Intestinal microbiota, intestinal permeability and the urogenital tract: is there a pathophysiological link?

Human gut microbiome is related to different clinical conditions and diseases. Recently several hypotheses have been theorized about a link between gut microbiota and genitourinary disease including urinary tract infections, and benign prostatic hyperplasia. Despite several data, underlying mechanisms still remain unclear. The aim of this review is to report the current state of knowledge in relation to urinary tract infections, benign prostatic hyperplasia and intestinal microbiota with a focus on its role in the development of disease and the underlying pathophysiologic mechanisms.

Fluid dynamics of COVID-19 airborne infection suggests urgent data for a scientific design of social distancing.

The COVID-19 pandemic is largely caused by airborne transmission, a phenomenon that rapidly gained the attention of the scientific community. Social distancing is of paramount importance to limit the spread of the disease, but to design social distancing rules on a scientific basis the process of dispersal of virus-containing respiratory droplets must be understood. Here, we demonstrate that available knowledge is largely inadequate to make predictions on the reach of infectious droplets emitted during a cough and on their infectious potential. We follow the position and evaporation of thousands of respiratory droplets by massive state-of-the-art numerical simulations of the airflow caused by a typical cough. We find that different initial distributions of droplet size taken from literature and different ambient relative humidity lead to opposite conclusions: (1) most versus none of the viral content settles in the first 1-2 m; (2) viruses are carried entirely on dry nuclei versus on liquid droplets; (3) small droplets travel less than [Formula: see text] versus more than [Formula: see text]. We point to two key issues that need to be addressed urgently in order to provide a scientific foundation to social distancing rules: (I1) a careful characterisation of the initial distribution of droplet sizes; (I2) the infectious potential of viruses carried on dry nuclei versus liquid droplets.

Phase I Study in Healthy Women of a Novel Antimycotic Vaginal Ovule Combining Econazole and Benzydamine.

Purpose: A novel fixed-dose combination of 150 mg of econazole with 6 mg of benzydamine formulated in vaginal ovules was investigated in a randomised, double-blind, four-parallel group, tolerability, and pharmacokinetic Phase I study in healthy women. Methods: The fixed-dose combination was compared to econazole and benzydamine single-drug formulations and with placebo after daily applications for 3 consecutive days. Safety and tolerability were evaluated recording the adverse drug reactions, local and general tolerability scores, clinical laboratory assays, and vital signs. Econazole, benzydamine, and its metabolite benzydamine N-oxide pharmacokinetics were investigated after single and multiple applications. Results: Local reactions were generally absent. Pruritus and pain at the application site were infrequently reported. According to the subjects' evaluations, the overall tolerability of the ovules was rated as excellent or good. No significant effect of any treatment on laboratory parameters, vital signs, body weight, vaginal pH, or ECG was observed. Very low econazole, benzydamine, and benzydamine-N-oxide concentrations were measured in plasma, though quantifiable in almost all samples. Conclusion: The tested fixed-dose combination showed a good safety profile consistently with the known tolerability of both active substances. In addition, the confirmed low bioavailability of the drugs excludes the possibility of any accumulation effects and limits the risk of undesired systemic effects. This trial is registered at ClinicalTrials.gov with the identifier NCT02720783 last updated on 07 February 2017.

Bluetongue virus in Lebanon.

Since 2000, several incursions of bluetongue virus (BTV) occurred in the Mediterranean Basin involving European and surrounding Countries. The Middle East represents one of the most important gateways for the access of BTV in Europe. Limited data on the BTV situation in this area are available. In this perspective, an epidemiological survey on the presence of BTV in Lebanon was conducted. Of the 181 serum samples tested, 97 (mean = 53.6%; 95% CI: 46.3-60.7) resulted positive when tested for the presence of BTV antibodies by c-ELISA, of these 42 (mean = 42%; 95% CI: 32.8-51.8) serum samples were from sheep and 55 (mean = 67.9%; 95% CI: 57.1-77.1) serum samples were from goats. Fourteen blood samples (14/110; mean = 12.7%; 95% CI: 7.8-20.3), 6 (6/66; mean = 9.1%; 95% CI: 4.4-18.5) from sheep and 8 (8/44; mean = 18.2%; 95% CI: 9.6-32.0) from goats, were positive by qRT-PCR. The results with serum-neutralization assay and typing performed by RT-PCR confirmed that six BTV serotypes are currently circulating in Lebanon, and these serotypes are as follows: 1, 4, 6, 8, 16 and 24. This study is the first report that confirms the presence and circulation of BTV in Lebanon.

In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson's disease.

BACKGROUND: Reactive microgliosis, hallmark of neuroinflammation, may contribute to neuronal degeneration, as shown in several neurodegenerative diseases. We in vivo evaluated microglia activation in early dementia with Lewy bodies, still not reported, and compared with early Parkinson's disease, to assess possible differential pathological patterns. METHODS: We measured the [(11)C]-PK11195 binding potentials with Positron Emission Tomography, using a simplified reference tissue model, as marker of microglia activation, and cerebral spinal fluid protein carbonylation levels, as marker of oxidative stress. Six dementia with Lewy bodies and 6 Parkinson's disease patients within a year from the onset, and eleven healthy controls were included. Clinical diagnosis was confirmed at a 4-year follow-up. RESULTS: In dementia with Lewy bodies as well as in Parkinson's disease, we found significant (p < 0.001) [(11)C]-PK11195 binding potential increases in the substantia nigra and putamen. Patients with Lewy bodies dementia had extensive additional microglia activation in several associative cortices. This was evident also at a single subject level. Significant increase of Cerebral Spinal Fluid protein carbonylation was shown in both patients' groups. CONCLUSIONS: [(11)C]-PK11195 Positron Emission Tomography imaging revealed neuroinflammation in dementia with Lewy bodies and Parkinson's disease, mirroring, even at a single subject level, the common and the different topographical distribution of neuropathological changes, yet in the earliest stages of the disease process. Focusing on those events that characterize parkinsonisms and Parkinson's disease may be the key to further advancing the understanding of pathogenesis and to taking these mechanisms forward as a means of defining targets for neuroprotection.

[Clinical value of antibodies to lysobisphosphatidic acid in patients with primary antiphospholipid syndrome]. / Significato clinico degli anticorpi anti acido lisobisfosfatidico nei pazienti con sindrome da antifosfolipidi primaria.

To assess the clinical value of anti-lysobisphosphatidic acid (anti-LBPA) antibodies in patients with primary antiphospholipid syndrome (APS), the sera of 140 primary APS patients were tested and compared with those of 70 control subjects affected with rheumatic systemic diseases (n. 24) or autoimmune thyroiditis (n. 46). Anti-LBPA anticardiolipin (aCL) and anti-beta2 Glycoprotein I (anti-beta2GPI) antibodies were determined using a "home made" ELISA method. Lupus anticoagulant (LA) was assessed using a series of clotting tests in accordance with the literature. IgG anti-LBPA was significantly prevalent in primary APS (p=0.000) with a sensitivity of 58.6% and a specificity of 92.9%. IgM anti-LBPA showed a significant frequency in primary APS (p=0.000) with a sensitivity of 28.6% and a specificity of 97.1%. Anti-LBPA's sensitivity and specificity for APS were lower or equal to those of aCL and anti-beta2GPI. The prevalence of anti-LBPA in the different clinical and laboratory subsets of APS was lower than those of aCL and anti-beta2GPI. It is interesting to observe that both IgG and IgM anti-LBPA were never found alone. The comparison between anti-LBPA and LA showed that the former had a higher sensitivity but a lower specificity. In conclusion, in view of our results anti-LBPA cannot at present be considered a further tool to be utilized to diagnose APS and to differentiate the different clinical and laboratory subsets of this disease.

[Confirmation of antiphospholipid antibody positivity: a year's results in a cohort of 113 patients]. / Conferma della positività nell'autoimmunità antifosfolipidica: risultati acquisiti in un anno in una coorte di 113 pazienti.

OBJECTIVE: To evaluate the confirmation rate of antiphospholipid antibodies (aPL), to analyze their behaviour at confirmation time, and to study the clinical value of their confirmation. METHODS: Blood samples from 380 subjects, enrolled in this study from June 1, 2007 to May 31, 2008, were tested for anti-cardiolipin (aCL) and anti-beta2glycoprotein (abeta2GPI) antibodies using an ELISA method and for Lupus anticoagulant (LA) using a series of clotting tests. The samples of the 113 subjects resulting positive at the first testing time were assayed again to confirm antiphospholipid positivity. RESULTS: aPL positivity was confirmed in 67 out of the 113 subjects (59.3%). Medium-high antibody levels of all, except IgM aCL, aPL/ELISA had a significantly higher confirmation rate with respect to that in subjects with low levels. The confirmation rate in the category I antibody patients (multiple positivity) was higher than that in the category II antibody subjects (single positivity). LA positivity was confirmed only when it was associated to other aPL. The cut-off of 40 GPL produced a confirmation rate equal to that resulting from a 99th percentile cut-off. Confirmation of aPL positivity made it possible for us to confirm the diagnosis of antiphospholipid syndrome (APS) in 8 out of the 113 subjects originally resulting positive (7.1%). APS clinical features were vascular thrombosis in 4 of these and pregnancy morbidity in the other 4. CONCLUSIONS: Our data emphasize aPL positivity confirmation selectivity, and medium-high antibody levels and category I antibodies (multiple positivity) had the best confirmation rates.

Influence of different IgG anticardiolipin antibody cut-off values on antiphospholipid syndrome classification.

BACKGROUND: While medium to high titers of anticardiolipin (aCL) antibodies, defined as >40 GPL units or >99th percentile, is a laboratory criteria for the 'definite' diagnosis of antiphospholipid syndrome (APS), agreement between the two cut-offs has not been validated. OBJECTIVE: To validate the current aCL laboratory criterion by verifying the effect of the two cut-offs on APS classification. PATIENTS/METHODS: Ninety aCL positive APS patients were selected on the basis of their GPL values above the 99th percentile (17.4 GPL), which was calculated by testing 100 age- and sex-matched healthy subjects. RESULTS: A significant difference in the IgG positivity (P < 0.0001) was found between the APS laboratory profiles as 20 out of the 24 (83.3%) patients with single positivity (aCL alone), six out of the 23 (26.1%) with double positivity (aCL plus lupus anticoagulant or anti-beta(2)glycoprotein I), and none out of the 43 with triple positivity (aCL plus lupus anticoagulant and anti-beta(2)glycoprotein I) had titers between the 99th percentile and 40 GPL units. Moreover, the rate of aCL values between the 99th percentile and 40 GPL units was significantly higher (P < 0.0001) in patients with pregnancy morbidity (73.7%) as compared to those with vascular thrombosis (16.9%) and those with both conditions (16.7%). CONCLUSION: The 99th percentile cut-off level seems more sensitive than the >40 GPL value for APS classification, as it includes subjects with aCL positivity alone as well as patients with pregnancy morbidity.

The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease.

OBJECTIVE: To determine the efficacy of donepezil in the treatment of neuropsychiatric symptoms in patients with Alzheimer disease (AD) in a randomized withdrawal study. METHOD: Patients with mild to moderate AD with marked neuropsychiatric symptoms at baseline (Neuropsychiatric Inventory [NPI] > 11 points) were treated openly with donepezil 5 mg daily for 6 weeks followed by 10 mg daily for a further 6 weeks. Patients were then randomized (60:40) to either placebo or 10 mg donepezil daily. All patients were assessed at 6 weeks and provided there was no marked cognitive deterioration their blinded treatment was continued for a further 6 weeks. NPI and carer distress were assessed at 6 weekly intervals throughout the study. RESULTS: A total of 134 patients participated. Following randomization patients who continued on donepezil 10 mg for 12 weeks had improvements in NPI compared with the placebo group (mean change -2.9 vs 3.3 points; ITT-LOCF p = 0.02) and in NPI-Distress scores (median change -2.0 vs 1.0 points; ITT-LOCF p = 0.01). During the open-label phase the total NPI and NPI-Distress scores were lower after 12 weeks treatment with open label donepezil compared with baseline (total NPI 22 points vs13 points; ITT-LOCF p < 0.0001; NPI-Distress 13.5 vs 7.9 points; ITT-LOCF p < 0.0001). In the open-label phase all domains of the NPI (with the exception of elation) were improved (all p < 0.05 after Bonferroni correction). CONCLUSIONS: Donepezil has significant efficacy in the treatment of neuropsychiatric symptoms in patients with mild to moderate AD.

Interest of Chromogranin A for diagnosis and follow-up of endocrine tumours.

OBJECTIVE: To determine the interest of Chromogranin A (CgA) determination for diagnosis and follow-up in patients with gastroenteropancreatic endocrine tumours (GEP-ET) and multiple endocrine neoplasia type 1 (MEN-1). PATIENTS AND METHODS: CgA levels were measured with an immunoradiometric assay in 124 sporadic GEP-ET, 34 MEN-1 and 127 controls. Serial determinations were performed in 56 patients (212 visits). Changes in CgA levels over 25% were considered as significant. RESULTS: Using a cut-off value of 130 micro g/l, established from a receiver-operating characteristic curve, the specificity of CgA was 98.4%, with a sensitivity of 62.9%, higher in secreting than in nonsecreting tumours (73%vs. 45%; P < 0.003) and related to the extent of metastatic spreading (P < 0.001). In nonsecreting tumours, the positive predictive value (PPV) of CgA for the presence of metastases was 100% but the negative predictive value (NPV) was only 50%. In MEN-1, high CgA levels indicated a pancreatic tumour with a 100% specificity but the sensitivity was 59%. During the follow-up, the concordance between CgA and tumour evolution was 80%, whatever the secretory status. In patients with carcinoid tumours, the concordance was higher for CgA than for serotonin (81%vs. 54%; P < 0.001). CONCLUSION: Due to its high specificity, CgA determination may help to discriminate the endocrine character of a GEP tumour and to indicate a pancreatic tumour in MEN-1. However, its low NPV in nonsecreting tumours limits its interest for diagnosis and staging. By contrast, serial evaluation of CgA seems of particular interest for the follow-up of GEP-ET tumours.

Evaluation of three quinoline-carboxamide derivatives as potential radioligands for the in vivo pet imaging of neurodegeneration.

The peripheral-type benzodiazepine receptors (PBRs) are only minimally expressed in normal brain parenchyma, where they are primarily localized in glial cells. Their basal expression rises in different neurodegenerative disorders, due to the presence of infiltrating inflammatory cells and activated microglia. [11C]PK11195, a selective PBR antagonist, has been used for the in vivo PET monitoring of neurodegeneration in clinical observations. We recently developed and labeled with carbon-11 three new carboxamide derivatives: [11C]VC193M, [11C]VC195 and [11C]VC198M. Aim of this study was to evaluate these ligands for the in vivo measuring of PBRs expression in neurodegenerations and compare their kinetic behavior with that of the reference tracer [11C]PK11195. Radioligands were evaluated in a preclinical model of Huntington's disease consisting in the monolateral striatal injection of quinolinic acid (QA). Activated microglia and astrocytic gliosis was present only within the affected striatum. A concomitant increase in radioactivity accumulation was observed for all the tracers examined (P<0.01). Among the new compounds, [11C]VC195 showed higher levels of lesioned/unlesioned striatum ratios (3.28+/-0.44), in comparison with [11C]VC193M and [11C]VC198M (2.69+/-0.53 and 1.52+/-0.36, respectively), but slightly inferior to that observed for [11C]PK11195 (3.76+/-1.41).In conclusion, the results of the study indicate that [11C]VC195 is a promising candidate for in vivo PET monitoring of neurodegenerative processes but its in vivo behavior overlap that of [11C]PK11195.

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity.

PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly amplified in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE amplification was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, amplification and overexpression of PRUNE has the same effect in the tumours. We suggest that amplification and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that affect the development or progression of these tumours.

Chronic intraaneurysmal pressure measurement: an experimental method for evaluating the effectiveness of endovascular aortic aneurysm exclusion.

PURPOSE: To evaluate and compare the intraaneurysmal pressure (IAP) after exclusion using two different endovascular grafts. METHODS: Eight mongrel dogs had a 3 x 3 cm polytetrafluoroethylene (PTFE) aneurysm sewn as an interposition graft of the infrarenal aorta. A pressure transducer implanted into the aneurysm wall permitted continuous electronic IAP monitoring. Four aneurysms were excluded with a transluminally placed endovascular graft made of a PTFE graft and two Palmaz stents (PTFE-EG), three were excluded with a tantalum-Dacron endovascular graft (TD-EG), and one was surgically treated with a standard PTFE graft (PTFE-Surg). The dogs were observed for 18 to 50 days (mean, 37.5 days) and were evaluated after surgery with duplex and spiral computed tomographic scans. RESULTS: All grafts successfully excluded the aneurysms without perigraft channels or leaks as documented by arteriogram and duplex and computed tomographic scans. The mean IAPs after repair with all PTFE-EGs were significantly lower (p < 0.001) than the mean systemic pressures. In addition, the mean IAP reduction was significantly greater (p < 0.005) in the PTFE-EG group than in the TD-EG group. CONCLUSIONS: Aneurysm exclusion with PTFE-EG significantly lowered IAP, did so significantly better than the TD-EG, and approached the IAP reduction obtained by standard repair. Such pressure reduction is necessary for effective protection against aneurysm rupture.

Chronic benzodiazepine dependence. A comparative study of abrupt withdrawal under propranolol cover versus gradual withdrawal.

Thirty-one patients dependent on benzodiazepines were randomly assigned to either slow withdrawal (SW) or abrupt withdrawal under propranolol cover (PW). Of 16 patients in the SW group, 11 successfully withdrew from their drugs, while only 4 out of 15 in the PW group did so. Patients in the SW group had only mild withdrawal symptoms, while those in the PW group suffered more severe symptoms, which lasted around four weeks. In all, 81% of the whole group suffered withdrawal symptoms of some kind. Patients in both groups were significantly less anxious at the end of the study than at baseline. Younger subjects and those who were more severely anxious at the start of the trial had more difficulty in withdrawing than older and less anxious patients.

[Cytogenetic study of the children of the municipality of Massa (Massa Carrara)]. / Studio citogenetico dei bambini del comune di Massa (Massa Carrara).

An account is given of a protocol for the early diagnosis of chromosome diseases designed to promote social intervention in cases of "silent" chromosome sex anomalies, and at the same time assess their incidence (at present unknown) in Italy. A preliminary trial was conducted in screening for the Barr chromatin, coupled with examination by a specialist, using a representative sample of 196 elementary school-children from the mountainous districts of the municipality of Massa. Determination of the karyotype in 64 cases led to the detection of certain chromosome varienties, though no alterations. The undertaking screening on a larger scale and for clarifying the organisational methods required.