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Few realized the extent of disruption that the Covid-19 global pandemic would impose upon higher anatomical education. While many institutions were obliged to adopt a fully-remote online model, the New York Institute of Technology College of Osteopathic Medicine strove to develop a curriculum that would allow medical students to receive an in-person anatomy education. A hybrid model that emphasized learning from prosected cadavers and self-study stations was implemented, with the remainder of the students' time directed toward studying at home. Through an anonymous survey aimed at gleaning student satisfaction, this study demonstrates that this hybrid prosection-based anatomy course aligned with student preferences both assuming no health risk (64.6% agreed) and given the current risk of contracting Covid-19 (78.5% agreed). Generally, students felt that their education was equal to that of previous years (Likert scale = 3.24 ± 1.05), fostered an appreciation for anatomy (4.56 ± 0.59), promoted teamwork (4.13 ± 0.85), and prepared them for practical examinations (4.18 ± 0.74). Linear mixed-effect models demonstrated that specific differences in results could be attributed to students' preconceived preferences toward student-led dissections and to past medical training. Importantly, most students "disagree" (1.97 ± 1.00) that they were concerned about the risk of exposure to Covid-19 during in-person anatomy laboratory sessions. Areas requiring improvement were identified by the model, including the provision of access to the cadavers outside of the regularly scheduled laboratory times (3.89 ± 1.08). These findings should be utilized when designing future gross anatomy courses in response to the "new normal".

The hexameric low-pH stress response enzyme oxalate decarboxylase catalyzes the decarboxylation of the oxalate mono-anion in the soil bacterium Bacillus subtilis. A single protein subunit contains two Mn-binding cupin domains, and catalysis depends on Mn(III) at the N-terminal site. The present study suggests a mechanistic function for the C-terminal Mn as an electron hole donor for the N-terminal Mn. The resulting spatial separation of the radical intermediates directs the chemistry toward decarboxylation of the substrate. A π-stacked tryptophan pair (W96/W274) links two neighboring protein subunits together, thus reducing the Mn-to-Mn distance from 25.9 A (intrasubunit) to 21.5 A (intersubunit). Here, we used theoretical analysis of electron hole-hopping paths through redox-active sites in the enzyme combined with site-directed mutagenesis and X-ray crystallography to demonstrate that this tryptophan pair supports effective electron hole hopping between the C-terminal Mn of one subunit and the N-terminal Mn of the other subunit through two short hops of ∼8.5 A. Replacement of W96, W274, or both with phenylalanine led to a large reduction in catalytic efficiency, whereas replacement with tyrosine led to recovery of most of this activity. W96F and W96Y mutants share the wildtype tertiary structure. Two additional hole-hopping networks were identified leading from the Mn ions to the protein surface, potentially protecting the enzyme from high Mn oxidation states during turnover. Our findings strongly suggest that multistep hole-hopping transport between the two Mn ions is required for enzymatic function, adding to the growing examples of proteins that employ aromatic residues as hopping stations.

Oxalate decarboxylase catalyzes the redox-neutral unimolecular disproportionation reaction of oxalic acid. The pH maximum for catalysis is ~4.0 and activity is negligible above pH7. Here we report on the first crystal structure of the enzyme in its active pH range at pH4.6, and at a resolution of 1.45 Å, the highest to date. The fundamental tertiary and quaternary structure of the enzyme does not change with pH. However, the low pH crystals are heterogeneous containing both a closed and open conformation of a flexible loop region which gates access to the N-terminal active site cavity. Residue E162 in the closed conformation points away from the active-site Mn ion owing to the coordination of a buffer molecule, acetate. Since the quaternary structure of the enzyme appears unaffected by pH many conclusions drawn from the structures taken at high pH remain valid. Density functional theory calculations of the possible binding modes of oxalate to the N-terminal Mn ion demonstrate that both mono- and bi-dentate coordination modes are possible in the closed conformation with an energetic preference for the bidentate binding mode. The simulations suggest that R92 plays an important role as a guide for positioning the substrate in its catalytically competent orientation. A strong hydrogen bond is seen between the bi-dentate bound substrate and E101, one of the coordinating ligands for the N-terminal Mn ion. This suggests a more direct role of E101 as a transient base during the first step of catalysis.

AAV2.5 represents the first structure-guided in-silico designed Adeno-associated virus (AAV) gene delivery vector. This engineered vector combined the receptor attachment properties of AAV serotype 2 (AAV2) with the muscle tropic properties of AAV1, and exhibited an antibody escape phenotype because of a modified antigenic epitope. To confirm the design, the structure of the vector was determined to a resolution of 2.78 A using cryo-electron microscopy and image reconstruction. The structure of the major viral protein (VP), VP3, was ordered from residue 219 to 736, as reported for other AAV structures, and the five AAV2.5 residues exchanged from AAV2 to AAV1, Q263A, T265 (insertion), N706A, V709A, and T717N, were readily interpretable. Significantly, the surface loops containing these residues adopt the AAV1 conformation indicating the importance of amino acid residues in dictating VP structure.

Background & Aims: Because of the large number of biopsy specimens, surveillance colonoscopy in ulcerative colitis (UC) is currently time consuming and significant flat lesions still may be missed. In this study we assessed the value of combined chromoscopy and endomicroscopy for the diagnosis of intraepithelial neoplasias in a randomized controlled trial. Methods: A total of 161 patients with long-term UC in clinical remission were randomized at a 1:1 ratio to undergo conventional colonoscopy or chromoscopy with endomicroscopy. Eight patients were excluded because of insufficient bowel preparation. In the conventional colonoscopic group (n = 73), random biopsy examinations and targeted biopsy examinations were performed. In the endomicroscopy group (n = 80), circumscribed mucosal lesions were identified by chromoscopy and evaluated for targeted biopsy examination by endomicroscopy. The primary outcome analysis was based on the detection of neoplasias. Results: By using chromoscopy with endomicroscopy, 4.75-fold more neoplasias could be detected (P = .005) than with conventional colonoscopy, although 50% fewer biopsy specimens (P = .008) were required. If only circumscribed lesions would have been biopsied in the first group, the total number of biopsy specimens could have been reduced by more than 90%. A total of 5580 confocal endomicroscopic images from 134 circumscribed lesions were compared with histologic results. The presence of neoplastic changes could be predicted by endomicroscopy with high accuracy (sensitivity, 94.7%; specificity, 98.3%; accuracy, 97.8%). Conclusions: Endomicroscopy based on in vivo histology can determine if UC lesions identified by chromoscopy should undergo biopsy examination, thereby increasing the diagnostic yield and reducing the need for biopsy examinations. Thus, chromoscopy-guided endomicroscopy may lead to significant improvements in the clinical management of UC.

Background & Aims: Aconfocal laser endoscopy system has recently been developed that may allow subsurface imaging of living cells in colonic tissue in vivo. The aim of the present study was to assess its potential for prediction of histology during screening colonoscopy for colorectal cancer. Methods: Twenty-seven patients underwent colonoscopy with the confocal endoscope using acriflavine hydrochloride or fluorescein sodium with blue laser illumination. Furthermore, 42 patients underwent colonoscopy with this system using fluorescein sodium. Standardized locations and circumscript lesions were examined by confocal imaging before taking biopsy specimens. Confocal images were graded according to cellular and vascular changes and correlated with conventional histology in a prospective and blinded fashion. Results: Acriflavine hydrochloride and fluorescein sodium both yielded high-quality images. Whereas acriflavine hydrochloride strongly labeled the superficial epithelial cells, fluorescein sodium offered deeper imaging into the lamina propria. Fluorescein sodium was thus used for the prospective component of the study in which 13,020 confocal images from 390 different locations were compared with histologic data from 1038 biopsy specimens. Subsurface analysis during confocal laser endoscopy allowed detailed analysis of cellular structures. The presence of neoplastic changes could be predicted with high accuracy (sensitivity, 97.4%; specificity, 99.4%; accuracy, 99.2%). Conclusions: Confocal laser endoscopy is a novel diagnostic tool to analyze living cells during colonoscopy, thereby enabling virtual histology of neoplastic changes with high accuracy. These newly discovered diagnostic possibilities may be of crucial importance in clinical practice and lead to an optimized rapid diagnosis of neoplastic changes during ongoing colonoscopy.

Introduction: More than half the patients with gastroesophageal reflux disease (GERD) show no endoscopic abnormality or minimal change esophagitis (non-erosive reflux disease, NERD). We investigated the value of endoscopic and histological markers for the prediction of NERD before and after treatment with 20 mg esomeprazole. Methods: Between July and October 2002, consecutive patients presenting for upper endoscopy were stratified into GERD and non-reflux patients (control group) with the help of a questionnaire. The endoscopist was blind to the presence of reflux symptoms. Using magnifying endoscopes minimal change esophagitis was defined by the presence of vascular injection or vascular spots above the Z-line, villous mucosal surface and islands of squamous cell epithelium below the Z-line. Targeted and random biopsies were taken below and above the Z-line. Patients with endoscopically visible classical signs of esophagitis (Los Angeles A–D) or histologically proven Barrett’s esophagus were not further investigated in the study (drop out). The esophageal specimens were histologically evaluated for erosions, infiltration with leukocytes, hyperplasia of basal cells and length of papillae. Patients with NERD were treated with 20 mg esomeprazole/day for 4 weeks and reevaluated by endoscopy as described before. Results: 39 patients with heartburn and 39 patients without reflux symptoms (controls) were finally included in the analysis (per protocol). Patients with NERD significantly (p = 0.005) more often showed endoscopic signs of minimal change esophagitis (27/39) than the control group (8/39). An increased length of papillae (14/39 versus 2/39; p = 0.005) and basal cell hyperplasia (17/39 versus 4/39; p = 0.009) were significantly more common in the heartburn group. After treatment with esomeprazole, no significant endoscopic or histological differences between the NERD and control group could be observed. Conclusions: Minimal change esophagitis can be seen with high resolution magnifying endoscopy. By combining endoscopic and histological markers NERD can be predicted with a sensitivity of 62% and a specificity of 74%. Treatment with esomeprazole for 4 weeks reverses the slight alterations to normal.

Purpose To determine historical trends and current status of the health of America's youth Methods A thorough literature review was conducted to establish the best sources for adolescent data across a wide range of health-related issues using major national data sources. Data were collected and synthesized to create a comprehensive overview of adolescent health and demographic trends. Results and conclusion Adolescence is a distinct developmental stage posing unique challenges. Although generally considered a time of health and well-being, traditional health indicators often overlook areas specific to adolescence. Despite encouraging improvements in recent years, this population continues to have high rates of morbidity and mortality owing to violence, injury, and mental health disorders. Also, potentially health-damaging behaviors, such as premature and unprotected sexual behavior and substance use, pose significant threats. Fortunately, adolescence is a time of great behavioral plasticity. Because the vast majority of adolescent health risks are the result of behavioral causes, much of this morbidity and mortality is preventable. The adolescent population is projected to greatly increase over the next 2 decades. However, older age groups are increasing more rapidly, reducing the proportion of adolescents in the overall population. The aging population will likely demand increased access to scarce resources. The public needs to be educated about the need to support programs for youth. If resources are properly allocated, and health professionals trained to deal with adolescents' unique needs, America's youth have the potential to benefit greatly from successful implementation of new knowledge, developing healthy, positive, life-long behaviors.

Hintergrund. Adenome der Ampulla Vateri und des Duodenums sind seltene Tumore, deren Leitsymptome hauptsachlich unspezifisch sind oder Folgen einer Passagestorung und Tumorerosion (Blutung) darstellen. Da diese Adenome obligate Prakanzerosen darstellen, sind die rechtzeitige Diagnose und die radikale Entfernung von entscheidender Bedeutung. Patienten und Methoden. In der folgenden Arbeit berichten wir uber 7 Patienten mit periampullaren Adenomen des Duodenums, darunter 1 Fall unter Einbeziehung des distalen Ductus hepatocholedochus (DHC). Anhand der Fallbeispiele werden die diagnostischen Schritte und die operative Therapie beschrieben. Die Behandlung bestand nach Diagnosesicherung via endoskopischer retrograder Cholangiopankreatikographie (ERCP) in 3 Fallen in einer partiellen Duodenopankreatektomie nach Whipple und bei 3 Patienten in einer transduodenalen lokalen Exzision des Tumors mit Papilloplastik im Sinne einer Ampullektomie; der postoperative Verlauf war jeweils komplikationslos, es bestand keine operative Mortalitat. Ein Patient wurde endoskopisch mit Plasma-Argon-Koagulation behandelt. Ergebnisse. Die histopathologische Untersuchung ergab in 6 Fallen ein tubulo-villoses in 1 Fall ein villoses Adenom (von niedrig- bis hochgradiger intraepithelialer Dysplasie). Schlussfolgerung. Da eine Adenom-Karzinom-Sequenz existiert, wird die radikale chirurgische Therapie trotz des fehlenden Nachweises maligne entarteter Zellen befurwortet.

STUDY OBJECTIVES To determine polysomnographic parameter differences in children living at higher altitude to children living near sea level. DESIGN AND SETTING Prospective study of non-snoring, normal children recruited from various communities around Denver, CO. In-lab, overnight polysomnograms were performed at a tertiary care children's hospital. All children required residence for greater than one year at an elevation around 1,600 meters. PARTICIPANTS 45 children (62% female), aged 3-5 years, 88.9% non-Hispanic white with average BMI percentile for age of 47.8% ± 30.7%. MEASUREMENTS AND RESULTS Standard sleep indices were obtained and compared to previously published normative values in a similar population living near sea level (SLG). In the altitude group (AG), the apnea-hypopnea index was 1.8 ± 1.2 and the central apnea-hypopnea index was 1.7 ± 1.1, as compared to 0.9 ± 0.8 and 0.8 ± 0.7, respectively, (P ≤ 0.005) in SLG. Mean end-tidal CO2 level in AG was 42.3 ± 3.0 mm Hg and 40.6 ± 4.6 mm Hg in SLG (P = 0.049). The ≥ 4% desaturation index was 3.9 ± 2.0 in AG compared to 0.3 ± 0.4 in SLG (P < 0.001). Mean periodic limb movement in series index was 10.1 ± 12.3 in AG and 3.6 ± 5.4 in SLG (P = 0.001). CONCLUSION Comparison of altitude and sea level sleep studies in healthy children reveals significant differences in central apnea, apneahypopnea, desaturation, and periodic limb movement in series indices. Clinical providers should be aware of these differences when interpreting sleep studies and incorporate altitude-adjusted normative values in therapeutic-decision making algorithms.

The use of meta-analysis in environmental epidemiology can enhance the value of epidemiologic data in debates about environmental health risks. Meta-analysis may be particularly useful to formally examine sources of heterogeneity, to clarify the relationship between environmental exposures and health effects, and to generate information beyond that provided by individual studies or a narrative review. However, meta-analysis may not be useful when the relationship between exposure and disease is obvious, when there are only a few studies of the key health outcomes, or when there is substantial confounding or other biases which cannot be adjusted for in the analysis. Recent increases in the use of meta-analysis in environmental epidemiology have highlighted the need for guidelines for the application of the technique. Guidelines, in the form of desirable and undesirable attributes, are presented in this paper for various components of a meta-analysis including study identification and selection; data extraction and analysis; and interpretation, presentation, and communication of results. Also discussed are the appropriateness of the use of meta-analysis in environmental health studies and when meta-analysis should or should not be used.

Purpose: A potential method of quality assurance for clinical accelerators is using the signal from Cerenkov light generated during irradiation. The example of measuring output factors (OF) of a clinical accelerator was used to investigate the potential of Cerenkov light as a dosimetry tool. Methods: OF as a function of field size were measured under reference conditions using ionization chambers at 18 MV-X. Furthermore, for selected field sizes, the produced Cerenkov light within the water Phantom was imaged by a CCD-Camera. In order to improve the optical signal, any light source in the treatment room was blocked. The measurement was repeated three times for better statistics. Images were median filtered to reduced errors due to direct ionization of the CCD-chip. Afterwards, raw images were averaged and evaluated at ROI in 10 cm depth. Considering cone shaped geometrical corrections, the measured Cerenkov signal in relation to the signal from 10×10 cm field was compared with OF measured under reference conditions. Results: Comparing the OF as a function of field size with the measured signal change in Cerenkov images, a comparable trend is observable. A limiting factor was the small signal to noise ratio caused by the insufficient sensitivity of the CCD-Camera which results in large error bars. Conclusion: The correlation between Cerenkov light production and dose deposition has already been published. The geometrical correction of the optical system for the non-isotropic Cerenkov signal represents a big challenge of defining correction factors for the system. A highly developed image system is required to image and use Cerenkov signals as a dosimetry tool with an acceptable signal to noise ratio. Moreover, correction factors for the measurement system have to be established. In further work, Monte Carlo simulation should be used in order to define correction factors for the given measuring setup.

Sleep-disordered breathing is very common and is associated with poor health and cognitive outcomes in children and adolescents. Its prevalence is between 2% and 4% of the population this group. Problems such as life-threatening events, failure to thrive, cardiovascular insult, poor cognition, poor school performance, and psychiatric/behavioral problems have been reported. This chapter will outline how to diagnose and treat adolescents with sleep apnea.

As from 1984, synopses based on unpublished research reports have been published in the Netherlands Journal of Agricultural Science (NJAS), in addition to full papers unre lated to the synopses. To study readers' behaviour towards the synopsis, which is still a relatively uncommon vehicle of primary communication, both full papers ( n = 94) and synopses ( n = 67) published in NJAS in 1984-1986 were subjected to citation analysis. Self-ci tations ("autocitations," as opposed to "allocitations") were excluded from most analyses. On average, citation yields were significantly lower for synopses than for full papers. The citation yields vaned strongly between the three years. The distribution of the journal's contents over the various subdisciplines of agricultural science explamed fairly well the capricious behaviour of citation yields over the years, but not the difference in yield between synopses and full papers. Further, the coverage of NJAS papers by five major biblio graphic databases was analysed. AGRIS and SCISEARCH covered NJAS' contents integrally. Thirteen percent of all papers ( n = 21) covered by AGRIS and SCISEARCH only had not been cited at all. CHEMABS' coverage appeared to be fmrly consistent with the scope of this database (chemistry). However, BIOSIS' and CABI's coverage behaviour over the period in question appeared to be characterized by incon sistency and arbitrariness. Coverage by BIOSIS and CABI was significantly better for full papers than for synopses (BIOSIS 87% and 43%. and CABI 65% and 48%, respectively). After correction for bibliographic coverage the citation yield was still lower for synopses than for full papers, but the difference was no longer significant. Two-thirds of the initial difference in citation yield between full papers and synopses could be attributed to differences in bibliographic coverage. It is concluded that inconsistent bibliographic coverage procedures seriously undermine the penetrative capacity (and hence meaningfulness) of papers published in journals whose readers depend largely on bibliographic sources.

The purpose of this discovery phase study was to identify candidate protein biomarkers for high-grade dysplastic cervical cells using mass spectrometry. Laser Capture Microdissection (LCM) was utilized to isolate high-grade dysplastic and normal cells from ThinPrep slides prepared from cervical cytological specimens. Following cell capture, samples were solubilized and proteins separated by gel electrophoresis in preparation for enzymatic digestion and liquid chromatography mass spectrometry analysis (LC-MS). Processed samples were subsequently analyzed using a linear ion trap coupled with a Fourier transform mass spectrometer (LTQ-FT MS). It was determined that both PreservCyt Solution and ThinPrep Pap Stain (Cytyc Corporation) were compatible with the sample processing and LC-MS analysis. In total, from 9 normal and 9 abnormal cervical cytological specimens, more than 1000 unique proteins were identified with high confidence, based on approximately 12,000 captured cells per specimen. Quantitative protein differences between HSIL (High-Grade Squamous Intraepithelial Lesion) and NILM (Negative for Intraepithelial Lesions or Malignancy) samples were determined by comparing the intensities of the representative (label-free) peptide ions. More than 200 proteins were found to exhibit a 3-fold difference in protein level. Interestingly, significant up-regulation of nuclear and mitochondrial proteins in HSIL specimens was noted. In several cases, the increased protein abundance observed in high-grade cells, as determined by quantitative LC-MS, was validated by immunocytochemical methods using ThinPrep cervical specimens. With the study of additional clinical specimens, the differential abundance of proteins in high-grade dysplastic cells versus morphologically normal cervical cells may lead to validated novel biomarkers for cervical disease.

Background & Aims: Confocal laser endomicroscopy enables subsurface microscopic imaging of living tissue during ongoing endoscopy. This case report describes the in vivo detection of Helicobacter pylori by endomicroscopy.Methods: Endomicroscopy (Pentax, Tokyo, EC-3870CIFK) was performed by using two different contrast stains: Topical Acriflavine in addition to intravenously applied fluorescein netted the surface and allowed identification of focal accumulation of Helicobacter pylori at the surface and in deeper layer of the gastric epithelium. Biopsies were performed at the antrum and corpus for urease testing and histology. In addition, biopsies were cultured for Helicobacter pylori. Cultured bacteria were re-assessed ex vivo using confocal microscopy with and without acriflavine staining.Results: Helicobacter pylori infection could be detected in a 70-year-old male by endomicroscopy. Accumulated, as well as single bacteria, could be observed and the distinct shape and flagella of Helicobacter pylori could be identified. Helicobacter pylori infection was proved by histology. Furthermore, ex vivo examination of cultures proved the presence of Helicobacter pylori and the active uptake of acriflavine into the bacteria.Conclusions: Endomicroscopy is a new diagnostic approach, which enables the immediate diagnosis of Helicobacter pylori in vivo during standard video endoscopy.