Background: Neuroscience can assist clinical understanding and therapy by finding neurobiological markers for mental illness symptoms. Objectives: To quantify biomarkers for schizophrenia and schizoaffective disorder ...Background: Neuroscience can assist clinical understanding and therapy by finding neurobiological markers for mental illness symptoms. Objectives: To quantify biomarkers for schizophrenia and schizoaffective disorder and relate these to discrete symptoms of psychosis. Methods: Within a case-control design with multiple exclusion criteria to exclude organic causes and confounding variables, 67 DSM IV-R diagnosed and 67 control participants from a defined hospital, clinic and community catchment area were investigated for candidate markers. Participants underwent protocol-based diagnostic-checking and symptom rating via Brief Psychiatric Rating Scale and Positive and Negative Syndrome Scale, functional-rating scales, biological sample-collection and sensory-processing assessment. Blood and urine samples were analysed for monoamine neurotransmitters, their metabolites, vitamin cofactors and intermediate-substances related to oxidative stress and metabolism of monoamines. Neurocognitive assessment of visual and auditory processing was conducted at both peripheral and central levels. Biomarkers were defined by Receiver Operating Curve (ROC) analysis. Spearman’s analysis explored correlations between discrete symptoms and the biomarkers. Results: Receiver Operating Curve (ROC) analysis identified twenty-one biomarkers: elevated urinary dopamine, noradrenaline, adrenaline and hydroxy pyrroline-2-one as a marker of oxidative stress. Other biomarkers were deficits in vitamins D, B6 and folate, elevation of serum B12 and free serum copper to zinc ratio, along with deficits in dichotic listening, distance vision, visual and auditory speed of processing, visual and auditory working memory and six middle ear acoustic reflex parameters. Discrete symptoms such as delusions, hostility, suicidality and auditory hallucinations were biomarker-defined and symptom biomarker correlations assumed an understandable pattern in terms of the catecholamines and their relationship to biochemistry, brain function and disconnectivity. Conclusions: In the absence of a full diagnosis, biomarker-symptom-signatures inform psychiatry about the structure of psychosis and provide an understandable pattern that points in the direction of a new neurobiological system of symptom-formation and treatment.展开更多
Approximately 40%of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence.Staphylococcus aureus,the predominant pathogen in human osteomyelitis,is known to persist by phenotypic a...Approximately 40%of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence.Staphylococcus aureus,the predominant pathogen in human osteomyelitis,is known to persist by phenotypic adaptation as small-colony variants(SCVs)and by formation of intracellular reservoirs,including those in major bone cell types,reducing susceptibility to antibiotics.Intracellular infections with S.aureus are difficult to treat;however,there are no evidence-based clinical guidelines addressing these infections in osteomyelitis.We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S.aureus relevant to osteomyelitis,including protein biosynthesis inhibitors(lincosamides,streptogramins,macrolides,oxazolidines,tetracyclines,fusidic acid,and aminoglycosides),enzyme inhibitors(fluoroquinolones and ansamycines),and cell wall inhibitors(beta-lactam inhibitors,glycopeptides,fosfomycin,and lipopeptides).The PubMed and Embase databases were screened for articles related to intracellular S.aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment,which resulted in 34 full-text articles fitting the inclusion criteria.The combined findings of these studies were largely inconclusive,most likely due to the plethora of methodologies utilized.Therefore,the reported findings in the context of the models employed and possible solutions for improved understanding are explored here.While rifampicin,oritavancin,linezolid,moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments,the scientific evidence for these is still relatively weak.We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S.aureus osteomyelitis to improve treatments and patient outcomes.展开更多
文摘Background: Neuroscience can assist clinical understanding and therapy by finding neurobiological markers for mental illness symptoms. Objectives: To quantify biomarkers for schizophrenia and schizoaffective disorder and relate these to discrete symptoms of psychosis. Methods: Within a case-control design with multiple exclusion criteria to exclude organic causes and confounding variables, 67 DSM IV-R diagnosed and 67 control participants from a defined hospital, clinic and community catchment area were investigated for candidate markers. Participants underwent protocol-based diagnostic-checking and symptom rating via Brief Psychiatric Rating Scale and Positive and Negative Syndrome Scale, functional-rating scales, biological sample-collection and sensory-processing assessment. Blood and urine samples were analysed for monoamine neurotransmitters, their metabolites, vitamin cofactors and intermediate-substances related to oxidative stress and metabolism of monoamines. Neurocognitive assessment of visual and auditory processing was conducted at both peripheral and central levels. Biomarkers were defined by Receiver Operating Curve (ROC) analysis. Spearman’s analysis explored correlations between discrete symptoms and the biomarkers. Results: Receiver Operating Curve (ROC) analysis identified twenty-one biomarkers: elevated urinary dopamine, noradrenaline, adrenaline and hydroxy pyrroline-2-one as a marker of oxidative stress. Other biomarkers were deficits in vitamins D, B6 and folate, elevation of serum B12 and free serum copper to zinc ratio, along with deficits in dichotic listening, distance vision, visual and auditory speed of processing, visual and auditory working memory and six middle ear acoustic reflex parameters. Discrete symptoms such as delusions, hostility, suicidality and auditory hallucinations were biomarker-defined and symptom biomarker correlations assumed an understandable pattern in terms of the catecholamines and their relationship to biochemistry, brain function and disconnectivity. Conclusions: In the absence of a full diagnosis, biomarker-symptom-signatures inform psychiatry about the structure of psychosis and provide an understandable pattern that points in the direction of a new neurobiological system of symptom-formation and treatment.
基金supported by a University of Adelaide Postgraduate Research Scholarship。
文摘Approximately 40%of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence.Staphylococcus aureus,the predominant pathogen in human osteomyelitis,is known to persist by phenotypic adaptation as small-colony variants(SCVs)and by formation of intracellular reservoirs,including those in major bone cell types,reducing susceptibility to antibiotics.Intracellular infections with S.aureus are difficult to treat;however,there are no evidence-based clinical guidelines addressing these infections in osteomyelitis.We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S.aureus relevant to osteomyelitis,including protein biosynthesis inhibitors(lincosamides,streptogramins,macrolides,oxazolidines,tetracyclines,fusidic acid,and aminoglycosides),enzyme inhibitors(fluoroquinolones and ansamycines),and cell wall inhibitors(beta-lactam inhibitors,glycopeptides,fosfomycin,and lipopeptides).The PubMed and Embase databases were screened for articles related to intracellular S.aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment,which resulted in 34 full-text articles fitting the inclusion criteria.The combined findings of these studies were largely inconclusive,most likely due to the plethora of methodologies utilized.Therefore,the reported findings in the context of the models employed and possible solutions for improved understanding are explored here.While rifampicin,oritavancin,linezolid,moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments,the scientific evidence for these is still relatively weak.We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S.aureus osteomyelitis to improve treatments and patient outcomes.
