Genome‐wide association study of periodontitis severity and progression

Abstract Background To add to the knowledge base of periodontal genomics, we carried out a genome‐wide association study (GWAS) of periodontitis severity and progression among 416 mixed‐ethnicity adult participants of a periodontitis clinical study. Methods Participants were 168 adults (mean age = 50 years, 46% males) with severe periodontitis and 248 adults (mean age = 48 years, 40% males) without severe periodontitis, including 147 with mild periodontitis and 101 periodontally healthy. Disease progression information over a 12‐month period was available for 368 of these participants. Single marker discovery analysis relied on logistic regression models adjusted for age, sex, and genetically determined ancestry using a conventional p  < 5x10 −8 genome‐wide statistical significance criterion. Genome‐wide significant loci were annotated and examined for associations with periodontal disease traits in external cohorts of 10,019 Hispanic/Latinos, 4,554 European Americans, and 973 African Americans. Results All GWAS single nucleotide polymorphisms (SNPs) explained 34% of phenotypic variance between periodontitis cases and controls and 57% of the variance in disease progression in this study. We identified 2 genome‐wide significant loci associated with disease progression ( SUMO2P2 , small ubiquitin‐like modifier 2, rs72691774, p  = 1.9x10 −8 ] and CUBN (cubilin, rs565051161, p  = 3.9x10 −8 ). CUBN was strongly associated with periodontal disease in the independent samples of African Americans (rs7082270, p  = 3.1x10 −7 ) and Hispanic/Latinos (rs1276710, p  = 1.5x10 −5 ), albeit the lead SNPs were rare and differed in each population. Meanwhile, ZBTB16 (zinc finger and BTB domain‐containing 16) showed the strongest evidence of association with severe periodontitis (rs454802, p  = 2.2x10 −7 ). Conclusions This study's results emanate from a well‐characterized cohort of periodontitis severity and progression and add to the knowledge base of periodontal genomics and the underlying individual disease susceptibility. Plain language summary This study assessed the association of gene variants in association with gum disease severity and progression in 416 participants of a clinical study. Participants were 168 adults (mean age = 50 years, 46% males) with severe disease and 248 adults (mean age = 48 years, 40% males) without severe disease, including 147 with mild disease and 101 without disease. Disease progression information over a 12‐month period was available for 368 of these participants. Single marker discovery analysis relied on logistic regression models adjusted for age, sex, and genetically determined ancestry. Genome‐wide significant loci were annotated and examined for associations with periodontal disease traits in external cohorts of 10,019 Hispanic/Latinos, 4,554 European Americans, and 973 African Americans. All gene variants explained 34% of the variance between cases and controls and 57% of the variance in disease progression in this study. We identified 2 genome‐wide significant loci associated with disease progression ( SUMO2P2 and CUBN ). CUBN was strongly associated with periodontal disease in the independent samples of African Americans and Hispanic/Latinos. ZBTB16 showed the strongest evidence of association with severe periodontitis. This study's results emanate from a well‐characterized cohort of periodontitis severity and progression, suggest that about one‐third of variance in disease severity and over half of variance in disease progression are attributable to individual susceptibility, and add to the knowledge base of periodontal genomics.

Unveiling the Crystal Structure of Sanidine: A Polarized Raman and Ab Initio Simulation Exploration

ABSTRACT Sanidine, the high‐temperature polymorph of potassic feldspar, plays a crucial role in the formation of volcanic rocks. Despite extensive research, the complexity of K‐feldspar polymorphs remains poorly understood. This study, by combining polarized Raman spectroscopy with ab initio calculations, aims to definitively assign the vibrational modes predicted by theory to those observed experimentally. A sanidine megacryst from the rhyo‐dacite sub‐intrusive body of Terlano (Ora mega‐caldera complex, Southern Alps, Italy) was used for this purpose. Polarized Raman spectra were collected in six scattering geometries, allowing for precise mode selection within the 40–1200 cm −1 range. Our vibrational analysis, based on density functional theory, provides wave‐numbers and normal modes having trends that largely align with experimental data. The combination of experimental data and theoretical calculations also indicated that the models in which aluminum is located at the T 1 tetrahedral site are more stable than those with aluminum at the T 2 site. This finding provides further insight into the order–disorder phase transition in K‐feldspar, a phenomenon that is difficult to replicate under laboratory conditions. These results further improve our understanding of the relationship between theoretical models and the actual spectral characteristics of this disordered mineral. The full assignment of normal modes presented here lays the foundation for future studies of phase transitions in K‐feldspars using Raman spectroscopy.

Comparative Outcomes of Flap Maturation Versus Conventional Pediatric Tracheotomy Techniques

ABSTRACT Objective To compare postoperative outcomes of flap maturation (FMT) and conventional tracheotomy techniques in pediatric patients. Methods A retrospective cohort study was performed using data from the American College of Surgeons National Surgical Quality Improvement Program Pediatric database (2020–2021). Pediatric patients ≤ 18 years who underwent FMT (CPT 31610) or conventional tracheotomy (CPT 31600, 31,601) were included. Primary outcomes were 30‐day reoperation, surgical site infection, pneumonia, seizures, mortality, unplanned reintubation, readmission, and length of stay. Results Among 2353 patients (mean age 2.9 years, 95% CI 2.7–3.1), 381 (16.2%) underwent FMT and 1972 (83.8%) underwent conventional tracheotomy. An FMT was associated with lower odds of 30‐day reoperation (0.5% vs. 3.3%, p  = 0.003; adjusted OR = 0.17, 95% CI 0.1–0.6, p  = 0.005). Rates of surgical site infection, pneumonia, and seizures did not differ significantly between groups after adjustment. No differences were observed in mortality, reintubation, readmission, or length of stay. Conclusion FMT is independently associated with lower reoperation rates without increased postoperative complications. FMT may be a favorable tracheotomy option for select patients and warrants consideration during surgical decision‐making to optimize outcomes. Level of Evidence 3.

Nitrogen fixation is driven by cellular nitrogen stores in a diazotrophic cyanobacterium: Evidence from culture experiments and model validation

Abstract Diazotrophic cyanobacteria, including those responsible for harmful algal blooms, fix atmospheric dinitrogen (N 2 ) to sustain growth when they are limited by dissolved inorganic nitrogen (DIN) supply. Conventional models fail to accurately predict the timing and magnitude of N 2 fixation, partly because of oversimplified assumptions about diazotrophic species responses to N. We hypothesized that cellular carbon (C) and N would co‐vary with DIN availability, and cellular N quota reduced below a critical threshold would trigger heterocyst differentiation and N 2 fixation. Conversely, we hypothesized that heterocysts would be discarded, and N 2 fixation would cease at another higher cellular N quota threshold. To test this hypothesis, we undertook experiments to provide data to calibrate a model of cellular C and N of N 2 fixation in the cyanobacterium Raphidiopsis raciborskii . The model incorporated internal N quotas, external DIN supply and a time lag for N 2 fixation as key regulators of heterocyst production and N 2 fixation, explaining > 70% of the variation in measured cellular N and C : N molar ratios. Heterocysts were predicted to form at a cellular N quota of 0.085 mg N mg −1 C and were discarded from filaments at 0.275 mg N mg −1 C. There was a 5‐d time lag between DIN deprivation and initiation of N 2 fixation. Continuous DIN supply was predicted to enhance N 2 fixation more than an equivalent one‐off pulse. Our study highlighted the need to consider cellular N and N supply regimes in driving N 2 fixation to provide more accurate predictions of the response of cyanobacteria to DIN availability.

A new approach to predicting and understanding cyanobacteria bloom toxicity

Distinction and mutual Influences between Parkinson's Disease‐related and unrelated Chronic Pain

Abstract Background Chronic pain (i.e. > 3 months) is a common nonmotor symptom in patients with Parkinson's disease (PD), but the attribution to PD is critical for further treatment. Objectives We explored the PD Pain Classification System (PD‐PCS) criteria for the diagnosis of PD‐related pain and mutual influences between PD‐related and PD‐unrelated pain. Methods In this multicenter study, 120 nondemented PD patients were assessed using the PD‐PCS as well as motor and nonmotor questionnaires. The PD‐PCS consists of 3 steps: first, it classifies chronic pain as unrelated or related to PD according to 1 of 4 criteria (at onset or aggravated by PD, in the off phase, improvement with dopaminergic treatment, and with dyskinesia); second, it allows the classification of pain mechanisms (neuropathic, nociceptive, and nociplastic); and finally, it provides a score. Results Chronic pain was present in 92% of patients, with PD‐related pain in 73% and non‐PD‐related pain in 53%. Higher PD‐PCS scores were reported when PD‐related pain was present. In cases of concurrent PD‐related and PD‐unrelated pain (35%), there was a moderate correlation between pain severity. Improvement with dopaminergic medication and pain in the off phases were the most common factors defining an association of pain with PD. These factors often occur together, whereas pain during dyskinesia occurs independently. Conclusion The PD‐PCS criteria allow differentiation between PD‐related and PD‐unrelated chronic pain through 2 approaches, assessing periods of either low or high dopaminergic stimulation. PD‐unrelated pain should also be taken into account, as it is more common than in the general population and as it may influence PD‐related pain.

The Influence of Genetics in the Early Development of Axial Postural Abnormalities in Parkinson's Disease

ABSTRACT Background Postural abnormalities (PA) can complicate Parkinson's disease (PD). While age and motor severity are established predictors, the genetic role remains underexplored. Objective To evaluate the influence of major genetic variants on PA development in PD over 4 years. Methods We analyzed 429 patients from Parkinson's Progression Markers Initiative, including GBA , LRRK2 and SNCA mutation carriers. PA were assessed using the MDS‐UPDRS‐III item 3.13 and risk factors were analyzed with Cox uncertain regression. Results SNCA‐PD patients were the youngest at onset (50.8 years) and showed the highest PA cumulative incidence over 4 years (30%), followed by GBA‐PD (25.8%), idiopathic PD (23%), and LRRK2‐PD (17.2%). No significant differences in PA prevalence were found across groups at baseline or at the 4‐year follow‐up, and genetic status was not a predictor for PA development. Conclusions Although not significant, the higher PA incidence in SNCA‐PD, despite its younger age, suggests that genetic factors may influence PA progression, warranting further studies.

Polyelectromyography Under Propofol to Differentiate Functional from Idiopathic Dystonia: A Pilot Study

Abstract Background Functional dystonia ( FD ) is one of the most diagnostically challenging functional movement disorders. Phenomenological features often lack specificity, as many are also observed in idiopathic dystonia ( ID ) and validated biomarkers to distinguish FD from ID are currently unavailable Objective To investigate potential differences in muscle activity between ID and FD patients using polyelectromyography (PEMG) under anesthesia. Methods We consecutively enrolled 10 patients with FD and 17 with ID according to the current diagnostic criteria who underwent continuous PEMG before, during, and after propofol infusion. Sedation levels were monitored by electroencephalography and bispectral index and stratified via the Observer's Assessment of Alertness/Sedation Scale (OASS). PEMG recordings were performed under five definite scenarios: alert, mild and deep sedation, and partial and full recovery of consciousness status. Presence/absence of EMG activity was evaluated across these stages, and changes from baseline patterns were analyzed. Results During mild sedation, EMG activity persisted in all ID (100%) and in 9 (90%) FD patients. During deep sedation, EMG activity persisted in 9 (53%) ID patients and was absent in all FD patients (100%) ( P  = 0.01). During partial recovery of consciousness, EMG activity was present in all (100%) ID and only in 1 (10%) FD patients ( P  < 0.001). At full recovery, a different muscular activation pattern from baseline was observed in 7 (70%) FD and only in 1 (6%) ID patients ( P  = 0.001) Conclusions EMG silence during deep sedation and partial recovery may serve as a neurophysiological marker of FD . A muscular activation pattern differing from baseline may represent a neurophysiological clue for incongruence © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Glucocerebrosidase Target Engagement and Therapeutic Plasma and Cerebrospinal Fluid Levels After GT ‐02287 Administration in Healthy Volunteers

Abstract Background Variants in the GBA1 gene can increase the risk of Parkinson's disease (PD) by reducing glucocerebrosidase (GCase) activity, disrupting lysosomal and mitochondrial function, and increasing alpha‐synuclein aggregation. The molecule GT‐02287 prevents misfolding of GCase and ameliorates downstream pathway abnormalities. Objectives To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of GT‐02287. Methods The safety, tolerability, and plasma pharmacokinetics of single and multiple oral doses were evaluated in 73 healthy volunteers, and GT‐02287 levels in cerebrospinal fluid (CSF) and GCase activity in blood were measured. Results All dose levels tested were safe and generally well‐tolerated. No serious or severe adverse events occurred. The most common events were nausea and headache. Plasma and CSF exposures were within the projected therapeutic range, and GCase activity increased after GT‐02287 administration. Conclusions GT‐02287 was safe and well‐tolerated in healthy volunteers. Plasma and CSF levels were consistent with levels in rodents that modulate PD biology. © 2025 International Parkinson and Movement Disorder Society.

Protective Roles of Prebiotics and Probiotics Against Environmental Pollutant‐Induced Toxicities: A Systematic Review of Animal Studies

ABSTRACT Environmental pollutants, including heavy metals, organic pollutants, and mycotoxins, cause various adverse health effects linked to inflammation and oxidative stress. These toxicities disrupt gut microbiota composition and function, which prebiotics and probiotics may counteract. This study systematically reviewed the effects of prebiotics, probiotics, synbiotics, and commensal gut microbiota on pollutant‐induced toxicities in animal models. A literature search was conducted using Scopus, PubMed, Embase, Web of Science, and Google Scholar databases up to January 2025, following PRISMA guidelines. Study quality was assessed using the SYRCLE risk of bias tool, and reliability was evaluated with the ToxRTool. Fifty‐four studies investigating prebiotics, probiotics, synbiotics, or commensal microbiota in rats, mice, or zebrafish were included. While 98% of studies were considered reliable, only 18% were rated as good quality due to biases in selection, performance, and detection. Probiotics, prebiotics, synbiotics, and gut microbiota reduced heavy metal absorption and increased fecal excretion. They also improved gut barrier integrity and reduced intestinal permeability in animals exposed to heavy metals. Additionally, probiotics and prebiotics enhanced antioxidant activity and triggered anti‐inflammatory responses in animals exposed to heavy metals, mycotoxins, and organic pollutants. Overall, this review supports the role of microbiota, probiotics, prebiotics, and synbiotics in mitigating pollutant‐induced toxicities, though future studies should address common bias issues.