Nutritional issues in patients with obesity and cirrhosis

Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis.Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis.Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronicliver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation.Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble,water-soluble vitamins and trace elements and should be supplemented appropriately.Diet,physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations.Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation.The risk of sarcopenia,micronutrient status,and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review.Furthermore,the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.     

Mitochondrial DNA mutation “m.3243A>G”—Heterogeneous clinical picture for cardiologists (“m.3243A>G”: A phenotypic chameleon)

Objective: In general, a mitochondrial disorder is diagnosed on the basis of symptom combinations and confirmed by genetic findings. However, patients carrying the m.3243A>G mutation in the mitochondrial tRNA leucine 1 (MT‐TL1) do not always meet all the proposed criteria for the most frequently encountered mitochondrial syndrome “MELAS,” an acronym for Mitochondrial Encephalomyopathy, Lactic Acidosis, and at least one Stroke‐like episode. We here present various phenotypic characteristics of the mitochondrial mutation m.3243A>G with particular focus on cardiac manifestations.
Methods and Results: We followed nine patients (1 month to 68 years old; median 42 years; four female and five male) from nine different families with this m.3243A>G mutation in the MT‐TL1. The classical “MELAS” criteria are met by only three of these patients. Electrocardiography (ECG) shows preexcitation pattern with short PR intervals and delta waves (Wolff‐Parkinson‐White) in three patients and sick sinus syndrome plus atrioventricular block I in one patient. Hypertrophic cardiomyopathy was found in eight patients with moderate to severe regurgitation of various valves.
Conclusion: Cardiac manifestation can encompass hypertrophic or dilated cardiomyopathy, as well as preexcitation syndromes or conduction delay. In general, the clinical presentation to meet the “MELAS” criteria varies due to heteroplasmy. Thus, cardiologists should screen patients with unexplained cardiac features in the context of deafness, short stature and learning disabilities for mtDNA mutations, especially the m.3243A>G mutation. A clear diagnosis is essential as a basis for prognostic advice concerning the disease course and clinical impact on family testing.     

Homocysteine and A2A-D2 Receptor-Receptor Interaction at Striatal Astrocyte Processes

The interaction between adenosine A2A and dopamine D2 receptors in striatal neurons is a well-established phenomenon and has opened up new perspectives on the molecular mechanisms involved in Parkinson’s disease. However, it has barely been investigated in astrocytes. Here, we show by immunofluorescence that both A2A and D2 receptors are expressed in adult rat striatal astrocytes in situ, and investigate on presence, function, and interactions of the receptors in the astrocyte processes—acutely prepared from the adult rat striatum—and on the effects of homocysteine on the A2A-D2 receptor-receptor interaction. We found that A2A and D2 receptors were co-expressed on vesicular glutamate transporter-1-positive astrocyte processes, and confirmed that A2A-D2 receptor-receptor interaction controlled glutamate release—assessed by measuring the [³H]D-aspartate release—from the processes. The complexity of A2A-D2 receptor-receptor interaction is suggested by the effect of intracellular homocysteine, which reduced D2-mediated inhibition of glutamate release (homocysteine allosteric action on D2), without interfering with the A2A-mediated antagonism of the D2 effect (maintained A2A-D2 interaction). Our findings indicate the crucial integrative role of A2A-D2 molecular circuits at the plasma membrane of striatal astrocyte processes. The fact that homocysteine reduced D2-mediated inhibition of glutamate release could provide new insights into striatal astrocyte-neuron intercellular communications. As striatal astrocytes are recognized to be involved in Parkinson’s pathophysiology, these findings may shed light on the pathogenic mechanisms of the disease and contribute to the development of new drugs for its treatment.     

An EEG index of sensorimotor interhemispheric coupling after unilateral stroke: clinical and neurophysiological study

Brain connectivity has been employed to investigate on post‐stroke recovery mechanisms and assess the effect of specific rehabilitation interventions. Changes in interhemispheric coupling after stroke have been related to the extent of damage in the corticospinal tract (CST) and thus, to motor impairment. In this study, we aimed at defining an index of interhemispheric connectivity derived from electroencephalography (EEG), correlated with CST integrity and clinical impairment. Thirty sub‐acute stroke patients underwent clinical and neurophysiological evaluation: CST integrity was assessed by Transcranial Magnetic Stimulation and high‐density EEG was recorded at rest. Connectivity was assessed by means of Partial Directed Coherence and the normalized Inter‐Hemispheric Strength (nIHS) was calculated for each patient and frequency band on the whole network and in three sub‐networks relative to the frontal, central (sensorimotor) and occipital areas. Interhemipheric coupling as expressed by nIHS on the whole network was significantly higher in patients with preserved CST integrity in beta and gamma bands. The same index estimated for the three sub‐networks showed significant differences only in the sensorimotor area in lower beta, with higher values in patients with preserved CST integrity. The sensorimotor lower beta nIHS showed a significant positive correlation with clinical impairment. We propose an EEG‐based connectivity index which is a measure of the interhemispheric cross‐talking and correlates with functional motor impairment in subacute stroke patients. Such index could be employed to evaluate the effects of training aimed at re‐establishing interhemispheric balance and eventually drive the design of future connectivity‐driven rehabilitation interventions.     

Detailed analysis of retinal morphology in patients with diabetic macular edema (DME) randomized to ranibizumab or triamcinolone treatment

Graefe's Archive for Clinical and Experimental Ophthalmology - Our purpose was to compare the impact in diabetic macula edema (DME) of two intravitreal drugs (0.5 mg ranibizumab vs....     

Inclusion of hemimegalencephaly into the phenotypic spectrum of NPRL3 pathogenic variants in familial focal epilepsy with variable foci

Despite tremendous progress through next generation sequencing technologies, familial focal epilepsies are insufficiently understood. We sought to identify the genetic basis in multiplex Palestinian families with familial focal epilepsy with variable foci (FFEVF). Family I with 10 affected individuals and Family II with five affected individuals underwent detailed phenotyping over three generations. The phenotypic spectrum of the two families varied from nonlesional focal epilepsy including nocturnal frontal lobe epilepsy to severe structural epilepsy due to hemimegalencephaly. Whole‐exome sequencing and single nucleotide polymorphism array analysis revealed pathogenic variants in NPRL3 in each family, a partial ~38‐kb deletion encompassing eight exons (exons 8‐15) and the 3′‐untranslated region of the NPRL3 gene in Family I, and a de novo nonsense variant c.1063C>T, p.Gln355* in Family II. Furthermore, we identified a truncating variant in the PDCD10 gene in addition to the NPRL3 variant in a patient with focal epilepsy from Family I. The individual also had developmental delay and multiple cerebral cavernomas, possibly demonstrating a digenic contribution to the individual's phenotype. Our results implicate the association of NPRL3 with hemimegalencephaly, expanding the phenotypic spectrum of NPRL3 in FFEVF and underlining that partial deletions are part of the genotypic spectrum of NPRL3 variants.     

Prospective observational study to evaluate the efficacy and safety of the pollen extract Sérélys® in the management of women with menopausal symptoms

Safety concerns or contraindications to the use of hormones have resulted in a rise of the use of herbal medicinal products for the management of menopausal symptoms. The pollen extract Sérélys^® represents, due to its ingredients and mode of action, a new and innovative alternative for the management of these symptoms. The aim of the present study was to demonstrate the efficacy and safety of Sérélys^®. A prospective, open, observational, and multicentre study was performed on 104 menopausal women. The patients received over 3 months the pollen extract Sérélys^® containing the extracts PI82 and GC Fem in a dosage of twice 160?mg extract and 5?mg vitamin E. Using a validated menopausal rating score, the improvement of menopausal symptoms was recorded. A significant decrease of different menopausal symptoms was observed between the starting point of the study and after 12?weeks (p?<?.0001). Hot flashes were reduced by 48.5%, sleep disturbance by 50.1%, depressive mood by 51.2%, irritability by 47.9%, fatigue by 47.8%, vaginal dryness by 39.63% and muscles and joint pain by 27.4%. The pollen extract Sérélys^® reduced significant menopausal symptoms showing a very low side effect profile.