Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo^®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo^® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo^®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo^® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.     

A Three-Year Longitudinal Study Comparing Bone Mass,Density, and Geometry Measured by DXA,pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–16 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16 years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16 years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15 years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm²), bone mineral apparent density (L2–L4 BMAD g/cm³) and total body less head BMDa (TBLH g/cm²). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.     

Cross-Sectional Serosurvey of Companion Animals Housed with SARS-CoV-2–Infected Owners,Italy

We conducted a serologic survey among dogs and cats in Italy to detect antibodies against severe acute respiratory syndrome virus 2 (SARS-CoV-2). We found that SARS-CoV-2 seroprevalence was higher among cats (16.2%) than dogs (2.3%). In addition, seroprevalence was higher among animals living in close contact with SARS-CoV-2–positive owners.     

Income level and antibiotic misuse: a systematic review and dose–response meta-analysis

The European Journal of Health Economics - To quantify the association between income and antibiotic misuse including unprescribed use, storage of antibiotics and non-adherence. We identified...     

Comparison between VII-to-VII and XII-to-VII coaptation techniques for early facial nerve reanimation after surgical intra-cranial injuries: a systematic review and pooled analysis of the functional outcomes

Neurosurgical Review - The surgical injury of the intracranial portion of the facial nerve (FN) is a severe complication of many skull base procedures, and it represents a relevant issue in terms...     

The secret life of the mitral valve

In secondary mitral regurgitation, the concept that the mitral valve (MV) is an innocent bystander, has been challenged by many studies in the last decades. The MV is a living structure with intrinsic plasticity that reacts to changes in stretch or in mechanical stress activating biohumoral mechanisms that have, as purpose, the adaptation of the valve to the new environment. If the adaptation is balanced, the leaflets increase both surface and length and the chordae tendineae lengthen: the result is a valve with different characteristics, but able to avoid or to limit the regurgitation. However, if the adaptation is unbalanced, the leaflets and the chords do not change their size, but become stiffer and rigid, with moderate or severe regurgitation. These changes are mediated mainly by a cytokine, the transforming growth factor‐β (TGF‐β), which is able to promote the changes that the MV needs to adapt to a new hemodynamic environment. In general, mild TGF‐β activation facilitates leaflet growth, excessive TGF‐β activation, as after myocardial infarction, results in profibrotic changes in the leaflets, with increased thickness and stiffness. The MV is then a plastic organism, that reacts to the external stimuli, trying to maintain its physiologic integrity. This review has the goal to unveil the secret life of the MV, to understand which stimuli can trigger its plasticity, and to explain why the equation “large heart = moderate/severe mitral regurgitation” and “small heart = no/mild mitral regurgitation” does not work into the clinical practice.     

Human liver stem cell-derived extracellular vesicles reduce injury in a model of normothermic machine perfusion of rat livers previously exposed to a prolonged warm ischemia

Livers from donors after circulatory death (DCD) are a promising option to increase the donor pool, but their use is associated with higher complication rate and inferior graft survival. Normothermic machine perfusion (NMP) keeps the graft at 37°C, providing nutrients and oxygen supply. Human liver stem cell-derived extracellular vesicles (HLSC-EVs) are able to reduce liver injury and promote regeneration. We investigated the efficacy of a reconditioning strategy with HLSC-EVs in an experimental model of NMP. Following total hepatectomy, rat livers were divided into 4 groups: (i) healthy livers, (ii) warm ischemic livers (60 min of warm ischemia), (iii) warm ischemic livers treated with 5 × 10⁸ HLSC-EVs/g-liver, and (iv) warm ischemic livers treated with a 25 × 10⁸ HLSC-EVs/g-liver. NMP lasted 6 h and HLSC-EVs (Unicyte AG, Germany) were administered within the first 15 min. Compared to controls, HLSC-EV treatment significantly reduced transaminases release. Moreover, HLSC-EVs enhanced liver metabolism by promoting phosphate utilization and pH self-regulation. As compared to controls, the higher dose of HLSC-EV was associated with significantly higher bile production and lower intrahepatic resistance. Histologically, this group showed reduced necrosis and enhanced proliferation. In conclusion, HLSC-EV treatment during NMP was feasible and effective in reducing injury in a DCD model with prolonged warm ischemia.     

Pretreatment Primary Tumor Stage is a Risk Factor for Recurrence in Patients with Esophageal Squamous Cell Carcinoma Who Achieve Pathological Complete Response After Neoadjuvant Chemoradiotherapy

Annals of Surgical Oncology - Although pathological complete response (pCR) after multimodal treatment for esophageal cancer is associated to the best prognosis, recurrence may occur in...     

New anatomical reference systems for the bones of the foot and ankle complex: definitions and exploitation on clinical conditions

Medial tibial stress syndrome (MTSS) is one of the most common lower leg injuries in sporting populations. It accounts for between 6 and 16% of all running injuries, and up to 53% of lower leg injuries in military recruits. Various treatment modalities are available with varying degrees of success. In recalcitrant cases, surgery is often the only option. To evaluate whether ultrasound-guided injection of 15% dextrose for treatment of recalcitrant MTSS decreases pain and facilitates a return to desired activity levels for those who may otherwise be considering surgery or giving up the sport. The study design was a prospective consecutive case series involving eighteen patients: fifteen male and three female; (mean age = 31.2 years) with recalcitrant MTSS. They were referred from sports injury clinics across the UK, having failed all available conservative treatment. An ultrasound-guided sub-periosteal injection of 15% dextrose was administered by the same clinician (NP) along the length of the symptomatic area. Typically, 1 mL of solution was injected per cm of the symptomatic area. Pain was assessed using a 10-cm visual analog scale (VAS) at baseline, short-term, medium-term (mean 18 weeks), and long-term (mean 52 weeks) follow-up. Symptom resolution and return to activity were measured using a Likert scale at medium and long-term follow-up. Statistical analyses were performed using SPSS for Mac version 19.0.0 (IBM, New York, NY, US). The Shapiro-Wilk test was used to evaluate the normality of the distribution of data. Friedman’s non-parametric test was used to compare the within-patient treatment response over time. Post-hoc Wilcoxon signed-rank tests with Bonferroni corrections were performed to determine VAS average pain response to treatment over five paired periods. Patients reported a significant (p < 0.01) reduction in median VAS pain score at medium and long-term follow-up compared to baseline. Median improvement per patient was 4.5/10. Patients rated their condition as ‘much improved’ at medium-term follow-up and the median return to sports score was ‘returned to desired but not pre-injury level’ at medium-term and long-term follow-up. No adverse events were reported. Ultrasound-guided 15% dextrose prolotherapy injection has a significant medium-term effect on pain in MTSS. This benefit may be maintained long-term; however, more robust trials are required to validate these findings in the absence of controls. Clinicians should consider the use of ultrasound-guided injection of 15% dextrose as a viable treatment option to reduce pain and aid return to activity for patients with recalcitrant MTSS.