Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF-1/CXCR4 signalling pathway

Aims: Homozygosity for a four-missense single-nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long-living individuals. Delivery of this longevity-associated variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell-derived factor-1 (SDF-1). Here, we investigated if delivery of the LAV-BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy. Methods and results: Compared with age-matched lean controls, diabetic db/db mice showed altered echocardiographic indices of diastolic and systolic function and histological evidence of microvascular rarefaction, lipid accumulation, and fibrosis in the myocardium. All these alterations, as well as endothelial dysfunction, were prevented by systemic LAV-BPIFB4 gene therapy using an adeno-associated viral vector serotype 9 (AAV9). In contrast, AAV9 wild-type-BPIFB4 exerted no benefit. Interestingly, LAV-BPIFB4-treated mice showed increased SDF-1 levels in peripheral blood and myocardium and up-regulation of the cardiac myosin heavy chain isoform alpha, a contractile protein that was reduced in diabetic hearts. SDF-1 up-regulation was instrumental to LAV-BPIFB4-induced benefit as both haemodynamic and structural improvements were inhibited by an orally active antagonist of the SDF-1 CXCR4 receptor. Conclusions: In mice with type-2 diabetes, LAV-BPIFB4 gene therapy promotes an advantageous remodelling of the heart, allowing it to better withstand diabetes-induced stress. These results support the viability of transferring healthy characteristics of longevity to attenuate diabetic cardiac disease

Proposta di una “checklist” per il prelievo di sangue venoso

The collection of venous blood is central in clinical laboratory activity. Although there is widespread perception that this practice is simple and free of complications and side effects, it is undeniable that the vast majority of laboratory errors arises from ignorance, incompetence or negligence during venipuncture. It has hence become advisable to prepare a document in simplified form of checklist, consisting of a concise but comprehensive list of activities to be completed or verified in order to prevent errors during venous blood collection. In the intention of authors, this synthetic checklist is a modular tool, adaptable to different local contexts, it can be easily and gradually implemented, it is supported by scientific evidence and consensus of experts and created with the support of different healthcare professionals and it is adherent to the best practices and requires minimal resources for implementation. It is reasonable to assume that this checklist may be able to withstand system and individual changes, strengthening the standards for safety of both operators and patients, limiting potential failure patterns. We hope that the checklist may be implemented in all healthcare facilities where routine venous blood collection is performed, after adaptation to suit characteristics of local organization

Potential therapeutic effects of branched-chain amino acids supplementation on resistance exercise-based muscle damage in humans

Branched-chain amino acids (BCAA) supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE)-derived biochemical markers of muscle soreness (creatine kinase (CK), aldolase, myoglobin), soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality

The role of platelet rich plasma in musculoskeletal science

The idea of using platelet rich plasma (PRP) in medicine has been around since the 1970s. It is only more recently that its use has been employed in the area of musculoskeletal science. Platelet rich plasma in this area has received much media attention being used by many celebrity sports athletes for musculoskeletal injuries. Therefore it is important for the musculoskeletal practitioner to be aware of the concepts surrounding its use and application. In this article we cover what platelet rich plasma is, how it is prepared and administered, its potential clinical application, and what the current literature discusses in the various areas of musculoskeletal science

Circulating microRNAs (miRs) for diagnosing acute myocardial infarction: Meta-analysis of available studies.

Circulating microRNAs (miRs) for diagnosing acute myocardial infarction: Meta-analysis of available studies

No Evidence for an Association of Vitamin D Deficiency and Migraine: A Systematic Review of the Literature.

Vitamin D deficiency is associated with a number of human disorders, including cardiovascular disease, cancer, diabetes, frailty, and infections. Since an association between vitamin D and migraine has also been recently speculated, we performed an electronic search on Medline, Scopus, and Web of Science using the keywords "migraine" and "vitamin D," "25OH-D" "cholecalciferol," "ergocalciferol," with no language or date restriction. The electronic search allowed identifying seven studies (3 observational, 2 cross-sectional, and 2 case reports). The two case reports, including four women, showed favourable effects of vitamin D supplementation on migraine severity, but these studies were small and not placebo controlled. As regards the three observational studies, vitamin D deficiency was observed in 13.2 to 14.8% of migraine patients, and these rates do not differ from those reported in the general population (i.e., vitamin D deficiency between 22 and 42%). The results of the two cross-sectional studies are even more controversial, since no association was found between vitamin D status and migraine in both trials. In conclusion, the current evidence suggests that the association between migraine and vitamin D lacks reliable scientific support

C-reactive protein and migraine. Facts or speculations?

Migraine is a highly prevalent and frequently disabling disorder. Since the pathogenesis of this condition has a strong inflammatory component and migraine is significantly associated with cardiovascular disease, we assess whether C-reactive protein (CRP) may be epidemiologically or casually linked with migraine. An electronic search on Medline, Scopus and Web of Science produced 17 studies reporting original data about the epidemiological association between CRP and migraine (1 retrospective, 1 interventional, 14 cross-sectional and 1 both interventional and cross-sectional). When all studies reporting sufficient data about CRP values were pooled (n=12; 6980 cases and 38,975 controls), the concentration of CRP was found to be significantly higher in patients with migraine than in controls (weighted mean difference 1.12 mg/L; 95% CI 1.01-1.25 mg/L; p<0.001). In further analysis of studies containing separate data for migraine with and without aura (n=7), CRP values remained significantly higher in both migraineur patients with aura (n=1939; weighted mean difference 0.88 mg/L; 95% CI 0.63-1.14 mg/L; p<0.001) or without aura (n=2483; weighted mean difference 1.04 mg/L; 95% CI 0.78-1.30 mg/L; p<0.001) when compared with controls (n=29,354). Despite a large inter-study heterogeneity (99.3%), our analysis provides evidence of a potential epidemiological association between increased concentration of CRP and migraine, thus paving the way for further clinical investigations about therapeutic agents that may contextually decrease the risk of cardiovascular disease and reduce the burden of migraine

Pregnancy-associated plasma protein A (PAPP-A) for the early diagnosis of myocardial infarction: more doubts than certainties.

Pregnancy-associated plasma protein A (PAPP-A) for the early diagnosis of myocardial infarction: more doubts than certainties

Critical review and meta-analysis on the combination of heart-type fatty acid binding protein (H-FABP) and troponin for early diagnosis of acute myocardial infarction.

An early diagnosis is crucial for effective triage and management of patients with suspected acute myocardial infarction (AMI). Although troponin testing is the cornerstone of diagnosis, the sensitivity of this biomarker is still suboptimal at patient admission. The heart-type fatty acid binding protein (H-FABP) is an early and sensitive biomarker of myocardial ischemia, whose appropriate setting is in combination with troponin testing. We performed a systematic review and meta-analysis of articles that have assessed the combination of troponin and H-FABP in the early diagnosis of AMI. Eight studies, totaling 2735 patients, met the inclusion criteria but none of them used a high-sensitivity troponin immunoassay. The between-study variation was high (98.5%), and attributable to heterogeneity. When considered alone, troponin exhibited a significantly greater pooled area under the curve (AUC) than H-FABP alone (0.820 versus 0.784; p<0.001). The pooled specificity was also higher for troponin alone than for H-FABP alone (0.94 versus 0.83; p<0.001), whereas the cumulative sensitivity was lower for troponin than for H-FABP (0.73 versus 0.80; p=0.02). The combination of both biomarkers exhibited a greater AUC than troponin alone (0.881; p<0.001), as well as a higher pooled sensitivity (0.91; p<0.001), which was however counterbalanced by a lower specificity (0.82; p<0.001). These results attest that the combination of H-FABP with a conventional troponin immunoassay seems advantageous for increasing the sensitivity of the former biomarker, at the expense of a lower specificity. The introduction of H-FABP testing would hence require careful assessment of laboratory data or clinical signs and symptoms for excluding sources of elevation different from AMI. Further studies are needed to assess the diagnostic effectiveness of combining H-FABP with a high-sensitivity troponin immunoassay