OBJECTIVE: The current research aimed to synthesize several Schiff base ligands from (3-formyl-4-hydroxyphenyl) methyltriphenylphosphonium (T). Additionally, the current research aimed to study the growth inhibitory effect of triphenylphosphonium containing thiosemicarbazone derivatives on PC-3 cells by deciphering the mechanisms involved in cell death.
METHOD: The compounds were characterized by various spectroscopic methods (infrared spectra, 1H NMR, 13C NMR, HRESIMS and X-ray crystallography) and the results were in conformity with the structure of the targeted compounds. Growth inhibitory effect of the compounds were performed against six human cell lines.
RESULTS: DM(tsc)T displayed most potent activity against PC-3 cells with IC50 value of 2.64 ± 0.33 μM, surpassing that of the positive control cisplatin (5.47 ± 0.06 μM). There were marked morphological changes observed in DM(tsc)T treated cells stained with acridine orange and ethidium bromide which were indicative of cell apoptosis. Treatment with DM(tsc)T showed that the cell cycle is arrested in the G0/G1 phase after 72 hours. Mitochondrial membrane potential loss was observed in cells treated with DM(tsc)T, indicating the apoptosis could be due to mitochondria mediated pathway.
CONCLUSION: This study indicates that DM(tsc)T would serve as a lead scaffold for rational anticancer agent development.
DESIGN: Parallel-group randomised controlled trial with a 1:1 allocation ratio.
SETTING: Two regional tertiary neonatal intensive care units.
PATIENTS: 150 preterm infants less than 35 weeks gestation with birth weight between 1.0 and 1.5 kg were recruited.
INTERVENTIONS: Infants were enrolled to either 2-hourly or 3-hourly interval feeding after randomisation. Blinding was not possible due to the nature of the intervention.
MAIN OUTCOME MEASURES: The primary outcome was time to achieve full enteral feeding (≥100 mL/kg/day). Secondary outcomes include time to regain birth weight, episode of feeding intolerance, peak serum bilirubin levels, duration of phototherapy, episode of necrotising enterocolitis, nosocomial sepsis and gastro-oesophageal reflux.
RESULTS: 72 infants were available for primary outcome analysis in each group as three were excluded due to death-three deaths in each group. The mean time to full enteral feeding was 11.3 days in the 3-hourly group and 10.2 days in the 2-hourly group (mean difference 1.1 days; 95% CI -0.4 to 2.5; p=0.14). The mean time to regain birth weight was shorter in 3-hourly group (12.9 vs 14.8 days, p=0.04). Other subgroup analyses did not reveal additional significant results. No difference in adverse events was found between the groups.
CONCLUSION: 3-hourly feeding was comparable with 2-hourly feeding to achieve full enteral feeding without any evidence of increased adverse events.
TRIAL REGISTRATION NUMBER: ACTRN12611000676910, pre-result.
RESULTS: Inulin decreased (P < 0.05) the average daily enteric H2 S and CH3 SH production by 12.4 and 12.1% respectively. The concentrations of acetate, propionate and butyrate in the large intestinal content were significantly increased (P < 0.05) with inulin treatment, whereas valerate concentration and MGL mRNA expression decreased (P < 0.05). The growth of Lactobacillus, Butyrivibrio, Pseudobutyrivibrio, Bifidobacterium and Clostridium butyricum was stimulated, while that of Desulfovibrio, the dominant SRB, was inhibited, and there was an accumulation of SO42- in the large intestinal content of the inulin-supplemented pigs, suggesting that inulin mitigates H2 S generation from the SO42- reduction pathway by reducing the growth of SRB.
CONCLUSION: The results showed that inulin mitigates CH3 SH generation via three methionine degradation metabolic pathways and H2 S generation from two cysteine degradation metabolic pathways, thus resulting in increased synthesis of these two sulfur-containing amino acids in the pig large intestine. © 2016 Society of Chemical Industry.
MATERIALS AND METHODS: Chondrocyte/agarose constructs were treated with varying concentrations of TNFα (0.1-100 ng/ml) and cultured at 5 and 21 % oxygen tension for 48 h. In separate experiments, constructs were subjected to dynamic compression (15 %) and treated with TNFα (10 ng/ml) and/or L-NIO (1 mM) at 5 and 21 % oxygen tension using an ex vivo bioreactor for 48 h. Markers for catabolic activity (NO, PGE2) and tissue remodelling (GAG, MMPs) were quantified by biochemical assay. ADAMTS-5 and MMP-13 expression were examined by real-time qPCR. 2-way ANOVA and a post hoc Bonferroni-corrected t test were used to analyse data.
RESULTS: TNFα dose-dependently increased NO, PGE2 and MMP activity (all p
METHODS: Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/μL) and oIR (CD4 T-cell count > 500 cells/μL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells.
RESULTS: HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses.
CONCLUSIONS: HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).
CRITICAL ISSUES: While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events.
FUTURE DIRECTIONS: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.
METHODS: A validated IMS CORE Diabetes Model was used to estimate the long-term costs and outcomes. The efficacy parameters were identified and synthesized using a systematic review and meta-analysis. Baseline characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. Costs were expressed in 2014 US Dollars. Outcomes were presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty.
RESULTS: From a societal perspective, treatment with DPP-4 inhibitors yielded more quality-adjusted life years (QALYs) (0.024) at a higher cost (>66,000 Thai baht (THB) or >1,829.27 USD) per person than SFU, resulting in the ICER of >2.7 million THB/QALY (>74,833.70 USD/QALY). The cost-effectiveness results were mainly driven by differences in HbA1c reduction, hypoglycemic events, and drug acquisition cost of DPP-4 inhibitors. At the ceiling ratio of 160,000 THB/QALY (4,434.59 USD/QALY), the probability that DPP-4 inhibitors are cost-effective compared to SFU was less than 10%.
CONCLUSIONS: Compared to SFU, DPP-4 inhibitor monotherapy is not a cost-effective treatment for people with T2DM and CKD in Thailand.
METHODS: We enrolled 1,425 women who had pelvic organ prolapse of POP-Q stage III or IV and had undergone vaginal pelvic reconstructive surgery with or without transvaginal mesh insertion from January 2006 to December 2014. All subjects were required to complete a 72-h voiding diary, and the IIQ-7, UDI-6, POPDI-6 and PISQ-12 questionnaires. Urodynamic study was performed preoperatively and postoperatively.
RESULTS: Of the 1,425 women, 54 were excluded due to incomplete data, and 1,017 of the remaining 1,371 (74.2 %) had transvaginal mesh surgery and 247 (18 %) had concurrent midurethral sling insertion. Of 380 women (27.7 %) with preoperative voiding dysfunction, 37 (9.7 %) continued to have voiding dysfunction postoperatively. Of the remaining 991 women (72.3 %) with normal preoperative voiding function, 11 (1.1 %) developed de novo voiding dysfunction postoperatively. The overall incidence of postoperative voiding dysfunction was 3.5 % (48/1,371). Those with concurrent midurethral sling insertion were at higher risk of developing voiding dysfunction postoperatively (OR 3.12, 95 % CI 1.79 - 5.46, p
METHODS: This article assesses the outcomes and impact of Royal Australasian College of Surgeons (RACS) specialist medical support from 2001 to 2015. Three programmes were designed collaboratively with the Timor-Leste Ministry of Health and Australian Aid. The RACS team began to provide 24/7 resident surgical and anaesthesia services in the capital, Dili, from July 2001. The arrival of the Chinese and Cuban Medical Teams provided a medical workforce, and the Cubans initiated undergraduate medical training for about 1000 nationals both in Cuba and in Timor-Leste, whilst RACS focused on specialist medical training.
RESULTS: Australian Aid provided AUD$20 million through three continuous programmes over 15 years. In the first 10 years over 10 000 operations were performed. Initially only 10% of operations were done by trainees but this reached 77% by 2010. Twenty-one nurse anaesthetists were trained in-country, sufficient to cover the needs of each hospital. Seven Timorese doctors gained specialist qualifications (five surgery, one ophthalmology and one anaesthesia) from regional medical schools in Papua New Guinea, Fiji, Indonesia and Malaysia. They introduced local specialist and family medicine diploma programmes for the Cuban graduates.
CONCLUSIONS: Timor-Leste has developed increasing levels of surgical and anaesthetic self-sufficiency through multi-level collaboration between the Ministry of Health, Universidade Nacional de Timor Lorosa'e, and sustained, consistent support from external donors including Australian Aid, Cuba and RACS.
METHODS: Children aged <18-years scheduled for FB and MDCT were recruited. FB and MDCT were undertaken within 30-min to 7-days of each other. Tracheobronchomalacia (mild, moderate, severe, very severe) diagnosed on FB were independently scored by two pediatric pulmonologists; VB was independently scored by two pairs (each pair = pediatric pulmonologist and radiologist), in a blinded manner.
RESULTS: In 53 children (median age = 2.5 years, range 0.8-14.3) evaluated for airway abnormalities, tracheomalacia was detected in 37 (70%) children at FB. Of these, VB detected tracheomalacia in 20 children, with a sensitivity of 54.1% (95%CI 37.1-70.2), specificity = 87.5% (95%CI 60.4-97.8), and positive predictive value = 90.9% (95%CI 69.4-98.4). The agreement between pediatric pulmonologists for diagnosing tracheomalacia by FB was excellent, weighted κ = 0.8 (95%CI 0.64-0.97); but only fair between the pairs of pediatric pulmonologists/radiologists for VB, weighted κ = 0.47 (95%CI 0.23-0.71). There were 42 cases of bronchomalacia detected on FB. VB had a sensitivity = 45.2% (95%CI 30.2-61.2), specificity = 95.5% (95%CI 94.2-96.5), and positive predictive value = 23.2 (95%CI 14.9-34.0) compared to FB in detecting bronchomalacia.
CONCLUSION: VB cannot replace FB as the gold standard for detecting tracheobronchomalacia in children. However, VB could be considered as an alternative diagnostic modality in children with symptoms suggestive of tracheobronchomalacia where FB is unavailable. Pediatr Pulmonol. 2017;52:480-486. © 2016 Wiley Periodicals, Inc.