Active breaks: a strategy to counteract sedentary behaviors for Health Promoting Schools. A discussion on their implementation in Italy.

Abstract: School Active Breaks are short bouts of physical activity (5-15 minutes) conducted by appropriately trained teachers and delivered during or between curricular lessons. They are a good strategy to counteract sedentary behaviors, and a growing body of evidence shows that they can represent also a tool to promote and improve health, school wellbeing and academic achievements. On 19 February 2022, the Working Group on Movement Sciences for Health of the Italian Society of Hygiene, Preventive Medicine and Public Health organized an Awareness Day on the effectiveness, usefulness and feasibility of School Active Breaks, opened to teachers, educators, school leaders, pediatricians, personnel from Departments of Prevention and Public Health and Health Policy-makers. During the event, the testimonies about the experiences already carried out in Italy showed that School Active Breaks are an effective intervention that each school can easily include in its educational offer and apply in any context.

Validation and in vivo assessment of an innovative satellite-based solar UV dosimeter for a mobile app dedicated to skin health.

We present an innovative satellite-based solar UV (ultraviolet) radiation dosimeter with a mobile app interface that has been validated by exploiting both ground-based measurements and an in vivo assessment of the erythemal effects on some volunteers having controlled exposure to solar radiation. The app with this satellite-based UV dosimeter also includes other related functionalities such as the provision of safe sun exposure time updated in real-time and end exposure visual/sound alert. Both validations showed that the system has a good accuracy and reliability needed for health-related applications. This app will be launched on the market by siHealth Ltd in May 2016 under the name of "HappySun" and is available for both Android and iOS devices (more info on ). Extensive R&D activities are on-going for the further improvement of the satellite-based UV dosimeter's accuracy.

Distinct pattern of immunophenotypic features of innate and adaptive immunity as a putative signature of clinical and laboratorial status of patients with localized cutaneous leishmaniasis.

In this study, we have analysed the phenotypic features of innate/adaptive immunity of patients with localized cutaneous leishmaniasis (LCL), categorized according to their clinical/laboratorial status, including number of lesion (L1; L2­4), days of illness duration (≤60;>60) and positivity in the Montenegro skin test (MT−;MT+). Our findings highlighted a range of phenotypic features observed in patients with LCL (↑%HLA-DR+ neutrophils; ↑CD8+ HLA-DR+/CD4+ HLA-DR+ T cell ratio; ↑HLA-DR in B lymphocytes, ↑%CD23+ neutrophils, monocytes and B cells; ↑α-Leishmania IgG and ↑serum NO2⁻ + NO3⁻). Selective changes were observed in L1 (↑%HLA-DR+ neutrophils, ↑CD8+ HLA-DR+/CD4+ HLA-DR+ T cell ratio and ↑serum NO2⁻ + NO3⁻) as compared to L2­4 (↑%CD5− B cells; ↑CD23+ B cells and ↑α-Leishmania IgG). Whilst ≤60 presented a mixed profile of innate/adaptive immunity (↓%CD28+ neutrophils and ↑%CD4+ T cells), >60 showed a well-known leishmanicidal events (↑CD8+ T cells; ↑serum NO2⁻ + NO3⁻ and ↑α-Leishmania IgG). MT+ patients showed increased putative leishmanicidal capacity (↑%HLA-DR+ neutrophils; ↑%CD23+ monocytes; ↑CD8+ HLA-DR+/CD4+ HLA-DR+ T cell ratio and ↑ serum NO2⁻ + NO3⁻). Overall, a range of immunological biomarkers illustrates the complex immunological network associated with distinct clinical/laboratorial features of LCL with applicability in clinical studies.

Helicobacter pylori infection: is sequential therapy superior to standard triple therapy? A single-centre Italian study in treatment-naive and non-treatment-naive patients.

BACKGROUND: Clarithromycin resistance has decreased the eradication rates of Helicobacter pylori. AIMS: To determine whether a 10-day course of sequential therapy (ST) is more effective at eradicating H pylori infection than triple therapy (TT) in the first or second line, and to assess side effects and compliance with therapy. METHODS: One hundred sixty treatment-naive and 40 non-treatment-naive patients who were positive for H pylori infection by ¹³C-urea breath test or endoscopy were enrolled. Eighty of 160 patients underwent TT, while 80 of 160 underwent ST with omeprazole (20 mg) plus amoxicillin (1 g) twice/day for five days, followed by omeprazole (20 mg) with tinidazole (500 mg) twice/day and clarithromycin (500 mg) twice/day for five consecutive days. H pylori eradication was evaluated by ¹³C-urea breath test no sooner than four weeks after the end of treatment. RESULTS: Eradication was achieved in 59 of 80 treatment-naive patients treated with TT (74%), in 74 of 80 patients treated with ST (93%), and in 38 of 40 non-treatment-naive patients (95%). Eradication rates in treatment-naive patients with ST were statistically significantly higher than TT (92.5% versus 73.7%; P=0.0015; OR 4.39 [95% CI 1.66 to 11.58]). Mild adverse effects were reported for both regimens. CONCLUSIONS: ST appears to be a well-tolerated, promising therapy; however, randomized controlled trials with larger and more diverse sample populations are needed before it can be recommended as a first-line treatment.

Putative intestinal hyperammonaemia in horses: 36 cases.

REASONS FOR PERFORMING THE STUDY: Intestinal hyperammonaemia (HA) has been infrequently reported in individual horses; however, there have been no studies describing clinical and laboratory data as well as short- and long-term outcome in a larger number of cases. OBJECTIVES: To describe clinical and laboratory data and short- and long-term outcome in a large group of horses with intestinal HA. METHODS: Multi-centred, retrospective study; case records of horses with HA were reviewed and any horse with a clinical or post mortem diagnosis of intestinal HA was included. Hyperammonaemia was defined as a blood ammonium (NH(4) (+)) concentration ≥60 µmol/l and horses with a diagnosis of primary hepatic disease were excluded. Relevant data were recorded and, if appropriate, data from survivors were compared to nonsurvivors to identify potential prognostic indicators. RESULTS: Thirty-six cases, 26 mature horses and 10 foals with intestinal HA were identified. Case histories included diarrhoea, colic and neurological signs and the most common clinical diagnosis was colitis and/or enteritis. The most common clinical and laboratory abnormalities included tachycardia, increased packed cell volume, hyperlactataemia and hyperglycaemia. Fourteen horses (39%) survived to discharge; NH(4) (+) concentration on admission was the only parameter significantly associated with survival. All surviving horses and foals for which follow-up information was available recovered completely and returned to their intended use without further complications. CONCLUSIONS AND POTENTIAL RELEVANCE: Intestinal HA occurs in mature horses and foals and can be associated with severe clinical and laboratory abnormalities; further studies are required to investigate predisposing factors and delineate possible differences in aetiologies.

Spontaneous right ventricular thrombus in a patient with active ulcerative colitis and protein C deficiency: a review with a case report.

BACKGROUND: Inflammatory bowel disease (IBD) is an idiopathic condition of gastrointestinal tract whose pathogenesis results from the complex interaction of genetic susceptibility and environmental influences. Is well known how IBD patients have an increased risk of thrombosis. OBJECTIVES: To assess the frequency and characteristics of thromboembolic events (TEE) in IBD and the role of certain etiopathological factors in such thrombotic patients. MATERIAL AND METHODS: We report the case of a young woman affected by protein C deficiency, who during a clinical recurrence of ulcerative colitis (UC), developed a spontaneous right ventricular thrombus and pulmonary embolism. Then, we made a review of literature that documented thromboembolic events in IBD patients. RESULTS: A search using the PubMed database identified 65 case reports documenting thromboembolic events in patients with known UC and 7 documenting thromboembolic events in known Crohn's disease. DISCUSSION: The data of the literature confirm that IBD patients have an approximately three fold greater risk for developing a TEE compared with the general population. The risk for thrombosis correlates well with disease activity in Crohn's disease, and to lesser extent in ulcerative colitis.

Placement of two overlapping uncovered metallic stents for malignant gastric outlet and duodenal obstruction due to colon cancer.

Malignant obstruction of the gastric outlet and duodenum is frequently due to extrinsic involvement by tumors from contiguous organs, in particular from pancreas and gallbladder. The treatment of malignant gastroduodenal stenoses is difficult. Many patients have advanced malignant disease and are too ill to undergo surgical approach. Surgical gastrojejunostomy has been considered the palliative treatment of choice. Metallic stents can be useful in this condition with adequate palliation obtained in most cases. We report a case in which self-expanding metallic stents were placed for stenoses of the gastric outlet and duodenum due to a colon cancer.

The effect of a ferric iron complex on isolated rat-liver mitochondria. III. Mechanistic aspects of iron-induced calcium efflux.

Addition of iron(III)-gluconate complex to isolated rat liver mitochondria induced a net efflux of Ca2+ which was not inhibited by ruthenium red. This process resulted in the enhancement of Ca2+ cycling and a consequent membrane potential drop. Under these experimental conditions the content of mitochondrial glutathione did not appear to be critically modified, whereas an extensive oxidation of mitochondrial pyridine nucleotides was parallelly detected. Iron failed to induce appreciable changes in the oxidation level of pyridine nucleotides in mitochondria isolated from rats fed a selenium deficient diet, a condition in which mitochondrial glutathione peroxidase resulted inhibited by 80%. The iron-induced Ca2+ release in Se-deficient mitochondria appeared largely delayed and the membrane potential of these mitochondrial did not present gross alterations. Iron was also found to induce a transient increase in the mitochondrial cyanide-insensitive oxygen consumption. This effect was largely prevented by the addition of the hydrogen peroxide scavenger catalase. It was concluded that iron induced the activation of a specific Ca2+ efflux pathway via the oxidation of pyridine nucleotides due to the hydrogen peroxide metabolism by glutathione enzyme system.

Phosphorylating efficiency of isolated rat liver mitochondria respiring under the conditions of steady-State 4.

A limited, but significant net formation of ATP was observed during the very first period of respiratory State 4. The synthesis appeared to depend on respiration, since it was completely inhibited by KCN or by 2,4-dinitrophenol. Accordingly, State 4 respiration was observed to be inhibited to a large extent by oligomycin. After the initial increase, the level of ATP remained unmodified under the conditions of steady-state 4. Also, the maintenance of the equilibrium level of ATP was very sensitive to KCN or 2,4-dinitrophenol. Under the very same conditions of State 4, the mitochondria exhibited a significant ATPase activity, which appeared to be competitively inhibited by ADP. Therefore, it might be concluded that the apparently constant level of ATP observed in State 4 results from a balanced equilibrium between a respiration-dependent synthesis and a continuous hydrolysis. A comparison between the amount of ATP hydrolysed in State 4 and the amount of oxygen consumed under the same conditions indicated that the phosphorylating efficiency of respiring mitochondria in State 4 is as high as in State 3.

An investigation on the effect of oligomycin on state-4 respiration in isolated rat-liver mitochondria.

The inhibitory action of oligomycin on State-4 respiration in rat-liver mitochondria has been investigated in detail with regard to the extent, mode and characteristics of the inhibition. The possibility that this effect may be due either to some damage of the mitochondrial preparation used or to the presence of heavy contaminations by microsomes has been excluded. It has been found that the concentration of specific binding sites is the same in State 4 as in State 3. The extent of the inhibition appears to be related to the ADP concentration, rather than to ATP/ADP ratios. The inhibition of this antibiotic on State-4 respiration does not depend on the experimental conditions used (i.e., choice of substrates or composition of the reaction medium). In agreement with these observations, it has been found that the membrane potential of State 4 is significantly increased when oligomycin is added. All these results provide further evidence to the conclusion that a large portion of State-4 respiration is linked to phosphorylation.

Biochemical mechanism of GSH depletion induced by 1,2-dibromoethane in isolated rat liver mitochondria. Evidence of a GSH conjugation process.

HPLC measurements of GSH and GSSG levels in isolated rat liver mitochondria, on addition of 1,2-dibromoethane (DBE), revealed the presence of a glutathione (GSH)-conjugating pathway of DBE. This process required the structural integrity of the mitochondrial matrix and inner membrane complex and was inhibited by the uncouplers of oxidative phosphorylation, particularly 2,4-dinitrophenol. On the other hand it was not affected by the energetic state of the mitochondria, since other mitochondrial inhibitors like KCN and oligomycin did not have any effect on it. This process also did not require the involvement of mitochondrial inner membrane transport systems, based on the measurement of the mitochondrial transmembrane potential. The involvement of mitochondrial GSH-S-transferases, located either in the matrix or in the intermembrane space, is discussed.

Transmembrane potential of liver mitochondria from hexachlorobenzene-and iron-treated rats.

The respiratory parameters and the membrane potential of liver mitochondria from rats treated with either hexachlorobenzene, iron or hexachlorobenzene plus iron, to induce experimental porphyria, have been studied. Partial uncoupling of oxidative phosphorylation has been observed in mitochondria from hexachlorobenzene- and hexachlorobenzene plus iron-treated rats. Direct evidence has been presented that this uncoupling is due to the action of pentachlorophenol endogenously formed by metabolism of hexachlorobenzene. No irreversible damage of mitochondria membrane has been revealed under both these conditions. Normal oxidative phosphorylation has been found in mitochondria from rats treated with iron alone. In contrast, they presented an anomalous membrane potential, fully restored by oligomycin. A possible involvement of lipid peroxidation process, induced by iron, in causing these abnormalities has been suggested.

Mitochondrial inner membrane permeability changes induced by octadecadienoic acid hydroperoxide. Role of mitochondrial GSH pool.

The effect of exogenous octadecadienoic acid hydroperoxide (HPODE) on the functional properties of inner membrane of isolated rat liver mitochondria, as evaluated by the measurement of the membrane potential (delta psi) has been studied. Very low concentrations of HPODE (1.5-4.5 nmol/mg prot.) do not modify the delta psi of control mitochondria appreciably while bringing about the drop of delta psi, in a concentration-dependent mode, in mitochondria with a GSH level diminished by approx. 60%. Mitochondrial GSH depletion was obtained by intraperitoneal administration of buthionine sulfoximine, a specific inhibitor of GSH synthesis, to rats. The presence in the incubation system of GSH-methyl ester which normalizes mitochondrial GSH, fully prevents any drop in levels of delta psi induced by HPODE. The same protective effect has been presented by EGTA, which chelates the available Ca2+. Neither an antioxidant nor a specific inhibitor of mitochondrial phospholipase A2 are able to prevent the HPODE effect. From the results obtained we can assume that HPODE itself, at the concentrations used here, induces permeability changes in the inner membrane, with the loss of coupled functions, when the GSH mitochondrial level is below a critical value.

Induction of calcium efflux from isolated rat-liver mitochondria by 1,2-dibromoethane.

Addition of 1,2-dibromoethane to rat-liver mitochondria induces a concentration-dependent depletion of mitochondrial glutathione. This event seems to be associated with the induction of Ca2+ release from mitochondria pre-loaded with a low pulse of Ca2+. The enhancement of the energy-dissipating process to reaccumulate the released Ca2+ ('Ca2+ cycling') results in a progressive drop of membrane potential. Addition of EGTA (ethyleneglycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid), when the membrane potential has reached the lowest level, restitutes it to a normal value. All these findings and the observation that Ca2+ release also occurs under non cycling conditions (e.g., in the presence of ruthenium red) suggest that 1,2-dibromoethane induces a Ca2+ efflux by activating a selective pathway which is sensitive to critical sulfhydryl groups.

The effect of ferric iron complex on isolated rat liver mitochondria. I. Respiratory and electrochemical responses.

Addition of iron(III)-gluconate complex to isolated rat liver mitochondria resulted in an increased iron content of mitochondria. Iron was accumulated through a relatively fast process (maximal uptake in less than 2 min incubation) by an energy-independent mechanism. The in vitro iron overload of mitochondria was associated with enhancement in the oxygen consumption, which was due to the induction of lipoperoxidative processes catalyzed by iron. It was found that a concentration of iron as low as 0.1 mM elicits a consistent production of malondialdehyde in mitochondria. Concomitant with the induction of lipoperoxidation a progressive fall in the mitochondrial membrane potential was observed. The occurrence of energy-consuming processes as a consequence of iron addition, and particularly the enhancement of endogenous Ca2+ cycling across the membrane, was suggested as the cause of the membrane potential drop.

The effect of ferric iron complex on isolated rat liver mitochondria. II. Ion movements.

It has been found that addition of iron(III)-gluconate complex to rat liver mitochondria disturbed the mitochondrial Ca2+ transport. Indirect evidence when the changes in the membrane potential during the transport of Ca2+ were followed, as well as direct evidence, when the fluxes of Ca2+ were monitored by a Ca2+-selective electrode, indicated that this iron complex induced an efflux of Ca2+ from liver mitochondria. The mechanisms by which iron induced Ca2+ release appeared to be linked to the induction of lipoperoxidation of mitochondrial membrane. The mitochondrial membrane, however, did not become irreversibly damaged under these conditions, as indicated by its complete repolarization. It was also shown that the induction by iron of lipoperoxidation brought about an efflux of K+ from mitochondria.

Dietary iron deficiency in the rat. I. Abnormalities in energy metabolism of the hepatic tissue.

Severe iron deficiency was induced in rats by rearing nursing dams and their offspring on a diet comprising all the requisite nutrients and trace metals except iron. The iron deficient 5-week-old rats exhibited a severe anemia and a drastic decrease in iron content of the hepatic tissue and of the mitochondrial fraction. Cytochromes c + c1 and b were moderately but significantly reduced. A large increase in liver concentration was observed in iron-deficient animals; whereas there was no modification in total lipid, cholesterol, phospholipid and fatty acid composition of the mitochondrial membrane. Mitochondria from iron-deficient rats presented a partial uncoupling of the oxidative phosphorylation process. This functional derangement was completely reversed by the presence of either bovine serum albumin or L-carnitine plus ATP. This behaviour suggested that endogenous long-chain fatty acids could be primarily involved in the onset of mitochondrial dysfunction. The hepatic energy state of the liver appeared dramatically decreased under the pathological condition of severe iron-deficiency anemia. The possibility of a direct link between the partial loss of coupled functions observed in isolated mitochondria and the heavy energy deficit detected in the liver is discussed.

Dietary iron deficiency in the rat. II. Recovery from energy metabolism derangement of the hepatic tissue by iron therapy.

Severe iron deficiency in rats was found to be associated with abnormal lipid accumulation in the liver and impairment of the oxidative metabolism in the hepatic tissue. Iron therapy, consisting in oral administration to iron-deficient 4-week-old rats of iron succinyl-albumin complex, at a daily dose of 10 mg/kg body weight, over a period of 7 days, almost completely corrected these functional anomalies. This treatment fully reverted severe anemia associated with iron deficiency. The level of iron in the hepatic tissue and in the mitochondrial fraction also increased largely. By contrast, no significant improvement in the lowered level of cytochromes occurred. Iron supplements significantly decreased the abnormal level of liver total lipids and serum triglycerides. Concomitantly, iron repletion fully reverted the partial loss of coupled function in isolated mitochondria and the energy state perturbation of the liver. A close relationship among abnormal lipid accumulation, impairment of mitochondrial oxidative phosphorylation and energy derangement in the hepatic cell in this experimental model of severe dietary iron deficiency anemia appears to be likely.

Perturbation in liver mitochondrial Ca2+ homeostasis in experimental iron overload: a possible factor in cell injury.

The functional state of isolated mitochondria and specifically the integrity of the inner membrane, were investigated in the liver of rats made siderotic by dietary supplementation with carbonyl iron. The concentration of iron in the hepatic tissue increased progressively up to nearly 40 days and reached a steady-state level. When the iron content reached a threshold value (higher than 90 nmol/mg protein) the occurrence of in vivo lipid peroxidation in the mitochondrial membrane was detected. This process did not result in gross alterations in the mitochondrial membrane, as indicated by electron microscopy, phosphorylative capability and membrane potential measurements. On the contrary, the induction of lipoperoxidative reaction appeared to be associated with the activation of Ca2+ release from mitochondria. This was shown to occur as a consequence of rather subtle modifications in the inner membrane structure via a specific efflux route, which appeared to be linked to the oxidation level of mitochondrial pyridine nucleotides. The induction of this Ca2+ release from iron-treated mitochondria resulted in enhancement of Ca2+ cycling, a process which dissipates energy to reaccumulate into mitochondria the released Ca2+. The perturbation in mitochondrial Ca2+ homeostasis reported here may be a factor in the onset of cell damage in this experimental model of hepatic iron overload.

Cyclical Cushing's syndrome in a patient with a bronchial neuroendocrine tumor (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors.

A 56-yr-old woman was referred with a diagnosis of Cushing's disease. Hypertension and severe hypokalemia were present and high urinary free cortisol/cortisone ratio was detected, raising a suspicion of an ectopic ACTH syndrome. Inferior petrosal sinus sampling, thoracic computed tomography, and octreotide scans were negative. Remission and relapse periods lasting 3-4 months were observed during the 3.5 yr of follow-up. Finally a thoracic computed tomography scan showed a basal paracardic nodule in the left lung. After surgery, a well-differentiated neuroendocrine tumor (typical bronchial carcinoid) was diagnosed, staining positively for ACTH. RT-PCR revealed expression of proopiomelanocortin, CRH receptor, and V3 vasopressin receptor. Somatostatin receptor type 1, 2, 3, and 5 mRNA was detected only in tumoral tissue. Interestingly, we observed the simultaneous presence of ghrelin and both GH secretagogue (GHS) receptors (1a and 1b) mRNA in tumoral tissue but not in the normal lung. This finding correlates with the in vivo ACTH hyperresponsiveness to hexarelin (a GHS). This is the first report of a cyclical ectopic ACTH-secreting tumor with an in vivo ACTH response to hexarelin coupled with the tumoral expression of ghrelin and GHS receptors. This finding might imply an autocrine/paracrine modulatory effect of ghrelin in bronchial ACTH-secreting tumors.