Mycobiota profile of oral fungal infections in head and neck cancer patients receiving radiotherapy: A 6-year retrospective MALDI-TOF mass spectrometry study.

OBJECTIVES: Head and neck cancer (HNC) impairs patient immunity and increases susceptibility to oral fungal infections (OFIs). Effectively treating such infections requires accurate identification of the causative pathogens. This study aimed to characterize the mycobiota profile of OFIs in HNC patients undergoing radiation treatment (RT). MATERIALS AND METHODS: A 6-year retrospective analysis of oral mucosal samples from HNC patients with a history of RT and OFIs between 2014 and 2019 was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) profiling. Samples from the Clinical Microbiology Laboratory at Karolinska University Hospital were evaluated for mycobiota diversity and species co-occurrence patterns in the ongoing-RT and post-RT groups. RESULTS: A total of 190 oral fungi (88% Candida, 5% Pichia) were isolated from 162 HNC patients receiving RT. In the ongoing-RT group, the emergent non-albicans Candida (NAC) species; F. solani and C. jadinii, were detected for the first time. The dominant pathogens in both ongoing and post-RT groups were C. albicans, C. glabrata, P. kudriavzevii, C. parapsilosis, and C. tropicalis, as shown by Venn analysis. Network analysis revealed greater fungi diversity and multi-species co-occurrence in the ongoing-RT group. C. albicans commonly co-occurred with C. glabrata in both ongoing-RT (21%) and post-RT groups (30%). CONCLUSION: MALDI-TOF MS identified a wide range of oral fungal species in HNC patients receiving RT. While C. albicans remains the most prevalent OFIs pathogen, multi-species co-occurrence and novel NACs were noted. Understanding the ecological interactions among these causative pathogens could significantly advance the development of effective therapeutics for treating OFIs in HNC patients.

Incidence and influential factors in pulp necrosis and periapical pathosis following indirect restorations: a systematic review and meta-analysis.

BACKGROUND: Restoring vital teeth with indirect restorations may threaten dental pulp integrity. However, the incidence of and influential factors on pulp necrosis and periapical pathosis in such teeth are still unknown. Therefore, this systematic review and meta-analysis aimed to investigate the incidence of and influential factors on pulp necrosis and periapical pathosis of vital teeth following indirect restorations. METHODS: The search was conducted in five databases, using MEDLINE via PubMed, Web of Science, EMBASE, CINAHL, and Cochrane Library. Eligible clinical trials and cohort studies were included. The risk of bias was assessed using Joanna Briggs Institute's critical appraisal tool and Newcastle-Ottawa Scale. The overall incidences of pulp necrosis and periapical pathosis following indirect restorations were calculated using a random effects model. Subgroup meta-analyses were also performed to determine the potential influencing factors for pulp necrosis and periapical pathosis. The certainty of the evidence was assessed using the GRADE tool. RESULTS: A total of 5,814 studies were identified, of which 37 were included in the meta-analysis. The overall incidences of pulp necrosis and periapical pathosis following indirect restorations were determined to be 5.02% and 3.63%, respectively. All studies were assessed as having a moderate-low risk of bias. The incidence of pulp necrosis following indirect restorations increased when the pulp status was objectively assessed (thermal/electrical testing). The presence of pre-operative caries or restorations, treatment of anterior teeth, temporization for more than two weeks, and cementation with eugenol-free temporary cement, all increased this incidence. Final impression with polyether and permanent cementation with glass ionomer cement both increased the incidence of pulp necrosis. Longer follow-up periods (> 10 years) and treatment provided by undergraduate students or general practitioners were also factors that increased this incidence. On the other hand, the incidence of periapical pathosis increased when teeth were restored with fixed partial dentures, the bone level was < 35%, and the follow-up was > 10 years. The certainty of the evidence overall was assessed as low. CONCLUSIONS: Although the incidences of pulp necrosis and periapical pathosis following indirect restorations remain low, many factors affect these incidences that should thus be considered when planning indirect restorations on vital teeth. DATABASE REGISTRATION: PROSPERO (CRD42020218378).

Food Hardness Modulates Behavior, Cognition, and Brain Activation: A Systematic Review of Animal and Human Studies.

Food hardness is one of the dietary features that may impact brain functions. We performed a systematic review to evaluate the effect of food hardness (hard food versus soft food diet) on behavior, cognition, and brain activation in animals and humans (PROSPERO ID: CRD42021254204). The search was conducted on 29 June 2022 using Medline (Ovid), Embase, and Web of Science databases. Data were extracted, tabulated by food hardness as an intervention, and summarized by qualitative synthesis. The SYRCLE and JBI tools were used to assess the risk of bias (RoB) of individual studies. Of the 5427 studies identified, 18 animal studies and 6 human studies met the inclusion criteria and were included. The RoB assessment indicated that 61% of animal studies had unclear risks, 11% had moderate risks, and 28% had low risks. All human studies were deemed to have a low risk of bias. The majority (48%) of the animal studies showed that a hard food diet improved behavioral task performance compared to soft food diets (8%). However, 44% of studies also showed no differential effects of food hardness on behavioral tests. It was also evident that certain regions of the brain were activated in response to changes in food hardness in humans, with a positive association between chewing hard food, cognition performance, and brain function. However, variations in the methodologies of the included studies hindered the meta-analysis execution. In conclusion, our findings highlight the beneficial effects of dietary food hardness on behavior, cognition, and brain function in both animals and humans, however, this effect may depend on several factors that require further understanding of the causality.

Clinical Microbial Identification of Severe Oral Infections by MALDI-TOF Mass Spectrometry in Stockholm County: an 11-Year (2010 to 2020) Epidemiological Investigation.

Growing evidence suggests that oral infections can modify the course of systemic diseases. To date, epidemiological data on microbial oral infections are scarce. Here, we performed a comprehensive analysis of the trend and microbial diversity in oral infection specimens referred for clinical microbiology analysis from 2010 to 2020. The microbes were isolated by culture and were identified via matrix-assisted laser desorption ionization-time of flight mass spectrometry technology (MALDI-TOF MS) throughout the study period. A total of 1,014 referred samples from dental clinics in Stockholm County with dentoalveolar abscesses and jaw osteomyelitis being the main reason were identified. Overall, the microbial composition was dominated by Firmicutes (51%), followed by Bacteroidetes (19%), Proteobacteria (12%), and Actinobacteria (5%). At the genus level, Streptococcus spp. (36%), Prevotella spp. (18%), and Staphylococcus spp. (11%) were among the most frequently reported. Interestingly, a strong increase in trend was noted for Streptococcus anginosus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Actinomyces spp., Aggregatibacter aphrophilus, Staphylococcus epidermidis, and Granulicatella adiacens during the study time (R = 0.66 to 0.89, P < 0.05), and a minor increase was noted for Enterococcus faecalis and Klebsiella spp., whereas steady levels were noted for most of the others. The present study shows the diversity of bacteria that have been involved in dental infections during the last decade in the capital of Sweden, as well as the emerging oral microbiota trend, with clear clinical implications on the oral-systemic link. IMPORTANCE Oral diseases and associated microbes are a risk factor for systemic diseases and can change the courses of these diseases. To date, epidemiological data on microbial oral infections are scarce, and longitudinal reports are lacking. We present for the first time the microbial composition of severe oral bacterial infections determined via the MALDI-TOF mass spectrometry technique in a comprehensive study between 2010 and 2020 (11 years) in Stockholm County. The trend and microbial diversity of oral infections were analyzed on referred clinical microbiological samples and were processed by standardized protocols. Trend increase was noted for Streptococcus anginosus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Actinomyces spp., Aggregatibacter aphrophilus, Staphylococcus epidermidis, Granulicatella adiacens, Enterococcus faecalis, and Klebsiella spp. Our results provide new insights into the diversity and trend of oral microbiota that were involved in serious oral infections over the past decade in the capital of Sweden and may influence the oral-systemic link.

Effect of apical microsurgery on force regulation of incisor teeth during unpredictable force control task.

BACKGROUND: Apical microsurgery (AMS) involves removal of the root-end which can affect the force regulation of teeth. OBJECTIVE: To investigate the force regulation of incisor teeth treated with AMS during the unpredictable force control task in comparison with their contralateral teeth with complete root apices, in humans. METHODS: Fifteen eligible participants (8 women and 7 men; mean age 52.9 ± SD 4.4 years) performed a standardised unpredictable force control task, which involved pulling and holding a force transducer with AMS-treated incisors and their contralateral control teeth (n = 30 teeth). A series of four load masses: 100, 200, 50 and 300 gm were attached to the force transducer through a string in an unpredictable manner. The obtained force profile was divided into initial and later time-segments. The peak force and peak force rate during the initial time-segment, and the holding force and coefficient of variability during the later time-segments were calculated and compared by the repeated measures analysis of variance. RESULTS: During the initial time-segment, the peak force and peak force rate were significantly lower in the AMS-treated teeth than in the controls (p = .001, p = .013, respectively). However, during the later time-segment, no significant differences in the holding force nor the coefficient of variability were observed between the AMS-treated teeth and their controls (p = .755, p = .213, respectively). CONCLUSION: In contrast to incisors with complete normal root apices, AMS-treated incisors do not show robust changes in force regulation.

Salivary IgG to SARS-CoV-2 indicates seroconversion and correlates to serum neutralization in mRNA-vaccinated immunocompromised individuals.

BACKGROUND: Immunocompromised individuals are highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Whether vaccine-induced immunity in these individuals involves oral cavity, a primary site of infection, is presently unknown. METHODS: Immunocompromised patients (n = 404) and healthy controls (n = 82) participated in a prospective clinical trial (NCT04780659) encompassing two doses of the mRNA BNT162b2 vaccine. Primary immunodeficiency (PID), secondary immunodeficiencies caused by human immunodeficiency virus (HIV) infection, allogeneic hematopoietic stem cell transplantation (HSCT)/chimeric antigen receptor T cell therapy (CAR-T), solid organ transplantation (SOT), and chronic lymphocytic leukemia (CLL) patients were included. Salivary and serum immunoglobulin G (IgG) reactivities to SARS-CoV-2 spike were measured by multiplex bead-based assays and Elecsys anti-SARS-CoV-2 S assay. FINDINGS: IgG responses to SARS-CoV-2 spike antigens in saliva in HIV and HSCT/CAR-T groups were comparable to those of healthy controls after vaccination. The PID, SOT, and CLL patients had weaker responses, influenced mainly by disease parameters or immunosuppressants. Salivary responses correlated remarkably well with specific IgG titers and the neutralizing capacity in serum. Receiver operating characteristic curve analysis for the predictive power of salivary IgG yielded area under the curve (AUC) = 0.95 and positive predictive value (PPV) = 90.7% for the entire cohort after vaccination. CONCLUSIONS: Saliva conveys vaccine responses induced by mRNA BNT162b2. The predictive power of salivary spike IgG makes it highly suitable for screening vulnerable groups for revaccination. FUNDING: Knut and Alice Wallenberg Foundation, Erling Perssons family foundation, Region Stockholm, Swedish Research Council, Karolinska Institutet, Swedish Blood Cancer Foundation, PID patient organization of Sweden, Nordstjernan AB, Center for Medical Innovation (CIMED), Swedish Medical Research Council, and Stockholm County Council (ALF).

Persistence of salivary antibody responses after COVID-19 vaccination is associated with oral microbiome variation in both healthy and people living with HIV.

Coevolution of microbiome and immunity at mucosal sites is essential for our health. Whether the oral microbiome, the second largest community after the gut, contributes to the immunogenicity of COVID-19 vaccines is not known. We investigated the baseline oral microbiome in individuals in the COVAXID clinical trial receiving the BNT162b2 mRNA vaccine. Participants (n=115) included healthy controls (HC; n=57) and people living with HIV (PLHIV; n=58) who met the study selection criteria. Vaccine-induced Spike antibodies in saliva and serum from 0 to 6 months were assessed and comparative analyses were performed against the individual salivary 16S ASV microbiome diversity. High- versus low vaccine responders were assessed on general, immunological, and oral microbiome features. Our analyses identified oral microbiome features enriched in high- vs. low-responders among healthy and PLHIV participants. In low-responders, an enrichment of Gram-negative, anaerobic species with proteolytic activity were found including Campylobacter, Butyrivibrio, Selenomonas, Lachnoanaerobaculum, Leptotrichia, Megasphaera, Prevotella and Stomatobaculum. In high-responders, enriched species were mainly Gram-positive and saccharolytic facultative anaerobes: Abiotrophia, Corynebacterium, Gemella, Granulicatella, Rothia, and Haemophilus. Combining identified microbial features in a classifier using the area under the receiver operating characteristic curve (ROC AUC) yielded scores of 0.879 (healthy controls) to 0.82 (PLHIV), supporting the oral microbiome contribution in the long-term vaccination outcome. The present study is the first to suggest that the oral microbiome has an impact on the durability of mucosal immunity after Covid-19 vaccination. Microbiome-targeted interventions to enhance long-term duration of mucosal vaccine immunity may be exploited.

Nonsurgical endodontic management of mandibular first premolar with incomplete root-end resection.

The complexity of the nonsurgical endodontic retreatment should be weighed against the benefit of surgical approach. This case report describes uncommon diagnosis and successful nonsurgical endodontic management of mandibular first premolar with a previous history of failed apicoectomy and incomplete root-end resection using mineral trioxide aggregate and cone-beam computed tomography.

Oral Fine Motor Control of Teeth Treated with Endodontic Microsurgery: A Single-Blinded Case-control Study.

INTRODUCTION: Periodontal mechanoreceptors (PMRs) are refined neural receptors present in abundance at the root apex and have a pivotal role in oral fine motor control. This case-control study aimed to evaluate the oral fine motor control of teeth treated with endodontic microsurgery (EMS) in comparison with the control teeth using a standardized behavioral biting task. METHODS: Fourteen eligible participants performed 5 trials of an oral fine motor control task that involved holding and splitting half of a peanut positioned on a force transducer with their EMS treated tooth and its contralateral control incisor tooth (28 teeth in total). The outcome variables were the mean food holding force, intra- and intertrial variability of the holding force, food splitting force, splitting duration, and the frequency of the stepwise splitting phase. The data were analyzed with parametric and nonparametric tests. RESULTS: The results showed no statistically significant differences in the holding force, inter- and intratrial variability of the holding force, splitting force, or splitting duration between the teeth treated with EMS and the control (P > .05). However, there was a significantly higher frequency of stepwise ramp increase during the splitting phase with EMS treated teeth compared with the control (48% and 37%, respectively; P < .05). CONCLUSIONS: EMS treated teeth showed similar force regulation and oral fine motor control as the contralateral control. The findings of this study suggest that EMS treatment does not perturb the sensory information of PMRs and maintains the force regulation and oral fine motor control of the teeth.

Shear Bond Strength of E. Max Ceramic Restoration to Hydraulic Calcium Silicate Based Cement (Biodentine): An In Vitro Study.

OBJECTIVE: The purpose of this study was to evaluate the shear bond strength (SBS) of hydraulic calcium silicate (Biodentine) as a core material to the e.max ceramic restoration. METHODS: Forty discs (6 mm diameter; 2 mm thickness) were fabricated from each core material, Hydraulic calcium silicate [Biodentine™, Septodont], resin composite [Filtek™Z250 XT, 3M ESPE], and resin-modified glass ionomer cement (RMGIC) [GC Fuji II LC, GC Corporation]. Dentine surfaces of 40 extracted human permanent molars were exposed and used as a control group. All specimens were mounted in self-curing acrylic resin. One hundred sixty IPS e.max discs were fabricated (4 mm diameter; 2 mm thickness) and cemented to the core specimens with Variolink N (IvoclarVivadent). After storage in distilled water (37oC; 24h), the specimens were thermocycled 1.500 times. SBS was tested using a universal testing machine at 0.05 mm/min crosshead speed. The fracture modes were determined by a stereomicroscope at ×20 magnification. Data were analyzed using one-way analysis of variance followed by Tukey's test (P=0.05). RESULTS: The mean SBS values of four tested groups showed statistically significant differences (P<0.05). The resin composite group exhibited the highest SBS value (36.17±6.08 MPa), while the Biodentine had the lowest SBS value (21.86±3.18 MPa). Mixed failure mode was the most common failure type in all tested groups except in the Biodentine group, which had a predominantly cohesive failure. CONCLUSION: The SBS of e.max ceramic restorations cemented with resin is affected by the type of core material. Biodentine core material had the lowest SBS to e.max restoration. However, when Biodentine is indicated to be used as core material for pulp preservation, it is recommended to be covered with a layer of resin composite material to enhance its bonding strength to the e.max restoration.

A Systematic Review of the Root Canal Microbiota Associated with Apical Periodontitis: Lessons from Next-Generation Sequencing.

Next-generation sequencing (NGS) has now been applied for a decade to characterize the microbiota composition of infected dental root canals associated with apical periodontitis. Here, the study aims at systematically and critically reviewing these reports within the outcome of interest selected; the microbiota composition in different endodontic infection types. Standard methodological guidelines as stated by the PRISMA and the Joanna Briggs Institute are followed, including a risk of bias assessment. A literature search is conducted using the PubMed Advanced-Search Builder on April 8, 2019; only original research articles that investigated the microbiota of infected root-canals by means of NGS are screened. Among the 26 articles initially identified, 18 are included and evaluated for the following parameters; sampling protocol, sequencing strategy, and microbiota composition. The endodontic infections include primary apical periodontitis (PAP), secondary apical periodontitis (SAP), and apical abscess (AA). All infection types are associated with a highly diverse microbiota. Although some taxa appear differentially abundant between PAPs, SAPs, and AAs, no evident clustering of the microbiota by infection type is observed. These studies collectively formulate a comprehensive map of the taxa associated with endodontic infections and provide evidence of compositionally unspecific, yet abundance differentiates, community profiles according to clinical diagnosis.

Effect of Chewing on the Expression of Salivary Protein Composition: A Systematic Review.

Salivary proteins have an imperative role in the maintenance of oral health and repairing mechanisms of injured tissues. However, there is paucity of information reported in the literature about the influence of chewing activities on the secretion or expression of salivary proteins. The purpose of this systematic review is to evaluate the effect of chewing on the expression of salivary proteins composition in healthy individuals. A thorough systematic search shows 14 eligible studies for the review. The results of the systematic review show the effect of chewing on total protein concentration, alpha-amylase (α-amylase), peroxidase, lysozyme, immunoglobulin A (IgA), and mucin. Six papers concluded that chewing has a little or no effect on total protein concentration, α-amylase, peroxidase, lysozyme, and IgA activities. Five papers reported a negative (decreasing) effect of chewing on the function of total protein, α-amylase, IgA, and mucin. Only two papers showed an increase in total protein and IgA function upon chewing stimulation. The results of this systematic review indicate that more standardized evidence-based research is required for better assessment of chewing effects on salivary proteins. Within the limitations of this review, the existing evidence suggests that chewing in healthy people has minimum effect on the expression and activities of salivary proteins.

Cytotoxic effect of Salvadora persica extracts on human gingival fibroblast cells.

OBJECTIVES: To assess the cytotoxic potential of Salvadora persica (S. persica) extracts on human gingival fibroblast (HGF) cells. METHODS: This study was conducted between January and May 2012 in collaboration with Dental Caries Research Chair, College of Dentistry, King Saud University, Riyadh, Saudi Arabia. Extracts of S. persica using hexane, ethylacetate, and ethanol as solvents at concentrations of 0.5 mg/ml and 1 mg/ml were evaluated for their cytotoxic activity against HGFs using the 3 cytotoxic assays: (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole) (MTS), lactic dehydrogenase (LDH), and crystal violet (CV). International standards for the evaluation of medical materials recommended cut-off value of cell survival >70% was used for interpretation of the results. RESULTS: Ethanol extract of S. persica at 0.5 mg/ml and 1 mg/ml and hexane extract of S. persica at 0.5 mg/ml were completely devoid of cytotoxic activity, hexane extract at 1 mg/ml in comparison with controls  demonstrated some cytotoxicity with cell survival of 88% (p=0.045) in MTS, 86% (p=0.01) in LDH, and 88% (p=0.002) in CV assays. Similarly, ethyl acetate extract of S. persica at 0.5 mg/ml maintained cell viability of 91% in MTS, 81% in LDH, and 80% in CV assays. Maximum cytotoxicity against HGFs was observed with ethyl acetate extract of S. persica at 1 mg/ml with cell survival of 60% in MTS, 40% in LDH, and 66% CV assays (p=0.0001).   CONCLUSION: The acceptable level of cytotoxicity associated with S. persica ethanol and hexane extracts requires further evaluation to be used as irrigation solutions in endodontic treatment.