Rare Coding Variants in Patients with Non-Syndromic Vestibular Dysfunction

The following are available online at https://www.mdpi.com/article/ 10.3390/genes14040831/s1A.A.M.S. received a scholarship from the Philippine Council for Health and Research Development of the Department of Science and Technology (PCHRD-DOST) under the Research Enrichment (Sandwich) Grant of the Accelerated Science and Technology Human Resource Devel- opment Program. O.A.K. was supported by the US National Institutes of Health (NIH)—National Institute on Deafness and Other Communication Disorders (NIDCD) grant T32 DC012280 (to Sue C. Kinnamon and Herman A. Jenkins). This work was supported by the NIH through the NIDCD grants R01 DC019642 (to R.L.P.S.-C. and Ivana V. Yang) and R01 DC013912 (to S.P.G.); and the National Insti- tute of Arthritis and Musculoskeletal and Skin Diseases grant R01 AR068292 (to N.H.-M.). Funding was also provided by Junta de Andalucia, grant Retos en Investigacion PY20_00303 (to J.A.L.-E.).Vertigo due to vestibular dysfunction is rare in children. The elucidation of its etiology will improve clinical management and the quality of life of patients. Genes for vestibular dysfunction were previously identified in patients with both hearing loss and vertigo. This study aimed to identify rare, coding variants in children with peripheral vertigo but no hearing loss, and in patients with potentially overlapping phenotypes, namely, Meniere’s disease or idiopathic scoliosis. Rare variants were selected from the exome sequence data of 5 American children with vertigo, 226 Spanish patients with Meniere’s disease, and 38 European–American probands with scoliosis. In children with vertigo, 17 variants were found in 15 genes involved in migraine, musculoskeletal phenotypes, and vestibular development. Three genes, OTOP1, HMX3, and LAMA2, have knockout mouse models for vestibular dysfunction. Moreover, HMX3 and LAMA2 were expressed in human vestibular tissues. Rare variants within ECM1, OTOP1, and OTOP2 were each identified in three adult patients with Meniere’s disease. Additionally, an OTOP1 variant was identified in 11 adolescents with lateral semicircular canal asymmetry, 10 of whom have scoliosis. We hypothesize that peripheral vestibular dysfunction in children may be due to multiple rare variants within genes that are involved in the inner ear structure, migraine, and musculoskeletal disease.Philippine Council for Health and Research Development of the Department of Science and Technology (PCHRD-DOST) under the Research Enrichment (Sandwich) Grant of the Accelerated Science and Technology Human Resource Development ProgramUS National Institutes of Health (NIH)-National Institute on Deafness and Other Communication Disorders (NIDCD) T32 DC012280NIH through the NIDCD R01 DC019642, R01 DC013912United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) R01 AR068292Junta de Andalucia PY20_0030

Nontaxable income and necessary consumption: the Rousseau’s paradox of fiscal egalitarianism

The traditional concept of a strict minimum of necessary consumption and nontaxable income equal for all taxpayers embedded in most current income-tax systems is the result of a paradox of fiscal egalitarianism. The paper shows that substituting the traditional notion of a strict minimum of nontaxable income (Surplus Income Tax Method) for a scheme of growing personal allowances to meet the amounts of necessary consumption required by the different living standards of the taxpayers (Discretionary Income Tax Method) generates an income-tax scheme more progressive than the traditional one. In the paper we also show that this alternative proposal for nontaxable incomes generates an after-tax income distribution less unequal (Lorenz dominance) and superior in terms of social welfare (Atkinson, 1970)

Nontaxable income and necessary consumption: the Rousseau’s paradox of fiscal egalitarianism

The traditional concept of a strict minimum of necessary consumption and nontaxable income equal for all taxpayers embedded in most current income-tax systems is the result of a paradox of fiscal egalitarianism. The paper shows that substituting the traditional notion of a strict minimum of nontaxable income (Surplus Income Tax Method) for a scheme of growing personal allowances to meet the amounts of necessary consumption required by the different living standards of the taxpayers (Discretionary Income Tax Method) generates an income-tax scheme more progressive than the traditional one. In the paper we also show that this alternative proposal for nontaxable incomes generates an after-tax income distribution less unequal (Lorenz dominance) and superior in terms of social welfare (Atkinson, 1970)

Nontaxable income and necessary consumption: the Rousseau’s paradox of fiscal egalitarianism

The traditional concept of a strict minimum of necessary consumption and nontaxable income equal for all taxpayers embedded in most current income-tax systems is the result of a paradox of fiscal egalitarianism. The paper shows that substituting the traditional notion of a strict minimum of nontaxable income (Surplus Income Tax Method) for a scheme of growing personal allowances to meet the amounts of necessary consumption required by the different living standards of the taxpayers (Discretionary Income Tax Method) generates an income-tax scheme more progressive than the traditional one. In the paper we also show that this alternative proposal for nontaxable incomes generates an after-tax income distribution less unequal (Lorenz dominance) and superior in terms of social welfare (Atkinson, 1970)

Cholecystokinin in the central nervous system of the sea lamprey Petromyzon marinus: precursor identification and neuroanatomical relationships with other neuronal signalling systems

Cholecystokinin (CCK) is a neuropeptide that modulates processes such as digestion, satiety, and anxiety. CCK-type peptides have been characterized in jawed vertebrates and invertebrates, but little is known about CCK-type signalling in the most ancient group of vertebrates, the agnathans. Here, we have cloned and sequenced a cDNA encoding a sea lamprey (Petromyzon marinus L.) CCK-type precursor (PmCCK), which contains a CCK-type octapeptide sequence (PmCCK-8) that is highly similar to gnathostome CCKs. Using mRNA in situ hybridization, the distribution of PmCCK-expressing neurons was mapped in the CNS of P. marinus. This revealed PmCCK-expressing neurons in the hypothalamus, posterior tubercle, prethalamus, nucleus of the medial longitudinal fasciculus, midbrain tegmentum, isthmus, rhombencephalic reticular formation, and the putative nucleus of the solitary tract. Some PmCCK-expressing neuronal populations were only observed in adults, revealing important differences with larvae. We generated an antiserum to PmCCK-8 to enable immunohistochemical analysis of CCK expression, which revealed that GABA or glutamate, but not serotonin, tyrosine hydroxylase or neuropeptide Y, is co-expressed in some PmCCK-8-immunoreactive (ir) neurons. Importantly, this is the first demonstration of co-localization of GABA and CCK in neurons of a non-mammalian vertebrate. We also characterized extensive cholecystokinergic fibre systems of the CNS, including innervation of habenular subnuclei. A conspicuous PmCCK-8-ir tract ascending in the lateral rhombencephalon selectively innervates a glutamatergic population in the dorsal isthmic grey. Interestingly, this tract is reminiscent of the secondary gustatory/visceral tract of teleosts. In conclusion, this study provides important new information on the evolution of the cholecystokinergic system in vertebrates.</p

Effect of α-tocopherol megadoses on hematologic parameters and antioxidant capacity of rats in an ultraendurance probe

This study was aimed to analyze the effect of two different megadoses of α-tocopherol (vit E) in the antioxidant activity and red and white blood series of Wistar rats after a 180-min ultraendurance probe. Three groups of 10 rats were analyzed; VEAG: acute administration of a megadoses of 5,000 IU/kg of vit E the day before the probe; VECG: chronic administration of 1,000 IU/kg/day of vit E for 6 days before the probe; CG: placebo administration. VEAG presented white cells, red blood cells, hematocrit, hemoglobin values significantly higher than CG and VECG (p < 0.05). The mean corpuscular hemoglobin and lymphocytes concentrations were significantly higher in the VECG than in the other two groups (p < 0.05). Similarly, VEAG presented a significantly higher vit E blood concentration than VECG and CG (p < 0.05), and VECG than CG (p < 0.05). Finally, we found a significantly positive correlation between trolox equivalent antioxidant capacity (TEAC) and red blood cells concentration (r = 0.374) and a significantly inverse correlation between TEAC and blood lactate concentration (r = −0.365). Our findings suggest that acute vit E megadoses could protect against transitory sport anemia symptoms and increase the white blood cell count in comparison with the chronic dose and control groups after an ultraendurance probe

Academic Directors Facing Internet Addictions, Learning and Health Promotion

The result that is presented is expressed from a bibliographic review of works published during the last two years 2020-2022 and, through which it was possible to verify the relationships that are established between the work of the Academic Directors, before the latent challenge and visible that is the crossroads of Internet addictions, by university students, increased in the stage already overcome of social isolation imposed by Covid 19 but, with emphasis on the achievement of learning at this high educational level, its risks and consequent decreases in the attacks that occur as a result of procrastination. All associated with the addictive phenomenon, in a projection of health promotion that the current, humanistic, modern and developing university should not give up in any way, being precisely in this direction an unavoidable pillar of social development, which lies precisely in the high professional qualification. of the new generations committed to a prosperous and sustainable social change