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Abstract Metastasis in cancer is influenced by epigenetic factors. Using an in vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast cancer metastatic dormancy in the lungs of female mice. Brd7 loss induces metastatic reawakening, along with modifications in epigenomic landscapes and upregulated oncogenic signaling. Breast cancer cells harboring Brd7 inactivation also reprogram the surrounding immune microenvironment by downregulating MHC-1 expression and promoting a pro-metastatic cytokine profile. Flow cytometric and single-cell analyses reveal increased levels of pro-tumorigenic inflammatory and transitional neutrophils, CD8+ exhausted T cells, and CD4+ stress response T cells in lungs from female mice harboring Brd7-deficient metastases. Finally, attenuating this immunosuppressive milieu by neutrophil depletion, neutrophil extracellular trap (NET) inhibition, or immune checkpoint therapy abrogates metastatic outgrowth. These findings implicate Brd7 and PBAF in triggering metastatic outgrowth in cancer, pointing to targetable underlying mechanisms involving specific immune cell compartments.

Uterine arteriovenous malformations (AVMs) are an abnormal presence of shunts between myometrial arteries and veins within the myometrium that usually occurs after a traumatic event on the uterus and it is often diagnosed after a miscarriage. In this case report, we propone the case of a woman, gravida 3 para 2, admitted at the emergency department presenting deep vaginal bleeding and suspicion of incomplete miscarriage at 11 weeks of pregnancy. The suspect of AVM was made with noninvasive procedure; transvaginal ultrasound examination with the advantage of color Doppler showed a myometrial hypervascular lesion of the posterior wall. Pulsed Doppler permitted the waveform analysis of uterine arteries and three-dimensional sonography with color Doppler and reconstructions clearly showed dilated ad tortuous blood vessels within the contest of the myometrium. Magnetic resonance angiography showed multiple tubular structures with tortuous appearance that confirmed the suspicion of AVM. Uterine artery embolization was performed of the right uterine artery. One month after uterine embolization, the ultrasound control confirmed the complete resolution of the AVM.

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Introduction and objectiveThe number of literature reviews examining the use of social media in detecting emerging infectious diseases has recently experienced an unprecedented growth. Yet, a higher-level integration of the evidence is still lacking. This study aimed to synthesize existing systematic literature reviews published on this topic, offering an overview that can help policymakers and public health authorities to select appropriate policies and guidelines.MethodsWe conducted an umbrella review: a review of systematic reviews published between 2011 and 2023 following the PRISMA statement guidelines. The review protocol was registered in the PROSPERO database (CRD42021254568). As part of the search strategy, three database searches were conducted, specifically in PubMed, Web of Science, and Google Scholar. The quality of the included reviews was determined using A Measurement Tool to Assess Systematic Reviews 2.ResultsSynthesis included 32 systematic reviews and 3,704 primary studies that investigated how the social media listening could improve the healthcare system’s efficiency in terms of a timely response to treat epidemic situations. Most of the included systematic reviews concluded showing positive outcomes when using social media data for infectious disease surveillance.ConclusionSystematic reviews showed the important role of social media in predicting and detecting disease outbreaks, potentially reducing morbidity and mortality through swift public health action. The policy interventions strongly benefit from the continued use of online data in public health surveillance systems because they can help in recognizing important patterns for disease surveillance and significantly improve the disease prediction abilities of the traditional surveillance systems.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier [CRD42021254568].

Background: Serodiagnosis of TORCH infections should be performed in pre-pregnancy and reproductive-age women to prevent vertical transmission. Herein, we conducted a 5-year cross-sectional retrospective study in childbearing age women to provide prevalence data. Also, stratifying the cohort into three age groups, we identified those most susceptible to acute TORCH infections. Methods: Between 2019 and 2023, serum samples from 2286 childbearing age women attending the “R. Dulbecco” University Hospital of Catanzaro were collected. Screening for TORCH pathogens, such as: Toxoplasma gondii (TOX), Cytomegalovirus (CMV), Rubella Virus (RUB), Parvovirus B19 (ParvoB19), Herpes Simplex Virus types 1 and 2 (HSV1, HSV2) and Treponema pallidum was carried out using serological tests. Chemiluminescent immunoassay was performed to detect TOX, CMV and ParvoB19 Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies, while Enzyme Linked Fluorescent Assay was performed to detect RUB IgM and IgG antibodies and CMV and TOX IgG Avidity. Enzyme Linked Immunosorbent Assay was performed to detect HSV1 IgG, HSV2 IgG, HSV1/2 IgM, T. pallidum total antibodies and RUB IgG Avidity. Binomial logistic regression models were developed to compare seroprevalence rates among different age groups. Results: The highest immunological protection was observed for RUB infection (87 %), probably associated with vaccination practice, followed by HSV1 and CMV (82 % and 63 %). The 16–25 year age group results as the most susceptible to acute infections as demonstrated by odds of CMV IgM positivity (primary infection) which decreased with age. Conclusions: The TORCH serological screening program should be implemented in women before pregnancy to formulate strategies for serological screening of childbearing age women and guiding clinicians in making decisions.

Questo contributo analizza il libro d’esordio di Vitaliano Trevisan, Trio senza pianoforte (1995), studiandone le forme espressive, enunciative, i riferimenti intertestuali (Bernhard), le ambientazioni. Lo scopo è quello di riscontrare, sul piano interpretativo, gli elementi utili a sostenere l’idea che l’autore abbia messo in atto una serie di strategie diversive che consistono nel distanziamento e nell’allontanamento dalle proprie origini, dalla propria città, dalla propria lingua. Con questa operazione, in un certo senso preliminare, di allontanamento da sé, Trevisan assume un’identità culturale, diversa dall’identità reale, che diventa fondamentale per la costruzione della sua opera.

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.

Semaphorins were originally identified as axonal guidance molecules, but they also control processes such as vascular development and tumorigenesis. The downstream signaling cascades of Semaphorins in these biological processes remain unclear. Here, we show that the class 3 Semaphorins (SEMA3s) activate the Hippo pathway to attenuate tissue growth, angiogenesis, and tumorigenesis. SEMA3B restoration in lung cancer cells with SEMA3B loss of heterozygosity suppresses cancer cell growth via activating the core Hippo kinases LATS1/2 (large tumor suppressor kinase 1/2). Furthermore, SEMA3 also acts through LATS1/2 to inhibit angiogenesis. We identified p190RhoGAPs as essential partners of the SEMA3A receptor PlexinA in Hippo regulation. Upon SEMA3 treatment, PlexinA interacts with the pseudo-guanosine triphosphatase (GTPase) domain of p190RhoGAP and simultaneously recruits RND GTPases to activate p190RhoGAP, which then stimulates LATS1/2. Disease-associated etiological factors, such as genetic lesions and oscillatory shear, diminish Hippo pathway regulation by SEMA3. Our study thus discovers a critical role of Hippo signaling in mediating SEMA3 physiological function.

Background/Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of fertile age. Some studies suggest that a ketogenic diet (KD) may have a role in treating PCOS. We aimed to demonstrate the long-term effectiveness of a KD in PCOS. Methods: Eighteen patients with PCOS phenotype A were enrolled: 28% were of normal weight, 28% were overweight, and 44% had obesity. All participants followed a KD without meal replacements for 45 days. After this period, patients underwent gradual carbohydrate reintroduction over 45 days, and thereafter healthy eating indications were given. Twelve patients completed the study. The patients were assessed at baseline and after 6 months. Anthropometric data, body composition, pelvic ultrasound, blood chemistry, hirsutism, and menstrual cycles frequency were recorded; Results: Besides improvement in anthropometric parameters, menstrual cycles (p 0.012), ovarian volume (p 0.029), FSH (p 0.05), LH (p 0.037), and progesterone (p 0.017) improved independently of weight or fat loss. However, testosterone and hirsutism improvements were influenced by weight and fat mass reduction. Conclusions: Our study showed that a KD followed by gradual carbohydrate reintroduction in PCOS has beneficial effects medium term, mostly independent of body weight loss, even in normal-weight women, suggesting that nutritional ketosis exerts beneficial effects per se.

Chewing is one of the most important orofacial functions. Over the last twenty years, a number of authors have examined the correlation between an efficient chewing function and different aspects of body functions: implementation of cognitive functions, reduction of nociceptive impulse propagation, reduced levels of stress, reduced risk of developing atherosclerosis and desaturation, limitation of eating disorders and constipation. Starting from the above considerations, this study aims at investigating the correlation between occlusal balance – without which there would be no proper mastication – and fundamental aspects as cognitive function, stress, arousal and concentration. For this purpose, we used specific tools and software to observe the electrical activity of the brain in 10 healthy volunteers. All the measurements for each participant have been carried out in three different phases: a first phase in which all the individuals were in a condition of initial occlusion; a second phase in which the occlusion was modified using a functional orthodontic device; and a third phase, in which individuals removed the device. The variations between three phases have been evaluated by using the Student’s t-test, and we considered them significant for p

Metastasis in cancer is influenced by epigenetic factors. Using an in vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast cancer metastatic dormancy in the lungs of female mice. Brd7 loss induces metastatic reawakening, along with modifications in epigenomic landscapes and upregulated oncogenic signaling. Breast cancer cells harboring Brd7 inactivation also reprogram the surrounding immune microenvironment by downregulating MHC-1 expression and promoting a pro-metastatic cytokine profile. Flow cytometric and single-cell analyses reveal increased levels of pro-tumorigenic inflammatory and transitional neutrophils, CD8+ exhausted T cells, and CD4+ stress response T cells in lungs from female mice harboring Brd7-deficient metastases. Finally, attenuating this immunosuppressive milieu by neutrophil depletion, neutrophil extracellular trap (NET) inhibition, or immune checkpoint therapy abrogates metastatic outgrowth. These findings implicate Brd7 and PBAF in triggering metastatic outgrowth in cancer, pointing to targetable underlying mechanisms involving specific immune cell compartments. Metastasis-initiating cells can reawaken from a dormant state that initially allowed them to survive, triggering metastatic outgrowth. Here, authors show that loss of Brd7 promotes an immunosuppressive tumor microenvironment that drives breast cancer metastatic reawakening from dormancy in the lung. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 virus, which is a major threat to human health, has undergone many mutations during the replication process due to errors in the replication steps and modifications in the structure of viral proteins. The XBB variant was identified for the first time in Singapore in the fall of 2022. It was then detected in other countries, including the United States, Canada, and the United Kingdom. We study the impact of sequence changes on spike protein structure on the subvariants of XBB, with particular attention to the velocity of variant diffusion and virus activity with respect to its diffusion. We examine the structural and functional distinctions of the variants in three different conformations: (i) spike glycoprotein in complex with ACE2 (1-up state), (ii) spike glycoprotein (closed-1 state), and (iii) S protein (open-1 state). We also estimate the affinity binding between the spike protein and ACE2. The market binding affinity observed in specific variants raises questions about the efficacy of current vaccines in preparing the immune system for virus variant recognition. This work may be useful in devising strategies to manage the ongoing COVID-19 pandemic. To stay ahead of the virus evolution, further research and surveillance should be carried out to adjust public health measures accordingly.

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Abstract Background T2Dx was approved by the US Food and Drug Administration for the rapid detection of a modified panel of ESKAPE bacterial species or Candida spp. causing bloodstream infection (BSI). Patients and methods We performed a retrospective, observational study from January 1, 2018 to December 31, 2019 of all hospitalised patients with suspected BSI who underwent assessment using T2Dx in addition to standard blood culture (BC). T2-positive patients (cases) were compared to a matched group of patients with BSI documented only by BC (1:2 ratio) to investigate the possible impact of T2Dx on the appropriateness of empirical antimicrobial therapy and 21-day mortality. Results In total, 78 T2Dx-analysed samples (49 patients) were analysed. The T2Dx assay result was positive for18 patients and negative for 31 patients. The concordance rates of the T2Bacteria Panel and T2Candida Panel results with those of standard BC were 74.4% and 91.4%, respectively. In the matched analysis, inappropriate empiric antimicrobial therapy administration was significantly less frequent in cases than in comparators (5.5% vs. 38.8%). The 21-day mortality rate was twofold lower in cases than in comparators (22.2% vs. 44.4%), although the difference was not significant. No other analysed variables were significantly different between the two groups. Conclusions This study illustrated that T2Dx might be associated with an increase in the appropriateness of empiric antimicrobial therapy in patients with BSI. Further studies are needed to evaluate whether the T2Dx assay can improve patient outcomes.