Sex as a Biological Variable in Oral Diseases: Evidence and Future Prospects.

The interest of the scientific community on sex and gender differences in health and disease has increased substantially over the past 25 to 30 y as a result of a long process of events and policies in the biomedical field. This is crucial as compelling evidence from human and animal model studies has demonstrated that sex and gender influence health, molecular and cellular processes, and response and predisposition to disease. The present scoping review aims to provide a synthesis of sex differences in oral diseases, ranging from periodontal disease to orofacial pain conditions, from risk of caries development to apical periodontitis. Overall, findings from this review further support a role for sexual dimorphism influencing disease predisposition and/or progression in oral diseases. Of note, this review also highlights the lack of consideration of additional factors such as gender and other psychosocial and external factors potentially influencing oral health and disease. New conceptual frameworks capable of capturing multiple fundamental domains and measurements should be developed in clinical and preclinical studies to inform sex-based individualized preventive and treatment strategies.

Unusual Findings in Trials Evaluating Adjuncts to Scaling and Root Planing: Reporting Quality (Part 2).

INTRODUCTION: On the topic of adjuncts to scaling and root planing (SRP), numerous randomized clinical trials (RCTs) were published by a single group of authors and frequently reported unusually large effect sizes. A meta-analysis in part 1 of this project failed to explain the causes for these unusual findings. We assessed the reporting quality and trial registration discrepancies to examine the possibility of replicating the work of this research group as well as the overall rigor of the research methodology. METHODS: This study was preregistered at the Open Science Framework (https://osf.io/4meyd/). The Scopus platform was utilized for the RCT search on SRP adjuncts in intrabony defects in patients with periodontitis as compared with SRP alone. The search analysis was limited from 2010 to 2017, and RCTs on SRP adjuncts published by a single research group were selected for screening and inclusion. RCT registration records were assessed for consistency. RESULTS: Out of 92 studies that were retrieved from Scopus and PubMed, 32 were included for quality assessment per the CONSORT guidelines (Consolidated Standards of Reporting Trials). Results showed that all RCTs were characterized by a low reporting quality. The majority of CONSORT items scored <50%, including critical items (randomization, registration, and blinding). When registration records were compared with published RCTs, several discrepancies were found. The per-protocol follow-up duration was compared against the study's initiation and termination dates. Only 38% of the RCTs presented a follow-up period within the initiation and termination dates. The remaining RCTs showed inconsistent follow-up in comparison with the initiation and termination dates. CONCLUSION: RCTs by this group were characterized by poor adherence to reporting quality guidelines. Crucial RCT elements, such as randomization, blinding, and primary outcomes, were not reported properly. RCT registration records revealed systematic inconsistencies when compared with RCT publication. Therefore, the unusually large effects reported by this group should be viewed with extreme caution. KNOWLEDGE TRANSFER STATEMENT: The included randomized clinical trials were characterized by poor adherence to reporting quality guidelines, missing information about important trial items, and discrepancies between the reports and trial registrations. This quality assessment should guide clinical research and show clinicians that they should be cautious when applying evidence in their clinical practice.

Unusual Findings in Trials Evaluating Adjuncts to Scaling and Root Planing: Meta-analysis (Part 1).

BACKGROUND: A number of studies in patients with periodontitis have compared scaling and root planning (SRP) combined with an adjunctive treatment to SRP alone. Within that literature, an array of studies with overlapping investigators has consistently yielded substantially greater effects of adjunctive treatments than had been previously noted. This report investigates discrepancies between that cluster of research and the most recent American Dental Association (ADA) systematic review. METHODS: This review was preregistered at https://osf.io/4meyd/. A search using the Scopus platform identified 32 articles published from 2010 to 2017 by investigators affiliated with the Government Dental College and Research Institute (GDCRI) in Bangalore, India. The primary outcome used in this meta-analysis was the change in clinical attachment level (CAL) after 6 mo. Effect sizes were estimated using Comprehensive Meta-Analysis software after categorizing agents into groups based on pharmacologic similarity. RESULTS: The search identified 32 studies encompassing 5 sets of adjunctive agents. Across the GDCRI studies, the CAL averaged 1.67 mm (95% confidence interval [CI]: 1.43-1.91 mm), substantially exceeding values reported in the ADA review (mean: 0.39 mm, 95% CI: 0.27-0.51 mm). For categories of studies in which comparable subgroup estimates were available, the evaluations yielded overlapping estimates of SRP alone, but CAL estimates were discrepant for both locally delivered antimicrobials (GDCRI studies: mean: 1.45 mm, 95% CI: 0.63-2.27 mm; ADA review: mean: 0.38 mm, 95% CI: 0.16 -0.60 mm) and systemic antibiotics (GDCRI studies: mean: 1.35 mm, 95% CI: 0.97-1.73 mm; ADA review: mean: 0.39 mm, 95% CI: 0.21-0.57 mm). CONCLUSION: In the literature on adjunctive agents supplementing SRP, findings from investigators linked to GDCRI stand out as having significantly more favorable estimated effects. Meanwhile, some agents studied by GDCRI-linked investigators have not been investigated by other researchers. In the absence of a clear explanation for discrepant results, it is recommended that unusually favorable reported effects of adjunctive agents be viewed with caution. KNOWLEDGE TRANSFER STATEMENT: The present meta-analysis observed an unusually large effect size of adjunctive agents to scaling and root planning in studies conducted by the same research group. These results were not consistent with trials on adjunctive agents and previous reports. As this research group has exclusively tested most of the agents, their results must be viewed with caution until other independent groups replicate the studies and reproduce the effect size.

Mitochondrial neurogastrointestinal encephalomyopathy: Clinical and biochemical impact of allogeneic stem cell transplantation in a Greek patient with one novel TYMP mutation.

We describe the case of a Greek female patient with the Classic form of the ultra- rare and fatal autosomal recessive disorder Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and the impact of allogeneic hematopoietic stem cell transplantation on the biochemical and clinical aspects of the disease. The patient presented at the age of 15 years with severe gastrointestinal symptoms, cachexia, peripheral neuropathy and diffuse leukoencephalopathy. The diagnosis of MNGIE disease was established by the increased levels of thymidine and deoxyuridine in plasma and the complete deficiency of thymidine phosphorylase activity. The novel c.[978dup] (p.Ala327Argfs*?) variant and the previously described variant c.[417 + 1G > A] were identified in TYMP. The donor for the allogeneic hematopoietic stem cell transplantation was her fully compatible sister, a carrier of the disease. The patient had a completely uneventful post- transplant period and satisfactory PB chimerism levels. A marked and rapid decrease in thymidine and deoxyuridine plasma levels and an increase of the thymidine phosphorylase activity to the levels measured in her donor sister was observed and is still present sixteen months post-transplant. Disease symptoms stabilized and some improvement was also observed both in her neurological and gastrointestinal symptoms. Follow up studies will be essential for determining the long term impact of allogeneic hematopoietic stem cell transplantation in our patient.

Gender Inequalities in the Dental Workforce: Global Perspectives.

The aim of this review is to investigate the growth of diversity and inclusion in global academic dental research with a focus on gender equality. A diverse range of research methodologies were used to conduct this review, including an extensive review of the literature, engagement of key informants in dental academic leadership positions around the world, and review of current data from a variety of national and international organizations. Results provide evidence of gender inequalities that currently persist in dental academics and research. Although the gender gap among graduating dental students in North America and the two most populous countries in Europe (the United Kingdom and France) has been narrowed, women make up 30% to 40% of registered dentists in countries throughout Europe, Oceania, Asia, and Africa. In academic dentistry around the globe, greater gender inequality was found to correlate with higher ranking academic and leadership positions in the United States, United Kingdom, several countries in European Union, Japan, and Saudi Arabia. Further disparities are noted in the dental research sector, where women make up 33% of dental researchers in the European Union, 35% in North America, 55% in Brazil, and 25% in Japan. Family and societal pressures, limited access to research funding, and lack of mentoring and leadership training opportunities are reported as also contributing to gender inequalities. To continue advancing gender equality in dental academia and research, efforts should be geared toward the collection and public dissemination of data on gender-specific distributions. Such evidence-driven information will guide the selection of future strategies and best practices for promoting gender equity in the dental workforce, which provides a major pipeline of researchers and scholars for the dental profession.

Empowering Women Researchers in the New Century: IADR's Strategic Direction.

Gender inequality in science, medicine, and dentistry remains a central concern for the biomedical research workforce today. Although progress in areas of inclusivity and gender diversity was reported, growth has been slow. Women still face multiple challenges in reaching higher ranks and leadership positions while maintaining holistic success in these fields. Within dental research and academia, we might observe trends toward a more balanced pipeline. However, women continue to face barriers in seeking leadership roles and achieving economic equity and scholarship recognition. In an effort to evaluate the status of women in dental research and academia, the authors examined the role of the International Association for Dental Research (IADR), a global research organization, which has improved awareness on gender inequality. The goal of this article is to review five crucial issues of gender inequality in oral health research and academics-workforce pipeline, economic inequality, workplace harassment, gender bias in scholarly productivity, and work-life balance-and to discuss proactive steps that the IADR has taken to promote gender equality. Providing networking and training opportunities through effective mentoring and coaching for women researchers, the IADR has developed a robust pipeline of women leaders while promoting gender equality for women in dental academia through a culture shift. As knowledge gaps remained on the levels of conscious and unconscious bias and sexist culture affecting women advancement in academics, as well as the intersectionality of gender with race, gender identity, ability status, sexual orientation, and cultural backgrounds, the IADR has recognized that further research is warranted.

Spreading of Thelazia callipaeda in Greece.

Thelazia callipaeda (Spirurida, Thelaziidae), the so-called oriental eyeworm, has been increasingly reported as an agent of infection in animals and humans from many European countries. Clinical signs range from subclinical to moderate or severe ocular disorders (e.g., epiphora, photophobia, conjunctivitis, keratitis, ulcers). The disease has been also diagnosed in animals from countries of the Balkan area (e.g., Croatia, Bosnia and Herzegovina and Serbia), but only a single case of canine thelaziosis, presumably autochthonous, was reported in Northern Greece. In this study, we provide robust information of the occurrence of thelaziosis in Greece by reporting autochthonous cases of thelaziosis in dogs (n = 46), cats (n = 3) and in one rabbit (Oryctolagus cuniculus) living in Northern and Central regions of Greece. The occurrence of a single haplotype of the cytochrome oxidase subunit 1 gene confirms that the same zoonotic haplotype of the parasite circulating in Europe is also spreading in Greece. The increased awareness of this parasitosis is crucial to limit the risk of further infections in both humans and animals in European countries.

Task Force on Design and Analysis in Oral Health Research: Medication-Related Osteonecrosis of the Jaw.

Knowledge Transfer Statement: This article discusses the proceedings of the conference organized by the Task Force on Design and Analysis in Oral Health Research on the understanding of the translational evidence on the etiology and pathogenesis of medication-related osteonecrosis of the jaw as well as the clinical protocols on patient management.

Task Force on Design and Analysis in Oral Health Research: Host-Microbiome Interactions in Dysbiosis.

Knowledge Transfer Statement: This article discusses the proceedings of the conference organized by the Task Force on Design and Analysis in Oral Health Research on the new advances in host-microbiome interactions, analytical methods, and their implication in inflammatory periodontal disease management.

A bi-level intervention to improve oral hygiene of older and disabled adults in low-income housing: results of a pilot study.

OBJECTIVE: This paper describes the results of a bi-level intervention, using a cognitive-behavioral theoretical approach, to improve the oral hygiene of older adults and the disabled in community-based low income senior housing. METHODS: The bi-level pilot intervention consisted of an on-site tailored adapted motivational interviewing (AMI) session and two oral health fairs, supported by a resident campaign committee, to change community norms. All materials were available in English and Spanish. Participants completed a survey consisting of 12 domains that provided the basis for tailoring the AMI and shaping the campaigns. The domains were activities of daily living (ADLs), access to oral health information, oral hygiene status, dental knowledge, hygiene behaviors, importance of oral hygiene, self-efficacy/locus of control, diet, intentions, self-management worries/fears, perceived risk and dry mouth. MAIN OUTCOME MEASURES: Each participant received clinical assessments consisting of full-mouth plaque score (PS) and gingival index (GI) before the intervention and at three months. RESULTS: Twenty-seven residents with at least one tooth completed all phases of the study. The mean number of domains requiring attention was 4.5 (SD 1.6) with a range of one to seven. Mean baseline PS was 83% (SD 16%) which improved significantly to 58% (SD 31%); mean baseline GI was 1.15 (SD 0.61) and improved significantly to 0.49 (SD 0.46). CONCLUSIONS: This pilot study supports the feasibility and acceptability of a tailored oral hygiene intervention among older and disabled adults living in low income senior housing. Although a small sample, the study demonstrated significant improvements in both plaque and gingival scores three months after the bi-level intervention.

Emergence of pan-resistance in KPC-2 carbapenemase-producing Klebsiella pneumoniae in Crete, Greece: a close call.

OBJECTIVES: KPC-2-producing Klebsiella pneumoniae (KPC-KP) ST258 has been rapidly expanding and is often associated with serious nosocomial infections. Last-line antibiotics such as colistin and tigecycline often remain the only treatment option. We describe here the evolving genetic background of KPC-KP isolates in Crete, Greece. METHODS: We tested the antibiotic susceptibility of 34 clinical isolates from patients hospitalized in 2010 and 2013-14. Whole-genome sequences of these isolates were analysed for acquired resistance genes and gene mutations. RESULTS: All KPC-KP isolates belonged to ST258 with the exception of one ST147 isolate. From 2014, 26% of isolates were non-susceptible to all antibiotics, compared with 0 of 11 isolates from 2010. Colistin resistance was associated with mutations in mgrB, which was present in 61% of isolates from 2014. Core-genome MLST analysis showed that pan-resistant isolates were closely related and appeared in two separate clusters. CONCLUSIONS: KPC-KP is rapidly evolving to pan-resistance in Crete. We identified molecular resistance markers for pan-resistant isolates and showed that core-genome MLST is a promising tool for molecular fingerprinting of KPC-KP ST258.

Tooth loss strongly associates with malnutrition in chronic kidney disease.

BACKGROUND: In chronic kidney disease (CKD), inadequate nutritional intake, inflammation, and increased oxidative stress have been the major contributing factors in malnutrition pathogenesis. However, there is still a paucity of evidence assessing the magnitude of the effect of tooth loss on malnutrition in CKD populations. The authors hypothesize that among patients with CKD, tooth loss may affect nutritional status, using the National Health and Nutrition Examination Survey 1988 to 1994 (NHANES III). METHODS: Glomerular filtration rate (GFR) was estimated based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio (albuminuria) was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on estimated GFR <60 mL/minute/1.73m(2) and albuminuria ≥30 mg/g. The cutoff point for serum albumin was set at 3.7 g/dL. Tooth loss categories were based on the number of missing and replaced teeth. RESULTS: A total of 2,749 patients was included and stratified based on their oral health status. There was a statistically significant correlation between tooth loss and the proportion of patients with low protein and caloric intake (P = 0.02 and 0.01, respectively). Serum albumin reached a frequency peak in the fully edentulous group without dentures (group 4, 19.2%). In the same group, individuals had lower protein (30.1%) and caloric intake (30.2%) (P = 0.01 and 0.02, respectively). Furthermore, logistic regression analysis confirmed the significant role of tooth loss on serum albumin and protein and energy intake in this population even after adjusting for confounding variables. CONCLUSION: Tooth loss independently predicts low energy and protein intake, as well as serum albumin levels, biomarkers of malnutrition in CKD.

Absence of JAK2V617F mutation in patients with beta-thalassemia major and thrombocytosis due to splenectomy.

The report of Janus Kinase 2 (JAK2) mutations in myeloid malignancies with high frequency in myeloproliferative neoplasms has been well known since 2005. By monitoring allele burden, it is found that the expression of JAK2V617F mutation is increasing significantly from essential thrombocytosis to polycythemia vera. Furthermore, JAK2 abnormalities are reported in the majority of unexplained thrombotic episodes. Thalassemic syndromes are characterized by ineffective erythropoiesis and thrombocytosis, mainly due to splenectomy. The high incidence of thromboembolic events has led to the identification of a prothrombotic state in these patients. The contribution of JAK2 mutations to the hypercoagulable state of thalassemic patients is still unknown. Furthermore, the potential role of Janus Kinase mutations in hepcidin expression and consequently in ineffective erythropoiesis is still under investigation. This study was scheduled to determine whether the presence of JAK2V617F mutation in thalassemic patients is associated with thrombocytosis. We studied 20 patients DNA with beta-thalassemia for JAK2V617F mutation by using RG-PCR method. None of the patients were positive for this particular mutation. More studies are needed to prove the role of JAK2 in ineffective erythropoiesis, iron metabolism and thrombocytosis and to determine if using JAK2 inhibitors in thalassemic patients can be a potential therapeutic option.

Periodontitis predicts elevated C-reactive protein levels in chronic kidney disease.

Based on the existing evidence supporting a state of chronic inflammation in chronic kidney disease (CKD), we hypothesized that periodontal infection may affect the systemic inflammatory status of a nationally representative CKD population as measured by serum C-reactive protein (CRP). We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) dataset including 2303 individuals. We followed the American Academy of Periodontology (AAP)/Centers for Disease Control and Prevention (CDC) case definition for periodontitis. We used a cutoff point of 30% sites with (PD) ≥ 5 mm and (CAL) ≥ 4 mm to define generalized periodontitis cases. We estimated glomerular filtration rate based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on eGFR < 60 mL/min/1.73 m(2) and albuminuria ≥ 30 mg/g. Periodontitis was found in 427 (12.3%) individuals. Of individuals with periodontitis, 41.8% had serum CRP higher than 0.3 mg/dL compared with 27.1% of non-periodontitis and 53.1% of edentulous individuals (p = 0.001 for all comparisons). When the extent of periodontitis was used as one of the independent variables, the parsimonious model showed a strong independent association between extent of periodontitis and serum CRP levels (OR = 2.0, CI95% = 1.2-3.6).