Fungal Lesions of the Oral Mucosa Diagnosis and Management.

Oral fungal infections are opportunistic and due to impaired host resistance. The increasing number of immunosuppressed individuals contributes to rising numbers of mycoses worldwide, and the ease of global migration has allowed the geographic range of endemic mycoses to expand. Deep fungal infections can clinically mimic other pathologic conditions including malignancy. This review highlights the pathogenesis, clinical features, diagnosis, and treatment recommendations of eight fungal infections that can be encountered in the dental setting.

The gender health innovation gap: A perspective from the NIH Office of Research on Women's Health.

Systemic sources of the gender health innovation gap include inattention to the effects of sex and gender on health, underinvestment in health conditions relevant to or limited to women, workforce diversity inequities, and societal attitudes. The US federal government instituted policies and programs to address these challenges and demonstrate commitment to closing this gap with the development of the first National Strategy on Gender Equity and Equality.

The Integration of Sex and Gender Considerations Into Biomedical Research: Lessons From International Funding Agencies.

To improve the outcomes of research and medicine, government-based international research funding agencies have implemented various types of policies and mechanisms with respect to sex as a biological variable and gender as a sociocultural factor. After the 1990s, the US National Institutes of Health (NIH), the Canadian Institutes of Health Research (CIHR), and the European Commission (EC) began requesting that applicants address sex and gender considerations in grant proposals, and offering resources to help the scientific community integrate sex and gender into biomedical research. Although it is too early to analyze data on the success of all of the policies and mechanisms implemented, here we review the use both of carrots (incentives) and sticks (requirements) developed to motivate researchers and the entire scientific research enterprise to consider sex and gender influences on health and in science. The NIH focused on sex as a biological variable (SABV) aligned with an initiative to enhance reproducibility through rigor and transparency; CIHR instituted a sex- and gender-based analysis (SGBA) policy; and the EC required the integration of the "gender dimension," which incorporates sex, gender, and intersectional analysis into research and innovation. Other global efforts are briefly summarized. Although we are still learning what works, we share lessons learned to improve the integration of sex and gender considerations into research. In conjunction with refining and expanding the policies of funding agencies and mechanisms, private funders/philanthropic groups, editors of peer-reviewed journals, academic institutions, professional organizations, ethics boards, health care systems, and industry also need to make concerted efforts to integrate sex and gender into research, and we all must bridge across silos to promote systemwide solutions throughout the biomedical enterprise. For example, policies that encourage researchers to disaggregate data by sex and gender, the development of tools to better measure gender effects, or policies similar to SABV and/or SGBA adopted by private funders would accelerate progress. Uptake, accountability for, and a critical appraisal of sex and gender throughout the biomedical enterprise will be crucial to achieving the goal of relevant, reproducible, replicable, and responsible science that will lead to better evidence-based, personalized care for all, but especially for women.

Does Increasing Access to Prenatal Care Reduce Racial Disparities in Birth Outcomes?

PURPOSE: To examine the effectiveness of early and adequate prenatal care (PNC) in reducing racial disparities in pre-term birth (PTB) among low-income women. DESIGN AND METHODS: This retrospective study examined birth records for 14,950 low-income Black and White women. The primary outcome of interest was racial disparities in PTB. Exposures of interest were first trimester entry into, and adequacy of, PNC. Maternal residential proximity to nearest PNC provider was calculated. Bivariate analyses were performed for PTB by race. Binary logistic regression was performed, controlling for maternal age, smoking status and racial segregation. Attributable risk of PTB for no or late entry into PNC, and percent difference by race was calculated. RESULTS: We find that early and adequate PNC significantly decreases the risk of preterm birth, however, we find no evidence that this reduces racial disparities. Low income black females in a large metropolitan county have greater geographic access to and utilization of PNC than low-income white females, yet racial disparities in preterm birth remain. Attributable risk of PTB for no or late entry into PNC was lower for Black women (32.2%) than White women (39.4%). CONCLUSIONS: Our findings suggest that adequate PNC alone does not reduce the marked racial disparities in preterm birth. PRACTICE IMPLICATIONS: Public health agencies and health care providers need to look beyond access to care, to achieve racial equity in birth outcomes. Expansion of evidence-based, comprehensive nursing interventions shown to reduce preterm birth, such as the Nurse Family Partnership home visiting program, could contribute to these efforts.

Characterization of Adult and Neonatal Articular Cartilage From the Equine Stifle.

A significant portion of equine lameness is localized to the stifle joint. Effective cartilage repair strategies are largely lacking, however, recent advances in surgical techniques, biomaterials, and cellular therapeutics have broadened the clinical strategies of cartilage repair. To date, no studies have been performed directly comparing neonatal and adult articular cartilage from the stifle across multiple sites. An understanding of the differences in properties between the therapeutic target cartilage (i.e., adult cartilage) as well as potential donor cartilage (i.e., neonatal cartilage) could aid in selection of optimal harvest sites within a donor joint as well as evaluation of the success of the grafted cells or tissues within the host. Given the dearth of characterization studies of the equine stifle joint, and in particular neonatal stifle cartilage, the goal of this study was to measure properties of both potential source tissue and host tissue. Articular cartilage of the distal femur and patella (P) was assessed in regards to two specific factors, age of the animal and specific site within the joint. Two age groups were considered: neonatal (<1 week) and adult (4-14 years). Cartilage samples were harvested from 17 sites across the distal femur and patella. It was hypothesized that properties would vary significantly between neonatal and adult horses as well as within age groups on a site-by-site basis. Adult thickness varied by site. With the exception of water content, there were no significant biochemical differences among sites within regions of the distal femur (condyles and trochlea) and the patella in either the adult or neonate. Neonatal cartilage had a significantly higher water content than adult. Surprisingly, biochemical measurements of cellularity did not differ significantly between neonatal and adult, however, adult cartilage had greater variance in cellularity than neonatal. Overall, there were no significant differences between neonatal and adult glycosaminoglycan content. Collagen per wet weight was found to be significantly higher in adult cartilage than neonatal when averaged across all levels. In terms of biomechanical properties, aggregate modulus varied significantly across the condyles of adult cartilage but not the neonate. Neonatal cartilage was significantly less permeable, and the Young's modulus of neonatal cartilage was significantly higher than the adult. The tensile strength did not vary in a statistically significant manner between age groups. An understanding of morphological, histological, biochemical, and biomechanical properties enhances the understanding of cartilage tissue physiology and structure-function relationships. This study revealed important differences in biomechanical and biochemical properties among the 17 sites and among the six joint regions, as well as age-related differences between neonatal and adult cartilage. These location and age-related variations are informative toward determining the donor tissue harvest site.

The Need to Consider Pregnancy As a Biological Variable to Reduce Preventable Suffering Related to Pregnancy.

Maternal morbidity and mortality constitute a national health crisis, and pain is a significant component of maternal morbidity. One important way to reduce maternal morbidity is to reduce the pain associated with pregnancy. Unfortunately, our understanding of how to reduce pain in women is hampered because, historically, mostly male subjects have been used in the study of pain. However, more recently, females increasingly have been included in pain research studies, and astounding differences in how males and females process pain have been uncovered. Moreover, pain in nonpregnant women differs in many ways from pain experienced by pregnant women. We argue here that to better address maternal morbidity, we must better address the pain associated with pregnancy. Furthermore, just as it is important to include both men and women in pain research to better understand pain in both sexes, conducting pain research in pregnant women is essential to finding ways to reduce pain in pregnant women.

The Rare Radiographic Sunburst Appearance of Odontogenic Myxomas: A Case Report and Review of the Literature.

Odontogenic myxomas often have a distinctive radiographic presentation described as a "soap bubble", "tennis racket", or "honeycomb" pattern. Less frequently, examples of odontogenic myxomas with a "sunray" or "sunburst" pattern have been reported. Because malignant entities such as osteosarcomas more classically present with a sunray/sunburst appearance, odontogenic myxomas are rarely considered in the radiographic differential diagnosis of a sunburst lesion. The objective of this paper is to report a case of an odontogenic myxoma presenting with a sunburst appearance and to review similar reported cases in the literature. To the best of the authors' knowledge, this additional case of an odontogenic myxoma presenting with a sunburst appearance brings the total number of sunray/sunburst cases reported in the English language literature to 21.

A Comparison of Bone Marrow and Cord Blood Mesenchymal Stem Cells for Cartilage Self-Assembly.

Joint injury is a common cause of premature retirement for the human and equine athlete alike. Implantation of engineered cartilage offers the potential to increase the success rate of surgical intervention and hasten recovery times. Mesenchymal stem cells (MSCs) are a particularly attractive cell source for cartilage engineering. While bone marrow-derived MSCs (BM-MSCs) have been most extensively characterized for musculoskeletal tissue engineering, studies suggest that cord blood MSCs (CB-MSCs) may elicit a more robust chondrogenic phenotype. The objective of this study was to determine a superior equine MSC source for cartilage engineering. MSCs derived from bone marrow or cord blood were stimulated to undergo chondrogenesis through aggregate redifferentiation and used to generate cartilage through the self-assembling process. The resulting neocartilage produced from either BM-MSCs or CB-MSCs was compared by measuring mechanical, biochemical, and histological properties. We found that while BM constructs possessed higher tensile properties and collagen content, CB constructs had superior compressive properties comparable to that of native tissue and higher GAG content. Moreover, CB constructs had alkaline phosphatase activity, collagen type X, and collagen type II on par with native tissue suggesting a more hyaline cartilage-like phenotype. In conclusion, while both BM-MSCs and CB-MSCs were able to form neocartilage, CB-MSCs resulted in tissue more closely resembling native equine articular cartilage as determined by a quantitative functionality index. Therefore, CB-MSCs are deemed a superior source for the purpose of articular cartilage self-assembly.

Is Social Mobility Spatial? Characteristics of Immigrant Metros and Second Generation Outcomes: 1940-1970 and 1970-2000.

Research on immigrant and second generation outcomes has often examined their locations, following ideas that geographic dispersion facilitates social mobility, and that characteristics of the ethnic environment enable or constrain progress. I contend that second generation socioeconomic outcomes depend in part on the location choices and characteristics of a previous immigrant generation. Further, I suggest that this relationship reflects the changing geography of immigrants and labour markets, rather than geographically unfolding assimilation. Using the 1940, 1970, and 2000 Integrated Public Use Microdata Series files from the US Census, I regress second and 1.5 generation wage and educational outcomes in 1970 and 2000 on metro-area characteristics of a previous generation (1940 and 1970, respectively). Current labour market and second generation characteristics are included as controls and to facilitate interpretation. Characteristics of a previous immigrant generation's location were more important for second generation outcomes in the 1940-1970 period, while current place characteristics become more significant by 2000. There is evidence of selection operating through the positive intergenerational effects of places where immigrants' educational levels were high a generation ago. Metro-level immigrant concentration and manufacturing employment also have generally positive effects, although variations across generations and by nationality suggest their significance for social mobility is inadequately understood. The historical immigrant geographies of the US, and the ways in which metro labour market conditions intersect with immigrants' locational choices, both within and between generations, are thus a critical piece of the economic and spatial assimilation puzzle.

Temperament in early childhood and peer interactions in third grade: the role of teacher-child relationships in early elementary grades.

Children's interactions with peers in early childhood have been consistently linked to their academic and social outcomes. Although both child and classroom characteristics have been implicated as contributors to children's success, there has been scant research linking child temperament, teacher-child relationship quality, and peer interactions in the same study. The purpose of this study is to examine children's early temperament, rated at preschool age, as a predictor of interactions with peers (i.e., aggression, relational aggression, victimization, and prosociality) in third grade while considering teacher-child relationship quality in kindergarten through second grades as a moderator and mediator of this association. The sample (N=1364) was drawn from the NICHD Study of Early Child Care and Youth Development. Results from structural equation models indicated that teacher-child conflict in early elementary grades mediated links between children's temperament and later peer interactions. Findings underscore the importance of considering children's temperament traits and teacher-child relationship quality when examining the mechanisms of the development of peer interactions.

Sensation in a single neuron pair represses male behavior in hermaphrodites.

Pheromones elicit innate sex-specific mating behaviors in many species. We demonstrate that in C. elegans, male-specific sexual attraction behavior is programmed in both sexes but repressed in hermaphrodites. Repression requires a single sensory neuron pair, the ASIs. To repress attraction in adults, the ASIs must be present, active, and capable of sensing the environment during development. The ASIs release TGF-ß, and ASI function can be bypassed by experimental activation of TGF-ß signaling. Sexual attraction in derepressed hermaphrodites requires the same sensory neurons as in males. The sexual identity of both these sensory neurons and a distinct subset of interneurons must be male to relieve repression and release attraction. TGF-ß may therefore act to change connections between sensory neurons and interneurons during development to engage repression. Thus, sensation in a single sensory neuron pair during development reprograms a common neural circuit from male to female behavior.

Methylation by Set9 modulates FoxO3 stability and transcriptional activity.

The FoxO family of transcription factors plays an important role in longevity and tumor suppression by regulating the expression of a wide range of target genes. FoxO3 has recently been found to be associated with extreme longevity in humans and to regulate the homeostasis of adult stem cell pools in mammals, which may contribute to longevity. The activity of FoxO3 is controlled by a variety of post-translational modifications that have been proposed to form a 'code' affecting FoxO3 subcellular localization, DNA binding ability, protein-protein interactions and protein stability. Lysine methylation is a crucial post-translational modification on histones that regulates chromatin accessibility and is a key part of the 'histone code'. However, whether lysine methylation plays a role in modulating FoxO3 activity has never been examined. Here we show that the methyltransferase Set9 directly methylates FoxO3 in vitro and in cells. Using a combination of tandem mass spectrometry and methyl-specific antibodies, we find that Set9 methylates FoxO3 at a single residue, lysine 271, a site previously known to be deacetylated by Sirt1. Methylation of FoxO3 by Set9 decreases FoxO3 protein stability, while moderately increasing FoxO3 transcriptional activity. The modulation of FoxO3 stability and activity by methylation may be critical for fine-tuning cellular responses to stress stimuli, which may in turn affect FoxO3's ability to promote tumor suppression and longevity.

Emerging U.S. Immigrant Geographies: Racial Wages and Migration Selectivity.

OBJECTIVE: The maturing of the post-1965 children of immigrants and the recent emergence of immigrant settlement outside of traditional locations have implications for understanding immigrant economic incorporation. This analysis examines how changing immigrant geographies will affect the economic prospects of immigrants and a maturing second generation, and addresses sociological and economic perspectives on internal migration and immigrant progress. METHODS: Using the 2000 5 percent Public Use Microdata Files (PUMS), I employ endogenous switching regression models in analyzing the selectivity of internal migration and state residence patterns to the wages of immigrant, 1.5 generation, and U.S.-born workers. RESULTS: Nonwhite immigrant and 1.5-generation workers evade racial wage penalties through migration, but not through residing in emerging immigrant states. CONCLUSIONS: Understanding the selectivity of internal migration to wages across racialized labor markets is important in assessing new immigrant geographies and prospects for the second generation.

Chemical genetic screen for AMPKα2 substrates uncovers a network of proteins involved in mitosis.

The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. Here we use a chemical genetics screen to identify direct substrates of AMPK in human cells. We find that AMPK phosphorylates 28 previously unidentified substrates, several of which are involved in mitosis and cytokinesis. We identify the residues phosphorylated by AMPK in vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21-activated protein kinase (PAK2). AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both AMPK activity and PPP1R12C phosphorylation are increased in mitotic cells and are important for mitosis completion. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism's response to low nutrients during development, or in adult stem and cancer cells.

Temperamental attention and activity, classroom emotional support, and academic achievement in third grade.

The purpose of this study is to examine the interplay of children's temperamental attention and activity (assessed when children were 4-and-a-half years old) and classroom emotional support as they relate to children's academic achievement in third grade. Particular focus is placed on the moderating role of classroom emotional support on the relationship between temperament (attention and activity level) and academic achievement. Regression analyses indicated that children's attention and activity level were associated with children's third grade reading and mathematics achievement, and classroom emotional support was associated with children's third grade reading and mathematics achievement. In addition, classroom emotional support moderated the relation between children's attention and reading and mathematics achievement, such that attention mattered most for reading and mathematics achievement for children in classrooms with lower emotional support. Findings point to the importance of understanding how children's temperament and classroom emotional support may work together to promote or inhibit children's academic achievement.

Silencing by small RNAs is linked to endosomal trafficking.

Small RNAs direct RNA-induced silencing complexes (RISCs) to regulate stability and translation of mRNAs. RISCs associated with target mRNAs often accumulate in discrete cytoplasmic foci known as GW-bodies. However, RISC proteins can associate with membrane compartments such as the Golgi and endoplasmic reticulum. Here, we show that GW-bodies are associated with late endosomes (multivesicular bodies, MVBs). Blocking the maturation of MVBs into lysosomes by loss of the tethering factor HPS4 (ref. 5) enhances short interfering RNA (siRNA)- and micro RNA (miRNA)-mediated silencing in Drosophila melanogaster and humans. It also triggers over-accumulation of GW-bodies. Blocking MVB formation by ESCRT (endosomal sorting complex required for transport) depletion results in impaired miRNA silencing and loss of GW-bodies. These results indicate that active RISCs are physically and functionally coupled to MVBs. We further show that MVBs promote the competence of RISCs in loading small RNAs. We suggest that the recycling of RISCs is promoted by MVBs, resulting in RISCs more effectively engaging with small RNA effectors and possibly target RNAs. It may provide a means to enhance the dynamics of RNA silencing in the cytoplasm.

OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans vulval development.

Notch signaling is critical for cell fate decisions during development. Caenorhabditis elegans and vertebrate Notch ligands are more diverse than classical Drosophila Notch ligands, suggesting possible functional complexities. Here, we describe a developmental role in Notch signaling for OSM-11, which has been previously implicated in defecation and osmotic resistance in C. elegans. We find that complete loss of OSM-11 causes defects in vulval precursor cell (VPC) fate specification during vulval development consistent with decreased Notch signaling. OSM-11 is a secreted, diffusible protein that, like previously described C. elegans Delta, Serrate, and LAG-2 (DSL) ligands, can interact with the lineage defective-12 (LIN-12) Notch receptor extracellular domain. Additionally, OSM-11 and similar C. elegans proteins share a common motif with Notch ligands from other species in a sequence defined here as the Delta and OSM-11 (DOS) motif. osm-11 loss-of-function defects in vulval development are exacerbated by loss of other DOS-motif genes or by loss of the Notch ligand DSL-1, suggesting that DOS-motif and DSL proteins act together to activate Notch signaling in vivo. The mammalian DOS-motif protein Deltalike1 (DLK1) can substitute for OSM-11 in C. elegans development, suggesting that DOS-motif function is conserved across species. We hypothesize that C. elegans OSM-11 and homologous proteins act as coactivators for Notch receptors, allowing precise regulation of Notch receptor signaling in developmental programs in both vertebrates and invertebrates.

The sensory circuitry for sexual attraction in C. elegans males.

BACKGROUND: Why do males and females behave differently? Sexually dimorphic behaviors could arise from sex-specific neurons or by the modification of circuits present in both sexes. C. elegans males exhibit different behaviors than hermaphrodites. Although there is a single class of sex-specific sensory neurons in the head of males, most of their neurons are part of a core nervous system also present in hermaphrodites. Are the behavioral differences due to sex-specific or core neurons? RESULTS: We demonstrate that C. elegans males chemotax to a source of hermaphrodite pheromones. This sexual-attraction behavior depends on a TRPV (transient receptor potential vanilloid) channel encoded by the osm-9, ocr-1, and ocr-2 genes. OSM-9 is required in three classes of sensory neurons: the AWA and AWC olfactory neurons and the male-specific CEM neurons. The absence of OSM-9 from any of these neurons impairs attraction, suggesting that their ensemble output elicits sexual attraction. Likewise, the ablation of any of these classes after sexual maturation impairs attraction behavior. If ablations are performed before sexual maturation, attraction is unimpaired, demonstrating that these neurons compensate for one another. Thus, males lacking sex-specific neurons are still attracted to pheromones, suggesting that core neurons are sexualized. Similarly, transgender nematodes-animals that appear morphologically to be hermaphrodites but have a masculinized core nervous system-are attracted to hermaphrodite pheromones. CONCLUSIONS: Both sexually dimorphic and core sensory neurons are normally required in the adult for sexual attraction, but they can replace each other during sexual maturation if necessary to generate robust male-specific sexual attraction behavior.

A calcium wave mediated by gap junctions coordinates a rhythmic behavior in C. elegans.

Intercellular calcium waves can be observed in adult tissues, but whether they are instructive, permissive, or even required for behavior is predominantly unknown. In the nematode Caenorhabditis elegans, a periodic calcium spike in a pacemaker cell initiates a calcium wave in the intestine. The calcium wave is followed by three muscle contractions that comprise the defecation motor program. Normal wave propagation requires the pannexin gap-junction subunit INX-16 at the interfaces of the intestinal cells. In the absence of this gap-junction subunit, calcium waves are frequently absent. The remaining waves are slow, initiate at abnormal locations, or travel in the opposite direction. Abnormal waves are associated with parallel effects in the first step of the motor program: The contractions of the overlying muscles fail to propagate beyond the pacemaker cell, are slow, initiate in abnormal locations, or are reversed. Moreover, the last two motor steps are predominantly absent. Finally, the absence of this gap-junction subunit also affects the reliability of the pacemaker cell; cycle timing is often irregular. These data demonstrate that pannexin gap junctions propagate calcium waves in the C. elegans intestine. The calcium waves instruct the motor steps and regulate the pacemaker cell's authority and reliability.