Effective Adjunctive Therapy Research Articles

The lived experience of patients going under hyperbaric oxygen therapy in Saudi Arabia: A phenomenological study.

Hyperbaric oxygen therapy (HBOT) has emerged as an effective treatment or adjunct therapy for various disorders, prioritizing improving oxygen delivery to tissues. This qualitative inquiry aims to explore the psychological experiences of patients undergoing their first hyperbaric session, focusing on the emotional responses and information needs of patients. The study addresses the gap in understanding patient experiences and seeks to contribute to holistic care approaches and improved health outcomes for patients undergoing HBOT. Using a phenomenological-hermeneutical approach, this study engaged 6 participants from KAASH in Taif City who had undergone at least 1 HBOT session. Data were collected through in-person interviews using a semistructured guide, focusing on patients' initial HBOT experiences. Giorgi 4-step method was applied for data analysis, allowing for rich descriptions and thematic categorization of the participants' lived experiences. The analysis is centered around "Walking into the unknown" with emerged subthemes (feeling anxious or being calm; immediate or evolving outcomes; formal orientation and management; success stories and self-learning) organized under 2 revised categories, "Transitioning from fear to reassurance" and "Navigating the path of understanding." The study also highlighted the critical role of healthcare providers in addressing information gaps and enhancing patient preparedness. The findings revealed the importance of comprehensive patient education and effective communication by healthcare providers to alleviate initial fears and improve treatment experiences for HBOT patients. Future research should expand to other regions and include healthcare providers' perspectives to further validate these findings and enhance HBOT practices. Integrating psychological support into the treatment process may also benefit patients, promoting holistic care and improving overall health outcomes.

Daily Vinegar Ingestion Improves Depression and Enhances Niacin Metabolism in Overweight Adults: A Randomized Controlled Trial.

Depressive disorders are the most prevalent mental health conditions in the world. The commonly prescribed antidepressant medications can have serious side effects, and their efficacy varies widely. Thus, simple, effective adjunct therapies are needed. Vinegar, a fermented acetic acid solution, is emerging as a healthful dietary supplement linked to favorable outcomes for blood glucose management, heart disease risk, and adiposity reduction, and a recent report suggests vinegar may improve symptoms of depression. This randomized controlled study examined the 4-week change in scores for the Center for Epidemiological Studies Depression (CES-D) questionnaire and the Patient Health Questionnaire (PHQ-9) in healthy overweight adults ingesting 2.95 g acetic acid (4 tablespoons vinegar) vs. 0.025 g acetic acid (one vinegar pill) daily. A secondary objective explored possible underlying mechanisms using metabolomics analyses. At week 4, mean CES-D scores fell 26% and 5% for VIN and CON participants respectively, a non-significant difference between groups, and mean PHQ-9 scores fell 42% and 18% for VIN and CON participants (p = 0.036). Metabolomics analyses revealed increased nicotinamide concentrations and upregulation of the NAD+ salvage pathway for VIN participants compared to controls, metabolic alterations previously linked to improved mood. Thus, daily vinegar ingestion over four weeks improved self-reported depression symptomology in healthy overweight adults, and enhancements in niacin metabolism may factor into this improvement.

The protective effect of ginsenoside Rg1 against sepsis-induced lung injury through PI3K-Akt pathway: insights from molecular dynamics simulation and experimental validation

Sepsis-induced acute lung injury (SALI) poses a significant threat with high incidence and mortality rates. Ginsenoside Rg1 (GRg1), derived from Ginseng in traditional Chinese medicine, has been found to reduce inflammation and protect lung epithelial cells against tissue damage. However, the specific roles and mechanisms by which GRg1 mitigates SALI have yet to be fully elucidated. In this context, we employed a relevant SALI mouse model, alongside network pharmacology, molecular docking, and molecular dynamics simulation to pinpoint GRg1's action targets, complemented by in vitro assays to explore the underlying mechanisms. Our research shows that GRg1 alleviates CLP-induced SALI, decreasing lung tissue damage and levels of serum proinflammatory factor IL-6, TNF-α, and IL-1β, also enhancing the survival rate of CLP mice. A total of 116 common targets between GRg1 and ALI, with specific core targets including AKT1, VEGFA, SRC, IGF1, ESR1, STAT3, and ALB. Further in vitro experiments assessed GRg1's intervention effects on MLE-12 cells exposed to LPS, with qRT-PCR analysis and molecular dynamics simulations confirming AKT1 as the key target with the favorable binding activity for GRg1. Western blot results indicated that GRg1 increased the Bcl-2/Bax protein expression ratio to reduce apoptosis and decreased the high expression of cleaved caspase-3 in LPS-induced MLE-12 cells. More results showed significant increases in the phosphorylation of PI3K and AKT1. Flow cytometric analysis using PI and Annexin-V assays further verified that GRg1 decreased the apoptosis rate in LPS-stimulated MLE-12 cells (from 14.85 to 6.54%, p < 0.05). The employment of the AKT1 inhibitor LY294002 confirmed these trends, indicating that AKT1’s inhibition negates GRg1’s protective effects on LPS-stimulated MLE-12 cells. In conclusion, our research highlights GRg1's potential as an effective adjunct therapy for SALI, primarily by inhibiting apoptosis in alveolar epithelial cells and reducing pro-inflammatory cytokine secretion, thus significantly enhancing the survival rates of CLP mice. These beneficial effects are mediated through targeting AKT1 and activating the PI3K-AKT pathway.

Expression of somatostatin receptors in canine and feline meningioma.

The standard treatment for canine and feline meningiomas includes radiotherapy, surgical excision or combined therapy. However, new therapeutic approaches are required due to the possible recurrence or progression of meningiomas despite initial therapy. Adjunctive therapy with synthetic long-acting somatostatin (SST) analogues has been described in humans with SST-expressing tumours. The expression of SST receptors (SSTRs) by feline meningiomas is currently unknown, and there are little data about canine meningiomas. We hypothesized that SSTR is expressed by canine and feline meningiomas (S1). Seven canines and 11 felines with histologically confirmed meningiomas underwent STTR screening. RNA expressions of SSTR1, SSTR2, SSTR3 and SSTR5 (canine) and SSTR1-SSTR 5 (feline) in fresh frozen and formalin-fixed and paraffin-embedded (FFPE) samples were investigated using real-time (RT)-qPCR. The expression of SSTR1 and SSTR2 in FFPE samples was evaluated using immunohistochemistry (IHC). The specificity of applied antibodies for canine and feline species was confirmed by western blotting. In canine meningiomas (n=7), RNA expression of SSTR1, SSTR2 and SSTR5 was detected in all samples; SSTR3 RNA expression was detected in only 33% of samples. In feline meningiomas (n=12), RNA expression of SSTR1, SSTR4, SSTR5 and SSTR2 was detected in 91%, 46%, 46% and 36% of samples, respectively; SSTR3 was not expressed. Overall, the detection rate was lower in FFPE samples. IHC revealed the expression of SSTR1 and SSTR2 in all samples from both species. However, it is important to exercise caution when interpreting IHC results due to the presence of diffuse background staining. SSTRs are widely expressed in canine and feline meningiomas, thereby encouraging further studies investigating SSTR expression to conduct trials about the effect of adjunctive therapy with long-acting SST-analogues.

Effective alleviation of depressive and anxious symptoms and sleep disorders in benzodiazepine-dependent patients through repetitive transcranial magnetic stimulation.

Benzodiazepine (BZD) dependence poses a significant challenge in mental health, prompting the exploration of treatments like repetitive transcranial magnetic stimulation (rTMS). This research aims to assess the impact of rTMS on alleviating symptoms of BZD dependence. A randomized control trial was employed to study 40 BZD-dependent inpatients. Their symptoms were quantified using the Hamilton Anxiety Rating Scale (HAMA), Montgomery-Åsberg Depression Rating Scale (MADRS) and Pittsburgh Sleep Quality Index (PSQI). Participants were divided into a conventional treatment group (daily diazepam with gradual tapering) with supportive psychotherapy and another group receiving the same treatment supplemented with rTMS (five weekly sessions for 2weeks). Significant improvements were observed in both groups over baseline in MADRS, HAMA and PSQI scores at the 2nd, 4th, 8th and 12th week assessments (p <0.05). The group receiving rTMS in addition to conventional treatment exhibited superior improvements in all measures at the 8th and 12th weeks. The addition of rTMS to conventional treatment methods for BZD dependence significantly betters the recovery in terms of depression, anxiety and sleep quality, highlighting the role of rTMS as an effective adjunct therapy.

Remote ischemic conditioning prevents ischemic cerebrovascular events in children with moyamoya disease: a randomized controlled trial.

Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. In a single-center pilot study, 46 MMD patients aged 4 to 14years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.

Efficacy of dexamethasone as adjunctive therapy in the treatment of parapneumonic pleural effusion in children

Background Parapneumonic effusion (PPE) occurs as a complication in around 13% of instances of community-acquired pneumonia. Aim To assess the effect of dexamethasone as an adjunctive therapy in the treatment of PPEs in children. Patients and methods This is a double-blinded, parallel-group, placebo-controlled, randomized clinical trial carried out on 60 children aged from 1 to 13 years with pneumonia complicated by PPEs. Patients were randomly divided into two equal groups (with the usual treatment in the form of double antibiotics given to all) and either intravenous dexamethasone at a dose of 0.25 mg/kg every 12 h for 3 days (group A) or intravenous saline every 12 h for 3 days as placebo (group B). Results Duration of hospitalization, chest tube insertion, and number of patients referred to the pediatric intensive care unit were significantly lower in group A than in group B (P=0.007, P&lt;0.001 and P=0.025, respectively). Normal PPE was significantly higher in group A than in group B (P=0.025) after 2 weeks, and small PPEs were significantly higher in group A than group B (P=0.008) on the 7th day. Fluid thickness by chest ultrasound on the 7th day was significantly lower in group A than in group B (P=0.016). Conclusion Dexamethasone was an effective adjunctive therapy for PPEs in children.

Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation

BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious complication of chronic obstructive pulmonary disease, often characterized by increased morbidity and mortality. In traditional Chinese medicine, AECOPD is linked to phlegm-heat and blood-stasis, presenting symptoms like thick sputum, fever, and chest pain. It has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD, suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type AECOPD. AIM To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type AECOPD. METHODS One hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two groups. The treatment group received acetylcysteine inhalation (10% solution, 5 mL, twice daily) along with conventional therapy, whereas the control group received only conventional therapy. The treatment duration was 14 d. Inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) in the serum and sputum as well as lung function parameters (forced expiratory volume in one second, forced vital capacity, and peak expiratory flow) were assessed pre- and post-treatment. Acetylcysteine inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group (P &lt; 0.05). This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type AECOPD. RESULTS Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control group. These differences were statistically significant (P &lt; 0.05). The study concluded that acetylcysteine inhalation had a positive effect on microinflammation and lung ventilation function in patients with this type of AECOPD, suggesting its potential as an adjuvant therapy for such cases. CONCLUSION Acetylcysteine inhalation demonstrated significant improvements in reducing inflammatory markers in the serum and sputum, as well as enhancing lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD. These findings suggest that acetylcysteine could serve as a valuable adjuvant therapy for individuals with this specific type of AECOPD, offering benefits for managing microinflammation and optimizing lung function.

Potassium iodide enhances the killing effect of methylene blue mediated photodynamic therapy against F. monophora

BackgroundChromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. MethodsIn vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. ResultsKI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. ConclusionKI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.

Effects of jujube (Ziziphus jujuba mill.) fruit extracts on oxidative stress: A systematic review and meta-analysis of rodent studies.

This study aimed to evaluate the effects of jujube (Ziziphus jujuba Mill.) fruit extracts on oxidative stress levels in rodent models. Animal studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Periodical Service Platform. The Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool was used to evaluate the risk of bias in the included studies. A meta-analysis was performed based on the guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions (CHSRI) by using Stata 17.0 software. Nineteen studies were included in the meta-analysis. Jujube fruit extracts significantly decreased the level of malonaldehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Meanwhile, there was no significant improvement in the catalase (CAT) levels. In addition, there was considerable heterogeneity in the results of the meta-analysis. The results of the subgroup analysis indicated that the animal model, type of extracts, and source of target parameters may have contributed to the heterogeneity. Jujube fruit extracts are healthy and effective antioxidant dietary supplements that may be an effective adjunctive therapy for diseases in which oxidative stress is a major pathological factor. However, the overall methodological quality of the included studies was low, and additional research is warranted.

Evaluation of the Efficacy and Safety of Intravenous Immunoglobulin (IVIG) in Moderate-to-Severe Hospitalized COVID-19 Patients: A Randomized, Open-Label Parallel-Group Study.

Since February 2020, the world has been overwhelmed by the SARS-CoV-2 outbreak, and several patients suffered interstitial pneumonia and respiratory failure requiring mechanical ventilation, threatening the capability of healthcare systems to handle this amount of critical cases. Intravenous immunoglobulins (IVIG) possess potential immunomodulatory properties beneficial for COVID-19 patients, yet evidence supporting IVIG as adjunctive therapy remains sparse. This study evaluated the outcomes of adjunctive IVIG with the standard of care (SoC) in moderate-to-severe COVID-19 patients. This randomized study included 59 moderate-to-severe COVID-19 patients with known comorbidities. One arm (n = 33) received high-dose IVIG (400 mg/kg/day) within 48 hours for five days alongside SoC, while the other arm (n = 26) received SoC, comprising steroids, enoxaparin, and remdesivir. The primary endpoint was clinical improvement, as measured by the National Early Warning Score 2 (NEWS2) and discharged/death proportions. Secondary outcomes included IVIG safety, hospitalization duration, changes in oxygen saturation, inflammatory markers, IgG titer, CTSS (CT severity score), and radiological findings. There was an improvement in the NEWS2 at the end of treatment in the IVIG arm (5.67 vs. 5.96). A significant absolute effect improvement (Day 1 vs. Day 9) was seen in serum LDH, D-dimer, hs-CRP, IL-6, CTSS, procalcitonin, respiratory rate, and chest radiographic findings. SARS-CoV-2 IgG titer increased significantly in the IVIG arm. There was a statistically significant reduction in mortality in the IVIG group (5 vs. 10). IVIG was a safe and effective adjunctive therapy to SoC treatment in moderate-to-severe COVID-19 patients needing ventilatory support. Furthermore, studies are required to validate our findings. This trial is registered with CTRI/2021/05/033622.

Safinamide as adjunctive therapy to levodopa monotherapy for patients with Parkinson's disease with wearing-off: The Japanese observational J-SILVER study

BackgroundSafinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice. MethodsThis multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment. ResultsIn total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change −7.0 [p = 0.012], −2.4 [p = 0.007] and − 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild. ConclusionSafinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns. Study registrationUniversity Hospital Medical Information Network in Japan; study ID: UMIN000044341.

RENAL DENERVATION RESULTS IN SUBSTANTIAL NOCTURNAL BP REDUCTION IN PATIENTS WITH A REVERSED DIPPING PATTERN

Objective: We characterized patients with reverse blood pressure (BP) dipping pattern and uncontrolled hypertension (HTN) at baseline referred for radiofrequency renal denervation (RF RDN), and their subsequent BP changes. Design and method: Patients with HTN were enrolled into the Global SYMPLICITY Registry (GSR) DEFINE and underwent RF RDN. Patients were grouped into different BP dipping patterns defined by night/daytime BP ratio: dippers (ratio 0.9 or below), non-dippers (ratio 0.9 to 1.0 or below), reverse dippers (ratio &gt;1.0). Baseline characteristics and BP changes through 3yrs were compared between groups based on dipper patterns. Statistical significance was defined as p&lt;0.05. Results: As of March 2023, 3331 patients with uncontrolled BP were enrolled, 2276 of whom had 24-h BP measures and could be categorized by dipping patterns. Majority of the patients were non-dippers (44.3%), followed by dippers (34.6%) and reverse dippers (21.1%). Reverse dippers (n=480) were the oldest (62±12yrs; p=0.0024), more likely to have cardiac disease (54.2%; p&lt;0.0001), diabetes (48.1%; p&lt;0.0001) and renal disease (38.9%; p&lt;0.0001). Reverse dippers had the highest baseline 24-h ambulatory systolic BP (SBP) (156±19mmHg; p&lt;0.0001) and nighttime SBP (163±21; p&lt;0.0001). In contrast, they had the lowest daytime SBP (153±19mmHg; p&lt;0.0001) and heart rate (66±11bpm; p&lt;0.0001). Reverse dippers were prescribed the most antihypertensive drugs (5.2±1.7; p=0.0058). 3yrs after RF RDN, significant overall 24-h ambulatory SBP reduction from baseline was observed within all dipping patterns, and the largest reduction was observed within reverse dippers (-11.8±25.1mmHg; Figure), particularly in the nighttime (-21.1±23.8mmHg). Conclusions: Reverse dippers with uncontrolled HTN referred for RDN were prescribed more antihypertensive drugs and had more comorbidities compared to patients with other dipping patterns. After RF RDN, significant SBP changes from baseline were observed irrespective of dipping status. The largest BP reduction was observed in nighttime BP in patients with reverse dipping pattern. RF RDN may offer an effective adjunctive therapy to drugs to lower nighttime BP patients with a reverse dipping pattern, who have the highest risk of cardiovascular events.

K-WISC-V Processing Speed Index Analysis to Verify the Effectiveness of ADHD Symptom Improvement Using Pediatric Digital Content

The most common treatment approach for children diagnosed with attention deficit hyperactivity disorder (ADHD) involves drug therapy; however, persuading parents and motivating children in the early stages of treatment is challenging. Consequently, there is a growing interest among parents of children with ADHD in non-drug therapies. Moreover, recent advancements in information and communication technology have increased the accessibility of digital treatments for ADHD and non-drug therapy content. However, some challenges persist in confirming specific and objective effects. In this retrospective study, we developed game-type digital therapy content for children aged 6–16 years and monitored improvements in ADHD symptoms using the K-WISC-V subtest processing speed index. The analysis revealed that the rate of change in the sum of converted scores on the 14th day was 0.64% lower in the experimental group compared with the control group; however, on the 28th day, the rate of change increased by 6.93%. This suggests that the supplementary use of Neuroworld DTx therapy proved effective for visual enhancement. Furthermore, improvements were observed in visual discrimination, short-term memory, and motor cooperation abilities. Consequently, game-based digital content is an effective adjunctive therapy for children dealing with ADHD.

Interaction of olive oil-based propolis and caffeic acid phenethyl ester with methylprednisolone used in the treatment of human acute myeloid leukemia.

Methylprednisolone (MP) is a pharmaceutical agent employed in the management of Leukemia, which is a systemic malignancy that arises from abnormalities in the hematological system. Numerous investigations in the field of cancer research have directed their attention towards propolis, a natural substance with significant potential as a treatment-supportive agent. Its utilization aims to mitigate the potential adverse effects associated with chemotherapy medications. The objective of this study was to examine the impact of olive oil-based propolis (OEP) and caffeic acid phenethyl ester (CAPE) on the treatment of acute myeloid leukemia, as well as to determine if they exhibit a synergistic effect when combined with the therapeutic support product methylprednisolone. The proliferation of HL-60 cells was quantified using the WST-8 kit. The PI Staining technique was employed to do cell cycle analysis of DNA in cells subjected to OEP, CAPE, and MP, with subsequent measurement by flow cytometry. The apoptotic status of cells was determined by analyzing them using flow cytometry after staining with the Annexin V-APC kit. The quantification of apoptotic gene expression levels was conducted in HL-60 cells. In HL-60 cells, the IC50 dosages of CAPE and MP were determined to be 1 × 10- 6 M and 5 × 10- 4 M, respectively. The HL-60 cells were subjected to apoptosis and halted in the G0/G1 and G2/M phases of the cell cycle after being treated with MP, CAPE, and OEP. Propolis and its constituents have the potential to serve as effective adjunctive therapies in chemotherapy.

A Systematic Review and Meta-Analysis of Efficacy and Safety of Cilostazol Prescription in Patients With Femoropopliteal Peripheral Artery Disease After Endovascular Therapy.

The purpose of this study is to assess the efficacy and safety of cilostazol prescription in patients with femoropopliteal peripheral artery disease (PAD) after endovascular therapy (EVT). We conducted a systematic review and meta-analysis of all studies reporting the outcomes of cilostazol after femoropopliteal EVT of PAD up to September 2022. Clinical outcomes of interest included primary patency, in-stent restenosis (ISR), vessel re-occlusion, freedom from target lesion revascularization (TLR), repeat revascularization, all-cause mortality, amputation, major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs), and bleeding complication. A total of 4 randomized controlled trials (RCTs) and 8 observational studies containing a total of 4898 patients met the inclusion criteria and were included in this systematic review and meta-analysis. We found that the use of cilostazol was associated with higher primary patency after femoropopliteal artery EVT (odds ratio [OR]=1.67, 95% confidence interval [CI]=1.50-1.87, p<0.001, I2=33.2%), a lower risk of ISR (OR=0.43, 95% CI=0.29-0.63, p<0.001, I2=37.6%), repeat revascularization (OR=0.43, 95% CI=0.24-0.76, p<0.005, I2=27.4%), and vessel re-occlusion (OR=0.59, 95% CI=0.38-0.93, p<0.05, I2=0%). There was an increase in freedom from TLR rate (OR=2.19, 95% CI=1.58-3.05, p<0.001, I2=0%), as well as a reduction in the occurrence of MALEs (OR=0.50, 95% CI=0.29-0.85, p<0.05, I2=0%). However, there was no significant difference in amputation, MACEs, all-cause mortality, and major bleeding complications. Subgroup analysis showed that cilostazol treatment in patients with femoropopliteal drug-eluting stents (DES) implantation remained associated with higher primary patency and a lower risk of ISR. After EVT of femoropopliteal artery lesions, additional oral cilostazol enhances primary patency, reduces the occurrences of ISR and vessel re-occlusion, diminishes the risks associated with MALEs, lowers the need for repeat revascularization, and increases freedom from TLR rates. However, it does not impact amputation, MACEs, all-cause mortality, or major bleeding complications. These findings suggest cilostazol as a potentially safe and effective adjunct therapy in patients with femoropopliteal PAD after EVT. After undergoing endovascular therapy (EVT) for femoropopliteal artery lesions, the addition of cilostazol to antiplatelet therapy can significantly improve primary patency, reducing the incidence of in-stent restenosis, repeat revascularization, vessel re-occlusion, and major adverse limb events while increasing freedom from target lesion revascularization rate. The simultaneous use of drug-eluting stents in the femoropopliteal artery lesions, combined with cilostazol, potentially results in a synergistic anti-stenotic effect. This therapeutic approach does not appear to be associated with an increased risk of major bleeding events or all-cause mortality. These findings provide additional evidence supporting the treatment of anti-stenosis in patients with femoropopliteal artery lesions after EVT.

A Robust Predictive Model for Early Detection of Heart Disease using Machine Learning

Heart failure is a chronic disease affecting millions worldwide. An efficient machine learning- based technique is needed to predict heart failure health status early and take necessary actions to overcome this worldwide issue. While medication is the primary treatment, exercise is increasingly recognized as an effective adjunct therapy in managing heart failure. This research project aims to develop a robust predictive model for the early detection of heart diseases by leveraging machine learning techniques, with a specific focus on the application of Support Vector Machines (SVM). The growth in technology has improved the information or data which can be extracted from a patient to help pinpoint the cause of illness. Using different number of attributes or data from the medical profile of a patient can predict the chance of a patient developing a heart condition. In simple terms, these attributes are loaded into logistic regression, Decision Tree, Random Forest, SVM, KNN and Naive bayes, that is, Machine learning (ML) algorithms for the analysis and further prediction of heart disease. There are many other techniques, methods used by other researchers. By using this method, the standards in the medical industries are elevated and rose as they can provide better diagnostics and treatment of the patient, resulting in providing an overall good quality service. This has its main focus towards: Using Data analysis, creating prediction Models to provide early detection of Heart Diseases, Also, by creating a reliable method to predict heart disease. Thus, we found that supervised machine learning algorithms can be used to make heart disease predictions with very high accuracy and excellent potential utility. Our proposed research study has significant scientific contributions to the medical community. Key Words: Machine learning, heart failure, cross validations, feature engineering, Naive Bayes, k Nearest Neighbor (KNN), Decision tree, Artificial Neural Network (ANN), Random Forest, Heart Disease.

Tumor-derived exosomal PD-L1: a new perspective in PD-1/PD-L1 therapy for lung cancer.

Exosomes play a crucial role in facilitating intercellular communication within organisms. Emerging evidence indicates that a distinct variant of programmed cell death ligand-1 (PD-L1), found on the surface of exosomes, may be responsible for orchestrating systemic immunosuppression that counteracts the efficacy of anti-programmed death-1 (PD-1) checkpoint therapy. Specifically, the presence of PD-L1 on exosomes enables them to selectively target PD-1 on the surface of CD8+ T cells, leading to T cell apoptosis and impeding T cell activation or proliferation. This mechanism allows tumor cells to evade immune pressure during the effector stage. Furthermore, the quantification of exosomal PD-L1 has the potential to serve as an indicator of the dynamic interplay between tumors and immune cells, thereby suggesting the promising utility of exosomes as biomarkers for both cancer diagnosis and PD-1/PD-L1 inhibitor therapy. The emergence of exosomal PD-L1 inhibitors as a viable approach for anti-tumor treatment has garnered significant attention. Depleting exosomal PD-L1 may serve as an effective adjunct therapy to mitigate systemic immunosuppression. This review aims to elucidate recent insights into the role of exosomal PD-L1 in the field of immune oncology, emphasizing its potential as a diagnostic, prognostic, and therapeutic tool in lung cancer.

The Effectiveness of Augmenting Modafinil to Risperidone or Olanzapine for Treating Negative Symptoms in Schizophrenic Patients: A Randomized Controlled Trail

Background: Recent evidence suggests the potential efficacy of modafinil in addressing specific symptom domains associated with schizophrenia, particularly negative and cognitive symptoms. However, it's important to note that findings in this area have been inconsistent. Objectives: This study was done to assess the impact of modafinil on improving negative symptoms in schizophrenia patients. Methods: In this clinical trial, 40 individuals diagnosed with schizophrenia and referred to Golestan Hospital were selected. Patients received a daily dose of 100 to 200 mg of modafinil in addition to their ongoing antipsychotic treatment with either Risperidone or Olanzapine. In the control group, patients received a placebo along with their prescribed antipsychotic therapy. The duration of the follow-up was 4 weeks. Both the evaluator and the patients were blinded to the administered medication. The Scale for the Assessment of Negative Symptoms (SANS) was utilized to measure negative symptoms before the intervention, and at 2 and 4 weeks following the intervention. Results: The mean age of participants in the intervention and control groups was 34.00 ± 6.60 and 36.90 ± 6.88 years, respectively. Two weeks after the intervention, the average SANS score was lower in the intervention group compared to the placebo group (99.70 ± 10.24 vs. 111.24 ± 7.08, P = 0.04). At 4 weeks post-intervention, the average SANS score in the intervention group was significantly reduced compared to the placebo group (84.39 ± 3.54 vs. 113.79 ± 3.75, P = 0.002). Conclusions: This study suggests that modafinil may be an effective adjunctive therapy for schizophrenia, particularly for treating anhedonia symptoms.

Astaxanthin treatment reduces kidney damage and facilitates antioxidant recovery in lithium-intoxicated rats

ObjectiveThis study aimed to evaluate the protective effects of astaxanthin against lithium-induced nephrotoxicity, focusing on histopathological changes, oxidative stress modulation, and alteration in the expression of key proteins related to apoptosis and inflammation. MethodsIn this study, 56 male rats were utilized and divided into experimental groups subjected to lithium-induced nephrotoxicity, with and without astaxanthin treatment, over 14 and 28 days. The parameters assessed included oxidative stress markers (MDA, GSH, SOD), protein expression levels of BCL-2, BAX, TNF- α, PI3K, NF-κ B-p65, IL-1β, and comprehensive histopathological examinations to evaluate the integrity of renal tissue. ResultsLithium exposure led to significant renal damage, as evidenced by histological distortions in renal architecture, increased oxidative stress indicated by elevated MDA levels, and dysregulated expressions of apoptotic and inflammatory proteins. Notably, histopathological analysis revealed glomerular and tubular degeneration in lithium-treated groups. Astaxanthin treatment effectively mitigated these effects, demonstrating its efficacy in reducing lipid peroxidation, rebalancing apoptotic proteins, suppressing pro-inflammatory cytokines, and preserving renal histological structure. The concurrent use of lithium and astaxanthin showed a considerable amelioration of lithium-induced damage, suggesting astaxanthin's role in attenuating the nephrotoxic effects of lithium, both at a molecular and structural level. ConclusionAstaxanthin demonstrates significant renoprotective effects against lithium-induced nephrotoxicity, suggesting its utility as an effective adjunctive therapy. Through its potent antioxidative, anti-inflammatory, and anti-apoptotic actions, astaxanthin effectively reduces renal damage associated with lithium treatment, underscoring its potential for enhancing renal health in patients receiving lithium therapy.