Mediterranean Diet for the Prevention of Gestational Diabetes in the Covid-19 Era: Implications of Il-6 In Diabesity.

The aim of this review is to highlight the influence of the Mediterranean Diet (MedDiet) on Gestational Diabetes Mellitus (GDM) and Gestational Weight Gain (GWG) during the COVID-19 pandemic era and the specific role of interleukin (IL)-6 in diabesity. It is known that diabetes, high body mass index, high glycated hemoglobin and raised serum IL-6 levels are predictive of poor outcomes in coronavirus disease 2019 (COVID-19). The immunopathological mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include rising levels of several cytokines and in particular IL-6. The latter is associated with hyperglycemia and insulin resistance and could be useful for predicting the development of GDM. Rich in omega-3 polyunsaturated fatty acids, vitamins, and minerals, MedDiet improves the immune system and could modulate IL-6, C reactive protein and Nuclear Factor (NF)-κB. Moreover, polyphenols could modulate microbiota composition, inhibit the NF-κB pathway, lower IL-6, and upregulate antioxidant enzymes. Finally, adhering to the MedDiet prior to and during pregnancy could have a protective effect, reducing GWG and the risk of GDM, as well as improving the immune response to viral infections such as COVID-19.

Prognostic implications of additional genomic lesions in adult Philadelphia chromosome-positive acute lymphoblastic leukemia.

To shed light onto the molecular basis of Philadelphia chromosome-positive acute lymphoblastic leukemia and to investigate the prognostic role of additional genomic lesions, we analyzed copy number aberrations using the Cytoscan HD Array in 116 newly diagnosed adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia enrolled in four different GIMEMA protocols, all based on a chemotherapy-free induction strategy. This analysis showed that patients with Philadelphia chromosome-positive acute lymphoblastic leukemia carry an average of 7.8 lesions/case, with deletions outnumbering gains (88% versus 12%). The most common deletions were those targeting IKZF1, PAX5 and CDKN2A/B, which were detected in 84%, 36% and 32% of cases, respectively. Patients carrying simultaneous deletions of IKZF1 plus CDKN2A/B and/or PAX5 had a significantly lower disease-free survival rate (24.9% versus 43.3%; P=0.026). The only IKZF1 isoform affecting prognosis was the dominant negative one (P=0.003). Analysis of copy number aberrations showed that 18% of patients harbored MEF2C deletions, which were of two types, differing in size: the longer deletions were associated with the achievement of a complete molecular remission (P=0.05) and had a favorable impact on disease-free survival (64.3% versus 32.1% at 36 months; P=0.031). These findings retained statistical significance also in multivariate analysis (P=0.057). KRAS deletions, detected in 6% of cases, were associated with the achievement of a complete molecular remission (P=0.009). These results indicate that in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia a detailed evaluation of additional deletions - including CDKN2A/B, PAX5, IKZF1, MEF2C and KRAS - has prognostic implications and should be incorporated in the design of more personalized treatment strategies.

Clinical significance of recurrent copy number aberrations in B-lineage acute lymphoblastic leukaemia without recurrent fusion genes across age cohorts.

Copy number aberrations (CNAs) represent cooperating events in B-lineage acute lymphoblastic leukaemia (B-ALL); however, their clinical relevance across different age cohorts is unclear. We analysed the recurrent CNAs in 157 age-stratified B-ALL negative cases for recurrent rearrangements (B-NEG ALL), and their association with patients' clinico-biological features. We found that: (i) CDKN2A/RB1-deleted and EBF1-deleted adults had a shorter disease-free survival than those with wild-type, (ii) among the unfavourable markers, CDKN2A/RB1 deletions and K/NRAS mutations retained their impact in multivariate analysis, encouraging the evaluation of CDKN2A/RB1 deletions and RAS mutations in the diagnostic/prognostic workflow to refine ALL risk assessment.

Dietary Intakes and Food Habits of Wheelchair Basketball Athletes Compared to Gym Attendees and Individuals who do not Practice Sport Activity.

BACKGROUND: Mediterranean diet (Med-D) has been previously suggested for athletes, but Paralympics usually have a low intake of plant foods. Orthorexia nervosa (ON) can drive dietary intake of both athletes and gym attendees. OBJECTIVE: We aimed to compare dietary intakes and food habits of elite wheelchair basketball athletes (WBA) and able-bodied individuals who practice or not sport activity and with different fat mass percentage (FM%). METHODS: We recruited 15 WBA from the Italian National team and 3 control groups (15 each group): healthy individuals who do not practice any sports activity (NSA) and gym attendees with low (GAL, FM%<17) and high (GAH, FM%>18) FM%. Food consumption was monitored by a 3- d diary, while Med-D scores and ON score were evaluated through standardized questionnaires. In WBA we also assessed Neurogenic Bowel Dysfunction (NBD), GastroEsophageal Reflux Disease (GERD), allergy questionnaire for athletes (AQUA) and Starvation Symptoms Inventory (SSI). RESULTS: In WBA, ON correlated with GERD and SSI. WBA and GAH with eating behavior of ON had higher adherence to Med-D, whereas NSA had less adherence to Med-D. Sub-score, including fruits, vegetables and legumes, was higher in the GAL and GAH groups compared to the WBA and NSA groups. Med-D was inversely related to animal protein intake (PRO-AN) in NSA and GAL. FM% was inversely related to PRO-AN in WBA and GAH, and to ON only in GAH. In WBA, PRO-AN and vegetable protein intake correlated with both carbohydrate and energy intakes. CONCLUSION: In WBA, commitment to wellness (ON and Med-D adherence) could be a response to gastrointestinal and starvation symptoms. WBA should be involved in setting their own individualized dietary strategies.

Post-Exercise Ketosis, Salivary Uric Acid and Interleukin-6 after a Simulated Wheelchair Basketball Match.

BACKGROUND: Interleukin (IL)-6, total antioxidant capacity (TAC) and uric acid (UA) increase after exercise in able-bodied individuals. Wheelchair Basketball Athletes (WBA), having low muscle mass, could be at risk of post-exercise ketosis. OBJECTIVE: This study aimed to evaluate the post-exercise ketosis, IL-6, and antioxidant response, in WBA of the Italian National team, after a simulated match. METHODS: Dietary intakes, Starvation Symptoms Inventory (SSI), percentage of fat mass (FM%) and basal Respiratory Exchange Ratio (RER) and Basal Energy Expenditure (BEE), were evaluated. Salivary TAC, UA and IL-6 were measured: before (PreM), at the end (EM) and 20 minutes after (PostM) the match. Capillary glucose and ß-hydroxybutyrate (ßHB) were monitored. Percentage of Heart Rate Reserve (%HRR) was measured to evaluate exercise intensity. RESULTS: WBA had low carbohydrates (43.5% of daily energy intake (En)) and high fat (36.3% En) intakes. The increase in UA at PostM correlated with En (0.810, p<0.01) and was inversely related to ßHB at EM (-0.719, p<0.05). Furthermore, at PostM growing IL-6 levels correlated with BEE (0.778, p<0.05) and inversely related to FM% (-0.762, p<0.5) were found, which in turn was correlated to SSI (0.781, p<0.05). Also ßHB PostM correlated with SSI (0.761, p<0.05) but was inversely related to RER (-0.745, p<0.05) and En (-0.826, p<0.01). CONCLUSION: Our study suggests that some WBA should improve their dietary habit in order to prevent post-exercise ketosis and ameliorate the endogenous antioxidant response after exercise.

Hormetic Effects of Bioactive Compounds from Foods, Beverages, and Food Dressing: The Potential Role in Spinal Cord Injury.

Spinal cord injury (SCI) is a damage or trauma to the spinal cord resulting in a total or partial loss of motor and sensory function. SCI is characterized by a disequilibrium between the production of reactive oxygen species and the levels of antioxidant defences, causing oxidative stress and neuroinflammation. This review is aimed at highlighting the hormetic effects of some compounds from foods, beverages, and food dressing that are able to reduce oxidative stress in patients with SCI. Although curcumin, ginseng, and green tea have been proposed for SCI management, low levels of antioxidant vitamins have been reported in individuals with SCI. Mediterranean diet includes food rich in vitamins and antioxidants. Moreover, food dressing, including spices, herbs, and extra virgin olive oil (EVOO), contains multiple components with hormetic effects. The latter involves the activation of the nuclear factor erythroid-derived 2, consequently increasing the antioxidant enzymes and decreasing inflammation. Furthermore, EVOO improves the bioavailability of carotenoids and could be a delivery system for bioactive compounds. In conclusion, Mediterranean dressing in addition to plant foods can have an important effect on redox balance in individuals with SCI.

Cranberry for Bacteriuria in Individuals with Spinal Cord Injury: A Systematic Review and Meta-Analysis.

BACKGROUND: Urinary tract infection (UTI) is common in individuals with spinal cord injury (SCI) and neurogenic lower urinary tract dysfunction (NLUTD) and in veterans with SCI who use antibiotics improperly for asymptomatic bacteriuria. Cranberry (CB) has been suggested for UTI prevention. METHODS: We performed a systematic search up to May 2020 in the following databases: AccessMedicine, BioMed Central, CINAHL, Cochrane Library, ProQuest, and PubMed. Quality assessment was performed using a specifically designed quality score. Risk ratio was calculated with both random effect model analysis (DerSimonian-Laird method) and quality effect model analysis (Doi Thalib method). RESULTS: Six studies on bacteriuria and SCI were reviewed. From the four studies available for meta-analysis, two of which with individuals taking both CB and control, 477 data from 415 participants were analysed (241 CB and 236 control). No significant differences were detected with meta-analysis. However, bias, limitations, and incompleteness were observed in the reviewed studies. CONCLUSION: Although further studies are needed, we suggest an accurate monitoring of diet and fluid intake, the evaluation of risk for potential food or nutraceutical interactions with drugs, and the inclusion of inflammatory markers among the outcomes in addition to UTI.

Diet in neurogenic bowel management: A viewpoint on spinal cord injury.

The aim of this review is to offer dietary advice for individuals with spinal cord injury (SCI) and neurogenic bowel dysfunction. With this in mind, we consider health conditions that are dependent on the level of lesion including skeletal muscle atrophy, autonomic dysreflexia and neurogenic bladder. In addition, SCI is often associated with a sedentary lifestyle, which increases risk for osteoporosis and diseases associated with chronic low-grade inflammation, including cardiovascular and chronic kidney diseases. The Mediterranean diet, along with exercise and dietary supplements, has been suggested as an anti-inflammatory intervention in individuals with SCI. However, individuals with chronic SCI have a daily intake of whole fruit, vegetables and whole grains lower than the recommended dietary allowance for the general population. Some studies have reported an increase in neurogenic bowel dysfunction symptoms after high fiber intake; therefore, this finding could explain the low consumption of plant foods. Low consumption of fibre induces dysbiosis, which is associated with both endotoxemia and inflammation. Dysbiosis can be reduced by exercise and diet in individuals with SCI. Therefore, to summarize our viewpoint, we developed a Mediterranean diet-based diet and exercise pyramid to integrate nutritional recommendations and exercise guidelines. Nutritional guidelines come from previously suggested recommendations for military veterans with disabilities and individuals with SCI, chronic kidney diseases, chronic pain and irritable bowel syndrome. We also considered the recent exercise guidelines and position stands for adults with SCI to improve muscle strength, flexibility and cardiorespiratory fitness and to obtain cardiometabolic benefits. Finally, dietary advice for Paralympic athletes is suggested.

Cardiovascular Risk Factors and Haematological Indexes of Inflammation in Paralympic Athletes with Different Motor Impairments.

Haematological indexes of both inflammation and platelet activation have been suggested as predictive markers of cardiovascular disease (CVD), which has high prevalence in Paralympic athletes (PA). Different mechanisms could play a role in increasing CVD risk in PA with spinal cord injury (PA-SCI), lower limb amputation (PA-LLA), or upper limb impairment (PA-ULI). We compared, in 4 groups of PA competing in power, intermittent (mixed metabolism), and endurance sports, Framingham Risk Score (FRS), metabolic syndrome criteria (MetS-C), inflammation (INFLA) Score, 5 haematological indexes of platelet activation (mean platelet volume (MPV), platelet distribution width (PDW), and the ratios between MPV and platelet (MPVPR), between MPV and lymphocyte (MPVLR), and between PDW and lymphocyte (PDWLR)) and the endogenous antioxidants uric acid (UA) and bilirubin (BR). A retrospective chart review of PA from preparticipation examinations' records (London 2012 and Sochi 2014 Paralympics) was performed. We included 25 PA-SCI (13 with high and 12 with low lesion, PA-SCI-H and PA-SCI-L), 15 PA-LLA, and 10 PA-ULI. FRS and INFLA Score did not differ among groups, but PA-SCI-H had lower HDL, compared to PA-SCI-L and PA-ULI. PA-LLA had more MetS diagnostic criteria with significant higher glucose levels than other groups. PA-SCI-H had significantly lower lymphocytes' count compared to PA-LLA and higher MPV, PDW, MPVPR, MPVLR, and PDWLR. SCI-H had lower BR, haemoglobin, haematocrit, proteins, and creatinine. No interaction was found between the 3 kinds of sitting sports and the 2 groups of health conditions (PA-SCI and PA-LLA). In conclusion, PA-LLA had a higher cardiometabolic risk, whereas PA-SCI-H had a higher platelet-derived cardiovascular risk. Further larger studies are needed to investigate the relationship between indexes of inflammation/oxidation and dietary habit, body composition, and physical fitness/performance in PA with motor impairments.

CRLF2 overexpression identifies an unfavourable subgroup of adult B-cell precursor acute lymphoblastic leukemia lacking recurrent genetic abnormalities.

BACKGROUND: A deregulated CRLF2 (d-CRLF2) expression was described in B-cell acute lymphoblastic leukemia without recurrent fusion genes (B-NEG ALL). While the role of d-CRLF2 in children has been extensively described, little is known about its role and impact in adult ALL. METHODS: Expression levels of CRLF2 were evaluated by quantitative real-time PCR in 102 newly-diagnosed adult B-NEG ALL and correlated with the clinico-biological characteristics and outcome. Incidence and clinical impact of the P2RY8/CRLF2 transcript was also assessed. RESULTS: High CRLF2 levels, as continuous variable, were significantly associated with hyperleucocytosis (p=0.0002) and thrombocytopenia (p=0.005); when a cut-point at ΔCt≤8 was applied, 35 cases (34.3%), mostly males (80%), proved positive for CRLF2 expression. High CRLF2 levels, as continuous or categorical variable, were associated with a worse disease-free (p=0.003 and p=0.015) and overall survival (p=0.017 and 0.0038). Furthermore, when CRLF2 was analyzed as a categorical variable, a high statistical association was found with IKZF1 deletion and mutations in the JAK/STAT pathway (p=0.001 and p<0.0001, respectively). Finally, the P2RY8/CRLF2 transcript, identified in 8/102 patients (7.8%), was associated with a poor outcome. CONCLUSIONS: In adult B-NEG ALL, high CRLF2 expression is associated with distinct clinico-biological features and an unfavourable prognosis in both univariate and multivariate analysis; similarly, P2RY8/CRLF2 positivity correlates with a poor outcome. The quantification of CRLF2 is an important prognostic marker in adult B-lineage ALL without known genetic lesions.

Prognostic and therapeutic role of targetable lesions in B-lineage acute lymphoblastic leukemia without recurrent fusion genes.

To shed light into the molecular bases of B-lineage acute lymphoblastic leukemia lacking known fusion transcripts, i.e. BCR-ABL1, ETV6-RUNX1, E2A-PBX1, and MLL rearrangements (B-NEG ALL) and the differences between children, adolescents/young adults (AYA) and adults, we analyzed 168 B-NEG ALLs by genome-wide technologies. This approach showed that B-NEG cases carry 10.5 mutations and 9.1 copy-number aberrations/sample. The most frequently mutated druggable pathways were those pertaining to RAS/RTK (26.8%) and JAK/STAT (12.5%) signaling. In particular, FLT3 and JAK/STAT mutations were detected mainly in AYA and adults, while KRAS and NRAS mutations were more frequent in children. RAS/RTK mutations negatively affected the outcome of AYA and adults, but not that of children. Furthermore, adult B-NEG ALL carrying JAK/STAT mutations had a shorter survival. In vitro experiments showed that FLT3 inhibitors reduced significantly the proliferation of FLT3-mutated primary B-NEG ALL cells. Likewise, PI3K/mTOR inhibitors reduced the proliferation of primary cells harboring RAS and IL7R mutations. These results refine the genetic landscape of B-NEG ALL and suggest that the different distribution of lesions and their prognostic impact might sustain the diverse outcome between children, adults and partly AYA - whose genomic scenario is similar to adults - and open the way to targeted therapeutic strategies.