An autochthonous case of cutaneous bacillary angiomatosis not related to major immunosuppression: An emerging or overlooked disease?

Cutaneous bacillary angiomatosis (cBA) is a vascular proliferative disorder due to Bartonella henselae or Bartonella quintana that has been mostly described in people living with HIV. Since cBA is considered to be rare in hosts not affected by major immunosuppression, it could be underdiagnosed in this population. Moreover, antimicrobial treatment of cBA has been poorly validated, thus reporting experiences on this clinical entity is important. We reported a challenging and well-characterized case of an Italian 67-year-old gentleman without a history of major immunocompromizing conditions, although he was affected by conditions that can be associated with impaired immune function. The patient reported herein was diagnosed after a long time since the initiation of symptoms and was successfully treated with combined antibiotic therapy including macrolides and quinolones under the guidance of molecular test results. Physicians should consider cBA as a possible manifestation of Bartonella spp. Infection in patients not suffering from major immunocompromizing conditions. Until evidence-based guidelines are available, molecular tests together with severity and extension of the disease can be useful to personalize the type of treatment and its duration.

A Rare Complication of Ascariasis: A Case of Acute Interstitial Nephritis.

Acute interstitial nephritis (AIN) due to helminths is a rare cause of acute kidney injury (AKI). Helminthiases often progresses insidiously, making diagnosis difficult. This was the case of a 72-year-old man, who presented with renal failure, itching and diarrhoea. Urinalysis revealed leukocyturia, microhaematuria and mild proteinuria. A full blood count revealed leucocytosis with eosinophilia. A stool parasitological examination revealed fertilised eggs of Ascaris lumbricoides. Tubulointerstitial nephropathy secondary to A. lumbricoides infection was suspected. A percutaneous renal biopsy was not performed since the patient refused the anti-platelet therapy discontinuation. Mebendazole, albendazole and prednisone therapy was administered. After worm eradiation and discharge, recovery from the parasitosis, absence of pruritus and eosinophilia, and progressive improvement of renal function were observed, strongly suggesting a causal relationship between Ascaris infection and AIN. Parasite infection should be considered in the differential diagnosis of unexplained renal failure because early diagnosis and treatment are necessary to avoid irreversible complications.

Polyphenols: a route from bioavailability to bioactivity addressing potential health benefits to tackle human chronic diseases.

Chronic pathologies or non-communicable diseases (NCDs) include cardiovascular diseases, metabolic syndrome, neurological diseases, respiratory disorders and cancer. They are the leading global cause of human mortality and morbidity. Given their chronic nature, NCDs represent a growing social and economic burden, hence urging the need for ameliorating the existing preventive strategies, and for finding novel tackling therapies. NCDs are highly correlated with unhealthy lifestyle habits (such as high-fat and high-glucose diet, or sedentary life). In general, lifestyle approaches that might improve these habits, including dietary consumption of fresh vegetables, fruits and fibers, may contrast NCD symptoms and prolong life expectancy of affected people. Polyphenols (PPLs) are plant-derived molecules with demonstrated biological activities in humans, which include: radical scavenging and anti-oxidant activities, capability to modulate inflammation, as well as human enzymes, and even to bind nuclear receptors. For these reasons, PPLs are currently tested, both preclinically and clinically, as dietary adjuvants for the prevention and treatment of NCDs. In this review, we describe the human metabolism and bioactivity of PPLs. Also, we report what is currently known about PPLs interaction with gastro-intestinal enzymes and gut microbiota, which allows their biotransformation in many different metabolites with several biological functions. The systemic bioactivity of PPLs and the newly available PPL-delivery nanosystems are also described in detail. Finally, the up-to-date clinical studies assessing both safety and efficacy of dietary PPLs in individuals with different NCDs are hereby reported. Overall, the clinical results support the notion that PPLs from fruits, vegetables, but also from leaves or seeds extracts, are safe and show significant positive results in ameliorating symptoms and improving the whole quality of life of people with NCDs.

Spike-specific T-cell responses in patients with COVID-19 successfully treated with neutralizing monoclonal antibodies against SARS-CoV-2.

OBJECTIVES: Neutralizing monoclonal antibodies (moAbs) improves clinical outcomes in patients with COVID-19 when administered during the initial days of infection. The action of moAbs may impair the generation or maintenance of effective immune memory, similar to that demonstrated in other viral diseases. We aimed to evaluate short-term memory T-cell responses in patients effectively treated with bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab (SOT). METHODS: Spike (S)-specific T-cell responses were analyzed in 23 patients with COVID-19 (vaccinated or unvaccinated) before and after a median of 50 (range: 28-93) days from moAb treatment, compared with 11 vaccinated healthy controls. T-cell responses were measured by interferon-γ-enzyme-linked immunospot and flow cytometric activation-induced marker assay. RESULTS: No statistically significant difference in S-specific T-cell responses was observed between patients treated with moAb and vaccinated healthy controls. Bamlanivimab/etesevimab and casirivimab/imdevimab groups showed significant increases in cellular responses in paired baseline/postrecovery series, as well as vaccinated patients receiving SOT. In contrast, unvaccinated patients prescribed SOT presented no statistically significant increases in T-cell-responses, suggesting diverse impacts of different moAbs on the evolution of S-specific T-cell responses in vaccinated and unvaccinated patients. CONCLUSION: The moAbs did not hinder short-term memory S-specific T-cell responses in the overall group of patients; however, differences among moAbs must be further investigated both in vaccinated and unvaccinated individuals.

Weight of Clinical and Social Determinants of Metabolic Syndrome in People Living with HIV.

Background. Comorbidities in people living with HIV (PLWH) represent a major clinical challenge today, and metabolic syndrome (MTBS) is one of the most important. Objective. Our objective was to assess the prevalence of MTBS and the role of both clinical/socio-behavioral risk factors for MTBS in a cohort of PLWH. Methods. All PLWH, over 18 years of age, attending all Infectious Disease Units in Calabria Region (Southern Italy) for their routine checks from October 2019-January 2020 were enrolled. MTBS was defined by NCEP-ATP III criteria. Logistic regression analysis was performed to assess factors significantly associated with the main outcome (MTBS). Results. We enrolled 356 PLWH, mostly males (68.5%), with a mean age of 49 years (standard deviation: 12), including 98 subjects with and 258 without MTBS. At logistic regression analysis, a statistically significant association was found between MTBS and alcohol use, osteoporosis, polypharmacy, and a history of AIDS. Conclusions. Identifying and addressing risk factors, including those that are socio-behavioral or lifestyle-related, is crucial to prevent and treat MTBS. Our results suggest the importance of implementing educational/multidimensional interventions to prevent MTBS in PLWH, especially for those with particular risk factors (alcohol abuse, osteoporosis, previous AIDS events, and polypharmacy). Moreover, alcohol consumption or abuse should be routinely investigated in clinical practice.

Chronic Pesticide Exposure in Farm Workers Is Associated with the Epigenetic Modulation of hsa-miR-199a-5p.

The increasing use of pesticides in intensive agriculture has had a negative impact on human health. It was widely demonstrated how pesticides can induce different genetic and epigenetic alterations associated with the development of different diseases, including tumors and neurological disorders. Therefore, the identification of effective indicators for the prediction of harmful pesticide exposure is mandatory. In this context, the aim of the study was to evaluate the modification of hsa-miR-199a-5p expression levels in liquid biopsy samples obtained from healthy donors and farm workers with chronic exposure to pesticides. For this purpose, the high-sensitive droplet digital PCR assay (ddPCR) was used to detect variation in the expression levels of the selected microRNA (miRNA). The ddPCR analyses revealed a significant down-regulation of hsa-miR-199a-5p observed in individuals exposed to pesticides compared to control samples highlighting the good predictive value of this miRNA as demonstrated by statistical analyses. Overall, the obtained results encourage the analysis of miRNAs as predictive biomarkers of chronic pesticide exposure thus improving the current strategies for the monitoring of harmful pesticide exposure.

Similarities, differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice.

Hepatitis E virus (HEV) and hepatitis C virus (HCV) are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations. Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise, jaundice, nausea and vomiting. Rarely, HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women. Parenteral HCV infection is typically asymptomatic for decades until chronic complications, such as cirrhosis and cancer, occur. Despite being two very different viruses in terms of phylogenetic and clinical presentations, HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion, pathogenesis (production of antinuclear antibodies and cryoglobulins) and response to treatment with some direct-acting antiviral drugs. Although both HEV and HCV are well studied individually, there is a lack of knowledge about coinfection and its consequences. The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.

Role-Playing Between Environmental Pollutants and Human Gut Microbiota: A Complex Bidirectional Interaction.

There is a growing interest in the characterization of the involvement of toxicant and pollutant exposures in the development and the progression of several diseases such as obesity, diabetes, cancer, as well as in the disruption of the immune and reproductive homeostasis. The gut microbiota is considered a pivotal player against the toxic properties of chemicals with the establishment of a dynamic bidirectional relationship, underlining the toxicological significance of this mutual interplay. In fact, several environmental chemicals have been demonstrated to affect the composition, the biodiversity of the intestinal microbiota together with the underlining modulated metabolic pathways, which may play an important role in tailoring the microbiotype of an individual. In this review, we aimed to discuss the latest updates concerning the environmental chemicals-microbiota dual interaction, toward the identification of a distinctiveness of the gut microbial community, which, in turn, may allow to adopt personalized preventive strategies to improve risk assessment for more susceptible workers.

Women's health and night shift work: Potential targets for future strategies in breast cancer (Review).

Breast cancer is the leading cause of cancer-associated amongst women worldwide. Several studies have shown that individual, environmental and occupational factors can serve an important role in the onset of breast cancer; although the majority of studies have demonstrated this association, and several studies have investigated the biological pathways, it is impossible to describe with certainty the causal relationship that involve circadian rhythm disruption and melatonin dysregulation with the oncogenic processes. Over the years, due to the introduction of more effective screening tools, an increase in the incidence of breast cancer as well as a decrease in the age at diagnosis has been witnessed. Subsequently, an increasing number of individuals have obtained care at a younger age, which has meant that after surgery and chemotherapy, these workers have had to return to work. In light of these paradigmatic changes, the aim of the present review was to identify potential targets for future organisational strategies that should be adopted in the workplace by occupational physicians, both for prevention and for the return-to-work process of working women who have suffered from breast cancer.

Sleep Quality and Mood State in Resident Physicians during COVID-19 Pandemic.

Since the novel coronavirus (SARS-CoV-2) has spread worldwide, healthcare workers-resident physicians in particular-have been hugely involved in facing the COVID-19 pandemic, experiencing unprecedented challenges in fighting the disease. We aimed to evaluate the prevalence of poor sleep quality, daytime sleepiness, and alterations in mood state profiles in this category. This cross-sectional study, conducted in 2020, enrolled 119 subjects from a university hospital in southern Italy. Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Profile of Mood States (POMS) questionnaires were administered to physicians divided into four areas: anesthesiology, medicine, service, and surgery. In the overall sample, approximately 45% reported poor sleep quality, although only nine subjects (8%) reported an ESS score that suggested excessive daytime sleepiness. Alterations in mood profiles were also observed; the Vigor and Fatigue factors were the most altered. In particular, anesthesiologists seem to be the most affected category, showing a profound decrease in Vigor with a concomitant increase in Fatigue. Considering the possible consequences of the COVID-19 pandemic, preventive measures should be adopted, especially those aimed at facilitating a better turnover of physicians, optimizing the working schedule, and improving the organization of work.

Genetic and Epigenetic Alterations Induced by Pesticide Exposure: Integrated Analysis of Gene Expression, microRNA Expression, and DNA Methylation Datasets.

Environmental or occupational exposure to pesticides is considered one of the main risk factors for the development of various diseases. Behind the development of pesticide-associated pathologies, there are both genetic and epigenetic alterations, where these latter are mainly represented by the alteration in the expression levels of microRNAs and by the change in the methylation status of the DNA. At present, no studies have comprehensively evaluated the genetic and epigenetic alterations induced by pesticides; therefore, the aim of the present study was to identify modifications in gene miRNA expression and DNA methylation useful for the prediction of pesticide exposure. For this purpose, an integrated analysis of gene expression, microRNA expression, and DNA methylation datasets obtained from the GEO DataSets database was performed to identify putative genes, microRNAs, and DNA methylation hotspots associated with pesticide exposure and responsible for the development of different diseases. In addition, DIANA-miRPath, STRING, and GO Panther prediction tools were used to establish the functional role of the putative biomarkers identified. The results obtained demonstrated that pesticides can modulate the expression levels of different genes and induce different epigenetic alterations in the expression levels of miRNAs and in the modulation of DNA methylation status.

Toxicology and Microbiota: How Do Pesticides Influence Gut Microbiota? A Review.

In recent years, new targets have been included between the health outcomes induced by pesticide exposure. The gastrointestinal tract is a key physical and biological barrier and it represents a primary site of exposure to toxic agents. Recently, the intestinal microbiota has emerged as a notable factor regulating pesticides' toxicity. However, the specific mechanisms related to this interaction are not well known. In this review, we discuss the influence of pesticide exposure on the gut microbiota, discussing the factors influencing gut microbial diversity, and we summarize the updated literature. In conclusion, more studies are needed to clarify the host-microbial relationship concerning pesticide exposure and to define new prevention interventions, such as the identification of biomarkers of mucosal barrier function.

MicroRNAs alteration as early biomarkers for cancer and neurodegenerative diseases: New challenges in pesticides exposure.

This review summarizes the current knowledge linking cancer and neuro-degenerative diseases to dysregulation of microRNA network following pesticide exposure. Most findings revealed differential miRNA expression targeting biomolecules and pathways involved in various neoplastic localizations and neurodegenerative diseases. A growing body of evidence in recent literature indicates that alteration of specific miRNAs can represent an early biomarker of disease following exposure to chemical agents, including pesticides. Different miRNAs seem to regulate cell proliferation, apoptosis, migration, invasion, and metastasis via many biological pathways through modulation of the expression of target mRNAs. The evaluation of miRNA expression levels may be used to develop new non-invasive strategies for the prediction and prognosis of many diseases, including cancer. However, the application of miRNAs as diagnostic and therapeutic biomarkers in the clinical field is extremely challenging.

Night shift work in resident physicians: does it affect mood states and cognitive levels?

BACKGROUND: The effects of night shift work on health status have been widely studied. Night workers seem to smoke more, eat badly and show a low propensity to physical activity. Night work can be associated with an increase in cardiovascular and gastrointestinal disorders, alterations in immune response, diabetes, aging, hormonal imbalance, and premature death; alteration of circadian rhythm is also regarded as a risk factor for breast cancer and neuropsychiatric disorders. Moreover, several studies have highlighted the effects of sleep deprivation on clinical performance, quality of care and personal safety of healthcare personnel. No studies have investigated the effects of night work on Italian resident physicians and compared its effect across specialties. This study aims to assess the prevalence of sleep disorders, possible cognitive impairment and mood states, in relation to night shift work among resident physicians. METHODS: 80 resident physicians, attending the postgraduate training into an Hospital located in the South of Italy, were divided into 4 areas (medical, surgical, services and anaesthesia). They were recruited from July 2017 to June 2018 and participated to a survey consisting of 4 questionnaires to investigate the presence of sleep deprivation and sleep quality (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index), their cognitive status (Mini Mental State examination) and mood profiles (Profile of Mood States, POMS). Analysis of variance was used for comparison of questionnaires scores across specialties. RESULTS: Authors reported no sleep deprivation, no sleep disorders and their outcomes, no changes in intellectual efficiency and no cognitive impairment in this population, neither in the areas performing night shifts nor in those involving only day shifts. Mood states measured by POMS showed a borderline level of Anger-Hostility (A) value among the residents of the medical area and services, and an increase slightly beyond the physiological levels of the T-score 50 of Fatigue-Inertia (F) always in the same groups. An increase in the Vigour-Activity (V) value beyond T-score 50 levels was also observed among residents of all the areas considered. CONCLUSIONS: Emotional involvement could be attributed to the gap between high professional demand and lack of experience and knowledge among trainees. Tutors should help their students in order to identify earlier changes in the mood. Improvement in the organization of the trainee's activity could reduce the emotional overload.

Association between oxidative stress biomarkers and PON and GST polymorphisms as a predictor for susceptibility to the effects of pesticides.

Low levels of pesticides persist in the environment and can affect the health of exposed subjects. Oxidative stress is considered as one of the mechanisms responsible for the adverse effects on human health and some molecules may represent useful biomarkers for the evaluation of this physiological balance. This study investigated the role of these biomarkers, such as advanced oxidation protein products (AOPP), advanced glycation end­products (AGE) and reactive oxygen metabolites (ROMs) in relation to genetic polymorphisms of paraoxonase (PON)1, PON2, glutathione S­transferase pi 1 (GSTP1), glutathione S­transferase theta 1 (GSTT1) and glutathione S­transferase mu 1 (GSTM1). An increase in the levels of these biomarkers is usually inversely associated with the depletion of the biological antioxidant potential (BAP). The results revealed a statistically significant difference in the sex­dependent variation of AGE, BAP, AOPP and ROM protein levels. Furthermore, an association between the PON2 S331C gene polymorphism and the serum levels of AOPP, ROMs and BAP was found. Thus, compared with AGE, the levels of AOPP and ROMs provided a more sensitive biomarker, with an improved association with the PON2 genotype. Such an association strengthen the importance of PON in the occurrence of oxidative stress. According to these results, an individual's genetic background may be taken into account for the health surveillance of individuals occupationally exposed to pesticides, in order to define a cluster of highly susceptible workers so as to guarantee greater protection.

Genetic polymorphisms as determinants of pesticide toxicity: Recent advances.

Occupational and environmental exposure to pesticides may induce harmful effects on human health by promoting the development of a wide range of disorders. Some of the most recently hypothesized mechanisms are oxidative stress and epigenetic modifications, however biological effects seem to be modulated mainly by the occurrence of genetic polymorphisms. The susceptibility to exposure can be evaluated by studying the most common polymorphisms of genes involved in the metabolism of organophosphorus compounds (cytochrome P450, glutathione transferase, acetyltransferases or paraoxonase 1). The aim of this article is to review recent literature data concerning the influence of genetic polymorphisms on pesticides-induced oxidative damage.

Prevalence of parasitic infections in migrants: do official symptom-driven guidelines apply to the current situation?

In recent years, migration has become a significant challenge in Western countries. Migrant populations, coming from hyper-endemic areas, may present parasitic infections that remain latent and asymptomatic even for years, eventually leading to severe complications. Italian guidelines have been established to perform screening guided by the presence of symptoms and/or hypereosinophilia. Parasitological screening was conducted in a migrant population to carry out preventative measures. All migrants were asked to report any symptoms suggesting parasitic infections and list any previous treatment received. Travel data were recorded. Parasitological examination of stools and urine were conducted in all patients regardless of symptoms. In all, 208 consecutive patients were enrolled in our outpatient clinic from November 2016 to August 2017. Thirty-four patients were excluded due to the previous assumption of albendazole or because they did not exhibit suitable samples. Prevalence of parasitic infections was 33/174 (18.9%). A statistically significant difference for the prevalence of parasitic infections was not found between patients who were asymptomatic and without hypereosinophilia compared to those who presented symptoms and/or hypereosinophilia (27/151 [17.9%] vs. 6/23 [26.0%]; p=0.39). By contrast, a statistically significant difference was found for the length of time between arrival in Italy and parasitological examinations (4/51 [7.8%] migrants who arrived in Italy more than six months prior to screening vs. 29/123 [23.6%] migrants who arrived within six months; p= 0.016). Our results did not demonstrate any significant differences in prevalence of parasitic infections between symptomatic or hypereosinophilic and asymptomatic migrants. Thus we feel it inappropriate to support recent guidelines recommending parasitological examinations only in migrants with symptoms and/or hypereosinophilia. By contrast, it would appear important to perform parasitological screening in migrants as soon as possible after their arrival. Since such infestations, if untreated, could result in chronic diseases and complications, and could be transmitted in the host countries, our results have potential implications for public health.

Evolution of glomerular filtration rates and neutrophil gelatinase-associated lipocalin during treatment with direct acting antivirals.

Background/Aims: Correct renal function evaluation is based on estimated glomerular filtration rates (eGFR) and complementary renal damage biomarkers, such as neutrophil gelatinase associated lipocalin (NGAL). The aim of this study was to evaluate eGFR and NGAL modifications and renal impairment during treatment with a direct acting antiviral (DAA) for chronic hepatitis C virus (HCV) infection. METHODS: A retrospective cohort study evaluated eGFR modification during treatment with DAA. Subgroup analysis on serum NGAL was conducted in those receiving sofosbuvir/ledipasvir, with complete follow-up until week 12 after the end of treatment (FU-12). RESULTS: In the 102 enrolled patients, eGFR reduction was observed (from 86.22 mL/min at baseline to 84.43 mL/min at FU-12, P=0.049). Mean NGAL increased in 18 patients (from 121.89 ng/mL at baseline to 204.13 ng/mL at FU-12, P=0.014). At FU-12, 38.8% (7/18) of patients had a plasmatic NGAL value higher than the normal range (36-203 ng/mL) compared with 11.1% (2/18) at baseline (χ 2 =3,704; P=0.054). In contrast, eGFR did not change significantly over the follow-up in this subgroup. Conclusions: In conclusion, compared to a negligible eGFR decline observed in the entire cohort analyzed, a significant NGAL increase was observed after HCV treatment with DAA in a small subgroup. This could reflect tubular damage during DAA treatment rather than glomerular injury.

Current evidence on the effect of dietary polyphenols intake on chronic diseases.

Polyphenols are secondary metabolites of plants. They comprise several antioxidant compounds and they are generally considered to be involved in the defense against human chronic diseases. During the last years, there has been growing scientific interest in their potential health benefits. In this comprehensive review, we focus on the current evidence defining the position of their dietary intake in the prevention/treatment of human chronic diseases, including prostate cancer and other types of cancer, cardiovascular diseases, diabetes mellitus and neurodegenerative diseases such as Alzheimer's and Parkinson's disease; we also discuss their ability to modulate multiple signalling transduction pathways involved in the pathophysiology of these diseases. Despite the fact that data regarding the biological functions of polyphenols can be considered exhaustive, evidence is still inadequate to support clear beneficial effects on human chronic diseases. Currently, most data suggest that a combination of phytochemicals rather than any single polyphenol is responsible for health benefit. More studies investigating the role of polyphenols in the prevention of chronic human diseases are needed, especially for evaluating factors such as gender, age, genotype, metabolism and bioavailability.

8-Hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to low-dose benzene.

The present study aims to investigate the relation between exposure to low-dose benzene and the occurrence of oxidative DNA damage in gasoline station workers, as well as the possible role of interfering or confounding factors. Urine levels of 8-OHdG were evaluated by a competitive immunoassay in a group of 80 men, employed in gasoline stations located in East Sicily and compared with a control group (n = 63) of male office employees not occupationally exposed to benzene. Information regarding socio-demographic characteristics, lifestyle and job-related records were provided through a questionnaire. Significantly higher (p < 0.05) urinary t,t,-MA and 8-OHdG levels were observed in gasoline station attendants compared to subjects not exposed to benzene. Pearson's test demonstrated a strong correlation (r = 0.377, p < 0.001) between 8-OHdG and benzene exposure level. 8-OHdG significantly correlated also with job seniority, (r = 0.312, p < 0.01), whereas the relation with age resulted weaker (r = 0.242, p < 0.05). Multiple linear regression analysis, performed to exclude a role for confounding factors, showed that variables like gender, smoking habit, alcohol consumption and BMI did not have a significant influence on the measured biomarkers. No subject enrolled in the study presented signs or symptoms of work-related disease or other illness linked to oxidative stress. These results suggest that low-level chronic exposure to benzene among gasoline station attendants can determine oxidative damage on DNA, as indicated by alteration of 8-OHdG which may represent a non-invasive biomarker of early genotoxic damage in exposed subjects.