First passage time analysis of spatial mutation patterns reveals sub-clonal evolutionary dynamics in colorectal cancer.

The signature of early cancer dynamics on the spatial arrangement of tumour cells is poorly understood, and yet could encode information about how sub-clones grew within the expanding tumour. Novel methods of quantifying spatial tumour data at the cellular scale are required to link evolutionary dynamics to the resulting spatial architecture of the tumour. Here, we propose a framework using first passage times of random walks to quantify the complex spatial patterns of tumour cell population mixing. First, using a simple model of cell mixing we demonstrate how first passage time statistics can distinguish between different pattern structures. We then apply our method to simulated patterns of mutated and non-mutated tumour cell population mixing, generated using an agent-based model of expanding tumours, to explore how first passage times reflect mutant cell replicative advantage, time of emergence and strength of cell pushing. Finally, we explore applications to experimentally measured human colorectal cancer, and estimate parameters of early sub-clonal dynamics using our spatial computational model. We infer a wide range of sub-clonal dynamics, with mutant cell division rates varying between 1 and 4 times the rate of non-mutated cells across our sample set. Some mutated sub-clones emerged after as few as 100 non-mutant cell divisions, and others only after 50,000 divisions. The majority were consistent with boundary driven growth or short-range cell pushing. By analysing multiple sub-sampled regions in a small number of samples, we explore how the distribution of inferred dynamics could inform about the initial mutational event. Our results demonstrate the efficacy of first passage time analysis as a new methodology in spatial analysis of solid tumour tissue, and suggest that patterns of sub-clonal mixing can provide insights into early cancer dynamics.

Pharmacogeomic implications of population diversity in Latin America: TPMT and NUDT15 polymorphisms and thiopurine dosing.

TPMT and NUDT15 polymorphisms are major determinants of tolerance to thiopurine drugs used in leukemias and nonmalignant immunologic disorders. We adopted an extreme discordant phenotype approach to explore the impact of Native American versus European ancestry on the distribution of TPMT and NUDT15 polymorphisms, and inferred metabolic phenotypes in the 1000 Genomes Ad Mixed American superpopulation. Significant differences were observed in the distribution of TPMT and NUDT15 haplotypes (star alleles) between individuals with predominant (>70%) European versus Native ancestry. The largest difference is related to NUDT15 rs116855232. Based on the combined TPMT/NUDT15 metabolic phenotypes, the Clinical Pharmacogenetics Implementation Consortium recommendations for thiopurine dose adjustment applies to 40.1% of individuals with major Native American ancestry, compared to 12.8% of individuals with predominantly European ancestry. These findings may be relevant to the adoption and interpretation of pharmacogenetic tests for thiopurine drugs across Latin America peoples with different European and Native-American ancestries.

Quantifying ethnic segregation in cities through random walks.

Socioeconomic segregation has an important role in the emergence of large-scale inequalities in urban areas. Most of the available measures of spatial segregation depend on the scale and size of the system under study, or neglect large-scale spatial correlations, or rely on ad-hoc parameters, making it hard to compare different systems on equal grounds. We propose here a family of non-parametric measures for spatial distributions, based on the statistics of the trajectories of random walks on graphs associated to a spatial system. These quantities provide a consistent estimation of segregation in synthetic spatial patterns, and we use them to analyse the ethnic segregation of metropolitan areas in the US and the UK. We show that the spatial diversity of ethnic distributions, as measured through diffusion on graphs, allow us to compare the ethnic segregation of urban areas having different size, shape, or peculiar microscopic characteristics, and exhibits a strong association with socio-economic deprivation.

Diffusion segregation and the disproportionate incidence of COVID-19 in African American communities.

One of the most concerning aspects of the ongoing COVID-19 pandemic is that it disproportionately affects people from some specific ethnic and socio-economic minorities. In particular, since from the beginning of the pandemic it has been clear that people from Black and African American backgrounds seem to be hit especially hard by the virus, creating a substantial infection gap. The observed abnormal impact on these ethnic groups could probably be due to the co-occurrence of other known risk factors, including co-morbidity, poverty, level of education, access to healthcare, residential segregation and response to cures, although those factors do not seem able to explain fully and in depth the excess incidence of infections and deaths among African Americans. Here, we introduce the concept of diffusion segregation, that is the extent to which a given group of people is internally clustered or exposed to other groups, as a result of mobility and commuting habits. By analysing census and mobility data on major US cities, we found that the weekly excess COVID-19 incidence and mortality in African American communities at the beginning of the COVID-19 pandemic is significantly associated with their level of diffusion segregation. The results confirm that knowing where people commute to, rather than where they live, is potentially much more important to contain and curb the spreading of infectious diseases.

Improvement of Sugarcane Stillage (Vinasse) Anaerobic Digestion with Cheese Whey as its Co-substrate: Achieving High Methane Productivity and Yield.

This study investigated methane production in an anaerobic sequencing batch biofilm reactor (AnSBBR) by co-digesting sugarcane vinasse and cheese whey. The assessment was based on the influence of feed strategy, interaction between cycle time and influent concentration, applied volumetric organic load (OLRA), and temperature over system stability and performance. The system showed flexibility with regard to the feed strategy, but the reduction of cycle time and influent concentration, at the same OLRA, resulted in lower methane productivity. Increasing organic load, up to the value of 15.27 gCOD L-1 day-1, favored the process, increasing methane yield and productivity. Temperature reduction from 30 to 25 °C resulted in worse performance, although increasing it to 35 °C provided similar results to 30 °C. The best results were achieved at an OLRA of 15.27 gCOD L-1 day-1, cycle time of 8 h, fed-batch operation, and temperature of 30 °C. The system achieved soluble COD removal efficiency of 89%, methane productivity of 208.5 molCH4 m-3 day-1 and yield of 15.76 mmolCH4 gCOD-1. The kinetic model fit indicated methanogenesis preference for the hydrogenotrophic route. At the industrial scale estimative, considering a scenario with a sugarcane ethanol plant with ethanol production of 150,896 m3 year-1, it was estimated energy production of 25,544 MWh month-1.

Associação entre doença pulmonar obstrutiva crônica e a má condição de saúde periodontal: um estudo transversal / Association between chronic obstructive pulmonary disease and poor periodontal health: a cross-sectional study

Objetivo: estudos sugerem uma associação entre a doença periodontal e a doença pulmonar obstrutiva crônica (DPOC). O objetivo deste estudo foi avaliar a condição periodontal em pacientes com DPOC. Metodologia: Este estudo transversal incluiu 33 pacientes com DPOC e 30 pacientes sem DPOC (grupo controle). Todos os pacientes realizaram espirometria e foram examinados por um dentista. A condição periodontal foi avaliada através dos seguintes índices: número de dentes, índice de placa (IP), índice de sangramento gengival (IG), profundidade de sondagem (PS), PS dos sítios doentes (PSD), nível de inserção clínica (NIC), NIC dos sítios doentes (NICD) e percentual de sítios doentes (NICDP). Para análise estatística foram utilizados o teste de qui-quadrado de Pearson, o testet de Student, análise de regressão logística e cálculo do odds ratio. Resultados: O grupo DPOC apresentou maiores IP (p=0,01), NIC (p=0,001) e NICDP (p<0,001), com odds ratio de 1,2 (95%IC: 1,023­1,408). Conclusões: Os pacientes com DPOC apresentaram pior condição periodontal. Mais estudos são necessários para esclarecer o papel da terapia periodontal no protocolo de acompanhamento dos pacientes com DPOC

Objective: evidence suggests an association between periodontal disease and chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the periodontal status in patients with COPD. Methods: this cross-sectional study included 33 patients with COPD and 30 patients without COPD (control group). All patients underwent spirometry and were examined by a dentist. Periodontal status was evaluated by the following indexes: number of teeth, plaque index (PI), gingival bleeding index (GBI), probing depth (PD), PD of diseased sites (PDD), clinical attachment level (CAL), CAL of diseased sites (CALD) and percentage of diseased sites (CALDP). The findings were analyzed under Pearson's chi-square test, independent samples t test and logistic regression with odds ratio. Results: the COPD group had higher PI (p = 0,01), CAL (p = 0,001) and CALDP (p <0,001), and the odds ratio for patients with COPD was 1.2 (95% CI: 1,023-1,408). Conclusions: patients with COPD present worse periodontal status. More studies are needed in order to clarify the role of periodontal therapy in the management of COPD.

Recobrimento radicular e reanatomização dentária com finalidade estética: relato de um caso / Root coverage and recontouring with aesthetic purpose: report of a case

A recessão gengival é o resultado da migração apical da margem gengival em relação junção cemento-esmalte. Os fatores etiológicos primário são a placa bacteriana e a escovação traumática, sendo também associados fatores predisponentes como: posição dentária, inserção de freios e bridas, deiscências ósseas, faixas de gengiva inserida e fatores iatrogênicos como movimentação ortodôntica e tratamentos restauradores. Diversas técnicas de cirurgia plástica periodontal foram desenvolvidas com o objetivo de corrigir esse defeito periodontal, quando este ocasiona comprometimento estético, sensibilidade e acúmulo de placa na região. O objetivo deste trabalho é apresentar, através de um caso clínico, a técnica de enxerto conjuntivo subepitelial com microcirurgia periodontal para recobrimento radicular, em um canino superior direito, que foi deslocado para a posição do incisivo lateral perdido anteriormente. Em seguida, o canino recebeu um recontorno estético em sua coroa clínica com resina fotopolimerizável.

The gingival recession is the result of apical migration of gingival margin for cement-enamel junction. The primary etiological factors are plaque and traumatic brushing and are also associated predisposing factors as: dental position, insertion of brakes and adhesive bands, dehiscence bone, and inserted strips of gum and iatrogenics factors such as handling orthodontic treatments and restorative. Several techniques of periodontal plastic surgery were developed in order to correct this periodontal defect when aesthetic commitment, sensitivity, and accumulation of plaque in the region. The objective of this work is to present a case through the technique of subepithelial connective tissue graft with periodontal microsurgery for root coverage in an upper right canine that was moved to the position of the incisive side lost before. Then the canine received a recontouring aesthetic in its clinical crown with resin composite.

Influência da macro-geometria na estabilidade primária dos implantes / Influence of macro-geometry in the primary stability of implants

A estabilidade primária dos implantes está intimamente relacionada à macro-geometria dos implantes na medida que pode aumentar o contato íntimo entre o biomaterial e a estrutura óssea. O objetivo do presente estudo foi avaliar a influência da macro-geometria na estabilidade primária dos implantes. Foram utilizados dois tipos de implantes, um cilíndrico e com rosca única (grupo controle) e outro com conicidade apical e três tipos de roscas (grupo teste). Os implantes foram instalados por três operadores em osso bovino fresco. Cada profissional fez a instalação de oito implantes (4 teste e 4 controle) em osso bovino. Os parâmetros avaliados foram: torque de inserção, frequência de ressonância e torque de remoção. A análise dos resultados permitiu a detecção de que os torques de inserção foram maiores no grupo teste (p < 0,05). Não foi observada influência do operador nas variáveis analisadas. Pode-se então concluir que a macro-geometria dos implantes do grupo teste favoreceu a estabilidade primária do implante.

The primary stability of implants is related to implant geometry since it can raise the intimate contact between biomaterial and bone structure. The aim of the present study was to evaluate the influence of implant geometry on primary stability. It was used two types of implants, one cylindrical and with an unique thread (control group) and another tapered with three types of threads (test group). Implants were placed by three professionals in bovine bone. Each operator installed eight implants (4 test and 4 control). The parameters analyzed were: inserting torque, unscrewing torque and resonance frequency. As results it was detected that insertion torque was higher in the test group (p < 0,05). It was not observed influence of the operator in the parameters analyzed. Thus, it can be concluded that geometry of implants in the test group improved implant primary stability.

Peri-implantite: diagnóstico e tratamento / Periimplantitis: diagnosis and therapy

O uso de implantes osseointegrados vem crescendo nas últimas décadas e, juntamente com eles, suas complicações. A peri-implantite se apresenta como uma infecção bacteriana que afeta os tecidos moles e duros ao redor do implante, promovendo perda da osseointegração. O fator etiológico dessa patologia é o acúmulo de bactérias na superfície do implante, mas o seu desenvolvimento também está relacionado a indicadores de risco como a história de doença periodontal. Para um diagnóstico precoce, programas de avaliação de risco individual precisam ser instituídos e o paciente incluído em um programa de monitoramento, onde alguns parâmetros clínicos e radiográficos são avaliados. Várias terapias são propostas a fim de minimizar as sequelas deixadas pela infecção peri-implantar, incluindo o debridamento da superfície do implante, acesso cirúrgico, condicionamento da superfície do implante, regeneração óssea, antibiótico tópico e sistêmico. Diante da relevância do tema, o objetivo do presente estudo é, através de uma revisão de literatura, discorrer sobre as ferramentas utilizadas para diagnóstico da peri-implantite e fazer uma abordagem crítica sobre as diversas possibilidades terapêuticas.

During the past decades, the use of osseointegraded implants has increased and also their complications and problems. Periimplantitis is a chronic progressive marginal infection, defined as an inflammatory reaction affecting the tissue surrounding osseointegreted dental implants resulting in loss of supporting bone. The etiologic factor of this pathology is the bacterial accumulation in implant surface, but its development is also associated with risk indicators as the history of periodontal disease. For an early diagnosis, programs that evaluate individual risks has to be implemented and the patient monitored for clinical and radiographic parameters to adequately treat the disease. Therapies are proposed to minimize the sequels of periimplantitis infection, including the implant surface debridement, surgical access, conditioning of implant surface, osseous regeneration, local and systemic antibiotic. Thus, the aim of the present study is to, with a literature review, describe the tools used for diagnosis of periimplantitis and to critically analyze the therapeutic approaches.

Recobrimento radicular de recessão classe III com técnica de microcirurgia: relato de caso clínico / Root coverage of recession class III with microsurgical technique: a case report

O recobrimento de recessões classe III ainda é um desafio para a Periodontia. Com o advento da microscopia operatória, pode-se obter uma manipulação mais apurada dos tecidos e uma melhor visualização do campo operatório, possibilitando uma melhora na técnica de recobrimento. O presente estudo mostra os parâmetros clínicos de uma paciente com queixa estética de recessões classe III de Miller nos dentes 22 e 24. Foi realizada uma cirurgia de enxerto conjuntivo, com o uso do microscópio, através de uma técnica de preservação da papila. O recobrimento radicular foi alcançado com tecido saudável e melhora da aparência estética da paciente. Os resultados clínicos foram acompanhados por 6 meses.

The covering of recessions class III still is a challenge for the Periodontology. With the advent of surgical microscope, a more refined manipulation of tissue can be gotten and better visualization of the operative field, making possible an improvement in the covering technique. This report examines the clinical parameters of one patient with aesthetic complain of recessions class III in teeth 22 and 24. A connective tissue grafting surgery was carried through, with the use of the microscope, through one technique of preservation of papilla. Root covering was reached with soft tissue and improved the patient’s aesthetic appearance. The clinical result was followed for 6 months.