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author:("haida, A.")
1.  Potential Inhibitory Effects of l-Carnitine Supplementation on Tissue Advanced Glycation End Products in Patients with Hemodialysis 
Rejuvenation Research  2013;16(6):460-466.
Background and Aims: Advanced glycation end products (AGEs) contribute to cardiovascular disease in patients with hemodialysis (HD). We have recently found that carnitine levels are inversely associated with skin AGE levels in HD patients. We examined whether l-carnitine supplementation reduced skin AGE levels in HD patients with carnitine deficiency.
Methods: This was a single-center study. One hundred and two HD patients (total carnitine levels <50 μmol/L) were enrolled and randomized to either oral administration of l-carnitine (900 mg/day) (n=51) or control (n=51). After 6 months, metabolic and inflammatory variables, including serum levels of carnitine, were measured. Skin AGE levels were determined by evaluating skin auto-fluorescence with an AGE-reader.
Results: There were no significant differences of clinical variables at baseline between the control and l-carnitine therapy group. Thirty-two patients did not complete the assessment or treatment of the study. Oral l-carnitine supplementation for 6 months significantly increased low-density lipoprotein cholesterol (LDL-C), triglycerides, total, free, and acyl carnitine levels, while it decreased alanine transaminase, acyl/free carnitine ratio, β2-microglobulin, and skin AGE values. Change in total carnitine values from baseline (Δtotal carnitine) and Δfree carnitine were inversely associated with Δskin AGE levels in l-carnitine-treated patients (p=0.036 and p=0.016, respectively). In multiple regression analysis, Δfree carnitine was a sole independent determinant of Δskin AGEs (R2=0.178).
Conclusions: The present study demonstrated that oral l-carnitine supplementation significantly decreased skin AGE levels in HD patients with carnitine deficiency. These observations suggest that supplementation of l-carnitine might be a novel therapeutic strategy for preventing the accumulation of tissue AGEs in carnitine-deficient patients with HD.
PMCID: PMC3869449  PMID: 23909402
2.  HIV-infected women on antiretroviral treatment in Uganda have increased mortality during pregnant and postpartum periods 
AIDS (London, England)  2013;27(0 1):S105-S112.
To assess the impact of pregnancy on mortality among HIV-infected Ugandan women initiating antiretroviral therapy (ART).
Prospective cohort study.
HIV-infected women initiating ART in the Uganda AIDS Rural Treatment Outcomes study were assessed quarterly for self-reported pregnancy. The association between pregnant/postpartum (“pregnancy-related”) follow-up periods and mortality was assessed with Cox proportional hazards models adjusted for age, CD4 cell count, plasma HIV-1 RNA levels, and ART duration.
354 women with median age 33 years (IQR: 27-37) and CD4 142 cells/mm3 (IQR: 82-213) were followed for a median of 4.0 years (IQR: 2.5-4.8) after ART initiation, with 3% and 6% loss-to-follow-up at years 1 and 3. 109 women experienced pregnancy. Five deaths occurred during pregnancy-related follow-up and 16 during non-pregnancy-related follow-up, for crude mortality rates during the first year after ART initiation of 12.57/100 PYs and 3.53/100 PYs (Rate Ratio 3.56, 95% CI: 0.97-11.07). In adjusted models, the impact of pregnancy-related follow-up on mortality was highest at ART initiation (aHR: 21.48, 95% CI: 3.73 - 123.51), decreasing to 13.44 (95% CI 3.28 – 55.11) after 4 months, 8.28 (95% CI 2.38 – 28.88) after 8 months, 5.18 (95% CI: 1.36 - 19.71) after one year, and 1.25 (95% CI: 0.10 - 15.58) after two years on ART. Four of five maternal deaths occurred postpartum.
Pregnancy and the postpartum period were associated with increased mortality in HIV-infected women initiating ART, particularly during early ART. Contraception proximate to ART initiation, earlier ART initiation, and careful monitoring during the postpartum period may reduce maternal mortality in this setting.
PMCID: PMC4142689  PMID: 24088676
HIV; maternal health; maternal mortality; immune reconstitution; pregnancy; postpartum; antiretroviral therapy; mortality; Africa; women
3.  Should major depressive disorder with mixed features be classified as a bipolar disorder? 
Shanghai Archives of Psychiatry  2014;26(5):294-296.
The new diagnostic category in the Depressive Disorders chapter of DSM-5 entitled ‘Major Depressive Disorder With Mixed Features’ is applied to individuals who meet criteria for Major Depressive Disorder and have concurrent subsyndromal hypomanic or manic symptoms. But the operational definition of this new specifier is much closer to that of hypomania and mania than to the definition of atypical depression or the older ‘mixed depression.’ Moreover, multiple studies have shown that the characteristics of individuals with this condition and the clinical trajectory of their illness is much closer to that of bipolar patients than to that of depressed individuals without comorbid hypomanic or manic symptoms. Thus we believe that this condition would be more appropriately placed in the Bipolar Disorders chapter of DSM-5. We also believe that this blurring of the depressive disorder- bipolar disorder boundary is one cause for the low inter-rater reliability in the diagnosis of Major Depressive Disorder.
PMCID: PMC4248262  PMID: 25477723
major depressive disorder; depression with mixed features; mixed depression; bipolar disorder; DSM-5
4.  Antiretroviral Therapy Helps HIV-Positive Women Navigate Social Expectations for and Clinical Recommendations against Childbearing in Uganda 
AIDS Research and Treatment  2014;2014:626120.
Understanding factors that influence pregnancy decision-making and experiences among HIV-positive women is important for developing integrated reproductive health and HIV services. Few studies have examined HIV-positive women's navigation through the social and clinical factors that shape experiences of pregnancy in the context of access to antiretroviral therapy (ART). We conducted 25 semistructured interviews with HIV-positive, pregnant women receiving ART in Mbarara, Uganda in 2011 to explore how access to ART shapes pregnancy experiences. Main themes included: (1) clinical counselling about pregnancy is often dissuasive but focuses on the importance of ART adherence once pregnant; (2) accordingly, women demonstrate knowledge about the role of ART adherence in maintaining maternal health and reducing risks of perinatal HIV transmission; (3) this knowledge contributes to personal optimism about pregnancy and childbearing in the context of HIV; and (4) knowledge about and adherence to ART creates opportunities for HIV-positive women to manage normative community and social expectations of childbearing. Access to ART and knowledge of the accompanying lowered risks of mortality, morbidity, and HIV transmission improved experiences of pregnancy and empowered HIV-positive women to discretely manage conflicting social expectations and clinical recommendations regarding childbearing.
PMCID: PMC4189848  PMID: 25328693
5.  DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy 
Diabetes  2013;62(9):3241-3250.
Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We screened DNA aptamer directed against AGEs (AGEs-aptamer) in vitro and examined its effects on renal injury in KKAy/Ta mice, an animal model of type 2 diabetes. Eight-week-old male KKAy/Ta or C57BL/6J mice received continuous intraperitoneal infusion of AGEs- or control-aptamer for 8 weeks. AGEs-aptamer was detected and its level was increased in the kidney for at least 7 days. The elimination half-lives of AGEs-aptamer in the kidney were about 7 days. Compared with those in C57BL/6J mice, glomerular AGEs levels were significantly increased in KKAy/Ta mice, which were blocked by AGEs-aptamer. Urinary albumin and 8-hydroxy-2′-deoxy-guanosine levels were increased, and glomerular hypertrophy and enhanced extracellular matrix accumulation were observed in KKAy/Ta mice, all of which were prevented by AGEs-aptamer. Moreover, AGEs-aptamer significantly reduced gene expression of RAGE, monocyte chemoattractant protein-1, connective tissue growth factor, and type IV collagen both in the kidney of KKAy/Ta mice and in AGE-exposed human cultured mesangial cells. Our present data suggest that continuous administration of AGEs-aptamer could protect against experimental diabetic nephropathy by blocking the AGEs-RAGE axis and may be a feasible and promising therapeutic strategy for the treatment of diabetic nephropathy.
PMCID: PMC3749365  PMID: 23630304
7.  C-terminals in the mouse branchiomotor nuclei originate from the magnocellular reticular formation 
Neuroscience letters  2013;548:137-142.
Large cholinergic synaptic boutons called "C-terminals" contact motoneurons and regulate their excitability. C-terminals in the spinal somatic motor nuclei originate from cholinergic interneurons in laminae VII and X that express a transcription factor Pitx2. Cranial motor nuclei contain another type of motoneuron: branchiomotor neurons. Although branchiomotor neurons receive abundant C-terminal projections, the neural source of these C-terminals remains unknown. In the present study, we first examined whether cholinergic neurons express Pitx2 in the reticular formation of the adult mouse brainstem, as in the spinal cord. Although Pitx2-positive cholinergic neurons were observed in the magnocellular reticular formation and region around the central canal in the caudal medulla, none was present more rostrally in the brainstem tegmentum. We next explored the origin of C-terminals in the branchiomotor nuclei by using biotinylated dextran amine (BDA). BDA injections into the magnocellular reticular formation of the medulla and pons resulted in the labeling of numerous C-terminals in the branchiomotor nuclei: the ambiguous, facial, and trigeminal motor nuclei. Our results revealed that the origins of C-terminals in the branchiomotor nuclei are cholinergic neurons in the magnocellular reticular formation not only in the caudal medulla, but also at more rostral levels of the brainstem, which lacks Pitx2-positive neurons.
PMCID: PMC3776024  PMID: 23756176
C-terminals; branchiomotor neurons; cholinergic neurons; reticular formation; brainstem
8.  Advances in neuroimaging research of schizophrenia in China 
Shanghai Archives of Psychiatry  2014;26(4):181-193.
Since Hounsfield’s first report about X-ray computed tomography (CT) in 1972, there has been substantial progress in the application of neuroimaging techniques to study the structure, function, and biochemistry of the brain. This review provides a summary of recent research in structural and functional neuroimaging of schizophrenia in China and four tables describing all of the relevant studies from mainland China. The first research report using neuroimaging techniques in China dates back to 1983, a study that reported encephalatrophy in 30% of individuals with schizophrenia. Functional neuroimaging research in China emerged in the 1990s and has undergone rapid development since. Recently, structural and functional brain networks has become a hot topic among China’s neuroimaging researchers.
PMCID: PMC4194001  PMID: 25317005
schizophrenia; magnetic resonance imaging; magnetic resonance spectroscopy; diffusion tensorimaging; China
9.  Granulocyte-Macrophage Colony-Stimulating Factor Auto-Antibodies: A Marker of Aggressive Crohn’s Disease 
Inflammatory bowel diseases  2013;19(8):1671-1680.
Background & Aims
Neutralizing auto-antibodies (Ab) against granulocyte-macrophage colony-stimulating factor (GM-CSF Ab) have been associated with stricturing ileal Crohn’s disease (CD) in a largely pediatric patient cohort (total 394, adult CD 57). The aim of this study was to examine this association in two independent predominantly adult inflammatory bowel disease patient cohorts.
Serum samples from 745 subjects from the NIDDK IBD Genetics Consortium and 737 patients from Australia were analyzed for GM-CSF Ab and genetic markers. We conducted multiple regression analysis with backwards elimination to assess the contribution of GM-CSF Ab levels, established CD risk alleles and smoking on ileal disease location in the 477 combined CD subjects from both cohorts. We also determined associations of GM-CSF Ab levels with complications requiring surgical intervention in combined CD subjects in both cohorts.
Serum samples from CD patients expressed significantly higher concentrations of GM-CSF Ab when compared to Ulcerative Colitis or controls in each cohort. Non-smokers with ileal CD expressed significantly higher GM-CSF Ab concentrations in the Australian cohort (p= 0.002). Elevated GM-CSF Ab, ileal disease location and disease duration greater than 3 years were independently associated with stricturing/penetrating behavior and intestinal resection for CD.
The expression of high GM-CSF Ab is a risk marker for aggressive CD behavior and complications including surgery. Modifying factors include environmental exposure to smoking and genetic risk markers.
PMCID: PMC3707315  PMID: 23749272
Inflammatory bowel disease; granulocyte-macrophage colony-stimulating factor antibody; Crohn’s Disease, smoking
10.  Effects of Chk1 inhibition on the temporal duration of radiation-induced G2 arrest in HeLa cells 
Journal of Radiation Research  2014;55(5):1021-1027.
Chk1 inhibitor acts as a potent radiosensitizer in p53-deficient tumor cells by abrogating the G2/M checkpoint. However, the effects of Chk1 inhibitor on the duration of G2 arrest have not been precisely analyzed. To address this issue, we utilized a cell-cycle visualization system, fluorescent ubiquitination-based cell-cycle indicator (Fucci), to analyze the change in the first green phase duration (FGPD) after irradiation. In the Fucci system, G1 and S/G2/M cells emit red and green fluorescence, respectively; therefore, G2 arrest is reflected by an elongated FGPD. The system also allowed us to differentially analyze cells that received irradiation in the red or green phase. Cells irradiated in the green phase exhibited a significantly elongated FGPD relative to cells irradiated in the red phase. In cells irradiated in either phase, Chk1 inhibitor reduced FGPD almost to control levels. The results of this study provide the first clear information regarding the effects of Chk1 inhibition on radiation-induced G2 arrest, with special focus on the time dimension.
PMCID: PMC4202296  PMID: 24894074
Chk1; Chk1 inhibitor; cell cycle; radiation; G2 arrest; fluorescent ubiquitination-based cell-cycle indicator (Fucci)
11.  Gastroenteritis Outbreaks Caused by a DS-1–like G1P[8] Rotavirus Strain, Japan, 2012–2013 
Emerging Infectious Diseases  2014;20(6):1030-1033.
Rotavirus A (RVA) genotype G1P[8], a hallmark of the Wa-like strain, typically contains only genotype 1 genes. However, an unusual RVA G1P[8] with genotype 2 genes was recently detected in Japan. We determined the complete genomic constellation of this RVA. Our findings suggest that mixed RVAs may be more competitive than once thought.
PMCID: PMC4036772  PMID: 24856174
genetic constellation; genome constellation; G1P[8]I2; G1-P[8]-I2; DS-1–like G1P[8]; young children; Osaka; Japan; viruses; rotavirus; gastroenteritis; outbreaks; epidemics
12.  Quantitative analysis of lung elastic fibers in idiopathic pleuroparenchymal fibroelastosis (IPPFE): comparison of clinical, radiological, and pathological findings with those of idiopathic pulmonary fibrosis (IPF) 
The pathological appearance of idiopathic pleuroparenchymal fibroelastosis (IPPFE) with hematoxylin-eosin staining is similar to that of usual interstitial pneumonia (UIP) in patients with idiopathic pulmonary fibrosis (IPF). The amount of elastic fibers (EF) and detailed differences between IPPFE and IPF have not been fully elucidated. The aim of this study was to quantify the EF and identify the differences between IPPFE and IPF.
We evaluated six patients with IPPFE and 28 patients with IPF who underwent surgical lung biopsy or autopsy. The patients’ clinical history, physical findings, chest high-resolution computed tomography (HRCT) findings, and pathological features of lung specimens were retrospectively evaluated. The amounts of EF in lung specimens were quantified with Weigert’s staining using a camera with a charge-coupled device and analytic software in both groups.
Fewer patients with IPPFE than IPF had fine crackles (50.0% vs. 96.4%, p = 0.012). Patients with IPPFE had a lower forced vital capacity (62.7 ± 10.9% vs. 88.6 ± 21.9% predicted, p = 0.009), higher consolidation scores on HRCT (1.7 ± 0.8 vs. 0.3 ± 0.5, p < 0.0001), lower body mass indices (17.9 ± 0.9 vs. 24.3 ± 2.8, p < 0.0001), and more pneumothoraces than did patients with IPF (66.7 vs. 3.6%, p = 0.002). Lung specimens from patients with IPPFE had more than twice the amount of EF than did those from patients with IPF (28.5 ± 3.3% vs. 12.1 ± 4.4%, p < 0.0001). The amount of EF in the lower lobes was significantly lower than that in the upper lobes, even in the same patient with IPPFE (23.6 ± 2.4% vs. 32.4 ± 5.5%, p = 0.048). However, the amount of EF in the lower lobes of patients with IPPFE was still higher than that of patients with IPF (23.6 ± 2.4% vs. 12.2 ± 4.4%, p < 0.0001).
More than twice the amount of EF was found in patients with IPPFE than in those with IPF. Even in the lower lobes, the amount of EF was higher in patients with IPPFE than in those with IPF, although the distribution of lung EF was heterogeneous in IPPFE specimens.
PMCID: PMC4040136  PMID: 24886550
Elastic fiber; Pleuroparenchymal fibroelastosis; Idiopathic pulmonary upper lobe fibrosis; Usual interstitial pneumonia; Idiopathic pulmonary fibrosis; Quantitative analysis
13.  U2 snRNP Is Required for Expression of the 3′ End of Genes 
PLoS ONE  2014;9(5):e98015.
Pre-mRNA in eukaryotes is subjected to mRNA processing, which includes capping, polyadenylation, and splicing. Transcription and mRNA processing are coupled, and this coupling stimulates mRNA processing; however, the effects of mRNA processing on transcription are not fully understood. In this study, we found that inhibition of U2 snRNP by a splicing inhibitor, spliceostatin A (SSA), or by an antisense oligonucleotide to U2 snRNA, caused gene-specific 3′-end down-regulation. Removal of SSA from the culture media restored expression of the 3′ ends of genes, suggesting that U2 snRNP is required for expression of the 3′ end of genes. Finally, we found that SSA treatment caused accumulation of Pol II near the 5′ end of 3′-end down regulated genes, such as CDK6, SMEK2 and EGFR, indicating that SSA treatment led to transcription elongation arrest on these genes. These findings suggest that U2 snRNP is important for production of full length mRNA probably through regulation of transcription elongation, and that a novel checkpoint mechanism prevents pre-mRNA from accumulating as a result of splicing deficiencies, and thereby prevents production of aberrant proteins that might be translated from pre-mRNAs through the arrest of transcription elongation.
PMCID: PMC4028248  PMID: 24845214
14.  Nerve growth factor variations in patients with mood disorders: no changes in eight weeks of clinical treatment 
Nerve growth factor (NGF) has received much attention for its role in mood disorders. The primary objective of the present study was to examine serum NGF levels in Chinese inpatients with depressive or manic episodes in the acute phase and to explore the changes in NGF levels after effective clinical treatments.
One hundred and seven consecutive inpatients and outpatients with mood disorders (30 with unipolar depression, 23 with bipolar depression, and 54 with bipolar mania), and 50 healthy controls were recruited. The serum NGF levels were detected by enzyme-linked immunosorbent assay.
Patients with bipolar mania presented higher serum NGF levels compared to those of healthy controls. After 8 weeks of medical treatment, there were significant improvements in symptoms in patients, but no significant changes in NGF levels.
The present findings may help to strengthen and expand the understanding of the role of NGF in the acute stages of mood disorders.
PMCID: PMC4031241  PMID: 24868159
neurotrophins; depression; mania; bipolar disorder; acute phase; clinical sample
15.  Suppressive Effects of D-Glucosamine on the 5-HT Sensitive Nociceptive Units in the Rat Tooth Pulpal Nerve 
BioMed Research International  2014;2014:187989.
It is well known that D-glucosamine hydrochloride (DGL) has a variety of biological activities and is regarded as a nutritional supplement effective in improving various disorders, including osteoarthritis and atherosclerosis. Although it has been reported that DGL has a significant pain relief effect in treating osteoarthritis, little is known about the characteristics of the effects of this compound on dental pain. The present study was undertaken to evaluate the applicability of DGL as a medicament to control pulpalgia. Using an in vitro rat mandible-inferior alveolar nerve preparation (jaw-nerve preparation), we evaluated the effects of DGL on 5-hydroxytryptamine (5-HT) sensitive nociceptive responses in the tooth pulpal nerve. 5-HT-induced nociceptive responses were fairly suppressed by direct application of DGL, suggesting that DGL have a pain relief effect on patients with dental pain.
PMCID: PMC4004231  PMID: 24818130
16.  Gender Inequities in Quality of Care among HIV-Positive Individuals Initiating Antiretroviral Treatment in British Columbia, Canada (2000–2010) 
PLoS ONE  2014;9(3):e92334.
We measured gender differences in “Quality of Care” (QOC) during the first year after initiation of antiretroviral therapy and investigated factors associated with poorer QOC among women.
QOC was estimated using the Programmatic Compliance Score (PCS), a validated metric associated with all-cause mortality, among all patients (≥19 years) who initiated ART in British Columbia, Canada (2000–2010).
PCS includes six indicators of non-compliance with treatment initiation guidelines at baseline (not having drug resistance testing before treatment; starting on a non-recommended regimen; starting therapy at CD4<200 cells/mm3) and during first-year follow-up (receiving <3 CD4 tests; receiving <3 viral load tests; not achieving viral suppression within six months). Summary scores range from 0–6; higher scores indicate poorer QOC. Multivariable ordinal logistic regression was used to measure if female gender was an independent predictor of poorer QOC and factors associated with poorer QOC among women.
QOC was determined for 3,642 patients (20% women). At baseline: 42% of women (34% men) did not have resistance testing before treatment; 17% of women (9% men) started on a non-recommended regimen (all p<0.001). At follow-up: 17% of women (11% men) received <3 CD4; 17% of women (11% men) received <3 VL; 50% of women (41% men) did not achieve viral suppression (all p<0.001). Overall, QOC was better among men (mean PSC = 1.54 (SD = 1.30)) compared with women (mean = 1.89 (SD = 1.37); p<0.001). In the multivariable model, female gender (AOR = 1.16 [95% CI: 0.99–1.35]; p = 0.062) remained associated with poorer QOC after covariate adjustment. Among women, those with injection drug use history, of Aboriginal ancestry, from Vancouver Island, and who initiated ART in earlier years were more likely to have poorer QOC.
Poorer QOC among women, especially from marginalized communities, demands that barriers undermining women's access to high-quality care be addressed to improve treatment and health for women with HIV.
PMCID: PMC3958538  PMID: 24642949
17.  The achromatic locus: Effect of navigation direction in color space 
Journal of Vision  2014;14(1):25.
An achromatic stimulus is defined as a patch of light that is devoid of any hue. This is usually achieved by asking observers to adjust the stimulus such that it looks neither red nor green and at the same time neither yellow nor blue. Despite the theoretical and practical importance of the achromatic locus, little is known about the variability in these settings. The main purpose of the current study was to evaluate whether achromatic settings were dependent on the task of the observers, namely the navigation direction in color space. Observers could either adjust the test patch along the two chromatic axes in the CIE u*v* diagram or, alternatively, navigate along the unique-hue lines. Our main result is that the navigation method affects the reliability of these achromatic settings. Observers are able to make more reliable achromatic settings when adjusting the test patch along the directions defined by the four unique hues as opposed to navigating along the main axes in the commonly used CIE u*v* chromaticity plane. This result holds across different ambient viewing conditions (Dark, Daylight, Cool White Fluorescent) and different test luminance levels (5, 20, and 50 cd/m2). The reduced variability in the achromatic settings is consistent with the idea that internal color representations are more aligned with the unique-hue lines than the u* and v* axes.
PMCID: PMC3903293  PMID: 24464164
achromatic; unique hues; color constancy; luminance; color space
18.  Total sleep deprivation decreases flow experience and mood status 
The purpose of this study was to examine the effect of sleep deprivation on flow experience.
Sixteen healthy male volunteers of mean age 21.4±1.59 (21–24) years participated in two experimental conditions, ie, sleep-deprivation and normal sleep. In the sleep-deprived condition, participants stayed awake at home for 36 hours (from 8 am until 10 pm the next day) beginning on the day prior to an experimental day. In both conditions, participants carried out a simple reaction time (psychomotor vigilance) task and responded to a questionnaire measuring flow experience and mood status.
Flow experience was reduced after one night of total sleep deprivation. Sleep loss also decreased positive mood, increased negative mood, and decreased psychomotor performance.
Sleep deprivation has a strong impact on mental and behavioral states associated with the maintenance of flow, namely subjective well-being.
PMCID: PMC3865143  PMID: 24376356
sleep deprivation; sleepiness; flow; mood; vigilance
19.  Positive Association Between Serum Level of Glyceraldehyde-Derived Advanced Glycation End Products and Vascular Inflammation Evaluated by [18F]Fluorodeoxyglucose Positron Emission Tomography 
Diabetes Care  2012;35(12):2618-2625.
Advanced glycation end products (AGEs) evoke inflammatory reactions, contributing to the development and progression of atherosclerosis. We investigated the relationship between serum AGE level and vascular inflammation.
The study involved 275 outpatients at Kurume University, Japan (189 males and 86 females; mean age 61.2 ± 8.8 years) who underwent complete history and physical examinations and determinations of blood chemistry and anthropometric variables, including AGEs. Serum AGE level was examined by enzyme-linked immunosorbent assay. Vascular [18F]fluorodeoxyglucose (FDG) uptake, an index of vascular inflammation, was measured as blood-normalized standardized uptake value, known as the target-to-background ratio (TBR), by FDG–positron emission tomography (FDG-PET). Furthermore, we examined whether the changes in serum AGE level after treatment with oral hypoglycemia agents (OHAs) were correlated with those of TBR in another 18 subjects whose AGE value was >14.2 units/mL (mean ± 2 SD).
Mean serum AGE level and carotid TBR values were 9.15 ± 2.53 and 1.43 ± 0.22 units/mL, respectively. Multiple stepwise regression analysis revealed that TBR was independently correlated with AGEs (P < 0.001), carotid intima-media thickness (P < 0.01), and BMI (P < 0.02). When age- and sex-adjusted AGE values stratified by TBR tertiles were compared using ANCOVA, a significant trend was observed (P < 0.01). In addition, the changes in AGEs after OHA treatment were positively (r = 0.50, P < 0.05) correlated with those in TBR value.
The current study reveals that serum AGE level is independently associated with vascular inflammation evaluated by FDG-PET, suggesting that circulating AGE value may be a biomarker that could reflect vascular inflammation within an area of atherosclerosis.
PMCID: PMC3507595  PMID: 22912424
20.  Research progress of cognitive function in schizophrenia in China 
Shanghai Archives of Psychiatry  2013;25(5):266-275.
Cognitive impairment – one of the core symptoms of schizophrenia – has become a focus of research about schizophrenia in China and elsewhere. The main reason for the interest in cognitive functioning is that the degree of cognitive impairment is associated both with the current severity of the illness and with the prognosis of the illness due to its effect on individuals' ability to live independently and on their occupational and social functioning. The first study on cognitive function in schizophrenia in China was conducted in the late 1970s; more recently there has been a resurgence of interest in the area because of new information that has emerged as neuroimaging technologies have improved. The current review summarizes studies on cognitive impairment in schizophrenia conducted in China and proposes directions for future research in this area.
PMCID: PMC4054565  PMID: 24991166
21.  Mixed adeno(neuro)endocrine carcinoma arising from the ectopic gastric mucosa of the upper thoracic esophagus 
We report a case of mixed adenoendocrine carcinoma of the upper thoracic esophagus arising from ectopic gastric mucosa. A 64-year-old man who had been diagnosed with an esophageal tumor on the basis of esophagoscopy was referred to our hospital. Upper gastrointestinal endoscopy revealed the presence of ectopic gastric mucosa and an adjacent pedunculated lesion located on the posterior wall of the upper thoracic esophagus. Subtotal esophagectomy with three-field lymph node dissection was performed. A microscopic examination revealed that there was a partially intermingling component of neuroendocrine carcinoma adjacent to a tubular adenocarcinoma which was conterminous with the area of the ectopic gastric mucosa. Although the tubular adenocarcinoma was confined to the mucosa and submucosa, the neuroendocrine carcinoma had invaded the submucosaand there was vascular permeation. Each component accounted for 30% or more of the tumor, so the final histopathological diagnosis was mixed adenoendocrine carcinoma of the upper thoracic esophagus arising from ectopic gastric mucosa. Adjuvant chemotherapy was not performed, because the postoperative tumor stage was IA. The patient was well and had no evidence of recurrence 16 months after surgery.
PMCID: PMC3766275  PMID: 24139488
Adenocarcinoma; Ectopic gastric mucosa; Esophagus; Mixed adenoendocrine carcinoma
22.  Incidence and Predictors of Pregnancy among a Cohort of HIV-Positive Women Initiating Antiretroviral Therapy in Mbarara, Uganda 
PLoS ONE  2013;8(5):e63411.
Many people living with HIV in sub-Saharan Africa desire biological children. Implementation of HIV prevention strategies that support the reproductive goals of people living with HIV while minimizing HIV transmission risk to sexual partners and future children requires a comprehensive understanding of pregnancy in this population. We analyzed prospective cohort data to determine pregnancy incidence and predictors among HIV-positive women initiating antiretroviral therapy (ART) in a setting with high HIV prevalence and fertility.
Participants were enrolled in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort of HIV-positive individuals initiating ART in Mbarara. Bloodwork (including CD4 cells/mm3, HIV viral load) and questionnaires (including socio-demographics, health status, sexual behavior, partner dynamics, HIV history, and self-reported pregnancy) were completed at baseline and quarterly. Our analysis includes 351 HIV-positive women (18–49 years) who enrolled between 2005–2011. We measured pregnancy incidence by proximal and distal time relative to ART initiation and used multivariable Cox proportional hazards regression analysis (with repeated events) to identify baseline and time-dependent predictors of pregnancy post-ART initiation.
At baseline (pre-ART initiation), median age was 33 years [IQR: 27–37] and median prior livebirths was four [IQR: 2–6]. 38% were married with 61% reporting HIV-positive spouses. 73% of women had disclosed HIV status to a primary sexual partner. Median baseline CD4 was 137 cells/mm3 [IQR: 81–207]. At enrolment, 9.1% (31/342) reported current pregnancy. After ART initiation, 84 women experienced 105 pregnancies over 3.8 median years of follow-up, yielding a pregnancy incidence of 9.40 per 100 WYs. Three years post-ART initiation, cumulative probability of at least one pregnancy was 28% and independently associated with younger age (Adjusted Hazard Ratio (AHR): 0.89/year increase; 95%CI: 0.86–0.92) and HIV serostatus disclosure to primary sexual partner (AHR: 2.45; 95%CI: 1.29–4.63).
Nearly one-third of women became pregnant within three years of initiating ART, highlighting the need for integrated services to prevent unintended pregnancies and reduce periconception-related risks for HIV-infected women choosing to conceive. Association with younger age and disclosure suggests a role for early and couples-based safer conception counselling.
PMCID: PMC3660357  PMID: 23704906
23.  Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease 
Jostins, Luke | Ripke, Stephan | Weersma, Rinse K | Duerr, Richard H | McGovern, Dermot P | Hui, Ken Y | Lee, James C | Schumm, L Philip | Sharma, Yashoda | Anderson, Carl A | Essers, Jonah | Mitrovic, Mitja | Ning, Kaida | Cleynen, Isabelle | Theatre, Emilie | Spain, Sarah L | Raychaudhuri, Soumya | Goyette, Philippe | Wei, Zhi | Abraham, Clara | Achkar, Jean-Paul | Ahmad, Tariq | Amininejad, Leila | Ananthakrishnan, Ashwin N | Andersen, Vibeke | Andrews, Jane M | Baidoo, Leonard | Balschun, Tobias | Bampton, Peter A | Bitton, Alain | Boucher, Gabrielle | Brand, Stephan | Büning, Carsten | Cohain, Ariella | Cichon, Sven | D’Amato, Mauro | De Jong, Dirk | Devaney, Kathy L | Dubinsky, Marla | Edwards, Cathryn | Ellinghaus, David | Ferguson, Lynnette R | Franchimont, Denis | Fransen, Karin | Gearry, Richard | Georges, Michel | Gieger, Christian | Glas, Jürgen | Haritunians, Talin | Hart, Ailsa | Hawkey, Chris | Hedl, Matija | Hu, Xinli | Karlsen, Tom H | Kupcinskas, Limas | Kugathasan, Subra | Latiano, Anna | Laukens, Debby | Lawrance, Ian C | Lees, Charlie W | Louis, Edouard | Mahy, Gillian | Mansfield, John | Morgan, Angharad R | Mowat, Craig | Newman, William | Palmieri, Orazio | Ponsioen, Cyriel Y | Potocnik, Uros | Prescott, Natalie J | Regueiro, Miguel | Rotter, Jerome I | Russell, Richard K | Sanderson, Jeremy D | Sans, Miquel | Satsangi, Jack | Schreiber, Stefan | Simms, Lisa A | Sventoraityte, Jurgita | Targan, Stephan R | Taylor, Kent D | Tremelling, Mark | Verspaget, Hein W | De Vos, Martine | Wijmenga, Cisca | Wilson, David C | Winkelmann, Juliane | Xavier, Ramnik J | Zeissig, Sebastian | Zhang, Bin | Zhang, Clarence K | Zhao, Hongyu | Silverberg, Mark S | Annese, Vito | Hakonarson, Hakon | Brant, Steven R | Radford-Smith, Graham | Mathew, Christopher G | Rioux, John D | Schadt, Eric E | Daly, Mark J | Franke, Andre | Parkes, Miles | Vermeire, Severine | Barrett, Jeffrey C | Cho, Judy H
Nature  2012;491(7422):119-124.
Crohn’s disease (CD) and ulcerative colitis (UC), the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry with rising prevalence in other populations1. Genome-wide association studies (GWAS) and subsequent meta-analyses of CD and UC2,3 as separate phenotypes implicated previously unsuspected mechanisms, such as autophagy4, in pathogenesis and showed that some IBD loci are shared with other inflammatory diseases5. Here we expand knowledge of relevant pathways by undertaking a meta-analysis of CD and UC genome-wide association scans, with validation of significant findings in more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional and balancing selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe striking overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
PMCID: PMC3491803  PMID: 23128233
24.  A conceptual framework for understanding HIV risk behavior in the context of supporting fertility goals among HIV-serodiscordant couples 
Reproductive health matters  2012;20(39 Suppl):50-60.
Integrated reproductive health services for people living with HIV must address their fertility intentions. For HIV-serodiscordant couples who want to conceive, attempted conception confers a substantial risk of HIV transmission to the uninfected partner. Behavioral and pharmacologic strategies may reduce HIV transmission risk among HIV-serodiscordant couples who seek to conceive. In order to develop effective pharmaco-behavioral programs, it is important to understand and address the contexts surrounding reproductive decision-making; perceived periconception HIV transmission risk; and periconception risk behaviors. We present a conceptual framework to describe the dynamics involved in periconception HIV risk behaviors in a South African setting. We adapt the Information-Motivation-Behavioral Skill Model of HIV Preventative Behavior to address the structural, individual and couple-level determinants of safer conception behavior. The framework is intended to identify factors that influence periconception HIV risk behavior among serodiscordant couples, and therefore to guide design and implementation of integrated and effective HIV, reproductive health and family planning services that support reproductive decision-making.
PMCID: PMC3608509  PMID: 23177680
conceptual framework; HIV; serodiscordant couples; pregnancy; safer conception
25.  The WHOMEN’s Scale (Women’s HAART Optimism Monitoring and EvaluatioN Scale v.1) and the Association with Fertility Intentions and Sexual Behaviours Among HIV-Positive Women in Uganda 
AIDS and behavior  2009;13(Suppl 1):72-81.
The objective of this study was to develop a reliable HAART optimism scale among HIV-positive women in Uganda and to test the scale’s validity against measures of fertility intentions, sexual activity, and unprotected sexual intercourse. We used cross-sectional survey data of 540 women (18–50 years) attending Mbarara University’s HIV clinic in Uganda. Women were asked how much they agreed or disagreed with 23 statements about HAART. Data were subjected to a principal components and factor analyses. Subsequently, we tested the association between the scale and fertility intentions and sexual behaviour using Wilcoxon rank sum test. Factor analysis yielded three factors, one of which was an eight-item HAART optimism scale with moderately high internal consistency (α = 0.70). Women who reported that they intended to have (more) children had significantly higher HAART optimism scores (median = 13.5 [IQR: 12–16]) than women who did not intend to have (more) children (median = 10.5 [IQR: 8–12]; P <0.0001). Similarly, women who were sexually active and who reported practicing unprotected sexual intercourse had significantly higher HAART optimism scores than women who were sexually abstinent or who practiced protected sexual intercourse. Our reliable and valid scale, termed the Women’s HAART Optimism Monitoring and EvaluatioN scale (WHOMEN’s scale), may be valuable to broader studies investigating the role of HAART optimism on reproductive intentions and sexual behaviours of HIV-positive women in high HIV prevalence settings.
PMCID: PMC3606958  PMID: 19387819
HIV; HAART; Uganda; Scale; HAART optimism; Women; Fertility intentions; Sexual behaviour; HAART optimism scale

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