Outcome assessment of Invisalign and traditional orthodontic treatment compared with the American Board of Orthodontics objective grading system.

INTRODUCTION: This treatment-outcome assessment objectively compares Invisalign (Align Technology, Santa Clara, Calif) treatment with braces. METHODS: This study, a retrospective cohort analysis, was conducted in New York, NY, in 2004. Records from 2 groups of 48 patients (Invisalign and braces groups) were evaluated by using methods from the American Board of Orthodontics Phase III examination. The discrepancy index was used to analyze pretreatment records to control for initial severity of malocclusion. The objective grading system (OGS) was used to systematically grade posttreatment records. Statistical analyses evaluated treatment outcome, duration, and strengths and weaknesses of Invisalign compared with braces. RESULTS: The Invisalign group lost 13 OGS points more than the braces group on average, and the OGS passing rate for Invisalign was 27% lower than that for braces. Invisalign scores were consistently lower than braces scores for buccolingual inclination, occlusal contacts, occlusal relationships, and overjet. Invisalign's OGS scores were negatively correlated to initial overjet, occlusion, and buccal posterior crossibite. Invisalign patients finished 4 months sooner than those with fixed appliances on average. P < .05 was used to determine statistically significant differences. CONCLUSIONS: According to the OGS, Invisalign did not treat malocclusions as well as braces in this sample. Invisalign was especially deficient in its ability to correct large anteroposterior discrepancies and occlusal contacts. The strengths of Invisalign were its ability to close spaces and correct anterior rotations and marginal ridge heights. This study might help clinicians to determine which patients are best suited for Invisalign treatment.     

The intestine is a site of passage for potato leafroll virus from the gut lumen into the haemocoel in the aphid vector,Myzus persicae Sulz

Summary Four detection techniques, three of which gave reliable identification of the virus particles, were used to locate potato leafroll virus (PLRV) in the alimentary canal of its main aphid vector,Myzus persicae Sulz: immunofluorescence on cryostat sections, conventional transmission electron microscopy on ultrathin sections and immune electron microscopy with gold labeling, either prior to or after fixation-embedding. Each method clearly showed the presence of the virus in the intestine epithelium and its absence in cells of the other parts of the alimentary canal. Under the experimental conditions used, the intestinal cells seemed to be the pathway for PLRV transport from the gut lumen into the haemocoel. Electron microscopy examinations showed many virus particles close to the apical plasmalemma of the epithelial cells in the gut lumen of the intestine. Other particles were seen in shallow pit-like regions or surrounded by coated vesicles in the apical part of these cells. Thus the virus particles seemed to enter the epithelial cells of the intestine by a mechanism of endocytosis. In the cytoplasm of these cells, virions were also frequently observed in isolated — or more often aggregated — tubular vesicles. The latter could be involved in PLRV transport through the cell since they were observed fusing with different cell organelles. A few viral particles were also detected in lysosomes as well as in multivesicular bodies. Virus particles were observed between the plasmalemma and basal lamina of the intestine cells but not in the haemocoel, where probably they were quickly dispersed. Our results are discussed in relation to other reports which have shown hindgut and stomach as sites of passage from the gut lumen into the aphid's body cavity for PLRV and other circulative viruses.     

Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas

The 40-kilodalton processed glycoprotein, mesothelin, is highly expressed in epithelial mesotheliomas and adenocarcinomas of the ovary (serous papillary) and pancreas, but its expression in a large series of other common carcinomas has not been completely explored. In the present study, we used oligonucleotide and tissue microarrays to profile the expression of the mesothelin gene (MSLN) and encoded protein, respectively. Among 150 carcinomas of multiple anatomic sites, we found the highest average expression of MSLN in serous carcinomas of the ovary and adenocarcinomas of the pancreas, consistent with previous reports, as well as measurable but less-striking expression in pulmonary, gastric/esophageal, and colorectal adenocarcinomas. On tissue microarrays containing 621 carcinomas derived from the same and additional sites as those profiled by gene expression, mesothelin immunoreactivity was highest in cancers of the ovary (serous papillary, endometrioid, and undifferentiated) and pancreas, with less frequent staining seen in adenocarcinomas of the endometrium, lung, and stomach/esophagus. Some immunopositivity was observed in 42% of pulmonary adenocarcinomas, including 18% that had >50% of tumor cells that were immunoreactive. Some 14% of breast and 30% of colorectal adenocarcinomas showed immunopositivity, but no case contained >50% tumor cells that were immunoreactive. Mesothelin was either entirely absent or present in <5% of carcinomas of the prostate, bladder/ureter, liver, kidney, and thyroid. Overall, we observed good concordance between the results obtained by oligonucleotide and tissue microarrays. This large study of the MSLN gene and protein expression in common carcinomas provides data for future investigations that evaluate the utility of mesothelin/megakaryocyte potentiating factor as a potential serum tumor marker or target of immunotoxin-based therapy in human cancers.     

An approach for evaluating the effects of dietary fiber polysaccharides on the human gut microbiome and plasma proteome

Increases in snack consumption associated with Westernized lifestyles provide an opportunity to introduce nutritious foods into poor diets. We describe two 10-wk-long open label, single group assignment human studies that measured the effects of two snack prototypes containing fiber preparations from two sustainable and scalable sources; the byproducts remaining after isolation of protein from the endosperm of peas and the vesicular pulp remaining after processing oranges for the manufacture of juices. The normal diets of study participants were supplemented with either a pea- or orange fiber-containing snack. We focused our analysis on quantifying the abundances of genes encoding carbohydrate-active enzymes (CAZymes) (glycoside hydrolases and polysaccharide lyases) in the fecal microbiome, mass spectrometric measurements of glycan structures (glycosidic linkages) in feces, plus aptamer-based assessment of levels of 1,300 plasma proteins reflecting a broad range of physiological functions. Computational methods for feature selection identified treatment-discriminatory changes in CAZyme genes that correlated with alterations in levels of fiber-associated glycosidic linkages; these changes in turn correlated with levels of plasma proteins representing diverse biological functions, including transforming growth factor type β/bone morphogenetic protein-mediated fibrosis, vascular endothelial growth factor-related angiogenesis, P38/MAPK-associated immune cell signaling, and obesity-associated hormonal regulators. The approach used represents a way to connect changes in consumer microbiomes produced by specific fiber types with host responses in the context of varying background diets.

Advances in our understanding of the role of the gut microbiome in regulating many aspects of human physiology hold the promise of evolving our view of human nutrition by establishing mechanistic connections between the foods we consume and how they affect health status. One manifestation of this effort is a series of studies, performed on well-phenotyped cohorts, that seek to relate features of gut microbial community composition (organisms, genes), dietary practices, and pre- and postprandial cardiometabolic responses to test meals (1–4). A key question raised by these initiatives relates to the nature of the “bioactive” components of foods. Specifically, what are the nutrients utilized by various gut community members or microbiome-encoded metabolic pathways? What products are produced by biotransformation of these nutrients? How are these products linked to specific host physiologic (or pathophysiologic) processes?Plant-derived dietary fibers represent a “poster child” for these efforts and illustrate the formidable challenges faced. The health benefits of dietary fibers are widely known, as is their inadequate representation in Western diets. However, natural fibers are structurally complex and highly diverse. They contain numerous, typically undefined polysaccharide structures and largely unspecified protein, lipid, and small molecule constituents. Their composition varies as a function of their origin (food staple and cultivar), the different methods employed to recover them from these sources, as well as the different techniques used to incorporate them into processed foods with acceptable organoleptic properties (5). Moreover, analyzing the host effects of metabolism of different fibers is confounded by the fact that there is substantial intra- and interpersonal variation in microbiome configuration (6, 7).Snacking is becoming an ever more dominant feature of daily life worldwide and thus provides an opportunity to introduce nutritious ingredients, such as fibers, into diets. However, obtaining structure-activity relationships for specific fiber types and their corresponding targets in the gut community is foundational for designing snack foods that evoke and/or reinforce microbiome responses that are beneficial to the host.Degradation of dietary polysaccharides is a function primarily performed by bacterial carbohydrate-active enzymes (CAZymes). The gut microbiome harbors tens of thousands of CAZyme genes belonging to at least 136 glycoside hydrolase (GH) and 29 polysaccharide lyase (PL) families [extrapolated and updated from El Kaoutari et al. (8)]. In contrast, the human genome only contains 98 GH and no PL genes (9), of which <20% contribute to the processing of dietary glycans.In the current study, we test the effects of dietary supplementation with two snack food prototypes, one containing pea fiber and the other orange fiber, in two pilot studies of overweight and obese individuals consuming their normal, unrestricted diets. Our strategy was to focus on fiber-associated changes in the abundances of microbial GH and PL genes to determine whether responses to the pea or orange fiber prototypes in the gut microbiome and host are decipherable against a background of varying dietary practices and starting microbiome configurations. Higher order singular value decomposition (10) was utilized as a feature selection tool to identify treatment-discriminating changes in GH and PL gene representation. Mass spectrometric assays of the levels of fecal glycan structures (glycosidic linkages) were subsequently performed and the results were correlated with changes in the abundances of treatment-discriminating GH and PL genes with known or predicted substrate specificities. Our analysis concluded by measuring changes in levels of 1,305 plasma proteins in each study participant as a function of fiber treatment and applying computational tools to identify links between these microbiome and plasma proteome changes in response to fiber consumption. Our results provide an approach, using pilot human studies, for selecting specific fiber preparations, plus informative microbiome and host biomarkers, that can be advanced to proof-of-concept clinical trials which assess their capacity for precise manipulation of microbiome and host features.     

Burnout and well‐being in otolaryngology trainees: A systematic review

ObjectiveTo comprehensively review the recent published literature to characterize current trends of burnout and well‐being among otolaryngology trainees.MethodsStudy design: systematic review and meta‐analysis. A comprehensive literature review from 2000 to 2021 of studies related to otolaryngology resident burnout and well‐being, as well as the general topic of well‐being among surgical residents was completed. All included studies were summarized qualitatively. For the quantitative analysis, only articles reporting a Maslach burnout inventory (MBI), modified MBI or Mini‐Z‐ Burnout assessment were included.ResultsTwenty‐five articles were included in the qualitative summary and nine articles in the quantitative analysis. In the qualitative summary, trainees were reported to have increased levels of distress and emotional hardening compared to attending otolaryngologists. Total hours worked per week and female gender were associated with worsened well‐being. Residency program strategies to improve trainee well‐being include program‐sponsored wellness activities, dedicated wellness champions, and assistance with clerical burden. Implementation of protected nonclinical time has been shown to decrease burnout and increase well‐being among trainees. Moreover, formal trainee mentorship programs have also been shown to reduce trainee burnout and stress. In the quantitative analysis, rates of trainee burnout ranged from 29.7% to 86% with an overall trend towards reduced rates of burnout from 2006 to 2021. Utilizing a weighted average, the overall burnout among otolaryngology residents was 58.6%.ConclusionsRates of burnout remain high among otolaryngology trainees. Implementing formal mentorship programs and providing protected time during regular work hours appear to be effective tools to improve resident well‐being.