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Abstract There is now scientific evidence that, in dogs, distinctive facial actions are produced in response to different emotionally-arousing stimuli suggesting a relationship between lateralized facial expressions and emotional states. Although in humans, relationships between facial asymmetry and both emotional and physiological distress have been reported, there are currently no data on the laterality of dogs’ facial expressions in response to social stimuli with respect to canine behavioral disorders. The aim of the present work was to investigate the facial asymmetries of dogs with fear and aggressive behavior towards humans during two different emotional situations: (1) while the dogs were alone in the presence of their owners and (2) during the approach of an unfamiliar human being. Overall, our results demonstrated high levels of asymmetries in facial expressions of dogs displaying fear and aggressive behaviors towards humans indicating that measuring facial asymmetries in dogs could prove to be a useful non-invasive tool for investigating physiology-based behavioral disorders.

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Given the increasing interest in bioactive dietary components that can modulate gene expression enhancing human health, three metabolites isolated from hemp seeds—cannabidiolic acid, N-trans-caffeoyltyramine, and cannabisin B—were examined for their ability to change the expression levels of microRNAs in human neural cells. To this end, cultured SH-SY5Y cells were treated with the three compounds and their microRNA content was characterized by next-generation small RNA sequencing. As a result, 31 microRNAs underwent major expression changes, being at least doubled or halved by the treatments. A computational analysis of the biological pathways affected by these microRNAs then showed that some are implicated in neural functions, such as axon guidance, hippocampal signaling, and neurotrophin signaling. Of these, miR-708-5p, miR-181a-5p, miR-190a-5p, miR-199a-5p, and miR-143-3p are known to be involved in Alzheimer’s disease and their expression changes are expected to ameliorate neural function. Overall, these results provide new insights into the mechanism of action of hemp seed metabolites and encourage further studies to gain a better understanding of their biological effects on the central nervous system.

Dans le contexte brésilien de fermeture des écoles en raison de la pandemie de la Covid-19, face aux multiples formes de crises sociales et à un projet de destruction du pays mené par les autorités politiques, cette contribution témoigne de comment les jeunes rencontrés au moment du passage entre le lycée et l’université dans le cadre d’une recherche ont vécu cette période. Les entretiens menés ont fait émerger la question importante de leur rapport à l’école, en tant qu’institution, dans ce moment existentiel de projection. La recherche met en lumière le fait que ces jeunes ont pu traverser ces crises en s’appuyant sur une forme d’école intériorisée, un trait identificatoire qui a rendu possible le travail psychique du deuil, leur permettant de ne pas tomber dans un état mélancolique.

Pseudoaneurysm rarely develops after orthognathic surgery, and can cause symptoms such as facial swelling, delayed bleeding, and development of a pulsatile soft mass. The aim of this report is to highlight a case of a masseteric artery pseudoaneurysm following orthognatic surgery, describing the possible while rare occurrence and its treatment. At the ninth postoperative day, persistent facial swelling and bleeding from the intraoral surgical wounds and nose occurred, followed by a syncope. Support therapy was administered, and an Angio-CT was requested. The results of the scans raised suspicion of the presence of a pseudoaneurysm. After the stabilization of the clinical picture a therapeutic angiography was performed. A pseudoaneurysmatic dilatation was documented in the distal portion of the left masseteric artery and was promptly excluded from the main circle. This artery derived, as an anatomical variant, from a common branch originating from the internal maxillary artery. While this complication is more commonly reported in traumatology, in cases of suspicious intraoperative bleeding, persistent facial swelling, and late-onset nasal-oral hemorrhage, pseudoaneurysms of the maxillofacial district should be considered as a possible complication of orthognatic surgery.

Abstract Background Therapeutic drug monitoring (TDM) may represent an invaluable tool for optimizing antimicrobial therapy in septic patients, but extensive use is burdened by barriers. The aim of this study was to assess the impact of a newly established expert clinical pharmacological advice (ECPA) program in improving the clinical usefulness of an already existing TDM program for emerging candidates in tailoring antimicrobial therapy among critically ill patients. Methods This retrospective observational study included an organizational phase (OP) and an assessment phase (AP). During the OP (January–June 2021), specific actions were organized by MD clinical pharmacologists together with bioanalytical experts, clinical engineers, and ICU clinicians. During the AP (July–December 2021), the impact of these actions in optimizing antimicrobial treatment of the critically ill patients was assessed. Four indicators of performance of the TDM-guided real-time ECPA program were identified [total TDM-guided ECPAs July–December 2021/total TDM results July–December 2020; total ECPA dosing adjustments/total delivered ECPAs both at first assessment and overall; and turnaround time (TAT) of ECPAs, defined as optimal ( 48 h)]. Results The OP allowed to implement new organizational procedures, to create a dedicated pathway in the intranet system, to offer educational webinars on clinical pharmacology of antimicrobials, and to establish a multidisciplinary team at the morning bedside ICU meeting. In the AP, a total of 640 ECPAs were provided for optimizing 261 courses of antimicrobial therapy in 166 critically ill patients. ECPAs concerned mainly piperacillin–tazobactam (41.8%) and meropenem (24.9%), and also other antimicrobials had ≥ 10 ECPAs (ceftazidime, ciprofloxacin, fluconazole, ganciclovir, levofloxacin, and linezolid). Overall, the pre–post-increase in TDM activity was of 13.3-fold. TDM-guided dosing adjustments were recommended at first assessment in 61.7% of ECPAs (10.7% increases and 51.0% decreases), and overall in 45.0% of ECPAs (10.0% increases and 35.0% decreases). The overall median TAT was optimal (7.7 h) and that of each single agent was always optimal or quasi-optimal. Conclusions Multidisciplinary approach and timely expert interpretation of TDM results by MD Clinical Pharmacologists could represent cornerstones in improving the cost-effectiveness of an antimicrobial TDM program for emerging TDM candidates.

Background/Objectives: Point-of-care lung ultrasonography (LUS) represents an accurate diagnostic tool in older patients with respiratory failure. The integration of LUS with ultrasonographic assessment of diaphragm thickness and excursion, right vastus lateralis (RVL) muscle thickness and cross-sectional area (CSA) could provide real-time information on frailty and sarcopenia. The primary aim of this proof-of-concept prospective study was to evaluate clinical correlates of thoracic, diaphragmatic, and muscular ultrasound to characterize the associations between frailty, respiratory failure, and sarcopenia in older patients hospitalized for acute respiratory complaints. Methods: Each of 52 participants (age median 84, IQR 80–89 years old) underwent integrated LUS, diaphragm and RVL ultrasound examination upon admission (T0) and after 72 h of hospitalization (T1). LUS score was used to estimate lung interstitial syndrome severity. Diaphragm excursion, thickness, RVL thickness and CSA were measured following a standardized protocol. Frailty was assessed with the PC-FI (Primary Care-Frailty Index). Results: All patients exhibited multifactorial causes of respiratory symptoms. The LUS score on T0 predicted 3-month rehospitalization. Frail patients exhibited higher LUS scores on T1. Diaphragm excursion on T0 was reduced in patients with COPD and heart failure and in those developing delirium during hospitalization. Diaphragm excursion on T1 was negatively associated with PC-FI. Diaphragm thickness, RVL thickness, and CSA exhibited a positive association with obesity. Right vastus lateralis CSA on T1, however, was also negatively associated with PC-FI. Conclusions: Integrated lung, diaphragm, and RVL ultrasound shows clinical correlations with several aspects of frailty that may help to improve the management of geriatric patients with respiratory illness. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease propelled by circulating autoantibodies that recognize cell surface phospholipids and phospholipid-binding proteins. APS is an autoimmune disorder associated with recurrent thrombosis of arterial or venous vessels and/or recurrent obstetric complications as miscarriages. APS can be divided into primary or secondary clinical syndrome because of the possible association with other autoimmune systemic diseases as systemic lupus erythematosus (SLE). Vitamin K antagonists remain the mainstay of treatment for most patients with APS and, based on current data, appear superior to the more targeted direct oral anticoagulants. However, the choice of the type of antithrombotic drug is based on the anamnesis of affected patients: patients with previous arterial or venous thrombosis may benefit from anticoagulants, while patients with previous obstetric diseases may benefit from aspirin, but several clinical exceptions may be evaluated. This short review is dedicated to underlining the main clinical evidence for patients affected by APS or CAPS (catastrophic antiphospholipid syndrome) in order to prevent recurrent thrombosis. [ABSTRACT FROM AUTHOR]

(1) Background: Piperacillin-tazobactam represents the first-line option for treating infections caused by full- or multi-susceptible Enterobacterales and/or Pseudomonas aeruginosa in critically ill patients. Several studies reported that attaining aggressive pharmacokinetic/pharmacodynamic (PK/PD) targets with beta-lactams is associated with an improved microbiological/clinical outcome. We aimed to assess the relationship between the joint PK/PD target attainment of continuous infusion (CI) piperacillin-tazobactam and the microbiological/clinical outcome of documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP) of critically ill patients treated with CI piperacillin-tazobactam monotherapy. (2) Methods: Critically ill patients admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 treated with CI piperacillin-tazobactam monotherapy optimized by means of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program for documented Gram-negative BSIs and/or VAP were retrospectively retrieved. Steady-state plasma concentrations (Css) of piperacillin and of tazobactam were measured, and the free fractions (f) were calculated according to respective plasma protein binding. The joint PK/PD target was defined as optimal whenever both the piperacillin fCss/MIC ratio was >4 and the tazobactam fCss/target concentration (CT) ratio was > 1 (quasi-optimal or suboptimal whenever only one or none of the two weas achieved, respectively). Multivariate logistic regression analysis was performed for testing variables potentially associated with microbiological outcome. (3) Results: Overall, 43 critically ill patients (median age 69 years; male 58.1%; median SOFA score at baseline 8) treated with CI piperacillin-tazobactam monotherapy were included. Optimal joint PK/PD target was attained in 36 cases (83.7%). At multivariate analysis, optimal attaining of joint PK/PD target was protective against microbiological failure (OR 0.03; 95%CI 0.003–0.27; p = 0.002), whereas quasi-optimal/suboptimal emerged as the only independent predictor of microbiological failure (OR 37.2; 95%CI 3.66–377.86; p = 0.002). (4) Conclusion: Optimized joint PK/PD target attainment of CI piperacillin-tazobactam could represent a valuable strategy for maximizing microbiological outcome in critically ill patients with documented Gram-negative BSI and/or VAP, even when sustained by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales. In this scenario, implementing a real-time TDM-guided ECPA program may be helpful in preventing failure in attaining optimal joint PK/PD targets among critically ill patients. Larger prospective studies are warranted to confirm our findings.

Background: The Italian National Institute of Health (Istituto Superiore di Sanità) funded a 30-month project (July 2021–January 2024) to conduct a twin study of the relationships between Positive Mental Health (PMH) and cellular longevity. Only a few previous studies have focused on the biomarkers of aging in relation to psychological well-being, and none of them exploited the potential of the twin design. Method: In this project, following the standard procedures of the Italian Twin Registry (ITR), we aim to recruit 200 adult twin pairs enrolled in the ITR. They are requested to complete a self-report questionnaire battery on PMH and to undergo a blood withdrawal for the assessment of aging biomarkers, i.e., telomere length and mitochondrial DNA functionality. The association between psychological and aging biomarker measures will be assessed, controlling for genetic and familial confounding effects using the twin study design. Results and conclusions: Biomarker assays are underway. Once data are available for the total study sample, statistical analyses will be performed. The project’s results may shed light on new mechanisms underlying the mind–body connection and may prove helpful to promote psychological well-being in conjunction with biological functioning.

Introduction: Drug–drug interactions (DDIs) represent an important clinical problem, particularly in older patients, due to polytherapy, comorbidity, and physiological changes in pharmacodynamic and pharmacokinetic pathways. In this study, we investigated the association between drugs prescribed after discharge from the hospital or clinic and the risk of DDIs with drugs used daily by each patient. Methods: We performed an observational, retrospective, multicenter study on the medical records of outpatients referred to general practitioners. DDIs were measured using the drug interaction probability scale. Potential drug interactions were evaluated by clinical pharmacologists (physicians) and neurologists. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study, we evaluated 1772 medical records. We recorded the development of DDIs in 10.3% of patients; 11.6% of these patients required hospitalization. Logistic regression showed an association among DDIs, sex, and the number of drugs used (p = 0.023). Conclusions: This observational real-life study shows that the risk of DDIs is common in older patients. Physicians must pay more attention after hospital discharge, evaluating the treatment to reduce the risk of DDIs.

Introduction: Drug treatment can be related to the development of adverse drug reactions (ADRs). Aim: In this paper, we evaluated ADRs in patients admitted to the Ambulatory of Pain Medicine of the University Hospital Renato Dulbecco in Catanzaro. Methods: We conducted a prospective analysis between 1 February 2021 and 20 July 2023 on patients with neuropathic pain referred to the Ambulatory of Pain Medicine of “Renato Dulbecco” University Hospital in Catanzaro (Calabria, Italy). Patients aged >18 years with clinical signs of neurologic pain and a score upon completing the Douleur Neuropathique en 4 Questions (DN4) questionnaire of ≥4 were included. The association between drugs and ADR or between drugs and drug–drug-interactions (DDIs) was evaluated using Naranjo’s probability scale and Drug Interaction Probability Scale (DIPS), respectively. Results: During the study period, we analyzed 2370 patients referred to the ambulatory of pain medicine. After the evaluation of inclusion and exclusion criteria, 33.5% of patients were enrolled. All patients presented at least one comorbidity and daily used a mean of five drugs (range 3–11). Using the Naranjo score, the development of ADRs was documented in 112 patients (score 6). Using parametric and non-parametric statistical analysis, we failed to report an association between ADR and dosage or ADR and patient characteristics. Conclusion: Our results show the development of ADRs in 18% of patients with neuropathic pain. This low percentage of drug interaction could be a limitation in real life because it is probably due to the site of the study and the appropriate prescription of drugs. Therefore, it shows that it is necessary to motivate healthcare to pay attention to the prescription of drugs in poly-treated patients to reduce the risk of ADRs.