Predictive role of the Mediterranean diet on mortality in individuals at low cardiovascular risk: A 12-year follow-up population-based cohort study

Background: Adherence to the Mediterranean diet reduces the risk of all-cause and cardiovascular (CV) mortality and the incidence of CV events. However, most previous studies were performed in high-risk individuals. Our objective was to assess whether the adherence to the Mediterranean diet, evaluated by the MED score, was associated with all-cause and CV mortality and incidence of CV events in individuals at low CV risk from a population-based cohort, after a 12-year mean follow-up. Methods: A cohort of 1658 individuals completed a validated food-frequency questionnaire in 2001-2003. The MED score was calculated by a 0-9 scale. Anthropometric, laboratory measurements, and the vital status were collected at baseline and during 2014. The baseline CV risk was estimated by the Framingham risk score. Participants were divided into two groups: individuals at low risk (CV 6) individuals. Values of BMI, waist circumference, fasting glucose and insulin significantly decreased from low to high diet adherence only in participants with CV risk 6510. In a Cox-regression model, the hazard ratios (HRs) in low-risk individuals per unit of MED score were: HR = 0.83 (95 % CI 0.72-0.96) for all-cause mortality, HR = 0.75 (95 % CI 0.58-0.96) for CV mortality, and HR = 0.79 (95 % CI 0.65-0.97) for CV events, after multiple adjustments. In individuals with CV risk 6510, the MED score predicted incident CV events (HR = 0.85; 95 % CI 0.72-0.99), while the associations with all-cause (HR = 1.02; 95 % CI 0.90-1.15) and CV mortality (0.94; 95 % CI 0.76-1.15) were not significant. Conclusions: Greater adherence to the Mediterranean diet was associated with reduced fatal and non fatal CV events, especially in individuals at low CV risk, thus suggesting the usefulness of promoting this nutritional pattern in particular in healthier individuals

Mycobiota composition and changes across pregnancy in patients with gestational diabetes mellitus (GDM)

The gut mycobiota has never been studied either during pregnancy or in patients with gestational diabetes (GDM). This study aimed to analyze the fecal mycobiota of GDM patients during the second (T2) and third (T3) trimester of pregnancy and to compare it with the mycobiota of pregnant normoglycemic women (controls). Forty-one GDM patients and 121 normoglycemic women were studied. GDM mycobiota was composed almost exclusively by the Ascomycota phylum; Basidiomicota accounted for 43% of the relative frequency of the controls. Kluyveromyces (p < 0.001), Metschnikowia (p < 0.001), and Pichia (p < 0.001) showed a significantly higher frequency in GDM patients, while Saccharomyces (p = 0.019), were more prevalent in controls. From T2 to T3, a reduction in fungal alpha diversity was found in GDM patients, with an increase of the relative frequency of Candida, and the reduction of some pro-inflammatory taxa. Many associations between fungi and foods and nutrients were detected. Finally, several fungi and bacteria showed competition or co-occurrence. Patients with GDM showed a predominance of fungal taxa with potential inflammatory effects when compared to normoglycemic pregnant women, with a marked shift in their mycobiota during pregnancy, and complex bacteria-fungi interactions

Prognostic impact of ZAP-70 expression in chronic lymphocytic leukemia: mean fluorescence intensity T/B ratio versus percentage of positive cells

<p>Abstract</p> <p>Background</p> <p>ZAP-70 is an independent negative prognostic marker in chronic lymphocytic leukemia (CLL). Usually, its expression is investigated by flow cytometric protocols in which the percentage of ZAP-70 positive CLL cells is determined in respect to isotypic control (ISO-method) or residual ZAP-70 positive T cells (T-method). These methods, however, beside suffering of an inherent subjectivity in their application, may give discordant results in some cases. The aim of this study was to assess the prognostic significance of these methods in comparison with another in which ZAP-70 expression was evaluated as a Mean-Fluorescence-Intensity Ratio between gated T and CLL cells (T/B Ratio-method).</p> <p>Methods</p> <p>Cytometric files relative to ZAP-70 determination according to the three readouts were retrospectively reviewed on a cohort of 173 patients (test set), all with complete clinical and biological prognostic assessment and time-to-treatment (TTT) available. Findings were then validated in an independent cohort of 341 cases from a different institution (validation set).</p> <p>Results</p> <p>The optimal prognostic cut-offs for ZAP-70 expression were selected at 11% (ISO-method) or 20% of positive cells (T-method), as well as at 3.0 (T/B Ratio-method) in the test set; these cut-offs yielded 66, 60 and 73 ZAP-70⁺cases, respectively. Univariate analyses resulted in a better separation of ZAP-70⁺vs. ZAP-70^-CLL patients utilizing the T/B Ratio, compared to T- or ISO-methods. In multivariate analyses which included the major clinical and biological prognostic markers for CLL, the prognostic impact of ZAP-70 appeared stronger when the T/B-Ratio method was applied. These findings were confirmed in the validation set, in which ZAP-70 expression, evaluated by the T- (cut-off = 20%) or T/B Ratio- (cut-off = 3.0) methods, yielded 180 or 127 ZAP-70⁺cases, respectively. ZAP-70⁺patients according to the T/B Ratio-method had shorter TTT, both if compared to ZAP-70^-CLL, and to cases classified ZAP-70⁺by the T-method only.</p> <p>Conclusions</p> <p>We suggest to evaluate ZAP-70 expression in routine settings using the T/B Ratio-method, given the operator and laboratory independent feature of this approach. We propose the 3.0 T/B Ratio value as optimal cut-off to discriminate ZAP-70⁺(T/B Ratio less than 3.0) from ZAP-70^-(T/B Ratio more/equal than 3.0) cases.</p

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p