Browse publications by year: 2015

Differential cross sections for electron impact excitation of the electronic bands of phenol

Neves RF, Jones DB, Lopes MC, Nixon KL, da Silva GB, Duque HV, et al.

J Chem Phys, 2015 Mar 14;142(10):104305.
PMID: 25770538 DOI: 10.1063/1.4913825

We report results from a joint theoretical and experimental investigation into electron scattering from the important organic species phenol (C6H5OH). Specifically, differential cross sections (DCSs) have been measured and calculated for the electron-impact excitation of the electronic states of C6H5OH. The measurements were carried out at energies in the range 15-40 eV, and for scattered-electron angles between 10° and 90°. The energy resolution of those experiments was typically ∼80 meV. Corresponding Schwinger multichannel method with pseudo-potentials calculations, with and without Born-closure, were also performed for a sub-set of the excited electronic-states that were accessed in the measurements. Those calculations were conducted at the static exchange plus polarisation (SEP)-level using a minimum orbital basis for single configuration interaction (MOBSCI) approach. Agreement between the measured and calculated DCSs was typically fair, although to obtain quantitative accord, the theory would need to incorporate even more channels into the MOBSCI.
Fulltext Evaluation of digital clubbing

Chan CW

Aust Fam Physician, 2015 Mar;44(3):113-6.
PMID: 25770575
MeSH terms: Diagnostic Imaging/methods*; Follow-Up Studies; Humans; Male; Osteoarthropathy, Secondary Hypertrophic/diagnosis*; Review; Young Adult; General Practice/methods*
Fulltext First report of cervicofacial lymphadenitis due to Mycobacterium haemophilum in an immunocompromised adult patient

Atiya N, Sulaiman H, Chong J, Ng KP

J Infect Dev Ctries, 2015 Mar;9(3):313-6.
PMID: 25771471 DOI: 10.3855/jidc.5208

We report the first case of an immunocompromised adult patient presenting with cervicofacial lymphadenitis due to Mycobacterium haemophilum, confirmed using hsp65 gene sequencing and line-probe assays. In resource-limited settings, especially in developing countries, appropriate culture methods and rapid molecular diagnostic tools such as hsp65 gene sequencing for identification of this organism may not be readily available. This may cause M. haemophilum infections to go unrecognised or lead to delays in diagnosis. Lack of heightened awareness about the potential for this mycobacterial species to cause infections may also contribute to possible underestimation of M. haemophilum cases in the developing world.

MeSH terms: Adult; Bacterial Proteins/genetics; DNA, Bacterial/genetics; Face/pathology*; Female; Humans; Lymphadenitis/diagnosis*; Lymphadenitis/microbiology*; Lymphadenitis/pathology; Mycobacterium Infections/diagnosis*; Mycobacterium Infections/microbiology*; Mycobacterium Infections/pathology; Neck/pathology*; Immunocompromised Host; Mycobacterium haemophilum/isolation & purification*; Chaperonin 60/genetics; Molecular Diagnostic Techniques
Study of the Behaviors of Gunshot Residues from Spent Cartridges by Headspace Solid-Phase Microextraction-Gas Chromatographic Techniques

Chang KH, Yew CH, Abdullah AF

J Forensic Sci, 2015 Jul;60(4):869-77.
PMID: 25771708 DOI: 10.1111/1556-4029.12745

Gunshot residues, produced after shooting activity, have acquired their importance in analysis due to the notoriety of firearms-related crimes. In this study, solid-phase microextraction was performed to extract the headspace composition of spent cartridges using 85-μm polyacrylate fiber at 66°C for 21 min. Organic compounds, that is, naphthalene, 2,6-dinitrotoluene, 2,4-dinitrotoluene, diphenylamine, and dibutyl phthalate were detected and analyzed by gas chromatography-flame ionization detection technique. Evaluation of chromatograms for diphenylamine, dibutyl phthalate, and naphthalene indicates the period after a gunshot was discharged, whether it was 1 days, 2-4 days, <5 days, 10 days, 20 days, or more than 30 days ago. This study revealed the potential effects of environmental factors such as occasional wind blow and direct sunlight on the estimation of time after spent cartridges were discharged. In conclusion, we proposed reliable alternative in analyzing the headspace composition of spent cartridges in a simulated crime scene.

MeSH terms: Crime; Dibutyl Phthalate; Dinitrobenzenes; Diphenylamine; Firearms; Flame Ionization; Humans; Naphthalenes; Patient Discharge; Plant Extracts; Sunlight; Wind; Solid Phase Microextraction
Fulltext Cloning and serotonergic regulation of RING finger protein38 (rnf38) in the brain of medaka (Oryzias latipes)

Moriya S, Khel NB, Parhar IS

Neuroscience, 2015 May 21;294:109-15.
PMID: 25772790 DOI: 10.1016/j.neuroscience.2015.03.012

Serotonin (5-HT) is a key regulator of mood and sexual behaviors. 5-HT reuptake inhibitors have been used as antidepressants. Really interesting new gene (RING) finger proteins have been associated with 5-HT regulation but their role remains largely unknown. Some RING finger proteins are involved in the serotonergic system, therefore, we speculate that the gene expression of RING finger protein38 (rnf38) is regulated by the serotonergic system. In the present study, we aimed to identify the full length sequence of medaka (Oryzias latipes) rnf38 mRNA and investigate its association with the serotonergic system using an antidepressant, citalopram (CIT). We identified the full length rnf38 cDNA, which consisted of 2726 nucleotides spanning 12 exons and the deduced protein sequence consisting of 518 amino acid residues including a RING finger domain, a KIT motif and a coiled-coil domain. Medaka exposed to 10(-7)M of CIT showed anxiety-like behavior. The expressions of 5-HT-related genes, pet1, solute carrier family 6, member 4A (slc6a4) and tryptophan hydroxylase (tph2) were significantly low (P<0.05) in the hindbrain. On the other hand, rnf38 gene was significantly high (P<0.05) in the telencephalon and the hypothalamus. This shows that 5-HT synthesis and transport in the hindbrain is suppressed by CIT, which induces rnf38 gene expression in the forebrain where 5-HT neurons project. Thus, the expression of rnf38 is negatively regulated by the serotonergic system.

MeSH terms: Animals; Brain/metabolism*; Carrier Proteins/genetics; Carrier Proteins/metabolism*; Cloning, Molecular/methods; Male; Neurons/metabolism*; Oryzias; RNA, Messenger; Serotonin/metabolism*; Tryptophan Hydroxylase/metabolism; Citalopram/pharmacology; Gene Expression/physiology; Zinc Fingers
Prognostic factors in patients with non-small cell lung carcinoma and brain metastases: a Malaysian perspective

Tang WH, Alip A, Saad M, Phua VC, Chandran H, Tan YH, et al.

Asian Pac J Cancer Prev, 2015;16(5):1901-6.
PMID: 25773842

BACKGROUND: Brain metastases occur in about 20-40% of patients with non-small-cell lung carcinoma (NSCLC), and are usually associated with a poor outcome. Whole brain radiotherapy (WBRT) is widely used but increasingly, more aggressive local treatments such as surgery or stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) are being employed. In our study we aimed to describe the various factors affecting outcomes in NSCLC patients receiving local therapy for brain metastases.
MATERIALS AND METHODS: The case records of 125 patients with NSCLC and brain metastases consecutively treated with radiotherapy at two tertiary centres from January 2006 to June 2012 were analysed for patient, tumour and treatment-related prognostic factors. Patients receiving SRS/SRT were treated using Cyberknife. Variables were examined in univariate and multivariate testing.
RESULTS: Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median survival for patients with multiple metastases receiving WBRT was 1.5 months, 1-3 metastases receiving WBRT was 3.6 months and 1-3 metastases receiving surgery or SRS/SRT was 8.9 months. ECOG score (≤2 vs >2, p=0.001), presence of seizure (yes versus no, p=0.031), treatment modality according to number of brain metastases (1-3 metastases+surgery or SRS/SRT±WBRT vs 1-3 metastases+WBRT only vs multiple metastases+WBRT only, p=0.007) and the use of post-therapy systemic treatment (yes versus no, p=0.001) emerged as significant on univariate analysis. All four factors remained statistically significant on multivariate analysis.
CONCLUSIONS: ECOG ≤2, presence of seizures, oligometastatic disease treated with aggressive local therapy (surgery or SRS/SRT) and the use of post-therapy systemic treatment are favourable prognostic factors in NSCLC patients with brain metastases.

MeSH terms: Aged; Brain/pathology; Brain Neoplasms/mortality; Brain Neoplasms/radiotherapy*; Brain Neoplasms/secondary; Carcinoma, Non-Small-Cell Lung/mortality; Carcinoma, Non-Small-Cell Lung/pathology*; Carcinoma, Non-Small-Cell Lung/therapy; Combined Modality Therapy; Female; Humans; Lung Neoplasms/mortality; Lung Neoplasms/pathology*; Lung Neoplasms/therapy; Malaysia; Male; Retrospective Studies; Radiosurgery; Treatment Outcome
A novel computer-aided multivariate water quality index

Sim SF, Ling TY, Lau S, Jaafar MZ

Environ Monit Assess, 2015 Apr;187(4):181.
PMID: 25773897 DOI: 10.1007/s10661-015-4416-7

A computer-aided multivariate water quality index is developed based on partial least squares (PLS) regression. The index is termed as the partial least squares water quality index (PLS-WQI). Briefly, a training set was computationally generated based on the guideline of National Water Quality Standards for Malaysia (NWQS) to predict the water quality. The index is benchmarked with the well-established index developed by the Department of Environment, Malaysia (DOE-WQI). The PLS-WQI is a continuous variable with the value closer to I indicating good water quality and closer to V indicating poor water quality. Unlike other conventional indexing methods, the algorithm calculates the index in a multivariate manner. The algorithm allows rapid processing of a large dataset without tedious calculation; it can be an efficient tool for spatial and temporal routine monitoring of water quality. Although the algorithm is designed based on the guideline of NWQS, it can be easily adapted to accommodate other guidelines. The algorithm was evaluated and demonstrated on the simulated and real datasets. Results indicate that the algorithm is robust and reliable. Based on six parameters, the overall ratings derived are inversely correlated to DOE-WQI. When the number of parameter is increased, the overall ratings appear to provide better insights into the water quality.

MeSH terms: Computer Simulation*; Environmental Monitoring/methods*; Malaysia; Water Pollutants/standards*; Water Pollution/statistics & numerical data*; Water Quality/standards
Fulltext A qualitative exploration of the perspectives of mental health professionals on stigma and discrimination of mental illness in Malaysia

Hanafiah AN, Van Bortel T

Int J Ment Health Syst, 2015;9:10.
PMID: 25774215 DOI: 10.1186/s13033-015-0002-1

Stigma of mental illness has been identified as a significant barrier to help-seeking and care. Basic knowledge of mental illness - such as its nature, symptoms and impact - are neglected, leaving room for misunderstandings on mental health and 'stigma'. Numerous researches have been conducted on stigma and discrimination of people with mental disorders. However, most of the literature investigates stigma from a cultural conception point of view, experiences of patients or public attitudes towards mental illness but little to none from the standpoint of mental health professionals. In Malaysia, this research on stigma is particularly limited. Therefore, the state of stigma and discrimination of people with mental illness was investigated from the perspectives of mental health professionals in Malaysia.
Fulltext Comprehensive SDG goal and targets for non-communicable diseases and mental health

Minas H, Tsutsumi A, Izutsu T, Goetzke K, Thornicroft G

Int J Ment Health Syst, 2015;9:12.
PMID: 25774216 DOI: 10.1186/s13033-015-0003-0

The negotiations on the SDG goals and targets, leading to the sustainable development Declaration in September 2015, are now in the final stages. Ensuring that people with mental disorders are not left behind in the global development program from 2015 to 2030 will require specific and explicit commitments and targets against which progress in mental health can be measured and reported. The arguments for inclusion of explicit mental health targets in the SDGs are compelling. The final negotiations on the SDG goals and targets will now determine whether people with mental illness and psychosocial disabilities will continue to be neglected or will benefit equitably from inclusion in the post-2015 development program.

MeSH terms: Mental Disorders; Compulsive Behavior; Goals; Disabled Persons; Humans; Mental Health; Negotiating; Dissent and Disputes
Fulltext "Functionally" univentricular hearts: impact of pre-natal diagnosis

Corno AF

Front Pediatr, 2015;3:15.
PMID: 25774365 DOI: 10.3389/fped.2015.00015

Within the last few decades the pre-natal echocardiographic diagnosis of congenital heart defects has made substantial progresses, particularly for the identification of complex malformation. "Functionally" univentricular hearts categorize a huge variety of heart malformations. Since no one of the patients with these congenital heart defects can ever undergo a bi-ventricular type of repair, early recognition and decision-making from the neonatal period are required in order to allow for appropriate multiple-step diagnostic and treatment procedures, either of interventional cardiology and/or surgery, on the pathway of "univentricular" heart. In the literature strong disagreements exist about the potential impact of the pre-natal diagnosis on the early and late outcomes of complex congenital heart defects. This review of the recent reports has been undertaken to better understand the impact of pre-natal diagnosis in "functionally" univentricular hearts taking into consideration the following topics: pre-natal screening, outcomes and survival, general morbidity, neurologic and developmental consequences, pregnancy management and delivery planning, resources utilization and costs/benefits issues, ethical implications, parents counseling, and interruption of pregnancy versus treatment.
Fulltext Compound-specific isotope analysis of diesel fuels in a forensic investigation

Muhammad SA, Frew RD, Hayman AR

Front Chem, 2015;3:12.
PMID: 25774366 DOI: 10.3389/fchem.2015.00012

Compound-specific isotope analysis (CSIA) offers great potential as a tool to provide chemical evidence in a forensic investigation. Many attempts to trace environmental oil spills were successful where isotopic values were particularly distinct. However, difficulties arise when a large data set is analyzed and the isotopic differences between samples are subtle. In the present study, discrimination of diesel oils involved in a diesel theft case was carried out to infer the relatedness of the samples to potential source samples. This discriminatory analysis used a suite of hydrocarbon diagnostic indices, alkanes, to generate carbon and hydrogen isotopic data of the compositions of the compounds which were then processed using multivariate statistical analyses to infer the relatedness of the data set. The results from this analysis were put into context by comparing the data with the δ(13)C and δ(2)H of alkanes in commercial diesel samples obtained from various locations in the South Island of New Zealand. Based on the isotopic character of the alkanes, it is suggested that diesel fuels involved in the diesel theft case were distinguishable. This manuscript shows that CSIA when used in tandem with multivariate statistical analysis provide a defensible means to differentiate and source-apportion qualitatively similar oils at the molecular level. This approach was able to overcome confounding challenges posed by the near single-point source of origin, i.e., the very subtle differences in isotopic values between the samples.

MeSH terms: Alkanes; Carbon; Gasoline; Hydrocarbons; Hydrogen; Isotopes; New Zealand; Oils; Theft; Multivariate Analysis; Petroleum Pollution
Fulltext Tualang honey improves memory performance and decreases depressive-like behavior in rats exposed to loud noise stress

Azman KF, Zakaria R, AbdAziz C, Othman Z, Al-Rahbi B

Noise Health, 2015 Mar-Apr;17(75):83-9.
PMID: 25774610 DOI: 10.4103/1463-1741.153388

Recent evidence has exhibited dietary influence on the manifestation of different types of behavior induced by stressor tasks. The present study examined the effects of Tualang honey supplement administered with the goal of preventing or attenuating the occurrence of stress-related behaviors in male rats subjected to noise stress. Forty-eight adult male rats were randomly divided into the following four groups: i) nonstressed with vehicle, ii) nonstressed with Tualang honey, iii) stressed with vehicle, and iv) stressed with honey. The supplement was given once daily via oral gavage at 0.2 g/kg body weight. Two types of behavioral tests were performed, namely, the novel object recognition test to evaluate working memory and the forced swimming test to evaluate depressive-like behavior. Data were analyzed by a two-way analysis of variance (ANOVA) using IBM SPSS 18.0. It was observed that the rats subjected to noise stress expressed higher levels of depressive-like behavior and lower memory functions compared to the unexposed control rats. In addition, our results indicated that the supplementation regimen successfully counteracted the effects of noise stress. The forced swimming test indicated that climbing and swimming times were significantly increased and immobility times significantly decreased in honey-supplemented rats, thereby demonstrating an antidepressant-like effect. Furthermore, cognitive function was shown to be intensely affected by noise stress, but the effects were counteracted by the honey supplement. These findings suggest that subchronic exposure to noise stress induces depressive-like behavior and reduces cognitive functions, and that these effects can be attenuated by Tualang honey supplementation. This warrants further studies to examine the role of Tulang honey in mediating such effects.

MeSH terms: Animals; Behavior, Animal*; Depression*; Honey*; Male; Memory; Memory, Short-Term*; Noise*; Stress, Psychological*; Rats, Sprague-Dawley; Rats
Fulltext Trial of everolimus-eluting stents or bypass surgery for coronary disease

Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, et al.

N Engl J Med, 2015 Mar 26;372(13):1204-12.
PMID: 25774645 DOI: 10.1056/NEJMoa1415447

BACKGROUND: Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents.
METHODS: We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups.
RESULTS: After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG.
CONCLUSIONS: Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).

MeSH terms: Everolimus; Aged; Coronary Artery Bypass*; Coronary Artery Disease/surgery; Coronary Artery Disease/therapy*; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction/epidemiology; Myocardial Infarction/prevention & control; Postoperative Complications; Prospective Studies; Sirolimus/administration & dosage; Sirolimus/analogs & derivatives*; Stroke/epidemiology; Coronary Restenosis/epidemiology; Diabetes Complications/therapy; Kaplan-Meier Estimate; Drug-Eluting Stents*; Percutaneous Coronary Intervention*
Fulltext Non-protein coding RNA genes as the novel diagnostic markers for the discrimination of Salmonella species using PCR

Nithya R, Ahmed SA, Hoe CH, Gopinath SC, Citartan M, Chinni SV, et al.

PLoS One, 2015;10(3):e0118668.
PMID: 25774907 DOI: 10.1371/journal.pone.0118668

Salmonellosis, a communicable disease caused by members of the Salmonella species, transmitted to humans through contaminated food or water. It is of paramount importance, to generate accurate detection methods for discriminating the various Salmonella species that cause severe infection in humans, including S. Typhi and S. Paratyphi A. Here, we formulated a strategy of detection and differentiation of salmonellosis by a multiplex polymerase chain reaction assay using S. Typhi non-protein coding RNA (sRNA) genes. With the designed sequences that specifically detect sRNA genes from S. Typhi and S. Paratyphi A, a detection limit of up to 10 pg was achieved. Moreover, in a stool-seeding experiment with S. Typhi and S. Paratyphi A, we have attained a respective detection limit of 15 and 1.5 CFU/mL. The designed strategy using sRNA genes shown here is comparatively sensitive and specific, suitable for clinical diagnosis and disease surveillance, and sRNAs represent an excellent molecular target for infectious disease.

MeSH terms: Amino Acid Sequence; Feces/microbiology; Genes, Bacterial; Humans; Molecular Sequence Data; Nucleic Acid Conformation; Salmonella/genetics*; Salmonella/isolation & purification; Salmonella/chemistry; Salmonella Infections/diagnosis*; Salmonella Infections/microbiology*; Salmonella paratyphi A/genetics; Salmonella paratyphi A/isolation & purification; Salmonella paratyphi A/chemistry; Salmonella typhi/genetics; Salmonella typhi/isolation & purification; Salmonella typhi/chemistry; Sensitivity and Specificity; RNA, Untranslated/genetics*; RNA, Untranslated/isolation & purification; RNA, Untranslated/chemistry; Multiplex Polymerase Chain Reaction/methods*
Fulltext Effective equine immunization protocol for production of potent poly-specific antisera against Calloselasma rhodostoma, Cryptelytrops albolabris and Daboia siamensis

Sapsutthipas S, Leong PK, Akesowan S, Pratanaphon R, Tan NH, Ratanabanangkoon K

PLoS Negl Trop Dis, 2015 Mar;9(3):e0003609.
PMID: 25774998 DOI: 10.1371/journal.pntd.0003609

Snake envenomation has been estimated to affect 1.8 million people annually with about 94,000 deaths mostly in poor tropical countries. Specific antivenoms are the only rational and effective therapy for these cases. Efforts are being made to produce effective, affordable and sufficient antivenoms for these victims. The immunization process, which has rarely been described in detail, is one step that needs to be rigorously studied and improved especially with regard to the production of polyspecific antisera. The polyspecific nature of therapeutic antivenom could obviate the need to identify the culprit snake species. The aim of this study was to produce potent polyspecific antisera against 3 medically important vipers of Thailand and its neighboring countries, namely Cryptelytrops albolabris "White lipped pit viper" (CA), Calleoselasma rhodostoma "Malayan pit viper" (CR), and Daboia siamensis "Russell's viper" (DS). Four horses were immunized with a mixture of the 3 viper venoms using the 'low dose, low volume multi-site' immunization protocol. The antisera showed rapid rise in ELISA titers against the 3 venoms and reached plateau at about the 8th week post-immunization. The in vivo neutralization potency (P) of the antisera against CA, CR and DS venoms was 10.40, 2.42 and 0.76 mg/ml, respectively and was much higher than the minimal potency limits set by Queen Soavabha Memorial Institute (QSMI). The corresponding potency values for the QSMI monospecific antisera against CA, CR and DS venoms were 7.28, 3.12 and 1.50 mg/ml, respectively. The polyspecific antisera also effectively neutralized the procoagulant, hemorrhagic, necrotic and nephrotoxic activities of the viper venoms. This effective immunization protocol should be useful in the production of potent polyspecific antisera against snake venoms, and equine antisera against tetanus, diphtheria or rabies.

MeSH terms: Animals; Antivenins/biosynthesis*; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Horses; Immune Sera/biosynthesis*; Immunization*; Lethal Dose 50; Thailand; Viper Venoms/immunology*; Mice
Fulltext DACH1, a zona glomerulosa selective gene in the human adrenal, activates transforming growth factor-β signaling and suppresses aldosterone secretion

Zhou J, Shaikh LH, Neogi SG, McFarlane I, Zhao W, Figg N, et al.

Hypertension, 2015 May;65(5):1103-10.
PMID: 25776071 DOI: 10.1161/HYP.0000000000000025

Common somatic mutations in CACNAID and ATP1A1 may define a subgroup of smaller, zona glomerulosa (ZG)-like aldosterone-producing adenomas. We have therefore sought signature ZG genes, which may provide insight into the frequency and pathogenesis of ZG-like aldosterone-producing adenomas. Twenty-one pairs of zona fasciculata and ZG and 14 paired aldosterone-producing adenomas from 14 patients with Conn's syndrome and 7 patients with pheochromocytoma were assayed by the Affymetrix Human Genome U133 Plus 2.0 Array. Validation by quantitative real-time polymerase chain reaction was performed on genes >10-fold upregulated in ZG (compared with zona fasciculata) and >10-fold upregulated in aldosterone-producing adenomas (compared with ZG). DACH1, a gene associated with tumor progression, was further analyzed. The role of DACH1 on steroidogenesis, transforming growth factor-β, and Wnt signaling activity was assessed in the human adrenocortical cell line, H295R. Immunohistochemistry confirmed selective expression of DACH1 in human ZG. Silencing of DACH1 in H295R cells increased CYP11B2 mRNA levels and aldosterone production, whereas overexpression of DACH1 decreased aldosterone production. Overexpression of DACH1 in H295R cells activated the transforming growth factor-β and canonical Wnt signaling pathways but inhibited the noncanonical Wnt signaling pathway. Stimulation of primary human adrenal cells with angiotensin II decreased DACH1 mRNA expression. Interestingly, there was little overlap between our top ZG genes and those in rodent ZG. In conclusion, (1) the transcriptome profile of human ZG differs from rodent ZG, (2) DACH1 inhibits aldosterone secretion in human adrenals, and (3) transforming growth factor-β signaling pathway is activated in DACH1 overexpressed cells and may mediate inhibition of aldosterone secretion in human adrenals.

MeSH terms: Aldosterone/secretion*; Eye Proteins/biosynthesis; Eye Proteins/genetics*; Female; Humans; Immunohistochemistry; Male; Middle Aged; RNA, Neoplasm/genetics*; Transcription Factors/biosynthesis; Transcription Factors/genetics*; Tumor Cells, Cultured; Zona Glomerulosa/metabolism*; Zona Glomerulosa/pathology; Signal Transduction; Gene Expression Regulation, Neoplastic*; Transforming Growth Factor beta/biosynthesis; Transforming Growth Factor beta/genetics*; Adrenocortical Carcinoma/genetics*; Adrenocortical Carcinoma/metabolism; Adrenocortical Carcinoma/pathology; Disease Progression; Real-Time Polymerase Chain Reaction
The effect of immune status, age and genetic background on induction of oral tolerance to Actinomyces viscosus in mice

Sosroseno W, Herminajeng E, Bird P

Biomed Pharmacother, 2015 Mar;70:294-8.
PMID: 25776514 DOI: 10.1016/j.biopha.2014.12.039

The aim of the present study was to determine the effect of immune status, age and genetic background on the induction of oral tolerance to Actinomyces viscosus. Suppression of delayed type hypersensitivity (DTH) response and antigen-specific serum antibody levels could be induced in DBA/2 mice intragastrically and systemically immunized with A. viscocus, suggesting the induction of oral tolerance. In contrast, this immune suppression could be abrogated if the animals had been systemically immunized prior to the induction of oral tolerance with the same bacterium. Long-term systemic immunization prior to intragastric immunization with A. viscocus suppressed DTH response only. Cell transfer of this group of animals also suppressed DTH response in the donors, indicating the action of suppressor cells for inhibition of DTH response. Furthermore, oral tolerance to A. viscocus failed to occur in mice aged at 3 days and 1, 2, 4, 6 and 36 weeks old. Mice bearing H-2(d) haplotype were the most susceptible to oral tolerization, followed by H-2(b) and H-2(k). Therefore, the results of the presence study suggest that the induction of oral tolerance to A. viscosus in mice may be dependence on the immune status and genetic background but not age.

MeSH terms: Genetic Background*; Administration, Oral; Age Factors; Animals; Female; Immune Tolerance/genetics*; Immune Tolerance/immunology*; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Mouth Mucosa/immunology*; Mouth Mucosa/microbiology*; Species Specificity; Actinomyces viscosus*; Mice
Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells

Basar N, Oridupa OA, Ritchie KJ, Nahar L, Osman NM, Stafford A, et al.

Phytother Res, 2015 Jun;29(6):944-8.
PMID: 25779384 DOI: 10.1002/ptr.5329

Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is a well-known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet-tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra.

MeSH terms: Adenocarcinoma/pathology; Flavonoids/pharmacology*; Flavonoids/chemistry; Geography; Glycyrrhiza/chemistry*; Carcinoma, Hepatocellular/pathology; Humans; Liver Neoplasms/pathology; Lung Neoplasms/pathology; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Saponins/pharmacology*; Saponins/chemistry; Triterpenes/pharmacology*; Triterpenes/chemistry; Molecular Structure; Keratinocytes/drug effects*; Plant Roots/chemistry; Inhibitory Concentration 50; Cell Line, Tumor/drug effects
Fulltext Diabetes and onset of natural menopause: results from the European Prospective Investigation into Cancer and Nutrition

Brand JS, Onland-Moret NC, Eijkemans MJ, Tjønneland A, Roswall N, Overvad K, et al.

Hum Reprod, 2015 Jun;30(6):1491-8.
PMID: 25779698 DOI: 10.1093/humrep/dev054

STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes?
SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause.
WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health.
STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale.
MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM.
LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes.
WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association.
STUDY FUNDING/COMPETING INTERESTS: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). None of the authors reported a conflict of interest.

MeSH terms: Adult; Europe/epidemiology; Female; Humans; Menopause*; Middle Aged; Cohort Studies; Diabetes Complications*
Fulltext Closed reduction of traumatic bilateral anterior hip dislocations with sedation: a case report and review of the literature

Chiu CK, Ng TS, Wazir NN, Bhurhanudeen KA

Ulus Travma Acil Cerrahi Derg, 2015 Jan;21(1):63-7.
PMID: 25779715 DOI: 10.5505/tjtes.2015.27475

A rare case of bilateral anterior hip dislocation reduced under sedation was reported in this study. A 47-year-old man was knocked down by a car and sustained bilateral anterior hip dislocation which was reduced successfully with sedation using titrated dose of intravenous Midazolam in combination with Pethidine. A modified Lefkowitz maneuver using the manipulator's thigh as a fulcrum was used. Patient started weight bearing in the second month after injury and was walking without any hip pain at the twenty-fourth month follow-up. Thirteen case reports describing bilateral anterior hip dislocations were found while reviewing the literature and it was noticed that only one author had reported the usage of intravenous sedation (Propofol) for the reduction procedure. However, no author reported the use of Lefkowitz maneuver for this purpose. Consequently, reduction of a bilateral anterior hip dislocation is possible with sedation using a modified Lefkowitz maneuver.

MeSH terms: Accidents, Traffic; Analgesics, Opioid/administration & dosage*; Diagnosis, Differential; Hip Dislocation/diagnosis; Hip Dislocation/radiography; Hip Dislocation/surgery*; Humans; Infusions, Intravenous; Male; Meperidine/administration & dosage*; Middle Aged; Orthopedic Procedures/methods

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