Faculty Bibliography

Neuropathic pain and neuropsychiatric symptoms are common complications reported by the traumatic brain injury (TBI) population. Although a growing body of research has indicated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for the management of neurological and psychiatric disorders, little evidence has been presented to support the effects of rTMS on neuropathic pain and neuropsychiatric symptoms in patients with TBI in all age groups. In addition, a better understanding of the potential factors that might influence the therapeutic effect of rTMS is necessary. The objective of this preregistered systematic review and meta-analysis was to quantify the effects of rTMS on physical and psychological symptoms in individuals with TBI. We systematically searched six databases for randomized controlled trials (RCTs) of rTMS in TBI patients reporting pain and neuropsychiatric outcomes published until March 20, 2022. The mean difference (MD) with 95% confidence intervals (CIs) was estimated separately for outcomes to understand the mean effect size. Twelve RCTs with 276 TBI patients were ultimately selected from 1605 records for systematic review, and 11 of the studies were included in the meta-analysis. Overall, five of the included studies showed a low risk of bias. The effects of rTMS on neuropathic pain were statistically significant (MD = -1.00, 95% CI -1.76 to -0.25, P = 0.009), with high heterogeneity (I ² = 76%). A significant advantage of 1 Hz rTMS over the right dorsolateral prefrontal cortex (DLPFC) in improving depression (MD = -6.52, 95% CI -11.58 to -1.46, P = 0.01) was shown, and a significant improvement was noted in the Rivermead Post-Concussion Symptoms Questionnaire-13 (RPQ-13) scores of mild TBI patients after rTMS (MD = -5.87, 95% CI -10.63 to -1.11, P = 0.02). However, no significance was found in cognition measurement. No major adverse events related to rTMS were reported. Moderate evidence suggests that rTMS can effectively and safely improve neuropathic pain, while its effectiveness on depression, postconcussion symptoms, and cognition is limited. More trials with a larger number of participants are needed to draw firm conclusions. This trial is registered with PROSPERO (PROSPERO registration number: CRD42021242364.

OBJECTIVE/UNASSIGNED:We investigated regional disparities in rates of scoliosis among adolescents in western and eastern China and the dominant factors underlying these disparities. METHODS/UNASSIGNED:This cross-sectional study used data from a school scoliosis screening program conducted in two typical areas: Yangpu District of Shanghai (eastern China) and Tianzhu Tibetan Autonomous County of Gansu Province (western China), during October 2020 to February 2021. Participants included adolescents aged 12-16 years (4,240 in Shanghai and 2,510 in Gansu Province). School scoliosis screening data were obtained on age, sex, height, weight and BMI, and region as well. We screened angles of trunk rotation in level of proximal thoracic (T1-T4), main thoracic (T5-T12), and lumbar (T12-L4) by the forward bend test with scoliometer. An angle of trunk rotation ≥5° was used as the criterion to identify suspected scoliosis. RESULTS/UNASSIGNED:The proportion of suspected scoliosis was lower in Shanghai (6.9%) than in Gansu (8.6%). Angle of trunk rotation tended to increase with age in Shanghai, peaking at 15 years, but decreased with age in Gansu, and bottomed at 15 years. The angle of trunk rotation in the proximal thoracic, main thoracic, and lumbar part of the spine appeared to be larger in Gansu adolescents and in Shanghai female adolescents. Age was a relevant factor in angle trunk rotation in regression models and interacted with region as well. CONCLUSION/UNASSIGNED:We found regional and age- and sex-related disparities in rates of suspected scoliosis.

Succinate is a metabolite in the tricarboxylic acid cycle (TCA) which plays a central role in mitochondrial activity. Excess succinate is known to be transported out of the cytosol, where it activates a succinate receptor (SUCNR1) to enhance inflammation through macrophages in various contexts. In addition, the intracellular role of succinate beyond an intermediate metabolite and prior to its extracellular release is also important to the polarization of macrophages. However, the role of succinate in microglial cells has not been characterized. Lipopolysaccharide (LPS) stimulates the elevation of intracellular succinate levels. To reveal the function of intracellular succinate associated with LPS-stimulated inflammatory response in microglial cells, we assessed the levels of ROS, cytokine production and mitochondrial fission in the primary microglia pretreated with cell-permeable diethyl succinate mimicking increased intracellular succinate. Our results suggest that elevated intracellular succinate exerts a protective role in the primary microglia by preventing their conversion into the pro-inflammatory M1 phenotype induced by LPS. This protective effect is SUCNR1-independent and mediated by reduced mitochondrial fission and cellular ROS production.

Mitochondrial fusion and fission, which are strongly related to normal mitochondrial function, are referred to as mitochondrial dynamics. Mitochondrial fusion defects in the liver cause a non-alcoholic steatohepatitis-like phenotype and liver cancer. However, whether mitochondrial fission defect directly impair liver function and stimulate liver disease progression, too, is unclear. Dynamin-related protein 1 (DRP1) is a key factor controlling mitochondrial fission. We hypothesized that DRP1 defects are a causal factor directly involved in liver disease development and stimulate liver disease progression. Drp1 defects directly promoted endoplasmic reticulum (ER) stress, hepatocyte death, and subsequently induced infiltration of inflammatory macrophages. Drp1 deletion increased the expression of numerous genes involved in the immune response and DNA damage in Drp1LiKO mouse primary hepatocytes. We administered lipopolysaccharide (LPS) to liver-specific Drp1-knockout (Drp1LiKO) mice and observed an increased inflammatory cytokine expression in the liver and serum caused by exaggerated ER stress and enhanced inflammasome activation. This study indicates that Drp1 defect-induced mitochondrial dynamics dysfunction directly regulates the fate and function of hepatocytes and enhances LPS-induced acute liver injury in vivo.

The onset of the Coronavirus 2019 (COVID-19) pandemic has challenged the worldwide healthcare sector, including dentistry. The highly infectious nature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and risk of transmission through aerosol generating procedures has profoundly impacted the delivery of dental care services globally. As dental practices with renewed infection control strategies and preventive measures are re-opening in the "new normal" period, it is the responsibility of healthcare professionals to constantly analyze new data and limit the spread of COVID-19 in dental care settings. In the light of new variants of SARS-CoV-2 rapidly emerging in different geographic locations, there is an urgent need to comply more than ever with the rigorous public health measures to mitigate COVID-19 transmission. The aim of this article is to provide dental clinicians with essential information regarding the spread of SARS-CoV-2 virus and protective measures against COVID-19 transmission in dental facilities. We complied and provided guidance and standard protocols recommended by credible national and international organizations. This review will serve as an aid to navigating through this unprecedented time with ease. Here we reviewed the available literature recommended for the best current practices that must be taken for a dental office to function safely and successfully.

Type 2 diabetes mellitus (T2DM) significantly increases bone fragility and fracture risk. Progranulin (PGRN) promotes bone fracture healing in both physiological and type 1 diabetic conditions. The present study aimed to investigate the role of PGRN in T2DM bone fracture healing. MKR mice (with an FVB/N genetic background) were used as the T2DM model. Drill-hole and Bonnarens and Einhorn models were used to investigate the role of PGRN in T2DM fracture healing in vivo. Primary bone marrow cells were isolated for molecular and signaling studies, and reverse transcription-polymerase chain reaction, immunohistochemical staining, and western blotting were performed to assess PGRN effects in vitro. PGRN mRNA and protein expression were upregulated in the T2DM model. Local administration of recombinant PGRN effectively promoted T2DM bone fracture healing in vivo. Additionally, PGRN could induce anabolic metabolism during endochondral ossification through the TNFR2-Akt and Erk1/2 pathways. Furthermore, PGRN showed anti-inflammatory activity in the T2DM bone regeneration process. These findings suggest that local administration of exogenous PGRN may be an alternative strategy to support bone regeneration in patients with T2DM. Additionally, PGRN might hold therapeutic potential for other TNFR-related metabolic disorders.

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10^-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (r_G = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.

The objective of this pilot study was to describe the microbial profiles present in the plaque and saliva of children who continued to develop new carious lesions following treatment with silver diamine fluoride ("nonresponders") compared to caries active, caries-free, and children immediately receiving SDF treatment for untreated caries in order to identify potential microbial differences that may relate to a re-incidence of caries. Saliva and plaque samples from infected and contralateral sites were obtained from twenty children who were either caries free, had active carious lesions, were caries active and received SDF treatment immediately before sampling, or had previously received SDF treatment and developed new caries. In total, 8,057,899 Illumina-generated sequence reads from 60 samples were obtained. Reads were processed using the Quantitative Insights Into Microbial Ecology pipeline. Group differences were assessed using Analysis of Variance Models and Tukey Honest Significant Differences. To identify significant taxa between treatment groups, Linear discriminant analysis Effect Size (LefSe) and Analysis of Differential Abundance Taking Sample Variation Into Account were used. Differential abundant analysis indicated that members of the Lachnospiraceae family were significantly enriched in non-responders and the genus Tannerella and species Granulicatella adiances were also highly abundant in this group. LefSe analysis between non-responders and SDF-treated groups revealed that genera Leptotrichia and Granulicatella were enriched in non-responders. We observed the highest abundance of phosphotransferase system and lowest abundance of lipopolysaccharide synthesis in non-responders. The microbiome in dental biofilms is responsible for initiation and progression of dental caries. SDF has been shown to be effective in arresting the progression carious lesions, in part due to its antimicrobial properties. Findings suggest that the differential abundance of select microbiota and specific pathway functioning in individuals that present with recurrent decay after SDF treatment may contribute to a potential failure of silver diamine fluoride to arrest dental caries. However, the short duration of sample collection following SDF application and the small sample size emphasize the need for further data and additional analysis.