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Pre-exposure prophylaxis (PrEP) is highly effective at reducing HIV acquisition. We aimed to estimate usage of oral-PrEP, and factors associated with adherence among female sex workers (FSWs) in Nairobi, Kenya, using a novel point-of-care urine tenofovir lateral flow assay (LFA). The Maisha Fiti study randomly selected FSWs from Sex Worker Outreach Program clinics in Nairobi. Data were collected from 1003 FSWs from June-October 2019, including surveys on self-reported oral-PrEP adherence. Adherence was also measured using the LFA for HIV-negative FSWs currently taking oral-PrEP. Informed by a social-ecological theoretical framework, we used hierarchical multivariable logistic regression models to estimate associations between individual, interpersonal/community, and structural/institutional-level factors and either self-reported or LFA-assessed adherence. Overall, 746 HIV-negative FSWs aged 18-40 participated in the study, of whom 180 (24.1%) self-reported currently taking oral-PrEP. Of these, 56 (31.1%) were adherent to oral-PrEP as measured by LFA. In the multivariable analyses, associations with currently taking oral-PrEP included having completed secondary education, high alcohol/substance use, feeling empowered to use PrEP, current intimate partner, no recent intimate partner violence, having support from sex worker organisations, experiencing sex work-related stigma, and seeking healthcare services despite stigma. Associations with oral-PrEP LFA-measured adherence measured included having only primary education, experience of childhood emotional violence, belonging to a higher wealth tertile, and being nulliparous. Oral-PrEP adherence, measured by self-report or objectively, is low among FSWs in Nairobi. Programs to improve oral-PrEP usage among FSWs should work to mitigate social and structural barriers and involve collaboration between FSWs, healthcare providers and policymakers.

ObjectiveDetermine the prevalence, types, and geographical distribution of oral tumors in dogs in Switzerland to provide insights into demographics, tumor characteristics, and trends.MethodsThe medical and pathology records of dogs diagnosed with oral tumors from 2012 to 2022 were sourced from diagnostic laboratories in Switzerland. The focus was on histopathologically confirmed oral neoplasms. Inflammatory, viral, and cystic lesions were excluded. Geographic trends were analyzed by use of postal addresses, revealing local distributions.ResultsOf the 948 reports, 773 cases fulfilled the study's criteria. Benign tumors constituted 63% (487 of 773), with peripheral odontogenic fibroma being the most common (77.8% [379 of 487]). Among the malignant tumors, malignant melanoma was the most frequent (38.1% [109 of 286]), followed by squamous cell carcinoma (21% [60 of 286]) and fibrosarcoma (8% [23 of 286]). The locations of tumors varied, with a higher prevalence of malignant melanoma on the lips. Histopathologic findings indicated ulceration and necrosis were more common in malignant tumors. Significant differences were noted in the mitotic index between benign and malignant groups. No tumor predisposition was noted for any breed. Oral tumors were prevalent in older dogs (median age, 9.4 years).ConclusionsThe findings highlighted the predominance of benign tumors in dogs in Switzerland, with specific histopathologic features distinguishing benign from malignant cases.Clinical relevanceUnderstanding the prevalence, types, and geographic distribution of oral tumors based on the representation in dogs in Switzerland may aid in early detection, appropriate diagnostic workup, and informed treatment planning for oral tumors in dogs.

Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1-O-octadecyl-2-O-benzyl-sn-glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its in vivo efficacy in a SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on the prodrug scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) and 4-cyano-benzyl (V2067), that significantly enhanced the in vitro broad-spectrum antiviral activity against multiple RNA viruses when compared to V2043. Here, we demonstrate that V2043, V2053, and V2067 are all orally bioavailable, well-tolerated, and achieve high sustained plasma levels after single oral daily dosing. All three phospholipid prodrugs are significantly more active than RVn in vitro and significantly reduce SARS-CoV-2 lung titers in prophylaxis and treatment mouse models of SARS-CoV-2 B.1.351 infection. On a molar basis, V2043 and V2067 are substantially more active than obeldesivir/GS-5245 and molnupiravir in vivo. Together, these data support the continued development of phospholipid RVn prodrugs for the treatment of SARS-CoV-2 and other RNA viruses of clinical concern.

Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and meta-analyses. However, for orphan diseases, the expectation of having one or multiple RCTs that inform clinical guidelines or justify specific treatments can be unrealistic and subsequent therapeutic nihilism can be detrimental to patients. This article discusses the benefits of therapeutic decision-making in the context of orphan diseases, focusing on primary sclerosing cholangitis (PSC) as an example of an orphan disease with poor clinical outcomes. PSC is a rare disorder characterized by inflammation and progressive fibrosis of the bile ducts. It carries a high risk of liver failure, malignancies, and debilitating symptoms that impair quality of life. Liver transplantation is currently the only life-prolonging intervention for PSC, but it is not a curative option. The article highlights the potential benefits of treating PSC patients with oral vancomycin (OV), which has shown significant clinical responses and improved quality of life in some cases. However, access to OV therapy is limited due to the lack of RCTs supporting its use. The standard requirement of having evidence from RCTs may result in withholding potentially life-altering and/or life-saving treatments for patients with orphan diseases. Conducting RCTs is challenging in these patient populations due to difficulties in recruiting the required patient cohorts and limited commercial returns. A standardized adaptive treatment strategy is proposed to address this. This approach leverages the best available evidence for specific treatments, considers individual clinical responses, and adjusts treatment over time.

BACKGROUND: Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited. METHODS: A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with corresponding 95% confidence intervals (CIs) for all outcomes. RESULTS: A total of three RCTs reported data for 3945 patients with AF and stable CAD. The mean age of patients was 73.8 (±11.85) years and the mean follow-up was 22 months. OAC monotherapy was associated with a significantly reduced relative risk of major bleeding (RR: 0.55, 95% CI: 0.32-0.95) compared to dual therapy. The risk of all-cause death (RR: 0.85, 95% CI: 0.49-1.48), cardiovascular death (RR: 0.84, 95% CI: 0.50-1.41), any stroke event (RR: 0.74, 95% CI: 0.46-1.18), and myocardial infarction (RR: 1.57, 95% CI: 0.79-3.12) remained comparable across the two groups. CONCLUSION: OAC monotherapy led to a significant relative risk reduction for major bleeding with similar rates of ischemic events and mortality compared to dual antithrombotic therapy in patients with AF and stable CAD.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. OBJECTIVES: The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. METHODS: This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. RESULTS: A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. CONCLUSIONS: Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander women. Participants in this study included 1734 Asian (n = 785 case and 949 control participants), 266 Native Hawaiian/Pacific Islander (n = 99 case and 167 control participants), 1149 Hispanic (n = 505 case and 644 control participants), and 24 189 White (n = 9981 case and 14 208 control participants) from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% CIs for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (P ≤ .02) was observed for oral contraceptive (OC) use, parity, tubal ligation, and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in Native Hawaiian/Pacific Islander and Asian women. The inverse association for tubal ligation with risk was most pronounced for Native Hawaiian/Pacific Islander participants (odds ratio (OR) = 0.25; 95% CI, 0.13-0.48) compared with Asian and White participants (OR = 0.68 [95% CI, 0.51-0.90] and OR = 0.78 [95% CI, 0.73-0.85], respectively). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could be due, in part, to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies. This article is part of a Special Collection on Gynecological Cancers.

Chronic pain represents a significant unmet medical need, affecting one-fifth of the U.S. population. EC5026 is a small molecule inhibitor of the enzyme soluble epoxide hydrolase (sEH) which is being developed as a novel non-opioid, non-NSAID analgesic. EC5026 prolongs the action of epoxy fatty acids, endogenous analgesic lipid mediators that are rapidly metabolized by sEH. We evaluated the safety and pharmacokinetic profile of EC5026 in two phase I trials, a single-ascending dose (SAD) study and a fed-fasted study. The SAD study evaluated EC5026 doses ranging from 0.5 to 24 mg in healthy volunteers. EC5026 was well tolerated. No treatment-emergent adverse events were considered related to EC5026. No apparent treatment- or dose-related trends in laboratory results, vital signs, physical examinations, or electrocardiograms were observed. A linear, near-dose-proportional increase in exposure was observed with progressive doses in the SAD study; plasma exposure was below or near the lower limit of quantification after 0.5-2 mg doses. Mean half-lives ranged from 41.8 to 59.1 h. for doses of 8-24 mg, supporting a once-daily dosing regimen. In the fed-fasted study using 8 mg EC5026 tablets, higher peak concentrations (66%) and total exposures (53%) were observed under the fed condition. Plasma concentrations declined in a monoexponential manner with mean half-lives of 59.5 h. in the fed state and 66.9 h. in the fasted state. Future clinical trials using EC5026 for the treatment of pain are justified based on the favorable outcomes from both clinical trials along with preclinical evidence of analgesic activity.

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

PURPOSE OF REVIEW: The aim of this review is to highlight key published oral immunotherapy (OIT) protocols and post-desensitization strategies for the major food allergens and to cover important concepts to consider when evaluating OIT for food-allergic patients. Shared decision-making should help identify patient and family values which will help influence the type of evidence-based protocol and maintenance strategy to use. RECENT FINDINGS: With food OIT emerging as a treatment option, there is a pressing need for patients, physicians, and other providers to have a nuanced understanding of the management choices available to them. There are now randomized controlled trials (RCT) of OIT for peanut, egg, milk, and wheat, and reports of cohorts of patients who have undergone OIT for tree nuts and sesame clinically. The current published protocols contain significant diversity in terms of starting dose, build-up schedule, maintenance dose, and even the product used for desensitization. Emerging data can help direct the long-term maintenance strategy for patients on OIT. Based on patient and family values elicited through the shared decision-making process, an OIT protocol may be selected that balances the level of desensitization, potential side effects, frequency of clinic visits, and potential to induce sustained unresponsiveness, among other factors. Once maintenance dosing is reached, most patients will need to maintain regular exposure to the food allergen to remain desensitized. The option to transition to commercial food products with equivalent amounts of food protein as the OIT maintenance dose would simplify the dosing process and perhaps improve palatability as well. Less frequent or decreased OIT dosing can provide practical benefits but may affect the level of desensitization and safety for some patients.

IntroductionReproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women.MethodsParticipants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence).ResultsYounger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence.DiscussionSeveral aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

Objectives: The objectives of this retrospective study were to analyze telehealth utilization for two specialty care practices: oral medicine (OM) and oral and maxillofacial surgery (OMFS) during the first 2 years of the pandemic, its impact as a new treatment modality and on participating providers, as well as identify the type of patient visit that most readily adopted telehealth. Methods: Retrospective study of patients who sought specialty services, OM and OMFS, at an outpatient clinic in a university health system setting between March 1, 2019, and February 28, 2022. Source data were obtained from Epic, an electronic medical record application. Data were graphed using Tableau and Microsoft Excel software. Statistical analysis was performed utilizing chi-squared test and analysis of variance (ANOVA). Results: OMFS utilized telehealth 12% of the time, and OM 8% of the time. The majority (87%) of telehealth visits were for return patients (RPs). Compared with the first year of the pandemic, there was a decrease in the number of telehealth visits in the second year (p = 0.0001). As of August 2022, new patient (NP) telehealth encounters have largely returned to prepandemic levels (0-1.5%), whereas RP telehealth visits remained at an average level of 11.4% (9.4-12.4%). Surveyed providers consider telehealth as an effective complement to in-person care and will continue its use (4.2/5 Likert scale). Conclusions: Telehealth has become a viable pathway of care for OM and OMFS who previously did not utilize the remote platform to deliver healthcare. As a new treatment modality, telehealth is perceived as impactful in increasing access to specialty care by participating providers. NP visits are now almost completely in person, but telehealth continues for RPs. Ongoing demand for telehealth highlights urgency to develop appropriate standards and effective remote diagnostic/monitoring tools to maximize telehealth's capability to leverage finite health care resources and increase access to specialty care.

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment are of interest in oncology due to ease of administration and lack of need for therapeutic monitoring compared to other anticoagulants. Data supporting their use in patients with hematologic malignancies post-hematopoietic stem cell transplant (HCT) are limited. The purpose of the study is to characterize DOAC use in HCT patients. This multicenter, retrospective cohort analysis included allogeneic and autologous HCT recipients. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB)/minor bleeding and VTE recurrence. Of 126 patients, 91 (72.2%) patients received an autologous HCT, and 35 (27.8%) patients received an allo-HCT. No major bleeding occurred in either transplant recipient groups. In autologous HCT recipients, CRNMB/minor bleeding occurred in four (4.4%) patients and VTE recurrence occurred in one (1.1%) patient. For allogeneic HCT recipients, CRNMB/minor bleeding occurred in five (14.3%) patients and VTE recurrence occurred in two (5.7%) patients. For patients that experienced a CRNMB, five (100%) of the allogeneic HCT and two (50%) of the autologous HCT recipients were thrombocytopenic at the time of bleeding. Only 38.5% of patients who experienced a drug-drug interaction requiring DOAC dose adjustment received the appropriate dose adjustment. DOACs were associated with low rates of recurrent VTE and no major bleeding events, similar to published data on DOAC use in the general cancer patient population. This suggests that DOACs may be safe therapeutic options with proactive management of drug interactions and careful monitoring for bleeding events, especially in the allogeneic HCT population where minor bleeding rates were slightly higher.

BACKGROUND: Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China. METHODS: Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed. RESULTS: A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

INTRODUCTION: Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed. METHODS: Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. RESULTS: The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration. DISCUSSION: Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses.

Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though DOACs are characterized by fixed-dose prescribing and generally do not require routine laboratory drug-level monitoring (DLM), circumstances may arise where the DLM may aid in clinical decision-making, including DOAC dose adjustment, anticoagulant class change, or decisions to withhold or administer reversal agents. We review the current literature that describes high-risk patient groups in which DLM may be beneficial for improved patient anticoagulation management and stewardship. The review also summarizes the limitations of conventional coagulation testing and discuss the emerging utility of quantitative methods for routine and rapid emergent evaluation of DOAC drug levels-in particular, the Anti-Xa activity to detect Factor Xa Inhibitors (rivaroxaban, apixaban, and edoxaban). Both technical and regulatory barriers to widespread DLM implementation are limiting factors to further clinical research that must be overcome, in order to propose universal DOAC DLM strategies and provide clinical-laboratory correlation to formally classify high-risk patient groups.

It is generally believed that bioavailability (F) calculated based on systemic concentration area under the curve (AUC) measurements cannot exceed 1.0, yet some published studies report this inconsistency. We teach and believe, based on differential equation derivations, that rate of absorption has no influence on measured systemic clearance following an oral dose, i.e., determined as available dose divided by AUC. Previously, it was thought that any difference in calculating F from urine data versus that from systemic concentration AUC data was due to the inability to accurately measure urine data. A PubMed literature search for drugs exhibiting F > 1.0 and studies for which F was measured using both AUC and urinary excretion dose-corrected analyses yielded data for 35 drugs. We show and explain, using Kirchhoff's Laws, that these universally held concepts concerning bioavailability may not be valid in all situations. Bioavailability, determined using systemic concentration measurements, for many drugs may be overestimated since AUC reflects not only systemic elimination but also absorption rate characteristics, which is most easily seen for renal clearance measures. Clearance of drug from the absorption site must be significantly greater than clearance following an iv bolus dose for F(AUC) to correctly correspond with F(urine). The primary purpose of this paper is to demonstrate that studies resulting in F > 1.0 and/or greater systemic vs urine bioavailability predictions may be accurate. Importantly, these explications have no significant impact on current regulatory guidance for bioequivalence testing, nor on the use of exposure (AUC) measures in making drug dosing decisions.

Background: This study employed a bidirectional Mendelian Randomization (MR) approach to explore the causal relationships between Oral Lichen Planus (OLP), diabetes mellitus (DM), and glycemic control. It also aims to identify potential pharmacological and herbal treatments that effectively address both OLP and the metabolic dysfunctions associated with DM. Methods: This study employs a two-way MR approach to investigate the potential causal relationships between diabetes type and glycated hemoglobin (HbA1c) levels, and the risk of OLP. We analyzed differentially expressed genes from the OLP dataset in the Genomics Expression Omnibus (GEO) database, cross-referencing these with HbA1c-related genes for enrichment analysis. Additionally, the Drug-Gene Interaction Database (DGIdb) and Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to assess the effectiveness of specific drugs, herbs, and ingredients in treating OLP while managing blood glucose levels. Results: The MR analysis revealed a significant association between Type 1 Diabetes mellitus (T1DM) and an increased risk of OLP, unlike Type 2 Diabetes mellitus (T2DM). This finding indicates a unique immunological interaction in T1DM that may predispose individuals to OLP. The drug prediction analysis focused on core targets linked to OLP and HbA1c, evaluating the therapeutic potential of retinoic acid, prednisone, and thalidomide for treating OLP and regulating blood glucose levels. Additionally, herbal medicines such as Ecliptae herbaand Amygdalus communis vas, along with herbal ingredients like quercetin, luteolin, and 17-beta-estradiol, were identified for their anti-inflammatory properties and potential to mitigate metabolic dysfunction in diabetes. Conclusion: The study highlighted a complex interplay between diabetes and OLP, underscoring the efficacy of integrated therapeutic strategies that target both conditions. The findings suggest that both pharmaceutical and herbal treatments can effectively manage the clinical manifestations of OLP and associated metabolic challenges. This holistic approach to treatment could significantly enhance patient outcomes by addressing the interconnected aspects of these chronic conditions. [ABSTRACT FROM AUTHOR]

Breast cancer is a public health concern worldwide, characterized by increasing incidence and mortality rates, requiring novel and effective therapeutic strategies. Curcumin is a bioactive compound extracted from turmeric with several pharmacological activities. Curcumin is a multifaceted anticancer agent through mechanisms including the modulation of signaling pathways, inhibition of cell proliferation, induction of apoptosis, and production of reactive oxygen species. However, the poor water solubility and bioavailability of curcumin create important barriers in its clinical application. This review elaborates on the therapeutic potential of curcumin in breast cancer treatment, focusing on the efficacy of different administration routes and synergistic effects with other therapeutic agents. The intravenous administration of curcumin-loaded nanoparticles significantly improves bioavailability and therapeutic outcomes compared to oral routes. Innovative formulations, such as nano-emulsifying drug delivery systems, have shown promise in enhancing oral bioavailability. While intravenous delivery ensures higher bioavailability and direct action on tumor cells, it is more invasive and expensive than oral administration. Advancing research on curcumin in breast cancer treatment is essential for improving therapeutic outcomes and enhancing the quality of life of patients. [ABSTRACT FROM AUTHOR]

Adherence and treatment continuation rates of the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) semaglutide for both oral (O‐SEMA) and subcutaneous injection (SEMA‐SC) remain unknown in real‐world clinical practice. This retrospective observational study compared the 12 month adherence and treatment discontinuation of O‐SEMA and once‐weekly SEMA‐SC in patients with type 2 diabetes using a real‐world claims database. SEMA‐SC initiators were 1:1 propensity score‐matched to O‐SEMA initiators. Non‐adherence was defined as <0.8 of the proportion of days covered. SEMA‐SC had a significantly higher odds ratio (OR) for non‐adherence than O‐SEMA (OR: 1.39). The hazard ratio for treatment discontinuation, using O‐SEMA as the reference, was 1.45 for SEMA‐SC, although the discontinuation rate of O‐SEMA was higher during the early stage. O‐SEMA initiators showed significantly higher adherence and greater persistence in therapy than SEMA‐SC initiators at 12 months, which could lead to earlier initiation of GLP‐1RA treatment. [ABSTRACT FROM AUTHOR]

Background: Cyclosporine A (CsA) is used as a steroid-sparing or alternative immunosuppressing agent in cats with various immune-mediated diseases such as immune-mediated hemolytic anemia. Daily treatment dosages of 5–20  mg/ kg have been described. Interindividual variations in CsA blood levels are known to occur. To determine when steady-state conditions are reached and thus the earliest advisable time for monitoring CsA blood levels during the course of treatment, a prospective experimental study was conducted in six healthy adult Domestic Shorthair cats. Materials and methods: Cats were treated with an oral dosage of 7  mg/kg CsA q 12  h for 10  days. On days 1, 2, 3, 5, 7, and 10 after the start of CsA administration (i.e., after 1, 3, 5, 9, 13, and 19 CsA administrations), EDTA blood was collected to measure the CsA level 12  h after the CsA administration (trough values) using high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS). Results: Statistical analysis revealed a significant increase in mean CsA blood levels up to day 5 (2,050  ±  964.2  ng/mL [mean  ±  SD], 832–3,203  ng/mL [minimum–maximum]; repeated-measures ANOVA: p  =  0.0021), while values on days 5 and 7 did not differ significantly from CsA concentrations on day 10. CsA concentrations showed markedly interindividual variability. Conclusion: Cyclosporine A blood levels reached a steady state on day 5 of high dosages of CsA q 12  h (i.e., after nine CsA administrations), indicating that this time point is suitable for monitoring blood levels in clinical patients. Results confirmed the well-known remarkable interindividual variability of CsA, indicating the need for treatment monitoring. The assessed treatment regime resulted in significantly higher mean CsA trough levels than the target range for immunosuppressive therapy (200–600  ng/mL). [ABSTRACT FROM AUTHOR]

Nanoemulsions (NEs) are submicron-sized heterogeneous biphasic liquid systems stabilized by surfactants. They are physically transparent or translucent, optically isotropic, and kinetically stable, with droplet sizes ranging from 20 to 500 nm. Their unique properties, such as high surface area, small droplet size, enhanced bioavailability, excellent physical stability, and rapid digestibility, make them ideal for encapsulating various active substances. This review focuses on recent advancements, future prospects, and challenges in the field of NEs, particularly in oral, parenteral, and ophthalmic delivery. It also discusses recent clinical trials and patents. Different types of in vitro and in vivo NE characterization techniques are summarized. High-energy and low-energy preparation methods are briefly described with diagrams. Formulation considerations and commonly used excipients for oral, ocular, and ophthalmic drug delivery are presented. The review emphasizes the need for new functional excipients to improve the permeation of large molecular weight unstable proteins, oligonucleotides, and hydrophilic drugs to advance drug delivery rapidly. [ABSTRACT FROM AUTHOR]

Myiasis is a disease caused by fly larvae from the Diptera order settling in various tissues and organs of humans or animals. To report the diagnosis of myiasis larvae invading the oral and nasal cavities of patients in the management of intensive care units and to draw attention to the poor hygiene situation. A 78-year-old male patient diagnosed with cancer and a 93-year-old male patient diagnosed with ischemic cerebrovascular disease were followed up in the intensive care unit. On the 21st day of the cancer patient's hospitalization, eight larvae were removed from the oral cavity. In the first month of the other patient's hospitalization, six larvae were seen in the patient's nasal osteum near the feeding tube. A clinical diagnosis of myiasis was made and the larvae were initially manually removed for treatment, followed by medication. In conclusion, myiasis is a rare condition, but good hygiene, correct diagnosis, and treatment are necessary to prevent further harm to those who have risk factors such as immunosuppression, poor hygiene, malnutrition, diabetes, and peripheral vascular disease, particularly those who are hospitalized. [ABSTRACT FROM AUTHOR]

Objectives: Sedation before veterinary visits is advocated to help reduce fear and anxiety in cats and facilitate safe handling. The aim of this study was to evaluate the effectiveness of trazodone, gabapentin and a trazodone/gabapentin combination for oral sedation in healthy feline patients before blood donation. Methods: A total of 21 cats were included in the study. Baseline sedation scores were obtained, and cats were randomly assigned to receive oral trazodone at 5 mg/kg (T), oral gabapentin at 10 mg/kg (G), their combination (TG) or placebo (control group). A sedation score was obtained 1 h after drug administration. A blood sample was obtained at the time of blood collection for quantification of drug plasma concentrations. Agreement between observers was tested with a Cohen's Kappa test. Sign tests to compare change within treatment and a Skilling–Mack rank ANOVA to test for differences between groups were performed to compare pre- and post-sedation scores as well as a magnitude of differences over time between the groups. A Spearman's rank correlation coefficient test was used to correlate sedation scores with drug plasma concentrations. Results: Post-sedation final scores were significantly higher only in the T (P = 0.022) and TG groups (P <0.001). The magnitude of change between pre- and post-sedation scores was larger in the TG (P <0.0032) and T groups (P <0.038) compared with the control group. There were no other significant differences between the groups. There was no correlation between drug plasma concentrations and sedation scores in any of the groups. Conclusions and relevance: Administration of oral trazodone alone at 5 mg/kg or in combination with gabapentin at 10 mg/kg resulted in significant sedation in healthy cats with no evident side effects. The degree of sedation was more profound when both drugs were combined, but a gabapentin dose of 10 mg/kg alone failed to provide significant sedation in this population. [ABSTRACT FROM AUTHOR]

Introduction: Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed. Methods: Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. Results: The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration. Discussion: Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses. [ABSTRACT FROM AUTHOR]

Background: The new frontiers of computer-based surgery, technology, and material advances, have allowed for customized 3D printed manufacturing to become widespread in guided bone regeneration (GBR) in oral implantology. The shape, structural, mechanical, and biological manufacturing characteristics achieved through 3D printing technologies allow for the customization of implant-prosthetic rehabilitations and GBR procedures according to patient-specific needs, reducing complications and surgery time. Therefore, the present narrative review aims to elucidate the 3D-printing digital radiographic process, materials, indications, 3D printed manufacturing-controlled characteristics, histological findings, complications, patient-reported outcomes, and short- and long-term clinical considerations of customized 3D printed mesh, membranes, bone substitutes, and dental implants applied to GBR in oral implantology. Methods: An electronic search was performed through MEDLINE/PubMed, Scopus, BioMed Central, and Web of Science until 30 June 2024. Results: Three-dimensionally printed titanium meshes and bone substitutes registered successful outcomes in vertical/horizontal bone defect regeneration. Three-dimensionally printed polymeric membranes could link the advantages of conventional resorbable and non-resorbable membranes. Few data on customized 3D printed dental implants and abutments are available, but in vitro and animal studies have shown new promising designs that could improve their mechanical properties and tribocorrosion-associated complications. Conclusions: While 3D printing technology has demonstrated potential in GBR, additional human studies are needed to evaluate the short- and long-term follow-up of peri-implant bone levels and volumes following prosthetic functional loading. [ABSTRACT FROM AUTHOR]

Calcifying odontogenic cyst, also known as Gorlin cyst is a rare benign cystic lesion primarily found in the jawbones, accounting less than 1% of odontogenic cysts. It can be associated with odontogenic tumors such as odontomas. We report a rare case of COC associated with complex odontoma in a young patient and discuss its clinical features, diagnosis, and treatment options. An 18-year-old female patient presented with a painless radiopaque lesion of the right mandibular bone at Oral Medicine and Oral Surgery department. Radiographs revealed irregular tooth-like structures in the canine-premolar area. The lesion was surgically removed, and histopathology confirmed COC with a complex odontoma. As of the World Health Organization's 2022 definition, COC is a developmental odontogenic cyst characterized by calcified ghost cells. It typically affects individuals during their second and third decades of life, with no gender preference, almost equally in the maxilla and the mandible. The main treatment is total enucleation, with a generally favorable prognosis. Histopathology is essential for diagnosis due to its mimicry of other jaw conditions. Long-term follow-up is needed to prevent recurrences. [ABSTRACT FROM AUTHOR]

Oral lichen planus is a frequent, chronic autoimmune disease that affects the oral mucosa and is characterized as an oral potentially malignant disorder. The aim of our study is to examine the presence of CSCs bearing CD147 (a marker related to local inflammation and associated with various cancers) through immunohistochemistry in oral lichen planus (OLP) compared to oral leukoplakia (OL) and healthy tissues. These findings could contribute to clinical practice by providing a marker for the prognostic assessment of OLP lesions with regards to their potentially malignant nature. The study sample consisted of paraffin-embedded oral mucosa specimens from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece during the period 2009–2019. The study sample contained 24 cases of OLP (14 erosive and 10 reticular) and 30 cases of oral leukoplakia, which were compared to 5 normal oral epithelium samples derived from healthy epithelium adjacent to fibromas from other cases. Cell membrane staining of CD147 was observed mostly in the basal and parabasal cell layer. The statistically significantly higher expression of CD147 in the erosive lichen planus subgroup than in the moderately and severely dysplastic leukoplakia subgroup (p = 0.01) constituted the most important finding of this study. The characteristic expression of CD147 in erosive OLP suggests the presence of epithelial cells with CSC characteristics, but its lower expression in oral leukoplakias suggests a more intense relation of the CD147 marker with inflammation rather than with oral dysplastic progression. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, debilitating episodes of submucosal and/or subcutaneous tissue swelling, which may be life‐threatening depending on anatomic location. The two primary management strategies for HAE are ready access to effective on‐demand treatment in all patients and the prevention of attacks (short‐term prophylaxis [STP] and long‐term prophylaxis [LTP]) in appropriate patients. All approved on‐demand and most LTP medications require subcutaneous or intravenous administration. Injection‐related challenges include trypanophobia (fear of needles), difficulty with self‐administration, injection‐site reactions (e.g., pain, erythema, bleeding, bruising), and anxiety—all contributing to poor compliance and administration delays. Oral HAE treatments may improve outcomes by reducing treatment barriers. Aim: To review oral therapies, approved or in development, for on‐demand treatment and/or prevention of HAE attacks. Materials and Methods: To provide a comprehensive review, data was obtained from publicly available resources through a targeted PubMed literature review and supplemented by information provided on company websites (search cutoff of May 31, 2024). Results: Berotralstat, an oral plasma kallikrein (PKa) inhibitor, is approved for LTP. Sebetralstat, another PKa inhibitor, is the investigational first oral on‐demand HAE treatment to complete a phase 3 trial. Deucrictibant, an oral bradykinin B2 receptor antagonist, has completed phase 2 trials for on‐demand therapy and LTP. Several other oral PKa inhibitors (ATN249, VE‐4666, and VE‐4062) are in early development for LTP. Conclusion: Substantial advances have been made in the development of oral treatments for HAE. These treatments have the potential to improve and optimize clinical outcomes, satisfaction, and quality of life among patients with HAE. [ABSTRACT FROM AUTHOR]

Abstract Adherence and treatment continuation rates of the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) semaglutide for both oral (O‐SEMA) and subcutaneous injection (SEMA‐SC) remain unknown in real‐world clinical practice. This retrospective observational study compared the 12 month adherence and treatment discontinuation of O‐SEMA and once‐weekly SEMA‐SC in patients with type 2 diabetes using a real‐world claims database. SEMA‐SC initiators were 1:1 propensity score‐matched to O‐SEMA initiators. Non‐adherence was defined as

Background There is scant data regarding the use of oral disease-modifying treatments (oDMT) in patients with relapsing–remitting multiple sclerosis (PwRRMS) from Saudi Arabia. Objective This study aimed to identify the response rate to oDMT in PwRRMS compared to interferon (IFN) in terms of achieving no evidence of disease activity-3 (NEDA-3). Methods This retrospective study was conducted at a tertiary care hospital in Saudi Arabia and included all adult PwRRMS over a 2-year period who were on oDMTs or IFN for

Background This study employed a bidirectional Mendelian Randomization (MR) approach to explore the causal relationships between Oral Lichen Planus (OLP), diabetes mellitus (DM), and glycemic control. It also aims to identify potential pharmacological and herbal treatments that effectively address both OLP and the metabolic dysfunctions associated with DM. Methods This study employs a two-way MR approach to investigate the potential causal relationships between diabetes type and glycated hemoglobin (HbA1c) levels, and the risk of OLP. We analyzed differentially expressed genes from the OLP dataset in the Genomics Expression Omnibus (GEO) database, cross-referencing these with HbA1c-related genes for enrichment analysis. Additionally, the Drug-Gene Interaction Database (DGIdb) and Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to assess the effectiveness of specific drugs, herbs, and ingredients in treating OLP while managing blood glucose levels. Results The MR analysis revealed a significant association between Type 1 Diabetes mellitus (T1DM) and an increased risk of OLP, unlike Type 2 Diabetes mellitus (T2DM). This finding indicates a unique immunological interaction in T1DM that may predispose individuals to OLP. The drug prediction analysis focused on core targets linked to OLP and HbA1c, evaluating the therapeutic potential of retinoic acid, prednisone, and thalidomide for treating OLP and regulating blood glucose levels. Additionally, herbal medicines such as Ecliptae herbaand Amygdalus communis vas, along with herbal ingredients like quercetin, luteolin, and 17-beta-estradiol, were identified for their anti-inflammatory properties and potential to mitigate metabolic dysfunction in diabetes. Conclusion The study highlighted a complex interplay between diabetes and OLP, underscoring the efficacy of integrated therapeutic strategies that target both conditions. The findings suggest that both pharmaceutical and herbal treatments can effectively manage the clinical manifestations of OLP and associated metabolic challenges. This holistic approach to treatment could significantly enhance patient outcomes by addressing the interconnected aspects of these chronic conditions.

BACKGROUND: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). HYPOTHESIS: An externally validated model improves ICH risk stratification. METHODS: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. RESULTS: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. CONCLUSIONS: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

BACKGROUND: In clinical practice, females with MS often report menstrually-related symptom fluctuations. Hypothetically, use of oral contraceptives (OCs) could reduce these fluctuations, particularly continuous OCs (11+ weeks of consistent exogenous hormones followed by 1 week placebo). OBJECTIVES: To prospectively capture (1) whether neurologic and generalized symptoms vary with menstrual cycle phase and (2) whether type of contraception impacts symptom fluctuations. METHODS: In this two-center pilot study, females with MS and a regular menstrual cycle prospectively tracked their menstrual cycles and completed symptom surveys for up to 6 months. Participants were categorized as 1) users of oral contraceptives, either a) cyclic or b) continuous, or 2) endogenously cycling, either c) hormonal intrauterine device (IUD) users or d) none users (e.g. no hormonal contraception; included condoms, copper IUD, tubal ligation, fertility awareness methods). There was no correction for multiple analyses. RESULTS: Altogether, 47/70 participants (67%) provided >4 weeks of data and were included in the analyses. Mean (SD) age was 35.0 (0.9) years, median (IQR) EDSS was 1.5 (1-2) and mean (SD) SymptoMScreen score was 10.4 (9.6). For endogenously cycling patients (IUD and none users), fatigue (MFIS) was lower in the perimenstrual period than in the luteal period (p

This study presents the results of systematic reviews on adjunctive tools in screening and diagnosis of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) and to determine if the current literature supports their use as either an adjunctive tool or replacement of gold standard techniques. Systemic reviews and meta-analysis that evaluated adjunctive tools including chemiluminescence, tissue autofluorescence, tissue fluorescence spectroscopy, vital staining and cytology techniques were systematically examined using AMSTAR II. Twenty-seven systematic reviews were included. Five studies had a low quality of evidence, and nine studies had a critically low quality of evidence. This review found limited evidence to recommend chemiluminescence, tissue autofluorescence tools and vital staining as diagnostic tools, but only serve as clinical adjuncts to conventional oral examination. Cytology techniques and narrow-band imaging may be utilised as a non-invasive diagnostic adjunctive tool for the detection of OSCC and the malignant transformation of OPMD. In conclusion, this paper provides evidence on several types of adjunctive tools and provides recommendations on their use in clinical practice. These tools are considered useful as clinical adjuncts but there is insufficient evidence for their use as a diagnostic tool to replace gold standard conventional oral examination and surgical biopsy.

Statement of the Problem: One of the main signs of cancer development is increasing of cell proliferation activity. Expression of the Ki-67 as a cell proliferation marker is extensively utilized in pathology studies as an indicator of proliferation in human tumors. According to studies, Ki-67 plays an effective role in the pathology of malignant and pre-malignant oral mucosa lesions. Purpose: The current study aimed to systematically review the Ki-67 expression in oral lichen planus without dysplasia and compare it with oral epithelial dysplasia. Materials and Method: In this meta-analysis, all articles in the English language were searched in databases including Web of Science, PubMed, Embase, Scopus, and Google Scholar until July 2023. MeSH terms and free keywords were used in the search step. Expression of Ki-67 in oral lichen planus and oral epithelial dysplasia was analyzed by Comprehensive Meta-Analysis software. Results: Nine hundred and two articles related to the searched words were found. According to the selection criteria, 12 retrospective articles were selected. Low quality was not observed in any of the records by the Newcastle-Ottawa scale and most of them had a relatively good quality. Totally, 593 patients were examined. The heterogeneity between studies was not significant. The meta-analysis results indicated a significantly lower Ki-67 expression in oral lichen planus without dysplasia in comparison to oral epithelial dysplasia. Conclusion: The more intense expression level of Ki-67 in oral epithelial dysplasia compared with oral lichen planus was observed. The ki-67 expression could be utilized to indicate the existence and intensity of epithelial dysplasia and disease progression. [ABSTRACT FROM AUTHOR]

Background: Functional endoscopic sinus surgery (FESS) is a common procedure for the treatment of chronic sinusitis and minimal bleeding inside the narrow surgical field affects the surgical visualization, prolongs operative time, and increases ocular and intracranial injuries. Our study aims to evaluate and compare the effectiveness of oral versus intravenous Tranexamic acid on surgical field bleeding in endoscopic sinus surgery. Methods: A prospective, randomized, controlled trial enrolled 159 participants (ASA I-II, both sex and age 18–40 years) undergoing FESS who were equally randomized into 3 groups. Group O received 2 gm of TXA orally 2 hours before surgery, Group I received 15 mg/kg of IV TXA slowly after induction of anesthesia, and Group C didn't receive any. Intraoperative surgical field bleeding was assessed by the Wormald grading scale and Surgeon satisfaction on a 5-point Likert scale. At 24 hours post-operatively, the incidence of nasal bleeding, PONV, and D-dimer level were recorded. Results: Showed significantly higher surgical field score, duration of surgery, recovery time, and postoperative (24 hours) D-dimer in group-C (p-value <0.001) with no difference between groups-I and O, while surgeon satisfaction was significantly lower in group-C (p-value <0.001) with no difference between groups-I and O. No differences regarding hemodynamic parameters, postoperative bleeding, pain, and PONV were found. Conclusions: Oral TXA was safe, cheap, and as effective as IV TXA regarding surgical field visualization, surgeon satisfaction, and operative time during FESS; with limited adverse effects and no evidence of thromboembolic complications. [ABSTRACT FROM AUTHOR]

Zulfa Fidi Pranadwista,1 Novia Tri Hasanah,1 Nanan Nur’aeny2 1Oral Medicine Residency Program, Faculty of Dentistry, Padjadjaran University, Bandung, Indonesia; 2Department of Oral Medicine, Faculty of Dentistry, Padjadjaran University, Bandung, IndonesiaCorrespondence: Zulfa Fidi Pranadwista, Email zulfa21004@mail.unpad.ac.idBackground: Oral cavity is the gateway to the digestive system and a window to general human health. Anemia is one of the health problems in the world characterized by various clinical conditions, including in the oral cavity.Purpose: This case report aims to present the results of a clinical investigation of a patient who had oral hematoma and anemia with indigestion symptoms.Case Presentation: A 59-year-old male complained of a lump on his tongue two months prior, which was painless and frequently bleeding. The complaint was followed by abdominal discomfort, difficulty defecating, weight loss, and decreased appetite. The patient only ate porridge and lacked water intake. Intraoral examination showed a blackish-red, irregularly shaped, painless hematoma on the dorsum of the tongue and a negative diascopy test. Hematology examination showed anemia with hemoglobin 6.7g/dL, hematocrit 21.4%, erythrocytes 3.08 x 106/μL, MCV 69.5fL, MCH 21.8pg, and MCHC 31.3g/dL. The diagnosis of the tongue lesion was an oral hematoma.Case Management: Pharmacologic therapy included antifibrinolytic agents and hematinic supplementation. Non-pharmacologic therapy included dental health education, a balanced lifestyle, and avoiding triggers for tongue bleeding. Management in other fields was also carried out in parallel, including oral surgery and internal medicine. The general condition of the patient general condition improved through multidisciplinary monitoring.Conclusion: Clinical investigations that include signs and symptoms of disease in a patient with bleeding disorders such as hematoma and anemia need to be carried out in detailed aid examinations, especially if other symptoms are found, such as digestive disorders.Keywords: anemia, bleeding, hematoma, indigestion, oral

Chronic nonhealing ulcers of the oral mucosa and lateral tongue, in particular, can transform into invasive oral squamous cell carcinoma (OSCC). Sometimes these ulcers do not heal even after the removal of the etiological agent that actually initiated these lesions, something similar to what happens in “neoplasia.” Numerous factors have been postulated in the literature; however, the exact mechanism remains unclear. We hereby would suggest few plausible factors that could be considered for future studies to shed light on some untapped territories in the pathogenesis of OSCC arising from chronic nonhealing traumatic ulcers in purview of chromoanagenesis and the concepts of “quantum entanglement and coherence.”

Abstract Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the ACC exhibited diverse levels of species richness. We identified two main microbial subtypes within the ACC: oral-like and gut-like. Oral-like microbiomes, characterized by increased diversity and abundance of Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with a less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with a more diverse microbiome, less aggressive tumor phenotype, and better survival that reveal the genera as potential pancancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. Conversely, gut-like intratumoral microbiomes, which feature low diversity and colonization by gut mucus layer-degrading species, such as Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival and positively correlated with tumor cell biosynthesis of glycan-based cell membrane components.

Background: This research main objective was to evaluate a proliposomes (PLs) formulation for the enhancement of oral bioavailability of ginsenosides, using ginsenoside Rg3 (Rg3) as a marker. Methods: A novel PLs formulation was prepared using a modified evaporation-on-matrix method. Soy phosphatidylcholine, Rg3-enriched extract, poloxamer 188 (Lutrol® F 68) and sorbitol were mixed and dissolved using a aqueous ethanolic solution, followed by the removal of ethanol and lyophilization. The characterization of Rg3-PLs formulations was performed by powder X-ray diffractometry (PXRD), transmission electron microscopy (TEM) and in vitro release. The enhancement of oral bioavailability was investigated and analyzed by non-compartmental parameters after oral administration of the formulations. Results: PXRD of Rg3-PLs indicated that Rg3 was transformed from crystalline into its amorphous form during the preparation process. The Rg3-encapsulated liposomes with vesicular-shaped morphology were generated after the reconstitution by gentle hand-shaking in water; they had a mean diameter of approximately 350 nm, a negative zeta potential (−28.6 mV) and a high entrapment efficiency (97.3%). The results of the in vitro release study exhibited that significantly more amount of Rg3 was released from the PLs formulation in comparison with that from the suspension of Rg3-enriched extract (control group). The pharmacokinetic parameters after oral administration of PLs formulation in rats showed an approximately 11.8-fold increase in the bioavailability of Rg3, compared to that of the control group. Conclusion: The developed PLs formulation could be a favorable delivery system to improve the oral bioavailability of ginsenosides, including Rg3.

Oral melanoma is a malignant neoplasm of melanocytes, characterized by aggressive behavior and an extremely poor prognosis. Melanomas in the oral cavity are rare and are usually diagnosed at an advanced stage, reducing patient survival. The aim of this narrative literature review is to compile the essential aspects of oral melanoma and other pigmentations to guide early diagnosis by the dentist. Comprehensive searches were conducted in the PubMed, Embase, Lilacs, and Cochrane databases. Oral melanoma typically presents as a macule or nodule, brown or black in color, and may show variations in color and even depigmentation. It has a predilection for the palate and maxillary gingiva, is usually asymptomatic, and affects slightly more males, especially between the 4th and 7th decades of life. Although they share similar clinical characteristics with cutaneous melanoma, they are considered distinct variants. Dentists must be aware of the main clinical characteristics of oral melanoma and other pigmentations of the oral cavity to make an early diagnosis of the neoplasm and manage the case appropriately.

This article is part of a didactic perspective. He is interested in oral didactics in a university setting. Through this experimental research, we wanted to demonstrate that the interaction between subtitles and visual modality is an essential contribution to oral comprehension (global and detailed) and vocabulary learning through the subtitled audio-visual medium. Our method consists of using a video in two modes of presentation with two distinct groups: the first without subtitles and the second with subtitles. We also used an experimental post questionnaire to find out if students would have liked to have had the text transcribed.

Background The diagnostic use of saliva for systemic and oral disor- ders is reviewed in this article. Saliva has unique advantages over serum as a diagnostic fluid because it is non-invasive and can be obtained by anyone with a little training. Saliva may also provide a financially reasonable way to screen large populations. Saliva from a single large salivary gland can be used to diagnose diseases unique to that gland. However, because whole saliva is easy to obtain and contains serum components, it is commonly used to diagnose oral and systemic disorders. However, saliva contains a more diverse microbial habitat and a lower concentration of biomolecules compared to blood, which may have an unexpected impact on the detection results. Purpose These issues will eventually be solved by creating and develop- ing a highly sensitive detection platform, and saliva testing will likely open new horizons for saliva detection. Identify the disease . Researchers use a variety of techniques and techniques in an attempt to identify salivary biomarkers for systemic and oral disorders inLast few years. The review aspires to provide a comprehensive perspective on salivary biomarkers in relation to oral and systemic diseases. Saliva analysis may be useful in di- agnosing genetic disorders, autoimmune diseases, malignant and infectious diseases, and endocrine disorders, as well as in assessing therapeutic levels of drugs and monitoring illicit drug use. Conclusion The various tasks that saliva completes in the oral cavity are accomplished by the biochemical, physical, and interaction character- istics of these salivary constituents. These days, there are numerous assays available to examine different salivary parameters; nevertheless, in order to get significant data, collection and storage procedures must be standard- ized.

Jiawen Zhang,1,&ast; Duoduo Gu,2,&ast; Yang Yan,3,&ast; Ruoxin Pan,2 Hui Zhong,4,5 Chengfeng Zhang,1 Yang Xu2 1Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Cardiology, Ren Ji Hospital of Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China; 5School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengfeng Zhang; Yang Xu, Email e3dangdang@hotmail.com; yangxu@njmu.edu.cnAbstract: Rosacea is a chronic inflammatory skin disease that affects a patient’s appearance and quality of life. It mainly affects the midface region and presents as erythema, flushing, telangiectasia, papules, pustules, and rhinophyma. Despite its prevalence, the precise pathophysiology of rosacea remains unknown, and novel pharmacological therapies are currently under investigation. Tranexamic acid (TA) is a synthetic, lysine-like compound that competitively inhibits fibrinogen production by synthesizing fibrinolytic enzymes. In addition to its popular application in hemorrhage treatment, TA has been used to manage a number of skin conditions, including melasma, chronic urticaria, and angioedema. TA is a better option for melasma treatment. However, the role of TA in treating rosacea has not yet been systematically elucidated. In this study, we reviewed all available literature on the use of TA for rosacea treatment. The included articles examined the therapeutic effects of TA in patients with rosacea, including traditional methods such as oral and topical administration and more novel approaches such as intradermal injections, microneedling, and laser-assisted delivery. Several recent clinical studies demonstrated that TA alleviates rosacea symptoms by restoring the permeability barrier, ameliorating the immune reaction, and inhibiting angiogenesis. In this review, we summarized the function and potential application of TA in rosacea treatment, aiming to facilitate the implementation of clinical applications.Keywords: rosacea, tranexamic acid, topical, oral, microinjection

Pyrocurzerenone is a natural compound found in Curcuma zedoaria and Chloranthus serratus. However, the anticancer effect of pyrocurzerenone in oral cancer remains unclear. Using the MTT assay, wound healing assay, transwell assay and western blot analysis, we investigated the impact of pyrocurzerenone on antimetastatic activity, as well as the critical signalling pathways that underlie the processes of oral cancer cell lines SCC‐9, SCC‐1 and SAS in this work. Our findings suggested that pyrocurzerenone inhibits cell migration and invasion ability in oral cancer cell lines. Furthermore, phosphorylation of ERK1/2 had significant inhibitory effects in SCC‐9 and SCC‐1 cell lines. Combining ERK1/2 inhibitors with pyrocurzerenone decreased the migration and invasion activity of SCC‐9 and SCC‐1 cell lines. We also found that the expressed level of cathepsin S decreased under pyrocurzerenone treatment. This study showed that pyrocurzerenone reduced ERK1/2 expression of the proteins and cathepsin S, suggesting that it could be a valuable treatment to inhibit human oral cancer cell metastasis. [ABSTRACT FROM AUTHOR]

Objective: To study the mandibular changes in the β-thalassemia major patient. Study Design: Cross sectional study. Setting: Husaini Blood Bank and Institute of Hematological Diseases Karachi, Department of Oral and Maxillofacial Surgery, and Department of Orthodontics, Baqai Dental College Baqai Medical University, Karachi. Period: January 2023-December 2023. Methods: 50 Orthopanthogram (OPG) radiographs of beta-thalassemia major patient were taken, analyzed and compared to check any variation from normal. Fifty diagnosed β-thalassemia major patients were voluntarily selected through convenience sampling. The study was carried out in collaboration of Husaini Institute of Blood Diseases Karachi, National institute of Oral Diseases Karachi Pakistan and, Department of Oral and Maxillofacial Surgery and department of orthodontics Baqai Dental College Baqai Medical University. Results: 18 (36%) patient's alteration of trabecular pattern are present and in 32 (64%) patient alteration of trabecular pattern absent. Similarly, in 16 (32%) patients have short spiky roots are present and 34 (68%) patients short spiky roots absent. Conclusion: Effect of anemia is not so profound in mandible of thalassemia patients from population of Karachi. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential of polycaprolactone–vitamin E TPGS (PCL-TPGS) micelles as a delivery system for oral administration of paclitaxel (PTX). The PCL-TPGS copolymer was synthesized using ring opening polymerization, and PTX-loaded PCL-TPGS micelles (PTX micelles) were prepared via a co-solvent evaporation method. Characterization of these micelles included measurements of size, polydispersity, and encapsulation efficiency. The cellular uptake of PTX micelles was evaluated in Caco-2 cells using rhodamine 123 (Rh123) as a fluorescent probe. Moreover, an everted rat sac study was conducted to evaluate the ex vivo permeability of PTX micelles. Additionally, a comparative pharmacokinetic study of PTX micelles versus the marketed formulation, Ebetaxel® (a Taxol generic), was performed after a single oral administration to rats. The results demonstrated that the micellar formulation significantly improved PTX solubility (nearly 1 mg/mL). The in vitro stability and release of PTX micelles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) demonstrated that PTX micelles remained stable for up to 24 h and significantly slowed the release of PTX in both media compared to Ebetaxel®. The in vitro cellular uptake, ex vivo intestinal permeability, and in vivo pharmacokinetic profile demonstrated that PTX micelles enhanced the permeability and facilitated a rapid absorption of the drug. Conclusively, the PCL7000-TPGS3500 micelles exhibit potential as an effective oral delivery system for PTX. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the ACC exhibited diverse levels of species richness. We identified two main microbial subtypes within the ACC: oral-like and gut-like. Oral-like microbiomes, characterized by increased diversity and abundance of Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with a less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with a more diverse microbiome, less aggressive tumor phenotype, and better survival that reveal the genera as potential pancancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. Conversely, gut-like intratumoral microbiomes, which feature low diversity and colonization by gut mucus layer-degrading species, such as Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival and positively correlated with tumor cell biosynthesis of glycan-based cell membrane components. [ABSTRACT FROM AUTHOR]

The oral cavity remains an underappreciated site for SARS-CoV-2 infection despite the myriad of oral conditions in COVID-19 patients. Recently, SARS-CoV-2 was shown to replicate in the salivary gland cells causing tissue inflammation. Given the established association between inflammation and microbiome disruption, we comparatively profiled oral microbial differences at a metagenomic level in a cohort of hospitalized COVID-19 patients and matched healthy controls. Specifically, we aimed to evaluate colonization by the opportunistic fungal pathogen Candida albicans, the etiologic agent of oral candidiasis. Comprehensive shotgun metagenomic analysis indicated that, overall, COVID-19 patients exhibited significantly reduced bacterial and viral diversity/richness; we identified 12 differentially abundant bacterial species to be negatively associated with COVID-19, and the functional pathways of certain bacteria to be highly associated with COVID-19 status. Strikingly, C. albicans was recovered from approximately half of the COVID-19 subjects but not from any of the healthy controls. The prevalence of Candida is likely linked to immune hypo-dysregulation caused by COVID-19 favoring Candida proliferation, warranting investigations into the interplay between Candida and SARS-CoV2 and potential therapeutic approaches directed toward oral candidiasis. Collectively, our findings prompt a reassessment of oral opportunistic infection risks during COVID-19 disease and their potential long-term impacts on oral health. [ABSTRACT FROM AUTHOR]