Correctness and Completeness of Programming Instructions for Traffic Circulation.

In the present article we exploit the logical notions of correctness and completeness to provide an analysis of some fundamental problems that can be encountered by a software developer when transforming norms for traffic circulation into programming instructions. Relying on this analysis, we then introduce a question and answer procedure that can be helpful, in case of an accident, to clarify which components of an existing framework should be revised and to what extent software developers can be held responsible.

Polypharmacy Management in a Gender Perspective: At the Heart of the Problem: Analysis of Major Cardiac Diseases, SARS-CoV-2 Affection and Gender Distribution in a Cohort of Patients in Internal Medicine Ward.

BACKGROUND: COVID-19 patients with any pre-existing major cardio-vascular disease (CVD) are at the highest risk of viral infection and of developing severe disease. The pathophysiological mechanism is characterized by the viral link to angiotensin-converting enzyme 2 (ACE2) and the involvement of the endothelial system with the release of cytokines and the inflicting of direct damage to the myocardium, the induction of microthrombosis, and the initiation of alterations in oxygen diffusion. The aim of the study is to analyze the clinical course and outcomes in patients (gender-stratified) with pre-existing major CVD. METHODS: Out of the 1833 (973 M/860 F) patients admitted to the Internal Medicine COVID-19 Unit of "Castelli Hospital", Lazio, Italy, from 1 January 2021 to 31 December 2021, 600 patients (320 M/280 F) with a mean age of 77 (78.6 M/75.1 F) previously had CVD. Demographic characteristics, length of the stay (LOS) and oxygen therapy were evaluated. RESULTS: All of the CVD COVID-19 patients underwent non-invasive ventilation (NIV). CVD was linked with increased LOS (21 days F/22 M) compared to no CVD (19 days). In total, 32.7% of total patients had major CVD. CONCLUSIONS: Timely identification and evaluation of patients with pre-existing major CVD are fundamental for adequate treatment based on gender, severity, state of illness and for risk reduction.

Burden of COVID-19 on Italian Internal Medicine Wards: Delphi, SWOT, and Performance Analysis after Two Pandemic Waves in the Local Health Authority "Roma 6" Hospital Structures.

Background: COVID-19 causes major changes in day-to-day hospital activity due to its epidemiological characteristics and the clinical challenges it poses, especially in internal medicine wards. Therefore, it is necessary to understand and manage all of the implicated factors in order to maintain a high standard of care, even in sub-par circumstances. Methods: This was a three-phase, mixed-design study. Initially, the Delphi method allowed us to analyze the causes of poor outcomes in a cohort of an aggregate of Italian COVID-19 wards via an Ishikawa diagram. Then, for each retrieved item, a score was assigned according to a pros/cons, opportunities/threats system. Scores were also assigned according to potential value/perceived risk. Finally, the performances of MCs (Medicine-COVID-19 wards) and MCFs (Medicine-COVID-19-free: Internal Medicine wards) units were represented via a Barber's nomogram. Results: MCFs hospitalized 790 patients (-23.90% compared to 2019 Internal Medicine admissions). The main risk factors for mortality were patients admitted from local facilities (+7%) and the presence of comorbidities (>3: 100%, ≥5: 24.7%). A total of 197 (25%) patients were treated with non-invasive ventilation (NIV). The most deaths (57.14%) occurred in patients admitted from local facilities. Conclusions: Medicine-COVID-19 wards show higher complexity and demand compared to non-COVID-19 ones and they are comparable to sub-intensive therapy wards. It is necessary to promote the use of NIV in such settings.

Green Line Hospital-Territory Study: A Single-Blind Randomized Clinical Trial for Evaluation of Technological Challenges of Continuous Wireless Monitoring in Internal Medicine, Preliminary Results.

BACKGROUND: Wireless vital parameter continuous monitoring (WVPCM) after discharge is compared to regular monitoring to provide data on the clinical-economic impact of complex patients (CPs) discharged from Internal Medicine Units of Ospedale dei Castelli, Lazio. PRIMARY OUTCOME: Major complications (MC) reduction. SECONDARY OUTCOMES: Patients who reached discharge criteria within the 7th day from admission; difference in MC incidence at the conclusion of the standard telemonitoring/clinical monitoring phase, 5 and 30 days after discharge; and conditions predisposing to MC occurrence. METHODS: Open label randomized controlled trial with wearable wireless system that creates alerts on portable devices. Continuous glycemic monitoring is performed for patients with diabetes mellitus. RESULTS: There were 110 patients enrolled (mean age: 76.2 years). Comorbidity: Cumulative Illness Rating Scale CIRS-CI (comorbidities index): 3.93, CIRS SI (severity index): 1.93. About 19% scored a BRASS (Blaylock Risk Assessment Screening Score) ≥20 indicating need for discharge planning requiring step-down care. Globally, 48% of patients in the control group had major complications (27 out of 56 patients), in contrast to 22% in the intervention group (12 out of 54 patients). CONCLUSIONS: Since WVPCM detects early complications during the post-discharge CPs monitoring, it increases safety and reduces inappropriate access to the Emergency Room, preventing avoidable re-hospitalizations.

Machine Learning-based Voice Assessment for the Detection of Positive and Recovered COVID-19 Patients.

Many virological tests have been implemented during the Coronavirus Disease 2019 (COVID-19) pandemic for diagnostic purposes, but they appear unsuitable for screening purposes. Furthermore, current screening strategies are not accurate enough to effectively curb the spread of the disease. Therefore, the present study was conducted within a controlled clinical environment to determine eventual detectable variations in the voice of COVID-19 patients, recovered and healthy subjects, and also to determine whether machine learning-based voice assessment (MLVA) can accurately discriminate between them, thus potentially serving as a more effective mass-screening tool. Three different subpopulations were consecutively recruited: positive COVID-19 patients, recovered COVID-19 patients and healthy individuals as controls. Positive patients were recruited within 10 days from nasal swab positivity. Recovery from COVID-19 was established clinically, virologically and radiologically. Healthy individuals reported no COVID-19 symptoms and yielded negative results at serological testing. All study participants provided three trials for multiple vocal tasks (sustained vowel phonation, speech, cough). All recordings were initially divided into three different binary classifications with a feature selection, ranking and cross-validated RBF-SVM pipeline. This brough a mean accuracy of 90.24%, a mean sensitivity of 91.15%, a mean specificity of 89.13% and a mean AUC of 0.94 across all tasks and all comparisons, and outlined the sustained vowel as the most effective vocal task for COVID discrimination. Moreover, a three-way classification was carried out on an external test set comprised of 30 subjects, 10 per class, with a mean accuracy of 80% and an accuracy of 100% for the detection of positive subjects. Within this assessment, recovered individuals proved to be the most difficult class to identify, and all the misclassified subjects were declared positive; this might be related to mid and short-term vocal traces of COVID-19, even after the clinical resolution of the infection. In conclusion, MLVA may accurately discriminate between positive COVID-19 patients, recovered COVID-19 patients and healthy individuals. Further studies should test MLVA among larger populations and asymptomatic positive COVID-19 patients to validate this novel screening technology and test its potential application as a potentially more effective surveillance strategy for COVID-19.

Transcranial direct current stimulation enhances soothing positive affect and vagal tone.

Transcranial Direct Current Stimulation (tDCS) is a promising tool for the treatment of depression and the dorsolateral prefrontal cortex (dlPFC) is often targeted when exploring tDCS effects on mood. However, the basic effects of tDCS on momentary emotions are inconsistent. We tested whether a single-session of anodal tDCS over the left temporal lobe (T3), topographically closer to the insular cortex than dlPFC, had effects on both vagally-mediated heart rate variability (HRV) and momentary affect in healthy participants. Thirty-four subjects underwent both sham and active tDCS in a counterbalanced random order. ECG was continuously recorded to derive both time and frequency domain HRV indexes. Before and after the tDCS protocol, participants completed momentary affect assessments. Results showed that HRV and soothing positive affectivity were both enhanced after a single-session of tDCS over T3, while negative and activating positive affect were not modulated by the stimulation. After controlling for sex, age, and levels of anxiety and depression a significant association emerged between increases in soothing positive affect and concomitant increases in vagally-mediated HRV. Deficits in soothing positive emotions have consistently been associated with psychopathology and psychotherapeutic approaches aimed to develop this type of emotionality have shown to improve psychological well-being. Thus, present exploratory results may impact future research investigating potential moderators (site of stimulation) and mediators (specificity for a determined type of momentary affect) of the effects of tDCS on psychopathological conditions such as depression.

P wave analysis and left ventricular systolic function in chronic heart failure. Possible insights form the P wave - PP interval spectral coherence.

BACKGROUND: Chronic increase in left ventricular filling pressure represents one of the most important mechanism underlying the structural, as well as the electrical, atrial chamber remodeling leading to atrial fibrillation. The present pilot pathophysiological study sought to investigate possible relationship between short-period cross-spectral coherence of P-Q, R-R and P-P intervals and echocardiographic indices of left ventricular and atrial function. METHODS: Electrocardiographic single lead short-term cross-spectral analysis on P-Q and P-P intervals was performed in 31 patients with chronic heart failure (CHF). Twenty age and therapy matched hypertensive patients acted as control group. The interval between the beginning of P wave and its peak (Ppeak) was also analyzed. RESULTS: Patients with CHF showed a significant lower PQ → PP and Ppeak → PP coherence (P<0.001) than the counterpart. At multivariate analysis only Ppeak → PP was independently associated to LVEF (r2:0.312; b:60; ß:0.559; P<0.0001) and atrial volume (r2:-0.160; b:-0.15; ß:-0.400, P<0.05). CONCLUSIONS: Ppeak → PP coherence might be a simple marker of left ventricular and atrial function. Whether this index could be a useful noninvasive marker of increased left ventricular filling pressure and, possibly, of atrial fibrillation risk or not, it needs to be tested in larger prospective studies.

Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years.

BACKGROUND: Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses. OBJECTIVE: The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS) over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. SUBJECTS AND METHODS: In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years) matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI), and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. RESULTS: In the older group, the QTVI, low-frequency (LF) power expressed in normalized units, the ratio between LF and high-frequency (HF) power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P<0.05). CONCLUSION: In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity.

Myocardial repolarization dispersion and autonomic nerve activity in a canine experimental acute myocardial infarction model.

BACKGROUND: Evidence from a canine experimental acute myocardial infarction (MI) model shows that until the seventh week after MI, the relationship between stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA) progressively increases. OBJECTIVE: The purpose of this study was to evaluate how autonomic nervous system activity influences temporal myocardial repolarization dispersion at this period. METHODS: We analyzed autonomic nerve activity as well as QT and RR variability from recordings previously obtained in nine dogs. From a total of 48 short-term ECG segments, 24 recorded before and 24 recorded 7 weeks after experimentally-induced MI, we obtained three indices of temporal myocardial repolarization dispersion: QTe (from Q-wave to T-wave end), QTp (from Q-wave to T-wave peak), and Te (from T-wave peak to T-wave end) variability index (QTeVI, QTpVI, TeVI). We also performed heart rate variability power spectral analysis on the same segments. RESULTS: After MI, all the QT variables increased QTeVI (median [interquartile range]) (from -1.76[0.82] to -1.32[0.68]), QTeVI (from -1.90[1.01] to -1.45[0.78]), and TeVI (from -0.72[0.67] to -0.22[1.00]), whereas all RR spectral indices decreased (P <.001 for all). Distinct circadian rhythms in QTeVI (P <.05,) QTpVI (P <.001) and TeVI (P <.05) appeared after MI with circadian variations resembling that of SGNA/VNA. The morning QTpVI and TeVI acrophases approached the SGNA/VNA acrophase. Conversely, the evening QTeVI acrophase coincided with another SGNA/VNA peak. After MI, regression analysis detected a positive relationship between SGNA/VNA and TeVI (R(2): 0.077; ß: 0.278; p< 0.001). CONCLUSION: Temporal myocardial repolarization dispersion shows a circadian variation after MI reaching its peak at a time when sympathetic is highest and vagal activity lowest.

Correlation between glycemic trends assessed by 24 h continuous monitoring and autonomic activity in patients with recent onset type 2 diabetes.

We observe, in patients with type 2 diabetes of recent onset, the activity of the autonomic nervous system and glucose metabolic impairment. The data indicate the hyperactivity of the sympathetic and minimal changes in glucose values. The role played by glycemia appeared to be less important than that represented by insulin resistance.

Influence of aging and chronic heart failure on temporal dispersion of myocardial repolarization.

BACKGROUND AND PURPOSE: QT and T(peak)-T(end) (Te) intervals are associated with sudden cardiac death in patients with chronic heart failure (CHF). We studied age-dependent influence on short-term temporal dispersion of these two variables in patients with postischemic CHF. METHOD: We grouped 75 CHF and 53 healthy control subjects into three age subsets: ≤ 50 years, >50 years and ≤ 65 years, and >65 years. We then calculated the following indices: QT and Te variability index (QTVI and TeVI), the ratio between the short-term variability (STV) of QT or Te, and the STV of resting rate (RR) (QT/RR STV and Te/RR STV). RESULTS: In all different age subgroups, patients with CHF showed a higher level of QTVI than age-matched control subjects (≤ 50 years: P < 0.0001; >50 years and ≤ 65 years: P < 0.05; >65 years: P < 0.05). Patients with CHF < 50 years old also had all repolarization variability indices higher than normal age-matched controls (TeVI, P < 0.05; QT/RR STV, P < 0.05; Te/RR STV, P < 0.05), whereas we did not find any difference between the two older classes of subjects. Both QTVI (r²: 0.178, P < 0.05) and TeVI (r²: 0.433, P < 0.001) were positively related to age in normal subjects, even if the first correlation was weaker than the second one. CONCLUSION: Our data showed that QTVI could be used in all ages to evaluate repolarization temporal liability, whereas the other indices are deeply influenced by age. Probably, the age-dependent increase in QTVI was more influenced by a reduction of RR variability reported in older normal subjects.

LIPOCALIN-2 is a major acute-phase protein in a rat and mouse model of sterile abscess.

Lipocalin-2 (LCN-2) is a 25-kDa secretory protein currently used as a biomarker for renal injury and inflammation. Its source and cause of the increased serum levels are unclear. The current study compares LCN-2 gene expression with known major acute-phase proteins in the liver in a rat and mouse model of turpentine oil-induced sterile abscess. Serum LCN-2 concentrations increased dramatically up to 200-fold (20 µg/mL) at 48 h after turpentine oil injection. A strong elevation of LCN-2 mRNA in rat liver was observed starting from 4 h up to 48 h after injection, with a maximum (8,738 ± 2,104-fold) at 24 h, which was further confirmed by Western blot analysis. In contrast, the increases in gene expression of α2-macroglobulin, the major acute-phase protein, and hemoxygenase 1, a positive acute-phase protein, were only 1,025 ± 505-fold and 47 ± 12-fold, respectively, during acute-phase reaction (APR). No considerable change was observed in LCN-2 mRNA in rat kidney and other organs as compared with liver. Using wild-type mice, a massive increase in gene expression of LCN-2, with a maximum of 2,498 ± 84-fold in liver, which is similar to that for serum amyloid A (2,825 ± 233-fold), a major mouse acute-phase protein. However, such an increase was significantly inhibited in interleukin 6 knockout mice during APR. Interleukin 6-treated rat hepatocytes induced a significant time-dependent upregulation of LCN-2.Lipocalin-2 is the major acute-phase protein in rat as compared with α2-macroglobulin and hemoxygenase 1 and comparable with serum amyloid A in mouse whose gene expression is mainly controlled by interleukin 6. The liver is the main source of serum LCN-2 in the case of APR. ABBREVIATIONS-LCN-2-lipocalin-2-α2M-α2-macroglobulin-HO-1-hemoxygenase 1-IL-6-interleukin 6-SAA-serum amyloid A-TO-turpentine oil-APR-acute-phase reaction.