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1.  The challenges of nutrition policymaking 
Nutrition Journal  2015;14:15.
In my over three decades of work in the field of food and nutrition, I have participated in many efforts that seek new policy initiatives in the hopes that these programs can curb rates of obesity and chronic disease and help consumers make healthier dietary choices. Because of the profound effect that many of these policies have on consumers, the food environment, federal nutrition assistance programs and subsequent policy and regulatory recommendations, it is imperative that only the strongest, best available evidence is used to set policy. This review evaluates methods by which current nutrition policies use scientific research as well as provides recommendations for how best to ensure future nutrition policies are truly science-based and likely to have a meaningful impact on public health. Specifically, this review will:Describe the current food and nutrition policy environment in the USExamine how science is used in federal food and nutrition policymaking efforts, using the Dietary Guidelines for Americans (DGA) as an exampleDescribe strong versus weak science as well as what types of studies are most appropriate for use in policymakingDiscuss the potential effects and consequences of making policy recommendations in the absence of scientific consensus or agreementMake recommendations to support the present and ongoing development of science-based policy likely to positively impact public health
PMCID: PMC4322557
Dietary guidance; Nutrition policy; Evidence based review; Sodium; Added sugars
2.  Does MOG Ig-positive AQP4-seronegative opticospinal inflammatory disease justify a diagnosis of NMO spectrum disorder? 
While neuromyelitis optica (NMO) immunoglobulin (Ig) G is considered the hallmark serologic marker of NMO, its association is not absolute, as NMO IgG is not detected in approximately one-fourth of the patients diagnosed with NMO spectrum disorder (NMOSD). Thus, the recent discovery that antibodies to myelin oligodendrocyte glycoprotein (MOG) are detected in some NMO IgG-seronegative patients manifesting clinical and neuroimaging signs of NMO or NMOSD has created tremendous excitement. However, it may be premature to classify this subgroup as NMOSD. NMO is considered an autoimmune astrocytopathy, and aquaporin-4 (AQP4), expressed on astrocytes, is recognized as the target autoantigen of NMO IgG. As its name denotes, MOG is produced by oligodendrocytes, CNS myelin-producing cells, and MOG is well-recognized as one of the candidate autoantigens in multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). Thus, is it possible that the clinical NMOSD-like phenotype associated with MOG-specific antibodies represents a variant of opticospinal MS or ADEM but not AQP4 autoimmunity or NMOSD? Whether this MOG-Ig positive AQP4-seronegative phenotype should be classified as NMOSD, opticospinal MS, or a unique entity is not simply a theoretical question but rather has practical implications for patients, their physicians, insurance carriers, and clinical investigators conducting NMO treatment trials.
PMCID: PMC4309526  PMID: 25635259
3.  Limitations of Observational Evidence: Implications for Evidence-Based Dietary Recommendations12 
Advances in Nutrition  2014;5(1):7-15.
Data from randomized controlled trials (RCTs) provide the strongest evidence for establishing relations between exposures, including dietary exposures, and health outcomes. However, not all diet and health outcome relations can be practically or ethically evaluated by using RCTs; therefore, many dietary recommendations are supported by evidence primarily from observational data, particularly those from prospective cohort studies. Although such evidence is of critical importance, limitations are often underappreciated by nutrition scientists and policymakers. This editorial review is intended to 1) highlight some of these limitations of observational evidence for diet-disease relations, including imprecise exposure quantification, collinearity among dietary exposures, displacement/substitution effects, healthy/unhealthy consumer bias, residual confounding, and effect modification; and 2) advocate for greater caution in the communication of dietary recommendations for which RCT evidence of clinical event reduction after dietary intervention is not available.
PMCID: PMC3884102  PMID: 24425715
5.  An Examination of the PROMIS® Pediatric Instruments to Assess Mobility in Children with Cerebral Palsy 
The Patient Reported Outcomes Measurement Information System (PROMIS®) provides adult and pediatric self-report measures of health-related quality of life designed for use across medical conditions and the general population. The purpose of this study was to examine the feasibility and validity of the PROMIS® pediatric short form and computer adaptive test (CAT) mobility measures in children with cerebral palsy (CP).
Eighty-two children with CP completed self-report (PROMIS® Mobility Short Form, PROMIS® Mobility CAT, Pediatric Quality of Life Inventory™) and performance-based assessments of mobility (Timed Up-and-Go, Gross Motor Function Measure). Parents provided three proxy reports of child mobility (Pediatric Outcomes Data Collection Instrument, Functional Assessment Questionnaire, Shriners Hospitals for Children CP-CAT). Validity of PROMIS® instruments was examined through correlations with other measures and “known groups” analyses determined by Gross Motor Function Classification System (GMFCS).
On average, the PROMIS® CAT required less than seven items and two minutes to administer. Both PROMIS® measures showed moderate to high correlations with child- and parent-proxy report of child mobility; correlations with performance-based measure were small for the PROMIS® Short Form and non-significant for the PROMIS® CAT. All measures except for the PROMIS® CAT were able to distinguish between GMFCS categories.
Results support the convergent and discriminant validity of the pediatric PROMIS® Mobility Short Form in children with CP. The PROMIS® Mobility CAT correlates well with child- and parent-report of mobility but not with performance-based measures and does not differentiate between known mobility groups.
PMCID: PMC3758380  PMID: 23543391
cerebral palsy; PROMIS®; mobility; computer adaptive test; validity
6.  Project Kealahou: Improving Hawai‘i's System of Care for At-Risk Girls and Young Women through Gender-Responsive, Trauma-Informed Care 
Project Kealahou (PK) is a six-year, federally-funded program aimed at improving services and outcomes for Hawai‘i's female youth who are at risk for running away, truancy, abuse, suicide, arrest and incarceration. PK builds upon two decades of sustained cross-agency efforts among the state's mental health, juvenile justice, education, and child welfare systems to promote system-of-care (SOC) principles of community-based, individualized, culturally and linguistically competent, family driven, youth-guided, and evidence-based services. In addition, PK emphasizes trauma-informed and gender-responsive care in serving its target population of females ages 11–18 years who have experienced psychological trauma.
Results from the first four years of the implementation of PK in the Department of Health's (DOH) Child and Adolescent Mental Health Division (CAMHD) highlight the serious familial, socioeconomic, functional, and interpersonal challenges faced by the young women who receive services in Hawai‘i's SOC. Despite the challenges faced by PK youth and their families, preliminary results of the evaluation of PK show significant improvements across multiple clinical and functional domains of service recipients. A financial analysis indicates that these outcomes were obtained with a minimal overall increase in costs when compared to standard care alone. Overall, these results suggest that PK may offer a cost effective way to improve access, care, and outcomes for at-risk youth and their families in Hawai‘i.
PMCID: PMC4300548  PMID: 25628971
Trauma; Youth; Girls; Mental Health; System of Care (SOC); Community Mental Health Initiative (CMHI); Trauma-Informed Care; Gender-Responsive Care
7.  A case of imported Leishmania infantum cutaneous leishmaniasis; an unusual presentation occurring 19 years after travel 
BMC Infectious Diseases  2014;14(1):597.
Leishmania infantum is a flagellated protozoan parasite that is able to parasitize blood and tissue. Leishmania species cause a spectrum of clinical disease with cutaneous, visceral or mucosal involvement. L. infantum is recognised as a cause of visceral leishmaniasis (VL) and is less commonly reported as a cause of cutaneous leishmaniasis (CL) from countries around the Mediterranean basin. This is the first report of imported L. infantum CL to Australia and is remarkable for a 19 year period between the patient’s exposure to an endemic region, and the manifestation of symptoms.
Case presentation
A 76 year old Italian-born man presented to our institution with a non-healing lesion over his upper lip, abutting his nasal mucosa. The patient had travelled to Italy, an endemic area for L. infantum 19 years earlier but had resided in Australia, a non-endemic area since. Histopathology performed on a biopsy of the lesion demonstrated findings consistent with CL. A species specific polymerase chain reaction (PCR) performed on the tissue detected L. infantum. The patient had complete clinical recovery following treatment with Liposomal amphotericin B at a dose of 3 mg/kg for five days followed by a subsequent 3 mg/kg dose at day ten.
L. infantum should be recognised as a cause of imported CL in returned travellers from the Mediterranean. In this case, the incubation period for L. infantum CL was at least 19 years. This case adds to the described spectrum of clinical presentations of leishmaniasis and supports the theory of parasite persistence underlying natural immunity and recurrence of disease. Clinicians should consider L. infantum CL in the differential diagnosis of a non-healing skin lesion in any patient who reports travel to the Mediterranean, even when travel occurred several years before clinical presentation.
PMCID: PMC4262283  PMID: 25428722
Cutaneous leishmaniasis; Parasitology; Neglected tropical infectious diseases; Microbiology; Liposomal amphotericin
8.  Informing the development of an online self-management program for men living with HIV: a needs assessment 
BMC Public Health  2014;14(1):1209.
The aim of this mixed methods study was to conduct a multifaceted needs assessment to inform the development of an online self-management program for men living with HIV. The objectives were to describe the health-related quality of life for men living with HIV, the impact of living with HIV, and the perceived problem areas and service and support needs of these men. The needs assessment was conducted in accordance with the PRECEDE model for health promotion program planning.
A survey assessing the quality of life of men living with HIV (n = 72) was conducted and results were compared to Australian normative data. Focus groups were also undertaken with men living with HIV (n = 11) and a multidisciplinary team of service providers working in the area of HIV (n = 11). Focus groups enabled an in-depth description of the impact of HIV on quality of life and perceived problem areas in daily life.
HIV-positive men experience significantly lower quality of life when compared with Australian normative data, particularly in those domains concerned with social and emotional aspects of quality of life. Qualitative focus groups yielded an overarching theme ‘The psychosocial impact of HIV’ which contained three sub-themes; (1) Life before and after HIV – a changed identity and its repercussions; (2) Resilience and the importance of social support; (3) Negotiating the practicalities – intimate relationships and disclosure.
The findings from this needs assessment highlight the need to target socio-emotional contexts of HIV positive men’s daily lives to improve quality of life and well-being. Intervention priorities for the proposed online self-management program include: (1) managing the emotional impact of HIV; (2) disclosing HIV status to family and friends; (3) maintaining social connectedness; (4) managing HIV within intimate relationships; and (5) disclosure of HIV status to intimate partners.
PMCID: PMC4251684  PMID: 25421897
HIV/AIDS; Men; Quality of life; Psychosocial issues; Self-management; Needs assessment; Positive Outlook
9.  Snacking for a Cause: Nutritional Insufficiencies and Excesses of U.S. Children, a Critical Review of Food Consumption Patterns and Macronutrient and Micronutrient Intake of U.S. Children 
Nutrients  2014;6(11):4750-4759.
The objective of this review was to identify dietary insufficiencies and excesses in children aged two to 11 in the United States (U.S.) and eating habits that merit concern in terms of nutrient and energy density to improve overall diet quality. Data from the What We Eat in America (WWEIA) tables from the National Health and Nutrition Examination Survey (NHANES) were examined as well as survey data from the School Nutrition Dietary Assessment Study (SNDA). Analysis of survey data revealed that children consume insufficient Vitamin D, calcium, and potassium and excess energy, carbohydrates, and sodium. Dietary modifications are necessary to prevent serious deficiencies and the development of chronic illness. Snacking has steadily increased in this population since the 1970s, and snacks provide necessary nutrients. However, carbohydrates and added sugars tend to be over-consumed at snacking occasions. Replacement of current snack choices with nutrient-dense foods could lower the risks of nutrient deficiencies and help lower excess nutrient consumption. Increased consumption of low sugar dairy foods, especially yogurt, at snack times could increase intake of important micronutrients without contributing to dietary excesses.
PMCID: PMC4245561  PMID: 25360509
yogurt; what we eat in America; WWEIA; national health and nutrition examination survey; NHANES 2009–2010
10.  Effects of Anger Awareness and Expression Training versus Relaxation Training on Headaches: A Randomized Trial 
Background and purpose
Stress contributes to headaches, and effective interventions for headaches routinely include relaxation training (RT) to directly reduce negative emotions and arousal. Yet, suppressing negative emotions, particularly anger, appears to augment pain, and experimental studies suggest that expressing anger may reduce pain. Therefore, we developed and tested anger awareness and expression training (AAET) on people with headaches.
Young adults with headaches (N = 147) were randomized to AAET, RT, or a wait-list control. We assessed affect during sessions, and process and outcome variables at baseline and 4 weeks after treatment.
On process measures, both interventions increased self-efficacy to manage headaches, but only AAET reduced alexithymia and increased emotional processing and assertiveness. Yet, both interventions were equally effective at improving headache outcomes relative to controls.
Enhancing anger awareness and expression may improve chronic headaches, although not more than RT. Researchers should study which patients are most likely to benefit from emotional expression versus emotional reduction approaches to chronic pain.
PMCID: PMC3778035  PMID: 23620190
headaches; relaxation; emotional exposure; emotional processing; anger
11.  Facilitating Surveillance of Pulmonary Invasive Mold Diseases in Patients with Haematological Malignancies by Screening Computed Tomography Reports Using Natural Language Processing 
PLoS ONE  2014;9(9):e107797.
Prospective surveillance of invasive mold diseases (IMDs) in haematology patients should be standard of care but is hampered by the absence of a reliable laboratory prompt and the difficulty of manual surveillance. We used a high throughput technology, natural language processing (NLP), to develop a classifier based on machine learning techniques to screen computed tomography (CT) reports supportive for IMDs.
Patients and Methods
We conducted a retrospective case-control study of CT reports from the clinical encounter and up to 12-weeks after, from a random subset of 79 of 270 case patients with 33 probable/proven IMDs by international definitions, and 68 of 257 uninfected-control patients identified from 3 tertiary haematology centres. The classifier was trained and tested on a reference standard of 449 physician annotated reports including a development subset (n = 366), from a total of 1880 reports, using 10-fold cross validation, comparing binary and probabilistic predictions to the reference standard to generate sensitivity, specificity and area under the receiver-operating-curve (ROC).
For the development subset, sensitivity/specificity was 91% (95%CI 86% to 94%)/79% (95%CI 71% to 84%) and ROC area was 0.92 (95%CI 89% to 94%). Of 25 (5.6%) missed notifications, only 4 (0.9%) reports were regarded as clinically significant.
CT reports are a readily available and timely resource that may be exploited by NLP to facilitate continuous prospective IMD surveillance with translational benefits beyond surveillance alone.
PMCID: PMC4175456  PMID: 25250675
12.  Genetic associations of relaxin: preterm birth and premature rupture of fetal membranes 
Relaxin H2 (RLN2) is a systemic hormone (sRLN) produced by the corpus luteum, whereas decidual (dRLN) only acts locally. Elevated sRLN is associated with spontaneous preterm birth (sPTB) and elevated dRLN with preterm premature rupture of membranes (PPROM). Associations were sought between single nucleotide polymorphisms (SNPs) in the RLN2 promoter with levels of dRLN and sRLN in Filipino patients with sPTB, PPROM or normal term delivery.
Study Design
Stringent selection of women with sPTB (n=20) or PPROM (n=20) and term controls (n=20) was made from over 8,000 samples from Filipino patients delivered at 34–36 weeks gestation. Twelve SNPs were genotyped on maternal blood with exclusion of nine based on high linkage disequilibrium (LD) or being the same as in the control population. Quantitative immunocytochemistry on parietal decidual tissue was performed (n=60) and sRLN measured by ELISA in a subset of patients (n=21).
SNP rs4742076 was significantly associated with PPROM (p<0.001) and increased expression of dRLN (p<0.001). The genotype TT had increased dRLN in PPROM (p<0.05). SNP rs3758239 was significantly associated with both PPROM and sPTB (p<0.01), and genotype AA had increased dRLN expression (p<0.05). The sRLN showed a trend of higher levels in PPROM and sPTB, but was not significant.
SNP rs4742076 in the RLN2 promoter was associated with increased dRLN expression and PPROM while SNP rs3758239 was associated with both PPROM and sPTB in these Filipino patients. Specific homozygous genotypes were identified for both SNPs and were shown to be associated with increased dRLN tissue expression.
PMCID: PMC3758420  PMID: 23727041
Relaxin; preterm birth; preterm premature rupture of membranes; polymorphisms; quantitative immunocytochemistry
13.  Serious Physical Fighting and Gambling-Related Attitudes and Behaviors in Adolescents 
Background and Aims
Physical fighting and gambling are common risk behaviors among adolescents. Prior studies have found associations among these behaviors in adolescents but have not examined systematically the health and gambling correlates of problem-gambling severity amongst youth stratified by fight involvement.
Survey data were used from 2,276 Connecticut high-school adolescents regarding their physical fight involvement, gambling behaviors and perceptions, and health and functioning. Gambling perceptions and correlates of problem-gambling severity were examined in fighting and non-fighting adolescents.
Gambling perceptions were more permissive and at-risk/problem gambling was more frequent amongst adolescents reporting serious fights versus those denying serious fights. A stronger relationship between problem-gambling severity and regular smoking was observed for adolescents involved in fights.
Discussion and Conclusions
The more permissive gambling attitudes and heavier gambling associated with serious fights in high-school students suggest that youth who engage in physical fights warrant enhanced prevention efforts related to gambling. The stronger relationship between tobacco smoking and problem-gambling severity amongst youth engaging in serious fights suggest that fighting youth who smoke might warrant particular screening for gambling problems and subsequent interventions.
PMCID: PMC3840436  PMID: 24294502
Fighting; gambling; physical violence; adolescents; risk behaviors; high school
14.  Estrogen Receptor Alpha Prevents Bladder Cancer Development via INPP4B inhibited Akt Pathway in vitro and in vivo 
Oncotarget  2014;5(17):7917-7935.
Clinical reports show males have a higher bladder cancer (BCa) incidence than females. The sexual difference of BCa occurrence suggests that estrogen and its receptors may affect BCa development. Estrogen receptor alpha (ERα) is the classic receptor to convey estrogen signaling, however, the function of ERα in BCa development remains largely unknown. To understand the in vivo role of ERα in BCa development, we generated total and urothelial specific ERα knockout mice (ERαKO) and used the pre-carcinogen BBN to induce BCa. Earlier reports showed that ERα promotes breast and ovarian cancers in females. Surprisingly and of clinical importance, our results showed that ERα inhibits BCa development and loss of the ERα gene results in an earlier onset and higher incidence of BBN-induced in vivo mouse BCa. Supportively, carcinogen induced malignant transformation ability was reduced in ERα expressing urothelial cells as compared to ERα negative cells. Mechanism studies suggest that ERα could control the expression of INPP4B to reduce AKT activity and consequently reduce BCa cell growth. In addition, IHC staining of clinical sample analyses show that INPP4B expression, in correlation with reduced ERα, is significantly reduced in human BCa specimens. Together, this is the first report using the in vivo cre-loxP gene knockout mouse model to characterize ERα roles in BCa development. Our studies provide multiple in vitro cell studies and in vivo animal model data as well as human BCa tissue analyses to prove ERα plays a protective role in BCa initiation and growth at least partly via modulating the INPP4B/Akt pathway.
PMCID: PMC4202170  PMID: 25277204
15.  MOG transmembrane and cytoplasmic domains contain highly stimulatory T-cell epitopes in MS 
Recently, we reported that the 218 amino acid murine full-length myelin oligodendrocyte glycoprotein (MOG) contains novel T-cell epitopes p119-132, p181-195, and p186-200, located within its transmembrane and cytoplasmic domains, and that p119-132 is its immunodominant encephalitogenic T-cell epitope in mice. Here, we investigated whether the corresponding human MOG sequences contain T-cell epitopes in patients with multiple sclerosis (MS) and healthy controls (HC).
Peripheral blood T cells from patients with MS and HC were examined for proliferation to MOG p119-130, p181-195, p186-200, and p35-55 by fluorescence-activated cell sorting analysis using carboxylfluorescein diacetate succinimidyl ester dilution assay. Intracellular production of proinflammatory cytokines was analyzed by flow cytometry.
MOG p119-130, p181-195, and p186-200 elicited significantly greater T-cell responses than p35-55 in patients with MS. T cells from patients with MS proliferated significantly more strongly to MOG p119-130 and p186-200 than did T cells from HC. Further, MOG p119-130–specific T cells exhibited Th17 polarization, suggesting this T-cell epitope may be relevant to MS pathogenesis.
Transmembrane and cytoplasmic MOG domains contain potent T-cell epitopes in MS. Recognition of these determinants is important when evaluating T-cell responses to MOG in MS and may have implications for development of myelin antigen-based therapeutics.
PMCID: PMC4202926  PMID: 25340072
16.  Immunodominant T-cell epitopes of MOG reside in its transmembrane and cytoplasmic domains in EAE 
Studies evaluating T-cell recognition of myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis (MS) and its model, experimental autoimmune encephalomyelitis (EAE), have focused mostly on its 117 amino acid (aa) extracellular domain, especially peptide (p) 35-55. We characterized T-cell responses to the entire 218 aa MOG sequence, including its transmembrane and cytoplasmic domains.
T-cell recognition in mice was examined using overlapping peptides and intact full-length mouse MOG. EAE was evaluated by peptide immunization and by adoptive transfer of MOG epitope-specific T cells. Frequency of epitope-specific T cells was examined by ELISPOT.
Three T-cell determinants of MOG were discovered in its transmembrane and cytoplasmic domains, p119–132, p181–195, and p186–200. Transmembrane MOG p119-132 induced clinical EAE, CNS inflammation, and demyelination as potently as p35-55 in C57BL/6 mice and other H-2b strains. p119-128 contained its minimal encephalitogenic epitope. p119-132 did not cause disease in EAE-susceptible non-H-2b strains, including Biozzi, NOD, and PL/J. MOG p119-132–specific T cells produced Th1 and Th17 cytokines and transferred EAE to wild-type recipient mice. After immunization with full-length MOG, a significantly higher frequency of MOG-reactive T cells responded to p119-132 than to p35-55, demonstrating that p119-132 is an immunodominant encephalitogenic epitope. MOG p181-195 did not cause EAE, and MOG p181-195–specific T cells could not transfer EAE into wild-type or highly susceptible T- and B-cell–deficient mice.
Transmembrane and cytoplasmic domains of MOG contain immunodominant T-cell epitopes in EAE. A CNS autoantigen can also contain nonpathogenic stimulatory T-cell epitopes. Recognition that a myelin antigen contains multiple encephalitogenic and nonencephalitogenic determinants may have implications for therapeutic development in MS.
PMCID: PMC4202928  PMID: 25340074
17.  The Utility of Outcome Studies in Plastic Surgery 
Outcome studies help provide the evidence-based science rationalizing treatment end results that factor the experience of patients and the impact on society. They improve the recognition of the shortcoming in clinical practice and provide the foundation for the development of gold standard care. With such evidence, health care practitioners can develop evidence-based justification for treatments and offer patients with superior informed consent for their treatment options. Furthermore, health care and insurance agencies can recognize improved cost-benefit options in the purpose of disease prevention and alleviation of its impact on the patient and society. Health care outcomes are ultimately measured by the treatment of disease, the reduction of symptoms, the normalization of laboratory results and physical measures, saving a life, and patient satisfaction. In this review, we outline the tools available to measure outcomes in plastic surgery and subsequently allow the objective measurements of plastic surgical conditions. Six major outcome categories are discussed: (1) functional measures; (2) preference-based measures and utility outcome scores; (3) patient satisfaction; (4) health outcomes and time; (5) other tools: patient-reported outcome measurement information system, BREAST-Q, and Tracking Operations and Outcomes for Plastic Surgeons; and (6) cost-effectiveness analysis. We use breast hypertrophy requiring breast reduction as an example throughout this review as a representative plastic surgical condition with multiple treatments available.
PMCID: PMC4229293  PMID: 25426372
18.  Identifying Practical Solutions to Meet America’s Fiber Needs: Proceedings from the Food & Fiber Summit 
Nutrients  2014;6(7):2540-2551.
Fiber continues to be singled out as a nutrient of public health concern. Adequate intakes of fiber are associated with reduced risk for cardiovascular disease, cancer, diabetes, certain gastrointestinal disorders and obesity. Despite ongoing efforts to promote adequate fiber through increased vegetable, fruit and whole-grain intakes, average fiber consumption has remained flat at approximately half of the recommended daily amounts. Research indicates that consumers report increasingly attempting to add fiber-containing foods, but there is confusion around fiber in whole grains. The persistent and alarmingly low intakes of fiber prompted the “Food & Fiber Summit,” which assembled nutrition researchers, educators and communicators to explore fiber’s role in public health, current fiber consumption trends and consumer awareness data with the objective of generating opportunities and solutions to help close the fiber gap. The summit outcomes highlight the need to address consumer confusion and improve the understanding of sources of fiber, to recognize the benefits of various types of fibers and to influence future dietary guidance to provide prominence and clarity around meeting daily fiber recommendations through a variety of foods and fiber types. Potential opportunities to increase fiber intake were identified, with emphasis on meal occasions and food categories that offer practical solutions for closing the fiber gap.
PMCID: PMC4113755  PMID: 25006857
fiber; whole grains; Dietary Guidelines for Americans; nutrient of public health concern
19.  MHC class II–dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies 
The Journal of Experimental Medicine  2013;210(13):2921-2937.
Antigen presentation, but not antibody secretion, by B cells drives CNS autoimmunity induced by immunization with human MOG.
Whether B cells serve as antigen-presenting cells (APCs) for activation of pathogenic T cells in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) is unclear. To evaluate their role as APCs, we engineered mice selectively deficient in MHC II on B cells (B–MHC II−/−), and to distinguish this function from antibody production, we created transgenic (Tg) mice that express the myelin oligodendrocyte glycoprotein (MOG)–specific B cell receptor (BCR; IgHMOG-mem) but cannot secrete antibodies. B–MHC II−/− mice were resistant to EAE induced by recombinant human MOG (rhMOG), a T cell– and B cell–dependent autoantigen, and exhibited diminished Th1 and Th17 responses, suggesting a role for B cell APC function. In comparison, selective B cell IL-6 deficiency reduced EAE susceptibility and Th17 responses alone. Administration of MOG-specific antibodies only partially restored EAE susceptibility in B–MHC II−/− mice. In the absence of antibodies, IgHMOG-mem mice, but not mice expressing a BCR of irrelevant specificity, were fully susceptible to acute rhMOG-induced EAE, also demonstrating the importance of BCR specificity. Spontaneous opticospinal EAE and meningeal follicle–like structures were observed in IgHMOG-mem mice crossed with MOG-specific TCR Tg mice. Thus, B cells provide a critical cellular function in pathogenesis of central nervous system autoimmunity independent of their humoral involvement, findings which may be relevant to B cell–targeted therapies.
PMCID: PMC3865476  PMID: 24323356
20.  Elevated blood pressure: Our family’s fault? The genetics of essential hypertension 
World Journal of Cardiology  2014;6(5):327-337.
AIM: To provide an updated review on current genetic aspects possibly affecting essential hypertension (EH), and to further elucidate their role in EH.
METHODS: We searched for genetic and epigenetic factors in major studies associated with EH between Jan 2008-Oct 2013 using PubMed. We limited our search to reviews that discussed mostly human studies, and were accessible through the university online resource. We found 11 genome wide association studies (GWAS), as well as five methylation and three miRNA studies that fit our search criteria. A distinction was not made between genes with protective effects or negative effects, as this article is only meant to be a summary of genes associated with any aspect of EH.
RESULTS: We found 130 genes from the studies that met our inclusion/exclusion criteria. Of note, genes with multiple study references include: STK39, CYP17A1, MTHFR-NPPA, MTHFR-NPPB, ATP2B1, CSK, ZNF652, UMOD, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, CSK-ULK3, CYP1A2, NT5C2, CYP171A, PLCD3, SH2B3, ATXN2, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, and HFE. The following genes overlapped between the genetic studies and epigenetic studies: WNK4 and BDKRB2. Several of the identified genes were found to have functions associated with EH. Many epigenetic factors were also correlated with EH. Of the epigenetic factors, there were no articles discussing siRNA and its effects on EH that met the search criteria, thus the topic was not included in this review. Among the miRNA targets found to be associated with EH, many of the genes involved were also identified in the GWAS studies.
CONCLUSION: Genetic hypertension risk algorithms could be developed in the future but may be of limited benefit due to the multi-factorial nature of EH. With emerging technologies, like next-generation sequencing, more direct causal relationships between genetic and epigenetic factors affecting EH will likely be discovered creating a tremendous potential for personalized medicine using pharmacogenomics.
PMCID: PMC4062117  PMID: 24944762
Essential hypertension; Epigenomics; Genome-wide association study; Genes; MicroRNAs
21.  Allogeneic Hematopoietic Cell Transplantation for Fanconi Anemia in Patients With Pretransplantation Cytogenetic Abnormalities, Myelodysplastic Syndrome, or Acute Leukemia 
Journal of Clinical Oncology  2013;31(13):1669-1676.
Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed.
Patients and Methods
We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007.
Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival.
Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.
PMCID: PMC3635221  PMID: 23547077
22.  Carbohydrates, Dietary Fiber, and Resistant Starch in White Vegetables: Links to Health Outcomes12 
Advances in Nutrition  2013;4(3):351S-355S.
Vegetables are universally promoted as healthy. Dietary Guidelines for Americans 2010 recommend that you make half of your plate fruits and vegetables. Vegetables are diverse plants that vary greatly in energy content and nutrients. Vegetables supply carbohydrates, dietary fiber, and resistant starch in the diet, all of which have been linked to positive health outcomes. Fiber lowers the incidence of cardiovascular disease and obesity. In this paper, the important role of white vegetables in the human diet is described, with a focus on the dietary fiber and resistant starch content of white vegetables. Misguided efforts to reduce consumption of white vegetables will lower intakes of dietary fiber and resistant starch, nutrients already in short supply in our diets.
PMCID: PMC3650507  PMID: 23674804
23.  White Potatoes, Human Health, and Dietary Guidance12 
Advances in Nutrition  2013;4(3):393S-401S.
The white potato is a concentrated source of carbohydrate, dietary fiber, and resistant starch and continues to be the staple food of choice for many cultures. The white potato is also a concentrated source of vitamin C and potassium. Two of the nutrients in white potatoes, dietary fiber and potassium, have been designated as nutrients of concern in the 2010 Dietary Guidelines for Americans. Potatoes are often maligned in nutrition circles because of their suspected link to obesity, and popular potato foods often contain more fat calories than carbohydrate calories. Some food guides do not include potatoes in the vegetable group because of their association with high-fat diets. However, potatoes should be included in the vegetable group because they contribute critical nutrients. All white vegetables, including white potatoes, provide nutrients needed in the diet and deserve a prominent position in food guides.
PMCID: PMC3650512  PMID: 23674809
24.  Clinical Outcomes of Patients with Desmoplastic Small Round Cell Tumor of the Peritoneum Undergoing Autologous HCT: a CIBMTR Retrospective Analysis 
Bone marrow transplantation  2012;47(11):1455-1458.
Desmoplastic small round cell tumor of the peritoneum (DSRCTP) is a rare, frequently fatal tumor. This retrospective study, based on CIBMTR registry data, describes the largest reported cohort of DSRCTP patients who have undergone autologous stem cell transplant (ASCT). The probabilities of disease-free survival (DFS) at one year for patients in complete remission (CR) and not in CR were 75% (95% confidence interval: 48–94%) and 35% (15–59%), respectively. The probability of overall survival (OS) at three years was 57% (29–83%) and 28% (9–51%) for patients in CR and not in CR respectively. Median survival for the entire cohort was 31 months (36 months and 21 months for those in CR and not in CR respectively). Engraftment at 42 days was 97% (88–100%). Treatment-related mortality was low, with only one death in the first 100 days. ASCT is a tolerable approach in patients with DSRCTP, with the greatest benefit seen in those patients who obtain CR. For those not in CR, the median OS in this series is greater than previously reported (21 months versus 17 months), suggesting ASCT is useful in prolonging DFS and OS, even in patients with residual or persistent disease pre transplant.
PMCID: PMC3951901  PMID: 22465977
Autologous; Transplant; Outcomes; Desmoplastic; Tumor
25.  Relationship between Trough Plasma and Epithelial Lining Fluid Concentrations of Voriconazole in Lung Transplant Recipients 
Trough (predose) voriconazole concentrations in plasma and pulmonary epithelial lining fluid (ELF) of lung transplant recipients receiving oral voriconazole preemptive treatment were determined. The mean (± standard deviation [SD]) ELF/plasma ratio was 12.5 ± 6.3. A strong positive linear relationship was noted between trough plasma and ELF voriconazole concentrations (r2 = 0.87), suggesting the feasibility of using trough plasma voriconazole concentration as a surrogate to estimate the corresponding concentration in ELF of lung transplant recipients.
PMCID: PMC3754345  PMID: 23817382

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