Exploitation of a novel adjuvant for polymyxin B against multidrug-resistant Acinetobacter baumannii.

BACKGROUND: Although polymyxin has been used as a last-resort antibiotic against resistant bacteria, its use is restricted due to nephrotoxicity and neurotoxicity. While the present antibiotic resistance issue compels clinicians to reconsider polymyxin use in severe illness cases, polymyxin-resistant microorganisms exert an effect. OBJECTIVES: To address the issue of antibiotic resistance, the cycle of developing new antibiotics to counteract emerging resistance must be discontinued. Here we tried to develop novel therapies that do not rely on direct antimicrobial activity and thus do not promote antibiotic resistance. METHODS: By a high-throughout screening system based on bacterial respiration, chemical compounds accelerating the antimicrobial effects of polymyxin B were screened. In vitro and in vivo tests were performed to validate adjuvanticity. In addition, membrane depolarization and total transcriptome analysis were used to determine molecular mechanisms. RESULTS: PA108, a newly discovered chemical compound, was used to eradicate polymyxin-resistant A. baumannii and three other species in the presence of polymyxin B at concentrations less than the MIC. Since this molecule lacks self-bactericidal action, we hypothesized that PA108 acts as an antibiotic adjuvant, enhancing the antimicrobial activity of polymyxin B against resistant bacteria. At working concentrations, no toxicity was observed in cell lines or mice, although co-treatment with PA108 and polymyxin B increased survival of infected mouse and decreased bacterial loads in organs. CONCLUSIONS: Boosting antibiotic efficiency through the use of antibiotic adjuvants holds significant promise for tackling the rise in bacterial antibiotic resistance.

Uncertainty Evaluation for the Quantification of Urinary Amphetamine and 4-Hydroxyamphetamine Using Liquid Chromatography-Tandem Mass Spectrometry: Comparison of the Guide to the Expression of Uncertainty in Measurement Approach and the Monte Carlo Method with R.

Estimating the measurement uncertainty (MU) is becoming increasingly mandatory in analytical toxicology. This study evaluates the uncertainty in the quantitative determination of urinary amphetamine (AP) and 4-hydroxyamphetamine (4HA) using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method based on the dilute-and-shoot approach. Urine sample dilution, preparation of calibrators, calibration curve, and method repeatability were identified as the sources of uncertainty. To evaluate the MU, the Guide to the Expression of Uncertainty in Measurement (GUM) approach and the Monte Carlo method (MCM) were compared using the R programming language. The MCM afforded a smaller coverage interval for both AP (94.83, 104.74) and 4HA (10.52, 12.14) than that produced by the GUM (AP (92.06, 107.41) and 4HA (10.21, 12.45)). The GUM approach offers an underestimated coverage interval for Type A evaluation, whereas the MCM provides an exact coverage interval under an abnormal probability distribution of the measurand. The MCM is useful in complex settings where the measurand is combined with numerous distributions because it is generated from the uncertainties of input quantities based on the propagation of the distribution. Therefore, the MCM is more practical than the GUM for evaluating the MU of urinary AP and 4HA concentrations using LC-MS/MS.

Determination of zolpidem phenyl-4-carboxylic acid and zolpidem 6-carboxylic acid in hair using gas chromatography-electron ionization-tandem mass spectrometry.

A gas chromatography-electron ionization-tandem mass spectrometric (GC-EI-MS/MS) method was developed and validated for determination of the major metabolites of zolpidem, zolpidem phenyl-4-carboxylic acid (ZPCA) and zolpidem 6-carboxylic acid (ZCA) in human hair. The sample preparation procedure involves decontamination, mechanical pulverization, incubation, extraction and purification prior to instrumental analysis. The extracts were derivatized using hexafluoroisopropanol and heptafluorobutyric anhydride and analyzed by GC-EI-MS/MS. The linear ranges were 8-100 pg/mg for ZPCA and 16-200 pg/mg for ZCA, with the correlation coefficients >0.997. The limits of detection were 1.8 pg/mg for ZPCA and 1.7 pg/mg for ZCA. The recoveries ranged from 77.6 to 111.7%. The intra- and inter-day precisions were within 16.9 and 11.7%, while intra- and inter-day accuracies were -7.0-8.7 and -2.8-7.8%, respectively. The developed method was applied for the analysis of forensic hair samples obtained from suspected zolpidem abusers and the following concentration ranges were monitored: ZPCA 11.9-35.9 pg/mg and ZCA 16.6-21.8 pg/mg. The method proved to be suitable for picogram-level determination of ZPCA and ZCA in human hair.

Crossing the kingdom border: Human diseases caused by plant pathogens.

Interactions between pathogenic microorganisms and their hosts are varied and complex, encompassing open-field scale interactions to interactions at the molecular level. The capacity of plant pathogenic bacteria and fungi to cause diseases in human and animal systems was, until recently, considered of minor importance. However, recent evidence suggests that animal and human infections caused by plant pathogenic fungi, bacteria and viruses may have critical impacts on human and animal health and safety. This review analyses previous research on plant pathogens as causal factors of animal illness. In addition, a case study involving disruption of type III effector-mediated phagocytosis in a human cell line upon infection with an opportunistic phytopathogen, Pseudomonas syringae pv. tomato, is discussed. Further knowledge regarding the molecular interactions between plant pathogens and human and animal hosts is needed to understand the extent of disease incidence and determine mechanisms for disease prevention.

Soft tissue expander for vertically atrophied alveolar ridges: Prospective, multicenter, randomized controlled trial.

OBJECTIVES: Conventional guided bone regeneration (GBR) limits the amount of bone graft due to limited soft tissue expansion. We hypothesize that the use of tissue expander will successfully augment soft tissue prior to bone graft, allowing for sufficient amount of grafting which will lead to a more stable and effective vertical bone graft. The authors aimed to evaluate effectiveness of the novel self-inflating tissue expander for vertical augmentation in terms of soft tissue expansion, clinical outcomes, and related complications. MATERIAL AND METHODS: A prospective, multicenter, randomized controlled trial was performed on patients requiring vertical augmentation. For experimental group patients, the tissue expander was subperiosteally implanted and followed by a tunneling bone graft without full flap reflection. Control patients underwent conventional vertical GBR. Primary objectives were to evaluate the dimensional changes of soft tissue and radiographic vertical bone gain and retention. As a secondary outcome, clinical complications and thickness changes of expanded overlying tissue were assessed and analyzed. RESULTS: Twenty-three patients in each group were included. During a 4-week expansion, two of the experimental group showed over-expansion and one showed mucosal perforation associated with previous severe scars. The other patients showed uneventful expansion and mean tissue augmentation was 6.88 ± 1.64 mm vertically. Ultrasonographic measurements of overlying gingiva revealed no thinning after tissue expansion (p > .05). Significantly higher vertical bone gain was shown in the experimental group (5.12 ± 1.25 mm) compared with that in the control patients (4.22 ± 1.15 mm; p < .05). After a 6-month retention period, the mean vertical bone measurement of the controls had decreased to 1.90 mm (55.0% reduction), which was a significantly greater decrease than that in the experimental group (mean 3.55 mm, 30.7% reduction; p < .05). CONCLUSION: Our results demonstrated the effectiveness of tissue expanders followed by tunneling bone graft for vertical augmentation; however, studies comparing the two techniques without tissue expanders are needed to elucidate the net effect of tissue expansion.

Simultaneous Determination of Etomidate and Its Major Metabolite, Etomidate Acid, in Urine Using Dilute and Shoot Liquid Chromatography-Tandem Mass Spectrometry.

Etomidate (ET) is a commonly used sedative-hypnotic agent such as propofol to induce anesthesia, and it is rapidly metabolized to etomidate acid (ETA) in liver. Herein, a simple method to determine ET and ETA in urine simultaneously was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A simple sample preparation method reduced the total analysis time. For all analytes, the separation was achieved in 6.5 min using reversed-phase chromatography with gradient elution. The best separation and detection of ETA was achieved using a porous graphitic carbon column. The column temperature was maintained at 30 °C to improve the efficiency and sensitivity. The calibration curves were linear over the concentration ranges of 0.4-120.0 ng/mL (ET) and 1.0-300.0 ng/mL (ETA), obtained with a weighting factor of 1/x2. The coefficients of determination (r2) were greater than 0.9958. The lower limits of quantification were 0.4 ng/mL (ET) and 1.0 ng/mL (ETA), intra-day (n = 6) and inter-day (n = 24) precision values for all compounds were less than 10.2% and 8.4%, respectively, while the intra- and inter-day accuracies were in the -9.9-2.9%, and -7.0-0.6%. The applicability of the method was examined by analyzing the urine samples obtained from ET users.

Traumatic Buccal Fat Pad Herniation in Young Children: A Systematic Review and Case Report.

PURPOSE: Traumatic herniation of a buccal fat pad, predominantly seen in young children, is a rare condition. Because of its rarity and clinical features that resemble tumors, clinicians are faced with challenges at the initial diagnosis. This report describes a case of buccal fat pad herniation with excellent long-term prognosis after surgical relocation and conservative treatment and presents a systematic review of the literature on its management. MATERIALS AND METHODS: Through a PubMed search, 811 articles were initially identified. Case series, case reports, technical notes, case and review reports, and retrospective case series were included. After screening and manual review, the sample was narrowed to 35 reports (41 patients) based on eligibility criteria. Articles were included if the standard criteria for traumatic intraoral herniation of buccal fat pad were met. RESULTS: Patients' ages ranged from 4 months to 12 years, with no specific gender predilection. Management consisted of excision (82.9%), relocation (14.6%), and observation (2.4%). Follow-up ranged from 1 week to 4 months. No reports presented a follow-up longer than 4 months; hence, data on long-term prognosis were not reported. For the present case report, a 19-month-old boy diagnosed with traumatic buccal fat pad herniation was successfully treated with surgical relocation and antibiotic support. Twelve-month follow-up showed no esthetic or functional disturbance or recurrence. CONCLUSION: Traumatic herniation of the buccal fat pad requires special attention at the initial diagnosis. Considering its clinical importance in young children and few studies have reported long-term postresection follow-up, surgical relocation can be regarded as an excellent and more conservative treatment option.

Analysis of the relationship between liver regeneration rate and blood levels.

OBJECTIVES: The aim of this study was to investigate the difference of liver function changes according to the liver regeneration rate after liver transplantation through blood tests. METHODS: Fifty donors, who underwent computed tomography (CT) 3D volumetry, were analyzed before and after liver transplantation. CT 3D volumetry was used as a study method to measure the mean liver regeneration volume and regeneration rate. Then, blood levels were measured including alanine transaminase (ALT), aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) and total bilirubin. RESULTS: The liver regeneration rate rapidly increased from 39.13±4.91% befoone1 month and 90.31±13.09% 16 months after surgery furthermore. Blood levels rapidly increased 7 days after surgery and then decreased 16 months after surgery compared to the state before surgery. CONCLUSION: This study results could be used as a basis for the prognosis of future liver transplantations.

Unveiling the Impact of Tailoring Ionic Conductor Characteristics on the Performance of Wearable Triboelectric Nanogenerators.

This work reveals the correlation between the performance of triboelectric nanogenerators (TENGs) and the characteristics of deformable solid-state ionic conductors (referred to as ionogels). For this purpose, we modify ionogel characteristics by incorporating additional plasticizers (propylene carbonate) and solid salts (lithium bis(trifluoromethylsulfonyl)imide) into the ionogels. We conclude that the high capacitance of the ionogel is crucial for achieving a high-performance TENG platform. The optimized ionogel-based TENG (i-TENG) exhibits a power density of ∼372.4 mW·m-2 (based on 95 V and 36 mA·m-2 outputs) with outstanding long-term stability over 2 weeks. Additionally, successful demonstrations of wearable nanogenerators are performed by leveraging the high stretchability (up to ∼1000%) and optical transparency (∼90%) of the ionogels. Overall, the results provide insight into the design of deformable ionic conductors for high-performance, reliable, and wearable TENGs.

High-Voltage Pulse-Assisted Operation of Single-Layer Electrochromic Systems for High Performance and Reliability.

A single-layer electrochromic device (SL-ECD) based on ionic conductors containing EC chromophores provides a very simple platform that can be readily fabricated by sandwiching the EC layer between two electrodes. The operation of SL-ECDs is governed by the diffusion of redox species due to their SL structure, which causes a relatively slow dynamic response. In this study, we propose an effective high-voltage pulse injection strategy to improve the performance of SL-ECDs. Applying a programmed voltage wave composed of DC and high-voltage pulses promotes coloration/bleaching switching without degrading device stability, which is more advantageous than applying high DC voltages. We modified the input voltage profile by considering fundamental parameters, such as the amplitude and duty ratio of additional voltage pulses. The coloration and bleaching dynamic responses with the optimized voltage wave are ∼62 and ∼20% faster, respectively, compared with those with the simple DC input. Furthermore, the additionally injected pulse aids in increasing the coloration efficiency from ∼95.3 to ∼168.6 cm2 C-1. Another notable feature of this system is that the device operates stably when a programmed voltage wave is used. These results indicate that the concept of high-voltage pulse-assisted operation of SL-ECDs is a straightforward but effective method for improving device performance without changing the EC chromophore or device structure.

Collagen Peptide Exerts an Anti-Obesity Effect by Influencing the Firmicutes/Bacteroidetes Ratio in the Gut.

Alterations in the intestinal microbial flora are known to cause various diseases, and many people routinely consume probiotics or prebiotics to balance intestinal microorganisms and the growth of beneficial bacteria. In this study, we selected a peptide from fish (tilapia) skin that induces significant changes in the intestinal microflora of mice and reduces the Firmicutes/Bacteroidetes ratio, which is linked to obesity. We attempted to verify the anti-obesity effect of selected fish collagen peptides in a high-fat-diet-based obese mouse model. As anticipated, the collagen peptide co-administered with a high-fat diet significantly inhibited the increase in the Firmicutes/Bacteroidetes ratio. It increased specific bacterial taxa, including Clostridium_sensu_stricto_1, Faecalibaculum, Bacteroides, and Streptococcus, known for their anti-obesity effects. Consequently, alterations in the gut microbiota resulted in the activation of metabolic pathways, such as polysaccharide degradation and essential amino acid synthesis, which are associated with obesity inhibition. In addition, collagen peptide also effectively reduced all obesity signs caused by a high-fat diet, such as abdominal fat accumulation, high blood glucose levels, and weight gain. Ingestion of collagen peptides derived from fish skin induced significant changes in the intestinal microflora and is a potential auxiliary therapeutic agent to suppress the onset of obesity.

Monitoring alcohol-use-disorder medication compliance by LC-MS/MS determination of urinary ethyl glucuronide, acamprosate, naltrexone, and 6ß-naltrexol using zirconia-based hybrid solid-phase extraction.

Alcohol use disorder (AUD) is a major risk factor for numerous social concerns worldwide. In the Republic of Korea, the court imposes compulsory medication treatment on criminals diagnosed with AUD who are on probation. The purpose of the treatment is to reduce the number of repeat offenses committed by AUD-afflicted criminals. In this study, a method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine ethyl glucuronide (EtG), acamprosate (ACAM), naltrexone (NTX), and 6ß-naltrexol (6BNT) in urine was developed and validated to monitor the medication compliance and alcohol use of probationers diagnosed with AUD. A zirconia-based hybrid solid-phase extraction technique was introduced to increase the sensitivity toward target analytes having significantly differing pKa values while minimizing the matrix effect of the urine sample. The pretreated urine samples were analyzed by LC-MS/MS performed in a polarity-switching electrospray ionization mode via a three-period multiple-reaction monitoring method. All the target analytes were separated and detected within 6.5 min with an Xselect HSS T3 column and gradient elution using water containing 0.02% formic acid and methanol as the mobile phase. The lower limits of quantification of EtG, ACAM, NTX, and 6BNT were 10.0, 4.0, 0.4, and 0.2 ng mL-1, respectively. The determination coefficients of each calibration curve were greater than 0.9989. The intra-day accuracy ranged from -5.5-5.3% and the precision was ≤ 5.7%, whereas the inter-day accuracy ranged from -5.3-4.6% and the precision was ≤ 4.7%. The recovery, matrix effect, and process efficiency were 99.7-107.9%, 80.7-101.8%, and 80.5-108.1%, respectively. The developed method was successfully applied to analyze 107 urine samples obtained from probationers undergoing medication treatment for AUD and to monitor the probationers' medication compliance and alcohol use. This study also determined the urinary concentrations of EtG, ACAM, NTX, and 6BNT as well as the metabolic ratio of NTX following repeated oral administration of AUD medications.

LC-MS/MS method for determining picogram-level of zolpidem and its main metabolites in hair using a zirconia-based sorbent.

Although urine and blood samples have been conventionally used for testing zolpidem (ZPD), a sedative-hypnotic, these matrices have limited application because they have a relatively short detection period and can be used only in case of recent drug exposure. Therefore, it is necessary to use an alternative biological sample to obtain the evidence of ZPD misuse. Herein, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of ZPD and its metabolites, zolpidem phenyl-4-carboxylic acid (ZPCA) and zolpidem 6-carboxylic acid (ZCA), in hair to resolve the above-mentioned problems. Mechanical pulverization of hair, methanol extraction with sonication, and the zirconia-based hybrid solid-phase extraction technique were used for obtaining improved extraction efficiency and effective sample purification. The treated hair sample was analyzed using the LC-MS/MS method with the electrospray ionization source in positive and multiple-reaction monitoring modes. The target analytes were separated and detected within 8 min using an Xselect HSS T3 column. Gradient elution was performed using 5 mM ammonium formate and acetonitrile. The lower limit of quantification of ZPD, ZPCA, and ZCA were 1.0, 0.5, and 1.0 pg mg-1, respectively. The calibration ranges were 1.0-1000.0 pg mg-1 for ZPD, 0.5-200.0 pg mg-1 for ZPCA, and 1.0-200.0 pg mg-1 for ZCA, with the determination coefficients (r2 ≥ 0.9986). The intraday accuracy and precision ranged from -7.1 to 9.0% and within 6.5%, respectively, and the interday accuracy and precision ranged from -6.1 to 7.9% and within 5.4%, respectively. The recovery, matrix effect, and process efficiency were 65.2-96.6%, 64.6-106.5%, and 44.3-100.5%, respectively, with the relative standard deviation of 4.0-5.0%. The developed method was successfully applied to analyze 13 forensic hair samples of ZPD abusers, and the concentration ratios of ZPD and its two main metabolites (ZPCA and ZCA) in the ZPD-positive samples were also presented. These results revealed that ZPCA and ZCA were not easily incorporated into hair, and demonstrated that their analysis in hair samples requires the employed method to have picogram-level sensitivity. Therefore, the developed method was suitable for simultaneous analysis of ZPD, ZPCA, and ZCA in hair samples, and it could provide clear evidence for illegal ZPD administration, including ZPD-facilitated sexual assault.

LC-MS-MS Determination of 25 Antipsychotic Drugs and Metabolites in Urine for Medication Compliance Monitoring.

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed for 25 antipsychotic drugs and their metabolite in urine for monitoring medication compliance of mentally disordered criminals on probation. Target compounds were extracted with a solid-phase extraction technique using a newly developed hydrophilic-lipophilic balanced sorbent to remove interferences and minimize the matrix effect (ME). Extracted sample was injected into the LC-MS-MS with an electrospray ionization source in positive mode and multiple-reaction monitoring mode. The analytes were separated and detected within 10 minutes using a reversed-phase column with a gradient elution method using 0.1% formic acid in water and 0.1% formic acid in methanol as mobile phase. The validation parameters were evaluated as follows: selectivity, limit of detection, lower limit of quantification (LLOQ), linearity, accuracy and precision, stability, dilution integrity, recovery (RE), ME and process efficiency (PE). The LLOQs were 0.1 to 2.0 ng/mL, and determination coefficients of the calibration curve were above 0.9943 over the concentration ranges. The intra-and inter-day accuracy ranged from -10.4% to 9.9% and from -9.6% to 9.4%, while the intra-and inter-day precision were within 10.7% and 9.9%. The bench-top and long-term stability ranged from 92.1% to 109.5% and 88.7% to 111.6%, respectively. The reproducibility of auto-sampler stability was <10% for all analytes. The accuracy and precision of dilution integrity ranged from -11.7% to 10.5% and 0.4% to 9.9%, respectively. The relative standard deviation of RE and ME was from 0.6% to 6.6% and 0.5% to 3.9%, respectively, while that of PE was 1.3% to 4.5%. The developed LC-MS-MS method for medication compliance monitoring was successfully applied to urine samples from mentally disordered probationers and determined to be one of effective ways for preventing the recurrence of mentally disordered crimes.

Reliable, High-Performance Electrochromic Supercapacitors Based on Metal-Doped Nickel Oxide.

Herein, high-performance, reliable electrochromic supercapacitors (ECSs) are proposed based on tungsten trioxide (WO3) and nickel oxide (NiO) films. To maximize device performance and stability, the stoichiometric balance between anode and cathode materials is controlled by carefully adjusting the thickness of the anodic NiO film while fixing the thickness of WO3 to ∼660 nm. Then, a small amount (≤10 mol %) of metal (e.g., copper) is doped into the NiO film, improving the electrical conductivity and electrochemical activity. At a Cu doping level of 7 mol %, the resulting ECS exhibited the highest performance, including a high areal capacitance (∼14.9 mF/cm2), excellent coulombic efficiency (∼99%), wide operating temperature range (0-80 °C), reliable operation with high charging/discharging cyclic stability (>10,000 cycles), and good self-discharging durability. Simultaneously, the change in transmittance of the device is well synchronized with the galvanostatic charging/discharging curve by which the real-time energy storage status is visually indicated. Furthermore, the practical feasibility of the device is successfully demonstrated. These results imply that the ECS fabricated in this work is a promising potential energy storage platform and an attractive component for future electronics.

Author Correction: Highly pathogenic H5N6 avian influenza virus subtype clade 2.3.4.4 indigenous in South Korea.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Highly pathogenic H5N6 avian influenza virus subtype clade 2.3.4.4 indigenous in South Korea.

The outbreaks of the highly pathogenic avian influenza (HPAI) in 2016-2017 and 2017-2018, caused by novel reassortant clade 2.3.4.4 H5N6 viruses, resulted in the loss of one billion birds in South Korea. Here, we characterized the H5N6 viruses isolated from wild birds in South Korea from December 2017 to August 2019 by next-generation sequencing. The results indicated that clade 2.3.4.4 H5N6 viruses isolated in 2017 and 2019 shared almost identical nucleotide sequences with the HPAI H5N6 viruses from 2016 in South Korea. This repeated detection of evolutionarily identical H5N6 viruses in same region for more than three years may suggest indigenization of the HPAI H5N6 virus in South Korea. Phylogenetic analysis demonstrated that the clade 2.3.4.4 H5N6 viruses isolated in 2017 and 2019 were evolutionarily distinct from those isolated in 2018. Molecular analysis revealed that the H5N6 viruses isolated in 2017 and 2019 had features associated with an increased risk of human infection (e.g. a deletion at position 133 of HA and glutamic acid residue at position 92 of NS1). Overall, these genomic features of HPAI H5N6 viruses highlight the need for continuous monitoring of avian influenza viruses in wild migratory birds as well as in domestic birds.

Impaired osseointegration of dental implants associated with orthognathic surgery: Possible regional acceleratory phenomenon.

BACKGROUND: Regional acceleratory phenomenon (RAP) is demonstrated to decrease regional bone mineral density and accelerate bone turnover. Hypothesizing that RAP can negatively affect the osseointegration of biomaterials, this study aimed to investigate the possible influence of the RAP on dental implant osseointegration. MATERIALS AND METHODS: Orthognathic surgery, one of the major surgeries on oral and maxillofacial region was set as intervention for RAP. Considering that RAP exerts its physiologic effects until 4 months after noxious stimuli, patients were classified according to the time interval between orthognathic surgery and dental implant installation; group I was designated to patients who had implant installation within 4 months from orthognathic surgery. Group II were those with installation after 4-12 months and group III was longer than 12 months. Radiographic and clinical evaluations of dental implants including peri-implant marginal bone changes (MBR), implant stability, cumulative survival rates were analyzed. RESULTS: A total of 54 patients with 106 implants (mean follow-up of 72.6 months) were included in the study. MBR was significantly higher in group I (2.62 ± 0.91 mm) and II (2.25 ± 0.95 mm) compared to that of group III (0.94 ± 0.90 mm) at last follow up (P < 0.05) and this group difference over time was also significant (P < 0.001). Compared to group III, groups I and II exhibited lower ISQ values and higher biological complications including peri-implantitis and peri-implant gingivitis (P < 0.05). Group I showed significantly low-cumulative survival rate (89.2%; implant-level) compared to groups II and III. CONCLUSIONS: In this study, impaired osseointegration of dental implants was demonstrated associated with orthognathic surgery. Micro-environmental changes of hard tissue induced by major surgery on the jaw showed deteriorating effects on integrity of biomaterial osseointegration. Special considerations should be addressed for ideal treatment results and prognosis.

Effects of pH alteration on the pathogenesis of medication-related osteonecrosis of the jaw.

INTRODUCTION: An acidic environment has been recognized to increase catabolic activities and inhibit osteoblastic deposition, and also exhibited in the pathogenesis of various bone diseases. The aim of the study was to investigate the role of systemic and local pH alteration in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). MATERIAL AND METHODS: Initially, MRONJ was induced in 54 Sprague-Dawley rats via subcutaneous bisphosphonate injections, once a week for 8 weeks. A week prior to bisphosphonate termination, surgical intervention was performed and rats were divided into 3 groups-alkalotic, acidic and control group, wherein each received NaHCO3, NH4Cl and normal saline, respectively for 8 weeks. Upon sacrifice, blood was sent for arterial blood pH analysis and their mandibles were subjected to histomorphometric and µCT analyses. ONJ was histologically defined as necrotic bone persisting for eight weeks after surgical intervention. RESULTS: Each intervention exemplified its expected outcome wherein each group exhibited a borderline alkalotic (7.43 ±â€¯0.05) and acidic state (7.27 ±â€¯37), respectively (P < 0.05). Acidic group showed a higher occurrence of MRONJ (95%) compared to that of alkalotic group (60%) and control (76.9%). Histomorphometric and microstructural evaluation revealed that acidic group presented deteriorated bone architectures with significantly higher necrotic bone fraction, clusters of empty lacunae, N.Oc/B.Pm and lower B.Ar./T.Ar, BV/TV, Tb.Th (P < 0.05). Alkalotic group showed possible protective effects against ONJ versus acidic group, however these trends were not statistically significant. CONCLUSIONS: An acidic milieu aggravated ONJ development in an animal model. Further investigations are needed to elucidate the exact role of acid-base balance in MRONJ pathogenesis and possible benefits of alkali supplementation for the prevention.