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less then -1 = 0.90; 95% CI, 0.70-1.17; P = .295) and this persisted after adjustment for selected confounders in the subgroup (hazard ratio 0.80; 95% CI, 0.43-1.48; P = .476). CONCLUSIONS Childhood BMI is not associated with risk of respiratory events in adulthood. Effective transport of therapeutic nucleic acid to brain has been a challenge for the success of gene therapy for treating brain diseases. In this study, we proposed liposomal nanoparticles modified with brain targeting ligandsfor active brain targeting with enhanced BBB permeation and delivery of genes to brain. We targeted transferrin and nicotinic acetylcholine receptors by conjugating transferrin (Tf) and rabies virus glycoprotein (RVG) peptide to surface of liposomes. Liposomal formulations showed homogeneous particle size and ability to protect plasmid DNA against enzymatic degradation. These nanoparticles were internalized by brain endothelial cells, astrocytes and primary neuronal cells through energy-dependent endocytosis pathways. RVG-Tf coupled liposomes showed superior ability to transfect cells compared to liposomes without surface modification or single modification. Characterization of permeability through blood brain barrier (BBB) and functionality of designed liposomes were performed using an in vitro triple co-culture BBB model. Liposome-RVG-Tf efficiently translocated across in vitro BBB model and, consecutively, transfected primary neuronal cells. Notably, brain-targeted liposomes promoted in vivo BBB permeation. These studies suggest that modifications of liposomes with brain-targeting ligands are a promising strategy for delivery of genes to brain. OBJECTIVES To investigate the neuroprotective effect of Gingko biloba extract 761 (EGb761) in Alzheimer's disease (AD) models both in vivo and in vitro and the underlying molecular mechanism. METHODS Cultured BV2 microglial cells were treated with Aβ1-42 to establish an in vitro AD model. The in vivo rat AD model was established by injecting Aβ1-42. Cells were pre-treated with EGb761, and the proliferation and necroptosis were examined by MTT or flow cytometry assays, respectively. In addition, the membrane potential and oxidative stress were measured. Cognitive function was evaluated by the Morris water maze, and the activation of the JNK signaling pathway was quantified by Western blotting. RESULTS Cultured BV2 cells exhibited prominent cell death after Aβ1-42 induction, and this cell death was alleviated by EGb761 pre-treatment. EGb761 was found to relieve oxidative stress and suppress the membrane potential and calcium overload. EGb761 treatment in AD model rats also improved cognitive function deficits. Both cultured microglial cells and the rat hippocampus exhibited activation of the JNK signaling pathway, and EGb761 relieved this activation in cells. CONCLUSION Our results showed that EGb761 regulated cell proliferation, suppressed necroptosis and apoptosis, relieved mitochondrial damage, and ameliorated tissue damage to improve cognitive function in AD models. All of these effects may involve the suppression of the JNK signaling pathway. V.OBJECTIVE Poststroke depression (PSD) has a heterogeneous presentation and is often accompanied by cognitive impairment. This study aimed to identify distinct dimensions of depressive symptoms in older adults with PSD and to evaluate their relationship to cognitive functioning. DESIGN Cross-sectional factor and correlational analyses of patients with poststroke depression. SETTING Patients were recruited from the community and from acute inpatient stroke rehabilitation hospitals. PARTICIPANTS Participants had suffered a stroke and met DSM-IV criteria for major depression (≥18 Montgomery Åsberg Depression Scale; MADRS). INTERVENTION None. MEASUREMENTS MADRS was used to quantify depression severity at study entry. Neuropsychological assessment at the time of study entry consisted of measures of Global Cognition, Attention, Executive Function, Processing Speed, Immediate Memory, Delayed Memory, and Language. RESULTS There were 135 (age ≥50) older adult participants with PSD and varying degrees of cognitive impairment (MMSE Total ≥20). Factor analysis of the MADRS identified three factors, that is sadness, distress, and apathy. Items comprising each factor were totaled and correlated with neuropsychological domain z-score averages. Symptoms of the apathy factor (lassitude, inability to feel) were significantly associated with greater impairment in executive function, memory, and global cognition. Symptoms of the sadness and distress factors had no relationship to cognitive impairment. CONCLUSION PSD consists of three correlated dimensions of depressive symptoms. Apathy symptoms are associated with cognitive impairment across several neuropsychological domains. PSD patients with prominent apathy may benefit from careful attention to cognitive functions and by interventions that address both psychopathology and behavioral deficits resulting from cognitive impairment. OBJECTIVE This study investigates the prognostic significance of pre-operative symptom status and type of symptom in outcomes after carotid endarterectomy (CEA). METHODS This review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) to identify studies reporting peri-operative outcomes of CEA in symptomatic and asymptomatic patients. The last search was conducted in August 2019 and a methodological assessment was performed using the Newcastle Ottawa Scale. A meta-analysis of outcome data using the odds ratio (OR) as the summary statistic was conducted, and the precision of the effect was reported as 95% confidence interval (CI). Fixed effect or random effects models were used to calculate the pooled estimates. RESULTS Eighteen studies reporting a total of 91 895 patients were included in the meta-analysis. Asymptomatic patients had a lower peri-operative risk of stroke (OR 0.5, 95% CI 0.45-0.54; p less then .001) and death (OR 0.66, 95% CI 0.57-0.77; p less then .001) than symptomatic patients, but the risk of myocardial infarction was not significantly different (OR 0.98, 95% CI 0.84-1.15; p = .82). Those suffering a pre-procedural stroke had an increased peri-operative risk of stroke and death vs. patients suffering a pre-procedural transient ischaemic attack or amaurosis fugax. CONCLUSION Patients undergoing CEA after a stroke have worse peri-operative outcomes in terms of stroke and death. Further research needs to be performed to ascertain the value of this finding in risk stratification systems and to investigate potential aetiological associations between pre-operative symptom status and peri-operative risk following a CEA. PURPOSE To describe parents' perceptions of their responsibilities for their infant's care during admission to a single family room in a neonatal intensive care unit (NICU). DESIGN AND METHODS A qualitative study with semi-structured individual interviews conducted at a family-centered level III Finnish NICU in late 2016 and early 2017. The participants were 10 mothers and nine fathers of infants aged from six days to eight months. The data were analyzed with inductive content analysis. RESULTS The parents wanted to take responsibility for their infant's care during their stay in a single family room in the NICU, because it prepared them for their infant's discharge. The mothers and fathers reported that their responsibilities supported them as they grew into parenthood and enabled their infants' rights. On the other hand, the parents needed nurses to empower them to commit to, and take, responsibility for their infant's care and share decision making. The nurses also taught the parents caring skills. CONCLUSIONS Empowering parents to take responsibility enabled their infant's rights during their stay in a single family room in the NICU. More research is needed about how nurses transfer these responsibilities to parents and how those are connected to the infant's rights and well-being. PRACTICE IMPLICATIONS Organizations who provide single family rooms in NICUs need to develop guidelines that facilitate the responsibilities that parents and nurses have to care for the infants. Although parents are the infant's primary caregivers, they depend on nurses to ensure their infant is safely cared for. Accurate diagnosis of salivary gland tumors can be challenging because of the many diagnostic entities, the sometimes extensive morphologic overlap, and the rarity of most tumor types. The current understanding of molecular rearrangements in salivary gland tumor pathology, emphasizes the prospects for exploiting molecular alterations in salivary gland tumors for diagnosis and targeted therapy. As new targeted therapies emerge, it will become increasingly vital to incorporate appropriate molecular testing into the pathologic evaluation of salivary gland cancers. Gemella are gram-positive bacteria that rarely cause infective endocarditis (IE). This article summarizes the characteristics of a series of patients with Gemella IE. We identified cases of Gemella IE in patients aged >18 years old hospitalized at Cleveland Clinic between July 1, 2007, and January 1, 2018, within the institutional review board-approved Cleveland Clinic IE Registry. Clinical features were obtained by manual chart review. Thirteen cases of Gemella IE were identified and accounted for less then 1% of all cases of IE in the registry. Eight were native and 5 were prosthetic valve IE. All were left-sided. Sixty-nine percent had positive blood cultures for Gemella, but 31% were identified solely based on 16S rRNA polymerase chain reaction (PCR) of explanted valves with sequence identification. None had positive valve cultures. All were treated surgically and survived to hospital discharge. Gemella is a rare cause of IE, albeit likely underrecognized without utilization of valve PCR. Iclaprim is a novel diaminopyrimidine, which inhibits bacterial dihydrofolate reductase, and it is active against Gram-positive pathogens including emerging drug-resistant pathogens. In vitro activity of iclaprim and comparators against 1365 Gram-positive clinical isolates from patients with skin and skin structure infections (SSSI) from the United States, Asia Pacific, Latin America, Europe, Africa or Middle East collected between 2013 and 2017 were tested. Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI criteria. MIC90 for all S.aureus, methicillin-susceptible S. aureus, methicillin-resistant S. aureus, Streptococcus pyogenes, S. Chloroquine in vivo agalactiae, S. anginosus, S. constellatus, S. dysgalactiae and S. intermedius were 0.12, 0.12, 0.5, 0.03, 0.5, ≤0.004, ≤0.004, 0.12, and 0.008 μg/ml, respectively. The MIC for iclaprim was 8 to 32-fold lower than trimethoprim, the only FDA approved dihydrofolate reductase inhibitor, against all Gram-positive isolates including resistant phenotypes. Iclaprim demonstrated lower MICs than trimethoprim against a collection (2013-2017) of Gram-positive clinical isolates from patients with SSSI from the United States, Asia Pacific, Latin America, and Europe.
Read More: https://www.selleckchem.com/products/chloroquine-phosphate.html
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