Investigating the Association between Physical Health Comorbidities and Disability in Individuals with Severe Mental Illness

BACKGROUND: Research suggests that an increased risk of physical comorbidities might have a key role in the association between severe mental illness (SMI) and disability. We examined the association between physical multimorbidity and disability in individuals with SMI. METHODS: Data were extracted from the clinical record interactive search system at South London and Maudsley Biomedical Research Centre. Our sample (n = 13,933) consisted of individuals who had received a primary or secondary SMI diagnosis between 2007 and 2018 and had available data for Health of Nations Outcome Scale (HoNOS) as disability measure. Physical comorbidities were defined using Chapters II–XIV of the International Classification of Diagnoses (ICD-10). RESULTS: More than 60 % of the sample had complex multimorbidity. The most common organ system affected were neurological (34.7%), dermatological (15.4%), and circulatory (14.8%). All specific comorbidities (ICD-10 Chapters) were associated with higher levels of disability, HoNOS total scores. Individuals with musculoskeletal, skin/dermatological, respiratory, endocrine, neurological, hematological, or circulatory disorders were found to be associated with significant difficulties associated with more than five HoNOS domains while others had a lower number of domains affected. CONCLUSIONS: Individuals with SMI and musculoskeletal, skin/dermatological, respiratory, endocrine, neurological, hematological, or circulatory disorders are at higher risk of disability compared to those who do not have those comorbidities. Individuals with SMI and physical comorbidities are at greater risk of reporting difficulties associated with activities of daily living, hallucinations, and cognitive functioning. Therefore, these should be targeted for prevention and intervention programs

Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria

Objectives: The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death. Methods: Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) 2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03–1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19–1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen. Discussion: The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations

Adaptive Evolution of Escherichia coli to an α-Peptide/β-Peptoid Peptidomimetic Induces Stable Resistance.

Antimicrobial peptides (AMPs) and synthetic analogues thereof target conserved structures of bacterial cell envelopes and hence, development of resistance has been considered an unlikely event. However, recently bacterial resistance to AMPs has been observed, and the aim of the present study was to determine whether bacterial resistance may also evolve against synthetic AMP analogues, e.g. α-peptide/β-peptoid peptidomimetics. E. coli ATCC 25922 was exposed to increasing concentrations of a peptidomimetic (10 lineages), polymyxin B (10 lineages), or MilliQ water (4 lineages) in a re-inoculation culturing setup covering approx. 500 generations. All 10 lineages exposed to the peptidomimetic adapted to 32 × MIC while this occurred for 8 out of 10 of the polymyxin B-exposed lineages. All lineages exposed to 32 × MIC of either the peptidomimetic or polymyxin B had a significantly increased MIC (16-32 ×) to the selection agent. Five transfers (≈ 35 generations) in unsupplemented media did not abolish resistance indicating that resistance was heritable. Single isolates from peptidomimetic-exposed lineage populations displayed MICs against the peptidomimetic from wild-type MIC to 32 × MIC revealing heterogeneous populations. Resistant isolates showed no cross-resistance against a panel of membrane-active AMPs. These isolates were highly susceptible to blood plasma antibacterial activity and were killed when plasma concentrations exceeded ≈ 30%. Notably, MIC of the peptidomimetic against resistant isolates returned to wild-type level upon addition of 25% plasma. Whole-genome sequencing of twenty isolates from four resistant lineages revealed mutations, in murein transglycosylase D (mltD) and outer-membrane proteins, which were conserved within and between lineages. However, no common resistance-conferring mutation was identified. We hypothesise that alterations in cell envelope structure result in peptidomimetic resistance, and that this may occur via several distinct mechanisms. Interestingly, this type of resistance result in a concomitant high susceptibility towards plasma, and therefore the present study does not infer additional concern for peptidomimetics as future therapeutics

A Fusarium solani endophyte vs fungicides: Compatibility in a Fusarium oxysporum f.sp. radicis-lycopersici – tomato pathosystem

The potential of FsK, a non-pathogenic endophytic Fusarium solani strain, to be utilized as a biocontrol agent in combination with nine selected fungicides registered in tomato crops in Greece was evaluated. In vitro fungitoxicity tests revealed that FsK was insensitive to doses exceeding 100 μg/mL of thiophanate-methyl, fenhexamid, cyprodinil, boscalid and mancozeb. On the contrary, prochloraz, fludioxonil, pyraclostrobin and difenoconazole were most toxic to FsK. None of the later fungicides affected conidial production in an adverse way. Drenching of tomato plants with the above fungicides at recommended doses did not significantly affect colonization of tomato roots by FsK as revealed by in vitro isolation and Real Time PCR quantification. The disease suppressive ability of FsK against Fusarium oxysporum f.sp.radicis lycopersici (FORL) was not adversely affected by the post-inoculation application of commercial formulations of fludioxonil (Switch) and pyraclostrobin (Comet) at the recommended doses. Even more, the Comet–FsK combination resulted in enhanced disease suppression compared to either of the two treatments applied individually. In conclusion, not only biocontrol agent FsK is suitable for use in tomato integrated disease management programs that include all tested fungicides but also, some FsK –fungicide combinations can have additive effect against FORL disease incidence. © 2018 British Mycological Societ

Tomato inoculation with the endophytic strain Fusarium solani K results in reduced feeding damage by the zoophytophagous predator nesidiocoris tenuis

Belowground symbiosis of plants with beneficial microbes is known to confer resistance to aboveground pests such as herbivorous arthropods and pathogens. Similarly, microbe-induced plant responses may also impact natural enemies of pests via the elicitation of plant defense responses and/or alteration of plant quality and growth. Nesidiocoris tenuis is a zoophytophagous predator and an efficient biological control agent of greenhouse pests. Its usefulness in plant protection is often hindered by its ability to damage plants at high predator population densities or when prey is scarce. In this study, we investigated the effect of Fusarium solani strain K (FsK), an endophytic fungal isolate that colonizes tomato root tissues, on the capability of N. tenuis to cause necrotic rings, an easily discernible symptom, on tomato stems and leaves. We found significantly less necrotic rings formed on FsK-inoculated plants for all tomato cultivars tested. FsK has been previously shown to confer ethylene-mediated tomato resistance to both foliar and root fungal pathogens; thus, the ethylene-insensitive Never ripe (Nr) and epinastic (epi) tomato plant mutant lines were included in our study to assess the role of ethylene in the recorded FsK-mediated plant damage reduction. The jasmonic acid (JA)-biosynthesis tomato mutant def-1 was also used since JA is known to mediate major anti-herbivore plant responses. We show that ethylene and JA are required for FsK to efficiently protect tomato plants from N. tenuis feeding. No necrotic rings were recorded on FsK-inoculated epi plants suggesting that ethylene overproduction may be key to tomato resistance to N. tenuis feeding. © 2018 Garantonakis, Pappas, Varikou, Skiada, Broufas, Kavroulakis and Papadopoulou

Colonization of legumes by an endophytic Fusarium solani strain FsK reveals common features to symbionts or pathogens

Plant cellular responses to endophytic filamentous fungi are scarcely reported, with the majority of described colonization processes in plant-fungal interactions referring to either pathogens or true symbionts. Fusarium solani strain K (FsK) is a root endophyte of Solanum lycopersicum, which protects against root and foliar pathogens. Here, we investigate the association of FsK with two legumes (Lotus japonicus and Medicago truncatula) and report on colonization patterns and plant responses during the establishment of the interaction. L. japonicus plants colonized by FsK complete their life cycle and exhibit no apparent growth defects under normal conditions. We followed the growth of FsK within root-inoculated plants spatiotemporally and showed the capability of the endophyte to migrate to the stem. In a bipartite system comprising of the endophyte and either whole plants or root organ cultures, we studied the plant sub-cellular responses to FsK recognition, using optical, confocal and transmission electron microscopy. A polarized reorganization of the root cell occurs: endoplasmic reticulum/cytoplasm accumulation and nuclear placement at contact sites, occasional development of papillae underneath hyphopodia and membranous material rearrangements towards penetrating hyphae. Fungal hyphae proliferate within the vascular bundle of the plant. Plant cell death is involved in fungal colonization of the root. Our data suggest that the establishment of FsK within legume tissues requires fungal growth adaptations and plant cell-autonomous responses, known to occur during both symbiotic and pathogenic plant-fungal interactions. We highlight the overlooked plasticity of endophytic fungi upon plant colonization, and introduce a novel plant-endophyte association. © 2019 Elsevier Inc

Challenges in the diagnosis and treatment of mucormycosis

The diagnosis and treatment of mucormycosis are challenging. The incidence of the disease seems to be increasing. Hematological malignancies are the most common underlying disease in countries with high income and uncontrolled diabetes in developing countries. Clinical approach to diagnosis lacks sensitivity and specificity. Radiologically, multiple (≥10) nodules and pleural effusion are reportedly associated with pulmonary mucormycosis. Another finding on computerized tomography (CT) scan, which seems to indicate the presence of mucormycosis, is the reverse halo sign. Microscopy (direct and on histopathology) and culture are the cornerstones of diagnosis. Molecular assays can be used either for detection or identification of mucormycetes, and they can be recommended as valuable add-on tools that complement conventional diagnostic procedures. Successful management of mucormycosis is based on a multimodal approach, including reversal or discontinuation of underlying predisposing factors, early administration of active antifungal agents at optimal doses, complete removal of all infected tissues, and use of various adjunctive therapies. Our armamentarium of antifungals is slightly enriched by the addition of two newer azoles (posaconazole and isavuconazole) to liposomal amphotericin B, which remains the drug of choice for the initial antifungal treatment, according to the recently published guidelines by ECIL-6, as well as those published by ECMM/ESCMID. Despite the efforts for better understanding of the pathogenesis, early diagnosis and aggressive treatment of mucormycosis, the mortality rate of the disease remains high. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology

Mucormycosis: Ten-year experience at a tertiary-care center in Greece

Presented here are the results of a retrospective analysis of all mucormycoses infections recorded at a tertiary hospital in Greece during the last 10 years. A total of 24 patients were identified, 15 male and 9 female, with ages ranging from 37 to 80 years. Twelve of the patients had soft tissue infections (2 with concomitant pulmonary infections), and 12 had rhinocerebral infections. Transmission could be traced in two cases; to nitroglycerin patches in one patient and to a lemon-tree-thorn scratch in the other. Among the 17 patients who underwent surgery, 11 survived. All seven patients on whom surgery was not performed died. Rapid diagnosis and treatment of mucormycosis are essential for patient survival. The severity of the patient’s underlying condition, the degree of immunosuppression, and prompt surgical treatment are the most important factors contributing to the outcome