Ventilator-Associated Lower Respiratory Tract Infections and Their Association With COVID-19: A Retrospective Cohort Study in a Portuguese Intensive Treatment Unit.

Introduction Ventilator-associated pneumonia (VAP) is the most common infectious complication related to admission to an Intensive Treatment Unit (ITU). Ventilator-associated lower respiratory tract infection (VA-LRTI) is a broader diagnosis than VAP. By disregarding radiological criteria, it will include both VAP and ventilator-associated tracheobronchitis. This study, conducted in the setting of a Portuguese ITU, aims to study the incidence, microbiology and clinical outcome of VA-LRTI and its association with COVID-19. Methods A retrospective cohort study included patients admitted to a Portuguese ITU who underwent invasive mechanical ventilation (IMV) for over 48 hours between 01/01/2021 and 31/12/2021. The Hospitals in Europe Link for Infection Control through Surveillance (HELICS) criteria were applied, disregarding the radiological criteria, for the diagnosis of VA-LRTI. Results The group of patients with COVID-19 had 46.38 episodes of VA-LRTI/1000 days of ventilation, while patients without COVID-19 had 16.35 episodes/1000 days of ventilation (RR 2.78, p < 0.001). Of the 85 microorganisms isolated, 82% were gram-negative microorganisms, with species of the genus Klebsiella being the most prevalent (22.4%). There was a lower prevalence of beta-lactam-resistant organisms in patients with COVID-19 (RR 0.35, p = 0.031). The development of VA-LRTI is associated with longer times of IMV (difference in medians 10 days, p < 0.001), but with no significant differences in mortality (RR 1.21, p = 0.14). Discussion Patients with COVID-19 seem more predisposed to developing VA-LRTI, possibly due to intrinsic characteristics of the disease. Although no increase in mortality has been demonstrated, VA-LRTI can entail important costs related to morbidity, antibiotic pressure and economic costs that must be considered.

From JWH-018 to OXIZIDS: Structural evolution of synthetic cannabinoids in the European Union from 2008 to present day.

With new synthetic cannabinoids (SCs) appearing on the European drug market every year, early warning systems are key to detect, monitor, and respond to threats posed by them. The European Union Early Warning System (EU EWS) implemented by the European Monitoring Centre for Drugs and Drug Addiction has monitored these substances since their first European detection in 2008. Since then, national and international responses have been implemented, aimed at tackling risks posed by SCs. Throughout this time, new SCs have emerged on the European market containing diverse structural moieties, appearing to be designed in a way that circumvents existing legal controls, contributing to a complex public health scenario. This study provides an inventory of the SCs detected in the EU from 2008 to 2022, describing their structural evolution by analysing separately four structural features: their core, tail, linker, and linked groups. The range of structural changes is analysed considering key milestones, including the year of first report by the European Union Early Warning System to the key legislative changes that have occurred since. The analysis shows that from June 2021 to July 2022, 20 out of 23 newly emerged SCs evade the generic SC legislation introduced in China in May 2021. This supports the hypothesis that the protection of public health benefits from timely information exchange and careful assessment of the risks associated with these substances. Additionally, the introduction of legal responses, albeit an important instrument to reduce the availability of dangerous substances on the market, may also be accompanied by unintended consequences.

Acquired Haemophilia associated with SARS-CoV2 infection / Hemofilia Adquirida asociada a infección por SARS-CoV2

We present the case of a 73-year-old man, with a history of SARS-CoV2 infection (January 2021), who came to the emergency department three months post infection, with complaints of left hip and knee pain, that turned out to be a substantial thigh hematoma. Analysis showed a normocytic/ normochromic anaemia (9,0 g/dL), prolonged aPTT (63.2 seconds; normal range 24.7–39.0 sec.), with normal prothrombin time. We arrived at a diagnosis of Acquired Haemophilia A. Treatment was promptly started, with clinical and laboratory improvement. After the vaccination to SARS-CoV2, a relapse was observed.Acquired Haemophilia A is a rare, autoimmune disease, distinguished by the presence of inhibitors against factor VIII. It’s characterised by subcutaneous hematomas and muscle bleeding, with prolonged aPTT. SARS-CoV2 infection has already been mentioned as a possible cause. (AU)

DARK Classics in Chemical Neuroscience: Etonitazene and Related Benzimidazoles.

Etonitazene and related 2-benzylbenzimidazoles are potent analgetics invented in the research laboratories of the Swiss pharmaceutical giant CIBA in the late 1950s. Though the unprecedented structure distinguishes this class of compounds from poppy-derived and other synthetic analgetics, a range of studies indicate that these drugs are selective µ opioid receptor agonists possessing morphine-like pharmacotoxicological properties in animals as well as humans. Several unscheduled members of this synthetically readily accessible class of opioids that are not controlled under the international and national drug control systems have recently emerged on the illicit drug market. Among them, isotonitazene has been implicated in at least 200 fatalities in Europe and North America. None of the 2-benzylbenzimidazole derivatives have been developed into medicines, but etonitazene and some of its derivatives have been used as receptor probes and in addiction behavior studies in animals. The unique structure has inspired research on such benzimidazoles and related benzimidazolones of which "brorphine" made its debut as one of the newest psychoactive substance to emerge on the illicit opioid drug market in mid-2019. This in-depth review provides a historical introduction, an overview on the chemistry, pharmacological profiles, adverse effects, addiction liability, regulatory status, and the impact on chemical neuroscience of the 2-benzylbenzimidazoles. Structurally related benzimidazoles with opioid and/or analgesic properties are also discussed briefly.

Psychological morbidity is the main predictor of quality of life among caregivers of individuals in first-episode psychosis: data from a year-long longitudinal study in Brazil

Objective: To investigate quality of life (QoL) and QoL predictors among caregivers of individuals in first-episode psychosis (FEP). Methods: This longitudinal study investigated predictors of QoL in caregivers of 80 individuals in FEP over a 1-year follow-up period, measured using a single component extracted from the 36-item Short-Form Health Survey (SF-36). Results: Mediation analysis demonstrated that, at 1 year, high scores in the Self-Report Questionnaire (SRQ-20) were associated with high scores on the negative sub-scale of the Experience of Caregiving Inventory (ECI), which was also associated with low scores in the Essential Quality of Life (Essential QoL) component extracted from the SEF-36. Clinically, the resulting association indicates that depression and anxiety symptoms in caregivers at baseline are predictors of their 1-year quality of life, based on self-assessment of the caregiving experience. Conclusion: Supporting an individual in FEP can have a negative impact on QoL. Maintaining caregivers' mental health and subjective evaluation of the caregiving experience must be primary goals of FEP services. Complementary studies of FEP caregivers' QoL can support the design of personalized interventions in the near future.

Psychological morbidity is the main predictor of quality of life among caregivers of individuals in first-episode psychosis: data from a year-long longitudinal study in Brazil.

OBJECTIVE: To investigate quality of life (QoL) and QoL predictors among caregivers of individuals in first-episode psychosis (FEP). METHODS: This longitudinal study investigated predictors of QoL in caregivers of 80 individuals in FEP over a 1-year follow-up period, measured using a single component extracted from the 36-item Short-Form Health Survey (SF-36). RESULTS: Mediation analysis demonstrated that, at 1 year, high scores in the Self-Report Questionnaire (SRQ-20) were associated with high scores on the negative sub-scale of the Experience of Caregiving Inventory (ECI), which was also associated with low scores in the Essential Quality of Life (Essential QoL) component extracted from the SEF-36. Clinically, the resulting association indicates that depression and anxiety symptoms in caregivers at baseline are predictors of their 1-year quality of life, based on self-assessment of the caregiving experience. CONCLUSION: Supporting an individual in FEP can have a negative impact on QoL. Maintaining caregivers' mental health and subjective evaluation of the caregiving experience must be primary goals of FEP services. Complementary studies of FEP caregivers' QoL can support the design of personalized interventions in the near future.

Hemiballistic movements in a newly HIV patient.

Infections of central nervous system (CNS) include a broad group of conditions and pose a particular challenge to physicians, especially in immunocompromised individuals. This case refers to a 26-year-old male patient with a history of smoked hashish and drug abuse admitted to the infectious disease department with hemiballismus of left hemibody and a positive HIV serologic test. A magnetic resonance imaging (MRI) study showed lesions at lower left and right cerebellar hemisphere, one of them thalamus - mesencephalic suggesting an opportunistic infection or an HIV associated encephalopathy. Lumbar puncture, brain biopsy and successive neuroimaging were not conclusive for one disease and despite the use of directed therapy for cerebral toxoplasmosis, meningeal tuberculosis, anti-retrovirals and sedative medication, after over 6 weeks of hospitalization pallidotomy was performed. After 5 months of oral and surgical treatment the patient showed clinical, immunological and radiological recovery.

Sclerosing Mesenteritis and Disturbance of Glucose Metabolism: A New Relationship? A Case Series.

BACKGROUND: Sclerosing mesenteritis is an idiopathic inflammatory and fibrotic disease that affects the mesentery. It is a rare disease, with the total number of reported cases in the literature ranging from 122 to 300. It mainly affects men in the sixth decade of life, and its etiology remains unknown. Clinical presentation is variable, but it is frequently asymptomatic. Diagnosis is often made by computed tomography (CT) scan, although biopsy may be needed for confirmation. An association between other diseases (e.g., neoplasms) and sclerosing mesenteritis has been described, but the relationship between the latter and glucose changes is not disclosed in the currently available literature. CASE REPORT: Five cases of sclerosing mesenteritis and glucose metabolism disorders (impaired fasting glucose and type 2 diabetes mellitus) were retrospectively collected and analyzed. The mean age was 65 ± 9.3 years, 80% were male, and all patients were white. Three patients were asymptomatic and the other 2 (40%) had non-specific chronic abdominal pain. Blood tests revealed normal inflammatory parameters (mean HbA1c was 6.4% and fasting blood glucose was 140 mg/dL). The diagnosis was made by abdominal CT scan. The 2 symptomatic patients underwent therapy with colchicine 1 mg/day, with clinical improvement. During the mean 43-month follow-up period, there was no symptomatic progression, thereby maintaining the usual benign course of this condition. CONCLUSIONS: Sclerosing mesenteritis has only been described in small series and isolated cases, but its diagnosis is becoming more common due to greater access to diagnostic methods and higher awareness of the disease in the medical community. Furthermore, despite the small sample size, we describe a possible association between glucose metabolism impairment and sclerosing mesenteritis.

Economic analysis and environmental impact assessment of three different fermentation processes for fructooligosaccharides production.

Three different fermentation processes for the production of fructooligosaccharides (FOS) were evaluated and compared in terms of economic aspects and environmental impact. The processes included: submerged fermentation of sucrose solution by Aspergillus japonicus using free cells or using the cells immobilized in corn cobs, and solid-state fermentation (SSF) using coffee silverskin as support material and nutrient source. The scale-up was designed using data obtained at laboratory scale and considering an annual productivity goal of 200 t. SSF was the most attractive process in both economic and environmental aspects since it is able to generate FOS with higher annual productivity (232.6 t) and purity (98.6%) than the other processes; reaches the highest annual profit (6.55 M€); presents the lowest payback time (2.27 years); and is more favourable environmentally causing a lower carbon footprint (0.728 kg/kg, expressed in mass of CO2 equivalent per mass of FOS) and the lowest wastewater generation.

Intellectual disability and overgrowth-A new case of 19p13.13 microdeletion syndrome with digital abnormalities.

19p13.13 microdeletion has been consistently associated with intellectual disability, overgrowth, and macrocephaly. We report a 19p13.13 microdeletion, detected by array CGH, in a girl with moderate intellectual disability, overgrowth with macrocephaly, prominent digit pads and deep digital creases, hypotonia, ataxia, and strabismus. This clinical report helps to delineate the role of some of the deleted genes, as well as the phenotype of recently described 19p13.13 microdeletion syndrome, including the description of novel digital abnormalities.

Antioxidant and antimycotic activities of two native lavandula species from portugal.

The antioxidant and antimycotic activities of the essential oils and extracts of two native Portuguese Lavandula species, L. stoechas subsp. luisieri and L. pedunculata, were evaluated by in vitro assays. The total phenolics and flavonoids content were also determined. The antioxidant potential was assessed through DPPH radical scavenging, inhibition of lipid peroxidation (ILP), and DNA protection assays. All samples displayed a high DPPH scavenging activity, some of them showing concentration dependence. The majority of the samples were also able to inhibit lipid peroxidation. A strong correlation was observed between the results of DPPH and ILP assays and the flavonoids content of the samples. In the DNA protection assay, all the extracts were able to preserve DNA integrity. The antimycotic activity was performed against twelve fungi belonging to Basidiomycota and Ascomycota Divisions. L. stoechas subsp. luisieri exhibited the broadest activity spectra. L. pedunculata extracts were active against five fungi. Cryptococcus neoformans was the most sensitive, being inhibited by all the extracts. Our results led to the conclusion that L. stoechas subsp. luisieri and L. pedunculata can be useful as new sources of natural antioxidants and antimycotic agents, providing a possible valorization of the existing biodiversity and resources of Portuguese flora.

The Experience of Caregiving Inventory for first-episode psychosis caregivers: validation of the Brazilian version.

Family members of first-episode psychosis (FEP) patients are regarded as key components of the patient's evaluation, recovery and treatment. This paper aimed to investigate 75 FEP caregivers' appraisal, psychological morbidity and quality of life in the initial phase of treatment in a specialized FEP outpatient program in São Paulo, Brazil, and evaluate the validation of the Brazilian version of the Experience of Caregiving Inventory (ECI). Caregivers were also scored through Self Report Questionnaire-20 and Short Form-36. It was found that 29% of them might be a case for minor psychiatric disorder, that the worst domains of quality of life concerned emotional aspects, vitality and bodily pain, and that they were particularly affected by patients' negative symptoms, dependency and difficult behaviors. Additionally, internal consistency of ECI was very satisfactory (Cronbach's alpha=0.95) with subscales ranging from 0.57 (stigma) to 0.94 (total negative score). The Brazilian version of the ECI is not only a facile, reliable and valid instrument to describe the experience of caring for a relative with serious mental illness. It offers mental health professionals an opportunity to access caregivers' global experience and their evaluation of a severe mental disease, as well as to predict their psychological suffering, which is harmful to both patient and caregiver.