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A randomized clinical trial proposing a new laparoscopic prosthetic and fascial approach to severe posterior vaginal prolapse. The primary endpoint was to evaluate the objective and subjective outcomes of our laparoscopic posterior plication (LPP) combined to "two-mesh" sacral colpopexy (laparoscopic sacral colpopexy [LSC]) in severe posterior vaginal prolapse, with a 1-year follow-up. The secondary endpoint was to evaluate the safety of this surgical procedure.This is single-center prospective randomized double-blinded clinical trial. A total of 130 consecutive patients with anterior and/or apical pelvic organ prolapse (POP) (POP-Q stage ≥II) and severe posterior vaginal prolapse (posterior POP-Q stage ≥III) were prospectively assessed for inclusion into the study from November 2018 to January 2020. Patients underwent "two-meshes" LSC and were randomized in Group A (LSC plus LPP) and Group A (LSC alone). Of the 130 included subjects, 8 were excluded, not meeting inclusion criteria. Cure rate was evaluated objectively, using POP-Q study, and subjectively using PGI-I, POPDI-6, and FSDS questionnaires. Complications were assessed intra-, peri-, and postoperatively. Twelve-month follow-ups were analyzed for the study.We found in LSC plus LPP Group a significant improvement of Ap and genital hiatus POP-Q points. Our subjective study showed, at 12 months, a statistical difference in PGI-I successful outcomes rate in favor of LPP. Also the FSDS resulted significantly much more improved in Group A. We observed no statistical differences in terms of postoperative complications.Our LPP approach to LSC could be considered an effective and safe technique to POP patients with severe posterior prolapse.

α-Amino acid derivatives are key components of the molecules of life. The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we report a practical method for the preparation of α-amino acid derivatives via direct hydrative amination of activated alkynes under mild conditions, relying on sulfinamides as the nitrogen source. Computational studies suggest that the reaction is enabled by a new type of sulfonium [2,3]-sigmatropic rearrangement.

Previous evidence suggests that sialic acid-binding Ig-like lectin 7 (Siglec-7) protein is significantly increased in patients with chronic hepatitis C virus (HCV) infection and directly correlates with clinical parameters of liver inflammation and fibrosis. The aim of this study was to determine the diagnostic value of Siglec-7 as a non-invasive tool to assess liver fibrosis in patients with chronic hepatitis C in a cross-sectional study. Serum levels of Siglec-7 were retrospectively tested in 1007 consecutive patients with chronic HCV infection recruited at three different European sites and data examined by the ‘imperfect gold-standard’ statistical analysis. Liver stiffness obtained by transient elastography (TE) was considered the standard reference. Liver fibrosis was staged according to published cut-offs of liver stiffness measurement by TE. Accuracy of detection of liver fibrosis stage was not increased by Siglec-7 alone. However, we developed a new index (SiGAP) including Siglec-7, γ-glutamyl transferase, age and platelet count which showed increased sensitivity and specificity in predicting fibrosis compared with APRI or FIB4 indices. The AUROC of SiGAP for the diagnosis of significant (≥F2) and advanced liver fibrosis (≥F3) showed significantly higher values than those of APRI and FIB-4. Siglec-7 may be useful as a complementary tool to assess liver fibrosis stage in patients with chronic hepatitis C when included in a specifically designed algorithm, which showed high level of accuracy in the detection of F2 and F3 fibrosis stage., This study was supported by funds from the Italian Ministry of Health to Fondazione IRCCS Policlinico San Matteo (RC08056517).

This article presents a revision of the literature regarding the influence of sex differences on the recovery and long-term behavioral and cognitive outcomes of preterm children. After initial discussion of some methodological concerns, the literature regarding the concept of "male disadvantage," which is often used when talking about early neurological and psychomotor outcomes in preterm children, is presented. Subsequently, the literature data on sex-related differences in preterm children are discussed, focusing on their influence on the developmental pathways of cognition, language, executive function, behavior and affect, and response to rehabilitation therapies. Finally, evidence about brain structural and connectivity correlates of sex differences in the brain of preterm survivors is taken into account. Although visuo-spatial and visuo-perceptual functioning is widely studied in the preterm child and is strongly sex specific, little to no data are available regarding male-female differences in preterm children and the interaction effect between sex and preterm birth. For this reason, original data analyses of male-female differences in visuo-spatial performance from a small sample of preterm children are also presented.

Objective On May 13, 2020, the Italian government Pharmaceutical Agency (AIFA) stopped ulipristal acetate (UPA) treatments for uterine fibroids (UFs), so patients shifted to other natural treatments. The authors tested the patients' compliance with UF natural treatments. Methods Thirty patients of reproductive age (30-45 years) affected by UFs stopped UPA intake and started epigallocatechin gallate (EGCG) plus vitamin D3 treatment. Patients were asked to complete the Uterine Fibroid symptoms and Quality of Life (UFS-QOL) questionnaire, divided into symptoms severity (SS) and health-related quality of life (HRQL), after UPA suspension and to repeat it after 3 months of natural treatment. Collected data were analyzed using paired Student's t test, considering a P value less than 0.05 to be significant. Results The SS score was significantly lower (-12.19%) for natural treatment when compared with UPA administration. The HRQL score significantly improved (+11.79%) after shifting treatment from UPA to natural therapy. All the investigated parameters appeared improved by 10% after the natural treatment. No adverse effects were reported following the natural treatment. Conclusion Natural treatments showed positive compliance in patients with UFs, based on HRQL score, representing an alternative therapeutic opportunity for patients forced to stop UPA therapy.

Background and purpose Idiopathic normal-pressure hydrocephalus (iNPH) is a progressive, severe brain disorder, which mainly affects people above the age of 65 years. iNPH is characterized by the accumulation of excess cerebrospinal fluid in the brain's ventricles. In most cases, iNPH patients can be effectively treated with shunt surgery, which involves placing a tube into the brain to drain the excess fluid. As part of the European Brain Council-led Value of Treatment project, this study aimed to investigate the cost-effectiveness of delivering timely and adequate iNPH treatment in Germany. Methods The study identified treatment gaps that prevent iNPH patients from receiving adequate and timely treatment. The cost-effectiveness of delivering shunt surgery to iNPH-prevalent patients aged ≥65 years in Germany was calculated using decision-analytical modelling. The model compared two alternatives, current care (shunt surgery in 25% of iNPH cases) and target care (shunt surgery in 90% of iNPH cases), and looked at healthcare costs (diagnosis, shunt intervention and follow-up care) from the public health insurance perspective, as well as effectiveness outcomes in terms of lives saved and quality-adjusted life-years (QALYs) gained. Results Delivering timely and adequate iNPH treatment proved to be cost-effective. Cost per life saved varied between €27 921 at 5 years and €246 726 at 15 years. Cost-per-QALY estimates varied between €10 202 at 5 years and €35 128 at 15 years. Conclusions Idiopathic normal-pressure hydrocephalus is a treatable but often not-treated disease, resulting in unnecessary and avoidable disease burden for the healthcare system. Actions required to close this treatment gap are straightforward and their implementation has been modelled with successful outcomes.

Background and purpose Using functional magnetic resonance imaging (fMRI), we explored cortical activation in patients with acute Bell's palsy (BP) and analyzed its correlates with clinical status in the acute phase, and with 6-month outcome. Methods Twenty-four right-handed patients with acute BP within 15 days of onset and 24 healthy controls underwent fMRI during performance of unilateral active (hemi-smiling) and passive lip movement tasks with both the paretic and the normal lip. The degree of paresis was evaluated during the acute stage and at the 6-month follow up using the House-Brackmann (HB) grading scale. Complete recovery was defined as HB grade II or less at the end of the 6-month period. The difference in the HB grade (ΔHB) between the acute stage and the 6-month follow up was used to evaluate clinical improvement. Results There were 24 patients with unilateral acute BP. HB grades ranged from III to VI. At 6 months, 11 patients (46%) had completely recovered and 12 (50%) were partially improved. Compared with healthy subjects, BP patients had a significantly greater activation of the frontal areas and the insula ipsilateral to the paretic side. In BP patients, there was an inverse correlation between the activation of the ipsilateral hemisphere when moving the paretic side and the degree of paresis at baseline. An association was also observed between activation and clinical outcome (both complete recovery and ΔHB). Conclusions In patients with BP, fMRI may represent a useful tool to predict long-term outcome, guide therapeutic approach, and monitor treatment response.

There are 3 methods of interpreting breast strain elastography: the elastographic-to-B-mode length ratio (E/B), a 5-point color scale (5P), and the strain ratio (SR). This meta-analysis assessed which method is superior to the others. A systematic search of the medical literature was performed in July 2017. Studies were eligible for inclusion if they fulfilled the following criteria: (1) had biopsy-proven or long-term stability as the reference standard; (2) used either the E/B, 5P, or SR to interpret results; and (3) had at least 50 cases. A total of 220 records were retrieved; 60 full-text articles were examined, and 46 were included in the meta-analysis. Publication years ranged from 2007 and 2017. The quality of studies was generally high. The mean age of women was 48 years; 12,398 lesions (4242 malignant) were analyzed. For the 5P method, the sensitivity was 77%; specificity, 87%; positive likelihood ratio (LR), 5.3; and negative LR, 0.24. For the SR method, sensitivity was 87%; specificity, 81%; positive LR, 4.8; and negative LR, 0.16. For the E/B method, sensitivity was 96%; specificity, 88%; positive LR, 7.1; and negative LR, 0.03. Of the 3 methods, the E/B had the highest sensitivity, and the E/B and 5P had the highest specificity. With a negative LR of 0.03, the E/B method can downgrade lesions with a pretest probability of 50% to a 2% probability of malignancy.

OBJECTIVE To evaluate the feasibility and efficacy of laparoscopic absorbable fixation straps (AFS) for laparoscopic gastropexy in dogs. STUDY DESIGN Cadaveric and prospective clinical study. ANIMALS Five dog cadavers for the cadaveric study; 12 dogs for the clinical study. METHODS The pyloric antrum was affixed to the abdominal wall laparoscopically by applying a series of straps. The cadaveric study assessed potential challenges during the procedure and stomach mucosal penetration. For the clinical study, the total duration of surgery, time to complete the gastropexy, and the number of straps used were recorded. Ultrasound evidence of adhesion, complications, and weight were monitored at 7, 30, and 90 days after surgery. Owner satisfaction was evaluated at the 6-month follow-up. RESULTS The total duration of surgery was 25.8 minutes (range, 19-39; SD, 6.7), and the time to complete the gastropexy was 10.1 minutes (range, 7-19; SD, 3.9). The linear regression analysis revealed an inverse correlation between the time to complete the gastropexy and the order of the surgeries (r2 = 0.75, P

Dyslexia has been associated with a problem in visual–audio integration mechanisms. Here, we investigate for the first time the contribution of unisensory cues on multisensory audio and visual integration in 32 dyslexic children by modelling results using the Bayesian approach. Non‐linguistic stimuli were used. Children performed a temporal task: they had to report whether the middle of three stimuli was closer in time to the first one or to the last one presented. Children with dyslexia, compared with typical children, exhibited poorer unimodal thresholds, requiring greater temporal distance between items for correct judgements, while multisensory thresholds were well predicted by the Bayesian model. This result suggests that the multisensory deficit in dyslexia is due to impaired audio and visual inputs rather than impaired multisensory processing per se. We also observed that poorer temporal skills correlated with lower reading skills in dyslexic children, suggesting that this temporal capability can be linked to reading abilities., Multisensory audio visual processing in dyslexia is due to impaired audio and visual inputs rather than impaired multisensory processing per se.

The efficacy of minoxidil (MXD) ethanolic solutions (1%‐5% w/v) in the treatment of androgenetic alopecia is limited by adverse reactions. The toxicological effects of repeated topical applications of escalating dose (0.035%‐3.5% w/v) and of single and twice daily doses (3.5% w/v) of a novel hydroxypropyl‐β‐cyclodextrin MXD GEL formulation (MXD/HP‐β‐CD) and a MXD solution were investigated in male rats. The cardiovascular effects were evaluated by telemetric monitoring of ECG and arterial pressure in free‐moving rats. Ultrasonographic evaluation of cardiac morphology and function, and histopathological and biochemical analysis of the tissues, were performed. A pharmacovigilance investigation was undertaken using the EudraVigilance database for the evaluation of the potential cancer‐related effects of topical MXD. Following the application of repeated escalating doses of MXD solution, cardiac hypertrophy, hypotension, enhanced serum natriuretic peptides and K+‐ion levels, serum liver biomarkers, and histological lesions including renal cancer were observed. In addition, the administration of a twice daily dose of MXD solution, at SF rat vs human = 311, caused reductions in the systolic, diastolic, and mean blood pressure of the rats (−30.76 ± 3%, −28.84 ± 4%, and −30.66 ± 5%, respectively, vs the baseline; t test P

Objectives To evaluate the carotid bifurcation in healthy adults using a commercial system equipped with high-frame rate vector flow imaging (VFI) based on the plane wave and to compare VFI with color Doppler imaging. Methods Carotid bifurcation diameters and flow characteristics of 60 vessels in 60 healthy volunteers were evaluated quantitatively and qualitatively to assess complex flow patterns and their extension and duration. Results Complex flow in the internal carotid artery (ICA) was associated with a statistically significant difference in the ΔICA sinus-to-common carotid artery (CCA) diameter ratio (the relative change in diameter between the CCA and ICA sinus.) Vector flow imaging and color Doppler imaging were in accordance when detecting complex flow in 96.7% of cases; in 3.3% of cases, only VFI identified small recirculation areas of short duration. Vector flow imaging highlighted a larger extension of the complex flow (mean ± SD, 47.7 ± 28.5 mm2 ; median, 45.5 mm2 ) compared with color Doppler imaging (mean, 29.2 ± 19.9 mm2 ; median, 29.5 mm2 ) and better depicted different complex flow patterns; a strong correlation (r = 0.84) was found between the ΔICA sinus-to-CCA diameter ratio and the complex flow extension. Vector flow imaging showed a longer duration of the flow disturbances (mean, 380 ± 218 milliseconds; median, 352.5 milliseconds) compared with color Doppler imaging (mean, 325 ± 206 milliseconds; median, 333 milliseconds), and there was a strong correlation (r = 0.92). Conclusions Vector flow imaging is as effective as color Doppler imaging in the detection of flow disturbances, but it is more powerful in the assessment of complex flow patterns.

The identification of a highly sensitive method to check the delivery of administered nanodrugs into the tumor cells is a crucial step of preclinical studies aimed to develop new nanoformulated cures, since it allows the real therapeutic potential of these devices to be forecast. In the present work, the ability of an H-ferritin (HFn) nanocage, already investigated as a powerful tool for cancer therapy thanks to its ability to actively interact with the transferrin receptor 1, to act as an efficient probe for the monitoring of nanodrug delivery to tumors is demonstrated. The final formulation is a bioluminescent nanoparticle, where the luciferin probe is conjugated on nanoparticle surface by means of a disulfide containing linker (Luc-linker@HFn) which is subjected to glutathione-induced cyclization in tumor cell cytoplasm. The prolonged imaging of luciferase+ tumor models, demonstrated by an in vitro and an in vivo approach, associated with the prolonged release of luciferin into cancer cells by disulfide bridge reduction, clearly indicates the high efficiency of Luc-linker@HFn for drug delivery to the tumor tissues.