The Role of Oral Health in the Acquisition and Severity of SARS-CoV-2: A Retrospective Chart Review

ObjectiveStudies have shown that gingival crevices may be a significant route for SARS-CoV-2 entry. However, the role of oral health in the acquisition and severity of COVID-19 is not known.DesignA retrospective analysis was performed using electronic health record data from a large urban academic medical center between 12/1/2019 and 8/24/2020. A total of 387 COVID-19 positive cases were identified and matched 1:1 by age, sex, and race to 387 controls without COVID-19 diagnoses. Demographics, number of missing teeth and alveolar crestal height were determined from radiographs and medical/dental charts. In a subgroup of 107 cases and controls, we also examined the rate of change in alveolar crestal height. A conditional logistic regression model was utilized to assess association between alveolar crestal height and missing teeth with COVID-19 status and with hospitalization status among COVID-19 cases.ResultsIncreased alveolar bone loss, OR = 4.302 (2.510 – 7.376), fewer missing teeth, OR = 0.897 (0.835–0.965) and lack of smoking history distinguished COVID-19 cases from controls. After adjusting for time between examinations, cases with COVID-19 had greater alveolar bone loss compared to controls (0.641 ± 0.613 mm vs 0.260 ± 0.631 mm, p < 0.01.) Among cases with COVID-19, increased number of missing teeth OR = 2.1871 (1.146– 4.174) was significantly associated with hospitalization.ConclusionsAlveolar bone loss and missing teeth are positively associated with the acquisition and severity of COVID-19 disease, respectively.     

Systemic manifestation and contribution of peripheral tissues to Huntington’s disease pathogenesis

Huntington disease (HD) is an autosomal dominant neurodegenerative disease that is caused by expansion of cytosine/adenosine/guanine repeats in the huntingtin (HTT) gene, which leads to a toxic, aggregation-prone, mutant HTT-polyQ protein. Beyond the well-established mechanisms of HD progression in the central nervous system, growing evidence indicates that also peripheral tissues are affected in HD and that systemic signaling originating from peripheral tissues can influence the progression of HD in the brain. Herein, we review the systemic manifestation of HD in peripheral tissues, and the impact of systemic signaling on HD pathogenesis. Mutant HTT induces a body wasting syndrome (cachexia) primarily via its activity in skeletal muscle, bone, adipose tissue, and heart. Additional whole-organism effects induced by mutant HTT include decline in systemic metabolic homeostasis, which stems from derangement of pancreas, liver, gut, hypothalamic–pituitary–adrenal axis, and circadian functions. In addition to spreading via the bloodstream and a leaky blood brain barrier, HTT-polyQ may travel long distance via its uptake by neurons and its axonal transport from the peripheral to the central nervous system. Lastly, signaling factors that are produced and/or secreted in response to therapeutic interventions such as exercise or in response to mutant HTT activity in peripheral tissues may impact HD. In summary, these studies indicate that HD is a systemic disease that is influenced by intertissue signaling and by the action of pathogenic HTT in peripheral tissues. We propose that treatment strategies for HD should include the amelioration of HD symptoms in peripheral tissues. Moreover, harnessing signaling between peripheral tissues and the brain may provide a means for reducing HD progression in the central nervous system.     

Therapeutic applications of dental pulp stem cells in regenerating dental,periodontal and oral-related structures

Dental pulp stem cells (DPSCs) have emerged as a promising tool with great potential for use in tissue regeneration and engineering. Some of the main advantages of these cells are their multifaceted differentiation capacity, along with their high proliferation rate, a relative simplicity of extraction and culture that enables obtaining patient-specific cell lines for their use in autologous cell therapy. PubMed, Scopus and Google Scholar databases were searched for relevant articles related to the use of DPSCs in regeneration of dentin-pulp complex (DPC), periodontal tissues, salivary gland and craniomaxillofacial bone defects. Few studies were found regarding the use of DPSCs for regeneration of DPC. Scaffold-based combined with DPSCs isolated from healthy pulps was the strategy used for DPC regeneration. Studies involved subcutaneous implantation of scaffolds loaded with DPSCs pretreated with odontogenic media, or performed on human tooth root model as a root slice. Most of the studies were related to periodontal tissue regeneration which mainly utilized DPSCs/secretome. For periodontal tissues, DPSCs or their secretome were isolated from healthy or inflamed pulps and they were used either for preclinical or clinical studies. Regarding salivary gland regeneration, the submandibular gland was the only model used for the preclinical studies and DPSCs or their secretome were isolated only from healthy pulps and they were used in preclinical studies. Likewise, DPSCs have been studied for craniomaxillofacial bone defects in the form of mandibular, calvarial and craniofacial bone defects where DPSCs were isolated only from healthy pulps for preclinical and clinical studies. From the previous results, we can conclude that DPSCs is promising candidate for dental and oral tissue regeneration.     

Paraaortic dissection in “total mesopancreas excision” and “mesopancreas-first resection” pancreaticoduodenectomies for pancreatic cancer: Useless,optional, or necessary?A systematic review

The mesopancreas does not have well-defined boundaries but is continuous and connected through its components with the paraaortic area. The mesopancreatic resection margin has been indicated as the primary site for R1 resection after PD in pancreatic head cancer and total mesopancreas excision has been proposed to achieve adequate retropancreatic margin clearance and to minimize the likelihood of R1 resection. However, the anatomy of the mesopancreas requires extended dissection of the paraaortic area to maximize posterior clearance. The artery-first surgical approach has been developed to increase local radicality at the mesopancreatic resection margin. During PD, the artery-first approach begins with dissection of the connective tissues around the SMA. However, the concept of the mesopancreas as a boundless structure that includes circumferential tissues around the SMA, SMV, and paraaortic tissue highlights the need to shift from artery-first PD to mesopancreas-first PD to reduce the risk of R1 resection. From this perspective the “artery-first” approach, which allows for the avoidance of R2 resection risk, should be integrated into the “mesopancreas-first” approach to improve the R0 resection rate.In total mesopancreas excision and mesopancreas-first pancreaticoduodenectomies, the inclusion of the paraaortic area and circumferential area around the SMA in the resection field is necessary to control the tumour spread along the mesopancreatic resection margin rather than to control or stage the spread in the nodal basin.     

Immunomodulatory role of chitosan‐based nanoparticles and oligosaccharides in cyclophosphamide‐treated mice

Chitosan, the deacetylated form of chitin, a natural polysaccharide, is known for its various biomedical applications. The present study aimed at exploring the immunomodulatory properties of chitosan (CSNP) and gallic acid‐grafted chitosan (cGANP) nanoparticles in mice model of cyclophosphamide (CPA)‐induced immunosuppression. In addition, chitooligosaccharides, the hydrolysed form of chitin and chitosan, were also evaluated for its potential against immunosuppression in mice. CPA (80 mg/kg/ip) induced significant immunosuppression, which was reversed with cGANP treatment as indicated by a significant increase in the thymus and spleen indices compared to the CPA‐treated group. The CSNP and chitooligosaccharides (chitin and chitosan) failed to reverse CPA‐induced changes. ELISA revealed an elevation in the levels of IL‐6 and a reduction in IFN‐γ levels with CPA treatment. All the test compounds reduced the IL‐6 levels, whereas only the nanoparticle formulations (CSNP and cGANP) exhibited a significant augmentation in the IFN‐γ levels. Both the cytokines, IL‐6 and IFN‐γ, are secreted separately by two different types of T helper cells (Th cells), which mediate cellular and humoral immune responses in a coordinated manner. Th‐1 cells release IFN‐γ, facilitating cell‐mediated immunity, whereas IL‐6 is released by Th‐2 cells, expediting humoral immune response. The nanoparticles (CSNP and cGANP) seemed to be better immune enhancers than the chitooligosaccharides owing to their ability to reverse the cytokine changes induced by CPA. Overall, it was evident that the nanoparticles, most likely, boosted the cell‐mediated immunity through the induction of the Th‐1 branch of the immune response.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

Species,tissue and gender-related metal and element accumulation in fish species in a large reservoir (Turkey) and health risks and nutritional benefits for consumers

Concentrations of 18 metals and elements (MEs) in the gills, skin, muscle and liver of Carasobarbus luteus and Cyprinus carpio from the Atatürk Reservoir in Turkey were investigated. The results revealed that variations in the ME contents between fish species can be attributed to different diets. The highest contents of most MEs were recorded in the gills. Gender had no significant effect on the contents of most MEs in the tissues of fish species investigated. The relations between MEs in tissues and fish size were not clear and consistent. Health risk assessment methods indicated that consumption of the studied fish species is safe. It was estimated that daily consumption of 140 g of C. carpio or 170 g of C. luteus would not be expected to cause any health risks. Furthermore, it was found that fish species would provide significant benefits in terms of intake of essential MEs.     

新型肝癌组织的体外三维培养模型

目的:利用肝癌组织进行体外的三维（three-dimension，3D）组织块培养，通过添加PD98059和霍乱毒素（cholera toxin，CT）优化培养条件，建立一种高活性的肝癌组织体外培养模型。方法:收集中山大学肿瘤防治中心肝胆科的肝癌组织标本，经清洗、冻存、复苏等处理后分为对照组、PD组、CT组、PD+CT组，同时进行体外的二维（two-dimension，2D）和三维培养。各组组织采用DNA断裂的原位末端标记法（TUNEL）检测组织细胞凋亡情况，qRT-PCR检测BCL-2、BID、Caspase 3、Cyclin D1、CDK2、ELK-1、C-FOS、C-MYC、C-JUN等相关基因的mRNA表达水平，免疫荧光染色检测BCL-2和cleaved caspase-3蛋白表达情况，筛选并确定最优的体外培养方法。结果:3D培养组的组织细胞凋亡均少于2D培养组；PD98059通过上调BCL-2蛋白的表达，下调cleaved caspase-3蛋白的表达，激活MEK/ERK下游基因，从而减少体外培养的组织细胞凋亡，增强其抗凋亡能力；霍乱毒素通过上调Cyclin D1、CDK2的基因表达，促进其增殖。结论:我们开发了一种新型肝癌组织的体外三维培养模型，它可以作为进一步的药物试验和人源性异种移植(PDX)模型的工具。     

颊部外周型牙源性角化囊肿2例

外周型牙源性角化囊肿十分罕见，位于颊部软组织内的外周型牙源性角化囊肿更为罕见。本文报道2例颊部软组织内的外周型牙源性角化囊肿，并结合相关文献进行讨论。