Category: Nevin Manimala

Eur J Psychotraumatol. 2024;15(1):2314913. doi: 10.1080/20008066.2024.2314913. Epub 2024 Feb 16.

ABSTRACT

Background: Stressful events increase the risk for treatment-resistant depression (TRD), and trauma-focused psychotherapy can be useful for TRD patients exposed to early life stress (ELS). Epigenetic processes are known to be related to depression and ELS, but there is no evidence of the effects of trauma-focused psychotherapy on methylation alterations.Objective: We performed the first epigenome-wide association study to investigate methylation changes related to trauma-focused psychotherapies effects in TRD patients.Method: Thirty TRD patients assessed for ELS underwent trauma-focused psychotherapy, of those, 12 received trauma-focused cognitive behavioural therapy, and 18 Eye Movement Desensitization and Reprocessing (EMDR). DNA methylation was profiled with Illumina Infinium EPIC array at T0 (baseline), after 8 weeks (T8, end of psychotherapy) and after 12 weeks (T12 – follow-up). We examined differentially methylated CpG sites and regions, as well as pathways analysis in association with the treatment.Results: Main results obtained have shown 110 differentially methylated regions (DMRs) with a significant adjusted p-value area associated with the effects of trauma-focused psychotherapies in the entire cohort. Several annotated genes are related to inflammatory processes and psychiatric disorders, such as LTA, GFI1, ARID5B, TNFSF13, and LST1. Gene enrichment analyses revealed statistically significant processes related to tumour necrosis factor (TNF) receptor and TNF signalling pathway. Stratified analyses by type of trauma-focused psychotherapy showed statistically significant adjusted p-value area in 141 DMRs only for the group of patients receiving EMDR, with annotated genes related to inflammation and psychiatric disorders, including LTA, GFI1, and S100A8. Gene set enrichment analyses in the EMDR group indicated biological processes related to inflammatory response, particularly the TNF signalling pathway.Conclusion: We provide preliminary valuable insights into global DNA methylation changes associated with trauma-focused psychotherapies effects, in particular with EMDR treatment.

PMID:38362742 | DOI:10.1080/20008066.2024.2314913

Quintessence Int. 2024 Feb 16;0(0):0. doi: 10.3290/j.qi.b4984249. Online ahead of print.

ABSTRACT

The evidence base for the use of space maintainers (SMs) is relatively sparce despite being used for decades after the premature loss of primary molars. Thus, this study aims to increase the dental evidence base via investigating retrospectively the success rates of prefabricated fixed and removable space maintainers inserted from 2019 to 2021 and followed up until 02/2023 at a specialized university clinic and to identify reasons of any reported minor and major failure. Authors hypothesized that there is no significant difference in failure rates between fixed and removable SMs inserted after the premature loss of a single primary molar per quadrant. Patient’s digital records were searched yielding 645 space maintainers. After the application of inclusion criteria, 157 (67%) fixed prefabricated SMs in 112 children and 77 (33%) removable SMs in 61 children were analyzed for an average of 18.4 months (±9.5). Kaplan-Meier survival analysis with Mantel- Cox statistics showed an overall cumulative survival time of 31.6 months (SE=1.15, 95% CI=29.4-33.9). Major failure occurred significantly more in removable maintainers (n=40/67, 59.7%) mostly due to loss of the appliance compared to fixed space maintainers (n=27/67, 40.3%; P<0.001). The present study indicates that space maintainers were mainly placed in young children with high caries experience, where treatment was mostly possible using advanced behavior management. Fixed Space maintainers had a significantly lower failure rate than their removable counterpart. However, both require continual repairs, preservation or even replacement till the eruption of the permanent tooth.

PMID:38362703 | DOI:10.3290/j.qi.b4984249

Quintessence Int. 2024 Feb 16;0(0):0. doi: 10.3290/j.qi.b4984231. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate polymerization efficiency of different bulk-fill resin-based composites (BFRBCs) cured by monowave and polywave light curing units (LCUs), by assessment the degree of conversion (DC) and Vickers microhardness (VMH) at different depths.

METHOD AND MATERIALS: Two commercially available BFRBCs were used; Filtek One Bulk Fill Restorative (3M ESPE) (FOBF) and Tetric N-Ceram Bulk Fill (Ivoclar Vivadent) (TNBF). LCUs utilized were two light-emitting diodes (LEDs) LCUs; a monowave LED LCU (BlueLEX LD-105, Monitex) and a polywave LED LCU (Twin Wave GT-2000, Monitex). For each test, twenty cylindrical specimens (4 mm diameter, 4 mm thickness) were prepared from each BFRBC using a split Teflon mold. Ten specimens were light cured by monowave LCU and the other ten were light cured by polywave LCU according manufacturer’s recommendations. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was used to assess DC. VMH tester was used to assess VMH. Statistical analysis was performed using three-way ANOVA and Tukey’s post-hoc tests (P <.05).

RESULTS: DC and VMH in BFRBC containing only camphorquinone as photo-initiator were similar when cured with either monowave or polywave LCU. However, BFRBC containing a combination of photo-initiators exhibited significantly higher DC and VMH when cured with polywave LCU. Although all groups showed statistically significant differences between top and bottom surfaces regarding DC and VMH, all of them showed bottom/top ratios >80% regarding DC and VMH.

CONCLUSION: Polywave LCU enhances polymerization efficiency of BFRBCs especially when the later containing a combination of photo-initiators, but does not prevent the use of monowave LCU.

PMID:38362702 | DOI:10.3290/j.qi.b4984231

Curr Rheumatol Rev. 2024 Feb 15. doi: 10.2174/0115733971290285240207080745. Online ahead of print.

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB).

OBJECTIVE: This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB.

METHODS: A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression.

RESULTS: Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (ORA) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an ORA of 6.17 (95% CI 1.79- 21.24).

CONCLUSION: This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.

PMID:38362696 | DOI:10.2174/0115733971290285240207080745

Pharmacoepidemiol Drug Saf. 2024 Feb;33(2):e5750. doi: 10.1002/pds.5750.

ABSTRACT

PURPOSE: Outcome variables that are assumed to follow a negative binomial distribution are frequently used in both clinical and epidemiological studies. Epidemiological studies, particularly those performed by pharmaceutical companies often aim to describe a population rather than compare treatments. Such descriptive studies are often analysed using confidence intervals. While precision calculations and sample size calculations are not always performed in these settings, they have the important role of setting expectations of what results the study may generate. Current methods for precision calculations for the negative binomial rate are based on plugging in parameter values into the confidence interval formulae. This method has the downside of ignoring the randomness of the confidence interval limits. To enable better practice for precision calculations, methods are needed that address the randomness.

METHODS: Using the well-known delta-method we develop a method for calculating the precision probability, that is, the probability of achieving a certain width. We assess the performance of the method in smaller samples through simulations.

RESULTS: The method for the precision probability performs well in small to medium sample sizes, and the usefulness of the method is demonstrated through an example.

CONCLUSIONS: We have developed a simple method for calculating the precision probability for negative binomial rates. This method can be used when planning epidemiological studies in for example, asthma, while correctly taking the randomness of confidence intervals into account.

PMID:38362649 | DOI:10.1002/pds.5750

Lab Chip. 2024 Feb 16. doi: 10.1039/d3lc01020a. Online ahead of print.

ABSTRACT

The rapid advancement in the fabrication and culture of in vitro organs has marked a new era in biomedical research. While strides have been made in creating structurally diverse bioartificial organs, such as the liver, which serves as the focal organ in our study, the field lacks a uniform approach for the predictive assessment of liver function. Our research bridges this gap with the introduction of a novel, machine-learning-based “3P model” framework. This model draws on a decade of experimental data across diverse culture platform studies, aiming to identify critical fabrication parameters affecting liver function, particularly in terms of albumin and urea secretion. Through meticulous statistical analysis, we evaluated the functional sustainability of the in vitro liver models. Despite the diversity of research methodologies and the consequent scarcity of standardized data, our regression model effectively captures the patterns observed in experimental findings. The insights gleaned from our study shed light on optimizing culture conditions and advance the evaluation of the functional maintenance capacity of bioartificial livers. This sets a precedent for future functional evaluations of bioartificial organs using machine learning.

PMID:38362645 | DOI:10.1039/d3lc01020a

Euro Surveill. 2024 Feb;29(7). doi: 10.2807/1560-7917.ES.2024.29.7.2300259.

ABSTRACT

Many vaccine effectiveness (VE) analyses of severe disease outcomes such as hospitalisation and death include ‘false’ cases that are not actually caused by the infection or disease under study. While the inclusion of such false cases inflate outcome rates in both vaccinated and unvaccinated populations, it is less obvious how they affect estimates of VE. Illustrating the main points through simple examples, this article shows how VE is underestimated when false cases are included as outcomes. Depending how the outcome indicator is defined, estimates of VE against severe disease outcomes, whose definition allows for the inclusion of false cases, will be biased downwards and may in certain circumstances approximate the same level as the VE against infection. The bias is particularly pronounced for vaccines that offer high levels of protection against severe disease outcomes but poor protection against infection. Analysing outcomes that are measured with low sensitivity generally does not cause bias in VE studies; defining outcome indicators that minimise the number of false cases rather than the number of missed cases is preferable in VE studies.

PMID:38362627 | DOI:10.2807/1560-7917.ES.2024.29.7.2300259

Birth Defects Res. 2024 Feb;116(2):e2318. doi: 10.1002/bdr2.2318.

ABSTRACT

BACKGROUND: Arginase 1 (Arg1) encodes a key enzyme that catalyzes the metabolism of arginine to ornithine and urea. In our recent study, we found that knockdown of Arg1 in the lungs of fetal mice induces apoptosis of epithelial cells and dramatically delays initiation of labor. As the most abundant internal mRNA modification, N⁶ -methyladenosine (m⁶ A) has been found to play important roles in lung development and cellular differentiation. However, if the knockdown of Arg1 affects the RNA m6A modification in fetal lungs remains unknown.

METHODS: In the current study, the RNA m6A levels and the expression of RNA m6A related enzymes were validated in 13.0 dpc fetal lungs that Arg1 was knocked down by adeno-associated virus carrying Arg1-shRNA, using western blot, immunofluorescence, and RT-qPCR.

RESULTS: No statistical differences were found in the expression of methyltransferase, demethylases, and binding proteins in the fetal lungs between AAV-shArg1-injected mice and AAV-2/9-injected mice. Besides, there is no significant change of overall RNA m6A level in fetal lungs from AAV-shArg1-injected mice, compared with that from AAV-2/9-injected mice.

CONCLUSIONS: These results indicate that arginase 1 does not affect RNA m6A methylation in mouse fetal lung, and the mechanisms other than RNA m6A modification underlying the effects of Arg1 knockdown on the fetal lung development and their interaction with labor initiation need to be further explored.

PMID:38362594 | DOI:10.1002/bdr2.2318

Malawi Med J. 2023 Dec;35(4):220-223. doi: 10.4314/mmj.v35i4.4.

ABSTRACT

BACKGROUND: Tracheobronchial variations (TBVs) are more common than previously believed due to the increasing use of multi-detector computed tomography (MDCT). This study aimed to assess TBVs in cases of pneumoconiosis, one of the oldest occupational diseases that still poses a threat to public health.

METHODS: This was a descriptive study that involved reviewing chest MDCT images of 34 cases of pneumoconiosis and 34 control cases retrospectively from January 2020 to April 2022. Variations in the trachea, right main bronchus, left main bronchus, lobar and segmental branches of the cases in the patient and control groups were evaluated according to Boyden’s nomenclature.

RESULTS: The frequency of TBV was 32.4% in pneumoconiosis cases. Although the frequency of TBV was higher in the patient group than in the control group, the difference was not statistically significant (p=0.086). Furthermore, there was no significant difference in terms of TBV classification between the patient and control groups (p=0.407). Additionally, the presence of TBV did not affect the distribution of International Labour Organization categories in pneumoconiosis cases (p=0.360).

CONCLUSIONS: Although our study provides initial insights into the occurrence of TBVs in pneumoconiosis cases, further research is needed to clarify the relationship between these variations and the disease.

PMID:38362566 | PMC:PMC10865055 | DOI:10.4314/mmj.v35i4.4

BMJ Open Sport Exerc Med. 2024 Feb 14;10(1):e001795. doi: 10.1136/bmjsem-2023-001795. eCollection 2024.

ABSTRACT

There is increasing interest in the potential long-term outcomes of participation in contact and collision sports, driven by evidence of higher rates of neurodegenerative diseases among former athletes. Recent research has capitalised on large-scale administrative health data to examine health outcomes in contact sport athletes. However, there is limited research on outcomes associated with participation in rugby union, a contact sport with a relatively high incidence of head trauma and musculoskeletal injuries. Additionally, there is scope to investigate a greater range of health outcomes using large, population-based administrative data. The Kumanu Tāngata project is a retrospective cohort study that will use linked information from the New Zealand Rugby Register and health records within a comprehensive deidentified whole-population administrative research database known as the Integrated Data Infrastructure. First-class male rugby union players (N=13 227) will be compared with a general population comparison group (N=2 438 484; weighting will be applied due to demographic differences) on a range of mortality and morbidity outcomes (neurodegenerative diseases, musculoskeletal conditions, chronic physical conditions, mental health outcomes). A range of player-specific variables will also be investigated as risk factors. Analyses will consist primarily of Cox proportional hazards models. Ethics approval for the study has been granted by the Auckland Health Research Ethics Committee (Ref. AH23203). Primary research dissemination will be via peer-reviewed journal articles.

PMID:38362564 | PMC:PMC10868174 | DOI:10.1136/bmjsem-2023-001795