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1.
Public Health Action ; 12(4): 148-152, 2022 Dec 21.
Article in English | MEDLINE | ID: mdl-36561903

ABSTRACT

SETTING: Five urban TB diagnostic centres in Lusaka, Zambia. OBJECTIVE: To determine the proportion of bacteriologically confirmed pre-treatment lost to follow-up (LTFU) patients with TB found at the study settings in 2020. DESIGN: This was a retrospective cohort study in which the TB laboratory and treatment registers at the study sites were cross-matched. RESULTS: A total of 1,085 bacteriologically confirmed patients with TB were found in the laboratory TB registers at the study settings. Of these, 809 (74.6%) were males, whereas 8 (0.7%) were children, 1,005 (92.6%) were diagnosed using Xpert, 78 (7.2%) by microscopy. A total of 91 (8.4%, 95% CI 6.8-10.2) were determined to be pre-treatment LTFU. Those who had very low (14.0%, 95% CI 8.5-21.2) and low (11.8%, 95% CI 8.4-16.0) results on Xpert were respectively 3.1 (95% CI 1.6-6.0) and 2.6 (95% CI 1.4-4.8) times more likely to become pre-treatment LTFU than those who had medium (4.5%, 95% CI 2.5-7.4) results. The proportions of pre-treatment LTFU varied among the study sites from 0.7% to 16.1%. CONCLUSION: Health facilities should strive to account for every patient with TB, with particular attention to those who are bacteriologically confirmed.


CADRE: Cinq centres urbains de diagnostic de la TB à Lusaka, en Zambie. OBJECTIF: Déterminer la proportion de patients atteints de TB perdus de vue (LTFU) avant le traitement et confirmés bactériologiquement dans les centres d'étude en 2020. MÉTHODE: Il s'agit d'une étude de cohorte rétrospective dans laquelle les registres de laboratoire et de traitement de la TB des sites étudiés ont été appariés. RÉSULTATS: Au total, 1 085 patients atteints de TB confirmée par une analyse bactériologique ont été trouvés dans les registres de laboratoire de la TB des sites de l'étude. Parmi eux, 809 (74,6%) étaient des hommes, tandis que 8 (0,7%) étaient des enfants. 1 005 (92,6%) ont été diagnostiqués à l'aide d'Xpert, 78 (7,2%) par microscopie. Au total, 91 (8,4% ; IC 95% 6,8­10,2) ont été déterminés comme étant des cas de LTFU avant traitement. Ceux qui avaient obtenu des résultats très faibles (14,0% ; IC 95% 8,5­21,2) et faibles (11,8% ; IC 95% 8,4­16,0) au test Xpert étaient respectivement 3,1 (IC 95% 1,6­6,0) et 2,6 (IC 95% 1,4­4,8) fois plus susceptibles de devenir des cas de LTFU avant traitement que ceux qui avaient obtenu des résultats moyens (4,5% ; IC 95% 2,5­7,4). Les proportions de LTFU avant traitement variaient entre les sites de l'étude de 0,7% à 16,1%. CONCLUSION: Les établissements de santé devraient s'efforcer de comptabiliser tous les patients atteints de TB, en accordant une attention particulière à ceux dont la présence est confirmée par la bactériologie.

2.
Anticancer Res ; 42(4): 1777-1783, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35346996

ABSTRACT

BACKGROUND/AIM: As part of our continuing investigation in coumarin derivatives as potential anticancer substances, a series of alkylpsoralens were synthesized, and their antiproliferative activity was evaluated in leukemic HL60 cells. MATERIALS AND METHODS: Alkylpsoralens were systematically synthesized from the combination of several chloroketones and 7-hydroxycoumarin derivatives. RESULTS: Among the compounds synthesized, 4,4',8-trimethylpsoralen demonstrated the most potent activity (IC50=6.6 µM). CONCLUSION: The correlation between the alkylation pattern and antiproliferative activity showed the importance of the C4-methyl and C8-methyl moieties in the psoralen nucleus as well as the importance of lipophilicity for their antiproliferative activity.


Subject(s)
Antineoplastic Agents , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Coumarins/chemistry , HL-60 Cells , Humans
3.
Public Health Action ; 11(1): 22-25, 2021 Mar 21.
Article in English | MEDLINE | ID: mdl-33777717

ABSTRACT

SETTING: An urban TB diagnostic centre in Lusaka, Zambia. OBJECTIVE: To re-evaluate treatment outcomes of all bacteriologically confirmed TB patients registered in 2018. DESIGN: This was a retrospective cohort study on TB patients. Treatment outcomes of patients who were transferred out were retrieved. RESULTS: A total of 182 patients were registered, 26 of whom had missing documents; these were excluded from the study. Of the remaining 156 patients who were reviewed, 86 (55.1%) were correctly evaluated by the centre, 35 (22.4%) were incorrectly evaluated and 35 (22.4%) were 'transferred out' (not evaluated). As a result of this review, the number of evaluated patients increased from 86 (55.1%) to 150 (96.2%). The cure and treatment success rates rose from 43.6% and 44.2%, respectively, to 57.7% and 73.1%, respectively. Of note, 14 of the 35 patients who were initially declared 'transferred out' did not actually reach their treatment facilities and ended up being lost to follow-up. CONCLUSION: This study shows that it is possible to evaluate almost all TB patients. Re-evaluation of treatment outcomes of TB patients revealed the problems in the TB services that need to be improved in the future.


CONTEXTE: Un centre urbain de diagnostic de la TB à Lusaka, Zambie. OBJECTIF: Réévaluer les résultats du traitement de tous les patients atteints de TB bactériologiquement confirmée qui étaient enregistrés en 2018. SCHÉMA: Ceci est une étude rétrospective de cohorte de patients. Des résultats du traitement des patients TB qui ont été transferés dans un autre hôpital étaient retrouvés. RÉSULTATS: D'un total de 182 patients enregistrés, 26 ont été exclus car leur dossier était incomplet. Sur les 156 patients restants qui ont été revus, 86 (55,1%) ont eu une évaluation correcte dans le centre, pour 35 (22,4%) patients, elle était incorrecte et les 35 (22,4%) derniers ont été transférés donc pas évalués. A la suite de cette revue, la proportion de patients évalués augmenté de 86 (55,1%) à 150 (96,2%). Le taux de guérison et de succès du traitement ont augmenté de 43,6% et 44,2%, respectivement, à 57,7% et 73,1%, respectivement. Il faut noter que 14 des 35 patients initialement déclarés « transférés ¼ n'ont pas atteint leurs structures de traitement et ont fini par être perdus de vue. CONCLUSION: Cette étude montre qu'il est possible d'évaluer presque tous les patients TB. Une ré-évaluation des résultats du traitement des patients TB a révélé les problèmes des services TB qui doivent être améliorés à l'avenir.

4.
Clin Exp Immunol ; 202(2): 249-261, 2020 11.
Article in English | MEDLINE | ID: mdl-32578199

ABSTRACT

While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+ CD127- regulatory T cells (edu.Tregs ) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg ; anti-A/B antibodies were not involved in the Treg -mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.


Subject(s)
ABO Blood-Group System/immunology , B7-H1 Antigen/immunology , Endothelial Cells/immunology , HLA-DR Antigens/immunology , Isoantibodies/immunology , Organ Transplantation , T-Lymphocytes, Regulatory/immunology , Endothelial Cells/pathology , Graft Rejection/immunology , Graft Rejection/pathology , Humans , T-Lymphocytes, Regulatory/pathology
5.
Public Health Action ; 10(1): 21-26, 2020 Mar 21.
Article in English | MEDLINE | ID: mdl-32368520

ABSTRACT

SETTING: Four tuberculosis (TB) diagnostic health facilities of the Chongwe District, Zambia. OBJECTIVE: To determine the frequency of bacteriologically confirmed TB patients lost to follow-up (LTFU) before treatment from January to December 2017. DESIGN: This is a retrospective cohort study involving the review of TB registers. Information on presumptive TB patients who tested positive either by smear microscopy or Xpert® MTB/RIF assay was extracted from the laboratory TB registers of the TB diagnostic facilities and cross-matched with the TB treatment registers of TB treatment facilities. RESULTS: Two hundred and seventeen bacteriologically confirmed TB patients were found in the laboratory TB registers. Of these, 145 (67%) were males and seven (3%) were children; 177 (81%) patients were diagnosed using Xpert, while the remaining 40 (19%) were diagnosed using sputum smear microscopy. A total of 71 (33%) were not linked to treatment. Those diagnosed using smear microscopy were 2.5 times (95% CI 1.1-5.3) more likely to be LTFU before treatment than those diagnosed using Xpert. CONCLUSION: About one third of TB patients who were not linked to treatment could potentially extend the duration of bacilli transmission in their communities. National TB control programmes should consider including LTFU patients before treatment in routine monitoring and evaluation.

6.
Benef Microbes ; 10(7): 751-758, 2019 Oct 14.
Article in English | MEDLINE | ID: mdl-31965846

ABSTRACT

Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients demonstrated to have health benefits, such as decreasing the risk of coronary heart disease, improving parameters associated with metabolic syndrome, and decreasing anxiety symptoms and depression risk. Previous intervention studies indicated the association between blood or tissue PUFA levels and the gut microbiota; however, the details remain incompletely elucidated. We conducted a cross-sectional study to examine the association between PUFAs and the gut microbiota among breast cancer survivors. Adults who had been diagnosed with invasive breast cancer more than one year ago and were not currently undergoing chemotherapy were enrolled. Capillary blood and faecal samples were obtained to assess the blood PUFA levels and gut microbiota compositions. The mean age (n=124) was 58.7 years, and 46% of the participants had a history of chemotherapy. Multiple regression analysis controlling for possible confounders indicated that an increased relative abundance of Actinobacteria was significantly associated with increased levels of docosahexaenoic acid (DHA, beta=0.304, q<0.01). At the genus level, the abundance of Bifidobacterium was positively associated with the level of DHA (beta=0.307, q<0.01). No significant association between omega-6 PUFAs and the relative abundances of gut microbiota members was observed. In addition, analyses stratified by the history of chemotherapy indicated significant associations of PUFA levels with the abundance of some bacterial taxa, including the phylum Actinobacteria (DHA, beta=0.365, q<0.01) and Bacteroidetes (EPA, beta=-0.339, q<0.01) and the genus Bifidobacterium (DHA, beta=0.368, q<0.01) only among participants without a history of chemotherapy. These findings provide the first evidence of positive associations between the abundances of Bifidobacterium among the gut microbiota and the levels of omega-3 PUFAs in the blood. Further studies are required to gain additional insight into these associations in healthy subjects as well as into the causality of the relationship.


Subject(s)
Breast Neoplasms , Cancer Survivors/statistics & numerical data , Fatty Acids, Omega-3/blood , Gastrointestinal Microbiome , Aged , Bacteria/classification , Bacteria/isolation & purification , Breast Neoplasms/blood , Breast Neoplasms/microbiology , Cross-Sectional Studies , Data Interpretation, Statistical , Diet , Feces/chemistry , Female , Humans , Male , Middle Aged
7.
Transplant Proc ; 50(8): 2526-2530, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30316391

ABSTRACT

INTRODUCTION: Lymphatic leakage after kidney transplantation is a relatively frequent complication but sometimes resistant to treatment, and there is no fixed treatment algorithm. The effectiveness of therapeutic lymphangiography for postoperative lymphatic or chyle leakage has been reported, but few reports are available regarding patients who have undergone kidney transplantation. In this study, we report our experience with lymphangiography as a therapeutic tool for lymphatic leakage after kidney transplantation. PATIENTS AND METHODS: Intranodal lymphangiography for lymphatic leakage was performed in 4 patients (3 male, 1 female; age range, 38 to 70 years old) after living kidney transplantation at the Osaka City University Hospital in Japan. The amount of drainage before lymphangiography was 169 to 361 mL/day. The procedure for intranodal lymphangiography was as follows: the inguinal lymph node was punctured under ultrasound guidance, and the tip of the needle was instilled at the junction between the cortex and the hilum, after which Lipiodol was slowly and manually injected. RESULTS: Lymphangiography was technically successful in 3 out of the 4 patients. In all successful cases, the amount of drainage decreased and leakage finally stopped without additional therapy such as sclerotherapy or fenestration. In 2 cases, we were able to directly detect the leakage site using lymphangiography. The time between lymphangiography and leakage resolution ranged from 8 to 13 days. There were neither complications of lymphangiography nor recurrence of lymphatic leakage in the successful cases. CONCLUSIONS: Intranodal lymphangiography may be not only a diagnostic tool but also an effective, minimally-invasive, and safe method for treatment of lymphatic leakage resistant to drainage after kidney transplantation.


Subject(s)
Kidney Transplantation/adverse effects , Lymphography/methods , Postoperative Complications/diagnostic imaging , Adult , Aged , Female , Humans , Japan , Lymph Nodes/diagnostic imaging , Lymphatic Vessels/diagnostic imaging , Male , Middle Aged
8.
Article in English | MEDLINE | ID: mdl-29628046

ABSTRACT

The relationship of n-3 polyunsaturated fatty acids (PUFAs) and gut microbiota with brain function has been extensively reported. Here, we review how n-3 polyunsaturated fatty acids affect fear memory processing. n-3 PUFAs may improve dysfunctional fear memory processing via immunomodulation/anti-inflammation, increased BDNF, upregulated adult neurogenesis, modulated signal transduction, and microbiota-gut-brain axis normalization. We emphasize how n-3 PUFAs affect this axis and also focus on the hypothetical effects of PUFAs in fear of cancer recurrence (FCR), the primary psychological unmet need of cancer survivors. Its pathophysiology may be similar to that of post-traumatic stress disorder (PTSD), which involves dysfunctional fear memory processing. Due to fewer adverse effects than psychotropic drugs, nutritional interventions involving n-3 PUFAs should be acceptable for physically vulnerable cancer survivors. We are currently studying the relationship of FCR with n-3 PUFAs and gut microbiota in cancer survivors to provide them with a nutritional intervention that protects against FCR.


Subject(s)
Cancer Survivors/psychology , Fatty Acids, Omega-3/pharmacology , Fear/drug effects , Neoplasm Recurrence, Local/psychology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anxiety Disorders/diet therapy , Anxiety Disorders/microbiology , Brain-Derived Neurotrophic Factor/metabolism , Dysbiosis/diet therapy , Dysbiosis/psychology , Gastrointestinal Microbiome/drug effects , Humans , Memory/drug effects , Neurogenesis/drug effects
9.
Transl Psychiatry ; 7(9): e1242, 2017 09 26.
Article in English | MEDLINE | ID: mdl-28949340

ABSTRACT

Systematic review of observational studies has revealed that fish consumption and levels of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are associated with a reduced risk of depression. A reverse J-shaped effect of n-3 PUFAs was suggested. However, there is limited evidence from populations with high fish consumption and no studies have used a standard psychiatrist-based diagnosis of major depressive disorder (MDD). Therefore, this population-based, prospective study investigated the association of dietary fish, n-3 PUFA, and n-6 PUFA consumption with risk of psychiatrist-diagnosed MDD in Japan. A total of 12 219 subjects were enrolled from the Saku area in 1990. Of these, we extracted 1181 participants aged 63-82 years who completed food frequency questionnaires in both 1995 and 2000 and also underwent a mental health examination in 2014-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for MDD according to fish intake and PUFA quartiles were calculated. Current MDD was diagnosed in 95 patients. We found a reduced risk of MDD in the third quartile for fish intake (111.1 g per day, OR=0.44, 95% CI=0.23-0.84), second quartile for EPA (307.7 mg per day, OR=0.54, 95% CI=0.30-0.99) and third quartile for docosapentaenoic acid (DPA) (123.1 mg per day, OR=0.42, 95% CI=0.22-0.85). ORs adjusted for cancer, stroke, myocardial infarction and diabetes remained significant for fish and DPA intake. Our results suggest that moderate fish intake could be recommended for the prevention of MDD in aged Japanese individuals.


Subject(s)
Depressive Disorder, Major/epidemiology , Diet , Fatty Acids, Omega-3 , Seafood , Aged , Aged, 80 and over , Depressive Disorder, Major/prevention & control , Fatty Acids, Omega-6 , Female , Humans , Japan/epidemiology , Male , Middle Aged , Prospective Studies , Risk Factors
10.
Poult Sci ; 96(10): 3717-3724, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28637225

ABSTRACT

To investigate the epidemiologic aspects of colibacillosis in broiler chickens, 83 Escherichia coli isolates obtained from the pericarditis and perihepatitis lesions in broiler chickens from 4 commercial farms, 5 isolates recovered from 5 samples of yolk sac contents that were pooled from 25 emaciated chicks, and 4 fecal isolates obtained from a hatchery that supplied chicks to the 4 commercial farms mentioned above were genetically and bacteriologically characterized. Using pulsed-field gel electrophoresis (PFGE), a total of 92 isolates were classified into 33 pulsotypes. Identical pulsotypes were observed in isolates obtained from hatchery samples and the affected broiler chickens on multiple farms at various sampling times. Seventeen representative isolates with no common origin belonging to 6 pulsotypes and an additional 27 isolates with the other pulsotypes were used for further experiments. Isolates with identical pulsotypes exhibited common traits for virulence-associated genes, lipopolysaccharide core types, and phylogenetic groups. Nine of the isolates were serologically typed as O125 with various types of H antigens and 3 were typed as O25:H4. In the 27 isolates resistant to ceftiofur (CTF), which is a third generation cephalosporin, the blaCTX-M-2, blaCMY-2, blaCTX-M-14, blaCTX-M-65 genes were found in 15, 8, 3, and 1 isolate(s), respectively, and another isolate resistant to CTF had both the blaCTX-M-2 and the blaCMY-2 genes. In the 16 isolates with the blaCTX-M-2 gene, the chromosomal location of the gene was identified in 12 isolates. The plasmid-mediated quinolone resistance genes, oqxAB and aac(6')-Ib-cr, were found in 2 and 3 isolates, respectively. Conjugation experiments revealed that the blaCTX-M-2 (4 isolates), blaCTX-M-14 (3 isolates), blaSHV-12 (1 isolate), and oqxAB (2 isolates) genes were transferred. Our data suggest that E. coli strains with identical pulsotypes had been caused the incidences of colibacillosis and that the antimicrobial resistance genes on conjugative plasmids and those integrated into the chromosome may be spread among avian pathogenic E. coli strains in multiple farms.


Subject(s)
Chickens , Escherichia coli Infections/veterinary , Escherichia coli/genetics , Poultry Diseases/microbiology , Animals , Drug Resistance, Bacterial , Electrophoresis, Gel, Pulsed-Field , Escherichia coli/classification , Escherichia coli/drug effects , Escherichia coli Infections/microbiology , Japan
11.
QJM ; 110(5): 327, 2017 May 01.
Article in English | MEDLINE | ID: mdl-28158804
12.
Psychol Med ; 46(15): 3117-3125, 2016 11.
Article in English | MEDLINE | ID: mdl-27534897

ABSTRACT

BACKGROUND: The Fukushima Daiichi and Daini Nuclear Power Plant workers experienced multiple stressors as both victims and onsite workers after the 2011 Great East Japan Earthquake and subsequent nuclear accidents. Previous studies found that disaster-related exposures, including discrimination/slurs, were associated with their mental health. Their long-term impact has yet to be investigated. METHOD: A total of 968 plant workers (Daiichi, n = 571; Daini, n = 397) completed self-written questionnaires 2-3 months (time 1) and 14-15 months (time 2) after the disaster (response rate 55.0%). Sociodemographics, disaster-related experiences, and peritraumatic distress were assessed at time 1. At time 1 and time 2, general psychological distress (GPD) and post-traumatic stress response (PTSR) were measured, respectively, using the K6 scale and Impact of Event Scale Revised. We examined multivariate covariates of time 2 GPD and PTSR, adjusting for autocorrelations in the hierarchical multiple regression analyses. RESULTS: Higher GPD at time 2 was predicted by higher GPD at time 1 (ß = 0.491, p < 0.001) and discrimination/slurs experiences at time 1 (ß = 0.065, p = 0.025, adjusted R 2 = 0.24). Higher PTSR at time 2 was predicted with higher PTSR at time 1 (ß = 0.548, p < 0.001), higher age (ß = 0.085, p = 0.005), and discrimination/slurs experiences at time 1 (ß = 0.079, p = 0.003, adjusted R 2 = 0.36). CONCLUSIONS: Higher GPD at time 2 was predicted by higher GPD and discrimination/slurs experience at time 1. Higher PTSR at time 2 was predicted by higher PTSR, higher age, and discrimination/slurs experience at time 1.


Subject(s)
Fukushima Nuclear Accident , Mental Health , Nuclear Power Plants , Prejudice/psychology , Public Opinion , Stress Disorders, Post-Traumatic/psychology , Stress, Psychological/psychology , Adult , Disasters , Female , Humans , Japan , Longitudinal Studies , Male , Middle Aged , Regression Analysis , Surveys and Questionnaires , Workforce
13.
Int J Oral Maxillofac Surg ; 45(11): 1395-1399, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27170618

ABSTRACT

After oral cancer resection with flap reconstruction, the volume of the flap decreases over time. The purpose of this study was to estimate the volume change in myocutaneous flaps and to identify the clinical factors associated with this volume decrease. Postoperative computed tomography scans and magnetic resonance images of 30 patients, obtained at 1, 6, and 12 months after oral cancer resection with myocutaneous flap reconstruction, were reviewed retrospectively. Changes in the volume of the flaps over time were assessed. The residual flap ratio was calculated using the flap volume at 1 month after reconstruction as the denominator. The residual ratios in relation to clinical factors were compared at 6 and 12 months using the Student t-test. Overall, the flap residual ratio was 78.1% (range 64.1-93.9%) at 6 months and 71.4% (range 48.8-87.2%) at 12 months. Hypertension, diabetes mellitus, and postoperative radiotherapy were significantly associated with volume changes at 6 months, and postoperative infection and decreased serum albumin levels were associated with volume changes at both 6 months (P=0.015 and P=0.001, respectively) and 12 months (P=0.026 and P=0.017, respectively). Flap reconstruction must be performed with postoperative flap atrophy in mind in order to preserve optimum speech and swallowing function.


Subject(s)
Magnetic Resonance Imaging , Mouth Neoplasms/surgery , Myocutaneous Flap/pathology , Myocutaneous Flap/transplantation , Postoperative Complications/pathology , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Plastic Surgery Procedures , Retrospective Studies , Risk Factors
14.
Transl Psychiatry ; 5: e596, 2015 Jul 07.
Article in English | MEDLINE | ID: mdl-26151924

ABSTRACT

Our open-label pilot study showed that supplementation with docosahexaenoic acid (DHA) increased serum brain-derived neurotrophic factor (BDNF) levels and that there might be an association between changes in serum BDNF levels and reduced psychological distress. Animal research has indicated that a DHA-enriched diet increases BDNF in the brain. In this randomized double-blind controlled trial of severely injured patients vulnerable to posttraumatic stress disorder (PTSD) and depression, we examined whether DHA increases serum BDNF levels and whether changes in BDNF levels are associated with subsequent symptoms of PTSD and depression. Patients received 1470 mg per day of DHA plus 147 mg per day of eicosapentaenoic acid (EPA; n = 53) or placebo (n = 57) for 12 weeks. Serum levels of mature BDNF and precursor pro-BDNF at baseline and 12-week follow-up were measured using enzyme-linked immunosorbent assay kits. At 12 weeks, we used the Clinician-Administered PTSD Scale to assess PTSD symptoms and depressive symptoms by the Montgomery-Åsberg Depression Rating Scale. We found a significant increase in serum BDNF levels during the trial in the DHA and placebo groups with no interaction between time and group. Changes in BDNF levels were not associated with PTSD severity but negatively associated with depression severity (Spearman's ρ = -0.257, P = 0.012). Changes in pro-BDNF were also negatively associated with depression severity (Spearman's ρ = -0.253, P = 0.013). We found no specific effects of DHA on increased serum levels of BDNF and pro-BDNF; however, evidence in this study suggests that increased BDNF and pro-BDNF have a protective effect by minimizing depression severity.


Subject(s)
Brain-Derived Neurotrophic Factor/blood , Docosahexaenoic Acids/therapeutic use , Protein Precursors/blood , Stress Disorders, Post-Traumatic/prevention & control , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Depression/blood , Depression/prevention & control , Double-Blind Method , Eicosapentaenoic Acid/therapeutic use , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Stress Disorders, Post-Traumatic/blood , Wounds and Injuries/psychology , Young Adult
15.
Free Radic Res ; 49(8): 1038-47, 2015.
Article in English | MEDLINE | ID: mdl-25968953

ABSTRACT

Methamphetamine (METH)-induced neurotoxicity is associated with mitochondrial dysfunction and enhanced oxidative stress. The aims of the present study conducted in the mouse brain repetitively treated with METH were to (1) examine the redox status using the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethylpiperidine-1-oxyl (MCP) and (2) non-invasively visualize the brain redox status with electron paramagnetic resonance (EPR) imaging. The rate of reduction of MCP was measured from a series of temporal EPR images of mouse heads, and this rate was used to construct a two-dimensional map of rate constants called a "redox map." The obtained redox map clearly illustrated the change in redox balance in the METH-treated mouse brain that is a known result of oxidative damage. Biochemical assays also showed that the level of thiobarbituric acid-reactive substance, an index of lipid peroxidation, was increased in mouse brains by METH. The enhanced reduction in MCP observed in mouse brains was remarkably suppressed by treatment with the dopamine synthase inhibitor, α-methyl-p-tyrosine, suggesting that enhancement of the reduction reaction of MCP resulted from enzymatic reduction in the mitochondrial respiratory chain. Furthermore, magnetic resonance imaging (MRI) of METH-treated mice using a blood-brain barrier (BBB)-impermeable paramagnetic contrast agent revealed BBB dysfunction after treatment with METH for 7 days. MRI also indicated that the impaired BBB recovered after withdrawal of METH. EPR imaging and MRI are useful tools not only for following changes in the redox status and BBB dysfunction in mouse brains repeatedly administered METH, but also for tracing the drug effect after withdrawal of METH.


Subject(s)
Blood-Brain Barrier/drug effects , Central Nervous System Stimulants/toxicity , Methamphetamine/toxicity , Oxidative Stress , Animals , Blood-Brain Barrier/metabolism , Brain/blood supply , Brain/drug effects , Brain/metabolism , Capillary Permeability/drug effects , Contrast Media/pharmacokinetics , Electron Spin Resonance Spectroscopy , Lipid Peroxidation , Locomotion/drug effects , Magnetic Resonance Imaging , Male , Mice, Inbred C57BL , Nitrogen Oxides/pharmacokinetics , Organometallic Compounds/pharmacokinetics , Oxidation-Reduction
17.
Br J Cancer ; 111(12): 2308-15, 2014 Dec 09.
Article in English | MEDLINE | ID: mdl-25314067

ABSTRACT

BACKGROUND: Nucleostemin (NS) is essential for the maintenance of stem cell properties, the functions of which remain poorly understood in cancer cells. The purpose of this study was to explore the impact of NS on malignancy and its clinical significance in oral squamous cell carcinoma (OSCC) patients. METHODS: We investigated the effects of NS on the proliferation and invasion of OSCC using NS-overexpressing or -knockdown OSCC cells. We assessed the activation of the STAT3 (signal transducer and activator of transcription 3) signalling pathway and the downstream targets in the cells with different expression levels of NS. An immunohistochemical analysis of NS was also performed in 54 OSCC patients who were treated with preoperative chemoradiotherapy and surgery. RESULTS: The overexpression of NS significantly enhanced the proliferation and invasive potential of OSCC cells. On the other hand, downregulation of NS suppressed the invasiveness of the cells. The alterations of these malignant phenotypes were associated with the activation of STAT3 signalling and its downstream targets. An immunohistochemical analysis demonstrated that a high NS tumour expression level significantly correlated with an advanced T-stage and N-stage. Furthermore, a Cox regression analysis revealed that the NS status (hazard ratio, 9.09; P=0.002) was a significant progression factor for OSCC patients. CONCLUSIONS: Our results suggest that targeting NS may provide a promising treatment for highly malignant OSCC.


Subject(s)
Carcinoma, Squamous Cell/metabolism , GTP-Binding Proteins/biosynthesis , Head and Neck Neoplasms/metabolism , Mouth Neoplasms/metabolism , Nuclear Proteins/biosynthesis , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Proliferation/physiology , GTP-Binding Proteins/genetics , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Mouth Neoplasms/genetics , Nuclear Proteins/genetics , Phenotype , Prognosis , Signal Transduction , Squamous Cell Carcinoma of Head and Neck , Transfection
18.
Br J Radiol ; 87(1042): 20130791, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25074719

ABSTRACT

OBJECTIVE: To evaluate the role of diffusion-weighted MRI (DW-MRI) as an imaging biomarker for upper urinary tract cancer (UUTC) that has already metastasized or will metastasize soon. METHODS: 61 patients clinically diagnosed with UUTC were prospectively enrolled in this study. All the patients underwent MRI, including DW-MRI, prior to any interventions. Correlations between apparent diffusion coefficient (ADC) and other clinicopathological variables, including metastasis-free survival, were analysed. RESULTS: Median follow-up period was 938 days. Of the 61 patients, 12 had any metastases at the initial diagnosis. 11 patients developed metastases during the follow-up period. These 23 patients were categorized as "Metastatic". Of the remaining 38 patients, 35 with a follow-up period longer than 400 days were categorized as "Localized". ADC was significantly lower in the Metastatic category than in the Localized (p = 0.0002) category. Multivariate analysis of pre-operative variables identified ADC (cut-off value, 1.08 × 10(-3) mm(2) s(-1)) and clinical T stage based on T2 weighted MRI as an independent predictive factor of metastatic UUTC. 46 patients without any metastases during the initial diagnosis were stratified into a high-risk group (16 patients with low ADC and clinical T3-4) and a low-risk group (30 patients with high ADC or clinical Ta-2). The 3-year metastasis-free survivals were 45% and 93%, respectively. CONCLUSION: In the current study, UUTC with lower ADC value is more likely to have metastatic potential. Incorporating ADC with clinical T stage helps to differentiate metastatic UUTC at the initial diagnosis. ADVANCES IN KNOWLEDGE: DW-MRI is a potential imaging biomarker reflecting metastatic propensity of UUTC.


Subject(s)
Diffusion Magnetic Resonance Imaging , Urologic Neoplasms/pathology , Biomarkers, Tumor , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Image Processing, Computer-Assisted , Kaplan-Meier Estimate , Kidney Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Urinary Bladder Neoplasms/pathology , Urologic Neoplasms/diagnosis , Urologic Neoplasms/mortality
19.
Eur Psychiatry ; 29(7): 408-13, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24969103

ABSTRACT

Several cross-sectional studies, but no prospective studies, have reported an association between an abnormal lipid profile and posttraumatic stress disorder (PTSD). We hypothesized that an abnormal lipid profile might predict risk for developing PTSD. In this prospective study, we analyzed data from 237 antidepressant-naïve severely injured patients who participated in the Tachikawa Cohort of Motor Vehicle Accident Study. High-density lipoprotein cholesterol (HDL-C) levels at baseline were significantly lower in patients with PTSD than those without PTSD at 6 months after motor vehicle accident (MVA) and were inversely associated with risk for PTSD. In contrast, triglycerides (TG) at baseline were significantly higher in patients with PTSD than in those without PTSD at 6 months post-MVA and were positively associated with risk for PTSD. There was no clear association between low-density lipoprotein cholesterol or total cholesterol and risk for PTSD. In conclusion, low HDL-C and high TG may be risk factors for PTSD. Determining lipid profiles might help identify those at risk for PTSD after experiencing trauma.


Subject(s)
Accidents, Traffic/psychology , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Stress Disorders, Post-Traumatic/metabolism , Triglycerides/metabolism , Adult , Age Factors , Cholesterol/metabolism , Cohort Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Risk Factors , Sex Factors , Stress Disorders, Post-Traumatic/psychology , Young Adult
20.
Article in English | MEDLINE | ID: mdl-25571593

ABSTRACT

Nowadays, the technologies for detecting, processing and interpreting bioelectrical signals have improved tremendously. In particular, surface electromyography (sEMG) has gained momentum in a wide range of applications in various fields. However, sEMG sensing has several shortcomings, the most important being: measurements are heavily sensible to individual differences, sensors are difficult to position and very expensive. In this paper, the authors will present an innovative muscle contraction sensing device (MC sensor), aiming to replace sEMG sensing in the field of muscle movement analysis. Compared with sEMG, this sensor is easier to position, setup and use, less dependent from individual differences, and less expensive. Preliminary experiments, described in this paper, confirm that MC sensing is suitable for muscle contraction analysis, and compare the results of sEMG and MC sensor for the measurement of forearm muscle contraction.


Subject(s)
Muscle Contraction , Myography/instrumentation , Electromyography , Forearm/physiology , Humans , Male , Muscle, Skeletal/physiology , Myography/economics
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