Evaluation of Memantine in AAV-AD Rat: A Model of Late-Onset Alzheimer's Disease Predementia.

Background: Though our understanding of Alzheimer's disease (AD) remains elusive, it is well known that the disease starts long before the first signs of dementia. This is supported by the large number of symptomatic drug failures in clinical trials and the increased trend to enroll patients at predementia stages with either mild or no cognitive symptoms. However, the design of pre-clinical studies does not follow this attitude, in particular regarding the choice of animal models, often irrelevant to mimic predementia Late Onset Alzheimer's Disease (LOAD).

DM1 Transgenic Mice Exhibit Abnormal Neurotransmitter Homeostasis and Synaptic Plasticity in Association with RNA Foci and Mis-Splicing in the Hippocampus.

Myotonic dystrophy type 1 (DM1) is a severe neuromuscular disease mediated by a toxic gain of function of mutant RNAs. The neuropsychological manifestations affect multiple domains of cognition and behavior, but their etiology remains elusive. Transgenic DMSXL mice carry the DM1 mutation, show behavioral abnormalities, and express low levels of GLT1, a critical regulator of glutamate concentration in the synaptic cleft.

Effectiveness and Safety of P2Y12 Inhibitors Pretreatment in Primary Percutaneous Coronary Intervention with Long Transfer Times.

Background: Early initiation of a new P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients prior to primary percutaneous coronary intervention (PCI) is recommended over clopidogrel. However, comparative data remain limited, especially in semi-rural regions with subsequent longer transfer times.

Objectives: We aimed to assess the determinants, effectiveness, and safety of pretreatment with new P2Y12 inhibitors compared with clopidogrel in a primary PCI regional network.

Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor coagonist d-serine.

Prefrontal control of cognitive functions critically depends upon glutamatergic transmission and N-methyl D-aspartate (NMDA) receptors, the activity of which is regulated by dopamine. Yet whether the NMDA receptor coagonist d-serine is implicated in the dopamine-glutamate dialogue in the prefrontal cortex (PFC) and other brain areas remains unexplored. Here, using electrophysiological recordings, we show that d-serine is required for the fine-tuning of glutamatergic neurotransmission, neuronal excitability, and synaptic plasticity in the PFC through the actions of dopamine at D and D receptors.

Interplay between 5-HT4 Receptors and GABAergic System within CA1 Hippocampal Synaptic Plasticity.

The type 4 serotonin receptor (5-HT4R) is highly involved in cognitive processes such as learning and memory. Behavioral studies have shown a beneficial effect of its activation and conversely reported memory impairments by its blockade. However, how modulation of 5HT4R enables modifications of hippocampal synaptic plasticity remains elusive.

LSP5-2157 a new inhibitor of vesicular glutamate transporters.

Vesicular glutamate transporters (VGLUT1-3) mediate the uptake of glutamate into synaptic vesicles. VGLUTs are pivotal actors of excitatory transmission and of almost all brain functions. Their implication in various pathologies has been clearly documented.

Susceptibility to Aβo and TBOA of LTD and Extrasynaptic NMDAR-Dependent Tonic Current in the Aged Rat Hippocampus.

Aging, as the major risk factor of Alzheimer's disease (AD), may increase susceptibility to neurodegenerative diseases through many gradual molecular and biochemical changes. Extracellular glutamate homeostasis and extrasynaptic glutamate N-methyl-D-aspartate receptors (NMDAR) are among early synaptic targets of oligomeric amyloid β (Aβo), one of the AD related synaptotoxic protein species. In this study, we asked for the effects of Aβo on long-term depression (LTD), a form of synaptic plasticity dependent on extrasynaptic NMDAR activation, and on a tonic current (TC) resulting from the activation of extrasynaptic NMDAR by ambient glutamate in hippocampal slices from young (3-6-month-old) and aged (24-28-month-old) Sprague-Dawley rats.

A mosaic monoploid reference sequence for the highly complex genome of sugarcane.

Sugarcane (Saccharum spp.) is a major crop for sugar and bioenergy production. Its highly polyploid, aneuploid, heterozygous, and interspecific genome poses major challenges for producing a reference sequence.

Evidence for altered dendritic spine compartmentalization in Alzheimer's disease and functional effects in a mouse model.

Alzheimer's disease (AD) is associated with a progressive loss of synapses and neurons. Studies in animal models indicate that morphological alterations of dendritic spines precede synapse loss, increasing the proportion of large and short ("stubby") spines. Whether similar alterations occur in human patients, and what their functional consequences could be, is not known.

Synaptic plasticity modulation by circulating peptides and metaplasticity: Involvement in Alzheimer's disease.

Synaptic plasticity is a cellular process involved in learning and memory whose alteration in its two main forms (Long Term Depression (LTD) and Long Term Potentiation (LTP)), is observed in most brain pathologies, including neurodegenerative disorders such as Alzheimer's disease (AD). In humans, AD is associated at the cellular level with neuropathological lesions composed of extracellular deposits of β-amyloid (Aβ) protein aggregates and intracellular neurofibrillary tangles, cellular loss, neuroinflammation and a general brain homeostasis dysregulation. Thus, a dramatic synaptic environment perturbation is observed in AD patients, involving changes in brain neuropeptides, cytokines, growth factors or chemokines concentration and diffusion.

βAPP Processing Drives Gradual Tau Pathology in an Age-Dependent Amyloid Rat Model of Alzheimer's Disease.

The treatment of Alzheimer's disease (AD) remains challenging and requires a better in depth understanding of AD progression. Particularly, the link between amyloid protein precursor (APP) processing and Tau pathology development remains poorly understood. Growing evidences suggest that APP processing and amyloid-β (Aβ) release are upstream of Tau pathology but the lack of animal models mimicking the slow progression of human AD raised questions around this mechanism.

Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors.

Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities.

Rapid onset of squamous cell carcinoma in a thin skin graft donor site.

Background: Squamous cell carcinomas are malignant tumours of epithelial origin that can appear on sites subjected to chronic inflammation after a period of several years. The rapid development of squamous cell carcinoma at the donor site for a thin skin graft is a rare and poorly understood situation.

Patients And Methods: We report the case of a patient undergoing thin skin grafting to cover the area of removal of a vertex squamous cell carcinoma and in whom squamous cell carcinoma appeared at the donor site within 9 weeks.

Alzheimer's disease-like APP processing in wild-type mice identifies synaptic defects as initial steps of disease progression.

Background: Alzheimer's disease (AD) is the most frequent form of dementia in the elderly and no effective treatment is currently available. The mechanisms triggering AD onset and progression are still imperfectly dissected. We aimed at deciphering the modifications occurring in vivo during the very early stages of AD, before the development of amyloid deposits, neurofibrillary tangles, neuronal death and inflammation.

Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology.

Alzheimer's disease (AD) is characterized by both amyloid and Tau pathologies. The amyloid component and altered cholesterol metabolism are closely linked, but the relationship between Tau pathology and cholesterol is currently unclear. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene.

Omega-3 polyunsaturated fatty acids and brain aging.

Purpose Of Review: The literature on the influence of dietary omega-3 polyunsaturated fatty acid (ω-3 PUFA) on brain aging has grown exponentially during the last decade. Many avenues have been explored but no global picture or clear evidence has emerged. Experimental studies have shown that ω-3 PUFA is involved in many neurobiological processes that are involved in neurotransmission and neuroprotection, indicating that these PUFAs may prevent age-related brain damage.

[Cheek reconstruction].

We describe the different cheek reconstruction techniques with primary emphasis on the superficial layers. In addition to the clinical context, location and size of the lesion will be taken into account to choose the best method that will optimize the functional and aesthetic results while minimizing potential sequelae. Main evaluation criteria include absence of natural orifice deformation, scar location, skin cover quality and respect of volumes.

[External canthus reconstruction with tarso-conjunctival transposition flap and Hübner's graft].

The external canthus defects with resection of the superior and inferior eyelids external portion remains difficult to treat. The reconstruction has to focus on both the reconstruction of the tarso-conjunctival plan and the musculo-cutaneous plan but has also to treat the disappearance of the external canthus. Usually the tarso-conjunctival plan is reconstructed by a septal transplant, conqual or of palatine mucous membrane.

Omega-3 fatty acids and brain resistance to ageing and stress: body of evidence and possible mechanisms.

The increasing life expectancy in the populations of rich countries raises the pressing question of how the elderly can maintain their cognitive function. Cognitive decline is characterised by the loss of short-term memory due to a progressive impairment of the underlying brain cell processes. Age-related brain damage has many causes, some of which may be influenced by diet.

[Schmid-Meyer fronto-temporal flap for nasal reconstruction].

Introduction: Many surgical techniques have already been described to repair full thickness defects of the inferior part of the nose. The Schmid-Meyer fronto-temporal flap procedure, a little known technique, is based on the old principle of autonomization of a cutaneous flap and uses a tailor-made composite cartilaginous graft placed in the temporal region. This graft is progressively detached and allows mucosal/cartilaginous/and cutaneous nasal repair.

Omega-3 fatty acids deficiency aggravates glutamatergic synapse and astroglial aging in the rat hippocampal CA1.

Epidemiological data suggest that a poor ω3 status favoured by the low ω3/ω6 polyunsaturated fatty acids ratio in western diets contributes to cognitive decline in the elderly, but mechanistic evidence is lacking. We therefore explored the impact of ω3 deficiency on the evolution of glutamatergic transmission in the CA1 of the hippocampus during aging by comparing 4 groups of rats aged 6-22 months fed ω3-deficient or ω3/ω6-balanced diets from conception to sacrifice: Young ω3 Balanced (YB) or Deficient (YD), Old ω3 Balanced (OB) or Deficient (OD) rats. ω3 Deficiency induced a 65% decrease in the amount of docosahexaenoic acid (DHA, the main ω3 in cell membranes) in brain phospholipids, but had no impact on glutamatergic transmission and astroglial function in young rats.

[Moldable titanium mesh for chest wall reconstruction, an elegant solution about a case report].

Introduction: Several surgical techniques are available for full thickness chest wall reconstruction. The choice has to be adapted to the size of the loss of tissue, its location, and must finally be accepted by the patient's. We propose a new and unpublished solution.

Reversal of age-related oxidative stress prevents hippocampal synaptic plasticity deficits by protecting D-serine-dependent NMDA receptor activation.

Oxidative stress (OS) resulting from an imbalance between antioxidant defenses and the intracellular accumulation of reactive oxygen species (ROS) contributes to age-related memory deficits. While impaired synaptic plasticity in neuronal networks is thought to underlie cognitive deficits during aging, whether this process is targeted by OS and what the mechanisms involved are still remain open questions. In this study, we investigated the age-related effects of the reducing agent N-acetyl-L-cysteine (L-NAC) on the activation of the N-methyl-D-aspartate receptor (NMDA-R) by its co-agonist D-serine, because alterations in this mechanism contribute greatly to synaptic plasticity deficits in aged animals.

[Conchal flap with a superior pedicle to reconstruct the middle or upper third of the auricle].

The middle or upper third of the auricle can be reconstructed with a composite chondro-cutaneous peninsular flap of the conchal part of the auricle. This peninsular flap is based on the anastomotic network between the posterior auricular and the superficial temporal artery. The authors report their experience about 24 clinical cases.