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Abstract

Background

The arylidene indanone scaffold has contributed many lead molecules in chemotherapeutic anticancer agent research.

Objectives

To determine the oxidant-scavenging activities and antiproliferative activity of (2E)-2-benzylidene-4,7-dimethyl-2,3-dihydro-1H-inden-1-one (MLT-401), an arylidene indanone derivative.

Methods

Jurkat cells, primary lymphocytes, and Vero cells were treated with MLT-401. Antioxidant properties of MLT-401 were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS)-based, and ferric-reducing antioxidant potential (FRAP) assays. Inhibition of cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based assay. Nuclear status was determined using a DNA fragmentation assay, and cell cycle stage was analyzed by flow cytometry. Mitochondrial membrane enzyme activities were measured using colorimetric methods.

Results

The antioxidant assays gave MLT-401 half maximal inhibitory concentration (IC50) values of 1611 nM (DPPH-based assay), 2115 nM (ABTS-based assay), and 1586 nM (FRAP assay). MLT-401 inhibited proliferation of Jurkat cells with a concentration for 50% of maximal inhibition of cell proliferation (GI50) of 341.5 nM, being 12- and 9-fold less than GI50 concentrations for normal lymphocytes and Vero cells, respectively. MLT-401 caused nuclear fragmentation and DNA laddering as seen by electrophoresis. Jurkat cells showed a time-dependent accumulation of sub G0/G1 cells after MLT-401 treatment. Mitochondrial membrane-bound Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase activities were inhibited by MLT-401 in a dose-dependent manner.

Conclusion

MLT-401 possesses significant antiproliferative activity and scavenges free radicals released through mitochondrial membrane damage in a Jurkat cell line model of cancer cells. Further investigation of MLT-401 as a chemotherapeutic anticancer agent and development of other arylidene indanone analogues are warranted. A detailed elucidation of mechanistic pathways is required for further development.

Abstract

Background

Serum starvation is mostly considered as a standard preparatory method in many cellular and molecular experiments. However, recent studies give some evidence that serum starvation is a major event that triggers various cell responses and has therefore great potential to change and interfere with the experimental results. In this study, the behavior of breast cancer cells in serum-starved condition was examined.

Objective

To focus on the role of serum starvation on cell migration and also the possible changes in the expression and secretion of genes and cytokines mostly involved in migration and chemotaxis of breast cancer cells.

Methods

MDA-MB-231 cells were cultured under serum-starved condition. Transwell migration assay was performed to evaluate the effect of serum starvation on cell migration after 24, 48, and 72 h. The transcriptional expression of migration-related genes was evaluated using real-time polymerase chain reaction. The cytokine secretion was also analyzed using enzyme-linked immunosorbent assay.

Results

Serum starvation suppressed cell migration in breast cancer cells. Additionally, the gene expression of markers involved in migration including β-catenin, twist, zinc finger E-box binding homeobox 1, vimentin, fibronectin, intercellular adhesion molecule 1, and vascular endothelial growth factor were downregulated. Moreover, cytokines of transforming growth factor, beta 1, matrix metallopeptidase 9, interleukin 8, and nitric oxide were differentially secreted.

Conclusions

Serum deprivation causes significant changes in cancer cell migration and also the expression of migration-related genes and cytokines, special care needs to be taken when this practice is used as preparatory method especially in migration and chemotaxis experiments on cancer cells.

Abstract

Background

Multidrug-resistant bacteria are becoming more hazardous day by day for human health all over the world, and the scientific community is trying hard to resolve this issue by various approaches. One of the very common approaches is to bind drugs to nanoparticles and study enhanced antibacterial properties.

Objective

To compare simultaneously different types of nanoparticles, their concentration, bacterial strains and their incubation time intervals for each of the selected drug combination.

Methods

We have selected the most commonly used gold and silver nanoparticles and few examples from fluoroquinolone antibiotics to make their conjugates and study their efficacy against multidrug-resistant E. coli and S. aureus strains simultaneously, at different incubation time intervals and different concentration of nanoparticles.

Results

Gold nanoparticle hybrids do not show any significant effect. Silver nanoparticle hybrids show far better results, even at extremely low concentrations.

Conclusions

This unique and simple approach allows us to know the exact time intervals and concentration required for each nanoparticle combination to control the growth for any specific strain. This approach can be extended to any set of nanoparticles, drugs and bacterial strains for comparative purposes.

Abstract

Background

Simulation is widely used in airway management training.

Objectives

To show that assigning anesthesia residents’ simulation educator roles improved cognitive learning outcomes.

Methods

Postgraduate second- and third-year (PGY-2 and PGY-3) anesthesia residents were randomly assigned to three groups: a teacher group (T), a hot-seat (active participant) group (H), and an observer group (O). After a train-the-trainer session, the T group prepared simulation scenarios for difficult airway management and then conducted the simulation sessions and post-session debriefing. The H group participated in the scenarios, and the O group observed the sessions. All participants attended the post-session debriefing. Evaluation was conducted at pretest, immediate posttest, and 3 months (retention test). Score differentiation and average normalized gain were calculated. Participants completed a post-simulation class survey.

Results

Participants were 49 residents (PGY-2 = 24, PGY-3 = 25). The T group had the highest posttest score (17.06 ± 1.23); this score significantly differed from the O group (14.75 ± 2.57, P = 0.003) but not the H group (15.64 ± 1.54, P = 0.103). The average normalized gain was significantly higher in the T group than in the H and O groups (0.51 ± 0.22, 0.18 ± 0.32, and 0.17 ± 0.47, respectively; P = 0.012). Participants retained knowledge at 3 months after the session, with no significant differences among the groups. Most participants (45%) preferred to be active scenario participants, and 20% preferred to teach. Overall satisfaction was high in all groups.

Conclusion

This study showed that a teaching role can be effectively applied for residents in simulation-based education on difficult airway management to support better learning outcomes.

Abstract

Background

Acute liver failure (ALF) is a rare condition during neonatal period.

Objective

To report a case of recipient twin with fulminant ALF secondary to hydrops fetalis caused by twin-to-twin transfusion syndrome (TTTS).

Method

The patient was admitted to the neonatal intensive care unit (NICU) for respiratory failure requiring mechanical ventilation and fulminant ALF with prolonged international normalized ratio (INR) and elevated liver enzymes with highest aspartate aminotransferase of 4,580 U/L.

Results

Laboratory investigation for secondary causes of liver failure was not revealing. Her liver enzymes and coagulation levels were dramatically normalized as the clinical symptoms of hypervolemia improved within 1 week.

Conclusion

TTTS can be a possible cause of neonatal ALF. Early detection with proper management of TTTS is important to avoid adverse outcomes. However, pathogenesis of hepatic dysfunction in TTTS is rarely described, and further studies are needed to help understanding the correlation between liver diseases and TTTS.

Abstract

Background

Subclinical hypothyroidism (SCH) might have many symptoms of hypothyroidism. The controversy appears to lower the level of thyroid-stimulating hormone (TSH) and group subjects with TSH of more than 3 or even 2.5 mIU/L as SCH subjects.

Objectives

To assess SCH subjects both clinically using Zulewski clinical score and biochemically and to evaluate whether the euthyroid subjects with high-normal TSH (HNT) have any clinical symptom or subnormal biochemical finding.

Methods

A prospective cross-sectional study of 233 subjects, 67 with SCH and 166 euthyroidism, was conducted. Euthyroid subjects were divided according to the level of TSH as HNT (>2.5 mIU/L) and low-normal TSH (0.5–2.5 mIU/L). The subjects were examined for clinical feature including Zulewski clinical score and biochemical evaluations including thyroid peroxidase antibody (TPO-Ab) titer. The comparisons between groups were assessed using independent sample t test, and correlations between variables were evaluated using Pearson correlation.

Results

A significantly higher clinical score and higher frequencies of symptoms were found in the SCH group compared to the euthyroid group. The most frequent symptom was fatigue. Euthyroid subjects with HNT were found to have higher TPO-Ab titers than those with low-normal TSH, P < 0.05. The Zulewski clinical score was positively correlated with TSH and TPO-Ab titer but negatively correlated with the FT4 level, P < 0.05.

Conclusions

Zulewski clinical score is higher in SCH subjects compared to euthyroid subjects and can aid in assessing SCH subjects. A significant correlation exists between Zulewski clinical score and each of the TSH, FT4, and TPO-Ab titer levels. The frequency of TPO-Ab positivity is high in SCH. Additionally, euthyroid with higher TSH levels has higher level of TPO-Ab titer but not higher clinical score.

Abstract

Background

While numerous randomized controlled trials have demonstrated long-term survival rates for patients with early-stage breast cancer treated with breast-conserving surgery (BCS) comparable to mastectomy, the latter remains the most prevalent surgical option to treat early-stage breast cancer in Thailand.

Objectives

To investigate the potential determinants affecting the decision on selecting BCS or mastectomy for the treatment of early-stage breast cancer and to compare the disease-free survival and overall survival between the treatments using a propensity score-matched analysis.

Methods

Patients diagnosed nonmetastatic breast cancer at the Queen Sirikit Breast Cancer Center from January 2006 to December 2015, were retrospectively identified and grouped intro patients who received BCS or mastectomy. After propensity score matching, 356 BCS and 209 mastectomy patients were identified, and statistical analysis was conducted to determine treatment selection factors and compare disease-free and overall survival.

Results

Disease-free survival and overall survival in months comparing BCS and mastectomy were not statistically different with P values of 0.11 and 0.77, respectively. Determinants of treatment selection found that younger age, surgeon preference, smaller tumor size, and lower tumor grade were statistically significant factors in the selection of BCS over mastectomy. The majority of surgeons had a preference for one treatment over the other (P < 0.001).

Conclusion

The outcome of BCS is comparable to mastectomy in early-stage breast cancer patients. Key determinants affecting the selection of treatment were identified to be patient age, characteristics of the tumor, and surgeon’s preference.

Abstract

Background

In 1975, King Chulalongkorn Memorial Hospital (KCMH) in Bangkok, Thailand, published data on common orthopedic problems in neonates.

Objectives

To determine the more recent incidence of these conditions and to compare the results with those reported 40 years ago by KCMH. The data were also compared with a recent report from Siriraj Hospital.

Methods

We reviewed medical records of newborn infants from 2012 to 2016, all of whom were born in KCMH with deformities of upper and lower extremities or other birth-related injuries. The cases were grouped according to International Classification of Diseases, 10th edition. The incidence of common neonatal orthopedic problems was calculated as cases per 1,000 live births and compared, using a chi-squared test, with the earlier data from KCMH and with the data recently reported by Siriraj hospital.

Results

Of the 24,825 live births, 54% were male and 46% were female. The average birth weight was 3,052.2 ± 516.1 g (range, 535–5,320 g) for infants. The most common deformity was postural clubfoot, followed by calcaneovalgus and hip dysplasia, with incidences of 1.37, 0.93 and 0.52 per 1,000 live births, respectively. The incidence of calcaneovalgus, metatarsus adductus, and clubfoot was lower than in the 1975 study and in the report from Siriraj. In all 3 studies, the incidence of birth-related injury was similar and clavicular fracture was the most common, with a rate of 1.3/1,000 live births.

Conclusion

The incidence of common neonatal orthopedic problems varies among institutions. Birth-related injury is a major challenge. The results may be utilized as updated data and as a starting point for parental education.