Strength asymmetries are muscle-specific and metric-dependent

We investigated if dominance affected upper limbs muscle function, and we calculated the level of agreement in asymmetry direction across various muscle-function metrics of two heterologous muscle groups. We recorded elbow flexors and extensors isometric strength of the dominant and non-dominant limb of 55 healthy adults. Participants performed a series of explosive contractions of maximal and submaximal amplitudes to record three metrics of muscle performance: maximal voluntary force (MVF), rate of force development (RFDpeak), and RFD-Scaling Factor (RFD-SF). At the population level, the MVF was the only muscle function that showed a difference between the dominant and non-dominant sides, being on average slightly (3-6%) higher on the non-dominant side. At the individual level, the direction agreement among heterologous muscles was poor for all metrics (Kappa values ≤ 0.15). When considering the homologous muscles, the direction agreement was moderate between MVF and RFDpeak (Kappa = 0.37) and low between MVF and RFD-SF (Kappa = 0.01). The asymmetries are muscle-specific and rarely favour the same side across different muscle-performance metrics. At the individual level, no one side is more performative than the other: each limb is favoured depending on muscle group and performance metric. The present findings can be used by practitioners that want to decrease the asymmetry levels as they should prescribe specific exercise training for each muscle

Combinations of idelalisib with rituximab and/or bendamustine in patients with recurrent indolent non-Hodgkin lymphoma

Key Points Combining phosphatidylinositol-3-kinase δ inhibition with rituximab, bendamustine, or both is feasible and active in relapsed iNHL. The safety of novel combinations should be proven in phase 3 trials before adoption in clinical practice.</jats:p

Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population

Background: The distribution and the potential gene-gene and gene-environment interaction of selected metabolic genetic polymorphisms was investigated in relation to gastric cancer risk in an Italian population. Methods: One hundred and seven cases and 254 hospital controls, matched by age and gender, were genotyped for CYP1A1, CYP2E1, mEH, GSTM1, GSTT1, NAT2 and SULT1A1 polymorphisms. Haplotype analysis was performed for EPHX1 exons 3 and 4, as well as CYP2E1 RsaI (*5 alleles) and CYP2E1 DraI (*5A or *6 alleles). The effect modification by alcohol and cigarette smoking was tested with the heterogeneity test, while the attributable proportion (AP) was used to measure the biological interaction from the gene-gene interaction analysis. Results: Gastric cancer risk was found to be associated with the inheritance of GSTT1 null genotype (OR = 2.10, 95%CI: 1.27-3.44) and the SULT1A1 His/His genotype (OR = 2.46, 95%CI: 1.03-5.90). No differences were observed for the haplotype distributions among cases and controls. For the first time an increased risk was detected among individuals carrying the *6 variant allele of CYP2E1 if ever-drinkers (OR = 3.70; 95%CI: 1.45-9.37) with respect to never-drinkers (OR = 0.18; 95% CI: 0.22-1.46) (p value of heterogeneity among the two estimates = 0.001). Similarly, the effect of SULT1A1 variant genotype resulted restricted to ever-smokers, with an OR of 2.58 (95%CI: 1.27-5.25) for the carriers of His allele among smokers, and an OR of 0.86 (95%CI: 0.45-1.64) among never-smokers (p value of heterogeneity among the two estimates = 0.03). The gene-gene interaction analyses demonstrated that individuals with combined GSTT1 null and NAT2 slow acetylators had an additional increased risk of gastric cancer, with an OR of 3.00 (95%CI: 1.52-5.93) and an AP of 52%. Conclusion: GSTT1, SULT1A1 and NAT2 polymorphisms appear to modulate individual's susceptibility to gastric cancer in this Italian population, particularly when more than one unfavourable genotype is present, or when combined with cigarette smoke. The increased risk for the carriers of CYP2E1*5A or *6 alleles among drinkers need to be confirmed by larger prospective studies

An overview of Personalized Medicine landscape and policies in the European Union

Background: The spread of Personalized Medicine (PM) over the last decade defined a revolution in healthcare systems. PM is among the priorities of the European Commission's research agenda, which funded the IC2PerMed international project aiming to integrate China into the International Consortium of PM (ICPerMed). In the context of this project, we mapped the existing policies related to PM in the European Union (EU) and at the EU Member States (EU-MS) level. Methods: PubMed, Google Scholar, Google, Microsoft and national and international institutions' official repositories were searched in order to identify documents on PM-related policies, programmes and action plans at the EU and EU-MS level, published up to December 2020. Results: We identified 28 policies in the EU aimed at improving public health promoting and fostering PM implementation, through some actions including the standardization of good medical practice, use of big data and digital innovation, data sharing and cross-border interoperability, healthcare sustainability, disease prevention and patients'/citizens' engagement. We identified 23 policies at EU-MS level which, notwithstanding national differences, have a common focus, such as patient-tailored treatment and targeted prevention, education of healthcare workers, research and innovation, big data harmonization and healthcare system sustainability. Conclusions: The definition of an integrated regulatory framework is essential to turn PM into an opportunity for citizens and patients with the involvement of all the stakeholders. This work can provide a valuable tool for decision-makers to define common approaches, priorities for research, development and increase international collaboration, which could overcome the fragmented European scenario and align the future direction on PM

Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution