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The Journal of Infection Jun 2024
PubMed: 38908523
DOI: 10.1016/j.jinf.2024.106207 -
Medicina Oral, Patologia Oral Y Cirugia... Jun 2024Oral lichen planus (OLP) is an inmuno-mediated mucocutaneous chronical inflammatory disease. Multiple predisposing factors are considered, such as autoimmune response,...
BACKGROUND
Oral lichen planus (OLP) is an inmuno-mediated mucocutaneous chronical inflammatory disease. Multiple predisposing factors are considered, such as autoimmune response, microorganisms, medications, dental materials, psychological stress, genetic predisposition or nutritional deficiencies. The deficiency of vitamin D has been related to various autoimmune diseases like OLP.
MATERIAL AND METHODS
The electronic search was conducted in the MEDLINE (Pubmed), Scopus, Cochrane Library and Web of Science databases. To assess any potential risk of bias, the authors critically appraised each study by the Newcastle-Ottawa Scale for cohort and case-control studies. Pooled analyses were performed using a random-effects model. Heterogeneity of the studies was assessed by the I2 statistics. Forest Plots were performed to graphically represent the difference between vitamin D concentrations in the OLP compared to healthy group, with a 95% confidence interval.
RESULTS
After applying our inclusion and exclusion criteria, 7 articles were included in our review. The median concentration vitamin D in ng/ml found in serum for patients with OLP was of 26,6311,75ng/ml and for healthy patients was of 31,438,7ng/ml. Regarding the quantitative analysis, 7 studies were included. The difference in the concentration of vitamin D in healthy patients and patients with OLP statistically significant (Weighted Mean Difference (WMD): -6.20, 95% CI: -11.24 to -1.15, p=0.02 and I2 heterogeneity: 94%, p<0.00001).
CONCLUSIONS
The patients with OLP have statistically lower vitamin D levels than healthy patients.
PubMed: 38907640
DOI: 10.4317/medoral.26603 -
Vaccine Jun 2024Before the global mpox outbreak which began in 2022, the real-world vaccine effectiveness (VE) of mpox vaccines was unknown. We quantified the VE in the global... (Review)
Review
INTRODUCTION
Before the global mpox outbreak which began in 2022, the real-world vaccine effectiveness (VE) of mpox vaccines was unknown. We quantified the VE in the global population of 3rd generation or later mpox vaccines (MVA-BN, LC16m8, OrthopoxVac) compared with unvaccinated or other vaccinated states for infection, hospitalization and death. VE was stratified by 1-dose and 2-doses and post-exposure prophylaxis (PEP).
METHODS
Studies were included if they measured vaccine efficacy or effectiveness in humans. Animal studies and immunogenicity studies were excluded. MEDLINE, Web of Science, Google Scholar, Embase, MedRxiv and grey literature were searched from January 1st, 1970, with the last search run on November 3, 2023 (Prospero, CRD42022345240). Risk of publication bias was assessed via funnel plots and Egger's test, and study quality via Newcastle-Ottawa scales.
RESULTS
A total of 11,892 records were identified via primary search, 3,223 via citation chasing. Thirty-three studies were identified of 3rd generation vaccines, 32 of which were MVA-BN. Two additional studies were re-analysis of existing data. Most of these studies were focused on gay, bisexual, or other men who have sex with men between the ages of 18-49 in May to October of 2022. VE of 1 dose of MVA-BN was 76% (95%CI 64-88%) from twelve studies. VE of 2 doses was 82% (95%CI 72-92%) from six studies. VE of MVA-BN PEP against mpox was 20% (95%CI -24-65%) from seven studies. All VE are calculated from random effects estimates. 18/33(55%) studies were rated as poor, 3/33(9%) as fair and 12/33(36%) as good. Studies included in the meta-analysis had higher quality: 11/16 (69%) were rated as good quality.
CONCLUSION
Both 1 and 2 doses of MVA-BN are highly effective at preventing mpox. Effectiveness estimates, specifically of PEP are limited by immortal time bias, predominant mode of mpox transmission, and real-world vaccine timing of administration.
PubMed: 38906763
DOI: 10.1016/j.vaccine.2024.06.021 -
The Veterinary Quarterly Dec 2024Animal industry seeks cost-effective solutions to enhance performance and health of domestic animals. This study investigated the effects of supplementing spp....
Live performance, nutrient digestibility, immune response and fecal microbial load modulation in Japanese quails fed a -based probiotic alone or combination with xylanase.
Animal industry seeks cost-effective solutions to enhance performance and health of domestic animals. This study investigated the effects of supplementing spp. probiotics and xylanase on 2000 one-day-old Japanese quails, randomly assigned to four treatment groups (10 replicates). The control group received no supplementation, while the others were supplemented with a -based probiotic at 7.5 × 10 cfu/kg of feed, xylanase enzyme (2,000 U/kg) alone or in combination. Quails receiving both probiotic and enzyme exhibited significantly ( < 0.01) higher weekly and overall weight gain, and lower feed conversion ratios compared to the control group. Dressing percentage was higher ( < 0.01), and mortality lower in birds supplemented with a combination of enzyme and probiotic. Antibody titres against infectious bronchitis and infectious bursal disease were significantly ( < 0.01) higher in quails receiving combined probiotic and enzyme supplementation, while titres against Newcastle disease virus were higher ( < 0.01) in groups supplemented with probiotic and enzyme individually or in combination. Additionally, digestibility was significantly ( < 0.01) higher in groups receiving combined enzyme and probiotic supplementation, with higher apparent metabolizable energy compared to the control. The populations of beneficial increased, while harmful and decreased significantly in quails supplemented with both probiotic and enzyme. In conclusion, supplementing xylanase enzyme and probiotic together in Japanese quails positively influenced growth, nutrient digestibility, immune response, and cecal microbiota.
Topics: Animals; Probiotics; Bacillus; Coturnix; Animal Feed; Endo-1,4-beta Xylanases; Diet; Digestion; Feces; Dietary Supplements; Animal Nutritional Physiological Phenomena; Random Allocation; Poultry Diseases
PubMed: 38903017
DOI: 10.1080/01652176.2024.2364641 -
The European Respiratory Journal Jun 2024https://bit.ly/42IOVbA
https://bit.ly/42IOVbA
Topics: Humans; Asthma; Remission Induction; Anti-Asthmatic Agents; Severity of Illness Index; Male; Female; Biological Therapy; Middle Aged; Biological Products; Adult; Treatment Outcome
PubMed: 38901893
DOI: 10.1183/13993003.00160-2024 -
Journal of Cystic Fibrosis : Official... Jun 2024CF-related diabetes (CFRD) is a prevalent comorbidity in people with Cystic Fibrosis (CF), significantly impacting morbidity and mortality rates. This review article... (Review)
Review
CF-related diabetes (CFRD) is a prevalent comorbidity in people with Cystic Fibrosis (CF), significantly impacting morbidity and mortality rates. This review article critically evaluates the current understanding of CFRD molecular mechanisms, including the role of CFTR protein, oxidative stress, unfolded protein response (UPR) and intracellular communication. CFRD manifests from a complex interplay between exocrine pancreatic damage and intrinsic endocrine dysfunction, further complicated by the deleterious effects of misfolded CFTR protein on insulin secretion and action. Studies indicate that ER stress and subsequent UPR activation play critical roles in both exocrine and endocrine pancreatic cell dysfunction, contributing to β-cell loss and insulin insufficiency. Additionally, oxidative stress and altered calcium flux, exacerbated by CFTR dysfunction, impair β-cell survival and function, highlighting the significance of antioxidant pathways in CFRD pathogenesis. Emerging evidence underscores the importance of exosomal microRNAs (miRNAs) in mediating inflammatory and stress responses, offering novel insights into CFRD's molecular landscape. Despite insulin therapy remaining the cornerstone of CFRD management, the variability in response to CFTR modulators underscores the need for personalized treatment approaches. The review advocates for further research into non-CFTR therapeutic targets, emphasizing the need to address the multifaceted pathophysiology of CFRD. Understanding the intricate mechanisms underlying CFRD will pave the way for innovative treatments, moving beyond insulin therapy to target the disease's root causes and improve the quality of life for individuals with CF.
PubMed: 38897882
DOI: 10.1016/j.jcf.2024.06.004 -
American Journal of Human Genetics Jun 2024Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms...
Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10, OR = 1.27) and APOE (rs6857; p = 1.31 × 10, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.
PubMed: 38889728
DOI: 10.1016/j.ajhg.2024.05.017 -
Clinical and Translational Medicine Jun 2024Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
BACKGROUND
Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
METHODS
Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations.
RESULTS
There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues.
CONCLUSIONS
We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications.
HIGHLIGHTS
Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.
Topics: Humans; Parathyroid Neoplasms; Adenoma; Inflammation; Histone-Lysine N-Methyltransferase; Myeloid-Lymphoid Leukemia Protein; Proto-Oncogene Mas; Cell Proliferation
PubMed: 38888967
DOI: 10.1002/ctm2.1734 -
JAMA Network Open Jun 2024Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small... (Observational Study)
Observational Study
IMPORTANCE
Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.
OBJECTIVE
To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.
DESIGN, SETTING, AND PARTICIPANTS
This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.
EXPOSURES
Preoperative chemotherapy (with or without radiotherapy) followed by resection.
MAIN OUTCOMES AND MEASURES
The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.
RESULTS
Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).
CONCLUSIONS AND RELEVANCE
This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
Topics: Humans; Pancreatic Neoplasms; Male; Middle Aged; Female; Adenocarcinoma; Aged; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Cohort Studies; Oxaliplatin; Pancreatectomy
PubMed: 38888920
DOI: 10.1001/jamanetworkopen.2024.17625 -
Frontiers in Medicine 2024Many practicing physicians struggle to properly evaluate clinical research studies - they either simply do not know them, regard the reported findings as 'truth' since...
Many practicing physicians struggle to properly evaluate clinical research studies - they either simply do not know them, regard the reported findings as 'truth' since they were reported in a 'reputable' journal and blindly implement these interventions, or they disregard them as having little pragmatic impact or relevance to their daily clinical work. Three aspects for the latter are highlighted: study populations rarely reflect their practice population, the absolute average benefits on specific outcomes in most controlled studies, while statistically significant, are so small that they are pragmatically irrelevant, and overall mortality between the intervention and control groups are unaffected. These observations underscore the need to rethink our research approaches in the clinical context - moving from the predominant reductionist to an eco-systemic research approach will lead to knowledge better suited to clinical decision-making for an individual patient as it takes into account the complex interplay of multi-level variables that impact health outcomes in the real-world setting.
PubMed: 38887671
DOI: 10.3389/fmed.2024.1377356