hiPSC-derived GRN-deficient astrocytes delay spiking activity of developing neurons.

Frontotemporal dementia (FTD) refers to a group of neurodegenerative disorders that are characterized by pathology predominantly localized to the frontal and temporal lobes. Approximately 40% of FTD cases are familial, and up to 20% of these are caused by heterozygous loss of function mutations in the gene encoding for progranulin (PGRN), GRN. The mechanisms by which loss of PGRN leads to FTD remain incompletely understood. While astrocytes and microglia have long been linked to the neuropathology of FTD due to mutations in GRN (FTD-GRN), a primary mechanistic role of these supporting cells have not been thoroughly addressed. In contrast, mutations in MAPT, another leading cause of familial FTD, greatly alters astrocyte gene expression leading to subsequent non-cell autonomous effects on neurons, suggesting similar mechanisms may be present in FTD-GRN. Here, we utilized human induced pluripotent stem cell (hiPSC)-derived neural tissue carrying a homozygous GRN R493X-/- knock-in mutation to investigate in vitro whether GRN mutant astrocytes have a non-cell autonomous effect on neurons. Using microelectrode array (MEA) analysis, we demonstrate that the development of spiking activity of neurons cultured with GRN R493X-/- astrocytes was significantly delayed compared to cultures with WT astrocytes. Histological analysis of synaptic markers in these cultures showed an increase in GABAergic synaptic markers and a decrease in glutamatergic synaptic markers during this period when activity was delayed. We also demonstrate that this effect may be due in-part to soluble factors. Overall, this work represents one of the first studies investigating astrocyte-induced neuronal pathology in GRN mutant hiPSCs, and supports the hypothesis of astrocyte involvement in the early pathophysiology of FTD.

Association of periodontal therapy, with inflammatory biomarkers and complications in COVID-19 patients: a case control study.

BACKGROUND: In previous studies, COVID-19 complications were reported to be associated with periodontitis. Accordingly, this study was designed to test the hypothesis that a history of periodontal therapy could be associated with lower risk of COVID-19 complications. METHODS: A case-control study was performed using the medical health records of COVID-19 patients in the State of Qatar between March 2020 and February 2021 and dental records between January 2017 and December 2021. Cases were defined as COVID-19 patients who suffered complications (death, ICU admissions and/or mechanical ventilation); controls were COVID-19 patients who recovered without major complications. Associations between a history of periodontal therapy and COVID-19 complications were analysed using logistic regression models adjusted for demographic and medical factors. Blood parameters were compared using Kruskal-Wallis test. RESULTS: In total, 1,325 patients were included. Adjusted odds ratio (AOR) analysis revealed that non-treated periodontitis was associated with significant risk of need for mechanical ventilation (AOR = 3.91, 95% CI 1.21-12.57, p = 0.022) compared to periodontally healthy patients, while treated periodontitis was not (AOR = 1.28, 95% CI 0.25-6.58, p = 0.768). Blood analyses revealed that periodontitis patients with a history of periodontal therapy had significantly lower levels of D-dimer and Ferritin than non-treated periodontitis patients. CONCLUSION: Among COVID-19 patients with periodontal bone loss, only those that have not received periodontal therapy had higher risk of need for assisted ventilation. COVID-19 patients with a history of periodontal therapy were associated with significantly lower D-dimer levels than those without recent records of periodontal therapy. CLINICAL RELEVANCE: The fact that patients with treated periodontitis were less likely to suffer COVID-19 complications than non-treated ones further strengthen the hypothesis linking periodontitis to COVID-19 complications and suggests that managing periodontitis could help reduce the risk for COVID-19 complications, although future research is needed to verify this.

Association between periodontitis and severity of COVID-19 infection: A case-control study.

AIM: COVID-19 is associated with an exacerbated inflammatory response that can result in fatal outcomes. Systemic inflammation is also a main characteristic of periodontitis. Therefore, we investigated the association of periodontitis with COVID-19 complications. MATERIALS AND METHODS: A case-control study was performed using the national electronic health records of the State of Qatar between February and July 2020. Cases were defined as patients who suffered COVID-19 complications (death, ICU admissions or assisted ventilation), and controls were COVID-19 patients discharged without major complications. Periodontal conditions were assessed using dental radiographs from the same database. Associations between periodontitis and COVID 19 complications were analysed using logistic regression models adjusted for demographic, medical and behaviour factors. RESULTS: In total, 568 patients were included. After adjusting for potential confounders, periodontitis was associated with COVID-19 complication including death (OR = 8.81, 95% CI 1.00-77.7), ICU admission (OR = 3.54, 95% CI 1.39-9.05) and need for assisted ventilation (OR = 4.57, 95% CI 1.19-17.4). Similarly, blood levels of white blood cells, D-dimer and C Reactive Protein were significantly higher in COVID-19 patients with periodontitis. CONCLUSION: Periodontitis was associated with higher risk of ICU admission, need for assisted ventilation and death of COVID-19 patients, and with increased blood levels of biomarkers linked to worse disease outcomes.

Degradation of dichloromethane by an isolated strain Pandoraea pnomenusa and its performance in a biotrickling filter.

A strain Pandoraea pnomenusa LX-1 that uses dichloromethane (DCM) as sole carbon and energy source has been isolated and identified in our laboratory. The optimum aerobic biodegradation of DCM in batch culture was evaluated by response surface methodology. Maximum biodegradation (5.35 mg/(L·hr)) was achieved under cultivation at 32.8°C, pH 7.3, and 0.66% NaCl. The growth and biodegradation processes were well fitted by Haldane's kinetic model, yielding maximum specific growth and degradation rates of 0.133 hr(-1) and 0.856 hr(-1), respectively. The microorganism efficiently degraded a mixture of DCM and coexisting components (benzene, toluene and chlorobenzene). The carbon recovery (52.80%-94.59%) indicated that the targets were predominantly mineralized and incorporated into cell materials. Electron acceptors increased the DCM biodegradation rate in the following order: mixed > oxygen > iron > sulfate > nitrate. The highest dechlorination rate was 0.365 mg Cl(-)/(hr·mg biomass), obtained in the presence of mixed electron acceptors. Removal was achieved in a continuous biotrickling filter at 56%-85% efficiency, with a mineralization rate of 75.2%. Molecular biology techniques revealed the predominant strain as P. pnomenusa LX-1. These results clearly demonstrated the effectiveness of strain LX-1 in treating DCM-containing industrial effluents. As such, the strain is a strong candidate for remediation of DCM coexisting with other organic compounds.

Chronotherapy in dentistry: A scoping review.

The circadian clock modulates almost all vital aspects of our physiology and metabolism, including processes relevant to dentistry, such as healing, inflammation and nociception. Chronotherapy is an emerging field aiming to improve therapeutic efficacy and decrease adverse effects on health outcomes. This scoping review aimed to systematically map the evidence underpinning chronotherapy in dentistry and to identify gaps in knowledge. We conducted a systematic scoping search using four databases (Medline, Scopus, CINAHL and Embase). We identified 3908 target articles screened by two blinded reviewers, and only original animal and human studies investigating the chronotherapeutic use of drugs or interventions in dentistry were included. Of the 24 studies included, 19 were human studies and five were animal studies. Chrono-radiotherapy and chrono-chemotherapy reduced treatment side effects and improved therapeutic response, leading to higher survival rates in cancer patients. Animal studies reported that tooth movement and periodontal tissue response to orthodontic forces follow a diurnal rhythm that might influence bone metabolism. Profound and prolonged local anesthesia could be achieved when injected in the evening. Although the overall quality of the included studies was low, chronotherapy applications in dentistry seem to have favourable outcomes, especially in head and neck cancer treatments.

Conversion characteristics and mechanism analysis of gaseous dichloromethane degraded by a VUV light in different reaction media.

The photodegradation of gaseous dichloromethane (DCM) by a vacuum ultraviolet (VUV) light in a spiral reactor was investigated with different reaction media and initial concentrations. Through the combination of direct photolysis, O3 oxidation and HO* oxidation, DCM was ultimately mineralized into inorganic compounds (such as HCl, CO2, H2O, etc.) in the air with relative humidity (RH) of 75%-85%. During the photodegradation process, some small organic acids (including formic acid, acetic acid) were also detected and the intermediates were more soluble than DCM, providing a possibility for its combination with subsequent biodegradation. Based on the detected intermediates and the confirmed radicals, a photodegradation pathway of DCM by VUV was proposed. With RH 75%-80% air as the reaction medium, the DCM removal followed the second-order kinetic model at inlet concentration of 100-1000 mg/m3. Kinetic analysis showed that the reaction media affected the kinetic constants of DCM conversion by a large extent, and RH 80% air could cause a much lower half-life for its conversion. Such results supported the possibility that VUV photodegradation could be used not only for the mineralization of DCM but also as a pretreatment before biodegradation.

[Removal characteristics of DCM by biotrickling filter and biofilter].

A biofilter (BF) packed with nutrition slow-release material and a biotrickling filter (BTF) packed with ether-based polyurethane foam were set up to remove dichloromethane (DCM) from exhaust gas. Results showed that the biofilm formations in BTF and BF were completed by using the mixture of a special strain and a bacterial community, within 25d and 22d, respectively. Through the observation of the filter surface by SEM, the surface of packings in BF was loose with thin biofilm colonies, whereas the one in BTF was dense with thick biofilm. Under the condition of inlet DCM concentration of 100-1,500 mg x m(-3), EBRT of 25-85 s, the removal efficiency of DCM in BTF was better than that in BF, and the maximum removal load was 22.61 g x (m3 x h)(-1) and 29.05 g (m3 x h)(-1), respectively. The relationship between CO2 production and DCM removal was approximately linear, with the mineralization rate being 70.4% and 66.8% for BTF and BF, respectively. The dynamic behaviors of DCM in BTF and BF were described by the Michaelis-Menten model. Through the calculation, the unit volume maximum degradation rate r(max) was 22.7790 g x (m3 x h)(-1) and 28.5714 g x (m3 x h)(-1), while the gas phase saturation constant Ks was 0.1412 g x m(-3) and 0.1486 g x m(-3)