The necropolis of Assiut : a case study of local Egyptian funerary culture from the Old Kingdom to the end of the Middle Kingdom

Despite elaborate scholarly attention, the necropolis of Assiut, capital of the 13th Upper Egyptian Nome, has never been properly surveyed. Several of the major excavations, mainly undertaken in the first decades of the last century, still await publication or more detailed edition. These not only include the French excavations by Chassinat and Palanque (1903-1904), but also the work led by Hogarth for the British Museum (1906-1907), and the digs conducted by Schiaparelli (1905, 1908, 1910, 1911-1913). Whereas the historical significance of Assiut during the First Intermediate Period and the Middle Kingdom, and its distinct local style of coffin decoration have long been recognised, the basic requirements for a systematic study of this important site are still absent. The aim of this study is to generate a framework for the social, spatial and chronological development of the necropolis of Assiut, concentrating on the times from the Old Kingdom to the end of the Middle Kingdom. Mainly based on hitherto unpublished material, the available funerary remains are carefully scrutinised to establish a chronological ordering. The approach is multifaceted, among other things using tomb architecture, the morphology of pottery, stone vases, seals, coffin decoration (choice of decoration patterns, textual content, epigraphic and palaeographic features), and their spatial distribution. Their combined analysis results in four distinct (chronological) phases in the funerary culture at Assiut: Late Old Kingdom, First Intermediate Period, Early Middle Kingdom and Advanced - Late Middle Kingdom. The remains and features of each of these phases are discussed, and used as a means to put the history of Assiut into better perspective.A brief survey of contents:Chapter 1 - Introduction, Aims and methodsChapter 2 - Compiles a map of the Necropolis and the tombs of its mayors/nomarchs. With regard to the latter, 7 new candidates are put forward, resulting in a reconsideration of the chronology of the Siutian mayors and nomarchs.Chapter 3 - A full survey of the excavations conducted, their location(s) in the field, results, and problems in analysing the available material and reports.Chapter 4 - Survey of Late Old Kingdom burial grounds identified at AssiutChapter 5 - Survey of First Intermediate Period burial grounds identified at AssiutChapter 6 - Survey of Early Middle Kingdom burial grounds identified at Assiut (I)Chapter 7 - Survey of Early Middle Kingdom burial grounds identified at Assiut (II)Chapter 8 - Survey of Advanced - Late Middle Kingdom burial grounds identified at AssiutChapter 9 - ConclusionsLEI Universiteit LeidenMiddle Eastern Studie

Neuropathophysiological potential of Guillain-Barré syndrome anti-ganglioside-complex antibodies at mouse motor nerve terminals

Objectives:  Anti-ganglioside antibodies are present in approximately half of Guillain–Barré syndrome (GBS) patients. Recently, it has been shown that a considerable proportion of these patients has serum antibodies against antigenic epitopes formed by a complex of two different gangliosides. However, direct experimental evidence for neuropathogenicity of this special category of antibodies is currently lacking. Here, we explored a series of GBS and GBS-variant sera with anti-ganglioside-complex antibodies for their ability to induce complement-dependent deleterious effects at the living neuronal membrane. Methods:  The neuropathophysiological potential of 31 GBS sera containing either anti-GM1/GD1a- or anti-GM1/GQ1b-ganglioside-complex antibodies was studied at motor nerve terminal presynaptic membranes in the mouse phrenic nerve/diaphragm muscle ex vivo experimental model. With electrophysiological measurements and confocal fluorescence microscopy, we assessed and quantified the damaging effect on neuronal membranes by anti-ganglioside-complex antibodies. Results:  We show that anti-GM1/GD1a- and anti-GM1/GQ1b-ganglioside-complex positive sera can induce complement-mediated functional and morphological injury at mouse motor nerve terminals ex vivo. Of the 31 investigated anti-ganglioside-complex patient sera, 17 sera induced increases in miniature end-plate potential frequency in this experimental model, mostly associated with muscle fibre twitches. Variability in potency was observed, with the anti-GM1/GD1a-complex sera inducing the most outspoken effects.<b></b> Conclusions:  The present study shows the presence of ganglioside-complexes as available antigens in living neuronal membranes and supplies proof-of-principle that anti-ganglioside-complex antibodies in sera from GBS patients can induce complement-mediated damage. This strongly supports the hypothesis that autoimmune targeting of ganglioside-complexes is of pathogenic relevance in a proportion of GBS patients

Association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA).

Context: It has been hypothesized that depression is associated with lower heart rate variability and decreased cardiac vagal control. This may play an important role in the risk of cardiovascular diseaseamongdepressed individuals. Objective: To determine whether heart rate variability was lower in depressed individuals than in healthy controls in a large adult sample. Design: Cross-sectional analyses from a large depression cohort study. Setting: The Netherlands Study of Depression and Anxiety. Participants: Two thousand three hundred seventy-three individuals (mean age, 41.8 years; 66.8% female) who participated in the Netherlands Study of Depression and Anxiety. Included were 524 controls, 774 individuals with a diagnosis of major depressive disorder (MDD) earlier in life (remitted MDD), and 1075 individuals with current MDD based on the Composite International Diagnostic Interview. This sample was sufficiently powered to examine the confounding effects of lifestyle, comorbid anxiety, and antidepressants. Main Outcome Measures: The standard deviation of normal-to-normal beats (SDNN) and cardiac vagal control, as indexed by respiratory sinus arrhythmia (RSA), were measured during 11/2 hours of ambulatory recording of electrocardiograms and thorax impedance. Multivariate analyses were conducted to compare SDNN and RSA across depression groups after adjustment for demographics, health, lifestyle, comorbid anxiety, and psychoactive medication. Results: Individuals with remitted and current MDD had a lower mean SDNN and RSA compared with controls (SDNN, 3.1-5.7 milliseconds shorter, P ≤ .02; RSA, 5.1-7.1 milliseconds shorter, P < .001; effect size, 0.125-0.269). Comorbid anxiety and lifestyle did not reduce these associations. However, accounting for psychoactive medication removed the association with SDNN and strongly attenuated the association with RSA. Depressed individuals who were using selective serotonin reuptake inhibitors, tricyclic antidepressants, or other antidepressants had significantly shorter SDNNs and RSAs (effect size, 0.207-0.862) compared with controls and depressed individuals not taking medication. Conclusions: This study shows that depression is associated with significantly lowered heart rate variability. However, this association appears to be mainly driven by the effect of antidepressants. ©2008 American Medical Association. All rights reserved

Neuromuscular synaptic transmission in aged ganglioside-deficient mice

Gangliosides are sialylated glycosphingolipids that are present in high density on neuronal membranes, especially at synapses, where they are assumed to play functional or modulating roles. Mice lacking GM2/GD2-synthase express only the simple gangliosides GD3 and GM3 and develop progressive motor behaviour deficits upon ageing, apparently due to failing complex ganglioside-dependent maintenance and/or repair processes or, alternatively, toxic GM3/GD3 accumulation. We investigated the function of neuromuscular junctions (NMJs) of aged (&gt;9 month-old) GM2/GD2-synthase null-mutant mice, because synaptic dysfunction might develop with age and could potentially contribute to the late-onset motor phenotype. In addition, we studied NMJs of old mice lacking GD3-synthase (expressing only O- and a-series gangliosides), which do not show an overt neurological phenotype but may develop subclinical synaptic deficits. Detailed electrophysiological analyses showed subtle changes in presynaptic neurotransmitter release. Acetylcholine release at 40 Hz nerve stimulation at aged GM2/GD2-synthase null-mutant NMJs ran down slightly more pronounced than at wild-type NMJs, and spontaneous acetylcholine release rate at GD3-synthase null-mutant NMJs was somewhat higher than at wild-type, selectively at 25 degrees C bath temperature. Interestingly, we observed faster kinetics of postsynaptic electrophysiological responses at aged GD3-synthase null-mutant NMJs, not previously seen by us at NMJs of young GD3-synthase null-mutants or other types of (aged or young) ganglioside-deficient mice. These kinetic changes might reflect a change in postsynaptic acetylcholine receptor behaviour. Our data indicate that it is highly unlikely that transmission failure at NMJs contributes to the progressive motor defects of aged GM2/GD2-synthase null-mutants and that, despite some kinetic changes of synaptic signals, neuromuscular transmission remains successful in aged GD3-synthase null-mutant mice. Apparently, mutual redundancy of the different gangliosides in supporting presynaptic function, as observed previously by us in young mice, remains adequate upon ageing or, alternatively, gangliosides have only relatively little direct impact on neuromuscular synaptic function, even in aged mice. (C) 2009 Elsevier Inc. All rights reserve

Barriers in recognising, diagnosing and managing depressive and anxiety disorders as experienced by Family Physicians; a focus group study

BACKGROUND: The recognition and treatment of depressive- and anxiety disorders is not always in line with current standards. The results of programs to improve the quality of care, are not encouraging. Perhaps these programs do not match with the problems experienced in family practice. This study aims to systematically explore how FPs perceive recognition, diagnosis and management of depressive and anxiety disorders. METHODS: focus group discussions with FPs, qualitative analysis of transcriptions using thematic coding. RESULTS: The FPs considered recognising, diagnosing and managing depressive- and anxiety disorders as an important task. They expressed serious doubts about the validity and usefulness of the DSM IV concept of depressive and anxiety disorders in family practice especially because of the high frequency of swift natural recovery. An important barrier was that many patients have difficulties in accepting the diagnosis and treatment with antidepressant drugs. FPs lacked guidance in the assessment of patients' burden. The FPs experienced they had too little time for patient education and counseling. The under capacity of specialised mental health care and its minimal collaboration with FPs were experienced as problematic. Valuable suggestions for solving the problems encountered were made CONCLUSION: Next to serious doubts regarding the diagnostic concept of depressive- and anxiety disorders a number of factors were identified which serve as barriers for suitablemental health care by FPs. These doubts and barriers should be taken into account in future research and in the design of interventions to improve mental health care in family practice

Depression is associated with decreased blood pressure, but antidepressant use increases the risk for hypertension

The present study compared blood pressure levels between subjects with clinical anxiety and depressive disorders with healthy controls. Cross-sectional data were obtained in a large cohort study, the Netherlands Study of Depression and Anxiety (N=2981). Participants were classified as controls (N=590) or currently or remittedly depressed or anxious subjects (N=2028), of which 1384 were not and 644 were using antidepressants. Regression analyses calculated the contributions of anxiety and depressive disorders and antidepressant use to diastolic and systolic blood pressures, after controlling for multiple covariates. Heart rate and heart rate variability measures were subsequently added to test whether effects of anxiety/depression or medication were mediated by vagal control over the heart. Higher mean diastolic blood pressure was found among the current anxious subjects (β=0.932; P=0.03), although anxiety was not significantly related to hypertension risk. Remitted and current depressed subjects had a lower mean systolic blood pressure (β=-1.74, P=0.04 and β=-2.35, P=0.004, respectively) and were significantly less likely to have isolated systolic hypertension than controls. Users of tricyclic antidepressants had higher mean systolic and diastolic blood pressures and were more likely to have hypertension stage 1 (odds ratio: 1.90; 95% CI: 0.94 to 3.84; P=0.07) and stage 2 (odds ratio: 3.19; 95% CI: 1.35 to 7.59; P=0.008). Users of noradrenergic and serotonergic working antidepressants were more likely to have hypertension stage 1. This study shows that depressive disorder is associated with low systolic blood pressure and less hypertension, whereas the use of certain antidepressants is associated with both high diastolic and systolic blood pressures and hypertension. (Hypertension. 2009;53:631-638.) © 2009 American Heart Association, Inc