Imaging modalities in acute ischemic stroke

As "time is brain", acute ischemic stroke is considered a medical emergency. With the introduction of thrombolytic therapy and availability of modern neuroimaging modalities, timely diagnosis of an ischemic lesion, exclusion of intracerebral hemorrhage, assessing the degree of brain injury, and evaluation of cerebral vasculature is necessary in acute stroke management. In this review we will highlight the importance of available imaging modalities used to assess patients with acute ischemic stroke.Includes bibliographical reference

Are there predictive pupillometry markers in determining external ventricular device (EVD) weaning failure or success in subarachnoid hemorrhage patients?

Pupillometers objectively measure constriction (i.e., parasympathetic pathwy) and dilation (i.e., sympathetic pathway) velocities of the pupillary reflex. These pathways may be affected by increases in ventricular size due to changes in cerebrospinal fluid (CSF) volume, such as during external ventricular device (EVD) weaning in aneurysmal subarachnoid hemorrhage (aSAH) patients. This pilot study evaluated if changes in pupillary responses could be predictive of EVD weaning failure in aSAH patients. Additionally, we analyzed ventricular size and pupillary reactions in these two groups.Includes bibliographical reference

Acute ischemic stroke management review for the hospitalist

The treatment of acute ischemic stroke is dependent on timely recognition. After ensuring airway, respiratory and circulatory stability, NIHSS should be performed and urgent CT scan obtained. If no exclusions exist, recombinant tissue plasminogen activator (rtPA) should be administered as soon as possible. Select patients may be eligible for mechanical thrombectomy. Stroke patients shouldbe admitted to a dedicated stroke service to determine stroke mechanism, manage risk factors, and initiate preventive therapies.Includes bibliographical reference

Feasibility of performing apnea test in a brain dead patient on veno-venous extracorporeal membrane oxygenation (ECMO)

Extracorporeal membrane oxygenation (ECMO) is being increasingly used to provide support in patients with refractory cardiopulmonary distress syndromes. Neurological sequelae, either from the ECMO or the hypoxic/hypotensive event leading to ECMO, are common. We present a patient requiring veno-venous (V-V) ECMO for an acute respiratory distress syndrome (ARDS) following cardiopulmonary arrest who suffered an irreversible brain injury. Eventually she required an evaluation for death by neurological criteria while on V-V ECMO making apnea testing challenging. We report the ability to safely perform apnea testing in a patient with a devastating brain injury requiring V-V ECMO.Includes bibliographical reference

MiR-15a/miR-16-1 expression inversely correlates with cyclin D1 levels in Men1 pituitary NETs

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid, pituitary and pancreatic islet tumours, and is due to mutations of the MEN1 gene, which encodes the tumour suppressor protein menin. Menin has multiple roles in genome stability, transcription, cell division and proliferation, but its mechanistic roles in tumourigenesis remain to be fully elucidated. MicroRNAs (miRNA) are non-coding single stranded RNAs that post-transcriptionally regulate gene expression and have been associated with tumour development, although the contribution of miRNAs to MEN1-associated tumourigenesis and their relationship with menin expression are not fully understood. Alterations in miRNA expression, including downregulation of three putative ‘tumour suppressor’ miRNAs, miR-15a, miR-16-1 and let 7a, have been reported in several tumour types including non-MEN1 pituitary adenomas. We have therefore investigated the expression of miR-15a, miR-16-1 and let-7a in pituitary tumours that developed after 12 months of age in female mice with heterozygous knock out of the Men1 gene (Men1+/- 41 mice). The miRNAs miR-15a, miR-16-1 and let-7a were significantly downregulated in pituitary tumours (by 2.3-fold, p<0.05; 2.1-fold p<0.01 and 1.6-fold p<0.05, respectively) of Men1+/- 43 mice, compared to normal wild type pituitaries. MiR-15a and miR-16-1 expression inversely correlated with expression of cyclin D1, a known pro-tumourigenic target of these miRNAs, and knock down of menin in a human cancer cell line (HeLa), and AtT20 mouse pituitary cell line resulted in significantly decreased expression of miR-15a (p<0.05), indicating that the decrease in miR-15a may be a direct result of lost menin expression

Shift Work in Nurses: Contribution of Phenotypes and Genotypes to Adaptation

Daily cycles of sleep/wake, hormones, and physiological processes are often misaligned with behavioral patterns during shift work, leading to an increased risk of developing cardiovascular/metabolic/gastrointestinal disorders, some types of cancer, and mental disorders including depression and anxiety. It is unclear how sleep timing, chronotype, and circadian clock gene variation contribute to adaptation to shift work.Newly defined sleep strategies, chronotype, and genotype for polymorphisms in circadian clock genes were assessed in 388 hospital day- and night-shift nurses.Night-shift nurses who used sleep deprivation as a means to switch to and from diurnal sleep on work days (∼25%) were the most poorly adapted to their work schedule. Chronotype also influenced efficacy of adaptation. In addition, polymorphisms in CLOCK, NPAS2, PER2, and PER3 were significantly associated with outcomes such as alcohol/caffeine consumption and sleepiness, as well as sleep phase, inertia and duration in both single- and multi-locus models. Many of these results were specific to shift type suggesting an interaction between genotype and environment (in this case, shift work).Sleep strategy, chronotype, and genotype contribute to the adaptation of the circadian system to an environment that switches frequently and/or irregularly between different schedules of the light-dark cycle and social/workplace time. This study of shift work nurses illustrates how an environmental "stress" to the temporal organization of physiology and metabolism can have behavioral and health-related consequences. Because nurses are a key component of health care, these findings could have important implications for health-care policy

Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism

The process of axonal and dendritic development establishes the synaptic circuitry of the central nervous system (CNS) and is the result of interactions between intrinsic molecular factors and the external environment. One growth factor that has a compelling function in neuronal development is the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF participates in axonal and dendritic differentiation during embryonic stages of neuronal development, as well as in the formation and maturation of dendritic spines during postnatal development. Recent studies have also implicated vesicular trafficking of BDNF via secretory vesicles, and both secretory and endosomal trafficking of vesicles containing synaptic proteins, such as neurotransmitter and neurotrophin receptors, in the regulation of axonal and dendritic differentiation, and in dendritic spine morphogenesis. Several genes that are either mutated or deregulated in neurodevelopmental disorders associated with mental retardation have now been identified, and several mouse models of these disorders have been generated and characterized. Interestingly, abnormalities in dendritic and synaptic structure are consistently observed in human neurodevelopmental disorders associated with mental retardation, and in mouse models of these disorders as well. Abnormalities in dendritic and synaptic differentiation are thought to underlie altered synaptic function and network connectivity, thus contributing to the clinical outcome. Here, we review the roles of BDNF and vesicular trafficking in axonal and dendritic differentiation in the context of dendritic and axonal morphological impairments commonly observed in neurodevelopmental disorders associated with mental retardation