Combined Treatment Research Articles

Assessing Treatments to Mitigate End-Face Cracking in Air-Dried Acacia dealbata Logs

Acacia dealbata Link, known as Mimosa in Portugal, is an invasive hardwood species with potential for construction use, but research is limited. The available stock of small-diameter juvenile wood logs can help reduce this gap, but tangential cracking at log ends challenges fastener connections. This study evaluated different treatments to control and reduce end-face cracking in small wood logs during air drying, an economical and environmentally friendly procedure. The extreme two-thirds of sixteen Mimosa logs were subjected to two treatments: one with longitudinal kerfs 15 mm deep along the length (two and three kerfs) and the other with a hollow in the center up to half the length (16 mm and 30 mm diameters). Over 219 days of air drying and compared with the central part, kerfing treatments significantly reduced outer-wood tangential cracking (p < 0.001), with the three kerfs also reducing crack numbers (p < 0.05) but increasing significantly cracks near the pith (p < 0.01). The 30 mm central hollow significantly reduced central perforation cracking (p < 0.05). Prospectively, the results suggest that a combined treatment approach involving cross-cuts could help reduce and/or control end cracking, thereby improving the suitability of wild Mimosa logs for construction use.

Assessing Treatments to Mitigate End-Face Cracking in Air-Dried Acacia dealbata Logs

Acacia dealbata Link, known as Mimosa in Portugal, is an invasive hardwood species with potential for construction use, but research is limited. The available stock of small-diameter juvenile wood logs can help reduce this gap, but tangential cracking at log ends challenges fastener connections. This study evaluated different treatments to control and reduce end-face cracking in small wood logs during air drying, an economical and environmentally friendly procedure. The extreme two-thirds of sixteen Mimosa logs were subjected to two treatments: one with longitudinal kerfs 15 mm deep along the length (two and three kerfs) and the other with a hollow in the center up to half the length (16 mm and 30 mm diameters). Over 219 days of air drying and compared with the central part, kerfing treatments significantly reduced outer-wood tangential cracking (p < 0.001), with the three kerfs also reducing crack numbers (p < 0.05) but increasing significantly cracks near the pith (p < 0.01). The 30 mm central hollow significantly reduced central perforation cracking (p < 0.05). Prospectively, the results suggest that a combined treatment approach involving cross-cuts could help reduce and/or control end cracking, thereby improving the suitability of wild Mimosa logs for construction use.

Success of Combination Therapy with Isavuconazole in a Pediatric Patient with Breakthrough Invasive Aspergillosis

AbstractThe increasing incidence of invasive fungal infections, coupled with the growing population of immunocompromised patients, has led to an increased need for antifungal agents. The newest azole, isavuconazole, plays an important role in the treatment of invasive aspergillosis in adults due to its broad spectrum, tolerability, and no need for therapeutic drug monitoring. This agent, which has not yet been approved for use in children, has significant problems with drug supply in Türkiye. We present the treatment response to isavuconazole combination therapy used in salvage treatment in a patient with breakthrough invasive aspergillosis, who had treatment failure with different antifungal combination treatment options and surgical resection.

Memory effects of prior subculture may impact the quality of multiomic perturbation profiles

Mass spectrometry-based omics technologies are increasingly used in perturbation studies to map drug effects to biological pathways by identifying significant molecular events. Significance is influenced by fold change and variation of each molecular parameter, but also by multiple testing corrections. While the fold change is largely determined by the biological system, the variation is determined by experimental workflows. Here, it is shown that memory effects of prior subculture can influence the variation of perturbation profiles using the two colon carcinoma cell lines SW480 and HCT116. These memory effects are largely driven by differences in growth states that persist into the perturbation experiment. In SW480 cells, memory effects combined with moderate treatment effects amplify the variation in multiple omics levels, including eicosadomics, proteomics, and phosphoproteomics. With stronger treatment effects, the memory effect was less pronounced, as demonstrated in HCT116 cells. Subculture homogeneity was controlled by real-time monitoring of cell growth. Controlled homogeneous subculture resulted in a perturbation network of 321 causal conjectures based on combined proteomic and phosphoproteomic data, compared to only 58 causal conjectures without controlling subculture homogeneity in SW480 cells. Some cellular responses and regulatory events were identified that extend the mode of action of arsenic trioxide (ATO) only when accounting for these memory effects. Controlled prior subculture led to the finding of a synergistic combination treatment of ATO with the thioredoxin reductase 1 inhibitor auranofin, which may prove useful in the management of NRF2-mediated resistance mechanisms.

Success of Combination Therapy with Isavuconazole in a Pediatric Patient with Breakthrough Invasive Aspergillosis

AbstractThe increasing incidence of invasive fungal infections, coupled with the growing population of immunocompromised patients, has led to an increased need for antifungal agents. The newest azole, isavuconazole, plays an important role in the treatment of invasive aspergillosis in adults due to its broad spectrum, tolerability, and no need for therapeutic drug monitoring. This agent, which has not yet been approved for use in children, has significant problems with drug supply in Türkiye. We present the treatment response to isavuconazole combination therapy used in salvage treatment in a patient with breakthrough invasive aspergillosis, who had treatment failure with different antifungal combination treatment options and surgical resection.

Research progress and challenges of stem cell therapy for ischemic stroke

Ischemic stroke is a significant global cause of death and disability. Currently, treatment options for acute ischemic stroke are limited to intravenous thrombolysis and mechanical recanalization. Therefore, novel neuroprotective strategies are imperative. Stem cell transplantation possesses the capabilities of differentiation, proliferation, neuronal replacement, nerve pathway reconstruction, secretion of nerve growth factors, and enhancement of the microenvironment; thus, it is a potential therapeutic approach for ischemic stroke. In addition, the immunomodulatory function of stem cells and the combined treatment of stem cells and exosomes exhibit a favorable protective effect on brain injury and neurological dysfunction following stroke. Meanwhile, the theory of microbiota-gut-brain axis provides us with a novel perspective for comprehending and managing neurological diseases. Lastly, stem cell transplantation has demonstrated promising outcomes not only in treating ischemic stroke but also in dealing with other neurological disorders, such as brain tumors. Furthermore, challenges related to the tissue source, delivery method, immune response, and timing of transplantation still need to be addressed to optimize the treatment.

Memory effects of prior subculture may impact the quality of multiomic perturbation profiles

Mass spectrometry-based omics technologies are increasingly used in perturbation studies to map drug effects to biological pathways by identifying significant molecular events. Significance is influenced by fold change and variation of each molecular parameter, but also by multiple testing corrections. While the fold change is largely determined by the biological system, the variation is determined by experimental workflows. Here, it is shown that memory effects of prior subculture can influence the variation of perturbation profiles using the two colon carcinoma cell lines SW480 and HCT116. These memory effects are largely driven by differences in growth states that persist into the perturbation experiment. In SW480 cells, memory effects combined with moderate treatment effects amplify the variation in multiple omics levels, including eicosadomics, proteomics, and phosphoproteomics. With stronger treatment effects, the memory effect was less pronounced, as demonstrated in HCT116 cells. Subculture homogeneity was controlled by real-time monitoring of cell growth. Controlled homogeneous subculture resulted in a perturbation network of 321 causal conjectures based on combined proteomic and phosphoproteomic data, compared to only 58 causal conjectures without controlling subculture homogeneity in SW480 cells. Some cellular responses and regulatory events were identified that extend the mode of action of arsenic trioxide (ATO) only when accounting for these memory effects. Controlled prior subculture led to the finding of a synergistic combination treatment of ATO with the thioredoxin reductase 1 inhibitor auranofin, which may prove useful in the management of NRF2-mediated resistance mechanisms.

Efficacy of hip abductors exercise training combined with repetitive transcranial magnetic stimulation on knee osteoarthritis: A randomized controlled trial.

Knee osteoarthritis is a common degenerative joint disease where a single treatment method often fails to fully alleviate symptoms. Hence, finding effective non-invasive combined treatment approaches is particularly crucial. The efficacy of treating knee osteoarthritis with hip abductors exercise training combined with repetitive transcranial magnetic stimulation was assessed through functional scales and objective evaluation methods. In this four-week randomized clinical trial, 160 patients meeting inclusion criteria were randomly assigned 1:1 to group A to receive oral celecoxib and group B to receive a combination of hip abductors exercise training and repeated transcranial magnetic stimulation. The primary outcome was the western Ontario and McMaster universities osteoarthritis index. The secondary outcomes include Visual Analogue Scale, knee outcome survey activities of daily living scale, Active Range of Motion, and the Quadriceps Angle, the tibiofemoral angle, peak adductor moment, the integrated electromyography and root mean square of the surface electromyography of the lower extremity muscles. Paired sample t test was used for Within-Group comparison of outcome indicators, and independent sample t test was used for Between-Group comparison. Of the 160 randomly assigned patients, 150 completed the study. After 4 weeks, the WOMAC index decreased from 61 ± 10.83 to 40.55 ± 7.58 in the combined treatment group and from 60.97 ± 10.18 to 47.7 ± 10.13 in the celecoxib group. The effect of the combined treatment group was significantly higher than that in the celecoxib group (P< 0.001). In the combined treatment group, the score of knee joint daily living scale increased (P< 0.001), the active range of motion increased (P< 0.001), the quadriceps angle decreased (P< 0.001), the tibiofemoral angle increased (P< 0.001), and the peak adduction moment decreased (P< 0.001), integrated electromyography and root mean square increased (P< 0.001), and the effect was better than that of celecoxib group (P< 0.001). The visual analog scale score in celecoxib group was lower (P< 0.001) and knee outcome survey activities of daily living scale was higher (P< 0.001). The incidence of treatment-related adverse events was 10% in the celecoxib group and 2.5% in the combined treatment group, all of which were mild. Hip abductors exercise training combined with repetitive transcranial magnetic stimulation can enhance abduction muscle strength, improve mobility, reduce joint pain, and enhance quality of life. This combined approach shows superior clinical effectiveness compared to oral celecoxib.

Emerging Therapeutic Strategies to Overcome Drug Resistance in Cancer Cells.

The rise of drug resistance in cancer cells presents a formidable challenge in modern oncology, necessitating the exploration of innovative therapeutic strategies. This review investigates the latest advancements in overcoming drug resistance mechanisms employed by cancer cells, focusing on emerging therapeutic modalities. The intricate molecular insights into drug resistance, including genetic mutations, efflux pumps, altered signaling pathways, and microenvironmental influences, are discussed. Furthermore, the promising avenues offered by targeted therapies, combination treatments, immunotherapies, and precision medicine approaches are highlighted. Specifically, the synergistic effects of combining traditional cytotoxic agents with molecularly targeted inhibitors to circumvent resistance pathways are examined. Additionally, the evolving landscape of immunotherapeutic interventions, including immune checkpoint inhibitors and adoptive cell therapies, is explored in terms of bolstering anti-tumor immune responses and overcoming immune evasion mechanisms. Moreover, the significance of biomarker-driven strategies for predicting and monitoring treatment responses is underscored, thereby optimizing therapeutic outcomes. For insights into the future direction of cancer treatment paradigms, the current review focused on prevailing drug resistance challenges and improving patient outcomes, through an integrative analysis of these emerging therapeutic strategies.

Atorvastatin exerts a preventive effect against steroid-induced necrosis of the femoral head by modulating Wnt5a release.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent form of osteonecrosis in young individuals. More efficacious clinical strategies must be used to prevent and treat this condition. One of the mechanisms through which SONFH operates is the disruption of normal differentiation in bone marrow adipocytes and osteoblasts due to prolonged and extensive use of glucocorticoids (GCs). In vitro, it was observed that atorvastatin (ATO) effectively suppressed the impact of dexamethasone (DEX) on bone marrow mesenchymal stem cells (BMSCs), specifically by augmenting their lipogenic differentiation while impeding their osteogenic differentiation. To investigate the underlying mechanisms further, we conducted transcriptome sequencing of BMSCs subjected to different treatments, leading to the identification of Wnt5a as a crucial gene regulated by ATO. The analyses showed that ATO exhibited the ability to enhance the expression of Wnt5a and modulate the MAPK pathway while regulating the Wnt canonical signaling pathway via the WNT5A/LRP5 pathway. Our experimental findings provide further evidence that the combined treatment of ATO and DEX effectively mitigates the effects of DEX, resulting in the upregulation of osteogenic genes (Runx2, Alpl, Tnfrsf11b, Ctnnb1, Col1a) and the downregulation of adipogenic genes (Pparg, Cebpb, Lpl), meanwhile leading to the upregulation of Wnt5a expression. So, this study offers valuable insights into the potential mechanism by which ATO can be utilized in the prevention of SONFH, thereby holding significant implications for the prevention and treatment of SONFH in clinical settings.

Enhancement of engineering properties of cement mortars with masonry construction and demolition fines via carbon dioxide utilization, storage and chemical treatment

Shortage of natural sand is severely affecting the global construction industry. The construction sector also generates a substantial amount of construction and demolition (C&D) waste of which masonry wastes constitute a major fraction. Using a circular economy approach, this article explores the feasibility of using treated masonry waste fines (MWF) to replace 75 % of natural sand in Portland cement-based mortars. The treatment consists of a combination of acid washing and CO2 curing to improve the engineering properties of MWF-cement mortars. 0.1 mol/L and 0.5 mol/L (M) H2SO4 were used for chemical treatment of the MWF followed by CO2 curing at 50,000 ppm for 4 hours. Mortars containing treated MWF (MWF-0.1 M-C and MWF-0.5 M-C) were subject to conventional curing (moist curing followed by dry curing at 30 ◦C and 65 % RH) and carbon sequestration via accelerated carbonation curing. Experimental findings suggest that combined treatment with acid and CO2 reduces the pore volume by 13 – 27 % in the pore size range of 10 – 100 nm in MWF. Consequently, mortars with MWF-0.1 M-C and MWF-0.5 M-C show 29 – 30.50 % higher compressive strength at 28-d age and a 29 – 36 % reduction in total shrinkage compared to mortars with similar dosages of as-received MWF. This ensures statistically similar strength and shrinkage as that of the plain mortar (with 100 % natural sand), demonstrating the potential for 75 % sand replacement using treated MWF. Furthermore, carbon sequestration of 16.40 – 19 % by mass of Portland cement is achieved, which contributes to a 15 % enhancement in early strength and reduces the mesoporous volume and shrinkage by up to 43 % and 15–19 % respectively. In summary, the research offers a pathway to recover a “new sand” from C&D wastes , which could be used to manufacture masonry construction products with reduced demand for natural sand.

Polymyxin B neurotoxicity as manifestation of a serious life-threatening adverse reaction: clinical case

The aim of this work is to describe a clinical case of a serious life-threatening adverse reaction in the form of neurotoxicity (convulsions, apnea requiring mechanical ventilation) to the polymyxin B drug, and also to remind that manifestations of neurotoxicity can be extremely varied and nonspecific, and do not occur after every administration, can be delayed, require vigilance and careful monitoring both from the attending physicians and from anesthesiologistsresuscitators, neurologists, ophthalmologists, etc.A 62-year-old female patient diagnosed with stage IIIB T4G3N0M0 pleomorphic soft tissue sarcoma of the right thigh, condition after combination treatment, developed infection and necrosis of the postoperative wound (recto-abdominal flap). According to the results of a microbiological study and an antibiogram, the patient received polymyxin B as part of combination antibacterial therapy. On days 4, 5, 6, 7 of polymyxin administration, the patient experienced the following symptoms in various combinations: weakness, numbness of the face, paresthesia, paresis of the limbs, partial convulsions, respiratory depression, and apnea.After establishing a connection between neurologicalsymptoms and intravenous administration of polymyxin B (the total score on the Naranjo scale was 6 points, the degree of reliability of the “adverse reaction–drug” relationship was probable) and drug withdrawal, manifestations of neurotoxicity completely disappeared and did not reoccur. The patient was discharged in satisfactory condition.In a patient with symptoms of damage to the nervous system, it is necessary to conduct multiple differential diagnostic search to exclude stroke, epilepsy, encephalitis, hereditary and acquired neurodegenerative diseases, as well as side effects of medications. At the slightest suspicion of the likelihood of an adverse reaction to polymyxin B/colistimethate sodium, the Naranjo algorithm must be used to establish a cause-and-effect relationship between the adverse reaction and the drug.

PARP inhibition with rucaparib alone followed by combination with atezolizumab: Phase Ib COUPLET clinical study in advanced gynaecological and triple-negative breast cancers.

Combining PARP inhibitors (PARPis) with immune checkpoint inhibitors may improve clinical outcomes in selected cancers. We evaluated rucaparib and atezolizumab in advanced gynaecological or triple-negative breast cancer (TNBC). After identifying the recommended dose, patients with PARPi-naive BRCA-mutated or homologous recombination-deficient/loss-of-heterozygosity-high platinum-sensitive ovarian cancer or TNBC received rucaparib plus atezolizumab. Tumour biopsies were collected pre-treatment, during single-agent rucaparib run-in, and after starting combination therapy. The most common adverse events with rucaparib 600 mg twice daily and atezolizumab 1200 mg on Day 1 every 3 weeks were gastrointestinal effects, fatigue, liver enzyme elevations, and anaemia. Responding patients typically had BRCA-mutated tumours and higher pre-treatment tumour levels of PD-L1 and CD8 + T cells. Markers of DNA damage repair decreased during rucaparib run-in and combination treatment in responders, but typically increased in non-responders. Apoptosis signature expression showed the reverse. CD8 + T-cell activity and STING pathway activation increased during rucaparib run-in, increasing further with atezolizumab. In this small study, rucaparib plus atezolizumab demonstrated acceptable safety and activity in BRCA-mutated tumours. Increasing anti-tumour immunity and inflammation might be a key mechanism of action for clinical benefit from the combination, potentially guiding more targeted development of such regimens. ClinicalTrials.gov (NCT03101280).

Regulation of Proline Accumulation and Protein Secretion in Sorghum under Combined Osmotic and Heat Stress.

Plants reprogramme their proteome to alter cellular metabolism for effective stress adaptation. Intracellular proteomic responses have been extensively studied, and the extracellular matrix stands as a key hub where peptide signals are generated/processed to trigger critical adaptive signal transduction cascades inaugurated at the cell surface. Therefore, it is important to study the plant extracellular proteome to understand its role in plant development and stress response. This study examined changes in the soluble extracellular sub-proteome of sorghum cell cultures exposed to a combination of sorbitol-induced osmotic stress and heat at 40 °C. The combined stress significantly reduced metabolic activity and altered protein secretion. While cells treated with osmotic stress alone had elevated proline content, the osmoprotectant in the combined treatment remained unchanged, confirming that sorghum cells exposed to combined stress utilise adaptive processes distinct from those invoked by the single stresses applied separately. Reactive oxygen species (ROS)-metabolising proteins and proteases dominated differentially expressed proteins identified in cells subjected to combined stress. ROS-generating peroxidases were suppressed, while ROS-degrading proteins were upregulated for protection from oxidative damage. Overall, our study provides protein candidates that could be used to develop crops better suited for an increasingly hot and dry climate.

Efficacy and safety of the combination or monotherapy with GLP-1 receptor agonists and SGLT-2 inhibitors in Type 2 diabetes mellitus: An update systematic review and meta-analysis

PurposeTo evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter2(SGLT-2) inhibitors and glucagon-like peptide-1(GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM). MethodsTo construct an exhaustive database of randomized controlled trials (RCTs) concerning SGLT-2 inhibitors and GLP-1 agonists, a methodical search was undertaken across a range of databases, such as Embase, PubMed, and the Cochrane Central Register of Controlled Trials, from their inception to January 2023. Following this, a meta-analysis was executed to amalgamate the collected data, which allowed for the calculation of standardized mean differences (SMDs), odds ratios (ORs), and 95 % confidence intervals (CIs) for a spectrum of outcomes. This analytical approach was designed to yield a quantitative evaluation of the therapeutic efficacy and safety profile of SGLT-2 inhibitors and GLP-1 agonists for the treatment of diabetes mellitus. ResultsWhen compared to GLP-1 agonist therapy alone, the combination therapy did not significantly reduce fasting plasma glucose (FPG) levels (95 % confidence interval [CI]: -0.27, 0.10; p = 0.35), body weight (95 % CI: -0.18, 0.18; p = 1.00), Glycosylated Hemoglobin, Type A1C (HbA1c) (95 % CI: -0.29, 0.07; p = 0.22), or systolic blood pressure (SBP) values (95 % CI: -0.29, 0.06; p = 0.21). In contrast, when compared to SGLT-2 inhibitor therapy alone, combination therapy significantly decreased FPG by 0.24 mmol/L (95 % CI: -0.43, -0.05; p = 0.01), HbA1c by 0.45 % (95 % CI: -0.72, -0.18; p = 0.001), and SBP by 0.12 mmHg (95 % CI: -0.24, 0.00; p = 0.05). However, the combination therapy failed to demonstrate a significant reduction in body weight when compared with either SGLT-2 inhibitor therapy (95 % CI: -0.20, 0.05; p = 0.24) or GLP-1 agonist therapy (95 % CI: -0.18, 0.18; p = 1.00). Additionally, the combination therapy did not increase the incidence of hypoglycemia. It should be noted that data regarding mortality and cardiovascular outcomes were limited. ConclusionsThe combination treatment of SGLT-2 inhibitors and GLP-1 receptor agonists effectively reduces HbA1c, FPG, and SBP without elevating the risk of hypoglycemia when compared to monotherapy with SGLT-2 inhibitors. However, these beneficial effects were not observed when the combination therapy was compared with GLP-1 receptor agonist treatment alone.

Regulation of Proline Accumulation and Protein Secretion in Sorghum under Combined Osmotic and Heat Stress

Plants reprogramme their proteome to alter cellular metabolism for effective stress adaptation. Intracellular proteomic responses have been extensively studied, and the extracellular matrix stands as a key hub where peptide signals are generated/processed to trigger critical adaptive signal transduction cascades inaugurated at the cell surface. Therefore, it is important to study the plant extracellular proteome to understand its role in plant development and stress response. This study examined changes in the soluble extracellular sub-proteome of sorghum cell cultures exposed to a combination of sorbitol-induced osmotic stress and heat at 40 °C. The combined stress significantly reduced metabolic activity and altered protein secretion. While cells treated with osmotic stress alone had elevated proline content, the osmoprotectant in the combined treatment remained unchanged, confirming that sorghum cells exposed to combined stress utilise adaptive processes distinct from those invoked by the single stresses applied separately. Reactive oxygen species (ROS)-metabolising proteins and proteases dominated differentially expressed proteins identified in cells subjected to combined stress. ROS-generating peroxidases were suppressed, while ROS-degrading proteins were upregulated for protection from oxidative damage. Overall, our study provides protein candidates that could be used to develop crops better suited for an increasingly hot and dry climate.

Improvement of soil health and leaf nutrient status in strawberry (Fragaria × ananassa) using bioorganic formulations

In strawberry cultivation, a variety of factors influence production and fruit quality. Yield is the most crucial component in fruit production. Chemical fertilizers are typically used to boost yields, however because of their high production costs, negative effects on the environment and human health, organic fertilizers or natural amendments are being utilized instead of chemical fertilizers. The primary goals of substituting chemical fertilizers with bioorganic formulations made from natural sources for fruit production are to lower costs of production and maintain fruit production sustainability. Therefore, to study the impact of these bioorganic formulations the current investigations were conducted in open field conditions under sub humid mid hills conditions of Himachal Pradesh with 12 treatment combinations and three replicate plots. The tested plants were given various combinations of bioorganic formulations [Jeevamrit (JE) and Ghanjeevamrit (GHA)] as a source of nutrients. When compared to conventional practices, statistically significant improvements were discovered in the parameters of yield and nutrient content in the soil and plant. Significant higher yield (21.13 tonnes/ha), soil nutrients and total microbial content was recorded in T4. The results of this study provide support to the recommendation that bioorganic formulations, such as the tested ones, be used on their own or in combination as a substitute for chemical fertilizers in plant nutrition for the production of strawberries.

Presentation and Management of Granulomatous Mastitis in the United States: Results of an American Society of Breast Surgeons Registry Study.

Granulomatous mastitis (GM) is a benign, chronic, inflammatory disease lacking clear treatment guidelines. The purpose of this American Society of Breast Surgeons (ASBrS) prospective, multisite registry was to characterize the presentation of GM and identify treatment strategies associated with symptom resolution and optimal cosmesis. ASBrS members entered data into a registry on patient demographics, treatment, symptoms, and cosmesis over a 1-year period. Initial symptoms were graded as mild, moderate, or severe. The Chi-square test and logistic regression were used to identify factors related to symptom improvement and cosmesis. Overall, 112 patients with a mean age of 36years were included. More patients were Hispanic (49.1%) and from the Southwest (41.1%), and management included observation (4.5%), medical (70.5%), surgical (5.4%), or combination treatment (19.6%). Immunosuppression was used in 83 patients (74.1%), including 43 patients who received intralesional steroid injections. Patients with severe symptoms were more likely to undergo surgical intervention compared with those with mild or moderate symptoms (21.4% vs. 0% and 7.5%, respectively; p=0.004). Within 1year, 85 patients (75.9%) experienced symptom improvement and/or resolution at a median of 3 months. Receipt of immunosuppressive therapy was predictive of improvement or resolution at 1month (odds ratio 4.22; p=0.045). One-year physician-assessed cosmesis was excellent or good for 20/35 patients (57.1%) and was not associated with type of treatment or symptom severity. Although GM can have a protracted course, the majority of patients in this registry resolved within 1year, with good cosmetic result. Treatment with immunosuppression appears to be most beneficial, and a symptom-based algorithm may be helpful to guide treatment.

Protective efficacy of ramelteon on methotrexate-induced DNA damage

Ramelteon (RMLT) is a melatonin receptor agonist that it has antioxidative and anti-inflammatory effects associated with DNA damage through different mechanisms of action. In this regard, we investigated the potential usefulness of RMLT as a protective agent against methotrexate (MTX)-induced DNA damage. Four groups were constituted from 32 Wistar albino rats: Negative control, RMLT, MTX, and MTX + RMLT. Twenty mg/kg MTX (i.p., single dose) and RMLT 10 mg/kg (oral, 7 days) was administered. Comet assay was used and the parameter %TailDNA was used to detect DNA damage. %TailDNA was 4.90 ± 0.19 in the control group, 7.85 ± 0.33 in the MTX group, 5.49 ± 0.24 in the RMLT group, and 5.86 ± 0.23 in the MTX + RMLT group. While there was a significant increase in DNA damage in the MTX-treated group compared to the control group, there was a significant reduction in DNA damage in the MTX + RMLT group, compared to the MTX group (p < 0.001). In conclusion, it was observed that combined treatment with RMLT significantly reduced MTX-induced DNA damage.

Biofilm inhibition of denture cleaning tablets and carvacrol on denture bases produced with different techniques

ObjectivesThis study compares the biofilm inhibition effects of denture cleaning tablets, carvacrol, and their combined use against Candida albicans on denture bases produced with different techniques. Additionally, the surface roughness and contact angles of these denture bases were evaluated.Materials and methodsTest samples were prepared from four different denture base materials (cold-polymerized, heat-polymerized, CAD/CAM milling, and 3D-printed). The surface roughness and contact angles of the test samples were measured using a profilometer and goniometer, respectively. For the evaluation of biofilm inhibition, samples were divided into 5 subgroups: Corega and carvacrol, separately and combined treatments, positive (inoculated with C. albicans) and negative control (non-inoculated with C. albicans, only medium). Biofilm mass was determined using the crystal violet method. An additional prepared test sample for each subgroup was examined under scanning electron microscopy (SEM).ResultsThe surface roughness values of the 3D-printed test samples were found to be statistically higher than the other groups (P < .001). The water contact angle of all test materials was not statistically different from each other (P > .001). Corega and carvacrol, separately and combined, significantly decreased the amount of biofilm on all surfaces (P < .0001). Treatment of corega alone and in combination with carvacrol to the 3D-printed material caused less C. albicans inhibition than the other groups (P < .001; P < .05).ConclusionsThe surface roughness values of all test groups were within the clinically acceptable threshold. Although Corega and carvacrol inhibited C. albicans biofilms, their combined use did not show a synergistic effect.Clinical relevanceCarvacrol may be used as one of the disinfectant agents for denture cleaning due to its biofilm inhibition property.