Common Oncogenic Mutations Are Infrequent in Oral Squamous Cell Carcinoma of Asian Origin

Objectives

The frequency of common oncogenic mutations and TP53 was determined in Asian oral squamous cell carcinoma (OSCC).

Materials and Methods

The OncoCarta^™ panel v1.0 assay was used to characterize oncogenic mutations. In addition, exons 4-11 of the TP53 gene were sequenced. Statistical analyses were conducted to identify associations between mutations and selected clinico-pathological characteristics and risk habits.

Results

Oncogenic mutations were detected in PIK3CA (5.7%) and HRAS (2.4%). Mutations in TP53 were observed in 27.7% (31/112) of the OSCC specimens. Oncogenic mutations were found more frequently in non-smokers (p = 0.049) and TP53 truncating mutations were more common in patients with no risk habits (p = 0.019). Patients with mutations had worse overall survival compared to those with absence of mutations; and patients who harbored DNA binding domain (DBD) and L2/L3/LSH mutations showed a worse survival probability compared to those patients with wild type TP53. The majority of the oncogenic and TP53 mutations were G:C > A:T and A:T > G:C base transitions, regardless of the different risk habits.

Conclusion

Hotspot oncogenic mutations which are frequently present in common solid tumors are exceedingly rare in OSCC. Despite differences in risk habit exposure, the mutation frequency of PIK3CA and HRAS in Asian OSCC were similar to that reported in OSCC among Caucasians, whereas TP53 mutations rates were significantly lower. The lack of actionable hotspot mutations argue strongly for the need to comprehensively characterize gene mutations associated with OSCC for the development of new diagnostic and therapeutic tools.     

Effects of Intra-Operative Total Intravenous Anaesthesia with Propofol versus Inhalational Anaesthesia with Sevoflurane on Post-Operative Pain in Liver Surgery: A Retrospective Case-Control Study

Background

Patients receiving total intravenous anesthesia (TIVA) with propofol have been shown to experience less postoperative pain. We evaluated the post-operative analgesic effects of propofol compared with sevoflurane maintenance of anesthesia in liver surgery. This study was registered at ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT02179437","term_id":"NCT02179437"}}NCT02179437).

Methods

In this retrospective study, records of patients who underwent liver surgery between 2010 and 2013 were reviewed. Ninety-five patients anesthetized with propofol TIVA were matched with 95 patients anesthetized with sevoflurane. Numeric pain rating scale (NRS) pain scores, postoperative morphine consumption, side effects and patients’ satisfaction with pain relief were evaluated.

Results

The TIVA group reported lower NRS pain scores during coughing on postoperative days 1 and 2 but not 3 (p = 0.0127, p = 0.0472, p = 0.4556 respectively). They also consumed significantly less daily (p = 0.001 on day 1, p = 0.0231 on day 2, p = 0.0004 on day 3), accumulative (p = 0.001 on day 1, p<0.0001 on day 2 and p = 0.0064 on day 3) and total morphine (p = 0.03) when compared with the sevoflurane group. There were no differences in total duration of intravenous patient controlled analgesia (PCA) morphine use and patient satisfaction. No difference was found in reported side effects.

Conclusion

Patients anesthetized with propofol TIVA reported less pain during coughing and consumed less daily, accumulative and total morphine after liver surgery.     

Post‐dispersal seed recovery by animals: is it a plant‐ or an animal‐driven process?

The ability of animals to find and consume hoarded seeds (i.e. seed recovery) is a key stage within the seed dispersal process. However, the ecology of seed recovery is still poorly understood. Here, we analyze the factors controlling seed recovery by scatter‐hoarding rodents in an oak‐dominated temperate forest. We examined the relative importance of intrinsic seed traits (i.e. plant‐driven) and extrinsic seed factors (i.e. animal‐driven) on the probability of seed recovery. We found that seed recovery is mainly driven by extrinsic seed factors, mostly related to animal behavior (pilfering frequency, microsite preference, predation risk, burial depth and cache size). Important intrinsic traits such as seed size, seed quality and seed‐drop timing were, on average, of lower significance in the probability of seed recovery (2.8‐times less important than extrinsic factors); only seed quality was an important intrinsic trait. On the other hand, larger and nutritionally more valuable seeds showed a removal–recovery tradeoff as they enhance seed removal and hoarding (increasing dispersal quality) but also favour seed recovery (increasing predation). We find that other mechanisms beyond seed traits (e.g. masting) are needed to decrease seed recovery and, thus, increase seed survival. We conclude that, as seed recovery is mostly driven by animal behavioural factors, it substantially differs from other previous stages of the seed dispersal process that are more dependent on seed traits. We argue that seed recovery needs further attention to advance our understanding of the ecology of seed dispersal and the role of secondary dispersers as a selective force for seeds.     

Genome editing in Bombyx mori: New opportunities for silkworm functional genomics and the sericulture industry

In recent years, research in life sciences has been remarkably revolutionized owing to the establishment, development and application of genome editing technologies. Genome editing has not only accelerated fundamental research but has also shown promising applications in agricultural breeding and therapy. In particular, the clustered, regularly interspaced, short palindromic repeat (CRISPR) technology has become an indispensable tool in molecular biology owing to its high efficacy and simplicity. Genome editing tools have also been established in silkworm (Bombyx mori), a model organism of Lepidoptera insects with high economic importance. This has remarkably improved the level and scope of silkworm research and could reveal new mechanisms or targets in basic entomology and pest management studies. In this review, we summarize the progress and potential of genome editing in silkworm and its applications in functional genomic studies for generating novel genetic materials.     

Antileishmanial activity and cytotoxicity of ent-beyerene diterpenoids

We describe the in vitro activity of two natural isomeric ent-beyerene diterpenes, several derivatives and synthetic intermediates. Beyerenols 1 and 2 showed EC₅₀ of 4.6?±?9.4 and 5.3?±?9.4?μg/mL against amastigotes of L. (V) brazilensis, with SI of 5.1 and 7.7, respectively. Beyerenol 1 was synthesized from stevioside. In vivo experiments with bereyenols showed cure in 50% of hamsters infected with L. (V) brazilensis topically applied as Cream I (beyerenol 1, 0.81%, w/w) and Cream III (beyerenol 2, 1.96%, w/w). These results suggest that beyerenols are potential candidates for cutaneous leishmaniasis chemotherapy by topical application. In vitro assays of amastigotes of L. (V) brazilensis showed EC₅₀ of 1.1?±?0.1 and 1.3?±?0.04?μg/mL, with SI of 3.1 and 3.5 for hydrazone intermediates 10 and 11, respectively.     

The rattan trade of Northern Myanmar: Species, supplies, and sustainability

Although Myanmar exports millions of dollars of rattan cane each year, the last systematic treatment of rattans in this country was done over 100 years ago, and virtually nothing has been written about the collection and trade of this important forest resource. Here we report the results from a study of rattans in the Hukaung Valley Tiger Reserve in northern Myanmar. A total of 15 species of rattan were encountered; seven species are new records for Myanmar and two species are new to science. Inventory transects revealed that the density of commercial rattans in local forests averages 40.5 canes ≽4m long/hectare. Populations of all species appear to be actively regenerating. The current pattern of rattan exploitation, however, is largely uncontrolled and will eventually lead to resource depletion unless some form of management is implemented.     

A comparative study of leptospirosis and dengue in Thai children

Background

Leptospirosis is an emerging zoonosis that is often under-recognized in children and commonly confused with dengue in tropical settings. An enhanced ability to distinguish leptospirosis from dengue in children would guide clinicians and public health personnel in the appropriate use of limited healthcare resources.

Methodology/Principal Findings

We conducted a prospective, hospital-based, study of children with acute febrile illnesses and dengue in Thailand. Among the children without dengue, we identified those with leptospirosis using anti-leptospira IgM and microscopic agglutination titers in paired acute and convalescent blood samples. We then performed a case-control comparison of symptoms, signs, and clinical laboratory values between children with leptospirosis and dengue.In a semi-rural region of Thailand, leptospirosis accounted for 19% of the non-dengue acute febrile illnesses among children presenting during the rainy season. None of the children with leptospirosis were correctly diagnosed at the time of hospital discharge, and one third (33%) were erroneously diagnosed as dengue or scrub typhus. A predictive model to distinguish pediatric leptospirosis from dengue was generated using three variables: the absolute neutrophil count, plasma albumin, and aspartate aminotransferase levels in the first 72 hours of illness.

Conclusions/Significance

Unrecognized leptospirosis can be a significant cause of “dengue-like” febrile illness in children. Increased awareness of pediatric leptospirosis, and an enhanced ability to discriminate between leptospirosis and dengue early in illness, will help guide the appropriate use of healthcare resources in often resource-limited settings.     

3D-QSAR study of microsomal prostaglandin E<Subscript>2</Subscript> synthase(mPGES-1) inhibitors

Microsomal prostaglandin E₂ synthase (mPGES-1) has been identified recently as a novel target for treating pain and inflammation. The aim of this study is to understand the binding affinities of reported inhibitors for mPGES-1 and further to design potential new mPGES-1 inhibitors. 3D-QSAR-CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) - techniques were employed on a series of indole derivatives that act as selective mPGES-1 inhibitors. The lowest energy conformer of the most active compound obtained from systematic conformational search was used as a template for the alignment of 32 compounds. The models obtained were used to predict the activities of the test set of eight compounds, and the predicted values were in good agreement with the experimental results. The 3D-QSAR models derived from the training set of 24 compounds were all statistically significant (CoMFA; q ² = 0.89, r ² = 0.95, , and CoMSIA; q ² = 0.84, r ² = 0.93, , ). Contour plots generated for the CoMFA and CoMSIA models reveal useful clues for improving the activity of mPGES-1 inhibitors. In particular, substitutions of an electronegative fluorine atom or a bulky hydrophilic phenoxy group at the meta or para positions of the biphenyl rings might improve inhibitory activity. A plausible binding mode between the ligands and mPGES-1 is also proposed.