New 3D cone beam CT imaging parameters to assist the dentist in treating patients with Osteogenesis Imperfecta

(1) Background: The aim of the work is to identify some imaging parameters in osteogenesis imperfecta to assist the dentist in the diagnosis, planning, and orthodontic treatment of Osteogenesis Imperfecta (OI) using 3D cone beam Computed Tomography (CBCT) and the Double Energy X-ray Absorptiometry (DEXA) technique. (2) Methods: 14 patients (9 males and 5 females; aged mean ± SD 15 ± 1.5) with a clinical-radiological diagnosis of OI were analyzed and divided into mild and moderate to severe forms. The patients’ samples were compared with a control group of 14 patients (8 males and 6 females; aged mean ± SD 15 ± 1.7), free from osteoporotic pathologies. (3) Results: The statistical analysis allowed us to collect four datasets: in the first dataset (C1 sick population vs. C1 healthy population), the t-test showed a p-value < 0.0001; in the second dataset (C2 sick population vs. C2 healthy population), the t-test showed a p-value < 0.0001; in the third dataset (parameter X of the sick population vs. parameter X of the healthy population), the t-test showed a p-value < 0.0001; in the fourth dataset the bone mineralometry (BMD) value detected by the DEXA technique compared to the C2 value of the OI affected population only) the Welch–Satterthwaite test showed a p-value < 0.0001. (4) Conclusions: The research has produced specific imaging parameters that assist the dentist in making diagnostic decisions in OI patients. This study shows that patients with OI have a characteristic chin-bearing symphysis, thinned, and narrowed towards the center, configuring it with a constant “hourglass” appearance, not reported so far in the literature by any author

Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients

Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue and 90% of cases are due to dominant mutations in COL1A1 and COL1A2 genes. To increase OI disease knowledge and contribute to patient follow-up management, a homogeneous Italian cohort of 364 subjects affected by OI types I-IV was evaluated. The study population was composed of 262 OI type I, 24 type II, 39 type III, and 39 type IV patients. Three hundred and nine subjects had a type I collagen affecting function mutations (230 in α1(I) and 79 in α2(I)); no disease-causing changes were noticed in 55 patients. Compared with previous genotype-phenotype OI correlation studies, additional observations arose: a new effect for α1- and α2-serine substitutions has been pointed out and heart defects, never considered before, resulted associated to quantitative mutations (P = 0.043). Moreover, some different findings emerged if compared with previous literature; especially, focusing the attention on the lethal form, no association with specific collagen regions was found and most of variants localized in the previously reported "lethal clusters" were causative of OI types I-IV. Some discrepancies have been highlighted also considering the "50-55 nucleotides rule," as well as the relationship between specific collagen I mutated region and the presence of dentinogenesis imperfecta and/or blue sclera. Despite difficulties still present in defining clear rules to predict the clinical outcome in OI patients, this study provides new pieces for completing the puzzle, also thanks to the inclusion of clinical signs never considered before and to the large number of OI Italian patients

Avaliação do desempenho dos centros de especialidades odontológicas (CEO) no estado do Rio Grande do Norte (RN) / Performance evaluation of dental specialty centers (CEO) in the state of Rio Grande do Norte (RN)

No Brasil, a atual Política Nacional de Saúde Bucal- Brasil Sorridente, objetivando a ampliação e qualificação da oferta de serviços odontológicos especializados, vem implantando, desde 2004, os Centros de Especialidades Odontológicas – CEO, cujo o tratamento oferecido é uma continuidade do trabalho realizado pela rede de atenção básica. Diante dos indicadores e dados de saúde bucal desfavoráveis no país, com alto índice de edentulismo, de cárie dentária e baixa oferta de serviços reabilitadores, principalmente na Região Nordeste do Brasil, faz-se necessário a realização de uma maior e mais abrangente avaliação dos serviços de saúde especializados em saúde bucal. Portanto, o presente estudo objetivou realizar uma avaliação e monitoramento do desempenho dos Centros de Especialidades Odontológicas instalados no estado do Rio Grande do Norte (RN), a partir do cumprimento das metas de procedimentos ambulatoriais proposta pela Portaria GM Nº 1.464/2011, no ano de 2018. A presente pesquisa abrangeu os 30 CEO situados em todo o estado do RN, de onde foram coletados e descritos todos os procedimentos especializados em Odontologia, nas áreas de Periodontia, Endodontia e Cirurgia. Tais dados foram extraídos do Sistema de Informação Ambulatorial do SUS/ SIA-SUS. A partir daí, foram calculados o Índice Cumprimento Global de Metas –CGM para cada CEO. Posteriormente, esta variável foi associada com variáveis socioeconômicas e de assistência à saúde dos municípios do RN e seus respectivos CEO, utilizando-se análise estatística  descritiva e inferencial bivariada com um nível de significância de 5%. 

Análise de mortalidade e procedimentos de diagnóstico e cirúrgicos relacionados ao Câncer a região de cabeça e pescoço no Rio Grande do Norte

Introdução: Apesar dos avanços no âmbito da saúde, o câncer na região de cabeça e pescoço continua sendo um problema de saúde pública, e possui existência de 600 mil novos casos por ano no mundo. Objetivo: Avaliar, no Rio Grande do Norte (RN), registros de mortalidade e procedimentos de diagnóstico e cirúrgicos voltados para o câncer de cabeça e pescoço. Método: Estudo exploratório, descritivo e inferencial, com dados secundários disponíveis. Foi analisada proporção de procedimentos de diagnóstico e cirúrgicos na região de cabeça e pescoço no RN, entre 2010-2019. Resultados: A mesorregião Leste Potiguar (LP) foi a que apresentou as maiores frequências absolutas em relação a biópsias e procedimentos cirúrgicos, tendo como destaque a capital Natal para os maiores valores. Em relação às biópsias de tecidos moles da boca, LP também apresentou maior proporção (n=586;56,6%). As regiões anatômicas da tireóide e paratireóide foram as mais representativas (n=3.467;75,9%), seguida da região de tecidos moles da boca (n=919;20,1%). O procedimento cirúrgico mais registrado foi tireoidectomia total. A taxa de mortalidade por 100 mil habitantes foi mais representativa nas mesorregiões com maiores temperaturas e atividades rurais (Central e Oeste Potiguar). Conclusão: Os procedimentos com finalidade diagnóstica foram díspares quando comparados aos de remoção cirúrgica da lesão no mesmo sítio de diagnóstico. A mesorregião mais desenvolvida e de maior densidade populacional (Leste Potiguar) apresentou maiores registros de procedimentos de diagnóstico para o câncer de cabeça e pescoço e menor taxa de mortalidade

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514

Basis for enhanced barrier function of pigmented skin

Humans with darkly-pigmented skin display superior permeability barrier function in comparison to humans with lightly-pigmented skin. The reduced pH of the stratum corneum (SC) of darkly-pigmented skin could account for enhanced function, because acidifying lightly-pigmented human SC resets barrier function to darkly-pigmented levels. In SKH1 (non-pigmented) vs. SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J vs. SKH1 mice, correlating with a reduced pH in the lower SC that co-localizes with the extrusion of melanin granules. Darkly-pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate re-acidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly-pigmented-bearing human keratinocytes display enhanced barrier function in comparison to lightly-pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression

Role of N-acetylcysteine in the management of COPD

The importance of the underlying local and systemic oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD) has long been established. In view of the lack of therapy that might inhibit the progress of the disease, there is an urgent need for a successful therapeutic approach that, through affecting the pathological processes, will influence the subsequent issues in COPD management such as lung function, airway clearance, dyspnoea, exacerbation, and quality of life. N-acetylcysteine (NAC) is a mucolytic and antioxidant drug that may also influence several inflammatory pathways. It provides the sulfhydryl groups and acts both as a precursor of reduced glutathione and as a direct reactive oxygen species (ROS) scavenger, hence regulating the redox status in the cells. The changed redox status may, in turn, influence the inflammation-controlling pathways. Moreover, as a mucolytic drug, it may, by means of decreasing viscosity of the sputum, clean the bronchi leading to a decrease in dyspnoea and improved lung function. Nevertheless, as successful as it is in the in vitro studies and in vivo studies with high dosage, its actions at the dosages used in COPD management are debatable. It seems to influence exacerbation rate and limit the number of hospitalization days, however, with little or no influence on the lung function parameters. Despite these considerations and in view of the present lack of effective therapies to inhibit disease progression in COPD, NAC and its derivatives with their multiple molecular modes of action remain promising medication once doses and route of administration are optimized

Beyond Kinetic Relations

We introduce the concept of kinetic equations representing a natural extension of the more conventional notion of a kinetic relation. Algebraic kinetic relations, widely used to model dynamics of dislocations, cracks and phase boundaries, link the instantaneous value of the velocity of a defect with an instantaneous value of the driving force. The new approach generalizes kinetic relations by implying a relation between the velocity and the driving force which is nonlocal in time. To make this relations explicit one needs to integrate the system of kinetic equations. We illustrate the difference between kinetic relation and kinetic equations by working out in full detail a prototypical model of an overdamped defect in a one-dimensional discrete lattice. We show that the minimal nonlocal kinetic description containing now an internal time scale is furnished by a system of two ordinary differential equations coupling the spatial location of defect with another internal parameter that describes configuration of the core region.Comment: Revised version, 33 pages, 9 figure