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1.  Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI 
Experimental neurology  2015;275(0 2):285-295.
Hypoxia ischemia (HI) of the brain in near-term and term infants is a leading cause of infant mortality and lifelong disability but current therapeutic approaches remain limited. Males consistently display greater vulnerability to the deleterious consequences of HI in both humans and animal models. Neurogenesis increases after neonatal HI and offers a potential therapeutic target for recovery. The steroid hormone estradiol has been extensively explored as a neuroprotectant in adult models of stroke but with mixed results. Less consideration has been afforded to this naturally occurring agent in the developing brain, which has unique challenges from the adult. Using a model of term HI in the rat we have explored the impact of this insult on cell genesis in the hippocampus of males and females and the ability of estradiol treatment immediately after insult to restore function. Both short-term (3 days) and long-term (7 days) post-injury were assessed and revealed that only females had markedly increased cell genesis on the short-term but both sexes were increased long-term. A battery of behavioral tests revealed motor impairment in males and compromised episodic memory while both sexes were modestly impaired in spatial memory. Juvenile social play was also depressed in both sexes after HI. Estradiol therapy improved behavioral performance in both sexes but did not reverse a deficit in hippocampal volume ipsilateral to the insult. Thus the effects of estradiol do not appear to be via cell death or proliferation but rather involve other components of neural functioning.
PMCID: PMC4688089  PMID: 26376217
hypoxia ischemia; sex differences; rat; estradiol; hippocampus; neurogenesis; neonatal
2.  Cost-effectiveness of Increasing Access to Contraception during the Zika Virus Outbreak, Puerto Rico, 2016 
Emerging Infectious Diseases  2017;23(1):74-82.
We modeled the potential cost-effectiveness of increasing access to contraception in Puerto Rico during a Zika virus outbreak. The intervention is projected to cost an additional $33.5 million in family planning services and is likely to be cost-saving for the healthcare system overall. It could reduce Zika virus–related costs by $65.2 million ($2.8 million from less Zika virus testing and monitoring and $62.3 million from avoided costs of Zika virus–associated microcephaly [ZAM]). The estimates are influenced by the contraception methods used, the frequency of ZAM, and the lifetime incremental cost of ZAM. Accounting for unwanted pregnancies that are prevented, irrespective of Zika virus infection, an additional $40.4 million in medical costs would be avoided through the intervention. Increasing contraceptive access for women who want to delay or avoid pregnancy in Puerto Rico during a Zika virus outbreak can substantially reduce the number of cases of ZAM and healthcare costs.
PMCID: PMC5176229  PMID: 27805547
contraception; unintended pregnancy; cost-effectiveness; cost-saving; Zika virus; outbreak; microcephaly; viruses; Puerto Rico; vector-borne infections
3.  Estimation of utility weights for human papilloma virus-related health states according to disease severity 
A cost-utility study of a human papilloma virus (HPV) vaccine requires that the utility weights for HPV-related health states (i.e., cervical intraepithelial neoplasia (CIN), cervical cancer, and condyloma) be evaluated. The aim of the present study was to determine the utility weights for HPV-related health states.
Hypothetical standardised health states related to HPV were developed based on patient education material and previous publications. To fully reflect disease progression from diagnosis to prognosis, each health state comprised four parts (diagnosis, symptoms, treatment, and progression and prognosis). Nine-hundred members from the Korean general population evaluated the HPV-related health states using a visual analogue scale (VAS) and a standard gamble (SG) approach, which were administered face-to-face via computer-assisted interview. The mean utility values were calculated for each HPV-related health state.
According to the VAS, the highest utility (0.73) was HPV-positive status, followed by condyloma (0.66), and CIN grade I (0.61). The lowest utility (0.18) was cervical cancer requiring chemotherapy without surgery, followed by cervical cancer requiring chemoradiation therapy (0.42). SG revealed that the highest utility (0.83) was HPV-positive status, followed by condyloma (0.78), and CIN grade I (0.77). The lowest utility (0.43) was cervical cancer requiring chemotherapy without surgery, followed by cervical cancer requiring chemoradiation therapy (0.60).
This study was based on a large sample derived from the general Korean population; therefore, the calculated utility weights might be useful for evaluating the economic benefit of cancer screening and HPV vaccination programs.
Electronic supplementary material
The online version of this article (doi:10.1186/s12955-016-0566-8) contains supplementary material, which is available to authorized users.
PMCID: PMC5126850  PMID: 27894347
Cervical cancer; Human papilloma virus; Visual analogue scale; Standard gamble
4.  BRENDA in 2017: new perspectives and new tools in BRENDA 
Nucleic Acids Research  2016;45(Database issue):D380-D388.
The BRENDA enzyme database ( has developed into the main enzyme and enzyme-ligand information system in its 30 years of existence. The information is manually extracted from primary literature and extended by text mining procedures, integration of external data and prediction algorithms. Approximately 3 million data from 83 000 enzymes and 137 000 literature references constitute the manually annotated core. Text mining procedures extend these data with information on occurrence, enzyme-disease relationships and kinetic data. Prediction algorithms contribute locations and genome annotations. External data and links complete the data with sequences and 3D structures. A total of 206 000 enzyme ligands provide functional and structural data. BRENDA offers a complex query tool engine allowing the users an efficient access to the data via different search methods and explorers. The new design of the BRENDA entry page and the enzyme summary pages improves the user access and the performance. New interactive and intuitive BRENDA pathway maps give an overview on biochemical processes and facilitate the visualization of enzyme, ligand and organism information in the biochemical context. SCOPe and CATH, databases for protein structure classification, are included. New online and video tutorials provide online training for the users. BRENDA is freely available for academic users.
PMCID: PMC5210646  PMID: 27924025
5.  Antiplatelet Agents Inhibit the Generation of Platelet-Derived Microparticles 
Platelet microparticles (PMPs) contribute to thrombogenesis but the effects of antiplatelet drugs on PMPs generation is undefined. The present study investigated the cellular events regulating PMPs shedding, testing in vitro platelet agonists and inhibitors. Platelet-rich plasma from healthy subjects was stimulated with arachidonic acid (AA), U46619, collagen type-I (10 and 1.5 μg/mL), epinephrine, ADP or TRAP-6 and pre-incubated with acetylsalicylic acid (ASA, 100 and 10 μmol/L), SQ-29,548, apyrase, PSB-0739, or eptifibatide. PMPs were detected by flow-cytometry using CD61 and annexin-V as fluorescent markers. Platelet agonists induced annexin V-positive PMPs shedding. The strongest response was to high concentration collagen. ADP-triggered PMPs shedding was dose-independent. ASA reduced PMPs induced by AA- (645, 347–2946 vs. 3061, 446–4901 PMPs/μL; median ad range, n = 9, P < 0.001), collagen 10 μg/mL (5317, 2027–15935 vs. 10252, 4187–46316 PMPs/μL; n = 13, P < 0.001), collagen 1.5 μg/mL (1078, 528–2820 vs. 1465, 582–5948 PMPs/μL; n = 21, P < 0.001) and TRAP-6 (2008, 1621–2495 vs. 2840, 2404–3031 PMPs/μL; n = 3, P < 0.01) but did not affect the response to epinephrine or ADP. The ADP scavenger apyrase reduced PMPs induced by U46619 (1256, 395–2908 vs. 3045, 1119–5494 PMPs/μL, n = 6, P < 0.05), collagen 1.5 μg/mL (1006, 780–1309 vs. 2422, 1839–3494 PMPs/μL, n = 3, P < 0.01) and TRAP-6 (904, 761–1224 vs. 2840, 2404–3031 PMPs/μL, n = 3, P < 0.01). The TP receptor antagonist SQ-29,548 and the P2Y12 receptor antagonist PSB-0739 markedly inhibited PMPs induced by low doses of collagen. Except for high-dose collagen, eptifibatide abolished agonist-induced PMPs release. Both TXA2 generation and ADP secretion are required as amplifiers of PMP shedding. The crucial role of the fibrinogen receptor and the collagen receptor in PMPs generation, independently of platelet aggregation, was identified.
PMCID: PMC5025445  PMID: 27695417
platelets; microparticles; thromboxane; ADP; collagen; fibrinogen receptor; collagen receptor
6.  Acute trauma induced disc displacement without reduction and its sequelae 
Scientific Reports  2016;6:32684.
Acute traumatic temporomandibular joint disc displacement (ATDD) and its sequelae are not familiar for most surgeons. This study is to discuss its sequelae in cases without disc reduction after failed conservative treatment. From 2010 to 2015, 26 patients with 34 joints were included in the study. All patients had at least 3 months conservative treatment. Their maximal incisor opening (MIO) was measured during follow-ups and MRI examination was used to check the condylar bone degeneration. The mean follow-up for conservative treatment after admission was 8.69 months, the patients reached an average of 25.7 mm MIO. MRI showed condylar bone intact in 8 joints (23.5%), condylar surface bone destruction (Wilks IV, V stages) in 14 joints (41.2%), and severe bone resorption in 12 joints (35.3%). 15 patients with 23 joints were asked for surgical treatment after a mean conservative treatment of 5.4 months (3–12 months) to improve mouth opening and relieve chronic pain. 12 joints had total joint replacement (TJR). 11 joints had disc repositioning. Their mean MIO before operation was 19.8 mm and significantly improved to 33.9 mm after operation (p = 0.0000). ATDD may cause severe osteoarthritis or ankylosis. Disc repositioning and TJR could significantly improve MIO.
PMCID: PMC5007667  PMID: 27582054
7.  icuARM-II: improving the reliability of personalized risk prediction in pediatric intensive care units 
Clinicians in intensive care units (ICUs) rely on standardized scores as risk prediction models to predict a patient’s vulnerability to life-threatening events. Conventional Current scales calculate scores from a fixed set of conditions collected within a specific time window. However, modern monitoring technologies generate complex, temporal, and multimodal patient data that conventional prediction models scales cannot fully utilize. Thus, a more sophisticated model is needed to tailor individual characteristics and incorporate multiple temporal modalities for a personalized risk prediction. Furthermore, most scales models focus on adult patients. To address this needdeficiency, we propose a newly designed ICU risk prediction system, called icuARM-II, using a large-scaled pediatric ICU database from Children’s Healthcare of Atlanta. This novel database contains clinical data collected in 5,739 ICU visits from 4,975 patients. We propose a temporal association rule mining framework giving clinicians a potential to perform predict risks prediction based on all available patient conditions without being restricted by a fixed observation window. We also develop a new metric that can rigidly assesses the reliability of all all generated association rules. In addition, the icuARM-II features an interactive user interface. Using the icuARM-II, our results demonstrated showed a use case of short-term mortality prediction using lab testing results, which demonstrated a potential new solution for reliable ICU risk prediction using personalized clinical data in a previously neglected population.
PMCID: PMC4983419  PMID: 27532061
8.  The effects of trunk stabilization exercise using a Swiss ball in the absence of visual stimulus on balance in the elderly 
Journal of Physical Therapy Science  2016;28(7):2144-2147.
[Purpose] This study was undertaken to investigate the effects of the balance exercises with a Swiss ball on static and dynamic balance abilities in elderly (≥65 years) subjects. [Subjects and Methods] Twenty elderly subjects with no relevant orthopedic history of a back condition were selected for trunk stabilization exercises with a Swiss ball (Thera-Band, USA). The subjects performed these trunk stabilization exercises for 20 minutes, five times per week for 4 weeks. The experimental group (n=10) was blindfolded during these balance exercises, while the control group control group (n=10) was not. [Results] The experimental group showed significant improvements in velocity in the evaluation of static balance and in time, total distance, and left/right movement distance in the evaluation of dynamic balance after the intervention, whereas the control group showed significant improvements in time in the evaluation of dynamic balance. A significant intergroup difference was observed after the intervention for velocity gain. [Conclusion] Exercising with a blindfold stimulates other senses by blocking visual information, and hence it enhances improvements in balance ability.
PMCID: PMC4968524  PMID: 27512284
Trunk stabilization; Balance; Elderly
9.  The regulation of hematopoietic stem cell populations 
F1000Research  2016;5:F1000 Faculty Rev-1524.
Evidence presented over the last few years indicates that the hematopoietic stem cell (HSC) compartment comprises not just one but a number of different cell populations. Based on HSCs’ proliferation and engraftment potential, it has been suggested that there are two classes of HSC, with long- and short-term engraftment potential. HSC heterogeneity seems to involve differentiation capacities as well, since it has been shown that some HSC clones are able to give rise to both myeloid and lymphoid progeny, whereas others are lymphoid deficient. It has been recognized that HSC function depends on intrinsic cell regulators, which are modulated by external signals. Among the former, we can include transcription factors and non-coding RNAs as well as epigenetic modifiers. Among the latter, cytokines and extracellular matrix molecules have been implicated. Understanding the elements and mechanisms that regulate HSC populations is of significant relevance both in biological and in clinical terms, and research in this area still has to face several complex and exciting challenges.
PMCID: PMC4926728  PMID: 27408695
hematopoietic progenitor cells; precursor cells; hematopoietic stem cell niche
10.  Transcriptional Activity of rRNA Genes in Barley Cells after Mutagenic Treatment 
PLoS ONE  2016;11(6):e0156865.
In the present study, the combination of the micronucleus test with analysis of the activity of the rRNA genes in mutagen-treated Hordeum vulgare (barley) by maleic hydrazide (MH) cells was performed. Simultaneously fluorescence in situ hybridization (FISH) with 25S rDNA as probes and an analysis of the transcriptional activity of 35S rRNA genes with silver staining were performed. The results showed that transcriptional activity is always maintained in the micronuclei although they are eliminated during the next cell cycle. The analysis of the transcriptional activity was extended to barley nuclei. MH influenced the fusion of the nucleoli in barley nuclei. The silver staining enabled detection of the nuclear bodies which arose after MH treatment. The results confirmed the usefulness of cytogenetic techniques in the characterization of micronuclei. Similar analyses can be now extended to other abiotic stresses to study the response of plant cells to the environment.
PMCID: PMC4892555  PMID: 27257817
12.  Human serum antibodies against EBV latent membrane protein 1 cross-react with α-synuclein 
To identify the epitope on α-synuclein (α-syn) to which antibodies against the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) bind and to determine whether antibodies targeting this mimicry domain are present in human sera.
Reactivity of the α-syn-cross-reacting anti-LMP1 monoclonal antibody CS1-4 to a synthetic peptide containing the putative mimicry domain was compared to those in which this domain was mutated and to murine and rat α-syn (which differ from human α-syn at this site) in Western blots. Using ELISA, sera from EBV+ (n = 4) and EBV− (n = 12) donors as well as those with infectious mononucleosis (IM; n = 120), and Hodgkin disease (HD; n = 33) were interrogated for antibody reactivity to synthetic peptides corresponding to regions of α-syn and LMP1 containing the mimicry domain.
CS1-4 showed strong reactivity to wild-type human α-syn, but not to the mutant peptides or rodent α-syn. Control EBV− and EBV+ sera showed no reactivity to α-syn or LMP1 peptides. However, a significant proportion of IM and HD sera contained immunoglobulin M (IgM) (59% and 70%, in IM and HD, respectively), immunoglobulin G (IgG) (40% and 48%), and immunoglobulin A (IgA) (28% and 36%) antibodies to both peptides, as well as a significant correlation in the titers of IgM (ρ = 0.606 and 0.664, for IM and HD, respectively), IgG (0.526 and 0.836), and IgA (0.569 and 0.728) antibodies targeting LMP1 and α-syn peptides.
Anti-EBV-LMP1 antibodies cross-reacting with a defined epitope in α-syn are present in human patients. These findings may have implications for the pathogenesis of synucleinopathies.
PMCID: PMC4864620  PMID: 27218119
13.  Sex Differences and Correlates of Pain in Patients with Comorbid Obesity and Binge Eating Disorder 
Sex differences and correlates of pain were examined in a sample of patients with comorbid binge eating disorder (BED) and obesity. One hundred fifty-two treatment-seeking patients with BED completed the Brief Pain Inventory. Analysis of covariance was utilized to compare women and men on pain, and correlational analysis, overall and by sex, was performed to examine relationships among pain, eating behaviour and metabolic risk factors. Women reported significantly greater pain severity and pain interference than men. Among women, eating behaviour and metabolic markers were not associated with pain. Among men, however, binge frequency was significantly associated with pain, as was high-density lipoprotein cholesterol and fasting glucose. In sum, while women in this sample had more pain than men, the presence of pain in men was associated with increased behavioural and metabolic risk factors. Findings have clinical implications for the assessment of comorbid pain and obesity-related health risks among individuals with BED.
PMCID: PMC4821688  PMID: 26841114
binge eating disorder; eating disorders; obesity; pain; sex differences
14.  Direct interaction of avermectin with epidermal growth factor receptor mediates the penetration resistance in Drosophila larvae 
Open Biology  2016;6(4):150231.
With the widespread use of avermectins (AVMs) for managing parasitic and agricultural pests, the resistance of worms and insects to AVMs has emerged as a serious threat to human health and agriculture worldwide. The reduced penetration of AVMs is one of the main reasons for the development of the resistance to the chemicals. However, the detailed molecular mechanisms remain elusive. Here, we use the larvae of Drosophila melanogaster as the model organism to explore the molecular mechanisms underlying the development of penetration resistance to AVMs. We clearly show that the chitin layer is thickened and the efflux transporter P-glycoprotein (P-gp) is overexpressed in the AVM-resistant larvae epidermis. We reveal that the activation of the transcription factor Relish by the over-activated epidermal growth factor receptor (EGFR)/AKT/ERK pathway induces the overexpression of the chitin synthases DmeCHS1/2 and P-gp in the resistant larvae. Interestingly, we discover for the first time, to the best of our knowledge, that AVM directly interacts with EGFR and leads to the activation of the EGFR/AKT/ERK pathway, which activates the transcription factor Relish and induces the overexpression of DmeCHS1/2 and P-gp. These findings provide new insights into the molecular mechanisms underlying the development of penetration resistance to drugs.
PMCID: PMC4852453  PMID: 27249340
avermectin; penetration resistance; DmeCHS1/2; EGFR; Drosophila melanogaster larvae
15.  Limited Trabecular Bone Density Heterogeneity in the Human Skeleton 
Anatomy Research International  2016;2016:9295383.
There is evidence for variation in trabecular bone density and volume within an individual skeleton, albeit in a few anatomical sites, which is partly dependent on mechanical loading. However, little is known regarding the basic variation in trabecular bone density throughout the skeleton in healthy human adults. This is because research on bone density has been confined to a few skeletal elements, which can be readily measured using available imaging technology particularly in clinical settings. This study comprehensively investigates the distribution of trabecular bone density within the human skeleton in nine skeletal sites (femur, proximal and distal tibia, third metatarsal, humerus, ulna, radius, third metacarpal, and axis) in a sample of N = 20 individuals (11 males and 9 females). pQCT results showed that the proximal ulna (mean = 231.3 mg/cm3) and axis vertebra (mean = 234.3 mg/cm3) displayed significantly greater (p < 0.01) trabecular bone density than other elements, whereas there was no significant variation among the rest of the elements (p > 0.01). The homogeneity of the majority of elements suggests that these sites are potentially responsive to site-specific genetic factors. Secondly, the lack of correlation between elements (p > 0.05) suggests that density measurements of one anatomical region are not necessarily accurate measures of other anatomical regions.
PMCID: PMC4842361  PMID: 27148458
16.  Breastfeeding and Postpartum Depression: An Overview and Methodological Recommendations for Future Research 
Emerging research suggests that a relationship exists between breastfeeding and postpartum depression; however, the direction and precise nature of this relationship are not yet clear. The purpose of this paper is to provide an overview of the relationship between breastfeeding and postpartum depression as it has been examined in the empirical literature. Also, the potential mechanisms of action that have been implicated in this relationship are also explored. PubMed and PsycINFO were searched using the keywords: breastfeeding with postpartum depression, perinatal depression, postnatal depression. Results of this search showed that researchers have examined this relationship in diverse ways using diverse methodology. In particular, researchers have examined the relationships between postpartum depression and breastfeeding intention, initiation, duration, and dose. Due to a number of methodological differences among past studies we make some recommendations for future research that will better facilitate an integration of findings. Future research should (1) use standardized assessment protocols; (2) confirm diagnosis through established clinical interview when possible; (3) provide a clear operationalized definition for breastfeeding variables; (4) clearly define the postpartum period interval assessed and time frame for onset of symptoms; (5) be prospective or longitudinal in nature; and (6) take into consideration other potential risk factors identified in the empirical literature.
PMCID: PMC4842365  PMID: 27148457
17.  Reduced-Rank Spatio-Temporal Modeling of Air Pollution Concentrations in the Multi-Ethnic Study of Atherosclerosis and Air Pollution1 
The annals of applied statistics  2014;8(4):2509-2537.
There is growing evidence in the epidemiologic literature of the relationship between air pollution and adverse health outcomes. Prediction of individual air pollution exposure in the Environmental Protection Agency (EPA) funded Multi-Ethnic Study of Atheroscelerosis and Air Pollution (MESA Air) study relies on a flexible spatio-temporal prediction model that integrates land-use regression with kriging to account for spatial dependence in pollutant concentrations. Temporal variability is captured using temporal trends estimated via modified singular value decomposition and temporally varying spatial residuals. This model utilizes monitoring data from existing regulatory networks and supplementary MESA Air monitoring data to predict concentrations for individual cohort members.
In general, spatio-temporal models are limited in their efficacy for large data sets due to computational intractability. We develop reduced-rank versions of the MESA Air spatio-temporal model. To do so, we apply low-rank kriging to account for spatial variation in the mean process and discuss the limitations of this approach. As an alternative, we represent spatial variation using thin plate regression splines. We compare the performance of the outlined models using EPA and MESA Air monitoring data for predicting concentrations of oxides of nitrogen (NOx)—a pollutant of primary interest in MESA Air—in the Los Angeles metropolitan area via cross-validated R2.
Our findings suggest that use of reduced-rank models can improve computational efficiency in certain cases. Low-rank kriging and thin plate regression splines were competitive across the formulations considered, although TPRS appeared to be more robust in some settings.
PMCID: PMC4803447  PMID: 27014398
Spatiotemporal modeling; reduced-rank; air pollution; kriging; thin plate splines
18.  Nuclear mechanotransduction: Forcing the nucleus to respond 
Nucleus  2015;6(1):19-22.
Cell phenotype and fate are driven by the mechanical properties of their surrounding environment. Changes in matrix rigidity or application of force have been shown to impact profoundly cell behavior and phenotype, demonstrating that the molecular mechanisms which “sense” and transduce these signals into biochemical pathways are central in cell biology. In this commentary, we discuss recent evidence showing that mechanotransduction mechanisms occur in the nucleus, allowing dynamic regulation of the nucleoskeleton in response to mechanical stress. We will review this nucleoskeletal response and its impact on both nuclear structure and function.
PMCID: PMC4615784  PMID: 25738642
nucleoskeleton, nuclear lamins, emerin, nesprin, mechanotransduction
19.  Brain tumour differentiation: rapid stratified serum diagnostics via attenuated total reflection Fourier-transform infrared spectroscopy 
Journal of Neuro-Oncology  2016;127:463-472.
The ability to diagnose cancer rapidly with high sensitivity and specificity is essential to exploit advances in new treatments to lead significant reductions in mortality and morbidity. Current cancer diagnostic tests observing tissue architecture and specific protein expression for specific cancers suffer from inter-observer variability, poor detection rates and occur when the patient is symptomatic. A new method for the detection of cancer using 1 μl of human serum, attenuated total reflection—Fourier transform infrared spectroscopy and pattern recognition algorithms is reported using a 433 patient dataset (3897 spectra). To the best of our knowledge, we present the largest study on serum mid-infrared spectroscopy for cancer research. We achieve optimum sensitivities and specificities using a Radial Basis Function Support Vector Machine of between 80.0 and 100 % for all strata and identify the major spectral features, hence biochemical components, responsible for the discrimination within each stratum. We assess feature fed-SVM analysis for our cancer versus non-cancer model and achieve 91.5 and 83.0 % sensitivity and specificity respectively. We demonstrate the use of infrared light to provide a spectral signature from human serum to detect, for the first time, cancer versus non-cancer, metastatic cancer versus organ confined, brain cancer severity and the organ of origin of metastatic disease from the same sample enabling stratified diagnostics depending upon the clinical question asked.
Electronic supplementary material
The online version of this article (doi:10.1007/s11060-016-2060-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4835510  PMID: 26874961
ATR-FTIR; Serum; Diagnostics; Cancer; Glioma; Spectroscopy; Rapid
20.  Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model 
PLoS ONE  2016;11(2):e0147778.
Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD).
We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms.
The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR.
Low-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-γ) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly.
Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes effectively the balance of Th1/Th2 immunity and then attenuates allergic inflammatory responses significantly, as well as optimizes the structure of intestinal microbiota, which suggests potential for novel preventive and therapeutic intervention.
PMCID: PMC4752249  PMID: 26872019
21.  Persian version of frontal assessment battery: Correlations with formal measures of executive functioning and providing normative data for Persian population 
Iranian Journal of Neurology  2016;15(1):16-22.
Background: Cognitive impairment in patients with Parkinson’s disease (PD) mainly involves executive function (EF). The frontal assessment battery (FAB) is an efficient tool for the assessment of EFs. The aims of this study were to determine the validity and reliability of the psychometric properties of the Persian version of FAB and assess its correlation with formal measures of EFs to provide normative data for the Persian version of FAB in patients with PD.
Methods: The study recruited 149 healthy participants and 49 patients with idiopathic PD. In PD patients, FAB results were compared to their performance on EF tests. Reliability analysis involved test-retest reliability and internal consistency, whereas validity analysis involved convergent validity approach. FAB scores compared in normal controls and in PD patients matched for age, education, and Mini-Mental State Examination (MMSE) score.
Results: In PD patients, FAB scores were significantly decreased compared to normal controls, and correlated with Stroop test and Wisconsin Card Sorting Test (WCST). In healthy subjects, FAB scores varied according to the age, education, and MMSE. In the FAB subtest analysis, the performances of PD patients were worse than the healthy participants on similarities, fluency tasks, and Luria’s motor series.
Conclusion: Persian version of FAB could be used as a reliable scale for the assessment of frontal lobe functions in Iranian patients with PD. Furthermore, normative data provided for the Persian version of this test improve the accuracy and confidence in the clinical application of the FAB.
PMCID: PMC4852066  PMID: 27141272
Frontal Lobe; Executive Function; Outcome and Process Assessment; Mental Status; Persian; Iran
22.  Adult Body Height Is a Good Predictor of Different Dimensions of Cognitive Function in Aged Individuals: A Cross-Sectional Study 
Background: Adult height, weight, and adiposity measures have been suggested by some studies to be predictors of depression, cognitive impairment, and dementia. However, the presence of confounding factors and the lack of a thorough neuropsychological evaluation in many of these studies have precluded a definitive conclusion about the influence of anthropometric measures in cognition and depression. In this study we aimed to assess the value of height, weight, and abdominal perimeter to predict cognitive impairment and depressive symptoms in aged individuals.
Methods and Findings: Cross-sectional study performed between 2010 and 2012 in the Portuguese general community. A total of 1050 participants were included in the study and randomly selected from local area health authority registries. The cohort was representative of the general Portuguese population with respect to age (above 50 years of age) and gender. Cognitive function was assessed using a battery of tests grouped in two dimensions: general executive function and memory. Two-step hierarchical multiple linear regression models were conducted to determine the predictive value of anthropometric measures in cognitive performance and mood before and after correction for possible confounding factors (gender, age, school years, physical activity, alcohol consumption, and smoking habits). We found single associations of weight, height, body mass index, abdominal perimeter, and age with executive function, memory and depressive symptoms. However, when included in a predictive model adjusted for gender, age, school years, and lifestyle factors only height prevailed as a significant predictor of general executive function (β = 0.139; p < 0.001) and memory (β = 0.099; p < 0.05). No relation was found between mood and any of the anthropometric measures studied.
Conclusions and Relevance: Height is an independent predictor of cognitive function in late-life and its effects on the general and executive function and memory are independent of age, weight, education level, gender, and lifestyle factors. Altogether, our data suggests that modulators of adult height during childhood may irreversibly contribute to cognitive function in adult life and that height should be used in models to predict cognitive performance.
PMCID: PMC5025434  PMID: 27695413
height; weight; cognition; mood; aging; community
23.  Functional Equivalence of Imagined vs. Real Performance of an Inhibitory Task: An EEG/ERP Study 
Early neuroimaging and electrophysiological studies suggested that motor imagery recruited a different network than motor execution. However, several studies have provided evidence for the involvement of the same circuits in motor imagery tasks, in the absence of overt responses. The present study aimed to test whether imagined performance of a stop-signal task produces a similar pattern of motor-related EEG activity than that observed during real performance. To this end, mu and beta event-related desynchronization (ERD) and the Lateralized Readiness Potential (LRP) were analyzed. The study also aimed to clarify the functional significance of the Stop-N2 and Stop-P3 event-related potential (ERPs) components, which were also obtained during both real and imagined performance. The results showed a common pattern of brain electrical activity, and with a similar time course, during covert performance and overt execution of the stop-signal task: presence of LRP and Stop-P3 in the imagined condition and identical LRP onset, and similar mu and beta ERD temporal windows for both conditions. These findings suggest that a similar inhibitory network may be activated during both overt and covert execution of the task. Therefore, motor imagery may be useful to improve inhibitory skills and to develop new communicating systems for Brain-Computer Interface (BCI) devices based on inhibitory signals.
PMCID: PMC5025452  PMID: 27695410
functional equivalence; inhibition; stop-signal task; motor imagery; ERPs; time-frequency EEG analyses
24.  Genome-Wide Identification, Evolution, and Co-expression Network Analysis of Mitogen-Activated Protein Kinase Kinase Kinases in Brachypodium distachyon 
Mitogen-activated protein kinase (MAPK) cascades are the conserved and universal signal transduction modules in all eukaryotes, which play the vital roles in plant growth, development, and in response to multiple stresses. In this study, we used bioinformatics methods to identify 86 MAPKKK protein encoded by 73 MAPKKK genes in Brachypodium. Phylogenetic analysis of MAPKKK family from Arabidopsis, rice, and Brachypodium has classified them into three subfamilies, of which 28 belonged to MEKK, 52 to Raf, and 6 to ZIK subfamily, respectively. Conserved protein motif, exon-intron organization, and splicing intron phase in kinase domains supported the evolutionary relationships inferred from the phylogenetic analysis. And gene duplication analysis suggested the chromosomal segment duplication happened before the divergence of the rice and Brachypodium, while all of three tandem duplicated gene pairs happened after their divergence. We further demonstrated that the MAPKKKs have evolved under strong purifying selection, implying the conservation of them. The splicing transcripts expression analysis showed that the splicesome translating longest protein tended to be adopted. Furthermore, the expression analysis of BdMAPKKKs in different organs and development stages as well as heat, virus and drought stresses revealed that the MAPKKK genes were involved in various signaling pathways. And the circadian analysis suggested there were 41 MAPKKK genes in Brachypodium showing cycled expression in at least one condition, of which seven MAPKKK genes expressed in all conditions and the promoter analysis indicated these genes possessed many cis-acting regulatory elements involved in circadian and light response. Finally, the co-expression network of MAPK, MAPKK, and MAPKKK in Brachypodium was constructed using 144 microarray and RNA-seq datasets, and ten potential MAPK cascades pathway were predicted. To conclude, our study provided the important information for evolutionary and functional characterization of MAPKKK family in Brachypodium, which will facilitate the functional analysis of BdMAPKKK genes, and also will facilitate better understanding the MAPK signal pathway in Brachypodium and beyond.
PMCID: PMC5025453  PMID: 27695474
Brachypodium distachyon; co-expression network; expression profiles; MAPKKK family; MAPK cascades; signal pathway
25.  Allergic Fungal Sinusitis 
Head and Neck Pathology  2014;9(4):488-491.
A 42 year old male presents with worsening pain and an increase in thick chronic drainage of the left sinus. Image studies show complete opacification of the left frontal sinus, left sphenoid sinus, and the left maxillary sinus. The patient was taken to the operating room and tissue for microscopic evaluation was obtained. The microscopic findings were classic for allergic fungal sinusitis: areas of alternating mucinous material and inflammatory cell debris and abundant Charcot–Leyden crystals. Cultures were performed and the patient began steroid therapy and desensitization therapy.
PMCID: PMC4651931  PMID: 25537829
Tide lines; Congestion; Sinus drainage; Desensitization therapy

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