Effect of systemic bisphosphonate administration on patients with periodontal disease: a systematic review and meta-analysis protocol.

INTRODUCTION: Periodontal disease is a chronic oral infectious disease affecting adults worldwide as well as a lifestyle-related disease related to diabetes. Bisphosphonate is a drug often taken by patients with osteoporosis; however, it reportedly can cause jawbone necrosis. Due to its mechanism of action on bone tissue, bisphosphonate has been used topically on periodontal tissue to treat periodontal disease. However, the long-term systemic effects of bisphosphonates on periodontal tissues are unclear. This paper describes a protocol evaluating the effects of systemic bisphosphonate administration to prevent periodontal tissue destruction in patients with periodontal disease. No systematic review has attempted to summarise the evidence for systemic bisphosphonates in periodontal therapy. The results of the proposed systematic review will inform the practice and design of future clinical trials. METHODS AND ANALYSIS: This paper describes a protocol for a systematic review of the relevant published analytic research using an aggregative thematic approach according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Two authors will perform a comprehensive search for studies on Medline/PubMed, Scopus, Embase, LILACS and the Cochrane Central Register of Controlled Trials databases. Abstract screening, full-text screening and data extraction will be performed independently by two authors. A meta-analysis will be conducted as appropriate. ETHICS AND DISSEMINATION: The protocol of this systematic review will be provided in a peer-reviewed journal. Formal ethics approval is not necessary because researchers will not identify individuals in the report. PROSPERO REGISTRATION NUMBER: CRD42020212698 (http://www.crd.york.ac.uk/PROSPERO/).

Differences in executive function among patients with schizophrenia, their unaffected first-degree relatives and healthy participants.

BACKGROUND: Patients with schizophrenia (SCZ) display impaired executive functions compared with healthy controls (HCs). Furthermore, unaffected first-degree relatives (FRs) of patients with SCZ independently perform worse executive functions than do HCs. However, few studies have investigated the differences in executive functions assessed among patients with SCZ, FRs, and HCs, and the findings are inconsistent. METHODS: We investigated diagnostic differences in executive functions, namely, (i) numbers of categories achieved (CA), (ii) total errors (TE) and (iii) %perseverative errors of Nelson types (%PEN), using the Wisconsin card sorting test (WCST) among patients with SCZ (n=116), unaffected FRs (n=62) and HCs (n=146) at a single institute. Correlations between these executive functions and clinical variables were investigated. RESULTS: Significant differences existed in all executive functions among diagnostic groups (CA, F2,319=15.5, p=3.71×10-7; TE, F2,319=16.2, p=2.06×10-7; and %PEN, F2,319=21.3, p=2.15×10-9). Patients with SCZ had fewer CA and more TE and %PEN than those of HCs (CA, Cohen's d=-0.70, p=5.49×10-8; TE, d=0.70, p=5.62×10-8; and %PEN, d=0.82, p=2.85×10-10) and FRs (TE, d=0.46, p=3.73×10-3 and %PEN, d=0.38, p=0.017). Of the three executive functions, CA and %PEN of FRs were intermediately impaired between patients with SCZ and HCs (CA, d=-0.41, p=0.011 and %PEN, d=0.41, p=0.012). In contrast, no significant difference in TE existed between FRs and HCs (d=0.22, p=0.18). Although CA and TE were affected by the duration of illness (p<0.017), %PEN was not affected by any clinical variable in patients with SCZ (p>0.017). CONCLUSIONS: Executive function, particularly %PEN, could be a useful intermediate phenotype for understanding the genetic mechanisms implicated in SCZ pathophysiology.

Intelligence decline between present and premorbid IQ in schizophrenia: Schizophrenia Non-Affected Relative Project (SNARP).

Schizophrenia patients (SCZ) display widespread cognitive deficits that are strongly associated with functional outcomes. Cognitive impairments occur along a genetic continuum among SCZ, their unaffected first-degree relatives (FRs) and healthy controls (HCs). Although SCZ impairs the premorbid intelligence quotient (IQ) and causes a subsequent intelligence decline (ID), a decrease in present IQ from the premorbid level, it remains unclear when during the illness course these impairments develop. Differences in premorbid and present IQ and ID were investigated among 125 SCZ, 61 FRs and 107 HCs, using analysis of covariance and a paired t-test. Furthermore, these subjects were classified into preserved and deteriorated IQ groups based on the degree of ID, and we investigated which factors contribute to this classification. We found significant differences in premorbid and present IQ among the diagnostic groups. Compared with HCs, SCZ and FRs displayed lower premorbid and present IQ. There was no significant difference in premorbid IQ between SCZ and FRs, but SCZ had a significantly lower present IQ than FRs. Only SCZ showed a significant ID. As most FRs and HCs did not display an ID, there were fewer subjects with deteriorated IQ among FRs and HCs than among SCZ. Subjects with preserved IQ showed higher educational attainment than those with deteriorated IQ among SCZ and FRs. These findings suggest that the impairment of premorbid IQ and the ID in SCZ become evident before and around the time of onset, respectively, and different pathophysiological mechanisms might be related to these impairments.

Quantitative proteomic analysis of gingival crevicular fluids from deciduous and permanent teeth.

AIM: Gingivitis commonly progresses to periodontitis in permanent dentition but rarely in deciduous teeth. Little is known about the biochemical differences between gingiva of deciduous and permanent teeth. Here, we compared the protein profiles of gingival crevicular fluids (GCF) from the gingiva of deciduous and permanent teeth. MATERIALS AND METHODS: Forty children with mixed dentition (Hellman's dental age IIIA) were selected and GCF samples were collected from deciduous cuspids and central incisors in the maxilla. Pairs of GCF samples were labelled using isobaric tags to permit quantitative comparison of protein abundance in the samples using liquid chromatography-electron spray ionization-tandem mass spectrometry. RESULTS: Sixty-two proteins were upregulated in deciduous teeth GCF and 54 in permanent teeth GCF. In particular, neutrophil-derived proteins, including myeloperoxidase and lactoferrin, were repeatedly higher in deciduous teeth GCF than in permanent teeth GCF. These differences were verified using ELISA (p < 0.01). In contrast, immunoglobulin components were upregulated in permanent teeth GCF. CONCLUSIONS: Neutrophil-related proteins were enriched in deciduous teeth GCF and immunoglobulins in permanent teeth GCF. This suggests that neutrophil accumulation plays a protective role in innate immunity against bacterial infection in gingival tissue of deciduous teeth.

Two distinct stem cell lineages in murine bone marrow.

Mesenchymal stem cells (MSC), a distinct type of adult stem cell, are easy to isolate, culture, and manipulate in ex vivo culture. These cells have great plasticity and potential for therapeutic application, but their properties are poorly understood because of their low frequency and the lack of knowledge on cell surface markers and their location of origin. The present study was designed to address the undefined lineage relationship of hematopoietic and mesenchymal stem cells. Genetically marked, highly purified hematopoietic stem cells (HSCs) were transplanted into wild-type animals and, after bone marrow repopulation, the progeny were rigorously investigated for differentiation potential into mesenchymal tissues by analyzing in vitro differentiation into mesenchymal tissues. None/very little of the hematopoietic cells contributed to colony-forming units fibroblast activity and mesenchymal cell differentiation; however, unfractionated bone marrow cells resulted in extensive replacement of not only hematopoietic cells but also mesenchymal cells, including MSCs. As a result, we concluded that purified HSCs have no significant potency to differentiate into mesenchymal lineage. The data strongly suggest that hematopoietic cells and mesenchymal lineage cells are derived from individual lineage-specific stem cells. In addition, we succeeded in visualizing mesenchymal lineage cells using in vivo microimaging and immunohistochemistry. Flow cytometric analysis revealed CD140b (PDGFRbeta) could be a specific marker for mesenchymal lineage cells. The results may reinforce the urgent need for a more comprehensive view of the mesenchymal stem cell identity and characteristics. Disclosure of potential conflicts of interest is found at the end of this article.