Treatment Dose Research Articles

Augmented Depression Therapy for young adults: A mixed methods randomised multiple baseline case series evaluation

Augmented Depression Therapy (ADepT) is an individual psychotherapy for depression, which has been shown to be effective in the general adult population. A randomised multiple baseline case series evaluated the feasibility, acceptability, and effectiveness of ADepT in young adults (aged 20-24). Eleven depressed young adults were recruited from a UK university wellbeing service to receive ADepT during the COVID-19 pandemic, with outcomes evaluated relative to pre-specified continuation targets. All participants received a minimum adequate treatment dose (>60% target); 89% judged ADepT as acceptable and satisfactory and would recommend it to others (>60% target); only 9% showed reliable deterioration for depression or wellbeing (meeting <30% target); and there were no trial- or treatment- related serious adverse events. Qualitative interviews revealed most participants were satisfied with and experienced benefits from ADepT. At post-treatment, reliable improvement was shown by 33% of participants for depression and 67% of participants for wellbeing (not meeting target of both >60%), with medium effect size improvements for depression (g=.78) and large effect size improvement for wellbeing (g=.93; not meeting target of both >.80). ADepT is feasible, acceptable, and safe in young adults but may require modification to maximise effectiveness. Further research outside of the COVID-19 pandemic is warranted.

ESTRO-EANO guideline on target delineation and radiotherapy for IDHmutant WHO CNS grade 2 and 3 diffuse glioma

PurposeThis guideline will discuss radiotherapeutic management of IDH mutant grade 2 and grade 3 diffuse glioma, using the latest 2021 WHO (5th) classification of brain tumours focusing on: imaging modalities, tumour volume delineation, irradiation dose and fractionation. MethodsThe ESTRO Guidelines Committee, CNS subgroup, nominated 15 European experts who identified questions for this guideline. Four working groups were established addressing specific questions concerning imaging, target volume delineation, radiation techniques and fractionation. A literature search was performed, and available literature was discussed. A modified two-step Delphi process was used with majority voting resulted in a decision or highlighting areas of uncertainty. ResultsKey issues identified and discussed included imaging needed to define target definition, target delineation and the size of margins, and technical aspects of treatment including different planning techniques such as proton therapy. ConclusionsThe GTV should include any residual tumour volume after surgery, as well as the resection cavity. Enhancing lesions on T1 imaging should be included if they are indicative of residual tumour. In grade 2 tumours, T2/FLAIR abnormalities should be included in the GTV. In grade 3 tumours, T2/FLAIR abnormalities should also be included, except areas that are considered to be oedema which should be omitted from the GTV. A GTV to CTV expansion of 10 mm is recommended in grade 2 tumours and 15 mm in grade 3 tumours. A treatment dose of 50.4 Gy in 28 fractions is recommended in grade 2 tumours and 59.4 Gy in 33 fractions in grade 3 tumours. Radiation techniques with IMRT are the preferred approach.

Efficacy and Tolerance of First-Line Afatinib in Elderly NSCLC Patients with EGFR Mutations in Vietnam: A Multicenter Real-World Study.

Afatinib, a second-generation epidermal growth factor receptor(EGFR) tyrosine kinase, has proven effective for non-small-cell lung cancer (NSCLC) patients with EGFR mutations through randomized controlled trials and real-world studies. Elderly patients exhibit unique characteristics in terms of physical condition and comorbidities, leading to differences in clinical practice for selecting the initial dosage and making dose adjustments compared to younger patients. This study aims to evaluate the effectiveness and adverse effects of first-line Afatinib treatment in elderly patients with NSCLC harboring EGFR mutations in Vietnam in a real-world context. We conducted a retrospective analysis of 135 patients, aged 65 years and older, across nine cancer centers in Vietnam. These patients, who harbored drug-sensitive EGFR mutations (excluding de novo T790M), received first-line Afatinib treatment between April 2018 and June 2022. The primary endpoints, time to treatment failure (TTF), and overall survival (OS) were assessed using the Kaplan-Meier method, and comparisons were conducted using the log-rank test. Secondary endpoints included the overall response rate (ORR) according to RECIST 1.1 and adverse effects as classified by CTCAE 4.0. The median age was 71.2 years (SD ± 5.3). Comorbidities included cardiovascular disease (20.7%), diabetes (5.2%), chronic obstructive pulmonary disease (2.2%), and hepatitis B (0.7%). Common mutations constituted 71.9% of cases, with uncommon mutations representing 28.1%. Brain metastases were observed in 24.4% of patients. Initial treatment doses were 40 mg for 35.6% of patients and 30 mg for 62.2%. With a median follow-up of 34.3 months, the median TTF was 16.3 months (95% CI: 15.4-19.5), and the median OS was 32.9 months (95% CI: 28.9-37.5). Factors associated with decreased OS included poor performance status, current smoking, and the presence of uncommon mutations. The ORR was 77.8%, with a complete response of 11.1% and a disease control rate of 94.1%. The most common toxicities were dermatologic and mucosal, including diarrhea (55.6%), rash (48.9%), and stomatitis (40.7%), predominantly in grades 1 and 2. Initiating treatment at doses below 40 mg significantly reduced most toxicities compared to the 40 mg dose. The presence of brain metastases did not significantly affect ORR, TTF, or OS. Starting treatment at doses below 40 mg significantly lowered the response rate but did not impact TTF or OS. First-line treatment with Afatinib in elderly patients with NSCLC and EGFR mutations demonstrates significant efficacy and manageable toxicity in a Vietnamese multicenter real-life setting. The effectiveness of Afatinib was confirmed, with known and well-controlled adverse effects, supporting its use in this patient population.

The Impact of The Preventive Role of Star Anise on The Toxicity of Benzopyrene Compound in The Liver and Kidney Tissues and Biochemical Parameters in Male Rats

Objective: This study, conducted at the University of Anbar's College of Pure Science, evaluated the protective effects of star anise against benzopyrene (B[a]P)-induced liver and kidney damage in 30 male white Swiss rats (Sprague Dawley), aged 3-4 months and weighing between 170-210 g. Materials and methods: The rats were divided into six groups: Control (G1), B[a]P (G2), Star Anise 125 mg/kg bw (G3), Star Anise 120 mg/kg bw + B[a]P (G4), Star Anise 125 mg/kg bw + B[a]P (G5), and Star Anise 130 mg/kg bw + B[a]P (G6). Results:Biochemical analyses showed that B[a]P exposure significantly elevated liver enzymes (ALP, AST, ALT, GGT) and kidney markers (uric acid, creatinine), indicating hepatic and renal damage. Treatment with star anise, especially 130 mg/kg bw significantly reversed these elevated levels because it protected against the injury. Histopathology showed that the liver and kidney were severely damaged in the B[a]P group and in the star-anise-treated group, normal tissue architecture was well preserved only in high doses of star anise treatment. Conclusion:These outcomes suggest the use of star anise as a hepatoprotective as well as a nephroprotective agent, and this needs to be further strengthened by understanding its mechanisms and long-term effectiveness.

Outcome of radiotherapy for metastatic neuroblastoma

Background. Neuroblastoma (NB) is a prevalent solid extracranial tumor that primarily affects children. It is the third most common type of cancer in children, following leukemia and brain tumors. Aim. The study aimed to discuss the clinical outcomes after adjuvant radiotherapy to the primary site in case of metastatic NB after good response to chemotherapy. Methods. A retrospective clinical-dosimetric study of 25 patients metastatic NB treated with radiotherapy at Baghdad Radiotherapy and Nuclear Medicine Center, at Baghdad Medical City Complex, Baghdad, Iraq. Data collection begin from December 2023 and March 2024. Data were collected retrospectively with review of records. The following variables were studied: sex, age, date of diagnosis, site of primary tumor, site of metastasis, chemotherapy, surgery, RT, RT sites, doses of RT, fractions of RT, recurrence sites, date of relapse and survival outcome for each patient. Follow-up period include look up to metastasis, site of metastasis, recurrence, site of recurrence and survival rates. Results. In relation to sex, males (14, 56%) were more than females (11, 44%). The mean age of NB cases was 45.64±17.6 months. In NB, suprarenal masses were the most common site of primary in 21 (84%) of patients. The most common site of metastasis of NB was bone marrow in 12 (48). The multi sites of recurrence was the commonest presentation in 48%. The relapse-free survival (RFS) was 22.38 months. 5 out of 25 patients were alive whereas 20 (80%) of cases were dead. The median follow-up time was 6 years, and the OS of NB in this study after optimal treatment was 2.46 years (95%CI= 1.705-3.21) for survivors. The MS was 4.84 years. The OS was 6 yrs for those diagnosed at 2017, 2 yrs for those diagnosed at 2018, 1.5 yrs for those diagnosed at 2019, 1.75 yrs for those diagnosed at 2020, 3 yrs for those diagnosed at 2021 and 1.5 yrs for those diagnosed at 2022. There was a significant difference among doses (Log Rank (Mantel-Cox)= 11.425, p=0.044). Conclusions. This study is the first study in Iraq that examines the clinical results of radiotherapy on the primary site in cases of metastatic neuroblastoma following induction chemotherapy. The suprarenal masses of neuroblastoma are the most often occurring main site. The primary sites of metastases for neuroblastoma (NB) are the bone marrow and bones. Timely detection and proactive treatment of NB can improve overall results. Reoccurrence of skeletal issues and the infiltration of bone marrow are frequently observed. There were no significant differences observed in terms of relapse-free survival and overall survival based on factors such as sex, age, location of the main tumor, chemotherapy, radiation treatment, surgery, and radiation therapy dosages.

Combined Effects of Cypermethrin and Lead on Biochemical and Molecular Parameters in Albino Mice

In this study, the combined toxicity of cypermethrin and lead were investigated using molecular and biochemical parameters in albino mice. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP),blood urea nitrogen (BUN) and creatinine levels were studied and used as indicators of toxicity. Comet test was also utilized to evaluate the mechanism of genotoxicity of cypermethrin, lead and the ) cypermethrin and lead) group. Albino mice were divided into eight groups and given intraperitoneal cypermethrin injections at 1.75 mg/kg/day and lead nitrate at 1.75 mg/kg/day, and combined doses of each one respectively. Blood samples were collected after two and four weeks. Cypermethrin raised AST, AL, BUN and creatinine levels as treatment time and doses rose, as did lead nitrate which elevated liver and kidney parameters in response to the toxicant. As evaluated by comet test molecular characteristics, the impact of cypermethrin and lead nitrate was an increase in DNA damage.

The Life and Legacy of Samuel Hahnemann: Founder of Homoeopathy and His Medical Philosophy.

Dr. Christian Friedrich Samuel Hahnemann (1755) was the visionary founder of homoeopathy, a system of medicine that emerged amidst the orthodox practices of his time. This biography traces Hahnemann's journey from a curious scholar in Meissen to a pivotal figure in global healthcare. His relentless questioning and experimentation led to the development of homoeopathy, grounded in the principles of "like cures like" and potentization. Hahnemann challenged prevailing medical norms, emphasizing individualized treatment and minimal dosing, significantly influencing modern healthcare. Despite considerable opposition, his innovations established a new medical paradigm that inspires practitioners and patients today. This paper explores Hahnemann's early life, education, homoeopathy's rise, key innovations, and enduring legacy. His commitment to original thinking and perseverance birthed homoeopathy and transformed approaches to medicine, highlighting its holistic focus and individualized care. Hahnemann is recognized as a pioneer in compassionate healthcare.

Response of β-glucosidase enzyme activity of soil to biochar applications in a crop rotation at Blacksea agroecosystem

The use of biochar has emerged a potentially effective approach to improve soil function and promote crop performance. However, the specific impact of biochar on β-glucosidase enzyme activity (BGA) within crop rotation systems in the Black Sea agroecosystem requires further investigation. This study was conducted to determine the effects of rice husk biochar (RHB) and poultry manure biochar (PMB) on BGA in soils. Six biochar doses (0-control, 10, 20, 30, 40 and 50 t ha-1) were applied at the beginning of two wheat-cabbage red pepper rotation periods. The mean BGA at second rotation (73.71 µg pNP g-1) was significantly lower compared to the BGA of the first period (93.39 µg pNP g-1). The BGA value in control (94.51 µg pNP g-1) decreased with increasing biochar application doses (76.05 µg pNP g-1, 50 t ha-1) treatment. The mean BGA value in PMB treatment was slightly higher than that of RHB, but it was not statistically different between two biochar types. However, the decrease in BGA value (25.0%) in the highest RHB dose compared to control was more than two-fold compared to the decrease in PMB application (12.1%). The difference in carbon/nitrogen ratio between RHB and PMB can be attributed to the variation in BGA values observed at the application of same biochar doses. The decrease in BGA over the course of the two rotation cycles implies that biochar may have a long-term influence on soil carbon cycling.

Efficacy and safety of direct-acting antiviral regimen for patients with hepatitis C virus genotype 2: a systematic review and meta-analysis.

Direct-acting antivirals (DAAs) show high cure rates in treating chronic hepatitis C virus (HCV). However, the effect of DAAs on patients infected with genotype 2 (GT2) is difficult to determine despite the availability of several DAA regimens. A systematic search of six databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Clinicaltrial.gov) was conducted through April 20, 2022. We considered the sustained virological response 12 weeks after treatment (SVR12) as the efficacy outcome, and adverse events (AEs) as the safety outcome. By calculating the mean SVR12 and the proportion of AEs among patients, we considered the intervention effect for each DAA regimen. The random effect model was then used in all meta-analyses. This systematic review and meta-analysis aimed to summarize the evidence on efficacy and safety of DAAs in patients infected with HCV GT2. The Bayesian Markov Chain Monte Carlo (MCMC) network metanalysis was used to indirectly compare regimen in GT2 patients. Among 31 articles included (2,968 participants), consisting of 1,387 treatment-naive patients and 354 patients with cirrhosis. The overall pooled SVR12 rate was 94.62% (95% CI: 92.43-96.52%) among the participants who received all doses of treatment. Meta-analysis results of AEs revealed that fatigue was the most common AE (14.0%, 95% CI: 6.4-21.6%), followed by headache (13.1%, 95% CI: 9.2-17.1%), whereas death and serious adverse events were uncommon. We compared DAA-based treatments indirectly using meta-analysis and found the combination of Sofosbuvir plus Velpatasvir and Glecaprevir plus Pibrentasvir, each administered over a 12-week period, were identified as the most effective and relatively safe in managing chronic hepatitis C virus genotype 2 (HCV GT2) infection. Both treatments achieved a SVR12 of 100% (95% CI 99-100%).

A Simple Eco-Friendly HPLC-PDA Method for the Simultaneous Determination of Paclitaxel and Seliciclib in Plasma Samples for Assessing Their Pharmacodynamics and Pharmacokinetics in Combination Therapy for Uterine Sarcoma.

Background/Objectives: Uterine sarcoma, a rare cancer originating in the smooth muscle of the uterus, exhibits high rates of recurrence and metastasis. It represents one of the most challenging types of cancer due to its chemorefractory nature, showing little response to conventional chemotherapy methods and displaying a relative survival rate of 30-40%. A potentially promising approach for treating uterine sarcoma involves combination therapy with paclitaxel (PAC), a microtubule-targeting agent, and seliciclib (SEL), a cyclin-dependent kinase inhibitor. SEL has been identified as a drug that can enhance the effectiveness of PAC through synergistic effects. To further refine this treatment strategy, an efficient analytical tool capable of simultaneously measuring the concentrations of PAC and SEL in blood plasma is needed. This tool would make it easier to study the pharmacokinetic interactions of potential drugs and assist in monitoring therapy when administering this combination treatment. Regrettably, a method meeting these specific requirements has not been documented in the existing literature. Methods: This article introduces the first HPLC technique employing a PDA detector to concurrently measure PAC and SEL levels in plasma. The methodology underwent validation in accordance with the ICH standards for validating bioanalytical methods. Results: The method exhibited linearity in the concentrations ranging from 0.8 to 100 µg mL-1 for both PAC and SEL. The limits of quantification were determined and found to be 1.34 and 1.25 µg mL-1 for PAC and SEL, respectively. All the other validation criteria conformed to the ICH validation standards. The HPLC-PDA method was successfully employed to quantify both PAC and SEL in plasma samples with a high level of reliability (in terms of accuracy and precision). The eco-friendliness of the approach was verified using three thorough assessments. This technique serves as a valuable asset in establishing the correct dosage and administration schedule for the combined treatment involving PAC and SEL, ensuring the desired therapeutic effects and safety in managing uterine sarcoma. Conclusions: The proposed HPLC-PDA method is the first reliable and eco-friendly method developed to simultaneously determine PAC and SEL in high-throughput plasma samples in clinical laboratories.

Co-MOF-derived N-doped carbon nanosheet arrays on biomass carbon fiber membrane for highly sensitive detection of luteolin

Rapid and accurate determination of luteolin (LU) content is important for drug dosage control, treatment and prevention of disease. Traditional chromatographic and spectroscopic methods are gradually replaced by more sensitive and rapid electrochemical detection. 3D carbonized eggshell fiber membrane (3D CEFM) with good electrical conductivity and mechanical stability is prepared at high temperatures. To enhance the sensing performance of LU, nitrogen-doped carbon nanosheet arrays/3D CEFM (Co-NC NSAs/3D CEFM) derived from ZIF-67 nanosheet arrays (ZIF-67 NSAs) are prepared on the surface of 3D CEFM. Due to the synergistic effect, the Co-NC NSAs (thickness ∼ 1 μm, height ∼ 3 μm) provides a shorter electron transport path, while the 3D CEFM (pore size ∼5 μm) offers good electrical conductivity and a large solution contact area. Co-NC NSAs/3D CEFM electrode has a sensitivity of 1.31 μA·μM−1·cm−2 in the 0–60 μM LU and a limit of detection (LOD) of 0.04 μM (S/N = 3). Meanwhile, the electrode demonstrated recoveries of 98.0 % to 103.5 % in real samples, with a relative standard deviation (RSD) of 1.2 to 2.3 %. These results indicate that the electrode has significant potential for practical applications.

Phototesting for a variety of skin conditions before narrowband (TL-01) Ultraviolet-B

Background: For the majority of photo responsive skin disorders, narrowband ultraviolet-B (NBUV-B) phototherapy is currently regarded as the preferred option. The initial dosage of NBUV-B phototherapy is determined as a percentage of the minimal erythema dose (MED) at the majority of dermatology centers that offer phototherapy. This will shorten the time of therapy and lower the chance of burning while optimizing the therapeutic effect. Three times a week is the usual dosage for NBUV-B phototherapy treatment, which takes 18 to 30 sessions on average to clear the condition. For these types of treatment plans, a precise evaluation of the MED is necessary before starting treatment in order to prevent NBUV-B overdoses or underdoses. Aim: The objective of this study is to investigate the MED of 311nm NBUV-B phototherapy in a group of Libyan patients. Methods: For this prospective study, 150 patients with a range of skin conditions who saw the phototherapy unit at Bir Usta Melad Hospital of Dermatology and Venereology in Tripoli, Libya over an 8-month period were enrolled. Skin conditions include vitiligo, atopic dermatitis, and psoriasis are among those being researched. Using Fitzpatrick's questionnaire, skin types were assigned to each patient. Using a MED tester instrument (Dermalight® 80), 311 nm NBUV-B was applied to the right forearm. The test findings were recorded 24 hours later. Results: Of the patients studied, 82 (54.7%) were female and 68 (45.3%) were male. Their ages ranged from 10 to 60 years, with 30% of the sample falling between the ages of 31 and 40. The patients were clinically diagnosed with the following conditions: vitiligo 65(43.3%), psoriasis 61(40.7%), eczema 8(5.3%), pruritus 6(4%), and alopecia areata and lichen planus 5(3.3%) each. According to Fitzpatrick's categorization, the skin prototypes in the included series were 15(10%) patients of skin type III, 118(78.7%) patients of skin type IV, and 17(11.3%) patients of skin type V. Among the enrolled participants, the minimum necessary dose to elicit an erythema for NBUV-B ranged between 300 mJ/cm2 and 750 mJ/cm2, with the mean dosage was 484.7 ± 82.2 mJ/cm2. Conclusions: The average MED to 311nm NBUV-B in Libyan patients was around 500 mJ/cm2, which can be utilized to determine the initial dose and treatment regimen of phototherapy for various skin conditions.

Impact of Tocopherol Supplementation on Clinical Parameters of Periodontal Disease: A Systematic Review and Meta-Analysis.

Background and Objectives: The significance of periodontal disease as a public health issue prompts the exploration of effective treatments, including the potential use of tocopherol (Vitamin E) due to its anti-inflammatory and antioxidant properties. Materials and Methods: The PICO statement (Population, Intervention, Comparator, Outcome) was as follows: In patients with periodontal disease, does tocopherol (Vitamin E) supplementation compared to no supplementation or insufficient Vitamin E intake improve clinical outcomes such as gingival inflammation, pocket depth, and clinical attachment levels? This study searched through PubMed, Scopus, and Web of Science up to June 2024 focused on studies involving human subjects with various forms of periodontal disease, analyzing the impact of tocopherol through dietary or supplementary intake. Primary outcomes evaluated included improvements in gingival inflammation, pocket depth, and clinical attachment levels, with data synthesis conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality assessment and risk of bias were meticulously performed for the included observational studies and randomized controlled trials. Results: The meta-analysis incorporated 8 studies that were used for data extraction, totaling 12,832 patients, revealing a heterogeneous response to tocopherol supplementation, with a pooled odds ratio for efficacy in reducing periodontal disease severity at about 0.97 (95% CI: 0.96-0.98). Noteworthy findings indicated a statistically significant increase in clinical attachment loss and pocket depth with odds ratios ranging from 1.15 to 9.33 when Vitamin E was insufficient. However, the considerable heterogeneity (I2 = 88.35%) underscores variations in tocopherol's effectiveness across different populations and study designs. Conclusions: While tocopherol supplementation shows a modest benefit in managing periodontal disease, particularly in reducing clinical attachment levels and pocket depth, the variability in outcomes emphasizes the necessity for more research to establish standardized treatment protocols and dosages.

Impact of Tigecycline on Coagulation in Severe Infections and Effect of Vitamin K1 Intervention: A Retrospective Single-Center Analysis.

BACKGROUND Tigecycline is a tetracycline antibiotic used to treat gram-positive and gram-negative bacterial infections, and bleeding is a dose-dependent adverse effect. Vitamin K1 is a fat-soluble vitamin used to treat hemorrhagic conditions. This retrospective study from a single center included 920 patients treated with tigecycline for bacterial infections between January 2017 and December 2022 and aimed to evaluate the incidence of coagulopathy and the use of vitamin K1. MATERIAL AND METHODS A total of 220 patients were included and divided into a high-dose group (100 mg, every 12 h) and normal-dose group (50 mg, every 12 h) according to the treatment dose of tigecycline. Clinical characteristics and changes in coagulation indicators during tigecycline treatment were collected. Seventy-two patients were treated with vitamin K1, and the changes in coagulation indicators before and after treatment were compared. ANOVA and t test were used to analyze the effects of different doses of tigecycline on coagulation function and the intervention of vitamin K1. RESULTS Among 920 patients, the incidence of coagulopathy was 23.91%. In both groups, coagulopathy occurred on days 5 to 7 after administration, and the high-dose group had worse coagulation function than the normal-dose group, including activated partial thrombin time, prothrombin time, and fibrinogen (P<0.05). After treatment with vitamin K1, fibrinogen increased and activated partial thrombin time and prothrombin time were shortened in both groups (P<0.05 or P<0.01). CONCLUSIONS Tigecycline caused coagulopathy with dose and time dependence. Vitamin K1 can improve tigecycline-induced coagulopathy.

Chungtaejeon (CTJ) inhibits adhesion and migration of VSMC through cytoskeletal remodeling pathway

IntroductionVascular remodeling is crucial for the progression of vascular disease such as atherosclerosis. We utilize the in vitro experimental model of atherosclerosis to elucidate the activity of Chungtaejeon (CTJ), a Korean fermented tea on adhesion and migration of human aortic vascular smooth muscle cells (HASMC). Materials and methodsVarious in vitro assays such as cell viability, cell adhesion, Western blot, immunofluorescence, were carried out on HASMC to explore pathway associated with cytoskeletal remodeling during the progression of atherosclerosis. ResultsIn result, CTJ significantly inhibited adhesion of HASMC as revealed by collagen assay. Similarly, CTJ inhibited the β1-integrin protein expression as well as FAK phosphorylation. Treatment of CTJ also inhibited stress fiber formation. Likewise, adherence of cells on collagen optimally increased the expression of both RhoA and Cdc42, however, treatment of CTJ dose dependently decreased their expression. The lysophosphatidic acid stimulation of HASMC rapidly increased the level of phosphorylated forms of MLC20 within 15 min, followed by an extended level of MLC20 phosphorylation. The treatment of CTJ at a dose of 50, 100 and 250 μg/ml remarkably reduced the diphosphorylated form while decreased the level of monophosphorylated form of MLC20. ConclusionsOur results suggests that, with further validation CTJ could be a promising herbal resource for prevention of atherosclerosis.

Artificial Intelligence-Supported Applications in Radiotherapy Treatment Planning and Dose Optimization

The Article Abstract is not available.

Dual antiplatelet including clopidogrel and aspirin, cardiac MRI, and speckle tracking echocardiography parameters in ST-elevation myocardial infarction patients

Coronary artery disease is the medical term for atherosclerotic coronary disease, which causes the coronary arteries to constrict and inadequately provide blood to the heart. ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, &amp; unstable angina are the three conditions that comprise acute coronary syndromes. Studied cases with STEMI have been advised to take several drugs in addition to early reperfusion treatment, such as antiplatelet &amp; anticoagulant medications. The goal of antiplatelet medications is to stop platelets from aggregating together. Oral dual antiplatelet medication, which combines lifetime aspirin with an oral P2Y12 receptor inhibitor, is the main antiplatelet therapy in STEMI. Aspirin ought to be administered to all studied cases immediately following diagnosis, and a low dose of treatment should be continued indefinitely. Heart mortality and severe adverse cardiac events are strongly and independently correlated with the presence &amp; size of scarred tissue seen by cardiac MRI. Scar transmurality measured by cardiac MRI in studied cases with healed infarcts &amp; ventricular dysfunction predicts patient survival and functional recovery following revascularization. Patients with heart illnesses that have a history of ST-segment elevation myocardial infarction may be at risk for unfavorable results based on echocardiographic evaluation of cardiac structure &amp; function. Because speckle tracking echocardiography (STE) is quick and simple to do, it can be used in acute settings as well. It can be used for further risk stratification following revascularization, before invasive coronary angiography, or in cases when a diagnosis is unclear, if available.

Real-world treatment patterns in patients with systemic lupus erythematosus: associations with comorbidities and damage

ObjectiveTo assess treatment patterns and the association between long-term glucocorticoid (GC) and hydroxychloroquine (HCQ) use and damage accrual in patients with systemic lupus erythematosus (SLE).MethodsA retrospective study including patients with...

Omega-3 polyunsaturated fatty acids in depression: insights from recent clinical trials

Purpose of review This review examines evidence from recent clinical trials on the therapeutic potential of omega-3 polyunsaturated fatty acids (PUFAs) in major depressive disorder (MDD). We focus on the effects in MDD with comorbidities, younger populations, and high-inflammation presentations. Recent findings PubMed, Cochrane, and Embase databases were systematically searched for studies published between May 2022 and May 2024. The search was conducted on randomized controlled trials using omega-3 PUFAs with participants with a clinical diagnosis of depression. Higher doses of eicosapentaenoic acid (EPA) (&gt;1 g/day) improved measures of depression, particularly in MDD with elevated inflammation markers, comorbid cardiovascular diseases, late-life onset, and children and adolescent populations. Improvements in depressive symptoms were associated with increases in omega-3 PUFA-derived anti-inflammatory and proresolving lipid mediators. As adjuvant treatments, omega-3 PUFAs have potential benefits in mood, cognitive and metabolic functions, kynurenine and serotonin pathways, and alterations in corticolimbic functional connectivity. Summary While evidence suggests promise, particularly for high-dose EPA and in inflammatory MDD subtypes, more research is needed to establish optimal dosing regimens, treatment duration, and patient subgroups most likely to benefit. Future studies should focus on sex differences, long-term effects, and potential synergies with other treatments.

Using Limited Trial Evidence to Credibly Choose Treatment Dosage when Efficacy and Adverse Effects Weakly Increase with Dose.

It has become standard in medical treatment to base dosage on evidence in randomized trials. Yet it has been rare to study how outcomes vary with dosage. In trials to obtain drug approval, the norm has been to compare some dose of a new drug with an established therapy or placebo. Standard trial analysis views each trial arm as qualitatively different, but it may be credible to assume that efficacy and adverse effects weakly increase with dosage. Optimization of patient care requires joint attention to both, as well as to treatment cost. This paper develops methodology to use limited trial evidence to choose dosage when efficacy and adverse effects weakly increase with dose. I suppose that dosage is an integer t ∊ (0,1, . ,T), T being a specified maximum dose. I study dosage choice when trial evidence on outcomes is available for only K dose levels, where K < T+1. Then the population distribution of dose response is partially identified. I show that the identification region is a convex polygon. I characterize clinical and population decision making using the minimax-regret criterion. A simple analytical solution exists when T = 2. Computation is tractable when T is larger.