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Routine preparation of paraffin embedded tissue for histopathological diagnosis, here termed conventional histological technique (CT), whether performed manually or using an automated system, requires approximately 12 h. We developed earlier a rapid acetone dehydration technique (AT) for processing biopsies of nervous tissue that meets requirements for preserving tissue morphology and staining properties, and reduces processing time to 3.3 h. We compared the morphology and staining properties of human organ biopsies including adrenal gland, liver, ovary, pancreas, prostate, testis and thyroid prepared using both AT and CT. Following fixation with 10% formaldehyde and processing by either AT or CT, sections were stained using routine and special staining, and immunohistochemical methods. We evaluated nuclear and cytoplasmic staining, staining intensity, sharpness of images and presence of artifacts such as cracking and folding. AT preserved the morphology and staining properties of the tissues as well as CT. Consequently, the rapid AT procedure is a promising alternative technique for tissue processing.Background Although small trials have detected microvascular obstruction (MVO) with variable frequency following restoration of epicardial blood flow, the independent impact of abnormal microvascular perfusion (MVP) in predicting patient outcome following emergent percutaneous coronary intervention in acute ST-segment-elevation myocardial infarction is unknown. The study aims to determine the impact of abnormal MVP following successful epicardial recanalization in ST-segment-elevation myocardial infarction. Methods MVP was analyzed by low mechanical index ultrasound imaging within 48 hours of emergent percutaneous coronary intervention in 297 patients with acute ST-segment-elevation myocardial infarction who had restoration of Thrombolysis in Myocardial Infarction grade 3 flow in the infarct vessel. Patients were divided into normal segmental replenishment (normal MVP) after high mechanical index impulses versus delayed replenishment but normal plateau intensity (delayed MVP) and both delayed replenishment anon and associated with significantly worse outcome even with Thrombolysis in Myocardial Infarction 3 flow in the infarct vessel.Background. Titrating hypnotic agents for patients who suffer from a cerebral insult is a challenging task. To date there is no real gold standard to precisely quantify electroencephalography (EEG) response in a fashion that could be utilized for patients with post-cerebral hemorrhage hydrocephaly. While we must administer "as per usual" analgesics for noxious stimuli, we have to administer the hypnotic agents more "sparingly" due to lack of objective monitoring. selleck chemical Methods. We compared 15 adult post-cerebral hemorrhage hydrocephalus patients undergoing ventriculo-peritoneal shunt placement with 15 controls matched for gender and approximate age. We set propofol target controlled infusion estimated plasma concentrations (Cp) to gradually reach 4 µg/mL over 4 minutes. To precisely quantify post-cerebral hemorrhage mental dysfunction, we used electronically retrieved bispectral index (BIS) and propofol Cp data points to create individual inhibitory monophasic mathematical model for each patient that incorporates an independent hysteresis "lag" function. Results. In post-cerebral hemorrhage patients Cp-BIS curve, C50 (propofol concentration associated with inhibitory 50% BIS response) cutoff point was significantly shifted to the left by 39%. Whereas before infusion and at stable propofol 4 µg/mL aneurismal surgical sides ipsilateral (75 ± 13, 25 ± 9) and contralateral (73 ± 15, 27 ± 9) mean ± SD BIS values were significantly lower than ipsilateral (95 ± 3, 46 ± 12) and contralateral (94 ± 3, 46 ± 12) matched controls. Conclusions. Using BIS as surrogate marker of propofol hypnotic effect, BIS monitoring in patients with post-cerebral hemorrhage hydrocephaly showed a pattern of change and trend that was similar albeit 39% significantly lower than subjects without.Friedreich's ataxia is the most common inherited form of ataxia in humans. It is caused by severe downregulation of Frataxin (FXN) expression instigated by hyperexpansion of the GAA repeats located in intron 1 of the FXN gene. Despite numerous studies focused on identifying compounds capable of stimulating FXN expression, current knowledge regarding cis-regulatory elements involved in FXN gene expression is lacking. Using a combination of episomal and genome-integrated constructs, we defined a minimal endogenous promoter sequence required to efficiently drive FXN expression in human cells. We generated 19 constructs varying in length of the DNA sequences upstream and downstream of the ATG start codon. Using transient transfection, we evaluated the capability of these constructs to drive FXN expression. These analyses allowed us to identify a region of the gene indispensable for FXN expression. Subsequently, selected constructs containing the FXN expression control regions of varying lengths were site-specifically integrated into the genome of HEK293T and human induced pluripotent stem cells (iPSCs). FXN expression was detected in iPSCs and persisted after differentiation to neuronal and cardiac cells, indicating lineage independent function of defined regulatory DNA sequences. Finally, based on these results, we generated AAV encoding miniFXN genes and demonstrated in vivo FXN expression in mice. Results of these studies identified FXN sequences necessary to express FXN in human and mouse cells and provided rationale for potential use of endogenous FXN sequence in gene therapy strategies for FRDA.Objective To test the hypothesis that superficial cartilage composition (T2) is associated with subsequent incidence or worsening of cartilage damage, and deep T2 with that of bone marrow lesions (BMLs) in knees without radiographic osteoarthritis (ROA). Design A total of 201 knees from the Osteoarthritis Initiative without ROA were included 78 from the healthy reference cohort, 60 without ROA but with risk factors, and 63 without ROA but with contralateral ROA. Year 1 (Y1) superficial and deep cartilage T2 were derived in the medial and lateral (weightbearing) femur (MF/LF) and tibia (MT/LT), using sagittal multiecho spin echo magnetic resonance images. Cartilage and BMLs were assessed in the medial (MFTJ) and lateral femorotibial joint (LFTJ) at Y1 and 3 years later. Binary logistic regression statistics were applied. Results Incidence or worsening of cartilage damage was more frequent (MFTJ 15%, LFTJ 13%) than incidence or worsening of BMLs (6.0%, 4.5%). In knees with incident or worsening cartilage lesions in the MF and LT, deep layer T2 in the same plate was elevated (MF, 43.

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