Dental plaque quantitation by light induced fluorescence technology in exclusive Electronic Nicotine Delivery Systems (ENDS) users.

OBJECTIVES: In comparison to conventional combustible cigarettes, Electronic Nicotine Delivery Systems (ENDS) including both e-cigarettes (ECs) and heated tobacco products (HTPs) significantly reduce exposure to toxic chemical emissions. However, their impact on dental plaque remains unclear. This study measures dental plaque in ENDS (ECs and HTPs) users using quantitative light-induced fluorescence (QLF) technology, comparing them with current, former, and never smokers. METHODS: This cross-sectional study compared dental plaque measurements using QLF technology (Q-ray cam™ Pro) among current smokers (≥10 cigarettes/day), former smokers (quit ≥6 months), never smokers, and exclusive ENDS users (quit ≥6 months). Dental plaque measurements were expressed as ΔR30 (total area of mature dental plaque) and ΔR120 (greater plaque thickness/maturation-calculus). The Simple Oral Hygiene (SOH) score was calculated by the QLF proprietary software. Statistical analyses including ANCOVA was performed by R version (4.2.3) with p < 0.05. RESULTS: A total 30 smokers, 24 former smokers, 29 never smokers, and 53 ENDS users were included. Current smokers had significantly higher ΔR30 and ΔR120 values compared to other groups (p < 0.001). ENDS users showed plaque levels similar to never and former smokers (p > 0.05) but significantly lower than current smokers (p < 0.01). Although ENDS users showed a lower SOH score than smokers, this difference was not statistically significant. Daily toothbrushing and mouthwash usage were significant covariates. CONCLUSION: ENDS users exhibited reduced accumulation of dental plaque and calculus compared with current smokers. CLINICAL SIGNIFICANCE: Exclusive ENDS use could less impact dental plaque accumulation compared to cigarette smoking. Further research is needed to confirm these findings and fully understand ENDS impact on dental plaque formation.

Application of the DEMATEL method for quantitative analysis of risk factors for railway investments in Poland.

The paper presents the results of research on the influence of risk factors on the implementation of railway investments in Poland (build stage) and deals with a detailed diagnosis of relation between factors. The application of DEcision MAking Trial and Evaluation Laboratory (DEMATEL) method for the analyses allowed to develop a cause-and-effect model of key factors and analyse the importance of the factors. Eleven factors identified in eariel studies as the most important risk factors were examined. It was found that the factors: errors in the preparation of tender documents (10.38%), errors in project documentation (10.02%), improperly estimated time of completion of the investment by the Employer (9.82%), internal regulations of PKP Polskie Koleje Panstwowe S.A. (Polish State Railways) not coordinated with the provisions of contracts (9.51%) have the highest degree of importance. Factors: too many external institutions involved in the investment process and internal regulations of PKP Polskie Koleje Panstwowe S.A. (Polish State Railways) not coordinated with the provisions of contracts, have the greatest net impact on the other factors. The relations between the factors and factors importance are valuable knowledge for engineers, enabling the project to be implemented according to the planned schedule and investment cost.

Changes in Oral Health and Dental Esthetic in Smokers Switching to Combustion-Free Nicotine Alternatives: Protocol for a Multicenter and Prospective Randomized Controlled Trial.

BACKGROUND: Although the detrimental effects of conventional combustible cigarettes on oral health and dental esthetics are well known, there is limited information about the long-term impact of combustion-free nicotine alternatives (C-F NA) such as e-cigarettes or heated tobacco products. OBJECTIVE: This multicenter, prospective, 3-parallel-arm randomized controlled trial will investigate whether switching from combustible cigarettes to C-F NA will lead to measurable improvements in oral health parameters and dental esthetics over 18 months in adult smokers with limited gum disease. METHODS: Regular smokers not intending to quit and without clinical signs of periodontitis will be randomly assigned (1:4 ratio) to either standard of care with brief cessation advice (control group; arm A) or C-F NA use (intervention group; arm B). The study will also include a reference group of never smokers (reference group; arm C). The primary end point is the change in the Modified Gingival Index (MGI) score from baseline between the control arm (arm A) and the intervention arm (arm B) at the 18-month follow-up. In addition, the study will analyze the within- and between-group (arms A, B, and C) changes in MGI assessment, plaque imaging, dental shade quantitation, tooth stain scores, and oral health-related quality of life questionnaires measured at each study time point. All participants will attend a total of 7 clinic visits: screening, enrollment, and randomization (visit 0); baseline visit-day 14 (visit 1); day 90 (visit 2); day 180 (visit 3); day 360 (visit 4); and day 540 (visit 5). This multicenter study will be conducted in 4 dental clinics in 4 countries. The statistical analysis will involve descriptive statistics for continuous and categorical data. Primary end points will undergo tests for normality and, based on distribution, either a 2-sided t test or Mann-Whitney U test. Linear mixed model with random factors center and study arms by center will also be applied. Secondary end points, including MGI assessment and quality of life, will be subjected to similar tests and comparisons. Only if one value of the parameter MGI is missing after day 1, the last available observation will be carried forward. The analysis will be performed on the substituted data. Secondary parameters will not have missing value replacement. RESULTS: Participant recruitment began in October 2021, and enrollment was completed in June 2023. Results will be reported in 2025. CONCLUSIONS: This will be the first study to provide key insights into oral health benefits or risks associated with using C-F NA in smokers who are seeking alternatives to cigarette smoking. TRIAL REGISTRATION: ClinicalTrials.gov NCT04649645; https://clinicaltrials.gov/ct2/show/NCT04649645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53222.

A phase 2 trial investigating the efficacy and safety of the mPGES-1 inhibitor vipoglanstat in systemic sclerosis-related Raynaud's.

OBJECTIVE: Our objective was to test the hypothesis, in a double-blind, placebo-controlled study that vipoglanstat, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1) which decreases prostaglandin E2 (PGE2) and increases prostacyclin biosynthesis, improves RP. METHODS: Patients with systemic sclerosis (SSc) and ≥7 RP attacks during the last screening week prior to a baseline visit were randomised to four weeks treatment with vipoglanstat 120 mg or placebo. A daily electronic diary captured RP attacks (duration and pain) and Raynaud's Condition Score, with change in RP attacks/week as primary end point. Cold challenge assessments were performed at baseline and end of treatment. Exploratory endpoints included patients' and physicians' global impression of change, Assessment of Scleroderma-associated Raynaud's Phenomenon questionnaire, mPGES-1 activity, and urinary excretion of arachidonic acid metabolites. RESULTS: Sixty-nine subjects received vipoglanstat (n = 33) or placebo (n = 36). Mean weekly number of RP attacks (baseline; vipoglanstat 14.4[SD 6.7], placebo 18.2[12.6]) decreased by 3.4[95% CI -5.8;-1.0] and 4.2[-6.5;-2.0] attacks per week (p= 0.628) respectively. All patient reported outcomes improved, with no difference between the groups. Mean change in recovery of peripheral blood flow after cold challenge did not differ between the study groups. Vipoglanstat fully inhibited mPGES-1, resulting in 57% reduction of PGE2 and 50% increase of prostacyclin metabolites in urine. Vipoglanstat was safe and well tolerated. CONCLUSION: Although vipoglanstat was safe, and well tolerated in a dose achieving full inhibition of mPGES-1, it was ineffective in SSc-related RP. Further development and evaluation of vipoglanstat will therefore be in other diseases where mPGES-1 plays a pathogenetic role.

COVID-19-Induced Acute Respiratory Distress Syndrome Treated with Hyperbaric Oxygen: Interim Safety Report from a Randomized Clinical Trial (COVID-19-HBO).

BACKGROUND: A few prospective trials and case series have suggested that hyperbaric oxygen therapy (HBOT) may be efficacious for the treatment of severe COVID-19, but safety is a concern for critically ill patients. We present an interim analysis of the safety of HBOT via a randomized controlled trial (COVID-19-HBO). METHODS: A randomized controlled, open-label, clinical trial was conducted in compliance with good clinical practice to explore the safety and efficacy of HBOT for severe COVID-19 in critically ill patients with moderate acute respiratory distress syndrome (ARDS). Between 3 June 2020, and 17 May 2021, 31 patients with severe COVID-19 and moderate-to-severe ARDS, a ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) < 26.7 kPa (200 mmHg), and at least two defined risk factors for intensive care unit (ICU) admission and/or mortality were enrolled in the trial and randomized 1:1 to best practice, or HBOT in addition to best practice. The subjects allocated to HBOT received a maximum of five treatments at 2.4 atmospheres absolute (ATA) for 80 min over seven days. The subjects were followed up for 30 days. The safety endpoints were analyzed. RESULTS: Adverse events (AEs) were common. Hypoxia was the most common adverse event reported. There was no statistically significant difference between the groups. Numerically, serious adverse events (SAEs) and barotrauma were more frequent in the control group, and the differences between groups were in favor of the HBOT in PaO2/FiO2 (PFI) and the national early warning score (NEWS); statistically, however, the differences were not significant at day 7, and no difference was observed for the total oxygen burden and cumulative pulmonary oxygen toxicity dose (CPTD). CONCLUSION: HBOT appears to be safe as an intervention for critically ill patients with moderate-to-severe ARDS induced by COVID-19. CLINICAL TRIAL REGISTRATION: NCT04327505 (31 March 2020) and EudraCT 2020-001349-37 (24 April 2020).

Effects of the Co-Overexpression of the BCL and BDNF Genes on the Gamma-Aminobutyric Acid-Ergic Differentiation of Wharton's-Jelly-Derived Mesenchymal Stem Cells.

One of the problems with using MSCs (mesenchymal stem cells) to treat different neurodegenerative diseases of the central nervous system is their low ability to spontaneously differentiate into functional neurons. The aim of this study was to investigate how the co-overexpression of the BCL and BDNF genes affects the ability of genetically modified MSCs to differentiate into GABA-ergic neurons. A co-overexpression of two genes was performed, one of which, BCL, was supposed to increase the resistance of the cells to the toxic agents in the brain environment. The second one, BDNF, was supposed to direct the cells onto the neuronal differentiation pathway. As a result, the co-overexpression of both BCL2 + BDNF and BCLXL + BDNF caused an increase in the MAP2 gene expression level (a marker of the neuronal pathway) and the SYP gene that is associated with synaptogenesis. In both cases, approximately 18% of the genetically modified and then differentiated cells exhibited the presence of the GAD protein, which is characteristic of GABA-ergic neurons. Despite the presence of GAD, after both modifications, only the BCL2 and BDNF co-overexpression correlated with the ability of the modified cells to release gamma-aminobutyric acid (GABA) after depolarization. Our study identified a novel model of genetically engineered MSCs that can be used as a tool to deliver the antiapoptotic proteins (BCL) and neurotrophic factor (BDNF) directly into the brain microenvironment. Additionally, in the investigated model, the genetically modified MSCs could easily differentiate into functional GABA-ergic neurons and, moreover, due to the secreted BCL and BDNF, promote endogenous neuronal growth and encourage synaptic connections between neurons.

Entire Papilla Preservation Technique with Enamel Matrix Proteins and Allogenic Bone Substitute for the Treatment of Isolated Intrabony Defects: A Prospective Case Series.

The aim of this study was to evaluate the outcomes of a modified entire papilla preservation technique (EPPT) in the treatment of isolated intrabony defects in patients diagnosed with stage III periodontitis. A total of 18 intrabony defects were treated: 4 one-wall, 7 two-wall, and 7 three-wall. Mean probing pocket depth reductions of 4.33 mm (P < .0001), clinical attachment level gains of 4.87 mm (P < .0001), and radiographic defect depth reductions of 4.27 mm (P < .0001) were observed at 6 months. Changes in gingival recession and keratinized tissue were not statistically significant. It can be concluded that the proposed modification of the EPPT is useful in the treatment of isolated intrabony defects.

Survey of patients and parents on the autotransplantation of developing premolars to replace traumatised maxillary incisors.

BACKGROUND/AIM: There is a little research on the experiences and opinions of patients who have had autotransplantation of a tooth. The aim of the study was to assess the satisfaction of patients who underwent the autotransplantation of a developing premolar to replace a traumatised maxillary central incisor. MATERIALS AND METHODS: Eighty patients (with a mean age of 10.7-years) and 32 parents were surveyed with 13 and 7 questions, respectively, to determine their opinions about the surgery, post-operative period, orthodontic and restorative treatment they had received. RESULTS: Patients and their parents were very satisfied with the outcomes of the autotransplantation treatment. The majority of patients and all parents declared that they would choose this treatment again if needed. Patients who already had aesthetic restoration of the transplanted toothscored significantly better in position, similarity to other teeth, alignment and aesthetics, when compared to patients before restoration of the premolar to the shape of incisor. Patients after orthodontic treatment considered the alignment of the transplanted tooth between the adjacent teeth as better when compared to patients before or during their orthodontic treatment. CONCLUSIONS: Autotransplantation of developing premolars to replace traumatized maxillary central incisors proved to be a well-accepted treatment option. A delay of restoration of the transplanted premolars to the shape of the maxillary incisors did not have a negative impact on the satisfaction with the treatment.

Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial.

BACKGROUND: With ~ 50 million individuals suffering from post-COVID condition (PCC), low health related quality of life (HRQoL) is a vast problem. Common symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue, shortness of breath and cognitive dysfunction. No effective treatment options have been widely adopted in clinical practice. Hyperbaric oxygen (HBO2) is a candidate drug. METHODS: The objective of this interim analysis is to describe our cohort and evaluate the safety of HBO2 for post covid condition. In an ongoing randomised, placebo-controlled, double blind, clinical trial, 20 previously healthy subjects with PCC were assigned to HBO2 or placebo. Primary endpoints are physical domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at 13 weeks. Secondary endpoints include objective physical tests. Safety endpoints are occurrence, frequency, and seriousness of Adverse Events (AEs). An independent data safety monitoring board (DSMB) reviewed unblinded data. The trial complies with Good Clinical Practice. Safety endpoints are evaluated descriptively. Comparisons against norm data was done using t-test. RESULTS: Twenty subjects were randomised, they had very low HRQoL compared to norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60-40.90) vs 83.5 (23.9) p < 0.001 in Rand-36 PF and mean 0.00 (0.00) in RP. Very low physical performance compared to norm data. 6MWT 442 (180) (95% CI 358-525) vs 662 (18) meters p < 0.001. 31 AEs occurred in 60% of subjects. In 20 AEs, there were at least a possible relationship with the study drug, most commonly cough and chest pain/discomfort. CONCLUSIONS: An (unexpectedly) high frequency of AEs was observed but the DSMB assessed HBO2 to have a favourable safety profile. Our data may help other researchers in designing trials. Trial Registration ClinicalTrials.gov: NCT04842448. Registered 13 April 2021, https://clinicaltrials.gov/ct2/show/NCT04842448 . EudraCT: 2021-000764-30. Registered 21 May 2021, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000764-30/SE.

Choir Singers Without Rehearsals and Concerts? A Questionnaire Study on Perceived Losses From Restricting Choral Singing During the Covid-19 Pandemic.

BACKGROUND: Choir singing is an activity that engages individuals all over the world with a broad demographic representation. Both qualitative and quantitative studies have examined the benefits of the activity but very few have examined the effects when someone loses access to it and stops singing. OBJECTIVES: Examining the governmental and organisational responses precipitated by the COVID-19 pandemic, we asked what happens when a choir singer loses all of their routines associated with regular participation in choir singing. MATERIALS AND METHODS: One national choir organization in Sweden (n = 3163) and one in Norway (n = 1881) were approached with a short survey. This comprised questions relating to the issue "what do you as a choir singer misses the most?" Each participant was asked to rate the importance of a number of elements that pertain to the experience of choir singing. RESULTS: The social aspect of singing emerged as having the strongest weight in terms of perceived loss that is, it was the element that the participants missed the most. Professional singers report that they miss the aesthetic experiences, flow, and all the physical aspects (physical training, voice training, and breathing training) to a greater degree as compared to reports from the amateurs. The importance of aesthetic experiences and physical components appeared to rise with increasing number of years that an individual had engaged with choir singing. CONCLUSION: In the Scandinavian setting, the social aspect has a stronger weight than the other components and this seemed to be more significant in Norway compared to Sweden.

The Combination of Baicalin with Knockdown of mir148a Gene Suppresses Cell Viability and Proliferation and Induces the Apoptosis and Autophagy of Human Glioblastoma Multiforme T98G and U87MG Cells.

BACKGROUND: Glioblastoma multiforme (GBM) is a heterogeneous and highly vascularized brain tumor that avoids apoptosis due to P-glycoprotein (P-gp) mediated multidrug resistance. Therefore, the development of new therapeutic strategies that induce apoptosis and inhibit proliferation is urgently warranted. OBJECTIVES: We examined the efficacy of the combination of baicalin (BAI) and knockdown of miR-148a gene in human glioblastoma T98G and U87MG cell lines. METHODS: T98G and U87MG cells were transfected with miR148a siRNA. The influence of miR- 148a siRNA in combination with BAI on T98G and U87MG cell viability, proliferation, apoptosis, and autophagy was evaluated as well. Alterations in the mRNA expression of autophagy-related genes were analyzed using RT-qPCR. RESULTS: The transfection of T98G and U87MG cells with miR148a specific siRNA and exposition on baicalin led to a significant reduction in cell viability and proliferation, the accumulation of sub G1-phase cells and a reduced population of cells in the S and G2/M phases (only in U87MG cell line), increased population of cells in the S phase in T98G cell line and apoptosis or necrosis induction and induction of autophagy for both cell lines. CONCLUSION: The siRNA-induced miR-148a mRNA knockdown in combination with baicalin may offer a novel therapeutic strategy to more effectively control the growth of human GBM cells. Thus, knockdown of this gene in combination with baicalin inhibits proliferation (cell cycle arrest in the S phase in T98G but not in U87MG cells), induces apoptosis, and regulates autophagy in T98G and U87MG cells. However, further studies are urgently needed to confirm a positive phenomenon for the treatment of GBM.

Universal prevention through a digital health platform reduces injury incidence in youth athletics (track and field): a cluster randomised controlled trial.

OBJECTIVES: To examine whether universal prevention via a digital health platform can reduce the injury incidence in athletics athletes aged 12-15 years and if club size had an influence on the effect of the intervention. METHODS: This was a cluster randomised trial where young athletics athletes were randomised through their club following stratification by club size into intervention (11 clubs; 56 athletes) and control (10 clubs; 79 athletes) groups. The primary endpoint was time from baseline to the first self-reported injury. Intervention group parents and coaches were given access to a website with health information adapted to adolescent athletes and were encouraged to log in and explore its content during 16 weeks. The control group continued training as normal. Training exposure and injury data were self-reported by youths/parents every second week, that is, eight times. The primary endpoint data were analysed using the log-rank test. Cox proportional hazards regression was used to analyse the second study aim with intervention status and club size included in the explanatory models. RESULTS: The proportion of completed training reports was 85% (n=382) in the intervention group and 86% (n=545) in the control group. The injury incidence was significantly lower (HR=0.62; χ2=3.865; p=0.049) in the intervention group. The median time to first injury was 16 weeks in the intervention group and 8 weeks in the control group. An interaction effect between the intervention and stratification factor was observed with a difference in injury risk between athletes in the large clubs in the intervention group versus their peers in the control group (HR 0.491 (95% CI 0.242 to 0.998); p=0.049). CONCLUSIONS: A protective effect against injury through universal access to health information adapted for adolescent athletes was observed in youth athletics athletes. The efficacy of the intervention was stronger in large clubs. TRIAL REGISTRATION NUMBER: NCT03459313.

Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial.

INTRODUCTION: Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL. METHODS AND ANALYSIS: A randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board. ETHICS AND DISSEMINATION: The trial is approved by the Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access. TRIAL REGISTRATION NUMBER: NCT04842448.

What Has Immunology Brought to Periodontal Disease in Recent Years?

Recent decades have shed a new light on the pathomechanism of periodontal inflammation. While classic periodontology concentrates on biofilm control, oral hygiene improvement, professional tooth cleaning and surgical correction of damaged periodontal tissues, new aspects of the destruction mechanisms are being raised. Among them, the greatest attention is paid to the influence of host response on the clinical manifestations of the disease. Numerous studies have proved that the shift from gingivitis to periodontitis is not a simple progress of the disease, but an event occurring only in susceptible individuals. Susceptibility may result from appearance of local factors facilitating biofilm accumulation and/or maturation, or from systemic features, among which over-reaction and prolonged agitation of non-specific component of inflammatory response is crucial. The present paper summarizes the association between periodontology and immunology and updates the knowledge accrued mostly in the recent years. After a brief explanation of advances in understanding of the disease aetiology, the most studied and potentially viable immunological markers of periodontal disease are presented. Possible new therapeutic strategies, exploiting knowledge about the nature of host response-immunomodulation and reduction of chronic oxidative stress-are also presented.

Association Study of the SLC1A2 (rs4354668), SLC6A9 (rs2486001), and SLC6A5 (rs2000959) Polymorphisms in Major Depressive Disorder.

The membrane excitatory amino acid transporter 2 (EAAT2), encoded by SLC1A2, is responsible for the uptake and redistribution of synaptic glutamate. Glycine modulates excitatory neurotransmission. The clearance of synaptic glycine is performed by glycine transporters encoded by SLC6A9 and SLC6A5. Higher synaptic glycine and glutamate levels could enhance the activation of NMDA receptors and counteract the hypofunction of glutamate neurotransmission described in major depressive disorder (MDD). The aim of the study was to assess whether polymorphisms of SCL1A2 (rs4354668), SCL6A5 (rs2000959), and SCL6A9 (rs2486001) play a role in the development of MDD and its clinical picture in the Polish population. The study group consisted of 161 unrelated Caucasian patients with MDD and 462 healthy unrelated individuals for control. Polymorphisms were genotyped with PCR-RLFP assay. We observed that the frequency of genotype CC and allele C of the SLC1A2 polymorphism rs4354668 was twice as high in the MDD group as in control. Such differences were not detected in SLC6A5 and SLC6A9 polymorphisms. No statistically significant association of the studied SNPs (Single Nucleotide Polymorphisms) on clinical variables of the MDD was observed. The current study indicates an association of polymorphism rs4354668 in SCL1A2 with depression occurrence in the Polish population; however, further studies with larger samples should be performed to clarify these findings.

Survival and Neurogenesis-Promoting Effects of the Co-Overexpression of BCLXL and BDNF Genes on Wharton's Jelly-Derived Mesenchymal Stem Cells.

The main problem with using MSC (mesenchymal stem cells) to treat the deficient diseases of the central nervous system is the low cell survival rate after the transplant procedure and their low ability to spontaneously differentiate into functional neurons. The aim of this study was to investigate the effects of genetically modifying MSC. A co-overexpression of two genes was performed: BCLXL was supposed to increase the resistance of the cells to the toxic agents and BDNF was supposed to direct cells into the neuronal differentiation pathway. As a result, it was possible to obtain the functional overexpression of the BCLXL and BDNF genes. These cells had an increased resistance to apoptosis-inducing toxicants (staurosporine, doxorubicin and H2O2). At the same time, the genes of the neuronal pathway (CHAT, TPH1) were overexpressed. The genetically modified MSC increased the survival rate under toxic conditions, which increased the chance of surviving a transplant procedure. The obtained cells can be treated as neural cell progenitors, which makes them a universal material that can be used in various disease models. The production of neurotransmitters suggests that cells transplanted into the brain and subjected to the additional influence of the brain's microenvironment, will be able to form synapses and become functional neurons.

Clinical Condition of the Oral Cavity in the Adult Polish Population below 70 Years of Age after Myocardial Infarction-A Case-Control Study.

According to recent scientific consensus, there is an increasing amount of evidence on the correlation between oral health and cardiovascular disease morbidity. The aim of the present study was to investigate the number of missing teeth, the presence of residual roots with necrotic pulp and teeth with caries, the type of teeth deficiencies, and periodontal status in patients after myocardial infarction (MI). A total of 151 patients after MI and 160 randomly selected controls without history of MI were enrolled in the study. Epidemiological data were collected, and dental examination was performed. Findings showed significantly more women, subjects with lower level of education, lower income, higher percentage of nicotine addiction, more frequent presence of arterial hypertension, diabetes, and obesity than in the study group. Moreover, oral status of the subjects who suffered from MI was inferior to the control group. An average patient from the study group had 11 missing teeth, when compared to four missing teeth in an average control subject (p < 0.0001). The majority of patients in the control group had occlusal contacts in intercuspal position in premolars and molars (group A), in contrast to the patients after MI, who had at least one missing supporting zone (group B) (p < 0.0001). Severe periodontitis was found in 50.3% of tests and in 30.4% of controls (p < 0.0001). A correlation was found between the edentulousness and the risk of myocardial infarction after adjusting for other known risk factors of cardiovascular diseases (OR = 3.8; 95% CI = 3.01−7.21; p < 0.0001). This case−control study showed that MI patients had more missing teeth, more residual roots with necrotic pulp, much higher incidence of edentulism and occlusal contacts in intercuspal position in fewer than four occlusal supporting zones, as well as worse periodontal status when compared to healthy subjects without a history of MI. Due to the methodology of unmatched controls, the presented results must be interpreted with caution.

What Are the Potential Benefits of Using Bacteriophages in Periodontal Therapy?

Periodontitis, which may result in tooth loss, constitutes both a serious medical and social problem. This pathology, if not treated, can contribute to the development of, among others, pancreatic cancer, cardiovascular diseases or Alzheimer's disease. The available treatment methods are expensive but not always fully effective. For this reason, the search for and isolation of bacteriophages specific to bacterial strains causing periodontitis seems to be a great opportunity to target persistent colonization by bacterial pathogens and lower the use of antibiotics consequently limiting further development of antibiotic resistance. Furthermore, antimicrobial resistance (AMR) constitutes a growing challenge in periodontal therapy as resistant pathogens may be isolated from more than 70% of patients with periodontitis. The aim of this review is to present the perspective of phage application in the prevention and/or treatment of periodontitis alongside its complicated multifactorial aetiology and emphasize the challenges connecting composition and application of effective phage preparation.

HSPB1 Gene Variants and Schizophrenia: A Case-Control Study in a Polish Population.

Schizophrenia (SCZ) is a severe psychiatric disorder that has a significant genetic component. HSPB1 (HSP27) is known for its neuroprotective functions under stress conditions and appears to play an important role during the development of the central nervous system, which is in agreement with the neurodevelopmental hypothesis of SCZ. The aim of the present case-control study was to investigate whether HSPB1 variants contribute to the risk and clinical features (age of onset, symptoms, and suicidal behavior) of SCZ in a Polish population. To the best of our knowledge, this is the first study that investigated the association between the HSPB1 polymorphisms and SCZ. Three SNPs of HSPB1 (rs2868370, rs2868371, and rs7459185) were genotyped in a total of 1082 (403 patients and 679 controls) unrelated subjects using TaqMan assays. The results showed that the genotypes, alleles, and haplotypes of the three SNPs were not significantly different between the schizophrenic patients and healthy controls either in the overall analysis or in the gender-stratified analysis (all p > 0.05). However, we did find a significant effect of the rs2868371 genotype on the age of onset, negative symptoms, and disorganized symptoms in the five-factor model of PANSS (all p < 0.01). Post hoc comparisons showed that carriers of the rs2868371 G/G genotype had significantly higher negative and disorganized factor scores than those with the C/G and C/C genotypes, respectively. Further investigations with other larger independent samples are required to confirm our findings and to better explore the effect of the HSPB1 polymorphisms on the risk and symptomatology of SCZ.

Study of the influence of NGF-ß gene overexpression in human mesenchymal stem cells on the expression level of SOX1 and neural pathway genes.

BACKGROUND: Nerve growth factor (NGF) is a protein exhibiting an influence on the neural development and also, its' impact on the stem cells remains a great potential treatment strategy. The influence of its overexpression on the neural pathway differentiation on Wharton's Jelly derived MSC (WJ-MSC) has not been studied so far, but considering the fact that these cells are relatively easy to obtain, using them may indicate an innovative change in stem cell therapies. The aim of this study was to evaluate the effect of NGF overexpression in human mesenchymal stem cells (MSC) on SOX1 and genes related to the neural pathway. METHODS AND RESULTS: The lentiviral transduction was performed in order to obtain the NGF overexpression, as well as RT-PCR to evaluate the expression level SOX1, SOX2, NES, NGF under influence of overexpressed NGF protein in WJ-MSC. During the study we have observed a decrease in SOX1 expression as the marker of neural stem cells. Other than that an increase of SOX2, NES and NGF was noticed, as they all are markers of early-neural as well as already differentiated neural cells. The results show a great potential of using those examined genes' expression as a form of a new stem cell therapy. CONCLUSIONS: The achieved overexpression of NGF in this study, led the modified MSC onto the neural pathway as well as caused a decrease of SOX1 expression and an increase of expression of genes related to neural differentiated cells.