Evaluation of Cystic Salivary Gland Lesions by Fine-Needle Aspiration: An Analysis of 21 Cases

Objective: To analyze the potential sources of diagnostic errors and overall accuracy rate of the fine needle aspiration biopsy (FNAB) diagnosis of cystic salivary gland neoplasms. Study Design: A 10-year (1993-2002) retrospective review of the cytopathology slides from the Department of Pathology, Division of Cytopathology at Long Island Jewish Medical Center, New Hyde Park, NY, identified a total of 97 consecutive salivary gland FNAB cases that microscopically were interpreted as representing cystic lesions. Of these, 21 cases had histologic follow up at our institution. Results: A correct diagnosis was rendered by FNAB in 15/21 (72%) cases. This included 9 Warthin’s tumors, 2 mucoepidermoid carcinomas, 2 simple cysts, 1 cystadenoma and 1 abscess. Clinically insignificant discrepancies were identified in 3 of 21 (14%) FNABs. Clinically significant misdiagnoses were identified in a further 3 of 21 (14%) cases. Conclusions: A systematic approach to the diagnosis of cystic salivary gland lesions by FNAB can result in a correct diagnosis in greater than 70% of cases. Careful attention should be directed at identifying the extracellular fluid component(s) present (mucoid vs. watery proteinaceous) as well as the predominant cellular component (e.g. lymphocytes, histiocytes, epithelial cells and oncocytes). It is important to recognize, however, that occasionally epithelial cells may not be detected on FNAB of cystic salivary gland lesions, either as a result of cellular dilution by cyst fluid or due to inadequate sampling. However, with all FNABs tentatively diagnosed as a mucinous cystic lesion, the referring clinician should be informed that a low-grade mucoepidermoid cannot be ruled out

Undergraduates Writing Publishable Cases: The Trials, The Tribulations, And The Real-World Learning

If given the chance, undergraduates have the ability to write excellent case studies worthy of being published.  This essay describes the benefits, challenges, and process of undergraduate case writing.&nbsp

MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

Identification of oral clefts as a risk factor for hearing loss during newborn hearing screening

Objective: This study assessed whether children with oral clefts are appropriately classified as at-risk for hearing loss at the time of newborn hearing screening and describes their screening and diagnostic results. Design: Birth certificates were used to identify children with cleft lip and palate or isolated cleft palate born in Washington State from 2008–2013. These were cross-referenced with the state’s Early Hearing Detection, Diagnosis and Intervention (EHDDI) database. Multivariate logistic regression was used to examine associations. Results: Birth records identified 235 children with cleft lip and palate and 116 with isolated cleft palate. Six children were listed as having both diagnoses. Only 138 (39%) of these children were designated as having a craniofacial anomaly in the EHDDI database. Children who were misclassified were less likely to have referred on initial hearing screening, OR 0.3, 95% CI [0.2, 0.5]. Misclassification of risk factor status was also associated with delayed hearing screening past 30 days of age or unknown age at screening, OR 4.4, 95% CI [1.5, 13.3], p = 0.008. Of 50 children with diagnostic results; 25 (50%) had hearing loss: 18 conductive, 2 mixed, and 5 unspecified. Conclusion: A majority of children with oral clefts were misclassified regarding risk factor for hearing loss in the EHDDI database

Understanding and mitigating thiaminase activity in silver carp

A deficiency of thiamine (vitamin B1), an essential cofactor for enzymes involved in metabolic processes, can be caused by the enzyme thiaminase. Thiaminase in food stocks has been linked to morbidity and mortality due to thiamine depletion in many ecologically and economically important species. Thiaminase activity has been detected in certain bacteria, plants, and fish species, including carp. The invasive silver carp (Hypophthalmichthys molitrix) presents an enormous burden to ecosystems throughout the Mississippi River watershed. Its large biomass and nutritional content offer an attractive possibility as a food source for humans, wild animals, or pets. Additionally, harvesting this fish could alleviate some of the effects of this species on waterways. However, the presence of thiaminase would detract from its value for dietary consumption. Here we confirm the presence of thiaminase in several tissues from silver carp, most notably the viscera, and systematically examine the effects of microwaving, baking, dehydrating, and freeze-drying on thiaminase activity. Certain temperatures and durations of baking and microwaving reduced thiaminase activity to undetectable levels. However, caution should be taken when carp tissue is concentrated by processes without sufficient heat treatment, such as freeze-drying or dehydration, which results in concentration, but not inactivation of the enzyme. The effects of such treatments on the ease of extracting proteins, including thiaminase, and the impact on data interpretation using the 4-nitrothiophenol (4-NTP) thiaminase assay were considered

Pre-analytical challenges from adsorptive losses associated with thiamine analysis

Thiamine (vitamin B1) is an essential vitamin serving in its diphosphate form as a cofactor for enzymes in the citric acid cycle and pentose-phosphate pathways. Its concentration reported in the pM and nM range in environmental and clinical analyses prompted our consideration of the components used in pre-analytical processing, including the selection of filters, filter apparatuses, and sample vials. The seemingly innocuous use of glass fiber filters, glass filter flasks, and glass vials, ubiquitous in laboratory analysis of clinical and environmental samples, led to marked thiamine losses. 19.3 nM thiamine was recovered from a 100 nM standard following storage in glass autosampler vials and only 1 nM of thiamine was obtained in the filtrate of a 100 nM thiamine stock passed through a borosilicate glass fiber filter. We further observed a significant shift towards phosphorylated derivatives of thiamine when an equimolar mixture of thiamine, thiamine monophosphate, and thiamine diphosphate was stored in glass (most notably non-silanized glass, where a reduction of 54% of the thiamine peak area was observed) versus polypropylene autosampler vials. The selective losses of thiamine could lead to errors in interpreting the distribution of phosphorylated species in samples. Further, some loss of phosphorylated thiamine derivatives selectively to amber glass vials was observed relative to other glass vials. Our results suggest the use of polymeric filters (including nylon and cellulose acetate) and storage container materials (including polycarbonate and polypropylene) for thiamine handling. Losses to cellulose nitrate and polyethersulfone filters were far less substantial than to glass fiber filters, but were still notable given the low concentrations expected in samples. Thiamine losses were negated when thiamine was stored diluted in trichloroacetic acid or as thiochrome formed in situ, both of which are common practices, but not ubiquitous, in thiamine sample preparation

Improving Social Norms and Actions to Prevent Sexual and Intimate Partner Violence: A Pilot Study of the Impact of Green Dot Community on Youth

Sexual violence (SV) and intimate partner violence (IPV), which often cooccur with bullying, are serious public health issues underscoring the need for primary prevention. The purpose of this study was to examine the impact of a community-building SV and IPV prevention program, Green Dot Community, on adolescents’ perceptions of community social norms and their propensity to intervene as helpful actionists using two independent data sources. Green Dot Community takes place in towns and aims to influence all town members to prevent SV and IPV by addressing protective factors (i.e., collective efficacy, positive prevention social norms, and bystander helping, or actionism). In the current study, one town received Green Dot Community (the prevention-enhanced town), and two towns received prevention as usual (i.e., awareness and fundraising events by local IPV and SV advocacy centers). The program was evaluated using a two-part method: (a) A cross-sectional sample of high school students from three rural communities provided assessment of protective factors at two time points (Time 1, n = 1,187; Time 2, n = 877) and (b) Youth Risk Behavior Survey data from the state Department of Health were gathered before and after program implementation (Time 1, n = 2,034; Time 2, n = 2,017) to assess victimization rates. Youth in the prevention-enhanced town reported higher collective efficacy and more positive social norms specific to helping in situations of SV and IPV over time but did not differ on bystander behaviors or on victimization rates. Community-based prevention initiatives may be helpful in changing community norms to prevent SV/IPV

Complete Reversible Refolding of a G-Protein Coupled Receptor on a Solid Support

The factors defining the correct folding and stability of integral membrane proteins are poorly understood. Folding of only a few select membrane proteins has been scrutinised, leaving considerable deficiencies in knowledge for large protein families, such as G protein coupled receptors (GPCRs). Complete reversible folding, which is problematic for any membrane protein, has eluded this dominant receptor family. Moreover, attempts to recover receptors from denatured states are inefficient, yielding at best 40-70% functional protein. We present a method for the reversible unfolding of an archetypal family member, the β1-adrenergic receptor, and attain 100% recovery of the folded, functional state, in terms of ligand binding, compared to receptor which has not been subject to any unfolding and retains its original, folded structure. We exploit refolding on a solid support, which could avoid unwanted interactions and aggregation that occur in bulk solution. We determine the changes in structure and function upon unfolding and refolding. Additionally, we employ a method that is relatively new to membrane protein folding; pulse proteolysis. Complete refolding of β1-adrenergic receptor occurs in n-decyl-β-D-maltoside (DM) micelles from a urea-denatured state, as shown by regain of its original helical structure, ligand binding and protein fluorescence. The successful refolding strategy on a solid support offers a defined method for the controlled refolding and recovery of functional GPCRs and other membrane proteins that suffer from instability and irreversible denaturation once isolated from their native membranes

Protein crystallography with a micrometre-sized synchrotron-radiation beam

For the first time, protein microcrystallography has been performed with a focused synchrotron-radiation beam of 1 µm using a goniometer with a sub-micrometre sphere of confusion. The crystal structure of xylanase II has been determined with a flux density of about 3 × 1010 photons s−1 µm−2 at the sample

Stepwise disarmament and sudden destruction in a two-person game: a research tool

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66968/2/10.1177_002200276400800104.pd