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The paper aims to describe and analyze the specific loneliness of Walter Ferranini, the protagonist of “Il comunista”, by Guido Morselli (1976). Even though constantly searching for success and praise – as probably it was for Guido Morselli, too – Ferranini lives his grey, unsuccessful, unhappy life in a particular way, which makes him a silent, unrecognized hero, and which gives a special “light” to the full novel.

Il presente intervento si prefigge di analizzare il tema viaggio all’interno dell’italianitŕ nel Paese dei coppoloni (2015) cantautore e scrittore Vinicio Capossela. Sulla base dell’analisi di tale tematica, si vuol notare come il viaggio dell’autore, pur fra i vari incontri e momenti di spossante festeggiamento, sia un costante andare in fuga e in solitudine; da qui l’emergere, in ultima analisi, del tema della solitudine come filo rosso sommesso alla narrazione (e alla produzione) caposseliana. The present paper has the purpose to analyze the theme of traveling in Italianness of Paese dei coppoloni (the Country of Coppoloni, 2015) by the singer, songwriter and writer Vinicio Capossela. The author’s journey – even if among various encounters and moments of exhausting celebration, is basically a solo run; the theme of loneliness can be considered a silver thread submitting to Capossela’s narrative and musical works.

The theme of desolation in L’altra verità. Diario di una diversa, by Alda Merini The life of Alda Merini has always been connected with abandonment, reclusion, abuse, failure of motherhood: in one word, of that kind of loneliness, suffering and inexpressibility that could be called ‘desolation’. The author analyses the construction of the subject in Merini’s L’altra verità. Diario di una diversa: a diary, a reportage, but even a metaphor of the condition of the artist. The paper aims to show that desolation (as product of suffering, loneliness and inexpressibility), is a key element for the condition of the artist (and the subject itself) in 20th century. But it might be particularly a keyword for Alda Merini, marking her way to achieve a state of grace as a writer, and as a woman.

OBJECTIVE In the Italian Diabetes and Exercise Study_2 (IDES_2), behavioral counseling promoted a sustained increase in physical activity (PA) volume (+3.3 MET h ⋅ week−1), moderate- to vigorous-intensity PA (MVPA) (+6.4 min ⋅ day−1), and light-intensity PA (LPA) (+0.8 h ⋅ day−1) and decrease in sedentary time (SED-time) (−0.8 h ⋅ day−1). Here, we investigated the relationships of changes in PA/SED-time with changes in physical fitness and cardiometabolic risk profile in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In this 3-year randomized clinical trial, 300 physically inactive and sedentary patients were randomized 1:1 to receive 1-month theoretical and practical counseling once a year or standard care. Changes in physical fitness and cardiovascular risk factors/scores according to quartiles of accelerometer-measured changes in PA/SED-time were assessed, together with univariate and multivariable associations between these parameters, in the whole cohort and by study arm. RESULTS Physical fitness increased and HbA1c and coronary heart disease 10-year risk scores decreased with quartiles of MVPA and SED-time change. In quartile IV of MVPA increase and SED-time decrease, cardiorespiratory fitness increased by 5.23 and 4.49 mL ⋅ min−1 ⋅ kg−1 and HbA1c decreased by 0.73 and 0.85%, respectively. Univariate correlations confirmed these relationships, and mean changes in both MPVA and SED-time predicted changes in physical fitness and cardiovascular risk factors/scores independently of one another and of other confounders. Similar findings were observed with LPA and PA volume and in each group separately. CONCLUSIONS Even modest increments in MVPA may have a clinically meaningful impact, and reallocating SED-time to LPA may also contribute to improved outcomes, possibly by increasing total energy expenditure.

Di ironia ci si occupa sin dall’antichità: ancora oggi costituisce un fenomeno di ampie dimensioni, oggetto di un dibattito tutt’altro che sopito, riguardante la sua definizione e la sua identità. L’ironia è comunicazione, ma è anche gioco e strumento di ricerca filosofica; è rivoluzione ma allo stesso tempo anche tradizione retorica; sovversione, ma anche scherzo; espressione senza parole ma anche arma di difesa. Costituisce un gap, un divario tra emittente e ricevente, grazie al quale si crea una “differenza di potenziale”, una “corrente”, una forza, che parte da chi parla e tocca — o investe — l’altro termine della comunicazione ironica. Il presente lavoro prendere le mosse da un’operazione di inquadramento del fenomeno ironico per poi passare alla specifica analisi di 68 esempi; il materiale raccolto nel corpus rappresenta una ideale rassegna di espressioni ironiche in lingua italiana standard, ricer¬cate nei più vari campi mediali. Ironią zajmowano się od starożytności. Ów aspekt komunikacji (to właśnie w tym ujęciu została ona zbadana w tej pracy), który wyrażony może być nawet bez słów, od zawsze znajduje się w centrum zainteresowań badaczy wielu różnych dyscyplin. Z tego powodu niezbędnym okazało się rozpoczęcie tych badań od kontekstualizacji ironii, zarówno w odniesieniu do obrazów potencjalnie symbolizujących podstawowe formy ironii jak i na dalszym etapie, rozwijając badania nad etymologią. Kolejnym etapem tych badań było historyczne prześledzenie różnych znaczeń terminu ironia. W ciągu kolejnych wieków, nad pierwotnym nadbudowywały się kolejne znaczenia: na początku εἰρωνεία, eironeia traktowana była jako synonim polimorficzności (πολυτροπία, politropìa, warto zauważyć, że słowo πολύτροπος — politropòs, zmienność — oznacza przebiegłość Odysa w Odysei). Na to znaczenie nałożyły się inne — hipokryzja, fałsz i udawana niewiedza; ten kto przemawia z ironią odbierany jest jako kłamca, obłudnik, ktoś kto ukrywa właściwy cel. Ironia odbierana jako element łączący się z kłamstwem, później wraz z Sokratesem staje się narzędziem odkrywania prawdy (ἀλήθεια , alèteia); jednakże w sensie klasycznym odsyła do interpretacji, a zatem do δόξα, doxa ‘domniemywanie’ raczej niż do λόγος, lògos ‘myśl, istota’ . Od starożytności aż do dzisiaj, przemierzając kolejne epoki historyczne pojęcie ironii nabierało kolejnych walorów i znaczeń kulturowych. Materiał zgromadzony w korpusie przedstawia możliwie pełny zbiór wyrażeń ironicznych we włoskim języku standardowym, wyszukane w najróżniejszych obszarach komunikacji. Obejmuje okres pomiędzy latami 70. XX wieku a współczesnością.

The stability of the dodecameric Listeria innocua ferritin at low pH values has been investigated by spectroscopic methods and size-exclusion chromatography. The dodecamer is extremely stable in comparison to the classic ferritin tetracosamer and preserves its quaternary assembly at pH 2.0, despite an altered tertiary structure. Below pH 2.0, dissociation into dimers occurs and is paralleled by the complete loss of tertiary structure and a significant decrease in secondary structure elements. Dissociation of dimers into monomers occurs only at pH 1.0. Addition of NaCl to the protein at pH 2.0 induces structural changes similar to those observed upon increasing the proton concentration, although dissociation proceeds only to the dimer stage. Addition of sulfate at pH values ≥ 1.5 prevents the dissociation of the dodecamer. The role played by hydrophilic and hydrophobic interactions in determining the resistance to dissociation of L. innocua ferritin at low pH is discussed in the light of its three-dimensional structure.

Ferritin from the spleen of the Antarctic teleost Trematomus bernacchii is an iron storage protein composed of a single sub‐unit type whose amino N‐terminal sequence is blocked, as in L‐type mammalian and fish ferritin polypeptide chains. The partial amino acid sequence reveals a high similarity with the cDNA‐deduced sequence of the M chain (L‐type) of Salmo salar and the H1 chain of Salmo gairdneri ferritins. Like those of the latter sub‐units, the T. bernacchii chain contains the ferroxidase center, typical of mammalian H chains, and the glutamate residues of the iron micelle nucleation site, typical of mammalian L chains. It follows that, at variance with the mammalian ferritins, a single chain suffices to carry out both ferritin functions. In accordance with the sequence data, the T. bernacchii ferritin homopolymer is endowed with a high rate of iron oxidation and a high iron accumulation capacity.

The polypeptide chain that assembles into the unusual dodecameric shell of Listeria innocua apoferritin lacks the ferroxidase centre characteristic of H-type mammalian chains, but is able to catalyse both Fe(II) oxidation and nucleation of the iron core. A cluster of five carboxylate residues, which correspond in part to the site of iron core nucleation typical of L-type mammalian ferritins, has been proposed to be involved in both functions. The features of the iron uptake kinetics and of Fe(II) autoxidation in the presence of citrate followed spectrophotometrically confirm this assignment. In Listeria the kinetics of iron uptake is hyperbolic at low Fe(II)-to-dodecamer ratios and becomes sigmoidal when iron exceeds 150 Fe(II) atoms per dodecamer, namely when a fast crystal growth phase follows a slow initial nucleation step. Iron autoxidation in the presence of citrate displays a similar behaviour. Thus the time course is sigmoidal at low citrate-to-Fe ratios at which Fe(III) polymerization is predominant, but is hyperbolic at ligand concentrations high enough to prevent polymerization. The marked inhibitory effect of Tb(III) on the kinetics of iron incorporation confirms that carboxylates provide the iron ligands in L. innocua apoferritin. Iron uptake followed in steady-state fluorescence experiments allows one to distinguish Fe(II) binding and oxidation from the subsequent movement of Fe(III) into the apoferritin cavity as in mammalian ferritins despite the different localization of the tryptophan residues.

The thermal stability of horse spleen apoferritin, a heteropolymer composed of 90% L and 10% H chains, has been studied by differential scanning calorimetry and compared with that of the human recombinant H homopolymer. The denaturation temperatures (Tm) are significantly higher for the horse spleen polymer than for the recombinant protein under all experimental conditions (e.g., at pH 7, Tm values areor = 93 and 77 degrees C, respectively). The thermal denaturation process displays substantial reversibility for both polymers up to a few degrees below Tm, as indicated by CD measurements in the far and near uv regions. At temperatures higher than Tm the thermograms are influenced by the exothermic contribution of aggregation and/or precipitation. The H homopolymer thermogram, which is not distorted by the exotherm, is consistent with a multistate denaturation process. Acid dissociation of apoferritin produces stable dimeric subunits. The thermal unfolding of both dimeric subunits is reversible at least up to Tm and is characterized by an inversion of stability relative to the polymers (at pH 3.5, Tm is 42 degrees C for the horse spleen and 50 degrees C for the H subunit). These results indicate that the stabilization of the polymeric structure arises mainly from interactions between dimers, in accordance with the crystallographic evidence that the dimers are the building blocks of the polymeric molecule.

This study aimed to assess the efficacy of an intensive exercise intervention strategy in promoting physical activity (PA) and improving hemoglobin A(1c)(HbA(1c)) level and other modifiable cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM).Of 691 eligible sedentary patients with T2DM and the metabolic syndrome, 606 were enrolled in 22 outpatient diabetes clinics across Italy and randomized by center, age, and diabetes treatment to twice-a-week supervised aerobic and resistance training plus structured exercise counseling (exercise group) vs counseling alone (control group) for 12 months. End points included HbA(1c) level (primary) and other cardiovascular risk factors and coronary heart disease risk scores (secondary).The mean (SD) volume of PA (metabolic equivalent hours per week) was significantly higher (P.001) in the exercise (total PA [nonsupervised conditioning PA + supervised PA], 20.0 [0.9], and nonsupervised, 12.4 [7.4]) vs control (10.0 [8.7]) group. Compared with the control group, supervised exercise produced significant improvements (mean difference [95% confidence interval]) in physical fitness; HbA(1c) level (-0.30% [-0.49% to -0.10%]; P.001); systolic (-4.2 mm Hg [-6.9 to -1.6 mm Hg]; P = .002) and diastolic (-1.7 mm Hg [-3.3 to -1.1 mm Hg]; P = .03) blood pressure; high-density lipoprotein (3.7 mg/dL [2.2 to 5.3 mg/dL]; P.001) and low-density lipoprotein (-9.6 mg/dL [-15.9 to -3.3 mg/dL]; P = .003) cholesterol level; waist circumference (-3.6 cm [-4.4 to -2.9 cm]; P.001); body mass index; insulin resistance; inflammation; and risk scores. These parameters improved only marginally in controls.This exercise intervention strategy was effective in promoting PA and improving HbA(1c) and cardiovascular risk profile. Conversely, counseling alone, though successful in achieving the currently recommended amount of activity, was of limited efficacy on cardiovascular risk factors, suggesting the need for a larger volume of PA in these high-risk subjects. Trial Registration isrctn.org Identifier: ISRCTN04252749.

We investigated the effect of different exercise modalities on high sensitivity-C reactive protein (hs-CRP) and other inflammatory markers in patients with type 2 diabetes and the metabolic syndrome. Eighty-two patients were randomized into 4 groups: sedentary control (A); receiving counseling to perform low-intensity physical activity (B); performing prescribed and supervised high-intensity aerobic (C) or aerobic + resistance (D) exercise (with the same caloric expenditure) for 12 months. Evaluation of leisure-time physical activity and assessment of physical fitness, cardiovascular risk factors and inflammatory biomarkers was performed at baseline and every 3 months. Volume of physical activity increased and HbA1c decreased in Groups B–D. VO2max, HOMA-IR index, HDL-cholesterol, waist circumference and albuminuria improved in Groups C and D, whereas strength and flexibility improved only in Group D. Levels of hs-CRP decreased in all three exercising groups, but the reduction was significant only in Groups C and D, and particularly in Group D. Changes in VO2max and the exercise modalities were strong predictors of hs-CRP reduction, independent of body weight. Leptin, resistin and interleukin-6 decreased, whereas adiponectin increased in Groups C and D. Interleukin-1β, tumor necrosis factor-α and interferon-γ decreased, whereas anti-inflammatory interleukin-4 and 10 increased only in Group D. In conclusion, physical exercise in type 2 diabetic patients with the metabolic syndrome is associated with a significant reduction of hs-CRP and other inflammatory and insulin resistance biomarkers, independent of weight loss. Long-term high-intensity (preferably mixed) training, in addition to daytime physical activity, is required to obtain a significant anti-inflammatory effect. Sin financiación 3.438 JCR (2010) Q1, 14/70 Nutrition & dietetics; Q2, 41/116 Endocrinology & metabolism, 32/114 Cardiac & cardiovascular systems UEM

The interaction of hydroxypyridinones with human serum transferrin and ovotransferrin has been studied by analyzing the distribution of iron between the chelator and the proteins as a function of both ligand concentration and transferrin saturation. The kinetics of iron removal by 3-hydroxypyridin-4-ones from both transferrins is slow; in ovotransferrin it appears to be monophasic, in contrast to that observed for serum transferrin. After 24 hours incubation at a 40:1 chelator:protein molar ratio, the percentage of iron removed from Fe(III)-ovotransferrin is 50%–60%, and is somewhat higher in the case of serum transferrin, in line with the respective affinity constants for the metal. The 3-hydroxypyridin-2-ones and the 3-hydroxypyran-4-ones, both of which have lower affinities for Fe(III), remove smaller proportions of the metal. The percentage of desaturation obtained with bidentate and hexadentate pyridinones appears to be similar for both transferrin classes at chelator:protein molar ratios from 40:1. The degree of transferrin saturation influences the extent of chelator mediated iron mobilization in the case of serum transferrin, but not of ovotransferrin. 59 Fe competition studies demonstrate that bidentate pyridin-4-ones are capable of donating iron to serum apotransferrin; the relative concentrations of ligand and protein influence the distribution of iron because their effective binding constants (at pH 7.4) for Fe(III) are similar.

The realization of a reliable receptor biosensor requires stable, long-lasting, reconstituted biomembranes able to supply a suitable biomimetic environment where the receptor can properly work after incorporation. To this end, we developed a new method for preparing stable biological membranes that couple the biomimetic properties of BLMs (bilayer lipid membranes) with the high stability of HBMs (hybrid bilayer membranes); this gives rise to an innovative assembly, named MHBLM (mixed hybrid bilayer lipid membrane). The present work deals with the characterization of biosensors achieved by embedding an ionotropic glutamate receptor (GluR) on MHBLM. Thanks to signal (transmembrane current) amplification, which is typical of natural receptors, the biosensor here produced detects glutamate at a level of nmol L(-1). The transmembrane current changes linearly vs glutamate up to 100 nmol L(-1), while the limit of detection is 1 nmol L(-1). In addition, the biosensor response can be modulated both by receptor agonists (glycine) and antagonists (Mg(2+)) as well, and by exploiting the biosensor response, the distribution of different kinds of ionotropic GluR present in the purified sample, and embedded in MHBLM, was also evaluated. Finally, one of the most important aspects of this investigation is represented by the high stability of the biomimetic system, which allows the use of biosensor under flowing conditions, where the solutions flow on both biomembrane faces.

Listeria innocua Dps (DNA binding protein from starved cells) affords protection to DNA against oxidative damage and can accumulate about 500 iron atoms within its central cavity through a process facilitated by a ferroxidase center. The chemistry of iron binding and oxidation in Listeria Dps (LiDps, formerly described as a ferritin) using H(2)O(2) as oxidant was studied to further define the mechanism of iron deposition inside the protein and the role of LiDps in protecting DNA from oxidative damage. The relatively strong binding of 12 Fe(2+) to the apoprotein (K(D) approximately 0.023 microM) was demonstrated by isothermal titration calorimetry, fluorescence quenching, and pH stat experiments. Hydrogen peroxide was found to be a more efficient oxidant for the protein-bound Fe(2+) than O(2). Iron(II) oxidation by H(2)O(2) occurs with a stoichiometry of 2 Fe(2+)/H(2)O(2) in both the protein-based ferroxidation and subsequent mineralization reactions, indicating complete reduction of H(2)O(2) to H(2)O. Electron paramagnetic resonance (EPR) spin-trapping experiments demonstrated that LiDps attenuates the production of hydroxyl radical by Fenton chemistry. DNA cleavage assays showed that the protein, while not binding to DNA itself, protects it against the deleterious combination of Fe(2+) and H(2)O(2). The overall process of iron deposition and detoxification by LiDps is described by the following equations. For ferroxidation, Fe(2+) + Dps(Z)--> [(Fe(2+))-Dps](Z+1) + H(+) (Fe(2+) binding) and [(Fe(2+))-Dps](Z+1) + Fe(2+) + H(2)O(2) --> [(Fe(3+))(2)(O)(2)-Dps](Z+1) + 2H(+) (Fe(2+) oxidation/hydrolysis). For mineralization, 2Fe(2+) + H(2)O(2) + 2H(2)O --> 2Fe(O)OH((core)) + 4H(+) (Fe(2+) oxidation/hydrolysis). These reactions occur in place of undesirable odd-electron redox processes that produce hydroxyl radical.

Spermine oxidase (SMO) is a recently described flavoenzyme belonging to the class of polyamine oxidases (PAOs) and participating in the polyamine metabolism in animal cells. In this paper we describe the expression, purification, and characterization of the catalytic properties of a recombinant mouse SMO (mSMO). The purified enzyme has absorbance peaks at 457 nm ( e = 11 mM −1 cm −1 ) and 378 nm, shows a molecular mass of ∼63 kDa, and has K m and k cat values of 170 μM and 4.8 s −1 , using spermine as substrate; it is unable to oxidize other free or acetylated polyamines. The mechanism-based PAO inhibitor N , N 1 -bis(2,3-butadienyl)-1,4-butanediamine (MDL72,527) acts as a competitive inhibitor of mSMO, with an apparent dissociation constant K i = 63 μM. If incubated for longer times, MDL72,527 yields irreversible inhibition of the enzyme with a half-life of 15 min at 100 μM MDL72,527. The mMSO catalytic mechanism, investigated by stopped flow, is consistent with a simple four-step kinetic scheme.

A cationic peroxidase was isolated and characterized from the latex of the perennial Mediterranean plant Euphorbia characias. The purified enzyme contained one heme prosthetic group identified as ferric iron-protoporphyrin IX. In addition, the purified peroxidase contained I mol of endogenous calcium per mol of enzyme; removal of this calcium ion resulted in almost complete loss of the enzyme activity. However, when excess Ca 2 + was added to the native enzyme the catalytic efficiency was enhanced by 3 orders of magnitude. The mechanism of activation was studied using a wide range of spectroscopic and analytic techniques. Analysis of the steady state by stopped-flow measurements suggests that the main effect of calcium ions is to favor the oxidation of the ferric enzyme by hydrogen peroxide to form compound I, whereas the other steps of the catalytic cycle seem to be affected to a lesser extent. UV/vis absorption spectra and CD measurements show that the heme iron is pentacoordinated high-spin in native enzyme and remains so after the binding of Ca 2 + . Only minor changes in the secondary or tertiary structure of the protein could be detected by fluorescence or CD measurements in the presence of Ca 2 + ions, except for a significant perturbation of the Fe 3 + inner sphere geometry, as detected by EPR measurements. We propose that Ca 2 + binding to a low affinity site induces a reorientation of the distal histidine changing the almost inactive form of Euphorbia peroxidase to a high activity form. This is the first example of a peroxidase that responds as an on/off switch to variations in the external Ca 2 + level.

The Gram-positive bacterium Listeria innocua possesses an authentic ferritin with an unusual dodecameric assemblage that resembles the quaternary structure of the DNA-binding proteins designated Dps ( D NA-binding p roteins from s tarved cells). The L. innocua gene encoding the above protein, termed ferritin from Listeria innocua ( fri ), has been localized on a 3-kb Hin dIII chromosomal fragment cloned in the Escherichia coli strain DH5αF′. DNA sequence analysis reveals an open reading frame of 468 nucleotides matching perfectly the amino acid sequence of the protein. Primer extension analysis indicates the presence of two transcriptional startpoints located 36 (proximal) and 85 nt (distal) upstream the fri start codon, respectively. Each transcriptional startpoint is preceded by suitably located −10 and −35 elements, which match the σ A (proximal) and σ B (distal) consensus sequences. In L. innocua and Liseria monocytogenes , fri expression increases both upon entry into stationary phase and, more markedly, under low-iron growth conditions. The effect of iron is apparent in the exponential and stationary phases of growth. An up-regulation by iron limitation has never been observed in other proven ferritins and bacterioferritins, but has been reported for several members of the Dps family. The unusual regulation by iron of the Listeria ferritin gene provides further support to the evolutionary link with the Dps family and suggests that the iron storage function may not be the unique role of ferritin in the physiology of this bacterium.

Ferritin from the spleen of the Antarctic teleost Trematomus bernacchii is composed of a single subunit that contains both the ferroxidase center residues, typical of mammalian H chains, and the carboxylate residues forming the micelle nucleation site, typical of mammalian L chains. Comparison of the amino-acid sequence with those available from lower vertebrates indicates that T. bernacchii ferritin can be classified as an M-type homopolymer. Interestingly, the T. bernacchii ferritin chain shows 85.7% identity with a cold-inducible ferritin chain of the rainbow trout Salmo gairdneri. The structural and functional properties indicate that cold acclimation and functional adaptation to low temperatures are achieved without significant modification of the protein stability. In fact, the stability of T. bernacchii ferritin to denaturation induced by acid or temperature closely resembles that of mesophilic mammalian ferritins. Moreover iron is taken up efficiently and the activation energy of the reaction is 74.9 kJ.mol(-1), a value slightly lower than that measured for the human recombinant H ferritin (80.8 kJ.mol(-1)).

Background: This study aimed to assess the efficacy of an intensive exercise intervention strategy in promoting physical activity (PA) and improving hemoglobin A1c (HbA1c) level and other modifiable cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). Methods: Of 691 eligible sedentary patients with T2DM and the metabolic syndrome, 606 were enrolled in 22 outpatient diabetes clinics across Italy and randomized by center, age, and diabetes treatment to twice-a-week supervised aerobic and resistance training plus structured exercise counseling (exercise group) vs counseling alone (control group) for 12 months. End points included HbA1c level (primary) and other cardiovascular risk factors and coronary heart disease risk scores (secondary). Results: The mean (SD) volume of PA (metabolic equivalent hours per week) was significantly higher (P.001) in the exercise (total PA [nonsupervised conditioning PAsupervised PA], 20.0 [0.9], and nonsupervised, 12.4 [7.4]) vs control (10.0 [8.7]) group. Compared with the control group, supervised exercise produced significant improvements (mean difference [95% confidence interval]) in physical fitness; HbA1c level (�0.30% [�0.49% to �0.10%]; P.001); systolic (�4.2 mm Hg [�6.9 to �1.6 mm Hg];P=.002) and diastolic (�1.7 mm Hg [�3.3 to �1.1 mm Hg]; P=.03) blood pressure; high-density lipoprotein (3.7 mg/dL [2.2 to 5.3 mg/dL]; P.001) and lowdensity lipoprotein (�9.6 mg/dL [�15.9 to �3.3 mg/dL]; P=.003) cholesterol level; waist circumference (�3.6 cm [�4.4 to �2.9 cm];P.001); body mass index; insulin resistance; inflammation; and risk scores. These parameters improved only marginally in controls. Conclusions: This exercise intervention strategy was effective in promoting PA and improving HbA1c and cardiovascular risk profile. Conversely, counseling alone, though successful in achieving the currently recommended amount of activity, was of limited efficacy on cardiovascular risk factors, suggesting the need for a larger volume of PA in these high-risk subjects. Trial Registration: isrctn.org I dentifier: ISRCTN-04252749

We read with great interest the results of the meta-analysis by Snowling and Hopkins (1) on the effects of different modes of exercise training on glucose control and risk factors for complications in type 2 diabetic patients. This most recent meta-analysis of post-2000 randomized controlled trials is perhaps most important because of the size of the cohort (over 1,000 type 2 diabetic patients) and for the study of characteristics and magnitude of effects in more detail than in the previous Boule meta-analyses (2). Snowling and Hopkins determined that an A1C reduction of 0.8 ± 0.3% is “small” and affirmed in their conclusion that “there are sufficient studies to allow us to conclude that aerobic, resistance, and combined exercise have …

Background Physical activity (PA)/exercise have become an integral part of the management of type 2 diabetes mellitus (T2DM). However, current guidelines are difficult to put into action in this population due to a number of barriers, especially the lack of acceptable, feasible, and validated behavioral intervention strategies. The present manuscript reports the rationale, study design and methods, and design considerations of the Italian Diabetes and Exercise Study (IDES)-2, a randomized controlled trial testing the efficacy of a behavior change strategy in increasing total daily PA and reducing sedentary time (SED-time) in patients with T2DM. Methods/Design Starting 7 January 2014, the IDES_2 began enrolling 300 patients with known T2DM of at least 1-year duration in three tertiary referral outpatient Diabetes Clinics in Rome. Additional requirements are age 40 to 80 years, body mass index 27 to 40 kg/m2, sedentary lifestyle, and physically inactive for at least 6 months, ability to walk 1.6 km without assistance, and eligibility after cardiovascular evaluation. Patients are randomized by center and within each center, by age and type of diabetes treatment to either the intervention or the control group. Patients in the intervention (INT) group (n = 150) receive theoretical and practical exercise counseling consisting of aggregated behavior change techniques (one individual theoretical counseling session plus eight twice-a-week individual theoretical and practical exercise counseling sessions) once a year for 3 years. Patients in the control (CON) group (n = 150), receive standard care, including general physician recommendations for daily PA. The primary outcomes are total daily PA and SED-time, as measured objectively by the use of an accelerometer. Secondary outcomes include physical fitness, modifiable cardiovascular risk factors, musculoskeletal disturbances, well-being/depression, and health-related quality of life. Discussion The behavioral intervention strategy tested in the IDES_2 is based on solid theoretical grounds and uses several behavioral change techniques, two factors which were found to improve effectiveness of behavioral intervention. In addition, physicians and exercise specialists have been specifically trained for counselling/prescribing and supervising PA/exercise, respectively, in subjects suffering from metabolic disorders. Finally, the large sample size, the long study duration, and the objective measurement of PA allow statistically significant and scientifically robust conclusions to be drawn on the feasibility and efficacy of this intervention in T2DM patients. Trial registration ClinicalTrials.gov; NCT01600937; 10 October 2012. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1088-0) contains supplementary material, which is available to authorized users.