Looking Below the Surface: The Role of Superficial White Matter in Alzheimer’s Disease

Superficial white matter (SWM) contains short fibres and has largely been overlooked in Alzheimer’s disease (AD). Standard MRI approaches face confounding effects of complex fibre organisation and proximity to the cortex when measuring SWM in vivo. This thesis investigates SWM in AD by applying advanced MRI techniques to overcome these limitations. First, SWM in a cohort of young-onset AD and healthy controls was investigated using an advanced diffusion MRI model. Findings showed that young-onset AD participants have lower density, but increased dispersion, of SWM neurites compared to healthy controls. The second project found that these advanced diffusion MRI metrics are associated with independent quantitative MRI metrics sensitive to microstructure, and indicate previous findings are linked to losses in SWM myelin and iron. Project three explored the confounding effect of nearby CSF on cortical diffusion MRI measures and showed that a tissue-weighting approach can ameliorate CSF’s influence on regional averages. Project four investigated whether SWM is affected in autosomal dominant AD. Results supported earlier findings of lower density and higher dispersion of SWM neurites in symptomatic mutation carriers compared to non-carriers. Presymptomatic mutation carriers also had a lower density of neurites in entorhinal SWM. The final project used high-resolution 7T MRI to limit the influence of partial volume effects from nearby tissues on SWM measures in typical and atypical AD participants and healthy controls. An interim analysis qualitatively supports a loss of myelin and iron, with a potential increase in dispersion, occurring in the SWM during AD. In summary, SWM undergoes both degenerative and organisational changes during AD that coincide with a loss of iron. This extends the literature by overcoming limitations of standard MRI techniques previously used to investigate SWM in AD. SWM represents an overlooked region of brain changes in AD that may help detect and characterise the disease

Prise en charge de l'ostéoporose en tant que comorbidité de la broncho-pneumopathie chronique obstructive (étude rétrospective dans un centre de soins de suite et de réadaptation)

Objectif : Confronter la prise en charge diagnostique de l'ostéoporose aux recommandations de la Haute Autorité de Santé dans la population souffrant de broncho-pneumopathie chronique obstructive (BPCO) du centre Henri Bazire (CHB). Évaluer la prévalence de la pathologie fracturaire et la fréquence de la prise en charge thérapeutique anti-ostéoporotique dans cette population. Matériel et méthode : Nous avons mené une étude rétrospective auprès de 142 patients atteints de BPCO du CHB. Les données sont issues de l'interrogatoire et du dossier médical, complétées par la recherche de tassements vertébraux à la radiographie de thorax. Résultats : 64 % des patients présentent une indication à l'ostéodensitométrie. Seuls 26 % de ceux-là ont eu cet examen. 55 % des patients sont concernés par la pathologie fracturaire : 19% ont un antécédent de fracture périphérique de fragilité et 42 % présente au moins un tassement vertébral non traumatique. 48 % des patients à risque d'ostéoporose présentent des apports calciques insuffisants et ne reçoivent ni supplémentation en vitamine D, ni traitement anti-ostéoporotique. prise en charge diagnostique et thérapeutique est significativement supérieure chez les femmes. Conclusion : La promotion des règles hygiéno-diététiques est à encourager ainsi que la supplémentation en vitamine D voir en calcium si nécessaire. Nous incitons les médecins à évaluer systématiquement le risque d'ostéoporose et de fracture chez les patients atteints de BPCO. Les indications de dépistage et de traitement sont à discuter au cas par cas.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

The Lantern Vol. 73, No. 2, Spring 2006

• Of the Man • Beauty in America • Kindling • Genevieve • Bits of Copper • A Love Song to Hip Hop • From James\u27 Journal • I Want a Woman • Peregrine Rain • Resurge • Frustrations • (At Least) You Gave Me Something to Write About • The Fun of Giving Interactive History Lectures as a Summer Job • Exigence • White Water • My Summer, with Salt • The City With Two Faces • I Dig Your Cello • Life-Filled Ghost Town • Laura, On Happiness • Integration/Assimilation • Sunny Side Estates • Every Night I Shut My Eyes • New England State of Mind • Your Body\u27s Weight in Water for Your Soul, Thank You Very Much • A Story That\u27s 10 Percent Truehttps://digitalcommons.ursinus.edu/lantern/1168/thumbnail.jp

Factors associated with anxiety disorder comorbidity

Background Anxiety and depressive disorders often co-occur and the order of their emergence may be associated with different clinical outcomes. However, minimal research has been conducted on anxiety-anxiety comorbidity. This study examined factors associated with anxiety comorbidity and anxiety-MDD temporal sequence. Methods Online, self-report data were collected from the UK-based GLAD and COPING NBR cohorts (N = 38,775). Logistic regression analyses compared differences in sociodemographic, trauma, and clinical factors between single anxiety, anxiety-anxiety comorbidity, anxiety-MDD (major depressive disorder) comorbidity, and MDD-only. Additionally, anxiety-first and MDD-first anxiety-MDD were compared. Differences in familial risk were assessed in those participants with self-reported family history or genotype data. Results Anxiety-anxiety and anxiety-MDD had higher rates of self-reported anxiety or depressive disorder diagnoses, younger age of onset, and higher recurrence than single anxiety. Anxiety-MDD displayed greater clinical severity/complexity than MDD only. Anxiety-anxiety had more severe current anxiety symptoms, less severe current depressive symptoms, and reduced likelihood of self-reporting an anxiety/depressive disorder diagnosis than anxiety-MDD. Anxiety-first anxiety-MDD had a younger age of onset, more severe anxiety symptoms, and less likelihood of self-reporting a diagnosis than MDD-first. Minimal differences in familial risk were found. Limitations Self-report, retrospective measures may introduce recall bias. The familial risk analyses were likely underpowered. Conclusions Anxiety-anxiety comorbidity displayed a similarly severe and complex profile of symptoms as anxiety-MDD but distinct features. For anxiety-MDD, first-onset anxiety had an earlier age of onset and greater severity than MDD-first. Anxiety disorders and comorbidity warrant further investigation and attention in research and practice

Utility of perfusion PET measures to assess neuronal injury in Alzheimer's disease

Introduction: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used to estimate neuronal injury in Alzheimer's disease (AD). Here, we evaluate the utility of dynamic PET measures of perfusion using 11C-Pittsburgh compound B (PiB) to estimate neuronal injury in comparison to FDG PET. Methods: FDG, early frames of PiB images, and relative PiB delivery rate constants (PiB-R1) were obtained from 110 participants from the Dominantly Inherited Alzheimer Network. Voxelwise, regional cross-sectional, and longitudinal analyses were done to evaluate the correlation between images and estimate the relationship of the imaging biomarkers with estimated time to disease progression based on family history. Results: Metabolism and perfusion images were spatially correlated. Regional PiB-R1 values and FDG, but not early frames of PiB images, significantly decreased in the mutation carriers with estimated year to onset and with increasing dementia severity. Discussion: Hypometabolism estimated by PiB-R1 may provide a measure of brain perfusion without increasing radiation exposure

Luminescent Ruthenium(II) Polypyridyl Functionalized Gold Nanoparticles; Their DNA Binding Abilities and Application As Cellular Imaging Agents

The synthesis and photophysical and biological investigation of Ru(II)-polypyridyl stabilized watersoluble, luminescent gold nanoparticles (AuNPs) are described. These structures bind to DNA and undergo rapid cellular uptake, being localized within the cell cytoplasm and nucleus within 4 h

A Better Touch: C-tactile Fibers Related Activity is Associated to Pain Reduction During Temporal Summation of Second Pain

C-tactile (CT) fibers, responsible for the so-called “affective” touch (AT), have drawn a fair amount of attention within the scientific community for their marked social dimension. However, while the pain-relieving potential of discriminative touch (DT) has been documented, proofs of the analgesic properties of AT are still scarce. Additionally, no study has so far tested its possible pain-relieving effect on a clinically-relevant model. Temporal summation of second pain (TSSP), otherwise referred to as “wind-up,” relies on repetitive stimulation of C-nociceptors and it is thought to reflect central sensitization, a process linked to many chronic pain conditions. In the present experimental, within participants, design we induced TSSP through trains of ascending and descending repetitive heat stimulation. Forty-two healthy participants’ pain was measured during 2 different tactile stimulations (stroking velocities AT: 10 cm/s; DT: 0.3 cm/s) or without concomitant tactile input. Since measures of pleasantness of the tactile stimulation have been found to strongly correlate with C-tactile fibers’ firing rate, these, together with participants’ body awareness, were also taken into account. Our results show that AT brought about a decrease of our participants’ pain as opposed to both DT and no touch, while DT did not produce any significant pain reduction. Thus, only AT successfully modulated wind-up. As expected, AT was perceived as more pleasant than DT, while a clear relationship between body awareness and pain was found only during DT. Targeting CT fibers could pave the way to new treatments for chronic pain conditions whose aetiology depend on abnormal C-nociceptors’ physiology. Perspective: This study extends previous findings on the analgesic potential of affective touch, documenting a clear pain reduction during temporal summation of second pain (TSSP). Since TSSP is thought to reflect central sensitization, the psychophysiological mechanisms of affective touch could be exploited for new chronic pain treatments