The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

A multi-approach study of the interaction of the Cu(II) and Ni(II) ions with alanylglycylhistamine, a mimicking pseudopeptide of the serum albumine N-terminal residue.

The protonation equilibria of alanylglycylhistamine (Ala-Gly-Ha) and the complexation of this ligand with Cu(II) and Ni(II) have been studied by pH-potentiometry, 1H and 14N NMR spectroscopy, electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), UV-Vis spectrophotometry and electron paramagnetic resonance (EPR). From pH approximately 2-12, the following complexes: MLH, MLH(-1), MLH(-2) and MLH(-3) are successively formed in aqueous solutions, the ligand under its neutral form being noted L. At physiological pH, the MLH(-2) complex is predominant. The coordination in this complex is assumed by one amino, two deprotonated peptide and one imidazole nitrogen atoms. The ESI-MS study confirmed the formation of the MLH(-1), MLH(-2) and MLH(-3) complexes. The structure of MLH(-2) was determined by single crystal X-ray analysis. CD and UV-Vis techniques allowed us to propose that the imidazole-N3 nitrogen acts as the anchor group for the coordination to the metal(II) ions rather than the amino group. At high pH values, the further deprotonation of the N-H imidazole group, leading to the formation of MLH(-3), occurs, as revealed by 1H NMR spectroscopy.

Viktor Hamburger's Department of Zoology in the 1940s: a student perspective.

Eleanor and Byron Wenger were graduate students in the Department of Zoology in the 1940s. Both took several courses with Viktor, and he was thesis advisor for both of us. We have attempted to provide a summary of life in the department from a student perspective as well as our impression of Viktor's style of mentoring and guiding student research and education.

Morphometric analysis of the corpus callosum using MR: correlation of measurements with aging in healthy individuals.

PURPOSE: To analyze changes of the human corpus callosum and MR midsagittal brain structures during normal aging. METHODS: A morphometric evaluation strategy for quantification of these brain structures on MR scans was developed. This computerized measuring program did allow the acquisition of more than 100 one- and two-dimensional parameters. RESULTS: During normal aging, the anterior parts of the corpus callosum (genu and anterior parts of the trunk) were significantly decreased, suggesting alterations of frontal and temporal interhemispheric fiber systems. Further changes were seen in callosal thickness and callosal width of the anterior parts of the corpus callosum. The profile area of the telencephalon was significantly reduced during normal aging. The size of the mesencephalon showed age-specific changes. CONCLUSIONS: The proposed computer program proved to be a powerful and reliable tool to get objective and reproducible quantitative data of corpus callosum and midsagittal brain structures. Specific age changes were found in the corpus callosum, indicating alteration of the frontotemporal interhemispheric fiber systems.

Transcallosal approach to the third ventricle: normative morphometric data based on magnetic resonance imaging scans, with special reference to the fornix and forniceal insertion.

OBJECTIVE: The ability to visualize median-sagittal brain structures by magnetic resonance imaging (MRI) improves the planning for surgical removal of lesions located in and around the third ventricle. The transcallosal approach is the most appropriate path to the anterior part of the third ventricle. The present study was undertaken to obtain normative morphometric data, derived from sagittal MRI scans, which are necessary for operation planning that takes into account the surgical microanatomy and landmarks encountered during this approach. METHODS: The morphometric evaluation was performed on 72 median-sagittal MRI scans. The surface landmarks for the corridor were the two points, P5 and P7, located 5 and 7 cm anterior to the central sulcus, respectively. With these two points on the cortical surface as references, a variety of measurements were made to provide quantitative information about distances between brain structures encountered during the surgical approach. In addition, various parameters were determined to characterize the different shapes of the fornix and the different types of forniceal insertion. RESULTS: The following measurements (means) were obtained: 1) the distance between P5/P7 and the cingulate sulcus was 25.76 mm (range, 17.113-42.73 mm) with reference to P5, and 25.41 mm (range, 12.91-36.29 mm) with reference to P7; 2) the distance between the cingulate sulcus and the corpus callosum was 12.91 mm (range, 7.19-22.60 mm) with reference to P5, and 12.92 mm (range, 6.75-23.37 mm) with reference to P7; 3) the height of the corpus callosum was 6.22 mm (range, 3.07-9.00 mm) with reference to P5, and 6.92 mm (range, 3.50-13.57 mm) with reference to P7; 4) the distance between the anterior commissure and the foramen of Monro was 6.78 mm (range, 1.86-14.57 mm), independent of P5 and P7; 5) the distance between the lower margin of the corpus callosum and the upper insertion point of the fornix was 12.44 mm (range, 2.71-26.13 mm) with reference to P5, and 13.34 mm (range, 3.74-27.58 mm) with reference to P7; 6) the distance between the lower margin of the corpus callosum and the lower insertion point of the fornix was 18.08 mm (range, 9.47-29.71 mm) with reference to P5, and 18.58 mm (range, 10.48-30.40 mm) with reference to P7; and 7) the distance between the lower margin of the corpus callosum and the anterior commissure was 23.46 mm (range, 11.98-32.70 mm) with reference to P5, and 22.89 mm (range, 11.05-33.04 mm) with reference to P7. Four different insertion types between the fornix and the corpus callosum were noted and classified. CONCLUSION: Morphometric data concerning the surrounding structures of the third ventricle have received very little attention in the literature. This morphometric study permitted definition of the surgical corridor to the third ventricle by preserving important anatomic structures such as the motor strip, genu of the corpus callosum, forniceal commissure (hippocampal commissure), anterior commissure, and forniceal columns. The detailed morphometric data obtained on median-sagittal MRI scans of the brain structures involved in the transcallosal interforniceal and/or transcallosal transforaminal approach allow for exact planning of the surgical approach.

Morphometry of the corpus callosum in normal aging and Alzheimer's disease.

Changes of the human corpus callosum in normal aging and Alzheimer's disease were analysed by means of morphometry. A standardized computerized evaluation program was implemented allowing objective, quantitative and reproducible data. The various parts of the corpus callosum showed a different pattern of changes in normal aging as compared to Alzheimer's disease. In conclusion, in normal aging affects mostly the front-temporal interhemispheric fiber systems, whereas in Alzheimer's disease the parietotemporal commissural fibers are altered.

Atrial electrical remodeling by rapid pacing in the isolated rabbit heart: effects of Ca++ and K+ channel blockade.

INTRODUCTION: Electrical remodeling describes atrial electrophysiologic changes that occur following atrial fibrillation. The mechanism(s) responsible for this phenomenon is not well understood. The purpose of this study was to examine the effects of rapid atrial pacing on atrial action potential duration, conduction time and refractoriness in the isolated rabbit heart. The effects of Ca++ and K+ blockade in this model were also studied. METHODS AND RESULTS: Monophasic action potential recordings were made from 12 epicardial atrial sites in 50 isolated perfused rabbit heart preparations. These recordings were analyzed for activation time (AT), 90% action potential duration (APD) and conduction times (CT) measured at a 250 msec cycle length. Atrial effective refractory periods (ERP) were determined at a 200 msec cycle length. All measurements were made at baseline and repeated after 2 hours of biatrial pacing at 250 msec (control group, n = 10) or 2 hours of rapid biatrial pacing (approximately 80 msec) in 4 groups: rapid pacing alone (rapid pacing group); rapid pacing in the presence of 0.1 mM verapamil (verapamil group) for L-type Ca++ channel blockade; rapid pacing with 1 mM 4-aminopyridine (4-AP group) for K+ channel blockade; and rapid pacing with 50 microM nickel chloride (Ni++ group) for T-type Ca++ channel blockade (n = 10 each group). All baseline and post pacing measurements were taken in the presence of Ca++ or K+ blockers for the respective groups. After rapid atrial pacing alone the average APD shortened by 8.2 +/- 10.4 msec compared to 3.6 +/- 12.5 msec shortening for control group (p = 0.002). The shortening of APD was uniform at all recording sites. For the rapid pacing group, CT was unchanged for right to left atrial conduction but shortened significantly for left to right atrial conduction (26.8 +/- 1.9 msec at baseline to 22.3 +/- 4.1 msec post pacing, p = 0.005). Conduction times were unchanged in the control group. The dispersion of repolarization was unchanged by rapid pacing alone. The decrease in APD from baseline to post rapid pacing was similar to the control group for those hearts treated with verapamil and 4-AP (1.5 +/- 12.3 and 4.7 +/- 10.4 msec, respectively, both p > or = 0.18 vs control group). The decrease in APD was significantly greater for the Ni++ group (11.8 +/- 14.3 msec) than for either the control group or rapid pacing group (both p < or = 0.023). The dispersion of repolarization was increased only in the 4-AP group post rapid pacing (41.7 +/- 6.2 msec at baseline to 53.5 +/- 9.6 msec post pacing, p = 0.01). ERPs were unchanged in any of the 5 groups except for a decrease in left atrial ERP in the Ni++ group after rapid pacing (98 +/- 14 msec at baseline to 88 +/- 8 msec post rapid pacing, p = 0.005). CONCLUSIONS: In the isolated rabbit heart model: 1) atrial APD is shortened after rapid pacing; 2) the shortening of APD is attenuated by verapamil and 4-AP but exaggerated by Ni++; 3) atrial conduction times are shortened in a direction specific manner after rapid pacing; and 4) shortening of ERP in this model is measured only in the presence of Ni++. These findings suggest that both L-type Ca++ and 4-AP sensitive channels may participate in atrial electrical remodeling.

Collagen dysplasia in idiopathic carpal tunnel syndrome.

Surgical biopsies of dissected transverse carpal ligaments of patients with idiopathic carpal tunnel syndrome were examined with an electron microscope revealing collagen fibrils with extremely varying diameters. Morphometric analysis was performed on electron micrographs exhibiting fibrils with a small diameter comparable to that in control tissue as well as fibrils with a far larger diameter than could be observed in control tissue. Morphometric parameters were evaluated in order to analyse the relation between the number of and the area covered by collagen fibrils in the electron micrographs. In control tissue the numerical density per image area was twice the numerical density in carpal tunnel syndrome. However, the area fraction of the electron micrographs occupied by collagen fibrils in carpal tunnel syndrome and controls were equal.

[Ultrasound, computed tomography and magnetic resonance tomography in a child with macrocephaly and glutaric aciduria type I]. / Ultraschall, Computertomographie und Magnetresonanztomographie bei einem Kind mit Makrozephalie und Glutarazidurie Typ I.

The rare case of glutaric aciduria type I (GA Type I) is described. Its characteristics are discussed and compared with cases in the literature. This disease is basically due to a lack of glutaryl-CoA-dehydrogenase with increased excretion of glutaric acid. Most authors describe frontotemporal cerebral atrophy. In the majority of cases macrocephaly is also present. This sign was also seen in our case and was the reason for performing an ultrasound examination, CT and MR. Ultrasound and CT showed a large insular cistern with incomplete formation of the opercula and frontal atrophy. In addition MR revealed hyperintensity of the basal ganglia and the periventricular white matter. To our knowledge this is the first publication of radiological findings in GA Type I in the German language.

A method for the quantification of the size of liver metastases.

A method for the quantification of the size of liver metastases based on stereologic principles is presented. This evaluation procedure was applied retrospectively to routine computerized tomography (CT) scans of the liver and allowed reliable estimation of the volume of liver metastases. Furthermore, the data were used to create three-dimensional (3D) representations of the examined organ by computer reconstruction.

White matter changes in HIV-1 infected brains: a combined gross anatomical and ultrastructural morphometric investigation of the corpus callosum.

OBJECTIVE: The HIV-1 associated cognitive/motor complex is characterized by cognitive, motor and behavioral disturbances. Besides a significant loss of neurons in the cerebral cortex and subcortical nuclei, a possible morphological substrate of this complex is also given by changes of the white matter as seen in HIV-1 leucoencephalopathy (HIVL), which is characterized by widespread diffuse pallor of myelin and the presence of gliomesenchymal nodules with multinucleated giant cells. METHODS: The corpus callosum as a sensitive marker for damage of the cerebral white matter was investigated by morphometry both at the macroscopic and electronmicroscopic level. RESULTS: In HIV-1 infected brains, a significant decrease of the profile area of the whole corpus callosum as well as of its different parts was noted. The absolute number of nerve fibers was significantly decreased, in particular in the frontal and occipital parts of the corpus callosum. Moreover, several morphometric parameters for nerve fibers, axons and myelin sheaths indicate in some areas a reduction of nerve fibers and axons, as well as a diminished myelin sheath thickness, whereas, in other regions, swelling of axons and myelin sheaths was observed. CONCLUSIONS: The observed changes are considered to represent subtle changes affecting nerve fibers before histological evidence of HIVL, and might represent one aspect of the morphological substrates preceeding the development of the HIV-1 related cognitive/motor complex.

A histochemical method for gross demonstration of motor end plates.

The thiocholine-ferricyanide method of Karnovsky and Roots for histochemical demonstration of cholinesterases has been applied to whole fetal and neonatal mice and chicks for the visualization of motor end plate patterns in superficial muscles or deeper muscles exposed by dissection.