Weighing up fish and omega-3 PUFA advice with accurate, balanced scales: stringent controls and measures required for clinical trials

[Editorial] Your patients seek sage health and therapeutic advice. However, focussing on strong evidence-based advice is challenging while wading through disparate clinical studies and dispelling the confusing, sometimes apparently contradictory, out-of-context or incorrect messages trafficking to the public via news and internet media, fuelled by the noisy plethora of commercial \u27nutriceutical\u27 and \u27food pharmacy\u27 products. The cardiovascular benefits of dietary omega-3 long chain polyunsaturated fatty acids (LC PUFA) have been of increasing public and health professional attention and interest for the past several decades. It is therefore timely and important that such benefits are reviewed by Nestel et al., in this issue of Heart Lung and Circulation [1]. In this update of the 2008 National Heart Foundation of Australia (NHF) recommendations on clinical evidence for omega-3 PUFA in prevention and treatment of cardiovascular disease, Nestel et al. conclude that whilst there are clear benefits of eating fish, there is no additional support to recommend the use of refined fish oil supplements

Retinal micro-vascular and aortic macro-vascular changes in postmenopausal women with primary hyperparathyroidism

Aim of the study was to evaluate the micro and macro-vascular changes in patients with primary hyperparathyroidism (PHPT) compared to controls. 30 postmenopausal PHPT women (15 hypertensive and 15 normotensive) and 30 normotensive controls underwent biochemical evaluation of mineral metabolism and measurements of arterial stiffness by 24 hour ambulatory blood pressure monitoring. Retinal microcirculation was imaged by a Retinal Vessel Analyzer. PHPT patients also underwent bone mineral density measurements and kidney ultrasound. PHPT patients had higher mean calcium and parathyroid hormone values compared to controls. Evaluating macro-vascular compartment, we found higher values of 24 hours-systolic, diastolic blood pressure, aortic pulse wave velocity (aPWV) and aortic augmentation index (Aix) in hypertensive PHPT, but not in normotensive PHPT compared to controls. The eye examination showed narrowing arterial and venular diameters of retinal vessels in both hypertensive and normotensive PHPT compared to controls. In hypertensive PHPT, 24 hours systolic blood pressure was associated only with parathyroid hormone (PTH) levels (beta = 0.36, p = 0.04). aPWV was associated with retinal diameter (beta = −0.69, p = 0.003), but not with PTH. Retinal artery diameter was associated with PTH (beta = −0.6, p = 0.008). In the normotensive PHPT, only PTH was associated with retinal artery diameter (beta = −0.60, p = 0.01) and aortic AIx (beta = 0.65, p = 0.02). In conclusion, we found macro-vascular impairment in PHPT and that micro-vascular impairment is negatively associated with PTH, regardless of hypertension in PHPT

GLIMS-IT: contributo italiano al progetto GLIMS di monitoraggio satellitare dei ghiacciai del globo

Si illustra lo stato di avanzamento del contributo italiano al progetto GLIMS-Global Land Ice Measurements from Space che consiste nella redazione di un Atlante satellitare dei ghiacciai italiani. Dall'analisi di cinque immagini rilevate dal sensore ASTER installato sul satellite TERRA sono stati delineati i limiti dei ghiacciai nei gruppi montuosi delle Alpi Lepontine, Pusteresi, delle Dolomiti venete, del versante trentino del Cevedale e dell'Adamello-Presanella. Dal punto di vista metodologico si sono sfruttate, tra l'altro, le informazioni desumibili dai canali spettrali dell'infrarosso termico per il riconoscimento di alcuni ghiacciai coperti da detrito e, una volta delineata l'estensione del ghiacciaio, i parametri geomorfologici vengono estratti in modo automatico con un codice di calcolo che implementa i requisiti del progetto GLIMS. I risultati delle elaborazioni sono stati trasmessi al data base gestito dal National Snow and Ice Data Center ed al Comitato Glaciologico Italiano, che collabora all'iniziativa per l'aggiornamento del catasto dei ghiacciai italiani. Le informazioni per i gruppi montuosi del Cevedale e dell'Adamello-Presanella sono state organizzate in un sistema informativo territoriale in formato KML. Mediamente, nelle aree sinora investigate, è stata rilevata una diminuzione dell'estensione dei ghiacciai, dagli anni '80 al 2007, compresa tra il 34% ed il 50%, una marcata frammentazione di diversi ghiacciai e la scomparsa di alcune unità glaciologiche, confermando l'accelerazione del ritiro iniziato al termine della Piccola Età Glaciale. Si presentano i risultati dell'elaborazione di un'immagine del gruppo dell'Adamello-Presanella la cui estensione dei ghiacciai si è ridotta del 36% dagli anni '80 al 2007

Osteomalacia and Vitamin D Status: A Clinical Update 2020

Historically, rickets and osteomalacia have been synonymous with vitamin D deficiency dating back to the 17th century. The term osteomalacia, which literally means soft bone, was traditionally applied to characteristic radiologically or histologically documented skeletal disease and not just to clinical or biochemical abnormalities. Osteomalacia results from impaired mineralization of bone that can manifest in several types, which differ from one another by the relationships of osteoid (ie, unmineralized bone matrix) thickness both with osteoid surface and mineral apposition rate. Osteomalacia related to vitamin D deficiency evolves in three stages. The initial stage is characterized by normal serum levels of calcium and phosphate and elevated alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)2D]—the latter a consequence of increased PTH. In the second stage, serum calcium and often phosphate levels usually decline, and both serum PTH and alkaline phosphatase values increase further. However, serum 1,25(OH)2D returns to normal or low values depending on the concentration of its substrate, 25-hydroxyvitamin D (25OHD; the best available index of vitamin D nutrition) and the degree of PTH elevation. In the final stage, hypocalcemia and hypophosphatemia are invariably low with further exacerbation of secondary hyperparathyroidism. The exact,or even an approximate, prevalence of osteomalacia caused by vitamin D deficiency is difficult to estimate, most likely it is underrecognized or misdiagnosed as osteoporosis. Signs and symptoms include diffuse bone, muscle weakness, and characteristic fracture pattern, often referred to as pseudofractures, involving ribs, scapulae, pubic rami, proximal femurs, and codfish-type vertebrae. The goal of therapy of vitamin D-deficiency osteomalacia is to alleviate symptoms, promote fracture healing, restore bone strength, and improve quality of life while correcting biochemical abnormalities. There is a need for better understanding of the epidemiology of osteomalacia. Simplified tools validated by concurrent bone histology should be developed to help clinicians promptly diagnose osteomalacia

Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease

Huntington's disease (HD) is themost common neurodegenerative disorder for which no effective cure is yet available. Although several agents have been identified to provide benefits so far, the number of therapeutic options remains limited with only symptomatic treatment available. Over the past few years, we have demonstrated that sphingolipid-based approachesmay open the door to newandmore targeted treatments for the disease. In this study, we investigated the therapeutic potential of stimulating sphingosine-1-phosphate (S1P) receptor 5 by the new selective agonist A-971432 (provided by AbbVie) in R6/2mice, a widely used HD animalmodel. Chronic administration of low-dose (0.1mg/kg) A-971432 slowed down the progression of the disease and significantly prolonged lifespan in symptomatic R6/2mice. Such beneficial effects were associated with activation of pro-survival pathways (BDNF, AKT and ERK) and with reduction of mutant huntingtin aggregation. A-971432 also protected blood-brain barrier (BBB) homeostasis in the same mice. Interestingly, when administered early in the disease, before any overt symptoms, A-971432 completely protected HDmice fromthe classic progressivemotor deficit and preserved BBB integrity. Beside representing a promising strategy to take into consideration for the development of alternative therapeutic options for HD, selective stimulation of S1P receptor 5may be also seen as an effective approach to target brain vasculature defects in the disease

Geometry and modeling of an active offshore thrust-related fold system: the Amendolara Ridge, Ionian Sea, southern Italy

On the Ionian Sea coast of southern Italy, spanning the transition from the Calabrian Arc to the Apennines, NE-directed motion of the thin-skinned frontal thrust belt of the Apennines toward the Apulian foreland reportedly ceased during the Early-Middle Pleistocene. The submarine extension of the frontal thrust belt is represented by the Amendolara ridge, which stretches for over 80 km to the SE beneath the Taranto Gulf. High-resolution marine geophysical data collected on the Amendolara ridge during the TEATIOCA_2011 cruise provided unequivocal constraints to assert active fault-related fold growth. Single-channel seismic (sparker) and acoustic CHIRP profiles, corroborated by multibeam mapping and shallow coring, form the novel dataset to constrain the near-bottom evolution. The new data were benchmarked to the crustal geometry by means of interpretation of existing multichannel seismic profiles

New Insight into Immunity and Immunopathology of Rickettsial Diseases

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered

Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue

AbstractObjectivesPrevious clinical trials suggest that coenzyme Q10 might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q10 therapy on coenzyme Q10 levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q10 on mitochondrial function; to test the effect of coenzyme Q10 in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q10 therapy improves recovery of the heart after cardiac surgery.MethodsPatients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q10 (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed.ResultsPatients receiving coenzyme Q10 (n = 62) had increased coenzyme Q10 levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q10 than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q10 exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% ± 4.3% vs 64.0% ± 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I.ConclusionsPreoperative oral coenzyme Q10 therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q10 levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress

Vitamin D and Its Relationship with Obesity and Muscle

The skin synthesis of vitamin D represents the first step of a metabolic pathway whose features have been extensively studied and clarified in the last decades. In particular, the production of active and inactive forms of the hormone and the actions of the corresponding enzymes have offered new insights into the knowledge of vitamin D metabolism. Additionally, the description of the different organs and tissues expressing the vitamin D receptor and its possible functions, as well as its genetic determinants, have allowed focusing on the interrelationship between vitamin D and many physiological and pathological functions. In this context, many studies reported the association between vitamin D and adipose tissue metabolism, as well as the possible role of the hormone in obesity, weight, and fat mass distribution. Finally, many reports focused on the vitamin D-related effects on skeletal muscle, particularly on the mechanisms by which vitamin D could directly affect muscle mass and strength. This paper is mainly aimed to review vitamin D metabolism and its relationship with obesity and skeletal muscle function