Deontic Variation in the ‘Advice’ for the Cure of the Plague by the Royal College of Physicians of London (1665 vs 1636 editions)

The ‘Advice’ drawn up by the College of Physicians for the prevention and cure of the plague was first published in 1578. It was attached to the Orders, a list of directions drawn up by the Privy Council to prevent or limit the spread of the disease. Like the Orders to which it was appended, the ‘Advice’ went through several reprints until 1630, when it had to be rewritten. The 1630 edition of the ‘Advice’ no longer confined itself to medical prescriptions, but included advice about medical provision in the city, the movement of goods and people, and referred to the political measures taken in foreign cities. In this revised, extended version, the ‘Advice’ was reprinted in 1636 and in 1665, when it finally appeared without the preceding Orders. This paper focuses on the pragma-linguistic changes displayed by the 1665 edition as compared with the 1636 edition of the ‘Advice’ in terms of mood and modality (Palmer 1986) and argues that the more mitigated expression of deontic modality and the preference for assertive acts over directive ones (Searle 1985) characterizing the later edition reflect the new editorial and historical context in which the text was produced

Power, (Im)Politeness and Aggressiveness in Early Modern Master-Servant Relations (1660-1750)

The article explores the ways in which in early modern England masters exercised power over servants by means of threats and reproaches. More precisely, it investigates power-(im)politeness and the power-aggressiveness interfaces using data collected manually from a non-electronic corpus of advice manuals for masters (and mistresses), servants and apprentices published in English between 1660 and 1750. As we approach the mid-eighteenth century there is a growing concern for servants’ feelings and insistence on masters’ empathy towards servants. This was probably due to the new form of politeness emerging in the period, one which emphasised complaisance and social harmony. From a strictly linguistic viewpoint, I argue that in these texts (but this may apply to others too) threats are not presented as inherently impolite acts but as aggressive ones, and that impoliteness is only a contextual property aggravating intimidation and affirmation of power. Whatever the master’s degree of power and social status, therefore, they cannot be considered forms of ‘politic unmarked behaviour’. Reproaches share with threats a potentially intimidating perlocutionary effect, but unlike threats, they are not inherently aggressive, and can be a form of politic or contextually appropriate behaviour on the part of a master.

Inflammatory Cytokines Associated With Failure of Lower-Extremity Endovascular Revascularization (LER): A Prospective Study of a Population With Diabetes

OBJECTIVE Peripheral artery disease (PAD) is one of the most relevant complications of diabetes. Although several pharmacological and revascularization approaches are available for treating patients with diabetes and PAD, an endovascular approach is often associated with postprocedural complications that can increase the risk for acute limb ischemia or amputation. However, no definitive molecular associations have been described that could explain the difference in outcomes after endovascular treatment in patients with diabetes, PAD, and chronic limb-threatening ischemia (CLTI). RESEARCH DESIGN AND METHODS We evaluated the relationship between the levels of the main cytokines associated with diabetic atherosclerosis and the outcomes after endovascular procedures in patients with diabetes, PAD, and CLTI. RESULTS A total of 299 patients with below-the-knee occlusive disease who were undergoing an angioplasty procedure were enrolled. The levels of key cytokines—osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP)—were measured, and major adverse limb events (MALE) and major adverse cardiovascular events (MACE) were assessed 1, 3, 6, and 12 months after the procedure. There was a linear trend from the lowest to the highest quartile for each cytokine at baseline and incident MALE. A linear association was also observed between increasing levels of each cytokine and incident MACE. Receiver operating characteristics models were constructed using clinical and laboratory risk factors, and the inclusion of cytokines significantly improved the prediction of incident events. CONCLUSIONS We demonstrated that elevated OPG, TNF-α, IL-6, and CRP levels at baseline correlate with worse vascular outcomes in patients with diabetes, PAD, and CLTI undergoing an endovascular procedure

The Role of High-Mobility Group Box-1 and Its Crosstalk with Microbiome in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, definitely disabling, and potentially severe autoimmune disease. Although an increasing number of patients are affected, a key treatment for all patients has not been discovered. High-mobility group box-1 (HMGB1) is a nuclear protein passively and actively released by almost all cell types after several stimuli. HMGB1 is involved in RA pathogenesis, but a convincing explanation about its role and possible modulation in RA is still lacking. Microbiome and its homeostasis are altered in patients with RA, and the microbiota restoration has been proposed to patients with RA. The purpose of the present review is to analyze the available evidences regarding HMGB1 and microbiome roles in RA and the possible implications of the crosstalk between the nuclear protein and microbiome in understanding and possibly treating patients affected by this harmful condition

Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm(2) to 475/mm(2) in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3 alpha and PPAR coactivator-1 alpha (PGC-1 alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis. Copyright (C) 2012 S. Karger AG, Base

Serum high mobility group box-1 and osteoprotegerin levels are associated with peripheral arterial disease and critical limb ischemia in type 2 diabetic subjects.

BACKGROUND: High mobility group box-1 (HMGB-1) is a nuclear protein also acting as inflammatory mediator, whilst osteoprotegerin (OPG), member of tumor necrosis factor receptor superfamily, is indicated as marker of vascular calcification. Peripheral artery disease (PAD) and type 2 diabetes (T2D) are clinical conditions characterized by elevated serum inflammatory markers and vascular calcification enhancement. The aim of this study was to investigate the potential role of HMGB-1, OPG and several inflammatory mediators such as C-reactive protein (HsCRP), tumor necrosis factor-alpha and interleukin-6 (IL-6) on the presence and severity of peripheral artery disease in patients with T2D. METHODS: In this retrospective observational study, we have analyzed HMGB-1, OPG and inflammatory cytokines serum levels in 1393 type 2 diabetic patients with PAD and without PAD (WPAD). RESULTS: HMGB-1 (7.89 \ub1 15.23 ng/mL), OPG (6.54 \ub1 7.76 pmol/L), HsCRP (15.6 \ub1 14.4 mg/L) and IL-6 (56.1 \ub1 28.6 pg/mL) serum levels were significantly higher in patients with PAD than in those WPAD (3.02 \ub1 8.12 ng/mL, P \u2c2 0.001; 2.98 \ub1 2.01 pmol/L, P < 0.001; 7.05 \ub1 4.4 mg/L, P < 0.001; 37.5 \ub1 20.2 pg/mL, P < 0.001 respectively). Moreover HMGB-1 (P < 0.001), OPG (P < 0.001), HsCRP (P < 0.001) and IL-6 (P < 0.001) serum levels were positively correlated with clinical severity of PAD. HMGB-1 (adjusted OR 12.32; 95% CI 3.56-23.54, P = 0.023) and OPG (adjusted OR 3.53; 95% CI 1.54-6.15, P = 0.019) resulted independent determinants of PAD in patients with T2D after adjusting for the conventional cardiovascular risk factor and established inflammatory mediators. CONCLUSIONS: In T2D patients HMGB-1 and OPG serum levels are higher in patients affected by PAD and independently associated with its occurrence and clinical severity

Association between plasma omentin-1 levels in type 2 diabetic patients and peripheral artery disease.

BACKGROUND: Type-2 diabetes mellitus is one of the major risk factors of atherosclerosis, particularly in peripheral artery disease (PAD). Several studies have documented a correlation between omentin-1 serum levels, atherosclerosis, and cardiovascular diseases. However, a clear link between circulating omentin-1 and PAD in diabetic patients has yet to be established. The aim of this study was to investigate the potential role of omentin-1 in PAD in type-2 diabetic patients. METHODS: In this cross-sectional study, we analyzed omentin-1 serum levels by ELISA in 600 type-2 diabetic patients with (n = 300) and without (n = 300) PAD at Fontaine's stage II, III, or IV. RESULTS: We found that omentin-1 serum levels were significantly lower in diabetic patients with PAD than in diabetic controls (29.46 vs 49.24 ng/mL, P &lt; 0.001) and that the levels gradually decreased in proportion to disease severity (P &lt; 0.05). The association between omentin-1 levels and PAD remained significant after adjusting for major risk factors in a multivariate analysis. CONCLUSIONS: Our results suggest that omentin-1 is reduced in type 2 diabetic patients with PAD and that omentin-1 levels are related to disease severity

Identification of early predictors of clinical outcomes of COVID-19 outbreak in an Italian single center using a machine-learning approach

OBJECTIVE: SARS-CoV-2 disease (COVID-19) has become a pandemic disease, determining a public health emergency. The use of artificial intelligence in identifying easily available biomarkers capable of predicting the risk for severe disease may be helpful in guiding clinical decisions. The aim of the study was to investigate the ability of interleukin (IL)-6, troponin I, and D-dimer to identify patients with COVID-19 at risk for intensive care unit (ICU)-admission and death by using a machine-learning predictive model. PATIENTS AND METHODS: Data on demographic characteristics, underlying comorbidities, symptoms, physical and radiological findings, and laboratory tests have been retrospectively collected from electronic medical records of patients admitted to Policlinico A. Gemelli Foundation from March 1, 2020, to September 15, 2020, by using artificial intelligence techniques. RESULTS: From an initial cohort of 425 patients, 146 met the inclusion criteria and were enrolled in the study. The in-hospital mortality rate was 15%, and the ICU admission rate was 41%. Patients who died had higher troponin I (p-value&lt;0.01) and IL -6 values (p-value=0.04), compared to those who survived. Patients admitted to ICU had higher lev- els of troponin I (p-value&lt;0.01) and IL-6 (p-val- ue&lt;0.01), compared to those not admitted to ICU. Threshold values to predict in-hospital mortality and ICU admission have been identified. IL-6 levels higher than 15.133 ng/L have been associated with a 22.91% risk of in-hospital mortality, and IL-6 levels higher than 25.65 ng/L have been as- sociated with a 56.16% risk of ICU admission. Troponin I levels higher than 12 ng/L have been associated with a 26.76% risk of in-hospital mortality and troponin I levels higher than 12 ng/L have been associated with a 52.11% risk of ICU admission. CONCLUSIONS: Levels of IL-6 and troponin I are associated with poor COVID-19 outcomes. Cut-off values capable of predicting in-hospi- tal mortality and ICU admission have been iden- tified. Building a predictive model using a ma- chine-learning approach may be helpful in supporting clinical decisions in a more precise and personalized way

Confirmed or unconfirmed cases of 2019 novel coronavirus pneumonia in Italian patients: a retrospective analysis of clinical features

Background: Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel etiologic agent of viral pneumonia. We aimed to compare clinical features of 165 Italian patients with laboratory confirmed or unconfirmed 2019-nCoV pneumonia. Methods: On March 31,&nbsp;2020, hospitalized patients who presented with fever and/or respiratory symptoms, exposures, and presence of lung imaging features consistent with 2019-nCoV pneumonia were included. Before admission to a hospital ward, patients underwent RT-PCR based SARS-CoV-2 RNA detection in their nasopharyngeal swab samples. Results: Of 165 patients studied, 119 had positive RT-PCR results and 46 were RT-PCR negative for 2 days or longer (i.e., when the last swab sample was obtained). The median age was 70 years (IQR, 58\u201378), and 123 (74.6%) of 165 patients had at least one comorbidity. The majority of patients (101/165, 61.2%) had a mild pneumonia, and the remaining patients (64/165, 38.8%) a severe/critical pneumonia. We did not find any substantial difference in symptoms, incubation periods, and radiographic/CT abnormalities as well as in many of the biological abnormalities recorded. However, at multivariable analysis, higher concentrations of hemoglobin (OR, 1.34; 95% CI, 1.11\u20131.65; P = 0.003) and lower counts of leukocytes (OR, 0.81; 95% CI, 0.72\u20130.90; P &lt; 0.001) were statistically associated with confirmed COVID-19 diagnosis. While mortality rates were similar, patients with confirmed diagnosis were more likely to receive antivirals (95% vs 19.6%, P &lt; 0.001) and to develop ARDS (63% vs 37%, P&nbsp;= 0.003) than those with unconfirmed COVID-19 diagnosis. Conclusions: Our findings suggest that unconfirmed 2019-nCoV pneumonia cases may be actually COVID-19 cases and that clinicians should be cautious when managing patients with presentations compatible with COVID-19