Culturomics: bacterial species isolated in 3 healthy donors for faecal microbiota transplantation in Clostridium difficile infection

Background. Clostridium difficile infections are the main cause of nosocomial acquired diarrhea, because of prolonged antibiotic regimens. In the last years, mortality has increased due to recurrent infections caused by metronidazole and vancomicin resistant hypervirulent C. difficile strain 027. Faecal Microbiota Transplantation (FMT) is an infusion of faecal material obtained from healthy donors. This procedure reduces mortality in recurrent C. difficile infections (CDI). In this study we identified bacterial species obtained from donors' stool samples using culturomics. Materials and methods. Three donors were selected for FMT in three recipients affected by CDI. Faces obtained for FMT underwent culturomics, applying 17 different culture methods. Results and conclusions. Several different bacteria were isolated from donors. In two donors 4 potentially pathogenic bacteria were isolated; this suggests the use of culturomics for donors' screening or for selection of bacteria to infuse

High-to-Low (Regional) Fertility Transitions in a Peripheral European Country: The Contribution of Exploratory Time Series Analysis

[EN] Diachronic variations in demographic rates have frequently reflected social transformations and a (more or less evident) impact of sequential economic downturns. By assessing changes over time in Total Fertility Rate (TFR) at the regional scale in Italy, our study investigates the long-term transition (1952-2019) characteristic of Mediterranean fertility, showing a continuous decline of births since the late 1970s and marked disparities between high- and low-fertility regions along the latitude gradient. Together with a rapid decline in the country TFR, the spatiotemporal evolution of regional fertility in Italy-illustrated through an exploratory time series statistical approach-outlines the marked divide between (wealthier) Northern regions and (economically disadvantaged) Southern regions. Non-linear fertility trends and increasing spatial heterogeneity in more recent times indicate the role of individual behaviors leveraging a generalized decline in marriage and childbearing propensity. Assuming differential responses of regional fertility to changing socioeconomic contexts, these trends are more evident in Southern Italy than in Northern Italy. Reasons at the base of such fertility patterns were extensively discussed focusing-among others-on the distinctive contribution of internal and international migrations to regional fertility rates. Based on these findings, Southern Italy, an economically disadvantaged, peripheral region in Mediterranean Europe, is taken as a paradigmatic case of demographic shrinkage-whose causes and consequences can be generalized to wider contexts in (and outside) Europe.Rodrigo-Comino, J.; Egidi, G.; Salvati, L.; Quaranta, G.; Salvia, R.; Giménez Morera, A. (2021). High-to-Low (Regional) Fertility Transitions in a Peripheral European Country: The Contribution of Exploratory Time Series Analysis. Data. 6(2):1-14. https://doi.org/10.3390/data6020019S1146

Re-Framing the Latent Nexus between Land-Use Change, Urbanization and Demographic Transitions in Advanced Economies

[EN] The linkage between land-use change and demographic transitions in advanced countries has becoming increasingly complex because of the mutual interplay of environmental and socioeconomic spheres influencing the degree of sustainability of both regional and local developmental processes. The relationship between urbanization and economic development has been relatively well investigated by clarifying the consequent impacts on population dynamics. In the early phases of urbanization and economic development, population grew at a particularly high rate, declining (more or less rapidly) in the subsequent time interval. Improving income and education opportunities in urban settings resulted in further urbanization, leading to progressively lower fertility. At the same time, a more general view on the relationship between land-use change and demographic transition focusing on a broader spectrum of landscape processes (including farmland abandonment and forest expansion) at larger spatial scales (from regional to country and continental scale) is increasingly required. The present study provides an integrated view of the relationship between land-use change, urbanization, and demographic transitions with specific focus on Europe. Considering divergent processes of landscape transformations in a unified socioeconomic view may evidence the intimate linkage with recent population trends in both urban and rural areas.Egidi, G.; Salvati, L.; Falcone, A.; Quaranta, G.; Salvia, R.; Vecenakova, R.; Giménez Morera, A. (2021). Re-Framing the Latent Nexus between Land-Use Change, Urbanization and Demographic Transitions in Advanced Economies. Sustainability. 13(2):1-17. https://doi.org/10.3390/su13020533S11713

Evaluating the effect of pupil dilation on spectral-domain optical coherence tomography measurements and their quality score

BACKGROUND: Spectral-domain optical coherence tomography (SD-OCT) provides fast scan speed and high scan resolution improving its diagnostic accuracy. The purpose of this study was to evaluate if SD-OCT measurements and their quality score are influenced by pupil dilation. METHODS: Retinal nerve fiber layer thickness (RNFL), ganglion cell complex (GCC) and optic nerve head (ONH) were measured in one eye of 57 glaucoma patients and 36 healthy subjects using spectral domain optical coherence tomography (SD-OCT) before and after pupil dilation. Comparisons were made between measurements and their quality score pre- and post dilation (Signal Strength Index, SSI). Overall RNFL, average GCC and ONH rim volume were considered in the analysis. RESULTS: No statistically significant differences were found between pre- and post-dilation measurements in both groups (glaucoma: RNFL 80 ± 15 μm vs 80 ± 16 μm, p = 0.87; GCC 81.35 ± 13.4 μm vs 81.10 ± 13.14 μm, p = 0.92; ONH 0.05 ± 0.11 mm(3) vs 0.04 ± 0.07 mm(3), p = 0.74; controls RNFL 99 ± 12 μm vs 98 ± 14 μm, p = 0.70; GCC 92.12 ± 6.7 μm vs 91.54 ± 7.05 μm, p = 0.72; ONH 0.11 ± 0.1 mm(3) vs 0.04 ± 0.07 mm(3), p = 0.36) nor between pre- and post-dilation quality score (glaucoma SSI RNFL 54.3 ± 10.3 vs 51.7 ± 18.1, p = 0.12; SSI GCC 58 ± 9.5 vs 57 ± 8.09, p = 0.55; SSI ONH 48.5 ± 7.6 vs 46.6 ± 7.2, p = 0.16; controls SSI RNFL 57 ± 10.3 vs 54 ± 9.31, p = 0.2; SSI GCC 60.9 ± 8.1 vs 58.8 ± 7.3, p = 0.3; SSI ONH 51.5 ± 8.9 vs 50.4 ± 8.3, p = 0.59). CONCLUSION: Pupil dilation doesn’t affect SD-OCT measurements and their quality score

Fecal Microbiota Transplantation: A Potential Tool for Treatment of Human Female Reproductive Tract Diseases

The gastro-intestinal tract is an extensive organ involved in several activities, with a crucial role in immunity. Billions of commensal and transient microorganisms, known as the gut microbiota, and potential pathogens, which are constantly stimulating intestinal immunity, colonize the intestinal epithelial surface. The gut microbiota may be regarded as analogous to a solid organ with multiple different functions. In the last decade, many studies have demonstrated that intestinal bacteria can be a decisive factor in the health-disease balance of the intestine, and they can also be responsible for illnesses in other locations. For this reason, fecal microbiota transplantation (FMT) represents an important therapeutic option for Clostridium difficile infections and hold promise for different clinical conditions, such as multiple sclerosis, autism, obesity, and other systemic diseases. FMT consists of the infusion of a fecal suspension from a healthy donor to a recipient in order to restore gut flora alterations. Similar to the gut, the female reproductive tract is an example of a very complex biological ecosystem. Recent studies indicate a possible relationship between the gut and female tract microbiota, associating specific intestinal bacteria patterns with genital female diseases, such as polycystic ovary syndrome (PCOS), endometriosis and bacterial vaginosis (BV). FMT could represent a potential innovative treatment option in this field

Differential Protein Expression Profiles in Glaucomatous Trabecular Meshwork: An Evaluation Study on a Small Primary Open Angle Glaucoma Population

INTRODUCTION: Primary open angle glaucoma (POAG) is a progressive optic neuropathy characterized by impaired aqueous outflow and extensive remodeling in the trabecular meshwork (TM). The aim of this study was to characterize and compare the expression patterns of selected proteins belonging to the tissue remodeling, inflammation and growth factor pathways in ex vivo glaucomatous and post-mortem TMs using protein-array analysis. METHODS: TM specimens were collected from 63 white subjects, including 40 patients with glaucoma and 23 controls. Forty POAG TMs were collected at the time of surgery and 23 post-mortem specimens were from non-glaucomatous donor sclerocorneal tissues. Protein profiles were evaluated using a chip-based array consisting of 60 literature-selected antibodies. RESULTS: A different expression of some factors was observed in POAG TMs with respect to post-mortem specimens, either in abundance (interleukin [IL]10, IL6, IL5, IL7, IL12, IL3, macrophage inflammatory protein [MIP]1δ/α, vascular endothelial growth factor [VEGF], transforming growth factor beta 1 [TGFβ1], soluble tumor necrosis factor receptor I [sTNFRI]) or in scarcity (IL16, IL18, intercellular adhesion molecule 3 [ICAM3], matrix metalloproteinase-7 [MMP7], tissue inhibitor of metalloproteinase 1 [TIMP1]). MMP2, MMP7, TGFβ1, and VEGF expressions were confirmed by Western blot, zymography, and polymerase chain reaction. No difference in protein profile expression was detected between glaucomatous subtypes. CONCLUSION: The analysis of this small TM population highlighted some proteins linked to POAG, some previously reported and others of new detection (IL7, MIPs, sTNFαRI). A larger POAG population is required to select promising disease-associated biomarker candidates. FUNDING: This study was partially supported by the Fondazione Roma, the Italian Ministry of Health and the “National 5xMille 2010 tax donation to IRCCS-G.B. Bietti Foundation”. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-016-0285-x) contains supplementary material, which is available to authorized users

Desertification and Degradation Risks vs Poverty: A Key Topic in Mediterranean Europe

Land degradation and, subsequently, desertification processes are conditioned by biophysical factors and human impacts. Nowadays, there is an increasing interest by social scientists to assess its implications. Especially, it is relevant to the potential changes and landscape deterioration on population, economic systems and feedbacks of local societies to such adjustments. Assessing social facets should also be related to desertification risks, integrated socio-economic inputs and environmentally sustainable development perspectives. However, investigations about the effects of land degradation conditioned by global socioeconomic-factors from a holistic point of view are scarce. In this review, we pretend to discuss past and recent findings on land degradation risks related to poverty, especially based on Mediterranean Europe. To achieve this goal, we focused on key socioeconomic forces such as developmental policy, production and market structure, social change and population mobility. Our review showed that regional disparities based on complex dynamics of demographic forces (e.g. migration, fertility and ageing) and economic drivers of change (e.g. industrial concentration, urbanization, crop intensification, tourism pressure, coastalization) are keys to understand Mediterranean regions such as Southern Italy, a region exposed to high desertification risk in Europe. We concluded that the overexploitation of territories, soil and water degradation urban expansion, tourism and unplanned industrialization are some sectors and activities which can be highly affected by political and socioeconomic forces leading to unsustainable forms of land management and types of development. Special attention should be paid to social policies, education and training schemes to reduce rural migration and potentiate territorial knowledge to avoid land degradation, considering other social issues such as poverty or centralization. The potential role of win-win policies abating poverty and reducing desertification risk is evident in Mediterranean Europe and achieving land degradation neutrality necessary

Fecal microbiota transplantation to improve efficacy of immune checkpoint inhibitors in renal cell carcinoma (TACITO trial)

Background: Renal cell carcinoma (RCC) is the 6° most common cancer in men and the 8° in women in the USA. In Italy RCC incidence was 11,500 new cases in 2017, while mortality was 3,371 cases in 2015. Increasing evidence suggests that response to immune checkpoint inhibitors (ICIs), a novel treatment for advanced RCC (aRCC) and other epithelial tumors, can be influenced by the patient gut microbiota. Fecal microbiota transplantation (FMT) is a novel treatment option aimed to restore healthy gut microbiota, and is the most effective therapy for recurrent C. difficile infection. Preliminary nonrandomized findings show that FMT is able to improve efficacy of ICIs in patients with advanced melanoma. The aim of this study is to evaluate, through a double-blinded placebo-controlled randomized clinical trial, the efficacy of targeted FMT (from donors who are responding to ICIs) in improving response rates to ICIs in subjects with aRCC. Methods: 50 patients who are about to receive, or have started by <8 weeks, pembrolizumab + axitinib as first-line therapy for aRCC will be enrolled. Exclusion criteria include major comorbidities, concomitant GI or autoimmune disorders, or HIV, HBV, HCV infection, continuative corticosteroid therapy, previous treatment with systemic immune-suppressants or immune-modulatory drugs, antibiotic therapy within 4 weeks prior to enrollment. Stool samples and clinical data will be collected at baseline. Then, patients will be randomized to donor FMT or placebo FMT. They will receive the first infusion by colonoscopy and then oral frozen fecal or placebo capsules (8 capsules t.i.d.) 90 and 180 days after the first FMT. Stool donors will be searched among long-term (>12 months) responders to ICIs, and will be selected by following protocols recommended by international guidelines. Patients in the FMT group will always receive feces from the same donor throughout the three fecal transplants. Frozen fecal batches and frozen fecal capsules will be manufactured according to international guidelines. Patients will be followed-up 7, 15, 30, 90, 180, 270, and 360 days after randomization for clinical evaluation and collection of stool samples. Patients will also undergo radiological assessment at 90, 180, 270 and 360 days after randomization. Microbiome analysis will be performed with shotgun metagenomics. The primary endpoint is the progression-free survival (PFS) at 12 months. Secondary endpoints are: objective response rate at 12 months; overall survival at 12 months; adverse events after FMT; microbiome changes after FMT. Sample size calculation was based on the hypothesis that FMT can improve the 1-year PFS rate from 60% (reported 1-year PFS for SOC) to 80% wen associated to SOC. Clinical trial information: NCT04758507

Validation of Two Commercial Multiplex Real-Time PCR Assays for Detection of SARS-CoV-2 in Stool Donors for Fecal Microbiota Transplantation

Recurrent infection by Clostridioides difficile has recently been treated by fecal microbiota transplantation (FMT). As viable SARS-CoV-2 was recovered from stool of asymptomatic individuals, the FMT procedure could be a potential risk of SARS-CoV-2 transmission, thus underlying the need to reliably detect SARS-CoV-2 in stool. Here, we performed a multicentric study to explore performances of two commercially available assays for detection of SARS-CoV-2 RNA in stool of potential FMT donors. In three hospitals, 180 stool samples were spiked with serial 10-fold dilutions of a SARS-CoV-2 inactivated lysate to evaluate the Seegene Allplex ™ SARS-CoV-2 (SC2) and SARS-CoV- 2/FluA/FluB/RSV (SC2FABR) Assays for the detection of viral RNA in stool of FMT donors. The results revealed that both assays detected down to 2 TCID50/mL with comparable limit of detection values, SC2 showing more consistent target positivity rate than SC2FABR. Beyond high amplification efficiency, correlation between CT values and log concentrations of inactivated viral lysates showed R2 values ranging from 0.88 to 0.90 and from 0.87 to 0.91 for the SC2 and SC2FABR assay, respectively. The present results demonstrate that both methods are highly reproducible, sensitive, and accurate for SARS-CoV-2 RNA detection in stool, suggesting a potential use in FMT-donor screening

Improved aperture measurements at the LHC and results from their application in 2015

A good knowledge of the available aperture in the LHC is essential for a safe operation due to the risk of magnet quenches or even damage in case of uncontrolled beam losses. Experimental validations of the available aperture are therefore crucial and were in the past carried out by either a collimator scan combined with beam excitations or through the use of local orbit bumps. In this paper, we show a first comparison of these methods in the same machine configuration, as well as a new very fast method based on a beam-based collimator alignment and a new faster variant of the collimator scan method. The methods are applied to the LHC operational configuration for 2015 at injection and with squeezed beams and the measured apertures are presented.peer-reviewe