Wound models for periodontal and bone regeneration: the role of biologic research

The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal-regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase.

Pain hypersensitivity and spinal nociceptive hypersensitivity in chronic pain: prevalence and associated factors.

Hypersensitivity of pain pathways is considered a relevant determinant of symptoms in chronic pain patients, but data on its prevalence are very limited. To our knowledge, no data on the prevalence of spinal nociceptive hypersensitivity are available. We studied the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity in 961 consecutive patients with various chronic pain conditions. Pain threshold and nociceptive withdrawal reflex threshold to electrical stimulation were used to assess pain hypersensitivity and spinal nociceptive hypersensitivity, respectively. Using 10th percentile cutoff of previously determined reference values, the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity (95% confidence interval) was 71.2 (68.3-74.0) and 80.0 (77.0-82.6), respectively. As a secondary aim, we analyzed demographic, psychosocial, and clinical characteristics as factors potentially associated with pain hypersensitivity and spinal nociceptive hypersensitivity using logistic regression models. Both hypersensitivity parameters were unaffected by most factors analyzed. Depression, catastrophizing, pain-related sleep interference, and average pain intensity were significantly associated with hypersensitivity. However, none of them was significant for both unadjusted and adjusted analyses. Furthermore, the odds ratios were very low, indicating modest quantitative impact. To our knowledge, this is the largest prevalence study on central hypersensitivity and the first one on the prevalence of spinal nociceptive hypersensitivity in chronic pain patients. The results revealed an impressively high prevalence, supporting a high clinical relevance of this phenomenon. Electrical pain thresholds and nociceptive withdrawal reflex explore aspects of pain processing that are mostly independent of sociodemographic, psychological, and clinical pain-related characteristics.

Species interactions and random dispersal rather than habitat filtering drive community assembly during early plant succession

Theory on plant succession predicts a temporal increase in the complexity of spatial community structure and of competitive interactions: initially random occurrences of early colonising species shift towards spatially and competitively structured plant associations in later successional stages. Here we use long-term data on early plant succession in a German post mining area to disentangle the importance of random colonisation, habitat filtering, and competition on the temporal and spatial development of plant community structure. We used species co-occurrence analysis and a recently developed method for assessing competitive strength and hierarchies (transitive versus intransitive competitive orders) in multispecies communities. We found that species turnover decreased through time within interaction neighbourhoods, but increased through time outside interaction neighbourhoods. Successional change did not lead to modular community structure. After accounting for species richness effects, the strength of competitive interactions and the proportion of transitive competitive hierarchies increased through time. Although effects of habitat filtering were weak, random colonization and subsequent competitive interactions had strong effects on community structure. Because competitive strength and transitivity were poorly correlated with soil characteristics, there was little evidence for context dependent competitive strength associated with intransitive competitive hierarchies.

The Effects of Density, Spatial Pattern, and Competitive Symmetry on Size Variation in Simulated Plant Populations

Patterns of size inequality in crowded plant populations are often taken to be indicative of the degree of size asymmetry of competition, but recent research suggests that some of the patterns attributed to size‐asymmetric competition could be due to spatial structure. To investigate the theoretical relationships between plant density, spatial pattern, and competitive size asymmetry in determining size variation in crowded plant populations, we developed a spatially explicit, individual‐based plant competition model based on overlapping zones of influence. The zone of influence of each plant is modeled as a circle, growing in two dimensions, and is allometrically related to plant biomass. The area of the circle represents resources potentially available to the plant, and plants compete for resources in areas in which they overlap. The size asymmetry of competition is reflected in the rules for dividing up the overlapping areas. Theoretical plant populations were grown in random and in perfectly uniform spatial patterns at four densities under size‐asymmetric and size‐symmetric competition. Both spatial pattern and size asymmetry contributed to size variation, but their relative importance varied greatly over density and over time. Early in stand development, spatial pattern was more important than the symmetry of competition in determining the degree of size variation within the population, but after plants grew and competition intensified, the size asymmetry of competition became a much more important source of size variation. Size variability was slightly higher at higher densities when competition was symmetric and plants were distributed nonuniformly in space. In a uniform spatial pattern, size variation increased with density only when competition was size asymmetric. Our results suggest that when competition is size asymmetric and intense, it will be more important in generating size variation than is local variation in density. Our results and the available data are consistent with the hypothesis that high levels of size inequality commonly observed within crowded plant populations are largely due to size‐asymmetric competition, not to variation in local density.

How to be in a good shape? The influence of clone morphology on cell competition

Cell competition is a conserved mechanism where slow proliferating cells (so called losers) are eliminated by faster proliferating neighbors (so called winners) through apoptosis.(1) It is an important process which prevents developmental malformations and maintains tissue fitness in aging adults.(2) Recently, we have shown that the probability of elimination of loser cells correlates with the surface of contact between losers and winners in Myc-induced competition.(3) Moreover, we have characterized an active mechanism that increases the surface of contact between losers and winners, hence accelerating the elimination of loser cells. This is the first indication that cell shape and mechanics can influence cell competition. Here, we will discuss the consequence of the relationship between shape and competition, as well as the relevance of this model for other modes of competition.

Exercise and Mood: Exploring the Role of Exercise in Regulating Stress Reactivity in Bipolar Disorder

Bipolar Disorder (BD) is a recurrent and debilitating psychological disorder characterized by a chronic dysregulation of mood with fluctuations between extremely low (e.g., depression) and extremely elevated mood states (e.g., mania), and ranks as the 6th leading cause of disability in the world. Although research has consistently shown that exercise may have antidepressant and stress-attenuating benefits in other psychiatric illnesses (e.g., depression, anxiety), these benefits have not been directly investigated for BD. The current study represents the first known investigation to examine this relationship. Single-participant designs, with crossover and interaction treatment components (i.e., A/B/A/B/A, A/C/A/C/A, A/B/A/C/A, or A/C/A/B/A) were utilized to investigate the impact of participation in a prescribed regimen of exercise (EP) versus standard behavioral activation (SBA; i.e., non-exercise activity) has on stress perception and reactivity, and mood stability in a sample of individuals with BD. Individuals completed four total weeks of treatment, and psychophysiological measures of reactivity were recorded during a laboratory stress task (i.e., backward counting task) prior to and following each two-week intervention phase. No appreciable differences were found between levels of exercise participation between treatment groups. Interestingly, symptoms of depressed mood (BDI-II scores) decreased at similar rates following 4 weeks of treatment for all participants. BDI-II decreases were found to be most correlated with elective exercise participation, although this relationship was not significant. Regarding stress reactivity, elective participation in mild to moderate intensity exercise was found to reduce an individual’s perception of stress reactivity to an acute stressor, while participation in a prescribed program of exercise was more effective in reducing physiological response to the same task. Utilizing multiple forms of behavioral activation simultaneously was found to be most effective in decreasing perception of stress reactivity, and may also result in a positive change in the use of adaptive versus maladaptive coping strategies. Participation in a 4-week program of exercise appeared to provide the most benefit, consistent with exercise habituation theories. Overall, current findings provide preliminary support for the prophylactic benefits of including a prescribed and monitored program of exercise as an adjunct treatment for individuals with BD. Larger scale research is needed to more clearly determine the impact of exercise on stress reactivity and mood episode relapse in individuals with BD.

RNA binding characteristics and overall topology of the vaccinia virus polyadenylation complex

mRNA 3′ polyadenylation is central to mRNA biogenesis in prokaryotes and eukaryotes, and is implicated in numerous aspects of mRNA metabolism, including efficiency of mRNA export from the nucleus, message stability, and initiation of translation. However, due to the great complexity of the eukaryotic polyadenylation apparatus, the mechanisms of RNA 3 ′ end processing have remained elusive. Although the RNA processing reactions leading to polyadenylated messenger RNA have been studied in many systems, and much progress has been made, a complete understanding of the biochemistry of the poly(A) polymerase enzyme is still lacking. My research uses Vaccinia virus as a model system to gain a better understanding of this complicated polyadenylation process, which consist of RNA binding, catalysis and polymerase translocation. ^ Vaccinia virus replicates in the cytoplasm of its host cell, so it must employ its own poly(A) polymerase (PAP), a heterodimer of two virus encoded proteins, VP55 and VP39. VP55 is the catalytic subunit, adding 30 adenylates to a non-polyadenylated RNA in a rapid processive manner before abruptly changing to a slow, non-processive mode of adenylate addition and dissociating from the RNA. VP39 is the stimulatory subunit. It has no polyadenylation catalytic activity by itself, but when associated with VP55 it facilitates the semi-processive synthesis of tails several hundred adenylates in length. ^ Oligonucleotide selection and competition studies have shown that the heterodimer binds a minimal motif of (rU)2 (N)25 U, the “heterodimer binding motif”, within an oligonucleotide, and its primer selection for polyadenylation is base-type specific. ^ Crosslinking studies using photosensitive uridylate analogs show that within a VP55-VP39-primer ternary complex, VP55 comes into contact with all three required uridylates, while VP39 only contacts the downstream uridylate. Further studies, using a backbone-anchored photosensitive crosslinker show that both PAP subunits are in close proximity to the downstream −10 to −21 region of 50mer model primers containing the heterodimer binding motif. This equal crosslinking to both subunits suggests that the dimerization of VP55 and VP39 creates either a cleft or a channel between the two subunits through which this region of RNA passes. ^ Peptide mapping studies of VP39 covalently crosslinked to the oligonucleotide have identified residue R107 as the amino acid in close proximity to the −10 uridylate. This helps us project a conceptual model onto the known physical surface of this subunit. In the absence of any tertiary structural data for VP55, we have used a series of oligonucleotide selection assays, as well as crosslinking, nucleotide transfer assays, and gel shift assays to gain insight into the requirements for binding, polyadenylation and translocation. Collectively, these data allow us to put together a comprehensive model of the structure and function of the polyadenylation ternary complex consisting of VP39, VP55 and RNA. ^

The association of area socioeconomic status and cancer screening: A systematic review and multilevel study

Background. The gap between actual and ideal rates of routine cancer screening in the U.S., particularly for colorectal cancer screening (CRCS) (1;2), is responsible for an unnecessary burden of morbidity and mortality, particularly for disadvantaged groups. Knowledge about the effects of individual and area influences is being advanced by a growing body of research that has examined the association of area socioeconomic status (SES) and cancer screening after controlling for individual SES. The findings from this emerging and heterogeneous research in the cancer screening literature have been mixed. Moreover, multilevel studies in this area have not yet adequately explored the possibility of differential associations by population subgroup, despite some evidence suggesting gender-specific effects. ^ Objectives and methods. This dissertation reports on a systematic review of studies on the association of area SES and cancer screening and a multilevel study of the association between area SES and CRCS. The specific aims of the systematic review are to: (1) describe the study designs, constructs, methods, and measures; (2) describe the association of area SES and cancer screening; and (3) identify neglected areas of research. ^ The empiric study linked a pooled sample of respondents aged ≥50 years without a personal history of colorectal cancer from the 2003 and 2005 California Health Interview Surveys with a comprehensive set of census-tract level area SES measures from the 2000 U.S. Census. Two-level random intercept models were used to test 2 hypotheses: (1) area SES will be associated with adherence to two modalities of CRCS after controlling for individual SES; and (2) gender will moderate the relationship between area socioeconomic status and adherence to both modalities of CRCS. ^ Results. The systematic review identified 19 eligible studies that demonstrated variability in study designs, methods, constructs, and measures. The majority of tested associations were either not statistically significant or significant and in the positive direction, indicating that as area SES increased, the odds of CRCS increased. The multilevel study demonstrated that while multiple aspects of area SES were associated with CRCS after controlling for individual SES, associations differed by screening modality and in the case of endoscopy, they also differed by gender. ^ Conclusions. Conceptual and methodologic heterogeneity and weaknesses in the literature to date limit definitive conclusions about the underlying relationships between area SES and cancer screening. The multilevel study provided partial support for both hypotheses. Future research should continue to explore the role of gender as a moderating influence with the aim of identifying the mechanisms linking area SES and cancer prevention behaviors. ^

Meiofauna densities, nematode biomass, nematode genus diversity, sediment grain size, organic matter, and pigments for the surface layers of two sites in summer (November 2009) and winter (august 2010)

The meiobenthic community of Potter Cove (King George Island, west Antarctic Peninsula) was investigated, focusing on responses to summer/winter conditions in two study sites contrasting in terms of organic matter inputs. Meiofaunal densities were found to be higher in summer and lower in winter, although this result was not significantly related to the in situ availability of organic matter in each season. The combination of food quality and competition for food amongst higher trophic levels may have played a role in determining the standing stocks at the two sites. Meiobenthic winter abundances were sufficiently high to infer that energy sources were not limiting during winter, supporting observations from other studies for both shallow water and continental shelf Antarctic ecosystems. Recruitment within meiofaunal communities was coupled to the seasonal input of fresh detritus for harpacticoid copepods but not for nematodes, suggesting that species-specific life history or trophic features form an important element of the responses observed.

Community structure and biodiversity in marine benthic communities during experiments, 2011

A mesocosm experiment was conducted to quantify the effects of reduced pH and elevated temperature on an intact marine invertebrate community. Standardised faunal communities, collected from the extreme low intertidal zone using artificial substrate units, were exposed to one of eight nominal treatments (four pH levels: 8.0, 7.7, 7.3 and 6.7, crossed with two temperature levels: 12 and 16°C). After 60 days exposure communities showed significant changes in structure and lower diversity in response to reduced pH. The response to temperature was more complex. At higher pH levels (8.0 and 7.7) elevated temperature treatments contained higher species abundances and diversity than the lower temperature treatments. In contrast, at lower pH levels (7.3 and 6.7), elevated temperature treatments had lower species abundances and diversity than lower temperature treatments. The species losses responsible for these changes in community structure and diversity were not randomly distributed across the different phyla examined. Molluscs showed the greatest reduction in abundance and diversity in response to low pH and elevated temperature, whilst annelid abundance and diversity was mostly unaffected by low pH and was higher at the elevated temperature. The arthropod response was between these two extremes with moderately reduced abundance and diversity at low pH and elevated temperature. Nematode abundance increased in response to low pH and elevated temperature, probably due to the reduction of ecological constraints, such as predation and competition, caused by a decrease in macrofaunal abundance. This community-based mesocosm study supports previous suggestions, based on observations of direct physiological impacts, that ocean acidification induced changes in marine biodiversity will be driven by differential vulnerability within and between different taxonomical groups. This study also illustrates the importance of considering indirect effects that occur within multispecies assemblages when attempting to predict the consequences of ocean acidification and global warming on marine communities.

Effects of elevated CO2 and temperature on an intertidal meiobenthic community

In the near future, the marine environment is likely to be subjected to simultaneous increases in temperature and decreased pH. The potential effects of these changes on intertidal, meiofaunal assemblages were investigated using a mesocosm experiment. Artificial Substrate Units containing meiofauna from the extreme low intertidal zone were exposed for 60 days to eight experimental treatments (four replicates for each treatment) comprising four pH levels: 8.0 (ambient control), 7.7 & 7.3 (predicted changes associated with ocean acidification), and 6.7 (CO2 point-source leakage from geological storage), crossed with two temperatures: 12 °C (ambient control) and 16 °C (predicted). Community structure, measured using major meiofauna taxa was significantly affected by pH and temperature. Copepods and copepodites showed the greatest decline in abundance in response to low pH and elevated temperature. Nematodes increased in abundance in response to low pH and temperature rise, possibly caused by decreased predation and competition for food owing to the declining macrofauna density. Nematode species composition changed significantly between the different treatments, and was affected by both seawater acidification and warming. Estimated nematode species diversity, species evenness, and the maturity index, were substantially lower at 16 °C, whereas trophic diversity was slightly higher at 16 °C except at pH 6.7. This study has demonstrated that the combination of elevated levels of CO2 and ocean warming may have substantial effects on structural and functional characteristics of meiofaunal and nematode communities, and that single stressor experiments are unlikely to encompass the complexity of abiotic and biotic interactions. At the same time, ecological interactions may lead to complex community responses to pH and temperature changes in the interstitial environment.

(Table 1) Number of alleles per locus and heterozygosity of Arctic charr (Salvelinus alpinus) populations in Iceland

The ecological theory of adaptive radiation predicts that the evolution of phenotypic diversity within species is generated by divergent natural selection arising from different environments and competition between species. Genetic connectivity among populations is likely also to have an important role in both the origin and maintenance of adaptive genetic diversity. Our goal was to evaluate the potential roles of genetic connectivity and natural selection in the maintenance of adaptive phenotypic differences among morphs of Arctic charr, Salvelinus alpinus, in Iceland. At a large spatial scale, we tested the predictive power of geographic structure and phenotypic variation for patterns of neutral genetic variation among populations throughout Iceland. At a smaller scale, we evaluated the genetic differentiation between two morphs in Lake Thingvallavatn relative to historically explicit, coalescent-based null models of the evolutionary history of these lineages. At the large spatial scale, populations are highly differentiated, but weakly structured, both geographically and with respect to patterns of phenotypic variation. At the intralacustrine scale, we observe modest genetic differentiation between two morphs, but this level of differentiation is nonetheless consistent with strong reproductive isolation throughout the Holocene. Rather than a result of the homogenizing effect of gene flow in a system at migration-drift equilibrium, the modest level of genetic differentiation could equally be a result of slow neutral divergence by drift in large populations. We conclude that contemporary and recent patterns of restricted gene flow have been highly conducive to the evolution and maintenance of adaptive genetic variation in Icelandic Arctic charr.

Myanmar Sugar SMEs: History, Technology, Location and Government Policy

Small and medium enterprises (SMEs) engaged in sugar processing in Myanmar appeared in the last decade of the socialist era. An acute sugar deficit, restricted trade in white sugar, and high demand from the conventional dairy business led to the growth of sugar SMEs by appropriate blending of semi-finished products (syrup) in the fields, which were then processed in vacuum pans and centrifugals to obtain white sugar. This became a tradable commodity and sugar SMEs grew in clusters in big cities. They are family-owned businesses. However, they lack the bagasse-based power generation. In recent years, large modern sugar factories operated by private and military companies have emerged as key players. The current shortage of fuel feedstock and competition for raw materials have become driving forces that shift sugar SMEs from market-oriented to raw material-oriented locations. Internal competition among key players made sugar price highly volatile, too. Being placed on a level playing field, the whole industry should be upgraded in terms of price and quality to become export-oriented.

Single optical surface imaging designs with unconstrained object to image mapping

In this work, novel imaging designs with a single optical surface (either refractive or reflective) are presented. In some of these designs, both object and image shapes are given but mapping from object to image is obtained as a result of the design. In other designs, not only the mapping is obtained in the design process, but also the shape of the object is found. In the examples considered, the image is virtual and located at infinity and is seen from known pupil, which can emulate a human eye. In the first introductory part, 2D designs have been done using three different design methods: a SMS design, a compound Cartesian oval surface, and a differential equation method for the limit case of small pupil. At the point-size pupil limit, it is proven that these three methods coincide. In the second part, previous 2D designs are extended to 3D by rotation and the astigmatism of the image has been studied. As an advanced variation, the differential equation method is used to provide the freedom to control the tangential rays and sagittal rays simultaneously. As a result, designs without astigmatism (at the small pupil limit) on a curved object surface have been obtained. Finally, this anastigmatic differential equation method has been extended to 3D for the general case, in which freeform surfaces are designed.

Análisis cuantitativo y cualitativo de los momentos críticos en baloncesto = Quantitative and qualitative analysis of the critical moments in basketball

El MC en baloncesto es aquel fenómeno relacionado con el juego que presenta unas características particulares determinadas por la idiosincrasia de un equipo y puede afectar a los protagonistas y por ende al devenir del juego. En la presente Tesis se ha estudiado la incidencia del MC en Liga A.C.B. de baloncesto y para su desarrollo en profundidad se ha planteado dos investigaciones una cuantitativa y otra cualitativa cuya metodología se detalla a continuación: La investigación cuantitativa se ha basado en la técnica de estudio del “Performance analysis”, para ello se han estudiado cuatro temporadas de la Liga A.C.B. (del 2007/08 al 2010/11), tal y como refleja en la bibliografía consultada se han tomado como momentos críticos del juego a los últimos cinco minutos de partidos donde la diferencia de puntos fue de seis puntos y todos los Tiempos Extras disputados, de tal manera que se han estudiado 197 momentos críticos. La contextualización del estudio se ha hecho en función de la variables situacionales “game location” (local o visitante), “team quality” (mejores o peores clasificados) y “competition” (fases de LR y Playoff). Para la interpretación de los resultados se han realizado los siguientes análisis descriptivos: 1) Análisis Discriminante, 2) Regresión Lineal Múltiple; y 3) Análisis del Modelo Lineal General Multivariante. La investigación cualitativa se ha basado en la técnica de investigación de la entrevista semiestructurada. Se entrevistaron a 12 entrenadores que militaban en la Liga A.C.B. durante la temporada 2011/12, cuyo objetivo ha sido conocer el punto de vista que tiene el entrenador sobre el concepto del MC y que de esta forma pudiera dar un enfoque más práctico basado en su conocimiento y experiencia acerca de cómo actuar ante el MC en el baloncesto. Los resultados de ambas investigaciones coinciden en señalar la importancia del MC sobre el resultado final del juego. De igual forma, el concepto en sí entraña una gran complejidad por lo que se considera fundamental la visión científica de la observación del juego y la percepción subjetiva que presenta el entrenador ante el fenómeno, para la cual los aspectos psicológicos de sus protagonistas (jugadores y entrenadores) son determinantes. ABSTRACT The Critical Moment (CM) in basketball is a related phenomenon with the game that has particular features determined by the idiosyncrasies of a team and can affect the players and therefore the future of the game. In this Thesis we have studied the impact of CM in the A.C.B. League and from a profound development two investigations have been raised, quantitative and qualitative whose methodology is as follows: The quantitative research is based on the technique of study "Performance analysis", for this we have studied four seasons in the A.C.B. League (2007/08 to 2010/11), and as reflected in the literature the Critical Moments of the games were taken from the last five minutes of games where the point spread was six points and all overtimes disputed, such that 197 critical moments have been studied. The contextualization of the study has been based on the situational variables "game location" (home or away), "team quality" (better or lower classified) and "competition" (LR and Playoff phases). For the interpretation of the results the following descriptive analyzes were performed: 1) Discriminant Analysis, 2) Multiple Linear Regression Analysis; and 3) Analysis of Multivariate General Linear Model. Qualitative research is based on the technique of investigation of a semi-structured interview. 12 coaches who belonged to the A.C.B. League were interviewed in seasons 2011/12, which aimed to determine the point of view that the coach has on the CM concept and thus could give a more practical approach based on their knowledge and experience about how to deal with the CM in basketball. The results of both studies agree on the importance of the CM on the final outcome of the game. Similarly, the concept itself is highly complex so the scientific view of the observation of the game is considered essential as well as the subjective perception the coach presents before the phenomenon, for which the psychological aspects of their characters (players and coaches) are crucial.