Efficient Synthesis of Orphaned Cyclopropanes Using Sulfones as Carbene Equivalents.

Small molecules containing 1,1-dimethylcyclopropanes are prevalent throughout nature but are difficult to synthesize using state-of-the-art metal-catalyzed carbene transfer methods without competing 1,2-hydride shifts. Herein, we introduce a mechanistically distinct platform to transfer 1,1-dialkylcarbene units to olefins using carbometalation reactions of dialkyl sulfonyl anions. In the presence of NaNH or -BuLi in ethereal solvents, dialkyl sulfones react with styrenes and arylbutadienes between 23 and 70 °C to produce the corresponding 1,1-dialkylcyclopropanes.

Real-world retrospective study of effectiveness and safety of FINgOlimod in relapsing remitting multiple sclerosis in the Middle East and North Africa (FINOMENA).

Objectives: Evidence on the effectiveness and safety of fingolimod in real-world clinical practice in the Middle East and North African (MENA) region is limited. This study aimed to evaluate the effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) in real-world setting in the MENA region.

Patients And Methods: RRMS patients who had been treated with fingolimod for at least 12 months were retrospectively identified from the databases of 34 centers across the MENA region.

Metabolic control of acclimation to nutrient deprivation dependent on polyphosphate synthesis.

Polyphosphate, an energy-rich polymer conserved in all kingdoms of life, is integral to many cellular stress responses, including nutrient deprivation, and yet, the mechanisms that underlie its biological roles are not well understood. In this work, we elucidate the physiological function of this polymer in the acclimation of the model alga to nutrient deprivation. Our data reveal that polyphosphate synthesis is vital to control cellular adenosine 5'-triphosphate homeostasis and maintain both respiratory and photosynthetic electron transport upon sulfur deprivation.

Simplified identification of disulfide, trisulfide, and thioether pairs with 213 nm UVPD.

Disulfide heterogeneity and other non-native crosslinks introduced during therapeutic antibody production and storage could have considerable negative effects on clinical efficacy, but tracking these modifications remains challenging. Analysis must also be carried out cautiously to avoid introduction of disulfide scrambling or reduction, necessitating the use of low pH digestion with less specific proteases. Herein we demonstrate that 213 nm ultraviolet photodissociation streamlines disulfide elucidation through bond-selective dissociation of sulfur-sulfur and carbon-sulfur bonds in combination with less specific backbone dissociation.

Catastrophic relapses following initiation of dimethyl fumarate in two patients with neuromyelitis optica spectrum disorder.

We report two cases of neuromyelitis optica spectrum disorder (NMOSD) who were misdiagnosed as multiple sclerosis (MS) and developed catastrophic relapses following initiation of dimethyl fumarate. Both patients developed a severe myelitis extending from the cervical cord to the medulla with significant cord swelling, resulting in complete quadriplegia and respiratory difficulties, in addition to severe bilateral visual loss in one patient. It is of note that both catastrophic relapses occurred 2 and 3 months following initiation of dimethyl fumarate.

Cerebrovascular risk factors and triggers in transient global amnesia patients with and without jugular valve incompetence: results from a sample of 243 patients.

Background/aims: Different etiologies for transient global amnesia (TGA) have been proposed, such as venous flow abnormalities, spreading depression and migraine-related mechanisms like focal ischemia. Jugular vein valve incompetence (JVI) is commonly described in TGA patients, but its contributing role in TGA pathogenesis is still unknown. We investigated the possible relationship between JVI and pathogenetic mechanisms in TGA.

Internal carotid artery stenting in patients over 80 years of age: single-center experience and review of the literature.

Background: Thirty percent to 40% of strokes in the elderly are secondary to carotid bifurcation disease. The treatment of internal carotid artery (ICA) stenosis in this patient population is a clinical dilemma. Age more than 80 years is a risk factor for carotid endarterectomy (CEA).

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is not significantly correlated to Transient Global Amnesia: preliminary results of an on-going study in Brescia Province, Italy.

Transient Global Amnesia (TGA) is a well defined pure amnesic clinical syndrome characterized by acute loss of memory in middle aged people. The aetiology of TGA is still unknown but clinical and neuroimaging studies support a hippocampi involvement, and some reports suggested a possible common genetic background in cases of familial TGA. A single nucleotide polymorphism (SNP) in the Brain-derived neurotrophic factor (BDNF) gene that causes a valine to methionine substitution at codon 66 (Val66Met) has been demonstrated to affect human memory and hippocampal function in the development and maintenance of adult neurons.

Transient global amnesia and brain lesions: new hints into clinical criteria.

Background And Purpose: Transient global amnesia (TGA) is the abrupt onset of anterograde amnesia with repetitive queries. Different hypotheses have been considered for its aetiology, but it still remains obscure. In 1990, Hodges and Warlow proposed clinical criteria for TGA.

Complex-shaped platinum coils for brain aneurysms: higher packing density, improved biomechanical stability, and midterm angiographic outcome.

Background And Purpose: Five to 60% of coiled brain aneurysms recanalize, generally because of coil compaction. In vitro exclusive use of complex-shaped coils allows better packing of the aneurysmal sac and the neck as compared with helical coils. We report a single-center, prospective study using complex coils.

Recurrency in transient global amnesia: a retrospective study.

Transient global amnesia (TGA) is a well-defined clinical syndrome of unknown etiology, which often occurs once in life. Several mechanisms have been proposed but only trigger events have been clearly associated with the attack such as physical exertion, emotional stress, sexual intercourse or immersion in cold water. According to our knowledge, this is the first study, which associates trigger events and TGA recurrency.

A complicated case of intracranial hypotension: diagnostic and management strategies.

We report a case of a patient aged 66 years, with spontaneous intracranial hypotension presenting initially with postural headache, complicated by subdural haematomas and followed by progressive decline of his clinical condition evolving in obtundation state, cranial nerve involvement and gaze paralysis. The patient underwent a long course of different therapeutical approaches: medical and surgical treatment, intrathecal saline infusion and epidural blood patching (EBP). Rapid and dramatic relief of the patient's symptoms was obtained after a third lumbar EBP and he was discharged asymptomatic two weeks later.

Advances in treatment of acute ischemic stroke.

Stroke carries a severe toll in terms of loss of life and disability for patients and their families. Until 10 years ago, physicians, and in particular neurologists, had a conservative, non-aggressive approach to this devastating disease. The advent of thrombolytic therapy not only proved that acute ischemic stroke is treatable, but also that early reperfusion can dramatically change the outcome of acute stroke patients.

Advances in treatment of acute ischemic stroke.

Stroke carries a severe toll in terms of loss of life and disability for patients and their families. Until 10 years ago, physicians, and in particular neurologists, had a conservative, nonaggresive approach to this devastating disease. The advent of thrombolytic therapy not only proved that acute ischemic stroke is treatable, but also that early reperfusion can dramatically change the outcome of acute stroke patients.

Weather conditions and transient global amnesia. A six-year study.

Objectives: The aetiology of transient global amnesia (TGA) is still unknown. Various events or activities have been shown to trigger TGA. A common feature of these events is an increased sympathetic activity which in turn may be influenced by meteorological factors.

Polyglycolide/polylactide-coated platinum coils for patients with ruptured and unruptured cerebral aneurysms: a single-center experience.

Background And Purpose: Recanalization of cerebral aneurysm is a limitation of bare platinum coils (BPCs). In a swine aneurysm model, polyglycolide/polylactide (a polymer)-coated platinum coils (Matrix) accelerated clot fibrosis and reduced recanalization rate and aneurysmal volume. We aimed to evaluate the safety of Matrix coils in patients with intracranial aneurysm.

Is transient global amnesia a risk factor for amnestic mild cognitive impairment?

Transient Global Amnesia (TGA) is a common condition of unknown aetiology characterised by the abrupt onset of severe anterograde amnesia, which lasts less than 24 hours. Some authors have suggested that subclinical impairment of memory functions may persist for much longer, but neuropsychological assessment lasting years after TGA attack has not been performed so far. The aim of this study was to evaluate longterm cognitive functions in patients with a previous TGA episode.

Is mild vascular cognitive impairment reversible? Evidence from a study on the effect of carotid endarterectomy.

Mild vascular cognitive impairment (mVCI) is a broader term that is intended to detect cognitive loss before the development of dementia. The identification of preventable risk factors as well as therapeutic strategies of intervention is still unclear. It has been suggested that carotid endarterectomy (CEA) improves cognitive functions, beyond the well-known preventive effect upon future stroke events.

Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer Disease: from risk factors to disease modulators.

Increasing biological and clinical findings argue for a link between brain cholesterol turnover and Alzheimer Disease (AD), high cerebral levels of the former increasing Abeta load. Cerebral cholesterol elimination involves two mechanisms dependent on Apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46). The aim of this study was to evaluate an intronic variation in CYP46 (intron 2, T --> C ) along with ApoE genotype as risk factors for AD and to establish the correlation between CYP46/ApoE polymorphism and disease progression.

Synergistic effect of apolipoprotein E polymorphisms and cigarette smoking on risk of ischemic stroke in young adults.

Background And Purpose: The effect of apolipoprotein E (APOE) polymorphisms on stroke risk may be influenced by the coexistence of modifiable predisposing conditions. We explored the interactions of APOE genotypes and conventional risk factors in a case-control study of young adults with cerebral infarct.

Methods: We analyzed 124 consecutive patients (age, 34.

Serum cholesterol levels modulate long-term efficacy of cholinesterase inhibitors in Alzheimer disease.

The clinical, genetic or biological variables which regulate long-term efficacy of cholinesterase inhibitors (ChEIs) in Alzheimer disease (AD) are still unknown and it is not possible to predict who will benefit from the treatment. In this study we showed that high cholesterol levels correlated with faster decline at 1-year follow-up in AD patients on ChEIs. These findings suggest that serum cholesterol is a modulating factor of treatment response and additional therapies aimed at reducing treatable high cholesterol levels may represent an alternative strategy to improve ChEIs efficacy and slow down disease progression over time.

Early stages of probable Alzheimer disease are associated with changes in platelet amyloid precursor protein forms.

Previous findings demonstrated an altered pattern of amyloid precursor protein (APP) forms in platelets of Alzheimer disease (AD) patients, compared both with healthy control subjects or patients with non-Alzheimer-type dementia. The present study aims to evaluate whether platelet APP form ratio (APPr) is altered in patients with early stage AD. We selected 40 patients with early stage AD and 40 age-matched healthy controls.