-Hodgkin lymphoma and retinoblastoma. Thirteen (10%) children had T. whipplei DNA in the stool; 11.4% of the children under 5 years old were positive. Conclusion: This is the first study showing the circulation of T. whipplei in Iran.

Imported scrub typhus in Europe: Report of three cases and a literature review.

BACKGROUND: Scrub typhus is a vector-borne rickettsial infection, which can cause relevant morbidity and mortality. While the number of cases is around a million per year globally, the infection is seldom diagnosed in travellers from Europe. METHODS: We herein report three cases diagnosed in Italian travellers and review the literature about imported cases in Europe in the last 60 years. RESULTS: Three participants to the same hiking trip to the forest of northern Laos presented fever and other symptoms, including eschars (2 individuals) and skin rash (2 individuals). Overall, they didn't report complications, and recovered soon after doxycycline treatment. Diagnosis was retrospectively confirmed with PCR in one of them. The review collected data from 40 patients. Almost all of them (95%) presented fever, more than a half had headache, skin rash, eschars, arthromyalgias. 73% of them were hospitalized, and 16.2% needed intensive care. Diagnosis was confirmed by serology in almost all cases (94.6%). Most patients (88%) were treated with doxycycline. All patients survived, although one case resulted in incomplete tetraparesis. CONCLUSIONS: Scrub typhus should be considered in all travellers coming back from endemic areas and presenting with acute febrile illness. Laboratory diagnosis can be challenging, as specific tests are not widely available. In case of clinical suspicion, a prompt treatment with oral doxycycline could avoid severe complications.

Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection.

Although antibody levels progressively decrease following SARS-CoV-2 infection, the immune memory persists for months. Thus, individuals who naturally contracted SARS-CoV-2 are expected to develop a more rapid and sustained response to COVID-19 vaccines than naïve individuals. In this study, we analyzed the dynamics of the antibody response to the BNT162b2 mRNA COVID-19 vaccine in six healthcare workers who contracted SARS-CoV-2 in March 2020, in comparison to nine control subjects without a previous infection. The vaccine was well tolerated by both groups, with no significant difference in the frequency of vaccine-associated side effects, with the exception of local pain, which was more common in previously infected subjects. Overall, the titers of neutralizing antibodies were markedly higher in response to the vaccine than after natural infection. In all subjects with pre-existing immunity, a rapid increase in anti-spike receptor-binding domain (RBD) IgG antibodies and neutralizing antibody titers was observed one week after the first dose, which seemed to act as a booster. Notably, in previously infected individuals, neutralizing antibody titers 7 days after the first vaccine dose were not significantly different from those observed in naïve subjects 7 days after the second vaccine dose. These results suggest that, in previously infected people, a single dose of the vaccine might be sufficient to induce an effective response.

Effect of Embryo Aggregation on In Vitro Development of Adipose-Derived Mesenchymal Stem Cell-Derived Bovine Clones.

Somatic cell nuclear transfer (SCNT) is a method with unique ability to reprogram the epigenome of a fully differentiated cell. However, its efficiency remains extremely low. In this work, we assessed and combined two simple strategies to improve the SCNT efficiency in the bovine. These are the use of less-differentiated donor cells to facilitate nuclear reprogramming and the embryo aggregation (EA) strategy that is thought to compensate for aberrant epigenome reprogramming. We carefully assessed the optimal time of EA by using in vitro-fertilized (IVF) embryos and evaluated whether the use of adipose-derived mesenchymal stem cells (ASCs) as donor for SCNT together with EA improves the blastocyst rates and quality. Based on our results, we determined that the EA improves the preimplantation embryo development per well of IVF and SCNT embryos. We also demonstrated that day 0 (D0) is the optimal aggregation time that leads to a single blastocyst with uniform distribution of the original blastomeres. This was confirmed in bovine IVF embryos and then, the optimal condition was translated to SCNT embryos. Notably, the relative expression of the trophectoderm (TE) marker KRT18 was significantly different between aggregated and nonaggregated ASC-derived embryos. In the bovine, no effect of the donor cell is observed on the developmental rate, or the embryo quality. Therefore, no synergistic effect of the use of both strategies is observed. Our results suggest that EA at D0 is a simple and accessible strategy that improves the blastocyst rate per well in bovine SCNT and IVF embryos and influence the expression of a TE-related marker. The aggregation of two ASC-derived embryos seems to positively affect the embryo quality, which may improve the postimplantation development.

Emergence of Lyme borreliosis in the province of Verona, Northern Italy: Five-years of sentinel surveillance.

We investigated the epidemiology, clinical manifestations, laboratory data and antibiotic treatment of Lyme borreliosis in the province of Verona, Northern Italy, during the period 2015-2019. One hundred and 29 cases of Lyme borreliosis were diagnosed in a single hospital representing 27 % of all cases reported in the Veneto region in the same period. The mean annual incidence of Lyme borreliosis was 0.992/100,000 inhabitants. A peak incidence of 2/100,000 inhabitants was observed in 2018. Early localized Lyme borreliosis was the most common presentation (74 %), followed by early disseminated Lyme borreliosis (21 %). One possible early Lyme neuroborreliosis and two cranial neuropathies were diagnosed. IgM and/or IgG borrelia antibodies were positive in 90 % of the cases. This significant increase of Lyme borreliosis incidence in the province of Verona highlights the need to increase knowledge on its epidemiology and clinical manifestation among both the general population and clinicians to allow early diagnosis and treatment.

celldeath: A tool for detection of cell death in transmitted light microscopy images by deep learning-based visual recognition.

Cell death experiments are routinely done in many labs around the world, these experiments are the backbone of many assays for drug development. Cell death detection is usually performed in many ways, and requires time and reagents. However, cell death is preceded by slight morphological changes in cell shape and texture. In this paper, we trained a neural network to classify cells undergoing cell death. We found that the network was able to highly predict cell death after one hour of exposure to camptothecin. Moreover, this prediction largely outperforms human ability. Finally, we provide a simple python tool that can broadly be used to detect cell death.