The impact of oral contraceptive use on breast cancer risk: State of the art and future perspectives in the era of 4P medicine.

Breast cancer is the most commonly occurring cancer in women, the second most frequent cancer overall, and it causes the greatest number of cancer-related deaths among women. The significant increased concern of breast cancer worldwide may be attributed to the prolonged life expectancy and the adoption of the western lifestyle with its related risks factors. A woman's risk for breast cancer is linked to her reproductive history and with her lifetime hormonal exposure. Among the known risk factors for breast cancer, several studies investigated the possible role of the assumption of hormonal "pills" in both breast cancer incidence and development. Nevertheless, data about the association between the assumption of oral contraceptives and breast cancer incidence are still controversial and not conclusive. Given the public health importance of breast cancer and the popularity of hormonal "pills" as contraceptive, the impact of oral contraceptive use on breast cancer risk assumes relevance from both a clinical and a social point of view. Therefore, in this review we wanted to illustrate this issue by addressing the following major themes: a) the role of sex steroid hormones in female breast development and carcinogenesis; b) the clinical impact of hormonal oral contraception according to the state of the art literature; c) the actual scientific debate and future perspectives.

Chlamydia trachomatis elicits TLR3 expression but disrupts the inflammatory signaling down-modulating NFκB and IRF3 transcription factors in human Sertoli cells.

Chlamydia trachomatis, the leading cause of bacterial sexually transmitted diseases worldwide, can disseminate and localize to the upper genital tract impairing reproductive function. Specifically, ascending C. trachomatis genital infection has been demonstrated to cause epididymitis or epididymo-orchitis, well-known risk factors for male infertility. C. trachomatis possesses the ability to infect primary human Sertoli cells, key elements for the spermatogenetic process and the immune protection of germ cells. Therefore, herein, we investigated the innate immune response in Sertoli cells following C. trachomatis infection, as well as its indirect effects on human spermatozoa. Specifically, we evaluated C. trachomatis mediated induction of Toll-like Receptors (TLR) 2, 3 and 4 as well as of downstream intracellular signaling molecules (NFκB and IRF3) and the levels of the related inflammatory mediators (IL-1α, IL-6, IFN-α, IFN-ß and IFN-γ), in an in vitro infection model of primary human Sertoli cells. The main result of our study shows that C. trachomatis induced TLR3-mediated recognition in human Sertoli cells, accompanied by the down-modulation of NFκB and IRF3-dependent signaling pathways followed by no production of pro-inflammatory cytokines. In conclusion, our findings suggest that C. trachomatis can disrupt the innate immune response in Sertoli cells and evade intracellular killing, potentially giving rise to a long-term infection that may exert negative effects on the male reproductive system.

Principles of proportional recovery after stroke generalize to neglect and aphasia.

BACKGROUND AND PURPOSE: Motor recovery after stroke can be characterized into two different patterns. A majority of patients recover about 70% of initial impairment, whereas some patients with severe initial deficits show little or no improvement. Here, we investigated whether recovery from visuospatial neglect and aphasia is also separated into two different groups and whether similar proportions of recovery can be expected for the two cognitive functions. METHODS: We assessed 35 patients with neglect and 14 patients with aphasia at 3 weeks and 3 months after stroke using standardized tests. Recovery patterns were classified with hierarchical clustering and the proportion of recovery was estimated from initial impairment using a linear regression analysis. RESULTS: Patients were reliably clustered into two different groups. For patients in the first cluster (n = 40), recovery followed a linear model where improvement was proportional to initial impairment and achieved 71% of maximal possible recovery for both cognitive deficits. Patients in the second cluster (n = 9) exhibited poor recovery (<25% of initial impairment). CONCLUSIONS: Our findings indicate that improvement from neglect or aphasia after stroke shows the same dichotomy and proportionality as observed in motor recovery. This is suggestive of common underlying principles of plasticity, which apply to motor and cognitive functions.

An innovative chemical strategy for PCR-free genetic detection of pathogens by an integrated electrochemical biosensor.

An innovative chemical strategy integrated in a miniaturized electrochemical device was developed for sensitive detection of a pathogen genome (HBV virus) without any amplification step. The results show a limit of detection comparable to the standard qRT-PCR method (20 copies per reaction), paving the way to future development of genetic PoC devices addressing automatized and low-cost molecular diagnostics.

Sphingosine-1-phosphate restores endothelial barrier integrity in ovarian hyperstimulation syndrome.

STUDY QUESTION: Are follicular fluid (FF) sphingosine-1-phosphate (S1P) levels in patients at risk of developing ovarian hyperstimulation syndrome (OHSS) altered and in part responsible for the high vascular permeability observed in these patients. STUDY ANSWER: FF S1P levels are lower in FF from patients at risk of OHSS and treatment with S1P may reduce vascular permeability in these patients. WHAT IS KNOWN ALREADY: Although advances have been made in the diagnosis, and management of OHSS and in basic knowledge of its development, complete prevention has proven difficult. STUDY DESIGN, SIZE, DURATION: A total of 40 FF aspirates were collected from patients undergoing ART. The women (aged 25-39 years old) were classified into a control group (n = 20) or a group at risk of OHSS (n = 20). The EA.hy926 endothelial cell line was used to assess the efffects of FF from patients at risk of OHSS with or without the addition of S1P. An animal model that develops OHSS in immature Sprague-Dawley rats were also used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Migration assays, confocal microscopy analysis of actin filaments, immunoblotting and quail chorioallantoic membrane (CAM) assays of in-vivo angiogenesis were performed and statistical comparisons between groups were made. MAIN RESULTS AND THE ROLE OF CHANCE: The S1P concentration was significantly lower in FF from patients at risk of OHSS (P = 0.03). The addition of S1P to this FF decreased cell migration (P < 0.05) and prevented VE-cadherin phosphorylation in endothelial cells (P < 0.05). S1P in the FF from patients at risk of OHSS increased the levels of VE-cadherin (P < 0.05), N-cadherin (P < 0.05) and ß-catenin (P < 0.05), and partially reversed actin redistribution in endothelial cells. The addition of S1P in FF from patients at risk of OHSS also decreased the levels of vascular endothelial growth factor (VEGF121; P < 0.01) and S1P lyase (SPL; P < 0.05) and increased the levels of S1PR1 (P < 0.05) in endothelial cells. In CAMs incubated with FF from patients at risk of OHSS with S1P, the number of vessel branch points decreased while the periendothelial cell coverage increased. Additionally, in a rat OHSS model, we demonstrated that vascular permeability and VEGF121 and its receptor KDR expression were increased in the OHSS group compared to the control group and that S1P administration decreased these parameters. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The results of this study were generated from an in-vitro system. This model reflects the microvasculature in vivo. Even though the ideal model would be the use of human endothelial cells from the ovary, it is obviously not possible to carry out this kind of approach in ovaries of patients from ART. More studies will be necessary to delineate the effects of S1P in the pathogenesis of OHSS. Hence, clinical studies are needed in order to choose the most appropriate method of prevention and management. WIDER IMPLICATIONS OF THE FINDINGS: The use of bioactive sphingolipid metabolites may contribute to finding better and safer therapeutic strategies for the treatment of OHSS and other human diseases that display aberrant vascular leakage. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants ANPCyT (PICT 2012-897), CONICET (PIP 5471), Roemmers and Baron Foundation, Argentina. The authors declare no conflict of interest.

Incidence and predictors of cardiovascular disease, chronic kidney disease, and diabetes in HIV/HCV-coinfected patients who achieved sustained virological response.

Data on the effects of sustained virologic response (SVR) to hepatitis C virus (HCV) therapy on the outcome of extrahepatic complications are scarce. We conducted this study to assess the impact of SVR on the occurrence of chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular disease (CVD) in a cohort of human immunodeficiency virus (HIV)-infected patients. We analyzed coinfected HIV/HCV patients in the Management of Standardized Evaluation of Retroviral HIV Infection (MASTER) cohort. Only event-free patients with a serum HCV-RNA determination at baseline were included. Patients were divided into four groups: INF-exposed with SVR; INF-exposed without SVR; spontaneous HCV clearance; untreated viremic patients. We estimated the incidence of extrahepatic complications and employed Kaplan-Meier curves and Cox regression to assess the association of SVR/INF strata adjusted for a series of confounders. Data from 1676 patients were analyzed (20.29 % started an INF-based regimen). Overall, the incidence of CKD, DM, CVD, and death was 5.32 [95 % confidence interval (CI) 3.99-6.98], 10.13 (95 % CI 8.20-12.37), 6.79 (95 % CI 5.26-8.65), and 13.49 (95 % CI 11.29-16.0) per 1000 person-years of follow-up, respectively. In the Cox model for treated patients, SVR was not associated with a lower risk of CKD, DM, CVD, and death compared to non-SVR. Cirrhosis was significantly associated with a higher risk of CKD [hazard ratio (HR) 2.13; 95 % CI 1.06-4.31], DM (HR 3.48; 95 % CI 2.18-5.57), and death (HR 6.18; 95 % CI 4.1-9.31), but not of CVD (HR 1.14; 95 % CI 0.57-2.3). There are still many unknowns regarding the impact of SVR on the occurrence of extrahepatic complications in coinfected HIV/HCV patients. Further investigations are needed in order to elucidate the role of SVR as an independent prognostic factor for extrahepatic events.

Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry.

BACKGROUND: Barrett's oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. METHODS: We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008-2010 and 2011-2013). Durability of successful treatment and progression to OAC were also evaluated. RESULTS: 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p<0.0001). EMR for visible lesions prior to RFA increased from 48% to 60% (p=0.013). Rescue EMR after RFA decreased from 13% to 2% (p<0.0001). Progression to OAC at 12 months is not significantly different (3.6% vs 2.1%, p=0.51). CONCLUSIONS: Clinical outcomes for BE neoplasia have improved significantly over the past 6 years with improved lesion recognition and aggressive resection of visible lesions before RFA. Despite advances in technique, the rate of cancer progression remains 2-4% at 1 year in these high-risk patients. TRIAL REGISTRATION NUMBER: ISRCTN93069556.

Photoinduced Charge Separation in a Donor-Spacer-Acceptor Dyad with N-Annulated Perylene Donor and Methylviologen Acceptor.

The first donor-acceptor species in which a strongly emissive N-annulated perylene dye is connected to a methylviologen electron acceptor unit via its macrocyclic nitrogen atom, is prepared by a stepwise, modular procedure. The absorption spectra, redox behavior, spectroelectrochemistry and photophysical properties of this dyad and of its model species are investigated, also by pump-probe fs transient absorption spectroscopy. Photoinduced oxidative electron transfer from the excited state of the dyad, centered on the N-annulated perylene subunit, to the appended methyviologen electron acceptor takes place in a few ps. The charge-separated species recombines in 19 ps. Our results indicate that N-annulated perylene can be connected to functional units by taking advantage of the macrocyclic nitrogen, an option never used until now, without losing their properties, so opening the way to new designing approaches.

Endoscopic TriModal imaging and biomarkers for neoplasia conjoined: a feasibility study in Barrett's esophagus.

In Barrett's esophagus (BE), the normal squamous lining of the esophagus is replaced by specialized columnar epithelium. Endoscopic surveillance with autofluorescence imaging (AFI) and molecular biomarkers have been studied separately to detect early neoplasia (EN) in BE. The combination of advanced-imaging modalities and biomarkers has not been investigated; AFI may help detecting biomarkers as a risk-stratification tool. We retrospectively evaluated a cohort of patients undergoing endoscopy for EN in BE with AFI and correlated five biomarkers (HPP1, RUNX3, p16, cyclin A, and p53) in tissue samples with AFI and dysplasia status. Fifty-eight samples from a previous prospective study were selected: 15 true-positive (TP: AFI-positive, EN), 21 false-positive (FP: AFI-positive, no EN), 12 true-negative (TN1; AFI-negative, no EN in sample), 10 true-negative (TN2: AFI-negative, no EN in esophagus). Methylation-specific RT-PCR was performed for HPP1, RUNX3, p16, and immunohistochemistry for cyclin A, p53. P < 0.05 was considered statistically significant. Bonferroni correction was used for multiple comparisons. P16, cyclin A, p53 correlated with dysplasia (P < 0.01, P = 0.003, P < 0.001, respectively). Increased p16 methylation was observed between TP versus TN2 (P = 0.003) and TN1 versus TN2 (P = 0.04) subgroups, suggesting a field defect. Only p53 correlated with AFI-status (P = 0.003). After exclusion of EN samples, significance was lost. Although correlation with dysplasia status was confirmed for p16, cyclin A and p53, underlining the importance of these biomarkers as an early event in neoplastic progression, none of the investigated biomarkers correlated with AFI status. A larger prospective study is needed to assess the combination of AFI and a larger panel of biomarkers to improve risk stratification in BE.

Chlamydia pneumoniae and osteoporosis-associated bone loss: a new risk factor?

UNLABELLED: We found an association between the presence of Chlamydia pneumoniae DNA both in osteoporotic bone tissue and peripheral blood mononuclear cells (PBMCs) and the increase in circulating resorptive cytokines. INTRODUCTION: Our study was designed to determine whether C. pneumoniae infection may be involved in osteoporosis-associated bone loss. METHODS: The study included 59 women undergoing hip joint replacement surgery for femoral neck fracture: 32 with osteoporosis and 27 with osteoarthritis. A total of 118 tissue specimens (59 bone tissues, 59 PBMCs) were examined for C. pneumoniae DNA by real-time polymerase chain reaction (PCR). Serum levels of soluble receptor activator of nuclear factor kappa B ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6 were also measured. RESULTS: C. pneumoniae DNA was detected in osteoporotic bone tissue whereas it was not found in non-osteoporotic bone tissue (p < 0.05). A significantly higher rate of C. pneumoniae DNA (p < 0.05) was found in PBMCs of osteoporotic patients than in those of osteoarthritis patients. Among osteoporotic patients, serum sRANKL, IL-1, and IL-6 concentrations as well as sRANKL/OPG ratio significantly differ between patients with bone tissue and PBMCs positive to C. pneumoniae and C. pneumoniae-negative patients. CONCLUSION: The association between the presence of C. pneumoniae DNA, both in bone tissue and PBMCs, and the increase in sRANKL/OPG ratio as well as in IL-1ß and IL-6 levels observed in osteoporotic patients suggests C. pneumoniae infection as a new risk factor for osteoporosis.

New insights into Chlamydiae persistence: an energy metabolism strategy?

Chlamydiaceae is a family of obligate intracellular bacteria generally considered energy parasites. Several studies have suggested that Chlamydiae are capable of independently producing energy and, more importantly, several genes involved in the energy metabolism are up-regulated during the persistent state. Thus, it has been suggested that chlamydial persistence could be a complex and flexible metabolic strategy designed to favor a lengthy survival in the host cell by evading the immune response. In conclusion, more detailed studies on the shift in the chlamydial energy metabolism, from the active to the persistent form, may be helpful in future to determine whether chlamydial persistence observed in vitro does occur in vivo and whether chronic sequelae of chlamydial diseases may be related to the persistence.

Resveratrol in Chlamydia pneumoniae-induced foam cell formation and interleukin-17A synthesis.

The involvement of Chlamydia pneumoniae in the pathogenesis of atherosclerosis has been suggested by numerous seroepidemiological, in vivo and in vitro studies. In particular, it has been shown that C. pneumoniae is able to promote the accumulation of low-density lipoproteins into macrophages, thus facilitating foam cell formation. The aim of our study was to investigate the effects of resveratrol on macrophage derived foam cell formation induced by C. pneumoniae, examining its underlying biochemical mechanisms. Our results showed a relevant decrease in the number of foam cells, in the production of thiobarbituric acid reactive substances, superoxide anion and IL 17A while treating C. pneumoniae infected macrophages with resveratrol. Furthermore, the inhibition of Peroxisome Proliferator-Activated Receptors gamma by a specific antagonist (GW 9662), in presence of resveratrol and C. pneumoniae, enhanced intracellular lipid and cholesterol accumulation and the subsequent foam cell formation. In conclusion, the main result of our study is the evidence of an antiatherogenic effect of resveratrol on macrophage-derived foam cell formation and IL-17A production induced by C. pneumoniae.

Could past Chlamydial vascular infection promote the dissemination of Chlamydia pneumoniae to the brain?

Chlamydia pneumoniae, a pathogen responsible for respiratory tract infections, has been associated with atherosclerosis which, along with hypertension, hyperlipidemia, cardiovascular and/or cerebrovascular ischemia and stroke, is a risk factor for chronic neurological disorders. Several studies have demonstrated the ability of C. pneumoniae to disseminate from lungs to arteries through peripheral blood mononuclear cells. Once inside the vascular tissue, C. pneumoniae infection may disseminate via peripheral monocytes to the brain over the intact blood-brain barrier, and contribute to the development of chronic neurological disorders. The aim of our study was to evaluate whether past C. pneumoniae vascular infection may promote the dissemination of this microorganism to the brain, therefore we investigated the presence of C. pneumoniae in post-mortem brain tissue specimens of patients with past chlamydial vascular infection. Seventy six post-mortem brain tissue specimens from 19 patients with past chlamydial vascular infection were investigated for the presence of C. pneumoniae by immunohistochemistry, polymerase chain reaction, in situ polymerase chain reaction and in situ reverse transcription polymerase chain reaction. As control, 28 brain tissue specimens were taken from 7 age and sex matched subjects without chlamydial infection. C. pneumoniae was detected in 16 (84.2%) out of 19 patients with chlamydial vascular infection whereas it was not detected in control subjects (p= 0.0002). In conclusion, the main result of our study is the evidence that a chlamydial vascular infection can disseminate to the brain. It will be important for current and future researches to perform large-scale prospective studies on cardiovascular patients with chlamydial vascular infection in order to evaluate the long-term pathological alterations of the brain.

What can the Interventional Endoscopist Offer in the Management of Upper Gastrointestinal Malignancies?

The therapeutic possibilities of endoscopy have rapidly increased in the last decades and now allow organ-sparing treatment of early upper gastrointestinal malignancy as well as an increasing number of options for symptom palliation. This review contains an overview of the interventional endoscopic procedures in upper gastrointestinal malignancies. It describes endoscopic treatment of early oesophageal and gastric cancers, and the palliative options in managing dysphagia and gastric outlet obstruction. It also provides an overview of the therapeutic possibilities of biliary endoscopy, such as retrograde stenting and radiofrequency biliary ablation. Endoscopic ultrasound-guided therapeutic options are discussed, including biliary drainage, gastrojejunostomy and coeliac axis block. To aid in clinical decision making, the procedures are described in the context of their indication, efficacy, risks and limitations.

Health and welfare assessment of beef cattle during the adaptation period in a specialized commercial fattening unit.

Beef cattle welfare and health status are influenced by housing and management systems. The present study aimed to assess the welfare and health status in the first 15 days after arrival of Limousine bulls imported from France and fattened in a commercial fattening unit in Italy. A total of 264 bulls were included in the study. Welfare, biosecurity, and major hazard and warning system were assessed on days 2 (T1) and 15 (T2) after arrival to the unit. At T1 and T2 an inspective clinical examination was performed on all bulls. At T1 and T2 blood samples were collected from 88 bulls for haematological analysis. Both at T1 and T2, the welfare, biosecurity, and major hazards and warning systems were classified with a general score of medium but with a decrease on animal-based measurements in T2. At T1 and T2 the clinical examination revealed a significant increase (p-value≤0.05) of skin lesions and lameness in T2. A high incidence of respiratory disease was noticed in both assessed times. Leucocytes and all differentials count, and platelets were significantly increased (p-value≤0.05) at T2, while the fibrinogen was significantly decreased. The haematological changes suggest that the bulls were under higher stress in T2 when compared with T1 linked with a difficult adaptation response to the fattening unit. A multi-factorial approach that integrates the indicators of the checklist and the clinical and haematological findings of animals can be a useful method to deepen the assessment of welfare in beef cattle.

Analysis of gene expression in penicillin G induced persistence of Chlamydia pneumoniae.

Chlamydia pneumoniae is responsible for respiratory tract infections and has been associated to chronic diseases such as atherosclerosis. The involvement of C. pneumoniae in chronic diseases may be correlated to its ability to induce persistent forms in which Chlamydiae remain viable but are not cultivable. The aim of our study is to investigate C. pneumoniae specific gene activities associated with the development of Chlamydial persistence in a cell culture system in the presence of penicillin G. Chlamydia-infected HEp 2 cells were incubated with or without penicillin G for up to 72 hours. The relative mRNA expression levels of early and late genes in treated and untreated cell cultures were determined by Real-time RT-PCR. Our results revealed a consistent down-regulation of Chlamydial hctA and hctB genes (p=0.012 and p=0.003 respectively) in association with up-regulation of htrA gene (p=0.002) during penicillin G-induced persistence suggesting these gene sets as leading candidate for in vivo investigation of the development of persistent Chlamydial infection. In conclusion, the Chlamydial expression pattern of hctA, hctB, and htrA genes may be helpful to identify target molecules to diagnose and treat Chlamydia-associated chronic diseases.

The impact of COVID-19 vaccines on fertility-A systematic review and meta-analysis.

BACKGROUND: Despite literature's evidence about COVID-19 vaccines' safety, concerns have arisen regarding adverse events, including the possible impact on fertility, accentuated by misinformation and anti-vaccine campaigns. The present study aims to answer the question: Is there any impact of COVID-19 vaccines on the fertility of men and women of reproductive age? METHODS: PubMed, Scopus, Web of Science, Cochrane and Embase databases were searched for eligible studies until June 8th, 2022. The search was restricted to articles regarding humans, published in any languages, without additional restrictions. Studies' quality was assessed by the Newcastle-Ottawa and the Before and After Quality Assessment scales for cohort and pre-post studies, respectively. Random-effect meta-analyses were performed for parameters considered in ≥ 2 studies, calculating means, p-values and 95 % Confidence Intervals (CIs). RESULTS: Out of 1406 studies screened, 29 were included in the systematic review. These studies, conducted in Israel (34.5 %), USA (24.1 %), Russia (20.7 %) China (10.3 %), Italy (3.5 %), North America (3.5%) and Turkey (3.5 %) were of poor (34.5 %), moderate (58.6 %) and good (6.9 %) quality. Meta-analyses were performed for pre- and post-vaccination sperm progressive motility (44 %, 95 % CI 42 %-62 % vs 43 %, 95 % CI 31 %-59 % p = 0.07) and concentration (50.6 mln/ml, 95 % CI 35.1-72.8 vs 55.4 mln/ml, 95 % CI 37.4-82.2p = 0.12). Biochemical (0.51, 95 % CI 0.40-0.66 vs 0.60, 95 % CI 0.53-0.68p = 0.45) and clinical (0.45, 95 % CI 0.37-0.54 vs 0.47, 95 % CI 0.40-0.55 p = 0.31) pregnancy rate did not differ among vaccinated and not vaccinated groups. Subgroup meta-analyses based on the type of vaccine showed no significant difference: between vaccinated with mRNA vaccines and non-vaccinated regarding biochemical pregnancy rates; pre- and post-vaccination with Gam-COVID-Vac regarding testosterone, FSH and LH levels; pre- and post-vaccination with BNT162b2 vaccines regarding sperm volumes. CONCLUSION: Based on the studies published so far, there is no scientific proof of any association between COVID-19 vaccines and fertility impairment in men or women.

ECG monitoring of post-stroke occurring arrhythmias: an observational study using 7-day Holter ECG.

Post-stroke arrhythmias represent a risk factor for complications and worse prognosis after cerebrovascular events. The aims of the study were to detect the rate of atrial fibrillation (AF) and other cardiac arrhythmias after acute ischemic stroke, by using a 7-day Holter ECG which has proved to be superior to the standard 24-h recording, and to evaluate the possible association between brain lesions and arrhythmias. One hundred and twenty patients with cryptogenic ischemic stroke underwent clinical and neuroimaging assessment and were monitored with a 7-day Holter ECG. Analysis of the rhythm recorded over 7 days was compared to analysis limited at the first 24 h of monitoring. 7-day Holter ECG detected AF in 4% of patients, supraventricular extrasystole (SVEB) in 94%, ventricular extrasystole (VEB) in 88%, short supraventricular runs (SVRs) in 54%, supraventricular tachycardia in 20%, and bradycardia in 6%. Compared to the first 24 h of monitoring, 7-Holter ECG showed a significant higher detection for all arrhythmias (AF p = 0.02; bradycardia p = 0.03; tachycardia p = 0.0001; SVEB p = 0.0002; VEB p = 0.0001; SVRs p = 0.0001). Patients with SVRs and bradycardia were older (p = 0.0001; p = 0.035) and had higher CHA2DS2VASc scores (p = 0.004; p = 0.026) respectively, in the comparison with patients without these two arrhythmias. An association was found between SVEB and parietal (p = 0.013) and temporal (p = 0.013) lobe lesions, whereas VEB correlated with insular involvement (p = 0.002). 7-day Holter ECG monitoring proved to be superior as compared to 24-h recording for the detection of all arrhythmias, some of which (SVEB and VEB) were associated with specific brain areas involvement. Therefore, 7-day Holter ECG should be required as an effective first-line approach to improve both diagnosis and therapeutic management after stroke.

Multi-omic cross-sectional cohort study of pre-malignant Barrett's esophagus reveals early structural variation and retrotransposon activity.

Barrett's esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett's natural history and may inform the potential for cancer beyond the clinically discernible phenotype.

Interventions to address mental health issues in healthcare workers during infectious disease outbreaks: A systematic review.

Considering the importance of evidence on interventions to tackle mental health problems in healthcare workers (HCWs) during pandemics, we conducted a systematic review, aiming to identify and summarize the implemented interventions to deal with mental health issues of HCWs during infectious disease outbreaks and report their effectiveness. Web of Science, PubMed, Cochrane, Scopus, CINAHL and PsycInfo electronic databases were searched until October 2nd, 2020. Primary-data articles, describing any implemented interventions and their effectiveness were considered pertinent. Studies were screened according to the inclusion/exclusion criteria and subsequently data extraction was performed. Twenty-four articles, referring to SARS, Ebola, Influenza AH1N1 and COVID-19 were included. Interventions addressing mental health issues in HCWs during pandemics/epidemics were grouped into four categories: 1) informational support (training, guidelines, prevention programs), 2) instrumental support (personal protective equipment, protection protocols); 3) organizational support (manpower allocation, working hours, re-organization of facilities/structures, provision of rest areas); 4) emotional and psychological support (psychoeducation and training, mental health support team, peer-support and counselling, therapy, digital platforms and tele-support). These results might be helpful for researchers, stakeholders, and policymakers to develop evidence-based sustainable interventions and guidelines, aiming to prevent or reduce the immediate and long-term effect of pandemics on mental health status of HCWs.