Serum beta-secretase 1 (BACE1) activity increases in patients with mild cognitive impairment.

Beta-secretase 1 (BACE1) is considered as the key enzyme in amyloid-ß formation. Previous works suggest that high BACE1 activity may be present in brain, cerebrospinal fluid and serum of patients with late-onset Alzheimer's disease (LOAD) as well as mild cognitive impairment (MCI). Therefore, we evaluated whether serum BACE1 activity increases in MCI patients and is associated with the progression from MCI to dementia. BACE1 activity was measured in the serum of 259 MCI patients (162 amnestic-aMCI, 97 non-amnestic-naMCI) and 204 healthy Controls. After a median follow-up of 32 months (range: 10-153), 116 MCI progressed to dementia (87 aMCI and 29 naMCI). Serum BACE1 activity was higher in MCI compared with Controls (p < 0.001), and in aMCI with brain atrophy compared with naMCI without brain atrophy (p = 0.04). No difference in BACE1 activity emerged between converter and non-converter MCI, and this was true for both aMCI and naMCI. However, among aMCI with better cognitive performance (n. 163, MMSE score ≥24/30) those converting to dementia had higher BACE1 activity compared to stable ones (p = 0.05). This was not associated with an increased risk to develop dementia (hazard ratio: 1.65; 95% confidence interval: 0.67-4.01). In conclusion, serum BACE1 activity significantly increased in MCI patients (both amnestic and non-amnestic) compared with Controls. Moreover, higher serum BACE1 activity was observed only among aMCI with a better cognitive performance who progressed to dementia, suggesting that a dysregulation of this enzyme might be an early event primarily associated with neurodegeneration.

Clinical and demographic parameters predict the progression from mild cognitive impairment to dementia in elderly patients.

OBJECTIVES: To evaluate the possibility of predicting the risk of progression from mild cognitive impairment (MCI) to dementia using a combination of clinical/demographic parameters. METHODS: A total of 462 MCI elderly patients (follow-up: 33 months). Variable measured included cognitive functions, age, gender, MCI type, education, comorbidities, clinical chemistry, and functional status. RESULTS: Amnestic type (aMCI) represented 63% of the sample, non-amnestic (naMCI) 37%; 190 subjects progressed to dementia, 49% among aMCI, and 28% among naMCI. At Cox multivariate regression analysis, only MMSE (one point increase HR 0.84; 95% CI 0.79-0.90), aMCI (HR 2.35; 95% CI 1.39-3.98), and age (1 year increase HR 1.05; 95% CI 1.01-1.10) were independently associated with progression to dementia. A score was created based on these dichotomized variables (score 0-3): age (≥ or < 78 years), MMSE score (≥ or < 25/30) and aMCI type. The conversion rate progressed from 6% in subjects with score 0 (negative predictive value: 0.94), to 31% in individuals with score 1, to 53% in subjects with score 2, to 72% in individuals with score 3 (positive predictive value: 0.72). ROC curve analysis showed an area under the curve of 0.72 (95% CI 0.66-0.75, p 0.0001). CONCLUSIONS: We have described a simple score, based on previously recognized predictors such as age, MMSE, and MCI type, which may be useful for an initial stratification of the risk of progression to dementia in patients affected by MCI. The score might help the clinicians to evaluate the need for more expansive/invasive examinations and for a closer follow-up in MCI patients.

The Dynamic Changes of African Elephant Milk Composition over Lactation.

The combined data of milk composition of 14 African elephants over 25 months of lactation are presented. The milk density was constant during lactation. The total protein content increased with progressing lactation, with caseins as the predominant protein fraction. The total carbohydrates steadily decreased, with the oligosaccharides becoming the major fraction. Lactose and isoglobotriose reached equal levels at mid lactation. The milk fat content increased during lactation, as did the caprylic and capric acids, while the 12 carbon and longer fatty acids decreased. The fatty acid composition of the milk phospholipids fluctuated, and their total saturated fatty acid composition was low compared to the triacylglycerides. The milk ash and content of the major minerals, Na, K, Mg, P, and Ca, increased. Vitamin content was low, Vitamin E occurred in quantifiable amounts, with traces of vitamins A, D3, and K. The energy levels of African elephant milk did not change much in the first ten months of lactation, but they increased thereafter due to the increase in protein and fat content. The overall changes in milk composition appeared to be in two stages: (a) strong changes up to approximately 12 months of lactation and (b) little or no changes thereafter.

Risk Factors for Lacunar Strokes with Visible Cerebral Lesions on Computed Tomography Scan.

BACKGROUND: The aim of this study was the detection of risk factors for lacunar strokes with visible lesions on computed tomography (CT) scan, considering in particular clinical characteristics, echocardiographic parameters, and carotid-femoral pulse wave velocity (PWV, a marker of large-artery stiffness). Lacunar strokes with very small or nonvisible lesions may have different risk factors. METHODS: We examined 106 patients (mean age 66.9 ± 12.3 years, 60 men), including 55 patients with clinically lacunar stroke associated with deep ischemic lesions of .3-1.5 cm on brain CT scan, and 51 control patients with cortical ischemic stroke, with lesions of 2.5-10.0 cm. RESULTS: In multiple logistic regression, with respect to cortical strokes, the following variables were independently associated with lacunar strokes: tricuspid regurgitation velocity (inverse relationship, odds ratio [OR] .13, 95% confidence interval [CI] .04-.43, P = .0007, cutoff at 228 cm/s), mean systolic blood pressure (SBP) (OR 3.98, 95% CI 2.78-7.79, P = .008, cutoff at 145 mmHg), ever-smoker status (OR 2.68, 95% CI 1.06-6.80, P = .04), and atrial fibrillation (inverse relationship, OR .11, 95% CI .01-1.00, P = .0496). In univariate analysis, the patients with lacunar stroke also had a lower prevalence of mitral regurgitation. There were no differences between the 2 groups in relation to diabetes, cholesterol, left ventricular mass and dimensions, and PWV. CONCLUSIONS: The patients with lacunar strokes with visible cerebral lesions on CT scan, compared with the patients with cortical infarct, had a lower tricuspid regurgitation velocity, a higher mean SBP, a greater prevalence of ever-smokers, and a lower prevalence of atrial fibrillation.

Molecular detection of tick-borne pathogens in captive wild felids, Zimbabwe.

BACKGROUND: The populations of wild felids in Africa, of especially lions (Panthera leo) and cheetahs (Acinonyx jubatus), are declining and the species are classified as vulnerable to extinction by the International Union for Conservation of Nature. As infections with tick-borne pathogens (TBP) can become more of a problem in wild felids, there are relatively few studies on TBP in wild felids in Africa and on how these infections might influence population numbers. METHODS: To gain further knowledge on TBP in captive wild felids in Southern Africa, we collected whole blood from captive lions, Southern African wildcats, cheetahs and servals in Zimbabwe for PCRs against the 18S rRNA gene of the piroplasmids (Babesia, Theileria, Cytauxzoon) and Hepatozoon spp., and the 16S rRNA gene of Ehrlichia and Anaplasma spp. RESULTS: Overall, 78% of the lions (67/86) and all the Southern African wildcats (6/6), cheetahs (4/4) and servals (2/2) had evidence of infection with at least one organism. The organisms most commonly detected in the lions were B. leo (59%; 51/86), B. vogeli (12%; 10/86) and H. felis (11%; 9/86) while all the Southern African wildcats and servals were positive for B. vogeli and all the cheetahs were positive for B. leo. Mixed infections were found in 22% (15/67) of the PCR positive lions, most commonly B. leo and H. felis (27%; 4/15), and in 1 (50%) of the servals (B. vogeli and A. phagocytophilum). Two lions were infected with three TBP, mainly B. leo, H. canis and T. parva, and B. leo, A. phagocytophilum and T. sinensis. Mixed infections with B. vogeli and A. phagocytophilum were seen in a serval and a Southern African wildcat. Other TBP were detected at a low prevalence (≤2%) in lions, mainly H. canis, T. sinensis, T. parva, C. manul, E. canis, and E. canis-like and B. odocoilei-like organisms. CONCLUSIONS: Infections with tick-borne agents are common in captive wild felids in Zimbabwe.

Serological survey of Brucella canis in dogs in urban Harare and selected rural communities in Zimbabwe.

A cross-sectional study was conducted in order to detect antibodies for Brucella canis (B. canis) in dogs from urban Harare and five selected rural communities in Zimbabwe. Sera from randomly selected dogs were tested for antibodies to B. canis using an enzyme-linked immunosorbent assay. Overall, 17.6% of sera samples tested (57/324, 95% CI: 13.5-21.7) were positive for B. canis antibodies. For rural dogs, seroprevalence varied from 11.7% - 37.9%. Rural dogs recorded a higher seroprevalence (20.7%, 95% CI: 15.0-26.4) compared with Harare urban dogs (12.7%, 95% CI: 6.9-18.5) but the difference was not significant (p = 0.07). Female dogs from both sectors had a higher seroprevalence compared with males, but the differences were not significant (p > 0.05). Five and two of the positive rural dogs had titres of 1:800 and 1:1600, respectively, whilst none of the positive urban dogs had a titre above 1:400. This study showed that brucellosis was present and could be considered a risk to dogs from the studied areas. Further studies are recommended in order to give insight into the epidemiology of brucellosis in dogs and its possible zoonotic consequences in Zimbabwe. Screening for other Brucella spp. (Brucella abortus, Brucella melitensis and Brucella suis) other than B. canis is also recommended.

Seroprevalence of leptospirosis in dogs in urban Harare and selected rural communities in Zimbabwe.

A cross-sectional study was conducted to investigate seroprevalence of canine leptospirosis in urban Harare and five selected rural communities in Zimbabwe and to assess public awareness of the disease. Sera from randomly selected dogs were tested for antibodies to the serovars Canicola, Grippotyphosa, Icterohaemorrhagiae and Pomona of Leptospira interrogans using an enzyme-linked immunosorbent assay. Clinical chemistry was performed on all seropositive and selected seronegative sera to screen for hepatic and renal insufficiency. A questionnaire- based survey was conducted in Harare to assess dog owners' awareness of leptospirosis and other zoonoses. Overall, 15.6% of sera samples tested (39 out of 250; 95% confidence interval [CI]: 11.0% - 20.2%) were positive for leptospiral antibodies. A significantly higher (p < 0.05) seroprevalence was recorded in urban dogs than in rural dogs (25% vs. 11.2%). No significant difference in seroprevalence was observed amongst dogs from different rural communities or between sexes of dogs. There was a significant association between seropositivity and hepatic and/or renal insufficiency (p < 0.01), with dogs having hepatic and/or renal insufficiency being approximately twice as likely to be seropositive (relative risk = 1.96; 95% CI: 1.3-3.0). Of the dog owners, 78.8% (119/151) were aware of zoonoses. Except for rabies (92.4%), awareness of leptospirosis (5.0%) and other zoonoses amongst these owners was low. This study showed that leptospirosis was present and represented a risk to dogs from urban Harare and the selected rural communities in Zimbabwe. Availing training programmes for dog owners would be beneficial in improving disease control and reducing the public health risk of pet zoonoses.