Objective: The trial aimed to study the additive effect of domiciliary professional dental cleaning on root caries lesions (RCLs), oral hygiene outcomes and oral health-related quality of life (OHRQoL) in care-dependent older adults with in-home care that use high fluoride toothpaste, compared with oral care as usual for a year. Basic research design: Parallel-group evaluator-blinded randomized controlled trial. Clinical settings: Participants own home in Sweden. Participants: 194 care-dependent with in-home care aged ≥65 years and ≥1 natural tooth were randomized (1:1) in blocks by computer-generated sequence. 149 were available at baseline (intervention (I) = 80, control (C) = 69). All were provided with toothbrushes and high-fluoride toothpaste (5,000 ppm F) for daily use. Intervention: Domiciliary professional dental cleaning and oral hygiene instructions by dental assistant, every third month. Main outcomes: The primary outcome was RCLs progression. Secondary outcomes were gingival bleeding, oral hygiene, hyposalivation and OHRQoL, registered at baseline and after 1 year by dental hygienists. Results: Due to high attrition (45%), 82 individuals remained (I = 50, C = 32) after 1 year resulting in an underpowered study. The number of subjects assessed with RCLs progression was 11 (22.0%) in I group and 9 (28.1%) in C. With the use of per protocol analysis, no significant differences between groups were seen for any of the outcomes. Conclusions: Domiciliary professional dental cleaning to care-dependent older adults does not seem to have any additive preventing effect on RCLs to daily toothbrushing with high-fluoride toothpaste. This suggests that focus be maintaining good daily oral health routines rather than home-care visits to maintain oral health.
Age is consistently associated with higher cumulative caries experience, but whether age-related oral microbiome shifts contribute to this association remains unclear. This study characterized age-related oral microbiome alterations, developed a microbial health index, and explored the interplay between the microbiome, age, and caries experience in adults. Among 4,763 participants aged ≥ 14 years from the National Health and Nutrition Examination Survey (NHANES), caries experience was quantified using the Decayed, Missing, and Filled Surfaces (DMFS) index. Oral microbiomes were profiled by 16 S rRNA sequencing. Restricted cubic splines, diversity and network analyses, random forest modeling for an Oral Microbial Health Index (OMHI), and mediation analysis were used to examine relationships among age, microbiome, and caries. Age explained 40.5% of DMFS variance with a non-linear positive correlation (P < 0.001). Microbial α-diversity declined non-linearly with age and DMFS (P < 0.001). Community structure and networks differed across age groups and caries experience levels. OMHI discriminated caries-free from high-burden individuals (AUC = 0.789), and the OMHI-based mediation accounted for 23.8% (95% CI: 21.3%-26.2%) of the age-DMFS association. The microbiome mediates a substantial portion of the age-caries association. Age-related shifts in diversity, taxonomy, and network structure are associated with greater caries burden. The OMHI shows promise as a non-invasive tool for caries risk stratification and age-specific prevention. These findings support microbiome-informed, age-stratified caries prevention and offer a non-invasive indicator for identifying adults at elevated risk in clinical and public health settings.
To characterise gene expression differences between oral cavity squamous cell carcinoma (OSCC) and non-neoplastic oral mucosa using targeted transcriptome profiling and to evaluate gene expression patterns associated with tumour differentiation. Formalin-fixed, paraffin-embedded tissue from 16 resected OSCCs (3 well differentiated, 9 moderately differentiated and 4 poorly differentiated) and 7 non-neoplastic oral mucosa samples was analysed. RNA was isolated from microdissected tissue and profiled using a targeted next-generation sequencing assay. Differential gene expression and pathway enrichment analyses were performed, including comparisons across histologic grades. OSCC demonstrated broad transcriptomic differences compared with non-neoplastic oral mucosa, with enrichment of pathways related to extracellular matrix remodelling, cell adhesion, immune regulation, oncogenic signalling and cellular metabolism. Grade-stratified analyses identified additional differences involving epithelial differentiation, immune response, lipid metabolism and oxidative phosphorylation pathways. OSCC exhibits broad transcriptomic dysregulation involving extracellular matrix remodelling, cell adhesion, immune signalling, oncogenic signalling and cellular metabolism. Grade-stratified findings demonstrate molecular differences associated with tumour differentiation but require validation in larger independent cohorts. These findings may inform future studies of biomarkers and biologically relevant pathways in OSCC.
According to the literature, in our country, the first choice for the reconstruction of extensive defects after the removal of locally advanced oral tumors is free flap reconstruction, which achieves the best functional outcome. We investigated whether the anterolateral thigh flap, which can be closed primarily at the donor site and is usually indicated for large or complex defects, can be adapted for thin defects, as well. Within the framework of a pilot study, 10 patients who underwent radical ablative surgery for oral squamous cell carcinoma were reconstructed with an anterolateral thigh flap harvested in the superficial fascia plane. We compared our results with those of 42 oral cavity radial forearm flap reconstruction procedures. Of the 10 patients who underwent reconstruction with a thinned anterolateral thigh flap seven underwent surgery for sublingual tumor and three for tongue tumors. All the flaps healed uneventfully. The average flap thickness was 9.25 mm and the average pedicle length was 11.7 cm, which was similar to that of the radial forearm flap (8.6 mm and 12.1 cm). No complications were observed at the donor site, and in every case, we were able to close the donor site primary. The anterolateral free thigh flap harvested in the superficial fascia plane could be an appropriate choice for functional preservation and closure of the oral cavity. Considering that it is similar to the radial forearm flap in terms of thickness and pedicle length but has a more favorable donor site morbidity, its wider use is recommended.
Regular health assessments using interRAI instruments, including the Oral Health Screener (OHS), may help identify care needs and improve nursing home residents' oral health. This study explored longitudinal associations between oral health (OH) and general health (GH) indicators. InterRAI assessments from Flemish and Dutch nursing home residents aged ≥ 65 years (October 2020-February 2024) were included. OH was derived from the OHS and GH from Activities of Daily Living Hierarchy (ADLH), Depression Rating Scale (DRS), Cognitive Performance Scale (CPS) and Changes in Health, End-stage Disease, and Signs and Symptoms (CHESS). A joint model explored overall associations between indicators. Bivariate autoregressive models examined cross-lagged associations conditional on prior status. In total, 12,586 assessments from 5450 residents were analyzed. Mean baseline age was 85.8 years (SD 7.7); 76.0% were women. All OH items were significantly interrelated, although correlations were mostly weak (< 0.4). Several cross-lagged associations between OH and GH indicators were observed, but effect sizes were small. Bidirectional associations were found between chewing function-ADLH, and discomfort/pain-both ADLH and CHESS. ADLH-problems were associated with poorer subsequent OH (teeth, tongue, palate-cheeks-lips). Depressive symptoms and higher CPS-scores were associated with later chewing difficulties and poorer denture hygiene, with depressive symptoms also linked to discomfort/pain. Chewing difficulties and poor gum and palate-cheeks-lips conditions were associated with subsequent health instability. Dry mouth was negatively associated with cognitive impairment. The findings suggest that OH and GH are interrelated and support considering OH as an integral part of general care rather than a separate domain.
A clinical case of successful oral cavity sanitation using general anesthesia in a patient with a rare genetic disease, progressive fibrodysplasia ossificans progressiva (PFO), is presented. Special attention is paid to the technical features of performing oral cavity sanitation and general anesthesia in the context of progressive phenomena of false ankylosis of maxillofacial structures with a total lack of mouth opening function. An individualized algorithm of actions is selected at the stage of endotracheal anesthesia with nasotracheal intubation, oral cavity sanitation, and subsequent rehabilitation. The presented case demonstrates the existence of problematic patients, the lack of information about them in the medical community, and the importance of interdisciplinary collaboration between dentists, pediatricians, orthopedists, traumatologists, anesthesiologists, and other specialists to optimize treatment outcomes and prevent potential risks in the management of patients with FOP. The positive treatment outcome indicates a significant improvement in the patient's quality of life and the absence of complications. Представлен клинический случай успешной санации полости рта с использованием общей анестезии у пациентки с редким генетическим заболеванием — фибродисплазией оссифицирующей прогрессирующей (ФОП). Особое внимание уделено техническим особенностям выполнения санации и общего обезболивания на фоне прогрессирующих явлений ложного анкилоза челюстно-лицевых структур с тотальным отсутствием функции открывания рта. Индивидуально подобран алгоритм действий на этапе эндотрахеального наркоза с назотрахеальной интубацией, санацией полости рта и последующей реабилитацией. Представленный случай свидетельствует о существовании проблемных пациентов, дефиците информации о них во врачебной среде и демонстрирует целесообразность междисциплинарного сотрудничества стоматологов, педиатров, ортопедов, травматологов, анестезиологов и других узких специалистов, что необходимо для оптимизации результатов лечения, профилактики потенциальных рисков при лечении пациентов с ФОП. Полученный положительный результат лечения свидетельствует о значительном улучшении качества жизни пациентки и отсутствии осложнений.
Orally administered small-molecule programmed death ligand 1 (PD-L1) inhibitors may have the potential to improve patient outcomes in the treatment of a range of cancers compared with their antibody-based counterparts. A small molecule might achieve better tumor tissue penetration, and oral administration could significantly improve convenience and access for patients. Three phase 1 open-label, non-randomized, dose escalation, and expansion studies evaluated the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of three agents in patients with advanced solid tumors: INCB086550 (NCT03762447), INCB099280 (NCT04242199), and INCB099318 (NCT04272034). Overall, 138, 182, and 104 patients received INCB086550, INCB099280, and INCB099318, respectively. Most had previously received ≥2 lines of cancer therapy for advanced or metastatic disease; 9.6%-16.5% had received prior immunotherapy. All three agents were rapidly absorbed and showed stable dose-dependent PK. With INCB086550, 88 patients (63.8%) had ≥1 treatment-related treatment-emergent adverse event (TEAE), and 19 (13.8%) had ≥1 treatment-related grade ≥3 TEAE. In total, 14 patients (10.1%) had a nervous system-associated TEAE for which an immune-mediated etiology could not be ruled out; events were predominantly peripheral sensory and motor neuropathies. With INCB099280 and INCB099318, 144 (79.1%) and 69 (66.3%) of patients had ≥1 treatment-related TEAE, and 25 (13.7%) and 12 (11.5%) had ≥1 treatment-related grade ≥3 TEAE, respectively. The most frequent immune-related adverse events were skin reactions (INCB099280 and INCB099318) and hepatitis (INCB099280). No dose-limiting toxicities (DLTs) occurred during dose escalation with INCB086550 or INCB099318; two DLTs occurred in two patients with INCB099280 (grade 2 vomiting with 600 mg once daily and grade 2 maculopapular rash with 800 mg two times per day). Overall objective response rates for INCB086550, INCB099280, and INCB099318 were 10.9% (95% CI 6.2% to 17.3%; n=15), 8.8% (95% CI 5.1% to 13.9%; n=16), and 8.7% (95% CI 4.0% to 15.8%; n=9), respectively. Target engagement and PD activity were demonstrated, including PD-L1 binding, and increases in cytokine and chemokine production, as well as T-cell activation and proliferation. Both INCB099280 and INCB099318 had an acceptable safety profile, with preliminary evidence of antitumor activity. The risk of immune-mediated neuropathy led to discontinuation of the clinical program for INCB086550.
Small mothers against decapentaplegic homologue 4 (SMAD4) plays an important role in transforming growth factor (TGF)-β signaling and is associated with various cancers. However, little is known about SMAD4 expression in oral squamous cell carcinoma (OSCC). To investigate the clinical and biological significance of SMAD4 expression in OSCC. Immunohistochemical analysis was performed to detect SMAD4 expression in 90 OSCC specimens obtained from patients who underwent preoperative chemoradiotherapy and surgery (phase II study). We also investigated the correlation between SMAD4 expression and various clinicopathological features. In vitro experiments were performed to assess the effects of SMAD4 expression on chemosensitivity and changes in apoptosis-related molecules. Notably, low SMAD4 expression was significantly correlated with an increased risk of lymph node metastasis, poor response to chemoradiotherapy, and adverse prognosis in patients with OSCC who underwent preoperative 5-FU-based chemoradiotherapy. Additionally, SMAD4 downregulation in OSCC cells decreased sensitivity to cisplatin and 5-fluorouracil and was associated with an increase in cIAP2 expression. The reduced expression of SMAD4 has been linked to both chemotherapy resistance and prognosis in OSCC. However, it may not function as an independent prognostic biomarker. Further research is necessary to determine whether these findings can be generalized to the broader OSCC population.
The role of preoperative oral carbohydrate loading (OCHL) in optimizing postoperative metabolic outcomes in major vascular surgery remains unclear. This secondary analysis of a randomized controlled trial was conducted to evaluate the effects of OCHL on perioperative glucose-insulin metabolism and patient-reported well-being following elective open abdominal aortic aneurysm repair. Patients undergoing elective open aortic repair due to abdominal aortic aneurysm were randomized to receive OCHL (800 mL the evening before, and 400 mL 2 h before anesthesia induction) or standard overnight fasting. Plasma glucose and insulin concentrations were measured at four predefined perioperative time points, and indices of insulin resistance and sensitivity were calculated. Subjective well-being (anxiety, hunger, thirst, tiredness, pain, and headache) was evaluated using visual analog scales at three perioperative time points. Forty patients completed the study. On postoperative Day 1, insulin levels were significantly lower in the OCHL group compared with controls (median [IQR]: 55.3 [44.4] vs. 90.6 [73.1] pmol/L; p = 0.026). Homeostatic model assessment for insulin resistance was significantly lower (12.65 [13.48] vs. 25.56 [19.64]; p = 0.021), and insulin sensitivity index significantly higher (0.079 [0.068] vs. 0.039 [0.046]; p = 0.021) in OCHL patients. Patients receiving OCHL reported lower levels of hunger (1.25 vs. 4.35; p = 0.013), pain (0.8 vs. 3.85; p = 0.011), and fatigue (0.45 vs. 3.3; p = 0.005) compared with controls. Preoperative OCHL seems to be a safe nutritional strategy in patients undergoing open aortic repair, with benefits including improved initial glycemic control and enhanced patient well-being. Further studies are warranted to clarify the role of preoperative OCHL in optimizing metabolic outcomes in vascular surgery.
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To examine predisposing characteristics, enabling resources, need-related factors, and health behaviour or service-use indicators associated with unmet dental care needs among Korean adults aged ≥ 65 years, using Andersen's Behavioural Model of Health Services Use as an organizing framework. Previous Korea National Health and Nutrition Examination Survey (KNHANES)-based studies have identified socioeconomic, geographic, and oral health-related correlates of unmet dental care needs among older adults. However, the joint contributions of these factors have received less attention within an explicitly theory-based framework of healthcare access. This cross-sectional study analysed data from 1737 adults aged ≥ 65 years who participated in the 2023 Korea National Health and Nutrition Examination Survey. Unmet dental care needs were defined as reporting a need for dental care that was not received in the previous year. Weighted descriptive estimates, Rao-Scott adjusted tests, and complex-sample multivariable logistic regression were used. The weighted prevalence of unmet dental care needs was 23.2% (95% CI: 21.0-25.4). Rural residence (aOR = 1.43, 95% CI: 1.06-1.95), no oral examination in the past year (aOR = 2.70, 95% CI: 1.99-3.66), living alone (aOR = 1.54, 95% CI: 1.09-2.17), chewing difficulty (aOR = 2.19, 95% CI: 1.58-3.05), very poor self-rated oral health (aOR = 4.09 vs. very good, 95% CI: 1.47-8.81), and Medical Aid coverage (aOR = 2.80 vs. community-based insurance, 95% CI: 1.40-5.61) were associated with higher odds of unmet dental care needs. Unmet dental care needs remain common among Korean older adults and are associated with enabling resources, oral health needs, and preventive service use. Targeted rural outreach, care navigation for socially vulnerable older adults, and stronger linkage between preventive examinations and subsequent dental care may help address these multidimensional access barriers.
Of this work is to evaluate the effectiveness of an algorithm for comprehensive diagnosis and conservative treatment of galvanic syndrome developing against the background of electrogalvanic processes in the oral cavity. 72 people were examined. The algorithm of complex diagnostics consisted in the sequential carrying out of three stages of research (E1, E2, E3). On E1, the electromotive force (EMF) between metal containing structures was determined; on E2 - metal-containing structures, which are in a state of electro-galvanic activity; E3 - the ability of metal-containing structures to reduce their electro-galvanic activity. Patients who were found to have the ability to reduce their electro-galvanic activity with metal-containing structures were prescribed conservative treatment, which consisted of daily (10 days) mouth rinsing with a sodium thiosulfate solution. Electrogalvanic phenomena were detected in 56 out of 72 individuals. At stage E1, among these 56 patients, electromotive force between metal-containing constructions capable of inducing electrogalvanic processes and significantly different from the physiological norm of 50 mV was detected in 43 individuals, accounting for 76.8% (p<0.05). The difference in electrochemical potentials of metal-containing constructions in these patients was 117.8±22.3 mV. At stage E2, metal-containing constructions in a state of electrogalvanic activity were identified in 91.1%, that is, in 51 out of 56 patients. The difference in hydrogen index values in these patients was 0.8±0.11, which was significantly higher than the reference value of 0.6 (p<0.05).At stage E3, a decrease in electrogalvanic activity of metallic constructions was detected in 60.7%, that is, in 34 out of 56 patients. In 20 out of 34 patients (58.8%), both immediately after treatment and after one month of follow-up, complaints were absent, and the difference in hydrogen index values was significantly lower than 0.6, amounting to 0.3±0.07 (p<0.05), which indicated the effectiveness of the proposed method. The conducted study demonstrated that the use of a comprehensive examination algorithm for detecting electrogalvanic processes in the oral cavity is justified. Conservative treatment, in the presence of a positive test for reduction of electrogalvanic activity of metallic constructions, allows complete elimination of symptoms of galvanic syndrome in 58.8% of cases. Оценка эффективности алгоритма комплексной диагностики и консервативного лечения гальванического синдрома, развивающегося на фоне электрогальванических процессов в полости рта. Обследованы 72 пациента. Алгоритм комплексной диагностики заключался в последовательном проведении трех этапов исследований (Э1, Э2, Э3). На Э1 определяли электродвижущую силу (ЭДС) между металлосодержащими конструкциями; на Э2 — металлосодержащие конструкции, находящиеся в состоянии электрогальванической активности; на Э3 — способность металлосодержащих конструкций снижать свою электрогальваническую активность. Пациентам, у которых была обнаружена способность металлосодержащих конструкций снижать свою электрогальваническую активность, назначали консервативное лечение, заключавшееся в ежедневном (10 дней) полоскании рта раствором тиосульфата натрия. Электрогальванические явления выявлены у 56 человек на этапе Э1, а электродвижущая сила между металлосодержащими конструкциями, способная вызвать электрогальванические процессы, достоверно отличающаяся от физиологической нормы в 50 мВ, обнаружена у 43 (76,8%; p<0,05). Разность электрохимического потенциала (ЭХП) металлосодержащих конструкций составила 117,8±22,3 мВ. На Э2 металлосодержащие конструкции, находившиеся в состоянии электрогальванической активности, обнаружены у 51 (91,1%) из 56 пациентов. Разность водородных показателей у них составила 0,8±0,11, что достоверно выше референсного значения 0,6 (p<0,05). На Э3 снижение электрогальванической активности металлических конструкций обнаружено у 34 (60,7%) из 56 пациентов. У 20 (58,8%) из 34 пациентов как непосредственно после лечения, так и через месяц наблюдения жалобы отсутствовали, а разность водородных показателей была существенно ниже 0,6 и составила 0,3±0,07 (p<0,05), что свидетельствовало об эффективности предложенного метода. Проведенное исследование показало, что обоснованным является применение комплексного алгоритма обследования для выявления электрогальванических процессов в полости рта. Консервативное лечение при положительной пробе на снижение электрогальванической активности металлических конструкций позволяет в 58,8% случаев полностью купировать симптомы гальванического синдрома.
Garlic (Allium sativum) is widely known for its cardiovascular, antimicrobial, and potential anticancer properties. Despite these benefits, topical application may lead to adverse effects, including allergic reactions, anticoagulant effects, and chemical skin burns. Such burns are rare and under-recognized. This systematic review synthesizes the available clinical evidence on garlic-induced skin burns and complements it with an illustrative case to support clinical decision-making. A systematic PubMed search was conducted to identify clinical reports of garlic-induced skin burns with documented treatment and outcomes. Inclusion criteria comprised case reports or clinical studies on cutaneous garlic burns with available clinical intervention and outcome data. Exclusion criteria included studies published before 2000, non-English publications, mucosal or oral burns, animal or in vitro studies, review articles and editorial texts without patient data. In total, 45 studies were screened and 18 studies met the inclusion criteria. Extracted variables included patients' demographics, burn depth, treatment modality, and healing course. Additionally, a case of a woman with deep dermal, circumferential burns of the knee following the self-application of crushed garlic under occlusion is presented. Most reported cases involved superficial to deep dermal burns caused by prolonged or occlusive garlic application. Conservative treatment-topical antimicrobials, corticosteroids, and advanced dressings-was effective for superficial burns. However, deeper injuries often required surgical intervention including debridement, and in selected cases, split-thickness skin grafting. Healing times ranged from 7 to>56 days, with surgical management associated with faster recovery in deep lesions. Garlic-induced burns represent an uncommon but clinically relevant chemical injury. Prolonged occlusion increases risk for deep dermal necrosis. Early recognition and appropriate surgical management may optimize outcomes and prevent complications. Increased clinician awareness and patient education are essential. Due to heterogeneous case-based evidence, further research is warranted to inform standardized treatment guidelines. Knoblauch (Allium sativum) ist für seine kardiovaskulären, antimikrobiellen und potenziell antikanzerogenen Eigenschaften bekannt. Trotz dieser positiven Effekte kann die topische Anwendung mit unerwünschten Wirkungen wie allergischen Reaktionen, gerinnungshemmenden Effekten und chemischen Verätzungen einhergehen. Solche Verbrennungen sind selten und werden klinisch häufig unterschätzt. Diese systematische Übersichtsarbeit fasst die verfügbare klinische Evidenz zu knoblauchinduzierten Verätzungen zusammen und ergänzt diese durch einen illustrativen Fall zur Unterstützung der klinischen Entscheidungsfindung.Es wurde eine systematische PubMed-Recherche durchgeführt, um klinische Berichte über knoblauchinduzierte Verätzungen mit dokumentierter Therapie und Verlauf zu identifizieren. Die Einschlusskriterien umfassten Fallberichte oder klinische Studien zu kutanen Knoblauchverbrennungen mit verfügbaren Angaben zu Intervention und Outcome. Ausgeschlossen wurden Studien vor dem Jahr 2000, nicht englischsprachige Publikationen, mukosale oder orale Verbrennungen, tierexperimentelle oder In-vitro-Studien sowie Übersichtsarbeiten und editoriale Beiträge ohne Patientendaten. Insgesamt wurden 45 Studien gescreent, von denen 18 die Einschlusskriterien erfüllten. Erfasst wurden Patientendemografie, Verbrennungstiefe, Behandlungsmodalität und Heilungsverlauf. Zusätzlich wird der Fall einer Frau mit zirkulären IIb° Verbrennungen am Knie nach okklusiver Selbstapplikation von zerdrücktem Knoblauch dargestellt.Die meisten berichteten Fälle betrafen IIa° bis IIb° Verbrennungen infolge prolongierter oder okklusiver Knoblauchapplikation. Eine konservative Behandlung mit topischen antimikrobiellen Substanzen, Kortikosteroiden und modernen Wundauflagen war bei oberflächlichen Verbrennungen wirksam. Tiefere Läsionen erforderten hingegen häufig eine operative Therapie einschließlich Débridement und in ausgewählten Fällen eine Spalthauttransplantation. Die Heilungsdauer lag zwischen 7 und über 56 Tagen, wobei operative Verfahren bei tiefen Läsionen mit einer schnelleren Rekonvaleszenz assoziiert waren.Knoblauchinduzierte Verbrennungen stellen eine seltene, jedoch klinisch relevante Form chemischer Hautschädigung dar. Eine prolongierte Okklusion erhöht das Risiko tief dermaler Nekrosen. Die frühzeitige Diagnose und eine adäquate chirurgische Therapie können das Behandlungsergebnis verbessern und Komplikationen vermeiden. Eine erhöhte Sensibilisierung von Behandelnden sowie Patientinnen und Patienten ist essenziell. Aufgrund der heterogenen, überwiegend fallbasierten Evidenz sind weitere Untersuchungen erforderlich, um standardisierte Therapieempfehlungen abzuleiten.
Genetic instability has been reported in several neurodegenerative diseases, such as Alzheimer's and Parkinson's, but only a few studies have addressed sclerosis. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Micronuclei (MNi) and nuclear buds (NBUDs) are established markers of chromosomal instability, yet no data are available regarding a possible link between genetic instability and ALS. The novelty of this case-control study lies in the assessment of genetic instability in oral exfoliated cells from ALS patients (n = 20) and matched controls (n = 20), contributing to the identification of potential novel markers related to the molecular pathogenesis of this severe disorder. Groups were matched for age, sex, and lifestyle (p > 0.05). No significant differences were observed in MNi or NBUD frequencies between groups (p > 0.05). These findings suggest no association between ALS and MN/NBUD frequencies in oral cells.
Breast cancer is the most common cancer in women in the UK. For women who have early-stage oestrogen-receptor positive (ER+ve) disease, daily oral adjuvant endocrine therapy reduces risk of recurrence. Recently, CDK4/6 inhibitors, a form of biological therapy, have been approved for use alongside endocrine therapy. However, trial data suggest there may be challenges with adherence to CDK4/6 inhibitors. This study aims to explore the experiences of adherence and support needs of women who have been prescribed CDK4/6 inhibitors for early ER+ve breast cancer. It will also co-develop an intervention to support women with adherence to these drugs alongside endocrine therapy through an evidence-based, theory-informed and patient-centred approach. The SWEET-PLUS study has three phases. Phase I uses semi-structured interviews or focus groups to explore the experiences of women with early breast cancer who have been prescribed CDK4/6 inhibitors. It will also explore their support needs and experiences of adherence. Phase II involves interviews or focus groups with healthcare professionals who support CDK4/6 inhibitor prescription and associated care to understand the existing support and unmet needs. Phase I and II findings will inform phase III, which comprises workshops and user testing interviews to co-develop an intervention to support women with adherence to CDK4/6 inhibitors alongside endocrine therapy. This will be delivered as an additional module prototype designed for future integration into the existing HT&Me intervention, which supports women with adherence to endocrine therapy.Data from phases I and II will be analysed using a framework approach-based thematic analysis. Phase III data will be analysed through content analysis. SWEET-PLUS received ethical approval from the National Health Services (NHS) Health Research Authority (Cambridge East Research Ethics Committee (25/EE/0220)). Research findings will be disseminated through peer-reviewed journal articles and via international and national conferences. Further dissemination will be guided by patient and public involvement.
Imlunestrant is a next-generation, oral, selective estrogen receptor degrader approved for treating adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, ESR1-mutated advanced/metastatic breast cancer. Imlunestrant is metabolized partly by cytochrome P450 (CYP)3A4 oxidation and conjugation with glucuronic acid and sulfate; thus, pharmacokinetic and drug-drug interaction (DDI) studies for treatments utilizing similar pathways are essential for clinical development. Three open-label, phase 1 studies enrolled 182 healthy females of nonchildbearing potential to assess the tolerability, safety, and pharmacokinetics of imlunestrant as monotherapy or coadministered with other drugs. Drug concentrations were quantified by validated liquid chromatography-mass spectrometry. Participants tolerated imlunestrant at 200-800-mg doses, alone or with a CYP3A inhibitor (itraconazole), CYP3A inducer (carbamazepine), P-glycoprotein (P-gp) inhibitor (quinidine), and substrates of CYP2C8 (repaglinide), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), CYP3A (midazolam), P-gp (digoxin), and BCRP (rosuvastatin). Frequent treatment-related adverse events included headache (range, 4%-20%), diarrhea (2%-20%), and constipation (0%-16%). In the presence of imlunestrant, exposures (AUC0-∞) increased for dextromethorphan 1.33-fold (90% CI, 1.22-1.46), digoxin 1.39-fold (1.22-1.59), and rosuvastatin 1.49-fold (1.14-1.97). Imlunestrant exposure (AUC0-∞) decreased in combination with quinidine (CYP2D6 inhibitor) 0.87-fold (90% CI, 0.76-1.00) and carbamazepine (CYP3A4 inducer) 0.58-fold (0.49-0.69), but increased in combination with itraconazole (CYP3A4 inhibitor) 2.11-fold (1.77-2.53). Imlunestrant had no DDIs with CYP2C8 (repaglinide), CYP2C19 (omeprazole), and CYP3A4 (midazolam) substrates, or a P-gp inhibitor (quinidine), but weakly inhibited dextromethorphan (CYP2D6 substrate), digoxin (P-gp substrate), and rosuvastatin (BCRP substrate) clearance. Thus, considerations should be taken when imlunestrant is coadministered with strong CYP3A4 inhibitors, strong CYP3A4 inducers, and CYP2D6 and P-gp substrates where small changes in exposure may lead to toxicities.
The brain's consumption of approximately 20% of the body's oxygen contributes to oxidative stress, a significant pathological factor in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. This oxidative stress, linked to low levels of antioxidant enzymes, drives neuronal death by facilitating membrane peroxidation of fatty acids, proteins, and DNA. Alzheimer's disease is characterized by amyloid-beta (Aβ) plaque accumulation and hyperphosphorylated tau aggregates, both of which interact with mitochondria to generate reactive oxygen species (ROS). Aβ peptides bind metals such as iron and copper, catalyzing the formation of damaging hydroxyl radicals. Peripheral markers of oxidative damage, such as elevated malondialdehyde and protein carbonyls, are correlated with these processes in affected patients. In Parkinson's disease, the loss of dopaminergic neurons in the substantia nigra is associated with pathological iron accumulation and mitochondrial complex I dysfunction, which are worsened by misfolded α-synuclein and mutations in antioxidant genes such as PINK1 and Parkin. The autooxidation of dopamine also drives oxidative stress through the generation of hydrogen peroxide and reactive quinones. Huntington's disease involves the degeneration of medium spiny neurons in the striatum due to a polyglutamine repeat expansion in the huntingtin gene, which disrupts mitochondrial function and downregulates antioxidants, leading to excitotoxicity and ROS spikes. Amyotrophic lateral sclerosis primarily affects motor neurons due to the mutations in SOD1, which result in the production of aggregates that impair mitochondria and generate reactive nitrogen species (RNS), such as peroxynitrite. Mitigating oxidative stress in neurodegenerative disorders presents a considerable translational challenge. While low-molecular-weight antioxidant therapies for neurodegenerative disorders have shown promising results in preclinical and animal studies because they mitigate oxidative stress, their clinical efficacy is hampered by low bioavailability and difficulty in penetrating the blood‒brain barrier. To overcome these limitations, current medical research is focused on alternative delivery systems. Innovations such as nanoparticle-based drug delivery are being actively studied to help transport low-molecular-weight antioxidants across the blood‒brain barrier more safely and effectively. Several promising epidemiological trials linked high dietary intake of vitamins C and E to a reduced risk of Parkinson's disease, and plant-derived antioxidants such as polyphenols were explored for their ability to combat neuroinflammation and reduce cognitive decline. Refined oxidative stress-suppressing strategies involve the (ii) application of mitochondrial-targeted agents to preserve ATP production; (ii) boosting the Nrf2 pathway may trigger a cascade of detoxifying enzymes; (iii) supplementation with polyphenols such as quercetin, resveratrol, and curcumin can suppress oxidative stress and dampen microglial activation (neuroinflammation); (iv) and the use of substances affecting the bidirectional network linking oxidative stress and autophagy can clear ROS-generating components. Despite some promising epidemiological data, translating oral or systemic antioxidant therapy into effective clinical treatments for humans requires further effort. A survey of current knowledge of oxidative stress and antioxidant therapy in neurodegenerative diseases is the main subject of this review.
Tracheoesophageal fistula (TEF) and trachea-conduit fistula (TCF) after esophagectomy are rare but life-threatening complications. Large or multiple fistulas are difficult to treat when standard resection and tracheal reconstruction are not feasible. A 70-year-old man developed an anastomotic stricture after Ivor-Lewis esophagectomy for squamous cell carcinoma and underwent repeated balloon dilatations and stent placement. Progressive tissue injury resulted in 1 TCF and 2 large TEFs. Salvage surgery included stent removal, distal conduit takedown, proximal conduit closure, substernal colon interposition, and esophagocolostomy. The esophagus-proximal gastric conduit segment containing the fistulas was preserved in situ as a neo-posterior tracheal wall. Oral intake was resumed after esophagography on postoperative day 6, and bronchoscopy confirmed a viable blind pouch. Preserving the esophagus-conduit segment in situ may provide effective airway-alimentary separation in selected patients with extensive multifocal TEF/TCF. In highly selected patients, this salvage option for airway-alimentary separation when standard resection and reconstruction carry prohibitive risk. Given the limited survival in this case, it is not intended as a definitive or broadly generalizable reconstruction.
To carry out a comprehensive analysis of dental manifestations and identify the features of the dental system in children with premature aging syndromes. The study included 7 patients with premature aging syndromes: a boy and a girl with Hutchinson-Gilford syndrome, 2 girls with Cockayne syndrome type A and B, one girl each with neonatal progeroid syndrome, Penttinen syndrome and mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL syndrome). During a clinical examination by a dentist, the condition of the hard tissues of the teeth, periodontal and oral mucosa was assessed. According to orthopantomography data, the condition of occlusion and dentition was assessed. According to the results of the observations, a common pattern was revealed for all the examined patients: jaw hypoplasia and multiple caries. In patients with Hutchinson-Guilford and MDPL-syndrome, crowding and multiple carious lesions of the teeth were the most characteristic; for a patient with Penttinen syndrome, mandibular macrognathia, mesial occlusion and thickening of the mucous membrane of the frontal, sphenoid sinuses, a decrease in the cells of the latticed labyrinth;a feature of neonatal progeroid syndrome is the presence of neonatal incisors at birth, followed by hypo-/oligodontia or adentia. Knowledge of dento-mandibular anomalies in premature aging syndromes will allow dentists to timely detect pathologic changes in the dento-mandibular system and correct the dental status of patients with progeroid syndromes, which will significantly improve their quality of life. Комплексный анализ стоматологических проявлений и выявление особенностей зубочелюстной системы у детей с синдромами преждевременного старения. В исследование включено 7 пациентов с синдромами преждевременного старения: мальчик и девочка с синдромом Хатчинсона—Гилфорда, 2 девочки с синдромом Коккейна типа А и В, по 1 девочке с синдромом Видемана—Раутенштрауха, синдромом Пенттинена и синдромом гипоплазии нижней челюсти, глухоты, прогероидных черт и липодистрофии (MDPL-синдром). При клиническом осмотре стоматологом проведена оценка состояния твердых тканей зубов, пародонта и слизистой оболочки полости рта. По данным ортопантомографии оценено состояние окклюзии и зубных рядов. Выявлена общая закономерность для всех обследуемых пациентов: гипоплазия челюстей и множественный кариес. У пациентов с синдромом Хатчинсона—Гилфорда и MDPL-синдромом были характерны скученность и множественные кариозные поражения зубов. Для пациента с синдромом Пенттинена характерны макрогнатия нижней челюсти, мезиальная окклюзия, утолщение слизистой оболочки лобной и клиновидной пазух, уменьшение клеток решетчатого лабиринта. Особенностью синдрома Видемана—Раутенштрауха является наличие неонатальных резцов при рождении с последующей гипо-/олиго- или адентией. Знания о зубочелюстных аномалиях при синдромах преждевременного старения позволит стоматологам своевременно выявлять патологические изменения зубочелюстной системы и корректировать стоматологический статус пациентов с прогероидными синдромами, что значительно повысит их качество жизни.