Trigeminal Neurosensory Deficit and Patient Reported Outcome Measures: The Effect on Quality of Life

Objectives

To investigate the effect of persistent neurosensory disturbance of the lingual nerve (LN) or inferior alveolar nerve (IAN) on general health and oral health- related quality of life (QoL).

Methods

The study design was a case-control study. Patients with persistent neurosensory deficit of LN or IAN after lower third molar surgery (for 12 months or more) were the study group. The control group was an age and gender matched sample of patients who had dental extractions or lower third molar surgeries without trigeminal neurosensory deficit. The outcome variables were the general health and oral health-related QoL. General health-related QoL was assessed using the 36-item Short Form Health Survey (SF-36) and oral health-related QoL using the 14-item Short Form Oral Health Impact Profile (OHIP-14). Differences in SF-36 scores and OHIP-14 scores between the groups were compared.

Results

Forty-eight subjects (24 cases and 24 controls) were recruited. When compared to the control group, patients with neurosensory deficits had poorer Mental-Health Component Scores (MCS) (p = 0.005), General Health (p = 0.023), Vitality (p = 0.048), Social Functioning (p = 0.003), Role-emotion (p = 0.008) and Mental Health (p = 0.022). The OHIP-14 scores were also significantly worse in this patients with neurosensory deficits compared with the control group (p = 0.002). When compared within the study group, older patient with neurosensory deficit was found to correlate with worse Physical Health Component Scores (PCS) (p = 0.02) and OHIP-14 scores (p = 0.02), while more severe visualized analog scaling rating of numbness was correlated with a worse PCS (p = 0.034).

Conclusions

Patients with persistent LN or IAN deficit after lower third molar surgery have poorer health-related QoL and poorer oral health-related QoL than those without such deficits.     

Acute Simvastatin Inhibits KATP Channels of Porcine Coronary Artery Myocytes

Background

Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors) consumption provides beneficial effects on cardiovascular systems. However, effects of statins on vascular K_ATP channel gatings are unknown.

Methods

Pig left anterior descending coronary artery and human left internal mammary artery were isolated and endothelium-denuded for tension measurements and Western immunoblots. Enzymatically-dissociated/cultured arterial myocytes were used for patch-clamp electrophysiological studies and for [Ca²⁺]_i, [ATP]_i and [glucose]_o uptake measurements.

Results

The cromakalim (10 nM to 10 µM)- and pinacidil (10 nM to 10 µM)-induced concentration-dependent relaxation of porcine coronary artery was inhibited by simvastatin (3 and 10 µM). Simvastatin (1, 3 and 10 µM) suppressed (in okadaic acid (10 nM)-sensitive manner) cromakalim (10 µM)- and pinacidil (10 µM)-mediated opening of whole-cell K_ATP channels of arterial myocytes. Simvastatin (10 µM) and AICAR (1 mM) elicited a time-dependent, compound C (1 µM)-sensitive [³H]-2-deoxy-glucose uptake and an increase in [ATP]_i levels. A time (2–30 min)- and concentration (0.1–10 µM)-dependent increase by simvastatin of p-AMPKα-Thr¹⁷² and p-PP2A-Tyr³⁰⁷ expression was observed. The enhanced p-AMPKα-Thr¹⁷² expression was inhibited by compound C, ryanodine (100 µM) and KN93 (10 µM). Simvastatin-induced p-PP2A-Tyr³⁰⁷ expression was suppressed by okadaic acid, compound C, ryanodine, KN93, phloridzin (1 mM), ouabain (10 µM), and in [glucose]_o-free or [Na⁺]_o-free conditions.

Conclusions

Simvastatin causes ryanodine-sensitive Ca²⁺ release which is important for AMPKα-Thr¹⁷² phosphorylation via Ca²⁺/CaMK II. AMPKα-Thr¹⁷² phosphorylation causes [glucose]_o uptake (and an [ATP]_i increase), closure of K_ATP channels, and phosphorylation of AMPKα-Thr¹⁷² and PP2A-Tyr³⁰⁷ resulted. Phosphorylation of PP2A-Tyr³⁰⁷ occurs at a site downstream of AMPKα-Thr¹⁷² phosphorylation.     

Bacillus thuringiensis-derived Cry5B Has Potent Anthelmintic Activity against Ascaris suum

Ascaris suum and Ascaris lumbricoides are two closely related geo-helminth parasites that ubiquitously infect pigs and humans, respectively. Ascaris suum infection in pigs is considered a good model for A. lumbricoides infection in humans because of a similar biology and tissue migration to the intestines. Ascaris lumbricoides infections in children are associated with malnutrition, growth and cognitive stunting, immune defects, and, in extreme cases, life-threatening blockage of the digestive tract and aberrant migration into the bile duct and peritoneum. Similar effects can be seen with A. suum infections in pigs related to poor feed efficiency and performance. New strategies to control Ascaris infections are needed largely due to reduced treatment efficacies of current anthelmintics in the field, the threat of resistance development, and the general lack of new drug development for intestinal soil-transmitted helminths for humans and animals. Here we demonstrate for the first time that A. suum expresses the receptors for Bacillus thuringiensis crystal protein and novel anthelmintic Cry5B, which has been previously shown to intoxicate hookworms and which belongs to a class of proteins considered non-toxic to vertebrates. Cry5B is able to intoxicate A. suum larvae and adults and triggers the activation of the p38 mitogen-activated protein kinase pathway similar to that observed with other nematodes. Most importantly, two moderate doses of 20 mg/kg body weight (143 nM/kg) of Cry5B resulted in a near complete cure of intestinal A. suum infections in pigs. Taken together, these results demonstrate the excellent potential of Cry5B to treat Ascaris infections in pigs and in humans and for Cry5B to work effectively in the human gastrointestinal tract.     

The Potential Applications of Nanoporous Materials for the Adsorption,Separation, and Catalytic Conversion of Carbon Dioxide

Carbon capture and storage (CCS) technologies aiming at tackling CO₂ emission have attracted much attention from scientists of various backgrounds. Most CCS systems require an efficient adsorbent to remove CO₂ from sources such as fossil fuels (pre‐combustion) or flue gas from power generation (post‐combustion). Research on developing efficient adsorbents with a substantial capacity, good stability and recyclability has grown rapidly in the past decade. Because of their high surface area, highly porous structure, and high stability, various nanoporous materials have been viewed as good candidates for this challenging task. Here, recent developments in several classes of nanoporous materials, such as zeolites, metal organic frameworks (MOFs), mesoporous silicas, carbon nanotubes, and organic cage frameworks, for CCS are examined and potential future directions for CCS technology are discussed. The main criteria for a sustainable CO₂ adsorbent for industrial use are also rationalized. Moreover, catalytic transformations of CO₂ to other chemical species using nanoporous catalysts and their potential for large scale carbon capture and utilization (CCU) processes are also discussed. Application of CCU technologies avoids any potential hazard associated with CO₂ reservoirs and allows possible recovery of some running cost for CO₂ capture by manufacturing valuable chemicals.     

Protective Effects of Soluble Collagen during Ultraviolet-A Crosslinking on Enzyme-Mediated Corneal Ectatic Models

Collagen crosslinking is a relatively new treatment for structural disorders of corneal ectasia, such as keratoconus. However, there is a lack of animal models of keratoconus, which has been an obstacle for carefully analyzing the mechanisms of crosslinking and evaluating new therapies. In this study, we treated rabbit eyes with collagenase and chondroitinase enzymes to generate ex vivo corneal ectatic models that simulate the structural disorder of keratoconus. The models were then used to evaluate the protective effect of soluble collagen in the UVA crosslinking system. After enzyme treatment, the eyes were exposed to riboflavin/UVA crosslinking with and without soluble type I collagen. Corneal morphology, collagen ultrastructure, and thermal stability were evaluated before and after crosslinking. Enzyme treatments resulted in corneal curvature changes, collagen ultrastructural damage, decreased swelling resistance and thermal stability, which are similar to what is observed in keratoconus eyes. UVA crosslinking restored swelling resistance and thermal stability, but ultrastructural damage were found in the crosslinked ectatic corneas. Adding soluble collagen during crosslinking provided ultrastructural protection and further enhanced the swelling resistance. Therefore, UVA crosslinking on the ectatic model mimicked typical clinical treatment for keratoconus, suggesting that this model replicates aspects of human keratoconus and could be used for investigating experimental therapies and treatments prior to translation.     

Behavioural adaptations of the fiddler crabs Uca vocans borealis (crane) and Uca lactea lactea (De Haan) for coexistence on an intertidal shore

The distribution and coexistence of the fiddler crabs U. vocans borealis and U. lactea lactea was investigated in the upper shore of a sandy beach with respect to particle size, water content and total organic carbon content of the sediments. A clear segregation of habitats between the two species was apparent. U. lactea lactea were only found in sediments with significantly lower total organic carbon content. U. lactea lactea had a higher ratio for the size of third maxilliped to body size than U. vocans borealis. There was no statistical difference in the median sediment particle size of the habitats where both species were found on the study shore. U. lactea lactea was larger on shores where U. vocans borealis were absent. Smaller U. vocans borealis individuals occupied sediments with higher water content and finer particles. Smaller individuals of U. vocans borealis also possessed fewer spoon-tipped setae on second maxilliped than their larger conspecifics, which were found mostly on coarser sediments. U. lactea lactea spent significantly more time on the surface than in the burrow during low tide when compared with U. vocans borealis. Both Uca species exhibited similar desiccation resistance. U. lactea lactea tends to keep its frontal region in close contact with sediments to maintain moisture when being exposed to air.     

Patterns of Biofilm Succession on a Sheltered Rocky Shore in Hong Kong

Successional patterns are dependent on the nature of the substratum, water flow, concentrations of organics as well as the availability of bacteria, algal spores and invertebrate larvae in the coastal environment. Bacteria play an especially important role in biofilm formation as they are generally the earliest colonizers. In the present study, both winter and summer biofilm succession patterns were examined on glass coverslips inverted on experimental racks attached at two tidal levels on a sheltered shore in Hong Kong. In the succession, bacteria were followed by diatoms and cyanobacteria. Encrusting algae appeared in the late stages of the experiment (day 80 in summer and day 60 in winter). Colonization by bacteria was much slower in summer and their density remained low throughout the experimental period. The first appearance of diatoms and cyanobacteria, however, was more rapid in the summer. Bacteria and diatoms on the low-shore surfaces also had a faster succession rate than on the high-shore surfaces, suggesting that desiccation/aerial temperature are the causal factors for such differences.     

Downregulation of CFTR promotes epithelial-to-mesenchymal transition and is associated with poor prognosis of breast cancer

The epithelial-to-mesenchymal transition (EMT), a process involving the breakdown of cell–cell junctions and loss of epithelial polarity, is closely related to cancer development and metastatic progression. While the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl^? and HCO₃^? conducting anion channel expressed in a wide variety of epithelial cells, has been implicated in the regulation of epithelial polarity, the exact role of CFTR in the pathogenesis of cancer and its possible involvement in EMT process have not been elucidated. Here we report that interfering with CFTR function either by its specific inhibitor or lentiviral miRNA-mediated knockdown mimics TGF-β₁-induced EMT and enhances cell migration and invasion in MCF-7. Ectopic overexpression of CFTR in a highly metastatic MDA-231 breast cancer cell line downregulates EMT markers and suppresses cell invasion and migration in vitro, as well as metastasis in vivo. The EMT-suppressing effect of CFTR is found to be associated with its ability to inhibit NFκB targeting urokinase-type plasminogen activator (uPA), known to be involved in the regulation of EMT. More importantly, CFTR expression is found significantly downregulated in primary human breast cancer samples, and is closely associated with poor prognosis in different cohorts of breast cancer patients. Taken together, the present study has demonstrated a previously undefined role of CFTR as an EMT suppressor and its potential as a prognostic indicator in breast cancer.     

Catalysis-based inhibitors of the calcium signaling function of CD38

CD38 is a signaling enzyme responsible for catalyzing the synthesis of cyclic ADP ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate; both are universal Ca(2+) messenger molecules. Ablation of the CD38 gene in mice causes multiple physiological defects, including impaired oxytocin release, that result in altered social behavior. A series of catalysis-based inhibitors of CD38 were designed and synthesized, starting with arabinosyl-2'-fluoro-2'-deoxynicotinamide mononucleotide. Structure-function relationships were analyzed to assess the structural determinants important for inhibiting the NADase activity of CD38. X-ray crystallography was used to reveal the covalent intermediates that were formed with the catalytic residue, Glu226. Metabolically stable analogues that were resistant to inactivation by phosphatase and esterase were synthesized and shown to be effective in inhibiting intracellular cADPR production in human HL-60 cells during induction of differentiation by retinoic acid. The inhibition was species-independent, and the analogues were similarly effective in blocking the cyclization reaction of CD38 in rat ventricular tissue extracts, as well as inhibiting the α-agonist-induced constriction in rat mesentery arteries. These compounds thus represent the first generally applicable and catalysis-based inhibitors of the Ca(2+) signaling function of CD38.