Odontogenic Cysts and Tumors.

Odontogenic cysts and tumors are mandibular and maxillary lesions that occur across all patient demographics across age, sex, race, and social economic status, as altered remnants of dental development. They may be incidental findings from routine imaging in any office or found through workup for craniofacial surgery or injury. Many of these patients present with asymptomatic lesions, whereas others may be symptomatic. In this article, we review the literature on the most common odontogenic tumors and cysts and discuss their presentation, their defining traits, and how to approach diagnosis and definitive management.

Polysialylation controls dendritic cell trafficking by regulating chemokine recognition.

The addition of polysialic acid to N- and/or O-linked glycans, referred to as polysialylation, is a rare posttranslational modification that is mainly known to control the developmental plasticity of the nervous system. Here we show that CCR7, the central chemokine receptor controlling immune cell trafficking to secondary lymphatic organs, carries polysialic acid. This modification is essential for the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited conformation, which is released upon interaction with polysialic acid. Thus, we describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic basis.

Banning cigarette smoking on US Navy submarines: a case study.

BACKGROUND: The military has had a long pro-tobacco tradition. Despite official policy discouraging smoking, tobacco still is widely seen as part of military culture. While active smoking has presented a particular challenge for the military, in recent years there also has been increasing concern with secondhand smoke. This is especially true in closed environments and submarines may be deployed for months at a time. The current case study describes the successful implementation by the Navy of a comprehensive ban on smoking aboard submarines. METHODS: The authors searched documents on the internet, popular media, military-based news outlets and the scientific literature. We also conducted interviews with Navy officers who were instrumental in policy implementation. FINDINGS: Data demonstrating substantial exposure of non-smokers to tobacco smoke aboard submarines had major impact on successful adoption of the policy. A systematic and extended roll out of the ban included establishing a working group, soliciting input and active engagement from submarine personnel, and offering cessation assistance. Support was enlisted from Chief Petty Officers who could have been strongly opposed but who became strong proponents. Fewer problems were encountered than had been expected. In contrast to a previous unsuccessful attempt by a Navy captain to ban smoking on his ship, the ban was adopted without apparent tobacco industry interference. CONCLUSIONS: Lessons learned included the importance of strong empirical support, effective framing of the issue, setting a realistic timeline, soliciting support from key personnel and providing appropriate resources. These lessons have implications for those considering further tobacco policy changes in the military and elsewhere.

Is it time for a tobacco-free military?

Achieving a tobacco-free military requires rethinking current perceptions of service members' tobacco use and unmasking the forces perpetuating those perceptions. Prohibiting tobacco use would be entirely consistent with other military requirements regarding health.

A longitudinal analysis of cigarette prices in military retail outlets.

OBJECTIVES: We conducted a longitudinal assessment of tobacco pricing in military retail outlets, including trends within each service branch. METHODS: We determined the price of a single pack of Marlboro Red cigarettes at military retail stores located in the continental United States, Alaska, and Hawaii and at their nearest Walmarts in spring 2011 and 2013 (n = 128 for pairs available at both assessments). RESULTS: The average difference between cigarettes sold in military retail outlets and Walmarts decreased from 24.5% in 2011 to 12.5% in 2013. The decrease was partially attributable to significant price decreases at Walmarts. The largest increases in cigarette prices occurred on naval installations. Potential savings at stores on several installations remained substantial in 2013; the largest approached $6 per pack. Stores on 17 military installations decreased cigarette prices during the study period. CONCLUSIONS: Tobacco can be purchased in military retail stores at substantial savings over civilian stores. If tobacco pricing is to cease to be an incentive for use among personnel, a revised military tobacco pricing policy is needed.

Cigarette prices in military retail: a review and proposal for advancing military health policy.

Tobacco use is the leading cause of preventable death in the United States and has been shown to significantly harm the combat readiness of military personnel. Unfortunately, recent research showed that cigarettes are sold at substantial discounts in military retail outlets. In fact, the military is the only retailer that consistently loses money on tobacco. Cheap tobacco prices have been identified by enlisted personnel and Department of Defense health policy experts as promoting a culture of tobacco use in the U.S. Military. This article provides an analysis of why current military tobacco pricing policy has failed to eliminate cheap tobacco prices as an incentive for use. A rationale for increasing tobacco prices also is presented along with recommendations for improved military tobacco control policy.

Assessing the non-cancer risk for RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) using physiologically based pharmacokinetic (PBPK) modeling.

RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) is an explosive used in military applications. It has been detected in ground water surrounding US military installations and at manufacturing facilities. RDX has been shown to produce hepatotoxicity, testicular, and neurological effects in animals, the latter also in humans. The current chronic oral reference dose (RfD) of 0.003 mg/kg/day was derived based on prostate effects in rats. Here, we provide a reevaluation of the risk associated with RDX exposure by examining old and new data and using physiologically based pharmacokinetic (PBPK) modeling approaches. Candidate non-cancer endpoints in rodents were evaluated and the most plausible mode(s) of action were determined. A PBPK model was used to derive appropriate internal doses based on the mode of action, and then a benchmark dose (BMD) and the lower confidence limit on the BMD (BMDL) were determined using these internal doses in animals. Uncertainty factors (UF) were applied to the animal BMDL or no-observed effect level and a human PBPK model was used to determine a human equivalent dose resulting in the candidate RfDs (cRfDs). A proposed chronic RfD of 0.07 mg/kg/day, based on multiple effects observed in rats, was selected from among the cRfDs.

A content analysis of tobacco control policy in the U.S. Department of Defense.

We conducted a content analysis of the US military tobacco policies at the Department of Defense, each respective military service (Army, Air Force, Navy, and Marine Corps), and their Major Commands (MAJCOM). Ninety-seven policies were evaluated using the Military Tobacco Policy Rating Form (MTPRF). More than three quarters addressed the following domains: (1) deleterious health effects of tobacco use; (2) environmental tobacco smoke; (3) designation of smoking areas; (4) tobacco prevention/cessation programs; and (5) smokeless tobacco. Few policies (2.1 per cent) mentioned relevant Department of Defense and respective service tobacco use prevalence statistics. Smoking as non-normative or incompatible with military service, the impact of tobacco use on military readiness, and the tobacco industry were addressed infrequently (6.2 per cent, 33.0 per cent, and 8.2 per cent, respectively). Future military tobacco policies should address important omissions of critical information such as the current service tobacco use prevalence, effects on readiness, and smoking as non-normative.

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression.

PURPOSE: L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. METHODS: LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid (anti-[(18)F]FACBC) PET was assessed for its diagnostic biomarker potential. RESULTS: Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high-grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced-stage breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-amino-bicyclo[2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, anti-[(18)F]FACBC, has been demonstrated to be an excellent PET tracer for the non-invasive imaging of malignant breast cancer using an orthotopic animal model. CONCLUSIONS: The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. Anti-[(18)F]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.

Military tobacco policies: the good, the bad, and the ugly.

The United States military has the legacy of a pro-tobacco culture and still has prevalence rates of tobacco use that are higher than their civilian counterparts. One tactic for decreasing use and the subsequent health problems is through effective tobacco control policies. We collected available tobacco control policies from all four branches of the military and, through qualitative analysis, identified policies that were unique either as providing more or less detail and restriction than peer group policies. Best and worst practice policies in the areas of enforcement, smoking cessation, smokeless tobacco use, environmental tobacco smoke, framing tobacco as non-normative, designated tobacco use areas, and monitoring of tobacco use are presented. Because policy making can be an effective tool for improving the health of military members, understanding what policy components are comparatively positive or negative is an important tool for health advocates both in the military and civilian settings.

(R,S)-anti-1-amino-2-[18F]fluorocyclopentyl-1-carboxylic acid: synthesis from racemic 2-benzyloxycyclopentanone and biological evaluation for brain tumor imaging with positron emission tomography.

(R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (2-FACPC, 4b) was radiolabeled in 39% yield starting from cyclic sulfamidate 12. The 9L gliosarcoma cells assays showed that 4b is mainly a substrate for the L-type amino acid transport with some affinity to the A-type. In rats bearing 9L gliosarcoma tumors, 4b displayed high tumor to brain ratio (10:1) at 120 min after injection. FACPC is an attractive candidate for imaging brain tumors with PET, and its isolated enantiomers are under investigation.

Synthesis and biological evaluation of anti-1-amino-2-[18F]fluoro-cyclobutyl-1-carboxylic acid (anti-2-[18F]FACBC) in rat 9L gliosarcoma.

A new [(18)F] labeled amino acid anti-1-amino-2-[(18)F]fluoro-cyclobutyl-1-carboxylic acid 9 (anti-2-[(18)F]FACBC) was synthesized in 30% decay-corrected yield with high radiochemical purity over 99%. The cyclic sulfamidate precursor was very stable and highly reactive towards nucleophilic radiofluorination. Cell uptake assays with rat 9L gliosarcoma cells showed that [(18)F]9 was transported into tumor cells via multiple amino acid transport systems, including L and A systems. Biodistribution study in rats with intracranial 9L gliosarcoma tumors demonstrated that [(18)F]9 had a rapid and prolonged accumulation in tumors with 26:1 tumor to brain ratio at 120 min post-injection. In this model, [(18)F]9 is a potential PET tracer for brain tumor imaging.

Synthesis, radiolabeling, and biological evaluation of (R)- and (S)-2-amino-3-[(18)F]fluoro-2-methylpropanoic acid (FAMP) and (R)- and (S)-3-[(18)F]fluoro-2-methyl-2-N-(methylamino)propanoic acid (NMeFAMP) as potential PET radioligands for imaging brain tumors.

The non-natural amino acids (R)- and (S)-2-amino-3-fluoro-2-methylpropanoic acid 5 and (R)- and (S)-3-fluoro-2-methyl-2-N-(methylamino)propanoic acid 8 were synthesized in shorter reaction sequences than in the original report starting from enantiomerically pure (S)- and (R)-alpha-methyl-serine, respectively. The reaction sequence provided the cyclic sulfamidate precursors for radiosynthesis of (R)- and (S)-[(18)F]5 and (R)- and (S)-[(18)F]8 in fewer steps than in the original report. (R)- and (S)-[(18)F]5 and(R)- and (S)-[(18)F]8 were synthesized by no-carrier-added nucleophilic [(18)F]fluorination in 52-66% decay-corrected yields with radiochemical purity over 99%. The cell assays showed that all four compounds were substrates for amino acid transport and enter 9L rat gliosarcoma cells in vitro at least in part by system A amino acid transport. The biodistribution studies demonstrated that in vivo tumor to normal brain ratios for all compounds were high with ratios of 20:1 to115:1 in rats with intracranial 9L tumors. The (R)-enantiomers of [(18)F]5 and [(18)F]8 demonstrated higher tumor uptake in vivo compared to the (S)-enantiomers.

Persistent antibody depletion after rituximab in three children with autoimmune cytopenias.

We report 3 children who developed persistent antibody depletion and abnormal response to bacteriophage after rituximab treatment for autoimmune cytopenias. Whether these patients have developed immunodeficiency secondary to an underlying disease process, to rituximab, or both, is not understood. Rituximab is an efficacious drug for a number of pediatric conditions. However, some patients who receive the drug have prolonged suppression or absence of B-cell function. Families should be counseled of this possibility prior to therapy. Patients should have baseline measurement of quantitative immunoglobulins and specific antibody levels and should be monitored for long term changes in immune function after rituximab.

Obesity, inflammation, and asthma severity in childhood: data from the National Health and Nutrition Examination Survey 2001-2004.

BACKGROUND: The prevalences of asthma and obesity in children have increased significantly during the past 2 decades. The basis for the relationship between pediatric asthma and obesity is not well established. OBJECTIVES: To explore the association between obesity and asthma severity in children and adolescents and to test whether obesity-induced inflammation, as characterized by serum C-reactive protein (CRP), is associated with increased severity of asthma. METHODS: Retrospective cohort analysis of interview, physical examination, and laboratory test data from participants younger than 20 years in 2 rounds of the National Health and Nutrition Examination Survey (2001-2002 and 2003-2004). We also performed generalized ordered logistic regression to evaluate the effect of body mass index (BMI) z score and CRP level on asthma severity, controlling for the impact of age, sex, race, income, insurance, and tobacco smoke exposure. RESULTS: Of the 77 million individuals younger than 20 years represented by this weighted sample, 19% met the study-defined criteria for asthma; most cases were defined as mild (11%) or moderate (6%); 2% had severe asthma. In multivariable models, elevated BMI z scores (odds ratio, 1.12; 95% confidence interval, 1.05-1.21) were associated with worse asthma severity. Elevated CRP level was associated with obesity (P < .001) and asthma severity (odds ratio, 1.33; 95% confidence interval, 1.16-1.52). CONCLUSIONS: Higher BMI z scores and elevated serum CRP levels are associated with increased asthma severity. These findings highlight the importance of controlling for inflammation when considering the role of obesity and provide support for the hypothesis that obesity-induced inflammation may contribute to greater asthma severity.

Stereoselective synthesis and biological evaluation of syn-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid as a potential positron emission tomography brain tumor imaging agent.

Amino acid syn-1-amino-3-fluoro-cyclobutyl-1-carboxylic acid (syn-FACBC) 12, the isomer of anti-FACBC, has been selectively synthesized and [(18)F] radiofluorinated in 52% decay-corrected yield using no-carrier-added [(18)F]fluoride. The key step in the synthesis of the desired isomer involved stereoselective reduction using lithium alkylborohydride/zinc chloride, which improved the ratio of anti-alcohol to syn-alcohol from 17:83 to 97:3. syn-FACBC 12 entered rat 9L gliosarcoma cells primarily via L-type amino acid transport in vitro with high uptake of 16% injected dose per 5 x 10(5) cells. Biodistribution studies in rats with 9L gliosarcoma brain tumors demonstrated high tumor to brain ratio of 12:1 at 30 min post injection. In this model, amino acid syn-[(18)F]FACBC 12 is a promising metabolically based radiotracer for positron emission tomography brain tumor imaging.

Synthesis and evaluation of [123I] labeled iodovinyl amino acids syn-, anti-1-amino-3-[2-iodoethenyl]-cyclobutane-1-carboxylic acid, and 1-amino-3-iodomethylene-cyclobutane-1-carboxylic acid as potential SPECT brain tumor imaging agents.

syn- and anti-1-amino-3-[2-iodoethenyl]-cyclobutane-1-carboxylic acid (syn-, anti-IVACBC 16, 17) and their analogue 1-amino-3-iodomethylene-cyclobutane-1-carboxylic acid (gem-IVACBC 18) were synthesized and radioiodoinated with [(123)I] in 34-43% delay-corrected yield. All these amino acids entered 9L gliosarcoma cells primarily via L-type transport in vitro with high uptake of 8-10% ID/1 x 10(6) cells. Biodistribution studies of [(123)I]16, 17 and 18 in rats with 9L gliosarcoma brain tumors demonstrated high tumor to brain ratios (4.7-7.3:1 at 60 min post-injection). In this model, syn-, anti-, and gem-[(123)I]IVACBC are promising radiotracers for SPECT brain tumor imaging.