Teaching Control during the COVID-19 Pandemic.

This paper aims to analyze some different solutions that were adopted in control education activities during the pandemic. The authors of this paper are educators in the control education field from different countries on all the continents, who have developed a questionnaire with the idea of collecting data about the COVID-19 pandemic impact on the control education activities. The main objective is to study the diverse alternatives that were used worldwide to perform the online educational activities during that period, such as methodologies, tools, learning management systems (LMS), theoretical exercises, laboratory experiments, types of exams, simulators, software for online lecturing, etc. As a result, comparisons between pre-and during-pandemic educational resources and methods are performed, where useful ideas and discussions are given for the control education community.

The novel Mechanical Ventilator Milano for the COVID-19 pandemic.

This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world.

Application of SSOD-PI and PI-SSOD event-based controllers to greenhouse climatic control.

In this work, an application of the Symmetric Send-On-Delta (SSOD) event-based controllers to the inside air temperature control of the greenhouse production process is presented. The control technique analysis is split into two stages. The first stage is devoted to determine the proper controller parameters and to check the influence of the Send-On-Delta (SOD) threshold value through simulation study. At the second stage, experimental tests on the real greenhouse facilities are performed. The obtained results show that the analyzed control techniques handle the control task with desired accuracy and performance. In particular, the proposed control system saves costs related with energy consumption and wear minimization, by achieving a satisfactory performance at the same time.

Alpha-adducin gene polymorphism and cardiovascular phenotypes in a general population.

BACKGROUND: Previous studies have shown that molecular variants of the cytoskeletal protein adducin may be involved in regulation of blood pressure both in genetic rat hypertension and in human essential hypertension. OBJECTIVE: To investigate the relationship of genetic polymorphism of alpha-adducin with blood pressure, cardiovascular structure, and some biochemical indexes of cardiovascular risk in a sample of general population. DESIGN AND METHODS: A sample of 246 subjects (124 men and 122 women, aged 57.7+/-3.7 years) was randomly chosen from a middle-aged population. Twenty-four-hour ambulatory blood pressure, as well as left ventricular mass (by echocardiographic methods) and carotid wall thickness (by B-mode ultrasound methods) were measured. DNA was extracted from peripheral blood samples; the Gly460Trp diallelic variant of human alpha-adducin was genotyped by polymerase chain reaction amplification and then allele-specific oligo hybridization. RESULTS: A trend toward higher 24 h ambulatory blood pressure values in subjects not treated with antihypertensive drugs was observed among carriers of Trp460 allele, although the differences did not attain statistical significance (at closest, P = 0.066 for a dominant effect of Trp460 on systolic blood pressure). When blood pressure was considered a dichotomous variable, allowing the inclusion of treated hypertensives), a higher prevalence of Trp460 allele among hypertensives was observed (0.188 versus 0.106 among normotensives, P= 0.02). There was no evidence of association either of left ventricular mass or of common carotid wall thickness with Gly460Trp polymorphism. CONCLUSIONS: In this sample of a general population, the relationship of a genetic polymorphism of alpha-adducin with blood pressure values was rather weak. However, a population-based case-control analysis indicated that there was an association between Trp460 allele and hypertension, with a relative risk for subjects carrying at least one Trp460 allele of approximately 1.6. Further investigation of larger and different population samples in order to assess the role of adducin gene polymorphism as a marker of genetic predisposition to the development of hypertension is warranted.

[Conservative treatment using mesalazine in ischemic colitis]. / La terapia conservativa con mesalazina nella colite ischemica.

The authors propose the conservative treatment of ischemic colitis using slow-release mesalazine and enema. The excellent tolerability of the treatment and the good level of therapeutic efficacy was confirmed in 13 cases treated without signs of recurrence of disease.

[Prosthetic repair of inguinal and crural hernias]. / La riparazione con protesi delle ernie inguinali e crurali.

335 inguino-femoral hernias were repaired with polypropylene mesh from December 1991 through December 1995. Eleven patients underwent mesh reinforced Bassini, 167 modified Lichtenstein's technique and 108 Trabucco's repair. Forty-three patients were treated under regional anesthesia. Bilateral hernia was diagnosed in 33 patients and in 20 out of 33 the surgical procedure was entirely performed under regional anesthesia. Early complications referred were 32 scrotal hematomas which spontaneously healed. Two patients showed a recidive hernia and were retreated with and additional mesh; plug rejection (early experience) was referred in one patient who was reoperated on employing a mesh. The indications for the more suitable technique were directly deducted from Nyhus' hernia classification. The authors finally point out the: 1) importance of regional inguinal anesthesia; 2) correct cutting and application of the mesh in the inguinal canal; 3) internal inguinal ring repair; 4) bilateral hernia repair under regional anesthesia.

Angiotensin II type 1 receptor A/C1166 polymorphism. Relationships with blood pressure and cardiovascular structure.

The angiotensin II type 1 (AT1) receptor has a key role in mediating the vasoconstrictor and growth-promoting effects of angiotensin II. It has been reported that a polymorphism of the AT1 receptor gene (an A/C transversion at position 1166) may be associated with cardiovascular phenotypes, such as arterial blood pressure and aortic stiffness, that underlie a condition of increased cardiovascular risk. We examined a sample of 212 subjects randomly selected from a general population in northern Italy to investigate the role of AT1 receptor gene polymorphism, in the regulation of blood pressure and cardiovascular growth. We measured blood pressure (both clinic and 24-hour ambulatory recording), left ventricular mass (echocardiography), and carotid artery wall thickness (B-mode ultrasound); we assessed the AT1 receptor genotype by polymerase chain reaction and allele-specific oligonucleotide hybridization. Blood pressure values were lower in CC homozygotes than in heterozygotes and AA homozygotes; the difference was statistically significant for clinic measurements (mean difference for mean blood pressure, -6.6 mm Hg, P = .01; 95% confidence interval, -1.6 to -11.7 mm Hg) but not for ambulatory blood pressure measurements. CC homozygotes also presented a lower incidence of a positive family history of hypertension (P = .027). No statistically significant differences among AT1 receptor A/C1166 genotypes were observed for left ventricular mass or carotid artery wall thickness. We conclude that the present study does not support a major role of the AT1 receptor gene A/C1166 polymorphism as a marker of conditions associated with increased cardiovascular risk.

[Coronary risk stratification and aspects of decision making after infarction]. / Stratificazione del rischio coronarico ed aspetti decisionali del postinfarto.

The prognosis of myocardial infarction has considerably and favourably changed over the last decades thanks to new procedures in the hospital and post-discharge management. The identification of high-risk patients exposed to recurrent coronary events allows more appropriate treatment of these subjects and significantly contributes to the observed improvement in the general prognosis. In this short review, we examine different procedures for prognostic assessment in myocardial infarction and discuss a strategy for a favourable cost/benefit ratio in their utilization.

Relationship between sympathetic nervous system activity, baroreflex and cardiovascular effects after acute nitric oxide synthesis inhibition in humans.

OBJECTIVE: To examine the cardiovascular effects of acute systemic nitric oxide synthesis inhibition in humans in relation to the possible involvement of changes in sympathetic nervous system activity or in the baroreceptor reflex. DESIGN: Placebo or NG-monomethyl-L-arginine (250 mg by intravenous infusion for 5 min) was administered to seven healthy male volunteers according to a random, double-blind sequence. METHODS: Blood pressure and heart rate were measured non-invasively using a Finapres device from 20 min before to 80 min after starting infusion; beat-to-beat variability of blood pressure, pulse interval and systolic blood pressure and pulse interval covariation were assessed by means of spectral and sequence analysis methods. Under basal conditions and 15 min and 60 min after infusion, we measured stroke volume and indices of cardiac systolic and diastolic function by echocardiography, forearm blood flow by strain-gauge venous occlusion plethysmography, and plasma catecholamine levels. RESULTS: Compared with placebo, administration of NG-monomethyl-L-arginine caused a transient increase in blood pressure and reduction in heart rate. Stroke volume and indices of cardiac function did not change significantly, whereas cardiac index and forearm blood flow were significantly reduced after 15 min. Spectral analysis of blood pressure and pulse interval showed a significant reduction of power spectral density in the low frequencies (0.03-0.15 Hz) that persisted 60 min after infusion. The plasma noradrenaline level was significantly reduced after 15 min. No change in baroreflex engagement or sensitivity was detected by the cross-spectral or the sequence method. CONCLUSIONS: Acute systemic nitric oxide synthesis inhibition transiently increases blood pressure and reduces heart rate and cardiac index. The acute hypertensive response to NG-monomethyl-L-arginine is dependent neither on sympathetic nervous system activity, which is probably reduced as a consequence of baroreceptor reflex activation, nor on baroreceptor reflex sensitivity, which is not impaired.

Chronic ACE-inhibitor treatment and adrenergic mechanisms in spontaneously hypertensive rats.

We investigated the effects of chronic treatment with the angiotensin-converting enzyme (ACE) inhibitor fosinopril on cardiac and vascular noradrenergic neurotransmission as related to cardiovascular hypertrophy in spontaneously hypertensive rats (SHRs). SHRs were treated with fosinopril at "high dose" (SHR-HD, 25 mg/kg/day) or "low dose" (SHR-LD, 1 mg/kg/day) from the 6th to the 12th week of age, and compared to age-matched untreated SHRs (SHR-C) and Wistar-Kyoto controls (WKY). Blood pressure was significantly reduced in SHR-HD but not in SHR-LD when compared to SHR-C. The antihypertensive dose of fosinopril reduced both cardiac and vascular hypertrophy, whereas the low dose was effective only in reducing vascular hypertrophy. Several differences in presynaptic and postsynaptic cardiovascular noradrenergic neurotransmission were observed between SHR-C and WKY rats (increased cardiac norepinephrine concentration, down-regulation of cardiac beta-adrenoceptors, reduced alpha-adrenergic receptor-mediated vasoconstrictor response of small mesenteric arteries to exogenous norepinephrine). All these differences were abolished by ACE inhibitor treatment, both at antihypertensive or at subantihypertensive doses. The results of this study are consistent with the hypothesis that chronic ACE inhibition may exert an inhibitory modulation on the peripheral adrenergic transmission, which is not related to blood pressure reduction. This modulation does not appear to be a determinant in preventing the development of cardiac hypertrophy but may play a role in the regression of vascular structural alterations in spontaneously hypertensive rats.

Angiotensin-converting enzyme I/D polymorphism and arterial wall thickness in a general population. The Vobarno Study.

BACKGROUND: It has been reported that the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is associated with conditions of increased cardiovascular risk, including left ventricular hypertrophy. METHODS AND RESULTS: Considering that a genetically determined overactivity of the renin-angiotensin system may influence cardiac as well as vascular growth, we investigated possible relations between ACE I/D genotype and carotid artery wall thickness (B-mode ultrasound) in 199 subjects, 50 to 64 years old, sampled from the general population of Vobarno, a small town in northern Italy. ACE DD genotype was associated with significantly higher common carotid artery intima-media thickness (P = .003). The occurrence of carotid atherosclerotic plaques was similar in the different genotypes. There was no association of the ACE I/D genotype with blood pressure values (either casual of 24-hour ambulatory monitored). CONCLUSIONS: ACE DD genotype may be considered a risk factor for the development of common carotid intima-media thickening in our study population.

Effects of transdermal nitroglycerin in combination with an ACE inhibitor in patients with chronic stable angina pectoris.

We have previously shown that transdermal nitroglycerin may induce an increase in the activity of the adrenergic and the renin-angiotensin-aldosterone systems (SRAA) in patients with chronic stable angina pectoris (SA); when the activation of these systems is more pronounced, the antianginal effect of this drug seems to be reduced. The aim of this study was to evaluate the antianginal efficacy of transdermal nitroglycerin administration (TTS-NG 10 mg.24 h-1) in combination with an ACE inhibitor without sulphydryl groups (BNZ, benazepril 10 mg b.i.d.) in respect to placebo, or to TTS-NG or BNZ administered as monotherapy. Twenty-four patients (21M, 3F) were admitted to this multicentre, randomized, double-blind, latin square, placebo-controlled study. Patients received all the treatments (placebo, TTS-NG, BNZ and BNZ + TTS-NG) each for one week; at the end of each week patients performed two exercise tests 2 and 22 h post-dosing. Two hours post-dosing, exercise duration at 1 mm ST depression was significantly increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05) treatments. Two hours post-dosing, exercise duration at peak exercise was also increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05); 22 h post-dosing the increase in exercise duration was significant only during TTS-NG + BNZ treatment (P < 0.05) in respect to placebo, but not during TTS-NG given alone. Rate-pressure product at 1 mm ST depression was significantly increased 2 h post-dosing during TTS-NG treatment (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Gene expression of cardiac beta 1-adrenergic receptors during the development of hypertension in spontaneously hypertensive rats.

OBJECTIVE: To study adrenergic receptors in the heart tissues of genetically hypertensive rats by evaluating the gene expression and the membrane protein density of beta 1-adrenergic receptors using steady-state messenger RNA (mRNA) levels and a radioligand binding assay, respectively. DESIGN: We compared prehypertensive (5-week-old) and early-hypertensive (13-week-old) spontaneously hypertensive rats (SHR) with age-matched Wistar-Kyoto (WKY) normotensive control rats. METHODS: Polyadenylated RNA was extracted from individual hearts and analysed by the slot-blot technique using a beta 1-adrenergic receptor complementary DNA probe. beta-Adrenergic receptors in myocardial membranes were studied by radioligand binding assay using [125I]-cyanopindolol and the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively. RESULTS: beta 1-Adrenergic receptor mRNA levels were slightly higher, and membrane protein density was similar in prehypertensive SHR and age-matched WKY rats. However, both beta 1-adrenergic receptor mRNA levels and beta 1-adrenergic receptor density were lower in the hypertensive SHR than in the control rats. beta 1-Adrenergic receptor mRNA was significantly reduced in older rats of both strains, and this reduction was most evident in the SHR. CONCLUSIONS: The absence of downregulation of beta 1-adrenergic receptors in young SHR, despite published data indicating a higher cardiac noradrenaline turnover than in WKY rats, may suggest that the cardiac hyperadrenergic activity observed in prehypertensive SHR is maintained, at least in part, by the participation of peripheral, postsynaptic component(s) involving beta 1-adrenergic receptor dysregulation. In addition, the present data suggest that the previously reported evidence of an age-related decrease in cardiac beta 1-adrenergic receptors in rats may be determined at the transcriptional level.

Reduction of left ventricular hypertrophy after longterm antihypertensive treatment with doxazosin.

The aim of this study was to evaluate the effect of antihypertensive treatment with doxazosin on left ventricular anatomy and function. Therefore, after 4 weeks of washout with placebo (phase 1), doxazosin (dosage range from 1 to 16 mg, plus hydrochlorothiazide when necessary) was given to 11 essential hypertensive patients (6 M, 5 F, age range 34-63 years) for 8 weeks (phase 2) in order to achieve diastolic blood pressure values less than 90 mmHg; this dosage was then maintained for a further 20 weeks up to the end of the study (phase 3). Blood pressure was significantly reduced (Anova P less than 0.05), while heart rate did not change. A significant reduction of left ventricular mass index (from 128.5 +/- 26 to 114 +/- 23 g/m2, at the end of phase 1 and 3 respectively, P less than .001)) was observed. Before and during treatment left ventricular systolic function, both at rest and during stress (handgrip and cold pressor tests), evaluated by fractional shortening as related to end-systolic stress, in every case within 95% confidence limits, was calculated in normal subjects. Diastolic function, as evaluated by the ratio between peak early and atrial velocities of transmitral flow examined by pulsed doppler was significantly improved. Plasma catecholamine concentrations, plasma renin activity and plasma aldosterone did not change. A significant reduction of plasma cholesterol concentration was observed. These results confirm that doxazosin is a well tolerated and effective antihypertensive drug, with a favourable effect on blood lipids and they indicate that its longterm administration can induce a significant reduction of left ventricular mass.

Antidiuretic hormone and atrial natriuretic peptide during lower body negative or positive pressure in hypertensive patients with and without left ventricular hypertrophy.

Aim of the study was to evaluate the effect of cardiopulmonary receptors activation and deactivation on antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) incretion in hypertensive and normotensive subjects. Twenty-one male subjects, 7 normotensives and 14 mild hypertensives, 7 without and 7 with left ventricular hypertrophy (LVH) were admitted to the study. Each subject underwent selective loading and unloading of cardiopulmonary receptors, by application of a positive (LBPP) or negative (LBNP) pressure to the lower body. Blood samples were taken for measurement of ANP, ADH, PRA, immunoreactive renin, aldosterone, noradrenaline and adrenaline. ADH plasma concentration increased during cardiopulmonary receptors inhibition, but this increase became statistically significant (p less than 0.05) at a step of LBNP (-40 mm Hg), in which an involvement of the sinoaortic receptors cannot be excluded. ANP plasma levels increased progressively during LBPP (p less than 0.05 at least). These changes were significantly reduced in hypertensive patients with LVH.

Transdermal nitroglycerin efficacy in patients with chronic stable angina pectoris as related to sympathetic and renin-angiotensin-aldosterone activity.

The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympathetic and renin-angiotensin-aldosterone systems activity, in a group of patients with stable exercise induced angina pectoris. Eighteen outpatients (15M, 3F, age range 47-65 years) were included in this double-blind, randomized, crossover trial comparing the antianginal effects of a transdermal system delivering 20 mg.day-1 of nitroglycerin to an identical placebo. Plasma renin activity, plasma aldosterone and catecholamine concentrations were measured in resting basal conditions and at 4, 8, 24, and 32 h post-dosing. Patients were subdivided in two groups according to the increase in exercise duration after patch application greater than 30% (responders, n = 8) and less or equal to 30% (non-responders, n = 10) in respect to placebo. In responders plasma norepinephrine was slightly increased during transdermal nitroglycerin administration in comparison to placebo while no change was observed in plasma adrenaline and aldosterone concentrations and in plasma renin activity. In non-responders plasma norepinephrine levels significantly increased during nitroglycerin treatment in comparison with placebo. Multiple comparisons showed that this increase was significant at 4, 8 and 24 h post-dosing. Plasma epinephrine and aldosterone concentrations and plasma renin activity were also increased after nitroglycerin administration. In the population as a whole, a significant inverse correlation was found between the percent increase in exercise duration (active drug vs placebo) and the absolute values of plasma norepinephrine and aldosterone, 4 h post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

[Regulation of platelet alpha2 adrenergic receptors in a population of patients with essential arterial hypertension and in normotensive subjects]. / Regolazione dei recettori alfa2 adrenergici piastrinici in una popolazione di pazienti con ipertensione arteriosa essenziale ed in una di soggetti sani.

The development of specific binding techniques for the study of adrenergic receptors on circulating human blood cells has allowed a better understanding of the physiological alterations of adrenergic receptors and changes of adrenergic receptors in pathological conditions such as hypertension. Alpha adrenoceptors play an important part in blood pressure regulation at several sites. There are contradictory and conflicting reports on whether alpha receptor mechanisms are altered in essential hypertension. To address further the role of alpha 2 adrenoceptors in human essential hypertension the number and the affinity of alpha 2 adrenergic receptors and plasma catecholamine levels were measured in 20 normotensive and 24 hypertensive subjects. The median number of receptors (Bmax) was 159.10 +/- 14.38 fmol/mg protein for controls versus 179.09 +/- 13.26 fmol/mg protein for hypertensives. The median dissociation constant (KD) of the receptors for 3H-Yohimbine was 1.43 +/- 0.17 nmol/l for controls and 1.85 +/- 0.19 nmol/l for hypertensives patients. There were no differences in catecholamine plasma levels between the two groups. In controls platelet alpha 2 receptor number correlated with age (p less than 0.003) but not with blood pressure values. Our results show that measurement of platelet alpha 2 receptor levels and affinity is unable to differentiate a group of hypertensives from normotensives. Nevertheless, we cannot exclude a possible role of peripheral alpha 2 adrenergic receptors in the pathogenesis of high blood pressure.