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Cystic fibrosis (CF) is characterized by a progressive decline in lung function, which may be further impaired by viral infections. CF is therefore considered a comorbidity of coronavirus disease 2019 (COVID-19), and SARS-CoV-2 vaccine prioritization has been proposed for patients with (pw)CF. Poor outcomes have been reported in lung transplant recipients (LTR) after SARS-CoV-2 infections. LTR have also displayed poor immunization against SARS-CoV-2 after mRNA-based BNT162b2 vaccination, especially in those undergoing immunosuppressive treatment, mostly those receiving mycophenolate mofetil (MMF) therapy. We aimed to determine here the immunogenicity and safety of the BNT162b2 vaccine in our cohort of 260 pwCF, including 18 LTR. Serum levels of neutralizing anti-SARS-CoV-2 IgG and IgA antibodies were quantified after the administration of two doses. PwCF displayed a vaccine-induced IgG and IgA antiviral response comparable with that seen in the general population. We also observed that the immunogenicity of the BNT162b2 vaccine was significantly impaired in the LTR subcohort, especially in patients undergoing MMF therapy. The BNT162b2 vaccine also caused minor adverse events as in the general population, mostly after administration of the second dose. Overall, our results justify the use of the BNT162b2 vaccine in pwCF and highlight the importance of a longitudinal assessment of the anti-SARS-CoV-2 IgG and IgA neutralizing antibody response to COVID-19 vaccination.

Iron (Fe) status among healthy male and female blood donors, aged 18–65 years, is estimated. General characteristics and lifestyle factors, dietary habits and major one-carbon metabolism-related polymorphisms were also investigated. An explorative cross-sectional study design was used to examine a sample of blood donors attending the Transfusion Medicine Unit of the Verona University Hospital, Italy. From April 2016 to May 2018, 499 subjects were enrolled (255 men, 244 women, 155 of whom of childbearing age). Major clinical characteristics including lifestyle, dietary habits and Fe status were analysed. The MTHFR 677C > T, cSHMT 1420C > T, DHFR 19bp ins/del and RFC1 80G > A polymorphisms were also assayed. Mean plasma concentrations of Fe and ferritin were 16·6 µmol/l (95 % CI 16·0, 17·2) and 33·8 µg/l (95 % CI 31·5, 36·2), respectively. Adequate plasma Fe concentrations (> 10·74 µmol/l) were detected in 84·3 % and adequate ferritin concentrations (20–200 µg/l) was found in 72·5 % of the whole cohort. Among the folate-related polymorphisms analysed, carriers of the DHFR 19bp del/del mutant allele showed lower ferritin concentration when compared with DHFR 19bp ins/del genotypes. In a sample of Italian healthy blood donors, adequate plasma concentrations of Fe and ferritin were reached in a large proportion of subjects. The relationship of Fe status with lifestyle factors and folate-related polymorphisms requires more investigation to clarify further gene–nutrient interactions between folate and Fe metabolism.

Background: Scarce information is available on circadian body temperature fluctuation in healthy healthcare workers. Methods: Forehead temperature was measured with an infrared thermometer in 33 ostensibly healthy laboratory professionals (mean age, 43 ± 13 years; 76% females) throughout a regular working shift, from 800 AM to 300 PM, at 1-hour intervals. Results: A significant difference was found at different times of the day by 1-way analysis of variance (F statistics, 13.79; p < 0.001). The lowest mean forehead temperature was 36.2 ± 0.3℃, recorded at 100 PM, whilst the highest was 36.7 ± 0.3℃, at 900 AM. The mean difference between forehead temperature at acrophase and nadir was 0.5℃ (95% CI, 0.3-0.6℃; p < 0.001). The forehead temperature measured between 900-1200 AM was also significantly higher than that measured between 100-300 PM (0.3℃; 95% CI, 0.2-0.4℃; p < 0.001). The mean intra-individual variation of forehead temperature was higher but not significantly different in men (1.0 ± 0.2%) compared to women (0.8 ± 0.3%; p = 0.112). Conclusion: Fever screening protocols for purposes of coronavirus disease 2019 (COVID-19) and other infectious diseases monitoring should consider normal daily fluctuations in forehead temperature.

Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.

Graphical abstract Unlabelled Image, Highlights • An association between COVID-19 and venous thromboembolism (VTE) is now recognized. • The prevalence of VTE is high in COVID-19 patients hospitalized in standard care units. • The prevalence of VTE is high even though thromboprophylaxis and in patients estimated at low risk. • A high index of suspicion for VTE is crucial in patients with SARS-CoV-2 infection.

Previous studies showed that red blood cell distribution width (RDW) can be used as a prognostic and diagnostic index in various non-hematological diseases, including severe infections and sepsis. Here, we provide a narrative review to summarize the findings of available studies investigating the relationship between RDW and sepsis. Current evidence suggests that increased RDW on admission, both in adults and neonates, may be associated with unfavorable outcomes on the short- and long-term. In patients with suspected sepsis, RDW has modest value for predicting positive blood culture. Accordingly, its diagnostic value for sepsis seems limited, whilts dynamic changes of RDW are associated with outcome of sepsis. Taken together, these results suggest that RDW could be used as a prognostic index in septic patients.

Background: We provide here direct comparison of viral load in nasopharyngeal specimens of patients infected by Omicron and former severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.Methods: We retrospectively reviewed the results of SARS-CoV-2 testing conducted during two corresponding periods of years 2021 and 2022 (i.e., between 3-9 January), characterized by local prevalence of Alpha (>95%; January 2021) and Omicron (>90%; January 2022) SARS-CoV-2 variants, respectively. In both years viral load was quantified using the same method and instrumentation (Seegene Allplex SARS-CoV-2 Assay).Results: The total number of patients with positive SARS-CoV-2 tests was 47 in January 2021 and 118 in January 2022, respectively. The cycle threshold (Ct) values in January 2022 (median Ct value, 27.5; IQR, 23.5-32.7) when the Omicron variant was prevalent were significantly lower than those measured during the same period of the year 2021 (median Ct value, 31.8; IQR, 26.4-37.6; p=0.007), when the Alpha variant was prevalent. The rate of subjects with high nasopharyngeal viral load was over 2-fold higher in January 2022 than in January 2021 (45/118 vs. 10/47; Odds ratio, 2.28 and 95%CI, 1.03-5.03; p=0.041).Conclusions: These results support the suggestion that aerosols released by patients infected by SARS-CoV-2 Omicron variant may contain higher viral particles than those released by subjects infected with previous strains.

Objectives Coronavirus disease 2019 (COVID-19) is a life-threatening infectious disorder characterized by a sustained prothrombotic state. Since homocysteine is a potential biomarker of thrombotic diseases, the aim of this article is to provide an updated overview on the possible role played by hyperhomocysteinemia in influencing an unfavorable COVID-19 progression. Methods We carried out an electronic search in Medline (PubMed interface) using the keywords (“COVID-19” OR “SARS-CoV-2”) AND “homocysteine”, between 2019 and the present time, with no language restrictions, to identify all articles which explored the concentration of homocysteine in COVID-19 patients with or without unfavorable disease progression. Results Three studies, totaling 694 hospitalized COVID-19 patients, were included in our systematic review. Overall, the differences between the mean homocysteine values in non-severe vs. severe COVID-19 patients were always positive (i.e., 15.1%, 24.1% and 22.8%, generating a positive weight mean difference of 1.75 μmol/L (95%CI, 1.26–2.25 μmol/L; p=0.011), which translates into a cumulative difference of approximately ∼1.2 μmol/L. Conclusions Despite the limited evidence that has been garnered so far, increased homocysteine ​​levels may be a potentially useful marker for predicting the risk of unfavorable progression in patients with COVID-19.

Although the worldwide usage of direct oral anticoagulants has continuously increased over the past decade, heparin remains an important weapon in the current arsenal of anticoagulant drugs. Parenteral heparin administration (i.e., either intravenously or subcutaneously) has represented for decades the only possible route for generating a significant anticoagulant effect, although being notoriously associated with some important drawbacks such as discomfort and risk of low compliance, thus paving the way to searching for more amenable means of administration. We provide here an updated analysis of animal and human studies that have explored the feasibility, suitability, and efficiency of heparin administration through the unconventional nasal route, as a possible alternative to the more traditional parenteral injection. The major hurdles that contribute to impair intranasal absorption and systemic delivery of heparin are represented by its relatively high molecular weight and negative charge. Therefore, although pure drug administration would not be associated with efficient nasal adsorption, or by systemic biological activity (i.e., anticoagulant effect), the combination of low molecular weight heparins and absorption enhancers such as surfactants, mucoadhesive, cyclodextrins, polyethylenimines and encapsulation into (nano)carriers seems effective to at least partially improve drug transport through the nasal route and allow systemic delivery in animals. Besides generating anticoagulant effects, intranasal heparin administration can also produce local pleiotropic effects, mostly related to anti-inflammatory properties, such as attenuating airway allergic inflammation or inhibiting the binding of the spike protein of some coronaviruses (including severe acute respiratory syndrome coronavirus 2) to their host cell receptors. This preliminary evidence represents a valuable premise for planning future studies in humans aimed at establishing the pharmacokinetics and biological activity of locally and systemically delivered intranasal heparin formulations.

Objectives The development and use of artificial intelligence (AI) methodologies, especially machine learning (ML) and deep learning (DL), have been considerably fostered during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Several models and algorithms have been developed and applied for both identifying COVID-19 cases and for assessing and predicting the risk of developing unfavourable outcomes. Our aim was to summarize how AI is being currently applied to COVID-19. Methods We conducted a PubMed search using as query MeSH major terms “Artificial Intelligence” AND “COVID-19”, searching for articles published until December 31, 2021, which explored the possible role of AI in COVID-19. The dataset origin (internal dataset or public datasets available online) and data used for training and testing the proposed ML/DL model(s) were retrieved. Results Our analysis finally identified 292 articles in PubMed. These studies displayed large heterogeneity in terms of imaging test, laboratory parameters and clinical-demographic data included. Most models were based on imaging data, in particular CT scans or chest X-rays images. C-Reactive protein, leukocyte count, creatinine, lactate dehydrogenase, lymphocytes and platelets counts were found to be the laboratory biomarkers most frequently included in COVID-19 related AI models. Conclusions The lion’s share of AI applied to COVID-19 seems to be played by diagnostic imaging. However, AI in laboratory medicine is also gaining momentum, especially with digital tools characterized by low cost and widespread applicability.

Red blood cell distribution width (RDW) is frequently increased in inflammatory disorders, and the magnitude of its elevation correlates with disease severity. This study was hence aimed to explore RDW values in patients with psoriasis.The study population consisted of 366 adult patients with mild to severe plaque psoriasis and 366 age- and sex-matched blood donor controls. For each psoriatic patient, demographic, clinical, and laboratory data were regularly collected.RDW and MCV were significantly higher in psoriatic patients compared to controls (13.95 vs. 13.40% and 90.4 vs. 89 fL; both p0.01). In order to assess whether RDW elevations were related to psoriasis severity, we divided our psoriatic patient population into two groups based on a PASI cut-off of 10. No significant differences were observed between the two groups (i.e., PASI10 and 10) in terms of RDW (p=0.36). Adopting different PASI cut-offs (i.e. 3, 5, 7, 12) did not result in statistically significant differences (p=0.93, 0.48, 0.22, 0.42, respectively). In linear regression analysis, no significant correlation was found between RDW and PASI or CRP, nor with age, gender, or the psoriasis comorbidities listed in Table I. Furthermore, no significant difference in RDW values was noted between psoriatic patients with and without PsA (p=0.27).The results of this study confirm that RDW is elevated in psoriatic patients, though the magnitude of its increase did not appear to be associated with disease severity.Širina distribucije eritrocita (RDW) se često povećava kod zapaljenskih poremećaja i razmere povećanja su u korelaciji sa težinom bolesti. Cilj ove studije je bio da istraži vrednosti RDW kod pacijenata sa psorijazom.Populacija ispitanika je bila sačinjena od 366 odraslih pacijenata sa blagom do teškom psorijazom plaka i 366 kontrolnih davalaca krvi usklađenih po pitanju godina i pola. Za svakog psorijatičnog pacijenta redovno su se prikupljali demografski, klinički i laboratorijski podaci.RDW i MCV su bili značajno veći kod psorijatičnih u poređenju sa kontrolnim pacijentima (13,95% prema 13,40% i 90,4 prema 89 fL; oba p0,01). Da bismo procenili da li su povišenja RDW povezana sa težinom psorijaze, podelili smo populaciju psorijatičnih pacijenata u dve grupe na osnovu PASI vrednosti od 10. Nisu primećene značajne razlike između dve grupe (tj. PASI10 i 10) u smislu RDW (p=0,36). Usvajanje različitih PASI graničnih vrednosti (tj. 3, 5, 7, 12) takođe nije rezultiralo statistički značajnim razlikama (p=0,93, 0,48, 0,22, 0,42, respektivno). U linearnoj regresionoj analizi takođe nije pronađena značajna korelacija između RDW i PASI ili CRP, kao ni u vezi sa godinama, polom ili komorbi ditetima psorijaze navedenim u Tabeli I. Pored toga, nije zabeležena značajna razlika vrednosti RDW između psorijatičnih pacijenata sa i bez PsA (p=0,27).Rezultati ove studije potvrđuju da je RDW povišen kod psorijatičnih pacijenata, iako se čini da veličina njegovog povećanja nije povezana sa težinom bolesti.

The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at individual patients' level to capture the possible effect of ethnicity, gene-gene interaction or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived. This article is protected by copyright. All rights reserved.

BackgroundSince universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response.MethodsThree healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), IgG anti-S1/S2, IgG anti-RBD, IgM anti-RBD, IgM anti-N/S1 and IgA anti-S1.ResultsAll subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, IgG anti-S1/S2 and IgG anti-RBD levels increased between 91-368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ∼30-, ∼8- and ∼8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ∼50 days after the first dose. IgA anti-S1 levels increased between 7-11 days after the first dose, slightly declined before the second dose, after which levels augmented by ∼24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4 to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all time points.ConclusionsBNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving IgG and IgA, magnified by the second vaccine dose.

Objectives Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Pfizer Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), anti-S1/S2 and anti-RBD IgG, anti-RBD and anti-N/S1 IgM, and anti-S1 IgA. Results All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG levels increased between 91 and 368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ∼30-, ∼8- and ∼8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ∼50 days after the first vaccine dose. Anti-S1 IgA levels increased between 7 and 11 days after the first dose, slightly declined before the second dose, after which levels augmented by ∼24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4- to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all-time points. Conclusions BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving anti-SARS-Cov-2 IgG and IgA, magnified by the second vaccine dose.

Diabetes is one of the most prevalent diseases worldwide, whereby type 1 diabetes mellitus (T1DM) alone involves nearly 15 million patients. Although T1DM and type 2 diabetes mellitus (T2DM) are the most common types, there are other forms of diabetes which may remain often under-diagnosed, or that can be misdiagnosed as being T1DM or T2DM. After an initial diagnostic step, the differential diagnosis among T1DM, T2DM, Maturity-Onset Diabetes of the Young (MODY) and others forms has important implication for both therapeutic and behavioral decisions. Although the criteria used for diagnosing diabetes mellitus are well defined by the guidelines of the American Diabetes Association (ADA), no clear indications are provided on the optimal approach to be followed for classifying diabetes, especially in children. In this circumstance, both routine and genetic blood test may play a pivotal role. Therefore, the purpose of this article is to provide, through a narrative literature review, some elements that may aid accurate diagnosis and classification of diabetes in children and young people.

Since universal vaccinations represents the most effective strategy to mitigate coronavirus disease 2019 (COVID-19), baseline assessment and post-vaccine monitoring of anti-SARS-CoV-2 neutralizing antibodies are essential to vaccination programs. Therefore, this study aimed to compare data of five commercial anti-SARS-CoV2 immunoassays after administration of an mRNA vaccine.Venous blood was collected from three healthcare workers, receiving a double (30 g) dose of BNT162b2 mRNA Covid-19 vaccine (Comirnaty, Pfizer), on the day of the first vaccine dose and then at fixed intervals for the following 2 months. Anti-SARS-CoV-2 neutralizing antibody response was assayed with Roche Total Ig anti-RBD (receptor binding domain), DiaSorin TrimericS IgG (spike trimer), Beckman Coulter IgG anti-RBD, SNIBE IgG anti-RBD and Technogenetics IgG anti-N/S1.A total number of 45 samples were drawn at the end of the 2-month study period. The Spearman's correlations of absolute anti-SARS-CoV-2 antibodies were always excellent (all p0.001), comprised between 0.967-0.994. Satisfactory results were also observed when absolute antiSARS-CoV-2 antibodies values of the five methods were compared with the mean consensus value, with correlations always higher than 0.979 (all p0.001). The agreement of anti-SARS-CoV-2 antibodies positivity versus the consensus median positivity ranged between 0.764 and 1.000 (always p0.001), but become always0.900 after readjustment of one assay cutoff.All the immunoassays evaluated in this study appear suitable for monitoring anti-SARS-CoV-2 neutralizing antibodies response in subjects undergoing mRNA COVID-19 vaccination.Pošto univerzalna vakcinacija pretstavlja najefikasniju strategiju za zaustavljanje koronavirus oboljenja 2019 (COVID-19) veoma je važno praćenje nakon vakcinacije anti-SARS-CoV-2 antitela koja su va`na za programe vakcinacije. Iz tog razloga ovo proučavanje je imalo za cilj da poredi podatke pet komercijalnih anti-SARS-CoV-2 imunodređivanja nakon davanja mRNA vakcine.Uzeta je venska krv od tri zdravstvena radnika koja su primila duplu dozu (30 g) BNT-162b2 mRNA Covid-19 vakcine (Comirnaty, Pfizer) odmah nakon davanja prve doze vakcine a zatim u fiksiranim intervalima u roku od sledeća 2 meseca. Anti-SARS-CoV-2 neutrališuća antitela su određivana sa Roche Total Ig anti-RBD (receptor vezujući domen), DiaSorin TrimericS IgG (spike trimer), Beckman Coulter IgG anti-RBD, SNIBE IgG anti-RBD i Technogenetics IgG antiN/S1.Nakon 2 meseca uzeto je 45 uzoraka. Spearma - nova korelacija apsolutnih anti-SARS-CoV-2 antitela bila je uvek odlična (svi p0,001) sa obuhvatom između 0,967-0,994. Zadovoljavajući rezultati su dobijeni između vrednosti apsolutnih anti-SARS-CoV-2 antitela dobijenih sa svih pet metoda kad su upoređivane sa konsenzus vrednostima i korelacijom koja je bila veća od 0,979 (svi p0,001). Slaganje pozitivnosti anti-SARS-CoV-2 antitela prema konsenzus srednjoj pozitivnosti koja se kretala između 0,764 i 1,000 (uvek p0,001), bila je uvek0,900 nakon podešavanja cutoff vrednosti za jedno određivanje.Sva imunodređivanja koja su procenjivana u ovom izučavanju su pogodna za praćenje anti-SARS-CoV-2 netralizirajućih antitela koja nastaju kod osoba koja su bila vakcinisana sa mRNA COVID-19 vakcinom.

Psychological stress has long been recognized as a trigger for plaque psoriasis, and preliminary evidence suggests that psoriasis could be associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in impaired cortisol response to stress. This study aimed to investigate psychological stress, anxiety, depression and salivary cortisol in psoriatic patients. A cross sectional study involving 126 adult patients with plaque psoriasis and 116 adult healthy controls was conducted. Demographic, clinical data, Perceived Stress Scale (PSS) and Hospital Anxiety and Depression Scale (HADS) were collected. Cases and controls were asked whether they felt stressed in the last month, whilst psoriatic patients were also interrogated whether they found that psoriasis could have been worsened by stress. Moreover, 54 randomly selected subjects (27 psoriasis patients and 27 controls) underwent salivary cortisol testing at 8 am. PSS, HADS depression and anxiety subscales were significantly higher in psoriatic patients than in controls (17.2 ± 0.6 vs. 15.1 ± 0.8 p = 0.0289), (9.5 ± 0.3 vs. 6.2 ± 0.3 p < 0.001) and (8.2 ± 0.4 vs. 4.2 ± 0.3 p < 0.001), respectively. A higher rate of psoriatic patients reported feeling stress over the last month (45% vs. 19%, p < 0.001), and stress was considered a potential trigger for psoriasis flare-ups in 69% of cases. Psoriasis was strongly associated with higher PSS and HADS scores independently of sex, body mass index, diabetes, hypertension, dyslipidemia, and occupational status. Salivary cortisol was significantly lower in psoriatic patients compared to controls (9.6 ± 0.5 vs. 14.0 ± 1.1 nmol/L, p < 0.001). In conclusion, psoriasis was associated with higher psychological stress, anxiety and depressive symptoms, and with impaired cortisol response to stress.

Circular RNAs (circRNAs) are recently discovered and highly stable noncoding RNAs acting as gene regulators. These circRNAs can function as miRNA sponges, thereby upregulating or downregulating miRNA target gene expression. MiR-135b is expressed in placenta tissue and can be found in maternal circulation, thus playing a functional role in pregnancy. This miR is a target of circ_100219. This preliminary study was aimed to evaluate circ_100219 and miR-135b expression in pregnant and nonpregnant women, and explore the relationship between circ_100219 and miR-135b in serum and exosomes.Total RNA was isolated from serum and exosomes of 30 healthy pregnant women (32.9 ± 5.1 years) between 23-27 gestational weeks and 30 healthy nonpregnant women (31.3 ± 5.4 years). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify circ_100219 and miR-135b expression. GAPDH and U6 snRNA were chosen as reference for normalizing expression levels. The differences between pregnant and nonpregnant women were assessed with Mann-Whitney test and correlation with Spearman's test.The circ_100219 expression levels were significantly lower both in serum and exosomes of second trimester pregnant women compared to the control group (Our results confirm a role for circ_100219 and miR-135b in physiological pregnancy. Further studies are needed to investigate the circ_100219:miR-135b ratio in pregnancy complications.

Epigenetics, a term conventionally used to explain the intricate interplay between genes and the environment, is now regarded as the fundament of developmental biology. Several lines of evidence garnered over the past decades suggest that epigenetic alterations, mostly encompassing DNA methylation, histone tail modifications, and generation of microRNAs, play an important, though still incompletely explored, role in both primary and secondary hemostasis. Epigenetic variations may interplay with platelet functions and their responsiveness to antiplatelet drugs, and they may also exert a substantial contribution in modulating the production and release into the bloodstream of proteins involved in blood coagulation and fibrinolysis. This emerging evidence may have substantial biological and clinical implications. An enhanced understanding of posttranscriptional mechanisms would help to clarify some remaining enigmatic issues in primary and secondary hemostasis, which cannot be thoughtfully explained by genetics or biochemistry alone. Increased understanding would also pave the way to developing innovative tests for better assessment of individual risk of bleeding or thrombosis. The accurate recognition of key epigenetic mechanisms in hemostasis would then contribute to identify new putative therapeutic targets, and develop innovative agents that could be helpful for preventing or managing a vast array of hemostasis disturbances.

Background: Although it is known that glucose concentration exhibits a time-dependent decay in uncentrifuged serum and lithium-heparin blood tubes, no evidence exists on how this variation may depend on blood cell counts (CBC) and volumes. Methods: Venous blood was drawn from 30 non fasting healthy volunteers into three serum and three lithium-heparin tubes. One serum and lithium-heparin tubes were centrifuged within 15 min after collection and glucose was measured with a hexokinase assay. The second and third serum and lithium-heparin tubes were maintained at room temperature for 1 and 2 h after the first tubes were centrifuged. These other tubes were then centrifuged and glucose was measured. CBC was performed in the first lithium-heparin tube, before centrifugation. Results: The mean decrease of glucose was higher in lithium-heparin plasma than in serum (0.33 vs. 0.24 mmol/L/h; p Conclusions: Glucose concentration decrease in uncentrifuged lithium-heparin and serum tubes depends on the baseline number of RBC, WBC, neutrophils and monocytes within the tubes.

Obesity leads to the clustering of cardiovascular (CV) risk factors and the metabolic syndrome (MetS) also in children and is often accompanied by non-alcoholic fatty liver disease. Quality of dietary fat, beyond the quantity, can influence CV risk profile and, in particular, omega-3 fatty acids (FA) have been proposed as beneficial in this setting. The aim of the study was to evaluate the associations of individual CV risk factors, characterizing the MetS, with erythrocyte membrane FA, markers of average intake, in a group of 70 overweight/obese children. We conducted an observational study. Erythrocyte membrane FA were measured by gas chromatography. Spearman correlation coefficients (rS) were calculated to evaluate associations between FA and features of the MetS. Mean content of Omega-3 FA was low (Omega-3 Index = 4.7 ± 0.8%). Not omega-3 FA but some omega-6 FA, especially arachidonic acid (AA), were inversely associated with several features of the MetS: AA resulted inversely correlated with waist circumference (rS = − 0.352), triglycerides (rS = − 0.379), fasting insulin (rS = − 0.337) and 24-h SBP (rS = − 0.313). Total amount of saturated FA (SFA) and specifically palmitic acid, correlated positively with waist circumference (rS = 0.354), triglycerides (rS = 0.400) and fasting insulin (rS = 0.287). Fatty Liver Index (FLI), a predictive score of steatosis based on GGT, triglycerides and anthropometric indexes, was positively correlated to palmitic acid (rS = 0.515) and inversely to AA (rS = − 0.472). Our data suggest that omega-6 FA, and especially AA, could be protective toward CV risk factors featuring the MetS and also to indexes of hepatic steatosis in obese children, whereas SFA seems to exert opposite effects.

Purpose To define blood status of folate, vitamin B12, vitamin B6, homocysteine, and major one-carbon metabolism-related polymorphisms in healthy, males and females blood donors, aged 18–65 years were evaluated. General characteristics and lifestyle factors were also investigated. Methods An explorative cross-sectional study design was used to evaluate a sample of blood donors attending the Unit of Transfusion Medicine of the Verona University Hospital, Italy. From April 2016 to May 2018, 499 subjects were enrolled (255 men, 244 women of whom 155 of childbearing age). Major clinical characteristics including lifestyle and dietary habits, B vitamins and homocysteine were analyzed. The MTHFR 677 C>T, cSHMT 1420 C>T, DHFR 19 bp ins/del, RFC1 80 G>A polymorphisms were also determined. Results Mean plasma concentrations of folate, vitamin B12, vitamin B6 and homocysteine were 14.2 nmol/L (95% CI 13.7–14.8), 271.9 pmol/L (95% CI 262.6–281.5), 51.0 nmol/L (95% CI 48.7–53.4) and 13.5 µmol/L (95% CI 13.1–14.0), respectively. Plasma folate, was adequate (> 15 nmol/L) in 44.7% of all subjects, 39.0% of males and 42.5% of women 350 pmol/L) in 25.1% of all subjects and in 20.3% of men ≥ 45 years. The rare allele frequencies were 0.21 for MTHFR 677TT, 0.11 for cSHMT 1420TT, 0.18 for DHFR 19 bp del/del, 0.20 for RFC1 80AA, and a gene–nutrient interaction was confirmed for folate concentrations according to MTHFR 677C>T and DHFR 19 bp del/del. Conclusion An Italian sample of healthy blood donors shows that an adequate concentration of plasma folate and vitamin B12 is reached only in a limited percentage of subjects, thus encouraging consideration for specific public health strategies.

Colorectal cancer (CRC) is the third most common form of cancer, accounting for approximately 10% of all cancer- related deaths worldwide and accounting for as many as 19.1 million cause-specific disability-adjusted life years (DALYs) each year (1). The highest incidence rate is found in developed countries and seems prevalently associated with western lifestyle and dietary habits. However, the epidemiologic burden of CRC is raising also in other parts of the world, such as in Asia, where CRC incidence has increased by 2- to 4-fold during the past decade (1).

Background Calcitonin gene-related peptide (CGRP) is a powerful neuropeptide that is strongly involved in headache pain pathogenesis by triggering vasodilation, mast cell degranulation and neurogenic inflammation. This evidence has prompted us to investigate the acute influence of endurance exercise on CGRP concentration in blood. Methods The study population consisted of 48 male amateur runners, who ran a half-marathon distance at 75%–85% of maximal oxygen uptake. Blood was drawn before the run (pre-run) and immediately after each runner ended his trial (post-run). The serum concentration of CGRP was measured with a commercial enzyme-linked immunosorbent assay (ELISA) technique. Results Overall, 22/48 subjects (45.8%) reported suffering from headache, three of whom (6.2%) had an exertional headache, whilst 26/48 (54.2%) subjects did not report at least one headache episode during the previous 6 months (i.e. headache-free). All 48 athletes successfully covered the 21.1 km distance. Serum concentration of CGRP significantly increased by 1.5-fold in the entire group, as well as in the headache-positive and headache-free cohorts. Univariate Spearman’s correlation revealed that post-run variation of serum CGRP was significantly and inversely associated with running time (r = −0.30; p = 0.036). Conclusions The serum concentration of CGRP is significantly enhanced by medium-distance endurance exercise and the post-exercise increase is dependent on running intensity. Accordingly, high-exercise intensity might be directly related to triggering both exertional headache and/or migraine episodes.

Thrombocytopenia is a condition characterized by a decreased number of platelets in peripheral blood, which can be caused by a myriad of both congenital and acquired disorders. Drug-induced thrombocytopenia (DIT) deserves a special focus since its cumulative incidence can be as high as 10 cases per million population per year, with a prevalence of approximately 25% in critically ill patients. This condition is usually suspected following identification of an acute and severe decrease in platelet count, with values usually

Gestational diabetes mellitus (GDM) is currently defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Although this condition is typically diagnosed with evidence of abnormal plasma glucose values after glucose load, there is no international consensus regarding timing of screening and the optimal cut-off points. Some epigenetic alterations, such as DNA methylation and small non-coding RNAs, seem to play a key role in the pathogenesis of disorders of glucose metabolism, and it has also been hypothesized that epigenetic signatures could even find an important place in GDM diagnostics. In a foreseeable future, it is hence conceivable that the assessment of some predictive epigenetic biomarkers may allow early identification of women at enhanced risk of developing pregnancy complications, even before glucose metabolism is significantly impaired. Therefore, this article provides a brief update on screening/diagnostic approaches currently used in clinical practice, an overview of important studies in which epigenetic mechanisms have been associated with the pathogenesis of GDM and, finally, the emerging diagnostic contribution of these epigenetic biomarkers.

Vitamin D deficiency (VDD) is a global health care issue, with billion carrying deficiency or insufficiency around the world. This hormone plays a kaleidoscope of important roles throughout pregnancy, so that maintenance of an adequate vitamin D status is essential in this setting. Several studies, which have investigated vitamin D status in different populations of pregnant women, have convincingly reported high prevalence of vitamin D insufficiency, consistently higher than 50%. Although VDD developing during pregnancy has been associated with some adverse maternal and pregnancy outcomes, especially gestational diabetes mellitus (GDM) and preeclampsia (PE), the risk estimated are considerably heterogeneous, which makes it challenging to define operative recommendations. The mean differences in serum 25-hydroxy- cholecalciferol [25(OH)D] between GDM and non-GDM pregnant women varies between −4.93 and −7.36 nmol/L, whilst that between pre-eclamptic and non-pre-eclamptic pregnant women is even wider, being comprised between −3.86 and −14.53 nmol/L. It is hence still unclear whether assessment of vitamin D during pregnancy shall be recommended, as well as which dose of vitamin D shall be administered in pregnant women with VDD. Further studies shall be planned, which will need to be based on reliable quantification techniques [preferably liquid chromatography tandem mass spectrometry (LC-MS/MS)-based methods], but will also need to reduce the impact of many confounding factors such as ethnicity, sunlight exposure and sampling time.

Red blood cell distribution width (RDW) reflects erythrocyte size distribution, thus representing a reliable index of anisocytosis, widely used for the differential diagnosis of micro- and normocytic anaemias. Along with the large use in diagnostic hematology, RDW has been associated with presence and complications of a vast array of human pathologies during the last decades, including cardiovascular (CV) diseases. This article is hence aimed to provide an overview of important studies and systematic reviews with meta-analysis, in which RDW has been associated with CV events and mortality, in the attempt of establishing whether enough evidence exists for supporting its routine use in clinical practice. According to available data it seems reasonable to conclude that although the diagnostic specificity is low, and this measure is still plagued by important lack of standardization, RDW can be regarded as an index of enhanced patient fragility and higher vulnerability to adverse outcomes. Abnormal RDW values shall hence persuade physicians to broaden the diagnostic reasoning over anaemias, especially those due to malnutrition or malabsorption, encompassing a comprehensive assessment of traditional and non-traditional CV risk factors.

To investigate the diagnostic performance of relative telomere length (RTL) in cell-free DNA (cfDNA) for endometrioid endometrial cancer (EC). We measured RTL in cfDNA of 40 EC patients (65 ± 12 years) and 31 healthy controls (HC) (63 ± 13 years), excluding in both groups other oncologic and severe non-oncologic diseases to limit confounders. Circulating cfDNA was extracted from serum using the QIAamp DNA Blood Mini kit (Qiagen, Hilden, Germany). After the quantitative real-time polymerase chain reaction, telomere repeat copy number to single-gene copy number ratio was calculated. RTL in cfDNA was found to be significantly lower in EC patients than in HC (p

Background: The effect of radiofrequency exposure on human health and health care equipment is a matter of ongoing debate. This study was planned to investigate the influence of radiofrequency (RF) waves emitted by a commercial mobile phone on red blood cells (RBC) in vitro. Methods: The study population consisted of 16 ostensibly healthy volunteers. Two whole blood specimens were collected from each volunteer. One sample was placed in a plastic rack, 1 cm distant from the chassis of a commercial mobile phone which was activated by a remote phone call lasting 30 min. The other blood sample was placed in another plastic rack, but was kept distant from any type of RF source. The main RBC parameters including RBC count, hematocrit (Ht), hemoglobin, mean corpuscular platelet volume (MPV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and RBC distribution width (RDW-CV) were assessed with an Advia 2120. Results: The exposure of whole blood to the mobile phone call significantly increased Ht, hemoglobin, MCV and MCH, whereas the RBC count, MCHC and RDW-CV remained unchanged. A significant correlation was observed between variation of Ht and those of hemoglobin (p=0.008), MCV (p=0.009) or MCH (p=0.037), as well as between hemoglobin and MCV (p=0.048). Increased values were found in 13/16 (81%) samples for both Ht and hemoglobin, 14/16 (88%) samples for MCH and 16/16 (100%) samples for MCV. Conclusions: These results suggest that close mobile phone exposure may be an unappreciated and possibly underestimated cause of preanalytical bias in RBC testing.

Background Analysis of plasma metanephrine (MN) and normetanephrine (NMN) with liquid chromatography tandem mass spectrometry (LC-MS/MS) is the gold standard for the screening of pheochromocytomas and paragangliomas (PPGLs). As scarce information is available on the stability of MNs in diagnostic samples, this study was aimed at analyzing the short-term stability of plasma free MNs in whole blood and plasma, using LC-MS/MS. Methods The stability of plasma MNs was evaluated after sample collection at 1, 2 and 3 h in whole blood, and at 2, 4 and 6 h in centrifuged samples. Both studies were performed while maintaining the samples at room temperature (RT) and at 4 °C. The ClinMass Complete Kit (Recipe, Munchen, Germany) was used for measuring MNs with LC-MS/MS (Nexera X2 UHPLC-4500MD Sciex). Differences from the baseline (T0) were assessed using repeated measures one-way ANOVA, Students’ paired t-test and a comparison of the mean percentage changes with the total change limit (TCL). Results Statistically significant differences from T0 were found for both MNs (p Conclusions MN and NMN displayed different patterns of stability before and after centrifugation. Even short-time storage at RT in whole blood should hence be avoided.