Exercise stress testing in clinical practice

Exercise stress testing is an important diagnostic tool for evaluating patient’s cardiovascular performance. The present review describes the accuracy and the value of exercise stress testing in different settings: after an acute coronary event, after percutaneous coronary intervention or coronary artery bypass graft; in patients risk assessment before non-cardiac surgery; in diabetic population; in patients with baseline electrocardiographic abnormalities. Moreover, this review provides insights relating to test accuracy in women and geriatric patients. Finally, this review explores new variables/parameters (dyspnea, chronotropic incompentence, heart rate recovery, functional capacity, integrated scores) that in the last few years added an incremental value to conventional analysis of exercise-induced angina or electrocardiographic changes

Different Strategies to Obtain Corn (Zea mays L.) Germ Extracts with Enhanced Antioxidant Properties

Maize ( Zea mays L.) germs are by-products from the milling industry. The objective of this work was to compare the phenolic and lipophilic antioxidant fractions of yellow and white corn varieties, provided by Corn Valley S.r.l. (Piumbega, Mantova, Italy) and among the raw materials most processed by the company. The phenolic fraction, extracted with ultrasound-assisted extraction, alone and in combination with chemical and enzymatic hydrolyses, was analyzed with high-performance thin-layer chromatography and reversed-phase high-performance liquid chromatography-diode array detector. Among the various extraction techniques used, the combination of sonication and alkaline hydrolysis proved to be an effective method for the extraction of phenolic compounds from yellow and white germs, with the highest ferulic acid concentrations (636.54 ± 3.71 and 569.23 ± 1.69 mg FA/g dried extract, respectively), total phenolic contents (844.5 ± 64.6 and 742.8 ± 15.44 mg gallic acid equivalents/g dried extract, respectively), and the best antioxidant activity (14.33 ± 0.48 and 11.41 ± 1.1 µg/mL, respectively). The lipophilic fraction, extracted using supercritical carbon dioxide was analyzed by gas chromatography-mass spectrometry. The unsaponifiable fractions were found to be 2.41% ± 0.24% in yellow corn and 1.85% ± 0.08% in white corn; β-sitosterol, campesterol, and stigmasterol were identified as the main phytosterols characterizing both lipophilic extracts which showed the most effective antioxidant activity (1.29 ± 0.26 mg/mL and 1.33 ± 0.21 mg/mL, respectively) compared with the control. Finally, the phenolic and lipophilic extracts obtained from maize by-products may be reintroduced into the health-oriented market as extracts enriched of high-added value biomolecules with antioxidant activity both as active molecules and as additives of natural origin

A Novel null homozygous mutation confirms <i>CACNA2D2</i> as a gene mutated in epileptic encephalopathy

Contribution to epileptic encephalopathy (EE) of mutations in CACNA2D2, encoding α2δ-2 subunit of Voltage Dependent Calcium Channels, is unclear. To date only one CACNA2D2 mutation altering channel functionality has been identified in a single family. In the same family, a rare CELSR3 polymorphism also segregated with disease. Involvement of CACNA2D2 in EE is therefore not confirmed, while that of CELSR3 is questionable. In a patient with epilepsy, dyskinesia, cerebellar atrophy, psychomotor delay and dysmorphic features, offspring to consanguineous parents, we performed whole exome sequencing (WES) for homozygosity mapping and mutation detection. WES identified extended autozygosity on chromosome 3, containing two novel homozygous candidate mutations: c.1295delA (p.Asn432fs) in CACNA2D2 and c.G6407A (p.Gly2136Asp) in CELSR3. Gene prioritization pointed to CACNA2D2 as the most prominent candidate gene. The WES finding in CACNA2D2 resulted to be statistically significant (p = 0.032), unlike that in CELSR3. CACNA2D2 homozygous c.1295delA essentially abolished α2δ-2 expression. In summary, we identified a novel null CACNA2D2 mutation associated to a clinical phenotype strikingly similar to the Cacna2d2 null mouse model. Molecular and statistical analyses together argued in favor of a causal contribution of CACNA2D2 mutations to EE, while suggested that finding in CELSR3, although potentially damaging, is likely incidental

polyphenols from vitis vinifera lambrusco by products leaves from pruning extraction parameters evaluation through design of experiment

Vitis vinifera L. leaves from pruning are by-products of the wine industry and represent an important source of secondary raw material, thanks to their polyphenols content. Optimization of the extraction processes is a key factor for their valorization, and Design of Experiment (DOE) could be a tool to obtain the most performing extract in terms of polyphenols quality/quantity and bioactivity. Vitis vinifera Lambrusco leaves were subjected to ultrasound-assisted extractions guided by a 23 factorial design. Three independent parameters (% solvent, time of extraction, and solvent:solid ratio) were considered to evaluate the extraction process by analyzing the extraction yield, the total phenolic content (Folin-Ciocalteu assay), and the antioxidant capacity (DPPH assay). Moreover, the content of the main molecules was identified and quantified by reversed-phase high-performance liquid chromatography coupled with diode array detection and mass spectrometry. The DOE highlighted the best extraction conditions that showed slight changes considering the different evaluating parameters. The highest extraction yield was obtained by extraction with 100% water, 60 minutes of extraction time, and 30:1 solvent:solid ratio, but it was neither the richest in polyphenols nor antioxidant capacity. The latter 2 characteristics were associated with the extraction performed using 50% ethanol, 35 minutes of extraction time, and a 20:1 solvent:solid ratio. That extract also exhibited the highest quantity of flavonols

Vulnerable personality and Takotsubo cardiomyopathy consequent to emotional stressful events: a clinical case report

Introduction: Although the onset of Takotsubo cardiomyopathy (TTC) can be triggered by an acute, intense emotional stress, the exact pathogenic mechanisms still remain undefined. Presentation: A 58-year-old female was sent by ambulance to the Emergency Department (ED) for chest pain and ST elevations on ECG. Her chest pain began 3 hours before on admission after a domestic argument. Transthoracic echocardiogram showed severe systolic dysfunction with an ejection fraction of 20%. Cardiac catheterization revealed no significant coronary artery disease. The left ventriculogram showed apical ballooning with hyperdynamic proximal segments. A diagnosis of Takotsubo Cardiomyophaty (TTC) was made according to the Mayo Clinic 2008 criteria. The patient evolved with improvement of her condition and, therefore, was discharged from the hospital. Follow-up echocardiogram seven days later showed normal LV size and function with ejection fraction (EF) of 43%. Paykel Life Stress Event Scale identified as emotional trigger a domestic argument occurred 3 hours before symptom onset. History showed a major life stress event, death of a loved one, six months before symptoms. The patient underwent psychological assessment after hospital discharge by Emotional Regulation Questionnaire and BDI showing high suppression/ low reappraisal profile and moderate depression. Conclusion: This case highlights the hypothesis of a possible link between cognitive emotional processing and vulnerability to Takotsubo syndrome

Exercise stress testing in clinical practice

Exercise stress testing is an important diagnostic tool for evaluating patient's cardiovascular performance. The present review describes the accuracy and the value of exercise stress testing in different settings: after an acute coronary event, after percutaneous coronary intervention or coronary artery bypass graft; in patients risk assessment before non-cardiac surgery; in diabetic population; in patients with baseline electrocardiographic abnormalities. Moreover, this review provides insights relating to test accuracy in women and geriatric patients. Finally, this review explores new variables/parameters (dyspnea, chronotropic incompentence, heart rate recovery, functional capacity, integrated scores) that in the last few years added an incremental value to conventional analysis of exercise-induced angina or electrocardiographic changes

Generation of a human iPSC line, FINCBi001-A, carrying a homoplasmic m.G3460A mutation in MT-ND1 associated with Leber's Hereditary optic Neuropathy (LHON)

Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited disorder caused by homoplasmic mutations of mitochondrial DNA (mtDNA). LHON is characterized by the selective degeneration of the retinal ganglion cells (RGC). Almost all LHON maternal lineages are homoplasmic mutant (100% mtDNA copies are mutant) for one of three frequent mtDNA mutations now found in over 90% of patients worldwide (m.11778G > A/MT-ND4, m.3460G > A/MT-ND1, m.14484 T > C/MT-ND6). Human induced pluripotent stem cells (hiPSCs) were generated from a patient carrying the homoplasmic m.3460G > A/MT-ND1 mutation using the Sendai virus non-integrating virus

Rapamycin rescues mitochondrial dysfunction in cells carrying the m.8344A > G mutation in the mitochondrial tRNALys

Background: Myoclonus, Epilepsy and Ragged-Red-Fibers (MERRF) is a mitochondrial encephalomyopathy due to heteroplasmic mutations in mitochondrial DNA (mtDNA) most frequently affecting the tRNALys gene at position m.8344A &gt; G. Defective tRNALys severely impairs mitochondrial protein synthesis and respiratory chain when a high percentage of mutant heteroplasmy crosses the threshold for full-blown clinical phenotype. Therapy is currently lim- ited to symptomatic management of myoclonic epilepsy, and supportive measures to counteract muscle weakness with co-factors/supplements. Methods: We tested two therapeutic strategies to rescue mitochondrial function in cybrids and fibroblasts carry- ing different loads of the m.8344A &gt; G mutation. The first strategy was aimed at inducing mitochondrial biogenesis directly, over-expressing the master regulator PGC-1α, or indirectly, through the treatment with nicotinic acid, a NAD+ precursor. The second was aimed at stimulating the removal of damaged mitochondria through prolonged rapamy- cin treatment. Results: The first approach slightly increased mitochondrial protein expression and respiration in the wild type and intermediate-mutation load cells, but was ineffective in high-mutation load cell lines. This suggests that induction of mitochondrial biogenesis may not be sufficient to rescue mitochondrial dysfunction in MERRF cells with high-muta- tion load. The second approach, when administered chronically (4 weeks), induced a slight increase of mitochondrial respiration in fibroblasts with high-mutation load, and a significant improvement in fibroblasts with intermediate- mutation load, rescuing completely the bioenergetics defect. This effect was mediated by increased mitochondrial biogenesis, possibly related to the rapamycin-induced inhibition of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and the consequent activation of the Transcription Factor EB (TFEB). Conclusions: Overall, our results point to rapamycin-based therapy as a promising therapeutic option for MERRF