Methods: : We utilized data among 1020 infants from a mother-offspring cohort, who were Singapore citizens or permanent residents of Chinese, Malay or Indian ethnicity with homogeneous parental ethnic backgrounds, and did not receive chemotherapy, psychotropic drugs or have diabetes mellitus. Ethnicity was self-reported at recruitment and later confirmed using genotype analysis. Subject-specific BMI curves were fitted to infant BMI data using natural cubic splines with random coefficients to account for repeated measures in each child. We estimated characteristics of the child's BMI peak [age and magnitude at peak, average pre-peak velocity (aPPV)]. Systolic (SBP) and diastolic blood pressure (DBP), BMI, sum of skinfolds (SSF) and fat-mass index (FMI) were measured during a follow-up visit at age 48 months. Weighted multivariable linear regression was used to assess the predictors (maternal BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational age and breastfeeding duration) of infant BMI peak and its associations with outcomes at 48 months. Comparisons between ethnicities were tested using Bonferroni post-hoc correction.
Results: : Of 1020 infants, 80.5% were followed up at the 48-month visit. Mean (SD) BMI, SSF and FMI at 48 months were 15.6 (1.8) kg/m 2 , 16.5 (5.3) mm and 3.8 (1.3) kg/m 2 , respectively. Mean (SD) age at peak BMI was 6.0 (1.6) months, with a magnitude of 17.2 (1.4) kg/m 2 and pre-peak velocity of 0.7 (0.3) kg/m 2 /month. Compared with Chinese infants, the peak occurred later in Malay {B [95% confidence interval (CI): 0.64 mo (0.36, 0.92)]} and Indian infants [1.11 mo (0.76, 1.46)] and was lower in magnitude in Indian infants [-0.45 kg/m 2 (-0.69, -0.20)]. Adjusting for maternal education, BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational-age and breastfeeding duration, higher peak and aPPV were associated with greater BMI, SSF and FMI at 48 months. Age at peak was positively associated with BMI at 48 months [0.15 units (0.09, 0.22)], whereas peak magnitude was associated with SBP [0.17 units (0.05, 0.30)] and DBP at 48 months [0.10 units (0.01, 0.22)]. Older age and higher magnitude at peak were associated with increased risk of overweight at 48 months [Relative Risk (95% CI): 1.35 (1.12-1.62) for age; 1.89 (1.60-2.24) for magnitude]. The associations of BMI peak with BMI and SSF at 48 months were stronger in Malay and Indian children than in Chinese children.
Conclusions: : Ethnic-specific differences in BMI peak characteristics, and associations of BMI peak with early childhood cardio-metabolic markers, suggest an important impact of early BMI development on later metabolic outcomes in Asian populations.
Aim: This study was carried out in order to propose a model to predict regional lymph node metastasis of OSCC using histological parameters such as tumour stage, tumour size, pattern of invasion (POI), differentiation of tumour, and host immune response, together with the expression levels of six biomarkers (periostin, HIF-1α, MMP-9, β-catenin, VEGF-C, and EGFR), and, furthermore, to compare the impact of all these parameters on recurrence and 3 yr and 5 yr survival rates. Materials and Method. Histological materials collected from the archives were used to evaluate histological parameters and immunohistochemical profiles. Standard methods were used for immunohistochemistry and for evaluation of results. Data related to recurrence and survival (3 and 5 years) was also recorded. Clinical data was collected from patients' records.
Results: Male to female ratio was 3 : 1. The commonest site of OSCC was the buccal mucosa, and majority of them were T3 or T4 tumours presented at stage 4. 62.5% of the tumours were well differentiated. Three-year and 5-year survival rates were significantly associated with lymph node metastasis and recurrence. POI was significantly correlated with tumour size, stage, 3-year survival, EGFR, HIF-1α, periostin, and MMP-9 (p < 0.05). Expression of EGFR showed a direct association with metastasis (p < 0.05).
Conclusion: POI, level of differentiation, and expression of EGFR are independent prognostic markers for lymph node metastasis. Therefore, these parameters may help in treatment planning of a clinically negative neck.
Aim: The objective of this research was to investigate the acute effects of tributyltin chloride (TBTCl) on gonads in the adult stage of Artemia salina by use normal histology and immunohistochemistry (IHC) (Caspase 3 and HSP70) to see specific apoptosis markers.
Methods: After exposure of A. salina to different concentrations of TBTCl (25, 50, 100, 200, and 300 ng.l-1), 50 adult A. salina (25 male and 25 female) were selected randomly from each concentration to histologically study the gonads. The gonad tissue was sectioned (5 μm) and some slides were stained with hematoxylin and eosin and others were stained with IHC avidin-biotin complex, and were examined under a light microscope.
Results: The results showed significant differences (p < 0.05) in histological lesions between different concentrations of TBTCl. The histological lesions in the testis and ovary section were undifferentiated cells, degenerating yolk globules, and follicle cells enveloping the oocyte which was then compared with control tissue, and these effects were found to be increased in females more than in males with the highest concentration of TBTCl. Immunohistochemistry (IHC) showed that positive immunostaining was observed in the testis and ovary as brownish deposits to Caspase 3 and HSP70 antibody after exposure to TBTCl, while the testis and ovary section in control tissue had no immunoreactivity to Caspase 3 and HSP70 antibody; these effects were profoundly increased with the highest concentration of TBTCl in females more than in males. Finally, the histological lesions and IHC (Caspase 3 and HSP70) revealed that the apoptosis and immune system stress of A. salina gonad tissue damage in females were more sensitive to TBTCl toxicity as compared to white males.
Conclusion: In general, the present study aimed to observe the effects TBTCl on A. salina gonads by using histological sections and IHC (Caspase 3 and HSP70), which were evaluated for the first time and have been proven to possess an important function in apoptosis marker and immune system stress in Artemia. Finally, the specific mechanisms through which TBTCl affects A. salina Caspase 3 and HSP70 expression need further investigation.
METHODS: Three segments of the whole UC, each 3 cm in length, were identified anatomically as the maternal, middle and fetal segments. The hWJMSCs from the different segments were analyzed via trypan blue exclusion assay to determine the growth kinetics and cell viability, flow cytometry for immunophenotyping and immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR) for expression of stromal cell transcriptional factors. Furthermore, the trilineage differentiation potential (osteogenic, adipogenic and chondrogenic) of these cells was also assessed.
RESULTS: hWJMSCs isolated from the maternal and fetal segments displayed greater viability and possessed a significantly higher proliferation rate compared with cells from the middle segment. Immunophenotyping revealed that hWJMSCs derived from all three segments expressed the MSC markers CD105, CD73, CD90, CD44, CD13 and CD29, as well as HLA-ABC and HLA-DR, but were negative for hematopoietic markers CD14, CD34 and CD45. Analysis of the embryonic markers showed that all three segments expressed Nanog and Oct 3/4, but only the maternal and fetal segments expressed SSEA 4 and TRA-160. Cells from all three segments were able to differentiate into chondrogenic, osteogenic and adipogenic lineages with the middle segments showing much lower differentiation potential compared with the other two segments.
CONCLUSIONS: hWJMSCs derived from the maternal and fetal segments of the UC are a good source of MSCs compared with cells from the middle segment because of their higher proliferation rate and viability. Fetal and maternal segments are the preferred cell source for bone regeneration.
METHODS AND ANALYSIS: In this 12-week randomised double-blinded placebo-controlled trial for the effects of dietary TT supplementation in postmenopausal women, postmenopausal women aged 45 years and older with at least 1 year after menopause and bone mineral density T-score at the spine and/or hip 2.5 or more below the reference values will be randomly assigned to 3 daily supplements: (1) placebo group receiving 860 mg olive oil, (2) low TT group receiving 430 mg of 70% pure TTs (containing 300 mg TT) and (3) high TT group receiving 860 mg of 70% pure TTs (600 mg TT). The primary outcome measure will be urinary N-terminal telopeptide. The secondary outcome measures will be serum bone-specific alkaline phosphatase, receptor activator of nuclear factor-κB ligand, osteoprotegerin, urinary 8-hydroxy-2'-deoxyguanosine and quality of life. At 0, 6 and 12 weeks, the following will be assessed: (1) primary and secondary outcome measures; (2) serum TT and tocopherol concentrations; (3) physical activity and food frequency questionnaires. Liver function will be monitored every 6 weeks for safety. 'Intent-to-treat' principle will be employed for data analysis. A model of repeated measurements with random effect error terms will be applied. Analysis of covariance, χ2 analysis and regression will be used for comparisons.
ETHICS AND DISSEMINATION: This study was approved by the Bioethics Committee of the Texas Tech University Health Sciences Center. The findings of this trial will be submitted to a peer-reviewed journal in the areas of bone or nutrition and international conferences.
TRIAL REGISTRATION NUMBER: NCT02058420; results.
MATERIALS & METHODS: A total of 50 participants with T2DM with peripheral neuropathy were included. Age group of 30-75 years were selected for the study. Participants with a known history of neurological disease, locomotor disability, and pregnancy were excluded from the study. Demographic details of the participants like duration of diabetes mellitus, age, Fasting Blood Glucose, Fasting Insulin, HOMA-IR, Glycated Haemoglobin (HBA1c), Neuropathy and Blood pressure values were noted. We measured Basal Metabolic Rate (BMR) by using Mifflin-St Jeor predictive equation in T2DM with peripheral neuropathy.
RESULTS: The mean age of the participants is 60.16 ± 10.62. The mean duration of T2DM 13.44 ± 11.92. In the present study we found a statistical significant correlation between BMR and HOMA IR (r = 0.913*; p = 0.000), BMR & Fasting blood sugar (FBS) (r = 0.281*; p = 0.048), BMR and Visceral fat (VF) (r = 0.332*; p = 0.018).
CONCLUSION: Basal metabolic rate is correlated to Homa-IR, visceral fat, fasting blood sugar and musculoskeletal mass among T2DM with peripheral neuropathy.
METHODS: Twenty-eight patients with severe TBI (GCS ≤ 8, three patients had initial GCS = 9-10, but rapidly deteriorated to ≤8) were recruited. CSF was collected from admission to day 5 post-injury. TRP, kynurenine (KYN), kynurenic acid (KYNA), QUIN, anthranilic acid (AA) and 3-hydroxyanthranilic acid (3HAA) were measured in CSF. The Glasgow Outcome Scale Extended (GOSE) score was assessed at 6 months post-TBI. Post-mortem brains were obtained from the Australian Neurotrauma Tissue and Fluid Bank and used in qPCR for quantitating expression of KP enzymes (indoleamine 2,3-dioxygenase-1 (IDO1), kynurenase (KYNase), kynurenine amino transferase-II (KAT-II), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilic acid oxygenase (3HAO) and quinolinic acid phosphoribosyl transferase (QPRTase) and IDO1 immunohistochemistry.
RESULTS: In CSF, KYN, KYNA and QUIN were elevated whereas TRP, AA and 3HAA remained unchanged. The ratios of QUIN:KYN, QUIN:KYNA, KYNA:KYN and 3HAA:AA revealed that QUIN levels were significantly higher than KYN and KYNA, supporting increased neurotoxicity. Amplified IDO1 and KYNase mRNA expression was demonstrated on post-mortem brains, and enhanced IDO1 protein coincided with overt tissue damage. QUIN levels in CSF were significantly higher in patients with unfavourable outcome and inversely correlated with GOSE scores.
CONCLUSION: TBI induced a striking activation of the KP pathway with sustained increase of QUIN. The exceeding production of QUIN together with increased IDO1 activation and mRNA expression in brain-injured areas suggests that TBI selectively induces a robust stimulation of the neurotoxic branch of the KP pathway. QUIN's detrimental roles are supported by its association to adverse outcome potentially becoming an early prognostic factor post-TBI.
METHODS: In this study, the chronotherapeutic effect of fisetin on ammonium chloride (AC)-induced hyperammonaemic rats was investigated, to ascertain the time point at which the maximum drug effect is achieved. The anti-hyperammonaemic potential of fisetin (50mg/kg b.w. oral) was analysed when administered to AC treated (100mg/kg b.w. i.p.) rats at 06:00, 12:00, 18:00 and 00:00h. Amelioration of pathophysiological conditions by fisetin at different time points was measured by analysing the levels of expression of liver urea cycle enzymes (carbamoyl phosphate synthetase-I (CPS-I), ornithine transcarbamoylase (OTC) and argininosuccinate synthetase (ASS)), nuclear transcription factor kappaB (NF-κB p65), brain glutamine synthetase (GS) and inducible nitric oxide synthase (iNOS) by Western blot analysis.
RESULTS: Fisetin increased the expression of CPS-I, OTC, ASS and GS and decreased iNOS and NF-κB p65 in hyperammonaemic rats. Fisetin administration at 00:00h showed more significant effects on the expression of liver and brain markers, compared with other time points.
CONCLUSIONS: Fisetin could exhibit anti-hyperammonaemic effect owing to its anti-oxidant and cytoprotective influences. The temporal variation in the effect of fisetin could be due to the (i) chronopharmacological, chronopharmacokinetic properties of fisetin and (ii) modulations in the endogenous circadian rhythms of urea cycle enzymes, brain markers, redox enzymes and renal clearance during hyperammonaemia by fisetin. However, future studies in these lines are necessitated.