Sanchez, Jully M.; Tan, Judy Ann; Farmakiotis, Dimitrios; Aggarwal, Vikas
2011-01-01
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare but important cause of stroke-like symptoms which can often be missed Thambisetty and Newman 2004. We describe a case of a young male presenting with stroke-like episodes, later diagnosed with MELAS in an attempt to improve the understanding about diagnosing MELAS in the appropriate clinical context. PMID:21789268
Joo, Jung-Chul; Seol, Myung Do; Yoon, Jin Won; Lee, Young Soo; Kim, Dong-Keun; Choi, Yong Hoon; Ahn, Hyo Seong; Cho, Wook Hyun
2013-03-01
Myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystem clinical syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis and recurrent stroke-like episodes. A 27-year-old female with MELAS syndrome presented with cerebral infarction. Echocardiography revealed a thrombus attached to the apex of the hypertrophied left ventricle, with decreased systolic function. The embolism of the intracardiac thrombus might have been the cause of stroke. There should be more consideration given to the increased possibility of intracardiac thrombus formation when a MELAS patient with cardiac involvement is encountered.
Nicotinamide Riboside and Mitochondrial Biogenesis
2018-03-15
Mitochondrial Diseases; Mitochondrial Myopathies; Progressive External Ophthalmoplegia; Progressive Ophthalmoplegia; Progressive; Ophthalmoplegia, External; Mitochondria DNA Deletion; MELAS; Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes; Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)
Regression of stroke-like lesions in MELAS-syndrome after seizure control.
Finsterer, Josef; Barton, Peter
2010-12-01
There are some indications that seizure activity promotes the development of stroke-like episodes, or vice versa, in patients with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome or other syndromic mitochondrial disorders. A 41-year-old Caucasian female with MELAS syndrome, presenting with short stature, microcytic anaemia, increased blood-sedimentation rate, myopathy, hyper-gammaglobulinaemia, an iron-metabolism defect, migraine-like headaches, and stroke-like episodes, developed complex partial and generalised seizures at age 32 years. Valproic acid was ineffective but after switching to lamotrigine and lorazepam, she became seizure-free for five years and stroke-like episodes did not recur. Cerebral MRI initially showed enhanced gyral thickening and a non-enhanced T2-hyperintensity over the left parieto-temporo-occipital white matter and cortex and enhanced caudate heads. After two years without seizures, the non-enhanced hyperintense parieto-temporo-occipital lesion had disappeared, being attributed to consequent seizure control. The caudate heads, however, remained hyperintense throughout the observational period. This case indicates that adequate seizure control in a patient with MELAS syndrome may prevent the recurrence of stroke-like episodes and may result in the disappearance of stroke-like lesions on MRI.
Steriade, Claude; Andrade, Danielle M; Faghfoury, Hanna; Tarnopolsky, Mark A; Tai, Peter
2014-05-01
Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome can present management challenges. Refractory seizures and stroke-like episodes leading to disability are common. We analyzed the clinical, electrophysiologic, and radiologic data of a 22-year-old woman with multiple episodes of generalized and focal status epilepticus and migratory cortical stroke-like lesions who underwent muscle biopsy for mitochondrial genome sequencing. Although initial mitochondrial genetic testing was negative, muscle biopsy demonstrated a mitochondrial DNA disease-causing mutation (m.3260A > G). New antiepileptic medications were added with each episode of focal status epilepticus with only temporary improvement, until a modified ketogenic diet and magnesium were introduced, leading to seizure freedom despite development of a new stroke-like lesion, and subsequent decrease in frequency of stroke-like episodes. We propose a metabolic model in which the ketogenic diet may lead to improvement of the function of respiratory chain complexes. The ketogenic diet may lead to improvement of mitochondrial dysfunction in MELAS, which in turn may promote better seizure control and less frequent stroke-like episodes. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.
Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes-MELAS Syndrome.
Henry, Caitlin; Patel, Neema; Shaffer, William; Murphy, Lillian; Park, Joe; Spieler, Bradley
2017-01-01
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder that results in waxing and waning nervous system and muscle dysfunction. MELAS syndrome may overlap with other neurologic disorders but shows distinctive imaging features. We present the case of a 28-year-old female with atypical stroke-like symptoms, a strong family history of stroke-like symptoms, and a relapsing-remitting course for several years. We discuss the imaging features distinctive to the case, the mechanism of the disease, typical presentation, imaging diagnosis, and disease management. This case is a classic example of the relapse-remitting MELAS syndrome progression with episodic clinical flares and fluctuating patterns of stroke-like lesions on imaging. MELAS is an important diagnostic consideration when neuroimaging reveals a pattern of disappearing and relapsing cortical brain lesions that may occur in different areas of the brain and are not necessarily limited to discrete vascular territories. Future studies should investigate disease mechanisms at the cellular level and the value of advanced magnetic resonance imaging techniques for a targeted approach to therapy.
Genetics Home Reference: mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
... my area? Other Names for This Condition MELAS MELAS syndrome mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like ... basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci. 2008 Oct;1142: ...
MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options.
El-Hattab, Ayman W; Adesina, Adekunle M; Jones, Jeremy; Scaglia, Fernando
2015-01-01
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. MELAS syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature. The most common mutation associated with MELAS syndrome is the m.3243A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNA(Leu(UUR)). The m.3243A>G mutation results in impaired mitochondrial translation and protein synthesis including the mitochondrial electron transport chain complex subunits leading to impaired mitochondrial energy production. The inability of dysfunctional mitochondria to generate sufficient energy to meet the needs of various organs results in the multi-organ dysfunction observed in MELAS syndrome. Energy deficiency can also stimulate mitochondrial proliferation in the smooth muscle and endothelial cells of small blood vessels leading to angiopathy and impaired blood perfusion in the microvasculature of several organs. These events will contribute to the complications observed in MELAS syndrome particularly the stroke-like episodes. In addition, nitric oxide deficiency occurs in MELAS syndrome and can contribute to its complications. There is no specific consensus approach for treating MELAS syndrome. Management is largely symptomatic and should involve a multidisciplinary team. Unblinded studies showed that l-arginine therapy improves stroke-like episode symptoms and decreases the frequency and severity of these episodes. Additionally, carnitine and coenzyme Q10 are commonly used in MELAS syndrome without proven efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.
[MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes].
Murakami, Hidetomo; Ono, Kenjiro
2017-02-01
Mitochondrial disease is caused by a deficiency in the energy supply to cells due to mitochondrial dysfunction. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a mitochondrial disease that presents with stroke-like episodes such as acute onset of neurological deficits and characteristic imaging findings. Stroke-like episodes in MELAS have the following features: 1) neurological deficits due to localization of lesions in the brain, 2) episodes often accompany epilepsy, 3) lesions do not follow the vascular supply area, 4) lesions are more often seen in the posterior brain than in the anterior brain, 5) lesions spread to an adjacent area in the brain, and 6) neurological symptoms often disappear together with imaging findings, but later relapse. About 80% of patients with MELAS have an A-to-G transition mutation at the nucleotide pair 3243 in the dihydrouridine loop of mitochondrial tRNALeu(UUR), which causes the absence of posttranscriptional taurine modification at the wobble nucleotide of mitochondrial tRNALeu(UUR) and disrupts protein synthesis. However, the precise pathophysiology of stroke-like episodes is under investigation, with possible hypotheses for these episodes including mitochondrial angiopathy, mitochondrial cytopathy, and neuron-astrocyte uncoupling. With regard to treatment, L-arginine and taurine have recently been suggested for relief of clinical symptoms.
Ge, Yu-Xing; Shang, Bo; Chen, Wen-Zhen; Lu, You; Wang, Jue
2017-03-01
Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a clinical syndrome associated with mitochondrial disorders (MIDs). This report illustrates a case of MELAS syndrome with hypothyroidism and psychiatric disorders, which is different from the common clinical manifestations of MELAS syndrome, such as exercise intolerance, migraine-like headaches, hearing loss and seizures etc. There are considerable interests in the possibility that mitochondrial dysfunction may play a role in the pathogenesis of endocrine dysfunctions and psychiatric disorders in MELAS syndrome.
Arginine and citrulline for the treatment of MELAS syndrome
El-Hattab, Ayman W.; Almannai, Mohammed; Scaglia, Fernando
2017-01-01
MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO) deficiency occurs in MELAS syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS syndrome. L-citrulline raises NO production to a greater extent than L-arginine; therefore, L-citrulline may have a better therapeutic effect. The clinical effect of L-citrulline has not yet been studied and clinical studies on L-arginine, which are limited, only evaluated the stroke-like episodes aspect of the disease. Controlled studies are still needed to assess the clinical effects of L-arginine and L-citrulline on different aspects of MELAS syndrome. PMID:28736735
Arginine and citrulline for the treatment of MELAS syndrome.
El-Hattab, Ayman W; Almannai, Mohammed; Scaglia, Fernando
2017-01-01
MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO) deficiency occurs in MELAS syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS syndrome. L-citrulline raises NO production to a greater extent than L-arginine; therefore, L-citrulline may have a better therapeutic effect. The clinical effect of L-citrulline has not yet been studied and clinical studies on L-arginine, which are limited, only evaluated the stroke-like episodes aspect of the disease. Controlled studies are still needed to assess the clinical effects of L-arginine and L-citrulline on different aspects of MELAS syndrome.
Late onset MELAS with m.3243A > G mutation and its association with aneurysm formation.
Zhu, Kun; Li, Shuang; Chen, Huan; Wang, Yao; Yu, Miao; Wang, Hongyan; Zhao, Weijie; Cao, Yunpeng
2017-08-01
We reported a 53-year-old with late-onset mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) accompanied by aneurysm and large vessel dilations. Most studies have focused on microangiopathy causing stroke-like episodes. We report a case to describe large vessel involvement in clinical considerations, and possible mechanisms of aneurysm formation. We recommended regular angiographic examination for patients with MELAS.
Kim, Ji Hye; Jeon, Tae Yeon; Rha, Jung Ho; Eo, Hong; Yoo, So-Young; Shu, Chang Hae
2011-01-01
Objective We analyzed the diffusion and perfusion characteristics of acute MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode) lesions in a large series to investigate the controversial changes of the apparent diffusion coefficient (ADC) that were reported in prior studies. Materials and Methods We analyzed 44 newly appearing lesions during 28 stroke-like episodes in 13 patients with MELAS. We performed a visual assessment of the MR images including the ADC and perfusion maps, comparison of the ADC between the normal and abnormal areas, comparison of % ADC between the 44 MELAS lesions and the 30 acute ischemic infarcts. In addition, the patterns of evolution on follow-up MR images were analyzed. Results Decreased, increased, and normal ADCs were noted in 16 (36%), 16 (36%), and 12 (27%) lesions, respectively. The mean % ADC was 102 ± 40.9% in the MELAS and 64 ± 17.8% in the acute vascular infarcts (p < 0.001), while perfusion imaging demonstrated hyper-perfusion in six acute MELAS lesions. On follow-up images, resolution, progression, and tissue loss were noted in 10, 4, and 17 lesions, respectively. Conclusion The cytotoxic edema gradually evolves following an acute stroke-like episode in patients with MELAS, and this may overlap with hyper-perfusion and vasogenic edema. The edematous swelling may be reversible or it may evolve to encephalomalacia, suggesting irreversible damage. PMID:21228936
Lorenzoni, Paulo José; Werneck, Lineu Cesar; Kay, Cláudia Suemi Kamoi; Silvado, Carlos Eduardo Soares; Scola, Rosana Herminia
2015-11-01
Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a rare mitochondrial disorder. Diagnostic criteria for MELAS include typical manifestations of the disease: stroke-like episodes, encephalopathy, evidence of mitochondrial dysfunction (laboratorial or histological) and known mitochondrial DNA gene mutations. Clinical features of MELAS are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALeu(UUR) gene of the DNAmt, mainly A3243G, are responsible for more of 80% of MELAS cases. Morphological changes seen upon muscle biopsy in MELAS include a substantive proportion of ragged red fibers (RRF) and the presence of vessels with a strong reaction for succinate dehydrogenase. In this review, we discuss mainly diagnostic criterion, clinical and laboratory manifestations, brain images, histology and molecular findings as well as some differential diagnoses and current treatments.
Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes—MELAS Syndrome
Henry, Caitlin; Patel, Neema; Shaffer, William; Murphy, Lillian; Park, Joe
2017-01-01
Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder that results in waxing and waning nervous system and muscle dysfunction. MELAS syndrome may overlap with other neurologic disorders but shows distinctive imaging features. Case Report: We present the case of a 28-year-old female with atypical stroke-like symptoms, a strong family history of stroke-like symptoms, and a relapsing-remitting course for several years. We discuss the imaging features distinctive to the case, the mechanism of the disease, typical presentation, imaging diagnosis, and disease management. Conclusion: This case is a classic example of the relapse-remitting MELAS syndrome progression with episodic clinical flares and fluctuating patterns of stroke-like lesions on imaging. MELAS is an important diagnostic consideration when neuroimaging reveals a pattern of disappearing and relapsing cortical brain lesions that may occur in different areas of the brain and are not necessarily limited to discrete vascular territories. Future studies should investigate disease mechanisms at the cellular level and the value of advanced magnetic resonance imaging techniques for a targeted approach to therapy. PMID:29026367
Ohsawa, Yutaka; Hagiwara, Hiroki; Nishimatsu, Shin-Ichiro; Hirakawa, Akihiro; Kamimura, Naomi; Ohtsubo, Hideaki; Fukai, Yuta; Murakami, Tatsufumi; Koga, Yasutoshi; Goto, Yu-Ichi; Ohta, Shigeo; Sunada, Yoshihide
2018-04-17
The aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare genetic disorder caused by point mutations in the mitochondrial DNA that lead to a taurine modification defect at the first anticodon nucleotide of mitochondrial tRNA Leu(UUR) , resulting in failure to decode codons accurately. After the nationwide survey of MELAS, we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke-like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNA Leu(UUR) was measured before and after the trial. The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNA Leu(UUR) from peripheral blood leukocytes (P<0.05). No severe adverse events were associated with taurine. The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke-like episodes and increase taurine modification in mitochondrial tRNA Leu(UUR) in MELAS. UMIN000011908. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Multimodal imaging-monitored progression of stroke-like episodes in a case of MELAS syndrome.
Namer, Izzie Jacques; Wolff, Valérie; Dietemann, Jean-Louis; Marescaux, Christian
2014-03-01
We report imaging findings during, between, and after 2 stroke-like episodes in a 45-year-old woman with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome with an A32243G mitochondrial mutation 6 years before. In November 2010, for a first episode, she showed mixed aphasia with logorrhea, disinhibition, agitation, euphoria, and a large left temporoparietal lesion. Symptomatology progressively regressed under L-arginine treatment. She was readmitted in June 2011 for a second episode with great anxiety, disorientation, impaired face recognition, worsening mixed aphasia, and a new right temporal lesion. After additional L-carnitine treatment, she remained without relapse for 14 months.
Xie, Sheng
2014-01-01
Oxygen extraction fraction (OEF) is defined as the ratio of blood oxygen that a tissue takes from the blood flow to maintain function and morphological integrity. OEF reflects the efficiency of oxygen utilization by the tissue and, therefore, is a hemodynamic measure in brain ischemia. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a common mitochondrial disorder. It is characterized by neurological remissions and relapses and associated with progressive neurocognitive deficits. Because of abnormalities of mitochondrial function in MELAS, defects in the oxidative metabolic pathways of energy production decrease the cerebral oxygen utilization and lead to the reduction of OEF. Quantification of OEF can reflect the functional status of cerebral mitochondria and provide insight into the pathophysiological changes in the brain in MELAS. In light of recent advances in MRI, the discovery of the blood-oxygen level-dependent signal has allowed development of MRI methods targeted toward quantitative OEF imaging. A new MR sequence, termed the gradient-echo sampling of spin echo, was successfully developed to enable quantitative assessment of the OEF in the brain tissue. MR OEF imaging in patients with MELAS detects extensive OEF reduction in the stroke-like lesions, as well as in the normal-appearing brain regions. More severe dysfunction of the mitochondria in the stroke-like lesions was implied at the onset of the stroke-like episode. Determination of OEF throughout the episode demonstrated a chronological change in mitochondrial function in individual cases. Such neuroimaging findings might provide some clues in the investigation of the underlying mechanisms of stroke-like episodes.
[l-arginine efficiency in MELAS syndrome. A case report].
Moutaouakil, F; El Otmani, H; Fadel, H; Sefrioui, F; Slassi, I
2009-05-01
Mitochondrial encephalomyopathy lactic acidosis and stoke-like episodes (MELAS) is a rare neurodegenerative disease caused by mutations of mitochondrial DNA. We report the case of a 12-year-old child with MELAS syndrome who presented with recurrent migraine-like headache and sudden blindness suggesting stroke-like episodes. Furthermore, he developed progressive muscular impairment with bilateral hearing loss. Serum lactate and pyruvate levels were elevated and the muscle biopsy showed an aspect of red-ragged fibers with Gomori trichrome. Brain imaging showed calcifications of basal ganglia on the CT scan and a parieto-occipital high signal on diffusion-weighted MRI. A genetic analysis was not performed but the presence of hearing loss in the patient's mother was suggestive of maternal transmission. Stroke-like episodes in the form of migraine-like headache and blindness were the patient's major complaint and did not improve despite analgesic drugs. After oral administration of l-arginine at the dose of 0.4mg/kg per day, stroke-like symptoms totally and rapidly disappeared. The efficiency of l-arginine in stroke-like episodes was initially reported then confirmed in a controlled study. The pathophysiology of stoke-like episodes and the mechanisms underlying the action of l-arginine are discussed.
Cai, Stephen S; von Coelln, Rainer; Kouo, Theresa J
2016-12-01
Imaging findings of adult-onset mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is poorly documented. The authors present a 48-year-old woman with subacute onset of word-finding difficulties and right arm stiffness. Magnetic resonance imaging performed 2 weeks prior revealed left temporal lobe diffusion and fluid-attenuated inversion recovery hyperintensity predominantly involving the cortex. The apparent diffusion coefficient map showed preserved signal in the temporal cortex. Subsequent magnetic resonance imagings demonstrated a new diffusion signal abnormality extending to the left parietal cortex and occipital cortex with resolving diffusion hyperintensity in the temporal lobe. MR spectroscopy showed scattered areas of lactate deposition. Diagnosis of MELAS syndrome was confirmed by genetic analysis. Fluctuating, migratory stroke-like lesions with a predilection for the parietal, temporal, and occipital cortex that do not conform to a vascular territory and a lactate spike at 1.3 ppm on MR spectroscopy are characteristic of MELAS syndrome. Preserved signal intensity on apparent diffusion coefficient is useful to distinguish MELAS syndrome from ischemic infarction where the signal is typically reduced.
A Mitochondrial Disorder in a Middle Age Iranian Patient: Report of a Rare Case
Almasi, Mostafa; Motamed, Mohammad Reza; Mehrpour, Masoud; Haghi-Ashtiani, Bahram; Haji Akhondi, Fahimeh; Nilipour, Yalda; Fereshtehnejad, Seyed-Mohammad
2017-01-01
Introduction: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) can involve multiple systems and cause stroke-like episodes and status epilepticus. Case Presentation: A 48-year-old female with history of early fatigability, migraine-type headaches, and bilateral sensory-neural hearing loss presented 3 episodes of serial seizures. On admission she was affected by Wernicke aphasia and, then, right hemiparesis. Investigations showed elevated arterial lactate and ragged red fibers on muscle biopsy. Conclusion: Though more commonly diagnosed during childhood, some cases of adult-onset MELAS syndrome are reported. This syndrome should be considered in patients with stroke-like events in adults without cerebrovascular risk factors and difficult-to-treat seizures. PMID:29158884
Acute auditory agnosia as the presenting hearing disorder in MELAS.
Miceli, Gabriele; Conti, Guido; Cianfoni, Alessandro; Di Giacopo, Raffaella; Zampetti, Patrizia; Servidei, Serenella
2008-12-01
MELAS is commonly associated with peripheral hearing loss. Auditory agnosia is a rare cortical auditory impairment, usually due to bilateral temporal damage. We document, for the first time, auditory agnosia as the presenting hearing disorder in MELAS. A young woman with MELAS (A3243G mtDNA mutation) suffered from acute cortical hearing damage following a single stroke-like episode, in the absence of previous hearing deficits. Audiometric testing showed marked central hearing impairment and very mild sensorineural hearing loss. MRI documented bilateral, acute lesions to superior temporal regions. Neuropsychological tests demonstrated auditory agnosia without aphasia. Our data and a review of published reports show that cortical auditory disorders are relatively frequent in MELAS, probably due to the strikingly high incidence of bilateral and symmetric damage following stroke-like episodes. Acute auditory agnosia can be the presenting hearing deficit in MELAS and, conversely, MELAS should be suspected in young adults with sudden hearing loss.
Sproule, Douglas M; Kaufmann, Petra
2008-10-01
Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.
The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome.
El-Hattab, Ayman W; Emrick, Lisa T; Williamson, Kaitlin C; Craigen, William J; Scaglia, Fernando
2013-12-01
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials.
The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome☆
El-Hattab, Ayman W.; Emrick, Lisa T.; Williamson, Kaitlin C.; Craigen, William J.; Scaglia, Fernando
2013-01-01
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials. PMID:25411654
Scaglia, Fernando; Northrop, Jennifer L
2006-01-01
Mitochondrial encephalomyopathies are a multisystemic group of disorders that are characterised by a wide range of biochemical and genetic mitochondrial defects and variable modes of inheritance. Among this group of disorders, the mitochondrial myopathy, encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome is one of the most frequently occurring, maternally inherited mitochondrial disorders. As the name implies, stroke-like episodes are the defining feature of the MELAS syndrome, often occurring before the age of 15 years. The clinical course of this disorder is highly variable, ranging from asymptomatic, with normal early development, to progressive muscle weakness, lactic acidosis, cognitive dysfunction, seizures, stroke-like episodes, encephalopathy and premature death. This syndrome is associated with a number of point mutations in the mitochondrial DNA, with over 80% of the mutations occurring in the dihydrouridine loop of the mitochondrial transfer RNA(Leu(UUR)) [tRNA(Leu)((UUR))] gene. The pathophysiology of the disease is not completely understood; however, several different mechanisms are proposed to contribute to this disease. These include decreased aminoacylation of mitochondrial tRNA, resulting in decreased mitochondrial protein synthesis; changes in calcium homeostasis; and alterations in nitric oxide metabolism. Currently, no consensus criteria exist for treating the MELAS syndrome or mitochondrial dysfunction in other diseases. Many of the therapeutic strategies used have been adopted as the result of isolated case reports or limited clinical studies that have included a heterogeneous population of patients with the MELAS syndrome, other defects in oxidative phosphorylation or lactic acidosis due to disorders of pyruvate metabolism. Current approaches to the treatment of the MELAS syndrome are based on the use of antioxidants, respiratory chain substrates and cofactors in the form of vitamins; however, no consistent benefits have been observed with these treatments.
Santa, Kristin M
2010-11-01
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare neurodegenerative disease caused by the decreased ability of cells to produce sufficient energy in the form of adenosine 5'-triphosphate. Although it is one of the most common maternally inherited mitochondrial disorders, its exact incidence is unknown. Caused most frequently by an A-to-G point mutation at the 3243 position in the mitochondrial DNA, MELAS syndrome has a broad range of clinical manifestations and a highly variable course. The classic neurologic characteristics include encephalopathy, seizures, and stroke-like episodes. In addition to its neurologic manifestations, MELAS syndrome exhibits multisystem effects including cardiac conduction defects, diabetes mellitus, short stature, myopathy, and gastrointestinal disturbances. Unfortunately, no consensus guidelines outlining standard drug regimens exist for this syndrome. Many of the accepted therapies used in treating MELAS syndrome have been identified through a small number of clinical trials or isolated case reports. Currently, the drugs most often used include antioxidants and various vitamins aimed at minimizing the demands on the mitochondria and supporting and maximizing their function. Some of the most frequently prescribed agents include coenzyme Q(10), l-arginine, B vitamins, and levocarnitine. Although articles describing MELAS syndrome are available, few specifically target education for clinical pharmacists. This article will provide pharmacists with a practical resource to enhance their understanding of MELAS syndrome in order to provide safe and effective pharmaceutical care.
Elevated thyroid peroxidase antibodies with encephalopathy in MELAS syndrome.
Chan, Derrick W S; Lim, C C Tchoyoson; Tay, Stacey K H; Choong, Chew-Thye; Phuah, Huan Kee
2007-06-01
Both the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) and Hashimoto's encephalopathy can present with nonspecific encephalopathy. Hashimoto's encephalopathy is an association of steroid-responsive encephalopathy with elevated thyroid peroxidase antibodies. Steroid-responsive encephalopathy, however, is not characteristic of the MELAS syndrome, which typically presents with stroke-like episodes and lactic acidosis in cerebrospinal fluid and blood. Here, a patient is described with goiter, recurrent encephalopathy and elevated thyroid peroxidase antibodies who apparently responded to steroid therapy; however, magnetic resonance imaging was atypical for Hashimoto's encephalopathy, and she was diagnosed with MELAS syndrome. This syndrome can present with apparent steroid-responsive encephalopathy and elevated thyroid peroxidase antibodies, mimicking Hashimoto's encephalopathy, and should be suspected if lactic acidosis is present and typical features are detected on magnetic resonance imaging.
Mitochondria: role of citrulline and arginine supplementation in MELAS syndrome.
El-Hattab, Ayman W; Emrick, Lisa T; Chanprasert, Sirisak; Craigen, William J; Scaglia, Fernando
2014-03-01
Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS syndrome are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.
[Arreflexic coma and MELAS syndrome].
Muñoz-Guillén, N; León-López, R; Ferrer-Higueras, M J; Vargas-Vaserot, F J; Dueñas-Jurado, J M
2009-01-01
MELAS is a progressive neurodegenerative and fatal disease characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. It is the result of a mitochondrial DNA mutation. Although the incidence of MELAS is currently unknown, it is suspected that approximately 1 out of every 5,000 persons world-wide have some type of defect in mitochondrial DNA. Cardinal clinical features observed in more than 90% of the patients include severe headache that may be associated with stroke-like episodes, seizures and the onset of symptoms before the age of 40 years. Diagnosis is established through genetic test or by with muscle biopsies that reveal the presence of ragged-red fibers. Prognosis is poor, with death at an early age. In this article, we present the clinical case of a 31-year old women diagnosed of MELAS syndrome who was admitted to the Intensive Care Unit of our hospital with arreflexic coma.
USDA-ARS?s Scientific Manuscript database
Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient energy to meet the needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial...
Bell, Josh D; Higgie, Kushlin; Joshi, Mital; Rucker, Joshua; Farzi, Sahar; Siddiqui, Naveed
2017-07-15
MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like symptoms) is a rare and complex mitochondrial disorder. We present the in-hospital course of a 36-year-old gravida 2, para 0 with MELAS syndrome and severe preeclampsia, complicated by hyponatremia, hyperkalemia, and diabetes. A retained placenta with postpartum hemorrhage required urgent instrumental delivery under spinal anesthesia, transfusion, and intensive care unit admission for pulmonary edema, effusions, and atelectasis. Postpartum endometritis and sepsis also were encountered. This is to our knowledge the first case report of obstetric complications in MELAS syndrome and highlights the salient metabolic sequelae of this syndrome.
Arrhythmia as a cardiac manifestation in MELAS syndrome.
Thomas, Tamara; Craigen, William J; Moore, Ryan; Czosek, Richard; Jefferies, John L
2015-09-01
A 44-year-old female with a diagnosis of mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS) syndrome had progressive left ventricular hypertrophy (LVH) on echocardiogram. A Holter monitor demonstrated episodes of non-sustained atrial tachycardia, a finding not been previously described in this population. This unique case of MELAS syndrome demonstrates the known associated cardiac manifestation of LVH and the new finding of atrial tachycardia which may represent the potential for subclinical arrhythmia in this population.
Ichikawa, Hiroo
2016-02-01
Stroke-like episodes are one of the cardinal features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and occur in 84-99% of the patients. The affected areas detected on neuroimaging do not have classical vascular distribution, and involve predominantly the temporal, parietal and occipital lobes. Thus, the neurological symptoms including higher brain dysfunction correlate with this topographical distribution. In association with the occipital lobe involvement, the most frequent symptom is cortical blindness. Other symptoms have been occasionally reported in case reports: visual agnosia, prosopagnosia, cortical deafness, auditory agnosia, topographical disorientation, various types of aphasia, hemispatial neglect, and so on. On the other hand, cognitive decline associated with more diffuse brain impairment rather than with focal stroke-like lesions has been postulated. This condition is also known as mitochondrial dementia. Domains of cognitive dysfunction include abstract reasoning, verbal memory, visual memory, language (naming and fluency), executive or constructive functions, attention, and visuospatial function. Cognitive functions and intellectual abilities may decline from initially minimal cognitive impairment to dementia. To date, the neuropsychological and neurologic impairment has been reported to be associated with cerebral lactic acidosis as estimated by ventricular spectroscopic lactate levels.
Dichloroacetate treatment for mitochondrial cytopathy: long-term effects in MELAS.
Mori, Masato; Yamagata, Takanori; Goto, Tamako; Saito, Shigeko; Momoi, Mariko Y
2004-10-01
The long-term effects of the sodium salt of dichloroacetic acid (DCA) were evaluated in four patients with mitochondrial encephalomyelopathy with lactic acidosis and stroke-like episodes (MELAS) carrying A3243G mutation. Oral administration of DCA in MELAS patients was followed for an average of 5 years 4 months. Serum levels of lactate and pyruvate were maintained at around 10 and 0.6 mg/dl, respectively. Serum levels of DCA were 40-136 microg/ml. Symptoms responding to treatment included persistent headache, abdominal pain, muscle weakness, and stroke-like episodes. In contrast, no improvements in mental status, deafness, short stature, or neuroelectrophysiological findings were observed. Adverse effects included mild liver dysfunction in all patients, hypocalcemia in three and peripheral neuropathy in one. None of these adverse events was severe enough to require discontinuation of treatment. To determine suitable indications for DCA therapy, analysis of many more patients who have undergone DCA administration is required.
Matsui, Jun; Takano, Tomoyuki; Ryujin, Fukiko; Anzai, Yuko; Yoshioka, Seiichiro; Takeuchi, Yoshihiro; Goto, Yuichi
2014-09-01
We experienced a case in which mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was identified as complications following the onset of Leigh syndrome along with a 10191 T>C mutation of the mitochondrial gene. The case pertains to a 26-year-old woman. The disease appeared when she was 11 years old due to divergent strabismus, at which point a diagnosis of juvenile Leigh syndrome was made. Many infraction images not conforming to the vessel region were observed upon a brain MRI which was performed at 26 years of age, thus leading to her being diagnosed with MELAS as a complication. Upoon bibliographical consideration, it was speculated that the clinical features of MELAS/Leigh overlap syndrome clearly differ from Leigh syndrome in terms of age of onset, symptoms, and prognosis. Pleiotropic genetic factors including heteroplasmy were presumed to be involved in the diverse phenotype of overlap syndrome.
Park, Jin Suk; Kang, Hyun; Cha, Su Man; Park, Jung Won; Jung, Yong Hun; Woo, Young-Cheol
2010-01-01
A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome. PMID:20508802
Park, Jin Suk; Baek, Chong Wha; Kang, Hyun; Cha, Su Man; Park, Jung Won; Jung, Yong Hun; Woo, Young-Cheol
2010-04-01
A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome.
MERRF/MELAS overlap syndrome due to the m.3291T>C mutation.
Liu, Kaiming; Zhao, Hui; Ji, Kunqian; Yan, Chuanzhu
2014-03-01
We report the case of a 19-year-old Chinese female harboring the m.3291T>C mutation in the MT-TL1 gene encoding the mitochondrial transfer RNA for leucine. She presented with a complex phenotype characterized by progressive cerebellar ataxia, frequent myoclonus seizures, recurrent stroke-like episodes, migraine-like headaches with nausea and vomiting, and elevated resting lactate blood level. It is known that the myoclonus epilepsy with ragged-red fibers (MERRF) is characterized by cerebellar ataxia and myoclonus epilepsy, while that the mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is characterized by recurrent stroke-like episodes, migraine-like headaches, and elevated resting lactate blood level. So the patient's clinical manifestations suggest the presence of a MERRF/MELAS overlap syndrome. Muscle biopsy of the patient showed the presence of numerous scattered ragged-red fibers, some cytochrome c oxidase-deficient fibers, and several strongly succinate dehygrogenase-reactive vessels, suggestive of a mitochondrial disorder. Direct sequencing of the complete mitochondrial genome of the proband revealed no mutations other than the T-to-C transition at nucleotide position 3291. Restriction fragment length polymorphism analysis of the proband and her family revealed maternal inheritance of the mutation in a heteroplasmic manner. The analysis of aerobic respiration and glycolysis demonstrated that the fibroblasts from the patient had mitochondrial dysfunction. Our results suggest that the m.3291T>C is pathogenic. This study is the first to describe the m.3291T>C mutation in association with the MERRF/MELAS overlap syndrome.
Wang, Ying-Xin; Le, Wei-Dong
2015-01-01
Objective: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a progressive, multisystem affected mitochondrial disease associated with a number of disease-related defective genes. MELAS has unpredictable presentations and clinical course, and it can be commonly misdiagnosed as encephalitis, cerebral infarction, or brain neoplasms. This review aimed to update the diagnosis progress in MELAS, which may provide better understanding of the disease nature and help make the right diagnosis as well. Data Sources: The data used in this review came from published peer review articles from October 1984 to October 2014, which were obtained from PubMed. The search term is “MELAS”. Study Selection: Information selected from those reported studies is mainly based on the progress on clinical features, blood biochemistry, neuroimaging, muscle biopsy, and genetics in diagnosing MELAS. Results: MELAS has a wide heterogeneity in genetics and clinical manifestations. The relationship between mutations and phenotypes remains unclear. Advanced serial functional magnetic resonance imaging (MRI) can provide directional information on this disease. Muscle biopsy has meaningful value in diagnosing MELAS, which shows the presence of ragged red fibers and mosaic appearance of cytochrome oxidase negative fibers. Genetic studies have reported that approximately 80% of MELAS cases are caused by the mutation m.3243A>G of the mitochondrial transfer RNA (Leu (UUR)) gene (MT-TL1). Conclusions: MELAS involves multiple systems with variable clinical symptoms and recurrent episodes. The prognosis of MELAS patients depends on timely diagnosis. Therefore, overall diagnosis of MELAS should be based on the maternal inheritance family history, clinical manifestation, and findings from serial MRI, muscle biopsy, and genetics. PMID:26112726
Lee, Ha Neul; Eom, Soyong; Kim, Se Hoon; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Heung Dong; Lee, Young-Mock
2016-11-01
Epileptic seizures in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) are heterogeneous with no pathognomonic features. We reviewed epilepsy characteristics and clinical outcome exclusively in a pediatric population. Twenty-two children and adolescents (13 males) with confirmed mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes due to mitochondrial DNA A3243G mutation and epilepsy were recruited. Clinical data including seizure semiology, treatment response, neuroimaging findings, and electroencephalography were analyzed. We also examined the effect of the age at seizure onset and initial symptoms on the clinical variables. Seizure semiology and electroencephalography abnormalities showed no syndrome-specific findings. Focal seizures occurred in 21 of 22 subjects (95.5%), whereas generalized seizures developed in seven of 22 subjects (31.8%). Twenty of 22 subjects (90.9%) achieved partial to complete reduction of clinical seizures for more than one year with a combination of more than two antiepileptic drugs. The subgroup with earlier seizure onset presented significantly earlier and showed significantly higher rates of drug-resistant epilepsy compared with the late onset group, although there were no significant differences in the initial symptoms. The subjects with severe epileptic conditions tended to have more severe clinical dysfunction and more severe organ involvement. Both focal and generalized seizures occurred in patients with MELAS. Epilepsy in this population is drug resistant, but a certain degree of clinical seizure reduction was achievable with antiepileptic drugs, with more favorable outcomes than historically expected. Close observation and active epilepsy treatment of individuals with MELAS episodes and earlier seizure onset might improve the prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.
Hsu, Yu-Chuan; Yang, Fu-Chi; Perng, Cherng-Lih; Tso, An-Chen; Wong, Lee-Jun C; Hsu, Chang-Hung
2012-09-01
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder with a wide range of multisystemic symptoms. Epileptic seizures are common features of both MELAS and meningoencephalitis and are typically treated with anticonvulsants. To provide the reader with a better understanding of MELAS and the adverse effects of valproic acid. A 47-year-old man with a history of diabetes, hearing loss, sinusitis, and otitis media was brought to our emergency department due to acute onset of fever, headache, generalized seizure, and agitation. Because acute meningoencephalitis was suspected, the patient was treated with antibiotics on an empirical basis. The seizure activity was aggravated by valproic acid and abated after its discontinuation. MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. Detailed history-taking and systematic review help emergency physicians differentiate MELAS from meningoencephalitis in patients with the common presentation of epileptic seizures. Use of valproic acid to treat epilepsy in patients suspected of having mitochondrial disease should be avoided. Underlying mitochondrial disease should be suspected if seizure activity worsens with valproic acid therapy. Copyright © 2012 Elsevier Inc. All rights reserved.
Maurtua, M; Torres, A; Ibarra, V; DeBoer, G; Dolak, J
2008-10-01
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) is a mitochondrial disorder associated with neurologic, cardiac, neuromuscular, hepatic, metabolic and gastrointestinal dysfunction and potential anesthetic and obstetric complications. The case of a parturient with MELAS syndrome requiring labor analgesia is presented. A Medline literature search limited to the English language was undertaken to review cases of MELAS syndrome. Based on our experience and literature review, parturients with MELAS syndrome appear to benefit from neuraxial analgesia and anesthesia, which blunt excessive oxygen consumption and acidosis.
Vandana, V P; Bindu, Parayil Sankaran; Sonam, Kothari; Taly, Arun B; Gayathri, N; Madhu, N; Sinha, S
2015-01-01
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disease. The available studies on MELAS syndrome are limited to evaluation of radiological, audiological, genetic, and neurological findings. Among the various neurological manifestations, speech-language and swallowing manifestations are less discussed in the literature. This report describes the speech-language and swallowing function in an 11-year-old girl with MELAS syndrome. The intervention over a period of 6 months is discussed.
Vandana, V. P.; Bindu, Parayil Sankaran; Sonam, Kothari; Taly, Arun B.; Gayathri, N.; Madhu, N.; Sinha, S.
2015-01-01
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disease. The available studies on MELAS syndrome are limited to evaluation of radiological, audiological, genetic, and neurological findings. Among the various neurological manifestations, speech-language and swallowing manifestations are less discussed in the literature. This report describes the speech-language and swallowing function in an 11-year-old girl with MELAS syndrome. The intervention over a period of 6 months is discussed. PMID:25878740
Perfusion status of the stroke-like lesion at the hyperacute stage in MELAS.
Yeh, Hsu-Ling; Chen, Yen-Kung; Chen, Wei-Hung; Wang, Han-Cheng; Chiu, Hou-Chang; Lien, Li-Ming; Wei, Yau-Huei
2013-02-01
Hypoperfusion on single-photon emission computed tomography (SPECT) of the stroke-like lesion (SLL) at the hyperacute stage of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) is considered to be a supportive evidence of the mitochondrial angiopathy theory. Our objectives were to examine whether other neuroimages, especially transcranial color-coded sonography (TCCS), done at the hyperacute stage of stroke-like episode (SLE) is consistent with hypoperfusion of the SLL. We reviewed the magnetic resonance imaging (MRI), SPECT, cerebral angiography, and TCCS of a patient with MELAS syndrome, all of which were performed at the hyperacute stage of one SLE. MRI on the 1st day post SLE showed right temporoparietal lesion with vasogenic edema. SPECT on the 2nd day showed focal decreased uptake of technetium-99m hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) in the same region, but cerebral angiography and TCCS on the 3rd day showed increased regional cerebral blood flow (rCBF) and distal arteriole dilation in the same region. TCCS can delineate increased rCBF of the SLL at the hyperacute stage of SLE. We propose that the discrepancy between the decreased (99m)Tc-HMPAO uptake and increased rCBF might be caused by mitochondrial dysfunction. The phenomenon of "hypoperfusion" on SPECT might be caused by cell dysfunction but not decreased rCBF. We suggest that SPECT can be complemented by angiography and TCCS in future studies to delineate the perfusion status of SLLs. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
[MELAS syndrome as a differential diagnosis of ischemic stroke].
Finsterer, J
2009-01-01
Mitochondrial encephalomyopathy, lactacidosis and stroke-like episode (MELAS) syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder with a clinical onset between the first and third decade. The clinical hallmark is the stroke-like-episode, which mimicks ischemic stroke but is usually transient and non-disabling in nature. The morphological equivalent on MRI is a T2-hyperintensity, predominantly over the temporo-parieto-occipital region, not confined to a vascular territory, which is also hyperintense on diffusion weighted imaging and on apparent diffusion coefficient sequences (vasogenic edema, stroke-like lesion). Additional features include seizures, cognitive decline, psychosis, lactic acidosis, migraine, visual impairment, hearing loss, short stature, diabetes, or myopathy. Muscle biopsy typically shows ragged-red fibers, COX-negative fibers, SDH hyperreactivity, and abnormally shaped mitochondria with paracristalline inclusions. The diagnosis is confirmed by demonstration of a biochemical respiratory chain defect or one of the disease-causing mutations, of which 80 % affect the mitochondrial tRNALeu gene.
Gieraerts, Christopher; Demaerel, Philippe; Van Damme, Philip; Wilms, Guido
2013-01-01
We present a case in which mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome mimicked the clinical and radiological signs of herpes simplex encephalitis. In a patient with subacute encephalopathy, on computed tomography and magnetic resonance imaging, lesions were present in both temporal lobes extending to both insular regions with sparing of the lentiform nuclei and in both posterior straight and cingulate gyri. Final diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome was based on biochemical investigations on cerebrospinal fluid, electromyogram, muscle biopsy, and genetic analysis. On diffusion-weighted imaging, diffusion restriction was present in some parts of the lesions but not throughout the entire lesions. We suggest that this could be an important sign in the differential diagnosis with herpes simplex encephalitis.
Macular pattern dystrophy and homonymous hemianopia in MELAS syndrome.
Kamal-Salah, Radua; Baquero-Aranda, Isabel; Grana-Pérez, María Del Mar; García-Campos, Jose Manuel
2015-03-12
We report an unusual association of a pattern dystrophy of the retinal pigment epithelium and homonymous hemianopia in a woman diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome. 2015 BMJ Publishing Group Ltd.
Koszka, Christiane
2009-08-01
Friedrich Nietzsche was one of the most influential and profound German philosophers. After prolonged illness, he died at the age of 55 in Weimar, Germany. The interest in his medical biography has always been strong while the cause of his illness and death has remained a mystery, intriguing philosophers as well as physicians. The diagnosis of syphilis proposed in the 19th century has been controversial until today and many other diagnoses have been discussed. This paper suggests that Nietzsche suffered from mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome.
MELAS syndrome presenting as an acute surgical abdomen.
Dindyal, S; Mistry, K; Angamuthu, N; Smith, G; Hilton, D; Arumugam, P; Mathew, J
2014-01-01
MELAS (mitochondrial cytopathy, encephalomyopathy, lactic acidosis and stroke-like episodes) is a syndrome in which signs and symptoms of gastrointestinal disease are uncommon if not rare. We describe the case of a young woman who presented as an acute surgical emergency, diagnosed as toxic megacolon necessitating an emergency total colectomy. MELAS syndrome was suspected postoperatively owing to persistent lactic acidosis and neurological symptoms. The diagnosis was later confirmed with histological and genetic studies. This case highlights the difficulties in diagnosing MELAS because of its unpredictable presentation and clinical course. We therefore recommend a high index of suspicion in cases of an acute surgical abdomen with additional neurological features or raised lactate.
El-Hattab, Ayman W.; Hsu, Jean W.; Emrick, Lisa T.; Wong, Lee-Jun C.; Craigen, William J.; Jahoor, Farook; Scaglia, Fernando
2014-01-01
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism. PMID:22325939
Yoo, Da Hye; Choi, Young-Chul; Nam, Da Eun; Choi, Sun Seong; Kim, Ji Won; Choi, Byung-Ok; Chung, Ki Wha
2017-07-01
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many parts of the body, particularly the brain and muscles. This study examined a Korean MELAS-like syndrome patient with seizure, stroke-like episode, and optic atrophy. Target sequencing of whole mtDNA and 73 nuclear genes identified compound heterozygous mutations p.R205X and p.L255P in the FASTKD2. Each of his unaffected parents has one of the two mutations, and both mutations were not found in 302 controls. FASTKD2 encodes a FAS-activated serine-threonine (FAST) kinase domain 2 which locates in the mitochondrial inner compartment. A FASTKD2 nonsense mutation was once reported as the cause of a recessive infantile mitochondrial encephalomyopathy. The present case showed relatively mild symptoms with a late onset age, compared to a previous patient with FASTKD2 mutation, implicating an inter-allelic clinical heterogeneity. Because this study is the second report of an autosomal recessive mitochondrial encephalomyopathy patient with a FASTKD2 mutation, it will extend the phenotypic spectrum of the FASTKD2 mutation. Copyright © 2017. Published by Elsevier B.V.
CT and MRI imaging of the brain in MELAS syndrome.
Pauli, Wojciech; Zarzycki, Artur; Krzyształowski, Adam; Walecka, Anna
2013-07-01
MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) is a rare, multisystem disorder which belongs to a group of mitochondrial metabolic diseases. As other diseases in this group, it is inherited in the maternal line. In this report, we discussed a case of a 10-year-old girl with clinical and radiological picture of MELAS syndrome. We would like to describe characteristic radiological features of MELAS syndrome in CT, MRI and MR spectroscopy of the brain and differential diagnosis. The rarity of this disorder and the complexity of its clinical presentation make MELAS patients among the most difficult to diagnose. Brain imaging studies require a wide differential diagnosis, primarily to distinguish between MELAS and ischemic stroke. Particularly helpful are the MRI and MR spectroscopy techniques.
Rodan, Lance H; Wells, Greg D; Banks, Laura; Thompson, Sara; Schneiderman, Jane E; Tein, Ingrid
2015-01-01
To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR)) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak)) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 3(1)P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg(2+) (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO(2peak). On (31)P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. ClinicalTrials.gov NCT01603446.
MELAS syndrome presenting as an acute surgical abdomen
Mistry, K; Angamuthu, N; Smith, G; Hilton, D; P, Arumugam; Mathew, J
2014-01-01
MELAS (mitochondrial cytopathy, encephalomyopathy, lactic acidosis and stroke-like episodes) is a syndrome in which signs and symptoms of gastrointestinal disease are uncommon if not rare. We describe the case of a young woman who presented as an acute surgical emergency, diagnosed as toxic megacolon necessitating an emergency total colectomy. MELAS syndrome was suspected postoperatively owing to persistent lactic acidosis and neurological symptoms. The diagnosis was later confirmed with histological and genetic studies. This case highlights the difficulties in diagnosing MELAS because of its unpredictable presentation and clinical course. We therefore recommend a high index of suspicion in cases of an acute surgical abdomen with additional neurological features or raised lactate. PMID:24417855
Stroke-like episodes, peri-episodic seizures, and MELAS mutations.
Finsterer, Josef; Wakil, Salma Majid
2016-11-01
Stroke-like episodes (SLEs) are a hallmark of various mitochondrial disorders, in particular MELAS syndrome. SLEs manifest with vasogenic oedema (DWI and ADC hyperintensity) or partial cytotoxic oedema (DWI hyperintensity, ADC hypointensity) in the acute and subacute stage, and with gyriform T1-hyperintensity (cortical necrosis) in the chronic stage. SLEs must be clearly distinguished from ischaemic stroke, since management of these two entities is different. SLEs may go along with or without seizures or epileptiform discharges on EEG. However, in MELAS syndrome seizures may also occur in the absence of SLEs. Focal and generalised seizures have been reported but it is currently unknown if the one or the other prevail. SLEs with and without seizures may respond to NO-precursors l-arginine, succinate, or citrulline. As a supportive measure a ketogenic diet should be initiated. Seizures prior to or during a SLE or paroxysmal EEG-activity during a SLE should be initially treated with antiepileptic drugs (AEDs) with low mitochondrion-toxicity. Only in case these AEDs are ineffective, AEDs with higher mitochondrion-toxicity should be added. All patients with SLEs need to have an EEG recorded irrespective if they have manifesting seizures or not. There are no mtDNA or nDNA mutations which predispose for SLEs with seizures. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
El-Hattab, Ayman W; Hsu, Jean W; Emrick, Lisa T; Wong, Lee-Jun C; Craigen, William J; Jahoor, Farook; Scaglia, Fernando
2012-04-01
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.
CT and MRI imaging of the brain in MELAS syndrome
Pauli, Wojciech; Zarzycki, Artur; Krzyształowski, Adam; Walecka, Anna
2013-01-01
Summary Background: MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) is a rare, multisystem disorder which belongs to a group of mitochondrial metabolic diseases. As other diseases in this group, it is inherited in the maternal line. Case Report: In this report, we discussed a case of a 10-year-old girl with clinical and radiological picture of MELAS syndrome. We would like to describe characteristic radiological features of MELAS syndrome in CT, MRI and MR spectroscopy of the brain and differential diagnosis. Conclusions: The rarity of this disorder and the complexity of its clinical presentation make MELAS patients among the most difficult to diagnose. Brain imaging studies require a wide differential diagnosis, primarily to distinguish between MELAS and ischemic stroke. Particularly helpful are the MRI and MR spectroscopy techniques. PMID:24115962
β-Lapachone attenuates mitochondrial dysfunction in MELAS cybrid cells.
Jeong, Moon Hee; Kim, Jin Hwan; Seo, Kang-Sik; Kwak, Tae Hwan; Park, Woo Jin
2014-11-21
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease caused by mutations in the mitochondrial genome. This study investigated the efficacy of β-lapachone (β-lap), a natural quinone compound, in rescuing mitochondrial dysfunction in MELAS cybrid cells. β-Lap significantly restored energy production and mitochondrial membrane potential as well as normalized the elevated ROS level in MELAS cybrid cells. Additionally, β-lap reduced lactic acidosis and restored glucose uptake in the MELAS cybrid cells. Finally, β-lap activated Sirt1 by increasing the intracellular NAD(+)/NADH ratio, which was accompanied by increased mtDNA content. Two other quinone compounds (idebenone and CoQ10) that have rescued mitochondrial dysfunction in previous studies of MELAS cybrid cells had a minimal effect in the current study. Taken together, these results demonstrated that β-lap may provide a novel therapeutic modality for the treatment of MELAS. Copyright © 2014 Elsevier Inc. All rights reserved.
Lin, Chih-Ming; Thajeb, Peterus
2007-03-01
Epilepsy is one of the most common presentations of patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). MELAS is typically caused by an A-to-G substitution at nucleotide position 3243 of mitochondrial DNA. Valproic acid, a common anticonvulsant, can actually increase the frequency of seizures in individuals with MELAS. Here, we report a single case-study of a 38-year-old man who presented with focal seizures and had MELAS Syndrome due to the A3243G mitochondrial DNA mutation. Manifestation of epilepsia partialis continua was aggravated by use of valproic acid. Convulsions abated after discontinuation of valproic acid. Our experience suggests that valproic acid should be avoided for the treatment of epilepsy in individuals with mitochondrial disease.
Pathology of mitochondria in MELAS syndrome: an ultrastructural study.
Felczak, Paulina; Lewandowska, Eliza; Stępniak, Iwona; Ołdak, Monika; Pollak, Agnieszka; Lechowicz, Urszula; Pasennik, Elżbieta; Stępień, Tomasz; Wierzba-Bobrowicz, Teresa
Ultrastructural changes in skeletal muscle biopsy in a 24-year-old female patient with clinically suspected mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) syndrome are presented. We observed proliferation and/or pleomorphism of mitochondria in skeletal muscle and smooth muscle cells of arterioles, as well as in pericytes of capillaries. Paracrystalline inclusions were found only in damaged mitochondria of skeletal muscle. Genetic testing revealed a point mutation in A3243G tRNALeu(UUR) typical for MELAS syndrome. We conclude that differentiated pathological changes of mitochondria in the studied types of cells may be associated with the different energy requirements of these cells.
Connolly, Barbara S; Feigenbaum, Annette S J; Robinson, Brian H; Dipchand, Anne I; Simon, David K; Tarnopolsky, Mark A
2010-11-12
The A to G transition mutation at position 3260 of the mitochondrial genome is usually associated with cardiomyopathy and myopathy. One Japanese kindred reported the phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS syndrome) in association with the A3260G mtDNA mutation. We describe the first Caucasian cases of MELAS syndrome associated with the A3260G mutation. Furthermore, this mutation was associated with exercise-induced rhabdomyolysis, hearing loss, seizures, cardiomyopathy, and autism in the large kindred. We conclude that the A3260G mtDNA mutation is associated with wide phenotypic heterogeneity with MELAS and other "classical" mitochondrial phenotypes being manifestations. Copyright © 2010 Elsevier Inc. All rights reserved.
Qi, Xiao-Kun; Yao, Sheng; Wang, Hai-Yan; Piao, Yue-Shan; Lu, De-Hong; Yuan, Yun
2009-04-01
To investigate the pathological changes and pathogenesis of the MELAS syndrome (mitochondrial encephalopathy lactic acidosis stroke-like episodes) by using the method of immunohistochemical staining in the brain biopsy specimens with anti-mitochondrial antibody (AMA). We performed immunohistochemical staining in 3 confirmed MELAS patients' paraffin-imbued brain biopsy specimens. Small vessel proliferation and the uneven thickness of the wall were found in the 3 MELAS patients. A lot of brown deposits was shown in the wall of small vessels and also noted in neurons. The main pathological change in the MELAS brain biopsy immunohistochemical staining with AMA was the small vessel proliferation, indicating that abnormal mitochondria accumulated in the vascular smooth muscle, endothelial cell and neurons of the lesion sites. This finding was consistent with the electron microscopic discovery and valuable for the diagnosis of MELAS.
Ganetzky, Rebecca D; Falk, Marni J
2018-03-01
Intravenous (IV) arginine has been reported to ameliorate acute metabolic stroke symptoms in adult patients with Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like Episodes (MELAS) syndrome, where its therapeutic benefit is postulated to result from arginine acting as a nitric oxide donor to reverse vasospasm. Further, reduced plasma arginine may occur in mitochondrial disease since the biosynthesis of arginine's precursor, citrulline, requires ATP. Metabolic strokes occur across a wide array of primary mitochondrial diseases having diverse molecular etiologies that are likely to share similar pathophysiologic mechanisms. Therefore, IV arginine has been increasingly used for the acute clinical treatment of metabolic stroke across a broad mitochondrial disease population. We performed retrospective analysis of a large cohort of subjects who were under 18 years of age at IRB #08-6177 study enrollment and had molecularly-confirmed primary mitochondrial disease (n = 71, excluding the common MELAS m.3243A>G mutation). 9 unrelated subjects in this cohort received acute arginine IV treatment for one or more stroke-like episodes (n = 17 total episodes) between 2009 and 2016 at the Children's Hospital of Philadelphia. Retrospectively reviewed data included subject genotype, clinical symptoms, age, arginine dosing, neuroimaging (if performed), prophylactic therapies, and adverse events. Genetic etiologies of subjects who presented with acute metabolic strokes included 4 mitochondrial DNA (mtDNA) pathogenic point mutations, 1 mtDNA deletion, and 4 nuclear gene disorders. Subject age ranged from 19 months to 23 years at the time of any metabolic stroke episode (median, 8 years). 3 subjects had recurrent stroke episodes. 70% of subjects were on prophylactic arginine or citrulline therapy at the time of a stroke-like episode. IV arginine was initiated on initial presentation in 65% of cases. IV arginine was given for 1-7 days (median, 1 day). A positive clinical response to IV arginine occurred in 47% of stroke-like episodes; an additional 6% of episodes showed clinical benefit from multiple simultaneous treatments that included arginine, confounding sole interpretation of arginine effect. All IV arginine-responsive stroke-like episodes (n = 8) received treatment immediately on presentation (p = .003). Interestingly, the presence of unilateral symptoms strongly predicted arginine response (p = .02, Chi-Square); however, almost all of these cases immediately received IV arginine, confounding interpretation of causality direction. Suggestive trends toward increased IV arginine response were seen in subjects with mtDNA relative to nDNA mutations and in older pediatric subjects, although statistical significance was not reached possibly due to small sample size. No adverse events, including hypotensive episodes, from IV arginine therapy were reported. Single-center retrospective analysis suggests that IV arginine therapy yields significant therapeutic benefit with little risk in pediatric mitochondrial disease stroke subjects across a wide range of genetic etiologies beyond classical MELAS. Acute hemiplegic stroke, in particular, was highly responsive to IV arginine treatment. Prospective studies with consistent arginine dosing, and pre- and post-neuroimaging, will further inform the clinical utility of IV arginine therapy for acute metabolic stroke in pediatric mitochondrial disease. Copyright © 2018 Elsevier Inc. All rights reserved.
Rodan, Lance H.; Wells, Greg D.; Banks, Laura; Thompson, Sara; Schneiderman, Jane E.; Tein, Ingrid
2015-01-01
Objective To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. Methods We performed a case control study in 3 MELAS siblings (m.3243A>G tRNAleu(UUR) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO2peak) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. Results At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 31P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg2+ (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO2peak. On 31P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. Significance These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Classification of Evidence Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. Trial Registration ClinicalTrials.gov NCT01603446. PMID:25993630
MELAS syndrome associated with a new mitochondrial tRNA-Val gene mutation (m.1616A>G).
Toyoshima, Yuka; Tanaka, Yuji; Satomi, Kazuo
2017-09-11
We describe the case of a 40-year-old-man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, with cardiomyopathy and severe heart failure. He had a mitochondrial transfer RNA (tRNA) mutation (m.1616A>G) of the (tRNA-Val) gene, and it was not found in MELAS syndrome ever before. The presence of this newly observed tRNA-Val mutation (m.1616A>G) may induce multiple respiratory chain enzyme deficiencies and contribute to MELAS syndrome symptoms that are associated with mitochondrial DNA (mtDNA) mutations. We report that the pathognomonic symptom in MELAS syndrome caused by this newly observed mtDNA mutation may be rapid progression of cardiomyopathy and severe heart failure. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
[Psychiatric disturbances in five patients with MELAS syndrome].
Magner, Martin; Honzik, Tomas; Tesarova, Marketa; Dvorakova, Veronika; Hansiková, Hana; Raboch, Jiři; Zeman, Jiři
2014-01-01
Mitochondrial disorders of energetic metabolism (MD) represent a heterogeneous group of diseases manifesting at any age with a broad spectrum of clinical symptoms, including psychiatric disorders. The aim of the study was to characterize psychiatric symptoms and diagnoses in five patients with MELAS syndrome between the ages of 17 and 53 years. Four of MELAS patients them harbored the prevalent mitochondrial DNA (mtDNA) mutation 3243A>G, and one patient had the mtDNA mutation 12706T>C. Three patients had positive family histories for MELAS syndrome. In one patient, depression was diagnosedas the first symptom ofMELAS syndrome. Depression also preceded a stroke-like episode in one patient. Four patients had disturbed cognitive functions, confusional states occurred in three patients. One patient manifested psychotic (schizophrenia-like) symptoms. Mitochondrial disorders deserve consideration as part of the differential diagnosis, especially, if there is suspected involvement of other organ groups or positive family history of MD.
Adrenal insufficiency in a child with MELAS syndrome.
Afroze, Bushra; Amjad, Nida; Ibrahim, Shahnaz H; Humayun, Khadija Nuzhat; Yakob, Yusnita
2014-11-01
Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) are established subgroups of mitochondrial encephalomyopathy. m.3243A>G a common point mutation is detected in tRNA in majority of patients with MELAS phenotype whereas m.8344A>G point mutation in tRNA is observed, in MERRF phenotype. Adrenal insufficiency has not been reported in mitochondrial disease, except in Kearns-Sayre Syndrome (KSS), which is a mitochondrial deletion syndrome. We report an unusual presentation in a five year old boy who presented with clinical phenotype of MELAS and was found to have m.8344A>G mutation in tRNA. Addison disease was identified due to hyperpigmentation of lips and gums present from early childhood. This is the first report describing adrenal insufficiency in a child with MELAS phenotype. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Leng, Yinglin; Liu, Yuhe; Fang, Xiaojing; Li, Yao; Yu, Lei; Yuan, Yun; Wang, Zhaoxia
2015-04-01
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes/Leigh (MELAS/LS) overlap syndrome is a mitochondrial disorder subtype with clinical and magnetic resonance imaging (MRI) features that are characteristic of both MELAS and Leigh syndrome (LS). Here, we report an MELAS/LS case presenting with cortical deafness and seizures. Cranial MRI revealed multiple lesions involving bilateral temporal lobes, the basal ganglia and the brainstem, which conformed to neuroimaging features of both MELAS and LS. Whole mitochondrial DNA (mtDNA) sequencing and PCR-RFLP revealed a de novo heteroplasmic m.10197 G > A mutation in the NADH dehydrogenase subunit 3 gene (ND3), which was predicted to cause an alanine to threonine substitution at amino acid 47. Although the mtDNA m.10197 G > A mutation has been reported in association with LS, Leber hereditary optic neuropathy and dystonia, it has never been linked with MELAS/LS overlap syndrome. Our patient therefore expands the phenotypic spectrum of the mtDNA m.10197 G > A mutation.
Defective mitochondrial rRNA methyltransferase MRM2 causes MELAS-like clinical syndrome
Garone, Caterina; D’Souza, Aaron R; Dallabona, Cristina; Lodi, Tiziana; Rebelo-Guiomar, Pedro; Rorbach, Joanna; Donati, Maria Alice; Procopio, Elena; Montomoli, Martino; Guerrini, Renzo; Zeviani, Massimo; Calvo, Sarah E; Mootha, Vamsi K; DiMauro, Salvatore; Ferrero, Ileana; Minczuk, Michal
2017-01-01
Abstract Defects in nuclear-encoded proteins of the mitochondrial translation machinery cause early-onset and tissue-specific deficiency of one or more OXPHOS complexes. Here, we report a 7-year-old Italian boy with childhood-onset rapidly progressive encephalomyopathy and stroke-like episodes. Multiple OXPHOS defects and decreased mtDNA copy number (40%) were detected in muscle homogenate. Clinical features combined with low level of plasma citrulline were highly suggestive of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, however, the common m.3243 A > G mutation was excluded. Targeted exome sequencing of genes encoding the mitochondrial proteome identified a damaging mutation, c.567 G > A, affecting a highly conserved amino acid residue (p.Gly189Arg) of the MRM2 protein. MRM2 has never before been linked to a human disease and encodes an enzyme responsible for 2’-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA. We generated a knockout yeast model for the orthologous gene that showed a defect in respiration and the reduction of the 2’-O-methyl modification at the equivalent position (U2791) in the yeast mitochondrial 21S rRNA. Complementation with the mrm2 allele carrying the equivalent yeast mutation failed to rescue the respiratory phenotype, which was instead completely rescued by expressing the wild-type allele. Our findings establish that defective MRM2 causes a MELAS-like phenotype, and suggests the genetic screening of the MRM2 gene in patients with a m.3243 A > G negative MELAS-like presentation. PMID:28973171
Defective mitochondrial rRNA methyltransferase MRM2 causes MELAS-like clinical syndrome.
Garone, Caterina; D'Souza, Aaron R; Dallabona, Cristina; Lodi, Tiziana; Rebelo-Guiomar, Pedro; Rorbach, Joanna; Donati, Maria Alice; Procopio, Elena; Montomoli, Martino; Guerrini, Renzo; Zeviani, Massimo; Calvo, Sarah E; Mootha, Vamsi K; DiMauro, Salvatore; Ferrero, Ileana; Minczuk, Michal
2017-11-01
Defects in nuclear-encoded proteins of the mitochondrial translation machinery cause early-onset and tissue-specific deficiency of one or more OXPHOS complexes. Here, we report a 7-year-old Italian boy with childhood-onset rapidly progressive encephalomyopathy and stroke-like episodes. Multiple OXPHOS defects and decreased mtDNA copy number (40%) were detected in muscle homogenate. Clinical features combined with low level of plasma citrulline were highly suggestive of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, however, the common m.3243 A > G mutation was excluded. Targeted exome sequencing of genes encoding the mitochondrial proteome identified a damaging mutation, c.567 G > A, affecting a highly conserved amino acid residue (p.Gly189Arg) of the MRM2 protein. MRM2 has never before been linked to a human disease and encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA. We generated a knockout yeast model for the orthologous gene that showed a defect in respiration and the reduction of the 2'-O-methyl modification at the equivalent position (U2791) in the yeast mitochondrial 21S rRNA. Complementation with the mrm2 allele carrying the equivalent yeast mutation failed to rescue the respiratory phenotype, which was instead completely rescued by expressing the wild-type allele. Our findings establish that defective MRM2 causes a MELAS-like phenotype, and suggests the genetic screening of the MRM2 gene in patients with a m.3243 A > G negative MELAS-like presentation. © The Author 2017. Published by Oxford University Press.
Cerebral lactic acidosis correlates with neurological impairment in MELAS.
Kaufmann, P; Shungu, D C; Sano, M C; Jhung, S; Engelstad, K; Mitsis, E; Mao, X; Shanske, S; Hirano, M; DiMauro, S; De Vivo, D C
2004-04-27
To evaluate the role of chronic cerebral lactic acidosis in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The authors studied 91 individuals from 34 families with MELAS and the A3243G point mutation and 15 individuals from two families with myoclonus epilepsy and ragged red fibers (MERRF) and the A8344G mutation. Subjects were divided into four groups. Paternal relatives were studied as controls (Group 1). The maternally related subjects were divided clinically into three groups: asymptomatic (no clinical evidence of neurologic disease) (Group 2), oligosymptomatic (neurologic symptoms but without the full clinical picture of MELAS or MERRF) (Group 3), and symptomatic (fulfilling MELAS or MERRF criteria) (Group 4). The authors performed a standardized neurologic examination, neuropsychological testing, MRS, and leukocyte DNA analysis in all subjects. The symptomatic and oligosymptomatic MELAS subjects had significantly higher ventricular lactate than the other groups. There was a significant correlation between degree of neuropsychological and neurologic impairment and cerebral lactic acidosis as estimated by ventricular MRS lactate levels. High levels of ventricular lactate, the brain spectroscopic signature of MELAS, are associated with more severe neurologic impairment.
Decrease of 3243 A→G mtDNA Mutation from Blood in MELAS Syndrome: A Longitudinal Study
Rahman, S.; Poulton, J.; Marchington, D.; Suomalainen, A.
2001-01-01
It is widely held that changes in the distribution of mutant mtDNAs underlie the progressive nature of mtDNA diseases, but there are few data documenting such changes. We compared the levels of 3243 A→G mutant mtDNA in blood at birth from Guthrie cards and at the time of diagnosis in a blood DNA sample from patients with mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) syndrome. Paired blood DNA samples separated by 9–19 years were obtained from six patients with MELAS. Quantification of mutant load, by means of a solid-phase minisequencing technique, demonstrated a decline (range 12%–29%) in the proportion of mutant mtDNA in all cases (P=.0015, paired t-test). These results suggest that mutant mtDNA is slowly selected from rapidly dividing blood cells in MELAS. PMID:11085913
Aharoni, Sharon; Traves, Teres A; Melamed, Eldad; Cohen, Sarit; Silver, Esther Leshinsky
2010-09-15
The syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) is characterized clinically by recurrent focal neurological deficits, epilepsy, and short stature. The phenotypic spectrum is extremely diverse, with multisystemic organ involvement leading to isolated diabetes, deafness, renal tubulopathy, hypertrophic cardiomyopathy, and retinitis pigmentosa. In 80% of cases, the syndrome is associated with an AG transmission mutation (A3243G) in the tRNALeu gene of the mitochondrial DNA (mtDNA). We describe a woman with a unique combination of the MELAS A3243G mutation and multiple mtDNA deletions with normal POLG sequence. The patient presented with diabetes mellitus, sensorineural deafness, short stature, and mental disorientation. All her three children died in early adolescence. 2010 Elsevier B.V. All rights reserved.
Berbel-Garcia, Angel; Barbera-Farre, Jose Ramon; Etessam, Jesús Porta; Salio, Antonio Martínez; Cabello, Ana; Gutierrez-Rivas, Eduardo; Campos, Yolanda
2004-01-01
Mitochondrial encephalomyopathies encompass a group of disorders that have impaired oxidative metabolism in skeletal muscles and central nervous system. Many compounds have been used in clinical trials on mitochondrial diseases, but the outcomes have been variable. It remains controversial whether treatment of mitochondrial diseases with coenzyme Q 10 is effective. This paper describes a case of mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike episodes, and exercise intolerance successfully treated with coenzyme Q 10. Efficacy of this therapy in this patient is correlated to control of lactic acidosis and serum creatine kinase levels. Disappointingly, larger studies with coenzyme Q 10 failed to demonstrate a clear beneficial effect on the entire study population with regard to clinical improvement or several parameters of the oxidative metabolism. They suggest that the use of coenzyme Q in treatment of mitochondrial diseases should be confined to protocols. There is a confounding variation in phenotype and genotype, and the natural history of the disorders in individual patients is not accurately predictable. The unpredictable a priori efficacy of therapy suggests that a long-term trial of oral coenzyme Q may be warranted.
Renal involvement in MELAS syndrome - a series of 5 cases and review of the literature.
Seidowsky, Alexandre; Hoffmann, Maxime; Glowacki, François; Dhaenens, Claire-Marie; Devaux, Jean-Philippe; de Sainte Foy, Celia Lessore; Provot, François; Gheerbrant, Jean-Dominique; Hummel, Aurelie; Hazzan, Marc; Dracon, Michel; Dieux-Coeslier, Anne; Copin, Marie-Christine; Noël, Christian; Buob, David
2013-12-01
Renal dysfunction is increasingly recognized as a potential clinical feature of mitochondrial cytopathies such as mitochondrial encephalomyopathy, lacticacidosis and stroke-like episodes (MELAS) syndrome. Five cases of MELAS syndrome with renal involvement from 4 unrelated families are presented in this case series. Three of the 5 patients had a history of maternally-inherited diabetes and/or deafness. Focal and segmental glomerulosclerosis and arteriolar hyaline thickening were the most striking findings on renal biopsy. In addition to clinical presentation with the typical symptoms of MELAS syndrome, genetic testing in these patients identified the A3243G point mutation in the tRNALeu gene of the mitochondrial DNA (mtDNA). The diagnosis of MELAS syndrome was thus considered to be unequivocal. The incidence of kidney disease in MELAS syndrome may be underestimated although a study is required to investigate this hypothesis. As the A3243G mtDNA mutation leads to a progressive adult-onset form of focal segmental glomerulosclerosis (FSGS), screening for the MELAS A3243G mtDNA mutation should therefore be performed especially in patients with maternally-inherited diabetes or hearing loss presenting with FSGS.
Advances in the Treatment of MELAS Syndrome: Could Cognitive Rehabilitation Have a Role?
De Luca, Rosaria; Russo, Margherita; Leonardi, Simona; Spadaro, Letteria; Cicero, Cettina; Naro, Antonino; Bramanti, Placido; Calabrò, Rocco Salvatore
2016-01-01
Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes syndrome (MELAS) is a rare inherited mitochondrial disorder, commonly due to the m.3243A>G mutation, which typically presents with seizures, headaches, and acute neurological stroke-mimicking deficits. At onset, there is often no general intellectual deterioration in these patients, although specific cognitive deficits in peculiar language domains, visual construction, attention, abstraction, or flexibility may be present. To date, there is no evidence for an effective treatment in individuals with MELAS. Herein, we describe the case of young woman affected by MELAS who underwent an intensive cognitive training by means of the following methods: (a) traditional cognitive training, (b) computerized cognitive training (CCT), and (c) CCT plus a low-intensity aerobic motor exercise. We compared her cognitive and psychological profile at baseline (T0) and at the end of each training (i.e., (Time 1, Time 2, and Time 3 [T3]) using a proper psychometric battery, and we found a greater improvement at T3. Our findings support the idea that the combined CCT with motor training could represent a valuable therapeutic opportunity in MELAS.
A MELAS syndrome family harboring two mutations in mitochondrial genome.
Choi, Byung-Ok; Hwang, Jung Hee; Kim, Joonki; Cho, Eun Min; Cho, Sun Young; Hwang, Su Jin; Lee, Hyang Woon; Kim, Song Ja; Chung, Ki Wha
2008-06-30
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous mitochondrial disorder with variable clinical symptoms. Here, from the sequencing of the entire mitochondrial genome, we report a Korean MELAS family harboring two homoplasmic missense mutations, which were reported 9957T>C (Phe251Leu) transition mutation in the cytochrome c oxidase subunit 3 (COX3) gene and a novel 13849A>C (Asn505His) transversion mutation in the NADH dehydrogenase subunit 5 (ND5) gene. Neither of these mutations was found in 205 normal controls. Both mutations were identified from the proband and his mother, but not his father. The patients showed cataract symptom in addition to MELAS phenotype. We believe that the 9957T>C mutation is pathogenic, however, the 13849A>C mutation is of unclear significance. It is likely that the 13849A>C mutation might function as the secondary mutation which increase the expressivity of overlapping phenotypes of MELAS and cataract. This study also demonstrates the importance of full sequencing of mtDNA for the molecular genetic understanding of mitochondrial disorders.
A MELAS syndrome family harboring two mutations in mitochondrial genome
Choi, Byung-Ok; Hwang, Jung Hee; Kim, Joonki; Cho, Eun Min; Cho, Sun Young; Hwang, Su Jin; Lee, Hyang Woon; Kim, Song Ja
2008-01-01
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous mitochondrial disorder with variable clinical symptoms. Here, from the sequencing of the entire mitochondrial genome, we report a Korean MELAS family harboring two homoplasmic missense mutations, which were reported 9957T > C (Phe251Leu) transition mutation in the cytochrome c oxidase subunit 3 (COX3) gene and a novel 13849A > C (Asn505His) transversion mutation in the NADH dehydrogenase subunit 5 (ND5) gene. Neither of these mutations was found in 205 normal controls. Both mutations were identified from the proband and his mother, but not his father. The patients showed cataract symptom in addition to MELAS phenotype. We believe that the 9957T > C mutation is pathogenic, however, the 13849A > C mutation is of unclear significance. It is likely that the 13849A > C mutation might function as the secondary mutation which increase the expressivity of overlapping phenotypes of MELAS and cataract. This study also demonstrates the importance of full sequencing of mtDNA for the molecular genetic understanding of mitochondrial disorders. PMID:18587274
Ikawa, Masamichi; Arakawa, Kenichiro; Hamano, Tadanori; Nagata, Miwako; Nakamoto, Yasunari; Kuriyama, Masaru; Koga, Yasutoshi; Yoneda, Makoto
2012-01-01
To clarify the change of systemic redox states in patients carrying the A3243G mutation in mitochondrial DNA (A3243G), we evaluated oxidative stress and antioxidant activity in the serum of patients. Oxidative stress and antioxidant activity in the serum samples obtained from 14 patients carrying A3243G and from 34 healthy controls were analyzed using the diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests, respectively. The mean d-ROMs level of all patients was significantly greater than that of the controls (p < 0.005), and the mean BAP/d-ROMs ratio of all patients was significantly lower than that of the controls (p < 0.02). In the patients with a history of stroke-like episodes (n = 10), both mean d-ROMs and BAP levels were increased compared with those of the controls (both p < 0.01). The mean BAP level of the patients without a history of stroke-like episodes (n = 4) was significantly decreased compared with that of the controls (p < 0.001), but the mean d-ROMs levels were not significantly different. d-ROMs and BAP tests indicated that patients carrying A3243G are always exposed to underlying oxidative stress, even at a remission state of stroke-like episodes. Copyright © 2012 S. Karger AG, Basel.
Lee, Nuri; Kim, Ji-Eun; Yoo, Hyun Ju; Gu, JaYoon; Kim, Hyori; Chung, Junho; Koh, Youngil; Kim, Hyun Kyung
2016-12-01
We present a case of acquired dysfibrinogenemia caused by an autoantibody that inhibited fibrin polymerization in a patient previously diagnosed with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes). The patient showed prolonged PT, aPTT, and thrombin time. There was no factor deficiency but fibrinogen antigen and activity were decreased. ELISA for detection of fibrinogen antibodies were performed and IgG purified from the patient's plasma bound to fibrinogen more strongly than did control IgG, indicating the presence of a fibrinogen-specific antibody. Thrombin-mediated fibrin polymerization was severely impaired in the patient, although thrombin-induced fibrinopeptide A release was normal. Scanning electron microscopy was used to investigate the structure of fibrin clots and revealed many pores on the surface of patient's fibrin clots. Since MELAS is often associated with autoimmune disorders, a work-up for the presence of anti-fibrinogen antibody is necessary when bleeding tendency occurs in MELAS patients along with prolonged thrombin time. © 2016 by the Association of Clinical Scientists, Inc.
Hämäläinen, Riikka H.; Manninen, Tuula; Koivumäki, Hanna; Kislin, Mikhail; Otonkoski, Timo; Suomalainen, Anu
2013-01-01
Mitochondrial DNA (mtDNA) mutations manifest with vast clinical heterogeneity. The molecular basis of this variability is mostly unknown because the lack of model systems has hampered mechanistic studies. We generated induced pluripotent stem cells from patients carrying the most common human disease mutation in mtDNA, m.3243A>G, underlying mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. During reprogramming, heteroplasmic mtDNA showed bimodal segregation toward homoplasmy, with concomitant changes in mtDNA organization, mimicking mtDNA bottleneck during epiblast specification. Induced pluripotent stem cell–derived neurons and various tissues derived from teratomas manifested cell-type specific respiratory chain (RC) deficiency patterns. Similar to MELAS patient tissues, complex I defect predominated. Upon neuronal differentiation, complex I specifically was sequestered in perinuclear PTEN-induced putative kinase 1 (PINK1) and Parkin-positive autophagosomes, suggesting active degradation through mitophagy. Other RC enzymes showed normal mitochondrial network distribution. Our data show that cellular context actively modifies RC deficiency manifestation in MELAS and that autophagy is a significant component of neuronal MELAS pathogenesis. PMID:24003133
Potestio, C P; Check, J H; Mitchell-Williams, J
2014-01-01
To evaluate the efficacy of sympathomimetic amine therapy on a mitochondrial abnormality known as the mitochondrial encephalopathy lactic acidosis and stroke-like symptoms syndrome (MELAS syndrome). Dextroamphetamine sulfate 15 mg extended release capsule was prescribed to a woman with a 25 year history of MELAS syndrome refractory to most other therapies. Within one month of therapy the woman noticed considerable improvement in her chronic fatigue, pain, and edema. The MELAS syndrome is thus another condition to add to the list of various chronic refractory disorders that improve considerably after dextroamphetamine therapy. This is the first mitochondrial disorder shown to improve with sympathomimetic amines which could suggest that dextroamphetamine could prove useful in decreasing the risk of aneuploidy in women of advanced reproductive age.
Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.
Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H
2016-02-01
Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.
Wolff-Parkinson-White syndrome in Patients With MELAS.
Sproule, Douglas M; Kaufmann, Petra; Engelstad, Kristen; Starc, Thomas J; Hordof, Allan J; De Vivo, Darryl C
2007-11-01
Tissues with high energy demands, such as the heart, are susceptible to the effects of mitochondrial DNA point mutations. To investigate the frequency of Wolff-Parkinson-White (WPW) syndrome among a phenotypically and genotypically homogeneous cohort of patients with MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) and the A3243G mutation most commonly associated with MELAS syndrome. Survey. The Pediatric Neuromuscular Disease Center at Columbia University. Patients Thirty patients with the A3243G mutation and MELAS syndrome enrolled in a clinical trial to assess the effect of dichloroacetate on neurologic symptoms. Medical histories and electrocardiograms were reviewed and DNA samples from fibroblasts, urine and cheek epithelial cells, leukocytes, and hair were analyzed to determine mitochondrial mutation abundance and estimate total mutation burden. Four of 30 patients (13%) had a clinical history of, or electrocardiographic findings consistent with, WPW syndrome. In 2 patients, WPW syndrome preceded MELAS syndrome by 15 and 21 years. The tissue burden of mutant mitochondria was similar in patients with (49.4%) and without (39.1%) WPW syndrome. The prevalence of WPW syndrome among patients with MELAS syndrome and the A3243G mutation appears much higher than in the normal population and may become manifest earlier than neurologic symptoms. Patients with WPW syndrome and neurologic abnormalities consistent with MELAS syndrome, such as seizures, deafness, short stature, and stroke, should be screened for the A3243G mutation. Moreover, patients with MELAS syndrome should be monitored for cardiac anomalies including cardiomyopathy and WPW syndrome.
MELAS syndrome in a patient with a point mutation in MTTS1.
Lindberg, C; Moslemi, A-R; Oldfors, A
2008-02-01
BACKGROUND, OBJECTIVE AND METHODS: We describe a female patient with a mitochondrial encephalopathy, lactic acidosis and stroke-like episodes syndrome. As a child, she developed epilepsy and stroke-like episodes giving cognitive impairment and ataxia but no hearing impairment. At the age of 44 years, she suffered a cerebral sinus thrombosis which was warfarin treated. One month later, she developed an episode of severe acidosis associated with encephalopathy and myelopathy. She was found to harbour a 7512T>C mutation in the mitochondrial encoded tRNA(Ser(UCN)) gene (MTTS1). The mutation load was 91% in muscle and 24% in blood. Enzyme histochemical analysis of the muscle tissue showed numerous cytochrome c oxidase (COX)-negative fibres. Restriction fragment length polymorphism (RFLP) analysis of single muscle fibres showed significantly higher level (median 97%, range: 94-99%) of the mutation in the COX-negative fibres compared with COX-positive fibres (median 36%, range: 12-91%), demonstrating the pathogenic effect of the mutation. Different levels of heteroplasmy (range 34-61%) were detected in hair shafts analysed by RFLP. This case adds to the spectrum of clinical presentations, i.e. sinus thrombosis, in patients having MTTS1 mutations.
Cortical venous disease severity in MELAS syndrome correlates with brain lesion development.
Whitehead, M T; Wien, M; Lee, B; Bass, N; Gropman, A
2017-08-01
MELAS syndrome is a mitochondrial disorder typified by recurrent stroke-like episodes, seizures, and progressive brain injury. Abnormal mitochondria have been found in arterial walls implicating a vasculogenic etiology. We have observed abnormal cortical vein T2/FLAIR signal in MELAS patients, potentially representing wall thickening and sluggish flow. We sought to examine the relationship of hyperintense veins and brain lesions in MELAS. Imaging databases at two children's hospitals were searched for brain MRIs from MELAS patients. Artifact, sedated exams, and lack of 2D-T2/FLAIR sequences were exclusion criteria. Each exam was assigned a venous score based on number of T2/FLAIR hyperintense veins: 1 = <10, 2 = 10 to 20, 3 = >20. Cumulative brain lesions and venous score in MELAS and aged-matched normal exams were compared by Mann-Whitney test. A total of 106 exams from 14 unique MELAS patients (mean 16 ± 3 years) and 30 exams from normal aged-matched patients (mean 15 ± 3 years) were evaluated. Median venous score between MELAS and control patients significantly differed (3 versus 1; p < 0.001). In the MELAS group, venous score correlated with presence (median = 3) or absence (median = 1) of cumulative brain lesions. In all 8 MELAS patients who developed lesions, venous hyperintensity was present prior to, during, and after lesion onset. Venous score did not correlate with brain lesion acuity. Abnormal venous signal correlates with cumulative brain lesion severity in MELAS syndrome. Cortical venous stenosis, congestion, and venous ischemia may be mechanisms of brain injury. Identification of cortical venous pathology may aid in diagnosis and could be predictive of lesion development.
MELAS Syndrome and Kidney Disease Without Fanconi Syndrome or Proteinuria: A Case Report.
Rudnicki, Michael; Mayr, Johannes A; Zschocke, Johannes; Antretter, Herwig; Regele, Heinz; Feichtinger, René G; Windpessl, Martin; Mayer, Gert; Pölzl, Gerhard
2016-12-01
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT-TL1 gene, which encodes the mitochondrial tRNA Leu(UUR) . Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m 2 within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.
Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y
2016-01-01
Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.
Episodic weakness due to mitochondrial DNA MT-ATP6/8 mutations.
Auré, Karine; Dubourg, Odile; Jardel, Claude; Clarysse, Lucie; Sternberg, Damien; Fournier, Emmanuel; Laforêt, Pascal; Streichenberger, Nathalie; Petiot, Philippe; Gervais-Bernard, Hélène; Vial, Christophe; Bedat-Millet, Anne-Laure; Drouin-Garraud, Valérie; Bouillaud, Frédéric; Vandier, Christophe; Fontaine, Bertrand; Lombès, Anne
2013-11-19
To report that homoplasmic deleterious mutations in the mitochondrial DNA MT-ATP6/8 genes may be responsible for acute episodes of limb weakness mimicking periodic paralysis due to channelopathies and dramatically responding to acetazolamide. Mitochondrial DNA sequencing and restriction PCR, oxidative phosphorylation functional assays, reactive oxygen species metabolism, and patch-clamp technique in cultured skin fibroblasts. Occurrence of a typical MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome in a single member of a large pedigree with episodic weakness associated with a later-onset distal motor neuropathy led to the disclosure of 2 deleterious mitochondrial DNA mutations. The MT-ATP6 m.9185T>C p.Leu220Pro mutation, previously associated with Leigh syndrome, was present in all family members, while the MT-TL1 m.3271T>C mutation, a known cause of MELAS syndrome, was observed in the sole patient with MELAS presentation. Significant defect of complexes V and I as well as oxidative stress were observed in both primary fibroblasts and cybrid cells with 100% m.9185T>C mutation. Permanent plasma membrane depolarization and altered permeability to K(+) in fibroblasts provided a link with the paralysis episodes. Screening of 9 patients, based on their clinical phenotype, identified 4 patients with similar deleterious MT-ATP6 mutations (twice m.9185T>C and once m.9176T>C or m.8893T>C). A fifth patient presented with an original potentially deleterious MT-ATP8 mutation (m.8403T>C). All mutations were associated with almost-normal complex V activity but significant oxidative stress and permanent plasma membrane depolarization. Homoplasmic mutations in the MT-ATP6/8 genes may cause episodic weakness responding to acetazolamide treatment.
Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Alvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A
2012-11-01
MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. According to our results, supplementation with riboflavin or coenzyme Q(10) effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Álvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A
2012-01-01
BACKGROUND AND PURPOSE MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. EXPERIMENTAL APPROACH We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. KEY RESULTS According to our results, supplementation with riboflavin or coenzyme Q10 effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. CONCLUSIONS AND IMPLICATIONS Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. PMID:22747838
MELAS syndrome with mitochondrial tRNA(Leu(UUR)) gene mutation in a Chinese family.
Huang, C C; Chen, R S; Chen, C M; Wang, H S; Lee, C C; Pang, C Y; Hsu, H S; Lee, H C; Wei, Y H
1994-01-01
The clinical features of a patient in a Chinese family with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) are reported. The study revealed that hearing and visual impairments and miscarriages may be early clinical presentations in MELAS. A heteroplasmic A to G transition in the tRNA(Leu(UUR)) gene was noted at the nucleotide pair 3243 in the mitochondrial DNA of muscle, blood, and hair follicles of the proband and his maternal relatives. Quantitative analysis of the mutated mitochondrial DNA revealed variable proportions in different tissues and subjects of maternal lineage in the family. Muscle tissue contained a higher proportion of the mutant mitochondria than other tissues examined. The function of the reproductive system of the proband seems to be impaired. In one clinically healthy sibling, the 3243rd point mutation was found in sperm mitochondrial DNA, although sperm motility was not affected. It seems that biochemical defects in mitochondrial respiration and oxidative phosphorylation are tissue specific expressions of the 3243rd point mutation in the mitochondrial DNA of the affected target tissues. Images PMID:8201329
Black Toenail Sign in MELAS Syndrome.
Whitehead, Matthew T; Wien, Michael; Lee, Bonmyong; Bass, Nancy; Gropman, Andrea
2017-10-01
Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder often causing progressive brain injury that is not confined to large arterial territories. Severe insults ultimately lead to gyral necrosis affecting the cortex and juxtacortical white matter; the neuroimaging correlate is partial gyral signal suppression on T2/FLAIR sequences that resemble black toenails. We aimed to characterize the imaging features and the natural history of MELAS-related gyral necrosis. Databases at two children's hospitals were searched for brain magnetic resonance imaging studies of individuals with MELAS. Examinations with motion artifact and those lacking T2/FLAIR sequences were excluded. The location, the cumulative number, and the maximum transverse diameter of necrotic gyral lesions were assessed using T2-weighted images and T2/FLAIR sequences. Wilcoxon signed-rank test was employed to evaluate the relationship between disease duration and the number of necrotic lesions. One hundred twenty-four examinations from patients with 14 unique MELAS patients (16 ± 3 years) were evaluated. Six of the eight patients who developed brain lesions also developed gyral necroses (mean 13, range 0 to 44). Necrotic lesions varied in maximal diameter from 4 to 25 mm. Cumulative necrotic lesions correlated with disease duration (P < 0.001). The black toenail sign signifying gyral necrosis is a common imaging feature in individuals with MELAS syndrome. The extent of gyral necrosis correlates with disease duration. Copyright © 2017 Elsevier Inc. All rights reserved.
Haas, A; Wappler, F
2015-10-01
The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a disease triggered by a disorder in energy production within mitochondria. The cause of this syndrome is a mutation in the mitochondrial DNA where in 80% of cases an A-to-G mutation is present at nucleotide 3243 and with a prevalence of 18.4/100,000 in the population. Predominantly affected are organ systems with a high energy metabolism, such as the heart, brain and musculature. During the premedication visit a thorough patient history and examination with respect to neurological impairments must be carried out. Epilepsy and the appropriate permanent medication lead to possible alterations in effectiveness of anesthetics and muscle relaxants which are difficult to predict. An extensive patient cardiac history and a preoperative electrocardiogram (ECG) for an appraisal of possible disorders in the cardiac conduction system and when necessary extended cardiac diagnostics, are recommended. The monitoring must be adapted depending on the functional limitations and the forthcoming intervention and when necessary a postoperative surveillance in an intensive care unit should be initiated. Knowledge of the special features of MELAS syndrome in association with a consideration of the characteristics of anesthesia in MELAS patients and an individually adapted intensified perioperative surveillance, can contribute to a reduction in perioperative morbidity in patients suffering from MELAS syndrome.
Zhiping, W; Quwen, L; Hai, Z; Jian, Z; Peiyi, G
2016-01-01
We report molecular imaging combined with gene diagnosis in a family with 7 members who carried an A3243G mutation in mitochondrial tRNA and p.Thr 137 Met in cationic trypsinogen (PRSS1) gene presented with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), diabetes, and recurrent pancreatitis. DNA sequencing was used to detect and validate mitochondrial DNA and PRSS1. We also verified that mitochondrial heterozygous mutations and c.410 C>T mutation causing p.Thr 137 Met could be detected in oral epithelial cells or in urine sediment cells. In addition, molecular imaging was carried out in the affected family members. In this pedigree, MELAS syndrome accompanied by pancreatitis was an important clinical feature, followed by diabetes. Heteroplasmy of the mtDNA A3243G and c.410 C>T mutation of PRSS1 was found in all tissue samples of these patients, but no mutations were found in 520 normal control and normal individuals of the family. However, based on molecular imaging observations, patients with relatively higher lactate/pyruvate levels had more typical and more severe symptoms, particularly those of pancreatic disease (diabetes or pancreatitis). MELAS syndrome may be associated with pancreatitis. For the diagnosis, it is more reasonable to perform molecular imaging combined with gene diagnosis.
Whole blood genome-wide expression profiling and network analysis suggest MELAS master regulators.
Mende, Susanne; Royer, Loic; Herr, Alexander; Schmiedel, Janet; Deschauer, Marcus; Klopstock, Thomas; Kostic, Vladimir S; Schroeder, Michael; Reichmann, Heinz; Storch, Alexander
2011-07-01
The heteroplasmic mitochondrial DNA (mtDNA) mutation A3243G causes the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome as one of the most frequent mitochondrial diseases. The process of reconfiguration of nuclear gene expression profile to accommodate cellular processes to the functional status of mitochondria might be a key to MELAS disease manifestation and could contribute to its diverse phenotypic presentation. To determine master regulatory protein networks and disease-modifying genes in MELAS syndrome. Analyses of whole blood transcriptomes from 10 MELAS patients using a novel strategy by combining classic Affymetrix oligonucleotide microarray profiling with regulatory and protein interaction network analyses. Hierarchical cluster analysis elucidated that the relative abundance of mutant mtDNA molecules is decisive for the nuclear gene expression response. Further analyses confirmed not only transcription factors already known to be involved in mitochondrial diseases (such as TFAM), but also detected the hypoxia-inducible factor 1 complex, nuclear factor Y and cAMP responsive element-binding protein-related transcription factors as novel master regulators for reconfiguration of nuclear gene expression in response to the MELAS mutation. Correlation analyses of gene alterations and clinico-genetic data detected significant correlations between A3243G-induced nuclear gene expression changes and mutant mtDNA load as well as disease characteristics. These potential disease-modifying genes influencing the expression of the MELAS phenotype are mainly related to clusters primarily unrelated to cellular energy metabolism, but important for nucleic acid and protein metabolism, and signal transduction. Our data thus provide a framework to search for new pathogenetic concepts and potential therapeutic approaches to treat the MELAS syndrome.
El-Hattab, Ayman W; Emrick, Lisa T; Hsu, Jean W; Chanprasert, Sirisak; Almannai, Mohammed; Craigen, William J; Jahoor, Farook; Scaglia, Fernando
2016-04-01
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS syndrome. When compared to control subjects, children with MELAS syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS syndrome. Thus, the initiation of treatment with NO precursors may be beneficial earlier in life. Controlled clinical trials to assess the therapeutic effects of arginine and citrulline on clinical complications of MELAS syndrome are needed. Copyright © 2016 Elsevier Inc. All rights reserved.
El-Hattab, Ayman W.; Emrick, Lisa T; Hsu, Jean W.; Chanprasert, Sirisak; Almannai, Mohammed; Craigen, William J.; Jahoor, Farook; Scaglia, Fernando
2016-01-01
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS syndrome. When compared to control subjects, children with MELAS syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS syndrome. Thus, the initiation of treatment with NO precursors may be beneficial earlier in life. Controlled clinical trials to assess the therapeutic effects of arginine and citrulline on clinical complications of MELAS syndrome are needed. PMID:26851065
Unique presentation of LHON/MELAS overlap syndrome caused by m.13046T>C in MTND5.
Kolarova, Hana; Liskova, Petra; Tesarova, Marketa; Kucerova Vidrova, Vendula; Forgac, Martin; Zamecnik, Josef; Hansikova, Hana; Honzik, Tomas
2016-12-01
Leber hereditary optic neuropathy (LHON) and mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes (MELAS) syndromes are mitochondrially inherited disorders characterized by acute visual failure and variable multiorgan system presentation, respectively. A 12-year-old girl with otherwise unremarkable medical history presented with abrupt, painless loss of vision. Over the next few months, she developed moderate sensorineural hearing loss, vertigo, migraines, anhedonia and thyroiditis. Ocular examination confirmed bilateral optic nerve atrophy. Metabolic workup documented elevated cerebrospinal fluid lactate. Initial genetic analyses excluded the three most common LHON mutations. Subsequently, Sanger sequencing of the entire mitochondrial DNA (mtDNA) genome was performed. Whole mtDNA sequencing revealed a pathogenic heteroplasmic mutation m.13046T>C in MTND5 encoding the ND5 subunit of complex I. This particular variant has previously been described in a single case report of MELAS/Leigh syndrome (subacute necrotizing encephalopathy). Based on the constellation of clinical symptoms in our patient, we diagnose the condition as LHON/MELAS overlap syndrome. We describe a unique presentation of LHON/MELAS overlap syndrome resulting from a m.13046T>C mutation in a 12-year-old girl. In patients with sudden vision loss in which three of the most prevalent LHON mitochondrial mutations have been ruled out, molecular genetic examination should be extended to other mtDNA-encoded subunits of MTND5 complex I. Furthermore, atypical clinical presentations must be considered, even in well-described phenotypes.
Inflexibility of AMPK-mediated metabolic reprogramming in mitochondrial disease
Lin, Dar-Shong; Kao, Shu-Huei; Ho, Che-Sheng; Wei, Yau-Huei; Hung, Pi-Lien; Hsu, Mei-Hsin; Wu, Tsu-Yen; Wang, Tuan-Jen; Jian, Yuan-Ren; Lee, Tsung-Han; Chiang, Ming-Fu
2017-01-01
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is most commonly caused by the A3243G mutation of mitochondrial DNA. The capacity to utilize fatty acid or glucose as a fuel source and how such dynamic switches of metabolic fuel preferences and transcriptional modulation of adaptive mechanism in response to energy deficiency in MELAS syndrome have not been fully elucidated. The fibroblasts from patients with MELAS syndrome demonstrated a remarkable deficiency of electron transport chain complexes I and IV, an impaired cellular biogenesis under glucose deprivation, and a decreased ATP synthesis. In situ analysis of the bioenergetic properties of MELAS cells demonstrated an attenuated fatty acid oxidation that concomitantly occurred with impaired mitochondrial respiration, while energy production was mostly dependent on glycolysis. Furthermore, the transcriptional modulation was mediated by the AMP-activated protein kinase (AMPK) signaling pathway, which activated its downstream modulators leading to a subsequent increase in glycolytic flux through activation of pyruvate dehydrogenase. In contrast, the activities of carnitine palmitoyltransferase for fatty acid oxidation and acetyl-CoA carboxylase-1 for fatty acid synthesis were reduced and transcriptional regulation factors for biogenesis were not altered. These results provide novel information that MELAS cells lack the adaptive mechanism to switch fuel source from glucose to fatty acid, as glycolysis rates increase in response to energy deficiency. The aberrant secondary cellular responses to disrupted metabolic homeostasis mediated by AMPK signaling pathway may contribute to the development of the clinical phenotype. PMID:29088732
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mezghani, Najla; Mnif, Mouna; Kacem, Maha
2011-04-22
Highlights: {yields} We report a young Tunisian patient with clinical features of MELAS syndrome. {yields} Reported mitochondrial mutations were absent after a mutational screening of the whole mtDNA. {yields} We described a novel m.1640A>G mutation in the tRNA{sup Val} gene which was absent in 150 controls. {yields} Mitochondrial deletions and POLG1 gene mutations were absent. {yields} The m.1640A>G mutation could be associated to MELAS syndrome. -- Abstract: Mitochondrial encephalopathy, lactic acidosis and strokelike episodes (MELAS) syndrome is a mitochondrial disorder characterized by a wide variety of clinical presentations and a multisystemic organ involvement. In this study, we report a Tunisianmore » girl with clinical features of MELAS syndrome who was negative for the common m.3243A>G mutation, but also for the reported mitochondrial DNA (mtDNA) mutations and deletions. Screening of the entire mtDNA genome showed several known mitochondrial variants besides to a novel transition m.1640A>G affecting a wobble adenine in the anticodon stem region of the tRNA{sup Val}. This nucleotide was conserved and it was absent in 150 controls suggesting its pathogenicity. In addition, no mutations were found in the nuclear polymerase gamma-1 gene (POLG1). These results suggest further investigation nuclear genes encoding proteins responsible for stability and structural components of the mtDNA or to the oxidative phosphorylation machinery to explain the phenotypic variability in the studied family.« less
Invasive aspergillosis in a patient with MELAS syndrome
McKee, D; Cooper, P; Denning, D
2000-01-01
Invasive infection with the opportunistic fungus Aspergillus fumigatus predominantly affects people with impaired cell mediated immunity. The case of a 31 year old woman with no identified cause for immunosuppression who presented with severe refractory aspergillosis of the paranasal sinuses is reported. She subsequently developed clinical and molecular evidence of mitochondrial encephalomyopathy with lactic acidosis and stroke-like events (MELAS) syndrome. It is proposed that MELAS syndrome may represent an unusual risk factor for the development of invasive aspergillosis and mechanisms are supported by which mitochondrial dysfunction may predispose to this. PMID:10811702
Nesbitt, Victoria; Pitceathly, Robert D S; Turnbull, Doug M; Taylor, Robert W; Sweeney, Mary G; Mudanohwo, Ese E; Rahman, Shamima; Hanna, Michael G; McFarland, Robert
2013-08-01
Population-based studies suggest the m.3243A>G mutation in MTTL1 is the most common disease-causing mtDNA mutation, with a carrier rate of 1 in 400 people. The m.3243A>G mutation is associated with several clinical syndromes including mitochondrial encephalopathy lactic acidosis and stroke-like episodes (MELAS), maternally inherited deafness and diabetes (MIDD) and progressive external ophthalmoplegia (PEO). Many patients affected by this mutation exhibit a clinical phenotype that does not fall within accepted criteria for the currently recognised classical mitochondrial syndromes. We have defined the phenotypic spectrum associated with the m.3243A>G mtDNA mutation in 129 patients, from 83 unrelated families, recruited to the Mitochondrial Disease Patient Cohort Study UK. 10% of patients exhibited a classical MELAS phenotype, 30% had MIDD, 6% MELAS/MIDD, 2% MELAS/chronic PEO (CPEO) and 5% MIDD/CPEO overlap syndromes. 6% had PEO and other features of mitochondrial disease not consistent with another recognised syndrome. Isolated sensorineural hearing loss occurred in 3%. 28% of patients demonstrated a panoply of clinical features, which were not consistent with any of the classical syndromes associated with the m.3243A>G mutation. 9% of individuals harbouring the mutation were clinically asymptomatic. Following this study we propose guidelines for screening and for the management of confirmed cases.
Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers
Weiduschat, Nora; Kaufmann, Petra; Mao, Xiangling; Engelstad, Kristin Marie; Hinton, Veronica; DiMauro, Salvatore; De Vivo, Darryl
2014-01-01
Objective: To establish cerebral metabolic features associated with the A3243G mitochondrial DNA mutation with proton magnetic resonance spectroscopic imaging (1H MRSI) and to assess their potential as prognostic biomarkers. Methods: In this prospective cohort study, we investigated 135 clinically heterogeneous A3243G mutation carriers and 30 healthy volunteers (HVs) with 1H MRSI. Mutation carriers included 45 patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); 11 participants who would develop the MELAS syndrome during follow-up (converters); and 79 participants who would not develop the MELAS syndrome during follow-up (nonconverters). The groups were compared with respect to MRSI metabolic indices of 1) anaerobic energy metabolism (lactate), 2) neuronal integrity (N-acetyl-l-aspartate [NAA]), 3) mitochondrial function (NAA; lactate), 4) cell energetics (total creatine), and 5) membrane biosynthesis and turnover (total choline [tCho]). Results: Consistent with prior studies, the patients with MELAS had higher lactate (p < 0.001) and lower NAA levels (p = 0.01) than HVs. Unexpectedly, converters showed higher NAA (p = 0.042), tCho (p = 0.004), and total creatine (p = 0.002), in addition to higher lactate levels (p = 0.032), compared with HVs. Compared with nonconverters, converters had higher tCho (p = 0.015). Clinically, converters and nonconverters did not differ at baseline. Lactate and tCho levels were reliable biomarkers for predicting the risk of individual mutation carriers to develop the MELAS phenotype. Conclusions: 1H MRSI assessment of cerebral metabolism in A3243G mutation carriers shows promise in identifying disease biomarkers as well as individuals at risk of developing the MELAS phenotype. PMID:24477106
Rodan, L H; Poublanc, J; Fisher, J A; Sobczyk, O; Wong, T; Hlasny, E; Mikulis, D; Tein, I
2015-05-01
To study the mechanisms underlying stroke-like episodes (SLEs) in MELAS syndrome. We performed a case control study in 3 siblings with MELAS syndrome (m.3243A>G tRNA(Leu(UUR))) with variable % mutant mtDNA in blood (35 to 59%) to evaluate regional cerebral blood flow (CBF) and arterial cerebrovascular reactivity (CVR) compared to age- and sex-matched healthy study controls and a healthy control population. Subjects were studied at 3T MRI using arterial spin labeling (ASL) to measure CBF; CVR was measured as a change in % Blood Oxygen Level Dependent signal (as a surrogate of CBF) to repeated 10 mmHg step increase in arterial partial pressure of CO2 (PaCO2). MELAS siblings had decreased CVR (p ≤ 0.002) and increased CBF (p < 0.0026) compared to controls; changes correlated with disease severity and % mutant mtDNA (inversely for CVR: r = -0.82 frontal, r = -0.91 occipital cortex; directly for CBF: r = +0.85 frontal, not for occipital infarct penumbra). Mean CVR was reduced more in frontal (p < 0.001) versus occipital cortex (p = 0.002); mean CBF was increased more in occipital (p = 0.001) than frontal (p = 0.0026) cortices compared to controls. CBF correlated inversely with CVR (r = -0.99 in frontal; not in occipital infarct penumbra) suggesting that increased frontal resting flows are at the expense of flow reserve. MELAS disease severity and mutation load were inversely correlated with Interictal CVR and directly correlated with frontal CBF. These metrics offer further insight into the cerebrovascular hemodynamics in MELAS syndrome and may serve as noninvasive prognostic markers to stratify risk for SLEs. Class III. Copyright © 2015 © Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.
Karicheva, Olga Z.; Kolesnikova, Olga A.; Schirtz, Tom; Vysokikh, Mikhail Y.; Mager-Heckel, Anne-Marie; Lombès, Anne; Boucheham, Abdeldjalil; Krasheninnikov, Igor A.; Martin, Robert P.; Entelis, Nina; Tarassov, Ivan
2011-01-01
Mutations in human mitochondrial DNA are often associated with incurable human neuromuscular diseases. Among these mutations, an important number have been identified in tRNA genes, including 29 in the gene MT-TL1 coding for the tRNALeu(UUR). The m.3243A>G mutation was described as the major cause of the MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes). This mutation was reported to reduce tRNALeu(UUR) aminoacylation and modification of its anti-codon wobble position, which results in a defective mitochondrial protein synthesis and reduced activities of respiratory chain complexes. In the present study, we have tested whether the mitochondrial targeting of recombinant tRNAs bearing the identity elements for human mitochondrial leucyl-tRNA synthetase can rescue the phenotype caused by MELAS mutation in human transmitochondrial cybrid cells. We demonstrate that nuclear expression and mitochondrial targeting of specifically designed transgenic tRNAs results in an improvement of mitochondrial translation, increased levels of mitochondrial DNA-encoded respiratory complexes subunits, and significant rescue of respiration. These findings prove the possibility to direct tRNAs with changed aminoacylation specificities into mitochondria, thus extending the potential therapeutic strategy of allotopic expression to address mitochondrial disorders. PMID:21724600
Karicheva, Olga Z; Kolesnikova, Olga A; Schirtz, Tom; Vysokikh, Mikhail Y; Mager-Heckel, Anne-Marie; Lombès, Anne; Boucheham, Abdeldjalil; Krasheninnikov, Igor A; Martin, Robert P; Entelis, Nina; Tarassov, Ivan
2011-10-01
Mutations in human mitochondrial DNA are often associated with incurable human neuromuscular diseases. Among these mutations, an important number have been identified in tRNA genes, including 29 in the gene MT-TL1 coding for the tRNA(Leu(UUR)). The m.3243A>G mutation was described as the major cause of the MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes). This mutation was reported to reduce tRNA(Leu(UUR)) aminoacylation and modification of its anti-codon wobble position, which results in a defective mitochondrial protein synthesis and reduced activities of respiratory chain complexes. In the present study, we have tested whether the mitochondrial targeting of recombinant tRNAs bearing the identity elements for human mitochondrial leucyl-tRNA synthetase can rescue the phenotype caused by MELAS mutation in human transmitochondrial cybrid cells. We demonstrate that nuclear expression and mitochondrial targeting of specifically designed transgenic tRNAs results in an improvement of mitochondrial translation, increased levels of mitochondrial DNA-encoded respiratory complexes subunits, and significant rescue of respiration. These findings prove the possibility to direct tRNAs with changed aminoacylation specificities into mitochondria, thus extending the potential therapeutic strategy of allotopic expression to address mitochondrial disorders.
2012-01-01
Background MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. Case presentation We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Conclusions Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves. PMID:22353239
Piccoli, Giorgina Barbara; Bonino, Laura Davico; Campisi, Paola; Vigotti, Federica Neve; Ferraresi, Martina; Fassio, Federica; Brocheriou, Isabelle; Porpiglia, Francesco; Restagno, Gabriella
2012-02-21
MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves.
Ohno, Ayami; Mori, Akira; Doi, Ryuichiro; Yonenaga, Yoshikuni; Asano, Noboru; Uemoto, Shinji
2010-09-01
Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS) is a rare, fetal disease caused by a mutation in mitochondrial DNA that leads to impaired oxidative metabolism in skeletal muscle, the central nervous system, and liver function. This report presents the case of a 50-year-old woman with biliary cystadenocarcinoma complicated by MELAS who underwent a successful left hemihepatectomy. In this case, the diagnostic key for the malignant tumor was an (18)F-fluorodeoxyglucose positron emission tomography study, which was useful even in a patient with MELAS, which causes abnormal glucose metabolism. The perioperative management of such patients includes special precautions to prevent lactic acidosis and deterioration of the reserved liver function after a hepatectomy, since the mitochondrial function in MELAS patients is abnormal. The patient in this report has remained free of liver dysfunctions and cancer recurrence for 2 years following the hepatectomy. This is the first report of a successful major hepatectomy for a patient with MELAS.
Wu, Hai-rong; Ma, Yi-nan; Qi, Yu; Liu, Hong-gang
2013-04-23
To explore the expression and significance of respiratory chain enzyme of cells in urine sediment in mitochondrial encephalopathy myopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome. Through enzyme histochemistry, the authors analyzed the changes of respiratory chain enzyme in urine sediment in 20 MELAS patients due to mitochondrial A3243G mutation (MELAS group) and 20 health peoples (control group). And the impact on the expression of protein encoded by nuclear DNA (A21347) and mitochondrial DNA (A6404) was detected by immunochemistry. Image pro Plus 6.0 software was used for analysis of absorbance (A) of staining images as staining intensity. The data were expressed as M (Q1, Q3) and analyzed through statistical software. The staining intensity of complexes Iin the MELAS group was lower than that in the control group (0.06(0.01, 0.12) vs 0.12(0.01, 0.62), P = 0.010). The intergroup staining intensity of complex II showed no marked difference. Increased density of blue particle and cytoplasmic gathering was found in 13 cased (65%) of the MELAS group under light microscope. The staining intensity of complexes IV was expressed at a low level in the MELAS group (0.14(0.03, 0.32) vs 0.23(0.06, 0.43), P = 0.038). The expression of protein encoded by nuclear DNA (A21347) was lower than that in the control group (0.05(0.02, 0.45) vs 0.17(0.03, 0.70), P = 0.000). The expression of protein encoded by mitochondrial DNA (A6404) was also lower than that in the control group (0.03(0.01, 0.07) vs 0.15 (0.09, 0.23), P = 0.000). Abnormal change of respiratory chain enzyme in urine sediment in MELAS due to mitochondrial A3243G mutation and a low expression of proteins encoded by two kinds of DNA in complexes IV can help to confirm the genetic diagnosis of mitochondrial encephalomyopathies so that different subtypes may be classified and its pathogenesis elucidated.
[Mutism and acute behavioral disorders revealing MELAS syndrome].
Coomans, H; Barroso, B; Bertandeau, E; Bonnan, M; Dakar, A; Demasles, S; Garraud, S; Krim, E; Martin-Négrier, M-L
2011-11-01
MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a rare genetic mitochondrial disease which can cause cerebral (cerebrovascular accident, migraine, mental deterioration..), sensorial (bilateral symmetrical deafness) and peripheral (muscular involvement, neuropathy) disorders potentially associated with diabetes, renal or cardiac disorders, or growth retardation. Eighty percent of the patients have the 3243 A>G mutation in the leucine RNA transfer gene. Clinical manifestations leading to discovery of the mutation can be extremely varied, affecting patients of different age groups. We report the case of a 49-year-old man who presented acute fits of confusion followed by mutism and praxic disorders. History taking revealed recently diagnosed type 2 diabetes, axonal neuropathy, and bilateral symmetrical deafness requiring hearing aids. The initial MRI showed FLAIR sequences with bi-parietal abnormalities, no signs of recent stroke on the DW/B10000 sequences, and basal ganglia calcifications. Blood tests and morphological findings ruled out a vascular origin. Search for lactic acidosis remained constantly negative in blood samples despite positive cerebrospinal fluid samples (N×3). The 3243 A>G mitochondrial DNA mutation was identified. The neuropsychological evaluation revealed a serious dysexecutive syndrome with a major impact on the patient's self sufficiency. Neurocognitive disorders are not common in MELAS syndrome. Brain MRI results and the presence of extra-neurological signs can be helpful for diagnosis. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Ocular findings in MELAS syndrome – a case report.
Modrzejewska, Monika; Chrzanowska, Martyna; Modrzejewska, Anna; Romanowska, Hanna; Ostrowska, Iwona; Giżewska, Maria
We present a case of a child with MELAS syndrome (mitochondrial encephalo-myopathy with lactic acidosis and stroke-like episodes), discussing clinical manifestation, ocular findings and diagnostic challenges. Predominant ocular symptom was a transient complete visual loss, while the predominant ocular sign was a visual field defect. The diagnosia was based on clinical manifestation, laboratory tests, brain scans and genetic testing which confirmed the pathognomonic mutation in the MTTL1 gene encoding the mitochondrial tRNA for leucine 3243> G. Ocular examination demonstrated decreased visual acuity (with bilateral best corrected visual acuity of .1). Periodical, transient visual loss and visual field defects were clinically predominant. Specialist investigations were carried out, which demonstrated homonymous hemianopia (kinetic perimetry), bilateral partial optic nerve atrophy (RetCam). Funduscopy and electrophysiology mfERG study did not confirm features of retinitis pigmentosa. The brain scans revealed numerous small cortical ischemic lesions within the frontal, parietal and temporal lobes, post-stroke focal areas within the occipital lobes and diffuse calcifications of the basal ganglia. During several years of follow-up, visual field defects showed progressive concentric narrowing. The patient received a long-term treatment with arginine, coenzyme Q and vitamin D, both oral and intravenous, but no beneficial effect for the improvement of ophthalmic condition was observed. As it is the case in severe MELAS syndrome, the course of disease was fatal and the patientdied at the age of 14.
Acute cortical deafness in a child with MELAS syndrome.
Pittet, Marie P; Idan, Roni B; Kern, Ilse; Guinand, Nils; Van, Hélène Cao; Toso, Seema; Fluss, Joël
2016-05-01
Auditory impairment in mitochondrial disorders are usually due to peripheral sensorineural dysfunction. Central deafness is only rarely reported. We report here an 11-year-old boy with MELAS syndrome who presented with subacute deafness after waking up from sleep. Peripheral hearing loss was rapidly excluded. A brain MRI documented bilateral stroke-like lesions predominantly affecting the superior temporal lobe, including the primary auditory cortex, confirming the central nature of deafness. Slow recovery was observed in the following weeks. This case serves to illustrate the numerous challenges caused by MELAS and the unusual occurrence of acute cortical deafness, that to our knowledge has not be described so far in a child in this setting.
Charles Darwin's mitochondria.
Hayman, John
2013-05-01
Charles Darwin's long-term illness has been the subject of much speculation. His numerous symptoms have led to conclusions that his illness was essentially psychogenic in nature. These diagnoses have never been fully convincing, however, particularly in regard to the proposed underlying psychological background causes of the illness. Similarly, two proposed somatic causes of illness, Chagas disease and arsenic poisoning, lack credibility and appear inconsistent with the lifetime history of the illness. Other physical explanations are simply too incomplete to explain the range of symptoms. Here, a very different sort of explanation will be offered. We now know that mitochondrial mutations producing impaired mitochondrial function may result in a wide range of differing symptoms, including symptoms thought to be primarily psychological. Examination of Darwin's maternal family history supports the contention that his illness was mitochondrial in nature; his mother and one maternal uncle had strange illnesses and the youngest maternal sibling died of an infirmity with symptoms characteristic of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome), a condition rooted in mitochondrial dysfunction. Darwin's own symptoms are described here and are in accord with the hypothesis that he had the mtDNA mutation commonly associated with the MELAS syndrome.
Desquiret-Dumas, Valerie; Gueguen, Naig; Barth, Magalie; Chevrollier, Arnaud; Hancock, Saege; Wallace, Douglas C; Amati-Bonneau, Patrizia; Henrion, Daniel; Bonneau, Dominique; Reynier, Pascal; Procaccio, Vincent
2012-01-01
The m.3243A>G variant in the mitochondrial tRNALeu (UUR) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of L-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of L-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and L-arginine therapy may constitute promising therapeutic strategies against MELAS. PMID:22306605
Folmes, Clifford D L; Martinez-Fernandez, Almudena; Perales-Clemente, Ester; Li, Xing; McDonald, Amber; Oglesbee, Devin; Hrstka, Sybil C; Perez-Terzic, Carmen; Terzic, Andre; Nelson, Timothy J
2013-07-01
Mitochondrial diseases display pathological phenotypes according to the mixture of mutant versus wild-type mitochondrial DNA (mtDNA), known as heteroplasmy. We herein examined the impact of nuclear reprogramming and clonal isolation of induced pluripotent stem cells (iPSC) on mitochondrial heteroplasmy. Patient-derived dermal fibroblasts with a prototypical mitochondrial deficiency diagnosed as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) demonstrated mitochondrial dysfunction with reduced oxidative reserve due to heteroplasmy at position G13513A in the ND5 subunit of complex I. Bioengineered iPSC clones acquired pluripotency with multilineage differentiation capacity and demonstrated reduction in mitochondrial density and oxygen consumption distinguishing them from the somatic source. Consistent with the cellular mosaicism of the original patient-derived fibroblasts, the MELAS-iPSC clones contained a similar range of mtDNA heteroplasmy of the disease-causing mutation with identical profiles in the remaining mtDNA. High-heteroplasmy iPSC clones were used to demonstrate that extended stem cell passaging was sufficient to purge mutant mtDNA, resulting in isogenic iPSC subclones with various degrees of disease-causing genotypes. On comparative differentiation of iPSC clones, improved cardiogenic yield was associated with iPSC clones containing lower heteroplasmy compared with isogenic clones with high heteroplasmy. Thus, mtDNA heteroplasmic segregation within patient-derived stem cell lines enables direct comparison of genotype/phenotype relationships in progenitor cells and lineage-restricted progeny, and indicates that cell fate decisions are regulated as a function of mtDNA mutation load. The novel nuclear reprogramming-based model system introduces a disease-in-a-dish tool to examine the impact of mutant genotypes for MELAS patients in bioengineered tissues and a cellular probe for molecular features of individual mitochondrial diseases. Copyright © 2013 AlphaMed Press.
James, A M; Sheard, P W; Wei, Y H; Murphy, M P
1999-01-01
Mutations in the tRNA genes of mitochondrial DNA (mtDNA) cause the debilitating MELAS (mitochondrial, myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fibres) syndromes. These mtDNA mutations affect respiratory chain function, apparently without decreasing cellular ATP concentration [Moudy et al. (1995) PNAS, 92, 729-733]. To address this issue, we investigated the role of mitochondrial ATP synthesis in fibroblasts from MELAS and MERRF patients. The maximum rate of mitochondrial ATP synthesis was decreased by 60-88%, as a consequence of the decrease in the proton electrochemical potential gradient of MELAS and MERRF mitochondria. However, in quiescent fibroblasts neither ATP concentration or the ATP/ADP ratio was affected by the lowered rate of ATP synthesis. We hypothesized that the low ATP demand of quiescent fibroblasts masked the mitochondrial ATP synthesis defect and that this defect might become apparent during higher ATP use. To test this we simulated high energy demand by titrating cells with gramicidin, an ionophore that stimulates ATP hydrolysis by the plasma membrane Na+/K+-ATPase. We found a threshold gramicidin concentration in control cells at which both the ATP/ADP ratio and the plasma membrane potential decreased dramatically, due to ATP demand by the Na+/K+-ATPase outstripping mitochondrial ATP synthesis. In MELAS and MERRF fibroblasts the corresponding threshold concentrations of gramicidin were 2-20-fold lower than those for control cells. This is the first demonstration that cells containing mtDNA mutations are particularly sensitive to increased ATP demand and this has several implications for how mitochondrial dysfunction contributes to disease pathophysiology. In particular, the increased susceptibility to plasma membrane depolarization will render neurons with dysfunctional mitochondria susceptible to excitotoxic cell death.
Kidney involvement in MELAS syndrome: Description of 2 cases.
Alcubilla-Prats, Pau; Solé, Manel; Botey, Albert; Grau, Josep Maria; Garrabou, Glòria; Poch, Esteban
2017-04-21
MELAS syndrome -myopathy, encephalopathy, lactic acidosis and stroke-like episodes- is a maternally-inherited mitochondrial cytopathy related to several mitochondrial DNA mutations, with the A3243G mutation in tRNA Leu gene being the most frequent of them. Apart from its typical symptomatology, patients usually exhibit a maternally-inherited history of neurosensory deafness and insulin-dependent type 2 diabetes mellitus (T2DM). Recent studies have shown that few patients carrying a A3243G mutation also suffer from renal dysfunction, usually in form of focal segmental glomerulosclerosis (FSGS). In this study we examine kidney involvement in 2 unrelated patients with a A3243G mutation by genetic testing. Both have a maternally-inherited neurosensory deafness and insulin-dependent T2DM. A renal biopsy was performed in both patients. One patient developed nephrotic proteinuria and renal insufficiency, with FSGS findings being observed in the kidney biopsy, whereas the other suffered from mild proteinuria and renal insufficiency, with non-specific glomerular changes. The presence of FSGS or other kidney involvement accompanied by hereditary neurosensory deafness and T2DM could be suggestive of a A3243G tRNA Leu mutation and should prompt a genetic testing and an evaluation of potential extrarenal involvement. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
Stroke due to mitochondrial disorders in Saudi children.
Salih, Mustafa A; Abdel-Gader, Abdel-Galil M; Zahraa, Jihad N; Al-Rayess, Molham M; Alorainy, Ibrahim A; Hassan, Hamdy H; Ruitenbeek, Wim; Zeviani, Massimo
2006-03-01
To report on the clinical and biochemical features of patients who presented with stroke due to mitochondrial disorders amongst a prospective and retrospective cohort of Saudi children. Children, who presented with stroke, were evaluated at the Division of Pediatric Neurology, or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia, during the periods July 1992 to February 2001 (retrospective study) and February 2001 to March 2003 (prospective study). Open muscle biopsies were obtained from patients suspected to have mitochondrial disorders, and examined using conventional histological and histochemical techniques. Biochemical, molecular pathological investigations, or both, of muscle could be arranged for only some of the patients. Mitochondrial disorders were the underlying risk factor for stroke in 4 (3.8%) of 104 children (aged one month to 12 years). Three patients (one male and 2 females) had Leigh syndrome (LS) and one had mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). At the time of stroke, the 3 children with LS were 11 months, 15 months, and 7 years old. They presented with psychomotor regression and seizures. Muscle histology and histochemistry showed mild non-specific changes but no ragged red fibers. Biochemical analysis of muscle (in one patient) revealed deficiency of pyruvate dehydrogenase complex. Analysis of mitochondrial DNA (mtDNA), [the other 2 patients] was negative for the 2 point mutations (T-G and T-C) at nucleotide position 8993, and for two T-C point mutations (at positions 8851 and 9176 of the ATPase 6 gene) that have been described in patients with LS. The girl with MELAS syndrome presented with a stroke-like episode at the age of 29 months and had focal brain lesions in the medial aspect of the left occipital and temporal lobes, and in the posteromedial aspect of the left thalamus, which resolved within 7 weeks. She had raised cerebrospinal fluid lactate but no ragged red fibers on muscle histochemistry. Biochemical assay of muscle homogenate showed reduction in respiratory chain complexes I, III and IV. Mutation screening of mtDNA at nucleotides 3243 (tRNA(Leu(UUR))) and 8344 (tRNA(Lys)) was negative. Mitochondrial disorders constitute a risk factor for stroke in Saudi children. However, demanding and highly specialized investigations are needed to confirm the diagnosis. These are better performed at supraregional centers where facilities for clinical, biochemical and molecular work-up are available.
Luigetti, M; Sauchelli, D; Primiano, G; Cuccagna, C; Bernardo, D; Lo Monaco, M; Servidei, S
2016-06-01
Peripheral neuropathy in mitochondrial diseases (MDs) may vary from a subclinical finding in a multisystem syndrome to a severe, even isolated, manifestation in some patients. To investigate the involvement of the peripheral nervous system in MDs extensive electrophysiological studies were performed in 109 patients with morphological, biochemical and genetic diagnosis of MD [12 A3243G progressive external ophthalmoplegia (PEO)/mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), 16 myoclonic epilepsy with ragged-red fibres (MERRF), four mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), 67 PEO with single or multiple deletions of mitochondrial DNA, 10 others]. A neuropathy was found in 49 patients (45%). The incidence was very high in MNGIE (100%), MELAS (92%) and MERRF (69%), whilst 28% of PEO patients had evidence of peripheral involvement. The most frequent abnormality was a sensory axonal neuropathy found in 32/49 patients (65%). A sensory-motor axonal neuropathy was instead detected in 16% of the patients and sensory-motor axonal demyelinating neuropathy in 16%. Finally one Leigh patient had a motor axonal neuropathy. It is interesting to note that the great majority had preserved tendon reflexes and no sensory disturbances. In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis. © 2016 EAN.
Martin-Kleiner, I; Pape-Medvidović, E; Pavlić-Renar, I; Metelko, Z; Kusec, R; Gabrilovac, J; Boranić, M
2004-12-01
In this work, patients having type 2 diabetes mellitus and diabetic mothers were tested for the presence of mitochondrial DNA point mutation A3243G. This mutation is associated with the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), diabetes and deafness. Twenty-two diabetic persons were screened. DNA was isolated from peripheral blood lymphocytes and from swabs of oral mucosa. The mitochondrial DNA point mutation A3243G was detected using PCR-RFLP test. The mutation was detected in oral mucosal DNA of two patients (but not from lymphocyte DNA). One patient was a man with hearing and visual impairments and proteinuria; the other was a woman having proteinuria but no hearing impairment. The mutation was not detectable in oral mucosal DNA from the control persons: 20 diabetic patients having diabetic fathers and 22 healthy, nondiabetic volunteers. The incidence of mitochondrial DNA point mutation A3243G in this study of Croatian diabetic patients is in line with data in the literature.
The madness of Dionysus -- six hypotheses on the illness of Nietzsche.
Tényi, Tamás
2012-01-01
Friedrich Nietzsche (1844-1900) is considered as one of the most influential modern thinkers of the last two centuries. The great philosopher and poet developed a mental illness at the age of 44 and died at the age of 56. Pathological examination was not undertaken. At that time Nietzsche was diagnosed as having atypical paralysis progressiva, however recently five other probable diagnoses appeared in literature. Literature search in MEDLINE and Web of Science on the illness of Nietzsche. Six hypotheses were identified: 1. Paralysis progressiva (General paralysis of the insane) 2. Bipolar affective disorder followed by vascular dementia 3. Hereditary form of frontotemporal dementia 4. Brain tumor 5. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) 6. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome. Developments in neurology and molecular genetics give new perspectives to the secret of Nietzsche's illness and also there is a consensus on the questioning of the original paralysis progressiva concept. As there was no postmortem, the clinical speculations on the medical problems of the great philosopher remain a challenge.
PGD to reduce reproductive risk: the case of mitochondrial DNA disorders.
Bredenoord, A L; Dondorp, W; Pennings, G; De Die-Smulders, C E M; De Wert, G
2008-11-01
This paper discusses the pros and cons of introducing PGD for mitochondrial DNA (mtDNA) disorders such as NARP (Neurogenic muscle weakness, Ataxia, Retinis Pigmentosa)/Leigh, MELAS (Mitochondrial myopathy, Encephalopathy, Lactic acidosis, and Stroke-like episodes), private mtDNA mutations and LHON (Leber Hereditary Optic Neuropathy). Although there is little experience with PGD for mtDNA disorders, it is reasonable to assume that in many cases, the best one can achieve is the selection of the 'least' affected embryos for transfer. So instead of 'promising' parents a healthy child, PGD in these cases can only aim at reducing reproductive risk. From an ethical point of view, this raises challenging questions about parental and medical responsibilities. The main argument in favour of PGD is that it offers couples at risk the opportunity of reducing their chances of having a severely affected child. Potential objections are manifold, but we conclude that none of them supplies convincing moral arguments to regard risk-reducing PGD as unacceptable. Nevertheless, introducing this new application of PGD in clinical practice will raise further complex issues of determining conditions for its responsible use.
Yilmaz, Ali; Gdynia, Hans-Jürgen; Ponfick, Matthias; Rösch, Sabine; Lindner, Alfred; Ludolph, Albert C; Sechtem, Udo
2012-04-01
Mitochondrial myopathy comprises various clinical subforms of neuromuscular disorders that are characterised by impaired mitochondrial energy metabolism due to dysfunction of the mitochondrial respiratory chain. No comprehensive and targeted cardiovascular magnetic resonance (CMR) studies have been performed so far in patients with mitochondrial disorders. The present study aimed at characterising cardiac disease manifestations in patients with mitochondrial myopathy and elucidating the in vivo cardiac damage pattern of patients with different subforms of mitochondrial disease by CMR studies. In a prospective study, 37 patients with mitochondrial myopathy underwent comprehensive neurological and cardiac evaluations including physical examination, resting ECG and CMR. The CMR studies comprised cine-CMR, T2-weighted "edema" imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging. Various patterns and degrees of skeletal myopathy were present in the participants of this study, whereas clinical symptoms such as chest pain symptoms (in eight (22%) patients) and various degrees of dyspnea (in 16 (43%) patients) were less frequent. Pathological ECG findings were documented in eight (22%) patients. T2-weighted "edema" imaging was positive in one (3%) patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) only. LGE imaging demonstrated the presence of non-ischemic LGE in 12 (32%) patients: 10 out of 24 (42%) patients with CPEO (chronic progressive external ophthalmoplegia) or KSS (Kearns-Sayre syndrome) and 2 of 3 (67%) patients with MELAS were LGE positive. All 10 LGE-positive patients with CPEO or KSS demonstrated a potentially typical pattern of diffuse intramural LGE in the left-ventricular (LV) inferolateral segments. Cardiac involvement is a frequent finding in patients with mitochondrial myopathy. A potentially characteristic pattern of diffuse intramural LGE in the LV inferolateral segments was identified in patients suffering from the subforms CPEO or KSS.
Metabolic rescue in pluripotent cells from patients with mtDNA disease.
Ma, Hong; Folmes, Clifford D L; Wu, Jun; Morey, Robert; Mora-Castilla, Sergio; Ocampo, Alejandro; Ma, Li; Poulton, Joanna; Wang, Xinjian; Ahmed, Riffat; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Li, Ying; Van Dyken, Crystal; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Koski, Amy; Mitalipov, Nargiz; Amato, Paula; Wolf, Don P; Huang, Taosheng; Terzic, Andre; Laurent, Louise C; Izpisua Belmonte, Juan Carlos; Mitalipov, Shoukhrat
2015-08-13
Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.
Vasospasm is a significant factor in cyclosporine-induced neurotoxicity: case report.
Braakman, Hilde M H; Lodder, Jan; Postma, Alida A; Span, Lambert F R; Mess, Werner H
2010-05-11
The aetiology of central nervous system lesions observed in cerebral cyclosporine neurotoxicity remains controversial. We report a 48-year-old woman with a non-severe aplastic anaemia who presented with stroke-like episodes while on cyclosporine treatment.Transcranial Doppler ultrasound revealed severely elevated flow velocities in several cerebral vessels, consistent with vasospasm. Immediately after reducing the cyclosporine dose, the stroke-like episodes disappeared. Only after cyclosporine withdrawal the transcranial Doppler ultrasound abnormalities fully resolved. This case demonstrates a significant role of vasospasm in the pathway of cyclosporine-induced neurotoxicity. Transcranial Doppler ultrasound is an effective tool for the diagnosis and follow-up of cyclosporine-induced vasospasm.
Surveyor nuclease detection of mutations and polymorphisms of mtDNA in children.
Pilch, Jacek; Asman, Marek; Jamroz, Ewa; Kajor, Maciej; Kotrys-Puchalska, Elżbieta; Goss, Małgorzata; Krzak, Maria; Witecka, Joanna; Gmiński, Jan; Sieroń, Aleksander L
2010-11-01
Mitochondrial encephalomyopathies are complex disorders with wide range of clinical manifestations. Particularly time-consuming is the identification of mutations in mitochondrial DNA. A group of 20 children with clinical manifestations of mitochondrial encephalomyopathies was selected for molecular studies. The aims were (a) to identify mutations in mtDNA isolated from muscle and (b) to verify detected mutations in DNA isolated from blood, in order to assess the utility of a Surveyor nuclease assay kit for patient screening. The most common changes found were polymorphisms, including a few missense mutations altering the amino acid sequence of mitochondrial proteins. In two boys with MELAS (i.e., mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), a mutation A→G3243 was detected in the tRNALeu gene of mtDNA isolated from muscle and blood. In one boy, the carrier status of his mother was confirmed, based on molecular analysis of DNA isolated from blood. A method using Surveyor nuclease allows systematic screening for small mutations in mtDNA, using as its source blood of the patients and asymptomatic carriers. The method still requires confirmation studying a larger group. In some patients, the use of this method should precede and might limit indications for traumatic muscle and skin biopsy. Copyright © 2010 Elsevier Inc. All rights reserved.
Florian, Anca; Ludwig, Anna; Stubbe-Dräger, Bianca; Boentert, Matthias; Young, Peter; Waltenberger, Johannes; Rösch, Sabine; Sechtem, Udo; Yilmaz, Ali
2015-05-22
Mitochondrial myopathies (MM) are a heterogeneous group of inherited conditions resulting from a primary defect in the mitochondrial respiratory chain with consecutively impaired cellular energy metabolism. Small sized studies using mainly electrocardiography (ECG) and echocardiography have revealed cardiac abnormalities ranging from conduction abnormalities and arrhythmias to hypertrophic or dilated cardiomyopathy in these patients. Recently, characteristic patterns of cardiac involvement were documented by cardiovascular magnetic resonance (CMR) in patients with chronic progressive external ophthalmoplegia (CPEO)/Kearns-Sayre syndrome (KSS) and with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). The present study aimed to characterize the prevalence and pattern of cardiac abnormalities and to test the additional diagnostic value of CMR in this patient population. The hypothesis that different neuromuscular MM syndromes present with different cardiac disease phenotypes was evaluated. Sixty-four MM patients (50 ± 15 years, 44% male) and 25 matched controls (52 ± 14 years, 36% male) prospectively underwent cardiac evaluations including CMR (comprising cine- and late-gadolinium-enhancement (LGE) imaging). Based on the neuromuscular phenotype and genotype, the patients were grouped: (a) CPEO/KSS (N = 33); (b) MELAS/-like (N = 11); c) myoclonic epilepsy with ragged-red fibers (MERRF) (N = 3) and d) other non-specific MM forms (N = 17). Among the 64 MM patients, 34 (53%) had at least one abnormal CMR finding: 18 (28%) demonstrated an impaired left ventricular ejection-fraction (LV-EF <60%), 14 (22%) had unexplained LV hypertrophy and 21 (33%) were LGE-positive. Compared to controls, MM patients showed significantly higher maximal wall thickness (10 ± 3 vs. 8 ± 2 mm, p = 0.005) and concentricity (LV mass to end-diastolic volume: 0.84 ± 0.27 vs. 0.67 ± 0.11, p < 0.0001) with frequent presence of non-ischemic LGE (30% vs. 0%, p = 0.001). CPEO/KSS showed a predominantly intramural pattern of LGE mostly confined to the basal LV inferolateral wall (8/10; 80%) in addition to a tendency toward concentric remodelling. MELAS/-like patients showed the highest frequency of cardiac disease (in 10/11 (91%)), a mostly concentric LV hypertrophy (6/9; 67%) with or without LV systolic dysfunction and a predominantly focal, patchy LGE equally distributed among LV segments (8/11; 73%). Patients with MERRF and non-specific MM had no particular findings. Pathological CMR findings indicating cardiac involvement were detected significantly more often than pathological ECG results or elevated cardiac serum biomarkers (34 (53%) vs. 18 (28%) vs. 21 (33%); p = 0.008). Cardiac involvement is a frequent finding in MM patients - and particularly present in KSS/CPEO as well as MELAS/-like patients. Despite a high variability in clinical presentation, CPEO/KSS patients typically show an intramural pattern of LGE in the basal inferolateral wall whereas MELAS patients are characterized by overt concentric hypertrophy and a rather unique, focally accentuated and diffusely distributed LGE.
Cheldi, Antonella; Ronchi, Dario; Bordoni, Andreina; Bordo, Bianca; Lanfranconi, Silvia; Bellotti, Maria Grazia; Corti, Stefania; Lucchini, Valeria; Sciacco, Monica; Moggio, Maurizio; Baron, Pierluigi; Comi, Giacomo Pietro; Colombo, Antonio; Bersano, Anna
2013-01-15
POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations.
2013-01-01
Background POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. Case presentation We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. Conclusion The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations. PMID:23324391
Epilepsy in adults with mitochondrial disease: A cohort study.
Whittaker, Roger G; Devine, Helen E; Gorman, Grainne S; Schaefer, Andrew M; Horvath, Rita; Ng, Yi; Nesbitt, Victoria; Lax, Nichola Z; McFarland, Robert; Cunningham, Mark O; Taylor, Robert W; Turnbull, Douglass M
2015-12-01
The aim of this work was to determine the prevalence and progression of epilepsy in adult patients with mitochondrial disease. We prospectively recruited a cohort of 182 consecutive adult patients attending a specialized mitochondrial disease clinic in Newcastle upon Tyne between January 1, 2005 and January 1, 2008. We then followed this cohort over a 7-year period, recording primary outcome measures of occurrence of first seizure, status epilepticus, stroke-like episode, and death. Overall prevalence of epilepsy in the cohort was 23.1%. Mean age of epilepsy onset was 29.4 years. Prevalence varied widely between genotypes, with several genotypes having no cases of epilepsy, a prevalence of 34.9% in the most common genotype (m.3243A>G mutation), and 92.3% in the m.8344A>G mutation. Among the cohort as a whole, focal seizures, with or without progression to bilateral convulsive seizures, was the most common seizure type. Conversely, all of the patients with the m.8344A>G mutation and epilepsy experienced myoclonic seizures. Patients with the m.3243A>G mutation remain at high risk of developing stroke-like episodes (1.16% per year). However, although the standardized mortality ratio for the entire cohort was high (2.86), this ratio did not differ significantly between patients with epilepsy (2.96) and those without (2.83). Epilepsy is a common manifestation of mitochondrial disease. It develops early in the disease and, in the case of the m.3243A>G mutation, often presents in the context of a stroke-like episode or status epilepticus. However, epilepsy does not itself appear to contribute to the increased mortality in mitochondrial disease. © 2015 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
Kamble, Asmita S; Fandilolu, Prayagraj M; Sambhare, Susmit B; Sonawane, Kailas D
2017-01-01
Lack of naturally occurring modified nucleoside 5-taurinomethyluridine (τm5U) at the 'wobble' 34th position in tRNALeu causes mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). The τm5U34 specifically recognizes UUG and UUA codons. Structural consequences of τm5U34 to read cognate codons have not been studied so far in detail at the atomic level. Hence, 50ns multiple molecular dynamics (MD) simulations of various anticodon stem loop (ASL) models of tRNALeu in presence and absence of τm5U34 along with UUG and UUA codons were performed to explore the dynamic behaviour of τm5U34 during codon recognition process. The MD simulation results revealed that τm5U34 recognizes G/A ending codons by 'wobble' as well as a novel 'single' hydrogen bonding interactions. RMSD and RMSF values indicate the comparative stability of the ASL models containing τm5U34 modification over the other models, lacking τm5U34. Another MD simulation study of 55S mammalian mitochondrial rRNA with tRNALeu showed crucial interactions between the A-site residues, A918, A919, G256 and codon-anticodon bases. Thus, these results could improve our understanding about the decoding efficiency of human mt tRNALeu with τm5U34 to recognize UUG and UUA codons.
Kamble, Asmita S.; Fandilolu, Prayagraj M.; Sambhare, Susmit B.; Sonawane, Kailas D.
2017-01-01
Lack of naturally occurring modified nucleoside 5-taurinomethyluridine (τm5U) at the ‘wobble’ 34th position in tRNALeu causes mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). The τm5U34 specifically recognizes UUG and UUA codons. Structural consequences of τm5U34 to read cognate codons have not been studied so far in detail at the atomic level. Hence, 50ns multiple molecular dynamics (MD) simulations of various anticodon stem loop (ASL) models of tRNALeu in presence and absence of τm5U34 along with UUG and UUA codons were performed to explore the dynamic behaviour of τm5U34 during codon recognition process. The MD simulation results revealed that τm5U34 recognizes G/A ending codons by ‘wobble’ as well as a novel ‘single’ hydrogen bonding interactions. RMSD and RMSF values indicate the comparative stability of the ASL models containing τm5U34 modification over the other models, lacking τm5U34. Another MD simulation study of 55S mammalian mitochondrial rRNA with tRNALeu showed crucial interactions between the A-site residues, A918, A919, G256 and codon-anticodon bases. Thus, these results could improve our understanding about the decoding efficiency of human mt tRNALeu with τm5U34 to recognize UUG and UUA codons. PMID:28453549
Neurophysiological profile of peripheral neuropathy associated with childhood mitochondrial disease.
Menezes, Manoj P; Rahman, Shamima; Bhattacharya, Kaustuv; Clark, Damian; Christodoulou, John; Ellaway, Carolyn; Farrar, Michelle; Pitt, Matthew; Sampaio, Hugo; Ware, Tyson L; Wedatilake, Yehani; Thorburn, David R; Ryan, Monique M; Ouvrier, Robert
2016-09-01
Peripheral nerve involvement is common in mitochondrial disease but often unrecognised due to the prominent central nervous system features. Identification of the underlying neuropathy may assist syndrome classification, targeted genetic testing and rehabilitative interventions. Clinical data and the results of nerve conduction studies were obtained retrospectively from the records of four tertiary children's hospital metabolic disease, neuromuscular or neurophysiology services. Nerve conductions studies were also performed prospectively on children attending a tertiary metabolic disease service. Results were classified and analysed according to the underlying genetic cause. Nerve conduction studies from 27 children with mitochondrial disease were included in the study (mitochondrial DNA (mtDNA) - 7, POLG - 7, SURF1 - 10, PDHc deficiency - 3). Four children with mtDNA mutations had a normal study while three had mild abnormalities in the form of an axonal sensorimotor neuropathy when not acutely unwell. One child with MELAS had a severe acute axonal motor neuropathy during an acute stroke-like episode that resolved over 12months. Five children with POLG mutations and disease onset beyond infancy had a sensory ataxic neuropathy with an onset in the second decade of life, while the two infants with POLG mutations had a demyelinating neuropathy. Seven of the 10 children with SURF1 mutations had a demyelinating neuropathy. All three children with PDHc deficiency had an axonal sensorimotor neuropathy. Unlike CMT, the neuropathy associated with mitochondrial disease was not length-dependent. This is the largest study to date of peripheral neuropathy in genetically- classified childhood mitochondrial disease. Characterising the underlying neuropathy may assist with the diagnosis of the mitochondrial syndrome and should be an integral part of the assessment of children with suspected mitochondrial disease. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
Enterovirus D68-associated community-acquired pneumonia in children living in Milan, Italy.
Esposito, Susanna; Zampiero, Alberto; Ruggiero, Luca; Madini, Barbara; Niesters, Hubert; Principi, Nicola
2015-07-01
An increasing number of children infected by enterovirus D68 (EV-D68) and affected by severe respiratory illness, muscle weakness and paralysis were described in the USA and Canada in 2014 OBJECTIVES: To investigate the potential involvement of EV-D68 in determining community-acquired pneumonia (CAP) in hospitalised children in order to acquire information concerning the clinical problems associated with EV-D68 in Italy. This prospective study of children hospitalised for CAP in the largest Pediatric Department in Milan, Italy, was carried out between 1 June and 31 December 2014. All of the children's admission nasopharyngeal swabs were investigated for the presence of EV-D68. One hundred and seventy-six children with radiographically confirmed CAP were hospitalised during the 7-month study period: 97 (55.1%) had enterovirus/rhinovirus-positive nasopharyngeal samples, including four (2.3%) positive for EV-D68. These four samples were collected between 9 and 21 October, a month in which 21 cases of CAP were recorded. Phylogenetic analysis showed that all of the sequences fell into clade B. The most severe case was diagnosed in a 14-year-old girl with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS syndrome), who died after 12 days of hospitalisation. EV-D68 was detected in few children with usually mild-to-moderate lower respiratory tract infection, although the disease lead to the death of a girl with a severe chronic underlying disease. Further studies capable of better defining the epidemiological, genetic and pathogenetic characteristics of the virus are required in order to be able to prepare appropriate preventive and therapeutic measures. Copyright © 2015 Elsevier B.V. All rights reserved.
Transfer RNA and human disease.
Abbott, Jamie A; Francklyn, Christopher S; Robey-Bond, Susan M
2014-01-01
Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.
Hereditary myopathies with early respiratory insufficiency in adults.
Naddaf, Elie; Milone, Margherita
2017-11-01
Hereditary myopathies with early respiratory insufficiency as a predominant feature of the clinical phenotype are uncommon and underestimated in adults. We reviewed the clinical and laboratory data of patients with hereditary myopathies who demonstrated early respiratory insufficiency before the need for ambulatory assistance. Only patients with disease-causing mutations or a specific histopathological diagnosis were included. Patients with cardiomyopathy were excluded. We identified 22 patients; half had isolated respiratory symptoms at onset. The diagnosis of the myopathy was often delayed, resulting in delayed ventilatory support. The most common myopathies were adult-onset Pompe disease, myofibrillar myopathy, multi-minicore disease, and myotonic dystrophy type 1. Single cases of laminopathy, MELAS (mitochondrial encephalomyopathy with lactic acidosis and strokelike events), centronuclear myopathy, and cytoplasmic body myopathy were identified. We highlighted the most common hereditary myopathies associated with early respiratory insufficiency as the predominant clinical feature, and underscored the importance of a timely diagnosis for patient care. Muscle Nerve 56: 881-886, 2017. © 2017 Wiley Periodicals, Inc.
Reversible hemispheric hypoperfusion in two cases of SMART syndrome.
Wai, Karmen; Balabanski, Anna; Chia, Nicholas; Kleinig, Timothy
2017-09-01
Stroke-like migraine attacks after radiation therapy (SMART) syndrome manifests as prolonged episodes of cortical dysfunction, years after cranial irradiation. We present two cases demonstrating reversible hemispheric hypoperfusion. Case 1 presented with left hemispheric symptoms following previous similar episodes. CT perfusion (CTP) demonstrated reversible hemispheric hypoperfusion; subsequent investigations were consistent with SMART syndrome. Case 2 presented following the third episode of a hemispheric syndrome with near-identical CTP abnormalities. L-arginine was administered with rapid reversal of clinical and CTP abnormalities. We conclude that SMART syndrome may demonstrate significant hypoperfusion on hyperacute CTP without subsequent infarction. Impaired cerebrovascular autoregulation probably contributes to cortical dysfunction in SMART syndrome. L-arginine warrants investigation as a potential treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.
Vandana, V P; Bindu, Parayil Sankaran; Sonam, Kothari; Govindaraj, Periyasamy; Taly, Arun B; Gayathri, Narayanappa; Chiplunkar, Shwetha; Govindaraju, Chikkanna; Arvinda, H R; Nagappa, Madhu; Sinha, Sanjib; Thangaraj, Kumarasamy
2016-09-01
Reports of audiological manifestations in specific subgroups of mitochondrial disorders are limited. This study aims to describe the audiological findings in patients with MELAS syndrome and m.3243A>G mutation. Audiological evaluation was carried out in eight patients with confirmed MELAS syndrome and m.3243A>G mutation. The evaluation included a complete neurological evaluation, pure tone audiometry (n=8), otoacoustic emissions (n=8) and brainstem evoked response audiometry (n=6), magnetic resonance imaging (n=8) and muscle biospy (n=6). Eight patients (Age range: 5-45 years; M:F-1:3) including six children and two adults underwent formal audiological evaluation. Five patients had hearing loss; of these two had "subclinical hearing loss", one had moderate and two had severe hearing loss. The abnormalities included abnormal audiometry (n=5), otoacoustic emission testing (n=7) and absent brainstem auditory evoked responses (n=1). The findings were suggestive of cochlear involvement in four and retrocochlear in one. This study shows that hearing loss of both cochlear and retrocochlear origin occurs in patients with MELAS and may be subclinical. Early referrals for audiological evaluation is warranted to recognize the subclinical hearing loss in these patients. The therapeutic implications include early interventions in the form of hearing aids, cochlear implants and cautioning the physicians for avoidance of aminoglycosides. Copyright © 2016 Elsevier B.V. All rights reserved.
Armstrong, Amy E; Gillan, Eileen; DiMario, Francis Joseph
2014-03-01
SMART syndrome (stroke-like migraine attacks after radiation therapy) is a rare condition that involves complex migraines with focal neurologic findings in patients following cranial irradiation for central nervous system malignancies. Little is known about the mechanisms behind the disorder, making successful treatment challenging. We report 2 new cases of SMART syndrome in pediatric patients as well as review all documented cases of the syndrome. Each of our 2 pediatric patients suffered multiple episodes. Attacks were characterized by severe headache, visual disturbance, aphasia, and weakness. Recovery occurred over several days to weeks. The data from all documented reports of SMART syndrome indicate a greater prevalence for male gender. An age-dependent pattern of onset was also observed, with a greater variability of syndrome onset in patients who received cranial irradiation at a younger age. SMART appears to be a reversible, recurrent long-term complication of radiation therapy with possible age- and gender-related influences.
[Identification of an ideal noninvasive method to detect A3243G gene mutation in MELAS syndrome].
Ma, Yi-nan; Fang, Fang; Yang, Yan-ling; Zhang, Ying; Wang, Song-tao; Xu, Yu-feng; Pei, Pei; Yuan, Yun; Bu, Ding-fang; Qi, Yu
2008-12-16
To identify a better non-invasive method to detect the carrier of mitochondrial A3243G mutation, a cause of mitochondrial encephalopathy-lactic acidosis-stroke like episode (MELAS) syndrome. DNA was extracted from the peripheral blood, urine, hair follicle, and saliva of 25 MELAS syndrome patients carrying A3243G mutation and their mothers and other maternal relatives, 33 persons in number, and the muscle tissues from 5 patients obtained by biopsy. A3243G mutation was detected by PCR-RFLP method, and the A3243G mutation ratio was identified by measuring the density of each band and calculation with the software AlphaEase 5.0. A3243G mutations were detected in all tissues of the 25 MELAS patients. The A3243G mutation ratio in urine was 62% +/- 9%, significantly higher than that in the blood [(36% +/- 10%), t = -11.13, P < 0.01]. A3243G mutations were detected in at least one tissue of the 28 maternal relatives. The A3243G mutation rates in their urine samples was 33.0% (5.0% - 70.4%), significantly higher than that in their blood samples [8.0% (0 - 33.3%), z = -4.197, P < 0.01]. There was no significant difference in A3243G mutation ratio among the samples of hair follicle, saliva, and blood. The A3243G mutation ratio in urine is significantly higher than those in blood samples of the patients and their maternal relatives. A noninvasive method, A3243G mutation ratio analysis of urine is superior to that in blood.
1993-09-30
history of deep vein thrombosis, cerebral embolus, stroke , congestive heart failure, or ischemic heart disease will not be eligible. No concurrent...Jabbari B Seizures , and Parkinsonism. Neurology 43(4): 836-38, 1993. I Mullin JC Localizing Right Septal Accessory Pathways Using the Maximally Pre...Encephalomyopathy, Lactic Acidosis, Stroke -like I Chuang S, Merante F, Episodes (MELAS): Clinical, Radiological, Pathological, and Genetic Robinson BH
Izquierdo-Serra, Mercè; Martínez-Monseny, Antonio F.; López, Laura; Carrillo-García, Julia; Edo, Albert; Ortigoza-Escobar, Juan Darío; García, Óscar; Carrasco-Marina, M Llanos; Gutiérrez-Solana, Luis G.; Muchart, Jordi; Montero, Raquel; Artuch, Rafael; Pérez-Cerdá, Celia; Pérez, Belén; Pérez-Dueñas, Belén; Macaya, Alfons
2018-01-01
Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and may complicate the course of channelopathies related to Familial Hemiplegic Migraine (FHM) caused by mutations in CACNA1A (encoding CaV2.1 channel). The underlying pathomechanisms are unknown. We analyze clinical variables to detect risk factors for SLE in a series of 43 PMM2-CDG patients. We explore the hypothesis of abnormal CaV2.1 function due to aberrant N-glycosylation as a potential novel pathomechanism of SLE and ataxia in PMM2-CDG by using whole-cell patch-clamp, N-glycosylation blockade and mutagenesis. Nine SLE were identified. Neuroimages showed no signs of stroke. Comparison of characteristics between SLE positive versus negative patients’ group showed no differences. Acute and chronic phenotypes of patients with PMM2-CDG or CACNA1A channelopathies show similarities. Hypoglycosylation of both CaV2.1 subunits (α1A and α2α) induced gain-of-function effects on channel gating that mirrored those reported for pathogenic CACNA1A mutations linked to FHM and ataxia. Unoccupied N-glycosylation site N283 at α1A contributes to a gain-of-function by lessening CaV2.1 inactivation. Hypoglycosylation of the α2δ subunit also participates in the gain-of-function effect by promoting voltage-dependent opening of the CaV2.1 channel. CaV2.1 hypoglycosylation may cause ataxia and SLEs in PMM2-CDG patients. Aberrant CaV2.1 N-glycosylation as a novel pathomechanism in PMM2-CDG opens new therapeutic possibilities. PMID:29470411
Debray, François-Guillaume; Morin, Charles; Janvier, Annie; Villeneuve, Josée; Maranda, Bruno; Laframboise, Rachel; Lacroix, Jacques; Decarie, Jean-Claude; Robitaille, Yves; Lambert, Marie; Robinson, Brian H; Mitchell, Grant A
2011-03-01
The natural history of all known patients with French-Canadian Leigh disease (Saguenay-Lac-St-Jean cytochrome c oxidase deficiency, MIM220111, SLSJ-COX), the largest known cohort of patients with a genetically homogeneous, nuclear encoded congenital lactic acidosis, was studied. 55 of 56 patients were homozygous for the A354V mutation in LRPPRC. One was a genetic compound (A354V/C1277Xdel8). Clinical features included developmental delay, failure to thrive, characteristic facial appearance and, in 90% of patients, acute crises that have not previously been detailed, either metabolic (fulminant lactic acidosis) and/or neurological (Leigh syndrome and/or stroke-like episodes). Survival ranged from 5 days to >30 years. 46/56 patients (82%) died, at a median age of 1.6 years. Of 73 crises, 38 (52%) were fatal. The immediate causes of death were multiple organ failure and/or Leigh disease. Major predictors of mortality during crises (p<0.005) were hyperglycaemia, hepatic cytolysis, and altered consciousness at admission. Compared to a group of SURF1-deficient Leigh syndrome patients assembled from the literature, SLSJ-COX is distinct by the occurrence of metabolic crises, leading to earlier and higher mortality (p=0.001). SLSJ-COX is clinically distinct, with acute fatal acidotic crises on a backdrop of chronic moderate developmental delay and hyperlactataemia. Leigh syndrome is common. Stroke-like episodes can occur. The Leigh syndrome of SLSJ-COX differs from that of SURF1-related COX deficiency. SLSJ-COX has a different spectrum of associated abnormalities, acidotic crises being particularly suggestive of LRPPRC related Leigh syndrome. Even among A354V homozygotes, pronounced differences in survival and severity occur, showing that other genetic and/or environmental factors can influence outcome.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-24
... will discuss, make recommendations, and vote on premarket approval application for MelaFind, sponsored by MELA Sciences, Inc. MelaFind is a non-invasive computer vision system intended to assist in the... characteristics of melanoma, before a final decision to biopsy has been rendered. MelaFind acquires and displays...
2006-05-01
This MOC image shows dark sand dunes superposed on layered, light-toned outcrops -- interpreted to be sedimentary rocks -- in Melas Chasma. Melas Chasma is part of the enormous Valles Marineris trough system
Tsuboguchi, Shintaro; Wakasugi, Takahiro; Umeda, Yoshitaka; Umeda, Maiko; Oyake, Mutsuo; Fujita, Nobuya
2017-07-29
A 73-year-old woman presented with sudden onset of right hemiparesis and was diagnosed as having cerebral infarction on the basis of diffusion-weighted brain MRI, which demonstrated lesions in the left parietal cortex. On the 3rd day, the patient developed right upper limb myoclonus, aphasia, and disturbance of consciousness with high fever. On the 6th day, she was transferred to our hospital with suspected viral encephalitis, and treatment with acyclovir was started. By the 6th day, the lesions detected by MRI had expanded to the gyrus cinguli, insula and thalamus, but not to the temporal lobe. At that time, the CSF cell count was 8/μl, and this later increased to 17/μl by the 13th day. Although herpes simplex virus DNA was detected in the CSF on the 6th day, there was no evidence of CSF pleocytosis or temporal lobe abnormalities demonstrable by brain MRI throughout the whole follow-up period. This was very atypical case of herpes simplex encephalitis characterized by a stroke-like episode, atypical MRI findings, and absence of cerebrospinal fluid pleocytosis. It is important to be mindful that herpes simplex encephalitis (HSE) can have an atypical presentation, and that sufficient acyclovir treatment should be initiated until HSE can be ruled out.
2010-04-19
Melas Chasma is the central portion of Valles Marineris. This image taken by NASA 2001 Mars Odyssey shows a small portion of the floor of Melas Chasma, including layered deposits and wind eroded and deposited materials.
Tagging and Playback Studies to Toothed Whales
2013-09-30
different deep-diving species, long-finned pilot whales (Globicephala melas ). b) Compare responses of beaked whales vs other odontocetes to playbacks of...deployments Playbacks Globicephala melas 1 0 Med10 Tag deployments Playbacks Globicephala melas 16 0 Ziphius cavirostris Two days of attempts 0 Med11...Tag deployments Playbacks Globicephala melas 19 8 (4 animals, KW + PRN) 3 RESULTS Over the past three years, we have developed a powerful
NASA Astrophysics Data System (ADS)
Goldys, Ewa M.; Gosnell, Martin E.; Anwer, Ayad G.; Cassano, Juan C.; Sue, Carolyn M.; Mahbub, Saabah B.; Pernichery, Sandeep M.; Inglis, David W.; Adhikary, Partho P.; Jazayeri, Jalal A.; Cahill, Michael A.; Saad, Sonia; Pollock, Carol; Sutton-Mcdowall, Melanie L.; Thompson, Jeremy G.
2016-03-01
Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous fluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from imaging of native fluorescence has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Multispectral intrinsic fluorescence imaging was applied to patient olfactory neurosphere-derived cells, cell model of a human metabolic disease MELAS (mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like syndrome). By using an endogenous source of contrast, subtle metabolic variations have been detected between living cells in their full morphological context which made it possible to distinguish healthy from diseased cells before and after therapy. Cellular maps of native fluorophores, flavins, bound and free NADH and retinoids unveiled subtle metabolic signatures and helped uncover significant cell subpopulations, in particular a subpopulation with compromised mitochondrial function. The versatility of our method is further illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent.
Cetacean Social Behavioral Response to Sonar Exposure
2015-09-30
Lam FPA, Tyack PLT, Miller PJO (in review). Disturbance-specific social responses in long-finned pilot whales, Globicephala melas . Fieldwork...the social behavioral response of long-finned pilot whales (Globicephala melas ) revealed that a unifying characteristic of their behavioral response...Globicephala melas . 6 Visser F. et al. (in review). Vocal foragers and silent crowds: the socio-behavioural context of long- finned pilot whale
Cognitive impairment, clinical severity and MRI changes in MELAS syndrome.
Kraya, Torsten; Neumann, Lena; Paelecke-Habermann, Yvonne; Deschauer, Marcus; Stoevesandt, Dietrich; Zierz, Stephan; Watzke, Stefan
2017-12-29
To examine clinical severity, cognitive impairment, and MRI changes in patients with MELAS syndrome. Cognitive-mnestic functions, brain MRI (lesion load, cella media index) and clinical severity of ten patients with MELAS syndrome were examined. All patients carried the m.3243A>G mutation. The detailed neuropsychological assessment revealed cognitive deficits in attention, executive function, visuoperception, and -construction. There were significant correlations between these cognitive changes, lesion load in MRI, disturbances in everyday life (clinical scale), and high scores in NMDAS. Patients with MELAS syndrome showed no global neuropsychological deficit, but rather distinct cognitive deficits. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
Ruggiu, Mathilde; Cuccuini, Wendy; Mokhtari, Karima; Meignin, Véronique; Peffault de Latour, Régis; Robin, Marie; Fontbrune, Flore Sicre de; Xhaard, Aliénor; Socié, Gérard; Michonneau, David
2017-10-01
Central nervous system (CNS) involvement of graft versus host disease (GvHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic CNS GvHD symptoms are heterogeneous and include cerebrovascular manifestations, demyelinating disease and immune-mediated encephalitis. CNS-Acute GvHD is not formally defined in literature. We report 7 cases of CNS-GvHD among which two had histological-proven disease. We reviewed 32 additional cases of CNS GvHD published in literature since 1990. In this cohort, 34 patients were transplanted for hematologic malignancies, and 5 for non-malignant hematopoiesis disorders. Of these patients, 25 had a history of chronic GvHD and immunosuppressive treatment had been decreased or discontinued in 14 patients before neurological symptoms onset. Median neurological disorder onset was 385 days [7-7320]. Patients had stroke-like episodes (n = 7), lacunar syndromes (n = 3), multiple sclerosis-like presentations (n = 7), acute demyelinating encephalomyelitis-like symptoms (n = 4), encephalitis (n = 14), mass syndrome (n = 1), and 3 had non-specific symptoms. Median neurological symptoms onset was 81.5 days [7-1095] for patients without chronic GVHD history versus 549 days [11-7300] for patients with chronic GVHD (P = 0.001). Patients with early involvement of CNS after allo-HSCT and no chronic GVHD symptoms were more frequently suffering from encephalitis (64% versus 28%, P = 0.07), whereas stroke-like episodes and lacunar symptoms were less frequent (9% versus 36%, P = 0.13). 34 patients with CNS-GvHD were treated with immunosuppressive therapy, including corticosteroids for 31 of them. Other treatments were intravenous immunoglobulin, plasmapheresis, cyclophosphamide, calcineurin inhibitors, mycophenolic acid, methotrexate and etoposide. 27 patients achieved a response: 10 complete responses, 15 partial responses and 2 transient responses. Of 25 patients with sufficient follow-up, 7 were alive and 18 patients deceased after CNS-GvHD diagnosis. CNS-related GvHD is a rare cause of CNS disorders after allo-HSCT and is associated with a poor prognosis.
MOCHA - Multi-Study Ocean Acoustics Human Effects Analysis
2014-09-30
and P.J.O. Miller. 2014. High thresholds for avoidance of sonar by free-ranging long-finned pilot whales (Globicephala melas ). Marine Pollution...sonar by free-ranging long-finned pilot whales (Globicephala melas ). Marine Pollution Bulletin, 83(1): 165-180. [published, refereed] DeRuiter, S.L...Press. The social context of individual foraging behaviour in long-finned pilot whales (Globicephala melas ). Behaviour, 2014 [in press, refereed
3S2: Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters
2013-09-30
exposures of killer (Orcinus orca), long-finned pilot (Globicephala melas ), and sperm whales (Physeter macrocephalus) to naval sonar. Aquatic Mammals 38...pilot whales (Globicephala melas ). Marine Mammal Science. [in review, refereed] 8 Kvadsheim, PH, Miller, PJO, Tyack, P, Sivle, LD, Lam, FPA, and...killer (Orcinus orca), long-finned pilot (Globicephala melas ), and sperm whales (Physeter macrocephalus) to naval sonar. Aquatic Mammals 38: 362-401
Managing the Earth’s Biggest Mass Gathering Event and WASH Conditions: Maha Kumbh Mela (India)
Baranwal, Annu; Anand, Ankit; Singh, Ravikant; Deka, Mridul; Paul, Abhishek; Borgohain, Sunny; Roy, Nobhojit
2015-01-01
Background: Mass gatherings including a large number of people makes the planning and management of the event a difficult task. Kumbh Mela is one such, internationally famous religious mass gathering. It creates the substantial challenge of creating a temporary city in which millions of people can stay for a defined period of time. The arrangements need to allow this very large number of people to reside with proper human waste disposal, medical services, adequate supplies of food and clean water, transportation etc. Methods: We report a case study of Maha Kumbh, 2013 which focuses on the management and planning that went into the preparation of Kumbh Mela and understanding its water, sanitation and hygiene conditions. It was an observational cross-sectional study, the field work was done for 13 days, from 21 January to 2 February 2013. Results: Our findings suggest that the Mela committee and all other agencies involved in Mela management proved to be successful in supervising the event and making it convenient, efficient and safe. Health care services and water sanitation and hygiene conditions were found to be satisfactory. BhuleBhatke Kendra (Center for helping people who got separated from their families) had the major task of finding missing people and helping them to meet their families. Some of the shortfalls identified were that drainage was a major problem and some fire incidents were reported. Therefore, improvement in drainage facilities and reduction in fire incidents are essential to making Mela cleaner and safer. The number of persons per toilet was high and there were no separate toilets for males and females. Special facilities and separate toilets for men and women will improve their stay in Mela. Conclusion: Inculcation of modern methods and technologies are likely to help in supporting crowd management and improving water, sanitation and hygiene conditions in the continuously expanding KumbhMela, in the coming years. PMID:25932345
Managing the Earth's Biggest Mass Gathering Event and WASH Conditions: Maha Kumbh Mela (India).
Baranwal, Annu; Anand, Ankit; Singh, Ravikant; Deka, Mridul; Paul, Abhishek; Borgohain, Sunny; Roy, Nobhojit
2015-04-13
Mass gatherings including a large number of people makes the planning and management of the event a difficult task. Kumbh Mela is one such, internationally famous religious mass gathering. It creates the substantial challenge of creating a temporary city in which millions of people can stay for a defined period of time. The arrangements need to allow this very large number of people to reside with proper human waste disposal, medical services, adequate supplies of food and clean water, transportation etc. We report a case study of Maha Kumbh, 2013 which focuses on the management and planning that went into the preparation of Kumbh Mela and understanding its water, sanitation and hygiene conditions. It was an observational cross-sectional study, the field work was done for 13 days, from 21 January to 2 February 2013. Our findings suggest that the Mela committee and all other agencies involved in Mela management proved to be successful in supervising the event and making it convenient, efficient and safe. Health care services and water sanitation and hygiene conditions were found to be satisfactory. BhuleBhatke Kendra (Center for helping people who got separated from their families) had the major task of finding missing people and helping them to meet their families. Some of the shortfalls identified were that drainage was a major problem and some fire incidents were reported. Therefore, improvement in drainage facilities and reduction in fire incidents are essential to making Mela cleaner and safer. The number of persons per toilet was high and there were no separate toilets for males and females. Special facilities and separate toilets for men and women will improve their stay in Mela. Inculcation of modern methods and technologies are likely to help in supporting crowd management and improving water, sanitation and hygiene conditions in the continuously expanding KumbhMela, in the coming years.
3S(expn 2): Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters
2013-09-30
orca), long-finned pilot (Globicephala melas ), and sperm whales (Physeter macrocephalus) to naval sonar. Aquatic Mammals 38: 362-401. 9...of sonar signals by long-finned pilot whales (Globicephala melas ). Marine Mammal sci Aoki K, Sakai M, Miller PJO, Visser F, Sato K (2013) Body...Orcinus orca), long-finned pilot (Globicephala melas ), and sperm whales (Physeter macrocephalus) to naval sonar. Aquatic Mammals 38: 362-401
3S2: Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters
2015-09-30
long-finned pilot (Globicephala melas ), and sperm whales (Physeter macrocephalus) to naval sonar. Aquatic Mammals 38: 362-401. Moretti, D., Thomas, L...2014). The social context of individual foraging behaviour in long-finned pilot whales (Globicephala melas ). Behaviour 151: 1453-1477. DOI: 10.1163...response thresholds for avoidance of sonar by free-ranging long-finned pilot whales (Globicephala melas ). Mar. Poll. Bull.83: 165-180. DOI: 10.1016
3S2: Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters
2015-09-30
experimental exposures of killer (Orcinus orca), long-finned pilot (Globicephala melas ), and sperm whales (Physeter macrocephalus) to naval sonar. Aquatic...Kvadsheim P.H., Huisman J. and Tyack P.L. (2014). The social context of individual foraging behaviour in long-finned pilot whales (Globicephala melas ...Wensveen P.J., Miller P. J. O. (2014). High response thresholds for avoidance of sonar by free-ranging long-finned pilot whales (Globicephala melas
Moteki, Hideaki; Azaiez, Hela; Booth, Kevin T; Hattori, Mitsuru; Sato, Ai; Sato, Yoshihiko; Motobayashi, Mitsuo; Sloan, Christina M; Kolbe, Diana L; Shearer, A Eliot; Smith, Richard J H; Usami, Shin-ichi
2015-01-01
Objective We present a family with a mitochondrial DNA 3243A>G mutation resulting in MELAS, of which some members have hearing loss where a novel mutation in the P2RX2 gene was identified. Methods One hundred ninety-four (194) Japanese subjects from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known non-syndromic hearing loss genes were performed to identify the genetic causes of hearing loss. Results A novel mutation in the P2RX2 gene, that corresponded to c.601G>A (p.Asp201Tyr) was identified. Two patients carried the mutation, and had severe SNHL, while other members with MELAS (who did not carry the P2RX2 mutation) had normal hearing. Conclusion This is the first case report of a diagnosis of hearing loss caused by P2RX2 mutation in patients with MELAS. A potential explanation is that decreasing ATP production due to MELAS with mitochondrial 3243A>G mutation might suppress activation of P2X2 receptors. We also suggest that hearing loss caused by the P2RX2 mutation might be influenced by the decrease in ATP production due to MELAS, and that nuclear genetic factors may play a modifying role in mitochondrial dysfunction. PMID:25788561
Miralles, Laura; Oremus, Marc; Silva, Mónica A; Planes, Serge; Garcia-Vazquez, Eva
2016-01-01
Pilot whales are two cetacean species (Globicephala melas and G. macrorhynchus) whose distributions are correlated with water temperature and partially overlap in some areas like the North Atlantic Ocean. In the context of global warming, distribution range shifts are expected to occur in species affected by temperature. Consequently, a northward displacement of the tropical pilot whale G. macrorynchus is expected, eventually leading to increased secondary contact areas and opportunities for interspecific hybridization. Here, we describe genetic evidences of recurrent hybridization between pilot whales in northeast Atlantic Ocean. Based on mitochondrial DNA sequences and microsatellite loci, asymmetric introgression of G. macrorhynchus genes into G. melas was observed. For the latter species, a significant correlation was found between historical population growth rate estimates and paleotemperature oscillations. Introgressive hybridization, current temperature increases and lower genetic variation in G. melas suggest that this species could be at risk in its northern range. Under increasing environmental and human-mediated stressors in the North Atlantic Ocean, it seems recommendable to develop a conservation program for G. melas.
Miralles, Laura; Oremus, Marc; Silva, Mónica A.; Planes, Serge; Garcia-Vazquez, Eva
2016-01-01
Pilot whales are two cetacean species (Globicephala melas and G. macrorhynchus) whose distributions are correlated with water temperature and partially overlap in some areas like the North Atlantic Ocean. In the context of global warming, distribution range shifts are expected to occur in species affected by temperature. Consequently, a northward displacement of the tropical pilot whale G. macrorynchus is expected, eventually leading to increased secondary contact areas and opportunities for interspecific hybridization. Here, we describe genetic evidences of recurrent hybridization between pilot whales in northeast Atlantic Ocean. Based on mitochondrial DNA sequences and microsatellite loci, asymmetric introgression of G. macrorhynchus genes into G. melas was observed. For the latter species, a significant correlation was found between historical population growth rate estimates and paleotemperature oscillations. Introgressive hybridization, current temperature increases and lower genetic variation in G. melas suggest that this species could be at risk in its northern range. Under increasing environmental and human-mediated stressors in the North Atlantic Ocean, it seems recommendable to develop a conservation program for G. melas. PMID:27508496
2013-07-01
ofAnopheles gambiae sensu stricto (Giles), Anopheles melas Theobald and possibly Anopheles arabiensis Patton, although the presence and distribution of the...Liberia (Stojanovich and Scott 1966), of which An. gambiae (n 149) comprised 32% (Fig. 1), in- cluding a single An. melas (Table 2). An. gambiae s. s...other member of the An. gambiae complex captured in our studywasAn. melas , a brack- ish water species known to develop in semimonthly spring-tide pools
2015-09-30
playbacks Killer whale (O. orca) 10 4 8 1 2 LF pilot whale (G. melas ) 30 8 14 4 8 Sperm whale (P. Macrocephalus) 10 4 10 2 5 Humpback whale (M...exposure dataset of the long-finned pilot whale (Globicephala melas ). A hidden Markov model (HMM) approach was developed to quantify behavioral states...Experimental Exposures of Killer (Orcinus orca), Long-Finned Pilot (Globicephala melas ), and Sperm (Physeter macrocephalus) Whales to Naval Sonar. Aquat
2013-06-01
38, 40, 41]. Because these “ mela - noma stem cells” (MSC) are sometimes so numerous, some have argued that the CSC model may not apply to melanoma...40]. There are data from two groups indicating that mela - noma lesions contain a CSC subset character- ized by CD271 expression [25, 26]. In a...neuronal proteins and neuron- like differentiation has been long recognized in neoplastic melanocytes [46, 47]. Certain mela - noma cell lines that
3S2: Behavioral Response Studies of Cetaceans to Navy Sonar Signals in Norwegian Waters
2014-09-30
severity of behavioral changes observed during experimental exposures of killer (Orcinus orca), long-finned pilot (Globicephala melas ), and sperm...finned pilot whales (Globicephala melas ). Marine Mammal sci (DOI: 10.1111/mms.12099). Antunes R., Kvadsheim P.H., Lam F.P.A., Tyack, P.L., Thomas, L... melas ). Mar. Poll. Bull. (DOI: 10.1016/j.marpolbul.2014.03.056) Aoki K, Sakai M, Miller PJO, Visser F, Sato K (2013) Body contact and synchronous dives
2016-12-05
Today's VIS image shows part of the canyon wall of Melas Chasma. Orbit Number: 65682 Latitude: -9.38343 Longitude: 289.417 Instrument: VIS Captured: 2016-10-04 02:52 http://photojournal.jpl.nasa.gov/catalog/PIA21181
Possible Sulfate Deposits in West Melas Chasma
2016-05-04
Melas Chasma is the widest segment of Valles Marineris, the largest canyon in the Solar System as seen by Mars Reconnaissance Orbiter spacecraft. In this region, hydrated sulfate salts have been detected.
2002-12-07
This image is a mosaic of day and night infrared images of Melas Chasma taken by NASA Mars Odyssey spacecraft. The daytime temperature images are shown in black and white, superimposed on the Martian topography.
2014-09-30
Minvielle- Sebastia, L. and Guinet, C. (2008b). Diet of the social groups of long-finned pilot whales (Globicephala melas ) in the Strait of Gibraltar. Marine...structure of long-finned pilot whales (Globicephala melas ) in the Strait of Gibraltar. Acta Ethologica 11, 81-94. DeRuiter, S. L., Boyd, I. L...Aoki Kagari A, Lam F-Pa, Kvadsheim PH, Huisman J, Tyack PL (2014): The social contect of individual foraging behaviour in long-finned pilot whales (Globicephala melas ). Behaviour 151: 1453-77. [published, refereed
2014-12-09
The THEMIS VIS camera contains 5 filters. The data from different filters can be combined in multiple ways to create a false color image. This false color image captured by NASA 2001 Mars Odyssey spacecraft shows part of Melas Chasma.
2003-01-09
Erosion of the interior layered deposits of Melas Chasma, part of the huge Valles Marineris canyon system, has produced cliffs with examples of spur and gulley morphology and exposures of finely layered sediments, as seen in this NASA Mars Odyssey image.
Long Range View of Melas Chasma
2002-12-07
This image is a mosaic of day and night infrared images of Melas Chasma taken by NASA Mars Odyssey spacecraft. The daytime temperatures range from approximately -35 degrees Celsius -31 degrees Fahrenheit to -5 degrees Celsius 23 degrees Fahrenheit.
Ceteacean Social Behavioral Response to Sonar
2014-09-30
Kvadsheim PH, Huisman J and Tyack PL (in review). The social context of individual foraging behaviour in long-finned pilot whales (Globicephala melas ...of behavioral changes observed during experimental exposures of killer (Orcinus orca), long-finned pilot whale (Globicephala melas ), and sperm whale
Ceteacean Social Behavioral Response to Sonar
2013-09-30
review). The social context of individual foraging behaviour in long-finned pilot whales (Globicephala melas ). Aoki K, Sakai M, Miller JO, Visser F...during 8 experimental exposures of killer (Orcinus orca), long-finned pilot whale (Globicephala melas ), and sperm whale (Physeter macrocephalus
1998-06-04
This picture centered at latitude 10 degrees S., longitude 74 degrees W. shows much of Mars Melas Chasm and a portion of Candor Chasm upper right in central Valles Marineris as seen by NASA's Viking Orbiter 2. http://photojournal.jpl.nasa.gov/catalog/PIA00156
Geffroy, Guillaume; Benyahia, Rayane; Frey, Samuel; Desquiret-Dumas, Valerie; Gueguen, Naig; Bris, Celine; Belal, Sophie; Inisan, Aurore; Renaud, Aurelie; Chevrollier, Arnaud; Henrion, Daniel; Bonneau, Dominique; Letournel, Franck; Lenaers, Guy; Reynier, Pascal; Procaccio, Vincent
2018-05-01
Ketogenic diet (KD) which combined carbohydrate restriction and the addition of ketone bodies has emerged as an alternative metabolic intervention used as an anticonvulsant therapy or to treat different types of neurological or mitochondrial disorders including MELAS syndrome. MELAS syndrome is a severe mitochondrial disease mainly due to the m.3243A > G mitochondrial DNA mutation. The broad success of KD is due to multiple beneficial mechanisms with distinct effects of very low carbohydrates and ketones. To evaluate the metabolic part of carbohydrate restriction, transmitochondrial neuronal-like cybrid cells carrying the m.3243A > G mutation, shown to be associated with a severe complex I deficiency was exposed during 3 weeks to glucose restriction. Mitochondrial enzyme defects were combined with an accumulation of complex I (CI) matrix intermediates in the untreated mutant cells, leading to a drastic reduction in CI driven respiration. The severe reduction of CI was also paralleled in post-mortem brain tissue of a MELAS patient carrying high mutant load. Importantly, lowering significantly glucose concentration in cell culture improved CI assembly with a significant reduction of matrix assembly intermediates and respiration capacities were restored in a sequential manner. In addition, OXPHOS protein expression and mitochondrial DNA copy number were significantly increased in mutant cells exposed to glucose restriction. The accumulation of CI matrix intermediates appeared as a hallmark of MELAS pathophysiology highlighting a critical pathophysiological mechanism involving CI disassembly, which can be alleviated by lowering glucose fuelling and the induction of mitochondrial biogenesis, emphasizing the usefulness of metabolic interventions in MELAS syndrome. Copyright © 2018 Elsevier B.V. All rights reserved.
Validating tyrosinase homologue melA as a photoacoustic reporter gene for imaging Escherichia coli
NASA Astrophysics Data System (ADS)
Paproski, Robert J.; Li, Yan; Barber, Quinn; Lewis, John D.; Campbell, Robert E.; Zemp, Roger
2015-10-01
To understand the pathogenic processes for infectious bacteria, appropriate research tools are required for replicating and characterizing infections. Fluorescence and bioluminescence imaging have primarily been used to image infections in animal models, but optical scattering in tissue significantly limits imaging depth and resolution. Photoacoustic imaging, which has improved depth-to-resolution ratio compared to conventional optical imaging, could be useful for visualizing melA-expressing bacteria since melA is a bacterial tyrosinase homologue which produces melanin. Escherichia coli-expressing melA was visibly dark in liquid culture. When melA-expressing bacteria in tubes were imaged with a VisualSonics Vevo LAZR system, the signal-to-noise ratio of a 9× dilution sample was 55, suggesting that ˜20 bacteria cells could be detected with our system. Multispectral (680, 700, 750, 800, 850, and 900 nm) analysis of the photoacoustic signal allowed unmixing of melA-expressing bacteria from blood. To compare photoacoustic reporter gene melA (using Vevo system) with luminescent and fluorescent reporter gene Nano-lantern (using Bruker Xtreme In-Vivo system), tubes of bacteria expressing melA or Nano-lantern were submerged 10 mm in 1% Intralipid, spaced between <1 and 20 mm apart from each other, and imaged with the appropriate imaging modality. Photoacoustic imaging could resolve the two tubes of melA-expressing bacteria even when the tubes were less than 1 mm from each other, while bioluminescence and fluorescence imaging could not resolve the two tubes of Nano-lantern-expressing bacteria even when the tubes were spaced 10 mm from each other. After injecting 100-μL of melA-expressing bacteria in the back flank of a chicken embryo, photoacoustic imaging allowed visualization of melA-expressing bacteria up to 10-mm deep into the embryo. Photoacoustic signal from melA could also be separated from deoxy- and oxy-hemoglobin signal observed within the embryo and chorioallantoic membrane. Our results suggest that melA is a useful photoacoustic reporter gene for visualizing bacteria, and further work incorporating photoacoustic reporters into infectious bacterial strains is warranted.
USDA-ARS?s Scientific Manuscript database
The correspondence titled “Analytical challenges in the assessment of NO synthesis from L-arginine in the MELAS syndrome” suggested challenges that can limit the utility of stable isotope infusion methodology in assessing NO production....
Geology of a Proposed MER Landing Site in Western Melas Chasma
NASA Technical Reports Server (NTRS)
Weitz, C. M.; Parker, T. J.; Anderson, F. S.; Grant, J. A.
2002-01-01
A proposed landing site for the Mars Exploration Rover (MER) has been identified in western Melas Chasma. The landing ellipse contains a blocky, bright deposit which we propose formed as a landslide, perhaps beneath a former lake. Additional information is contained in the original extended abstract.
Payabvash, S; Oswood, M C; Truwit, C L; McKinney, A M
2015-10-01
To determine acute computed tomography perfusion (CTP) changes in seizure patients presenting with stroke-like symptoms and to correlate those changes with clinical presentation and electroencephalography (EEG). The medical records of all patients who presented to the emergency department with acute stroke-like symptoms and underwent CTP (n=1085) over a 5.5-year period were reviewed. Patients were included who had primary seizure as the final diagnosis, and underwent CTP within 3 hours of symptom onset. A subset of patients had a follow-up EEG within 7 days. The perfusion changes and EEG findings were compared between different clinical presentations. Eighteen of 1085 patients (1.7%) who underwent CTP following an acute stroke-like presentation were included. The abnormality on CTP was usually focal, unilateral hyperperfusion - increased relative cerebral blood flow (rCBF) and volume (rCBV) (n=14/18), which most often affected the temporal lobe. Those patients who presented with a motor or speech deficit (n=12) had a higher temporal lobe rCBV, and rCBF, and lower relative mean transit time (rMTT) compared to those with non-focal neurological deficit at presentation. Early EEG was available in 13 patients; a sharp-spike epileptiform EEG discharge pattern (n=5) was associated with higher temporal lobe ipsilateral rCBF and rCBV, and lower rMTT on admission CTP examination. Seizure patients who present with a unilateral motor or speech deficit most commonly have contralateral hyperperfusion in the corresponding eloquent brain regions on the acute-stage CTP examination. In such patients, epileptiform discharges on the early follow-up EEG are associated with ipsilateral hyperperfusion on the admission CTP. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Genetics of ischaemic stroke; single gene disorders.
Flossmann, Enrico
2006-08-01
Examples of single gene disorders have been described for all major subtypes of ischaemic stroke: accelerated atherosclerosis and subsequent thrombo-embolism (e.g. homocysteinuria), weakening of connective tissue resulting in arterial dissections (e.g. Ehler-Danlos type IV), disorders of cerebral small vessels (e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and the collagen COL4A1 mutation), disorders increasing the thrombogenic potential of the heart through affecting the myocardium or the heart valves or through disturbance of the heart rhythm (e.g. hypertrophic cardiomyopathy), mitochondrial cytopathies increasing cerebral tissue susceptibility to insults (e.g. mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), and finally disorders of coagulation that can either directly cause stroke or act synergistically with the aforementioned abnormalities (e.g. sickle cell disease). Most of these disorders are rare but they are important to consider particularly in young patients with stroke, those with a family history or those who have other characteristics of a particular syndrome.
Trends in Nanosecond Melanosome Microcavitation Up to 1540 Nanometers
2015-09-01
these absorption coeffi- cients are probably due to the high water content and low mela - nin concentration in the RPE layer, as a simple first-order...comparison of radiant exposure thresholds of bovine mela - nosomes as a function of wavelength, on a log scale, from 532 to 1540 nm, at ambient
2015-09-30
Minvielle-Sebastia, L. and Guinet, C. (2008). Long-term social structure of long-finned pilot whales (Globicephala melas ) in the Strait of Gibraltar. Acta...Severity of Behavioral Changes Observed During Experimental Exposures of Killer (Orcinus orca), Long-Finned Pilot (Globicephala melas ), and Sperm
Validating tyrosinase homologue MelA as a photoacoustic reporter gene for imaging Escherichia coli
NASA Astrophysics Data System (ADS)
Paproski, Robert J.; Li, Yan; Barber, Quinn; Lewis, John D.; Campbell, Robert; Zemp, Roger
2015-03-01
Antibiotic drug resistance is a major worldwide issue. Development of new therapies against pathogenic bacteria requires appropriate research tools for replicating and characterizing infections. Previously fluorescence and bioluminescence modalities have been used to image infectious burden in animal models but scattering significantly limits imaging depth and resolution. We hypothesize that photoacoustic imaging, which has improved depth-toresolution ratio, could be useful for visualizing MelA-expressing bacteria since MelA is a bacterial tyrosinase homologue involved in melanin production. Using an inducible expression system, E. coli expressing MelA were visibly black in liquid culture. Phosphate buffered saline (PBS), MelA-expressing bacteria (at different dilutions in PBS), and chicken embryo blood were injected in plastic tubes which were imaged using a VisualSonics Vevo LAZR system. Photoacoustic imaging at 6 different wavelengths (680, 700, 750, 800, 850 and 900nm) enabled spectral de-mixing to distinguish melanin signals from blood. The signal to noise ratio of 9x diluted MelA bacteria was 55, suggesting that ~20 bacteria cells could be detected with our system. When MelA bacteria were injected as a 100 μL bolus into a chicken embryo, photoacoustic signals from deoxy- and oxy- hemoglobin as well as MelA-expressing bacteria could be separated and overlaid on an ultrasound image, allowing visualization of the bacterial location. Photoacoustic imaging may be a useful tool for visualizing bacterial infections and further work incorporating photoacoustic reporters into infectious bacterial strains is warranted.
2013-09-30
Minvielle-Sebastia, L. and Guinet, C. (2008b). Diet of the social groups of long-finned pilot whales (Globicephala melas ) in the Strait of Gibraltar...structure of long-finned pilot whales (Globicephala melas ) in the Strait of Gibraltar. Acta Ethologica 11, 81-94. DeRuiter, S. L., Boyd, I. L., Claridge
2014-09-30
KW playbacks Killer whale (O. orca) 10 4 8 1 2 LF pilot whale (G. melas ) 30 8 14 4 8 Sperm whale (P. Macrocephalus) 10 4 10 2 5 Humpback whale...Behavioral Changes Observed During Experimental Exposures of Killer (Orcinus orca), Long-Finned Pilot (Globicephala melas ), and Sperm (Physeter
Melasma and assessment of the quality of life in Brazilian women.
Ikino, Juliana Kida; Nunes, Daniel Holthausen; Silva, Vanessa Priscilla Martins da; Fröde, Tania Silvia; Sens, Mariana Mazzochi
2015-01-01
Melasma is a chronic, acquired hyperpigmentation disease on sun-exposed areas of the skin, which affects patients' quality of life. To assess the impact on the quality of life of women living in Florianópolis, Brazil, through questionnaire (MelasQol), and investigate the clinical aspects and risk factors for melasma, correlating them with the MelasQol scores. This study was performed on 51 melasma patients cared for at the University Hospital of the Universidade Federal de Santa Catarina. The variables included were: age, gender, age of onset of melasma, Fitzpatrick phototype (I-VI), duration and family history of melasma, onset of melasma during pregnancy, use of hormonal contraceptive, thyroid disorder and distribution of melasma. The MelasQoL questionnaire, validated for Brazilian Portuguese (MelasQoL-BP), was applied. The mean age was 38.43±6.75 years. All patients were women. The most common Fitzpatrick skin phototypes were III (49.02%) and IV (33.33%). Melasma had a mean age of onset of 29.18±7.05 years and a mean duration of 9.25±6.18 years. The majority of patients did not have familial history of melasma (50.98%). Melasma onset was associated with pregnancy (45.10%). The MelasQoL-BP analysis revealed significant emotional impact on patients, such as feeling bothered (94.11%), frustrated and embarrassed (64.71%), and depressed (52.94%) about their skin appearance, as well as unattractive (78.43%). No social impact was observed (P>0.05). Melasma has a strong emotional impact on quality of life, resulting especially from feelings about skin appearance.
2014-03-01
to include two or more itipatient and outpatient prirnary diagnosis and kept other aspects of the algorithm the same, and found the overall mela - noma...17 population. Military service members are represented by a range of race and ethnic combinations, with a spectrum of skin mela - nin content. The
2015-02-27
The THEMIS VIS camera contains 5 filters. The data from different filters can be combined in multiple ways to create a false color image. This false color image from NASA 2001 Mars Odyssey spacecraft shows part of Melas Chasma. Orbit Number: 4622 Latitude: -12.797 Longitude: 288.629 Instrument: VIS Captured: 2002-12-30 00:28 http://photojournal.jpl.nasa.gov/catalog/PIA19218
Naturally engineered glycolipid biosurfactants leading to distinctive self-assembled structures.
Imura, Tomohiro; Ohta, Noboru; Inoue, Katsuaki; Yagi, Naoto; Negishi, Hideyuki; Yanagishita, Hiroshi; Kitamoto, Dai
2006-03-08
Self-assembling properties of "natural" glycolipid biosurfactants, mannosyl-erythritol lipids A and B (MEL-A, MEL-B), which are abundantly produced from yeast strains, were investigated by using the fluorescence-probe method, dynamic light-scattering (DLS) analysis, freeze-fracture transmission electron microscopy (FF-TEM), and synchrotron small/wide-angle X-ray scattering (SAXS/WAXS) analysis, among other methods. Both MEL-A and MEL-B exhibit excellent self-assembly properties at extremely low concentrations; they self-assemble into large unilamellar vesicles (LUV) just above their critical-aggregation concentration (CAC). The CAC(I) value was found to be 4.0x10(-6) M for MEL-A and 6.0x10(-6) M for MEL-B. Moreover, the self-assembled structure of MEL-A above a CAC(II) value of 2.0x10(-5) M was found to drastically change into sponge structures (L3) composed of a network of randomly connected bilayers that are usually obtained from a complicated multicomponent "synthetic" surfactant system. Interestingly, the average water-channel diameter of the sponge structure was 100 nm. This is relatively large compared with those obtained from "synthetic" surfactant systems. In addition, MEL-B, which has a hydroxyl group at the C-4' position on mannose instead of an acetyl group, gives only one CAC; the self-assembled structure of MEL-B seems to gradually move from LUV to multilamellar vesicles (MLV) with lattice constants of 4.4 nm, depending on the concentration. Furthermore, the lyotropic-liquid-crystal-phase observation at high concentrations demonstrates the formation of an inverted hexagonal phase (H2) for MEL-A, together with a lamella phase (L(alpha)) for MEL-B, indicating a difference between MEL-A and MEL-B molecules in the spontaneous curvature of the assemblies. These results clearly show that the difference in spontaneous curvature caused by the single acetyl group on the head group probably decides the direction of self-assembly of glycolipid biosurfactants. The unique and complex molecular structures with several chiral centers that are molecularly engineered by microorganisms must have led to the sophisticated self-assembling properties of the glycolipid biosurfactants.
NASA Astrophysics Data System (ADS)
Upton, B. G. J.; Craven, J. A.; Kirstein, L. A.
2006-11-01
Aillikites (carbonated, melilite-free ultramafic lamprophyres grading to carbonatites) are minor components of the Gardar alkaline igneous province. They occur principally as minor intrusions and as clasts in diatremes, but more voluminous aillikitic intrusions crop out near the Ilímaussaq Complex, which they predate by a few million years. These larger intrusions were emplaced at 1160 ± 5 Ma. They are essentially carbonate-free and, consisting almost wholly of ferromagnesian silicate and oxide minerals, are mela-aillikites. Typically the mela-aillikites are fine-grained rocks composed largely of olivine, clinopyroxene, phlogopite and magnetite that crystallised in open systems, permitting loss of volatile-rich residues. The petrography is highly complex, involving at least 28 mineral species. Pyroxenitic veins were emplaced while the host-rocks were still at high temperatures and represent channels through which fluorinated silico-carbonatitic residual melts escaped, with exsolving CO 2 as propellant. Precipitation of Ca-rich minerals including monticellite, perovskite, vesuvianite, wollastonite and cuspidine was a result of dissociation of the calcium carbonate in the residual melts. Late-stage crystallisation was in a highly oxidising environment in which the 'common minerals' attain extreme compositions (almost pure forsterite, ferrian-diopside, highly magnesian ilmenite, Ba-Ti-rich phlogopite and Sr-rich kaersutite). Spatially associated diatremes may be vents through which CO 2-rich gases erupted. The whole-rock compositions are considered to be well removed from those of co-existing melts: compaction and expulsion of highly mobile residual melts is inferred to have left the mela-aillikites as aberrant cumulates. The mela-aillikites are a late-Gardar manifestation of the aillikitic magmatism that occurred intermittently in the province for over 120 Ma. Repetitive formation of metasomite vein systems in the deep lithospheric mantle is postulated. These readily fusible metasomites had short residence histories, experiencing either adiabatic melting or thermal melting as a result of plume activity. The abnormally large volumes of ultramafic lamprophyre magma, from which the mela-aillikites crystallised, may denote the culmination of metasomatic processes in the closing stages of the evolution of the Gardar Province.
Meseguer, Salvador; Martínez-Zamora, Ana; García-Arumí, Elena; Andreu, Antonio L; Armengod, M-Eugenia
2015-01-01
Mitochondrial dysfunction activates mitochondria-to-nucleus signaling pathways whose components are mostly unknown. Identification of these components is important to understand the molecular mechanisms underlying mitochondrial diseases and to discover putative therapeutic targets. MELAS syndrome is a rare neurodegenerative disease caused by mutations in mitochondrial (mt) DNA affecting mt-tRNA(Leu(UUR)). Patient and cybrid cells exhibit elevated oxidative stress. Moreover, mutant mt-tRNAs(Leu(UUR)) lack the taurine-containing modification normally present at the wobble uridine (U34) of wild-type mt-tRNA(Leu(UUR)), which is considered an etiology of MELAS. However, the molecular mechanism is still unclear. We found that MELAS cybrids exhibit a significant decrease in the steady-state levels of several mt-tRNA-modification enzymes, which is not due to transcriptional regulation. We demonstrated that oxidative stress mediates an NFkB-dependent induction of microRNA-9/9*, which acts as a post-transcriptional negative regulator of the mt-tRNA-modification enzymes GTPBP3, MTO1 and TRMU. Down-regulation of these enzymes by microRNA-9/9* affects the U34 modification status of non-mutant tRNAs and contributes to the MELAS phenotype. Anti-microRNA-9 treatments of MELAS cybrids reverse the phenotype, whereas miR-9 transfection of wild-type cells mimics the effects of siRNA-mediated down-regulation of GTPBP3, MTO1 and TRMU. Our data represent the first evidence that an mt-DNA disease can directly affect microRNA expression. Moreover, we demonstrate that the modification status of mt-tRNAs is dynamic and that cells respond to stress by modulating the expression of mt-tRNA-modifying enzymes. microRNA-9/9* is a crucial player in mitochondria-to-nucleus signaling as it regulates expression of nuclear genes in response to changes in the functional state of mitochondria. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Melasma and assessment of the quality of life in Brazilian women*
Ikino, Juliana Kida; Nunes, Daniel Holthausen; da Silva, Vanessa Priscilla Martins; Fröde, Tania Silvia; Sens, Mariana Mazzochi
2015-01-01
BACKGROUND Melasma is a chronic, acquired hyperpigmentation disease on sun-exposed areas of the skin, which affects patients' quality of life. OBJECTIVE To assess the impact on the quality of life of women living in Florianópolis, Brazil, through questionnaire (MelasQol), and investigate the clinical aspects and risk factors for melasma, correlating them with the MelasQol scores. METHODS This study was performed on 51 melasma patients cared for at the University Hospital of the Universidade Federal de Santa Catarina. The variables included were: age, gender, age of onset of melasma, Fitzpatrick phototype (I-VI), duration and family history of melasma, onset of melasma during pregnancy, use of hormonal contraceptive, thyroid disorder and distribution of melasma. The MelasQoL questionnaire, validated for Brazilian Portuguese (MelasQoL-BP), was applied. RESULTS The mean age was 38.43±6.75 years. All patients were women. The most common Fitzpatrick skin phototypes were III (49.02%) and IV (33.33%). Melasma had a mean age of onset of 29.18±7.05 years and a mean duration of 9.25±6.18 years. The majority of patients did not have familial history of melasma (50.98%). Melasma onset was associated with pregnancy (45.10%). The MelasQoL-BP analysis revealed significant emotional impact on patients, such as feeling bothered (94.11%), frustrated and embarrassed (64.71%), and depressed (52.94%) about their skin appearance, as well as unattractive (78.43%). No social impact was observed (P>0.05). CONCLUSION Melasma has a strong emotional impact on quality of life, resulting especially from feelings about skin appearance. PMID:25830989
Al-Mateen, Majeed; Craig, Alexa Kanwit; Chance, Phillip F
2014-03-01
We describe 2 patients with X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) disease and central nervous system manifestations and review 19 cases from the literature. Our first case had not been previously diagnosed with Charcot-Marie-Tooth disease, and the second case, although known to have Charcot-Marie-Tooth disease, was suspected of having CMTX1 after presentation with central nervous system manifestations. The most common central nervous system manifestations were transient and included dysarthria, ataxia, hemiparesis, and tetraparesis resembling periodic paralysis. Of the 21 patients, 19 presented at 21 years of age or younger, implicating CMTX1 with transient central nervous system manifestations as a disorder that predominantly affects children and adolescents. CMTX1 should be included in the differential diagnosis of patients who present with transient central nervous system phenomena, including stroke-like episodes, tetraparesis suggestive of periodic paralysis, dysarthria, ataxia, or combinations of these deficits. Reversible, bilateral, nonenhancing white matter lesions and restricted diffusion on magnetic resonance imaging are characteristic features of the central nervous system phenotype of CMTX1.
Finsterer, Josef; Zarrouk-Mahjoub, Sinda
2016-01-01
Mitochondrial disorders (MIDs) are usually multisystem disorders (mitochondrial multiorgan disorder syndrome) either on from onset or starting at a point during the disease course. Most frequently affected tissues are those with a high oxygen demand such as the central nervous system, the muscle, endocrine glands, or the myocardium. Recently, it has been shown that rarely also the arteries may be affected (mitochondrial arteriopathy). This review focuses on the type, diagnosis, and treatment of mitochondrial vasculopathy in MID patients. A literature search using appropriate search terms was carried out. Mitochondrial vasculopathy manifests as either microangiopathy or macroangiopathy. Clinical manifestations of mitochondrial microangiopathy include leukoencephalopathy, migraine-like headache, stroke-like episodes, or peripheral retinopathy. Mitochondrial macroangiopathy manifests as atherosclerosis, ectasia of arteries, aneurysm formation, dissection, or spontaneous rupture of arteries. The diagnosis relies on the documentation and confirmation of the mitochondrial metabolic defect or the genetic cause after exclusion of non-MID causes. Treatment is not at variance compared to treatment of vasculopathy due to non-MID causes. Mitochondrial vasculopathy exists and manifests as micro- or macroangiopathy. Diagnosing mitochondrial vasculopathy is crucial since appropriate treatment may prevent from severe complications. PMID:27231520
[Autopsy case of Lissauer's general paresis with rapidly progressive left hemiparesis].
Kato, Hiroko; Yoshida, Mari; Ando, Tetsuo; Sugiura, Makoto; Hashizume, Yoshio
2009-06-01
A 48-years-old man presented with slowly progressive bradykinesia, personality change and rapidly progressive left hemiparesis. On admission, he presented dementia, poor judgment, left hemiparesis. MRI revealed a widespread high intensity area in right hemisphere and MRA was almost normal. Serological tests of serum and CSF demonstrated high titers of antibodies to Treponema pallidum. He was treated for syphilis with daily penicillin injections without improvement. He died of sepsis eight months after admission. At autopsy, the brain weighed 1,100 g and the right cerebral hemisphere was atrophic, especially in frontal base, temporal, parietal, angular, and posterior regions covered by thickened, fibrotic leptomeninges. Microscopically, chronic meningoencephalitis was observed. Severe neuronal loss with gliosis was seen in the right cerebral cortices. Scattered rod-shaped microglia and inflammatory cell infiltration were visible in the cerebral parenchyma. The dorsal column of the spinal cord was not involved and meningovascular syphilis was unclear. The distribution of the encephalitic lesions was well correlated with the clinical and neuroradiological findings. This was a rare autopsy case presenting Lissauer's general paresis, clinically manifesting as rapidly progressive stroke-like episode.
2017-07-13
The THEMIS VIS camera contains 5 filters. The data from different filters can be combined in multiple ways to create a false color image. These false color images may reveal subtle variations of the surface not easily identified in a single band image. Today's false color image shows part of Melas Chasma. Orbit Number: 59750 Latitude: -10.5452 Longitude: 290.307 Instrument: VIS Captured: 2015-06-03 12:33 https://photojournal.jpl.nasa.gov/catalog/PIA21705
2015-08-21
The THEMIS VIS camera contains 5 filters. The data from different filters can be combined in multiple ways to create a false color image. These false color images may reveal subtle variations of the surface not easily identified in a single band image. Today's false color image shows part of Melas Chasma. Orbit Number: 10289 Latitude: -9.9472 Longitude: 285.933 Instrument: VIS Captured: 2004-04-09 12:43 http://photojournal.jpl.nasa.gov/catalog/PIA19756
Amuzu, Hilaria; Wilson, Michael D; Boakye, Daniel A
2010-09-14
Two lymphatic filariasis endemic communities Mampong and Hwida in Ghana have been regularly monitored for impact on transmission after annual mass drug administration (MDA) with albendazole and ivermectin. After six MDAs even though the ABR for Mampong was 55883/person/year and that of Hwida was 2494/person/year, they both had ATPs of 15.21 infective larvae/person/year. Interestingly the human microfilaraemia levels had reduced significantly from 14% to 0% at Mampong and 12% to 3% at Hwida. In an attempt to understand this anomaly, we collected mosquitoes over a 5-month period using human landing catches to determine the species composition, the number of cibarial teeth, the lengths and widths of the cibarium and the cibarial dome of the vector populations. Out of 2553 mosquitoes caught at Mampong, 42.6% were An. gambiae s.l. All 280 identified further by PCR were An. gambiae s.s (275 M and 5 S molecular forms). At Hwida, 112 mosquitoes were obtained; 67 (59.8%) were An. gambiae s.l, comprised of 40 (59.7%) An. melas, 24 (35.8%) An. gambiae s.s (17 and 5 M and S molecular forms respectively) and 3 (4.5%) unidentified. The mean number of teeth for An. melas was 14.1 (median = 14, range = 12-15), An. gambiae s.s., 15.7 (median = 15, range = 13-19) M form 15.5 (median = 15 range = 13-19) and S form 16 (median = 16, range 15-17). The observed differences in teeth numbers were significantly different between An. melas and An. gambiae s.s (p = 0.004), and the M form (p = 0.032) and the S form (p = 0.002). In this study, An. gambiae s.s was the main vector at Mampong and was found to possess significantly more cibarial teeth than An. melas, the principal vector at Hwida. We postulate that the different impact observed after 6 MDAs may be due to An. gambiae s.s exhibiting 'facilitation' at Mampong and at Hwida An. melas the main vector exhibits 'limitation'. Thus it may be necessary to compliment MDA with vector control to achieve interruption of transmission in areas where An. melas may exhibit limitation.
NASA Astrophysics Data System (ADS)
Liu, Yang; Goudge, Timothy A.; Catalano, Jeffrey G.; Wang, Alian
2018-03-01
Orbital remote sensing data acquired from the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) onboard Mars Reconnaissance Orbiter (MRO), in conjunction with other datasets, are used to perform detailed spectral and stratigraphic analyses over a portion of south Melas Chasma, Mars. The Discrete Ordinate Radiative Transfer (DISORT) model is used to retrieve atmospherically corrected single scattering albedos from CRISM I/F data for mineral identification. A sequence of interbedded poly- and monohydrated sulfates associated with interior layered deposits (ILDs) is identified and mapped. Analyses from laboratory experiments and spectral unmixing of CRISM hyperspectral data support the hypothesis of precipitation and dehydration of multiple inputs of complex Mg-Ca-Fe-SO4-Cl brines. In this scenario, the early precipitated Mg sulfates could dehydrate into monohydrated sulfate due to catalytic effects, and the later-precipitated Mg sulfates from the late-stage "clean" brine could terminate their dehydration at mid-degree of hydration to form a polyhydrated sulfate layer due to depletion of the catalytic species (e.g., Ca, Fe, and Cl). Distinct jarosite-bearing units are identified stratigraphically above the hydrated sulfate deposits. These are hypothesized to have formed either by oxidation of a fluid containing Fe(II) and SO4, or by leaching of soluble phases from precursor intermixed jarosite-Mg sulfate units that may have formed during the later stages of deposition of the hydrated sulfate sequence. Results from stratigraphic analysis of the ILDs show that the layers have a consistent northward dip towards the interior of the Melas Chasma basin, a mean dip angle of ∼6°, and neighboring strata that are approximately parallel. These strata are interpreted as initially sub-horizontal layers of a subaqueous, sedimentary evaporite deposits that underwent post-depositional tilting from slumping into the Melas Chasma basin. The interbedded hydrated sulfate units and jarosite-bearing units, which have distinct stratigraphic relationships, are indicative of a complex sedimentary and aqueous history in south Melas Chasma.
Balsari, Satchit; Greenough, P Gregg; Kazi, Dhruv; Heerboth, Aaron; Dwivedi, Shraddha; Leaning, Jennifer
2016-12-01
India's Kumbh Mela remains the world's largest and longest mass gathering. The 2013 event, where participants undertook a ritual bath, hosted over 70 million Hindu pilgrims during 55 days on a 1936 hectare flood plain at the confluence of the Yamuna and Ganga Rivers. On the holiest bathing days, the population surged. Unlike other religious, cultural, and sports mass gatherings, the Kumbh Mela's administration cannot estimate or limit the participant number. The event created serious and uncommon public health challenges: initiating crowd safety measures where population density and mobility directly contact flowing bodies of water; providing water, sanitation, and hygiene to a population that frequently defecates in the open; and establishing disease surveillance and resource use measures within a temporary health delivery system. We review the world's largest gathering by observing first-hand the public health challenges, plus the preparations for and responses to them. We recommend ways to improve preparedness.
Stratigraphy of the layered terrain in Valles Marineris, Mars
NASA Technical Reports Server (NTRS)
Komatsu, G.; Strom, Roger G.
1991-01-01
The layered terrain in Valles Marineris provides information about its origin and the geologic history of this canyon system. Whether the terrain is sedimentary material deposited in a dry or lacustrine environment, or volcanic material related to the tectonics of the canyon is still controversial. However, recent studies of Gangis Layered Terrain suggests a cyclic sequence of deposition and erosion under episodic lacustrine conditions. The stratigraphic studies are extended to four other occurrences of layered terrains in Valles Marineris in an attempt to correlate and distinguish between depositional environments. The Juvantae Chasma, Hebes Chasma, Ophir and Candor Chasmata, Melas Chasma, and Gangis Layered Terrain were examined. Although there are broad similarities among the layered terrains, no two deposits are exactly alike. This suggests that there was no synchronized regional depositional processes to form all the layered deposits. However, the similar erosional style of the lower massive weakly bedded unit in Hebes, Gangis, and Ophir-Candor suggests it may have been deposited under similar circumstances.
New evidence for a magmatic influence on the origin of Valles Marineris, Mars
Dohm, J.M.; Williams, J.-P.; Anderson, R.C.; Ruiz, J.; McGuire, P.C.; Komatsu, G.; Davila, A.F.; Ferris, J.C.; Schulze-Makuch, D.; Baker, V.R.; Boynton, W.V.; Fairen, A.G.; Hare, T.M.; Miyamoto, H.; Tanaka, K.L.; Wheelock, S.J.
2009-01-01
In this paper, we show that the complex geological evolution of Valles Marineris, Mars, has been highly influenced by the manifestation of magmatism (e.g., possible plume activity). This is based on a diversity of evidence, reported here, for the central part, Melas Chasma, and nearby regions, including uplift, loss of huge volumes of material, flexure, volcanism, and possible hydrothermal and endogenic-induced outflow channel activity. Observations include: (1) the identification of a new > 50??km-diameter caldera/vent-like feature on the southwest flank of Melas, which is spatially associated with a previously identified center of tectonic activity using Viking data; (2) a prominent topographic rise at the central part of Valles Marineris, which includes Melas Chasma, interpreted to mark an uplift, consistent with faults that are radial and concentric about it; (3) HiRISE-identified landforms along the floor of the southeast part of Melas Chasma that are interpreted to reveal a volcanic field; (4) CRISM identification of sulfate-rich outcrops, which could be indicative of hydrothermal deposits; (5) GRS K/Th signature interpreted as water-magma interactions and/or variations in rock composition; and (6) geophysical evidence that may indicate partial compensation of the canyon and/or higher density intrusives beneath it. Long-term magma, tectonic, and water interactions (Late Noachian into the Amazonian), albeit intermittent, point to an elevated life potential, and thus Valles Marineris is considered a prime target for future life detection missions. ?? 2008 Elsevier B.V.
Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.
Tzoulis, Charalampos; Neckelmann, Gesche; Mørk, Sverre J; Engelsen, Bernt E; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A
2010-05-01
Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that characteristically shows episodes of rapid neurological deterioration and the development of acute cerebral lesions. The purpose of this study was to investigate the nature, distribution and natural evolution of central nervous system lesions in polymerase gamma associated encephalopathy focusing particularly on lesions identified by magnetic resonance imaging. We compared radiological, electrophysiological and pathological findings where available to study potential mechanisms underlying the episodes of exacerbation and acute cerebral lesions. We studied a total of 112 magnetic resonance tomographies and 11 computed tomographies in 32 patients with polymerase gamma-encephalopathy, including multiple serial examinations performed during both the chronic and acute phases of the disease and, in several cases, magnetic resonance spectroscopy and serial diffusion weighted studies. Data from imaging, electroencephalography and post-mortem examination were compared in order to study the underlying disease process. Our findings show that magnetic resonance imaging in polymerase gamma-related encephalopathies has high sensitivity and can identify patterns that are specific for individual syndromes. One form of chronic polymerase gamma-encephalopathy, that is associated with the c.1399G > A and c.2243G > C mutations, is characterized by progressive cerebral and cerebellar atrophy and focal lesions of the thalamus, deep cerebellar structures and medulla oblongata. Acute encephalopathies, both infantile and later onset, show similar pictures with cortical stroke-like lesions occurring during episodes of exacerbation. These lesions can occur both with and without electroencephalographic evidence of concurrent epileptic activity, and have diffusion, spectroscopic and histological profiles strongly suggestive of neuronal energy failure. We suggest therefore that both infantile and later onset polymerase gamma related encephalopathies are part of a continuum.
2015-10-08
The THEMIS VIS camera contains 5 filters. The data from different filters can be combined in multiple ways to create a false color image. These false color images may reveal subtle variations of the surface not easily identified in a single band image. Today's false color image shows part of the floor of Melas Chasma. The dark blue region in this false color image is sand dunes. Orbit Number: 12061 Latitude: -12.2215 Longitude: 289.105 Instrument: VIS Captured: 2004-09-02 10:11 http://photojournal.jpl.nasa.gov/catalog/PIA19793
Sturge-Weber syndrome: ear, nose, and throat issues and neurologic status.
Irving, Natasha D; Lim, Jae Hyung; Cohen, Bernard; Ferenc, Lisa M; Comi, Anne M
2010-10-01
The pathophysiology of Sturge-Weber syndrome is poorly understood, and ear, nose, and throat involvement is possible. These issues can result in frequent illnesses or airway obstruction, affecting patients' neurologic status. Patients with definite brain involvement who reported potential ear, nose, and throat issues on intake questionnaires underwent retrospective reviews of their medical records. We examined the relationships between these issues, secondary surgical interventions, and patients' neurologic status. The most common complaints involved the sinuses and frequent ear infections. Six patients underwent placement of ear tubes, leading to improvements in migraines and stroke-like episodes in one patient, and improved seizure control in four others. Obstructive sleep apnea was confirmed in three patients who underwent sleep studies. Tonsil or adenoid removal occurred in another three patients. Surgery resulted in marked improvements regarding excessive drooling, daytime sleepiness, and breathing problems. These findings suggest that ear, nose, and throat problems occur frequently in patients with Sturge-Weber Syndrome, and when repeated ear infections are associated with uncontrolled seizures, early placement of ear tubes may be beneficial. Furthermore, patients with facial tissue hypertrophy may be at risk for obstructive sleep apnea, and should be appropriately evaluated. Copyright © 2010 Elsevier Inc. All rights reserved.
Burrage, Lindsay C; Tang, Sha; Wang, Jing; Donti, Taraka R; Walkiewicz, Magdalena; Luchak, J Michael; Chen, Li-Chieh; Schmitt, Eric S; Niu, Zhiyv; Erana, Rodrigo; Hunter, Jill V; Graham, Brett H; Wong, Lee-Jun; Scaglia, Fernando
2014-11-01
Mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) is a rare mitochondrial disorder that has previously been associated with mutations in PUS1 and YARS2. In the present report, we describe a 6-year old male with an MLASA plus phenotype. This patient had features of MLASA in the setting of developmental delay, sensorineural hearing loss, epilepsy, agenesis of the corpus callosum, failure to thrive, and stroke-like episodes. Sequencing of the mitochondrial genome identified a novel de novo, heteroplasmic mutation in the mitochondrial DNA (mtDNA) encoded ATP6 gene (m.8969G>A, p.S148N). Whole exome sequencing did not identify mutations or variants in PUS1 or YARS2 or any known nuclear genes that could affect mitochondrial function and explain this phenotype. Studies of fibroblasts derived from the patient revealed a decrease in oligomycin-sensitive respiration, a finding which is consistent with a complex V defect. Thus, this mutation in MT-ATP6 may represent the first mtDNA point mutation associated with the MLASA phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.
Koros, Christos; Economou, Alexandra; Mastorakos, George; Bonakis, Anastasios; Kalfakis, Nikolaos; Papageorgiou, Sokratis G
2012-09-01
We report a longstanding selective memory deficit in a euthyroid 45-year-old woman who was being treated with levothyroxine for Hashimoto thyroiditis. The patient had complained of memory problems and deterioration of her concentration skills for about 2 years. Her endocrinologist thought that she was depressed. The patient's physical examination was normal. She scored a full 30 points on the Mini-Mental State Examination, but neuropsychological evaluation showed a significant deficit in her verbal memory. Routine blood tests and cerebrospinal fluid analysis showed only antithyroid peroxidase antibodies. Brain magnetic resonance imaging was normal. Electroencephalogram showed scarce intermittent bilateral multifocal theta waves. We increased the patient's daily dose of levothyroxine and started her on dexamethasone therapy. Five months later, we repeated the entire evaluation and found both her cognitive function and her electroencephalogram to be normal. Autoimmune encephalopathy associated with Hashimoto thyroiditis is already known to present with either stroke-like episodes or diffuse progressive deterioration. Our patient shows that the encephalopathy can present as a chronic selective memory deficit that can spare executive functions and short-term memory. This presentation can be missed or mistaken for depression, but can be diagnosed with a detailed neuropsychological evaluation.
Mitra, Sayani; Gachhui, Ratan; Mukherjee, Joydeep
2015-01-01
A direct relationship between biofilm formation and melanogenesis in Shewanella colwelliana with increased oyster recruitment is already established. Previously, S. colwelliana was grown in a newly patented biofilm-cultivation device, the conico-cylindrical flask (CCF), offering interchangeable hydrophobic/hydrophilic surfaces. Melanization was enhanced when S. colwelliana was cultivated in a hydrophobic vessel compared with a hydrophilic vessel. In the present study, melanogenesis in the CCF was positively correlated with increased architectural parameters of the biofilm (mean thickness and biovolume obtained by confocal laser scanning microscopy) and melanin gene (melA) expression observed by densitometry. Niche intertidal conditions were mimicked in a process operated in an ultra-low-speed rotating disk bioreactor, which demonstrated enhanced biofilm formation, melanogenesis, exopolysaccharide synthesis and melA gene expression compared with a process where 12-h periodic immersion and emersion was prevented. The wettability properties of the settling plane as well as intermittent wetting and drying, which influenced biofilm formation and melA expression, may affect oyster settlement in nature.
NASA Astrophysics Data System (ADS)
Lin, H.; Zhang, X.; Wu, X.; Tarnas, J. D.; Mustard, J. F.
2018-04-01
Quantitative analysis of hydrated minerals from hyperspectral remote sensing data is fundamental for understanding Martian geologic process. Because of the difficulties for selecting endmembers from hyperspectral images, a sparse unmixing algorithm has been proposed to be applied to CRISM data on Mars. However, it's challenge when the endmember library increases dramatically. Here, we proposed a new methodology termed Target Transformation Constrained Sparse Unmixing (TTCSU) to accurately detect hydrous minerals on Mars. A new version of target transformation technique proposed in our recent work was used to obtain the potential detections from CRISM data. Sparse unmixing constrained with these detections as prior information was applied to CRISM single-scattering albedo images, which were calculated using a Hapke radiative transfer model. This methodology increases success rate of the automatic endmember selection of sparse unmixing and could get more accurate abundances. CRISM images with well analyzed in Southwest Melas Chasma was used to validate our methodology in this study. The sulfates jarosite was detected from Southwest Melas Chasma, the distribution is consistent with previous work and the abundance is comparable. More validations will be done in our future work.
Potential MER Landing Site in Melas Chasma
NASA Technical Reports Server (NTRS)
Weitz, C. M.; Parker, Timothy J.; Anderson, F. Scott
2001-01-01
We have selected one area in Valles Marineris as a potential landing site for the Mars Exploration Rover (MER) mission. After 30 years of analyses, the formation of the Valles Marineris system of troughs and its associated deposits still remains an enigma. Understanding all aspects of the Valles Marineris would significantly contribute to deciphering the internal and external history of Mars. A landing site within Melas Chasma could provide insight into both the formation of Valles Marineris and the composition and origin of the interior layered deposits (ILDs). The ILDs have been proposed as: (1) sedimentary deposits formed in lakes mass wasted material from the walls; (3) remnants of the wall rock; (4) carbonate deposits; (5) aeolian deposits; and (6) volcanic. More recently, Malin and Edgett suggest that the fine-scale, rhythmic layering seen in the interior deposits, as well as other layered deposits in craters, supports a sedimentary origin. Because an understanding of the formation of Valles Marineris and its interior deposits is so important to deciphering the history of Mars, we have proposed a landing site for the MER mission on an exposure of interior deposits in western Melas Chasma. Either MER-A and MER-B could land at this same location.
Interspecific Introgression in Cetaceans: DNA Markers Reveal Post-F1 Status of a Pilot Whale
Miralles, Laura; Lens, Santiago; Rodríguez-Folgar, Antonio; Carrillo, Manuel; Martín, Vidal; Mikkelsen, Bjarni; Garcia-Vazquez, Eva
2013-01-01
Visual species identification of cetacean strandings is difficult, especially when dead specimens are degraded and/or species are morphologically similar. The two recognised pilot whale species (Globicephala melas and Globicephala macrorhynchus) are sympatric in the North Atlantic Ocean. These species are very similar in external appearance and their morphometric characteristics partially overlap; thus visual identification is not always reliable. Genetic species identification ensures correct identification of specimens. Here we have employed one mitochondrial (D-Loop region) and eight nuclear loci (microsatellites) as genetic markers to identify six stranded pilot whales found in Galicia (Northwest Spain), one of them of ambiguous phenotype. DNA analyses yielded positive amplification of all loci and enabled species identification. Nuclear microsatellite DNA genotypes revealed mixed ancestry for one individual, identified as a post-F1 interspecific hybrid employing two different Bayesian methods. From the mitochondrial sequence the maternal species was Globicephala melas. This is the first hybrid documented between Globicephala melas and G. macrorhynchus, and the first post-F1 hybrid genetically identified between cetaceans, revealing interspecific genetic introgression in marine mammals. We propose to add nuclear loci to genetic databases for cetacean species identification in order to detect hybrid individuals. PMID:23990883
Waheed, Waqar; Nathan, Muriel H; Allen, Gilman B; Borden, Neil M; Babi, M Ali; Tandan, Rup
2015-11-03
A 37-year-old man with a known history of neurofibromatosis 1 (NF1) presented within 2 days of diarrhoeal illness followed by encephalopathy, facial twitching, hypoglycaemia, hypotension, tachycardia and low-grade fever. Examination showed multiple café-au-lait spots and neurofibromas over the trunk, arms and legs and receptive aphasia with right homonymous hemianopia, which resolved. Workup for cardiac, inflammatory and infectious aetiologies was unrevealing. A brain MRI showed gyral swelling with increased T2 fluid-attenuated inversion recovery signal and diffusion restriction in the left cerebral cortex. Neuroendocrine findings suggested panhypopituitarism with centrally derived adrenal insufficiency. Supportive treatment, hormone supplementation, antibiotics, antivirals and levetiracetam yielded clinical improvement. A follow-up brain MRI showed focal left parieto-occipital atrophy with findings of cortical laminar necrosis. In conclusion, we describe a case of NF1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like findings, hitherto unreported manifestations of NF1. Prompt recognition and treatment of these associated conditions can prevent devastating complications. 2015 BMJ Publishing Group Ltd.
Waheed, Waqar; Nathan, Muriel H; Allen, Gilman B; Borden, Neil M; Babi, M Ali; Tandan, Rup
2015-01-01
A 37-year-old man with a known history of neurofibromatosis 1 (NF1) presented within 2 days of diarrhoeal illness followed by encephalopathy, facial twitching, hypoglycaemia, hypotension, tachycardia and low-grade fever. Examination showed multiple café-au-lait spots and neurofibromas over the trunk, arms and legs and receptive aphasia with right homonymous hemianopia, which resolved. Workup for cardiac, inflammatory and infectious aetiologies was unrevealing. A brain MRI showed gyral swelling with increased T2 fluid-attenuated inversion recovery signal and diffusion restriction in the left cerebral cortex. Neuroendocrine findings suggested panhypopituitarism with centrally derived adrenal insufficiency. Supportive treatment, hormone supplementation, antibiotics, antivirals and levetiracetam yielded clinical improvement. A follow-up brain MRI showed focal left parieto-occipital atrophy with findings of cortical laminar necrosis. In conclusion, we describe a case of NF1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like findings, hitherto unreported manifestations of NF1. Prompt recognition and treatment of these associated conditions can prevent devastating complications. PMID:26531733
Mtaweh, Haifa; Bayır, Hülya; Kochanek, Patrick M; Bell, Michael J
2014-08-01
Propofol infusion syndrome is a recognized complication of prolonged propofol use in the pediatric population, but little is reported on other metabolic effects of propofol, especially in children with mitochondrial disorders. We report on a child with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome who received a single dose of propofol for procedural sedation. The patient's initial presentation was consistent with a mild exacerbation of her underlying disease. She received a single dose of propofol and non-dextrose-containing fluids during a magnetic resonance imaging (MRI) study to rule out stroke and progressed to develop severe acidosis, neurologic deterioration, and cardiorespiratory compromise. This is the first case report of severe metabolic disturbances after a single dose of propofol administered for procedural sedation in a patient with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome and it questions the safety of propofol and absence of dextrose infusions during an acute illness in patients with mitochondrial disorders. © The Author(s) 2013.
Layers and a Dust Devil in Melas Chasma
NASA Technical Reports Server (NTRS)
2000-01-01
One of the earliest observations made by the Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) was that the upper crust of the planet appears to be layered to considerable depth. This was especially apparent, early in the mission, in the walls of the Valles Marineris chasms. However, layered mesas and mounds within the Valles Marineris troughs were recognized all the way back in 1972 with Mariner 9 images. The MOC image presented here shows many tens of layers of several meters (yards) thickness in the walls of a mesa in southern Melas Chasma in Valles Marineris. Erosion by mass wasting--landslides--has exposed these layers and created the dark fan-shaped deposits seen near the middle of the image. The floor of Melas Chasma is dark and covered with many parallel ridges and grooves (lower 1/3 of image). In the lower left corner of the picture, a bright, circular dust devil can be seen casting a columnar shadow toward the left. This image, illuminated by sunlight from the right/lower right, covers an area 3 kilometers (1.9 miles) wide and 8.2 kilometers (5.1 miles) long. The scene is located near 10.1oS, 74.4oW and was acquired on July 11, 1999. North is toward the lower left.Chol, M; Lebon, S; Bénit, P; Chretien, D; de Lonlay, P; Goldenberg, A; Odent, S; Hertz-Pannier, L; Vincent-Delorme, C; Cormier-Daire, V; Rustin, P; Rötig, A; Munnich, A
2003-03-01
Leigh syndrome is a subacute necrotising encephalomyopathy frequently ascribed to mitochondrial respiratory chain deficiency. This condition is genetically heterogeneous, as mutations in both mitochondrial (mt) and nuclear genes have been reported. Here, we report the G13513A transition in the ND5 mtDNA gene in three unrelated children with complex I deficiency and a peculiar MRI aspect distinct from typical Leigh syndrome. Brain MRI consistently showed a specific involvement of the substantia nigra and medulla oblongata sparing the basal ganglia. Variable degrees of heteroplasmy were found in all tissues tested and a high percentage of mutant mtDNA was observed in muscle. The asymptomatic mothers presented low levels of mutant mtDNA in blood leucocytes. This mutation, which affects an evolutionary conserved amino acid (D393N), has been previously reported in adult patients with MELAS or LHON/MELAS syndromes, emphasising the clinical heterogeneity of mitochondrial DNA mutations. Since the G13513A mutation was found in 21% of our patients with Leigh syndrome and complex I deficiency (3/14), it appears that this mutation represents a frequent cause of Leigh-like syndrome, which should be systematically tested for molecular diagnosis in affected children and for genetic counselling in their maternal relatives.
Bruce, Suzanne; Roberts, Wendy; Teller, Craig; Colvan, Lora
2016-09-01
Chemical peels are versatile treatments that involve chemical exfoliation of the skin for cosmetic improvement. Deeper peels produce more significant results, but can be associated with longer healing time and potential complications. Novel chemical resurfacing treatments (AGE and MELA) were developed in Europe to produce skin resurfacing via controlled inflammation to promote cell regeneration with minimum negative effects associated with conventional peelings. The AGE Resurfacing regimen is indicated for the treatment of photoaging, and consists of multi-ingredient peeling solution with trichloroacetic acid, pyruvic acid, salicylic acid, mandelic acid, and lactobionic acid. The MELA Resurfacing regimen addresses hyperpigmentation concerns and contains mandelic acid, potassium azeloyl diglycinate, retinol, salicylic acid, phytic acid, lactobionic acid, and lactic acid. Results of previously conducted US clinical experience trial of AGE and MELA resurfacing protocols rated 81% of subjects with some level of improvement according to physician assessment.
To evaluate whether a daily skin care regimen used for 12 weeks could maintain the benefits achieved with AGE and MELA chemical resurfacing treatments.
Subjects who completed participation in the AGE and MELA skin resurfacing clinical trial were recruited to participate in a continuation trial and used a daily regimen of MDRejuvena facial products for 12 weeks. No other facial products were permitted. Physicians assessed the severity of individual skin parameters at baseline and week 12 and provided global assessment. Subjects assessed improvement of individual skin parameters at week 12 and provided an overall assessment.
Thirteen subjects participated in the 12-week continuation trial. According to the physician's global assessment, all subjects demonstrated some level of improvement at week 12 compared to baseline. Physician assessment showed a decrease in severity of all skin parameters assessed at week 12 compared to baseline. According to the subject overall assessment at week 12, 11 of 12 subjects noted some level of improvement, 1 subject saw no improvement, and 1 subject did not provide an overall assessment. Mild to moderate improvement was observed by subjects in all individual skin parameters assessed except for skin discoloration.
The results of the continuation study demonstrate that use of a daily skin care regimen, which include combination of 2 various strengths of MDRejuvena Rejuvaphyl® Rejuvenating Complex: low strength (LS) and high strength (HS), not only maintains but can enhance the beneficial effects of skin resurfacing treatments for at least 12 weeks.
J Drugs Dermatol. 2016;15(9):1145-1150.
2009-09-18
This Mars Odyssey image transects Candor Chasma and Melas Chasma. Many canyon features are clearly visible in the image, including the steep cliff faces, landslides, and layered canyon floor deposits.
Stratigraphy and erosional landforms of layered deposits in Valles Marineris, Mars
NASA Technical Reports Server (NTRS)
Komatsu, G.; Geissler, P. E.; Strom, R. G.; Singer, R. B.
1993-01-01
Satellite imagery is used to identify stratigraphy and erosional landforms of 13 layered deposits in the Valles Marineris region of Mars (occurring, specifically, in Gangis, Juventae, Hebes, Ophir-Candor, Melas, and Capri-Eos Chasmata), based on albedo and erosional styles. Results of stratigraphic correlations show that the stratigraphy of layered deposits in the Hebes, Juventae, and Gangis Chasmata are not well correlated, indicating that at least these chasmata had isolated depositional environments resulting in different stratigraphic sequences. On the other hand, the layered deposits in Ophir-Candor and Melas Chasmata appear to have been connected in each chasma. Some of the layered deposits display complexities which indicate changes in space and time in the dominant source materials.
Deposits along the Northern Wall of Melas Chasma
2016-10-05
It has been known since the 1970s when the Viking orbiters took pictures of Mars that there are large (i.e., several kilometers-thick) mounds of light-toned deposits within the central portion of Valles Marineris. More recent higher resolution images of Mars, including this image of Melas Chasma, show that the wall rocks of Valles Mariners also contain similar, albeit thinner, light-toned deposits. Spectral data from the CRISM instrument indicate that the larger mounds are composed of sulfates. Some of the wall rock deposits are also made up of sulfates, but others contain clays or mixtures of several kinds of hydrated materials, suggesting that multiple aqueous processes, perhaps at different times within Valles Marineris, formed the variety of deposits we now observe. http://photojournal.jpl.nasa.gov/catalog/PIA21102
Renal manifestations of primary mitochondrial disorders
Finsterer, Josef; Scorza, Fulvio
2017-01-01
The aim of the present review was to summarize and discuss previous findings concerning renal manifestations of primary mitochondrial disorders (MIDs). A literature review was performed using frequently used databases. The study identified that primary MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or in the later course of the MID. Occasionally, the kidneys are affected in MIDs. Renal manifestations of MIDs include renal insufficiency, nephrolithiasis, nephrotic syndrome, renal cysts, renal tubular acidosis, Bartter-like syndrome, Fanconi syndrome, focal segmental glomerulosclerosis, tubulointerstitial nephritis, nephrocalcinosis, and benign or malign neoplasms. Among the syndromic MIDs, renal involvement has been most frequently reported in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, Kearns-Sayre syndrome, Leigh syndrome and mitochondrial depletion syndromes. Only in single cases was renal involvement also reported in chronic progressive external ophthalmoplegia, Pearson syndrome, Leber's hereditary optic neuropathy, coenzyme-Q deficiency, X-linked sideroblastic anemia and ataxia, myopathy, lactic acidosis, and sideroblastic anemia, pyruvate dehydrogenase deficiency, growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death, and hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis syndrome. The present study proposes that the frequency of renal involvement in MIDs is probably underestimated. Diagnosis of renal involvement follows general guidelines and treatment is symptomatic. Thus, renal manifestations of primary MIDs require recognition and appropriate management, as they determine the outcome of MID patients. PMID:28515908
NASA Astrophysics Data System (ADS)
Beard, A. D.; Downes, H.; Hegner, E.; Sablukov, S. M.
2000-03-01
The Arkhangelsk kimberlite province (AKP) is situated in the north of the Baltic Shield within the buried southeastern portion of the Kola-Kuloi craton. It forms part of the extensive Devonian magmatic event of the northern Baltic Shield and Kola Peninsula. Two main groups of kimberlites can be distinguished within the province: (1) kimberlites from the diamondiferous Zolotitsa field that have geochemical and isotopic affinities with Group 2 kimberlites and lamproites; (2) diamond-poor Ti-Fe-rich kimberlites from other Arkhangelsk fields that have geochemical and isotopic affinities with Group 1 kimberlites. However, the Zolotitsa and Ti-Fe-rich kimberlites have mineralogical characteristics that are not typical for their respective assigned kimberlite group classifications. Both groups of Arkhangelsk kimberlites are apparently transitional to Group 1 kimberlites, Group 2 kimberlites and lamproites as they are defined elsewhere in the world. An associated kimberlite from the Mela Sill Complex has strong affinities with carbonatites. The low Al 2O 3, high Ni and Cr contents, and high Mg# in both groups of kimberlites indicate strongly depleted lherzolitic-harzburgitic mantle sources. Trace element patterns show a variable enrichment of incompatible elements and strong LREE enrichment. However, kimberlites from the Zolotitsa field have overall lower trace element abundances and less steep REE patterns, suggesting a higher degree of partial melt and/or a less enriched source compared to that of the Ti-Fe-rich kimberlites. A calciocarbonatite of the Mela Sill Complex has trace element and REE patterns typical of other carbonatites closely associated with kimberlites. 87Sr/ 86Sri and 143Nd/ 144Ndi isotope compositions of the Arkhangelsk kimberlites and carbonatite reveal that at least two mantle sources are required to explain the isotopic variation: (1) most of the Zolotitsa and Mela kimberlites and the Mela carbonatite are derived from an ancient enriched lithospheric source (EMI); (2) the Ti-Fe-rich kimberlites are derived from a plume-related asthenospheric mantle source with an isotopic composition close to Bulk Earth. Present-day Pb isotope compositions reveal that the Zolotitsa kimberlites have values close to Group 1 kimberlites. However, the Ti-Fe-rich kimberlites generally have slightly more radiogenic Pb isotope values.
Torngat ultramafic lamprophyres and their relation to the North Atlantic Alkaline Province
NASA Astrophysics Data System (ADS)
Tappe, Sebastian; Jenner, George A.; Foley, Stephen F.; Heaman, Larry; Besserer, Dean; Kjarsgaard, Bruce A.; Ryan, Bruce
2004-09-01
Geological mapping and diamond exploration in northern Quebec and Labrador has revealed an undeformed ultramafic dyke swarm in the northern Torngat Mountains. The dyke rocks are dominated by an olivine-phlogopite mineralogy and contain varying amounts of primary carbonate. Their mineralogy, mineral compositional trends and the presence of typomorphic minerals (e.g. kimzeyitic garnet), indicate that these dykes comprise an ultramafic lamprophyre suite grading into carbonatite. Recognized rock varieties are aillikite, mela-aillikite and subordinate carbonatite. Carbonatite and aillikite have in common high carbonate content and a lack of clinopyroxene. In contrast, mela-aillikites are richer in mafic silicate minerals, in particular clinopyroxene and amphibole, and contain only small amounts of primary carbonate. The modal mineralogy and textures of the dyke varieties are gradational, indicating that they represent end-members in a compositional continuum. The Torngat ultramafic lamprophyres are characterized by high but variable MgO (10-25 wt.%), CaO (5-20 wt.%), TiO2 (3-10 wt.%) and K2O (1-4 wt.%), but low SiO2 (22-37 wt.%) and Al2O3 (2-6 wt.%). Higher SiO2, Al2O3, Na2O and lower CO2 content distinguish the mela-aillikites from the aillikites. Whereas the bulk rock major and trace element concentrations of the aillikites and mela-aillikites overlap, there is no fractional crystallization relation between them. The major and trace element characteristics imply related parental magmas, with minor olivine and Cr-spinel fractionation accounting for intra-group variation. The Torngat ultramafic lamprophyres have a Neoproterozoic age and are spatially and compositionally closely related with the Neoproterozoic ultramafic lamprophyres from central West Greenland. Ultramafic potassic-to-carbonatitic magmatism occurred in both eastern Laurentia and western Baltica during the Late Neoproterozoic. It can be inferred from the emplacement ages of the alkaline complexes and timing of Late Proterozoic processes in the North Atlantic region that this volatile-rich, deep-seated igneous activity was a distal effect of the breakup of Rodinia. This occurred during and/or after the rift-to-drift transition that led to the opening of the Iapetus Ocean.
Characterization of Layered Deposits inside Valles Marineris
NASA Technical Reports Server (NTRS)
Weitz, Catherine; Anderson, Scott; Parker, Tim; Grant, John
2005-01-01
This report represents the final progress report on our study of the Melas Chasma region on Mars that was proposed as a landing site for the Mars Exploration Rover mission (MER). During this two-year proposal (which was extended over three years by a no-cost extension), we conducted a thorough study of the layered deposits in western Melas Chasma that had been the location of a high priority MER mission landing ellipse within Valles Marineris. All available data sets from orbiter missions, including MOC, MOLA, THEMIS visible and infrared images were all used to analyze this site. The major outcome of this work was a published paper in the Journal of Geophysics and Research Planets [Weitz et al., 2004]. Our geologic mapping and interpretation of the MOC images suggest the landing ellipse contains three main geomorphologic units: (1) a blocky deposit consisting of bright blocks in a darker matrix (BD); (2) sand sheets composed of dark dunes; and (3) landslide deposits emanating from the wallrock to the west [Weitz et al., 2003]. Furthermore, we propose that the morphology of the BD unit in western Melas is a mass wasting deposit composed of blocks of Interior Layered Deposits (ILDs) mixed in with wallrock material. However, more recent MOC images indicate that in the eastern portion of the ellipse and adjacent to a large hill, there are blocks of material resembling those seen in BD. Hence, we cannot rule out the source of BD was this hill. Unfortunately, sand dunes obscure much of the deposit around this hill, making it impossible to precisely determine the connection between the hill and BD, whereas BD can be traced directly to the southern Melas wallrock. If BD resulted from a mass wasting event in the southern wallrock, then we would expect the material to be concentrated further to the north, as now appears to be the case. In summary, the exact source location for BD continues to remain a mystery, but we favor an origin from either the southern wallrock [Weitz et el., 2002] or the eastern hill.
NASA Technical Reports Server (NTRS)
2002-01-01
This image is a mosaic of day and night infrared images of Melas Chasma taken by the camera system on NASA's Mars Odyssey spacecraft. The daytime temperature images are shown in black and white, superimposed on the martian topography. A single nighttime temperature image is superimposed in color. The daytime temperatures range from approximately -35 degrees Celsius (-31 degrees Fahrenheit) in black to -5 degrees Celsius (23 degrees Fahrenheit) in white. Overlapping landslides and individual layers in the walls of Melas Chasma can be seen in this image. The landslides flowed over 100 kilometers (62 miles) across the floor of Melas Chasma, producing deposits with ridges and grooves of alternating warm and cold materials that can still be seen. The temperature differences in the daytime images are due primarily to lighting effects, where sunlit slopes are warm (bright) and shadowed slopes are cool (dark). The nighttime temperature differences are due to differences in the abundance of rocky materials that retain their heat at night and stay relatively warm (red). Fine grained dust and sand (blue) cools off more rapidly at night. These images were acquired using the thermal infrared imaging system infrared Band 9, centered at 12.6 micrometers.Jet Propulsion Laboratory, a division of the California Institute of Technology in Pasadena, manages the 2001 Mars Odyssey mission for NASA's Office of Space Science in Washington, D.C. Investigators at Arizona State University in Tempe, the University of Arizona in Tucson and NASA's Johnson Space Center, Houston, operate the science instruments. Additional science partners are located at the Russian Aviation and Space Agency and at Los Alamos National Laboratories, New Mexico. Lockheed Martin Astronautics, Denver, is the prime contractor for the project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL. Aviation and Space Agency and at Los Alamos National Laboratories, New Mexico. Lockheed Martin Astronautics, Denver, is the prime contractor for the project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL.NASA Astrophysics Data System (ADS)
Gritsan, Andrei V.; Röntsch, Raoul; Schulze, Markus; Xiao, Meng
2016-09-01
In this paper, we investigate anomalous interactions of the Higgs boson with heavy fermions, employing shapes of kinematic distributions. We study the processes p p →t t ¯+H , b b ¯+H , t q +H , and p p →H →τ+τ- and present applications of event generation, reweighting techniques for fast simulation of anomalous couplings, as well as matrix element techniques for optimal sensitivity. We extend the matrix element likelihood approach (MELA) technique, which proved to be a powerful matrix element tool for Higgs boson discovery and characterization during Run I of the LHC, and implement all analysis tools in the JHU generator framework. A next-to-leading-order QCD description of the p p →t t ¯+H process allows us to investigate the performance of the MELA in the presence of extra radiation. Finally, projections for LHC measurements through the end of Run III are presented.
Sakharova, A V; Kalashnikova, L A; Chaĭkovskaia, R P; Mir-Kasimov, M F; Nazarova, M A; Pykhtina, T N; Dobrynina, L A; Patrusheva, N L; Patrushev, L I; Protskiĭ, S V
2012-01-01
Skin and muscles biopsy specimens of a patient harboring A3243G mutation in mitochondrial DNA, with dissection of internal carotid and vertebral arteries, associated with MELAS were studied using histochemical and electron-microscopy techniques. Ragged red fibers, regional variability of SDH histochemical reaction, two types of morphologically atypical mitochondria and their aggregation were found in muscle. There was correlation between SDH histochemical staining and number of mitochondria revealed by electron microscopy in muscle tissue. Similar mitochondrial abnormality, their distribution and cell lesions followed by extra-cellular matrix mineralization were found in the blood vessel walls. In line with generalization of cytopathy process caused by gene mutation it can be supposed that changes found in skin and muscle microvessels also exist in large cerebral vessels causing the vessel wall "weakness", predisposing them to dissection.
Potential 2001 Landing Sites in Melas Chasma, Mars
NASA Technical Reports Server (NTRS)
Weitz, C. M.; Lucchitta, B. K.; Chapman, M. G.
1999-01-01
We have selected four areas in Valles Marineris as potential landing sites for the 2001 mission. After 20 years of analyses, the formation of the Valles Marineris system of troughs and its associated deposits still has not been sufficiently explained. They could have formed by collapse, as tectonic grabens, or in two stages involving ancestral collapse basins later cut by grabens. Understanding all aspects of the Valles Marineris, in particular the interior layered deposits, would significantly contribute to deciphering the internal and external history of Mars. The deposits have been postulated to be remnants of wall rock, lacustrine deposits, mass wasting deposits, eolian deposits, carbonate deposits, or volcanic deposits. Because an understanding of the formation of Valles Marineris and its interior deposits is so important to deciphering the history of Mars, we have proposed landing sites for the 2001 mission on flat shelves of interior deposits in Melas Chasma.
2017-04-10
In this image from NASA's Mars Reconnaissance Orbiter, a group of steeply inclined light-toned layers is bounded above and below by unconformities (sudden or irregular changes from one deposit to another) that indicate a "break" where erosion of pre-existing layers was taking place at a higher rate than deposition of new materials. The layered deposits in Melas Basin may have been deposited during the growth of a delta complex. This depositional sequence likely represents a period where materials were being deposited on the floor of a lake or running river. The map is projected here at a scale of 25 centimeters (9.8 inches) per pixel. [The original image scale is 28.9 centimeters (11.4 inches) per pixel (with 1 x 1 binning); objects on the order of 87 centimeters (34.2 inches) across are resolved.] North is up. https://photojournal.jpl.nasa.gov/catalog/PIA21580
Bedendo, Giulia; Panzarin, Valentina; Fortin, Andrea; Zamperin, Gianpiero; Pretto, Tobia; Buratin, Alessandra; Quartesan, Rosita; Sabbion, Matteo; Salogni, Cristian; Pascoli, Francesco; Toffan, Anna
2018-07-01
This study fully describes a severe disease outbreak occurred in 2016 in black bullhead catfish farmed in Italy. Affected fish showed nervous clinical signs as well as emaciations and haemorrhagic petechiae on the skin at the fin bases, abdomen and gills. Viral isolation in cell culture allowed the subsequent identification of a rhabdovirus, tentatively named ictalurid rhabdovirus (IcRV), through electron microscopy, immunofluorescence and whole genome sequencing (WGS). The newly isolated virus, together with 14 additional viral strains stored in our repository and detected during similar mortality episodes in the period 1993-2016, was phylogenetically analysed on the basis of the nucleoprotein and the glycoprotein nucleotide and amino acid sequences. The genetic distances among Italian IcRV strains were also estimated. Our results show that all the IcRV strains belong to the genus Sprivivirus and are closely related to the tench rhabdovirus (TenRV). Italian catfish production is constantly decreasing, mainly due to viral infections, which include the newly characterized IcRV. Data presented in this work will assist to investigate the molecular epidemiology and the diffusive dynamics of this virus and to develop adequate surveillance activities. © 2018 The Authors. Journal of Fish Diseases Published by John Wiley & Sons Ltd.
Geologic context of recurring slope lineae in Melas and Coprates Chasmata, Mars
NASA Astrophysics Data System (ADS)
Chojnacki, Matthew; McEwen, Alfred; Dundas, Colin; Ojha, Lujendra; Urso, Anna; Sutton, Sarah
2016-07-01
One of the major Mars discoveries of recent years is the existence of recurring slope lineae (RSL), which suggests that liquid water occurs on or near the surface of Mars today. These dark and narrow features emerge from steep, rocky exposures and incrementally grow, fade, and reform on a seasonal basis and are detected in images from the High Resolution Imaging Science Experiment camera. RSL are known to occur at scattered midlatitude and equatorial sites with little spatial connection to one another. One major exception is the steep, low-albedo slopes of Melas and Coprates Chasmata, in Valles Marineris where RSL are detected among diverse geologic surfaces (e.g., bedrock and talus) and landforms (e.g., inselbergs and landslides). New images show topographic changes including sediment deposition on active RSL slopes. Midwall locations in Coprates and Melas appear to have more areally extensively abundant RSL and related fans as compared with other RSL sites found on Mars. Water budget estimates for regional RSL are on the order of 105 to 106 m3 of fluid, for depths of 10 to 100 mm, and suggest that a significant amount of near-surface water might be present. Many RSL are concentrated near local topographic highs, such as ridge crests or peaks, which is challenging to explain via groundwater or ice without a recharge mechanism. Collectively, results provide additional support for the notion that significant amounts of near-surface water can be found on Mars today and suggest that a widespread mechanism, possibly related to the atmosphere, is recharging RSL sources.
Geologic context of recurring slope lineae in Melas and Coprates Chasmata, Mars
Chojnacki, Matthew; McEwen, Alfred; Dundas, Colin M.; Ojha, Lujendra; Urso, Anna; Sutton, Sarah
2016-01-01
One of the major Mars discoveries of recent years is the existence of recurring slope lineae (RSL), which suggests that liquid water occurs on or near the surface of Mars today. These dark and narrow features emerge from steep, rocky exposures and incrementally grow, fade, and reform on a seasonal basis and are detected in images from the High Resolution Imaging Science Experiment camera. RSL are known to occur at scattered midlatitude and equatorial sites with little spatial connection to one another. One major exception is the steep, low-albedo slopes of Melas and Coprates Chasmata, in Valles Marineris where RSL are detected among diverse geologic surfaces (e.g., bedrock and talus) and landforms (e.g., inselbergs and landslides). New images show topographic changes including sediment deposition on active RSL slopes. Midwall locations in Coprates and Melas appear to have more areally extensively abundant RSL and related fans as compared with other RSL sites found on Mars. Water budget estimates for regional RSL are on the order of 105 to 106 m3 of fluid, for depths of 10 to 100mm, and suggest that a significant amount of near-surface watermight be present. Many RSL are concentrated near local topographic highs, such as ridge crests or peaks, which is challenging to explain via groundwater or ice without a recharge mechanism. Collectively, results provide additional support for the notion that significant amounts of near-surface water can be found on Mars today and suggest that a widespread mechanism, possibly related to the atmosphere, is recharging RSL sources.
2006-03-13
Soaring high above Valles Marineris, the Grand Canyon of Mars, viewers look down and catch a sight resembling parts of the desert West of the United States, but on a vastly greater scale. Here the canyon averages over a hundred miles wide.
Investigating Mars: Candor Chasma
2018-01-16
This VIS image shows part of the border between Chandor and Melas Chasmata. The entire image is landslide deposits. It is very common for landslides to develop linear surface grooves that parallel the direction of flow. Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 17003 Latitude: -8.20616 Longitude: 288.108 Instrument: VIS Captured: 2005-10-14 07:36 https://photojournal.jpl.nasa.gov/catalog/PIA22167
Investigating Mars: Melas Chasma
2017-12-08
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km below the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. This VIS image is located along the northern side of the chasma. The linear features are on the surface of a large landslide. This region of Melas Chasma is covered by several very large landslide deposits. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 36020 Latitude: -9.09641 Longitude: 288.172 Instrument: VIS Captured: 2010-01-27 03:51 https://photojournal.jpl.nasa.gov/catalog/PIA22138
Mariner 9 Anniversary/Landslides on Mars Released 13 November 2002
2002-11-15
This canyon system imaged here by NASA Mars Odyssey was named Valles Marineris in honor of its discoverer, NASA Mariner 9 spacecraft. The image covers a portion of the canyon system called Melas Chasma. http://photojournal.jpl.nasa.gov/catalog/PIA04003
Mitochondrial DNA Sequence Variation in North Atlantic Long-Finned Pilot Whales, Globicephala melas
1994-06-01
Delphinapterus leucas : mitochondrial DNA sequence variation within and among North American populations. M.Sc. thesis. McMaster University. Brown, G.G...Delphinapteras leucas ) (Brennin 1992), minke whales {Balaenoptera acutorostratd) (Wada et al. 1991), bottlenose dolphins {Tursiops truncatus) (Dowling & Brown
Pigmentary retinopathy associated with the mitochondrial DNA 3243 point mutation.
Sue, C M; Mitchell, P; Crimmins, D S; Moshegov, C; Byrne, E; Morris, J G
1997-10-01
Fourteen patients from four unrelated families were studied to determine the prevalence of retinal pigmentary abnormalities associated with the MELAS A to G 3243 point mutation. Neurologic and ophthalmic examinations, retinal photography, pattern shift visual evoked potentials, and electroretinography were performed in all patients. Eight of the 14 patients had retinal pigmentary abnormalities characterized by symmetric areas of depigmentation involving predominantly the posterior pole and midperipheral retina. None of the patients had optic atrophy and only one patient with pigmentary retinal abnormalities had impaired visual acuity. None of the diabetic subjects (n = 6) had signs of diabetic retinopathy. Fluorescein angiography demonstrated mottled hyper- and hypofluorescent areas indicating multiple window defects in the retinal pigmentary epithelium. Visual evoked potentials showed delayed P100 responses in four of the eight patients with retinal pigmentary abnormalities. We conclude that there is a high prevalence of retinal pigmentary abnormalities in patients with MELAS A to G 3243 point mutation. These abnormalities are usually asymptomatic and best detected by retinal photography.
Characterization of MER Landing Sites Using MOC and MOLA
NASA Technical Reports Server (NTRS)
Anderson, F. S.; Parker, T. J.
2002-01-01
The MOC images for MER are compared with MOLA data to characterize and locate each image. MOLA profiles show that Hematite remains benign, Melas and Isidis are rougher, and Athabasca and Gusev have regions of significant small scale topography. Additional information is contained in the original extended abstract.
The effects of pertussis toxin, an uncoupler of Gi protein from adenylate cyclase, and luzindole, a competitive inhibitor of melatonin receptor binding, were examined for their ability to inhibit melatonin-induced suppression of PC12 cell growth. Both agents inhibited the mela...
Effects of Advertising on Advance Selling and Online Search
ERIC Educational Resources Information Center
Joo, Mingyu
2012-01-01
Advertising has been one of the most important marketing variables for both practices and academic literature, and it has been generally known to raise the firm's market share (Ataman, van Heerde, and Mela 2010). However, under the contemporary market environment, advertising's impact may be more complicated. For example, in advance…
Recke, Verena K; Beyrle, Catharina; Gerlitzki, Melanie; Hausmann, Rudolf; Syldatk, Christoph; Wray, Victor; Tokuda, Harukuni; Suzuki, Nobutaka; Lang, Siegmund
2013-05-24
Culturing Pseudozyma aphidis on glucose as main carbon source and soybean oil as co-substrate the mannosylerythritol lipids MEL-A and MEL-B were produced. Based on their excellent surface/interfacial active behavior they possess a high potential among all known biosurfactants. The components of a microbial MEL mixture were purified by medium pressure liquid chromatography (MPLC) and were used as substrates for in vitro enzymatic modifications. Lipase-catalyzed acylations of MEL-A and MEL-B with uncommon fatty acids from other microbial glycolipids-3-hydroxydecanoic acid from rhamnolipids and 17-hydroxyoctadecanoic acid from classical sophorolipids-yielded functionalized products at the C-1 position of the erythritol. The novel products were purified by MPLC and their structures elucidated by (1)H and (13)C nuclear magnetic resonance spectroscopy and mass spectrometry. In physicochemical characterization experiments two of the three new glycoconjugates lowered the surface tension of water from 72 mN m(-1) to 27-38 mN m(-1). Moreover the novel compounds inhibited the growth of gram-positive bacteria and showed a potential for anti-tumor-promoting activity. Copyright © 2013 Elsevier Ltd. All rights reserved.
Mass-gathering Events: The Public Health Challenge of the Kumbh Mela 2013.
Dwivedi, Suresh; Cariappa, Mudera P
2015-12-01
Mass-gathering (MG) events pose challenges to the most adept of public health practitioners in ensuring the health safety of the population. These MGs can be for sporting events, musical festivals, or more commonly, have religious undertones. The Kumbh Mela 2013 at Allahabad, India may have been the largest gathering of humanity in history with nearly 120 million pilgrims having thronged the venue. The scale of the event posed a challenge to the maintenance of public health security and safety. A snapshot of the experience of managing the hygiene and sanitation aspects of this mega event is presented herein, highlighting the importance of proactive public health planning and preparedness. There having been no outbreaks of disease is vindication of the steps undertaken in planning and preparedness, notwithstanding obvious limitations of unsanitary behaviors and traditional beliefs of those attending the festival. The evident flaw on post-event analyses was the failure to cater adequately for environmental mopping-up operations after the festival. Besides, a system of real-time monitoring of disease and morbidity patterns, harnessing low cost technology alternatives, should be planned for at all such future events.
Geib, Elena; Gressler, Markus; Viediernikova, Iuliia; Hillmann, Falk; Jacobsen, Ilse D; Nietzsche, Sandor; Hertweck, Christian; Brock, Matthias
2016-05-19
Melanins are ubiquitous pigments found in all kingdoms of life. Most organisms use them for protection from environmental stress, although some fungi employ melanins as virulence determinants. The human pathogenic fungus Aspergillus fumigatus and related Ascomycetes produce dihydroxynaphthalene- (DHN) melanin in their spores, the conidia, and use it to inhibit phagolysosome acidification. However, biosynthetic origin of melanin in a related fungus, Aspergillus terreus, has remained a mystery because A. terreus lacks genes for synthesis of DHN-melanin. Here we identify genes coding for an unusual NRPS-like enzyme (MelA) and a tyrosinase (TyrP) that A. terreus expressed under conidiation conditions. We demonstrate that MelA produces aspulvinone E, which is activated for polymerization by TyrP. Functional studies reveal that this new pigment, Asp-melanin, confers resistance against UV light and hampers phagocytosis by soil amoeba. Unexpectedly, Asp-melanin does not inhibit acidification of phagolysosomes, thus likely contributing specifically to survival of A. terreus conidia in acidic environments. Copyright © 2016 Elsevier Ltd. All rights reserved.
Investigating Mars: Melas Chasma
2017-12-01
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km below the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. Today's image covers part of the floor of the canyon. At the top of the image is one of the many hills found on the floor in this region. The linear grooved surface is part of a landslide deposit. Melas Chasma has many large landslide regions. Landslide deposits often have grooved surfaces with the grooves parallel to the direction of movement as the slide occurred. The ends of the landslide typically have a lobate edge, and will flow around large preexisting landforms. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 19112 Latitude: -11.1675 Longitude: 289.748 Instrument: VIS Captured: 2006-04-05 23:00 https://photojournal.jpl.nasa.gov/catalog/PIA22132
DOE Office of Scientific and Technical Information (OSTI.GOV)
Helmstetter, M.F.
1992-01-01
The eggs of the Japanese medaka (Oryzias latipes) were employed to develop a routine, standardized assay which can assess the acute and sublethal impacts of individual toxicants and complex mixtures. The eggs of this Cyprinodont minnow were topically treated with each toxicant or mixture dissolved in membrane permeable dimethylsulfoxide (DMSO) solvent. Nine chemicals were initially evaluated with two, pentachlorophenol (PCP) and tributyltin chloride (TBTCl), subsequently selected for extensive evaluations of salinity tolerance and the accuracy of the topical exposure method for representing a typical immersion exposure. The amount of chemical actually penetrating the eggs was determined, as were the optimummore » rearing conditions for the eggs. To determine the usefulness of this assay in field studies, surveys of lower Chesapeake Bay tributary water and sediment samples were performed using the MELA approach. The results indicate that the proposed assay is very useful for the evaluation of the developmental effects of individual toxicants as well as complex mixtures. The salinity tolerance studies indicated that salinity (up to 20ppt for PCP and 35ppt for TBTCl) elicited no significant effect on the toxicity of the two test substances on developing embryos. In addition, if the bioconcentration factor (BCF) is well established for a chemical, it may be possible to extrapolate to an equivalent medium concentration for a given topical dose. The permeability data indicate that the toxicants penetrate into the eggs at levels well correlated to their octanol-water partition coefficients, suggesting passive transport, even in the presence of a membrane permeable carrier. Finally, the field studies demonstrate that the MELA approach is very useful for evaluating the relative toxic/teratogenic potential of numerous site, simultaneously. The data from the MELA treatments often correlated well with other biological assays and with chemical data on a site specific basis.« less
Gupta, Otkrist; Patalano II, Vincent; Mohit, Mrinal; Merchant, Rikin; Subramanian, S V
2018-01-01
Objectives Technology-enabled non-invasive diagnostic screening (TES) using smartphones and other point-of-care medical devices was evaluated in conjunction with conventional routine health screenings for the primary care screening of patients. Design Dental conditions, cardiac ECG arrhythmias, tympanic membrane disorders, blood oxygenation levels, optic nerve disorders and neurological fitness were evaluated using FDA-approved advanced smartphone powered technologies. Routine health screenings were also conducted. A novel remote web platform was developed to allow expert physicians to examine TES data and compare efficacy with routine health screenings. Setting The study was conducted at a primary care centre during the 2015 Kumbh Mela in Maharashtra, India. Participants 494 consenting 18–90 years old adults attending the 2015 Kumbh Mela were tested. Results TES and routine health screenings identified unique clinical conditions in distinct patients. Intraoral fluorescent imaging classified 63.3% of the population with dental caries and periodontal diseases. An association between poor oral health and cardiovascular illnesses was also identified. Tympanic membrane imaging detected eardrum abnormalities in 13.0% of the population, several with a medical history of hearing difficulties. Gait and coordination issues were discovered in eight subjects and one subject had arrhythmia. Cross-correlations were observed between low oxygen saturation and low body mass index (BMI) with smokers (p=0.0087 and p=0.0122, respectively), and high BMI was associated with elevated blood pressure in middle-aged subjects. Conclusions TES synergistically identified clinically significant abnormalities in several subjects who otherwise presented as normal in routine health screenings. Physicians validated TES findings and used routine health screening data and medical history responses for comprehensive diagnoses for at-risk patients. TES identified high prevalence of oral diseases, hypertension, obesity and ophthalmic conditions among the middle-aged and elderly Indian population, calling for public health interventions. PMID:29678964
Risk of Neurological Insult in Competitive Deep Breath-Hold Diving.
Tetzlaff, Kay; Schöppenthau, Holger; Schipke, Jochen D
2017-02-01
It has been widely believed that tissue nitrogen uptake from the lungs during breath-hold diving would be insufficient to cause decompression stress in humans. With competitive free diving, however, diving depths have been ever increasing over the past decades. A case is presented of a competitive free-diving athlete who suffered stroke-like symptoms after surfacing from his last dive of a series of 3 deep breath-hold dives. A literature and Web search was performed to screen for similar cases of subjects with serious neurological symptoms after deep breath-hold dives. A previously healthy 31-y-old athlete experienced right-sided motor weakness and difficulty speaking immediately after surfacing from a breathhold dive to a depth of 100 m. He had performed 2 preceding breath-hold dives to that depth with surface intervals of only 15 min. The presentation of symptoms and neuroimaging findings supported a clinical diagnosis of stroke. Three more cases of neurological insults were retrieved by literature and Web search; in all cases the athletes presented with stroke-like symptoms after single breath-hold dives of depths exceeding 100 m. Two of these cases only had a short delay to recompression treatment and completely recovered from the insult. This report highlights the possibility of neurological insult, eg, stroke, due to cerebral arterial gas embolism as a consequence of decompression stress after deep breath-hold dives. Thus, stroke as a clinical presentation of cerebral arterial gas embolism should be considered another risk of extreme breath-hold diving.
Striatal necrosis in type 1 glutaric aciduria: Different stages in two siblings.
Sen, Anitha; Pillay, Rajesh Subramonia
2011-07-01
Two siblings born of a consanguineous marriage with history of neurologic deterioration were imaged. Imaging features are classical of glutaric aciduria type 1 (GA-1), acute (striatal necrosis) stage in younger sibling, and chronic stage in older sibling. GA-1 is an autosomal recessive disease with typical imaging features. Greater awareness about this condition among clinicians and radiologists is essential for early diagnosis and prevention of its catastrophic consequences. Striatal necrosis with stroke-like signal intensity on imaging correlates with clinical stage of patients.
Striatal necrosis in type 1 glutaric aciduria: Different stages in two siblings
Sen, Anitha; Pillay, Rajesh Subramonia
2011-01-01
Two siblings born of a consanguineous marriage with history of neurologic deterioration were imaged. Imaging features are classical of glutaric aciduria type 1 (GA-1), acute (striatal necrosis) stage in younger sibling, and chronic stage in older sibling. GA-1 is an autosomal recessive disease with typical imaging features. Greater awareness about this condition among clinicians and radiologists is essential for early diagnosis and prevention of its catastrophic consequences. Striatal necrosis with stroke-like signal intensity on imaging correlates with clinical stage of patients. PMID:22408669
Fayssoil, A; Laforêt, P; Bougouin, W; Jardel, C; Lombès, A; Bécane, H M; Berber, N; Stojkovic, T; Béhin, A; Eymard, B; Duboc, D; Wahbi, K
2017-02-01
Our aim was to determine the prognostic value of urine and blood heteroplasmy in patients with the m.3243A>G mutation. Adults with the m.3243A>G mutation referred to our institution between January 2000 and May 2014 were retrospectively included. The relationship between their baseline clinical characteristics, their mutation load in urine and blood, and major adverse events (MAEs) during follow-up, defined as medical complications requiring a hospitalization or complicated by death, was studied. Of the 43 patients (age 45.6 ± 13.3 years) included in the study, 36 patients were symptomatic, including nine with evidence of focal brain involvement, and seven were asymptomatic. Over a 5.5 ± 4.0 year mean follow-up duration, 14 patients (33%) developed MAEs. Patients with MAEs had a higher mutation load than others in urine (60.1% ± 13.8% vs. 40.6% ± 26.2%, P = 0.01) and in blood (26.9% ± 18.4% vs. 16.0% ± 12.1%, P = 0.03). Optimal cutoff values for the prediction of MAEs were 45% for urine and 35% for blood. In multivariate analysis, mutation load in urine ≥45% [odds ratio 25.3; 95% confidence interval (CI) 1.1-567.8; P = 0.04], left ventricular hypertrophy (odds ratio 16.7; 95% CI 1.3- 222.5; P = 0.03) and seizures (odds ratio 48.3; 95% CI 2.5-933; P = 0.01) were associated with MAEs. Patients with the m.3243A>G mutation are at high risk of MAEs, which can be independently predicted by mutation load in urine ≥45%, a personal history of seizures, and left ventricular hypertrophy. © 2016 EAN.
Habitat Suitability Index Models: Black bullhead
Stuber, Robert J.
1982-01-01
The native range of the black bullhead (Ictalurus melas) extends from North Dakota eastward through southern Canada to the upper tributaries of the St. Lawrence River and southward and westward to Texas and northern Mexico (Trautman 1957; Hubbs and Lagler 1958: Scott and Crossman 1973). It has been wide ly introduced throughout temperate North America and parts of Europe (Scott and Crossman 1973; Wheeler 1978).
Fan, Linlin; Li, Hongji; Niu, Yongwu; Chen, Qihe
2016-01-01
Mannosylerythritol lipids (MELs) are natural glycolipid biosurfactants which have potential applications in the fields of food, cosmetic and medicine. In this study, MELs were produced from vegetable oil by Pseudozyma aphidis. Their structural data through LC/MS, GC/MS and NMR analysis revealed that MEL-A with two acetyls was the major compound and the identified homologs of MEL-A contained a length of C8 to C14 fatty acid chains. This glycolipid exhibited a surface tension of 27.69 mN/m at a critical micelle concentration (CMC), self-assembling into particles in the water solution. It was observed to induce cell growth-inhibition and apoptosis of B16 melanoma cells in a dose-dependent manner, as well as cause cell cycle arrest at the S phase. Further quantitative RT-PCR analysis and western blotting revealed an increasing tendency of both mRNA and protein expressions of Caspase-12, CHOP, GRP78 and Caspase-3, and a down-regulation of protein Bcl-2. Combined with the up regulation of signaling IRE1 and ATF6, it can be speculated that MEL-A-induced B16 melanoma cell apoptosis was associated with the endoplasmic reticulum stress (ERS). PMID:26828792
Smith, Adam B; Pacini, Aude F; Nachtigall, Paul E
2018-04-01
Odontocete marine mammals explore the environment by rapidly producing echolocation signals and receiving the corresponding echoes, which likewise return at very rapid rates. Thus, it is important that the auditory system has a high temporal resolution to effectively process and extract relevant information from click echoes. This study used auditory evoked potential methods to investigate auditory temporal resolution of individuals from four different odontocete species, including a spinner dolphin (Stenella longirostris), pygmy killer whale (Feresa attenuata), long-finned pilot whale (Globicephala melas), and Blainville's beaked whale (Mesoplodon densirostris). Each individual had previously stranded and was undergoing rehabilitation. Auditory Brainstem Responses (ABRs) were elicited via acoustic stimuli consisting of a train of broadband tone pulses presented at rates between 300 and 2000 Hz. Similar to other studied species, modulation rate transfer functions (MRTFs) of the studied individuals followed the shape of a low-pass filter, with the ability to process acoustic stimuli at presentation rates up to and exceeding 1250 Hz. Auditory integration times estimated from the bandwidths of the MRTFs ranged between 250 and 333 µs. The results support the hypothesis that high temporal resolution is conserved throughout the diverse range of odontocete species.
Freezing of simple systems using density functional theory
NASA Astrophysics Data System (ADS)
de Kuijper, A.; Vos, W. L.; Barrat, J.-L.; Hansen, J.-P.; Schouten, J. A.
1990-10-01
Density functional theory (DFT) has been applied to the study of the fluid-solid transition in systems with realistic potentials (soft cores and attractive forces): the purely repulsive WCA Lennard-Jones reference potential (LJT), the full Lennard-Jones potential (LJ) and the exponential-6 potential appropriate for helium and hydrogen. Three different DFT formalisms were used: the formulation of Haymet and Oxtoby (HO) and the new theories of Denton and Ashcroft (MWDA) and of Baus (MELA). The results for the melting pressure are compared with recent simulation and experimental data. The results of the HO version are always too high, the deviation increasing when going from the repulsive Lennard-Jones to the exponential-6 potential of H2. The MWDA gives too low results for the repulsive Lennard-Jones potential. At low temperatures, it fails for the full LJ potential while at high temperatures it is in good agreement. Including the attraction as a mean-field correction gives good results also for low temperatures. The MWDA results are too high for the exponential-6 potentials. The MELA fails completely for the LJT potential and the hydrogen exponential-6 potential, since it does not give a stable solid phase.
Grosso, Salvatore; Carluccio, Maria Alessandra; Cardaioli, Elena; Cerase, Alfonso; Malandrini, Alessandro; Romano, Chiara; Federico, Antonio; Dotti, Maria Teresa
2017-03-01
Complex I deficiency is the most common energy generation disorder which may clinically present at any age with a wide spectrum of symptoms and signs. The T10158C mutation ND3 gene is rare and occurs in patients showing an early rapid neurological deterioration invariably leading to death after a few months. We report a 9year-old boy with a mtDNA T10158C mutation showing a mild MELAS-like phenotype and brain MRI features congruent with both MELAS and Leigh syndrome. Epilepsia partialis continua also occurred in the clinical course and related to a mild cortical atrophy of the left perisylvian area. The present case confirms that the clinical spectrum of Complex I deficiency related to T10158C mutation ND3 gene is wider than previously described. Our observation further suggests that testing mutation in the MT-ND3 gene should be included in the diagnostic work-up of patients presenting with epilepsia partialis continua accompanied by suspicion of mitochondrial disorder. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Tappe, Sebastian; Foley, Stephen F.; Kjarsgaard, Bruce A.; Romer, Rolf L.; Heaman, Larry M.; Stracke, Andreas; Jenner, George A.
2008-07-01
New U-Pb perovskite ages reveal that diamondiferous ultramafic lamprophyre magmas erupted through the Archean crust of northern Labrador and Quebec (eastern Canada) between ca. 610 and 565 Ma, a period of strong rifting activity throughout contiguous Laurentia and Baltica. The observed Torngat carbonate-rich aillikite/carbonatite and carbonate-poor mela-aillikite dyke varieties show a large spread in Sr-Nd-Hf-Pb isotope ratios with pronounced correlations between isotope systems. An isotopically depleted component is identified solely within aillikites ( 87Sr/ 86Sr i = 0.70323-0.70377; ɛNd i = +1.2-+1.8; ɛHf i = +1.4-+3.5; 206Pb/ 204Pb i = 18.2-18.5), whereas some aillikites and all mela-aillikites range to more enriched isotope signatures ( 87Sr/ 86Sr i = 0.70388-0.70523; ɛNd i = -0.5 to -3.9; ɛHf i = -0.6 to -6.0; 206Pb/ 204Pb i = 17.8-18.2). These contrasting isotopic characteristics of aillikites/carbonatites and mela-aillikites, along with subtle differences in their modal carbonate, SiO 2, Al 2O 3, Na 2O, Cs-Rb, and Zr-Hf contents, are consistent with two distinctive metasomatic assemblages of different age in the mantle magma source region. Integration of petrologic, geochemical, and isotopic information leads us to propose that the isotopically enriched component originated from a reduced phlogopite-richterite-Ti-oxide dominated source assemblage that is reminiscent of MARID suite xenoliths. In contrast, the isotopically depleted component was derived from a more oxidized phlogopite-carbonate dominated source assemblage. We argue that low-degree CO 2-rich potassic silicate melts from the convective upper mantle were preferentially channelled into an older, pre-existing MARID-type vein network at the base of the North Atlantic craton lithosphere, where they froze to form new phlogopite-carbonate dominated veins. Continued stretching and thinning of the cratonic lithosphere during the Late Neoproterozoic remobilized the carbonate-rich vein material and induced volatile-fluxed fusion of the MARID-type veins and the cold peridotite substrate. Isotopic modelling suggests that only 5-12% trace element contribution from such geochemically extreme MARID-type material is required to produce the observed compositional shift from the isotopically most depleted aillikites/carbonatites towards enriched mela-aillikites. We conclude that cold cratonic mantle lithosphere can host several generations of contrasting vein assemblages, and that each may have formed during past tectonic and magmatic events under distinctively different physicochemical conditions. Although cratonic MARID-type and carbonate-bearing veins in peridotite can be the respective sources for lamproite and carbonatite magmas when present as the sole metasome, their concomitant fusion in a complex source region may give rise to a whole new variety of deep volatile-rich magmas and we suggest that orangeites (formerly Group 2 kimberlites), kamafugites, and certain types of ultramafic lamprophyre are formed in this manner.
1991-03-01
black bullhead (Ictalurus melas), channel catfish (Ictalurus punctatus), and carp (Cvorinus corpio). Aquatic invertebrates that have been collected...in an aquatic medium); "* Bioaccumulation ( concentration from water and from diet ); and * Biomagnification (systematic increase in concentration as...pathway bioaccumulation is estimated by comparing chemical concentrations in soil and diet to chemical concentrations in tissue levels at
Unusual Clinical Presentation and Role of Decompressive Craniectomy in Herpes Simplex Encephalitis.
Singhi, Pratibha; Saini, Arushi Gahlot; Sahu, Jitendra Kumar; Kumar, Nuthan; Vyas, Sameer; Vasishta, Rakesh Kumar; Aggarwal, Ashish
2015-08-01
Decompressive craniectomy in pediatric central nervous infections with refractory intracranial hypertension is less commonly practiced. We describe improved outcome of decompressive craniectomy in a 7-year-old boy with severe herpes simplex encephalitis and medically refractory intracranial hypertension, along with a brief review of the literature. Timely recognition of refractory intracranial hypertension and surgical decompression in children with herpes simplex encephalitis can be life-saving. Additionally, strokelike atypical presentations are being increasingly recognized in children with herpes simplex encephalitis and should not take one away from the underlying herpes simplex encephalitis. © The Author(s) 2014.
Eight Annual Conference on Shock
1985-11-01
D.H. WISNER, J.A. SIUJRI, H.-J. Oestern Dept. of Trauma Surgery, Hannover Medical School, Germany The role of fat embolism syndrome on the development...discussed. Our goal was to elucidate the interactions between a fracture -like bone marrow fat intravasation and a standardized endotoxemia We performed...Supported by NIH GM 32288.) 16 INCREASED OXIDATION OF FAT AND KETONES BY MITOCHONDRIA IN HYPERDYNAMIC SEPSIS. L. Mela-Riker, L. Erwin, D. Bartos, F
Diverse Deposits in Melas Chasma
2015-07-29
This scene captured by NASA Mars Reconnaissance Orbiter includes chaotic deposits with a wide range of colors. The deposits are distinctive with both unique colors and small-scale textures such as fracture patterns. These are probably sedimentary rocks, transported and deposited in water or air. The original layers may have been jumbled in a landslide. Dark or reddish sand dunes cover some of the bedrock. http://photojournal.jpl.nasa.gov/catalog/PIA19860
1989-08-14
colonized specimens are subject to founder effects and thus may not be representative of the variability in natural populations. In order to be cer...An. merus, V-12 Kenya 5 An. merus, Zulu Zululand 4 An. quadriannulatus, Chil. Zimbabwe 5 -14- Table 2. Southern hybridization pattern of IVS fragments...An. arabiensis, Man - - - - + * + * + An. melas, Ba] * + - + + + + - + * + * + An. merus, Zulu * + * + An. merus, V-12 * + - - - - - + *+ An
NASA Technical Reports Server (NTRS)
2005-01-01
[figure removed for brevity, see original site] Context image for PIA03041 Dunes in Darwin Crater The landslide in the center of this image occurred in the Melas Chasma region of Valles Marineris. Image information: VIS instrument. Latitude 11S, Longitude 292.6E. 17 meter/pixel resolution. Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time. NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.Balevi, Ali; Ustuner, Pelin; Özdemir, Mustafa
2017-10-01
Melasma is a distressing condition for both dermatologists and patients. We evaluated the effectiveness of salicylic acid (SA) peel and vitamin C mesotherapy in the treatment of melasma. Fifty female patients were divided into two groups. All patients were treated with 30% SA peel every two weeks for two months. In addition, after SA peeling Group A was intradermally administered 10 vitamin C on the melasma lesion at 1-cm intervals. All patients were followed up for 6 months, during which the recurrence rates were evaluated. Digital photographs of the melasma site were taken and patients' Melasma Area and Severity Index (MASI) scores were assessed. After the treatment, the patients were asked to complete the melasma quality of life questionnaire (MelasQoL) to evaluate their satisfaction with the treatment. All the adverse effects were noted. The MelasQoL and MASI scores of patients in both groups significantly decreased after the treatment. Apart from a burning sensation, no adverse event was observed and all patients tolerated the treatment well. SA peel combined with vitamin C mesotherapy is a safe and effective alternative for the treatment of melasma with no significant side effects and minimal downtime.
Haatanen, Anniina; den Herder, Michael; Leskinen, Pekka; Lindner, Marcus; Kurttila, Mikko; Salminen, Olli
2014-03-15
In this study participatory approaches were used to develop alternative forest resource management scenarios with particular respect to the effects on increased use of forest bioenergy and its effect on biodiversity in Eastern Finland. As technical planning tools, we utilized a forest management planning system (MELA) and the Tool for Sustainability Impact Assessment (ToSIA) to visualize the impacts of the scenarios. We organized a stakeholder workshop where group discussions were used as a participatory method to get the stakeholder preferences and insights concerning forest resource use in the year 2030. Feedback from the workshop was then complemented with a questionnaire. Based on the results of the workshop and a questionnaire we developed three alternative forest resource scenarios: (1) bioenergy 2030 - in which energy production is more centralized and efficient; (2) biodiversity 2030 - in which harvesting methods are more nature friendly and protected forests make up 10% of the total forest area; and (3) mixed bioenergy + biodiversity 2030 scenario - in which wood production, recreation and nature protection are assigned to the most suitable areas. The study showed that stakeholder engagement combined with the MELA and ToSIA tools can be a useful approach in scenario development. Copyright © 2014 Elsevier Ltd. All rights reserved.
A covalently cross-linked gel derived from the epidermis of the pilot whale Globicephala melas.
Baum, C; Fleischer, L-G; Roessner, D; Meyer, W; Siebers, D
2002-01-01
The rheological properties of the stratum corneum of the pilot whale (Globicephala melas) were investigated with emphasis on their significance to the self-cleaning abilities of the skin surface smoothed by a jelly material enriched with various hydrolytic enzymes. The gel formation of the collected fluid was monitored by applying periodic-harmonic oscillating loads using a stress-controlled rheometer. In the mechanical spectrum of the gel, the plateau region of the storage modulus G' (<1200 Pa) and the loss modulus G" (>120 Pa) were independent of frequency (omega = 43.98 to 0.13 rad x s(-1), tau = 15 Pa, T = 20 degrees C), indicating high elastic performance of a covalently cross-linked viscoelastic solid. In addition, multi-angle laser light scattering experiments (MALLS) were performed to analyse the potential time-dependent changes in the weight-average molar mass of the samples. The observed increase showed that the gel formation is based on the assembly of covalently cross-linked aggregates. The viscoelastic properties and the shear resistance of the gel assure that the enzyme-containing jelly material smoothing the skin surface is not removed from the stratum corneum by shear regimes during dolphin jumping. The even skin surface is considered to be most important for the self-cleaning abilities of the dolphin skin against biofouling.
Highly focused anopheline breeding sites and malaria transmission in Dakar
Machault, Vanessa; Gadiaga, Libasse; Vignolles, Cécile; Jarjaval, Fanny; Bouzid, Samia; Sokhna, Cheikh; Lacaux, Jean-Pierre; Trape, Jean-François; Rogier, Christophe; Pagès, Frédéric
2009-01-01
Background Urbanization has a great impact on the composition of the vector system and malaria transmission dynamics. In Dakar, some malaria cases are autochthonous but parasite rates and incidences of clinical malaria attacks have been recorded at low levels. Ecological heterogeneity of malaria transmission was investigated in Dakar, in order to characterize the Anopheles breeding sites in the city and to study the dynamics of larval density and adult aggressiveness in ten characteristically different urban areas. Methods Ten study areas were sampled in Dakar and Pikine. Mosquitoes were collected by human landing collection during four nights in each area (120 person-nights). The Plasmodium falciparum circumsporozoite (CSP) index was measured by ELISA and the entomological inoculation rates (EIR) were calculated. Open water collections in the study areas were monitored weekly for physico-chemical characterization and the presence of anopheline larvae. Adult mosquitoes and hatched larvae were identified morphologically and by molecular methods. Results In September-October 2007, 19,451 adult mosquitoes were caught among which, 1,101 were Anopheles gambiae s.l. The Human Biting Rate ranged from 0.1 bites per person per night in Yoff Village to 43.7 in Almadies. Seven out of 1,101 An. gambiae s.l. were found to be positive for P. falciparum (CSP index = 0.64%). EIR ranged from 0 infected bites per person per year in Yoff Village to 16.8 in Almadies. The An. gambiae complex population was composed of Anopheles arabiensis (94.8%) and Anopheles melas (5.2%). None of the An. melas were infected with P. falciparum. Of the 54 water collection sites monitored, 33 (61.1%) served as anopheline breeding sites on at least one observation. No An. melas was identified among the larval samples. Some physico-chemical characteristics of water bodies were associated with the presence/absence of anopheline larvae and with larval density. A very close parallel between larval and adult densities was found in six of the ten study areas. Conclusion The results provide evidence of malaria transmission in downtown Dakar and its surrounding suburbs. Spatial heterogeneity of human biting rates was very marked and malaria transmission was highly focal. In Dakar, mean figures for transmission would not provide a comprehensive picture of the entomological situation; risk evaluation should therefore be undertaken on a small scale. PMID:19552809
AFRRI (Armed Forces Radiobiology Research Institute) Reports, October, November and December 1987.
1988-03-01
cells (Blakely et al., 1979), mouse BalbC 3T3 cells (Ngo et al., 1981), cells grown in multicellular spheroids (Durand and Olive , 1976), in situ mela...0 radiation. It appeared that an experimental elemental diet was associated with both an enhanced cellular proliferation in the blood-forming tissues...elemental diet for I week before irradiation, and the mean survival time was 59 days. Beginning the diet after irradiation offered no protection. Vitamin E
New Diagnostic Aides for Melanoma
Ferris, Laura K.; Harris, Ryan J.
2012-01-01
Synopsis Detection of melanoma at an early stage is crucial to improving survival rates in melanoma. Accurate diagnosis by current techniques including dermatoscopy remains difficult, and new tools are needed to improve our diagnostic abilities. This article discusses recent advances in diagnostic techniques including confocal scanning laser microscopy, MelaFind, Siascopy, noninvasive genomic detection, as well as other future possibilities to aid in diagnosing melanoma. Advantages and barriers to implementation of the various technologies are discussed as well. PMID:22800557
2014-09-30
responses to biologically relevant ( killer whale and conspecific) and anthropogenic (mid-frequency sonar) sound stimuli that will be analysed in a...Curé, C., Antunes, R., Samarra, F., Alves, A. C., Visser, F., Kvadsheim, P. H. and Miller, P. J. O. (2012). Pilot Whales Attracted to Killer Whale ... Killer (Orcinus orca), Long-Finned Pilot (Globicephala melas), and Sperm (Physeter macrocephalus) Whales to Naval Sonar. Aquatic Mammals 38, 362-401
Furious Frederich: Nietzsche's neurosyphilis diagnosis and new hypotheses.
André, Charles; Rios, André Rangel
2015-12-01
The causes of Friedrich Nietzsche's mental breakdown in early 1889 and of the subsequent slow decay to end-stage dementia along ten years will possibly remain open to debate. The diagnosis of syphilitic dementia paralytica, based only on medical anamnesis and physical examination, was considered indisputable by Otto Binswanger. On the other hand, taking into account recently described diseases, selectively collected evidence lend some support to alternative hypotheses: basal forebrain meningioma, CADASIL, MELAS and frontotemporal dementia.
Kazi, Dhruv S.; Greenough, P. Gregg; Madhok, Rishi; Heerboth, Aaron; Shaikh, Ahmed; Leaning, Jennifer; Balsari, Satchit
2017-01-01
Abstract Background Planning for mass gatherings often includes temporary healthcare systems to address the needs of attendees. However, paper-based record keeping has traditionally precluded the timely application of collected clinical data for epidemic surveillance or optimization of healthcare delivery. We evaluated the feasibility of harnessing ubiquitous mobile technologies for conducting disease surveillance and monitoring resource utilization at the Allahabad Kumbh Mela in India, a 55-day festival attended by over 70 million people. Methods We developed an inexpensive, tablet-based customized disease surveillance system with real-time analytic capabilities, and piloted it at five field hospitals. Results The system captured 49 131 outpatient encounters over the 3-week study period. The most common presenting complaints were musculoskeletal pain (19%), fever (17%), cough (17%), coryza (16%) and diarrhoea (5%). The majority of patients received at least one prescription. The most common prescriptions were for antimicrobials, acetaminophen and non-steroidal anti-inflammatory drugs. There was great inter-site variability in caseload with the busiest hospital seeing 650% more patients than the least busy hospital, despite identical staffing. Conclusions Mobile-based health information solutions developed with a focus on user-centred design can be successfully deployed at mass gatherings in resource-scarce settings to optimize care delivery by providing real-time access to field data. PMID:27694349
Computation-aware algorithm selection approach for interlaced-to-progressive conversion
NASA Astrophysics Data System (ADS)
Park, Sang-Jun; Jeon, Gwanggil; Jeong, Jechang
2010-05-01
We discuss deinterlacing results in a computationally constrained and varied environment. The proposed computation-aware algorithm selection approach (CASA) for fast interlaced to progressive conversion algorithm consists of three methods: the line-averaging (LA) method for plain regions, the modified edge-based line-averaging (MELA) method for medium regions, and the proposed covariance-based adaptive deinterlacing (CAD) method for complex regions. The proposed CASA uses two criteria, mean-squared error (MSE) and CPU time, for assigning the method. We proposed a CAD method. The principle idea of CAD is based on the correspondence between the high and low-resolution covariances. We estimated the local covariance coefficients from an interlaced image using Wiener filtering theory and then used these optimal minimum MSE interpolation coefficients to obtain a deinterlaced image. The CAD method, though more robust than most known methods, was not found to be very fast compared to the others. To alleviate this issue, we proposed an adaptive selection approach using a fast deinterlacing algorithm rather than using only one CAD algorithm. The proposed hybrid approach of switching between the conventional schemes (LA and MELA) and our CAD was proposed to reduce the overall computational load. A reliable condition to be used for switching the schemes was presented after a wide set of initial training processes. The results of computer simulations showed that the proposed methods outperformed a number of methods presented in the literature.
Meter-scale slopes of candidate MER landing sites from point photoclinometry
Beyer, R.A.; McEwen, A.S.; Kirk, R.L.
2003-01-01
Photoclinometry was used to analyze the small-scale roughness of areas that fall within the proposed Mars Exploration Rover (MER) 2003 landing ellipses. The landing ellipses presented in this study were those in Athabasca Valles, Elysium Planitia, Eos Chasma, Gusev Crater, Isidis Planitia, Melas Chasma, and Meridiani Planum. We were able to constrain surface slopes on length scales comparable to the image resolution (1.5 to 12 m/pixel). The MER 2003 mission has various engineering constraints that each candidate landing ellipse must satisfy. These constraints indicate that the statistical slope values at 5 m baselines are an important criterion. We used our technique to constrain maximum surface slopes across large swaths of each image, and built up slope statistics for the images in each landing ellipse. We are confident that all MER 2003 landing site ellipses in this study, with the exception of the Melas Chasma ellipse, are within the small-scale roughness constraints. Our results have provided input into the landing hazard assessment process. In addition to evaluating the safety of the landing sites, our mapping of small-scale roughnesses can also be used to better define and map morphologic units. The morphology of a surface is characterized by the slope distribution and magnitude of slopes. In looking at how slopes are distributed, we can better define landforms and determine the boundaries of morphologic units. Copyright 2003 by the American Geophysical Union.
Fish mortality and physicochemistry in a managed floodplain wetland
Sargent, J.C.; Galat, D.L.
2002-01-01
Patterns of fish mortality and associated physicochemical factors were studied during late spring in a managed wetland canal along the lower Missouri River, Missouri. Mean dawn dissolved oxygen was lower and mean un-ionized ammonia and turbidity were higher during the fish kill than before or after the kill, or than was observed in a nearby wetland canal where no fish kill occurred. Dissolved oxygen at dawn and un-ionized ammonia concentrations were at critically low and high levels respectively, so that both likely contributed to the fish mortality. Timing and magnitude of observed carcasses suggested that Ameiurus melas Rafinesques was the most tolerant species for the sizes observed compared to Ictiobus cyprinellus Valenciennes, Lepomis macrochirus Rafinesque, Cyprinus carpio Linneaus, and Lepomis cyanellus Rafinesque. Decreasing mean lengths of fish carcasses during the fish kill for C. carpio, L. cyanellus, and A. melas, indicate that smaller fishes may have been more tolerant of harsh environmental conditions than larger individuals of the same species. Differential mortalities among species and sizes during drawdowns in actively managed wetland pools may have intentional and unintentional ramifications on wetland and riverine fish community structure, fish-avian interactions, and implementing an ecosystem management perspective to restoring more naturalized river floodplain wetland functions. Late summer and early autumn draining of managed wetlands might be used to benefit a wider diversity of wildlife and fishes.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pourcher, T.; Bassilana, M.; Sarkar, H.K.
1990-01-23
Identification and selective labeling of the melibiose permease and alpha-galactosidase in Escherichia coli, which are encoded by the melB and melA genes, respectively, have been accomplished by selectively labeling the two gene products with a T7 RNA polymerase expression system. Following generation of a novel EcoRI restriction site in the intergenic sequence between the two genes of the mel operon by oligonucleotide-directed, site-specific mutagenesis, melA and melB were separately inserted into plasmid pT7-6 of the T7 expression system. Expression of melB was markedly enhanced by placing a strong, synthetic ribosome binding site at an optimal distance upstream from the initiationmore » codon of melB. Expression of cloned gene products was characterized functionally and by performing autoradiographic analysis on total cell, inner membrane, and cytoplasmic proteins from cells pulse labeled with (35S)methionine in the presence of rifampicin and resolved by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The results first confirm that alpha-galactosidase is a cytoplasmic protein with an Mr of 50K; in contrast, the membrane-bound melibiose permease is identified as a protein with an apparent Mr of 39K, a value significantly higher than that of 30K previously suggested.« less
Kazi, Dhruv S; Greenough, P Gregg; Madhok, Rishi; Heerboth, Aaron; Shaikh, Ahmed; Leaning, Jennifer; Balsari, Satchit
2017-09-01
Planning for mass gatherings often includes temporary healthcare systems to address the needs of attendees. However, paper-based record keeping has traditionally precluded the timely application of collected clinical data for epidemic surveillance or optimization of healthcare delivery. We evaluated the feasibility of harnessing ubiquitous mobile technologies for conducting disease surveillance and monitoring resource utilization at the Allahabad Kumbh Mela in India, a 55-day festival attended by over 70 million people. We developed an inexpensive, tablet-based customized disease surveillance system with real-time analytic capabilities, and piloted it at five field hospitals. The system captured 49 131 outpatient encounters over the 3-week study period. The most common presenting complaints were musculoskeletal pain (19%), fever (17%), cough (17%), coryza (16%) and diarrhoea (5%). The majority of patients received at least one prescription. The most common prescriptions were for antimicrobials, acetaminophen and non-steroidal anti-inflammatory drugs. There was great inter-site variability in caseload with the busiest hospital seeing 650% more patients than the least busy hospital, despite identical staffing. Mobile-based health information solutions developed with a focus on user-centred design can be successfully deployed at mass gatherings in resource-scarce settings to optimize care delivery by providing real-time access to field data. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health.
Udani, Vrajesh; Pujar, Suresh; Munot, Pinki; Maheshwari, Shailendra; Mehta, Nirad
2007-04-01
The natural history of Sturge-Weber Syndrome is variable where some patients have refractory epilepsy and persistent neurologic deficits while others do well. Also, evolution of MRI abnormalities is largely unknown. This long-term follow-up study tries to address these two issues. This retrospective and later prospective study followed 9 children with confirmed SWS. Clinical details of seizures, stroke-like episodes, neurologic and developmental deficits were ascertained specifically. Patients were divided into those with onset below or after 6 months of age for analysis. Disease was classified as active or inactive and correlations were made with the use of aspirin. All past, as well as prospectively acquired imaging was reviewed by two independent blinded neuroradiologists and the images were analysed as ictal (temporally related to seizure/stroke-like event) or interictal. Degree and extent of leptomeningeal enhancement was specifically looked for. Four boys and five girls were followed up for a mean of 6.1 years. Disease activity subsided in 8/9. Early-onset patients had a severe early course with significant residual deficits while late-onset patients did uniformly well. In 6 patients where aspirin was used, a stable course ensued. There was a significant increase in degree/extent of leptomeningeal enhancement during an ictus which returned to the baseline in the interictal state in all 7 patients where both images were available. Focal cerebral atrophy worsened in early-onset cases. In conclusion, SWS patients with onset of seizures/stroke-like events before 6 months of age seem to do worse with a severe early course and persistent neurologic deficits. However the course stabilizes after 5 years of age in most. Late-onset SWS patients have a benign course. Aspirin use is associated with a stable course though further studies are needed. The leptomeningeal enhancement appears to increase during acute events before returning to baseline suggesting that extent of the disease is probably best judged during the interictal state.
2015-10-01
glioblastoma MGMT promoter hypermethylation Abbreviations: BRAVO, Niraparib Versus Physician’s Choice in Her2 Negative, Germline BRCA Mutation-Positive...temozolomide in mela- noma, BC, glioblastoma , and acute leukemia, as well as with signal transduction inhibitors (eg, gefitinib in EGFR-mutant non–small...from both patient-derived xenografts and the ARIEL2 (Assessment of Rucaparib in Ovarian Cancer Phase 2 Trial) trial suggest that an assay using loss
Evidence for ponding and catastrophic floods in central Valles Marineris, Mars
Harrison, K.P.; Chapman, M.G.
2008-01-01
The Valles Marineris canyon system of Mars is closely related to large flood channels, some of which emerge full born from chaotic terrain in canyon floors. Coprates Chasma, one of the largest Valles Marineris canyons, is connected at its west end to Melas Chasma and on its east end to chaotic terrain-filled Capri and Eos Chasmata. The area from central Melas to Eos Chasmata contains a 1500 km long and about 1 km deep depression in its floor. Despite the large volumes of groundwater that likely discharged from chaotic terrain in this depression, no evidence of related fluvial activity has thus far been reported. We present an analysis of the regional topography which, together with photogeologic interpretation of available imagery, suggests that ponding due to late Hesperian discharge of water possibly produced a lake (mean depth 842 m) spanning parts of the Valles Marineris depression (VMD). Overflow of this lake at its eastern end resulted in delivery of water to downstream chaos regions and outflow channels. Our ponding hypothesis is motivated primarily by the identification of scarp and terrace features which, despite a lateral spread of about 1500 km, have similar elevations. Furthermore, these elevations correspond to the maximum ponding elevation of the region (-3560 m). Simulated ponding in the VMD yields an overflow point at its eastern extremity, in Eos Chasma. The neighborhood of this overflow point contains clear indicators of fluvial erosion in a consistent east-west orientation. ?? 2008 Elsevier Inc.
Anopheles gambiae complex (Diptera:Culicidae) near Bissau City, Guinea Bissau, West Africa.
Fonseca, L F; Di Deco, M A; Carrara, G C; Dabo, I; Do Rosario, V; Petrarca, V
1996-11-01
Cytogenetic studies on mosquitoes collected inside bednets near Bissau City confirmed the presence of Anopheles melas Theobald and An. gambiae Giles sensu stricto, the latter species prevailing in rainy season samples (approximately 80% in average) and the former in dry season samples (> 90%). Seasonal and ecogeographical variations in the frequency of species and chromosomal inversions were analyzed. The analysis of An. gambiae sensu stricto confirmed the existence of the Bissau chromosomal form. The deficiency of heterokaryotypes in most samples indicated the possible coexistence of another chromosomal form not completely panmictic (i.e., randomly mating) with the Bissau form.
Hashimoto's encephalopathy : epidemiology, pathogenesis and management.
Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis
2007-01-01
Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.
Pallotti, Francesco; Binelli, Giorgio; Fabbri, Raffaella; Valentino, Maria L.; Vicenti, Rossella; Macciocca, Maria; Cevoli, Sabina; Baruzzi, Agostino; DiMauro, Salvatore; Carelli, Valerio
2014-01-01
Segregation of mutant mtDNA in human tissues and through the germline is debated, with no consensus about the nature and size of the bottleneck hypothesized to explain rapid generational shifts in mutant loads. We investigated two maternal lineages with an apparently different inheritance pattern of the same pathogenic mtDNA 3243A>G/tRNALeu(UUR) (MELAS) mutation. We collected blood cells, muscle biopsies, urinary epithelium and hair follicles from 20 individuals, as well as oocytes and an ovarian biopsy from one female mutation carrier, all belonging to the two maternal lineages to assess mutant mtDNA load, and calculated the theoretical germline bottleneck size (number of segregating units). We also evaluated “mother-to-offspring” segregations from the literature, for which heteroplasmy assessment was available in at least three siblings besides the proband. Our results showed that mutation load was prevalent in skeletal muscle and urinary epithelium, whereas in blood cells there was an inverse correlation with age, as previously reported. The histoenzymatic staining of the ovarian biopsy failed to show any cytochrome-c-oxidase defective oocyte. Analysis of four oocytes and one offspring from the same unaffected mother of the first family showed intermediate heteroplasmic mutant loads (10% to 75%), whereas very skewed loads of mutant mtDNA (0% or 81%) were detected in five offspring of another unaffected mother from the second family. Bottleneck size was 89 segregating units for the first mother and 84 for the second. This was remarkably close to 88, the number of “segregating units” in the “mother-to-offspring” segregations retrieved from literature. In conclusion, a wide range of mutant loads may be found in offspring tissues and oocytes, resulting from a similar theoretical bottleneck size. PMID:24805791
Investigating Mars: Candor Chasma
2018-01-08
Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). This image shows part of western Candor and the erosion of a large mesa. Layered materials are visible throughout the image and small dunes exist in several places. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 4360 Latitude: -6.08522 Longitude: 284.85 Instrument: VIS Captured: 2002-12-08 10:51 https://photojournal.jpl.nasa.gov/catalog/PIA22160
Investigating Mars: Melas Chasma
2017-12-05
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km below the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. Today's image is just a bit further to the west of yesterday's. Here there are no dunes, but extensive outcrops of layered material. It is possible that these layered deposits were formed by sediments settling in a lake. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 4335 Latitude: -10.3718 Longitude: 285.195 Instrument: VIS Captured: 2002-12-06 09:30 https://photojournal.jpl.nasa.gov/catalog/PIA22135
Investigating Mars: Melas Chasma
2017-12-07
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km below the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. This VIS image is located along the northern cliff face of the chasma. The linear features are large landslide surfaces. A region of sand dunes is located along the change in elevation from the cliff face at the top of the image and the floor of the canyon at the bottom of the image. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 31790 Latitude: -10.3951 Longitude: 290.141 Instrument: VIS Captured: 2009-02-12 20:47 https://photojournal.jpl.nasa.gov/catalog/PIA22137
Investigating Mars: Melas Chasma
2017-12-06
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km below the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. This VIS image is located right at the edge of the canyon with the surrounding plains - the flat area at the bottom of the image. Some small landslide deposits are visible originating at the cliff side. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 26762 Latitude: -13.4233 Longitude: 287.973 Instrument: VIS Captured: 2007-12-26 19:46 https://photojournal.jpl.nasa.gov/catalog/PIA22136
Investigating Mars: Melas Chasma
2017-11-28
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km below the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. This VIS image highlights the extent of layered materials within the canyon. The image is located on the mid elevations on the south side of the canyon. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 10813 Latitude: -13.1037 Longitude: 289.967 Instrument: VIS Captured: 2004-05-22 16:09 https://photojournal.jpl.nasa.gov/catalog/PIA22129
Investigating Mars: Melas Chasma
2017-11-30
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km below the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. Today's image of the southern section of the canyon shows a large region of sand dunes. The presence of dunes indicates wind action as the most recent geologic process modifying the canyon. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 18513 Latitude: -12.752 Longitude: 288.597 Instrument: VIS Captured: 2006-02-15 15:24 https://photojournal.jpl.nasa.gov/catalog/PIA22131
Investigating Mars: Melas Chasma
2017-11-29
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km below the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. This VIS image shows part of a large ridge of material near the south central part the canyon. The roughest looking material is the top of the ridge. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 16741 Latitude: -10.6629 Longitude: 285.637 Instrument: VIS Captured: 2005-09-22 17:54 https://photojournal.jpl.nasa.gov/catalog/PIA22130
Investigating Mars: Melas Chasma
2017-12-04
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km below the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. Today's image contains a large region of dunes between the canyon cliff face and the large ridge of material at the mid-elevation of the canyon. Fine materials have been concentrated into the dunes. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 26525 Latitude: -11.3125 Longitude: 285.57 Instrument: VIS Captured: 2007-12-07 07:23 https://photojournal.jpl.nasa.gov/catalog/PIA22134
Investigating Mars: Melas Chasma
2017-11-27
Melas Chasma is part of the largest canyon system on Mars, Valles Marineris. At only 563 km long (349 miles) it is not the longest canyon, but it is the widest. Located in the center of Valles Marineris, it has depths up to 9 km from the surrounding plains, and is the location of many large landslide deposits, as will as layered materials and sand dunes. There is evidence of both water and wind action as modes of formation for many of the interior deposits. This VIS image shows layered materials and sand dunes. The image is located on the mid elevations on the south side of the canyon. The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 10838 Latitude: -12.7865 Longitude: 288.837 Instrument: VIS Captured: 2004-05-24 17:32 https://photojournal.jpl.nasa.gov/catalog/PIA22128
Brautbar, Ariel; Wang, Jing; Abdenur, Jose E; Chang, Richard C; Thomas, Janet A; Grebe, Theresa A; Lim, Cynthia; Weng, Shao-Wen; Graham, Brett H; Wong, Lee-Jun
2008-08-01
The mitochondrial 13513G>A (D393N) mutation in the ND5 subunit of the respiratory chain complex I was initially described in association with MELAS syndrome. Recent observations have linked this mutation to Leigh disease. We screened for the 13513G>A mutation in a cohort of 265 patients with Leigh and Leigh-like disease. The mutation was found in a total of 5 patients. An additional patient who had clinical presentation consistent with a Leigh-like phenotype but with a normal brain MRI was added to the cohort. None of an additional 88 patients meeting MELAS disease criteria, nor 56 patients with respiratory chain deficiency screened for the 13513G>A were found positive for the mutation. The most frequent clinical manifestations in our patients were hypotonia, ocular and cerebellar involvement. Low mutation heteroplasmy in the range of 20-40% was observed in all 6 patients. This observation is consistent with the previously reported low heteroplasmy of this mutation in some patients with the 13513G>A mutation and complex I deficiency. However, normal complex I activity was observed in two patients in our cohort. As most patients with Leigh-like disease and the 13513G>A mutation have been described with complex I deficiency, this report adds to the previously reported subset of patients with normal respiratory complex function. We conclude that in any patient with Leigh or Leigh-like disease, testing for the 13513G>A mutation is clinically relevant and low mutant loads in blood or muscle may be considered pathogenic, in the presence of normal respiratory chain enzyme activities.
Carvalho, Vania M; Osugui, Lika; Setzer, Ariela P; Lopez, Rodrigo P G; Pestana de Castro, Antonio F; Irino, Kinue; Catão-Dias, José L
2012-09-01
Diseases caused by extraintestinal pathogenic Escherichia coli (ExPEC) in wild felids are rarely reported. Although urinary tract infections are infrequently reported in domestic cats, such infections when present are commonly caused by ExPEC. The present work characterized ExPEC strains isolated from 2 adult felines, a snow leopard (Panthera uncia) and a black leopard (Panthera pardus melas), that died from secondary bacteremia associated with urinary tract infections. Isolates from both animals were classified into the B2 phylogenetic group and expressed virulence genotypes that allowed them to cause severe disease. In addition, strains from the black leopard showed multidrug resistance.
ANALYSIS OF BIOMECHANICAL PARAMETERS IN COLONIC ANASTOMOSIS.
Iwanaga, Tiago Cavalcanti; Aguiar, José Lamartine de Andrade; Martins-Filho, Euclides Dias; Kreimer, Flávio; Silva-Filho, Fernando Luiz; Albuquerque, Amanda Vasconcelos de
2016-01-01
The use of measures in colonic anastomoses to prevent dehiscences is of great medical interest. Sugarcane molasses, which has adequate tolerability and compatibility in vivo, has not yet been tested for this purpose. To analyze the biomechanical parameters of colonic suture in rats undergoing colectomy, using sugarcane molasses polysaccharide as tape or gel. 45 Wistar rats (Rattus norvegicus albinus) were randomized into three groups of 15 animals: irrigation of enteric sutures with 0.9% saline solution; application of sugarcane molasses polysaccharide as tape; and sugarcane molasses polysaccharide as gel. The rats underwent colon ressection, with subsequent reanastomosis using polypropylene suture; they were treated according to their respective groups. Five rats from each group were evaluated at different times after the procedure: 30, 90 and 180 days postoperatively. The following variables were evaluated: maximum rupture force, modulus of elasticity and specific deformation of maximum force. The biomechanical variables among the scheduled times and treatment groups were statistically calculated. The characteristics of maximum rupture force and modulus of elasticity of the specimens remained identical, regardless of treatment with saline, polysaccharide gel or tape, and treatment time. However, it was found that the specific deformation of maximum force of the intestinal wall was higher after 180 days in the group treated with sugarcane polysaccharide gel (p=0.09). Compared to control, it was detected greater elasticity of the intestinal wall in mice treated with sugarcane polysaccharide gel, without changing other biomechanical characteristics, regardless of type or time of treatment. A aplicação de produtos em anastomoses colônicas que possam prevenir o surgimento de deiscências são de grande interesse médico. O emprego do polissacarídeo de melaço de cana-de-açúcar (Saccharum officinarum), que possui adequada tolerabilidade e compatibilidade in vivo, ainda não foi testado para este fim. Analisar os parâmetros biomecânicos em suturas colônicas de ratos submetidos à colectomia esquerda após aplicação de fita ou gel do polissacarídeo do melaço da cana-de-açúcar no sítio cirúrgico. Quarenta e cinco ratos (Rattus norvegicus albinus da linhagem Wistar) foram sorteados em três grupos de 15 submetidos a: irrigação das suturas entéricas com soro fisiológico a 0,9%; aplicação de fita de polissacarídeo do melaço da cana-de-açúcar; e aplicação do gel do mesmo melaço. Os ratos foram submetidos à colectomia esquerda com anastomose primária, e tratados segundo os respectivos grupos. Cinco ratos de cada grupo foram avaliados em diferentes tempos após o procedimento: 30º, 90º e 180º dias de pós-operatório. Foram avaliadas as variáveis de força máxima de ruptura, módulo de elasticidade e deformação específica da força máxima. As variáveis biomecânicas entre os tempos de coleta da pesquisa e os grupos de tratamento foram analisados estatisticamente. As características biomecânicas de força máxima de ruptura e o módulo de elasticidade do corpo de prova permaneceram idênticas, independente do tratamento com soro, fita ou gel de polissacarídeo, e do tempo de tratamento. No entanto, foi evidenciada maior deformação específica da força máxima da parede intestinal, aos 180 dias nos ratos tratados com gel de polissacarídeo de cana-de-açúcar. (p=0,09). Em relação ao controle, foi detectada maior elasticidade da parede intestinal nos ratos tratados com gel de polissacarídeo de cana-de-açúcar, sem alteração de outras características biomecânicas, independente do tipo ou tempo de tratamento.
A PAC containing the human mitochondrial DNA polymerase gamma gene (POLG) maps to chromosome 15q25
DOE Office of Scientific and Technical Information (OSTI.GOV)
Walker, R.L.; Meltzer, P.S.; Anziano, P.
The human mitochondrial DNA (mtDNA) is a closed circular, 16,569-bp double-stranded DNA, encoding 13 genes whose protein products are subunits of the oxidative phosphorylation system required for synthesis of most of the ATP consumed by eukaryotic cells. Point mutations of the mtDNA that cause multi-tissue, loss-of-energy syndromes, called mitochondrial encephalomyopathies (e.g., MERRF and MELAS), have been identified. In addition, large-scale deletions of the human mtDNA have been identified and are the molecular bases for the neonatal and adolescent onset loss-of-energy syndromes Pearson and Kearns-Sayer, respectively. 5 refs., 1 fig.
NASA Astrophysics Data System (ADS)
Mesbeh, Radhia; Hamdi, Besma; Zouari, Ridha
2017-01-01
The new organic-inorganic hybrid of the formula [H2mela]Cu2Cl6, where mela = 1,3,5-triazine-2,4,6-triamine, has been synthesized by the reaction of 1,3,5-triazine-2,4,6-triamine and copper(II) chloride dihydrate in the presence of hydrochloric acid. This compound has been determined by X-ray diffraction analysis and characterized by FT-IR, Raman, NMR characterization, differential scanning calorimetric (DSC) analysis, dielectric measurements and Hirshfeld surface. 1,3,5-triazinidium-2,4,6-triamine hexachlorodicuprate(II) crystallizes in the monoclinic system with space group P21/c. The final refinement of the structure of the program led to the reliability factors unweighted R1 = 3.53% and weighted WR2 = 8.87%. The observed internal C3sbnd N31sbnd C1 and C3sbnd N23sbnd C2 angle (121.5 and 121.4°) at protanated N-atom are significantly greater the other ring angle C1sbnd N12sbnd C2 (117.1°). The titled compound crystallizes as an organic-inorganic one-dimensional (1D) structure. The crystal structure was stabilized by two types of hydrogen bonding Nsbnd H⋯Cl and Nsbnd H⋯N. The infrared spectra was recorded in the 4000-400 cm-1 frequency region and the Raman spectra was recorded in the external region of the anionic sublattice vibration 4000-50 cm-1 at room temperature. Solid-state 13C and 63Cu MAS-NMR spectroscopies are in agreement with the X-ray structure. The differential scanning calorimetric (DSC) show the presence of a structural phase transition of the title compound at 338 K. Hirshfeld surface analyses for visually analyzing intermolecular interactions in crystal structures employing molecular surface contours and 2D fingerprint plots have been used to examine molecular shapes.
Investigating Mars: Candor Chasma
2018-01-10
This image shows part of eastern Candor Chasma. At the bottom of the image is the steep cliff between the upper surface elevation and the depths of Candor Chasma. The small lobate feature at the base of the cliff in the bottom of the image is a landslide deposit formed by failure of the cliff face and gravitational downslope movement of the material. Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 8916 Latitude: -7.95016 Longitude: 293.509 Instrument: VIS Captured: 2003-12-18 11:38 https://photojournal.jpl.nasa.gov/catalog/PIA22162
Investigating Mars: Candor Chasma
2018-01-17
The bottom half of this image of central Candor Chasma shows a surface topography called chaos. Chaos is a region of small to medium sized mesas surrounded by valleys that are usually the same elevation. In this image sand and sand dunes are accumulating in the valleys and increasing in depth. Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 18251 Latitude: -6.45589 Longitude: 287.35 Instrument: VIS Captured: 2006-01-25 01:39 https://photojournal.jpl.nasa.gov/catalog/PIA22168
Investigating Mars: Candor Chasma
2018-01-09
This image shows part of western Candor and the erosion of a large mesa. Layered materials are visible throughout the image. The dark material with the linear appearance in the middle of the image are sand dunes. Sand dunes are created by wind action. At the present time, wind is the active process shaping the surface. Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 6245 Latitude: -5.77639 Longitude: 284.339 Instrument: VIS Captured: 2003-05-12 14:49 https://photojournal.jpl.nasa.gov/catalog/PIA22161
Investigating Mars: Candor Chasma
2018-01-18
This image of central Candor Chasma shows a surface topography called chaos. Chaos is a region of small to medium sized mesas surrounded by valleys that are usually the same elevation. In this image sand and sand dunes have accumulated in the valleys near the top of the image, but are not as prevalent towards the bottom of the image. Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 26213 Latitude: -7.25478 Longitude: 287.032 Instrument: VIS Captured: 2007-11-11 14:48 https://photojournal.jpl.nasa.gov/catalog/PIA22169
Grechi, Daniele; Biggeri, Annibale
2016-01-01
On September 2014, a fire began within an oil refinery involving a storage tank containing several hundreds of thousands cubic meters of virgin naphtha. Mayors of neighbouring municipalities asked the Epidemiology and Prevention Society "Giulio A. Maccacaro" to carry out an environmental survey in order to evaluate what was the nature and how dangerous was suspended dust deposited by the fumes. In the following days, after fire had been extinguished we conducted a sample survey on the presence of polycyclic aromatic hydrocarbons (PAH) and metals in particulate deposited on the soil on a radius of five kilometres from the refinery and we engaged the exposed population. The Milazzo-Valle del Mela (Sicily Region, Southern Italy) high-risk area includes several industrial plants; among them, an oil refinery and a fuel powered energy plant. As reference area we selected the Sarroch municipality (Sardinia Region, Southern Italy), in the coast of the Tyrrhenian Sea, which is geographically comparable, where a large oil refinery is located and where an environmental campaign with measurement of PAH and metals in particulate matter was ongoing. Qualitatively, metal composition of particulate matter resulted similar in the Sarroch and Milazzo samples. Instead, a large excess of PAH was documented in the Milazzo samples as compared to the Sarroch ones. In conclusion, the results of the analysis of the samples of particulate matter deposited in the Milazzo area in the days immediately following the oil refinery fire showed a high quantity of PAH, carcinogenic substances which pose major hazard to population health. The greater fall-out was registered in the proximity of the burnt storage tank and the West neighbourhood, and at lesser extent in the Southern neighbourhood. As a consequence, there was a population exposure to carcinogenic substances which could have reached the food chain.
Modeling RNA polymerase interaction in mitochondria of chordates
2012-01-01
Background In previous work, we introduced a concept, a mathematical model and its computer realization that describe the interaction between bacterial and phage type RNA polymerases, protein factors, DNA and RNA secondary structures during transcription, including transcription initiation and termination. The model accurately reproduces changes of gene transcription level observed in polymerase sigma-subunit knockout and heat shock experiments in plant plastids. The corresponding computer program and a user guide are available at http://lab6.iitp.ru/en/rivals. Here we apply the model to the analysis of transcription and (partially) translation processes in the mitochondria of frog, rat and human. Notably, mitochondria possess only phage-type polymerases. We consider the entire mitochondrial genome so that our model allows RNA polymerases to complete more than one circle on the DNA strand. Results Our model of RNA polymerase interaction during transcription initiation and elongation accurately reproduces experimental data obtained for plastids. Moreover, it also reproduces evidence on bulk RNA concentrations and RNA half-lives in the mitochondria of frog, human with or without the MELAS mutation, and rat with normal (euthyroid) or hyposecretion of thyroid hormone (hypothyroid). The transcription characteristics predicted by the model include: (i) the fraction of polymerases terminating at a protein-dependent terminator in both directions (the terminator polarization), (ii) the binding intensities of the regulatory protein factor (mTERF) with the termination site and, (iii) the transcription initiation intensities (initiation frequencies) of all promoters in all five conditions (frog, healthy human, human with MELAS syndrome, healthy rat, and hypothyroid rat with aberrant mtDNA methylation). Using the model, absolute levels of all gene transcription can be inferred from an arbitrary array of the three transcription characteristics, whereas, for selected genes only relative RNA concentrations have been experimentally determined. Conversely, these characteristics and absolute transcription levels can be obtained using relative RNA concentrations and RNA half-lives known from various experimental studies. In this case, the “inverse problem” is solved with multi-objective optimization. Conclusions In this study, we demonstrate that our model accurately reproduces all relevant experimental data available for plant plastids, as well as the mitochondria of chordates. Using experimental data, the model is applied to estimate binding intensities of phage-type RNA polymerases to their promoters as well as predicting terminator characteristics, including polarization. In addition, one can predict characteristics of phage-type RNA polymerases and the transcription process that are difficult to measure directly, e.g., the association between the promoter’s nucleotide composition and the intensity of polymerase binding. To illustrate the application of our model in functional predictions, we propose a possible mechanism for MELAS syndrome development in human involving a decrease of Phe-tRNA, Val-tRNA and rRNA concentrations in the cell. In addition, we describe how changes in methylation patterns of the mTERF binding site and three promoters in hypothyroid rat correlate with changes in intensities of the mTERF binding and transcription initiations. Finally, we introduce an auxiliary model to describe the interaction between polysomal mRNA and ribonucleases. PMID:22873568
Mitochondrial dysfunction in migraine.
Yorns, William R; Hardison, H Huntley
2013-09-01
Migraine is the most frequent type of headache in children. In the 1980s, scientists first hypothesized a connection between migraine and mitochondrial (mt) disorders. More recent studies have suggested that at least some subtypes of migraine may be related to a mt defect. Different types of evidence support a relationship between mitochondria (mt) and migraine: (1) Biochemical evidence: Abnormal mt function translates into high intracellular penetration of Ca(2+), excessive production of free radicals, and deficient oxidative phosphorylation, which ultimately causes energy failure in neurons and astrocytes, thus triggering migraine mechanisms, including spreading depression. The mt markers of these events are low activity of superoxide dismutase, activation of cytochrome-c oxidase and nitric oxide, high levels of lactate and pyruvate, and low ratios of phosphocreatine-inorganic phosphate and N-acetylaspartate-choline. (2) Morphologic evidence: mt abnormalities have been shown in migraine sufferers, the most characteristic ones being direct observation in muscle biopsy of ragged red and cytochrome-c oxidase-negative fibers, accumulation of subsarcolemmal mt, and demonstration of giant mt with paracrystalline inclusions. (3) Genetic evidence: Recent studies have identified specific mutations responsible for migraine susceptibility. However, the investigation of the mtDNA mutations found in classic mt disorders (mt encephalomyopathy with lactic acidosis and stroke-like episodes, myoclonus epilepsy with ragged red fibers, Kearns-Sayre syndrome, and Leber hereditary optic neuropathy) has not demonstrated any association. Recently, 2 common mtDNA polymorphisms (16519C→T and 3010G→A) have been associated with pediatric cyclic vomiting syndrome and migraine. Also, POLG mutations (eg, p.T851 A, p.N468D, p.Y831C, p.G517V, and p.P163S) can cause disease through impaired replication of mtDNA, including migraine. Further studies to investigate the relationship between mtDNA and migraine will require very large sample sizes to obtain statistically significant results. (4) Therapeutic evidence: Several agents that have a positive effect on mt metabolism have shown to be effective in the treatment of migraines. The agents include riboflavin (B2), coenzyme Q10, magnesium, niacin, carnitine, topiramate, and lipoic acid. Further study is warranted to learn how mt interact with other factors to cause migraines. This will facilitate the development of new and more specific treatments that will reduce the frequency or severity or both of this disease. © 2013 Published by Elsevier Inc.
Leiker, T.J.; Rostad, C.E.; Barnes, C.R.; Pereira, W.E.
1991-01-01
Blue catfish, (Ictarurus furcatus), black bullhead catfish, (Ictalurus melas), channel catfish (Ictalurus punctatus), and flathead catfish (Pylodictus olivaris), were collected along a 1200 mile river reach of the Mississippi River and its major tributaries. Tissue samples were extracted and analyzed by fused silica capillary gas chromatography/mass spectrometry (GC/MS) to determine the concentrations of hydrophobic organic halogenated contaminants that have bioconcentrated within the tissues. The compounds identified in the tissue include chlordane, polychlorinated biphenyls (PCBs), DDT and its metabolites along with several other chlorinated pesticides. The data indicates that the southern reach of the river system appears to be more contaminated than the middle and upper reaches of the study area.
Chou, Chung-Hsing; Lin, Jiann-Chyun; Hsueh, Chun-Jen; Peng, Giia-Sheun
2008-09-01
Neuropsychiatric symptoms as the initial presentation of dural arteriovenous fistula (DAVF) are unusual. Anticoagulation therapy may be warranted for prevention of further thromboembolism if an underlying thrombophilia condition is diagnosed. We present a 70-year-old woman with sensory aphasia, who was diagnosed with a DAVF, Cognard type II a + b, by cerebral angiography. Her stroke-like syndrome resolved after transarterial embolization of the left occipital and middle meningeal arteries. Meanwhile, hypercoagulability was found because of hyperhomocysteinemia and the presence of a lupus anticoagulant. One month later, she suffered an acute pulmonary embolism and was started on anticoagulation therapy before stereotactic radiosurgery. Sensory aphasia may be the initial manifestation of a transverse-sigmoid sinus DAVF even if there are no symptoms such as headache or tinnitus. We postulate that early anticoagulation therapy is indicated for preventing thromboembolism in DAVF patients with thrombophilia because the possibility of intracranial bleeding has been reduced by embolization.
2010-01-01
Background This is the second in a series of three articles documenting the geographical distribution of 41 dominant vector species (DVS) of human malaria. The first paper addressed the DVS of the Americas and the third will consider those of the Asian Pacific Region. Here, the DVS of Africa, Europe and the Middle East are discussed. The continent of Africa experiences the bulk of the global malaria burden due in part to the presence of the An. gambiae complex. Anopheles gambiae is one of four DVS within the An. gambiae complex, the others being An. arabiensis and the coastal An. merus and An. melas. There are a further three, highly anthropophilic DVS in Africa, An. funestus, An. moucheti and An. nili. Conversely, across Europe and the Middle East, malaria transmission is low and frequently absent, despite the presence of six DVS. To help control malaria in Africa and the Middle East, or to identify the risk of its re-emergence in Europe, the contemporary distribution and bionomics of the relevant DVS are needed. Results A contemporary database of occurrence data, compiled from the formal literature and other relevant resources, resulted in the collation of information for seven DVS from 44 countries in Africa containing 4234 geo-referenced, independent sites. In Europe and the Middle East, six DVS were identified from 2784 geo-referenced sites across 49 countries. These occurrence data were combined with expert opinion ranges and a suite of environmental and climatic variables of relevance to anopheline ecology to produce predictive distribution maps using the Boosted Regression Tree (BRT) method. Conclusions The predicted geographic extent for the following DVS (or species/suspected species complex*) is provided for Africa: Anopheles (Cellia) arabiensis, An. (Cel.) funestus*, An. (Cel.) gambiae, An. (Cel.) melas, An. (Cel.) merus, An. (Cel.) moucheti and An. (Cel.) nili*, and in the European and Middle Eastern Region: An. (Anopheles) atroparvus, An. (Ano.) labranchiae, An. (Ano.) messeae, An. (Ano.) sacharovi, An. (Cel.) sergentii and An. (Cel.) superpictus*. These maps are presented alongside a bionomics summary for each species relevant to its control. PMID:21129198
Investigating Mars: Candor Chasma
2018-01-15
This THEMIS image shows part of western Candor Chasma. Near the bottom of the image is an impact crater. Impact craters are relatively rare within all the canyons of Valles Marineris. The lack of craters may be due to the relative young age of the canyon system - younger surfaces on Mars have fewer craters than older surfaces. Another factor is that the high rate of erosion and deposition within the canyon erodes the ejecta blanket and fills in the crater, effectively removing the crater over time. Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 16479 Latitude: -5.02282 Longitude: 284.268 Instrument: VIS Captured: 2005-09-01 04:09 https://photojournal.jpl.nasa.gov/catalog/PIA22166
Dry season ecology of Anopheles gambiae complex mosquitoes in The Gambia.
Jawara, Musa; Pinder, Margaret; Drakeley, Chris J; Nwakanma, Davis C; Jallow, Ebrima; Bogh, Claus; Lindsay, Steve W; Conway, David J
2008-08-18
Malaria in The Gambia is highly seasonal, with transmission occurring as Anopheles gambiae s.l. populations expand during and immediately after a single annual rainy season that lasts from June to October. There has been very limited investigation of the ecology of vectors during the dry season, when numbers are very limited and distributions may be restricted. Weekly adult mosquito collections (pyrethrum spray, light trap, and search collections from rooms, as well as light trap collections from animal shelters, abandoned wells and grain stores), and artificial sentinel breeding site surveys were performed in four villages near the upper tidal and partially saline part of the Gambia River in the last four months of an annual dry season (March to June). Mosquito species were identified by morphological and DNA analysis, and ELISA assays were performed to test for Plasmodium falciparum sporozoites and human blood meal components. Adults of An. gambiae s.l. were collected throughout the period, numbers increasing towards the end of the dry season when humidity was increasing. Adult collections were dominated by An. melas (86%), with An. gambiae s.s. (10%) and An. arabiensis (3%) also present throughout. Most females collected in room search and spray collections contained blood meals, but most from light traps were unfed. None of the females tested (n = 1709) contained sporozoites. Larvae (mostly An. gambiae s.s.) were recovered from artificial sentinel breeding sites in the two villages that had freshwater pools. These two villages had the highest proportions of An. gambiae s.s. adults, and experienced the most substantial increase in proportions of An. gambiae s.s. after the onset of rains. During the dry season population minimum, An. melas was the predominant vector species, but differences among villages in availability of fresh-water breeding sites correlate with egg laying activity and relative numbers of An. gambiae s.s. adults, and with the increase in this species immediately after the beginning of the rains. Local variation in dry season vector persistence is thus likely to influence spatial heterogeneity of transmission intensity in the early part of the rainy season.
Carbonatite magmatism in northeast India
NASA Astrophysics Data System (ADS)
Kumar, D.; Mamallan, R.; Dwivedy, K. K.
The Shillong Plateau of northeast India is identified as an alkaline province in view of the development of several carbonatite complexes e.g. the Sung Valley (Jaintia Hills), Jasra (Karbi-Anglong), Samchampi and Barpung (Mikir Hills) and lamprophyre dyke swarms (Swangkre, Garo-Khasi Hills). On the basis of limited KAr data, magmatic activity appears to have taken place over a protracted period, ranging from the Late Jurassic to the Early Cretaceous. The carbonatite complexes of the Shillong Plateau share several common traits: they are emplaced along rift zones, either within Archaean gneisses or Proterozoic metasediments and granites, and exhibit enrichment in the light rare-earth elements, U, Th, Nb, Zr, Ti, K and Na. The enrichment in incompatible trace elements can best be accounted for if the parental magmas were of alkali basaltic type (e.g. mela-nephelinite or carbonate-rich alkali picrite).
Cerebral small vessel disease: Capillary pathways to stroke and cognitive decline
Engedal, Thorbjørn S; Moreton, Fiona; Hansen, Mikkel B; Wardlaw, Joanna M; Dalkara, Turgay; Markus, Hugh S; Muir, Keith W
2015-01-01
Cerebral small vessel disease (SVD) gives rise to one in five strokes worldwide and constitutes a major source of cognitive decline in the elderly. SVD is known to occur in relation to hypertension, diabetes, smoking, radiation therapy and in a range of inherited and genetic disorders, autoimmune disorders, connective tissue disorders, and infections. Until recently, changes in capillary patency and blood viscosity have received little attention in the aetiopathogenesis of SVD and the high risk of subsequent stroke and cognitive decline. Capillary flow patterns were, however, recently shown to limit the extraction efficacy of oxygen in tissue and capillary dysfunction therefore proposed as a source of stroke-like symptoms and neurodegeneration, even in the absence of physical flow-limiting vascular pathology. In this review, we examine whether capillary flow disturbances may be a shared feature of conditions that represent risk factors for SVD. We then discuss aspects of capillary dysfunction that could be prevented or alleviated and therefore might be of general benefit to patients at risk of SVD, stroke or cognitive decline. PMID:26661176
Landscape Evolution Associated with Recurring Slope Lineae (RSL) on Mars
NASA Astrophysics Data System (ADS)
McEwen, A. S.; Dundas, C. M.; Chojnacki, M.; Ojha, L.
2016-12-01
RSL are low-albedo features that initiate at bedrock outcrops and extend down steep slopes. Individual slopes may have hundreds of lineae, with widths up to 5 m and lengths up to 1.5 km. RSL appear and lengthen gradually or incrementally, fade when inactive, and recur each year, normally in the warmest season. Small channels (1-20 m wide) are often present and control RSL paths. We have also detected newly-formed topographic land slumps associated with RSL fans in at least 7 locations—4 around a hill in Juventae Chasma, 2 in Garni crater in Melas Chasma, and 1 along wall slopes in Coprates Chasma. This distinctive landform assemblage is seen at several other locations within central and eastern Valles Marineris (VM): Small channels on most slope aspects of isolated hills or crater walls, extending very nearly to the tops of the hills or crater rim, associated with RSL that match the channels in size, and with a set of lobate deposits at the base of RSL fans. RSL activity in VM changes slope aspect with season—N-facing slopes in northern summer and S-facing slopes in southern summer. The slumps form midway down the RSL fans, and have a different seasonality—most active from Ls 0-120, the coldest time of year in VM. Assuming this association between gullies, RSL, and slumps is not coincidental, an integrated landscape evolution model is needed. Perhaps RSL activity carves the small gullies and deposits sediment near the base of angle-of-repose slopes, locally oversteepening the slope, which episodically slumps. RSL activity is seasonal and associated with the transient presence of hydrated salts, which indicates some role for salty water. If the RSL were caused by fluid flow, they should not be precisely confined to angle-of-repose or steeper slopes (>28 deg.), so these seem to be dry granular flows whose activity is triggered by or somehow associated with small amounts of water. There are multiple mysteries, such as how the activity recurs at the same locations for multiple Mars years, how it is nearly synchronized for many individual flows, how dry granular flows could create channels, and why the slumps happen in the cold season. This set of processes does not have a documented terrestrial analog and may prove important to understanding ancient as well as present-day Mars.
Cambrian nepheline syenite complex at Jabal Sawda, Midyan region, Kingdom of Saudi Arabia
Liddicoat, W.K.; Ramsay, C.R.; Hedge, C.E.
1986-01-01
The only nepheline syenite complex presently known in the Arabian Shield is at Jabal Sawda, about 30 km S of Haql in the extreme NW of Saudi Arabia. It is a post-tectonic, composite intrusion with a crudely concentric structure. A core of leuco-nepheline syenite, a partial ring of mela-nepheline syenite, and an almost complete outer ring of alkali-feldspar syenite are the main rock units. Several mega-inclusions of porphyritic nepheline syenite, nepheline monzosyenite, malignite and ijolite are present in the leuco-nepheline syenite. The chemical composition is notable for very high values of Al2O3, Na2O, Ba, La, Nb, Sr and Zr. U{single bond}Pb isotope dating indicates an emplacement age of 553 ?? 4 Ma, one of an increasing number of reliable Cambrian isotope dates in the northern Red Sea region. ?? 1986.
Cambrian nepheline syenite complex at Jabal Sawda, Midyan region, Kingdom of Saudi Arabia
NASA Astrophysics Data System (ADS)
Liddicoat, W. K.; Ramsay, C. R.; Hedge, C. E.
The only nepheline syenite complex presently known in the Arabian Shield is at Jabal Sawda, about 30 km S of Haql in the extreme NW of Saudi Arabia. It is a post-tectonic, composite intrusion with a crudely concentric structure. A core of leuco-nepheline syenite, a partial ring of mela-nepheline syenite, and an almost complete outer ring of alkali-feldspar syenite are the main rock units. Several mega-inclusions of porphyritic nepheline syenite, nepheline monzosyenite, malignite and ijolite are present in the leuco-nepheline syenite. The chemical composition is notable for very high values of Al 2O 3, Na 2O, Ba, La, Nb, Sr and Zr. U sbnd Pb isotope dating indicates an emplacement age of 553 ± 4 Ma, one of an increasing number of reliable Cambrian isotope dates in the northern Red Sea region.
Cold comfort at the Magh Mela: social identity processes and physical hardship.
Pandey, Kavita; Stevenson, Clifford; Shankar, Shail; Hopkins, Nicholas P; Reicher, Stephen D
2014-12-01
Humans inhabit environments that are both social and physical, and in this article we investigate if and how social identity processes shape the experience and negotiation of physically demanding environmental conditions. Specifically, we consider how severe cold can be interpreted and experienced in relation to group members' social identity. Our data comprise ethnographic observation and semi-structured interviews with pilgrims attending a month-long winter Hindu religious festival that is characterized by near-freezing conditions. The analysis explores (1) how pilgrims appraised the cold and how these appraisals were shaped by their identity as pilgrims; (2) how shared identity with other pilgrims led to forms of mutual support that made it easier to cope with the cold. Our findings therefore extend theorizing on social identity processes to highlight their relevance to physical as well as social conditions. © 2013 The British Psychological Society.
NASA Technical Reports Server (NTRS)
2004-01-01
[figure removed for brevity, see original site]
Released August 11, 2004 This image shows two representations of the same infra-red image over Melas Chasma. On the left is a grayscale image showing surface temperature, and on the right is a false-color composite made from 3 individual THEMIS bands. The false-color image is colorized using a technique called decorrelation stretch (DCS), which emphasizes the spectral differences between the bands to highlight compositional variations. There is a distinct purple/blue layer present in the northern wall of the Chasma. Although this layer likely has a composition different than the surrounding areas, it is difficult to interpret its specific composition due to the high variability of sunlit and shaded surfaces in this area, which cause a wide range of temperatures to be present within each pixel of the image. It is possible that this layer has a unique composition due to differences in the volcanic or sedimentary environment at the time that the rock formed, or it could be a layer of magma injected between two previously existing rock layers. Another possibility is that the wall is mostly covered by dust and debris, and this portion contains the only exposed bedrock. The light blue colors present in many other areas of the Chasma are due to water ice clouds. Image information: IR instrument. Latitude -8.9, Longitude 282 East (78 West). 100 meter/pixel resolution. Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time. NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.Investigating Mars: Candor Chasma
2018-01-11
This image shows part of eastern Candor Chasma. At the top of the image is the steep cliff between the upper surface elevation and the depths of Candor Chasma. The bottom of the image is the cliff side of a large mesa. The two cliff faces have very different appearances. The cliff face between the top of the canyon and the bottom is likely layers of volcanic flows from the nearby Tharsis volcanoes. The mesa, however, is probably layers of sediments deposited in the canyon from wind, water and gravity driven erosion and deposition. These layered materials are much more easily eroded than the solid rock of the canyon sides. Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 9540 Latitude: -6.76471 Longitude: 292.539 Instrument: VIS Captured: 2004-02-07 20:41 https://photojournal.jpl.nasa.gov/catalog/PIA22163
Schacter, Daniel L; Benoit, Roland G; De Brigard, Felipe; Szpunar, Karl K
2015-01-01
This article considers two recent lines of research concerned with the construction of imagined or simulated events that can provide insight into the relationship between memory and decision making. One line of research concerns episodic future thinking, which involves simulating episodes that might occur in one's personal future, and the other concerns episodic counterfactual thinking, which involves simulating episodes that could have happened in one's personal past. We first review neuroimaging studies that have examined the neural underpinnings of episodic future thinking and episodic counterfactual thinking. We argue that these studies have revealed that the two forms of episodic simulation engage a common core network including medial parietal, prefrontal, and temporal regions that also supports episodic memory. We also note that neuroimaging studies have documented neural differences between episodic future thinking and episodic counterfactual thinking, including differences in hippocampal responses. We next consider behavioral studies that have delineated both similarities and differences between the two kinds of episodic simulation. The evidence indicates that episodic future and counterfactual thinking are characterized by similarly reduced levels of specific detail compared with episodic memory, but that the effects of repeatedly imagining a possible experience have sharply contrasting effects on the perceived plausibility of those events during episodic future thinking versus episodic counterfactual thinking. Finally, we conclude by discussing the functional consequences of future and counterfactual simulations for decisions. Copyright © 2013 Elsevier Inc. All rights reserved.
Schacter, Daniel L.; Benoit, Roland G.; De Brigard, Felipe; Szpunar, Karl K.
2014-01-01
This article considers two recent lines of research concerned with the construction of imagined or simulated events that can provide insight into the relationship between memory and decision making. One line of research concerns episodic future thinking, which involves simulating episodes that might occur in one’s personal future, and the other concerns episodic counterfactual thinking, which involves simulating episodes that could have happened in one’s personal past. We first review neuroimaging studies that have examined the neural underpinnings of episodic future thinking and episodic counterfactual thinking. We argue that these studies have revealed that the two forms of episodic simulation engage a common core network including medial parietal, prefrontal, and temporal regions that also supports episodic memory. We also note that neuroimaging studies have documented neural differences between episodic future thinking and episodic counterfactual thinking, including differences in hippocampal responses. We next consider behavioral studies that have delineated both similarities and differences between the two kinds of episodic simulation. The evidence indicates that episodic future and counterfactual thinking are characterized by similarly reduced levels of specific detail compared with episodic memory, but that the effects of repeatedly imagining a possible experience have sharply contrasting effects on the perceived plausibility of those events during episodic future thinking versus episodic counterfactual thinking. Finally, we conclude by discussing the functional consequences of future and counterfactual simulations for decisions. PMID:24373942
Replay of Episodic Memories in the Rat.
Panoz-Brown, Danielle; Iyer, Vishakh; Carey, Lawrence M; Sluka, Christina M; Rajic, Gabriela; Kestenman, Jesse; Gentry, Meredith; Brotheridge, Sydney; Somekh, Isaac; Corbin, Hannah E; Tucker, Kjersten G; Almeida, Bianca; Hex, Severine B; Garcia, Krysten D; Hohmann, Andrea G; Crystal, Jonathon D
2018-05-21
Vivid episodic memories in people have been characterized as the replay of multiple unique events in sequential order [1-3]. The hippocampus plays a critical role in episodic memories in both people and rodents [2, 4-6]. Although rats remember multiple unique episodes [7, 8], it is currently unknown if animals "replay" episodic memories. Therefore, we developed an animal model of episodic memory replay. Here, we show that rats can remember a trial-unique stream of multiple episodes and the order in which these events occurred by engaging hippocampal-dependent episodic memory replay. We document that rats rely on episodic memory replay to remember the order of events rather than relying on non-episodic memories. Replay of episodic memories survives a long retention-interval challenge and interference from the memory of other events, which documents that replay is part of long-term episodic memory. The chemogenetic activating drug clozapine N-oxide (CNO), but not vehicle, reversibly impairs episodic memory replay in rats previously injected bilaterally in the hippocampus with a recombinant viral vector containing an inhibitory designer receptor exclusively activated by a designer drug (DREADD; AAV8-hSyn-hM4Di-mCherry). By contrast, two non-episodic memory assessments are unaffected by CNO, showing selectivity of this hippocampal-dependent impairment. Our approach provides an animal model of episodic memory replay, a process by which the rat searches its representations in episodic memory in sequential order to find information. Our findings using rats suggest that the ability to replay a stream of episodic memories is quite old in the evolutionary timescale. Copyright © 2018 Elsevier Ltd. All rights reserved.
Hyperbaric oxygen treatment for air or gas embolism.
Moon, R E
2014-01-01
Gas can enter arteries (arterial gas embolism) due to alveolar-capillary disruption (caused by pulmonary overpressurization, e.g., breath-hold ascent by divers) or veins (venous gas embolism, VGE) as a result of tissue bubble formation due to decompression (diving, altitude exposure) or during certain surgical procedures where capillary hydrostatic pressure at the incision site is sub-atmospheric. Both AGE and VGE can be caused by iatrogenic gas injection. AGE usually produces strokelike manifestations, such as impaired consciousness, confusion, seizures and focal neurological deficits. Small amounts of VGE are often tolerated due to filtration by pulmonary capillaries. However, VGE can cause pulmonary edema, cardiac "vapor lock" and AGE due to transpulmonary passage or right-to-left shunt through a patent foramen ovale. Intravascular gas can cause arterial obstruction or endothelial damage and secondary vasospasm and capillary leak. Vascular gas is frequently not visible with radiographic imaging, which should not be used to exclude the diagnosis of AGE. Isolated VGE usually requires no treatment; AGE treatment is similar to decompression sickness (DCS), with first aid oxygen then hyperbaric oxygen. Although cerebral AGE (CAGE) often causes intracranial hypertension, animal studies have failed to demonstrate a benefit of induced hypocapnia. An evidence-based review of adjunctive therapies is presented.
42 CFR § 512.100 - EPM episodes being tested.
Code of Federal Regulations, 2010 CFR
2017-10-01
... SERVICES (CONTINUED) HEALTH CARE INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL Episode Payment Model Participants § 512.100 EPM episodes being tested. (a) Initiation of an episode. An episode is... under an EPM anchor MS-DRG and, in the case of the AMI model, with an AMI ICD-10-CM diagnosis code if...
Code of Federal Regulations, 2010 CFR
2017-10-01
... PROGRAMS EPISODE PAYMENT MODEL Pricing and Payment § 512.300 Determination of episode quality-adjusted... historical episode payments. (iii) For the AMI model, quality-adjusted target prices for anchor MS-DRGs 246... 100 percent regional historical episode payments. (iv) For the CABG model, quality-adjusted target...
Episodic and Semantic Memory Contribute to Familiar and Novel Episodic Future Thinking.
Wang, Tong; Yue, Tong; Huang, Xi Ting
2016-01-01
Increasing evidence indicates that episodic future thinking (EFT) relies on both episodic and semantic memory; however, event familiarity may importantly affect the extent to which episodic and semantic memory contribute to EFT. To test this possibility, two behavioral experiments were conducted. In Experiment 1, we directly compared the proportion of episodic and semantic memory used in an EFT task. The results indicated that more episodic memory was used when imagining familiar future events compared with novel future events. Conversely, significantly more semantic memory was used when imagining novel events compared with familiar events. Experiment 2 aimed to verify the results of Experiment 1. In Experiment 2, we found that familiarity moderated the effect of priming the episodic memory system on EFT; particularly, it increased the time required to construct a standard familiar episodic future event, but did not significantly affect novel episodic event reaction time. Collectively, these findings support the hypothesis that event familiarity importantly moderates episodic and semantic memory's contribution to EFT.
Cheng, Yuan; Engling, Guenter; He, Ke-bin; Duan, Feng-kui; Du, Zhen-yu; Ma, Yong-liang; Liang, Lin-lin; Lu, Zi-feng; Liu, Jiu-meng; Zheng, Mei; Weber, Rodney J
2014-02-01
The chemical composition of Beijing aerosol was measured during summer and winter. Two distinct episodes were identified. Water-soluble potassium (K(+)) increased significantly during the firework episode in winter with an episode to non-episode ratio of 4.97, whereas the biomass burning (BB) episode in summer was characterized by high episode to non-episode ratios of levoglucosan (6.38) and K(+) (6.90). The BB and firework episodes had only a minor influence on the water-soluble OC (organic carbon) to OC ratio. Based on separate investigations of episode and non-episode periods, it was found that: (i) sulfate correlated strongly with both relative humidity and nitrate during the typical winter period presumably indicating the importance of the aqueous-phase oxidation of sulfur dioxide by nitrogen dioxide, (ii) oxalate and WSOC during both winter and summer in Beijing were mainly due to secondary formation, and (iii) high humidity can significantly enhance the formation potential of WSOC in winter. Copyright © 2013 Elsevier Ltd. All rights reserved.
Perspectives on Episodic-Like and Episodic Memory
Pause, Bettina M.; Zlomuzica, Armin; Kinugawa, Kiyoka; Mariani, Jean; Pietrowsky, Reinhard; Dere, Ekrem
2013-01-01
Episodic memory refers to the conscious recollection of a personal experience that contains information on what has happened and also where and when it happened. Recollection from episodic memory also implies a kind of first-person subjectivity that has been termed autonoetic consciousness. Episodic memory is extremely sensitive to cerebral aging and neurodegenerative diseases. In Alzheimer’s disease deficits in episodic memory function are among the first cognitive symptoms observed. Furthermore, impaired episodic memory function is also observed in a variety of other neuropsychiatric diseases including dissociative disorders, schizophrenia, and Parkinson disease. Unfortunately, it is quite difficult to induce and measure episodic memories in the laboratory and it is even more difficult to measure it in clinical populations. Presently, the tests used to assess episodic memory function do not comply with even down-sized definitions of episodic-like memory as a memory for what happened, where, and when. They also require sophisticated verbal competences and are difficult to apply to patient populations. In this review, we will summarize the progress made in defining behavioral criteria of episodic-like memory in animals (and humans) as well as the perspectives in developing novel tests of human episodic memory which can also account for phenomenological aspects of episodic memory such as autonoetic awareness. We will also define basic behavioral, procedural, and phenomenological criteria which might be helpful for the development of a valid and reliable clinical test of human episodic memory. PMID:23616754
Wigington, P.J.; DeWalle, David R.; Murdoch, Peter S.; Kretser, W.A.; Simonin, H.A.; Van Sickle, J.; Baker, J.P.
1996-01-01
As part of the Episodic Response Project (ERP), we intensively monitored discharge and stream chemistry of 13 streams located in the Northern Appalachian region of Pennsylvania and in the Catskill and Adirondack Mountains of New York from fall 1988 to spring 1990. The ERP clearly documented the occurrence of acidic episodes with minimum episodic pH ??? 5 and inorganic monomeric Al (Alim) concentrations >150 ??g/L in at least two study streams in each region. Several streams consistently experienced episodes with maximum Alim concentrations >350 ??g/L. Acid neutralizing capacity (ANC) depressions resulted from complex interactions of multiple ions. Base cation decreases often made the most important contributions to ANC depressions during episodes. Organic acid pulses were also important contributors to ANC depressions in the Adirondack streams, and to a lesser extent, in the Catskill and Pennsylvania streams. Nitrate concentrations were low in the Pennsylvania streams, whereas the Catskill and Adirondack study streams had high NO3- concentrations and large episodic pulses (???54 ??eq/L). Most of the Pennsylvania study streams also frequently experienced episodic pulses of SO42- (???78 ??eq/L), whereas the Adirondack and Catskill streams did not. High baseline concentrations of SO42- (all three study areas) and NO3- (Adirondacks and Catskills) reduced episodic minimum ANC, even when these ions did not change during episodes. The ion changes that controlled the most severe episodes (lowest minimum episodic ANC) differed from the ion changes most important to smaller, more frequent episodes. Pulses of NO3- (Catskills and Adirondacks), SO42- (Pennsylvania), or organic acids became more important during major episodes. Overall, the behavior of streamwater SO42- and NO4- is an indicator that acidic deposition has contributed to the severity of episodes in the study streams.
NASA Technical Reports Server (NTRS)
Gkikas, A.; Hatzianastassiou, N.; Mihalopoulos, N.; Torres, O.
2015-01-01
An algorithm able to identify and characterize episodes of different aerosol types above sea surfaces of the greater Mediterranean basin (GMB), including the Black Sea and the Atlantic Ocean off the coasts of Iberia and northwest Africa, is presented in this study. Based on this algorithm, five types of intense (strong and extreme) aerosol episodes in the GMB are identified and characterized using daily aerosol optical properties from satellite measurements, namely MODIS-Terra, Earth Probe (EP)-TOMS and OMIAura. These aerosol episodes are: (i) biomass-burning/urban-industrial (BU), (ii) desert dust (DD), (iii) dust/sea-salt (DSS), (iv) mixed (MX) and (v) undetermined (UN). The identification and characterization is made with our algorithm using a variety of aerosol properties, namely aerosol optical depth (AOD), Angstrom exponent (a), fine fraction (FF), effective radius (reff) and Aerosol Index (AI). During the study period (2000e2007), the most frequent aerosol episodes are DD, observed primarily in the western and central Mediterranean Sea, and off the northern African coasts, 7 times/year for strong episodes and 4 times/year for extreme ones, on average. The DD episodes yield 40% of all types of strong aerosol episodes in the study region, while they account for 71.5% of all extreme episodes. The frequency of occurrence of strong episodes exhibits specific geographical patterns, for example the BU are mostly observed along the coasts of southern Europe and off the Atlantic coasts of Portugal, the MX episodes off the Spanish Mediterranean coast and over the Adriatic and northern Aegean Sea, while the DSS ones over the western and central Mediterranean Sea. On the other hand, the extreme episodes for all but DD aerosol display more patchy spatial patterns. The strong episodes exhibit AOD at 550 nm as high as 1.6 in the southernmost parts of central and eastern Mediterranean Sea, which rise up to 5 for the extreme, mainly DD and DSS, episodes. Although more than 90% of all aerosol episodes last 1 day, there are few cases, mainly extreme DD episodes, which last up to 4 days. Independently of their type, the Mediterranean aerosol episodes occur more frequently in spring (strong and extreme episodes) and summer (strong episodes) and most rarely during winter. A significant year by year variability of Mediterranean aerosol episodes has been identified, more in terms of their frequency than intensity. An analysis of 5-day back trajectories for the most extreme episodes provides confidence on the obtained results of the algorithm, based on the revealed origin and track of air masses causing the episodes. The 25 and 6% of all strong and extreme episodes, respectively, are MX, thus highlighting the co-existence of different aerosol types in the greater Mediterranean. The intensity of both MX and DSS episodes exhibits similar patterns to those of DD strong ones, indicating that desert dust is a determinant factor for the intensity of aerosol episodes in the Mediterranean, including DSS and MX episodes.
Ward, Amanda M
2016-11-01
Episodic future thinking is defined as the ability to mentally simulate a future event. Although episodic future thinking has been studied extensively in neuroscience, this construct has not been explored in depth from the perspective of clinical neuropsychology. The aim of this critical narrative review is to assess the validity and clinical implications of episodic future thinking. A systematic review of episodic future thinking literature was conducted. PubMed and PsycInfo were searched through July 2015 for review and empirical articles with the following search terms: "episodic future thinking," "future mental simulation," "imagining the future," "imagining new experiences," "future mental time travel," "future autobiographical experience," and "prospection." The review discusses evidence that episodic future thinking is important for adaptive functioning, which has implications for neurological populations. To determine the validity of episodic future thinking, the construct is evaluated with respect to related constructs, such as imagination, episodic memory, autobiographical memory, prospective memory, narrative construction, and working memory. Although it has been minimally investigated, there is evidence of convergent and discriminant validity for episodic future thinking. Research has not addressed the incremental validity of episodic future thinking. Practical considerations of episodic future thinking tasks and related constructs in a clinical neuropsychological setting are considered. The utility of episodic future thinking is currently unknown due to the lack of research investigating the validity of episodic future thinking. Future work is discussed, which could determine whether episodic future thinking is an important missing piece in standard clinical neuropsychological assessment. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
Stroke in Saudi children. Epidemiology, clinical features and risk factors.
Salih, Mustafa A; Abdel-Gader, Abdel-Galil M; Al-Jarallah, Ahmed A; Kentab, Amal Y; Alorainy, Ibrahim A; Hassan, Hamdy H; Bahakim, Hassan M; Kurbaan, Khadija M; Zahraa, Jihad N; Al-Nasser, Mohammed N; Nasir, Ali A; Khoja, Waleed A; Kabiraj, Mohammad M
2006-03-01
To describe the epidemiology and clinical features of stroke in a prospective and retrospective cohort of Saudi children and ascertain the causes, pathogenesis, and risk factors. The Retrospective Study Group (RSG) included children with stroke who were evaluated at the Division of Pediatric Neurology, or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia during the period July 1992 to February 2001. The Prospective Study Group (PSG) included those seen between February 2001 and March 2003. During the combined study periods of 10 years and 7 months, 117 children (61 males and 56 females, aged one month-12 years) were evaluated; the majority (89%) of these were Saudis. The calculated annual hospital frequency rate of stroke was 27.1/100,000 of the pediatric (1 month-12 years) population. The mean age at onset of the initial stroke in the 104 Saudi children was 27.1 months (SD = 39.3 months) and median was 6 months. Ischemic strokes accounted for the majority of cases (76%). Large-vessel infarcts (LVI, 51.9%) were more common than small-vessel lacunar lesions (SVLL, 19.2%). Five patients (4.8%) had combined LVI and SVLL. Intracranial hemorrhage was less common (18.2%), whereas sinovenous thrombosis was diagnosed in 6 (5.8%) patients. A major risk factor was identified in 94 of 104 (89.4%) Saudi children. Significantly more hematologic disorders and coagulopathies were identified in the PSG compared to the RSG (p=0.001), reflecting a better yield following introduction of more comprehensive hematologic and coagulation laboratory tests during the prospective study period. Hematologic disorders were the most common risk factor (46.2%), presumed perinatal ischemic cerebral injury was a risk factor in 23 children (22.1%) and infectious and inflammatory disorders of the circulatory system in 18 (17.3%). Congenital and genetic cerebrovascular anomalies were the underlying cause in 7 patients (6.7%) and cardiac diseases in 6 (5.8%). Six patients (5.8%) had moyamoya syndrome, which was associated with another disease in all of them. Inherited metabolic disorders (3.8%) included 3 children with Leigh syndrome and a 29-month-old girl with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Systemic vascular disease was a risk factor in 3 children (2.9%) including 2 who had hypernatremic dehydration; and post-traumatic arterial dissection was causative in 3 cases (2.9%). Several patients had multiple risk factors, whereas no risk factor could be identified in 11 (10.6%). Due to the high prevalence and importance of multiple risk factors, a comprehensive investigation, including hematologic, neuroimaging and metabolic studies should be considered in every child with stroke.
Conway, Martin A
2009-09-01
An account of episodic memories is developed that focuses on the types of knowledge they represent, their properties, and the functions they might serve. It is proposed that episodic memories consist of episodic elements, summary records of experience often in the form of visual images, associated to a conceptual frame that provides a conceptual context. Episodic memories are embedded in a more complex conceptual system in which they can become the basis of autobiographical memories. However, the function of episodic memories is to keep a record of progress with short-term goals and access to most episodic memories is lost soon after their formation. Finally, it is suggested that developmentally episodic memories form the basis of the conceptual system and it is from sets of episodic memories that early non-verbal conceptual knowledge is abstracted.
Candrilli, S D; Meyers, J L; Boye, K; Bae, J P
2015-01-01
To obtain costs of episodes of care for type 2 diabetes mellitus (T2DM)-related comorbidities. Data from the MarketScan Commercial Claims and Encounters Database were analyzed with the Medical Episode Grouper software, which uses proprietary algorithms to identify episodes of care. Episodes relevant to the T2DM population were examined, including: coronary artery disease with acute myocardial infarction, ventricular fibrillation, shock, and/or cardiac arrest (CAD episodes); cerebrovascular disease with stroke (CVD episodes); hypoglycemia; T2DM with complications (complication episodes); and renal failure. 45,350 CAD; 85,287 CVD; 29,886 hypoglycemia; 40,339 complication; and 211,673 renal failure episodes were identified. Mean (SD) episode durations were 15.2 (39.1), 25.5 (55.0), 5.9 (24.0), 21.2 (54.6), and 364.0 (0.0) days, respectively. Inpatient visits were the largest component of unadjusted costs for CAD, CVD, and complication episodes (93.4%, 78.3%, and 91.9%, respectively). Other ancillary care represented the largest component of unadjusted costs for hypoglycemia (53.3%) and renal failure (80.5%) episodes. Mean adjusted total costs were $16,435; $4558; $445; $5675; and $8765 for CAD, CVD, hypoglycemia, complication, and renal failure episodes, respectively. This study adds important information to the literature regarding costs of episodes of care for patients with T2DM in the US. Copyright © 2015 Elsevier Inc. All rights reserved.
Irish, Muireann; Addis, Donna Rose; Hodges, John R; Piguet, Olivier
2012-07-01
Semantic dementia is a progressive neurodegenerative condition characterized by the profound and amodal loss of semantic memory in the context of relatively preserved episodic memory. In contrast, patients with Alzheimer's disease typically display impairments in episodic memory, but with semantic deficits of a much lesser magnitude than in semantic dementia. Our understanding of episodic memory retrieval in these cohorts has greatly increased over the last decade, however, we know relatively little regarding the ability of these patients to imagine and describe possible future events, and whether episodic future thinking is mediated by divergent neural substrates contingent on dementia subtype. Here, we explored episodic future thinking in patients with semantic dementia (n=11) and Alzheimer's disease (n=11), in comparison with healthy control participants (n=10). Participants completed a battery of tests designed to probe episodic and semantic thinking across past and future conditions, as well as standardized tests of episodic and semantic memory. Further, all participants underwent magnetic resonance imaging. Despite their relatively intact episodic retrieval for recent past events, the semantic dementia cohort showed significant impairments for episodic future thinking. In contrast, the group with Alzheimer's disease showed parallel deficits across past and future episodic conditions. Voxel-based morphometry analyses confirmed that atrophy in the left inferior temporal gyrus and bilateral temporal poles, regions strongly implicated in semantic memory, correlated significantly with deficits in episodic future thinking in semantic dementia. Conversely, episodic future thinking performance in Alzheimer's disease correlated with atrophy in regions associated with episodic memory, namely the posterior cingulate, parahippocampal gyrus and frontal pole. These distinct neuroanatomical substrates contingent on dementia group were further qualified by correlational analyses that confirmed the relation between semantic memory deficits and episodic future thinking in semantic dementia, in contrast with the role of episodic memory deficits and episodic future thinking in Alzheimer's disease. Our findings demonstrate that semantic knowledge is critical for the construction of novel future events, providing the necessary scaffolding into which episodic details can be integrated. Further research is necessary to elucidate the precise contribution of semantic memory to future thinking, and to explore how deficits in self-projection manifest on behavioural and social levels in different dementia subtypes.
Episodic Memory and Future Thinking During Early Childhood: Linking the Past and Future
Cuevas, Kimberly; Rajan, Vinaya; Morasch, Katherine C.; Bell, Martha Ann
2015-01-01
Despite extensive examination of episodic memory and future thinking development, little is known about the concurrent emergence of these capacities during early childhood. In Experiment 1, 3-year-olds participated in an episodic memory hiding task [“what, when, where” (WWW) components] with an episodic future thinking component. In Experiment 2, a group of 4-year-olds (including children from Experiment 1) participated in the same task (different objects and locations), providing the first longitudinal investigation of episodic memory and future thinking. Although children exhibited age-related improvements in recall, recognition, and binding of the WWW episodic memory components, there were no age-related changes in episodic future thinking. At both ages, WWW episodic memory performance was higher than future thinking performance, and episodic future thinking and WWW memory components were unrelated. These findings suggest that the WWW components of episodic memory are potentially less fragile than the future components when assessed in a cognitively demanding task. PMID:25864990
Episodic memory and future thinking during early childhood: Linking the past and future.
Cuevas, Kimberly; Rajan, Vinaya; Morasch, Katherine C; Bell, Martha Ann
2015-07-01
Despite extensive examination of episodic memory and future thinking development, little is known about the concurrent emergence of these capacities during early childhood. In Experiment 1, 3-year-olds participated in an episodic memory hiding task ("what, when, where" [WWW] components) with an episodic future thinking component. In Experiment 2, a group of 4-year-olds (including children from Experiment 1) participated in the same task (different objects and locations), providing the first longitudinal investigation of episodic memory and future thinking. Although children exhibited age-related improvements in recall, recognition, and binding of the WWW episodic memory components, there were no age-related changes in episodic future thinking. At both ages, WWW episodic memory performance was higher than future thinking performance, and episodic future thinking and WWW memory components were unrelated. These findings suggest that the WWW components of episodic memory are potentially less fragile than the future components when assessed in a cognitively demanding task. © 2015 Wiley Periodicals, Inc.
Prefrontal and medial temporal contributions to episodic memory-based reasoning.
Suzuki, Chisato; Tsukiura, Takashi; Mochizuki-Kawai, Hiroko; Shigemune, Yayoi; Iijima, Toshio
2009-03-01
Episodic memory retrieval and reasoning are fundamental psychological components of our daily lives. Although previous studies have investigated the brain regions associated with these processes separately, the neural mechanisms of reasoning based on episodic memory retrieval are largely unknown. Here, we investigated the neural correlates underlying episodic memory-based reasoning using functional magnetic resonance imaging (fMRI). During fMRI scanning, subjects performed three tasks: reasoning, episodic memory retrieval, and episodic memory-based reasoning. We identified dissociable activations related to reasoning, episodic memory retrieval, and linking processes between the two. Regions related to reasoning were identified in the left ventral prefrontal cortices (PFC), and those related to episodic memory retrieval were found in the right medial temporal lobe (MTL) regions. In addition, activations predominant in the linking process between the two were found in the left dorsal and right ventral PFC. These findings suggest that episodic memory-based reasoning is composed of at least three processes, i.e., reasoning, episodic memory retrieval, and linking processes between the two, and that activation of both the PFC and MTL is crucial in episodic memory-based reasoning. These findings are the first to demonstrate that PFC and MTL regions contribute differentially to each process in episodic memory-based reasoning.
Hepatitis B & C among farmers - a seroprevalence study.
Garg, Ravinder; Kaur, Shaminder; Aseri, Rakesh; Aggarwal, Simmi; Singh, Jatinder Pal; Mann, Simarpreet; Kumar, Sumit; Kaur, Sarabjot
2014-11-01
Hepatitis B & C are the two major causes of chronic liver disease, having the similar parenteral route of transmission, thereby responsible for significant morbidity and mortality. Agriculture being the backbone of this part of country, the present study was undertaken to assess the seroprevalence of these diseases among the farmers which form the major occupation class in the Malwa belt of Punjab, India. Screening camp was organized at Kisan Mela at the regional station of Punjab Agriculture University at Faridkot, Punjab. Blood samples were collected, and tested for HBsAg and anti-HCV. Total of 1219 subjects, 63% being in the age group of 30-50 years, were screened of which the seroprevalence of HCV & HBV was 5% and 0.32% respectively, and 72% of HCV positive cases were between 30-50 years of age. The study stresses on the need of safe injection practices especially in villages and control on addiction, a more effective vaccination program for HBV, strict check on commercial blood banks, and community education regarding tattooing and sexual behaviour.
Reference results for time-like evolution up to
NASA Astrophysics Data System (ADS)
Bertone, Valerio; Carrazza, Stefano; Nocera, Emanuele R.
2015-03-01
We present high-precision numerical results for time-like Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution in the factorisation scheme, for the first time up to next-to-next-to-leading order accuracy in quantum chromodynamics. First, we scrutinise the analytical expressions of the splitting functions available in the literature, in both x and N space, and check their mutual consistency. Second, we implement time-like evolution in two publicly available, entirely independent and conceptually different numerical codes, in x and N space respectively: the already existing APFEL code, which has been updated with time-like evolution, and the new MELA code, which has been specifically developed to perform the study in this work. Third, by means of a model for fragmentation functions, we provide results for the evolution in different factorisation schemes, for different ratios between renormalisation and factorisation scales and at different final scales. Our results are collected in the format of benchmark tables, which could be used as a reference for global determinations of fragmentation functions in the future.
Laser stereolithography by multilayer sintering of metal powders
NASA Astrophysics Data System (ADS)
Jendrzejewski, Rafal; Serbinski, W.; Sliwinski, Gerard
1997-10-01
Process parameters of the lser stereolithography by means of metal powder sintering are experimentally investigated for the bronze B10, Fe-Cr and Al-Ni alloys, pure Sn, and Cu. The multilaye structures ae prepared trace-on-trace by remelting of the previously deposited mela powder under the cw CO2 laser irradiation in an Ar flow environment. Severl trces of a hiehght of 0.1 - 0.9 mm connected via fusion zones are produced for each samle which results inan efficient formautlion f avolumetric structures of dimensins usfficient for microanalysis ndconsiderationof th emultlayer goemtry. For th beam intensities of about 105 W/cm2 and smaple feeding rates of 0.8 - 1.8 m/min th fusin zone thickness donot 4xceed several percent of th layer height. Rsutls indicate, that th epowderized Fe-Cr anAl-Ni alloys and also bronze B10 are well suited for a fast prorotyping due to th low porosity, homogeneous structure and good mechaniclpropetis acheivable.
High Performance Fe- and N- Doped Carbon Catalyst with Graphene Structure for Oxygen Reduction
NASA Astrophysics Data System (ADS)
Peng, Hongliang; Mo, Zaiyong; Liao, Shijun; Liang, Huagen; Yang, Lijun; Luo, Fan; Song, Huiyu; Zhong, Yiliang; Zhang, Bingqing
2013-05-01
Proton exchange membrane fuel cells are promising candidates for a clean and efficient energy conversion in the future, the development of carbon based inexpensive non-precious metal ORR catalyst has becoming one of the most attractive topics in fuel cell field. Herein we report a Fe- and N- doped carbon catalyst Fe-PANI/C-Mela with graphene structure and the surface area up to 702 m2 g-1. In 0.1 M HClO4 electrolyte, the ORR onset potential for the catalyst is high up to 0.98 V, and the half-wave potential is only 60 mV less than that of the Pt/C catalyst (Loadings: 51 μg Pt cm-2). The catalyst shows high stability after 10,000 cyclic voltammetry cycles. A membrane electrode assembly made with the catalyst as a cathode is tested in a H2-air single cell, the maximum power density reached ~0.33 W cm2 at 0.47 V.
Episode-Centered Guidelines for Teacher Belief Change toward Technology Integration
ERIC Educational Resources Information Center
Er, Erkan; Kim, ChanMin
2017-01-01
Teachers' episodic memories influence their beliefs. The investigation of episodic memories can help identify the teacher beliefs that limit technology-integration. We propose the Episode-Centered Belief Change (ECBC) model that utilizes teachers' episodic memories for changing beliefs impeding effective technology integration. We also propose…
How do episodic and semantic memory contribute to episodic foresight in young children?
Martin-Ordas, Gema; Atance, Cristina M; Caza, Julian S
2014-01-01
Humans are able to transcend the present and mentally travel to another time, place, or perspective. Mentally projecting ourselves backwards (i.e., episodic memory) or forwards (i.e., episodic foresight) in time are crucial characteristics of the human memory system. Indeed, over the past few years, episodic memory has been argued to be involved both in our capacity to retrieve our personal past experiences and in our ability to imagine and foresee future scenarios. However, recent theory and findings suggest that semantic memory also plays a significant role in imagining future scenarios. We draw on Tulving's definition of episodic and semantic memory to provide a critical analysis of their role in episodic foresight tasks described in the developmental literature. We conclude by suggesting future directions of research that could further our understanding of how both episodic memory and semantic memory are intimately connected to episodic foresight.
How do episodic and semantic memory contribute to episodic foresight in young children?
Martin-Ordas, Gema; Atance, Cristina M.; Caza, Julian S.
2014-01-01
Humans are able to transcend the present and mentally travel to another time, place, or perspective. Mentally projecting ourselves backwards (i.e., episodic memory) or forwards (i.e., episodic foresight) in time are crucial characteristics of the human memory system. Indeed, over the past few years, episodic memory has been argued to be involved both in our capacity to retrieve our personal past experiences and in our ability to imagine and foresee future scenarios. However, recent theory and findings suggest that semantic memory also plays a significant role in imagining future scenarios. We draw on Tulving’s definition of episodic and semantic memory to provide a critical analysis of their role in episodic foresight tasks described in the developmental literature. We conclude by suggesting future directions of research that could further our understanding of how both episodic memory and semantic memory are intimately connected to episodic foresight. PMID:25071690
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lü, Hou-Jun; Lü, Jing; Zhong, Shu-Qing
GRB 160625B is an extremely bright GRB with three distinct emission episodes. By analyzing its data observed with the Gamma-Ray Burst Monitor (GBM) and Large Area Telescope (LAT) on board the Fermi mission, we find that a multicolor blackbody (mBB) model can be used to fit very well the spectra of the initial short episode (Episode I) within the hypothesis of photosphere emission of a fireball model. The time-resolved spectra of its main episode (Episode II), which was detected with both GBM and LAT after a long quiescent stage (∼180 s) following the initial episode, can be fitted with amore » model comprising an mBB component plus a cutoff power-law (CPL) component. This GRB was detected again in the GBM and LAT bands with a long extended emission (Episode III) after a quiescent period of ∼300 s. The spectrum of Episode III is adequately fitted with CPL plus single power-law models, and no mBB component is required. These features may imply that the emission of the three episodes are dominated by distinct physics processes, i.e., Episode I is possible from the cocoon emission surrounding the relativistic jet, Episode II may be from photosphere emission and internal shock of the relativistic jet, and Episode III is contributed by internal and external shocks of the relativistic jet. On the other hand, both X-ray and optical afterglows are consistent with the standard external shocks model.« less
NASA Astrophysics Data System (ADS)
Lü, Hou-Jun; Lü, Jing; Zhong, Shu-Qing; Huang, Xiao-Li; Zhang, Hai-Ming; Lan, Lin; Xie, Wei; Lu, Rui-Jing; Liang, En-Wei
2017-11-01
GRB 160625B is an extremely bright GRB with three distinct emission episodes. By analyzing its data observed with the Gamma-Ray Burst Monitor (GBM) and Large Area Telescope (LAT) on board the Fermi mission, we find that a multicolor blackbody (mBB) model can be used to fit very well the spectra of the initial short episode (Episode I) within the hypothesis of photosphere emission of a fireball model. The time-resolved spectra of its main episode (Episode II), which was detected with both GBM and LAT after a long quiescent stage (˜180 s) following the initial episode, can be fitted with a model comprising an mBB component plus a cutoff power-law (CPL) component. This GRB was detected again in the GBM and LAT bands with a long extended emission (Episode III) after a quiescent period of ˜300 s. The spectrum of Episode III is adequately fitted with CPL plus single power-law models, and no mBB component is required. These features may imply that the emission of the three episodes are dominated by distinct physics processes, I.e., Episode I is possible from the cocoon emission surrounding the relativistic jet, Episode II may be from photosphere emission and internal shock of the relativistic jet, and Episode III is contributed by internal and external shocks of the relativistic jet. On the other hand, both X-ray and optical afterglows are consistent with the standard external shocks model.
Willoughby, Karen A.; Desrocher, Mary; Levine, Brian; Rovet, Joanne F.
2012-01-01
Few studies have examined both episodic and semantic autobiographical memory (AM) performance during late childhood and early adolescence. Using the newly developed Children’s Autobiographical Interview (CAI), the present study examined the effects of age and sex on episodic and semantic AM and everyday memory in 182 children and adolescents. Results indicated that episodic and semantic AM both improved between 8 and 16 years of age; however, age-related changes were larger for episodic AM than for semantic AM. In addition, females were found to recall more episodic AM details, but not more semantic AM details, than males. Importantly, this sex difference in episodic AM recall was attenuated under conditions of high retrieval support (i.e., the use of probing questions). The ability to clearly visualize past events at the time of recollection was related to children’s episodic AM recall performance, particularly the retrieval of perceptual details. Finally, similar age and sex effects were found between episodic AM and everyday memory ability (e.g., memory for everyday activities). More specifically, older participants and females exhibited better episodic AM and everyday memory performance than younger participants and males. Overall, the present study provides important new insight into both episodic and semantic AM performance, as well as the relation between episodic AM and everyday memory, during late childhood and adolescence. PMID:22403560
Willoughby, Karen A; Desrocher, Mary; Levine, Brian; Rovet, Joanne F
2012-01-01
Few studies have examined both episodic and semantic autobiographical memory (AM) performance during late childhood and early adolescence. Using the newly developed Children's Autobiographical Interview (CAI), the present study examined the effects of age and sex on episodic and semantic AM and everyday memory in 182 children and adolescents. Results indicated that episodic and semantic AM both improved between 8 and 16 years of age; however, age-related changes were larger for episodic AM than for semantic AM. In addition, females were found to recall more episodic AM details, but not more semantic AM details, than males. Importantly, this sex difference in episodic AM recall was attenuated under conditions of high retrieval support (i.e., the use of probing questions). The ability to clearly visualize past events at the time of recollection was related to children's episodic AM recall performance, particularly the retrieval of perceptual details. Finally, similar age and sex effects were found between episodic AM and everyday memory ability (e.g., memory for everyday activities). More specifically, older participants and females exhibited better episodic AM and everyday memory performance than younger participants and males. Overall, the present study provides important new insight into both episodic and semantic AM performance, as well as the relation between episodic AM and everyday memory, during late childhood and adolescence.
ERIC Educational Resources Information Center
Zion-Golumbic, Elana; Kutas, Marta; Bentin, Shlomo
2010-01-01
Prior semantic knowledge facilitates episodic recognition memory for faces. To examine the neural manifestation of the interplay between semantic and episodic memory, we investigated neuroelectric dynamics during the creation (study) and the retrieval (test) of episodic memories for famous and nonfamous faces. Episodic memory effects were evident…
Episodic foresight deficits in regular, but not recreational, cannabis users.
Mercuri, Kimberly; Terrett, Gill; Henry, Julie D; Curran, H Valerie; Elliott, Morgan; Rendell, Peter G
2018-06-01
Cannabis use is associated with a range of neurocognitive deficits, including impaired episodic memory. However, no study to date has assessed whether these difficulties extend to episodic foresight, a core component of which is the ability to mentally travel into one's personal future. This is a particularly surprising omission given that episodic memory is considered to be critical to engage episodic foresight. In the present study, we provide the first test of how episodic foresight is affected in the context of differing levels of cannabis use, and the degree to which performance on a measure of this construct is related to episodic memory. Fifty-seven regular cannabis users (23 recreational, 34 regular) and 57 controls were assessed using an adapted version of the Autobiographical Interview. The results showed that regular-users exhibited greater impairment of episodic foresight and episodic memory than both recreational-users and cannabis-naïve controls. These data therefore show for the first time that cannabis-related disruption of cognitive functioning extends to the capacity for episodic foresight, and they are discussed in relation to their potential implications for functional outcomes in this group.
The evolution of episodic memory
Allen, Timothy A.; Fortin, Norbert J.
2013-01-01
One prominent view holds that episodic memory emerged recently in humans and lacks a “(neo)Darwinian evolution” [Tulving E (2002) Annu Rev Psychol 53:1–25]. Here, we review evidence supporting the alternative perspective that episodic memory has a long evolutionary history. We show that fundamental features of episodic memory capacity are present in mammals and birds and that the major brain regions responsible for episodic memory in humans have anatomical and functional homologs in other species. We propose that episodic memory capacity depends on a fundamental neural circuit that is similar across mammalian and avian species, suggesting that protoepisodic memory systems exist across amniotes and, possibly, all vertebrates. The implication is that episodic memory in diverse species may primarily be due to a shared underlying neural ancestry, rather than the result of evolutionary convergence. We also discuss potential advantages that episodic memory may offer, as well as species-specific divergences that have developed on top of the fundamental episodic memory architecture. We conclude by identifying possible time points for the emergence of episodic memory in evolution, to help guide further research in this area. PMID:23754432
Ellimoottil, Chad; Ryan, Andrew M; Hou, Hechuan; Dupree, James M; Hallstrom, Brian; Miller, David C
2017-01-01
Under the Comprehensive Care for Joint Replacement (CJR) model, hospitals are held accountable for nearly all Medicare payments that occur during the initial hospitalization until 90 days after hospital discharge (ie, the episode of care). It is not known whether unrelated expenditures resulting from this "broad" definition of an episode of care will affect participating hospitals' average episode-of-care payments. To compare the CJR program's broad definition of an episode of care with a clinically narrow definition of an episode of care. We identified Medicare claims for 23 251 patients in Michigan who were Medicare beneficiaries and who underwent joint replacement during the period from 2011 through 2013 at hospitals located in metropolitan statistical areas. Using specifications from the CJR model and the clinically narrow Hospital Compare payment measure, we constructed episodes of care and calculated 90-day episode payments. We then compared hospitals' average 90-day episode payments using the 2 definitions of an episode of care and fit linear regression models to understand whether payment differences were associated with specific hospital characteristics (average Centers for Medicare & Medicaid Services-hierarchical condition categories risk score, rural hospital status, joint replacement volume, percentage of Medicaid discharges, teaching hospital status, number of beds, percentage of joint replacements performed on African American patients, and median income of the hospital's county). We performed analyses from July 1 through October 1, 2015. The correlation and difference between average 90-day episode payments using the broad definition of an episode of care in the CJR model and the clinically narrow Hospital Compare definition of an episode of care. We identified 23 251 joint replacements (ie, episodes of care). The 90-day episode payments using the broad definition of the CJR model ranged from $17 349 to $29 465 (mean [SD] payment, $22 122 [$2600]). Episode payments were slightly lower (mean payment, $21 670) when the Hospital Compare definition was used. Both methods were strongly correlated (r = 0.99, P < .001). The average payment difference between these 2 types of episodes of care was small (mean [SD], $452 [$177]; range, $73-$1006). In our multivariable analysis, we found that the hospital characteristics examined had a minimal impact or no impact on the payment differential. The average 90-day episode payments determined by both definitions of an episode of care were strongly correlated, and there was a small payment differential for most hospitals. In the context of joint replacement bundled payments, these data suggest that hospital performance will be consistent whether a broad or clinically narrow definition of an episode of care is used.
Are all judgments created equal? An fMRI study of semantic and episodic metamemory predictions.
Reggev, Niv; Zuckerman, Maya; Maril, Anat
2011-04-01
Metamemory refers to the ability of individuals to monitor and control their own memory performance. Although little theoretical consideration of the possible differences between the monitoring of episodic and of semantic knowledge has been published, results from patient and drug studies that used the "feeling of knowing" (FOK) paradigm show a selective impairment in the accuracy of episodic monitoring but not in its semantic counterpart. Similarly, neuroimaging studies provide indirect evidence for separate patterns of activation during episodic or semantic FOKs. However, the semantic-episodic distinction hypothesis has not been directly addressed. In the current event-related fMRI study, we used a within-subject, within-experiment comparison of the monitoring of semantic and episodic content. Whereas the common neural correlates of episodic and semantic FOKs observed in this study generally replicate the previous neuroimaging findings, several regions were found to be differentially associated with each task. Activity of the right inferior frontal gyrus was modulated by the semantic-episodic factor only during the negative predictions of retrieval, suggesting that negative predictions are based on partially distinct mechanisms during each task. A posterior midline network, known to be activated during episodic retrieval, was activated during episodic and not semantic monitoring, suggesting that episodic FOKs rely, to some extent, on common episodic retrieval processes. These findings suggest that theoretical accounts of the etiology and function of FOKs may benefit from incorporating the prediction directionality (positive/negative) and the memory domain (semantic/episodic) distinctions. Copyright © 2011 Elsevier Ltd. All rights reserved.
The Role of Episodic and Semantic Memory in Episodic Foresight
ERIC Educational Resources Information Center
Martin-Ordas, Gema; Atance, Cristina M.; Louw, Alyssa
2012-01-01
In this paper we describe a special form of future thinking, termed "episodic foresight" and its relation with episodic and semantic memory. We outline the methodologies that have largely been developed in the last five years to assess this capacity in young children and non-human animals. Drawing on Tulving's definition of episodic and semantic…
The Ghosts of Brain States Past: Remembering Reactivates the Brain Regions Engaged during Encoding
ERIC Educational Resources Information Center
Danker, Jared F.; Anderson, John R.
2010-01-01
There is growing evidence that the brain regions involved in encoding an episode are partially reactivated when that episode is later remembered. That is, the process of remembering an episode involves literally returning to the brain state that was present during that episode. This article reviews studies of episodic and associative memory that…
42 CFR § 512.240 - Determination of the EPM episode.
Code of Federal Regulations, 2010 CFR
2017-10-01
... SERVICES (CONTINUED) HEALTH CARE INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL Scope of Episodes § 512.240 Determination of the EPM episode. (a) AMI Model—(1) General. The AMI episode begins with the admission of a Medicare beneficiary as described in § 512.230 to an AMI model participant for an anchor...
Temporal Clustering and Sequencing in Short-Term Memory and Episodic Memory
ERIC Educational Resources Information Center
Farrell, Simon
2012-01-01
A model of short-term memory and episodic memory is presented, with the core assumptions that (a) people parse their continuous experience into episodic clusters and (b) items are clustered together in memory as episodes by binding information within an episode to a common temporal context. Along with the additional assumption that information…
Topography of Valles Marineris: Implications for erosional and structural history
NASA Technical Reports Server (NTRS)
Lucchitta, B. K.; Isbell, N. K.; Howington-Kraus, A.
1994-01-01
Compilation of a simplified geologic/geomorphic map onto digital terrain models of the Valles Marineris permitted an evaluation of elevations in the vicinity of the troughs and the calculation of depth of troughs below surrounding plateaus, thickness of deposits inside the troughs, volumes of void spaces above geologic/geomorphic units, and volumes of deposits. The central troughs north Ophir, north and central Candor, and north Melas Chasmata lie as much as 11 km below the adjacent plateaus. In Ophir and Candor chasmata, interior layered deposits reach 8 km in elevation. If the deposits are lacustrine and if all troughs were interconnected, lake waters standing 8 km high would have spilled out of Coprates Chasma onto the surrounding plateaus having surface elevations of only 4-5 km. On the other hand, the troughs may not have been interconnected at the time of interior-deposit emplacement; they may have formed isolated ancestral basins. The existence of such basins is supported by independent structural and stratigraphic evidence. The ancestral basins may have eventually merged, perhaps through renewed faulting, to form northern subsidiary troughs in Ophir and Candor Chasmata and the Coprates/north Melas/Ius graben system. The peripheral troughs are only 2-5 km deep, shallower than the central troughs. Chaotic terrain is seen in the peripheral troughs near a common contour level of about 4 km on the adjacent plateaus, which supports the idea of release of water under artesian pressure from confined aquifers. The layered deposits in the peripheral troughs may have formed in isolated depressions that harbored lakes and predated the formation of the deep outflow channels. (If these layered deposits are of volcanic origin, they may have been emplaced beneath ice in the manner of table mountains.) Areal and volumetric computations show that erosion widened the troughs by about one-third and that deposits occupy one-sixth of the interior space. Even though the volume eroded is larger than the volume deposited, topographic and geologic considerations imply that material eroded from trough walls was probably part of the interior layered deposits but not their sole source. Additional material may have come from subterranean piping, from reworking of local disintegration products on the floors, such as chaotic materials, or from eolian influx. But overall it is likely that the additional material is volcanic and that it forms mostly the upper, more diversely bedded layers of the interior deposits.
Investigating Mars: Candor Chasma
2018-01-19
This image shows part of eastern Candor Chasma. At the top of the image is the steep cliff between the upper surface elevation and the depths of Candor Chasma. The bottom of the image is the cliff side of a large mesa. The two cliff faces have very different appearances. The cliff face between the top of the canyon and the bottom is likely layers of volcanic flows from the nearby Tharsis volcanoes. The mesa, however, is probably layers of sediments deposited in the canyon from wind, water and gravity driven erosion and deposition. These layered materials are much more easily eroded than the solid rock of the canyon sides. There is a landslide that originate from the northern cliff face and ran out into the canyon floor, visible as the lobate "tongue" at the right near the center of the image. Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 36232 Latitude: -6.78692 Longitude: 292.732 Instrument: VIS Captured: 2010-02-13 14:46 https://photojournal.jpl.nasa.gov/catalog/PIA22170
Investigating Mars: Candor Chasma
2018-01-12
This image shows part of eastern Candor Chasma. In the middle of the image is a set of linear ridges and valleys. These features are called yardangs and are created by uniform winds that winnow away materials. Once the valleys are formed the wind then is funneled through the valley and erosion continues more in the valley than on the ridges. At the bottom of the valleys there are sand materials covering the slope between the valleys and the surrounding chasma floor. Beyond this coating of sand there are darker sand deposits where wind has accumulated the sand into larger dunes. The brighter mesa on the right side of the image has also been wind eroded into yardangs, but are aligned in a different direction than the larger yardangs. This indicates that wind directions within the canyon have changed over time. Candor Chasma is one of the largest canyons that make up Valles Marineris. It is approximately 810 km long (503 miles) and has is divided into two regions - eastern and western Candor. Candor is located south of Ophir Chasma and north of Melas Chasma. The border with Melas Chasma contains many large landslide deposits. The floor of Candor Chasma includes a variety of landforms, including layered deposits, dunes, landslide deposits and steep sided cliffs and mesas. Many forms of erosion have shaped Chandor Chasma. There is evidence of wind and water erosion, as well as significant gravity driven mass wasting (landslides). The Odyssey spacecraft has spent over 15 years in orbit around Mars, circling the planet more than 69000 times. It holds the record for longest working spacecraft at Mars. THEMIS, the IR/VIS camera system, has collected data for the entire mission and provides images covering all seasons and lighting conditions. Over the years many features of interest have received repeated imaging, building up a suite of images covering the entire feature. From the deepest chasma to the tallest volcano, individual dunes inside craters and dune fields that encircle the north pole, channels carved by water and lava, and a variety of other feature, THEMIS has imaged them all. For the next several months the image of the day will focus on the Tharsis volcanoes, the various chasmata of Valles Marineris, and the major dunes fields. We hope you enjoy these images! Orbit Number: 10551 Latitude: -6.93639 Longitude: 288.562 Instrument: VIS Captured: 2004-05-01 02:24 https://photojournal.jpl.nasa.gov/catalog/PIA22165
Theim, Kelly R.; Wilfley, Denise E.; Beach, Elizabeth; Tanofsky-Kraff, Marian; Goldschmidt, Andrea B.
2014-01-01
Pediatric loss of control (LOC) eating heightens risk for excessive weight gain and further disordered eating. Assessment of LOC typically involves self-report interview or laboratory test meal, although no study has concurrently examined data from both methods. We gathered eating episode data via interview (Child Eating Disorder Examination; ChEDE) and a laboratory test meal, among 22 overweight girls (aged 7-12 years) reporting LOC eating. Children consumed more energy during ChEDE episodes, although ChEDE and test meal episodes did not differ in macronutrient content. Episodes' correlation for amount consumed (grams) did not reach significance, p=.076. In exploratory analyses among the 7 children reporting LOC during the test meal, episodes were significantly correlated for grams consumed. Findings provide preliminary data to suggest that semi-structured interviews accurately capture children's LOC episode quantity. Episodes did not qualitatively differ, although children reported consuming more energy during self-reported episodes. Replication is warranted in larger studies. PMID:24019221
Toyota, Hiroshi
2011-02-01
The present study examined the effects of emotion elicited by episodes (past events or expected future events) and the relationship between individual differences in emotional intelligence and memory. Participants' emotional intelligence was assessed on the Japanese version of Emotional Skills and Competence Questionnaire. They rated the pleasantness of episodes they associated with targets, and then performed unexpected free recall tests. When the targets were associated with episodes that were past events, all participants recalled more of the targets associated with pleasant and unpleasant episodes than those associated with neutral episodes. However, when the targets were associated with episodes expected to occur in the future, only participants with higher emotional intelligence scores recalled more of the targets associated with pleasant and unpleasant episodes. The participants with lower emotional intelligence scores recalled the three target types with similar accuracy. These results were interpreted as showing that emotional intelligence is associated with the processing of targets associated with future episodes as retrieval cues.
Renoult, Louis; Davidson, Patrick S R; Schmitz, Erika; Park, Lillian; Campbell, Kenneth; Moscovitch, Morris; Levine, Brian
2015-01-01
A common assertion is that semantic memory emerges from episodic memory, shedding the distinctive contexts associated with episodes over time and/or repeated instances. Some semantic concepts, however, may retain their episodic origins or acquire episodic information during life experiences. The current study examined this hypothesis by investigating the ERP correlates of autobiographically significant (AS) concepts, that is, semantic concepts that are associated with vivid episodic memories. We inferred the contribution of semantic and episodic memory to AS concepts using the amplitudes of the N400 and late positive component, respectively. We compared famous names that easily brought to mind episodic memories (high AS names) against equally famous names that did not bring such recollections to mind (low AS names) on a semantic task (fame judgment) and an episodic task (recognition memory). Compared with low AS names, high AS names were associated with increased amplitude of the late positive component in both tasks. Moreover, in the recognition task, this effect of AS was highly correlated with recognition confidence. In contrast, the N400 component did not differentiate the high versus low AS names but, instead, was related to the amount of general knowledge participants had regarding each name. These results suggest that semantic concepts high in AS, such as famous names, have an episodic component and are associated with similar brain processes to those that are engaged by episodic memory. Studying AS concepts may provide unique insights into how episodic and semantic memory interact.
Clinical presentation of postnatal and non-postnatal depressive episodes.
Cooper, Carly; Jones, Lisa; Dunn, Emma; Forty, Liz; Haque, Sayeed; Oyebode, Femi; Craddock, Nick; Jones, Ian
2007-09-01
The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.
Ben-Yakov, Aya; Dudai, Yadin
2011-06-15
Encoding of real-life episodic memory commonly involves integration of information as the episode unfolds. Offline processing immediately following event offset is expected to play a role in encoding the episode into memory. In this study, we examined whether distinct human brain activity time-locked to the offset of short narrative audiovisual episodes could predict subsequent memory for the gist of the episodes. We found that a set of brain regions, most prominently the bilateral hippocampus and the bilateral caudate nucleus, exhibit memory-predictive activity time-locked to the stimulus offset. We propose that offline activity in these regions reflects registration to memory of integrated episodes.
42 CFR 484.235 - Methodology used for the calculation of the partial episode payment adjustment.
Code of Federal Regulations, 2010 CFR
2010-10-01
... partial episode payment adjustment. (a) CMS makes a PEP adjustment to the original 60-day episode payment that is interrupted by an intervening event described in § 484.205(d). (b) The original 60-day episode... partial episode payment is calculated by determining the actual days served by the original HHA as a...
2014-01-01
Objective To identify associations between market factors, especially relative reimbursement rates, and the probability of surgery and cost per episode for three medical conditions (cataract, benign prostatic neoplasm, and knee degeneration) with multiple treatment options. Methods We use 2004–2006 Medicare claims data for elderly beneficiaries from sixty nationally representative communities to estimate multivariate models for the probability of surgery and cost per episode of care as a function local market factors, including Medicare physician reimbursement for surgical versus non-surgical treatment and the availability of primary care and specialty physicians. We used Symmetry’s Episode Treatment Groups (ETG) software to group claims into episodes for the three conditions (n = 540,874 episodes). Results Higher Medicare reimbursement for surgical episodes and greater availability of the relevant specialists are significantly associated with more surgery and higher cost per episode for all three conditions, while greater availability of primary care physicians is significantly associated with less frequent surgery and lower cost per episode. Conclusion Relative Medicare reimbursement rates for surgical vs. non-surgical treatments and the availability of both primary care physicians and relevant specialists are associated with the likelihood of surgery and cost per episode. PMID:24949281
Memory sources of dreams: the incorporation of autobiographical rather than episodic experiences.
Malinowski, Josie E; Horton, Caroline L
2014-08-01
The present study aimed to explore autobiographical memories (long-lasting memories about the self) and episodic memories (memories about discrete episodes or events) within dream content. We adapted earlier episodic memory study paradigms and reinvestigated the incorporation of episodic memory sources into dreams, operationalizing episodic memory as featuring autonoetic consciousness, which is the feeling of truly re-experiencing or reliving a past event. Participants (n = 32) recorded daily diaries and dream diaries, and reported on wake-dream relations for 2 weeks. Using a new scale, dreams were rated for their episodic richness, which categorized memory sources of dreams as being truly episodic (featuring autonoetic consciousness), autobiographical (containing segregated features of experiences that pertained to waking life) or otherwise. Only one dream (0.5%) was found to contain an episodic memory. However, the majority of dreams (>80%) were found to contain low to moderate incorporations of autobiographical memory features. These findings demonstrate the inactivity of intact episodic memories, and emphasize the activity of autobiographical memory and processing within dreams. Taken together, this suggests that memories for personal experiences are experienced fragmentarily and selectively during dreaming, perhaps in order to assimilate these memories into the autobiographical memory schema. © 2014 European Sleep Research Society.
Klein, Stanley B
2013-01-01
Episodic memory often is conceptualized as a uniquely human system of long-term memory that makes available knowledge accompanied by the temporal and spatial context in which that knowledge was acquired. Retrieval from episodic memory entails a form of first-person subjectivity called autonoetic consciousness that provides a sense that a recollection was something that took place in the experiencer's personal past. In this paper I expand on this definition of episodic memory. Specifically, I suggest that (1) the core features assumed unique to episodic memory are shared by semantic memory, (2) episodic memory cannot be fully understood unless one appreciates that episodic recollection requires the coordinated function of a number of distinct, yet interacting, "enabling" systems. Although these systems-ownership, self, subjective temporality, and agency-are not traditionally viewed as memorial in nature, each is necessary for episodic recollection and jointly they may be sufficient, and (3) the type of subjective awareness provided by episodic recollection (autonoetic) is relational rather than intrinsic-i.e., it can be lost in certain patient populations, thus rendering episodic memory content indistinguishable from the content of semantic long-term memory.
Mourao-Miranda, J; Reinders, A A T S; Rocha-Rego, V; Lappin, J; Rondina, J; Morgan, C; Morgan, K D; Fearon, P; Jones, P B; Doody, G A; Murray, R M; Kapur, S; Dazzan, P
2012-05-01
To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode. One hundred patients at their first psychotic episode and 91 healthy controls had an MRI scan. Patients were re-evaluated 6.2 years (s.d.=2.3) later, and were classified as having a continuous, episodic or intermediate illness course. Twenty-eight subjects with a continuous course were compared with 28 patients with an episodic course and with 28 healthy controls. We trained each SVM classifier independently for the following contrasts: continuous versus episodic, continuous versus healthy controls, and episodic versus healthy controls. At baseline, patients with a continuous course were already distinguishable, with significance above chance level, from both patients with an episodic course (p=0.004, sensitivity=71, specificity=68) and healthy individuals (p=0.01, sensitivity=71, specificity=61). Patients with an episodic course could not be distinguished from healthy individuals. When patients with an intermediate outcome were classified according to the discriminating pattern episodic versus continuous, 74% of those who did not develop other episodes were classified as episodic, and 65% of those who did develop further episodes were classified as continuous (p=0.035). We provide preliminary evidence of MRI application in the individualized prediction of future illness course, using a simple and automated SVM pipeline. When replicated and validated in larger groups, this could enable targeted clinical decisions based on imaging data.
Heavy episodic drinking is a trait-state: a cautionary note.
Mushquash, Aislin R; Sherry, Simon B; Mackinnon, Sean P; Mushquash, Christopher J; Stewart, Sherry H
2014-01-01
Heavy episodic (binge) drinking is common in and problematic for undergraduates. Researchers often assume that an individual's heavy episodic drinking is stable and trait-like. However, this fails to consider fluctuating, state-like variation in heavy episodic drinking. This study proposes and tests a novel conceptualization of heavy episodic drinking as a trait-state wherein the contribution of both trait-like stability and state-like fluctuations are quantified. It was hypothesized that heavy episodic drinking is a trait-state such that individuals have trait-like tendencies to engage in heavy episodic drinking, and state-like differences in the expression of this tendency over time. A sample of 114 first-year undergraduates from a Canadian university completed self-report measures of heavy episodic drinking at 3 time points across 130 days. Hypotheses were tested with repeated-measures analysis of variance (ANOVA), test-retest correlations, and generalizability theory analyses. A substantial proportion of the variance in heavy episodic drinking is attributable to trait-like stability, with a smaller proportion attributable to state-like fluctuations. The heavy episodic drinker seems characterized by a stable, trait-like tendency to drink in a risky manner, and this trait-like tendency seems to fluctuate in degree of expression over time. Findings complement research suggesting that people have trait-like predispositions that increase their risk for heavy episodic drinking. However, despite this stable tendency to drink heavily, the frequency of heavy episodic drinking appears to be at least partly sporadic or situation dependent. These findings serve as a caution to alcohol researchers and clinicians who often assume that a single assessment of heavy episodic drinking captures a person's usual drinking behavior.
Sapra, Mamta; Weiden, Peter J; Schooler, Nina R; Sunakawa-McMillan, Ayako; Uzenoff, Sarah; Burkholder, Page
2014-01-01
Most first-episode schizophrenia patients will stop their medication after their acute symptoms improve. Understanding the salient motivations and attitudes that drive adherence--as well as nonadherence--is an important part of developing strategies to prevent or delay nonadherence during the early phases of the illness. Self-reported reasons for adherence and nonadherence among first-episode and multi-episode patients with schizophrenia were obtained from cross-sectional adherence interviews from two prospective adherence studies: one composed of a first-episode sample (n=33) and the other with recently relapsing multi-episode patients (n=16). Both groups received the Rating of Medication Influences (ROMI) Scale at approximately 16 to 20 weeks after an acute psychotic episode. The specific ROMI items were ranked in order of percentage (%) strong, and were compared both within each patient group for rank order of importance, and also compared between groups to determine the differences in specific adherence and nonadherence influences. The doctor-patient relationship was more likely to be endorsed as a strong adherence influence in the first-episode sample (74%) than in the multi-episode sample (13%, X²=18.07, p<.01). Change in physical appearance attributed to medication was a more commonly endorsed nonadherence influence for the multi-episode sample (25%) relative to the first-episode sample (0%, X²=9.2, p<.01). The doctor-patient relationship stands out as being the major reason for ongoing adherence for first-episode schizophrenia patients. Our post hoc interpretation is that lack of prior experience with medication and treatment elevates the importance of the relationship with the treating clinician for first-episode patients.
NASA Astrophysics Data System (ADS)
Tsai, Ying I.; Sopajaree, Khajornsak; Chotruksa, Auranee; Wu, Hsin-Ching; Kuo, Su-Ching
2013-10-01
PM10 aerosol was collected between February and April 2010 at an urban site (CMU) and an industrial site (TOT) in Chiang Mai, Thailand, and characteristics and provenance of water-soluble inorganic species, carboxylates, anhydrosugars and sugar alcohols were investigated with particular reference to air quality, framed as episodic or non-episodic pollution. Sulfate, a product of secondary photochemical reactions, was the major inorganic salt in PM10, comprising 25.9% and 22.3% of inorganic species at CMU and TOT, respectively. Acetate was the most abundant monocarboxylate, followed by formate. Oxalate was the dominant dicarboxylate. A high acetate/formate mass ratio indicated that primary traffic-related and biomass-burning emissions contributed to Chiang Mai aerosols during episodic and non-episodic pollution. During episodic pollution carboxylate peaks indicated sourcing from photochemical reactions and/or directly from traffic-related and biomass burning processes and concentrations of specific biomarkers of biomass burning including water-soluble potassium, glutarate, oxalate and levoglucosan dramatically increased. Levoglucosan, the dominant anhydrosugar, was highly associated with water-soluble potassium (r = 0.75-0.79) and accounted for 93.4% and 93.7% of anhydrosugars at CMU and TOT, respectively, during episodic pollution. Moreover, levoglucosan during episodic pollution was 14.2-21.8 times non-episodic lows, showing clearly that emissions from biomass burning are the major cause of PM10 episodic pollution in Chiang Mai. Additionally, the average levoglucosan/mannosan mass ratio during episodic pollution was 14.1-14.9, higher than the 5.73-7.69 during non-episodic pollution, indicating that there was more hardwood burning during episodic pollution. Higher concentrations of glycerol and erythritol during episodic pollution further indicate that biomass burning activities released soil biota from forest and farmland soils.
Mourao-Miranda, J.; Reinders, A. A. T. S.; Rocha-Rego, V.; Lappin, J.; Rondina, J.; Morgan, C.; Morgan, K. D.; Fearon, P.; Jones, P. B.; Doody, G. A.; Murray, R. M.; Kapur, S.; Dazzan, P.
2012-01-01
Background To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode. Method One hundred patients at their first psychotic episode and 91 healthy controls had an MRI scan. Patients were re-evaluated 6.2 years (s.d.=2.3) later, and were classified as having a continuous, episodic or intermediate illness course. Twenty-eight subjects with a continuous course were compared with 28 patients with an episodic course and with 28 healthy controls. We trained each SVM classifier independently for the following contrasts: continuous versus episodic, continuous versus healthy controls, and episodic versus healthy controls. Results At baseline, patients with a continuous course were already distinguishable, with significance above chance level, from both patients with an episodic course (p=0.004, sensitivity=71, specificity=68) and healthy individuals (p=0.01, sensitivity=71, specificity=61). Patients with an episodic course could not be distinguished from healthy individuals. When patients with an intermediate outcome were classified according to the discriminating pattern episodic versus continuous, 74% of those who did not develop other episodes were classified as episodic, and 65% of those who did develop further episodes were classified as continuous (p=0.035). Conclusions We provide preliminary evidence of MRI application in the individualized prediction of future illness course, using a simple and automated SVM pipeline. When replicated and validated in larger groups, this could enable targeted clinical decisions based on imaging data. PMID:22059690
Testing episodic memory in animals: a new approach.
Griffiths, D P; Clayton, N S
2001-08-01
Episodic memory involves the encoding and storage of memories concerned with unique personal experiences and their subsequent recall, and it has long been the subject of intensive investigation in humans. According to Tulving's classical definition, episodic memory "receives and stores information about temporally dated episodes or events and temporal-spatial relations among these events." Thus, episodic memory provides information about the 'what' and 'when' of events ('temporally dated experiences') and about 'where' they happened ('temporal-spatial relations'). The storage and subsequent recall of this episodic information was thought to be beyond the memory capabilities of nonhuman animals. Although there are many laboratory procedures for investigating memory for discrete past episodes, until recently there were no previous studies that fully satisfied the criteria of Tulving's definition: they can all be explained in much simpler terms than episodic memory. However, current studies of memory for cache sites in food-storing jays provide an ethologically valid model for testing episodic-like memory in animals, thereby bridging the gap between human and animal studies memory. There is now a pressing need to adapt these experimental tests of episodic memory for other animals. Given the potential power of transgenic and knock-out procedures for investigating the genetic and molecular bases of learning and memory in laboratory rodents, not to mention the wealth of knowledge about the neuroanatomy and neurophysiology of the rodent hippocampus (a brain area heavily implicated in episodic memory), an obvious next step is to develop a rodent model of episodic-like memory based on the food-storing bird paradigm. The development of a rodent model system could make an important contribution to our understanding of the neural, molecular, and behavioral mechanisms of mammalian episodic memory.
The contributions of handedness and working memory to episodic memory.
Sahu, Aparna; Christman, Stephen D; Propper, Ruth E
2016-11-01
Past studies have independently shown associations of working memory and degree of handedness with episodic memory retrieval. The current study takes a step ahead by examining whether handedness and working memory independently predict episodic memory. In agreement with past studies, there was an inconsistent-handed advantage for episodic memory; however, this advantage was absent for working memory tasks. Furthermore, regression analyses showed handedness, and complex working memory predicted episodic memory performance at different times. Results are discussed in light of theories of episodic memory and hemispheric interaction.
Jing, Helen G.; Madore, Kevin P.; Schacter, Daniel L.
2015-01-01
Previous research has demonstrated that an episodic specificity induction – brief training in recollecting details of a recent experience – enhances performance on various subsequent tasks thought to draw upon episodic memory processes. Existing work has also shown that mental simulation can be beneficial for emotion regulation and coping with stressors. Here we focus on understanding how episodic detail can affect problem solving, reappraisal, and psychological well-being regarding worrisome future events. In Experiment 1, an episodic specificity induction significantly improved participants’ performance on a subsequent means-end problem solving task (i.e., more relevant steps) and an episodic reappraisal task (i.e., more episodic details) involving personally worrisome future events compared with a control induction not focused on episodic specificity. Imagining constructive behaviors with increased episodic detail via the specificity induction was also related to significantly larger decreases in anxiety, perceived likelihood of a bad outcome, and perceived difficulty to cope with a bad outcome, as well as larger increases in perceived likelihood of a good outcome and indicated use of active coping behaviors compared with the control. In Experiment 2, we extended these findings using a more stringent control induction, and found preliminary evidence that the specificity induction was related to an increase in positive affect and decrease in negative affect compared with the control. Our findings support the idea that episodic memory processes are involved in means-end problem solving and episodic reappraisal, and that increasing the episodic specificity of imagining constructive behaviors regarding worrisome events may be related to improved psychological well-being. PMID:26820166
Peritoneal dialysis peritonitis by anaerobic pathogens: a retrospective case series
2013-01-01
Background Bacterial infections account for most peritoneal dialysis (PD)-associated peritonitis episodes. However, anaerobic PD peritonitis is extremely rare and intuitively associated with intra-abdominal lesions. In this study, we examined the clinical characteristics of PD patients who developed anaerobic peritonitis. Methods We retrospectively identified all anaerobic PD peritonitis episodes from a prospectively collected PD registry at a single center between 1990 and 2010. Only patients receiving more than 3 months of PD were enrolled. We analyzed clinical features as well as outcomes of anaerobic PD peritonitis patients. Results Among 6 patients, 10 episodes of PD-associated peritonitis were caused by anaerobic pathogens (1.59% of all peritonitis episodes during study the period), in which the cultures from 5 episodes had mixed growth. Bacteroides fragilis was the most common species identified (4 isolates). Only 3 episodes were associated with gastrointestinal lesions, and 4 episodes were related to a break in sterility during exchange procedures. All anaerobic pathogens were susceptible to clindamycin and metronidazole, but penicillin resistance was noted in 4 isolates. Ampicillin/sulbactam resistance was found in 2 isolates. In 5 episodes, a primary response was achieved using the first-generation cephalosporin and ceftazidime or aminoglycoside. In 3 episodes, the first-generation cephalosporin was replaced with aminoglycosides. Tenckhoff catheter removal was necessary in 2 episodes. Only one episode ended with mortality (due to a perforated bowel). Conclusion Anaerobic PD-associated peritonitis might be predominantly caused by contamination, rather than intra-abdominal events. Half of anaerobic PD-associated peritonitis episodes had polymicrobial growth. The overall outcome of anaerobic peritonitis is fair, with a high catheter survival rate. PMID:23705895
Dommett, R; Geary, J; Freeman, S; Hartley, J; Sharland, M; Davidson, A; Tulloh, R; Taj, M; Stoneham, S; Chisholm, J C
2009-11-01
Patients with febrile neutropaenia (FN) can be stratified according to their risk of significant complications, allowing reduced intensity therapy for low risk (LR) episodes. Serious events are very rare in low risk episodes making randomised trials difficult. Introduction of new evidence-based guidelines followed by re-auditing of the outcome is an alternative strategy. New guidelines for the management of LR FN were implemented in 4 specialist paediatric oncology centres (POCs) and in their associated shared care units (POSCUs). All patients commenced empirical intravenous antibiotic therapy and after 48h those with blood culture negative episodes designated LR were eligible for discharge on oral co-amoxiclav. Prospective data collection on FN episodes in all treatment centres was undertaken over a 1-year period. Seven hundred and sixty two eligible episodes of FN were recorded in 368 patients; 213 episodes were initiated in POCs and 549 episodes were initiated in POSCUs. In 40% of episodes no clinical or microbiological focus of infection was found. At 48h, 212 (27%) episodes were classified as LR and 143 of these (19%) were managed on the LR protocol. There was a low hospital readmission rate (8/143 episodes; 5.6%), no intensive care admissions and no deaths in LR episodes. Almost all LR episodes (209/212) occurred in the shared care setting. Rapid step-down to oral antibiotics was a feasible and safe management strategy for LR FN in the shared care setting in England.
Episodic Future Thinking: Mechanisms and Functions.
Schacter, Daniel L; Benoit, Roland G; Szpunar, Karl K
2017-10-01
Episodic future thinking refers to the capacity to imagine or simulate experiences that might occur in one's personal future. Cognitive, neuropsychological, and neuroimaging research concerning episodic future thinking has accelerated during recent years. This article discusses research that has delineated cognitive and neural mechanisms that support episodic future thinking as well as the functions that episodic future thinking serves. Studies focused on mechanisms have identified a core brain network that underlies episodic future thinking and have begun to tease apart the relative contributions of particular regions in this network, and the specific cognitive processes that they support. Studies concerned with functions have identified several domains in which episodic future thinking produces performance benefits, including decision making, emotion regulation, prospective memory, and spatial navigation.
Hyperperfusion syndrome after MCA embolectomy – a rare complication?
Backhaus, Roland; Boy, Sandra; Fuchs, Kornelius; Ulrich, Bogdahn; Schuierer, Gerhard; Schlachetzki, Felix
2013-01-01
Patient: Female, 78 Final Diagnosis: Cerebral hyperperfusion syndrome Symptoms: — Medication: — Clinical Procedure: Endovascular embolectomy Specialty: Neurology Objective: Unknown ethiology Background: Cerebral hyperperfusion syndrome (cHS) is a well known but rare complication after carotid endarterectomy, carotid angioplasty with stenting, and stenting of intracranial arterial stenosis. The clinical presentation may vary from acute onset of focal oedema (stroke-like presentation) and intracerbral hemorrhage to delayed (>24h hours after the procedure) presentation with seizures, focal motor weakness, or late intracerebral hemorrhage. The incidence of cHS after carotid endarterectomy ranges from 0–3% and defined as an increase of the ipsilateral cerebral blood flow up to 40% over baseline in ultrasound. Case Report: We present a case of a 78-year-old woman with an acute ischemic stroke due to left side middle cerebral artery territory with right sided hemiparesis and aphasia (NIHSS 16). After systemic thrombolysis embolectomy using a retractable stent (Solitaire® device) was performed and resulted in complete and successful recanalization of MCA including its branches about 210 minutes after symptom onset but, partial dislocation of thrombotic material into the anterior cerebral artery (ACA). Conclusions: Cerebral hyperperfusion syndrome should be considered in patients with clinical deterioration after successful recanalisation and the early diagnosis and treatment may be important for neurological outcome after endovascular embolectomy PMID:24340127
Neuroanatomical and Cognitive Mediators of Age-Related Differences in Episodic Memory
Head, Denise; Rodrigue, Karen M.; Kennedy, Kristen M.; Raz, Naftali
2009-01-01
Aging is associated with declines in episodic memory. In this study, the authors used a path analysis framework to explore the mediating role of differences in brain structure, executive functions, and processing speed in age-related differences in episodic memory. Measures of regional brain volume (prefrontal gray and white matter, caudate, hippocampus, visual cortex), executive functions (working memory, inhibitory control, task switching, temporal processing), processing speed, and episodic memory were obtained in a sample of young and older adults. As expected, age was linked to reduction in regional brain volumes and cognitive performance. Moreover, neural and cognitive factors completely mediated age differences in episodic memory. Whereas hippocampal shrinkage directly affected episodic memory, prefrontal volumetric reductions influenced episodic memory via limitations in working memory and inhibitory control. Age-related slowing predicted reduced efficiency in temporal processing, working memory, and inhibitory control. Lastly, poorer temporal processing directly affected episodic memory. No direct effects of age on episodic memory remained once these factors were taken into account. These analyses highlight the value of a multivariate approach with the understanding of complex relationships in cognitive and brain aging. PMID:18590361
Episodic memory impairment in systemic lupus erythematosus: involvement of thalamic structures.
Zimmermann, Nicolle; Corrêa, Diogo Goulart; Netto, Tania Maria; Kubo, Tadeu; Pereira, Denis Batista; Fonseca, Rochele Paz; Gasparetto, Emerson Leandro
2015-02-01
Episodic memory deficits in systemic lupus erythematosus (SLE) have been frequently reported in the literature; however, little is known about the neural correlates of these deficits. We investigated differences in the volumes of different brain structures of SLE patients with and without episodic memory impairments diagnosed by the Rey Auditory Verbal Learning Test (RAVLT). Groups were paired based on age, education, sex, Mini Mental State Examination score, accumulation of disease burden (SLICC), and focused attention dimension score. Patients underwent magnetic resonance imaging (MRI). Cortical volumetric reconstruction and segmentation of the MR images were performed with the FreeSurfer software program. SLE patients with episodic memory deficits presented shorter time of diagnosis than SLE patients without episodic memory deficits. ANOVA revealed that SLE patients with episodic memory deficits had a larger third ventricle volume than SLE patients without episodic memory deficits and controls. Additionally, covariance analysis indicated group effects on the bilateral thalamus and on the third ventricle. Our findings indicate that episodic memory may be impaired in SLE patients with normal hippocampal volume. In addition, the thalamus may undergo volumetric changes associated with episodic memory loss in SLE.
Episodic representations support early semantic learning: evidence from midazolam induced amnesia.
Merritt, Paul; Hirshman, Elliot; Zamani, Shane; Hsu, John; Berrigan, Michael
2006-07-01
Current controversy exists regarding the role of episodic representations in the formation of long-term semantic memories. Using the drug midazolam to induce temporary amnesia we tested participants' memories for newly learned facts in a semantic cue condition or an episodic and semantic cue condition. Following midazolam administration, memory performance was superior in the episodic and semantic condition, suggesting early semantic learning is supported by episodic representations.
Border Collie Collapse: Owner Survey Results and Veterinary Description of Videotaped Episodes.
Taylor, Susan; Minor, Katie; Shmon, Cindy L; Shelton, G Diane; Patterson, Edward E; Mickelson, James R
Completed surveys were obtained from owners of 165 border collies experiencing repeated episodes of abnormal gait or collapse during strenuous exercise. Unremarkable veterinary evaluation and lack of disease progression over time made common systemic, cardiac, and neurologic causes of exercise intolerance unlikely. Survey questions addressed signalment, age of onset, description of episodes, and owner perception of factors associated with collapse. Most dogs were young adults (median 2 yr) when episodes began, and they had experienced from 2 to more than 100 episodes (median 6) prior to their owners completing the survey. Retrieving was the activity most commonly associated with episodes (112/165 dogs, 68%), followed by herding stock (39/165 dogs, 24%). Owners reported that high environmental temperatures (111/165 dogs, 67%) and excitement (67/165 dogs, 41%) increased the likelihood of their dog having an episode during strenuous activity. Veterinary evaluation of videotapes of presumed border collie collapse (BCC) episodes (40 dogs) were used to provide a description of the typical features of BCC episodes. Altered mentation, symmetrical ataxia affecting all four limbs, increased pelvic limb extensor tone and toe scuffing or knuckling, truncal swaying, and falling to the side were common features, suggesting that BCC may be an episodic diffuse central nervous system disorder.
Looking for episodic memory in animals and young children: prospects for a new minimalism.
Clayton, Nicola S; Russell, James
2009-09-01
Because animals and young children cannot be interrogated about their experiences it is difficult to conduct research into their episodic memories. The approach to this issue adopted by Clayton and Dickinson [Clayton, N. S., & Dickinson, A. (1998). Episodic-like memory during cache recovery by scrub jays. Nature, 395, 272-274] was to take a conceptually minimalist definition of episodic memory, in terms of integrating information about what was done where and when [Tulving, E. (1972). Episodic and semantic memory. In E. Tulving, & W. Donaldson (Eds.), Organisation of memory (pp. 381-403). New York: Academic Press], and to refer to such memories as 'episodic-like'. Some claim, however, that because animals supposedly lack the conceptual abilities necessary for episodic recall one should properly call these memories 'semantic'. We address this debate with a novel approach to episodic memory, which is minimalist insofar as it focuses on the non-conceptual content of a re-experienced situation. It rests on Kantian assumptions about the necessary 'perspectival' features of any objective experience or re-experience. We show how adopting this perspectival approach can render an episodic interpretation of the animal data more plausible and can also reveal patterns in the mosaic of developmental evidence for episodic memory in humans.
Klein, Stanley B.
2013-01-01
Episodic memory often is conceptualized as a uniquely human system of long-term memory that makes available knowledge accompanied by the temporal and spatial context in which that knowledge was acquired. Retrieval from episodic memory entails a form of first–person subjectivity called autonoetic consciousness that provides a sense that a recollection was something that took place in the experiencer's personal past. In this paper I expand on this definition of episodic memory. Specifically, I suggest that (1) the core features assumed unique to episodic memory are shared by semantic memory, (2) episodic memory cannot be fully understood unless one appreciates that episodic recollection requires the coordinated function of a number of distinct, yet interacting, “enabling” systems. Although these systems—ownership, self, subjective temporality, and agency—are not traditionally viewed as memorial in nature, each is necessary for episodic recollection and jointly they may be sufficient, and (3) the type of subjective awareness provided by episodic recollection (autonoetic) is relational rather than intrinsic—i.e., it can be lost in certain patient populations, thus rendering episodic memory content indistinguishable from the content of semantic long-term memory. PMID:23378832
Maina, Giuseppe; Rosso, Gianluca; Aguglia, Andrea; Bogetto, Filippo
2014-10-01
The postpartum period is considered a time of heightened vulnerability to bipolar disorder. The primary goal of this study was to examine the frequency and the polarity of postpartum episodes in a clinical sample of women with bipolar disorder who were medication-free during their pregnancies. In addition, we sought to examine whether there are differences in terms of clinical features of bipolar disorder between women with and without postpartum episodes. Lastly, we analyzed the potential relationship between polarity of the postpartum episodes and clinical features of bipolar disorder. The presence/absence of postpartum episodes and their characteristics were obtained from medical records of 276 women with bipolar disorder who were medication-free during their pregnancies. Two hundred seven women (75.0 %) had a history of one or more postpartum mood episodes: depressive (79.7 %), (hypo)manic (16.4 %), or mixed episodes (3.9 %). Psychotic symptoms during postpartum episodes were associated with depression in 37 (22.4 %) patients, with mania in 19 (67.8 %) patients, and with mixed episodes in 7 (87.5 %) patients. Postpartum manic and mixed episodes were significantly associated with type I disorder and with psychotic features. Our findings indicate high risk of clinically ascertained mood episodes during postpartum period in bipolar women who are not treated during pregnancy.
Wong, Michelle; Barqasho, Babilonia; Ohrmalm, Lars; Tolfvenstam, Thomas; Nowak, Piotr
2013-01-01
In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).
Thakral, Preston P.; Benoit, Roland G.; Schacter, Daniel L.
2017-01-01
Neuroimaging data indicate that episodic memory (i.e., remembering specific past experiences) and episodic simulation (i.e., imagining specific future experiences) are associated with enhanced activity in a common set of neural regions, often referred to as the core network. This network comprises the hippocampus, parahippocampal cortex, lateral and medial parietal cortex, lateral temporal cortex, and medial prefrontal cortex. Evidence for a core network has been taken as support for the idea that episodic memory and episodic simulation are supported by common processes. Much remains to be learned about how specific core network regions contribute to specific aspects of episodic simulation. Prior neuroimaging studies of episodic memory indicate that certain regions within the core network are differentially sensitive to the amount of information recollected (e.g., the left lateral parietal cortex). In addition, certain core network regions dissociate as a function of their timecourse of engagement during episodic memory (e.g., transient activity in the posterior hippocampus and sustained activity in the left lateral parietal cortex). In the current study, we assessed whether similar dissociations could be observed during episodic simulation. We found that the left lateral parietal cortex modulates as a function of the amount of simulated details. Of particular interest, while the hippocampus was insensitive to the amount of simulated details, we observed a temporal dissociation within the hippocampus: transient activity occurred in relatively posterior portions of the hippocampus and sustained activity occurred in anterior portions. Because the posterior hippocampal and lateral parietal findings parallel those observed previously during episodic memory, the present results add to the evidence that episodic memory and episodic simulation are supported by common processes. Critically, the present study also provides evidence that regions within the core network support dissociable processes. PMID:28324695
Diener, Hans-Christoph; Gold, Morris; Hagen, Martina
2014-11-19
Most patients with episodic tension-type headache treat headache episodes with over-the-counter medication. Combination analgesics containing caffeine may be more effective and as well tolerated as monotherapy. The aim of this study was to evaluate the efficacy of the combination of acetylsalicylic acid, acetaminophen (paracetamol) and caffeine in episodic tension-type headache using recently recommended endpoints. Four randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs. acetaminophen or placebo were pooled. Analysis populations were 'all headache episodes' and those with 'severe pain at baseline'. Post-hoc defined primary endpoint: headache episodes pain-free at 2 h. Secondary endpoints: headache episodes pain-free at 1 h, headache response at 2 h (mild or no pain), degree of interference with daily activities. 6,861 headache episodes were treated, including 2,215 severe headache episodes. The proportion of headache episodes pain-free at 2 h was significantly higher with the triple combination (28.5%) vs. acetaminophen (21.0%) and placebo (18.0%) (p < 0.0001), and similarly for those severe at baseline (20.2% vs. 12.1% and 10.8%; p ≤ 0.0003). A similar pattern of superiority was observed for secondary endpoints. The triple combination was generally well tolerated. The combination of acetylsalicylic acid, acetaminophen and caffeine is effective and well tolerated in episodic tension-type headache, and significantly superior to acetaminophen with regard to being pain-free at 2 h, headache response at 2 h and ability to return to daily activities, even in those with pain rated severe at baseline.
Acute manic episode is associated with an increased risk of lower limb edema.
Hochman, Eldar; Krivoy, Amir; Shoval, Gal; Valevski, Avi; Weizman, Abraham; Fischel, Tsvi
2013-12-02
Lower limb edema (LLE) was suggested to be associated with the use of psychotropic drugs among patients suffering from severe mental illnesses; however no direct mechanism was found. Therefore, we examined the association between the occurrence of LLE and acute untreated episode leading to hospitalization. A retrospective cross-sectional study was conducted using medical charts of 2529 patients admitted to Geha Mental Health Center between 2002 and 2012. Incident cases of LLE, demographic and clinical data were retrieved. Admission clinical status was modeled as three non-overlapping groups of patients: (i) Patients with a non-affective psychosis (NAP) episode (n = 1563), (ii) patients with a manic episode (n = 366), and (iii) patients with a depressive episode (n = 600). We performed a logistic regression analysis with LLE as the dependent variable controlling for the demographic and clinical variables that may be associated with LLE. LLE was diagnosed in 3.8% (n = 95) of the study population. The rate of LLE was 3-fold higher (χ(2) = 51.9, df = 2, p<0.001) in patients admitted with a manic episode (n = 38; 10.4%) compared to patients admitted with a NAP episode (n = 41; 2.6%) and patients admitted with a depressive episode (n = 16; 2.7%). Manic episode was associated with an increased risk for LLE compared to depressive episode (OR 8.72, 95% CI: 3.53-21.52, p<0.001) or NAP episode (OR 3.96, 95% CI: 2.16-7.26, p<0.001) after controlling for relevant confounders. Acute manic episode, leading to hospitalization, is associated with an increased risk of LLE, compared to NAP or depressive episode, suggesting causal relationship between mood and fluid imbalance. Yet, future prospective studies are needed to rule out the contribution of physical agitation and lithium treatment. © 2013.
Attentional Episodes in Visual Perception
ERIC Educational Resources Information Center
Wyble, Brad; Potter, Mary C.; Bowman, Howard; Nieuwenstein, Mark
2011-01-01
Is one's temporal perception of the world truly as seamless as it appears? This article presents a computationally motivated theory suggesting that visual attention samples information from temporal episodes (episodic simultaneous type/serial token model; Wyble, Bowman, & Nieuwenstein, 2009). Breaks between these episodes are punctuated by periods…
Saive, Anne-Lise; Royet, Jean-Pierre; Garcia, Samuel; Thévenet, Marc; Plailly, Jane
2015-01-01
Episodic memory is defined as the conscious retrieval of specific past events. Whether accurate episodic retrieval requires a recollective experience or if a feeling of knowing is sufficient remains unresolved. We recently devised an ecological approach to investigate the controlled cued-retrieval of episodes composed of unnamable odors (What) located spatially (Where) within a visual context (Which context). By combining the Remember/Know procedure with our laboratory-ecological approach in an original way, the present study demonstrated that the accurate odor-evoked retrieval of complex and multimodal episodes overwhelmingly required conscious recollection. A feeling of knowing, even when associated with a high level of confidence, was not sufficient to generate accurate episodic retrieval. Interestingly, we demonstrated that the recollection of accurate episodic memories was promoted by odor retrieval-cue familiarity and describability. In conclusion, our study suggested that semantic knowledge about retrieval-cues increased the recollection which is the state of awareness required for the accurate retrieval of complex episodic memories. PMID:26630170
Spectral lags in different episodes of gamma-ray bursts
NASA Astrophysics Data System (ADS)
Jia, LanWei; Yi, TingFeng; Liang, EnWei
2013-08-01
A systematical analysis of the spectral lags in different episodes within a gamma-ray burst (GRB) for the BATSE GRB sample is given. The identified episodes are usually a single pulse with mixing of small fluctuations. The spectral lags were calculated for lightcurves in the 25-55 keV and 110-320 keV bands. No universal spectral lag evolution feature in different episodes within a GRB were found for most GRBs. Among 362 bright GRBs that have at least three well-identified episodes, 19 of them show long-to-short lag and 19 of them show short-to-long lag in successive episodes. The other 324 GRBs have no clear evolution trend. Defining the specified lag with the ratio of the spectral lag to the episode duration in 110-320 keV band, no prominent case of specified lag was found showing clear evolution features. The results suggest that the observed spectral lag may contribute to the dynamics and/or the radiation physics of a given emission episode.
Episodic Memories in Anxiety Disorders: Clinical Implications
Zlomuzica, Armin; Dere, Dorothea; Machulska, Alla; Adolph, Dirk; Dere, Ekrem; Margraf, Jürgen
2014-01-01
The aim of this review is to summarize research on the emerging role of episodic memories in the context of anxiety disorders (AD). The available literature on explicit, autobiographical, and episodic memory function in AD including neuroimaging studies is critically discussed. We describe the methodological diversity of episodic memory research in AD and discuss the need for novel tests to measure episodic memory in a clinical setting. We argue that alterations in episodic memory functions might contribute to the etiology of AD. We further explain why future research on the interplay between episodic memory function and emotional disorders as well as its neuroanatomical foundations offers the promise to increase the effectiveness of modern psychological treatments. We conclude that one major task is to develop methods and training programs that might help patients suffering from AD to better understand, interpret, and possibly actively use their episodic memories in a way that would support therapeutic interventions and counteract the occurrence of symptoms. PMID:24795583
Saive, Anne-Lise; Royet, Jean-Pierre; Garcia, Samuel; Thévenet, Marc; Plailly, Jane
2015-01-01
Episodic memory is defined as the conscious retrieval of specific past events. Whether accurate episodic retrieval requires a recollective experience or if a feeling of knowing is sufficient remains unresolved. We recently devised an ecological approach to investigate the controlled cued-retrieval of episodes composed of unnamable odors (What) located spatially (Where) within a visual context (Which context). By combining the Remember/Know procedure with our laboratory-ecological approach in an original way, the present study demonstrated that the accurate odor-evoked retrieval of complex and multimodal episodes overwhelmingly required conscious recollection. A feeling of knowing, even when associated with a high level of confidence, was not sufficient to generate accurate episodic retrieval. Interestingly, we demonstrated that the recollection of accurate episodic memories was promoted by odor retrieval-cue familiarity and describability. In conclusion, our study suggested that semantic knowledge about retrieval-cues increased the recollection which is the state of awareness required for the accurate retrieval of complex episodic memories.
Dimsdale-Zucker, Halle R; Ritchey, Maureen; Ekstrom, Arne D; Yonelinas, Andrew P; Ranganath, Charan
2018-01-18
The hippocampus plays a critical role in spatial and episodic memory. Mechanistic models predict that hippocampal subfields have computational specializations that differentially support memory. However, there is little empirical evidence suggesting differences between the subfields, particularly in humans. To clarify how hippocampal subfields support human spatial and episodic memory, we developed a virtual reality paradigm where participants passively navigated through houses (spatial contexts) across a series of videos (episodic contexts). We then used multivariate analyses of high-resolution fMRI data to identify neural representations of contextual information during recollection. Multi-voxel pattern similarity analyses revealed that CA1 represented objects that shared an episodic context as more similar than those from different episodic contexts. CA23DG showed the opposite pattern, differentiating between objects encountered in the same episodic context. The complementary characteristics of these subfields explain how we can parse our experiences into cohesive episodes while retaining the specific details that support vivid recollection.
Neural Changes Underlying the Development of Episodic Memory During Middle Childhood
Ghetti, Simona; Bunge, Silvia A.
2012-01-01
Episodic memory is central to the human experience. In typically developing children, episodic memory improves rapidly during middle childhood. While the developmental cognitive neuroscience of episodic memory remains largely uncharted, recent research has begun to provide important insights. It has long been assumed that hippocampus-dependent binding mechanisms are in place by early childhood, and that improvements in episodic memory observed during middle childhood result from the protracted development of the prefrontal cortex. We revisit the notion that binding mechanisms are age-invariant, and propose that changes in the hippocampus and its projections to cortical regions also contribute to the development of episodic memory. We further review the role of developmental changes in lateral prefrontal and parietal cortices in this development. Finally, we discuss changes in white matter tracts connecting brain regions that are critical for episodic memory. Overall, we argue that changes in episodic memory emerge from the concerted effort of a network of relevant brain structures. PMID:22770728
Contrasts in the Behavior of Tremor Episodes in Cascadia and Japan
NASA Astrophysics Data System (ADS)
Armbruster, J. G.
2016-12-01
Tectonic tremor is observed in episodes with varying duration, intensity and spatial extent. In Cascadia the POLARIS broadband deployment, 2003-2006, provides good coverage of the southern Vancouver Island region with strong, widely distributed tremor sources extending 100 km along the plate interface. There the tremor can be classified into major episodes occurring at 14 month intervals with duration 20-30 days and minor episodes lasting hours to 10 days. Within that shorter duration minor episodes can produce strong signals. There is a clear pattern that minor episodes are located at the deeper part of the plate interface, 43-50 km deep. Major episodes are mostly generated from the shallower, 33-43 km deep, portion of the plate interface with some activation of the deeper sources. This suggests a simple mechanism of stress loading from below, transmitted upward by the tremor/slow-slip episodes. We compare this to the northern Kii Peninsula region of southwest Japan which has strong tremor sources extending 100 km along strike covered by HINET stations and find differences. The spectrum of episode durations in Japan, from less than an hour to 13 days, are not easily classified into major and minor. The range in depth observed in Japan is narrower than in Cascadia, 34-45 km for 98% of the clustered events. Here we divide the episodes into three groups based on their spatial extent. Large episodes occur at intervals of 6 months and occupy the southern 2/3, northern 2/3 or whole of the 100 km long zone. The small episodes are predominately seen from paired sources at the top and bottom of the active zone located where large episodes terminate. Intermediate episodes are the fewest in number and extend from the bottom to the top, often encompassing pairs of small sources. The observations in Japan will require a more complex model of stress loading. These results were achieved with the cross-station location method. The envelope location method might not have sufficient resolution to resolve these patterns in Japan.
NASA Astrophysics Data System (ADS)
Janecke, Susanne U.
1992-12-01
Cenozoic crustal extension in east central Idaho began about 50 Ma and continues at present. Three distinct episodes characterize one of the longest intervals of Cenozoic extension yet documented in the North America Cordillera. Crosscutting relationships between NE striking normal faults and volcanic rocks, regional dike trends, and slickenline data indicate NW-SE extension during peak Eocene volcanism about 49-48 Ma (episode 1). NE striking normal faults, with at most a few kilometers of offset, formed in an intraarc setting during rapid NE subduction of oceanic plates under the Pacific Northwest. North to NNW striking and west dipping normal faults, with offsets up to 10-15 km, formed during a younger middle Eocene to Oligocene basin-forming event (episode 2). This newly documented episode was the most important extensional event in east central Idaho and began during the waning phases of Challis volcanism. WSW-ENE to SW-NE extension during episode 2 was nearly perpendicular to the extension direction during episode 1 and perpendicular to the grain of the Idaho-Montana fold and thrust belt. The flip in extension direction between episode 1 and episode 2 is tightly constrained by 40Ar/39Ar age determinations to have taken place at the end of Eocene Challis magmatism about 46-48 Ma. I infer that plate boundary forces controlled the geometry of normal faults and dikes during episode 1, whereas internal stresses within previously thickened crust drove major SW to WSW directed extension during episode 2. A drop in convergence rates between the North American and Farallon plates between 59 Ma and 42 Ma (Stock and Molnar, 1988) may coincide with the onset of gravitational spreading during episode 2 and may also explain the abrupt end of Eocene magmatism in the Pacific Northwest. Miocene and younger SW dipping Basin and Range faults (episode 3) extended the region in a NE-SW direction. Although faults formed during episode 2 and episode 3 are not parallel, slickenlines indicate only small changes in slip vector trends, suggesting little rotation of the extension direction in east central Idaho since 46 Ma.
Guillery-Girard, B; Quinette, P; Desgranges, B; Piolino, P; Viader, F; de la Sayette, V; Eustache, F
2006-11-01
Several studies noted persistence of memory impairment following an episode of transient global amnesia (TGA) with standard tests. To specify long-term memory impairments in a group of patients selected with stringent criteria. Both retrograde and anterograde memory were investigated in 32 patients 13-67 months after a TGA episode with original tasks encompassing retrograde semantic memory (academic, public and personal knowledge), retrograde episodic memory (autobiographical events) and anterograde episodic memory. Patients had preserved academic and public knowledge. Pathological scores were obtained in personal verbal fluency for the two most recent periods, and patients produced less autobiographical events than controls. However, when they were provided time to detail, memories were as episodic as in controls regardless of their remoteness. Anterograde episodic tasks revealed a mild but significant impairment of the capacity of re-living the condition of encoding, i.e. the moment at which words were presented. Patients who have suffered from an episode of TGA manifest deficits of memory focused on the retrieval of both recent semantic information and episodic memories and especially the capacity of re-living. These deficits may not result from a deterioration of memory per se but rather from difficulties in accessing memories.
Alcohol Storylines in Television Episodes: The Preventive Effect of Countering Epilogues.
Russell, Cristel Antonia; Russell, Dale Wesley; Grube, Joel W; McQuarrie, Edward
2017-08-01
This experimental study assessed whether alcohol television storylines impact youth drinking attitudes and intentions and whether corrective epilogues can potentially moderate this impact. Television episodes were professionally produced to depict heavy drinking leading to either positive or negative consequences. The pro- and anti-alcohol episodes were shown alone or with an epilogue where a main character discussed the deleterious effects of excessive drinking. Attitudes toward drinkers and drinking intentions were measured subsequently, along with reactions to the episode and demographic data, among participants aged 14-17 using an online study. Exposure to the pro-alcohol episode was related to more positive attitudes toward drinkers. Including an epilogue after a pro-alcohol episode was related to more negative viewers' attitudes toward drinkers and lower drinking intentions compared to a pro-alcohol episode with no epilogue. By contrast, including an epilogue after an anti-alcohol episode was unrelated to attitudes toward drinkers or drinking intentions. Viewing a single television episode with a pro-alcohol message may lead to more positive attitudes toward drinkers. The finding that a brief epilogue may reduce the impact of the pro-alcohol storyline suggests easily implemented preventive strategies to counter the adverse impact of substance use portrayals in entertainment programming.
Iwata, Saeko; Tsukiura, Takashi
2017-11-01
Episodic memory is defined as memory for personally experienced events, and includes memory content and contextual information of time and space. Previous neuroimaging and neuropsychological studies have demonstrated three possible roles of the temporal context in episodic memory. First, temporal information contributes to the arrangement of temporal order for sequential events in episodic memory, and this process is involved in the lateral prefrontal cortex. The second possible role of temporal information in episodic memory is the segregation between memories of multiple events, which are segregated by cues of different time information. The role of segregation is associated with the orbitofrontal regions including the orbitofrontal cortex and basal forebrain region. Third, temporal information in episodic memory plays an important role in the integration of multiple components into a coherent episodic memory, in which episodic components in the different modalities are combined by temporal information as an index. The role of integration is mediated by the medial temporal lobe including the hippocampus and parahippocampal gyrus. Thus, temporal information in episodic memory could be represented in multiple stages, which are involved in a network of the lateral prefrontal, orbitofrontal, and medial temporal lobe regions.
Episodic autobiographical memory is associated with variation in the size of hippocampal subregions.
Palombo, Daniela J; Bacopulos, Agnes; Amaral, Robert S C; Olsen, Rosanna K; Todd, Rebecca M; Anderson, Adam K; Levine, Brian
2018-02-01
Striking individual differences exist in the human capacity to recollect past events, yet, little is known about the neural correlates of such individual differences. Studies investigating hippocampal volume in relation to individual differences in laboratory measures of episodic memory in young adults suggest that whole hippocampal volume is unrelated (or even negatively associated) with episodic memory. However, anatomical and functional specialization across hippocampal subregions suggests that individual differences in episodic memory may be linked to particular hippocampal subregions, as opposed to whole hippocampal volume. Given that the DG/CA 2/3 circuitry is thought to be especially critical for supporting episodic memory in humans, we predicted that the volume of this region would be associated with individual variability in episodic memory. This prediction was supported using high-resolution MRI of the hippocampal subfields and measures of real-world (autobiographical) episodic memory. In addition to the association with DG/CA 2/3 , we further observed a relationship between episodic autobiographical memory and subiculum volume, whereas no association was observed with CA 1 or with whole hippocampal volume. These findings provide insight into the possible neural substrates that mediate individual differences in real-world episodic remembering in humans. © 2017 Wiley Periodicals, Inc.
Multimodal Feature Integration in the Angular Gyrus during Episodic and Semantic Retrieval
Bonnici, Heidi M.; Richter, Franziska R.; Yazar, Yasemin
2016-01-01
Much evidence from distinct lines of investigation indicates the involvement of angular gyrus (AnG) in the retrieval of both episodic and semantic information, but the region's precise function and whether that function differs across episodic and semantic retrieval have yet to be determined. We used univariate and multivariate fMRI analysis methods to examine the role of AnG in multimodal feature integration during episodic and semantic retrieval. Human participants completed episodic and semantic memory tasks involving unimodal (auditory or visual) and multimodal (audio-visual) stimuli. Univariate analyses revealed the recruitment of functionally distinct AnG subregions during the retrieval of episodic and semantic information. Consistent with a role in multimodal feature integration during episodic retrieval, significantly greater AnG activity was observed during retrieval of integrated multimodal episodic memories compared with unimodal episodic memories. Multivariate classification analyses revealed that individual multimodal episodic memories could be differentiated in AnG, with classification accuracy tracking the vividness of participants' reported recollections, whereas distinct unimodal memories were represented in sensory association areas only. In contrast to episodic retrieval, AnG was engaged to a statistically equivalent degree during retrieval of unimodal and multimodal semantic memories, suggesting a distinct role for AnG during semantic retrieval. Modality-specific sensory association areas exhibited corresponding activity during both episodic and semantic retrieval, which mirrored the functional specialization of these regions during perception. The results offer new insights into the integrative processes subserved by AnG and its contribution to our subjective experience of remembering. SIGNIFICANCE STATEMENT Using univariate and multivariate fMRI analyses, we provide evidence that functionally distinct subregions of angular gyrus (AnG) contribute to the retrieval of episodic and semantic memories. Our multivariate pattern classifier could distinguish episodic memory representations in AnG according to whether they were multimodal (audio-visual) or unimodal (auditory or visual) in nature, whereas statistically equivalent AnG activity was observed during retrieval of unimodal and multimodal semantic memories. Classification accuracy during episodic retrieval scaled with the trial-by-trial vividness with which participants experienced their recollections. Therefore, the findings offer new insights into the integrative processes subserved by AnG and how its function may contribute to our subjective experience of remembering. PMID:27194327
Multimodal Feature Integration in the Angular Gyrus during Episodic and Semantic Retrieval.
Bonnici, Heidi M; Richter, Franziska R; Yazar, Yasemin; Simons, Jon S
2016-05-18
Much evidence from distinct lines of investigation indicates the involvement of angular gyrus (AnG) in the retrieval of both episodic and semantic information, but the region's precise function and whether that function differs across episodic and semantic retrieval have yet to be determined. We used univariate and multivariate fMRI analysis methods to examine the role of AnG in multimodal feature integration during episodic and semantic retrieval. Human participants completed episodic and semantic memory tasks involving unimodal (auditory or visual) and multimodal (audio-visual) stimuli. Univariate analyses revealed the recruitment of functionally distinct AnG subregions during the retrieval of episodic and semantic information. Consistent with a role in multimodal feature integration during episodic retrieval, significantly greater AnG activity was observed during retrieval of integrated multimodal episodic memories compared with unimodal episodic memories. Multivariate classification analyses revealed that individual multimodal episodic memories could be differentiated in AnG, with classification accuracy tracking the vividness of participants' reported recollections, whereas distinct unimodal memories were represented in sensory association areas only. In contrast to episodic retrieval, AnG was engaged to a statistically equivalent degree during retrieval of unimodal and multimodal semantic memories, suggesting a distinct role for AnG during semantic retrieval. Modality-specific sensory association areas exhibited corresponding activity during both episodic and semantic retrieval, which mirrored the functional specialization of these regions during perception. The results offer new insights into the integrative processes subserved by AnG and its contribution to our subjective experience of remembering. Using univariate and multivariate fMRI analyses, we provide evidence that functionally distinct subregions of angular gyrus (AnG) contribute to the retrieval of episodic and semantic memories. Our multivariate pattern classifier could distinguish episodic memory representations in AnG according to whether they were multimodal (audio-visual) or unimodal (auditory or visual) in nature, whereas statistically equivalent AnG activity was observed during retrieval of unimodal and multimodal semantic memories. Classification accuracy during episodic retrieval scaled with the trial-by-trial vividness with which participants experienced their recollections. Therefore, the findings offer new insights into the integrative processes subserved by AnG and how its function may contribute to our subjective experience of remembering. Copyright © 2016 Bonnici, Richter, et al.
The Episodic Nature of Episodic-Like Memories
ERIC Educational Resources Information Center
Easton, Alexander; Webster, Lisa A. D.; Eacott, Madeline J.
2012-01-01
Studying episodic memory in nonhuman animals has proved difficult because definitions in humans require conscious recollection. Here, we assessed humans' experience of episodic-like recognition memory tasks that have been used with animals. It was found that tasks using contextual information to discriminate events could only be accurately…
ERIC Educational Resources Information Center
Conway, Martin A.
2009-01-01
An account of episodic memories is developed that focuses on the types of knowledge they represent, their properties, and the functions they might serve. It is proposed that episodic memories consist of "episodic elements," summary records of experience often in the form of visual images, associated to a "conceptual frame" that provides a…
Provider Profiling: A Population Health Improvement Tool for the Southeast Military Health System
1999-06-01
weeks to five years of age who were diagnosed with a first episode of uncomplicated episode of acute otitis media and were prescribed an antibiotic...episode of uncomplicated episode of acute otitis media and were prescribed an antibiotic other than a preferred antimicrobial agent. DENOMINATOR Number of...enrolled children six weeks to five years of age who were diagnosed with a first episode of acute otitis media . Benchmark INDUSTRY STANDARD Measure
Plastic modulation of episodic memory networks in the aging brain with cognitive decline.
Bai, Feng; Yuan, Yonggui; Yu, Hui; Zhang, Zhijun
2016-07-15
Social-cognitive processing has been posited to underlie general functions such as episodic memory. Episodic memory impairment is a recognized hallmark of amnestic mild cognitive impairment (aMCI) who is at a high risk for dementia. Three canonical networks, self-referential processing, executive control processing and salience processing, have distinct roles in episodic memory retrieval processing. It remains unclear whether and how these sub-networks of the episodic memory retrieval system would be affected in aMCI. This task-state fMRI study constructed systems-level episodic memory retrieval sub-networks in 28 aMCI and 23 controls using two computational approaches: a multiple region-of-interest based approach and a voxel-level functional connectivity-based approach, respectively. These approaches produced the remarkably similar findings that the self-referential processing network made critical contributions to episodic memory retrieval in aMCI. More conspicuous alterations in self-referential processing of the episodic memory retrieval network were identified in aMCI. In order to complete a given episodic memory retrieval task, increases in cooperation between the self-referential processing network and other sub-networks were mobilized in aMCI. Self-referential processing mediate the cooperation of the episodic memory retrieval sub-networks as it may help to achieve neural plasticity and may contribute to the prevention and treatment of dementia. Copyright © 2016 Elsevier B.V. All rights reserved.
Benoit, Roland G.; Schacter, Daniel L.
2015-01-01
It has been suggested that the simulation of hypothetical episodes and the recollection of past episodes are supported by fundamentally the same set of brain regions. The present article specifies this core network via Activation Likelihood Estimation (ALE). Specifically, a first meta-analysis revealed joint engagement of core network regions during episodic memory and episodic simulation. These include parts of the medial surface, the hippocampus and parahippocampal cortex within the medial temporal lobes, and the lateral temporal and inferior posterior parietal cortices on the lateral surface. Both capacities also jointly recruited additional regions such as parts of the bilateral dorsolateral prefrontal cortex. All of these core regions overlapped with the default network. Moreover, it has further been suggested that episodic simulation may require a stronger engagement of some of the core network’s nodes as wells as the recruitment of additional brain regions supporting control functions. A second ALE meta-analysis indeed identified such regions that were consistently more strongly engaged during episodic simulation than episodic memory. These comprised the core-network clusters located in the left dorsolateral prefrontal cortex and posterior inferior parietal lobe and other structures distributed broadly across the default and fronto-parietal control networks. Together, the analyses determine the set of brain regions that allow us to experience past and hypothetical episodes, thus providing an important foundation for studying the regions’ specialized contributions and interactions. PMID:26142352
Rosen, Allison B.; Aizcorbe, Ana; Ryu, Alexander J.; Nestoriak, Nicole; Cutler, David M.; Chernew, Michael E.
2015-01-01
Bundled payment entails paying a single price for all services delivered as part of an episode of care for a specific condition. It is seen as a promising way to slow the growth of health care spending while maintaining or improving the quality of care. To implement bundled payment, policy makers must set base payment rates for episodes of care and update the rates over time to reflect changes in the costs of delivering care and the components of care. Adopting the fee-for-service paradigm of adjusting payments with uniform update rates would be fair and accurate if costs increased at a uniform rate across episodes. But our analysis of 2003 and 2007 US commercial claims data showed spending growth to be highly skewed across episodes: 10 percent of episodes accounted for 82.5 percent of spending growth, and within-episode spending growth ranged from a decline of 75 percent to an increase of 323 percent. Given that spending growth was much faster for some episodes than for others, a situation known as skewness, policy makers should not update episode payments using uniform update rates. Rather, they should explore ways to address variations in spending growth, such as updating episode payments one by one, at least at the outset. PMID:23650329
Examining Duration of Binge Eating Episodes in Binge Eating Disorder
Schreiber-Gregory, Deanna N.; Lavender, Jason M.; Engel, Scott G.; Wonderlich, Steve A.; Crosby, Ross D.; Peterson, Carol B.; Simonich, Heather; Crow, Scott; Durkin, Nora; Mitchell, James E.
2013-01-01
Objective The primary goal of this paper is to examine and clarify characteristics of binge eating in individuals with binge eating disorder (BED), particularly the duration of binge eating episodes, as well as potential differences between individuals with shorter compared to longer binge eating episodes. Method Two studies exploring binge eating characteristics in BED were conducted. Study 1 examined differences in clinical variables among individuals (N = 139) with BED who reported a short (< 2 hours) versus long (≥ 2 hours) average binge duration. Study 2 utilized an ecological momentary assessment (EMA) design to examine the duration and temporal pattern of binge eating episodes in the natural environment in a separate sample of nine women with BED. Results Participants in Study 1 who were classified as having long duration binge eating episodes displayed greater symptoms of depression and lower self-esteem, but did not differ on other measures of eating disorder symptoms, compared to those with short duration binge eating episodes. In Study 2, the average binge episode duration was approximately 42 minutes, and binge eating episodes were most common during the early afternoon and evening hours, as well as more common on weekdays versus weekends. Discussion Past research on binge episode characteristics, particularly duration, has been limited to studies of binge eating episodes in BN. This study contributes to the existing literature on characteristics of binge eating in BED. PMID:23881639
Impact of episodic thinking on altruism
Yi, Richard; Pickover, Alison; Stuppy-Sullivan, Allison M.; Baker, Sydney; Landes, Reid D.
2016-01-01
Episodic future thinking, which refers to the use of prospective imagery to concretely imagine oneself in future scenarios, has been shown to reduce delay discounting (enhance self-control). A parallel approach, in which prospective imagery is used to concretely imagine other’s scenarios, may similarly reduce social discounting (i.e., enhance altruism). In study 1, participants engaged in episodic thinking about the self or others, in a repeated-measures design, while completing a social discounting task. Reductions in social discounting were observed as a function of episodic thinking about others, though an interaction with order was also observed. Using an independent-measures design in study 2, the effect of episodic thinking about others was replicated. Study 3 addressed a limitation of studies 1 and 2, the possibility that simply thinking about others decreased social discounting. Capitalizing on Construal Level Theory, which specifies that social distance and time in the future are both dimensions of a common psychological distance, we hypothesized that episodic future thinking should also decrease social discounting. Participants engaged in episodic future thinking or episodic present thinking, in a repeated-measures design, while completing a social discounting task. The pattern of results was similar to study 1, providing support for the notion that episodic thinking about psychologically distant outcomes (for others or in the future) reduces social discounting. Application of similar episodic thinking approaches may enhance altruism. PMID:27821875
Compare, A; Brugnera, Agostino; Adorni, R; Sakatani, K
2016-01-01
The neurophysiological mechanism of positive versus negative emotions is insufficiently understood. In the present study, we examined the effect of event recall tasks on the prefrontal cortex (PFC) activity using near infrared spectroscopy (NIRS). Nine healthy adults were instructed to recall episodes of their life associated with positive (happiness) and negative (anger) emotion, both silently and verbally. Heart rate (HR) changes were simultaneously measured. NIRS showed an increased oxyhemoglobin (oxy-Hb) in the bilateral PFC during silent and verbal recall of both positive and negative episodes. The changes of oxy-Hb in the bilateral PFC during silent recall of negative episodes were significantly larger than those during silent recall of positive episodes (p < 0.01). There was no difference in average changes of oxy-Hb between silent and verbal recall of negative episodes (p > 0.95), while changes of oxy-Hb during verbal recall of positive episodes were larger than those during silent recall of positive episodes (p < 0.05). Both verbal and silent recall of positive and negative episodes increased HR; however, verbal recall caused larger increases of HR than silent recall (p < 0.01). The present results suggest that recall of negative episodes affect the PFC activity, which plays a key role in cognitive control of emotions, more than positive episodes.
La Corte, Valentina; Dalla Barba, Gianfranco; Lemaréchal, Jean-Didier; Garnero, Line; George, Nathalie
2012-10-01
The relationship between episodic and semantic memory systems has long been debated. Some authors argue that episodic memory is contingent on semantic memory (Tulving 1984), while others postulate that both systems are independent since they can be selectively damaged (Squire 1987). The interaction between these memory systems is particularly important in the elderly, since the dissociation of episodic and semantic memory defects characterize different aging-related pathologies. Here, we investigated the interaction between semantic knowledge and episodic memory processes associated with faces in elderly subjects using an experimental paradigm where the semantic encoding of famous and unknown faces was compared to their episodic recognition. Results showed that the level of semantic awareness of items affected the recognition of those items in the episodic memory task. Event-related magnetic fields confirmed this interaction between episodic and semantic memory: ERFs related to the old/new effect during the episodic task were markedly different for famous and unknown faces. The old/new effect for famous faces involved sustained activities maximal over right temporal sensors, showing a spatio-temporal pattern partly similar to that found for famous versus unknown faces during the semantic task. By contrast, an old/new effect for unknown faces was observed on left parieto-occipital sensors. These findings suggest that the episodic memory for famous faces activated the retrieval of stored semantic information, whereas it was based on items' perceptual features for unknown faces. Overall, our results show that semantic information interfered markedly with episodic memory processes and suggested that the neural substrates of these two memory systems overlap.
[A new assessment for episodic memory. Episodic memory test and caregiver's episodic memory test].
Ojea Ortega, T; González Álvarez de Sotomayor, M M; Pérez González, O; Fernández Fernández, O
2013-10-01
The purpose of the episodic memory test and the caregiver's episodic memory test is to evaluate episodic memory according to its definition in a way that is feasible for families and achieves high degrees of sensitivity and specificity. We administered a test consisting of 10 questions about episodic events to 332 subjects, of whom 65 had Alzheimer's disease (AD), 115 had amnestic MCI (aMCI) and 152 showed no cognitive impairment according to Reisberg's global deterioration scale (GDS). We calculated the test's sensitivity and specificity to distinguish AD from episodic aMCI and from normal ageing. The area under the ROC curve for the diagnosis of aMCI was 0.94 and the best cut-off value was 20; for that value, sensitivity was 89% and specificity was 82%. For a diagnosis of AD, the area under the ROC curve was 0.99 and the best cut-off point was 17, with a sensitivity of 98% and a specificity of 91%. A subsequent study using similar methodology yielded similar results when the test was administered directly by the caregiver. The episodic memory test and the caregiver's episodic memory test are useful as brief screening tools for identifying patients with early-stage AD. It is suitable for use by primary care medical staff and in the home, since it can be administered by a caregiver. The test's limitations are that it must be administered by a reliable caregiver and the fact that it measures episodic memory only. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.
Brunette, Amanda M; Calamia, Matthew; Black, Jenah; Tranel, Daniel
2018-06-11
Episodic future thinking is the ability to mentally project oneself into the future. This construct has been explored extensively in cognitive neuroscience and may be relevant for adaptive functioning. However, it has not been determined whether the measurement of episodic future thinking might be valuable in a clinical neuropsychological setting. The current study investigated (1) the relationship between episodic future thinking and instrumental activities of daily living (IADLs); and (2) whether episodic future thinking is related to IADLs over and above standard measures of cognition. Sixty-one older adults with heterogeneous neurological conditions and 41 healthy older adults completed a future thinking task (the adapted Autobiographical Interview), a performance-based measure of instrumental activities of daily living (the Independent Living Scales), and standard clinical measures of memory and executive functioning. Episodic future thinking significantly predicted IADLs after accounting for age, education, gender, and depression (increase in R2 = .050, p = .010). Episodic future thinking significantly predicted IADLs over and above executive functioning (increase in R2 = .025, p = .030), but was not predictive of IADLs over and above memory (p = .157). This study suggests that episodic future thinking is significantly associated with IADLs, beyond what can be accounted for by executive functioning. However, episodic future thinking did not predict IADLs over and above memory. Overall, there is limited evidence for the clinical utility of episodic future thinking. The findings suggest that an episodic future thinking task does not provide enough valuable information about IADLs to justify its inclusion in a clinical neuropsychological setting.
2013-01-01
Objective: There appears to be a common network of brain regions that underlie the ability to recall past personal experiences (episodic memory) and the ability to imagine possible future personal experiences (episodic future thinking). At the cognitive level, these abilities are thought to rely on “scene construction” (the ability to bind together multimodal elements of a scene in mind—dependent on hippocampal functioning) and temporal “self-projection” (the ability to mentally project oneself through time—dependent on prefrontal cortex functioning). Although autism spectrum disorder (ASD) is characterized by diminished episodic memory, it is unclear whether episodic future thinking is correspondingly impaired. Moreover, the underlying basis of such impairments (difficulties with scene construction, self-projection, or both) is yet to be established. The current study therefore aimed to elucidate these issues. Method: Twenty-seven intellectually high-functioning adults with ASD and 29 age- and IQ-matched neurotypical comparison adults were asked to describe (a) imagined atemporal, non-self-relevant fictitious scenes (assessing scene construction), (b) imagined plausible self-relevant future episodes (assessing episodic future thinking), and (c) recalled personally experienced past episodes (assessing episodic memory). Tests of narrative ability and theory of mind were also completed. Results: Performances of participants with ASD were significantly and equally diminished in each condition and, crucially, this diminution was independent of general narrative ability. Conclusions: Given that participants with ASD were impaired in the fictitious scene condition, which does not involve self-projection, we suggest the underlying difficulty with episodic memory/future thinking is one of scene construction. PMID:24015827
Lind, Sophie E; Williams, David M; Bowler, Dermot M; Peel, Anna
2014-01-01
There appears to be a common network of brain regions that underlie the ability to recall past personal experiences (episodic memory) and the ability to imagine possible future personal experiences (episodic future thinking). At the cognitive level, these abilities are thought to rely on "scene construction" (the ability to bind together multimodal elements of a scene in mind--dependent on hippocampal functioning) and temporal "self-projection" (the ability to mentally project oneself through time--dependent on prefrontal cortex functioning). Although autism spectrum disorder (ASD) is characterized by diminished episodic memory, it is unclear whether episodic future thinking is correspondingly impaired. Moreover, the underlying basis of such impairments (difficulties with scene construction, self-projection, or both) is yet to be established. The current study therefore aimed to elucidate these issues. Twenty-seven intellectually high-functioning adults with ASD and 29 age- and IQ-matched neurotypical comparison adults were asked to describe (a) imagined atemporal, non-self-relevant fictitious scenes (assessing scene construction), (b) imagined plausible self-relevant future episodes (assessing episodic future thinking), and (c) recalled personally experienced past episodes (assessing episodic memory). Tests of narrative ability and theory of mind were also completed. Performances of participants with ASD were significantly and equally diminished in each condition and, crucially, this diminution was independent of general narrative ability. Given that participants with ASD were impaired in the fictitious scene condition, which does not involve self-projection, we suggest the underlying difficulty with episodic memory/future thinking is one of scene construction.
Process analysis of regional aerosol pollution during spring in the Pearl River Delta region, China
NASA Astrophysics Data System (ADS)
Fan, Qi; Lan, Jing; Liu, Yiming; Wang, Xuemei; Chan, Pakwai; Hong, Yingying; Feng, Yerong; Liu, Yexin; Zeng, Yanjun; Liang, Guixiong
2015-12-01
A numerical simulation analysis was performed for three air pollution episodes in the Pearl River Delta (PRD) region during March 2012 using the third-generation air quality modeling system Models-3/CMAQ. The results demonstrated that particulate matter was the primary pollutant for all three pollution episodes and was accompanied by relatively low visibility in the first two episodes. Weather maps indicate that the first two episodes occurred under the influence of warm, wet southerly air flow systems that led to high humidity throughout the region. The liquid phase reaction of gaseous pollutants resulted in the generation of fine secondary particles, which were identified as the primary source of pollution in the first two episodes. The third pollution episode occurred during a warming period following a cold front. Relative humidity was lower during this episode, and coarse particles were the major pollution contributor. Results of process analysis indicated that emissions sources, horizontal transport and vertical transport were the primary factors affecting pollutant concentrations within the near-surface layer during all three episodes, while aerosol processes, cloud processes, horizontal transport and vertical transport had greater influence at approximately 900 m above ground. Cloud processes had a greater impact during the first two pollution episodes because of the higher relative humidity. In addition, by comparing pollution processes from different cities (Guangzhou and Zhongshan), the study revealed that the first two pollution episodes were the result of local emissions within the PRD region and transport between surrounding cities, while the third episode exhibited prominent regional pollution characteristics and was the result of regional pollutant transport.
Depressive episode characteristics and subsequent recurrence risk.
Patten, Scott B; Williams, Jeanne V A; Lavorato, Dina H; Bulloch, Andrew G M; MacQueen, Glenda
2012-11-01
Clinical practice guidelines increasingly recognize the heterogeneity associated with major depressive episodes (MDE), e.g. through strategies such as watchful waiting. However, the implications of episode heterogeneity for long-term prognosis have not been adequately explored. In this project, we used data from a Canadian longitudinal study to evaluate recurrence risks for MDE after an initial episode in the mid-1990s. This study collected data from a community cohort between 1994/1995 and 2008/2009 using biannual interviews. Characteristics of the index episode: syndromal versus sub-syndromal, duration of symptoms, and indicators of seriousness (activity restriction, high distress or suicidal ideation) were recorded. The ability of these variables to predict MDE recurrence was explored using proportional hazards modeling. Additional analyses using generalized estimating equations were used to assess robustness. Even brief, sub-syndromal episodes not characterized by indicators of seriousness were associated with an increased risk of subsequent MDE. However, episodes meeting diagnostic criteria for MDE, those lasting longer than four weeks and those associated with indicators of seriousness were associated with much higher recurrence risk. Sub-syndromal episodes associated with these characteristics generally predicted subsequent MDE as strongly as the occurrence of MDE itself. The data source did not include assessment of all potentially relevant covariates. The assessment of MDE used an abbreviated instrument. Brief sub-syndromal episodes of depression are not usually targets of acute treatment, but such episodes have implications for subsequent MDE risk. Episode characteristics identify a range of outcomes that have potential implications for long-term management. Copyright © 2012 Elsevier B.V. All rights reserved.
Rats Remember Items in Context Using Episodic Memory.
Panoz-Brown, Danielle; Corbin, Hannah E; Dalecki, Stefan J; Gentry, Meredith; Brotheridge, Sydney; Sluka, Christina M; Wu, Jie-En; Crystal, Jonathon D
2016-10-24
Vivid episodic memories in people have been characterized as the replay of unique events in sequential order [1-3]. Animal models of episodic memory have successfully documented episodic memory of a single event (e.g., [4-8]). However, a fundamental feature of episodic memory in people is that it involves multiple events, and notably, episodic memory impairments in human diseases are not limited to a single event. Critically, it is not known whether animals remember many unique events using episodic memory. Here, we show that rats remember many unique events and the contexts in which the events occurred using episodic memory. We used an olfactory memory assessment in which new (but not old) odors were rewarded using 32 items. Rats were presented with 16 odors in one context and the same odors in a second context. To attain high accuracy, the rats needed to remember item in context because each odor was rewarded as a new item in each context. The demands on item-in-context memory were varied by assessing memory with 2, 3, 5, or 15 unpredictable transitions between contexts, and item-in-context memory survived a 45 min retention interval challenge. When the memory of item in context was put in conflict with non-episodic familiarity cues, rats relied on item in context using episodic memory. Our findings suggest that rats remember multiple unique events and the contexts in which these events occurred using episodic memory and support the view that rats may be used to model fundamental aspects of human cognition. Copyright © 2016 Elsevier Ltd. All rights reserved.
Children's and Adults' Abilities To Use Episodic and Semantic Information To Derive Inferences.
ERIC Educational Resources Information Center
Bourg, Tammy M.; And Others
A study investigated children's and adults' abilities to derive inferences requiring the integration of two episodic premises (episodic inferences) and inferences requiring the integration of one episodic premise with extra-stimulus, semantic knowledge. Subjects, 95 kindergarten, third grade, seventh grade, and college students, watched either an…
Evaluation of episodic acidification and amphibian declines in the Rocky Mountains
Frank A. Vertucci; Paul Stephen Corn
1996-01-01
We define criteria for documenting episodic acidification of amphibian breeding habitats and examine whether episodic acidification is responsible for observed declines of amphibian populations in the Rocky Mountains. Anthropogenic episodic acidification, caused by atmospheric deposition of sulfate and nitrate, occurs when the concentration of acid anions increases...
The Composition of Episodic Memory.
ERIC Educational Resources Information Center
Underwood, Benton J.; And Others
This study examined the interrelationships among a number of episodic memory tasks and among various attributes of memory. A sample of 200 college students was tested for ten sessions; 28 different measures of episodic memory were obtained. In addition, five measures of semantic memory were available. Results indicated that episodic and semantic…
42 CFR § 512.305 - Determination of the NPRA and reconciliation process.
Code of Federal Regulations, 2010 CFR
2017-10-01
... OF HEALTH AND HUMAN SERVICES (CONTINUED) HEALTH CARE INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL Pricing and Payment § 512.305 Determination of the NPRA and reconciliation process. (a... determine actual episode payments for each EPM episode for the performance year (except for episodes that...
Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings.
Tulving, E; Kapur, S; Craik, F I; Moscovitch, M; Houle, S
1994-01-01
Data are reviewed from positron emission tomography studies of encoding and retrieval processes in episodic memory. These data suggest a hemispheric encoding/retrieval asymmetry model of prefrontal involvement in encoding and retrieval of episodic memory. According to this model, the left and right prefrontal lobes are part of an extensive neuronal network that subserves episodic remembering, but the two prefrontal hemispheres play different roles. Left prefrontal cortical regions are differentially more involved in retrieval of information from semantic memory and in simultaneously encoding novel aspects of the retrieved information into episodic memory. Right prefrontal cortical regions, on the other hand, are differentially more involved in episodic memory retrieval. PMID:8134342
Ageing and autobiographical memory for emotional and neutral events
St. Jacques, Peggy L.; Levine, Brian
2007-01-01
We investigated age-related effects in recall of emotional and neutral autobiographical memories. Protocols were scored according to episodic and non-episodic detail categories using the Autobiographical Interview. Young adults recalled a greater number of episodic details compared to older adults, whereas older adults recalled more semantic details, replicating previous findings. Both young and older adults’ emotional memories contained more overall detail than neutral ones, with the enhancement from emotion-specific to episodic details, but this did not alter the effect of age group on the pattern of episodic and semantic details. However, the age effect on episodic details was attenuated for neutral autobiographical memories. The findings suggest that age differences for emotional autobiographical recollection might reflect a more general pattern of age-related changes in memory, with impaired recall of episodic components and relative sparing of semantic aspects of autobiographical memory in older adults when compared to young adults. PMID:17534107
Moral judgment in episodic amnesia.
Craver, Carl F; Keven, Nazim; Kwan, Donna; Kurczek, Jake; Duff, Melissa C; Rosenbaum, R Shayna
2016-08-01
To investigate the role of episodic thought about the past and future in moral judgment, we administered a well-established moral judgment battery to individuals with hippocampal damage and deficits in episodic thought (insert Greene et al. 2001). Healthy controls select deontological answers in high-conflict moral scenarios more frequently when they vividly imagine themselves in the scenarios than when they imagine scenarios abstractly, at some personal remove. If this bias is mediated by episodic thought, individuals with deficits in episodic thought should not exhibit this effect. We report that individuals with deficits in episodic memory and future thought make moral judgments and exhibit the biasing effect of vivid, personal imaginings on moral judgment. These results strongly suggest that the biasing effect of vivid personal imagining on moral judgment is not due to episodic thought about the past and future. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Sex differences in episodic memory: the impact of verbal and visuospatial ability.
Herlitz, A; Airaksinen, E; Nordström, E
1999-10-01
The impact of verbal and visuospatial ability on sex differences in episodic memory was investigated. One hundred men and 100 women, 2040 years old, participated in a series of verbal and visuospatial tasks. Episodic memory was assessed in tasks that, to a greater or lesser extent, were verbal or visuospatial in nature. Results showed that women excelled in verbal production tasks and that men performed at a superior level on a mental rotation task. In addition, women tended to perform at a higher level than men on most episodic memory tasks. Taken together, the results demonstrated that (a) women perform at a higher level than men on most verbal episodic memory tasks and on some episodic memory tasks with a visuospatial component, and (b) women's higher performance on episodic memory tasks cannot fully be explained by their superior performance on verbal production tasks.
Sylvers, Patrick; Landfield, Kristin E; Lilienfeld, Scott O
2011-01-01
This study extends the college heavy episodic drinking literature by examining the associations between features of psychopathy and antisocial personality disorder (ASPD), on the one hand, and heavy episodic drinking and associated problem behaviors, on the other. Participants were 159 (85 male, 74 female) undergraduates from a private university. Participants completed self-report measures assessing alcohol use, frequency, and consequences of heavy episodic drinking, and personality pathology. It was found that psychopathy, independent of ASPD, was related to the prediction of heavy episodic drinking frequency and problems associated with alcohol use. It was also found that the relation between traits of psychopathy and heavy episodic drinking are limited largely to the impulsive and antisocial aspects of this condition. These findings point to the need for further investigation of the association between psychopathy and ASPD traits and heavy episodic drinking behaviors in college students.
Database of episode-integrated solar energetic proton fluences
NASA Astrophysics Data System (ADS)
Robinson, Zachary D.; Adams, James H.; Xapsos, Michael A.; Stauffer, Craig A.
2018-04-01
A new database of proton episode-integrated fluences is described. This database contains data from two different instruments on multiple satellites. The data are from instruments on the Interplanetary Monitoring Platform-8 (IMP8) and the Geostationary Operational Environmental Satellites (GOES) series. A method to normalize one set of data to one another is presented to create a seamless database spanning 1973 to 2016. A discussion of some of the characteristics that episodes exhibit is presented, including episode duration and number of peaks. As an example of what can be understood about episodes, the July 4, 2012 episode is examined in detail. The coronal mass ejections and solar flares that caused many of the fluctuations of the proton flux seen at Earth are associated with peaks in the proton flux during this episode. The reasoning for each choice is laid out to provide a reference for how CME and solar flares associations are made.
Contextualization: Memory Formation and Retrieval in a Nested Environment
NASA Astrophysics Data System (ADS)
Piefke, Martina; Markowitsch, Hans J.
Episodic memory functions are highly context-dependent. This is true for both experimental and autobiographical episodic memory. We here review neuropsychological and neuroimaging evidence for effects of differential encoding and retrieval contexts on episodic memory performance as well as the underlying neurofunctional mechanisms. In studies of laboratory episodic memory, the influence of context parameters can be assessed by experimental manipulations. Such experiments suggest that contextual variables mainly affect prefrontal functions supporting executive processes involved in episodic learning and retrieval. Context parameters affecting episodic autobiographical memory are far more complex and cannot easily be controlled. Data support the view that not only prefrontal, but also further medial temporal and posterior parietal regions mediating the re-experience and emotional evaluation of personal memories are highly influenced by changing contextual variables of memory encoding and retrieval. Based on our review of available data, we thus suggest that experimental and autobiographical episodic memories are influenced by both overlapping and differential context parameters.
ERIC Educational Resources Information Center
Riggins, Tracy; Blankenship, Sarah L.; Mulligan, Elizabeth; Rice, Katherine; Redcay, Elizabeth
2015-01-01
Episodic memory shows striking improvement during early childhood. However, neural contributions to these behavioral changes are not well understood. This study examined associations between episodic memory and volume of subregions (head, body, and tail) of the hippocampus--a structure known to support episodic memory in school-aged children and…
ERIC Educational Resources Information Center
Long, Nicole M.; Kahana, Michael J.
2017-01-01
Although episodic and semantic memory share overlapping neural mechanisms, it remains unclear how our pre-existing semantic associations modulate the formation of new, episodic associations. When freely recalling recently studied words, people rely on both episodic and semantic associations, shown through temporal and semantic clustering of…
42 CFR § 512.200 - Time periods for EPM episodes.
Code of Federal Regulations, 2010 CFR
2017-10-01
... 42 Public Health 5 2017-10-01 2017-10-01 false Time periods for EPM episodes. § 512.200 Section § 512.200 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) HEALTH CARE INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL Scope of Episodes...
42 CFR § 512.1 - Basis and scope.
Code of Federal Regulations, 2010 CFR
2017-10-01
...) HEALTH CARE INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL General Provisions § 512.1 Basis and scope. (a) Basis. This part implements the test of episode payment models under section 1115A of the Act... sets forth the following: (1) The participants in each episode payment model. (2) The episodes being...
Two-Year Diagnostic Stability in Early-Onset First-Episode Psychosis
ERIC Educational Resources Information Center
Castro-Fornieles, Josefina; Baeza, Immaculada; de la Serna, Elena; Gonzalez-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Dolores; Otero, Soraya; Arango, Celso
2011-01-01
Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). Aim: To describe diagnostic stability…
Elements of episodic-like memory in animal models.
Crystal, Jonathon D
2009-03-01
Representations of unique events from one's past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer's disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.
Aging-related episodic memory decline: are emotions the key?
Kinugawa, Kiyoka; Schumm, Sophie; Pollina, Monica; Depre, Marion; Jungbluth, Carolin; Doulazmi, Mohamed; Sebban, Claude; Zlomuzica, Armin; Pietrowsky, Reinhard; Pause, Bettina; Mariani, Jean; Dere, Ekrem
2013-01-01
Episodic memory refers to the recollection of personal experiences that contain information on what has happened and also where and when these events took place. Episodic memory function is extremely sensitive to cerebral aging and neurodegerative diseases. We examined episodic memory performance with a novel test in young (N = 17, age: 21–45), middle-aged (N = 16, age: 48–62) and aged but otherwise healthy participants (N = 8, age: 71–83) along with measurements of trait and state anxiety. As expected we found significantly impaired episodic memory performance in the aged group as compared to the young group. The aged group also showed impaired working memory performance as well as significantly decreased levels of trait anxiety. No significant correlation between the total episodic memory and trait or state anxiety scores was found. The present results show an age-dependent episodic memory decline along with lower trait anxiety in the aged group. Yet, it still remains to be determined whether this difference in anxiety is related to the impaired episodic memory performance in the aged group. PMID:23378831
Examining Factors Associated with Heavy Episodic Drinking Among College Undergraduates
Scholly, Kristen; Katz, Alan R.; Kehl, Lisa
2014-01-01
Heavy episodic drinking among college students is a serious health concern. The purpose of this study was to identify factors associated with heavy episodic drinking behaviors amongst a predominately Asian undergraduate college student population in the United States. A survey measuring alcohol use behaviors was completed by a random sample of 18-24 year old undergraduates during April, 2011. A multivariate logistic regression analysis was conducted to determine factors associated with students’ heavy episodic drinking behavior. Independent factors associated with heavy episodic drinking included living on campus, ethnicity, perceived drinking behavior among peers, and a belief that alcohol is a central part of one’s social life. Heavy episodic drinking was also associated with poor academic performance. Campus-wide educational strategies to reduce heavy episodic drinking among college undergraduates should incorporate accurate information regarding alcohol use norms to correct students’ perceived over estimation of their peers alcohol consumption rates and the under estimation of students protective alcohol use behaviors. These efforts should focus in on-campus residence halls where a higher occurrence of heavy episodic drinking is often found. PMID:26973931
The Interaction between Semantic Representation and Episodic Memory.
Fang, Jing; Rüther, Naima; Bellebaum, Christian; Wiskott, Laurenz; Cheng, Sen
2018-02-01
The experimental evidence on the interrelation between episodic memory and semantic memory is inconclusive. Are they independent systems, different aspects of a single system, or separate but strongly interacting systems? Here, we propose a computational role for the interaction between the semantic and episodic systems that might help resolve this debate. We hypothesize that episodic memories are represented as sequences of activation patterns. These patterns are the output of a semantic representational network that compresses the high-dimensional sensory input. We show quantitatively that the accuracy of episodic memory crucially depends on the quality of the semantic representation. We compare two types of semantic representations: appropriate representations, which means that the representation is used to store input sequences that are of the same type as those that it was trained on, and inappropriate representations, which means that stored inputs differ from the training data. Retrieval accuracy is higher for appropriate representations because the encoded sequences are less divergent than those encoded with inappropriate representations. Consistent with our model prediction, we found that human subjects remember some aspects of episodes significantly more accurately if they had previously been familiarized with the objects occurring in the episode, as compared to episodes involving unfamiliar objects. We thus conclude that the interaction with the semantic system plays an important role for episodic memory.
Bauer, Patricia J.; King, Jessica E.; Larkina, Marina; Varga, Nicole L.; White, Elizabeth A.
2012-01-01
Children build up knowledge about the world and also remember individual episodes. How individual episodes during which children learn new things become integrated with one another to form general knowledge is only beginning to be explored. Integration between separate episodes is called on in educational contexts and in everyday life as a major means of extending knowledge and organizing information. Bauer and San Souci (2010) provided an initial demonstration that 6-year-olds extend their knowledge by integrating between separate but related episodes; the episodes shared a high level of surface similarity. Experiments 1A and 1B of the current research were tests of integration under low and high levels of surface similarity, respectively. In Experiment 1A, when surface similarity of the episodes was low, 6-year-olds integrated between passages of text, yet their performance was not as robust as observed previously. In Experiment 1B, when surface similarity of the episodes was high, a replication of Bauer and San Souci’s results was observed. In Experiment 2, we tested whether a “hint” to consult the information learned in the passages improved performance even when surface level similarity was low. The hint had a strong facilitating effect. Possible mechanisms of integration between separate yet related episodes are discussed. PMID:22153911
Hippocampal functional connectivity and episodic memory in early childhood
Riggins, Tracy; Geng, Fengji; Blankenship, Sarah L.; Redcay, Elizabeth
2016-01-01
Episodic memory relies on a distributed network of brain regions, with the hippocampus playing a critical and irreplaceable role. Few studies have examined how changes in this network contribute to episodic memory development early in life. The present addressed this gap by examining relations between hippocampal functional connectivity and episodic memory in 4-and 6-year-old children (n=40). Results revealed similar hippocampal functional connectivity between age groups, which included lateral temporal regions, precuneus, and multiple parietal and prefrontal regions, and functional specialization along the longitudinal axis. Despite these similarities, developmental differences were also observed. Specifically, 3 (of 4) regions within the hippocampal memory network were positively associated with episodic memory in 6-year-old children, but negatively associated with episodic memory in 4-year-old children. In contrast, all 3 regions outside the hippocampal memory network were negatively associated with episodic memory in older children, but positively associated with episodic memory in younger children. These interactions are interpreted within an interactive specialization framework and suggest the hippocampus becomes functionally integrated with cortical regions that are part of the hippocampal memory network in adults and functionally segregated from regions unrelated to memory in adults, both of which are associated with age-related improvements in episodic memory ability. PMID:26900967
Assessing Racial/Ethnic Disparities in Treatment across Episodes of Mental Health Care
Cook, Benjamin Lê; Zuvekas, Samuel H; Carson, Nicholas; Wayne, Geoffrey Ferris; Vesper, Andrew; McGuire, Thomas G
2014-01-01
ObjectiveTo investigate disparities in mental health care episodes, aligning our analyses with decisions to start or drop treatment, and choices made during treatment. Study DesignWe analyzed whites, blacks, and Latinos with probable mental illness from Panels 9–13 of the Medical Expenditure Panel Survey, assessing disparities at the beginning, middle, and end of episodes of care (initiation, adequate care, having an episode with only psychotropic drug fills, intensity of care, the mixture of primary care provider (PCP) and specialist visits, use of acute psychiatric care, and termination). FindingsCompared with whites, blacks and Latinos had less initiation and adequacy of care. Black and Latino episodes were shorter and had fewer psychotropic drug fills. Black episodes had a greater proportion of specialist visits and Latino episodes had a greater proportion of PCP visits. Blacks were more likely to have an episode with acute psychiatric care. ConclusionsDisparities in adequate care were driven by initiation disparities, reinforcing the need for policies that improve access. Many episodes were characterized only by psychotropic drug fills, suggesting inadequate medication guidance. Blacks’ higher rate of specialist use contradicts previous studies and deserves future investigation. Blacks’ greater acute mental health care use raises concerns over monitoring of their treatment. PMID:23855750
Hippocampal functional connectivity and episodic memory in early childhood.
Riggins, Tracy; Geng, Fengji; Blankenship, Sarah L; Redcay, Elizabeth
2016-06-01
Episodic memory relies on a distributed network of brain regions, with the hippocampus playing a critical and irreplaceable role. Few studies have examined how changes in this network contribute to episodic memory development early in life. The present addressed this gap by examining relations between hippocampal functional connectivity and episodic memory in 4- and 6-year-old children (n=40). Results revealed similar hippocampal functional connectivity between age groups, which included lateral temporal regions, precuneus, and multiple parietal and prefrontal regions, and functional specialization along the longitudinal axis. Despite these similarities, developmental differences were also observed. Specifically, 3 (of 4) regions within the hippocampal memory network were positively associated with episodic memory in 6-year-old children, but negatively associated with episodic memory in 4-year-old children. In contrast, all 3 regions outside the hippocampal memory network were negatively associated with episodic memory in older children, but positively associated with episodic memory in younger children. These interactions are interpreted within an interactive specialization framework and suggest the hippocampus becomes functionally integrated with cortical regions that are part of the hippocampal memory network in adults and functionally segregated from regions unrelated to memory in adults, both of which are associated with age-related improvements in episodic memory ability. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
How does intentionality of encoding affect memory for episodic information?
Craig, Michael; Butterworth, Karla; Nilsson, Jonna; Hamilton, Colin J.; Gallagher, Peter
2016-01-01
Episodic memory enables the detailed and vivid recall of past events, including target and wider contextual information. In this paper, we investigated whether/how encoding intentionality affects the retention of target and contextual episodic information from a novel experience. Healthy adults performed (1) a What-Where-When (WWW) episodic memory task involving the hiding and delayed recall of a number of items (what) in different locations (where) in temporally distinct sessions (when) and (2) unexpected tests probing memory for wider contextual information from the WWW task. Critically, some participants were informed that memory for WWW information would be subsequently probed (intentional group), while this came as a surprise for others (incidental group). The probing of contextual information came as a surprise for all participants. Participants also performed several measures of episodic and nonepisodic cognition from which common episodic and nonepisodic factors were extracted. Memory for target (WWW) and contextual information was superior in the intentional group compared with the incidental group. Memory for target and contextual information was unrelated to factors of nonepisodic cognition, irrespective of encoding intentionality. In addition, memory for target information was unrelated to factors of episodic cognition. However, memory for wider contextual information was related to some factors of episodic cognition, and these relationships differed between the intentional and incidental groups. Our results lead us to propose the hypothesis that intentional encoding of episodic information increases the coherence of the representation of the context in which the episode took place. This hypothesis remains to be tested. PMID:27918286
Identification of sleep bruxism with an ambulatory wireless recording system.
Inano, Shinji; Mizumori, Takahiro; Kobayashi, Yasuyoshi; Sumiya, Masakazu; Yatani, Hirofumi
2013-01-01
To examine whether an ambulatory bruxism recording system, including a biologic monitor, that measures sleep variables and sympatho-vagal balance can specifically identify sleep bruxism (SB) at home. Twenty-six volunteers, including 16 SB subjects, were recruited. Each participant recorded his or her electromyogram (EMG), sympatho-vagal balance, and sound level for 3 consecutive nights using an audio-video recorder to identify SB. Data of sleep variables were compared among the 3 experimental nights. The episodes were classified into SB episodes with and without grinding and non-SB episodes. EMG patterns, amplitude, sympatho-vagal balance, and sound level of all episodes were analyzed so as to determine the appropriate thresholds to detect SB episodes and grinding sound. Then, all episodes without video-recording data were classified into SB and non-SB episodes by using the appropriate thresholds, and the sensitivity and specificity to detect SB episodes were calculated. With regard to sleep variables, there were no significant differences except for sleep latency between the first and second nights. The appropriate EMG pattern and thresholds of amplitude, sympatho-vagal balance, and sound level were phasic or mixed EMG pattern, 20% of maximum voluntary contraction, mean + 1 SD, and mean + 2 SDs, respectively. The sensitivity and specificity to detect SB episodes were 88.4% and 74.2%, respectively. The results suggest that this system enables the detection of SB episodes at home with considerably high accuracy and little interference with sleep.
Benoit, Roland G; Schacter, Daniel L
2015-08-01
It has been suggested that the simulation of hypothetical episodes and the recollection of past episodes are supported by fundamentally the same set of brain regions. The present article specifies this core network via Activation Likelihood Estimation (ALE). Specifically, a first meta-analysis revealed joint engagement of expected core-network regions during episodic memory and episodic simulation. These include parts of the medial surface, the hippocampus and parahippocampal cortex within the medial temporal lobes, and the temporal and inferior posterior parietal cortices on the lateral surface. Both capacities also jointly recruited additional regions such as parts of the bilateral dorsolateral prefrontal cortex. All of these core regions overlapped with the default network. Moreover, it has further been suggested that episodic simulation may require a stronger engagement of some of the core network's nodes as well as the recruitment of additional brain regions supporting control functions. A second ALE meta-analysis indeed identified such regions that were consistently more strongly engaged during episodic simulation than episodic memory. These comprised the core-network clusters located in the left dorsolateral prefrontal cortex and posterior inferior parietal lobe and other structures distributed broadly across the default and fronto-parietal control networks. Together, the analyses determine the set of brain regions that allow us to experience past and hypothetical episodes, thus providing an important foundation for studying the regions' specialized contributions and interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.
Hsieh, Meng-Ying; Lin, Syh-Jae; Jaing, Tang-Her; Chen, Shih-Hsiang; Hung, Iou-Jih; Yang, Chao-Ping; Chen, Chin-Jung; Huang, Yhu-Chering; Li, Shin-Pai; Huang, Jing-Long
2013-01-01
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, virus-triggered immune disease. Hypersensitivity to mosquito bite (HMB), a presentation of Chronic Active Epstein-Barr Virus infection (CAEBV), may progress to HLH. This study aimed to investigate the immunologic difference between the HMB episodes and the HLH episodes associated with EBV infection. Immunologic changes of immunoglobulins, lymphocyte subsets, cytotoxicity, intracellular perforin and granzyme expressions, EBV virus load and known candidate genes for hereditary HLH were evaluated and compared. In 12 HLH episodes (12 patients) and 14 HMB episodes (4 patients), there were both decreased percentages of CD4+ and CD8+ and increased memory CD4+ and activated (CD2+HLADR+) lymphocytes. In contrast to HMB episodes that had higher IgE levels and EBV virus load predominantly in NK cells, those HLH episodes with virus load predominantly in CD3+ lymphocyte had decreased perforin expression and cytotoxicity that were recovered in the convalescence period. However, there was neither significant difference of total virus load in these episodes nor candidate genetic mutations responsible for hereditary HLH. In conclusion, decreased perforin expression in the HLH episodes with predominant-CD3+ EBV virus load is distinct from those HMB episodes with predominant-NK EBV virus load. Whether the presence of non-elevated memory CD4+ cells or activated lymphocytes (CD2+HLADR+) increases the mortality rate in the HLH episodes remains to be further warranted through larger-scale studies. PMID:24204658
Weigel, Paula A M; Hockenberry, Jason M; Bentler, Suzanne E; Kaskie, Brian; Wolinsky, Fredric D
2012-01-01
The purpose of this study was to define and characterize episodes of chiropractic care among older Medicare beneficiaries and to evaluate the extent to which chiropractic services were used in tandem with conventional medicine. Medicare Part B claims histories for 1991 to 2007 were linked to the nationally representative survey on Assets and Health Dynamics among the Oldest Old baseline interviews (1993-1994) to define episodes of chiropractic sensitive care using 4 approaches. Chiropractic and nonchiropractic patterns of service use were examined within these episodes of care. Of the 7447 Assets and Health Dynamics among the Oldest Old participants, 971 used chiropractic services and constituted the analytic sample. There were substantial variations in the number and duration of episodes and the type and volume of services used across the 4 definitions. Depending on how the episode was constructed, the mean number of episodes per chiropractic user ranged from 3.74 to 23.12, the mean episode duration ranged from 4.7 to 28.8 days, the mean number of chiropractic visits per episode ranged from 0.88 to 2.8, and the percentage of episodes with co-occurrent use of chiropractic and nonchiropractic providers ranged from 4.9% to 10.9% over the 17-year period. Treatment for back-related musculoskeletal conditions was sought from a variety of providers, but there was little co-occurrent service use or coordinated care across provider types within care episodes. Chiropractic treatment dosing patterns in everyday practice were much lower than that used in clinical trial protocols designed to establish chiropractic efficacy for back-related conditions. Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.
Etiology of Acute Respiratory Infections in Infants: A Prospective Birth Cohort Study.
Kumar, Prawin; Medigeshi, Guruprasad R; Mishra, Vishnu S; Islam, Mojahidul; Randev, Shivani; Mukherjee, Aparna; Chaudhry, Rama; Kapil, Arti; Ram Jat, Kana; Lodha, Rakesh; Kabra, Sushil K
2017-01-01
There is paucity of studies on etiology of acute respiratory infections (ARI) in infants. The objective of this study is to document incidence and etiology of ARI in infants, their seasonal variability and association of clinical profile with etiology. A birth cohort was followed for the first year of life; for each episode of ARI, nasopharyngeal aspirates were collected to identify the causative respiratory virus(es) using multiplex real-time polymerase chain reaction assay. For lower respiratory tract infections blood culture, serum procalcitonin, serum antibodies to Mycoplasma and Chlamydia and urinary Streptococcus pneumoniae antigen were also assayed. A total of 503 ARI episodes were documented in 310 infants for an incidence rate of 1.8 episodes per infant per year. Of these, samples were processed in 395 episodes (upper respiratory tract infection: 377; lower respiratory tract infection: 18). One or more viruses were detected in 250 (63.3%) episodes and viral coinfections in 72 (18.2%) episodes. Rhinovirus was the most common virus [105 (42%)] followed by respiratory syncytial virus [50 (20%)], parainfluenza virus [42 (16.8%)] and coronavirus [44 (17.6%)]. In lower respiratory tract infections, viral infections were detected in 12 (66.7%) episodes, bacterial infections in 17 (94.4%) episodes and mixed bacterial-viral infections in 8 (44.4%) episodes. Peak incidence of viruses was observed during February-March and September-November. There was no significant difference in symptom duration with virus types. In this cohort of infants, ARI incidence was 1.8 episodes per year per infant; 95% were upper respiratory tract infections. Viruses were identified in 63.3% episodes, and the most common viruses detected were rhinovirus, respiratory syncytial virus and parainfluenza virus.
Lee, Joseph W Y
2010-02-01
Neuroleptic-induced catatonia (NIC), manifested in an extrapyramidal-catatonic syndrome, has been sporadically reported in the literature. Confusion surrounds its relationship to neuroleptic malignant syndrome (NMS) and extrapyramidal reactions to neuroleptics. This study examined (a) its clinical presentation and response to benzodiazepines, (b) the hypothesis that NIC and NMS are on the same spectrum with a continuum of symptom progression, and (c) its possible relationship to extrapyramidal reactions. Of 127 episodes of acute catatonia prospectively identified, 18 were diagnosed with NIC. All catatonia episodes received benzodiazepines. The NIC episodes were analyzed noting their clinical presentations, laboratory findings, and responses to treatments. Their responses to benzodiazepines were compared, with retrospective rating on a 7-point scale, to that for catatonia episodes associated with mania and schizophrenia. The progression of symptoms in each NIC episode was reviewed. The NIC episodes presented predominantly in the stuporous form associated with parkinsonism. Delirium, autonomic abnormality, and elevated serum creatine phosphokinase were all common. Neuroleptic malignant syndrome was diagnosed in 3 episodes (17%). The 3 catatonia groups did not differ significantly in their benzodiazepines responses: 78% (14/18) of NIC, 75% (12/16) of manic catatonia, and 67% (34/51) of schizophrenic catatonia episodes showed full responses. A spectrum of presentation across episodes was noted with simple NIC without delirium, autonomic disturbances, or fever at one end and NMS or malignant NIC at the other end. Symptoms in individual episodes showed a similar continuum progression. No extrapyramidal reactions immediately preceded the NIC episodes. Findings of this study support the hypothesis that NIC and NMS are disorders on the same spectrum and reveal no indication that extrapyramidal reactions progress to NIC.
Effect of stressful life events on the onset and duration of recurrent aphthous stomatitis.
Huling, Laura B; Baccaglini, Lorena; Choquette, Linda; Feinn, Richard S; Lalla, Rajesh V
2012-02-01
Recurrent aphthous stomatitis (RAS) is a common and painful oral mucosal disease. Possible etiologies include genetics, vitamin deficiencies, trauma, immune dysfunction, and stress. The goal of this study was to examine the relationship between the occurrence, type, and magnitude of stressful events and the onset and duration of RAS episodes. One hundred and sixty subjects with a history of RAS completed a weekly phone survey for up to 1 year, providing data on the occurrence of RAS episodes and details of any stressful events they experienced during the previous week. During RAS episodes, subjects also completed daily paper diaries that recorded incidence and duration of the RAS episode. Stressful events were quantified using the validated Recent Life Changes Questionnaire (RLCQ) and were classified as mental or physical stressors. Stressful life events were significantly associated with the onset of RAS episodes (P < 0.001), however, not with the duration of the RAS episodes. Experiencing a stressful life event increased the odds of an RAS episode by almost three times (OR = 2.72; 95% CI = 2.04-3.62). When controlled for each other, mental stressors had a larger effect (OR = 3.46, 95% CI = 2.54-4.72) than physical stressors (OR = 1.44; 95% CI = 1.04-1.99) on the occurrence of RAS episodes. RAS episodes did not occur more frequently or last longer with increasing stress severity. In patients with a history of RAS, stressful events may mediate changes involved in the initiation of new RAS episodes. Mental stressors are more strongly associated with RAS episodes than physical stressors. © 2011 John Wiley & Sons A/S.
Episodic Specificity in Acquiring Thematic Knowledge of Novel Words from Descriptive Episodes
Zhang, Meichao; Chen, Shuang; Wang, Lin; Yang, Xiaohong; Yang, Yufang
2017-01-01
The current study examined whether thematic relations of the novel words could be acquired via descriptive episodes, and if yes, whether it could be generalized to thematically related words in a different scenario. In Experiment 1, a lexical decision task was used where the novel words served as primes for target words in four conditions: (1) corresponding concepts of the novel words, (2) thematically related words in the same episodes as that in learning condition, (3) thematically related words in different episodes, or (4) unrelated words served as targets. Event related potentials elicited by the targets revealed that compared to the unrelated words, the corresponding concepts and thematically related words in the same episodes elicited smaller N400s with a frontal-central distribution, whereas the thematically related words in different episodes elicited an enhanced late positive component. Experiment 2 further showed a priming effect of the corresponding concepts on the thematically related words in the same episodes as well as in a different episode, indicating that the absence of a priming effect of the learned novel words on the thematically related words in different episode could not be attributed to inappropriate selection of thematically related words in the two conditions. These results indicate that only the corresponding concepts and the thematically related words in the learning episodes were successfully primed, whereas the thematic association between the novel words and the thematically related words in different scenarios could only be recognized in a late processing stage. Our findings suggest that thematic knowledge of novel words is organized via separate scenarios, which are represented in a clustered manner in the semantic network. PMID:28428766
Episodic Specificity in Acquiring Thematic Knowledge of Novel Words from Descriptive Episodes.
Zhang, Meichao; Chen, Shuang; Wang, Lin; Yang, Xiaohong; Yang, Yufang
2017-01-01
The current study examined whether thematic relations of the novel words could be acquired via descriptive episodes, and if yes, whether it could be generalized to thematically related words in a different scenario. In Experiment 1, a lexical decision task was used where the novel words served as primes for target words in four conditions: (1) corresponding concepts of the novel words, (2) thematically related words in the same episodes as that in learning condition, (3) thematically related words in different episodes, or (4) unrelated words served as targets. Event related potentials elicited by the targets revealed that compared to the unrelated words, the corresponding concepts and thematically related words in the same episodes elicited smaller N400s with a frontal-central distribution, whereas the thematically related words in different episodes elicited an enhanced late positive component. Experiment 2 further showed a priming effect of the corresponding concepts on the thematically related words in the same episodes as well as in a different episode, indicating that the absence of a priming effect of the learned novel words on the thematically related words in different episode could not be attributed to inappropriate selection of thematically related words in the two conditions. These results indicate that only the corresponding concepts and the thematically related words in the learning episodes were successfully primed, whereas the thematic association between the novel words and the thematically related words in different scenarios could only be recognized in a late processing stage. Our findings suggest that thematic knowledge of novel words is organized via separate scenarios, which are represented in a clustered manner in the semantic network.
Forney, K Jean; Bodell, Lindsay P; Haedt-Matt, Alissa A; Keel, Pamela K
2016-07-01
Of the two primary features of binge eating, loss of control (LOC) eating is well validated while the role of eating episode size is less clear. Given the ICD-11 proposal to eliminate episode size from the binge-eating definition, the present study examined the incremental validity of the size criterion, controlling for LOC. Interview and questionnaire data come from four studies of 243 women with bulimia nervosa (n = 141) or purging disorder (n = 102). Hierarchical linear regression tested if the largest reported episode size, coded in kilocalories, explained additional variance in eating disorder features, psychopathology, personality traits, and impairment, holding constant LOC eating frequency, age, and body mass index (BMI). Analyses also tested if episode size moderated the association between LOC eating and these variables. Holding LOC constant, episode size explained significant variance in disinhibition, trait anxiety, and eating disorder-related impairment. Episode size moderated the association of LOC eating with purging frequency and depressive symptoms, such that in the presence of larger eating episodes, LOC eating was more closely associated with these features. Neither episode size nor its interaction with LOC explained additional variance in BMI, hunger, restraint, shape concerns, state anxiety, negative urgency, or global functioning. Taken together, results support the incremental validity of the size criterion, in addition to and in combination with LOC eating, for defining binge-eating episodes in purging syndromes. Future research should examine the predictive validity of episode size in both purging and nonpurging eating disorders (e.g., binge eating disorder) to inform nosological schemes. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:651-662). © 2016 Wiley Periodicals, Inc.
Kemner, S M; Mesman, E; Nolen, W A; Eijckemans, M J C; Hillegers, M H J
2015-01-01
Life events are an established risk factor for the onset and recurrence of unipolar and bipolar mood episodes, especially in the presence of genetic vulnerability. The dynamic interplay between life events and psychological context, however, is less studied. In this study, we investigated the impact of life events on the onset and recurrence of mood episodes in bipolar offspring, as well as the effects of temperament, coping and parenting style on this association. Bipolar offspring (n = 108) were followed longitudinally from adolescence to adulthood. Mood disorders were assessed with: the Kiddie Schedule of Affective Disorders and Schizophrenia - Present and Lifetime Version or the Structured Clinical Interview for DSM-IV Axis I disorders; life events with the Life Events and Difficulties Schedule; and psychological measures using the Utrecht Coping List, Temperament and Character Inventory and short-EMBU (memories of upbringing instrument). Anderson-Gill models (an extension of the Cox proportional hazard model) were utilized. Life events were associated with an increased risk for first and, although less pronounced, subsequent mood episodes. There was a large confounding effect for the number of previous mood episodes; findings suggest a possible kindling effect. Passive coping style increased the risk of mood episode onset and recurrent episodes, but also altered the effect of life events on mood disorders. Harm avoidance temperament was associated with mood episode recurrence. Life events are especially a risk factor in the onset of mood disorders, though less so in recurrent episodes. Psychological features (passive coping and harm-avoidant temperament) contribute to the risk of an episode occurring, and also have a moderating effect on the association between life events and mood episodes. These findings create potential early intervention strategies for bipolar offspring.
Determinants of perception of heartburn and regurgitation
Bredenoord, A J; Weusten, B L A M; Curvers, W L; Timmer, R; Smout, A J P M
2006-01-01
Background and aim It is not known why some reflux episodes evoke symptoms and others do not. We investigated the determinants of perception of gastro‐oesophageal reflux. Methods In 32 patients with symptoms suggestive of gastro‐oesophageal reflux, 24 hour ambulatory pH and impedance monitoring was performed after cessation of acid suppressive therapy. In the 20 patients who had at least one symptomatic reflux episode, characteristics of symptomatic and asymptomatic reflux episodes were compared. Results A total of 1807 reflux episodes were detected, 203 of which were symptomatic. Compared with asymptomatic episodes, symptomatic episodes were associated with a larger pH drop (p<0.001), lower nadir pH (p<0.05), and higher proximal extent (p<0.005). Symptomatic reflux episodes had a longer volume and acid clearance time (p<0.05 and p<0.002). Symptomatic episodes were preceded by a higher oesophageal cumulative acid exposure time (p<0.05). The proximal extent of episodes preceding regurgitation was larger than those preceding heartburn; 14.8% of the symptomatic reflux episodes were weakly acidic. In total, 426 pure gas reflux episodes occurred, of which 12 were symptomatic. Symptomatic pure gas reflux was more frequently accompanied by a pH drop than asymptomatic gas reflux (p<0.05). Conclusions Heartburn and regurgitation are more likely to be evoked when the pH drop is large, proximal extent of the refluxate is high, and volume and acid clearance is delayed. Sensitisation of the oesophagus occurs by preceding acid exposure. Weakly acidic reflux is responsible for only a minority of symptoms in patients off therapy. Pure gas reflux associated with a pH drop (“acid vapour”) can be perceived as heartburn and regurgitation. PMID:16120760
Apolipoprotein E (APOE) ε4 and episodic memory decline in Alzheimer's disease: A review.
El Haj, Mohamad; Antoine, Pascal; Amouyel, Philippe; Lambert, Jean-Charles; Pasquier, Florence; Kapogiannis, Dimitrios
2016-05-01
A growing body of research has examined the relationship between episodic memory decline, the cognitive hallmark of Alzheimer's disease (AD), and the presence of Apolipoprotein E ε4 (APOE ε4) allele, a major genetic risk factor for the disease. Our review attempts to summarize and critically evaluate this literature. We performed a systematic search for studies assessing episodic memory in AD patients who were genotyped for APOE ε4 and identified fourteen papers. Although most of these papers reported significant relationships between APOE ε4 and episodic memory decline in AD, some papers did not confirm this relationship. Our review links this controversy to the conflicting literature about the effects of APOE ε4 on general cognitive functioning in AD. We identify several shortcoming and limitations of the research on the relationship between APOE ε4 and episodic memory in AD, such as small sample sizes, non-representative populations, lack of comparison of early-onset vs. late-onset disease, and lack of comparison among different genotypes that include APOE ε4 (i.e., zero, one, or two ε4 alleles). Another major shortcoming of the reviewed literature was the lack of comprehensive evaluation of episodic memory decline, since episodic memory was solely evaluated with regard to encoding and retrieval, omitting evaluation of core episodic features that decline in AD, such as context recall (e.g., how, where, and when an episodic event has occurred) and subjective experience of remembering (e.g., reliving, emotion and feeling during episodic recollection). Future research taking these limitations into consideration could illuminate the nature of the relationship between APOE ε4 and episodic memory decline in AD. Copyright © 2016 Elsevier B.V. All rights reserved.
Gedik, Habip; Şimşek, Funda; Kantürk, Arzu; Yildirmak, Taner; Arica, Deniz; Aydin, Demet; Demirel, Naciye; Yokuş, Osman
2014-01-01
Background The primary objective of this study was to report the incidence of bloodstream infections (BSIs) and clinically or microbiologically proven bacterial or fungal BSIs during neutropenic episodes in patients with hematological malignancies. Methods In this retrospective observational study, all patients in the hematology department older than 14 years who developed febrile neutropenia during chemotherapy for hematological cancers were evaluated. Patients were included if they had experienced at least one neutropenic episode between November 2010 and November 2012 due to chemotherapy in the hematology ward. Results During 282 febrile episodes in 126 patients, 66 (23%) episodes of bacteremia and 24 (8%) episodes of fungemia were recorded in 48 (38%) and 18 (14%) patients, respectively. Gram-negative bacteria caused 74% (n=49) of all bacteremic episodes. Carbapenem-resistant Gram-negative bacteria (n=6) caused 12% and 9% of Gram-negative bacteremia episodes and all bacteremia episodes, respectively. Carbapenem-resistant Gram-negative bacteria included Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=1), and Serratia marcescens (n=1). Culture-proven invasive fungal infection occurred in 24 episodes in 18 cases during the study period, with 15 episodes in ten cases occurring in the first study year and nine episodes in eight cases in the second study year. In 13 of 18 cases (72%) with bloodstream yeast infections, previous azole exposure was recorded. Candida parapsilosis, C. glabrata, and C. albicans isolates were resistant to voriconazole and fluconazole. Conclusion BSIs that occur during febrile neutropenic episodes in hematology patients due to Gram-negative bacteria should be treated initially with non-carbapenem-based antipseudomonal therapy taking into consideration antimicrobial stewardship. Non-azole antifungal drugs, including caspofungin and liposomal amphotericin B, should be preferred as empirical antifungal therapy in the events of possible or probable invasive fungal infections with an absence of pulmonary findings due to increase azole resistance. PMID:25258539
Kovacs, Maria; Obrosky, Scott; George, Charles
2016-10-01
The episodic nature of major depressive disorder (MDD) in clinically referred adults has been well-characterized, particularly by the NIMH Collaborative Depression Study. Previous work has established that MDD also is episodic prior to adulthood, but no study has yet provided comprehensive information on the actual course of MDD in clinically referred juveniles. Thus, the present investigation sought to characterize recovery, recurrence, and their predictors across multiple episodes of MDD in initially 8- to 13-year-old outpatients (N=102), and to estimate freedom from morbidity ("well-time") across the years. Clinically referred youngsters with MDD were repeatedly assessed in an observational study across two decades (median follow up length: 15 years). Survival analytic techniques served to model recovery from the 1st, 2nd and 3rd lifetime episodes of MDD, the risk of developing the 2nd, 3rd, and 4th episodes, and the effects of traditional psychosocial and clinical predictors of outcomes. "Well-time" across the follow-up and its predictors also were examined. Recovery rates ranged from 96% to 100% across MDD episodes; episode lengths ranged from 6 to 7 months. Up to 72% of those recovered from the first episode of MDD had a further episode; median inter-episode intervals were about 3-5 years. No single demographic, social, or clinical variable, nor treatment, consistently predicted recovery/recurrence. Psychiatric morbidity over time derived mostly from non-affective disorders, which, however, did not alter the course of MDD. The sample was relatively small and power to detect small effects further declined with each MDD episode recurrence. Echoing findings on adults, the course of pediatric-onset MDD in this clinical sample was unequivocally episodic. Traditional course predictors had limited temporal stability, highlighting the need to examine novel predictor variables. The ongoing risk of depression episodes into the second and third decades of life suggests that prevention efforts should start in late childhood. Copyright © 2016 Elsevier B.V. All rights reserved.
Kumar, Narender; Manimaran, A.; Kumaresan, A.; Sreela, L.; Patbandha, Tapas Kumar; Tiwari, Shiwani; Chandra, Subhash
2016-01-01
Aim: Present study aimed to evaluate the different episodes of clinical mastitis (CM) and influence of duration of treatment and seasonality on the occurrence of different episodes of CM in crossbred cows. Materials and Methods: A total of 1194 lactation data of crossbred CM cows were collected from mastitis treatment record from 2002 to 2012. Data of CM cows were classified into types of episodes (pattern of repeated or multiple episodes occurrence) and number of episodes (magnitude of multiple cases). Types of episodes were divided as single (clinical cure by a single episode of treatment), relapse (retreatment of the same cow within 21 days), recurrence (new CM at least 21 days after treatment), and both (relapse and recurrence). The season was classified as winter (December to March), summer (April to June), rainy (July to September), and autumn (October to November). The difference between incidences of different types of CM episodes and the association between number or type of CM episodes with duration of treatment and seasons of CM occurrence were analyzed by Chi-square test. Results: Among 1194 animals suffered with CM, 53, 16, and 18% had the single episode, relapse, and recurrence, respectively; while 13% suffered by both relapse and recurrence. We estimated the duration of treatment and found 80% of the cows treated 1-8 days, in which 65% treated for 1-4 days, while 35% cows were treated for 5-8 days. Further, 12% cows treated for 9-15 days and 7.5% cows treated >15 days. The relationship between duration of treatment and different episodes of CM revealed that 1-8 days treated cows were mostly cured by the single episode with less relapse and recurrence. In contrast, the incidences of recurrence and relapse episodes were higher in cows treated for more than 9 days. The highest incidence of relapse was noticed in winter (36%) than other seasons (10-28%), while the recurrence was less during autumn (9%) compared to other seasons (20-40%). Conclusion: Cows those suffered by both relapse and recurrence were more susceptible to CM, and they need to be culled from farm to control the transmission of infections. Although the influence of seasonality was difficult to understand, the higher magnitude of relapse and recurrence during winter suggested the adverse effects of cold stress on treatment outcome. PMID:27051189
Kumar, Narender; Manimaran, A; Kumaresan, A; Sreela, L; Patbandha, Tapas Kumar; Tiwari, Shiwani; Chandra, Subhash
2016-01-01
Present study aimed to evaluate the different episodes of clinical mastitis (CM) and influence of duration of treatment and seasonality on the occurrence of different episodes of CM in crossbred cows. A total of 1194 lactation data of crossbred CM cows were collected from mastitis treatment record from 2002 to 2012. Data of CM cows were classified into types of episodes (pattern of repeated or multiple episodes occurrence) and number of episodes (magnitude of multiple cases). Types of episodes were divided as single (clinical cure by a single episode of treatment), relapse (retreatment of the same cow within 21 days), recurrence (new CM at least 21 days after treatment), and both (relapse and recurrence). The season was classified as winter (December to March), summer (April to June), rainy (July to September), and autumn (October to November). The difference between incidences of different types of CM episodes and the association between number or type of CM episodes with duration of treatment and seasons of CM occurrence were analyzed by Chi-square test. Among 1194 animals suffered with CM, 53, 16, and 18% had the single episode, relapse, and recurrence, respectively; while 13% suffered by both relapse and recurrence. We estimated the duration of treatment and found 80% of the cows treated 1-8 days, in which 65% treated for 1-4 days, while 35% cows were treated for 5-8 days. Further, 12% cows treated for 9-15 days and 7.5% cows treated >15 days. The relationship between duration of treatment and different episodes of CM revealed that 1-8 days treated cows were mostly cured by the single episode with less relapse and recurrence. In contrast, the incidences of recurrence and relapse episodes were higher in cows treated for more than 9 days. The highest incidence of relapse was noticed in winter (36%) than other seasons (10-28%), while the recurrence was less during autumn (9%) compared to other seasons (20-40%). Cows those suffered by both relapse and recurrence were more susceptible to CM, and they need to be culled from farm to control the transmission of infections. Although the influence of seasonality was difficult to understand, the higher magnitude of relapse and recurrence during winter suggested the adverse effects of cold stress on treatment outcome.
NASA Astrophysics Data System (ADS)
Sulca, J. C.; Vuille, M. F.; Roundy, P. E.; Trasmonte, G.; Silva, Y.; Takahashi, K.
2015-12-01
The Mantaro basin (MB) is located in the central Peruvian Andes. Occasionally, cold episodes are observed during austral summer (January-March), that strongly damage crops. However, little is known about the causes and impacts of such cold episodes. The main goal of this study is thus to characterize cold episodes in the MB and assess their large-scale circulation and teleconnections over South America (SA) during austral summer. To identify cold events in the MB daily minimum temperature (Tmin) for the period 1958-2014 from Huayao station, located within the MB was used. A cold episode is defined when daily minimum temperature drops below its 10-percentile for at least one day. Additionally, to study the sensitivity between physical mechanisms associated with cold episodes and temperature, cold episodes are classified in three groups: Weak cold episodes (7.5 ≤ Tmin ≤ 10 percentile), strong cold episodes (Tmin ≤ 2.5 percentile), but excluding the 9 coldest events (Tmin ≤ 0 ͦ C), henceforth referred to as extraordinary cold episodes. Several gridded reanalysis were used to characterize the large-scale circulation, cloud cover and rainfall over SA associated with these events. Weak and strong cold episodes in the MB are mainly associated with a weakening of the Bolivian High-Nordeste Low system by tropical-extratropical interactions. Both types of cold episodes are associated with westerly wind anomalies at mid- and upper-tropospheric levels aloft the Peruvian Central Andes, which inhibit the influx of humid air masses from the lowlands to the east and hence limit the development of cloud cover (e.g., positive OLR anomalies over MB). The resulting clear sky conditions cause nighttime temperatures to drop, leading to cold extremes below 10-percentile. Simultaneously, northeastern Brazil (NEB) registers negative OLR anomalies, strong convection and enhanced cloud cover because displacement of the South Atlantic Convergence Zone (SACZ) toward the northeast of its climatologic position. By contrast, extraordinary cold episodes in the MB are associated with cold and dry polar air advection at all tropospheric levels toward the central Peruvian Andes. On interannual timescales, El Niño may limit the occurrence of all types of cold episodes in the MB through enhanced tropical tropospheric background warming.
Cognitive reactivity, self-depressed associations, and the recurrence of depression.
Elgersma, Hermien J; de Jong, Peter J; van Rijsbergen, Gerard D; Kok, Gemma D; Burger, Huibert; van der Does, Willem; Penninx, Brenda W J H; Bockting, Claudi L H
2015-09-01
Mixed evidence exists regarding the role of cognitive reactivity (CR; cognitive responsivity to a negative mood) as a risk factor for recurrences of depression. One explanation for the mixed evidence may lie in the number of previous depressive episodes. Heightened CR may be especially relevant as a risk factor for the development of multiple depressive episodes and less so for a single depressive episode. In addition, it is theoretically plausible but not yet tested that the relationship between CR and number of episodes is moderated by the strength of automatic depression-related self-associations. To investigate (i) the strength of CR in remitted depressed individuals with a history of a single vs. multiple episodes, and (ii) the potentially moderating role of automatic negative self-associations in the relationship between the number of episodes and CR. Cross-sectional analysis of data obtained in a cohort study (Study 1) and during baseline assessments in two clinical trials (Study 2). Study 1 used data from the Netherlands Study of Depression and Anxiety (NESDA) and compared never-depressed participants (n=901) with remitted participants with either a single (n=336) or at least 2 previous episodes (n=273). Study 2 included only remitted participants with at least two previous episodes (n=273). The Leiden Index of Depression Sensitivity Revised (LEIDS-R) was used to index CR and an Implicit Association Test (IAT) to measure implicit self-associations. In Study 1, remitted depressed participants with multiple episodes had significantly higher CR than those with a single or no previous episode. The remitted individuals with multiple episodes of Study 2 had even higher CR scores than those of Study 1. Within the group of individuals with multiple episodes, CR was not heightened as a function of the number of episodes, even if individual differences in automatic negative self-associations were taken into account. The study employed a cross-sectional design, which precludes a firm conclusion with regard to the direction of this relationship. The findings are consistent with the view that high CR puts people at risk for recurrent depression and is less relevant for the development of an incidental depressive episode. This suggests that CR is an important target for interventions that aim to prevent the recurrence of depression. Copyright © 2015 Elsevier B.V. All rights reserved.
Glassman, Alexander H; Bigger, J Thomas; Gaffney, Michael; Shapiro, Peter A; Swenson, J Robert
2006-03-01
Depression observed following acute coronary syndrome (ACS) is common and associated with an increased risk of death. The Sertraline Antidepressant Heart Attack Trial (SADHART) tested the safety and efficacy of a selective serotonin reuptake inhibitor in this population. No evidence of harm was seen, and sertraline hydrochloride had an overall beneficial effect on mood that occurred primarily in patients with a history of episodes of major depressive disorder (MDD). To determine how frequently the MDD began before ACS and whether onset of the current MDD episode before or after the ACS event influenced response to sertraline. A randomized, double-blind, placebo-controlled treatment of 369 patients with ACS and MDD was conducted in 40 outpatient clinics in 10 countries between April 1, 1997, and April 30, 2001. Diagnosis of MDD, number of previous episodes of depression, and episode onset before or after hospitalization were established using the Diagnostic Interview Schedule. Treatment response was measured with the Clinical Global Impression-Improvement scale. Fifty-three percent of MDD episodes began before hospitalization for the index episode of ACS (for 197 of 369 patients), and 94% of the MDD episodes began more than 30 days before the index ACS episode. Episodes of MDD that began prior to ACS responded more frequently to sertraline than to placebo (63% vs 46%, respectively; odds ratio, 2.0; 95% confidence interval, 1.13-3.55) whereas depression with onset beginning after hospitalization showed a high placebo response rate (69% vs 60%, respectively) and low sertraline-placebo response ratio (1.15). Multivariate analysis indicated that time of onset of the current episode, history of MDD, and baseline severity independently predicted the sertraline-placebo response ratio. Half of the episodes of major depression associated with ACS began long before ACS and therefore were not caused by ACS. Patients whose current episodes of MDD begin before ACS, those with a history of MDD, and those whose episodes are severe should be treated because they will benefit considerably from sertraline. Since these 3 predictors of sertraline response are independent, having more than 1 of them substantially increases the benefit of sertraline while reducing the chance of spontaneous recovery.
Freezing of soft spheres: A critical test for weighted-density-functional theories
NASA Astrophysics Data System (ADS)
Laird, Brian B.; Kroll, D. M.
1990-10-01
We study the freezing properties of systems with inverse-power and Yukawa interactions (soft spheres), using recently developed weighted-density-functional theories. We find that the modified weighted-density-functional approximation (MWDA) of Denton and Ashcroft yields results for the liquid to face-centered-cubic (fcc) structure transition that represent a significant improvement over those of earlier ``second-order'' density-functional freezing theories; however, this theory, like the earlier ones, fails to predict any liquid to body-centered-cubic (bcc) transition, even under conditions where the computer simulations indicate that this should be the equilibrium solid structure. In addition, we show that both the modified effective-liquid approximation (MELA) of Baus [J. Phys. Condens. Matter 2, 2111 (1990)] and the generalized effective-liquid approximation of Lutsko and Baus [Phys. Rev. Lett. 64, 761 (1990)], while giving excellent results for the freezing of hard spheres, fail completely to predict freezing into either fcc or bcc solid phases for soft inverse-power potentials. We also give an alternate derivation of the MWDA that makes clearer its connection to earlier theories.
Design simulations for a small emittance 2.7-cell photo-cathode rf-gun in jector
NASA Astrophysics Data System (ADS)
Yongzhang, Huang
1997-05-01
In order to produce the electron bunch with small emittance which is the key issue in the so-called SASE studies, the design studies on a two-and-half cell photocathode rf-gun has been conducted. The rf gun injector is optimized by using the code of Par mela. As a main result, the optimum is found to be a 2.7-cell cavity. The geometry and the coupling scheme of the requested cavity is studied in more detail with the codes of Mafia and Superfish. The beam iris of each cells is enlarged in order to wide n the mode separations. For the purpose of cancelling the influence of the coupling iris upon the field symmetry, the so-called symmetrical double-side input coupler is studied. The coupler will be assembled to the second cell and the critical matchin g has been achieved in the Mafia-T3 simulation. With this cavity, the final normalized rms emittance reaches the value of 0.81πmm-mrad at a charge of 1nC in the Parmela simulation.
Determination of the origin and texture of marble artifacts using stable isotopes
NASA Astrophysics Data System (ADS)
Dotsika, E.; Poutoukis, D.; Zisi, N.; Psomiadis, D.
2009-04-01
For the characterization of marble and the identification of the origin of marble artifacts, samples from several ancient monuments of Greece were analyzed using several techniques: stable isotopes of carbonates (13C, 18O), XRD analysis and optical microscopy, from which information can be obtained on the origin and texture of the marble used for the production of the artifacts. The full range of grain sizes and isotopic signatures that occur in a lot of different quarries has been measured and presented. In a δ13C versus δ18O diagram, the fields corresponding to all known ancient quarries (from Penteli, Cyclades, especially Naxos (Mela, Apol, Apir, Senax), Keros, Paros (Parlak, Parlyc) and Asia Minor (Prokon)) are reported. The plots representing the analyzed samples are also shown on the same diagram. The final results of the study indicate the origin of the carbonate material of the artefacts from each of the ancient monument. In cases that the samples plot on overlapping areas, a further study is proposed, using the maximum grain size of the material.
Interior trough deposits on Mars: Subice volcanoes?
Chapman, M.G.; Tanaka, K.L.
2001-01-01
Widespread, several-kilometer-thick successions of layered deposits occur as mounds that partly fill the troughs or chasmata that compose the Valles Marineris on Mars. Like terrestrial subice volcanoes, the layered deposits occur in a volcano-tectonic setting within basins that may have held ponded water or ice. On the basis of their dimensions, morphologies, and associated catastrophic floods and other geologic events as shown in Viking and new Mars Global Surveyor (MGS) data sets, we suggest that the interior deposits are volcanic in origin and possibly generated by subice eruptions. A tuya origin for the mounds can explain the lack of external sediment, mound heights that can rival the plateau, local flat-topped mesas, morphologically distinct mounds of different ages, horizontal to steep dips, fine-grained materials, indications of rare volcanic vents and lava flows, and spectral composition. The extremely diverse layering of west Candor Chasma and possible volcanic cones in Melas may have formed by related subaerial eruptions. Consistent with the suggestion that interior deposits are eroding out of the wall rock, some deposits could have been erupted from sites along the walls.
NASA Technical Reports Server (NTRS)
Justh, H. L.; Justus, C. G.
2007-01-01
The new Mars-GRAM auxiliary profile capability, using data from TES observations, mesoscale model output, or other sources, allows a potentially higher fidelity representation of the atmosphere, and a more accurate way of estimating inherent uncertainty in atmospheric density and winds. Figure 3 indicates that, with nominal value rpscale=1, Mars-GRAM perturbations would tend to overestimate observed or mesoscale-modeled variability. To better represent TES and mesoscale model density perturbations, rpscale values as low as about 0.4 could be used. Some trajectory model implementations of Mars-GRAM allow the user to dynamically change rpscale and rwscale values with altitude. Figure 4 shows that an mscale value of about 1.2 would better replicate wind standard deviations from MRAMS or MMM5 simulations at the Gale, Terby, or Melas sites. By adjusting the rpscale and rwscale values in Mars-GRAM based on figures such as Figure 3 and 4, we can provide more accurate end-to-end simulations for EDL at the candidate MSL landing sites.
[Genetic system for maintaining the mitochondrial human genome in yeast Yarrowia lipolytica].
Isakova, E P; Deryabina, Yu I; Velyakova, A V; Biryukova, J K; Teplova, V V; Shevelev, A B
2016-01-01
For the first time, the possibility of maintaining an intact human mitochondrial genome in a heterologous system in the mitochondria of yeast Yarrowia lipolytica is shown. A method for introducing directional changes into the structure of the mitochondrial human genome replicating in Y. lipolytica by an artificially induced ability of yeast mitochondria for homologous recombination is proposed. A method of introducing and using phenotypic selection markers for the presence or absence of defects in genes tRNA-Lys and tRNA-Leu of the mitochondrial genome is developed. The proposed system can be used to correct harmful mutations of the human mitochondrial genome associated with mitochondrial diseases and for preparative amplification of intact mitochondrial DNA with an adjusted sequence in yeast cells. The applicability of the new system for the correction of mutations in the genes of Lys- and Leu-specific tRNAs of the human mitochondrial genome associated with serious and widespread human mitochondrial diseases such as myoclonic epilepsy with lactic acidosis (MELAS) and myoclonic epilepsy with ragged-red fibers (MERRF) is shown.
Static inflation and deflation pressure–volume curves from excised lungs of marine mammals
Fahlman, Andreas; Loring, Stephen H.; Ferrigno, Massimo; Moore, Colby; Early, Greg; Niemeyer, Misty; Lentell, Betty; Wenzel, Frederic; Joy, Ruth; Moore, Michael J.
2011-01-01
SUMMARY Excised lungs from eight marine mammal species [harp seal (Pagophilus groenlandicus), harbor seal (Phoca vitulina), gray seal (Halichoerus grypush), Atlantic white-sided dolphin (Lagenorhynchus acutus), common dolphin (Delphinus delphis), Risso's dolphin (Grampus griseus), long-finned pilot whale (Globicephala melas) and harbor porpoise (Phocoena phocoena)] were used to determine the minimum air volume of the relaxed lung (MAV, N=15), the elastic properties (pressure–volume curves, N=24) of the respiratory system and the total lung capacity (TLC). Our data indicate that mass-specific TLC (sTLC, l kg–1) does not differ between species or groups (odontocete vs phocid) and agree with that estimated (TLCest) from body mass (Mb) by applying the equation: TLCest=0.135 Mb0.92. Measured MAV was on average 7% of TLC, with a range from 0 to 16%. The pressure–volume curves were similar among species on inflation but diverged during deflation in phocids in comparison with odontocetes. These differences provide a structural basis for observed species differences in the depth at which lungs collapse and gas exchange ceases. PMID:22031747
Mixtures of Sulfates in Melas Chasma
2017-09-04
In this image from NASA's Mars Reconnaissance Orbiter, layering within the light-toned sulfate deposit is the result of different states of hydration. Some of the layers have sulfates with little water (known as monohydrated sulfates) whereas other layers have higher amounts of water (called polyhydrated sulfates). The different amounts of water within the sulfates may reflect changes in the water chemistry during deposition of the sulfates, or may have occurred after the sulfates were laid down when heat or pressure forced the water out of some layers, causing a decrease in the hydration state. Many locations on Mars have sulfates, which are sedimentary rocks formed in water. Within Valles Marineris, the large canyon system that cuts across the planet, there are big and thick sequences of sulfates. The CRISM instrument on MRO is crucial for telling scientists which type of sulfate is associated with each layer, because each hydration state will produce a spectrum with absorptions at specific wavelengths depending upon the amount of water contained within the sulfate. https://photojournal.jpl.nasa.gov/catalog/PIA21935
Curé, Charlotte; Antunes, Ricardo; Samarra, Filipa; Alves, Ana Catarina; Visser, Fleur; Kvadsheim, Petter H; Miller, Patrick J O
2012-01-01
In cetaceans' communities, interactions between individuals of different species are often observed in the wild. Yet, due to methodological and technical challenges very little is known about the mediation of these interactions and their effect on cetaceans' behavior. Killer whales (Orcinus orca) are a highly vocal species and can be both food competitors and potential predators of many other cetaceans. Thus, the interception of their vocalizations by unintended cetacean receivers may be particularly important in mediating interspecific interactions. To address this hypothesis, we conducted playbacks of killer whale vocalizations recorded during herring-feeding activity to free-ranging long-finned pilot whales (Globicephala melas). Using a multi-sensor tag, we were able to track the whales and to monitor changes of their movements and social behavior in response to the playbacks. We demonstrated that the playback of killer whale sounds to pilot whales induced a clear increase in group size and a strong attraction of the animals towards the sound source. These findings provide the first experimental evidence that the interception of heterospecific vocalizations can mediate interactions between different cetacean species in previously unrecognized ways.
Curé, Charlotte; Antunes, Ricardo; Samarra, Filipa; Alves, Ana Catarina; Visser, Fleur; Kvadsheim, Petter H.; Miller, Patrick J. O.
2012-01-01
In cetaceans’ communities, interactions between individuals of different species are often observed in the wild. Yet, due to methodological and technical challenges very little is known about the mediation of these interactions and their effect on cetaceans’ behavior. Killer whales (Orcinus orca) are a highly vocal species and can be both food competitors and potential predators of many other cetaceans. Thus, the interception of their vocalizations by unintended cetacean receivers may be particularly important in mediating interspecific interactions. To address this hypothesis, we conducted playbacks of killer whale vocalizations recorded during herring-feeding activity to free-ranging long-finned pilot whales (Globicephala melas). Using a multi-sensor tag, we were able to track the whales and to monitor changes of their movements and social behavior in response to the playbacks. We demonstrated that the playback of killer whale sounds to pilot whales induced a clear increase in group size and a strong attraction of the animals towards the sound source. These findings provide the first experimental evidence that the interception of heterospecific vocalizations can mediate interactions between different cetacean species in previously unrecognized ways. PMID:23300613
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vinikour, W.S.; Goldstein, R.M.; Anderson, R.V.
1980-05-01
This study was conducted to determine if bioconcentration patterns were similar between four common essential and nonessential trace elements. The whole body concentrations of Zn, Cu, Cd and Pb were related to the whole body dry weights of blue-gill (Lepomis macrochirus), black crappie (Pomoxis nigromaculatus), black bullhead (Ictalurus melas), and yellow perch (Perca flavescens). Zinc, Cu, Cd, and Pb were selected because most studies of heavy metal concentrations in fish have examined one or more of these elements. These metals are often closely associated with each other as natural impurities or as alloys. Zinc and Cu are essential components ofmore » metallo-enzymes. Cadmium and Pb have not been shown to have essential functions in fishes, but rather inhibit biological systems and competitively interfere with Zn and Cu. The fish species were chosen on the basis of their importance as recreational and food species and their frequent use in both field and laboratory studies. Patterns of metal bioconcentrations with fish size were determined by simple linear regression.« less
Planning Physical Education Lessons as Teaching "Episodes"
ERIC Educational Resources Information Center
Chatoupis, Constantine
2016-01-01
An "episode" is a unit of time within which teachers and students are working on the same objective and are engaged in the same teaching/learning style. The duration of each episode, as well as the number of them in a single lesson, may vary. Additionally, the multiple episodes of a lesson may have similar objectives, offer similar…
42 CFR § 512.900 - Termination of an episode payment model.
Code of Federal Regulations, 2010 CFR
2017-10-01
... 42 Public Health 5 2017-10-01 2017-10-01 false Termination of an episode payment model. § 512.900... SERVICES (CONTINUED) HEALTH CARE INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL Model Termination § 512.900 Termination of an episode payment model. CMS may terminate any EPM for reasons including but...
Episodic Memory and Episodic Foresight in 3- and 5-Year-Old Children
ERIC Educational Resources Information Center
Hayne, Harlene; Gross, Julien; McNamee, Stephanie; Fitzgibbon, Olivia; Tustin, Karen
2011-01-01
In the present study, we examined the development of episodic memory and episodic foresight. Three- and 5-year-olds were interviewed individually using a personalised timeline that included photographs of them at different points in their life. After constructing the timeline with the experimenter, each child was asked to discuss a number of…
The Pretend Play Episode: Location and Resemblance to Story.
ERIC Educational Resources Information Center
Roskos, K.
This paper describes a procedure used to locate pretend play episodes in streams of play activity of 4- and 5-year-olds. A story grammar was used to compare pretend play episode activity with story construction. Participants were five girls and three boys attending the same preschool. Pretend play schemes and episodes were defined in terms of…
42 CFR 484.215 - Initial establishment of the calculation of the national 60-day episode payment.
Code of Federal Regulations, 2014 CFR
2014-10-01
... national 60-day episode payment. 484.215 Section 484.215 Public Health CENTERS FOR MEDICARE & MEDICAID... calculation of the national 60-day episode payment. (a) Determining an HHA's costs. In calculating the initial unadjusted national 60-day episode payment applicable for a service furnished by an HHA using data on the...
42 CFR 484.215 - Initial establishment of the calculation of the national 60-day episode payment.
Code of Federal Regulations, 2013 CFR
2013-10-01
... national 60-day episode payment. 484.215 Section 484.215 Public Health CENTERS FOR MEDICARE & MEDICAID... calculation of the national 60-day episode payment. (a) Determining an HHA's costs. In calculating the initial unadjusted national 60-day episode payment applicable for a service furnished by an HHA using data on the...
42 CFR 484.215 - Initial establishment of the calculation of the national 60-day episode payment.
Code of Federal Regulations, 2012 CFR
2012-10-01
... national 60-day episode payment. 484.215 Section 484.215 Public Health CENTERS FOR MEDICARE & MEDICAID... calculation of the national 60-day episode payment. (a) Determining an HHA's costs. In calculating the initial unadjusted national 60-day episode payment applicable for a service furnished by an HHA using data on the...
[Comparison of clinical and histological diagnosis in kidney post-transplantation period].
de Castro, M C; Chocair, P R; Saldanha, L B; Nahas, W; Arap, S; Sabbaga, E; Ianhez, L E
1998-01-01
To assess the agreement between clinical and histopathological diagnosis in a renal transplantation center, 40 episodes of acute renal failure were studied. Kidney biopsies were performed at the moment that a clinical diagnosis was made by the staff. Nineteen episodes of acute tubular necrosis (ATN), eighteen episodes of acute cellular rejection (ACR), 2 humoral rejections and 1 acute cyclosporin nephrotoxicity episodes were diagnosed. ATN episodes were confirmed by renal biopsy in 84.21%, ACR episodes in 83.33%, humoral rejections in 100%. Renal biopsy showed ATN in the occurrence of clinical cyclosporin nephrotoxicity. Total agreement was 82.5%. There is a good relationship between clinical and histopathological diagnosis in the post-transplantation period. Diagnostic mistakes occurred mainly when oliguria was present.
Divergent Thinking and Constructing Episodic Simulations
Addis, Donna Rose; Pan, Ling; Musicaro, Regina; Schacter, Daniel L.
2014-01-01
Divergent thinking likely plays an important role in simulating autobiographical events. We investigated whether divergent thinking is differentially associated with the ability to construct detailed imagined future and imagined past events as opposed to recalling past events. We also examined whether age differences in divergent thinking might underlie the reduced episodic detail generated by older adults. The richness of episodic detail comprising autobiographical events in young and older adults was assessed using the Autobiographical Interview. Divergent thinking abilities were measured using the Alternate Uses Task. Divergent thinking was significantly associated with the amount of episodic detail for imagined future events. Moreover, while age was significantly associated with imagined episodic detail, this effect was strongly related to age-related changes in episodic retrieval rather than divergent thinking. PMID:25483132
Divergent thinking and constructing episodic simulations.
Addis, Donna Rose; Pan, Ling; Musicaro, Regina; Schacter, Daniel L
2016-01-01
Divergent thinking likely plays an important role in simulating autobiographical events. We investigated whether divergent thinking is differentially associated with the ability to construct detailed imagined future and imagined past events as opposed to recalling past events. We also examined whether age differences in divergent thinking might underlie the reduced episodic detail generated by older adults. The richness of episodic detail comprising autobiographical events in young and older adults was assessed using the Autobiographical Interview. Divergent thinking abilities were measured using the Alternative Uses Task. Divergent thinking was significantly associated with the amount of episodic detail for imagined future events. Moreover, while age was significantly associated with imagined episodic detail, this effect was strongly related to age-related changes in episodic retrieval rather than divergent thinking.
Spatiotemporal variations of severe haze episodes in China
NASA Astrophysics Data System (ADS)
Li, J.; Liao, H.
2017-12-01
Rapid economic growth and associated emissions increase in China have led to severe air pollution in recent decades. This study presents the spatial and temporal variations of severe haze episodes in China obtained from monitoring sites and the global chemical transport model GEOS-Chem. Cities in the Beijing-Tianjin-Hebei (BTH) and Yangtze River Delta (YRD) regions suffered from severe haze, with highest numbers of severe haze episodes in winter and the lowest numbers of episodes in summer. Backward trajectory analysis by the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model indicated the origins of air mass during severe haze episodes for BTH and YRD. The principal component analysis was applied for different regions to classify synoptic conditions associated with the severe haze episodes.
Overlap in the functional neural systems involved in semantic and episodic memory retrieval.
Rajah, M N; McIntosh, A R
2005-03-01
Neuroimaging and neuropsychological data suggest that episodic and semantic memory may be mediated by distinct neural systems. However, an alternative perspective is that episodic and semantic memory represent different modes of processing within a single declarative memory system. To examine whether the multiple or the unitary system view better represents the data we conducted a network analysis using multivariate partial least squares (PLS ) activation analysis followed by covariance structural equation modeling (SEM) of positron emission tomography data obtained while healthy adults performed episodic and semantic verbal retrieval tasks. It is argued that if performance of episodic and semantic retrieval tasks are mediated by different memory systems, then there should differences in both regional activations and interregional correlations related to each type of retrieval task, respectively. The PLS results identified brain regions that were differentially active during episodic retrieval versus semantic retrieval. Regions that showed maximal differences in regional activity between episodic retrieval tasks were used to construct separate functional models for episodic and semantic retrieval. Omnibus tests of these functional models failed to find a significant difference across tasks for both functional models. The pattern of path coefficients for the episodic retrieval model were not different across tasks, nor were the path coefficients for the semantic retrieval model. The SEM results suggest that the same memory network/system was engaged across tasks, given the similarities in path coefficients. Therefore, activation differences between episodic and semantic retrieval may ref lect variation along a continuum of processing during task performance within the context of a single memory system.
Kravitz, H. M.; Schott, L. L.; Joffe, H.; Cyranowski, J.M.; Bromberger, J. T.
2014-01-01
Background In women, anxiety symptoms are common and increase during midlife, but little is known about whether these symptoms predict onsets of major depressive disorder (MDD) episodes. We examined whether anxiety symptoms are associated with subsequent episodes of MDD in midlife African-American and Caucasian women, and whether they confer a different risk for first versus recurrent MDD episodes. Method A longitudinal analysis was conducted using 12 years of data from the Study of Women’s Health Across the Nation (SWAN) Mental Health Study (MHS). The baseline sample comprised 425 Caucasian (n=278) and African American (n=147) community-dwelling women, aged 46.1±2.5 years. Anxiety symptoms measured annually using a self-report questionnaire were examined in relation to MDD episodes in the subsequent year, assessed with the SCID. Multivariable models were estimated with random effects logistic regression. Results Higher anxiety symptoms scores were associated with a significantly higher adjusted odds of developing an episode of MDD at the subsequent annual visit [odds ratio (OR) 1.47, p=0.01], specifically for a recurrent episode (OR 1.49, p=0.03) but non-significant for a first episode (OR 1.32, p=0.27). There were no significant racial effects in the association between anxiety symptoms and subsequent MDD episodes. Conclusions Anxiety symptoms often precede MDD and may increase the vulnerability of midlife women to depressive episodes, particularly recurrences. Women with anxiety symptoms should be monitored clinically during the ensuing year for the development of an MDD episode. PMID:24467997
Myers Virtue, Shannon; Manne, Sharon L; Darabos, Kathleen; Heckman, Carolyn J; Ozga, Melissa; Kissane, David; Rubin, Stephen; Rosenblum, Norman
2015-09-01
The aim of this study was to describe emotion episodes during early and late psychotherapy sessions among women newly diagnosed with gynecological cancer and to examine whether the total number of emotion episodes during early and later sessions was associated with baseline psychological distress, dispositional emotion expressivity, and patient-rated therapeutic progress. The study utilized data from an ongoing study examining the efficacy of two psychotherapy interventions, a coping and communication intervention and a supportive counseling intervention, for women diagnosed with gynecological cancer. Emotion episode coding was completed for the first and sixth psychotherapy sessions for each patient randomized to receive psychotherapy (N = 173). Patients completed baseline survey measures of psychological distress and dispositional emotional expressivity and post-session ratings of therapeutic progress. The average number of emotion episodes was 7.4 in the first session and 5.2 episodes in the sixth session. In both sessions, the majority of emotion episodes contained only negative emotions and focused on a cancer-related topic. A higher number of emotion episodes in the first session was associated with higher psychological distress reported in the baseline survey (p = 0.02). A higher number of emotion episodes in the sixth session was associated with a higher number of emotion episodes in the first session (p < 0.001) and higher patient-rated progress as rated in the sixth session (p = 0.016). The findings highlight the importance of expressed emotions, particularly negative emotions about cancer-related topics, in therapeutic progress during psychotherapy among women diagnosed with gynecological cancer. Copyright © 2014 John Wiley & Sons, Ltd.