Abstract Background Brain imaging studies of early Alzheimer's disease (AD) have shown decreased metabolism predominantly in the posterior cingulate cortex (PCC), medial temporal lobe, and inferior ...parietal lobe. This study investigated functional connectivity between these regions, as well as connectivity between these regions and the whole brain. Methods Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies were performed in subjects with early AD, mild cognitive impairment (MCI), and normal controls. Results The data indicate both decreased fiber connections and disrupted connectivity between the hippocampus and PCC in early AD. The MCI group showed reduced fiber numbers derived from PCC and hippocampus to the whole brain. Conclusions The fMRI and DTI results confirmed decreased connectivity from both the PCC and hippocampus to the whole brain in MCI and AD and reduction in connectivity between these two regions, which plausibly represents an early imaging biomarker for AD.
Patients with ulcerative colitis are at increased risk for colorectal cancer, although mechanisms underlying neoplastic transformation are poorly understood. We sought to evaluate the role of ...microRNAs in neoplasia development in this high-risk population.
Tissue from 12 controls, 9 ulcerative colitis patients without neoplasia, and 11 ulcerative colitis patients with neoplasia was analyzed. miRNA array analysis was performed and select miRNAs assayed by real-time PCR on the discovery cohort and a validation cohort. DNA methylation of miR-193a was assessed. Following transfection of miR-193a-3p, proliferation, IL17RD expression, and luciferase activity of the 3'UTR of IL17RD were measured. Tumor growth in xenografts as well as EGFR signaling were assessed in HCT116 cells expressing IL17RD with either a mutant 3' untranslated region (UTR) or wild-type (WT) 3'UTR.
miR-31, miR-34a, miR-106b, and miR-193a-3p were significantly dysregulated in ulcerative colitis-neoplasia and adjacent tissue. Significant down-regulation of miR-193a-3p was also seen in an independent cohort of ulcerative colitis cancers. Changes in methylation of miR-193a or expression of pri-miR-193a were not observed in ulcerative colitis cancer. Transfection of miR-193a-3p resulted in decreased proliferation, and identified IL17RD as a direct target of miR-193a-3p. IL17RD expression was increased in ulcerative colitis cancers, and miR-193a-3p treatment decreased growth and EGFR signaling of HCT116 cells in xenografts expressing both IL17RD with WT 3'UTR compared with cells expressing IL17RD with mutant 3'UTR.
miR-193a-3p is downregulated in ulcerative colitis neoplasia, and its loss promotes carcinogenesis through upregulation of IL17RD. These findings provide novel insight into inflammation-driven colorectal cancer and could suggest new therapeutic targets in this high-risk population.
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We evaluated neuropathological consequences of fetal ZIKV exposure in rhesus monkeys, a translatable animal model for human neural development, by carrying out quantitative neuroanatomical analyses ...of the nearly full-term brains of fetuses infected with ZIKV and procedure-matched controls. For each animal, a complete cerebral hemisphere was evaluated using immunohistochemical (IHC) and neuroanatomical techniques to detect virus, identify affected cell types, and evaluate gross neuroanatomical abnormalities. IHC staining revealed the presence of ZIKV in the frontal lobe, which contained activated microglia and showed increased apoptosis of immature neurons. ZIKV-infected animals exhibited macrostructural changes within the visual pathway. Regional differences tracked with the developmental timing of the brain, suggesting inflammatory processes related to viral infiltration swept through the cortex, followed by a wave of cell death resulting in morphological changes. These findings may help explain why some infants born with normal sized heads during the ZIKV epidemic manifest developmental challenges as they age.
The computer self test (CST) is an interactive, internet-based instrument designed to assess functional cognitive domains impaired by Alzheimer's disease (AD) and mild cognitive impairment (MCI). ...This study consisted of 215 total subjects with a mean age of 75.24. The 84 cognitively impaired patients (excluding patients diagnosed as MCI) met all criteria set forth by NINCDS/ADRDA for the diagnosis of AD. Control participants consisted of 104 age-matched individuals who were cognitively unimpaired. All patients completed the CST prior to other routine neurocognitive procedures. The CST accurately classified 96% of the cognitively impaired individuals as compared to controls, while the Mini-Mental Status Examination (MMSE) accurately classified 71% and the Mini-Cog 69% in the same respect. In addition, the CST accurately classified 91% of the six experimental groups (control, MCI, early AD, mild to moderate, moderate to severe, and severe) as compared to 54% for the MMSE and 48% for the Mini-Cog. In conclusions, the CST demonstrates a high degree of sensitivity and specificity and is capable of accurately identifying cognitive impairment in patients with variable degrees of cognitive abnormality. This interactive internet-based cognitive screening tool may aid in early detection of cognitive impairment in the primary care setting. The ease of use and interpretation may also provide the means to obtain an accurate baseline from which to monitor cognitive changes over time.
Abstract
Background: Functional neuroimaging studies have observed preserved neural activation to personally relevant stimuli in patients within the disorders of consciousness (DOC) spectrum. As the ...majority of studies have focused on adult DOC patients, little is known about preserved activation in the developing brain of children with impaired consciousness.
Case study: The aim of this study is to use fMRI to measure preserved neural activation to personally relevant stimuli (subject's own name and familiar voice) in a paediatric patient who sustained a traumatic brain injury and anoxic-ischaemia following a motor vehicle accident at 18 months of age rendering her probable for minimally conscious state. Contrasts revealed activation in the right middle frontal gyrus when hearing the subject's own name and the anterior supramarginal gyrus when hearing a familiar voice.
Conclusion: This study provides preliminary support for fMRI as a method to measure preserved cognitive functioning in paediatric DOC patients.
•Nitrofurantoin and fosfomycin are recommended for simple cystitis.•Co-trimoxazole, fluoroquinolones, and oral cephalosporins are not recommended empirically.•Extended-spectrum β-lactamase prevalence ...was 54%.•Susceptibility rates were significantly higher in West, South, and Northeast India.
Evidence-based prescribing is essential to optimize patient outcomes in cystitis. This requires knowledge of local antibiotic resistance rates. Diagnostic and Antimicrobial Stewardship (DASH) to Protect Antibiotics (https://dashuti.com/) is a multicentric mentorship program guiding centers in preparing, analyzing and disseminating local antibiograms to promote antimicrobial stewardship in community urinary tract infection. Here, we mapped the susceptibility profile of Escherichia coli from 22 Indian centers.
These centers spanned 10 Indian states and three union territories. Antibiograms for urinary E. coli from the outpatient departments were collated. Standardization was achieved by regional online training; anomalies were resolved via consultation with study experts. Data were collated and analyzed.
Nationally, fosfomycin, with 94% susceptibility (inter-center range 83-97%), and nitrofurantoin, with 85% susceptibility (61-97%), retained the widest activity. The susceptibility rates were lower for co-trimoxazole (49%), fluoroquinolones (31%), and oral cephalosporins (26%). The rates for third- and fourth-generation cephalosporins were 46% and 52%, respectively, with 54% (33-58%) extended-spectrum β-lactamase prevalence. Piperacillin-tazobactam (81%), amikacin (88%), and meropenem (88%) retained better activity; however, one center in Delhi recorded only 42% meropenem susceptibility. Susceptibility rates were mostly higher in South, West, and Northeast India; centers in the heavily populated Gangetic plains, across north and northwest India, had greater resistance. These findings highlight the importance of local antibiograms in guiding appropriate antimicrobial choices.
Fosfomycin and nitrofurantoin are the preferred oral empirical choices for uncomplicated E. coli cystitis in India, although elevated resistance in some areas is concerning. Empiric use of fluoroquinolones and third-generation cephalosporins is discouraged, whereas piperacillin/tazobactam and aminoglycosides remain carbapenem-sparing parenteral agents.
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