Role of the Digital for the Third Sector in the Campania Region (Italy): From the Side of Research to the Side of the Objects in the Aftermath of the COVID-19Pandemic

This paper aims to investigate the role of the digital in facing the social and practical impact of the Covid-19 pandemic on particularly fragile and affected realities, Third Sector Organizations (TSO), in a context pervaded by structural and socio-economic weaknesses, the Campania Region in south Italy. It analyzes the digital object as: 1. a process - digitization/digitalization and digital transformation, 2. as a scenario - in which identities, activities, and alternative spaces of use or data collection transit and are constructed, and as 3. skills and capabilities - as social capital and value. This re-framing work is intended to be a useful tool for reflecting on the role of digital in research processes, while also offering a contribution to the debate on the Third Sector in contexts of crisis, such as the one generated by the COVID-19 pandemic, that impact its existence, activity, shape, and perspectives

Provoked Vestibulodynia and Topical Treatment: A New Option

Background: Provoked vestibulodynia is commonly associated with dyspareunia and affects 7% to 15% of women. This pathology has major implications on sexual function and quality of life, and several types of treatments are available for its management. However, a consensus has not been reached concerning the best treatment of vulvar pain. The aim of this study was to assess the efficacy and safety of a brand-new product, the vulvar emulgel Meclon (R) Lenex, for the management of provoked vestibulodynia and non-infective vulvitis. Methods: This was a monocentric, prospective, randomized, double-blind and placebo-controlled study. We enrolled 40 women with provoked vestibulodynia; 20 patients received Meclon (R) Lenex, whereas the remaining received a placebo. Each woman was assessed subjectively (through questionnaires) and objectively by evaluating vaginal and vulvar symptoms (Friedrichs criteria and Marinoff dyspareunia grade). We evaluated efficacy, safety, compliance and tolerability of the brand-new product vulvar gel Meclon (R) Lenex in provoked vestibulodynia. Results: After administration of Meclon (R) Lenex, we evaluated all parameters of the Friedrichs criteria (burning, dyspareunia, erythema, vulvar pain at the 5 o'clock position and 7 o'clock position), as well as the levels of Marinoff dyspareunia. The active treatment showed to be statistically significantly effective (p value <= 0.05) in reducing all symptoms of Friedrichs criteria, vulvar pain and Marinoff dyspareunia. Conclusion: This prospective study showed that Meclon (R) Lenex vulvar emulgel revealed an excellent tolerability and compliance, demonstrating to be a safe and effective option in the treatment of provoked vestibulodynia and non-infective vulvitis

A Randomized Controlled Trial Comparing a New D-Mannose-based Dietary Supplement to Placebo for the Treatment of Uncomplicated Escherichia coli Urinary Tract Infections

Background: The rise in antimicrobial resistance means that alternative approaches for the treatment and prevention of urinary tract infection (UTIs) are required. Objective: To evaluate the safety and efficacy of a D-mannose-based dietary supplement (D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion; DAPAD complex) for the treatment of uncomplicated acute E. coli UTIs. Design, setting, and participants: This was a single-center, randomized, double-blind, placebo-controlled trial conducted from April 2021 to October 2021 in Rajalakshmi Hospital and Research Centre (Bangalore, India). The participants were nonmenopausal women with an acute uncomplicated E. coli UTI. UTI was diagnosed according to the presence of at least one urinary symptom and bacteriuria (>100 000 CFU/ml). Intervention: The DAPAD complex was administered twice a day for 5 d, with phenazopyridine and alkalizing agents as the standard of care (SOC). The control group received placebo with SOC. Outcome measurements and statistical analysis: Subjective (clinical resolution/response) and objective (midstream bacteriuria) outcomes were evaluated at the end of therapy (day 6) and at day 35 of follow-up. Adverse events were recorded. Categorical variables were analyzed using χ2 and Fisher's exact tests; a p value <0.05 was considered significant. Results and limitations: Seventy women were enrolled and equally randomized to the two groups. Clinical resolution was higher in the DAPAD group at 6 d (34.3% vs 0%; p < 0.0001) and 35 d from baseline (88.6% vs 20%, p < 0.0001). At day 35, no patients in the DAPAD group had moderate or severe symptoms, whereas 25.7% (nine/35) and 11.4% (four/35) of patients in the placebo group had moderate and severe symptoms, respectively. Bacteriological resolution was also higher in the DAPAD group at day 6 (85.7% vs 14.3%; p < 0.0001) and day 35 (100% vs 40%; p < 0.0001). Three mild adverse events (4.26%) unrelated to the investigated product were recorded, all of which were medically treated. Conclusions: The DAPAD complex dietary supplement is effective and safe for treatment of acute uncomplicated E. coli UTIs. Patient summary: Our results show that for nonmenopausal women with an uncomplicated Escherichia coli urinary tract infection, those treated with a dietary supplement (containing D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion) had a higher rate of clinical resolution or response than women who received a placebo

A new tool for investigation platelet activation in endometriosis patients

Objectives: Endometriosis (EM) is a gynecological disease characterized by chronic inflammation, due to the interaction of inflammatory cells with ectopic endometrium (1). Platelets (PLTs), recruited by procoagulant factors released from endometriotic stromal cells, secrete angiogenetic factors and induce overexpression of genes involved in pro-survival/ anti-apoptotic propensity, inflammationand extracellular matrix remodeling (2). We aimed to develop a tool to measure PLT activation (by small extracellular vesicles, s-EVs) in EM peritoneal fluids, as a potential predictive marker of EM severity. Materials & methods: S-EVs were isolated from EM peritoneal fluids and characterized with imaging (Atomic Force Microscopy; AFM) and protein expression analyses (Western blot, WB) (3). We explored gene expression in peritoneum and EM lesions using EndometDB (4). Results: We demonstrated the presence of s-EVs isolated from EM peritoneal fluids by liquid AFM, as showed by contact angle vs diameter scatterplot (Fig.1A-B), and by WB detecting the s-EV markers CD63, CD9, and TSG101 (Fig.1C). Using Endomet-DB, we highlighted the differentially expressed genes between control and EM peritoneum samples (Fig.1D). The protein expression of a panel of biomarkers of PTL in s-EVs was further confirmed by WB (Fig.1E). Conclusions: We propose applying s-EV research to EM investigation, generating a novel biochemical tool for PLT activation assessment and for the development of new diagnostics and therapies

Detention and mapping of iron and toxic environmental elements in human ovarian endometriosis: A suggested combined role

Background: Endometriosis is a disease affecting 10-15 % of women worldwide, consisting in the ectopic growth of endometrial cells outside the uterine cavity. Whist the pathogenetic mechanisms of endometriosis remain elusive and contemplating even environmental causes, iron deposits are common in endometrial lesions, indicating an altered iron metabolism at this level. This study was undertaken to reveal a possible relationship between iron dysmetabolism and accumulation of environmental metals. Methods: By combining histological and histochemical analysis (H&E and Perl's staining) with μ- and nano- synchrotron-based (SR-based) X-ray Fluorescence (XRF) microscopy, we investigated the distribution of iron and other elements in the ovarian endometriomas of 12 endometriosis patients and in 7 healthy endometrium samples. Results: XRF microscopy expanded the findings obtained by Perl's staining, revealing with an exceptional sensitivity intracellular features of iron accumulation in the epithelial endometrium, stroma and macrophages of the endometriotic lesions. XRF evidenced that iron was specifically accumulated in multiple micro aggregates, reaching concentrations up to 10-20 % p/p. Moreover, by XRF analysis we revealed for the first time the retention of a number of exogenous and potentially toxic metals such as Pb, Br, Ti, Al Cr, Si and Rb partially or totally co-localizing with iron. Conclusion: μXRF reveals accumulation and colocalization of iron and environmental metals in human ovarian endometriosis, suggesting a role in the pathogenesis of endometriosis

Anti-Spike Antibodies Present in the Milk of SARS-CoV-2 Vaccinated Mothers Are Complement-Activating

Although only 0.8–1% of SARS-CoV-2 infections are in the 0–9 age-group, pneumonia is still the leading cause of infant mortality globally. Antibodies specifically directed against SARS-CoV-2 spike protein (S) are produced during severe COVID-19 manifestations. Following vaccination, specific antibodies are also detected in the milk of breastfeeding mothers. Since antibody binding to viral antigens can trigger activation of the complement classical - pathway, we investigated antibody-dependent complement activation by anti-S immunoglobulins (Igs) present in breast milk following SARS-CoV-2 vaccination. This was in view of the fact that complement could play a fundamentally protective role against SARS-CoV-2 infection in newborns. Thus, 22 vaccinated, lactating healthcare and school workers were enrolled, and a sample of serum and milk was collected from each woman. We first tested for the presence of anti-S IgG and IgA in serum and milk of breastfeeding women by ELISA. We then measured the concentration of the first subcomponents of the three complement pathways (i.e., C1q, MBL, and C3) and the ability of anti-S Igs detected in milk to activate the complement in vitro. The current study demonstrated that vaccinated mothers have anti-S IgG in serum as well as in breast milk, which is capable of activating complement and may confer a protective benefit to breastfed newborns

Puzzling Out the Genetic Architecture of Endometriosis: Whole-Exome Sequencing and Novel Candidate Gene Identification in a Deeply Clinically Characterised Cohort

Endometriosis (EM) is a common multifactorial gynaecological disorder. Although Genome-Wide Association Studies have largely been employed, the current knowledge of the genetic mechanisms underlying EM is far from complete, and other approaches are needed. To this purpose, whole-exome sequencing (WES) was performed on a deeply characterised cohort of 80 EM patients aimed at the identification of rare and damaging variants within 46 EM-associated genes and novel candidates. WES analysis detected 63 rare, predicted, and damaging heterozygous variants within 24 genes in 63% of the EM patients. In particular, (1) a total of 43% of patients carried variants within 13 recurrent genes (FCRL3, LAMA5, SYNE1, SYNE2, GREB1, MAP3K4, C3, MMP3, MMP9, TYK2, VEGFA, VEZT, RHOJ); (2) a total of 8.8% carried private variants within eight genes (KAZN, IL18, WT1, CYP19A1, IL1A, IL2RB, LILRB2, ZNF366); (3) a total of 24% carried variants within three novel candidates (ABCA13, NEB, CSMD1). Finally, to deepen the polygenic architecture of EM, a comprehensive evaluation of the analysed genes was performed, revealing a higher burden (p < 0.05) of genes harbouring rare and damaging variants in the EM patients than in the controls. These results highlight new insights into EM genetics, allowing for the definition of novel genotype–phenotype correlations, thereby contributing, in a long-term perspective, to the development of personalised care for EM patients

A longitudinal study of C1q and anti-C1q autoantibodies in homologous and heterologous pregnancies for predicting pre-eclampsia

C1q, the recognition molecule of the classical pathway of the complement system, plays a central role in pregnancy. Lack of C1q is characterized by poor trophoblast invasion and pregnancy failure. C1q can be the target of an antibody response: anti-C1q autoantibodies (anti-C1q) are present in several infectious and autoimmune diseases. The presence of these autoantibodies has been detected also in 2-8% of the general population. Recent evidence indicates that women who undergo assisted reproductive technology (ART) have an increased risk of developing pre-eclampsia (PE), particularly oocyte donation (OD) pregnancies. The aim of this study was to characterize the levels of C1q and anti-C1q in PE gestations, in healthy spontaneous, homologous and heterologous ART pregnancies. Serum of the following four groups of women, who were followed throughout two or three trimesters, were collected: PE, patients diagnosed with PE; OD, oocyte donation recipients; HOM, homologous ART women; Sp, spontaneous physiological pregnancy. Our results indicate that PE patients have lower levels of anti-C1q. In ART pregnant women, the trend of C1q and anti-C1q levels were similar to PE patients, even though these women did not develop PE-like symptoms during pregnancy. This finding suggests an immunological dysfunction at the foetal-maternal interface in ART pregnancies, a hypothesis confirmed by the observation of C1q deposition in placentae derived from OD, comparable to PE. Since significantly lower levels of anti-C1q were detected in PE compared to healthy control sera, we hypothesize the possible binding on placental syncytiotrophoblast microvesicles (STBM), which are increased in the circulation of PE mothers. Furthermore, the characterization of the binding-epitope of anti-C1q revealed that "physiological" autoantibodies were mainly directed against C1q globular domain. We concluded that anti-C1q could have a physiological role in pregnancy: during the healthy spontaneous pregnancy the raised levels of these autoantibodies can be important for the clearance of STBM. In PE and in pathological pregnancies (but also in OD pregnancies), the increase in syncytiotrophoblast apoptosis and consequent increase of the circulating STMB levels lead to a consumption of C1q and anti-C1q

Is the complement protein C1q a pro- or anti-tumorigenic factor? Bioinformatics analysis involving human carcinomas

C1q is the first subcomponent of the classical pathway of the complement system and belongs to the C1q/Tumor Necrosis Factor superfamily. C1q can perform a diverse range of immune and non-immune functions in a complement-dependent as well as -independent manner. Being a pattern recognition molecule of the innate immunity, C1q can recognize a number of self, non-self and altered-self ligands and bring about effector mechanisms designed to clear pathogens via opsonisation and inflammatory response. C1q is locally synthesized by macrophages and dendritic cells, and thus, can get involved in a range of biological processes, such as angiogenesis and tissue remodeling, immune modulation, and immunologic tolerance. The notion of C1q involvement in the pathogenesis of cancer is still evolving. C1q appears to have a dual role in cancer: tumor promoting as well as tumor-protective, depending on the context of the disease. In the current study, we performed a bioinformatics analysis to investigate whether C1q can serve as a potential prognostic marker for human carcinoma. We used the Oncomine database and the survival analysis platforms Kaplan-Meier plotter. Our results showed that high levels of C1q have a favorable prognostic index in basal-like breast cancer for disease-free survival, and in HER2-positive breast cancer for overall survival, while it showed a pro-tumorigenic role of C1q in lung adenocarcinoma, and in clear cell renal cell carcinoma. This in silico study, if validated via a retrospective study, can be a step forward in establishing C1q as a new tool as a prognostic biomarker for various carcinoma.Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Ital

Intratumor Heterogeneity of ALK-Rearrangements and Homogeneity of EGFR-Mutations in Mixed Lung Adenocarcinoma

BACKGROUND: Non Small Cell Lung Cancer is a highly heterogeneous tumor. Histologic intratumor heterogeneity could be 'major', characterized by a single tumor showing two different histologic types, and 'minor', due to at least 2 different growth patterns in the same tumor. Therefore, a morphological heterogeneity could reflect an intratumor molecular heterogeneity. To date, few data are reported in literature about molecular features of the mixed adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK-rearrangements in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas and adenosquamous carcinomas. METHODS: 590 Non Small Cell Lung Carcinomas tumor samples were revised in order to select mixed adenocarcinomas with available tumor components. Finally, only 105 mixed adenocarcinomas and 17 adenosquamous carcinomas were included in the study for further analyses. Two TMAs were built selecting the different intratumor histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR-mutations were detected through IHC and confirmed by RT-PCR. RESULTS: 10/122 cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the EGFR-mutated protein in all histologic components. CONCLUSION: Our data suggests that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK-rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements could lead to a possible impact on the therapeutic responses and the disease outcomes