Solving the unsolved genetic epilepsies:Current and future perspectives

Many patients with epilepsy undergo exome or genome sequencing as part of a diagnostic workup; however, many remain genetically unsolved. There are various factors that account for negative results in exome/genome sequencing for patients with epilepsy: (1) the underlying cause is not genetic; (2) there is a complex polygenic explanation; (3) the illness is monogenic but the causative gene remains to be linked to a human disorder; (4) family segregation with reduced penetrance; (5) somatic mosaicism or the complexity of, for example, a structural rearrangement; or (6) limited knowledge or diagnostic tools that hinder the proper classification of a variant, resulting in its designation as a variant of unknown significance. The objective of this review is to outline some of the diagnostic options that lie beyond the exome/genome, and that might become clinically relevant within the foreseeable future. These options include: (1) re-analysis of older exome/genome data as knowledge increases or symptoms change; (2) looking for somatic mosaicism or long-read sequencing to detect low-complexity repeat variants or specific structural variants missed by traditional exome/genome sequencing; (3) exploration of the non-coding genome including disruption of topologically associated domains, long range non-coding RNA, or other regulatory elements; and finally (4) transcriptomics, DNA methylation signatures, and metabolomics as complementary diagnostic methods that may be used in the assessment of variants of unknown significance. Some of these tools are currently not integrated into standard diagnostic workup. However, it is reasonable to expect that they will become increasingly available and improve current diagnostic capabilities, thereby enabling precision diagnosis in patients who are currently undiagnosed.</p

A lógica do duelo e o enigma da política

Raymond Aron inicia o Capítulo 1 de Paz e guerra entre as nações citando a célebre definição de Clausewitz, segundo a qual “a guerra é um ato de violência destinado a obrigar o adversário a realizar nossa vontade”, tomando-a como o “ponto de partida para este estudo”. Embora Aron advirta, em seguida, que “esta dialética da luta é puramente abstrata e não se aplica às guerras reais”, a definição clausewitziana, repetida à exaustão, provocaria inúmeros mal-entendidos. Não obstante esses mal-entendidos subsistam, em sua maioria, à revelia da obra de Aron e tributáveis a intérpretes belicitas e a duzentos anos de guerras totais, Paz e guerra não passará incólume a eles. De fato, em suas Memórias, ao comentar Paz e guerra, Aron registrará que “Clausewitz trouxe-lhe a idéia germinal de toda teoria das relações interestatais”, a “alternância da paz e da guerra, a complementaridade da diplomacia e estratégia”, etc. Trata-se, porém, de um Clausewitz incompleto. Não surpreende, portanto, que não haja aí menção à definição trinitária da guerra, única que contempla a infinita diversidade das guerras reais. As insuficiências e incorreções na compreensão da teoria clausewitziana da guerra levarão Aron a debruçar-se sobre a sua obra nos anos dos 70. Clausewitz escreveu sob o impacto da Revolução Francesa, das guerras napoleônicas e da emergência do povo na guerra. É sob o impacto das guerras totais do século XX que Aron escrevera a sua obra. É o espectro da guerra absoluta a assombrar a Europa e o mundo. A compreensão da alternância da guerra e da paz exige, portanto, que exorcizemos esse espectro.Facultad de Humanidades y Ciencias de la Educación (FAHCE

Association between Vaspin rs2236242 Gene Polymorphism and Psoriasis Vulgaris

Background: Psoriasis known as a chronic inflammatory skin disease is accompanied by metabolic disorders such as obesity, diabetes, and dyslipidemia. Vaspin (a serine protease inhibitor derived from visceral adipose tissue) is a newly identified adipokine and a link between inflammation and obesity has been reported. We aimed to determine whether vaspin gene polymorphism is associated with the development and/or clinical features of psoriasis vulgaris. Methods: Our study group consisted of 96 psoriasis vulgaris patients and 100 matched controls. Vaspin rs2236242 gene was genotyped using PCR. Results: The vaspin genotypes showed a meaningful difference between psoriasis and control groups (p = 0.02). The frequency of the vaspin rs2236242 TT genotype was lower in psoriasis patients than in control participants (p < 0.05). The TA genotype was associated with a 2.38-fold increased risk of psoriasis compared to the TT genotype (p = 0.007, odds ratio: 2.38; 95% confidence interval: 1.25-4.55), but not the AA genotype. All subjects were the Turkish population, the study in other populations is needed and the sample size was small in number. Conclusion: Our study demonstrated that vaspin rs2236242 polymorphism is related to psoriasis in the Turkish population. Polymorphisms of the vaspin gene might serve as diagnostic biomarkers of psoriasis

Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats

Introduction and aim Hydrogen sulfide (H2S) is an endogenously produced gas-structure mediator. It is proposed to have antioxidant, anti-inflammatory and antiapoptotic effects. Acetaminophen (N-acetyl-P-aminophenol; APAP) is an antipyretic and analgesic medication known as paracetamol. When taken at therapeutic doses there are few side-effects, but at high doses APAP can cause clear liver and kidney damage in humans and experimental animals. In this study, the effects of the H2S donor of sodium hydrosulfide (NaHS) on acute renal toxicity induced by APAP in rats were researched in comparison with N-acetyl cysteine (NAC)

Adam 33 Gene V4 C/G Rs2787094 Polymorphism in Psoriasis

© AEPress s.r.o.AIMS: Psoriasis is a common chronic inflammatory disease. A disintegrin and metalloproteinase 33 (ADAM33) gene is the first novel susceptibility gene for asthma. The aim of this study was to investigate the relationship of ADAM 33 gene V4 C/G rs2787094 polymorphism with the risk of psoriasis in the Turkish population. METHODS: ADAM33 gene polymorphism (V4 C/G rs2787094) was analyzed in 97 psoriasis patients and 50 healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: There was no significant difference in ADAM33 genotype and allele distributions between psoriasis and control groups (p > 0.05). CONCLUSIONS: ADAM33 V4 C/G rs2787094 polymorphism was not associated with psoriasis risk in the Turkish population. Larger studies with different ethnicities are needed to determine the impact of ADAM33 polymorphism on the risk of developing psoriasis

Preconcentrations of Cu (II) and Mn (II) by magnetic solid-phase extraction on Bacillus cereus loaded gamma-Fe2O3 nanomaterials

For the simultaneous preconcentrations of Cu(II) and Mn(II), a novel preconcentration technique was developed and described. Bacillus cereus loaded magnetic gamma-Fe2O3 nanoparticles were prepared and used as support materials on solid-phase extraction procedure. Important experimental parameters were investigated in details and pH 6.0, 3 mL min(-1) of flow rate, 5 mL of 1 mol L-1 of HCl as eluent, 200 mg of biomass, and 200 mg of magnetic gamma-Fe2O3 nanoparticles as support material was found as the best conditions. The preconcentrations factor were found to be 80 for Cu (II) and Mn(II). It was confirmed by the results that SPE columns could be used in 32 cycles. The LOD values calculated for Cu (II) and Mn (II) were 0.09 and 0.08 ng mL(-1), respectively. The RSD values found were less than 3.4%. The extraction recoveries were achieved as higher than 98%. The biosorption capacities of Cu (II), and Mn (II) were 26.0 mg g(-1), 30.3 mg g(-1) respectively. The approach devised for analyzing analyte concentrations in food samples proved to be successful