Prevalence and development of chronic critical illness in acute patients admitted to a respiratory intensive care setting

Introduction- Chronic Critical Illness (chronic CI) is a condition associated to patients surviving an episode of acute respiratory failure (ARF). The prevalence and the factors associated with the development of chronic CI in the population admitted to a Respiratory Intensive Care Unit (RICU) have not been yet elucidated. Methods- An observational prospective cohort study was undertaken at the RICU of the University Hospital of Modena (Italy). Patients mechanically ventilated with ARF in RICU were enrolled. Demographics, severity scores (APACHEII, SOFA, SAPSII), and clinical condition (septic shock, pneumonia, ARDS) were recorded on admission. Respiratory mechanics and inflammatory-metabolic blood parameters were measured both on admission and over the first week of stay. All variables were tested as predictors of chronic CI through univariate and multivariate analysis. Results- chronic CI occurred in 33 out of 100 patients observed. Higher APACHEII, the presence of septic shock, diaphragmatic dysfunction (DD) at sonography, multidrug-resistant (MDR) bacterial infection, the occurrence of a second infection during stay, and a C-reactive protein (CRP) serum level inceasing 7 days over admission were associated with chronic CI. Septic shock was the strongest predictor of chronic CI (AUC=0.92 p<0.0001). Conclusions- Chronic CI is frequent in patients admitted to RICU and mechanically ventilated due to ARF. Infection-related factors seem to play a major role as predictors of this syndrome

A Peptidic Thymidylate-Synthase Inhibitor Loaded on Pegylated Liposomes Enhances the Antitumour Effect of Chemotherapy Drugs in Human Ovarian Cancer Cells

There is currently no effective long-term treatment for ovarian cancer (OC) resistant to poly-chemotherapy regimens based on platinum drugs. Preclinical and clinical studies have demonstrated a strong association between development of Pt-drug resistance and increased thymidylate synthase (hTS) expression, and the consequent cross-resistance to the hTS inhibitors 5-fluorouracil (5-FU) and raltitrexed (RTX). In the present work, we propose a new tool to combat drug resistance. We propose to treat OC cell lines, both Pt-sensitive and -resistant, with dual combinations of one of the four chemotherapeutic agents that are widely used in the clinic, and the new peptide, hTS inhibitor, [D-Gln4]LR. This binds hTS allosterically and, unlike classical inhibitors that bind at the catalytic pocket, causes cell growth inhibition without inducing hTS overexpression. The dual drug combinations showed schedule-dependent synergistic antiproliferative and apoptotic effects. We observed that the simultaneous treatment or 24h pre-treatment of OC cells with the peptide followed by either agent produced synergistic effects even in resistant cells. Similar synergistic or antagonistic effects were obtained by delivering the peptide into OC cells either by means of a commercial delivery system (SAINT-PhD) or by pH sensitive PEGylated liposomes. Relative to non-PEGylated liposomes, the latter had been previously characterized and found to allow macrophage escape, thus increasing their chance to reach the tumour tissue. The transition from the SAINT-PhD delivery system to the engineered liposomes represents an advancement towards a more drug-like delivery system and a further step towards the use of peptides for in vivo studies. Overall, the results suggest that the association of standard drugs, such as cDDP and/or 5-FU and/or RTX, with the novel peptidic TS inhibitor encapsulated into PEGylated pH-sensitive liposomes can represent a promising strategy for fighting resistance to cDDP and anti-hTS drugs

Impiego degli Inibitori della Pompa protonica (IPP) in Piemonte: indagine sulle abitudini prescrittive dei Medici di Medicina Generale

Proton Pump Inhibitors (PPIs) (Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole and Esomeprazole), one of the most commonly prescribed classes of medications in the primary care setting, are considered a major advance in the treatment of acid-peptic diseases. In Italy PPIs are reimbursed by National Health Service on the basis of CUF (Commissione Unica del Farmaco) 1 and 48 Notes. In 2002 and 2003 a significant increase in PPIs consumption and expenditure have been documented, showing differences between regions. The aim of this study is to investigate and monitor, at regional level, type and entity of PPIs use through a drug utilization study, evaluating prescribing behaviour and compliance of PPIs treatments with CUF Notes indications. The study has been carried out on a sample of 436 General Practitioners belonging to 22 Piemonte's ASL (Aziende Sanitarie Locali). The data analysis shows that acid-related pathologies are significantly more common in patients with at least 50 years of age and the most frequent condition is represented by gastroesophageal reflux disease. Despite the general conditions of PPIs use by General Practitioners in terms of duration and dosage of therapy result in most cases (from 49% to 80% for duration and from 54% to 97% for dosage) compliant with what proposed by CUF Notes, in some cases the same CUF Notes indications seem to be not observed. Consequently the Piemonte Region has decided to plan a guideline on PPIs rational use. Such guideline, expected to be introduced in the regional area, may also be considered as an instrument able to lead to a more appropriate expenditure for this drug class. Moreover, in order to control PPIs expenditure, pharmacoeconomic methodologies can be applied allowing to identify the most cost - effective active substance and therapeutic scheme, overcoming CUF Notes which consider all PPIs use under the same reimbursement conditions

Molecular mechanisms and physiological changes behind benign tracheal and subglottic stenosis in adults.

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different etiology. Although iatrogenic etiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent etiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS

Synthesis, molecular structure exploration and in vitro cytotoxicity screening of five novel N, N\u2032- disubstituted thiocarbamide derivatives

The synthesis of five N,N\u2033-substituted thiocarbamides, namely N-(naphthyl)-N\u2033-(pentoxycarbonyl) thiocarbamide (H2L1), N-(2-Chloro-4-nitrophenyl)-N\u2033-(pentoxycarbonyl) thiocarbamide(H2L2), N-(2-methoxy-4-nitrophenyl)-N\u2033-(pentoxycarbonyl) thiocarbamide (H2L3), N-(3-nitrophenyl)-N\u2033-(pentoxycarbonyl) thiocarbamide (H2L4) and N-(naphthyl)-N\u2033-(2, 2, 2-trichloroethoxycarbonyl) thiocarbamide (H2L5) was performed by the reaction of pentoxycarbonyl chloroformate with naphthyl amine, 2-chloro-4-nitroaniline, 2-methoxy-4-nitroaniline, 3-nitroaniline, respectively, for the first four and by the reaction of 2, 2, 2-trichloroethoxycarbonyl chloroformate with naphthyl amine for the last compound. These compounds were fully characterized by using various spectroscopic (FT-IR,1H and13C NMR) and single crystal X-ray studies of H2L1 and H2L5. In the crystal structure of both the compounds the (C\u2edS) and (C\u2edO) groups are trans to each other across the C 12N bond. The crystal packing of H2L1 shows that the molecules form centrosymmetric dimers connected by N2 12H\ub7\ub7\ub7\ub7S hydrogen bonds. In H2L5 an offset face-to-face \u3c0\u2013\u3c0 stacking is observed between two naphthalene rings of two molecules. In vitro cytotoxicity of synthesized compounds was evaluated using five human carcinoma cell lines 2008, C13* (cervical carcinoma), A2780, A2780/CP and IGROV-1 (ovarian carcinoma). The IC50values of compounds H2L2 \u2500 H2L4 demonstrated them to be very promising anticancer agents

Legislative History: An Act To Support Maine People in Recovery (HP1019)(LD1496)

https://digitalmaine.com/legishist127/2495/thumbnail.jp

How to measure knowledge about mental disorders: validation of the Italian version of the MAKS

The aim of this study is to validate the Italian version of the Mental Health Knowledge Schedule (MAKS-I). The validation process included: linguistic validation; analysis of the feasibility; face validity; internal consistency; floor and the ceiling effects; divergent validity. Multiple linear regression was performed to examine the relationship between mental health knowledge and independent variables. MAKS-I was administered to 453 people. The linguistic validation was successful and face validity of the questionnaire showed no critical issues. The estimated composite reliability was 0.638. Divergent validity was supported by lack of statistical significant correlation between MAKS-I and RIBS-I with a positive correlation index. Participation in seminars or conferences related to the issue of mental health stigma, gender, qualification and having a first or second-degree relatives with a psychiatric disorder can be considered possible predictors of the MAKS-I score. MAKS-I is a reliable questionnaire to assess mental health knowledge and familiarity with psychiatric clinical conditions in Italian language

Synthesis, molecular structure exploration and <i>in vitro</i> cytotoxicity screening of five novel N, N′- disubstituted thiocarbamide derivatives

<p></p> <p>The synthesis of five N,N″-substituted thiocarbamides, namely N-(naphthyl)-N″-(pentoxycarbonyl) thiocarbamide <b>(H₂L1</b>), N-(2-Chloro-4-nitrophenyl)-N″-(pentoxycarbonyl) thiocarbamide(<b>H₂L2</b>), N-(2-methoxy-4-nitrophenyl)-N″-(pentoxycarbonyl) thiocarbamide (H₂L3), N-(3-nitrophenyl)-N″-(pentoxycarbonyl) thiocarbamide (<b>H₂L4</b>) and N-(naphthyl)-N″-(2, 2, 2-trichloroethoxycarbonyl) thiocarbamide (<b>H₂L5</b>) was performed by the reaction of pentoxycarbonyl chloroformate with naphthyl amine, 2-chloro-4-nitroaniline, 2-methoxy-4-nitroaniline, 3-nitroaniline, respectively, for the first four and by the reaction of 2, 2, 2-trichloroethoxycarbonyl chloroformate with naphthyl amine for the last compound. These compounds were fully characterized by using various spectroscopic (FT-IR, ¹H and ¹³C NMR) and single crystal X-ray studies of <b>H₂L1</b> and <b>H₂L5</b>. In the crystal structure of both the compounds the (C˭S) and (C˭O) groups are trans to each other across the C−N bond. The crystal packing of <b>H₂L1</b> shows that the molecules form centrosymmetric dimers connected by N2−H····S hydrogen bonds. In <b>H₂L5</b> an offset face-to-face π–π stacking is observed between two naphthalene rings of two molecules. <i>In vitro</i> cytotoxicity of synthesized compounds was evaluated using five human carcinoma cell lines 2008, C13* (cervical carcinoma), A2780, A2780/CP and IGROV-1 (ovarian carcinoma). The IC₅₀ values of compounds <b>H₂L2 ─ H₂L4</b> demonstrated them to be very promising anticancer agents.</p