Evaluation of diffusion tensor imaging changes and neurocognitive effects of asymptomatic vitamin B12 deficiency

Vitamin B12 plays an important role in the mechanisms which are responsible for myelinization in the central nervous system. It can particularly lead to hematological and neuropsychiatric symptoms when serum levels fall due to insufficient intake with diet or absorption problems. The purpose of this study was to show the cognitive effects in vitamin B12 deficiency cases that have not reached clinical symptom level using neuropsychological tests, and to show possible cerebral neuronal damage using diffusion tensor imaging (DTI) method. A total of 62 asymptomatic vitamin B12 deficiency patients and 40 healthy subjects were included in the study and both groups were subjected to Standardized Mini-Mental State Examination, Montreal Cognitive Assessment Test, Rey Auditory Verbal Learning Test, forward and backward digit span (WMS-R forward and backward), Visual Reproduction Subtest (WMS-III), Category Fluency Test, Trail Making (Trail A-B) (21) and Similarities (BENZ) tests. DTI examinations were performed on both groups. Patient group was determined to get lower scores in all neuropsychological tests compared to control group. In DTI examination, a significant decrease in FA values of bilateral hippocampus and a prominent increase in apparent diffusion coefficient (ADC) values were determined in the patient group compared to control group. In this study, it was determined that there was microstructural damage in the brain in the presence of vitamin B12 deficiency even in the asymptomatic period, and the patients revealed cognitive decline. In accordance with this result, early treatment of the easily diagnosed and treated vitamin B12 deficiency may prevent possible irreversible damage in the future.     

Cardiac screening investigations in adult‐onset progressive external ophthalmoplegia patients

Introduction: Patients with mitochondrial myopathies may develop cardiac complications such as cardiomyopathy and/or cardiac conduction defects. To identify these potentially life‐threatening and treatable conditions, it is common practice to screen patients intermittently with electrocardiography and echocardiography. The optimal time interval for such screening investigations is unknown. We developed this study to review our screening results in adult‐onset patients with progressive external ophthalmoplegia (PEO). Methods: This study was a retrospective review of PEO patients with 5 years or more of cardiac screening investigations who did not have any cardiac symptoms. Results: Fifteen patients were included, and cardiomyopathy was identified on screening echocardiogram in 1 patient. Four patients had other abnormalities identified, which were unrelated to their mitochondrial myopathy. Conclusions: Only 1 patient in 15 developed cardiac complications related to mitochondrial disease during 5 years of follow‐up. We suggest that a screening interval of 3–5 years is probably appropriate for adult‐onset PEO patients who do not have cardiac symptoms. Muscle Nerve 60: 608–611, 2012     

A novel prognostic marker in acute ischemic stroke: small pericardial effusion

The study aimed to evaluate the prognostic importance of small pericardial effusion (SPE) found on echocardiography in a cohort of patients hospitalized for acute ischemic stroke. We prospectively followed a series of 408 consecutive first-ever acute ischemic stroke patients aged ≥50?years who were admitted to the hospital within 24?h of the onset of stroke symptoms. All of the patients underwent transthoracic echocardiography within the first 48?h. Exclusion criteria were cardiothoracic surgery or acute myocardial infarction within the previous 6?months, a moderate or greater pericardial effusion (>1?cm if circumferential), and inadequate visualization of the pericardial space. The patients were followed for 1?year or until death, whichever came first. SPE was noted in 64 (15.7?%) of the patients. Mortality at 1?year was greater for patients with a small effusion (n?=?21, 32.8?%) compared to those without an effusion (n?=?40, 11.6?%, p?<?0.001). After adjustment for age, demographics, medical history, and other echocardiographic findings, SPE remained associated with higher mortality (OR 2.515; 95?% CI 1.188–5.477; p?=?0.008). This study is the first to demonstrate that the presence of SPE is associated with increased mortality in patients with first-ever acute ischemic stroke.     

The History of Dengue Outbreaks in the Americas

Dengue is a viral disease usually transmitted by Aedes aegypti mosquitoes. Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization are described. The outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in the Americas (1600–1946); Continental plan for the eradication of the Ae. aegypti (1947–1970) marked by a successful eradication of the mosquito in 18 continental countries by 1962; Ae. aegypti reinfestation (1971–1999) caused by the failure of the mosquito eradication program; Increased dispersion of Ae. aegypti and dengue virus circulation (2000–2010) characterized by a marked increase in the number of outbreaks. During 2010 > 1.7 million dengue cases were reported, with 50,235 severe cases and 1,185 deaths. A dramatic increase in the number of outbreaks has been reported in recent years. Urgent global action is needed to avoid further disease spread.     

Opponency Revisited: Competition and Cooperation Between Dopamine and Serotonin

Affective valence lies on a spectrum ranging from punishment to reward. The coding of such spectra in the brain almost always involves opponency between pairs of systems or structures. There is ample evidence for the role of dopamine in the appetitive half of this spectrum, but little agreement about the existence, nature, or role of putative aversive opponents such as serotonin. In this review, we consider the structure of opponency in terms of previous biases about the nature of the decision problems that animals face, the conflicts that may thus arise between Pavlovian and instrumental responses, and an additional spectrum joining invigoration to inhibition. We use this analysis to shed light on aspects of the role of serotonin and its interactions with dopamine.     

Neuropathological effects of persistent infection of mice by mouse hepatitis virus.

Mouse hepatitis virus (MHV3) can persist for months in strains of mice with genetically controlled "semisusceptibility" to this virus. The pathology of the chronic neurological disease induced in these animals has been investigated by conventional histology and immunofluorescence. A2G mice develop a chronic choroidoependymitis and meningitis leading to severe hydrocephalus and hydromyelia. In C3H mice a widespread vasculitis was observed, with both viral antigens and bound immunoglobulins in vessal walls. No significant glomerulonephritis was found. Systemic amyloidosis was present in the spleen, liver, and kidneys. The virus was not detected in neural tissues, but brain and spinal cord lesions were found near inflammatory areas surrounding damaged vessels. It is suggested that viral persistance in ependymal cells is directly responsible for the lesions in A2G mice, whereas an immunopathological lesion of blood vessels of the central nervous system underlines the damage to mice of the C3H strain.     

Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive disease, which presents clinically as severe combined immunodeficiency (SCID). We report here two novel mutations in the PNP gene that result in SCID phenotype, in a single patient. The maternal-derived allele carries a C to T transition in exon 2 resulting in a premature stop codon at amino acid 57. The paternal-derived mutation is a G to A transition at position +1 in intron 3, causing a complete skipping of exon 3 and a reading frameshift at the exon 2-exon 4 junction. The predicted polypeptide encoded by the aberrantly spliced mRNA terminates prematurely after only 89 amino acids. Both mutations predict severely truncated proteins resulting in a complete deficiency of PNP enzymatic activity, yet the development of profound immunodeficiency in this patient is greatly delayed.     

Intracellular delivery mediated by an ethosomal carrier

The goal of this work was to investigate the efficiency of transcellular delivery into Swiss albino mice 3T3 fibroblasts of molecules with various physico-chemical characteristics from ethosomes, phospholipid vesicular carriers containing ethanol. The probes chosen were: 4-(4-diethylamino) styryl-N-methylpyridinium iodide (D-289), rhodamine red dihexadecanoylglycerophosphoethanolamine (RR) and fluorescent phosphatidylcholine (PC*). The penetration of these fluorescent probes into fibroblasts and nude mice skin was examined by CLSM and FACS. CLSM micrographs showed that ethosomes facilitated the penetration of all probes into the cells, as evident from the high-intensity fluorescence. In comparison, when incorporated in hydroethanolic solution or classic liposomes, almost no fluorescence was detected. The intracellular presence of each of the three probes tested, was evident after 3 min of incubation. Furthermore, with ethosomal D-289, fluorescence was also seen in the fibroblast nucleus. Enhanced delivery of molecules from the ethosomal carrier was also observed in permeation experiments with the hydrophilic calcein and lypophilic RR to whole nude mouse skin. Calcein penetrated the skin to a depth of 160, 80 and 60 microm from ethosomes, hydroethanolic solution and liposomes, respectively. Maximum fluorescence intensities measured for RR delivered from ethosomes, hydroethanolic solution and liposomes were 150, 40 and 20 AU, respectively. Fibroblast viability tests showed that the ethosomal carrier is not toxic to the cultured cells.