Evaluation of dental trials comparing baseline differences using p values

Introduction: Significance testing for comparison of the baseline differences between the intervention arms has received a strong condemnation. The goal of this study was to assess the prevalence of randomized controlled trials (RCTs) comparing the baseline characteristics between intervention groups using significance tests in top ten impact factor dental journals.

Materials and methods: RCTs published in 10 high impact factor dental journals were searched in PubMed database. Literature search was limited to time duration of 5 years from September 2012 to August 2017.

Results: We analysed 521 RCTs after excluding 47 non-RCT articles from the total of 568 articles. Baseline demographic characteristics table was not reported in 45.9% of the RCTs and 26.2% of the RCTs did not report table of baseline clinical characteristics. In 38.9% of the studies, significance testing was employed to compare baseline differences between the intervention arms.

Conclusions: Many trials published in the reputed dental journals failed to follow the recommendations of CONSORT statement regarding reporting of baseline tables and avoiding comparison of baseline differences with significance test.     

Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate.Rat models of autism were established by intracerebroventricular injection of propionic acid.These rat models had memory dysfunction,decreased muscle coordination and gait imbalance.Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid biomarkers.Oral administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner.These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism.This study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval No.RITS/IAEC/2014/03/03).     

The genomic landscape of fibrolamellar hepatocellular carcinoma: whole genome sequencing of ten patients

Fibrolamellar hepatocellular carcinoma is a rare, malignant liver tumor that often arises in the otherwise normal liver of adolescents and young adults. Previous studies have focused on biomarkers and comparisons to traditional hepatocellular carcinoma, and have yielded little data on the underlying pathophysiology. We performed whole genome sequencing on paired tumor and normal samples from 10 patients to identify recurrent mutations and structural variations that could predispose to oncogenesis. There are relatively few coding, somatic mutations in this cancer, putting it on the low end of the mutational spectrum. Aside from a previously described heterozygous deletion on chromosome 19 that encodes for a functional, chimeric protein, there were no other recurrent structural variations that contribute to the tumor genotype. The lack of a second-hit mutation in the genomic landscape of fibrolamellar hepatocellular carcinoma makes the DNAJB1-PRKACA fusion protein the best target for diagnostic and therapeutic advancements. The mutations, altered pathways and structural variants that characterized fibrolamellar hepatocellular carcinoma were distinct from those in hepatocellular carcinoma, further defining it as a distinct carcinoma.     

Investigating the Acoustic Response and Contrast Enhancement of Drug-Loadable PLGA Microparticles with Various Shapes and Morphologies

Polymer nanoparticles and microparticles have been used primarily for drug delivery. There is now growing interest in further developing polymer-based solid cavitation agents to also enhance ultrasound imaging. We previously reported on a facile method to produce hollow poly(lactic-co-glycolic acid) (PLGA) microparticles with different diameters and degrees of porosity. Here, we investigate the cavitation response from these PLGA microparticles with both therapeutic and diagnostic ultrasound transducers. Interestingly, all formulations exhibited stable cavitation; larger porous and multicavity particles also provided inertial cavitation at elevated acoustic pressure amplitudes. These larger particles also achieved contrast enhancement comparable to that of commercially available ultrasound contrast agents, with a maximum recorded contrast-to-tissue ratio of 28 dB. Therefore, we found that multicavity PLGA microparticles respond to both therapeutic and diagnostic ultrasound and may be applied as a theranostic agent.     

Bilateral central acetabular fracture dislocation in a young patient due to seizure activity: a case report and review of the literature

Various musculoskeletal injuries are well known complications of epilepsy either because of direct trauma or because of unbalanced forceful muscle contraction. We report a case of non-traumatic bilateral central acetabular fracture dislocation due to seizure activity induced by neurocysticercosis of the brain, which was managed conservatively and obtained reasonable good outcome. This case highlights the importance of proper evaluation in young non-osteoporotic patients who have experienced an epileptic attack without any previous history. It is also imperative to mention that these patients should be thoroughly examined neurologically to find out the exact etiology and should be treated accordingly to prevent future seizure activity.     

Detection,removal and prevention of calculus: Literature Review

Dental plaque is considered to be a major etiological factor in the development of periodontal disease. Accordingly, the elimination of supra- and sub-gingival plaque and calculus is the cornerstone of periodontal therapy. Dental calculus is mineralized plaque; because it is porous, it can absorb various toxic products that can damage the periodontal tissues. Hence, calculus should be accurately detected and thoroughly removed for adequate periodontal therapy. Many techniques have been used to identify and remove calculus deposits present on the root surface. The purpose of this review was to compile the various methods and their advantages for the detection and removal of calculus.     

High dose acetaminophen inhibits STAT3 and has free radical independent anti-cancer stem cell activity

High-dose acetaminophen (AAP) with delayed rescue using n-acetylcysteine (NAC), the FDA-approved antidote to AAP overdose, has demonstrated promising antitumor efficacy in early phase clinical trials. However, the mechanism of action (MOA) of AAP''s anticancer effects remains elusive. Using clinically relevant AAP concentrations, we evaluated cancer stem cell (CSC) phenotype in vitro and in vivo in lung cancer and melanoma cells with diverse driver mutations. Associated mechanisms were also studied. Our results demonstrated that AAP inhibited 3D spheroid formation, self-renewal, and expression of CSC markers when human cancer cells were grown in serum-free CSC media. Similarly, anti-CSC activity was demonstrated in vivo in xenograft models - tumor formation following in vitro treatment and ex-vivo spheroid formation following in vivo treatment. Intriguingly, NAC, used to mitigate AAP''s liver toxicity, did not rescue cells from AAP''s anti-CSC effects, and AAP failed to reduce glutathione levels in tumor xenograft in contrast to mice liver tissue suggesting nonglutathione-related MOA. In fact, AAP mediates its anti-CSC effect via inhibition of STAT3. AAP directly binds to STAT3 with an affinity in the low micromolar range and a high degree of specificity for STAT3 relative to STAT1. These findings have high immediate translational significance concerning advancing AAP with NAC rescue to selectively rescue hepatotoxicity while inhibiting CSCs. The novel mechanism of selective STAT3 inhibition has implications for developing rational anticancer combinations and better patient selection (predictive biomarkers) for clinical studies and developing novel selective STAT3 inhibitors using AAP''s molecular scaffold.