Activity of 30 different cheeses on cholesterol plasma levels and Oxidative Balance Risk Index (OBRI) in a rat model.

BACKGROUND: Cheese is considered to increase the total cholesterol levels (CH) due to the high-saturated fat content. New models are needed to measure the relationship between cholesterol and cheese. METHODS: Thirty different cheeses produced in Val Brembana, Italy ("furmai da mut", "caprino" and "stracchino"), were added to the diet of 30 groups of 4 rats. Cheeses were analyzed to differentiate the volatile organic compounds (VOCs) and the cholesterol content (Ch(f)). The body weight, CH, urine volume and oxidative balance were measured. Three new indexes in relation to CH were calculated: OI (oxidative index), PI (protective index) and OBRI (oxidative balance risk index). RESULTS: None of the cheeses increased CH. Some of the "furmai de mut" were significantly decreasing CH and improved the oxidative balance. Ch(f) was not affecting the CH levels in plasma. In terms of VOCs, the acetic acid content was correlated (p < 0.05) with the CH reduction and PI improvement. OBRI was reduced mainly in the "stracchino group". CONCLUSIONS: The model shows that some cheese can reduce significantly CH levels and improve the antioxidant capacity.

Levothyroxine and lung cancer in females: the importance of oxidative stress.

BACKGROUND: Levothyroxine (LT4) treatment can lead to iatrogenic hyperthyroidism and oxidative stress that can cause patient discomfort. Oxidative stress is also recognized as one of the causes of chronic diseases and cancer. METHODS: The prevalence of breast, colorectal, gastric and lung cancer in 18 Italian Regions during 2010 was correlated with the sales of LT4 in 2009. The cancer prevalence was analyzed in women aged 30-84. This age range corresponds to more than 80% of the consumers of the drug and to about 99% of all malignant cancers. The correlation between sales of LT4 and cancers was determined with the technique of Density Ellipses. The age and smoking contribution for lung cancer was determined with the Sequential test. RESULTS: No significant correlation was seen between LT4 sales and breast, colorectal and gastric cancers. A significant correlation was instead found for lung cancer (p<0.05) corrected for smoking and age. CONCLUSIONS: LT4 consumption in Italy is about 0.7 boxes/women/year. There is a correlation between lung cancer and LT4 treatment and oxidative stress caused by LT4 supplementation can be one of the causes. Although we cannot exclude that dysthyroidism needing LT4 supplementation might be the ground for lung cancer itself and measuring oxidative stress could be helpful in avoiding excessive use of the drug.

Effect of L. crispatus M247 Administration on Pregnancy Outcomes in Women Undergoing IVF: A Controlled, Retrospective, Observational, and Open-Label Study.

The aim of our study was to retrospectively evaluate whether the oral administration of L. crispatus (M247) could increase pregnancy and live birth rates in women undergoing assisted reproductive technology procedures. Enrolled women (N = 160) were divided into two groups: treated (N = 80) or untreated (N = 80) with the probiotic strain. The odds ratio (OR) for a treated woman to have a clinical pregnancy (CP) was 1.56. In women aged 30-40 years, M247 increased the probability of a CP in correlation with the progressive rise in BMI, reaching 47% (35% in controls) with a BMI of 35 (OR: 2.00). The CAID statistics showed that in a woman of the blastocyst subgroup, below 43 years, with a BMI over 18.6, treatment with M247 increased the chance of a CP from 28.4% to 44.5% (OR: 2.08; p < 0.05). Considering live births, the rate of the probiotic group was 12.5% versus 7.5% (OR: 1.76). Considering only the blastocyst subgroup, the treatment increased the number of live births by 200% (OR: 3.64; p = 0.05). As confirmed also by statistical indices NNT, NNH, and LHH, the use of M247 demonstrated a risk-benefit ratio to the full advantage of the benefits.

Effect of Berberine Phytosome on reproductive, dermatologic, and metabolic characteristics in women with polycystic ovary syndrome: a controlled, randomized, multi-centric, open-label clinical trial.

Background: Berberine is a poorly absorbed natural alkaloid widely used as nutraceutical to counteract diarrhoea and to lower cholesterol and hyperglycaemia. It has also been reported to reduce signs and symptoms of polycystic ovary syndrome (PCOS). Objective: To explore, through a multi-centric, randomized, controlled and prospective study, the possible role played by a form berberine that is more easily absorbed (Berberine Phytosome®, BP) in 130 Pakistani women with a diagnosis of PCOS and fertility problems due to menstrual and ovary abnormalities. Results: Ninety days of supplementation with BP, administered at 550 mg x2/die, determined (i) resumption of regular menstruation in about 70% of women (versus 16% in the control group; p < 0.0001), (ii) normalization of the ovaries anatomy in more than 60% of women (versus 13% in the control group; p < 0.0001), (iii) acne improvement in 50% of women (versus 16% in the control group; p = 0.0409) and (iv) hirsutism reduction in 14% of women (versus 0% in the control group; p = 0.0152). The metabolic and the hormonal profiles of the women in the two groups did not significantly differentiate at the end of the study. BP was well-tolerated and no specific side-effects were registered. Respectively after one, two and 8 years of trying, three women supplemented with BP became and are currently pregnant. Conclusion: Our study showed the positive effects of BP supplementation in women with PCOS and confirmed the high safety profile of this nutraceutical. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT05480670.

[Covid-19: Thomas Bayes warns and we should listen. False negatives and the probability of encountering them.] / Covid-19: Thomas Bayes ammonisce e noi dovremmo ascoltarlo. I falsi negativi al test e la probabilità d'incontrarli.

We believe that a high percentage of covid-19 infections could be due to the presence of false negative (FN) individuals on rapid swabs. To support this hypothesis and quantify their number, we performed simulations using Bayes' rule and various assumptions about the sensitivity, specificity of swabs and prevalence of infection. Imagining FNs in liberty, we then calculated the probability of encountering them in groups of people with a typical number of habitual sites, such as: bus, supermarket, theatre, etc. The probability of encountering FN from rapid tests was more than 3 times higher (345% change) that reported by the RT-PCR test.

Clinical Effects of Streptococcus salivarius K12 in Hospitalized COVID-19 Patients: Results of a Preliminary Study.

Anatomical and physiological considerations indicate that the oral cavity is a primary source of the lung microbiota community, and recent studies have shown that the microbiota in the lungs contributes to immunological homeostasis, potentially altering the organ's susceptibility to viral infection, including SARS-CoV-2. It has been proposed that, in the case of viral infection, lung Gram-negative bacteria could promote the cytokine cascade with a better performance than a microbiota mainly constituted by Gram-positive bacteria. Recent observations also suggest that Prevotella-rich oral microbiotas would dominate the oral cavity of SARS-CoV-2-infected patients. In comparison, Streptococcus-rich microbiotas would dominate the oral cavity of healthy people. To verify if the modulation of the oral microbiota could have an impact on the current coronavirus disease, we administered for 14 days a well-recognized and oral-colonizing probiotic (S. salivarius K12) to hospitalized COVID-19 patients. The preliminary results of our randomized and controlled trial seem to prove the potential role of this oral strain in improving the course of the main markers of pathology, as well as its ability to apparently reduce the death rate from COVID-19. Although in a preliminary and only circumstantial way, our results seem to confirm the hypothesis of a direct involvement of the oral microbiota in the construction of a lung microbiota whose taxonomic structure could modulate the inflammatory processes generated at the pulmonary and systemic level by a viral infection.

The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study.

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients.

Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial.

Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical University, Lahore, PK. Patients were randomized to receive either standard of care (SC) plus an oral quercetin supplement (500 mg Quercetin Phytosome®, 1st week, TDS: 2nd week, BDS) (n = 50, quercetin group) or SC alone (n = 50, control group). Results: After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (p = 0.0004), and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved (p = 0.0051). Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406.56 ± 183.92 to 257.74 ± 110.73 U/L, p = 0.0001. Quercetin was well-tolerated by all the 50 patients, and no side effects were reported. Conclusion: Our results, suggest the possible therapeutic role of quercetin in early-stage COVID-19, including speedy clearance of SARS-CoV-2, early resolution of the acute symptoms and modulation of the host's hyperinflammatory response. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04861298.

Arterial stiffness and 5-year mortality in patients with peripheral arterial disease.

Among patients with peripheral arterial disease (PAD) the risk of mortality remains extremely high. We investigated whether arterial stiffness evaluated by aortic Pulse Wave Velocity (aPWV) and Augmentation index normalized for a standard heart rate of 75 bpm (Aix@75), predict cardiovascular disease (CVD) and total mortality in PAD and No-PAD patients. In 231 PAD patients (ankle-brachial index-ABI ≤ 0.9) and 167 No-PAD (ABI ≥ 0.91 < 1.3) the aPWV and Aix @75HR were evaluated using arterial tonometry and ABI values were obtained using an 8-MHz Doppler probe. The CVD and total mortality rates in relation to aPWV and Aix@75HR were analyzed using Cox regression model. During a mean follow-up of 5.4 ± 2 years 39 (16.9%) deaths occurred in PAD patients and 8 (4.8%) in No-PAD. In the population study, the age was a predictor of CVD mortality (HR = 0.143, 95% CI, 0.06-0.23; p = 0.0004) while the aPWV, was a predictor of total mortality (HR = 1.18, 95% CI, 1.07-1.30; p = 0.0008). In the PAD group, the aPWV remained associated with an increased risk for total mortality (HR = 1.14, 95% CI, 1.03-1.27; p = 0.010). An increase of aPWV may be an indicator of total mortality in PAD patients.

Arterial stiffness and subendocardial viability ratio in patients with peripheral arterial disease.

Arterial stiffening is a hallmark of the aging process and atherosclerosis, including peripheral arterial disease (PAD). We investigated the associations between carotid-femoral pulse wave velocity (c-fPWV), augmentation index corrected for heart rate (Aix@HR75), ankle brachial index (ABI), and subendocardial viability ratio (SEVR), an indicator of cardiac perfusion. The c-fPWV, Aix@HR75, and SEVR was estimated using applanation tonometry. The ankle systolic pressure measurements for the calculation of the ABI were obtained using an 8-mHz Doppler probe. The study group included 555 subjects, mean age 63 ± 11 years (248 PAD (ABI < 1.0), and 307 non-PAD (ABI ≥ 1.0 ≤ 1.3). After the stepwise selection process in both PAD and non-PAD patients SEVR was not related to c-fPWV and ABI (P = .154; P = .156) and (P = .101; P = .402), respectively. In PAD patients, SEVR was negatively related to Aix@HR75 (P < .0001) and aortic PP (P = .0005). In conclusion, arterial stiffness is associated with non-invasive indices of myocardial perfusion in PAD patients, suggesting a potential pathophysiological link for increased cardiovascular events.

Long-Term Treatment of Overweight and Obesity with Polyglucosamine (PG L112): Randomized Study Compared with Placebo in Subjects after Caloric Restriction.

Background: Short-term treatment of overweight and obesity with polyglucosamine (PG) was found to be more effective than placebo and orlistat in double-blind clinical studies. Objective: The aim of the study was to compare the efficacy of long-term (12-mo) treatment of weight loss with PG and placebo (PL). Methods: This was a double-blind randomized study in 100 participants of both sexes with a body mass index (in kg/m2) >30 to <35. One group of 50 participants was treated for 1 y with PG at 1.6 g/d and a similar group received PL. PG is a combination of low-molecular-weight chitosan with organic acids. Participants were instructed to reduce their caloric intake by 10% and increase the physical activity level by 9 metabolic equivalent task hours/wk. Dietary compliance was checked every 3 mo by using a weekly questionnaire [food intake assessment (FIA)] based on 25 different food servings. Body weight (BW), waist circumference (WC), blood pressure (BP), glucose, lipids, and high-sensitivity C-reactive protein (hs-CRP) were also monitored. Results: Ninety-seven participants completed the study (49 in the PG group, 48 in the PL group). The decrease in calories was similar in both groups, as was the change in number of food servings (P > 0.05, ANOVA). Decreases in BW and WC were 8.0 kg and 10.2 cm, respectively, in the PL group, whereas they were 12.1 kg and 13.3 cm in the PG group (P < 0.001, ANOVA). The decrease in BP, plasma lipids, glucose, and hs-CRP was more evident in the group treated with PG (P < 0.05, ANOVA). The intake of lipids was found to correlate directly with hs-CRP, with the exception of extra-virgin olive oil. Conclusions: PG was found to be more effective than PL in reducing BW, WC, glucose, BP, plasma lipids, and hs-CRP in moderately obese individuals undergoing a 10% caloric reduction and a slight increase in physical activity. Dietary monitoring with the use of an FIA was an effective tool in supporting dietary compliance. This trial was registered at clinicaltrials.gov as U111111292405 (WHO).

Cost-effectiveness of the real-world use of drug-eluting stents at 9-month follow-up: results from the Sicilian DES Registry.

BACKGROUND: With the aim of reducing restenosis after percutaneous coronary intervention with bare-metal stents (BMSs) for the treatment of ischemic heart disease, drug-eluting stents (DESs) were introduced in the field of percutaneous coronary intervention in 2002. However, the higher cost of DES in comparison with BMS made it necessary to determine whether their use brings a real economic advantage. METHODS: In order to verify the clinical and economic benefit of DES in comparison with BMS and surgical treatment with coronary artery bypass graft (CABG), the Sicily Regional Government arranged for the creation of a directory where patients receiving at least one DES (with sirolimus or with paclitaxel) were enrolled from June 2004 to February 2005. The cost-effectiveness analysis for DES was carried out by means of two decisional models: one referring to patients treated with DES who, without such a device, would have undergone CABG, and the second one referring to patients treated with DES who, without such device, would have received BMS. Cost analysis was carried out from the point of view of the SSR (Servizio Sanitario Regionale, Regional Health Service). RESULTS: The use of DES on patients destined to CABG generated average unitary differential savings of euro9003, after 9 months of follow-up, and average total differential savings of euro4 438 479. The use of DES on patients destined to BMS gave average unitary differential savings of euro1075, after 9 months of follow-up, and average total differential savings of euro1 052 425. The use of DES instead of BMS and CABG allowed SSR to make average differential savings of euro3760 per successful case. The refund threshold value of DES, setting to zero the SSR average differential savings for patients treated with DES who would otherwise have been treated with BMS, was euro2489. CONCLUSION: The medium-term results of the proposed models, tested with sensitivity analysis, demonstrate the use of DES to be justified; moreover, these results could positively influence the attitude of the SSR toward these new therapeutic strategies, which are an improvement on standard therapies, both from a clinical and a financial standpoint.

Coronary stent implantation throughout technical evolution: immediate and follow-up results.

Coronary stenting (stent implantation) has evolved over the last 5 years with changes in stent design, stent material and the implantation technique. The use of high-pressure balloon inflation (HP), intravascular ultrasound (IVUS) and appropriate antiplatelet therapy have contributed to the abolishment of the need for subsequent anticoagulation, allowing extended stent applications. We compared results in three groups of patients having stent implantation throughout the period of evolution: group A: no IVUS, no HP, with subsequent anticoagulation treatment (n 3 434); group B: no IVUS, yes HP, without subsequent anticoagulation treatment (n 3 192); and group C: yes IVUS, yes HP, without subsequent anticoagulation treatment (n 3 588). The primary success rates were comparable in all groups. There was a clear change in indications for stenting in groups B and C compared with group A (elective stenting: group A 3 32%; group B 3 66%; group C 3 69%; P < 0.0001), in reference vessel size (group A 3 3.22 3 0.37 mm; group B 3 2.92 3 0.56 mm; group C 3 2.98 3 0.57 mm; P < 0.0001), and for presence of type B2 and C lesions (group A 3 57%; group B 3 72%; group C 3 74%; P < 0.001). The complication rate significantly decreased in group C (group A 3 3.6%; group B 3 4.1%; group C 3 1.2%; P < 0.001) and the mean patient hospital stay decreased to 2 days in groups B and C due to the abolition of the need for anticoagulant treatment. The angiographic restenosis rate increased in groups B and C (group A 3 20%; group B 3 34%; group C 3 32%; P < 0.001). The need for a repeat procedure increased as stenting of more complex lesions and smaller vessels was attempted: target lesion revascularization (TLR) was performed in 16% of patients in group A (73/434), in 18% of group B (35/192) and in 22% of group C (129/588) (P 3 0.04 for A versus C). Major cardiac events (MACE) occurred in 142 patients in group A (33%), 60 patients in group B (31%) and in 181 patients in group C (30%). The evolving technique of coronary stenting has expanded the spectrum of indications and range of coronary vessels attempted, and decreased the complication rates and hospital stay. However, in less-favorable subsets, additional improvements are needed to affect the long-term outcome.