Paleo-Geomorphology Determines Spatial Variability of Geogenic Ammonium Concentration in Quaternary Aquifers.

Naturally occurring (i.e., geogenic) ammonium in groundwater has been widely detected globally, but the major controls on its regional distribution have been poorly characterized. Here, we identified the dominant role of paleo-geomorphology driven by paleo-climate in controlling the spatial variability of geogenic ammonium in groundwater using random forest algorithm and revealed the underlying mechanisms based on borehole sediment analysis of data obtained from the Dongting Lake Plain of the central Yangtze River basins in China. In the paleo-channel (PC) area, the aquifer depth-matched sediments were deposited during the last deglaciation when warm climate resulted in rapid filling into incised valleys, and terrestrial organic matter (OM) mainly as lignin experienced less degradation prior to sedimentation and had lower humification, higher N abundance, and nominal oxidation state of carbon (NOSC). In the paleo-interfluve (PI) area, the depth-matched sediments were deposited during the last glaciation, followed by intensive erosion in the surface during the last glacial maximum, and terrestrial OM mainly as lignin had been partly degraded into aliphatics prior to sedimentation and had higher humification, lower N abundance, and NOSC. As a result, under the present anaerobic conditions, less-humic and N-rich OM with more oxidized C tends to be more intensively mineralized into ammonium in the PC area than those in the PI area. These findings highlight the importance of paleo-geomorphology with paleo-climate in controlling the enrichment of geogenic ammonium in groundwater, which has a universal significance for understanding the genesis and distribution of high N loads in the aquatic environment worldwide.

Comparison of the efficacy of laser-activated and ultrasonic-activated techniques for the removal of tricalcium silicate-based sealers and gutta-percha in root canal retreatment: a microtomography and scanning electron microscopy study.

BACKGROUND: Tricalcium silicate-based sealers have been usually indicated for the single-cone technique and result in more residual filling materials in root canal retreatment. Passive ultrasonic irrigation and photon-initiated photoacoustic streaming have been reported to improve the removal efficacy of root canal filling materials. However, the abilities of both techniques combined with NiTi re-instrumentation to remove residual tricalcium silicate-based sealer and gutta-percha have not been compared. The aim of this study was to evaluate the efficacy of laser-activated and ultrasonic-activated techniques in vitro for the removal of the tricalcium silicate-based sealer iRoot SP and gutta-percha after standard canal retreatment procedures with the use of nickel-titanium (NiTi) rotary instruments.

High failure rate after Beta-tricalcium phosphate grafting for the treatment of femoral head osteonecrosis: a retrospective analysis.

BACKGROUND: Non-vascularized bone grafting is a promising head-preserving technique for younger patients diagnosed as non-traumatic osteonecrosis of the femoral head (NONFH). Among the various types of bone grafting techniques, "light-bulb" procedure grafting with synthetic bone substitute is an attractive option. We aimed to assess the effectiveness of using beta-tricalcium phosphate (ß-TCP) for the treatment of pre-collapse and early post-collapse lesions NONFH. METHODS: From April 2010 to June 2014, 33 patients (47 hips) with NONFH were treated using the afore-mentioned technique. The clinical and radiological outcomes were recorded and compared statistically between pre- and post-operation. Harris hip score (HHS) was used to evaluate the clinical results, and Association Research Circulation Osseous (ARCO) stage was applied to assess the radiological outcomes. RESULTS: The 5-years survival rate of using ß-TCP grafting was accounting for 25.5%. HHS was decreased from 78.47 to 52.87 points, and a very significant worsening of radiological results were revealed (P <  0.05). Two hips collapsed more than 2 mm were awaiting for THA, and 33 of the 47 hips had converted to THAs in an average time to failure of 24.24 months postoperatively. Meanwhile, only 4 hips survived without collapse, and 8 hips collapsed less than 2 mm. After surgery, the time onset of head collapse was 3.65 months on average, and the first conversion to THA was performed at 5 months postoperative. CONCLUSIONS: Our results suggest that "light-bulb" procedure grafting with ß-TCP sticks presented with a high failure rate in the early postoperative period. It is not proposed for the treatment of pre-collapse and early post-collapse lesions NONFH.

Inhibition of Ctsk alleviates periodontitis and comorbid rheumatoid arthritis via downregulation of the TLR9 signalling pathway.

AIM: In this study, we investigate the mechanistic link between rheumatoid arthritis (RA) and periodontitis to identify a novel target (cathepsin K; Ctsk) for the treatment of comorbid periodontitis and RA. METHODS: An experimental model of periodontitis with arthritis was established in DBA/1 mice. We then tested the effect of BML-244, a specific inhibitor of Ctsk, by quantifying several inflammatory markers of TLR9 signalling both in vivo and in vitro. RESULTS: Our results showed that periodontitis-rheumatoid arthritis comorbidity causes severer periodontal bone and joint cartilage destruction than either disease alone. Inhibition of Ctsk reduced infiltration by dendritic cells and T cells and inflammatory cytokine production; these improvements alleviated the hard-tissue erosion in periodontitis and RA as measured by bone erosion in periodontal lesions and cartilage destruction in knee joints. Inhibition of Ctsk also decreased the expression of TLR4 and TLR9 in vivo, whereas in vitro experiments indicated that Ctsk is involved specifically in the production of cytokines in response to TLR9 engagement. CONCLUSION: Our data reveal that periodontitis and RA may have additive pathological effects through dysregulation of the TLR9 pathway and that Ctsk is a critical mediator of this pathway and contributes to the pathogenesis of RA and periodontitis.

Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study.

OBJECTIVE: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. DESIGN: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA

Application of a novel M-NED in ENBD patients: A case series report.

RATIONALE: The traditional methods for exchanging the endoscopic nasobiliary drainage (ENBD) tube from the mouth to the nose, such as the guidewire method, sponge holding forceps method, and finger method, have significant drawbacks including pharyngeal stimulation symptoms, high incidence of epistaxis, low success rate, and potential bite injuries to the operator. PATIENT CONCERNS: A case series of 9 patients who underwent ENBD at Shenzhen Second People's Hospital from January 2021 to December 2021 was collected. DIAGNOSES: The study included 9 patients diagnosed with choledocholithiasis, with 3 males and 6 females, with an average age of (55 ± 9.798) years (range 43-71). INTERVENTIONS: The M-NED was used to exchange the ENBD tube, and the success rate, operation time, and complications were recorded. OUTCOMES: All patients successfully completed the operation in one go with an average mouth-nose exchange time of (44.67 ± 13.388) seconds (range 28-65). Two patients had mild adverse events, one of which was controllable bleeding caused by nasal mucosal injury with an estimated blood loss of 1 mL. The other patient had nausea during the operation, which improved after completion. LESSONS: The novel M-NED is an effective and safe method for exchanging the ENBD tube from the mouth to the nose with a high success rate and low incidence of complications. It is a device with potential clinical application value.

An extremely rare pedunculated lipoma of the hypopharynx: A case report.

BACKGROUND: Hypopharyngeal lipoma is a rare disease that can lead to asphyxiation after aspiration. Sclerotic lipoma in the hypopharynx is an extremely rare histological type. Hypopharyngeal lipoma should be resected in time after diagnosis. CASE SUMMARY: An 86-year-old female patient presented to our department with a long pedunculated mass protruding from her mouth. Until this time, the patient had no dyspnea, dysphagia, or throat discomfort. Physical examination showed stable vital signs and clear consciousness. The pedicel was derived from the posterior wall of the hypopharynx. The tumor was smooth, hyperemic and dark red, about 10 cm long, and 4 cm wide. In order to prevent airway obstruction, the hypopharyngeal tumor was excised in emergent operation. The pharyngeal cavity was exposed by a mouth gag during the operation. A disposable plasma knife was used to completely remove the tumor along the base of the new organism, and no active bleeding occurred. The postoperative pathological results were sclerotic lipoma. CONCLUSION: Lipoma in the pharynx is relatively rare. Patients with this condition must be referred immediately to Ear-Nose-Throat specialists and complete surgical excision should be performed as soon as possible to prevent serious complications, such as airway obstruction and death.

Inhibition of angiotensin II receptor I prevents inflammation and bone loss in periodontitis.

BACKGROUND: Periodontal disease is characterized by alveolar bone destruction and degenerative lesions of the periodontal ligament (PDL); it is initiated by bacterial infection of the oral cavity, but the clinical effects are secondary to an aberrant host immune response. Primary hypertension (PH), which causes significant morbidity and mortality worldwide, has also been shown to be an inflammatory disease characterized by aberrant immune cell infiltration and activation. Clinical retrospective studies have shown a link between PH and periodontitis with PH exacerbating periodontitis and vice versa, but the pathophysiologic mechanisms responsible for this remain unknown. METHODS: In this study, we investigate the underlying mechanisms behind PH exacerbation of periodontitis by using a bacteria-induced periodontitis model in normotensive and hypertensive (Nos3-/- ) mice treated with or without an Angiotensin II (Ang II) specific receptor 1 (AT1) antagonist, losartan. The histologic analyses including immunohistochemistry, immunofluorescence were carried out. The qRT-PCR and ELISAs were applied for the target gene and protein detection. RESULTS: We find that PH worsens bone resorption and PDL destruction in periodontitis and that treatment with losartan, rescues this. We also show that PH increases dendritic cell (DC) and osteoclast (OC) infiltration in periodontitis, which is also dependent on Ang II. Finally, we show that PH augments the pro-inflammatory state in periodontitis infiltrating DCs in an Ang II-dependent manner and use in vitro studies to show that Ang II directly augments DC Toll-like receptor 4 (TLR4) signaling. CONCLUSION: Our studies show a central role for Ang II as a pro-inflammatory Toll-like receptor mediator in the pathogenesis of PH-exacerbated periodontitis, indicating that Ang II may be a reasonable target in patients with PH and periodontitis comorbidity.

A Nuclease from Streptococcus mutans Facilitates Biofilm Dispersal and Escape from Killing by Neutrophil Extracellular Traps.

Streptococcus mutans is the primary etiologic agent of dental caries and occasionally infective endocarditis, with the ability to form biofilms and disperse cells into distal sites to exacerbate and spread infection. In this study, we identified a nuclease (DeoC) as a S. mutans biofilm dispersal modulating factor through microarray analysis. In vitro assays revealed a dispersal defect of a deoC deletion mutant, and functional studies with purified protein were indicative of the biofilm dispersal activity of DeoC. Neutrophils are a key host response factor restraining bacterial spreading through the formation of neutrophil extracellular traps (NETs), which consist of a nuclear DNA backbone associated with antimicrobial peptides. Therefore, we hypothesized that the dispersed S. mutans might utilize DeoC to degrade NETs and escape killing by the immune system. It was found that S. mutans induced NET formation upon contact with neutrophils, while the presence of NETs in turn enhanced the deoC expression of S. mutans. Fluorescence microscopy inspection showed that deoC deletion resulted in a decreased NET degradation ability of S. mutans and enhanced susceptibility to neutrophil killing. Data obtained from this study assigned two important roles for DeoC in S. mutans: contributing to the spread of infection through mediating biofilm dispersal, and facilitating the escape of S. mutans from neutrophil killing through NET degradation.

Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1: a Phase III, open-label study.

BACKGROUND: Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. METHODS: AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 µg, for 24 weeks. If required by RGT, PegIFN/RBV without DCV was extended for an additional 24 weeks of therapy. The primary endpoint was the proportion of patients with sustained virologic response at post-treatment Week 12 (SVR12). RESULTS: Overall, 224 (74%) patients achieved SVR12 and the lower bound of the 95% confidence interval was higher than the historic SVR rate with PegIFN/RBV alone (70 vs. 29%). Most common adverse events (AEs) were fatigue, neutropenia, anemia, asthenia and headache. On-treatment serious AEs occurred in 24/301 (8%) patients; 18/301 (6%) discontinued treatment due to AE. CONCLUSIONS: DCV + PegIFN/RBV led to sustained HCV virologic response in the majority of HIV-1-HCV-coinfected patients, regardless of concomitant ART. HIV control was not compromised and no new safety signals were identified. This study supports DCV use in HIV-1-HCV-coinfected patients, while allowing the vast majority of patients to remain on their existing ART regimen.

The shaping and cleaning abilities of self-adjusting files in the preparation of canals with isthmuses after glidepath enlargement with ISO or ProTaper Universal NiTi files.

BACKGROUND/PURPOSE: This study compared the shaping and cleaning ability of self-adjusting files (SAF) after glidepath enlargement with ISO NiTi files (Group I) or ProTaper Universal (PTU; Group II) for preparing maxillary premolar canals with isthmuses. MATERIALS AND METHODS: Twenty-eight teeth containing isthmuses were scanned preoperationally after glidepath enlargement and preparation with SAF (n = 14). Changes in canal and isthmus volume, prepared surface, debris volume, and transportation were determined. Data were compared by t test between groups and paired t test within each group. RESULTS: No difference was observed regarding changes in canal volume or prepared surface between the two groups (P > 0.05). Paired t tests showed that the coronal and middle prepared areas of the canal after using SAF in Group I were statistically larger than those using ISO files, whereas the use of an adjuvant preparation with SAF after PTU resulted in a significant increase in the apical prepared area in Group II. ISO and SAF systems deviated less from the center than did PTU and SAF systems at most sections. After the use of SAF, isthmus volumes were significantly increased within each group (P < 0.05). Although less debris resulted from the use of SAF instruments as compared to glidepath instruments, there was no significant difference between both groups (P > 0.05). CONCLUSION: SAF following glidepath enlargement with ISO files could improve preparation of the coronal and middle part of the canals, and adjuvant preparation with SAF after using large-taper instruments increased the apical prepared area.

[The effect of Galla chinensis on the demineralization of enamel].

OBJECTIVE: To investigate the effect of Galla Chinensis with or without fluoride on demineralization of enamel. METHODS: Galla Chinensis with or without fluoride and acid buffer were used to treat the samples alternately and the treatment was repeated 8 times. Then the calcium of acid buffer was measured by American PE HTS 7000 plus and the specimens were observed with laser scanning confocal microscope. RESULTS: Compared with the calcium concentration of control group (deionized water or fluoride), the calcium concentration of all tested groups (except the 1 mg/ml group without fluoride) decreased significantly (P < 0.25). There was marked difference in total fluorescence (TF) and average fluorescence (AF) between the tested groups and control group (P < 0.05). As for the area of lesion, only groups without fluoride and the 4 mg/ml group containing fluoride decreased (P < 0.01). Confocal images showed that the zone of red area of tested groups was narrower than that of control group. CONCLUSION: Galla Chinensis can reinforce the resistance of enamel to acid, either with or without fluoride.

Role of miR-424 on angiogenic potential in human dental pulp cells.

INTRODUCTION: Growing evidence shows microRNAs (miRNAs) regulate numerous cellular processes. The purpose of this study was to investigate whether miRNAs can regulate the commitment of human dental pulp cells (hDPCs) to the angiogenic fate. METHODS: The hDPCs were induced to differentiate into the vascular lineage. Gene expression of endothelial markers (vWF and CD31) on day 7 after induction was analyzed by using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).The miRNA expression profiling of endothelial differentiation was performed by microarray and was validated by qRT-PCR analysis. The hDPCs were infected by recombinant lentivirus to overexpress or knock down miR-424 stably, and the biological effects of miR-424 on the endothelial differentiation of hDPCs were further investigated. The tube formation ability and the amount of endothelial markers (vWF and KDR) were evaluated by Matrigel assay and Western blotting. Target genes of miR-424 were further determined by bioinformatic algorithms and Western blotting. RESULTS: After endothelial differentiation, the expression of vWF and CD31 increased significantly in hDPCs. Microarray data showed that the miR-424 expression level was down-regulated on day 7. The qRT-PCR revealed a time-dependent decrease, with significant differences detected on day 1 and day 7 (P < .05). Knockdown of miR-424 expression in hDPCs promoted endothelial differentiation, with increased tube formation and up-regulated expression of vWF and KDR. In contrast, overexpression of miR-424 inhibited their differentiation. In addition, miR-424 was predicted to target vascular endothelial growth factor and KDR. Overexpression of miR-424 decreased vascular endothelial growth factor and KDR protein levels, whereas miR-424 inhibition significantly elevated them. CONCLUSIONS: This study demonstrated that miR-424 may play a negative role in regulating endothelial differentiation of hDPCs, and inhibition of miR-424 may contribute to dental pulp repair and regeneration.

Open reduction and internal fixation of severely dislocated fractures of condylar neck and base using bioabsorbable miniplate in children: a 3-10 years follow-up study.

OBJECTIVE: To evaluate the long-term clinical and radiologic outcomes of treating severely dislocated fractures of condylar neck and base with the comminuted fractures of parasymphysis or mental foramen, specially with crown fracture of deciduous molar and permanent molar or dislocation of the teeth sustained in childhood using bioabsorbable miniplate with open reduction and internal fixation (ORIF). METHODS: Five children (age ranged from 3 to 11 years old averaged 8.2 years; 3 boys and 2 girls) with severely (the condyle dislocated from the glenoid fossa) dislocated fractures of condylar neck or base with the comminuted fractures of parasymphysis or mental foramen, specially with crown fracture of deciduous molar and permanent molar or dislocation of the teeth were treated with ORIF using 1 or 2 bioabsorbable miniplates (through preauricular approach and an oral vestibular approach). All patients have been followed-up clinically and radiographically for a mean of 5.6 years (range, 3-10 years). RESULTS: All patients were cured satisfactorily with excellent occluding relation without restricted mandibular movement, facial asymmetry, retrognathism and ankylosis. 3-10 years follow-up study did not occur any mandibular development disorder. CONCLUSION: The results suggested that ORIF using bioabsorbable miniplate was a reliable fixation technique for use in the treatment of severely dislocated fractures of the condylar neck and base with the comminuted fractures of parasymphysis or mental foramen, specially with crown fracture of deciduous molar and permanent molar or dislocation of the teeth in children when the non-invasive or occlusal therapies were ineffective.

Polyethylene glycol (PEG)-mediated transformation in filamentous fungal pathogens.

Genetic transformation is an essential tool for the modern study of gene function and the genetic improvement of an organism. The genetic transformation of many fungal species is well established and can be carried out by utilizing different transformation methods including electroporation, Agrobacterium, biolistics, or polyethylene glycol (PEG)-mediated transformation. Due to its technical simplicity and common equipment requirements, PEG-mediated transformation is still the most commonly used method for genetic transformation in filamentous fungi. Here, we describe a PEG-based protocol developed for genetic transformation of Stagonospora nodorum, a fungal pathogen of wheat. This protocol is directly applicable to other fungi especially those in the Dothideomycete class of fungi.