Coastal squeeze on temperate reefs: Long-term shifts in salinity, water quality, and oyster-associated communities.

Foundation species, such as mangroves, saltmarshes, kelps, seagrasses, and oysters, thrive within suitable environmental envelopes as narrow ribbons along the land-sea margin. Therefore, these habitat-forming species and resident fauna are sensitive to modified environmental gradients. For oysters, many estuaries impacted by sea-level rise, channelization, and municipal infrastructure are experiencing saltwater intrusion and water-quality degradation that may alter reef distributions, functions, and services. To explore decadal-scale oyster-reef community patterns across a temperate estuary in response to environmental change, we resampled reefs in the Newport River Estuary (NRE) during 2013-2015 that had previously been studied during 1955-1956. We also coalesced historical NRE reef distribution (1880s-2015), salinity (1913-2015), and water-quality-driven shellfish closure boundary (1970s-2015) data to document environmental trends that could influence reef ecology and service delivery. Over the last 60-120 years, the entire NRE has shifted toward higher salinities. Consequently, oyster-reef communities have become less distinct across the estuary, manifest by 20%-27% lower species turnover and decreased faunal richness among NRE reefs in the 2010s relative to the 1950s. During the 2010s, NRE oyster-reef communities tended to cluster around a euhaline, intertidal-reef type more so than during the 1950s. This followed faunal expansions farther up estuary and biological degradation of subtidal reefs as NRE conditions became more marine and favorable for aggressive, reef-destroying taxa. In addition to these biological shifts, the area of suitable bottom on which subtidal reefs persist (contracting due to up-estuary intrusion of marine waters) and support human harvest (driven by water quality, eroding from up-estuary) has decreased by >75% since the natural history of NRE reefs was first explored. This "coastal squeeze" on harvestable subtidal oysters (reduced from a 4.5-km to a 0.75-km envelope along the NRE's main axis) will likely have consequences regarding the economic incentives for future oyster conservation, as well as the suite of services delivered by remaining shellfish reefs (e.g., biodiversity maintenance, seafood supply). More broadly, these findings exemplify how "squeeze" may be a pervasive concern for biogenic habitats along terrestrial or marine ecotones during an era of intense global change.

Cannabinoid receptor type 2 is upregulated in synovium following joint injury and mediates anti-inflammatory effects in synovial fibroblasts and macrophages.

OBJECTIVE: Joint injury-induced perturbations to the endocannabinoid system (ECS), a regulator of both inflammation and nociception, remain largely uncharacterized. We employed a mouse model of ACL rupture to assess alterations to nociception, inflammation, and the ECS while using in vitro models to determine whether CB2 agonism can mitigate inflammatory signaling in macrophages and fibroblast-like synoviocytes (FLS). DESIGN: Mice underwent noninvasive ACL rupture (ACLR) via tibial compression-based loading. Nociception was measured longitudinally using mechanical allodynia and knee hyperalgesia testing. Synovitis was assessed using histological scoring and histomorphometry. Gene and protein markers of inflammation were characterized in whole joints and synovium. Immunohistochemistry assessed injury-induced alterations to CB1+, CB2+, and F4/80+ cells in synovium. To assess whether CB2 agonism can inhibit pro-inflammatory macrophage polarization, murine bone marrow-derived macrophages (mBMDM) were stimulated with IL-1ß or conditioned medium from IL-1ß-treated FLS and treated with vehicle (DMSO), the CB2 agonist HU308, or cannabidiol (CBD). Macrophage polarization was assessed as the ratio of M1-associated (IL1b, MMP1b, and IL6) to M2-associated (IL10, IL4, and CD206) gene expression. Human FLS (hFLS) isolated from synovial tissue of OA patients were treated with vehicle (DMSO) or HU308 following TNF-α or IL-1ß stimulation to assess inhibition of catabolic/inflammatory gene expression. RESULTS: ACLR induces synovitis, progressively-worsening PTOA severity, and an immediate and sustained increase in both mechanical allodynia and knee hyperalgesia, which persist beyond the resolution of molecular inflammation. Enrichment of CB2, but not CB1, was observed in ACLR synovium at 3d, 14d, and 28d, and CB2 was found to be associated with F4/80 (+) cells, which are increased in number in ACLR synovium at all time points. The CB2 agonist HU308 strongly inhibited mBMDM M1-type polarization following stimulation with either IL-1ß or conditioned medium from IL-1ß-treated mFLS, which was characterized by reductions in Il1b, Mmp1b, and Il6 and increases in Cd206 gene expression. Cannabidiol similarly inhibited IL-1ß-induced mBMDM M1 polarization via a reduction in Il1b and an increase in Cd206 and Il4 gene expression. Lastly, in OA hFLS, HU308 treatment inhibited IL-1ß-induced CCL2, MMP1, MMP3, and IL6 expression and further inhibited TNF-α-induced CCL2, MMP1, and GMCSF expression, demonstrating human OA-relevant anti-inflammatory effects by targeting CB2. CONCLUSIONS: Joint injury perturbs the intra-articular ECS, characterized by an increase in synovial F4/80(+) cells, which express CB2, but not CB1. Targeting CB2 in murine macrophages and human FLS induced potent anti-inflammatory and anti-catabolic effects, which indicates that the CB2 receptor plays a key role in regulating inflammatory signaling in the two primary effector cells in the synovium. The intraarticular ECS is therefore a potential therapeutic target for blocking pathological inflammation in future disease-modifying PTOA treatments.

Nuclear F-actin Cytology in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.

Selective deletion of Pten in theca-interstitial cells leads to androgen excess and ovarian dysfunction in mice.

Theca cell-selective Pten mutation (tPtenMT) in mice resulted in increases in PDK1 and Akt phosphorylation, indicating an over-activation of PI3K signaling in the ovaries. These mice displayed elevated androgen levels, ovary enlargement, antral follicle accumulation, early fertility loss and increased expression of Lhcgr and genes that are crucial to androgenesis. These abnormalities were partially reversed by treatments of PI3K or Akt inhibitor. LH actions in Pten deficient theca cells were potentiated. The phosphorylation of Foxo1 was increased, while the binding of Foxo1 to forkhead response elements in the Lhcgr promoter was reduced in tPtenMT theca cells, implying a mechanism by which PI3K/Akt-induced upregulation of Lhcgr in theca cells might be mediated by reducing the inhibitory effect of Foxo1 on the Lhcgr promoter. The phenotype of tPtenMT females is reminiscent of human PCOS and suggests that dysregulated PI3K cascade in theca cells may be involved in certain types of PCOS pathogenesis.

Introduction of the chronic care model into an academic rheumatology clinic.

BACKGROUND: While the chronic care model has been extensively used for the management of patients with diabetes in non-academic, primary care settings, it is not clear whether this model can be used effectively in academic, specialty clinics for other chronic disorders. METHODS: Through the Academic Chronic Care Collaborative, the chronic care model was introduced to help manage patients with osteoarthritis in an academic rheumatology service with seven prespecified goals. These goals included measurements of Western Ontario MacMaster (WOMAC) osteoarthritis scores, self-efficacy scores and exercise time. RESULTS: Five a priori goals were achieved in this study: average WOMAC scores less than 1000 mm as measured on a visual analogue scale, average self-efficacy score of less than 5 mm, average exercise time greater than 90 min, more than 40% of patients exercising at least 60 min per week and a 20% improvement in self-efficacy scores. However, a 20% improvement in WOMAC scores and a 60% completion of documented self-management goals in our patients were not achieved. Our inability to achieve our self-management goal underscores the fact that we have not yet fully implemented the chronic care model into our practice. The inability to detect a 20% improvement in WOMAC scores in the context of having reached our absolute WOMAC goal at baseline suggests a probable ceiling effect for this measure. CONCLUSIONS: The chronic care model can be effectively introduced into an academic specialty service and can be used effectively in the management of patients with non-diabetic disorders, in this case osteoarthritis.

Candida glabrata: an emerging oral opportunistic pathogen.

Following the widespread use of immunosuppressive therapy and broad-spectrum antimycotic prophylaxis, C. glabrata has emerged as an important opportunistic pathogen in the oral mucosa. In the past, studies on the virulence factors and host-pathogen interactions of this organism were scarce, but continued to rise in recent years. Denture-wearing, immunosuppression, antibiotic therapy, and aging are risk factors for oral colonization or infection with C. glabrata. Compared with C. albicans, C. glabrata exhibits lower oral keratinocyte-adherence capacity, but higher denture-surface-adherence ability. The role of extracellular hydrolase production in the virulence of this organism does not appear to be as important as it is in C. albicans pathogenesis. Although traditionally thought of as a non-transforming yeast organism, both phenotypic switching and pseudohyphal formation have recently been identified in C. glabrata, but their role in pathogenesis is not known. With the exception of granulocyte monocyte colony-stimulating factor, C. glabrata triggers a lower proinflammatory cytokine response in oral epithelial cells than does C. albicans, in a strain-dependent manner. C. glabrata is less susceptible to killing by human beta-defensins than is C. albicans and exhibits various degrees of resistance to the antifungal activity of salivary histatins and mucins. In addition, C. glabrata possesses both innate and acquired resistance against antifungal drugs, due to its ability to modify ergosterol biosynthesis, mitochondrial function, or antifungal efflux. This resistance allows for its relative overgrowth over other susceptible species and may contribute to the recent emergence of C. glabrata infections in chronically immunocompromised populations. Further investigations on the virulence and host-pathogen interactions of C. glabrata are needed to better define the pathogenesis of oral C. glabrata infection in susceptible hosts.

In vitro interaction of posaconazole and caspofungin against clinical isolates of Candida glabrata.

Combinations of caspofungin and posaconazole were evaluated by fractional inhibitory concentration index against 119 Candida glabrata isolates. Synergy was seen in 18% of all isolates and in 4% of fluconazole-resistant isolates at 48 h without evidence of antagonism. This antifungal combination may have utility against this organism.

Comparison of antifungal susceptibilities to fluconazole and voriconazole of oral Candida glabrata isolates from head and neck radiation patients.

The antifungal susceptibilities of 79 oral Candida glabrata isolates to fluconazole and voriconazole were compared. The MICs at which 90% of the isolates tested were inhibited were 1 microg of voriconazole/ml and 32 microg of fluconazole/ml. Oral C. glabrata isolates for which the fluconazole MICs are elevated are commonly those for which the voriconazole MICs are elevated, but these increases may be transient for voriconazole, as they are for fluconazole.

Candida glabrata sepsis secondary to oral colonization in bone marrow transplantation.

Candida glabrata has emerged as a common cause of fungal sepsis in bone marrow transplant patients, particularly those receiving fluconazole prophylaxis. Colonization of the lower GI tract and indwelling catheters have been thought to be the primary sources of systemic infection with Candida. We report on a bone marrow transplant patient who developed Candida glabrata sepsis from pre-existing oral colonization.

Isolation of non-tuberculosis mycobacteria in treated dental unit waterlines.

OBJECTIVE: The purpose of the study was to investigate the presence of non-tuberculosis mycobacteria (NTM) in dental unit waterlines that were being routinely treated with an intermittent use waterline cleaner. STUDY DESIGN: The study was conducted at a hospital dentistry clinic where immunocompromised patients are seen. Water samples from two lines on one of two dental units were taken before and after routine weekend chemical treatment. Sampling was repeated on two subsequent occasions, on the same unit, at three monthly intervals. Laboratory techniques included centrifugation and membrane filtration to detect small numbers of organisms. RESULTS: Mycobacterium simiae was isolated from one of the four pre-treatment samples and from two of the four post-treatment samples. Mycobacterium mucogenicum was isolated from one of the four post-treatment samples. CONCLUSIONS: This pilot study found that NTM were present in DUWLs that were being routinely treated with an intermittent use chemical cleaner. Practitioners are urged to understand the limitations of available DUWL treatments, and to consider the use of sterile water for non-surgical, as well as surgical, treatment of immunocompromised patients.

Identification of Exophiala mesophila isolated from treated dental unit waterlines.

Members of the genus Exophiala are often difficult to identify to the species level because of their variable morphological appearances. This paper describes the methods used to identify Exophiala mesophila and provides salient differential features for distinguishing other mesophilic members of the genus.

Candida dubliniensis in radiation-induced oropharyngeal candidiasis.

Candida dubliniensis is a recently described species that has been shown to cause oropharyngeal candidiasis in patients with HIV. We present a detailed evaluation of a patient undergoing head and neck radiation for oral cancer who developed oropharyngeal candidiasis from a mixed infection of C dubliniensis and Candida albicans. To our knowledge, this is the first described case of C dubliniensis contributing to oropharyngeal candidiasis in this patient population.

The role of yeasts other than Candida albicans in oropharyngeal candidiasis.

Candida albicans has been recognized as the predominant infecting organism in oropharyngeal candidiasis. Yeasts other than C. albicans are commonly recognized as colonizing the oral cavity but have not been thought to be a significant cause of disease. This review will describe the emergence of yeasts other than C. albicans as causative pathogens in oropharyngeal candidiasis both as co-infecting organisms with C. albicans and as sole pathogens themselves. Diagnosis and treatment of these emerging infections will also be discussed.

Coronary artery stents: review and patient-management recommendations.

BACKGROUND: Coronary artery stents are metallic scaffold devices that physically support narrowed coronary arteries to alleviate symptoms of ischemic coronary artery disease. They are placed during invasive procedures similar to that of percutaneous transluminal coronary angioplasty, and patients are maintained with antiplatelet medications to lessen the chances of stent stenosis. METHODS: The authors provide a brief overview of coronary artery stents and discuss the dental management of patients who have received stents. CONCLUSIONS: After stent placement, patients usually are maintained with antiplatelet regimens, which may necessitate choosing medications that do not potentiate their effects. Any discussion as to the possible need for antibiotic prophylaxis of patients with stents largely is missing from the literature. Recent literature, however, indicates that antibiotic prophylaxis, if required, may only be needed during the first few weeks after stent placement. CLINICAL IMPLICATIONS: Dental professionals should become knowledgeable about coronary artery stents. Although these devices have a higher success rate than other procedures in alleviating symptoms of ischemic coronary artery disease, some patients are still at risk of experiencing significant cardiac events.

The epidemiology of non-albicans Candida in oropharyngeal candidiasis in HIV patients.

Oropharyngeal candidiasis (OPC) is the most common fungal infection in patients with HIV infection. Fluconazole has been proven to be very effective in treating this infection, but decreased susceptibility of Candida to this drug has emerged. Certain non-albicans species such as C. glabrata and C. krusei are commonly less susceptible to fluconazole than C. albicans and are being isolated with increased frequency in HIV patients. The purpose of this study was to determine if the presence of non-albicans Candida with OPC in HIV patients had an impact on clinical presentation. This study shows that late-stage HIV patients have a high prevalence of Candida with decreased susceptibility to fluconazole, especially non-albicans species. OPC episodes with non-albicans isolates were more likely to require higher doses of fluconazole to achieve clinical cure. Also, the presence of non-albicans Candida was more frequently associated with severe symptoms.

Control theory in dying: what do we know?

As we try to develop appropriate models for end-of-life care, it is important to review theoretical applications as they relate to current models of care. It is also vital to listen carefully to what patients and theirfamily caregivers tell us about their needs at the end of life. This article explores the issue of control: its application to wellness at the end of life, and patient and family caregiver perceptions about end-of-life control. Interventions and implications for professional caregivers are proposed.

Epidemiology of oropharyngeal Candida colonization and infection in patients receiving radiation for head and neck cancer.

Oral mucosal colonization and infection with Candida are common in patients receiving radiation therapy for head and neck cancer. Infection is marked by oral pain and/or burning and can lead to significant patient morbidity. The purpose of this study was to identify Candida strain diversity in this population by using a chromogenic medium, subculturing, molecular typing, and antifungal susceptibility testing of clinical isolates. These results were then correlated with clinical outcome in patients treated with fluconazole for infection. Specimens from 30 patients receiving radiation therapy for head and neck cancer were cultured weekly for Candida. Patients exhibiting clinical infection were treated with oral fluconazole. All isolates were plated on CHROMagar Candida and RPMI medium, subcultured, and submitted for antifungal susceptibility testing and molecular typing. Infections occurred in 27% of the patients and were predominantly due to Candida albicans (78%). Candida carriage occurred in 73% of patients and at 51% of patient visits. Yeasts other than C. albicans predominated in carriage, as they were isolated from 59% of patients and at 52% of patient visits. All infections responded clinically, and all isolates were susceptible to fluconazole. Molecular typing showed that most patients had similar strains throughout their radiation treatment. One patient, however, did show the acquisition of a new strain. With this high rate of infection (27%), prophylaxis to prevent infection should be evaluated for these patients.

Accreditation issues in post-doctoral general dentistry programs.

There has been increasing interest in the organization and accreditation of post-doctoral general dentistry programs (PGD). Numerous national organizations have called for increases in the number of PGD positions and programs. At the same time, there has been a movement to incorporate concepts of competency-based education into dental education programs to stress the outcomes of education rather then the process. These movements have coincided with the current accreditation standards revision cycles for GPR and AEGD programs. These events suggest that PGD educators have a major opportunity and responsibility to assess the goals and educational directions of PGD programs in light of the many changes in dental health care delivery, health policy, and dental education activities. These opportunities will be realized only if the organizations involved with PGD education can find common ground and pool their resources to promote the interests of PGD education.