Axion searches with the EDELWEISS-II experiment

We present new constraints on the couplings of axions and more generic axion-like particles using data from the EDELWEISS-II experiment. The EDELWEISS experiment, located at the Underground Laboratory of Modane, primarily aims at the direct detection of WIMPs using germanium bolometers. It is also sensitive to the low-energy electron recoils that would be induced by solar or dark matter axions. Using a total exposure of up to 448 kg.d, we searched for axion-induced electron recoils down to 2.5 keV within four scenarios involving different hypotheses on the origin and couplings of axions. We set a 95% CL limit on the coupling to photons $g_{A\gamma}<2.13\times 10^{-9}$ GeV$^{-1}$ in a mass range not fully covered by axion helioscopes. We also constrain the coupling to electrons, $g_{Ae} < 2.56\times 10^{-11}$, similar to the more indirect solar neutrino bound. Finally we place a limit on $g_{Ae}\times g_{AN}^{\rm eff}<4.70 \times 10^{-17}$, where $g_{AN}^{\rm eff}$ is the effective axion-nucleon coupling for $^{57}$Fe. Combining these results we fully exclude the mass range $0.91\,{\rm eV}<m_A<80$ keV for DFSZ axions and $5.73\,{\rm eV}<m_A<40$ keV for KSVZ axions

Assessing the digenic model in rare disorders using population sequencing data

An important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases. In this case, digenic disease combinations should be absent or underrepresented in healthy individuals. We develop a framework to evaluate the significance of digenic combinations and test its statistical power in different scenarios. We suggest that this approach will be relevant with the advent of new sequencing efforts including hundreds of thousands of samples

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered

Neurochirurgie

INTRODUCTION: The respective effects of direct and indirect decompression in the clinical outcome after anterior cervical disc fusion (ACDF) is still debated. The main purpose of this study was to analyze the effects of indirect decompression on foraminal volumes during ACDF performed in patients suffering from cervico-brachial neuralgias due to degenerative foraminal stenosis, i.e. to determine whether implant height was associated with increased postoperative foraminal height and volume. METHODS: A prospective follow-up of patients who underwent ACDF for cervicobrachial neuralgias due to degenerative foraminal stenosis was conducted. Patient had performed a CT-scan pre and post-operatively. Disc height, foraminal heights and foraminal volumes were measured pre and post operatively. RESULTS: 37 cervical disc fusions were successfully performed in 20 patients, with a total of 148 foramina studied. Foraminal height and volume were measured bilaterally on the pre- and post-operative CT scans (148 foramina studied). After univariate analysis, it was found a significant improvement for every radiological parameter, with a significant increase in disc height, foraminal height and foraminal volume being respectively +3,22 mm (p < 0,001), +2,12 mm (p < 0,001) and +54 mm(3) (p < 0,001). Increase in disc height was significantly associated with increase in foraminal height (p < 0,001) and foraminal volume (p < 0,001). At the same time, increase in foraminal height was significantly correlated with foraminal volume (p < 0,001), and seems to be the major component affecting increasing in foraminal volume. CONCLUSION: Indirect decompression plays an important part in the postoperative foraminal volume increase after ACDF performed for cervicobrachial neuralgias

Tomodensitometric bone anatomy of the intervertebral foramen of the lower cervical spine: measurements and comparison of foraminal volume in healthy individuals and patients suffering from cervicobrachial neuralgia due to foraminal stenosis

Purpose : Degenerative foraminal stenosis of the cervical spine can lead to cervicobrachial neuralgias. Computed tomography (CT)-scan assists in the diagnosis and evaluation of foraminal stenosis. The main objective of this study is to determine the bony dimensions of the cervical intervertebral foramen and to identify which foraminal measurements are most affected by degenerative disorders of the cervical spine. These data could be applied to the surgical treatment of this pathology, helping surgeons to focus on specific areas during decompression procedures. Methods : A descriptive study was conducted between two groups: an asymptomatic one (young people with no evidence of degenerative cervical spine disorders) and a symptomatic one (experiencing cervicobrachial neuralgia due to degenerative foraminal stenosis). Using CT scans, we determined a method allowing measurements of the following foraminal dimensions: foraminal height (FH), foraminal length (FL), foraminal width in its lateral part ((UWPP, MWPP and IWPP (respectively Upper, Medial and Inferior Width of Pedicle Part)) and medial part (UWMP, MWMP and IWMP (respectively Upper, Medial and Inferior Width of Medial Part)), and disk height (DH). Foraminal volume (FV) was calculated considering the above data. Mean volumes were measured in the asymptomatic group and compared to the values obtained in the symptomatic group. Results : Both groups were made up of 10 patients, and a total of 50 intervertebral discs (100 intervertebral foramina) were analyzed in each group. Comparison of C4C5, C5C6 and C6C7 levels between both groups showed several significant decreases in foraminal dimensions (p < 0.05) as well as in foraminal volume (p < 0.001) in the symptomatic group. The most affected dimensions were UWPP, MWPP, UWMP, MWMP and FV. The most stenotic foraminal areas were the top of the uncus and the posterior edge of the lower plate of the overlying vertebra. Conclusion : Using a new protocol for measuring foraminal volume, the present study refines the current knowledge of the normal and pathological anatomy of the lower cervical spine and allows us to understand the foraminal sites most affected by degenerative stenosis. Those findings can be applied to foraminal stenosis surgeries. According to our results, decompression of the foramen in regard of both uncus osteophytic spurs and inferior plate of the overlying vertebra might be an important step for spinal nerves release

Anterior cervical spine blood supply: A cadaveric study

PURPOSE: To describe the origin of the vessels supplying the anterior sub-axial cervical vertebrae (C3-C7) to further understand their potential influence on anterior bone loss after anterior cervical spinal surgery. METHOD: Cadaveric dissection was performed on ten adult human necks after latex perfusion of their subclavian, common carotid and vertebral arteries. The nutrient vessels of the sub-axial cervical spine were identified and traced to their origin. The course and distribution of these vessels and their nutrient foraminae are described. RESULTS: In all cases the anterior nutrient vessels were derived from the thyro-cervical trunk with branches that passed over the longus coli muscles forming a leash of vessels in the pre-vertebral fascia which subsequently extended in a frond-like pattern to pass onto the anterior aspect of vertebrae. The more cranial the cervical level the fewer the number of nutrient vessels and foraminae. The distribution of the foraminae on the anterior vertebral body followed the oblique supero-medial course of the nutrient vessels. CONCLUSION: Nutrient vessels perforate the cervical vertebrae on their anterior surface. These are derived from a leash of vessels that lie within the pre-vertebral fascia overlying the longus coli muscles. The origin of these vessels is the ascending cervical artery with a variable contribution from the transverse cervical artery

Circulating biomarkers of nitric oxide bioactivity and impaired muscle vasoreactivity to exercise in adults with uncomplicated type 1 diabetes

International audienceAims/hypothesisEarly compromised endothelial function challenges the ability of individuals with type 1 diabetes to perform normal physical exercise. The exact mechanisms underlying this vascular limitation remain unknown, but may involve either formation or metabolism of nitric oxide (NO), a major vasodilator, whose activity is known to be compromised by oxidative stress.MethodsMuscle microvascular reactivity (near-infrared spectroscopy) to an incremental exhaustive bout of exercise was assessed in 22 adults with uncomplicated type 1 diabetes (HbA1c 64.5 ± 15.7 mmol/mol; 8.0 ± 1.4%) and in 21 healthy individuals (18–40 years of age). NO-related substrates/metabolites were also measured in the blood along with other vasoactive compounds and oxidative stress markers; measurements were taken at rest, at peak exercise and after 15 min of recovery. Demographic characteristics, body composition, smoking status and diet were comparable in both groups.ResultsMaximal oxygen uptake was impaired in individuals with type 1 diabetes compared with in healthy participants (35.6 ± 7.7 vs 39.6 ± 6.8 ml min−1 kg−1, p < 0.01) despite comparable levels of habitual physical activity (moderate to vigorous physical activity by accelerometery, 234.9 ± 160.0 vs 280.1 ± 114.9 min/week). Compared with non-diabetic participants, individuals with type 1 diabetes also displayed a blunted exercise-induced vasoreactivity (muscle blood volume at peak exercise as reflected by ∆ total haemoglobin, 2.03 ± 5.82 vs 5.33 ± 5.54 μmol/l; interaction ‘exercise’ × ‘group’, p < 0.05); this was accompanied by lower K+ concentration (p < 0.05), reduced plasma L-arginine (p < 0.05)—in particular when HbA1c was high (mean estimation: −4.0, p < 0.05)—and lower plasma urate levels (p < 0.01). Nonetheless, exhaustive exercise did not worsen lipid peroxidation or other oxidative stress biomarkers, and erythrocytic enzymatic antioxidant resources were mobilised to a comparable extent in both groups. Nitrite and total nitrosation products, which are potential alternative NO sources, were similarly unaltered.Conclusions/interpretationParticipants with uncomplicated type 1 diabetes displayed reduced availability of L-arginine, the essential substrate for enzymatic nitric oxide synthesis, as well as lower levels of the major plasma antioxidant, urate. Lower urate levels may reflect a defect in the activity of xanthine oxidase, an enzyme capable of producing NO from nitrite under hypoxic conditions. Thus, both canonical and non-canonical NO production may be reduced. However, neither of these changes exacerbated exercise-induced oxidative stress

Gold-silica quantum rattles for multimodal imaging and therapy

Gold quantum dots exhibit distinctive optical and magnetic behaviors compared with larger gold nanoparticles. However, their unfavorable interaction with living systems and lack of stability in aqueous solvents has so far prevented their adoption in biology and medicine. Here, a simple synthetic pathway integrates gold quantum dots within a mesoporous silica shell, alongside larger gold nanoparticles within the shell’s central cavity. This “quantum rattle” structure is stable in aqueous solutions, does not elicit cell toxicity, preserves the attractive near-infrared photonics and paramagnetism of gold quantum dots, and enhances the drug-carrier performance of the silica shell. In vivo, the quantum rattles reduced tumor burden in a single course of photothermal therapy while coupling three complementary imaging modalities: near-infrared fluorescence, photoacoustic, and magnetic resonance imaging. The incorporation of gold within the quantum rattles significantly enhanced the drug-carrier performance of the silica shell. This innovative material design based on the mutually beneficial interaction of gold and silica introduces the use of gold quantum dots for imaging and therapeutic applications