Nodding syndrome in Mundri county,South Sudan: environmental,nutritional and infectious factors

Background

Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda.

Objective

To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001.

Methods

Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001–2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan.

Results

Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded.

Conclusion

Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

Progress in the autosomal segmental aneusomy syndromes (SASs): single or multi-locus disorders?

Based on cytogenetic observations, several syndromes have been previously identified as microdeletion-based disorders. In this review, recent progress is presented regarding whether one or multiple genes can be implicated in the pathogenesis of these segmentally aneusomic syndromes. The syndromes discussed include Angelman, Alagille, Williams, Langer-Giedeon, Prader-Willi, Smith-Magenis, Miller-Dieker, and DiGeorge/velocardiofacial or the 22q11 deletion syndromes. For Angelman and Alagille syndromes, single genes have been identified, whereas for Williams and Langer-Giedion syndromes, more than one gene can be implicated. Although there has been significant progress in dissecting the molecular basis for the other disorders, the ultimate answer regarding one versus several genes remains to be determined.      

Heart rate and blood pressure time courses during prolonged dry apnoea in breath-hold divers

The purpose of this study was to investigate how the ocular surface area (OSA) and the eye blink frequency (BF) are affected by a high versus a low-monitor position during visual display unit (VDU) work with varying cognitive demands. In a balanced randomized (2 × 2) design ten healthy subjects (five males, five females) completed two different tasks on the VDU in a simulated office environment (23°C and 30–35% relative humidity); an active task with demands on vision and hand-eye coordination, and a passive task. Two monitor positions were used: high (the monitors’ upper edge at the same height as the subjects’ eyes) and low (lowered by 25° and perpendicular to gaze angle). Each task lasted 10 min. An OSA-proxy was measured from video recordings, and BF was sampled by electrooculography. The effect of lowering the gaze angle by 25° decreased the OSA-proxy significantly (P < 0.01) during the active task, indicating that a low position of the monitor may be preferable even though the BF also decreased. Overall, the OSA-proxy was 6% higher during the active task compared to the passive while BF during the active task was 69% lower than during the passive task. The low BF during the active task was succeded by a burst with high BF after cessation of the active task, indicating a compensatory blinking process. This stresses that interchange of work tasks with different cognitive load is as important as the monitor position in the prevention of visual and musculoskeletal disorders.     

Bone mass,bone strength,muscle-bone interactions,osteopenias and osteoporoses

Densitometrically, the skeleton is currently conceived as 'a systemically regulated mass of mineralized material that is born, grows, reaches a more or less high peak, and then declines faster or slower as to develop a correspondingly high or low fracture risk'. Alternatively, from a biomechanical point of view, the skeleton can be conceived as 'a biomechanically-regulated structure that can be systemically disturbed (in the cybernetic sense), the strength of which depends on the intrinsic stiffness (material properties) and the spatial distribution (architectural properties) of the mineralized tissue'. The biomechanical feedback system involved (bone 'mechanostat') would not control bone mass to optimize bone strength; it would rather control bone material quality and architecture (through a modulation of bone modeling and remodeling) in order to optimize bone stiffness. The natural stimuli for the bone mechanostat would be the customary strains of bone tissue (sensed by osteocytes) that are induced by gravitational forces and, more importantly, the contractions of regional muscles. According to this view, the development of any bone-weakening disease should be related to either (1) an intrinsic illness of the system (primary disturbances of bone cells), (2) a lack of mechanical stimulation (disuse-induced bone losses), or (3) a systemically-induced shift of the system's setpoint (systemic or secondary bone diseases). This short review aims to conciliate those views: (1) taking profit of the diagnostic possibilities provided by densitometric bone 'mass' determinations; (2) proposing other resources to assess bone mechanical properties; and (3) analyzing the muscle-bone interactions. These are crucial for achieving a differential diagnosis between disuse and primary or secondary bone disturbances, based either (1) on the densitometric determination of bone and muscle masses that would provide an anthropometric diagnosis of osteopenia (not osteoporosis because no extrapolations to bone strength can be made this way) or (2) on the cross-sectional analyses of bone structure or strength and muscle strength provided by bone tomography, magnetic resonance or other techniques that could afford a diagnosis of osteoporosis according to biomechanical criteria.     

Changes in response to spinal cord injury with development: vascularization, hemorrhage and apoptosis

Chick embryos are capable of functional spinal cord regeneration following crush injury until embryonic day 13. Developmental changes occurring thereafter result in failure to regenerate. Secondary injury mechanisms can result in apoptotic cell death and make a major contribution to cell loss after trauma. We report here that around embryonic day 13 there is a dramatic increase in blood vessel numbers in the spinal cord, and that the extent of hemorrhage in response to injury increases with developmental age. This is paralleled by increased apoptosis and subsequent cavitation in spinal cords injured at embryonic day 15 as compared with embryonic day 11. Following spinal cord injury at embryonic day 15, apoptotic cell death is extensive and spreads to the same extent as the hemorrhage. When hemorrhage is reduced by treatment with the hemostatic drug desmopressin the extent of apoptosis and cavity formation in spinal cords injured at embryonic day 15 decreases. Furthermore, manipulations of embryonic day 11 spinal cords that increase hemorrhage also increase apoptosis and result in cavitation in contrast to the effective repair typical of this stage. Altogether these results suggest that cavity formation occurring at developmental stages non-permissive for regeneration is largely due to changes in the extent of apoptosis that are related to vascularization and hemorrhage.     

The aperitif: an investigation into young people’s relationship with alcohol

The consumption and abuse of alcohol among young people is a matter of both national and international concern. According to ISTAT (, 2007), the model of alcohol consumption in Italy is traditionally moderate, but in the last few years habits that pose health risks, such as drinking between meals at a young age and binge drinking, have been increasing constantly. The aim of this study was to investigate the ways in which alcohol is consumed by young people in Siena, focusing in particular on their habit of meeting for an aperitif. The sample comprised 467 students (mean age 17 ± 1.3 years). The results obtained show that the situation in Siena is similar to that in the rest of Italy, being characterised by frequent alcohol abuse, concentrated above all in the weekend. We found that meeting for an aperitif is seen as an opportunity to catch up with friends, relax and have fun.     

术中大剂量放疗治疗局部复发头颈癌

该文旨在介绍Beth Israel医疗中心采用大剂量术中放疗(HDR-IORT)治疗复发头颈癌的经验。对2001-2010年间头颈癌局部复发接受大剂量HDR-IORT的患者进行回顾分析。结果,76例患者的87个部位在肿瘤切除后接受了治疗。术后2年控制率为62%。平均总生存期为19个月,其中42%的患