Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon4 allele

Abeta is the major component of amyloid plaques characterizing Alzheimer's disease (AD). Abeta accumulation can be affected by numerous factors including increased rates of production and/or impaired clearance. Insulin-degrading enzyme (IDE) has been implicated as a candidate enzyme responsible for the degradation and clearance of Abeta in the brain. We have previously shown that AD patients exhibit abnormalities in insulin metabolism that are associated with apoliprotein E (APOE) status. The possible association of IDE with AD, as well as the link between APOE status and insulin metabolism, led us to examine the expression of IDE in AD. We report that hippocampal IDE protein is reduced by approximately 50% in epsilon4+ AD patients compared to epsilon4- patients and controls. The allele-specific decrease of IDE in epsilon4+ AD patients is not associated with neuronal loss since neuron-specific enolase levels were comparable between the AD groups, regardless of APOE status. Hippocampal IDE mRNA levels were also reduced in AD patients with the epsilon4 allele compared to AD and normal subjects without the epsilon4 allele. These findings show that reduced IDE expression is associated with a significant risk factor for AD and suggest that IDE may interact with APOE status to affect Abeta metabolism.     

Differentiation of Normal and Malignant Human Squamous Epithelium in Vivo and in Vitro: A Morphologic Study

We would like to thank John Ellis for expert photographic assistance, Mervin Jones and Linda Lovell for expert animal husbandry, and Dr. Dorothy Easty for establishing the cell line LICR-LON-HN-5, without which this study would not have been possible.

We report a light microscopic and ultrastructural analysis of the comparative degrees of differentiation seen in keratinocytes derived from the tongue and epidermis with those of a well-differentiated human squamous carcinoma cell line (LICR-LON-HN5). When growing on plastic substrates, all cultures had a similar morphology, with multilayering and the production of cornified envelopes. When cultured on collagen gels the structure was more organized, with keratohyalin granules and keratin whorl formation in both the normal and the malignant cultures. Normal keratinocytes injected into athymic mice produced epidermal cysts, while cells from the cell line produced well-differentiated squamous cell carcinomas, which were partially solid and partially cystic. The tumor was well organized, with identifiable basal cells, spin-ous cells, keratohyalin granules, and a prominent basal lamina at the stromal/epithelial interface. This model is to be developed for comparative studies between normal and malignant cells, with particular reference to basement membrane production and to investigations of the relative importance of extrinsic and intrinsic factors in the control of squamous differentiation.     

Early results of femoropopliteal bypass using a five millimeter «thin wall» polytetrafluoroethylene (Gore-Tex) prosthesis

We report the early results of a series of 86 femoropopliteal bypass operations in which a 5 mm diameter thin wall polytetrafluoroethylene (Gore-Tex) prosthesis was used. Sixty-five bypasses were implanted in men and 21 in women. Thirty bypasses were done in conjunction with an aortic bifurcation graft and 18 patients had a bilateral procedure. The indication for operation was severe claudication in 74 cases and critical ischaemia in 12 cases. The angiographic run-off was good (three patent vessels) in 22 limbs and poor (one or two patent vessels) in 64 limbs. The cumulative patency rate for the whole group was 62% after 18 months. Angiographic run-off and the indication for operation were both found to influence cumulative patency rate significantly (p=0.035 and p=0.055, respectively). We also compared the results obtained when run-off was poor with equivalent data from our own previously published series in which a standard 6 mm diameter Gore-Tex prosthesis was used. This shows a difference in patency rate, for example 57% against 37% after 18 months, in favour of the smaller bore thin wall graft.     

Acceptability and Feasibility of a 13-Week Pilot Randomised Controlled Trial Testing the Effects of Incremental Doses of Beetroot Juice in Overweight and Obese Older Adults

Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO₃⁻) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m²) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO₃⁻ (HN: 2 × 70 mL BJ/day) (2) medium-NO₃⁻ (MN: 70 mL BJ/day), (3) low-NO₃⁻ (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO₃⁻-depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO₃⁻ intake, and by measuring NO₃⁻ and NO₂⁻ concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO₃⁻ dose and the increase in plasma and urinary NO₃⁻ concentration (R² = 0.71, p < 0.001 and R² = 0.46 p < 0.001, respectively), but relationships between NO₃⁻ dose and changes in salivary NO₃⁻ and NO₂⁻ were non-linear (R² = 0.35, p = 0.002 and R² = 0.23, p = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults.     

Determinants of the Consumption of Regular Soda,Sport, and Energy Beverages in Spanish Adolescents

Increasing sugar-sweetened beverages (SSB) consumption and associated health impacts warrant health-policy action. We assessed associations of socioeconomic and lifestyle variables with adolescents’ consumption of regular soda (RSD), sport (SD), and energy (ED) drinks. Cross-sectional study of 3930 Spanish adolescents (2089 girls, 1841 boys) aged 13–18 years). We compared frequency of consuming each SSB type (European Food Safety Authority questionnaire) with sociodemographic and lifestyle variables (standardized questions). RSD, SD, and ED were consumed at least weekly by 72.7%, 32.3%, and 12.3% of participants, respectively, and more frequently (p < 0.001) by boys, compared to girls. Multivariate ordinal logistic regression showed inverse association between RSD, SD, and ED consumption and parental occupation-based socioeconomic status (p < 0.01). Daily smoking was associated (p < 0.001) with higher ED (OR 3.64, 95% CI 2.39–5.55) and RSD (OR 2.15, 95% CI 1.56–2.97) consumptions. SD intake was associated inversely with smoking (OR 0.60, 95% CI 0.40–0.89, p = 0.012) and directly with physical activity (OR 2.93, 95% CI 2.18–3.95, p < 0.001). School performance was lower among ED (OR 2.14, 95% CI, 1.37–3.35, p = 0.001) and RSD (OR 1.81, 95% CI 1.24–2.64, p = 0.002) consumers, compared to SD. Maleness and low socioeconomic status predicted SSB consumption. Smoking and low school performance were associated with higher ED and RSD intakes.     

The cost of lost productivity due to premature mortality associated with COVID-19: a Pan-European study

The European Journal of Health Economics - Economic cost estimates have the potential to provide a valuable alternative perspective on the COVID-19 burden. We estimate the premature mortality...     

Non-Hispanic Blacks undergoing distal pancreatectomy have higher risk-adjusted rates of morbidity and are more likely to be high-cost outliers

BackgroundFew studies evaluate racial disparities in costs and clinical outcomes for patients undergoing distal pancreatectomy (DP).MethodsWe queried the Healthcare Cost and Utilization Project State Inpatient Databases to identify patients undergoing DP. Multivariable regression (MVR) was used to evaluate the association between race and postoperative outcomes.Results2,493 patients underwent DP; 265 (10%) were black, and 221 (8%) were of Hispanic ethnicity. On MVR, black and Hispanic patients were less likely than whites to undergo surgery in high volume centers (OR 0.53, 95% CI [0.40, 0.71]; OR 0.45, 95% CI [0.32, 0.62]). Black patients had a greater risk of postoperative complication (OR 1.40, 95% CI [1.07, 1.83]), 90-day readmission (OR 1.53, 95% CI [1.15, 2.02]), prolonged length of stay (OR 1.74, 95% CI [1.25–2.44]), and of being a high cost outliers (OR 1.40, 95% CI [1.02, 1.91]) compared to white patients.ConclusionBlack patients have increased risk of having a postoperative complication, prolonged hospitalization, and of being a high-cost outlier than non-Hispanic whites.     

Evaluating mechanism and severity of injuries among trauma patients admitted to Sina Hospital, the National Trauma Registry of Iran

Purpose: Injuries are one of the leading causes of death and lead to a high social and financial burden. Injury patterns can vary significantly among different age groups and body regions. This study aimed to evaluate the relationship between mechanism of injury, patient comorbidities and severity of injuries. Methods: The study included trauma patients from July 2016 to June 2018, who were admitted to Sina Hospital, Tehran, Iran. The inclusion criteria were all injured patients who had at least one of the following: hospital length of stay more than 24 h, death in hospital, and transfer from the intensive care unit of another hospital. Data collection was performed using the National Trauma Registry of Iran minimum dataset. Results: The most common injury mechanism was road traffic injuries (49.0%), followed by falls (25.5%). The mean age of those who fell was significantly higher in comparison with other mechanisms (p < 0.001). Severe extremity injuries occurred more often in the fall group than in the vehicle collision group (69.0% vs. 43.5%, p < 0.001). Moreover, cases of severe multiple trauma were higher amongst vehicle collisions than injuries caused by falls (27.8% vs. 12.9%, p = 0.003). Conclusion: Comparing falls with motor vehicle collisions, patients who fell were older and sustained more extremity injuries. Patients injured by motor vehicle collision were more likely to have sustained multiple trauma than those presenting with falls. Recognition of the relationship between mechanisms and consequences of injuries may lead to more effective interventions.