Selectivity of excitotoxic mechanisms in Alzheimer's disease

Dysfunction of glutamatergic neurons in Alzheimer's disease may actually participate in some of the neurodegenerative processes via potential excitotoxic mechanisms. Two hypotheses are advanced which describe how a generalized excitotoxic mechanism could interact with unique metabolic properties of specific cell types leading to their selective vulnerability in Alzheimer's disease.     

Characterization of SV40 enhancer motifs involved in positive and negative regulation of the constitutive late promoter activity; effect of T-antigen.

By analyzing the late promoter activity of a series of nonreplicative recombinants mutated within the different enhancer motifs of SV40 we identified both positive and negative regulatory elements. In the absence of T-antigen, the motifs Sph and/or octamer, and to a lesser extent the motifs GTI and P, account for the constitutive expression of the late promoter. The motif GTII overlaps elements that negatively regulate the expression of the late promoter. These results indicate that the late promoter is down-regulated not only at the level of the GC motifs but also at the enhancer level. Moreover, we showed that T-antigen interacts with both positive and negative regulatory elements.     

The polymorphism of HLA-DR3 in South African populations

The polymorphism of HLA-DR3 was investigated in families and unrelated individuals of three population groups: South African (SA) Negroes, Cape Coloureds and SA Caucasoids. Serological and restriction fragment length polymorphism (RFLP) analysis indicated that DR3 could be subdivided into DRw17 (previously DR3.1) and DRw18 (previously DR3.2). In contrast, the two-dimensional (2-D) gel electrophoresis patterns could not distinguish between the DRB1 gene products of the HLA-DRw17 and DRw18 cells. Two DRB3 variants, correlating with the T-cell defined specificities Dw24 and Dw25 were identified at the genomic and product level. Of ten haplotypes studied with the newly defined HLA-DRw18 specificity, all had the DRB3 RFLP pattern associated with Dw24. HLA-DRw17 was found in all three population groups tested, although in the SA Negroes HLA-DRw18 was the prevalent DR3 subgroup. This subgroup was also present in the Cape Coloureds but was absent in the SA Caucasoid tested. HLA-DRw18 forms part of the most characteristic SA Negro haplotype, Bw42, DQw4, Dw“RSH,” while HLA-DRw17 is part of the classic Caucasoid haplotype, B8, DQw2, Dw3.     

Student's perceptions of a virtual PBL experience.

OBJECTIVE: Our purpose is to present findings regarding student attitudes towards a virtual PBL program used to standardize their pediatric clinical experience. DESCRIPTION: With funding provided by the Fund for the Improvement of Post-Secondary Education, we developed Project LIVE (Learning through Interactive Video Education), a CD-ROM/Web hybrid program that uses digital video cases to conduct "virtual" problem-based learning groups with students doing a clinical rotation in a remote setting. Cases were progressively disclosed by videos of patient/physician encounters on a CD-ROM. Groups of five students and a faculty facilitator collaborated, teaching each other within the discussion section of the program. We conducted a multifaceted evaluation of Project LIVE to study the impact of case modality or distance on student learning and attitudes. We placed students in one of three groups (1) a face-to-face group with a paper case (FFT), (2) a face-to-face group with a video case (FFV), and (3) a virtual group (VG) with the digital video case. We then studied student attitudes about the three teaching formats. Over a six-month period three education specialists, who were not a part of the development team, conducted eight focus groups lasting one hour to assess student attitudes about Project LIVE. No one from the project team was present during these groups, and an independent evaluator analyzed the notes taken by each focus group leader. DISCUSSION: Trends across the groups included the following: (1) Authenticity (video)-Students reported that the authenticity of the case was a critical feature and that, "seeing (videos) made learning more memorable." Virtual and FFV groups reported more confidence in their ability to recognize abnormal findings in their patients. "You can't expect to teach clinical exam skills with a piece of paper." (2) Use of time-Students from all groups believed the cases were a good use of their time and improved their ability to solve clinical problems. They said it gave them an opportunity to "get away from just doing and focus on learning." However, the virtual groups complained of the lack of "a barometer for how much is too much" time. Some students reported spending an average of eight to ten hours per case over the period of a week. (In contrast, face-to-face groups met for three hours.) (3) Modeling clinical reasoning-Students believed the cases were valuable in structuring their knowledge, conceptualizing how to handle difficult situations, distinguishing abnormal from normal physical examination findings, and collaborating with their peers and their mentor to develop critical thinking. "It forced us to be logical" and ". how to think through the process-it mimics the real setting." (4) Technical support-The responsiveness of the Project LIVE staff was essential in assisting students in troubleshooting problems. (5) Distance component-Students preferred to work through the cases in face-to-face groups but agreed that the virtual experience is "good if you are in the middle of nowhere." This program was enjoyed by students and gave us an approach to standardizing experiences across multiple clinical sites.     

Risks of AKI and Major Adverse Clinical Outcomes in Patients with Severe Acute Respiratory Syndrome or Coronavirus Disease 2019

BackgroundSevere acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) are closely related. The effect of AKI on the clinical outcomes of these two conditions is unclear.MethodsThis retrospective, territory-wide cohort study used an electronic public healthcare database in Hong Kong to identify patients with SARS or COVID-19 by diagnosis codes, virologic results, or both. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death.ResultsWe identified 1670 patients with SARS and 1040 patients with COVID-19 (median ages, 41 versus 35 years, respectively). Among patients with SARS, 26% met the primary endpoint versus 5.3% of those with COVID-19. Diabetes mellitus, abnormal liver function, and AKI were factors significantly associated with the primary endpoint among patients with either SARS or COVID-19. Among patients with SARS, 7.9%, 2.1%, and 3.7% developed stage 1, stage 2, and stage 3 AKI, respectively; among those with COVID-19, 6.6%, 0.4%, and 1.1% developed stage 1, stage 2, and stage 3 AKI, respectively. In both groups, factors significantly associated with AKI included diabetes mellitus and hypertension. Among patients with AKI, those with COVID-19 had a lower rate of major adverse clinical outcomes versus patients with SARS. Renal function recovery usually occurred within 30 days after an initial AKI event.ConclusionsAKI rates were higher among patients with SARS than those with COVID-19. AKI was associated with major adverse clinical outcomes for both diseases. Patients with diabetes mellitus and abnormal liver function were also at risk of developing severe consequences after SARS and COVID-19 infection.     

Parameters influencing piezoelectric shock wave lithotripsy of biliary calculi

A total of 225 human gallbladder stones were divided into sets of two, three, or four identical calculi (with maximum diameters of 6-26 mm) and submitted to piezoelectric shock wave lithotripsy in vitro in order to investigate the influence of the following parameters on stone disintegration: shock wave intensity, pulse frequency, and various physicochemical parameters such as the volume and viscosity of the fluid surrounding the stone, the hardness of the calculus, and its chemical composition. The fragmentation efficacy increased with enhanced shock wave energy (P less than 0.01). If the volume of the fluid (30 mL) surrounding the calculus was small, the disintegration end-point (defined by maximum fragment diameters less than or equal to 4 mm) was achieved after a lower number of pulses (median: 250 pulses) than in the case of a large fluid volume (80 mL) (500 pulses; P less than 0.01). On the other hand, however, factors such as the shock wave pulse rate (0.9 Hz vs 1.6 Hz), variations in viscosity of a water-jelly mixture surrounding the stone, the chemical composition of the stones as determined by X-ray diffractometry, and stone hardness were found to have no significant influence on the fragmentation efficacy.