Comparison of fidaxomicin, thuricin CD, vancomycin and nisin highlights the narrow spectrum nature of thuricin CD.

Vancomycin and metronidazole are commonly used treatments for Clostridioides difficile infection (CDI). However, these antibiotics have been associated with high levels of relapse in patients. Fidaxomicin is a new treatment for CDI that is described as a narrow spectrum antibiotic that is minimally active on the commensal bacteria of the gut microbiome. The aim of this study was to compare the effect of fidaxomicin on the human gut microbiome with a number of narrow (thuricin CD) and broad spectrum (vancomycin and nisin) antimicrobials. The spectrum of activity of each antimicrobial was tested against 47 bacterial strains by well-diffusion assay. Minimum inhibitory concentrations (MICs) were calculated against a select number of these strains. Further, a pooled fecal slurry of 6 donors was prepared and incubated for 24 h with 100 µM of each antimicrobial in a mini-fermentation system together with a no-treatment control. Fidaxomicin, vancomycin, and nisin were active against most gram positive bacteria tested in vitro, although fidaxomicin and vancomycin produced larger zones of inhibition compared to nisin. In contrast, the antimicrobial activity of thuricin CD was specific to C. difficile and some Bacillus spp. The MICs showed similar results. Thuricin CD exhibited low MICs (<3.1 µg/mL) for C. difficile and Bacillus firmus, whereas fidaxomicin, vancomycin, and nisin demonstrated lower MICs for all other strains tested when compared to thuricin CD. The narrow spectrum of thuricin CD was also observed in the gut model system. We conclude that the spectrum of activity of fidaxomicin is comparable to that of the broad-spectrum antibiotic vancomycin in vitro and the broad spectrum bacteriocin nisin in a complex community.

Tooth Discoloration from 2 Silver Fluorides Used in Adults with Special Needs: A Randomized Trial.

BACKGROUND: Discoloration of carious lesions after application of silver diamine fluoride lowers patient acceptance and limits its wider use for caries arrest. OBJECTIVE: To assess lesion and tooth color changes from 2 novel silver fluoride (AgF) products and its relationship to caries activity (clinical visuo-tactile scores) and bacterial load (using laser fluorescence with the DIAGNOdent). METHODS: A split-mouth design was followed, with matched smooth surface carious lesions in the same arch in adults with special needs randomized for 1-min treatments with AgF/potassium iodide (KI) (Riva Star Aqua, SDI) and AgF/stannous fluoride (SnF2) (Caries Status Disclosing Solution; Whiteley). Standardized images taken at baseline, immediately postoperatively, and at 3-mo review were subjected to digital image analysis to calculate delta-E and to track changes in luminosity of carious lesions. RESULTS: Twelve participants were recruited in the study. A total of 56 teeth (28 pairs) were included. Significantly greater changes were seen in treated lesions than in the adjacent noncarious natural tooth structure, both immediately after treatment and at the 3-mo review (P < 0.0001). Color change and caries activity were not affected by tooth type, tooth location, plaque status, salivary status, or special needs condition. AgF/SnF2 caused transitory darkening immediately on application, while AgF/KI caused the immediate formation of yellow deposits (silver iodide). Both products caused significant darkening of treated lesions at 3 mo (P = 0.0009; P = 0.0361), with no differences between them (P = 0.506). Responding lesions showed larger and more perceptible color changes immediately after either AgF application (P = 0.002; P = 0.024). CONCLUSIONS: Both AgF products were highly effective for caries arrest in this patient population. Despite minor differences in the appearance of treated lesions at the time of application, both products lead to similar darkening of treated sites at 3 mo. KNOWLEDGE TRANSFER STATEMENT: This study shows the usefulness of silver fluoride used in conjunction with potassium iodide or stannous fluoride for achieving caries arrest in smooth surface lesions in adults with special needs. Patients need to be informed that long-term staining of the lesion occurs with both, similar to silver diamine fluoride.

Association of behavioural and social-communicative profiles in children with 16p11.2 copy number variants: a multi-site study.

BACKGROUND: Despite the established knowledge that recurrent copy number variants (CNVs) at the 16p11.2 locus BP4-BP5 confer risk for behavioural and language difficulties, limited research has been conducted on the association between behavioural and social-communicative profiles. The current study aims to further delineate the prevalence, nature and severity of, and the association between, behavioural and social-communicative features of school-aged children with 16p11.2 deletion syndrome (16p11.2DS) and 16p11.2 duplication (16p11.2Dup). METHODS: A total of 68 individuals (n = 47 16p11.2DS and n = 21 16p11.2Dup) aged 6-17 years participated. Standardised intelligence tests were administered, and behavioural and social-communicative skills were assessed by standardised questionnaires. Scores of both groups were compared with population norms and across CNVs. The influence of confounding factors was investigated, and correlation analyses were performed. RESULTS: Compared with the normative sample, children with 16p11.2DS showed high rates of social responsiveness (67%) and communicative problems (69%), while approximately half (52%) of the patients displayed behavioural problems. Children with 16p11.2Dup demonstrated even higher rates of social-communicative problems (80-90%) with statistically significantly more externalising and overall behavioural challenges (89%). In both CNV groups, there was a strong positive correlation between behavioural and social-communicative skills. CONCLUSIONS: School-aged children with 16p11.2 CNVs show high rates of behavioural, social responsiveness and communicative problems compared with the normative sample. These findings point to the high prevalence of autistic traits and diagnoses in these CNV populations. Moreover, there is a high comorbidity between behavioural and social-communicative problems. Patients with difficulties in both domains are vulnerable and need closer clinical follow-up and care.

Biocompatibility and acid resistance of preformed crowns in children: an in vitro study.

PURPOSE: To investigate the in vitro biocompatibility of human gingival fibroblasts with preformed paediatric crowns and resistance to acid exposure at levels that simulate the oral environment. METHODS: This laboratory study investigated primary HGFs viability, metabolic activity, cytotoxicity, and apoptotic events on preformed metal crown discs, composite resin-coated wells, and monolithic zirconia fragments at 24, 48, and 72 h using the ApoTox-Glo Triplex assay. The PPCs were also immersed in 0.1% lactic acid, 0.2% phosphoric acid, or 10% citric acid for 7 days at 37 °C to reproduce conditions associated with dietary intake or gastric reflux. Samples were then subject to inductively coupled plasma optical emission spectrometry to quantitate the release of ions. RESULTS: The viability of HGFs on stainless steel and CR significantly declined at 48 and 72 h, representing potential cytotoxicity (p < 0.05). Cytotoxicity of HGFs was also higher for stainless steel and ZR compared to control (p < 0.05). PMCs and ZR crowns gave minimal ion release. Meanwhile, significant quantities of metallic ions, including copper (Cu), iron (Fe), nickel (Ni), and zinc (Zn), were present in eluates from veneered-preformed metal crowns. CONCLUSION: As PPCs can be exposed to highly acidic environments for many years, thus the release of metallic ions from V-PMCs should form the further investigation in future studies.

Discussion of uncertainties and the impact of different neutron RBEs on all solid cancer radiation incidence risks obtained from the Japanese A-bomb survivor data.

The most recent publicly available data on all solid cancer incidence from the Life Span Study (LSS) of Japanese A-bomb survivors provides colon dose contributions weighted with a relative biological effectiveness (RBE) of 10 for neutrons, relative to gammas. However, there is evidence from several investigations that the neutron RBE for A-bomb survivors may be higher than 10. The change in the shape of the corresponding dose-response curves was evaluated by Hafner and co-workers in a previous study by applying sex-specific linear-quadratic dose models to previous LSS data for all solid cancer incidence that include separate neutron and gamma absorbed doses for several organs, in contrast to the most recent data. The resulting curvature change became significantly negative for males at an RBE of 140 for colon, 100 for liver, and 80 for organ averaged dose. For females, the corresponding RBE values were 110, 80, and 60 for colon, liver, and organ averaged doses. The present study compares three different methods to calculate the 95% confidence intervals in an analysis of the curvature with increasing RBE. Further, the impact of a higher neutron RBE on the work of the International Commission on Radiological Protection, and the importance of including uncertainties and performing sensitivity analysis of different parameters in radiation risk assessment are discussed.

Oral complications associated with metal ion release from oral piercings: a systematic review.

PURPOSE: This systematic review explored dental complications associated with metal ion release from oral piercings using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. METHODS: Item retrieval from October 2022 to December 2022 from databases, such as Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, Scopus and Web of Science, using predefined search terms was undertaken by two independent reviewers. Data were extracted and risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. From 1509 identified studies, 25 were included for analysis. RESULTS: Of the 25 studies, 20 included both clinical examination and questionnaire-based data. The remaining five studies were deemed low quality based on the Joanna Briggs Institute criteria. The average time piercings were worn ranged between 5 and 48 months. Most studies did not investigate complications from metal ion release. Only two studies examined the direct effects of metal ion release and showed that metal ions may cause hypersensitivity reactions and mucosal changes. Other soft tissue complications were reported, with gingival recession noted in 16 out of 25 studies, especially due to lip piercings. Studies reporting other complications were as follows: swelling (9), pain (8), infection (6), bleeding (6), inflammation (5), alterations to speech, eating and/or swallowing (5), changes to taste or metallic taste (5), and mucosal changes (4). Ten studies reported tooth chipping from tongue piercings. CONCLUSION: Oral piercings leach metal ions into surrounding tissues which may cause local mucosal changes. Furthermore, oral piercings cause damage to both soft and hard oral tissues, particularly gingival recession for lip piercings and tooth chipping for tongue piercings. Thus, to prevent such adverse injuries, dental professionals should discourage patients against oral piercings.

Positive impacts of oral health services provision by a student-led primary care clinic to an Australian rural indigenous community.

BACKGROUND: This study aimed to determine whether oral health services provision by a dental student clinical outplacement embedded within a Community Controlled Health Service positively impacted a rural Indigenous community and to explore the nature of these benefits. METHODS: Aggregated and de-identified 2017, 2018 and 2019 student-led clinic services provision data were retrospectively analysed. The change in services mix over time was measured. Rural outplacement clinic operational costs to the university were estimated. Government-funded local public dental clinic waiting list and services provision data were used to identify any student clinic establishment effect. RESULTS: The student-led clinic services mix shifted over time from mainly acute care for toothache towards prevention of disease and tooth restoration, indicating an improvement in patient oral health and correspondingly reduced system costs. Imputed value of 2017-2019 student-led clinic services provision totalled almost AUD$1 million. Government public clinic waiting list times decreased after full establishment of the student-led clinic, indicating decreased pressure on the public system. CONCLUSION: The Community Controlled Health Service and university partnership improved community oral health care access, its timely delivery and simultaneously provided valuable human capital development from the student training experience. The student-led clinic's targeted Indigenous community showed oral health improvement over time. © 2023 Australian Dental Association.

Ion release from oral piercings from in vitro acidic challenges.

OBJECTIVES: This laboratory-based study measured ion release from metallic piercings when exposed to organic acids (lactic, citric) and inorganic acids (phosphoric, hydrochloric) that could be encountered in the oral cavity. METHODS: Barbell and ring oral piercings composed of stainless steel, titanium or gold-plated titanium were submerged in 2 mL volumes of 0.1% lactic acid, 10% citric acid, 0.2% phosphoric acid, and 0.1% hydrochloric acid for 7 and 34 days. Ion release into the liquid was measured using inductively coupled plasma optical emission spectroscopy (ICPOES) and expressed in relationship to surface area. Surface changes from baseline were assessed using light and backscatter scanning electron microscopy (SEM). RESULTS: ICPOES results showed that hydrochloric and phosphoric acid caused the greatest release of material per surface area. Released elements included (ranked highest to lowest): Fe, P, Ti, Na, Cr, S, Ni, Ca, Mg, K, Si, Al, V, Mn, Ba, and Co. SEM imaging identified qualitative surface changes consistent with corrosion, for most piercing types examined. CONCLUSIONS: Under the exposure conditions used, inorganic acids cause greater metal dissolution than organic acids. Inorganic acids could therefore pose a risk of corrosion and leaching of ions from metallic oral piercings.

Higher scores on autonomic symptom scales in pediatric patients with neurodevelopmental disorders of known genetic etiology.

INTRODUCTION: Features of underlying autonomic dysfunction, including sleep disturbances, gastrointestinal problems, and atypical heart rate, have been reported in neurodevelopmental conditions, including autism spectrum disorder (ASD). The current cross-sectional, between-groups study aimed to quantify symptoms of autonomic dysfunction in a neurodevelopmental pediatric cohort characterized by clinical diagnoses as well as genetic etiology. METHOD: The Pediatric Autonomic Symptom Scales (PASS) questionnaire was used to assess autonomic features across a group of patients with clinical neurodevelopmental diagnoses (NPD; N = 90) and genetic etiologies. Patients were subdivided based on either having a clinical ASD diagnosis (NPD-ASD; n = 37) or other non-ASD neurodevelopmental diagnoses, such as intellectual disability without ASD, speech and language disorders, and/or attention deficit hyperactivity disorder (NPD-OTHER; n = 53). Analyses focused on characterizing differences between the NPD group compared to previously published reference samples, as well as differences between the two NPD subgroups (NPD-ASD and NPD-OTHER). RESULTS: Our results indicate higher PASS scores in our NPD cohort relative to children with and without ASD from a previously published cohort. However, we did not identify significant group differences between our NPD-ASD and NPD-OTHER subgroups. Furthermore, we find a significant relationship between quantitative ASD traits and symptoms of autonomic function. CONCLUSION: This work demonstrates the utility of capturing quantitative estimates of autonomic trait dimensions that may be significantly linked with psychosocial impairments and other core clinical features of ASD.

Decontamination practices of paediatric crowns: a systematic review.

PURPOSE: A systematic review was conducted into paediatric crown decontamination practices using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. METHOD: After database retrieval using predefined search terms, two reviewers independently applied the selection criteria, extracted the data, and assessed for risk of bias. From 92 potentially eligible studies, 10 were included for analysis. RESULTS: Steam sterilisation (autoclaving) was used as the gold standard for reducing biological contaminants on paediatric crowns across in vivo studies. However, autoclaving was associated with microstructural changes such as crazing and contour alterations. Furthermore, several tooth coloured crowns were liable to undergo colour changes from steam sterilisation. CONCLUSION: Ambiguous manufacturer guidelines on protocols for reprocessing and reuse after biological exposure raises concerns regarding cross contamination and leaves practitioners open to potential litigation. A better understanding of the compatibility of paediatric crowns and decontamination practices is needed. More research into alternative chairside technologies that use low temperature, such as hydrogen peroxide gas plasma sterilisation, is warranted.

Pulmonary arterial hypertension in hereditary hemorrhagic telangiectasia associated with ACVRL1 mutation: a case report.

INTRODUCTION: Hereditary hemorrhagic telangiectasia is an autosomal dominant condition with an estimated prevalence of 1 in 5000. It is characterized by the presence of abnormalities of vascular structures, and may affect many organ systems, including the lungs, brain, spinal cord, gastrointestinal tract, and liver. A causative mutation is identified in approximately 97% of patients with definite hereditary hemorrhagic telangiectasia in one of three genes including a mutation in endoglin, a mutation in a locus mapped to chromosome 5, and an activin receptor-like kinase-1 (ACVRL1) mutation that is associated with an increased incidence of primary pulmonary hypertension. Pulmonary arterial hypertension is a rare (15-25 cases per million people) but severe vascular disorder. Heritable pulmonary arterial hypertension is associated with several gene mutations, with 75% having a mutation in the bone morphogenetic protein receptor 2 (BMPR2). However, the remaining 25% of patients have other associated genetic mutations including ACVLR1, which is also associated with hereditary hemorrhagic telangiectasia. Pulmonary arterial hypertension is a rare complication in patients with hereditary hemorrhagic telangiectasia (< 1% of the hereditary hemorrhagic telangiectasia population). We describe a case report with this rare occurrence. CASE PRESENTATION: A 70-year-old white/caucasian Irish male presented for screening for hereditary hemorrhagic telangiectasia due to a history of recurrent epistaxis (once/week) and a family history suggestive of pulmonary hypertension. Genetic testing confirmed an ACVRL1 mutation, while an echocardiogram and right heart catheterization confirmed pulmonary arterial hypertension. On examination, he had several mucocutaneous telangiectasia across his face. He was commenced on tadalafil and macitentan. However, this led to increased iron deficiency anemia and pedal edema. Selexipag was also added to his drug regime. He continues to require intermittent admissions for diuresis and blood transfusions. CONCLUSION: The association of hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension is rare (< 1%). Here we describe a case of hereditary hemorrhagic telangiectasia complicated with pulmonary arterial hypertension as a result of an ACVRL1 mutation. We also describe the clinical challenges of treating these two conditions together, as treatment options for pulmonary arterial hypertension tend to worsen hereditary hemorrhagic telangiectasia symptoms.

A qualitative exploration of the feasibility and acceptability of Meaning-Centered Psychotherapy for Cancer Caregivers.

OBJECTIVE: Caregivers of patients with cancer are at significant risk for existential distress. Such distress negatively impacts caregivers' quality of life and capacity to serve in their role as healthcare proxies, and ultimately, contributes to poor bereavement outcomes. Our team developed Meaning-Centered Psychotherapy for Cancer Caregivers (MCP-C), the first targeted psychosocial intervention that directly addresses existential distress in caregivers. METHOD: Nine caregivers of patients with glioblastoma multiforme (GBM) enrolled in a pilot randomized controlled trial evaluating the feasibility, acceptability, and effects of MCP-C, and completed in-depth interviews about their experience in the therapy. One focus group with three MCP-C interventionists was also completed. RESULTS: Four key themes emerged from interviews: (1) MCP-C validated caregivers' experience of caregiving; (2) MCP-C helped participants reframe their "caregiving identity" as a facet of their larger self-identity, by placing caregiving in the context of their life's journey; (3) MCP-C enabled caregivers to find ways to assert their agency through caregiving; and (4) the structure and sequence of sessions made MCP-C accessible and feasible. Feedback from interventionists highlighted several potential manual changes and overall ways in which MCP-C can help facilitate caregivers' openness to discussing death and engaging in advanced care planning discussions with the patient. SIGNIFICANCE OF RESULTS: The overarching goal of MCP-C is to allow caregivers to concurrently experience meaning and suffering; the intervention does not seek to deny the reality of challenges endured by caregivers, but instead to foster a connection to meaning and purpose alongside their suffering. Through in-depth interviews with caregivers and a focus group with MCP interventionists, we have refined and improved our MCP-C manual so that it can most effectively assist caregivers in experiencing meaning and purpose, despite inevitable suffering.

A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer.

Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.

The Queensland Birth Cohort Study for Early Childhood Caries: Results at 7 Years.

AIMS: This study investigated caries predictors in 378 children remaining from a birth cohort of 1,052 at 7 y and compared the efficacy of home visits (HVs) and telephone contacts (TCs) for early childhood caries (ECC) prevention. METHODS: The HVs or TCs were made at ages 6, 12, 18, 30, and 42 mo with annual dental clinic examinations at ages 2 to 7 y. At every visit, the parents completed validated questionnaires regarding the children's family, medical, dental, and dietary histories. RESULTS: The caries prevalence increased from 2% and 6% at ages 2 and 3 y to 15%, 33%, 42%, and 52% at ages 4 to 7 y. The mean caries experience (decayed, missing, and teeth extracted due to caries) of the total cohort increased from 0.1 ± 0.5 at age 2 y to 0.2 ± 1.1 at 3 y, 0.5 ± 1.6 at 4 y, 1.1 ± 2.4 at 5 y, 1.6 ± 2.6 at 6 y, and 2.0 ± 2.7 at 7 y. The prevalence of mutans streptococci (MS) in the total cohort at years 2 to 7 was 22%, 36%, 42%, 42%, 39%, and 44%, respectively. MS was strongly correlated with caries prevalence for all years (all P < 0.001). Statistical modeling employing the generalized estimating equations identified caries predictors as holding a Health Care Card (low socioeconomic status) (P = 0.009; odds ratio [OR] = 2.05; confidence interval [CI]: 1.20-3.52), developmental defects of enamel (DDEs) (P < 0.001; OR = 1.09; CI: 1.05-1.14), and MS counts ≤105/mL (P = 0.001; OR = 1.63; CI: 1.24-2.14). By contrast, HVs were more protective than TCs for caries (P = 0.008; OR = 0.42; CI: 0.22-0.80). CONCLUSIONS: This study provides prospective, clinical evidence that MS, DDEs, and low socioeconomic status are strongly correlated with early childhood caries and that HVs are more efficacious than TCs in ECC prevention. KNOWLEDGE TRANSFER STATEMENT: This 7-y birth cohort study provides longitudinal clinical evidence that mutans streptococci, developmental defects of enamel, and low socioeconomic status are key risk indicators of early childhood caries.

Reliability of software-based assessment of paediatric preparations for preformed metal crowns in the simulation laboratory.

PURPOSE: Using software for assessment of restorative work on typodonts in the simulation laboratory may enhance the objective evaluation of student work. The study aimed to evaluate the inter-rater and intra-rater reliability using 3-D scans from the Planmeca Emerald™ intra-oral scanner with Romexis Compare® software for assessing preparations for preformed metal crowns (PMCs). METHODS: Three operators independently recorded 3-D scans and digitally measured the features of 30 PMC preparations on typodont primary teeth (# 75). Using Romexis Compare® software, preparations were measured from mesial, distal and occlusal aspects. Measurements were repeated after 2 weeks. The intraclass correlation coefficient (ICC) was used to measure the reliability of measurements between operators and within the one operator. RESULTS: For measuring the extent of tooth reduction, there was excellent intra-rater reliability for each operator (ICC 0.96-0.99). The highest inter-rater reliability was for measurements of the occlusal surface (0.946 and 0.956), followed by the mesial surface (0.852 and 0.862) and then the distal surface (0.746 and 0.724). CONCLUSION: This method was useful and reliable for measuring features of PMC preparation, but with some limitations. Improving the software to provide specific assistance tools would empower greater uptake of this method as an adjunct to traditional visual grading tool in paediatric dentistry preclinical teaching.

Trends in Australian dental prescribing of antibiotics: 2005-2016.

BACKGROUND: Prescribing of antibiotics by dentists for surgical prophylaxis or as an adjunct to managing dental infections is a substantial part of the overall landscape for prescribed antibiotics in health care settings. METHODS: We explored trends in the antibiotic prescribing patterns of Australian dentists over the 12-year period, 2005-2016. We obtained data on dispensed prescriptions of antibiotics from registered dentists subsidized on the Pharmaceutical Benefits Scheme. RESULTS: Australian dentists were responsible for almost 7 million dispensed prescriptions of antibiotics over 12 years; an average of 24 prescriptions per year per dentist. The most commonly prescribed antibiotic was amoxicillin, followed by amoxicillin + clavulanic acid and metronidazole. These top three antibiotics constituted more than 80% of all antibiotics prescribed and their use increased dramatically over time. There was a large increase in the prescribing of broad-spectrum antibiotics over time, most of which occurred from 2011 to 2016. CONCLUSIONS: Excessive prescribing of broad-spectrum antibiotics runs contrary to national antimicrobial stewardship (AMS) initiatives and guidelines. Multifaceted educational strategies are essential to align prescribing with current best practice. High-level evidence to inform clear guidelines on antibiotic prescribing in dental infections, with audit and feedback, should reduce the inappropriate use of antibiotics in dentistry.

Oral health care and service utilisation in individuals with Rett syndrome: an international cross-sectional study.

BACKGROUND: There is a dearth of literature available on the comparative oral health status of those with Rett syndrome (RTT) despite diurnal bruxism being a supportive diagnostic criterion for the disorder. This study was designed to investigate the dental experiences of individuals with RTT in terms of perceived at-home and professional dental care. METHODS: Using data in the InterRett database, provided by English-speaking families of individuals with a confirmed MECP2 genetic mutation, the study investigated relationships between dental problems, oral care, child factors including bruxism and use of gastrostomy, and socioeconomic indicators. The study also explored relationships between dental presentations and socioeconomic, child, and family-related factors. RESULTS: Individuals with RTT exhibiting bruxism were more likely to access dental treatment. Those who had full oral feeding had a higher incidence rate of dental treatment than those with full tube feeding. A conservative (under) estimation of the overall dental caries progression rate revealed that this may be similar to that of the normal population. CONCLUSIONS: Drivers for dental treatment in RTT include bruxism as well as dental caries. Those who have full oral feeding experience more dental treatment than those with full tube feeding. A higher maternal education level may confer a protective effect for oral health outcomes in those with RTT. Nevertheless, families generally tended to value the importance of oral health despite reported difficulties in day-to-day mouth care.

Lifetime radiation risk of stochastic effects - prospective evaluation for space flight or medicine.

The concept of lifetime radiation risk of stochastic detrimental health outcomes is important in contemporary radiation protection, being used either to calculate detriment-weighted effective dose or to express risks following radiation accidents or medical uses of radiation. The conventionally applied time-integrated risks of radiation exposure are computed using average values of current population and health statistical data that need to be projected far into the future. By definition, the lifetime attributable risk (AR) is an approximation to more general lifetime risk quantities and is only valid for exposures under 1 Gy. The more general quantities, such as excess lifetime risk (ELR) and risk of exposure-induced cancer, are free of dose range constraints, but rely on assumptions concerning the unknown total radiation effect on demographic and health statistical data, and are more computationally complex than AR. Consideration of highly uncertain competing risks for other radiation-attributed outcomes are required in appropriate assessments of time-integrated risks of specific outcomes following high-dose (>1 Gy) exposures, causing non-linear dose responses in the resulting ELR estimate.Being based on the current population and health statistical data, the conventionally applied time-integrated risks of radiation exposure are: (i) not well suited for projections many years into the future because of the large uncertainties in future secular trends in the population-specific disease rates; and (ii) not optimal for application to atypical groups of exposed persons not well represented by the general population. Specifically, medical patients are atypical in this respect because their prospective risks depend strongly on the original diagnosis, the treatment modality, general cure rates, individual radiation sensitivity, and genetic predisposition. Another situation challenging the application of conventional risk quantities is a projection of occupational radiation risks associated with space flight, both due to higher radiation doses and astronauts' generally excellent health condition due to pre-selection, training, and intensive medical screening.An alternative quantity, named 'radiation-attributed decrease of survival' (RADS), known in past general statistical literature as 'cumulative risk', is recommended here for applications in space and medicine to represent the cumulative radiation risk conditional on survival until a certain age. RADS is only based on the radiation-attributed hazard rendering an insensitivity to competing risks or projections of current population statistics far into the future. Therefore, RADS is highly suitable for assessing semi-personalised radiation risks after radiation exposures from space missions or medical applications of radiation.

Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo.

Targeted drug delivery to the endothelium has the potential to generate localized therapeutic effects at the blood-tissue interface. For some therapeutic cargoes, it is essential to maintain contact with the bloodstream to exert protective effects. The pharmacokinetics (PK) of endothelial surface-targeted affinity ligands and biotherapeutic cargo remain a largely unexplored area, despite obvious translational implications for this strategy. To bridge this gap, we site-specifically radiolabeled mono- (scFv) and bivalent (mAb) affinity ligands specific for the endothelial cell adhesion molecules, PECAM-1 (CD31) and ICAM-1 (CD54). Radiotracing revealed similar lung biodistribution at 30 minutes post-injection (79.3% ± 4.2% vs 80.4% ± 10.6% ID/g for αICAM and 58.9% ± 3.6% ID/g vs. 47.7% ± 5.8% ID/g for αPECAM mAb vs. scFv), but marked differences in organ residence time, with antibodies demonstrating an order of magnitude greater area under the lung concentration vs. time curve (AUCinf 1698 ± 352 vs. 53.3 ± 7.9 ID/g*hrs for αICAM and 1023 ± 507 vs. 114 ± 37 ID/g*hrs for αPECAM mAb vs scFv). A physiologically based pharmacokinetic model, fit to and validated using these data, indicated contributions from both superior binding characteristics and prolonged circulation time supporting multiple binding-detachment cycles. We tested the ability of each affinity ligand to deliver a prototypical surface cargo, thrombomodulin (TM), using one-to-one protein conjugates. Bivalent mAb-TM was superior to monovalent scFv-TM in both pulmonary targeting and lung residence time (AUCinf 141 ± 3.2 vs 12.4 ± 4.2 ID/g*hrs for ICAM and 188 ± 90 vs 34.7 ± 19.9 ID/g*hrs for PECAM), despite having similar blood PK, indicating that binding strength is more important parameter than the kinetics of binding. To maximize bivalent target engagement, we synthesized an oriented, end-to-end anti-ICAM mAb-TM conjugate and found that this therapeutic had the best lung residence time (AUCinf 253 ± 18 ID/g*hrs) of all TM modalities. These observations have implications not only for the delivery of TM, but also potentially all therapeutics targeted to the endothelial surface.