Detecting and Quantifying pADPr In Vivo.

Poly(ADP-ribose) polymerases (PARP) participate in diverse biological processes contributing to cellular homeostasis or exacerbating injury. PARP catalyzes the addition of ADP-ribose molecules (pADPr) to the target proteins, a process termed poly-ADP-ribosylation. Overactivation of PARP - reflected by increased poly-ADP-ribosylation and accumulation of pADPr-modified proteins or free pADPr - contributes to depletion of NAD+ and mitochondrial dysfunction, potentially leading to cell death. Thus, PARP overactivation and increases in free pADPr have been identified as key contributors to the pathobiology of many diseases. In stark contrast, PARP inhibitors are in clinical use in cancer patients where they potentiate cell death induced by chemotherapeutic agents. Accordingly, monitoring PARP-1 activation - responsible for up to 80-90% of cellular pADPr synthesis - by detecting and quantifying pADPr may provide valuable mechanistic insights as well as facilitating therapeutic drug monitoring for PARP inhibitors.Several non-isotopic immunodetection methods for quantifying pADPr are discussed: Western blotting of poly-ADP-ribosylated proteins, cellular localization of pADPr by immunohistochemistry, quantification of pADPr by enzyme-linked immunoassay, and small-scale two-dimensional gel electrophoresis.

A patient with severe congenital neutropenia harbors a missense ELANE mutation due to paternal germline mosaicism.

BACKGROUND: Clinical and genetic characteristics of ELANE mutation of a 3-year-old male who had a severe congenital neutropenia (SCN) were examined. We then investigated whether CRISPR/Cas9-mediated gene editing could correct the mutation. PROCEDURE: The proband underwent extensive clinical assessments, such as exome sequencing and bioinformatics analysis, so that pathogenic genes could be identified. Sanger sequencing was also utilized for confirmation. The cell line, 293-ELANE, harboring ELANE mutation was generated, and the mutation was then corrected by CRISPR/Cas9-mediated homology-directed repair (HDR). RESULTS: The ELANE gene test in the proband unveiled a heterozygous de novo missense mutation: c. 248T > A (p.V83D), which was not detected in his asymptomatic parents who had provided peripheral blood samples. We found that 46.01% of his father's sperm cells had the same mutation. These results demonstrate that the proband inherited the ELANE mutation from his father, who had an average neutrophil count but had a germline mosaicism. The highest repair efficiency of CRISPR/Cas9-mediated HDR for 293-ELANE is 4.43%. CONCLUSIONS: We identified a missense mutation (p.V83D) in ELANE that causes SCN. This is the first report on paternal semen mosaicism of an ELANE mutation. Our study paves the way for preimplantation genetic diagnosis (PGD) based on ELANE mutation prevention and clinical treatment of congenital disabilities.

Ascorbate deficiency confers resistance to hippocampal neurodegeneration after asphyxial cardiac arrest in juvenile rats.

BACKGROUND: Asphyxial cardiac arrest (CA) is a significant cause of death and disability in children. Using juvenile Osteogenic disorder Shionogi (ODS) rats that, like humans, do not synthesize ascorbate, we tested the effect of ascorbate deficiency on functional and histological outcome after CA. METHODS: Postnatal day 16-18 milk-fed ODS and wild-type Wistar rats underwent 9-min asphyxial CA (n = 8/group) or sham surgery (n = 4/group). ODS mothers received ascorbate in drinking water to prevent scurvy. Levels of ascorbate and glutathione (GSH) were measured in plasma and hippocampus at baseline and after CA. Neurologic deficit score (NDS) was measured at 3, 24, and 48 h and hippocampal neuronal counts, neurodegeneration, and microglial activation were assessed at day 7. RESULTS: ODS rats showed depletion of plasma and hippocampal ascorbate, attenuated hippocampal neurodegeneration and microglial activation, and increased CA1 hippocampal neuron survival vs. Wistar rats while NDS were similar. Hippocampal GSH levels were higher in ODS vs. Wistar rats at baseline and 10 min, whereas hypoxia-inducible factor-1α levels were higher in Wistar vs. ODS rats at 24 , after CA. CONCLUSION: Ascorbate-deficient juvenile ODS rats appear resistant to neurodegeneration produced by asphyxia CA, possibly related to upregulation of the endogenous antioxidant GSH in brain. IMPACT: Like humans and unlike other rodents, osteogenic disorder Shionogi (ODS) rats do not synthesize ascorbate, and thus may serve as a useful model for studying the role of ascorbate in human disease. Conflicting evidence exists regarding ascorbate's protective versus detrimental effects in animal models and clinical studies. Ascorbate-deficient ODS rats are resistant to neurodegeneration after experimental cardiac arrest.

Exploration and preliminary clinical investigation of an adhesive approach for primary tooth restoration.

The current study aims to investigate a suitable adhesive for primary tooth enamel. Shear bond strength (SBS) of primary teeth and the length of resin protrusion were analyzed using one-way ANOVA with Bonferroni multiple comparison tests after etching with 35% H 3PO 4. SBS and marginal microleakage tests were conducted with Single Bond Universal (SBU)/Single Bond 2 (SB2) adhesives with or without pre-etching using a nonparametric Kruskal-Wallis test. Clinical investigations were performed to validate the adhesive for primary teeth restoration using Chi-square tests. Results showed that the SBS and length of resin protrusion increased significantly with the etching time. Teeth in the SBU with 35% H 3PO 4 pre-etching groups had higher bond strength and lower marginal microleakage than those in the SB2 groups. Mixed fractures were more common in the 35% H 3PO 4 etched 30 s + SB2/SBU groups. Clinical investigations showed significant differences between the two groups in cumulative retention rates at the 6-, 12- and 18-month follow-up evaluations, as well as in marginal adaptation, discoloration, and secondary caries at the 12- and 18-month follow-up assessments. Together, pre-etching primary teeth enamel for 30 s before SBU treatment improved clinical composite resin restoration, which can provide a suitable approach for restoration of primary teeth.

Novel Bioactive Glass-Modified Hybrid Composite Resin: Mechanical Properties, Biocompatibility, and Antibacterial and Remineralizing Activity.

Secondary caries seriously limits the lifetime of composite resin. However, integrating all desirable properties (i.e., mechanical, antibacterial, bioactivity, and biocompatibility) into one composite resin is still challenging. Herein, a novel bioactive glass (BAG)-modified hybrid composite resin has been successfully developed to simultaneously achieve excellent mechanical properties, good biocompatibility, and antibacterial and remineralizing capabilities. When the mass fractions of BAG particles were added from 8 to 23 wt %, the original mechanical properties of the composite resin, including flexural strength and compressive strength, were not obviously affected without compromising the degree of conversion. Although the BAG incorporation of mass fractions of 16 wt % to 23 wt % in composite resins reduced cell viability, the viability could be recovered to normal by adjusting the pH value. Moreover, the BAG-modified composite resins that were obtained showed good antibacterial effects against Streptococcus mutans and enhanced remineralizing activity on demineralized dentin surfaces with increasing incorporation of BAG particles. The possible mechanisms for antibacterial and remineralizing activity might be closely related to the release of bioactive ions (Ca2+, Si4+), suggesting that its antibacterial and biological properties can be controlled by modulating the amounts of bioactive ions. The capability to balance the mechanical properties, cytotoxicity, antibacterial activity, and bioactivity makes the BAG-modified composite resin a promising prospect for clinical application. Our findings provide insight into better design and intelligent fabrication of bioactive composite resins.

Nitrogen-containing flavonoid and their analogs with diverse B-ring in acetylcholinesterase and butyrylcholinesterase inhibition.

In this study, a series of new flavones (2-phenyl-chromone), 2-naphthyl chromone, 2-anthryl-chromone, or 2-biphenyl-chromone derivatives containing 6 or 7-substituted tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results indicated that the alteration of aromatic ring connecting to chromone scaffold brings about a significant impact on biological activity. Compared with flavones, the inhibitory activity of 2-naphthyl chromone, 2-anthryl-chromone derivatives against AChE significantly decreased, while that of 2-biphenyl chromone derivatives with 7-substituted tertiary amine side chain is better than relative flavones derivatives. For all new synthesized compounds, the position of tertiary amine side chain obviously influenced the activity of inhibiting AChE. The results above provide great worthy information for the further development of new AChE inhibitors. Among the newly synthesized compounds, compound 5a is potent in AChE inhibition (IC50 = 1.29 ± 0.10 µmol/L) with high selectivity for AChE over BChE (selectivity ratio: 27.96). An enzyme kinetic study of compound 5a suggests that it produces a mixed-type inhibitory effect against AChE.

Remineralising effect of 45S5 bioactive glass on artificial caries in dentine.

BACKGROUND: This study investigated the remineralisation effect of bioactive glass on artificial dentine caries. METHODS: Dentine disks with artificial caries were treated with bioactive glass (group BAG), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) (group CPP-ACP), sodium fluoride glycerol (group F) or deionized water (group W). All disks were subjected to pH cycling for 28 days subsequently. The topography, microhardness and remineralisation depth of the dentine carious lesion were assessed by atomic force microscopy (AFM), microhardness testing and confocal laser scanning microscope (CLSM), respectively. RESULTS: AFM images indicated mineral depositions on the surface of the carious lesion in group BAG. The changes of Vickers hardness number (ΔVHN, mean ± SD) after pH cycling were 9.67 ± 3.60, 6.06 ± 3.83, 5.00 ± 2.19 and - 1.90 ± 2.09 (p < 0.001) in group BAG, group CPP-ACP, group F and group W, respectively. The remineralisation depth (mean ± SD) of the carious lesion in group BAG, group CPP-ACP, group F and group W were 165 ± 11 µm, 111 ± 11 µm, 75 ± 6 µm and 0 µm (p < 0.001), respectively. CONCLUSION: Bioactive glass possessed a promising remineralisation effect on artificial dentine caries and could be a therapeutic choice for caries management.

Somatosensory profiling of patients with plaque-induced gingivitis: a case-control study.

OBJECTIVES: This study aimed to assess the mechanical and thermal sensory thresholds of the gingiva in patients with plaque-induced gingivitis compared with a control group to help characterize effects of an inflammatory condition in the oral mucosa on somatosensory function. MATERIALS AND METHODS: Quantitative sensory testing (QST) was used in 22 patients (men 10, women 12, age 20-30 years) with plaque-induced gingivitis at the lower lateral incisors and in 22 age- and gender-matched healthy volunteers as a control group. One lower lateral incisor (32 or 42) was randomly identified for each included subject. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), and heat pain threshold (HPT) of the attached gingiva at the identified lower lateral incisors were assessed in both groups. Pressure pain threshold (PPT) at the teeth was also tested from vertical and lateral directions and analyzed. One-way ANOVA was used to compare the mean values of the identified lower lateral incisors between the two groups. RESULTS: The results showed that the CDT (P = 0.027), WDT (P = 0.021), and HPT (P = 0.005) at the gingiva and PPT (P < 0.001) at the identified lower lateral incisors from the vertical direction were significantly less sensitive, whereas the PPT (P = 0.016) at the gingiva of the identified lateral incisors were significantly more sensitive in the gingivitis group compared to the control group. Plaque-induced gingivitis and the inflammatory response appear to be associated with significant changes in somatosensory sensitivity at the gingiva and periodontal tissue in a bidirectional mode, i.e., both increased and decreased sensitivity to different types of stimuli. CONCLUSIONS: Inflammatory reactions in the gingiva seem to be associated with demonstrable changes in somatosensory function including both hypo- and hyperesthesia. CLINICAL RELEVANCE: These findings may have significance for general oral health and well-being in patients with even plaque-induced gingivitis.

Multiple methods used for type detection of uniparental disomy in paternity testing.

Uniparental disomy (UPD) has attracted more attention recently in paternity testing, though it is an infrequent genetic event. Although short tandem repeat (STR) profiling has been widely used in paternity testing, it is not sufficient to use STR only to judge the genetic relationship, because the existence of UPD will inevitably affect the results of genotyping. Compared with complete UPD, segmental UPD is more difficult to detect because it does not affect all genotypes on the same chromosome. It is necessary to determine the type of UPD with multiple methods because a single method is not sufficient. Therefore, it is advisable to detect UPD in paternity testing with multiple methods. In this study, after autosomal STR profiling was used, we found that there were several gene loci on the same chromosome that did not conform to Mendelian genetic law, thus we highly suspected the existence of UPD and performed X-STR profiling immediately. Then whole-genome single nucleotide polymorphism (SNP) array analysis was performed to identify the type, and the results provided straightforward evidence for distinguishing complete from segmental UPD. Lastly, we used deletion insertion polymorphism (DIP)-SNP SNaPshot assay and Miseq FGx sequencing (for SNP and STR) to determine whether the mutation source is maternal uniparental disomy (mUPD) or paternal uniparental disomy (pUPD). To avoid false exclusion of kinship, it is vital to determine the type of UPD in paternity testing and effective strategies based on multiple methods to detect the type of UPD are provided in this study.

Fifth-order finite-difference scheme for Fokker-Planck equations with drift-admitting jumps.

Recently a useful finite-difference scheme was proposed in [Phys. Rev. E 98, 033302 (2018)2470-004510.1103/PhysRevE.98.033302] to solve Fokker-Planck equations with drift-admitting jumps. However, while the scheme is fifth order for the case with smooth drifts, it is only second order for the case with discontinuous drifts. To rectify this, we propose in this paper an improved scheme that achieves a fifth-order convergence rate for the case with drift-admitting jumps. Numerical experiments are also employed to verify the validity of the scheme.

Associations of maternal, perinatal and postnatal factors with the eruption timing of the first primary tooth.

We recruited 1296 mothers in their first trimester from the Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University between May 2014 and September 2015 to investigate the associations of maternal, perinatal and postnatal factors with the eruption timing of the first primary tooth (ETFPT) in a Chinese population. We collected maternal demographic information and clinical data during the perinatal and postnatal period, and oral examinations of the infants were performed by a doctor at 6, 9 and 12 months of age. Multiple regression analysis was used to identify significant explanatory variables for ETFPT. The mean age at eruption of the first primary tooth for all the infants was 6.82 ± 1.90 months. After adjustment for confounders, higher maternal childbearing age (ß = 0.57; 95%CI = 0.13-1.02), female sex (ß = 0.26; 95%CI = 0.07-0.52), and low birth weight (ß = 0.98; 95%CI = 0.20-1.76) were significantly associated with delayed eruption of the first primary tooth, while macrosomia (ß = -0.79; 95%CI = -1.30--0.28) was significantly associated with earlier eruption of the first primary tooth. Maternal childbearing age, infant sex and infant birth weight were significant determinants of ETFPT.

Temporal Summation of Painful Heat Stimulation Is Facilitated in Trigeminal and Extratrigeminal Regions in Painful Myofascial Temporomandibular Disorders: Evidence from a Case-Control Study.

AIMS: To determine whether patients with painful myofascial temporomandibular disorders (TMD) demonstrate facilitated temporal summation (TS) responses to painful heat stimuli applied to the painful trigeminal and extratrigeminal regions and whether there is a side difference in the trigeminal region for myofascial TMD pain patients compared to healthy controls. METHODS: Twenty female Chinese myofascial TMD pain patients and 20 age-matched female volunteers participated in this case-control study. Thermal detection thresholds, thermal pain thresholds, and TS of 20 repetitive noxious thermal stimuli were measured on the skin above the masseter muscle on both sides and the thenar eminence of the less painful side/dominant hand. Numeric rating scale (NRS) scores of pain were provided after the 1st, 5th, 10th, 15th, and 20th stimuli, and TS was calculated as the highest NRS score minus the first NRS score in each test. RESULTS: Evidence of TS was found in the trigeminal and extratrigeminal regions for both groups, but with facilitated TS responses in myofascial TMD pain patients (P < .001). Within the myofascial TMD group and control group, there were no side-to-side differences (P > .289). Interestingly, the repetition of the TS test was associated with facilitated responses in myofascial TMD pain patients (P < .001). CONCLUSION: The current findings suggest TS of painful heat stimulation is facilitated in myofascial TMD pain patients with no side difference in the trigeminal region.

Quantitative and qualitative assessment of glymphatic flux using Evans blue albumin.

BACKGROUND: The glymphatic system is a proposed pathway for clearance of proteins and macromolecules from brain, and disrupted glymphatic flux is implicated in neurological disease. We capitalized on colorimetric, fluorescent, and protein-binding properties of Evans blue to evaluate glymphatic flux. NEW METHOD: Twenty-five µL of 1% Evans blue-labeled albumin (EBA) in artificial cerebrospinal fluid (aCSF) was injected into the intracisternal space of anesthetized postnatal day 17 rats. Serum was collected at various time points after injection (n = 37) and EBA was measured spectrophotometrically. In separate rats (n = 3), a cranial window was placed over the parietal cortex and EBA transit was evaluated using in vivo multiphoton microscopy. Separate rats (n = 6) were processed for immunohistochemistry to examine localization of EBA. In some rats, intracranial pressure (ICP) was increased via intracisternal injection of aCSF. RESULTS: EBA was detected in serum as early as 30 min, was maximal at 4 h, and was undetectable at 72 h after intracisternal injection. Using intra-vital microscopy and immunohistochemistry EBA could be tracked from CSF to perivascular locations. Consistent with removal via glymphatic flux, increasing ICP to 40 mmHg accelerated transit of EBA from CSF to blood. COMPARISON WITH EXISTING METHODS: Transit of EBA from CSF to serum could be quantified spectrophotometrically without radioactive labeling. Glymphatic flux could also be qualitatively evaluated using EBA fluorescence. CONCLUSION: We present a novel technique for simultaneous quantitative and qualitative evaluation of glymphatic flux in rats.

An in vitro study evaluating the effect of ferrule design on the fracture resistance of endodontically treated mandibular premolars after simulated crown lengthening or forced eruption methods.

BACKGROUND: The purpose of this study was to evaluate the effect of ferrule design on the fracture resistance of endodontically treated mandibular first premolars after simulated crown lengthening and orthodontic forced eruption methods restored with a fiber post-and-core system. METHODS: Forty extracted and endodontically treated mandibular first premolars were decoronated to create lingual-to-buccal oblique residual root models, with a 2.0 mm height of the lingual dentine wall coronal to the cemento-enamel junction, and the height of buccal surface at the cemento-enamel junction. The roots were divided randomly into five equal groups. The control group had undergone incomplete ferrule preparation in the cervical root, with 0.0 mm buccal and 2.0 mm lingual ferrule lengths (Group F0). Simulated surgical crown lengthening method provided ferrule preparation of 1.0 mm (Group CL/F1) and 2.0 mm (Group CL/F2) on the buccal surface, with ferrule lengths of 3.0 mm and 4.0 mm on the lingual surface, respectively. Simulated orthodontic forced eruption method provided ferrule preparation of 1.0 mm (Group OE/F1) and 2.0 mm (Group OE/F2) on the buccal surface and ferrule lengths of 3.0 mm and 4.0 mm on the lingual surface, respectively. After restoration with a glass fiber post-and-core system and a cast Co-Cr alloy crown, each specimen was embedded in an acrylic resin block to a height on the root 2.0 mm from the apical surface of the crown margin and loaded to fracture at a 135° angle to its long axis in a universal testing machine. Data were analyzed statistically using two-way ANOVA with Tukey HSD tests and Fisher's test, with α = 0.05. RESULTS: Mean fracture loads (kN) for groups F0, CL/F1, CL/F2, OE/F1 and OE/F2 were as follows: 1.01 (S.D. = 0.26), 0.91 (0.29), 0.73 (0.19), 0.96 (0.25) and 0.76 (0.20), respectively. Two-way ANOVA revealed significant differences for the effect of ferrule lengths (P = 0.012) but no differences for the effect of cervical treatment methods (P = 0.699). The teeth with no buccal ferrule preparation in control group F0 had the highest fracture resistance. In contrast, the mean fracture loads for group CL/F2 with a 2.0-mm buccal and 4.0-mm lingual ferrule created by simulated crown lengthening method were lowest (P = 0.036). CONCLUSIONS: Increased apically complete ferrule preparation resulted in decreased fracture resistance of endodontically treated mandibular first premolars, regardless of whether surgical crown lengthening or orthodontic forced eruption methods been used.

Quantitative sensory testing for assessment of somatosensory function in human oral mucosa: a review.

OBJECTIVE: This narrative review provides an overview of the quantitative sensory testing (QST) to assess somatosensory function in human oral mucosa. MATERIAL AND METHODS: A literature search was conducted in the PubMed database to identify studies in vivo on human oral mucosa using QST methods. A list of 149 articles was obtained and screened. A total of 36 relevant articles remained and were read in full text. Manual search of the reference lists identified eight additional relevant studies. A total of 44 articles were included for final assessment. RESULTS: The included studies were divided into six categories according to the study content and objective. In each category, there was a great variety of aims, methods, participants and outcome measures. The application of QST has nevertheless helped to monitor somatosensory function in experimental models of intraoral pain, effects of local anesthesia, after oral and maxillofacial surgery and after prosthodontic and orthodontic treatment. CONCLUSIONS: QST has been proved to be sufficiently stable and reliable, and valuable information has been obtained regarding somatosensory function in healthy volunteers, special populations and orofacial pain patients. However, as most of the studies were highly heterogeneous, the results are difficult to compare quantitatively. A standardized intraoral QST protocol is recommended and expected to help advance a mechanism-based assessment of neuropathies and other intraoral pain conditions.

Comparison of in vitro dentinal tubule occluding efficacy of two different methods using a nano-scaled bioactive glass-containing desensitising agent.

OBJECTIVE: This study aimed to compare the in vitro dentinal tubule occluding efficacy of two different methods using a nano-scaled bioactive glass (BG)-containing desensitising agent. METHODS: Citric acid treated dentine discs were randomly divided into 7 groups (n=8). Group A1, A2 and A3: dentine discs coated with BG desensitising paste; Group B1, B2 and B3: dentine discs coated with BG desensitising paste and covered with matched transparent trays; and control group (GroupC): dentine discs treated with deionised water. Field Emission Scanning Electron Microscopy (FE-SEM) was used to capture topographical images of each dentine discs after they were immersed in artificial saliva for corresponding treatment time and dentinal tubules exposure rates were thus measured. Elemental compositions of dentine discs were identified using Energy-Dispersive X-ray Spectroscopy (EDX). RESULTS: FE-SEM revealed better tubule occluding effects in Group B. Dentinal tubules in Group B3 were totally occluded with continuous homogeneous minerals to a depth of 20.6-24.7µm. Dentinal tubule exposure rates in Group B1, Group B2 and Group B3 were lower than that in Group A1, Group A2 and Group A3. EDX indicated that occluding deposits observed in each group were calcium-deficient hydroxyapatite. CONCLUSIONS: The application of transparent trays in combination with nano-scaled BG-containing desensitising paste could increase the dentinal tubule occluding effectiveness of the latter one and shorten the treatment time. CLINICAL RELEVANCE: Transparent trays could be used in combination with BGs-containing desensitising paste as the containers of the latter one in order to increase the dentinal tubule occluding effectiveness. This could lead to the development of a new therapeutic technique for treating dentine hypersensitivity.

Ischemia-induced autophagy contributes to neurodegeneration in cerebellar Purkinje cells in the developing rat brain and in primary cortical neurons in vitro.

Increased autophagy/mitophagy is thought to contribute to cerebellar dysfunction in Purkinje cell degeneration mice. Intriguingly, cerebellar Purkinje cells are highly vulnerable to hypoxia-ischemia (HI), related at least in part to their high metabolic activity. Whether or not excessive or supraphysiologic autophagy plays a role in Purkinje cell susceptibility to HI is unknown. Accordingly, we evaluated the role of autophagy in the cerebellum after global ischemia produced by asphyxial cardiac arrest in postnatal day (PND) 16-18 rats, using siRNA-targeted inhibition of Atg7, necessary for microtubule-associated protein light chain 3-II (LC3-II) and Atg12-Atg5 complex formation. Two days before a 9min asphyxial cardiac arrest or sham surgery, Atg7 or control siRNA was injected intracisternally to target the cerebellum. Treatment with Atg7 siRNA: 1) reduced Atg7 protein expression in the cerebellum by 56%; 2) prevented the typical ischemia-induced formation of LC3-II in the cerebellum 24h after asphyxial cardiac arrest; 3) improved performance on the beam-balance apparatus on days 1-5; and 4) increased calbindin-labeled Purkinje cell survival assessed on day 14. Improved Purkinje cell survival was more consistent in female vs. male rats, and improved beam-balance performance was only seen in female rats. Similar responses to Atg7 siRNA i.e. reduced autophagy and neurodegeneration vs. control siRNA were seen when exposing sex-segregated green fluorescent protein-LC3 tagged mouse primary cortical neurons to oxygen glucose deprivation in vitro. Thus, inhibition of autophagy after global ischemia in PND 16-18 rats leads to increased survival of Purkinje cells and improved motor performance in a sex-dependent manner.

Antimicrobial effects of a bioactive glass combined with fluoride or triclosan on Streptococcus mutans biofilm.

OBJECTIVE: The objective of this study was to investigate the antibacterial effects on a cariogenic biofilm of a bioactive glass (BAG) combined with either sodium fluoride (NaF) or triclosan (TCS). DESIGN: According to minimal bactericidal concentrations, 37.5mg/ml of BAG, 4.69 mg/ml of NaF, and 15.53 µg/ml of TCS solutions were prepared. When used alone, the three antimicrobial solutions were increased to double-dosage strength (2 MBC). The study contained the following experimental groups: group 1, BAG (2 MBC); group 2, NaF (2 MBC); group 3, TCS (2 MBC); group 4, BAG+NaF; group 5, BAG+TCS; group 6, control (saline). Streptococcus mutans biofilm was cultured with 0.1% sucrose anaerobically on 66 sterilized coverslips (1 × 1 cm(2)) for 24h uninterrupted. After 10 min of exposure to the experimental groups, the microbial kinetics, morphology, and viability of the S. mutans biofilms were assessed by evaluation of colony-forming units (CFUs), scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM). RESULTS: BAG (2 MBC) used alone showed significantly stronger antibacterial effects than the other two antimicrobials used alone. The combination groups also displayed the same or greater biofilm inactivation effects as BAG (2 MBC) in the plate count test. SEM showed smaller stacks (towers) and fewer surrounding bacteria in groups BAG (2 MBC), BAG+NaF, and BAG+TCS. Confocal microscopy also determined higher live/dead ratios in groups NaF (2 MBC), TCS (2 MBC), and control than in groups BAG (2 MBC), BAG+NaF, and BAG+TCS. CONCLUSIONS: The combinations of BAG with either NaF or TCS enhanced the inactivation effects of BAG (2 MBC) on S. mutans biofilm, and these findings should be further investigated clinically for the control of dental biofilms.

Large-deviation properties of Brownian motion with dry friction.

We investigate piecewise-linear stochastic models with regard to the probability distribution of functionals of the stochastic processes, a question that occurs frequently in large deviation theory. The functionals that we are looking into in detail are related to the time a stochastic process spends at a phase space point or in a phase space region, as well as to the motion with inertia. For a Langevin equation with discontinuous drift, we extend the so-called backward Fokker-Planck technique for non-negative support functionals to arbitrary support functionals, to derive explicit expressions for the moments of the functional. Explicit solutions for the moments and for the distribution of the so-called local time, the occupation time, and the displacement are derived for the Brownian motion with dry friction, including quantitative measures to characterize deviation from Gaussian behavior in the asymptotic long time limit.

First-passage time of Brownian motion with dry friction.

We provide an analytic solution to the first-passage time (FPT) problem of a piecewise-smooth stochastic model, namely Brownian motion with dry friction, using two different but closely related approaches which are based on eigenfunction decompositions on the one hand and on the backward Kolmogorov equation on the other. For the simple case containing only dry friction, a phase-transition phenomenon in the spectrum is found which relates to the position of the exit point, and which affects the tail of the FPT distribution. For the model containing as well a driving force and viscous friction the impact of the corresponding stick-slip transition and of the transition to ballistic exit is evaluated quantitatively. The proposed model is one of the very few cases where FPT properties are accessible by analytical means.