Search

INTRODUCTION: In this study, we leverage proteomic techniques to identify communities of proteins underlying Alzheimer's disease (AD) risk among clinically unimpaired (CU) older adults. METHODS: We constructed a protein co‐expression network using 3869 cerebrospinal fluid (CSF) proteins quantified by SomaLogic, Inc., in a cohort of participants along the AD clinical spectrum. We then replicated this network in an independent cohort of CU older adults and related these modules to clinically‐relevant outcomes. RESULTS: We discovered modules enriched for phosphorylation and ubiquitination that were associated with abnormal amyloid status, as well as p‐tau181 (M4: β = 2.44, p < 0.001, M7: β = 2.57, p < 0.001) and executive function performance (M4: β = −2.00, p = 0.005, M7: β = −2.39, p < 0.001). DISCUSSION: In leveraging CSF proteomic data from individuals spanning the clinical spectrum of AD, we highlight the importance of post‐translational modifications for early cognitive and pathological changes. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of early-onset sepsis (EOS) of the newborn remains a controversial issue among providers due to the non-infectious symptomology which exists in the newborn period. Pre/post interventional quality improvement project in a level III NICU to reduce antibiotic utilization and ancillary laboratory tests with the introduction of an evidence-based guideline for the evaluation of EOS in the NICU. Primary outcome measures include mean number of empiric antibiotic treatment days and utilization rate (AUR), number of laboratory tests ordered, and incidence of unwarranted antibiotic therapy beyond the 48-h rule out period. Mean empiric antibiotic treatment days decreased from 2.94 to 1.58 days and overall antibiotic use decreased from 73.7% to 57.1%. Likewise, the mean AUR decreased from 212.5 to 147.6 days of therapy per 1000 patient days. There was an 86% decline in the number of ancillary tests and unwarranted antibiotic use beyond 48- h was reduced by 74%. Guidelines for EOS of the newborn should include a thorough baseline evaluation of the drivers of antibiotic use to create an evidence-based foundation. Reducing unnecessary antibiotic use and EOS evaluations in a safe and effective manner have the potential to lower consumer and healthcare expenditures while improving the long-term health of the newborn in the NICU. These findings emphasize the importance of implementing an evidence-based protocol for antibiotic stewardship in the NICU. With further research there is the potential to improve the healthcare of newborns while reducing expenditures in a safe, effective evaluation of EOS in the newborn population. • Early-onset sepsis remains a large contributor of morbidity and mortality. • Evidence-based practices can facilitate change within healthcare organizations. • Antibiotic stewardship can impact healthcare outcomes during the newborn period. • The neonatal early-onset sepsis calculator can reduce empiric antibiotic use. [ABSTRACT FROM AUTHOR]

Highlights • This study is the first study to determinate glial fibrillary acidic protein, aquaporin 4, and myelin oligodendrocyte glycoprotein levels in cerebrospinal fluid and astrocytic damage analysis in patients with GFAP astrocytopathy. • CSF-GFAP level and pathological examination of GFAP-Astrocytopathy patients revealed astrocyte damage. • CSF GFAP may be a sensitive biomarker with respect to the effects of therapy in GFAP astrocytopathy during the acute stage. Abstract Objective Determination of glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and myelin oligodendrocyte glycoprotein (MOG) levels in cerebrospinal fluid (CSF), and astrocytic damage analysis in patients with GFAP astrocytopathy (GFAP-A) and other conditions. Methods GFAP, AQP4, and MOG levels in CSF were detected via enzyme-linked immunosorbent assays. Anti-GFAP, anti-AQP4, and anti-MOG IgGs were detected via indirect immunofluorescence assays. Results In 32 GFAP-Astrocytopathy patients, CSF GFAP was significantly higher during acute exacerbation than it was in patients with MOG encephalomyelitis, multiple sclerosis, autoimmune encephalitis, and an "other inflammatory neurological disorders" group (all p < 0.0001). CSF GFAP levels were slightly higher in the GFAP-A group than in an anti-AQP4 IgG-positive neuromyelitis optica spectrum disorder group (p = 0.012). There were no significant differences between the CSF MOG and AQP4 levels in the GFAP-A group and those of other groups. CSF GFAP levels were significantly reduced after steroid treatment (p = 0.011). CSF GFAP levels differed significantly in GFAP-Astrocytopathy patients with and without encephalitis (p = 0.016). In GFAP-Astrocytopathy patients, CSF GFAP was correlated with Expanded Disability Status Scale (EDSS) score during attack (r = 0.545, p = 0.001). In follow-up examinations however, in GFAP-Astrocytopathy patients CSF GFAP level was not correlated with EDSS score 6 months later. Conclusions CSF GFAP level and pathological examination of GFAP-Astrocytopathy patients revealed astrocyte damage. CSF GFAP level was associated with steroid treatment at the acute stage, therefore CSF GFAP may be a sensitive biomarker with respect to the effects of therapy during the acute stage. [ABSTRACT FROM AUTHOR]

Leptomeningeal Carcinomatosis (LC) is the dissemination of cancer, commonly breast, lung, melanoma, acute lymphoblastic leukaemia and Non-Hodgkin lymphoma occurring through either direct extension from surrounding tumours or metastasis of a preexisting, parenchymal central nervous system tumour. A rise in the diagnosis of leptomeningeal disease has been seen with increased survival rates of cancer due to improved medical treatment, with 5-8% of patients with cancer going on to develop LC. Leptomeningeal Carcinomatosis spreads to the meninges, the outer covering of the brain and spinal cord, directly migrating into the cerebral spinal fluid (CSF), arachnoid and pia mater. This migration of tumour cells occurs throughout the arachnoid vessels or choroid plexus into the surrounding outer layers extending into the CSF. On entry into the CSF, tumour cells are infiltrated in a diffuse or multifocal manner where the leptomeninges cover the surface of the brain and spinal cord. This covering causes the meninges to become irritated causing patients to exhibit signs of photophobia, neck stiffness, neurological decline and cranial nerve defects. LC has a significant morbidity and mortality rate with a median survival of 4-6 weeks if untreated and 2-3 months if treated. Diagnosis is based on analysis of the cerebral spinal fluid, through detection of positive cytology of LC tumour cells, elevated protein and CSF pressures. Magnetic resonance imaging findings identify areas of meningeal enhancement indicative of meningeal irritation. The neuroscience nurse role in the patient care includes providing a supportive environment and thorough assessment of vital and neurological signs. Treatment aims to improve or maintain a patient's neurological status while prolonging survival and palliation. The literature review will highlight the diagnosis, progression and treatment for LC to further increase awareness and inform neuroscience nurses of increasing trends in management. [ABSTRACT FROM AUTHOR]

Abstract: Alzheimer''s disease (AD) is an epidemic facing the entire world. Increased knowledge gained during the past 25 years indicates that AD falls along a clinical and neuropathological spectrum represented as a continuum that extends from preclinical disease in which there are no symptoms, through early symptomatic phases, and finally to AD dementia. The Alzheimer''s research community recognizes that imaging, body fluids, and cognitive biomarkers contribute to enhanced diagnostic confidence for AD. There has also been emerging consensus regarding the use of AD biomarkers in clinical trials. The use of biomarkers in clinical trials and practice is hampered by the lack of standardization. In response to the emerging need for standardization, an international meeting of AD researchers was held in Melbourne, Australia, in March 2012 to bring together key researchers, clinicians, industry, and regulatory stakeholders with the aim of generating consensus on standardization and validation of cognitive, imaging, and fluid biomarkers, as well as lifestyle parameters used in research centers worldwide. [Copyright &y& Elsevier]

Abstract: Recognizing that international collaboration is critical for the acceleration of biomarker standardization efforts and the efficient development of improved diagnosis and therapy, the Alzheimer''s Association created the Global Biomarkers Standardization Consortium (GBSC) in 2010. The consortium brings together representatives of academic centers, industry, and the regulatory community with the common goal of developing internationally accepted common reference standards and reference methods for the assessment of cerebrospinal fluid (CSF) amyloid β42 (Aβ42) and tau biomarkers. Such standards are essential to ensure that analytical measurements are reproducible and consistent across multiple laboratories and across multiple kit manufacturers. Analytical harmonization for CSF Aβ42 and tau will help reduce confusion in the AD community regarding the absolute values associated with the clinical interpretation of CSF biomarker results and enable worldwide comparison of CSF biomarker results across AD clinical studies. [Copyright &y& Elsevier]

Summary: Objectives and methods: In order to establish an effective management for febrile infants under 4 months of age we analysed the causes of fever by using bacterial work up and a highly sensitive RT-PCR method during a 3-year-period. From February 1998 to January 2001, 263 infants under 4 months of age were admitted to our hospital because of fever (>38.0°C) and enrolled in this study. Results: Eighty-nine cases (33.8%) were diagnosed as lower respiratory infections, and 62 (23.5%) as urinary tract infections. Aseptic meningitis was found in 35 cases (13.2%) and fever of unknown origin in 22 (8.3%). Sepsis and purulent meningitis were found in three and two infants, respectively. Aseptic meningitis was the most common disease in infants below 30 days. Aseptic meningitis and fever of unknown origin revealed no seasonable tendency. Twelve cases out of 20 tested infants with aseptic meningitis showed positive results for enterovirus in CSF. Conclusion: Clinicians should consider age, sex and seasons when evaluating and treating infants with fever. Previously lumbar puncture, urinalysis and chest X-ray were recommended to avoid useless assays. These results also revealed that RT-PCR is a useful and significant assay to establish an exact diagnosis in very young infants. [Copyright &y& Elsevier]