Small-molecule inhibitors of neurofibrillary lesion formation may have utility for treatment of Alzheimer’s disease and certain forms of frontotemporal lobar degeneration. These lesions are composed ...largely of tau protein, which aggregates to form intracellular fibrils in affected neurons. Previously it was shown that chronic overexpression of human tau protein within identified neurons (anterior bulbar cells) of the sea lamprey induced a phenotype-resembling tauopathic neurodegeneration, including the formation of tau filaments, fragmentation of dendritic arbors, and eventual cell death. Development of this neurodegenerative phenotype was blocked by chronic administration of a benzothiazole derivative termed N3 ((E)-2-4-(dimethylamino)phenylazo-6-methoxybenzothiazole) to lamprey aquaria. Here we examined the mechanism of action of N3 and an alkene analog termed N4 ((E)-2-2-4-(dimethylamino)phenylethenyl-6-methoxybenzothiazole) in vitro and in the lamprey model. Results showed that although both compounds entered the lamprey central nervous system, only N3 arrested tauopathy. On the basis of in vitro aggregation assays, neither compound was capable of directly inhibiting tau filament formation. However, N3, but not N4, was capable of partially antagonizing the binding of Thioflavin S to synthetic tau filaments. The results suggest that occupancy of N3-binding sites on nascent tau filaments may significantly retard the progressive degeneration accompanying tau overexpression in lamprey.
Cranial fasciitis rarely occurs as a circumscribed lesion in the diploic space without soft tissue involvement. It is even more rare in adults. We discuss the radiographic and pathological ...differential diagnosis for cranial fasciitis and review the literature regarding clinical presentation and prognosis.
A 27-year-old woman presented with scalp pain and headaches for several months. On physical examination, she had a raised, firm, tender mass above the right ear that was 3 cm in diameter over which there was mild alopecia. Magnetic resonance imaging scans showed a well circumscribed contrast enhancing mass within the diploic space.
Because of the patient's symptoms and the lack of a diagnosis, magnetic resonance imaging-guided surgical resection of the cranial lesion followed by placement of a titanium cranioplasty was recommended.
A nonspecific radiographic appearance warrants biopsy. Complete excision is the optimal treatment choice when the possibility of malignancy cannot be ruled out.
Lipid signaling has become a major research area of cell biology and there is a need for methods that accurately and easily measure substrates and products of lipases involved in cell signaling. In ...this report, we provide new methodology for separation of more than 10 lipids in one chromatographic run by high pressure liquid chromatography (HPLC) and detection with an evaporative light scattering detector (ELSD). There is no significant loss of sphingomyelin and no large baseline change, no peak obscures another, and acidic phospholipids are cleanly separated. We have optimized the procedure for a two-pump HPLC, an inexpensive silica column without the use of a column heater jacket and for low grade nitrogen. An application of the procedure separates lipids from Xenopus laevis cells. These cells are commonly used in the study of various lipid signaling paths in cell division, fertilization, and after expression of exogenous membrane receptors.
Many critically ill patients are transferred to other care facilities instead of to home at hospital discharge.
To identify patient-related factors associated with hospital discharge to a care ...facility after critical illness and to estimate the magnitude of risk associated with each factor.
Retrospective cohort study of 548 survivors of critical illness in a medical intensive care unit. Multivariable logistic regression was used to identify independent risk factors for discharge to a care facility. Only the first 72 hours of intensive care were analyzed.
Approximately one-quarter of the survivors of critical illness were discharged to a care facility instead of to home. This event occurred more commonly in older patients, even after adjustment for severity of illness and comorbid conditions (odds ratio OR 1.8 for patients ≥ 65 years of age vs patients < 65 years; 95% confidence interval CI, 1.1-3.1; P = .02). The risk was greatest for patients who received mechanical ventilation (OR, 3.4; 95% CI, 2.0-5.8; P < .001) or had hospitalizations characterized by severe cognitive dysfunction (OR, 8.1; 95% CI, 1.3-50.6; P = .02) or poor strength and/or mobility (OR, 31.7; 95% CI, 6.4-157.3; P < .001). The model showed good discrimination (area under the curve, 0.82; 95% CI, 0.77-0.86).
The model, which did not include baseline function or social variables, provided good discrimination between patients discharged to a care facility after critical illness and patients discharged to home. These results suggest that future research should focus on the debilitating effects of respiratory failure and on conditions with cognitive and neuromuscular sequelae.
Host genetic factors influence treatment responses to antiviral therapy in chronic hepatitis C virus (HCV) infection. We retrospectively investigated associations between host genetic markers and ...treatment-induced virologic responses to dual therapy with interferon-α and ribavirin in chronically infected HCV genotype 1 (g1)- and genotype 3 (g3)-infected individuals. A total of 171 patients (89 HCV g1 and 82 HCV g3 infected) were investigated for genetic markers influencing treatment-induced sustained virologic response (SVR). Overall, SVR was observed for 46/89 (52%) HCV g1- and 57/82 (70%) HCV g3-infected patients. Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18 and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT). Using additive (P=3.54×10(-4)) and dominant models (P=3.83×10(-4)), a dosage effect of the T allele was observed, with the dominance term not significant for this SNP. Logistic regression showed an association between HLA-C1/C1 and rapid virologic response in HCV g1 infections with an OR relative to the heterozygote of 10.0 (95% CI: 1.6-62.5, P=0.014). HLA-C2 homozygosity was a significant predictor of nonresponse to treatment in HCV g1-infected individuals (P=0.023).
The School of Social Work Community Clinic opened its doors in June, 2014 in a donated space in a local parish hall. With very few resources initially the clinic now has its own rented space, serves ...a caseload of over 200 marginalized community members and has provided field placement experiences for over 75 BSW/MSW, pharmacy, psychology, nutrition, nursing, and occupational therapy students. In this article, we will highlight the steps we took to create and develop the Clinic with a social justice/anti-oppressive foundation, and the practice-teaching approaches we use with our students. We will also describe how we are integrating an interprofessional and community-university partnership culture in our day-to-day work with marginalized populations. This process will be described and discussed in relation to both interprofessional health education and the provision of relevant and meaningful services to clients. The community development techniques we used to develop our clinic and how we have been able to grow and expand will be highlighted. The partners we have established in government, the university, and the community that have contributed to a more sustainable future are also described.
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Background: Immunohistochemistry (IHC)-based universal mismatch repair (UMMR) screening of incident colorectal (CRC) and endometrial (EC) tumors for deficient MMR (dMMR) associated ...with Lynch syndrome (LS) is supported by expert recommendations and is cost-effective. Heterogeneity in the approach to implementation of UMMR screening nationwide has been observed, suggesting knowledge gaps that could adversely impact anticipated outcomes. Studies of clinical UMMR screening can inform efforts to optimize implementation in the real world setting. Methods: In September 2011, Fox Chase Cancer Center (FCCC) began UMMR screening of incident (surgical) CRC/EC tumors. Providers were emailed a tailored UMMR Results letter intended to facilitate discussion of hereditary cancer risks and for distribution to patients. Content supported genetics consultation for an abnormal UMMR screen or for high-risk history (Hx) regardless of MMR status (i.e., personal Hx of any cancer; or 1st/2nd degree relative with a LS cancer and/or cancer <50). For comparison, clinical data on all CRC/EC surgical cases 3 months prior to implementation of UMMR screening were extracted from the medical record. Results: 55 surgeries for CRC/EC occurred in the 3 months pre-implementation (PRE) and 130 in the 9 months post-implementation (POST). 1 yr PRE and POST data will be presented at the 2012 Quality Symposium. Conclusions: The UMMR screening initiative greatly improved patient outcomes. Provider referral and documentation behavior was highly responsive to an abnormal screening result, but not high-risk cancer history alone. Table: see text
Parametric device shifts occur in a 0.25 μm CMOS sense amp circuit during a High Temperature Operation Life (HTOL) test, due to the positive bias stress on the pMOSFET devices. The positive gate bias ...from the HTOL stress causes a larger negative shift in the threshold voltage of the 5V pMOSFET devices and a mismatch in the transconductance of the differential pair, resulting in a decrease in the gain of the amplifier. Negative shifts in threshold voltage are also observed for 5V pMOSFET test structures for devices with no protect diodes (antenna ratio = 1000:1) after either Positive Bias Temperature Instability (PBTI) tests or Positive Bias Temperature Stress (PBTS). The PBTI and PBTS are caused by positive charge from interface states and bulk oxide traps.
The molecular characterization of measles virus (MeV) is a valuable epidemiological tool to monitor virus transmission and to discriminate between imported and endemic infection. There has been ...significant immigration into Ireland in recent years and many individuals originate from regions of high measles incidence. Ireland has had a number of outbreaks of MeV which appear attributable to sub-optimal vaccine uptake and possibly imported strains as new genotypes have been identified in recent years. To ascertain any significant changes in circulating measles genotypes we investigated 65 confirmed measles cases between the years 2002 and 2007. The laboratory diagnosis of measles was confirmed by detection of measles-specific IgM in oral fluid in conjunction with a real-time polymerase chain reaction assay targeting the MeV hemagglutinin gene. Phylogenetic analysis based on the 3' hypervariable region of the nucleoprotein gene was performed and three genotypes, all within measles clade D, were found to be circulating during this time period. In 2002 and 2003, genotype D8 (n = 2) was observed whereas genotype D7 was dominant in 2003 (n = 31). A distinct change in the circulating MeV genotype and increased genetic diversity was observed between 2004 and 2007. All cases were within genotype D4 (n = 32) but were phylogenetically distinct from each other. These data provide important epidemiologic baseline information on MeV in Ireland and facilitates detailed examination of measles transmission. J. Med. Virol. 81:125-129, 2009.
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