Serum vitamin D in patients with mild cognitive impairment and Alzheimer's disease

Objectives: To determine the relevance of Mini-Mental State Examination (MMSE), serum 25-hydroxyvitamin D (25(OH)D3), and 1,25(OH)2D3 concentrations to mild cognitive impairment (MCI) and various stages of Alzheimer's disease (AD). Materials and Methods: The study included 230 participants (>74 years) allocated to three main groups: 1-healthy subjects (HS, n = 61), 2-patients with MCI (n = 61), and 3- patients with Alzheimer's disease (AD) subdivided into three stages: mild (n = 41), moderate (n = 35), and severe AD (n = 32). The cognitive status was evaluated using MMSE. Serum 25 (OH)D3 (ng/ml) and 1,25(OH)2D3 concentrations (pg/ml) were determined by competitive radioimmunoassay. Results: MMSE scores and 25(OH)D3 were decreased in MCI and all stages of the AD in both genders. MMSE variability was due to gender in HS (11%) and to 25(OH)D3 in MCI (15%) and AD (26%). ROC analysis revealed an outstanding property of MMSE in diagnosis of MCI (AUC, 0.906; CI 95%, 0.847–0.965; sensitivity 82%; specificity, 98%) and AD (AUC, 0.997; CI 95%, 0.992–1; sensitivity, 100%; specificity, 98%). 25(OH)D3 exhibited good property in MCI (AUC, 0.765; CI 95%, 0.681–0.849; sensitivity, 90%; specificity, 54%) and an excellent property in diagnosis of AD (AUC, 0.843; CI 95%, 0.782–0.904; sensitivity, 97%; specificity, 79%). Logistic analyses revealed that, in MCI, MMSE could predict (or classify correctly) with 97.6% accuracy (Wald, 15.22, β, −0.162; SE, 0.554; OR = 0.115:0.039–0.341; p =.0001), whereas 25(OH)D3 with 80% accuracy (Wald, 41,013; β, −0.213; SE, 0.033; OR = 0.808: 0.757–863; p =.0001). 25(OH)D3 was the only significant predictor for the severe AD and contributed to MMSE variability. Age and gender were significant predictors only in the moderate AD. In patients with MCI, 25(OH)D3 and 1,25(OH)2D3 were correlated men, but in case of the AD, they were correlated in women. Conclusions: MMSE and serum 25(OH)D3 concentrations could be useful biomarkers for prediction and diagnosis of MCI and various stages of the AD. The results support the utility of vitamin D supplementation in AD therapy regimen. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc

Census and ear-notching of black rhinos (Diceros bicornis michaeli) in Tsavo East National Park, Kenya

This paper updates the status of the black rhino population in Tsavo East National Park (NP). Data were acquired through aerial counts of the black rhino between 3 and 9 October 2010 using three fixed-wing husky aircrafts and a Bell 206L helicopter in an area of about 3,300 km2. Based on previous sightings of rhinos, the area was divided into 14 blocks, with each block subdivided into 400 m transects. An aircraft flying at about 500 m above the ground was assigned to carry out the aerial survey following these transects within each block. Observers scanned for rhinos about 200 m on either sides of the flight paths. Intensive searches in areas with dense vegetation, especially along the Galana and Voi Rivers and other known rhino range areas was also carried out by both the huskies and the helicopter. The count resulted in sighting of 11 black rhinos. Seven of these individuals were ear notched and fitted with radio transmitters and the horns were tipped off to discourage poaching. Three of the seven captured rhinos were among the 49 animals translocated to Tsavo East between 1993 and 1999. The other four animals were born in Tsavo East. Two female rhinos and their calves were not ear-notched or fitted with transmitters. It is recommended that another count be carried out immediately after the wet season as the rhinos spend more time in the open areas while the vegetation is still green. The repeat aerail count is to include blocks north of River Galana

Post-Partum Pituitary Insufficiency and Livedo Reticularis Presenting a Diagnostic Challenge in a Resource Limited Setting in Tanzania: A Case Report, Clinical Discussion and Brief Review of Existing Literature.

Pituitary disorders following pregnancy are an important yet under reported clinical entity in the developing world. Conversely, post partum panhypopituitarism has a more devastating impact on women in such settings due to high fertility rates, poor obstetric care and scarcity of diagnostic and therapeutic resources available. A 37 year old African female presented ten years post partum with features of multiple endocrine deficiencies including hypothyroidism, hypoadrenalism, lactation failure and secondary amenorrhea. In addition she had clinical features of an underlying autoimmune condition. These included a history of post-partum thyroiditis, alopecia areata, livedo reticularis and deranged coagulation indices. A remarkable clinical response followed appropriate hormone replacement therapy including steroids. This constellation has never been reported before; we therefore present an interesting clinical discussion including a brief review of existing literature. Post partum pituitary insufficiency is an under-reported condition of immense clinical importance especially in the developing world. A high clinical index of suspicion is vital to ensure an early and correct diagnosis which will have a direct bearing on management and patient outcome

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.Institute of Health Carlos III, ISCIII; Junta de Andaluci

MultiTest V.1.2, a program to binomially combine independent tests and performance comparison with other related methods on proportional data

<p>Abstract</p> <p>Background</p> <p>Combining multiple independent tests, when all test the same hypothesis and in the same direction, has been the subject of several approaches. Besides the inappropriate (in this case) Bonferroni procedure, the Fisher's method has been widely used, in particular in population genetics. This last method has nevertheless been challenged by the SGM (symmetry around the geometric mean) and Stouffer's <it>Z</it>-transformed methods that are less sensitive to asymmetry and deviations from uniformity of the distribution of the partial <it>P</it>-values. Performances of these different procedures were never compared on proportional data such as those currently used in population genetics.</p> <p>Results</p> <p>We present new software that implements a more recent method, the generalised binomial procedure, which tests for the deviation of the observed proportion of <it>P</it>-values lying under a chosen threshold from the expected proportion of such <it>P</it>-values under the null hypothesis. The respective performances of all available procedures were evaluated using simulated data under the null hypothesis with standard <it>P</it>-values distribution (differentiation tests). All procedures more or less behaved consistently with ~5% significant tests at <it>α </it>= 0.05. Then, linkage disequilibrium tests with increasing signal strength (rate of clonal reproduction), known to generate highly non-standard <it>P</it>-value distributions are undertaken and finally real population genetics data are analysed. In these cases, all procedures appear, more or less equally, very conservative, though SGM seems slightly more conservative.</p> <p>Conclusion</p> <p>Based on our results and those discussed in the literature we conclude that the generalised binomial and Stouffer's <it>Z </it>procedures should be preferred and <it>Z </it>when the number of tests is very small. The more conservative SGM might still be appropriate for meta-analyses when a strong publication bias in favour of significant results is expected to inflate type 2 error.</p

Automatic extraction of shorelines from Landsat TM and ETM+ multi-temporal images with subpixel precision

A high precision geometric method for automated shoreline detection from Landsat TM and ETM+ imagery is presented. The methodology is based on the application of an algorithm that ensures accurate image geometric registration and the use of a new algorithm for sub-pixel shoreline extraction, both at the sub-pixel level. The analysis of the initial errors shows the influence that differences in reflectance of land cover types have over shoreline detection, allowing us to create a model to substantially reduce these errors. Three correction models were defined according to the type of gain used in the acquisition of the original Landsat images. Error assessment tests were applied on three artificially stabilised coastal segments that have a constant and well-defined land-water boundary. A testing set of 45 images (28 TM, 10 ETM high-gain and 7 ETM low-gain) was used. The mean error obtained in shoreline location ranges from 1.22 to 1.63. m, and the RMSE from 4.69 to 5.47. m. Since the errors follow a normal distribution, then the maximum error at a given probability can be estimated. The results confirm that the use of Landsat imagery for detection of instantaneous coastlines yields accuracy comparable to high-resolution techniques, showing the potential of Landsat TM and ETM images in those applications where the instantaneous lines are a good geomorphological descriptor. © 2012 Elsevier Inc.The authors appreciate the financial support provided by the Spanish Ministerio de Ciencia e Innovacion and the Spanish Plan E in the framework of the Projects CGL2009-14220-C02-01 and CGL2010-19591.Pardo Pascual, JE.; Almonacid Caballer, J.; Ruiz Fernández, LÁ.; Palomar-Vázquez, J. (2012). Automatic extraction of shorelines from Landsat TM and ETM+ multi-temporal images with subpixel precision. Remote Sensing of Environment. 123:1-11. doi:10.1016/j.rse.2012.02.024S11112

Suppression of circulating IgD+CD27+ memory B cells in infants living in a malaria-endemic region of Kenya

Background: Plasmodium falciparum infection leads to alterations in B cell subset distribution. During infancy, development of peripheral B cell subsets is also occurring. However, it is unknown if infants living a malaria endemic region have alterations in B cell subsets that is independent of an age effect. Methods: To evaluate the impact of exposure to P. falciparum on B cell development in infants, flow cytometry was used to analyse the distribution and phenotypic characteristic of B cell subsets in infant cohorts prospectively followed at 12, 18 and 24 months from two geographically proximate regions in western Kenya with divergent malaria exposure i.e. Kisumu (malaria-endemic, n = 24) and Nandi (unstable malaria transmission, n = 21). Results: There was significantly higher frequency and absolute cell numbers of CD19+ B cells in Kisumu relative to Nandi at 12(p = 0.0440), 18(p = 0.0210) and 24 months (p = 0.0493). No differences were observed between the infants from the two sites in frequencies of naïve B cells (IgD+CD27-) or classical memory B cells (IgD-CD27+). However, immature transitional B cells (CD19+CD10+CD34-) were higher in Kisumu relative to Nandi at all three ages. In contrast, the levels of non-class switched memory B cells (CD19+IgD+CD27+) were significantly lower overall in Kisumu relative to Nandi at significantly at 12 (p = 0.0144), 18 (p = 0.0013) and 24 months (p = 0.0129). Conclusions: These data suggest that infants living in malaria endemic regions have altered B cell subset distribution. Further studies are needed to understand the functional significance of these changes and long-term impact on ability of these infants to develop antibody responses to P. falciparum and heterologous infections

Investigation of Host Candidate Malaria-Associated Risk/Protective SNPs in a Brazilian Amazonian Population

The Brazilian Amazon is a hypo-endemic malaria region with nearly 300,000 cases each year. A variety of genetic polymorphisms, particularly in erythrocyte receptors and immune response related genes, have been described to be associated with susceptibility and resistance to malaria. In order to identify polymorphisms that might be associated with malaria clinical outcomes in a Brazilian Amazonian population, sixty-four human single nucleotide polymorphisms in 37 genes were analyzed using a Sequenom massARRAY iPLEX platform. A total of 648 individuals from two malaria endemic areas were studied, including 535 malaria cases (113 individuals with clinical mild malaria, 122 individuals with asymptomatic infection and 300 individuals with history of previous mild malaria) and 113 health controls with no history of malaria. The data revealed significant associations (p<0.003) between one SNP in the IL10 gene (rs1800896) and one SNP in the TLR4 gene (rs4986790) with reduced risk for clinical malaria, one SNP in the IRF1 gene (rs2706384) with increased risk for clinical malaria, one SNP in the LTA gene (rs909253) with protection from clinical malaria and one SNP in the TNF gene (RS1800750) associated with susceptibility to clinical malaria. Also, a new association was found between a SNP in the CTL4 gene (rs2242665), located at the major histocompatibility complex III region, and reduced risk for clinical malaria. This study represents the first association study from an Amazonian population involving a large number of host genetic polymorphisms with susceptibility or resistance to Plasmodium infection and malaria outcomes. Further studies should include a larger number of individuals, refined parameters and a fine-scale map obtained through DNA sequencing to increase the knowledge of the Amazonian population genetic diversity

Genetic analysis of scattered populations of the Indian eri silkworm, Samia cynthia ricini Donovan: Differentiation of subpopulations

Deforestation and exploitation has led to the fragmentation of habitats and scattering of populations of the economically important eri silkworm, Samia cynthia ricini, in north-east India. Genetic analysis of 15 eri populations, using ISSR markers, showed 98% inter-population, and 23% to 58% intra-population polymorphism. Nei’s genetic distance between populations increased significantly with altitude (R2 = 0.71) and geographic distance (R2 = 0.78). On the dendrogram, the lower and upper Assam populations were clustered separately, with intermediate grouping of those from Barpathar and Chuchuyimlang, consistent with geographical distribution. The Nei’s gene diversity index was 0.350 in total populations and 0.121 in subpopulations. The genetic differentiation estimate (Gst) was 0.276 among scattered populations. Neutrality tests showed deviation of 118 loci from Hardy-Weinberg equilibrium. The number of loci that deviated from neutrality increased with altitude (R2 = 0.63). Test of linkage disequilibrium showed greater contribution of variance among eri subpopulations to total variance. D’2IS exceeded D’2ST, showed significant contribution of random genetic drift to the increase in variance of disequilibrium in subpopulations. In the Lakhimpur population, the peripheral part was separated from the core by a genetic distance of 0.260. Patchy habitats promoted low genetic variability, high linkage disequilibrium and colonization by new subpopulations. Increased gene flow and habitat-area expansion are required to maintain higher genetic variability and conservation of the original S. c. ricini gene pool

B Cell Depletion in HIV-1 Subtype A Infected Ugandan Adults: Relationship to CD4 T Cell Count, Viral Load and Humoral Immune Responses

To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001). HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb) titers against subtype A (p = 0.05) and subtype CRF02_AG (p = 0.02) viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02) and mean titer against the 10 viruses (p = 0.0002). In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001). These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection