Percent Reduction Research Articles

A UK multicentre audit of the management of patients with primary hypercholesterolaemia or mixed dyslipidaemia with bempedoic acid against published lipid-lowering treatment targets.

Bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, was introduced to UK practice via a pre-reimbursement access scheme for adults with primary hypercholesterolaemia or mixed dyslipidaemia who are at high risk of cardiovascular disease, in whom statins are either not tolerated or contraindicated, who have not achieved target cholesterol, despite being on ezetimibe therapy, and do not qualify for PCSK9 inhibitor treatment. This retrospective multicentre audit aimed to evaluate the achievement of lipid-lowering targets with bempedoic acid in UK patients based on recommendations in the Joint British Societies (JBS) guidelines for the prevention of cardiovascular disease. Pseudo-anonymized medical record data for 221 adults treated with bempedoic acid as part of the UK scheme were entered into a bespoke data collection tool at four UK hospitals. Patient demographics, clinical characteristics, treatment pathways and lipid assessment results (against JBS lipid-lowering targets) were collected against pre-specified criteria. Overall, 54% (99/184) of patients achieved the JBS2 audit standard (total cholesterol (TC) <5 mmol/L and low-density lipoprotein cholesterol (LDL-C) <3 mmol/L or ≥25% reduction in TC and ≥30% reduction in LDL-C) at 12 weeks post-initiation. At week 12, the mean absolute change in LDL-C was -1.0 mmol/L; the mean percentage reduction from baseline was 22.0%. Additionally, 52% (96/185) of patients had an LDL-C of <3 mmol/L and 10% (18/185) an LDL-C of <1.8 mmol/L at 12 weeks (as per JBS3). This audit highlights the role of bempedoic acid as part of combination therapy for a population with previously limited treatment options.

High concentrations of piperonyl butoxide (PBO) enhance toxicity of S-methoprene against the lesser grain borer, Rhyzopertha dominica.

Insect growth regulators (IGRs) have been playing a major role in the effective management of a range of stored product insect pests including species that have developed resistance to major groups of insecticides, such as organophosphates (OPs) and synthetic pyrethroids (SPs). In the present study, we evaluated the efficacy of S-methoprene alone and in combination with piperonyl butoxide (PBO), an adjuvant component of insecticides for synergy, against two strains, Lab-S (susceptible) and Met-R (Methoprene resistant) of an economically important pest species, the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae). Adults of both Lab-S and Met-R strains were exposed to wheat treated with multiple concentrations of S-methoprene ranging from 0.001 to 0.01 and 10 to 60 mg/kg, respectively, alone and in combination with PBO. A variety of concentrations, including 0.27, 0.53, 0.80, and 1.07 g/kg, were evaluated for PBO. Mortality of adults and percent reduction in progeny were assessed after 14 and 65 days of treatment, respectively. As anticipated, the adult mortality rates of both strains were not significantly affected by S-methoprene alone. However, the number of progeny produced confirmed that the Met-R strain exhibited a high level of resistance to S-methoprene alone, with over 50 F1 progeny adults surviving in wheat treated with the maximal rate, 10 mg/kg. In contrast, the toxicity of S-methoprene was increased against the same resistant strain (Met-R), by 0.80 or 1.07 g/kg of PBO in combination treatment, resulting in a significant reduction in progeny numbers (25 adults per container). Although the tested concentrations of S-methoprene and PBO were well above the currently registered rate globally, our results highlight the fact that PBO enhances the toxicity of S-methoprene to some extent, reaffirming that the mode of action of the latter involves the inhibition of mixed-function oxidases (MFOs) and highlights the need for further research into developing potential binary or triplet formulations containing these two active ingredients (AIs).

Therapeutic potential of platelet rich plasma against experimental Cryptosporidium parvum infection: in vivo study in immunosuppressed mice.

The present study was designed to assess the possible effects of platelet rich plasma (PRP) when used individually and in combination with nitazoxanide (NTZ) on experimental Cryptosporidium parvum (C. parvum) infection. It was conducted on 100 male albino mice, laboratory bred in Theodore Bilharz Research Institute. Starting from the 7th day post infection (p.i), therapeutics were given to immunosuppressed infected mice, which were divided as follows; oral NTZ treated group (0.2 mg/g/day for 6 consecutive days), six-PRP-treated groups (0.5 μl/g/week) to be administered intravenously (IV) in 1st, 2nd, 3rd week as PRP alone in (3 groups) and combined with oral NTZ (0.2 mg/g/day for 6 consecutive days) in (3 groups). Parasitological, histopathological and immunohistochemical assessments of therapeutics under study were done. Fecal pellets collected from groups at different intervals were stained using modified Ziehl-Neelsen and examined under microscope. Among PRP-treated groups, the highest significant percentage of oocyst reduction (89.96%) was observed in the group received 3 doses of PRP in combination with NTZ on the 35th day post infection. Likewise, the histopathological examination of small intestinal tissue sections showed improvement in villous architecture with mild to moderate stunting and moderate inflammatory infiltrates in lamina propria. Immunohistochemical staining of small intestinal tissue sections showed moderate increase in the expression of TGF-β1. Therefore, PRP can be a novel strategy in the treatment of cryptosporidiosis particularly when combined with NTZ.

Estimated number of lives directly saved by COVID-19 vaccination programmes in the WHO European Region from December, 2020, to March, 2023: a retrospective surveillance study

By March, 2023, 54 countries, areas, and territories (hereafter CAT) in the WHO European Region had reported more than 2·2 million COVID-19-related deaths to the WHO Regional Office for Europe. Here, we estimated how many lives were directly saved by vaccinating adults in the WHO European Region from December, 2020, to March, 2023. In this retrospective surveillance study, we estimated the number of lives directly saved by age group, vaccine dose, and circulating variant-of-concern (VOC) period, regionally and nationally, using weekly data on COVID-19 mortality and infection, COVID-19 vaccination uptake, and SARS-CoV-2 virus characterisations by lineage downloaded from The European Surveillance System on June 11, 2023, as well as vaccine effectiveness data from the literature. We included data for six age groups (25-49 years, 50-59 years, ≥60 years, 60-69 years, 70-79 years, and ≥80 years). To be included in the analysis, CAT needed to have reported both COVID-19 vaccination and mortality data for at least one of the four older age groups. Only CAT that reported weekly data for both COVID-19 vaccination and mortality by age group for 90% of study weeks or more in the full study period were included. We calculated the percentage reduction in the number of expected and reported deaths. Between December, 2020, and March, 2023, in 34 of 54 CAT included in the analysis, COVID-19 vaccines reduced deaths by 59% overall (CAT range 17-82%), representing approximately 1·6 million lives saved (range 1·5-1·7 million) in those aged 25 years or older: 96% of lives saved were aged 60 years or older and 52% were aged 80 years or older; first boosters saved 51% of lives, and 60% were saved during the Omicron period. Over nearly 2·5 years, most lives saved by COVID-19 vaccination were in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among the most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures. US Centers for Disease Control and Prevention.

Evaluating the health outcomes of aging in place: the role of medicaid aging waiver program on U.S. older adults

The Medicaid Aging Waiver program (MAW) subsidizes the cost of long-term care (LTC) at home or in communities to satisfy older people’s increasing desire to age in place. The MAW program might be health improving for older people by allowing them to age at home. However, less quality and quantity of home-based care comparing to nursing home care could offset some of the potential benefits. I use policy expenditure across states over time linked with detailed health information from the Health and Retirement Study (HRS) to identify the associated effects of MAWs on health outcomes of older adults who are at risk of needing LTC and who are resources constrained to be potentially eligible for Medicaid. Overall, the findings suggest that the MAW program is beneficial to health: a $1,000 increase in MAW spending for each older person results is associated with a 1.4 percent improvement in self-reported health status, a 1.5 percent reduction in functional mobility limitations, a 1.6 percent decrease in Instrumental Activities of Daily Living (IADL) limitations, and a 1.7 percent improvement in negative psychological feelings. For older people who are most likely not eligible for MAWs, such as those who are wealthy or in good health and do not require LTC, these health-improving effects have not been observed.

The Effect of 4-Month Treatment with Glycocalyx Dietary Supplement on Endothelial Glycocalyx Integrity and Vascular Function in Patients with Psoriasis.

Psoriasis predisposes to cardiovascular dysfunction. We investigated whether glycocalyx dietary supplement (GDS), which contains glycosaminoglycans and fucoidan, improves endothelial glycocalyx and arterial stiffness in psoriatic patients. Fifty participants with psoriasis under biological agents were randomly assigned to GDS (n = 25) or placebo (n = 25) for 4 months. We measured at baseline and at follow-up: (a) perfused boundary region (PBR) of the sublingual microvessels (range 4 to 25 μm), a marker of endothelium glycocalyx integrity; (b) carotid-femoral pulse wave velocity (PWV-Complior SP-ALAM) and augmentation index (AIx), markers of arterial stiffness and (c) psoriasis area and severity index (PASI) score. Both groups displayed a similar decrease in PASI at four months (p < 0.05), and no significant differences were found between groups (p > 0.05). Compared to the placebo, participants in the GDS showed a greater percentage reduction in PBR4-25 μm (-9.95% vs. -0.87%), PBR 4-9 μm (-6.50% vs. -0.82%), PBR10-19 μm (-5.12% vs. -1.60%), PBR 20-25 μm (-14.9% vs. -0.31%), PWV (-15.27% vs. -4.04%) and AIx (-35.57% vs. -21.85%) (p < 0.05). In the GDS group, the percentage reduction in PBR 4-25 μm was associated with the corresponding decrease in PWV (r = 0.411, p = 0.015) and AΙx (r = 0.481, p = 0.010) at follow-up. Four-month treatment with GDS improves glycocalyx integrity and arterial stiffness in patients with psoriasis. Clinical trial Identifier: NCT05184699.

Effect of combinations of 3,4‐dihydroxyphenylacetic acid and its esters on the oxidative stability of fish oil–containing trace water

AbstractThe current study aims to comprehend the effect of the various combinations of 3,4‐dihydroxyphenylacetic acid (3,4‐DHPA) and its esters in varying molar ratios on retarding oxidation in bulk refined fish oil in the presence of 0.3% w/w water. All the esters and 3,4‐DHPA exhibited better performance than the synthetic antioxidant butylated hydroxytoluene. In the presence of trace water, the parent compound was found to have a synergistic effect with hexyl ester when used at a molar ratio of 2:1, respectively, exhibiting a higher percent reduction among all the esters and their combinations. The study also showed that the presence of extraneous water can significantly accelerate the oxidation (twofold) in a bulk fish oil system. This suggests that the microenvironment of the oil is altered when water is present and that association colloids play a key role in enhancing the rate of oxidation. Thus, while designing a competent mixture of antioxidants, the specific site of oxidation involved and the surface‐active components should be taken into consideration to efficiently retard oxidation.Practical Applications: Analyzing the impact of trace amounts of water on the efficiency of natural antioxidants, including 3,4‐DHPA and its lipophilic esters, helps to comprehend the required optimal antioxidant concentrations for such a dynamic bulk oil system. The study finds application in controlling oxidation in PUFA‐rich oils containing surface‐active minor components that can accelerate oxidation. The results of the study show that 3,4‐DHPA and its esters could be a potential replacement for the synthetic antioxidant BHT in all aspects.

A kinetic modelling approach to explore mechanism of Cr(VI) detoxification by a novel strain Pseudochrobactrum saccharolyticum NBRI-CRB 13 using response surface methodology.

A novel Pseudochrobactrum saccharolyticum strain NBRI-CRB 13, isolated from tannery sludge, was studied to grow up to 500 mgL-1 of Cr(VI) and showed Cr(VI) detoxification by reducing > 90% of Cr(VI) at different concentrations 25, 50 and 100 mgL-1. Kinetic studies showed that first-order models were fitted (R2 = 0.998) to the time-dependent Cr(VI) reduction with degradation rate constant (k) (1.03-0.429h-1). Cr(VI) detoxification was primarily related to the extracellular fraction of microbial cells, which showed a maximum extracellular reductase enzyme activity led to 94.6% reduction of Cr(VI). Moreover, the strain showed maximum extracellular polymeric substances (EPS) production at 100 mgL-1 Cr(VI), which is presumably the reason for Cr(VI) removal as EPS serves as the metal binding site for Cr(VI) ions. Further, an optimization study using Box-Behnken design was conducted considering parameters viz., pH, temperature, and initial concentration of Cr(VI). The maximum percent reduction of Cr(VI) was obtained at pH 6.5, temperature 30°C with 62.5 mgL-1Cr(VI) concentration. Further, the Cr(VI) reduction and adsorption ability of strain P. saccharolyticum NBRI-CRB13 were confirmed by SEM-EDS, FTIR, and XRD analyses. FTIR analysis confirmed the presence of functional groups (-OH, -COOH, -PO4) on bacterial cell walls, which were more likely to interact with positively charged chromium ions. The study elucidated the reduction of Cr(VI) by the novel bacterium within 24h using the response surface methodology approach and advocated its application in real-time situations.

Neoadjuvant chemotherapy for advanced eyelid and periocular sebaceous gland carcinoma: a study of 25 cases.

To report the outcomes of platinum-based neoadjuvant chemotherapy (NACT) for eyelid and periocular sebaceous gland carcinoma (eSGC). Retrospective study of 25 patients. The mean age at presentation of eSGC was 59years. The mean tumor basal diameter was 46mm. By the 8th edition of AJCC classification, tumors belonged T2 (n = 2, 8%), T3 (n = 6, 24%), and T4 (n = 17, 68%); N1 (n = 12,48%); and M1 (n = 1, 4%). NACT with 5-fluorouracil (5-FU) and cisplatin/carboplatin was administered in 21 (84%)/4 (16%) patients, respectively. The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 2 (median, 3). The mean percentage reduction of tumor basal volume after neoadjuvant chemotherapy was 65% (median, 60%). After NACT, 12 (48%) patients underwent surgical treatment, 6 (12%) patients underwent EBRT, and 4 (8%) underwent adjuvant chemotherapy. A total of 11 (44%) patients were lost to follow-up during the course of treatment, of whom 3 died from metastatic disease. In 16 patients followed up for ≥ 3months, complete tumor control was achieved in 11 (69%) patients, local tumor control in 14 (88%), and globe salvage in 7 (44%) at a mean follow-up of 25months (median, 7months; range, 3 to 110months). No tumor recurrence was seen in any case. One (4%) serious adverse event of cardiotoxicity was noted. Platinum-based NACT is a suitable option for eSGC with advanced tumors and locoregional metastasis. Adverse events are rare and in patients compliant with treatment, NACT-based combination therapy offers globe salvage and systemic tumor control.

Portulaca grandiflora phytochemicals as a potential source for wound healing activity: in vitro and in vivo studies

The management of chronic wounds presents considerable challenges and has a substantial influence on the quality of life among afflicted persons and their families. The discovery of naturally produced bioactive chemicals having good effects on the regeneration of tissue has been driven by the need for safe, effective, and cost-effective wound healing therapies. Portulaca grandiflora is an annual succulent that comes under the family of Portulacaceae. The purpose of this study was to evaluate the phytochemicals of n-hexane extracts and their effects on in vitro and in vivo wound healing models. In vitro study, Wound Scratch Assay shows that n-hexane extract of 100 ug/ml concentration significantly promotes wound healing through increased cell migration and wound closure compared to MEBO ointment-treated groups and negative control groups. The in vivo study shows that the formula of the extract ointment promotes wound healing without any complication and the percentage of wound surface area reduction was (5.39 ± 0.391) better than MEBO-treated groups (10.06 ± 0.536), and negative control groups (14.04 ± 0.304) through its ability to stimulate epidermal closure, re-epithelization, and granulation that appears in histological examination. As a result, Iraqi Portulaca grandiflora can be considered a potential resource of chemical substances, especially terpenoids, and steroids, which are helpful in healing wounds.

PENERAPAN K-MEANS CLUSTERING UNTUK PEMETAAN PRODUKTIVITAS PADI DAN PREDIKSI PANEN DI KABUPATEN INDRAMAYU

Indonesia is a country where the majority of people consume rice, making the issue of rice harvest productivity a concern for many parties. Efforts to maintain food security, especially the availability of rice, are a shared responsibility, where efforts that can be made are to maintain and predict rice production results in areas that are National Rice Granaries. Indramayu is one of the national rice producing districts, which has 31 sub-districts with varying amounts of rice production. The large difference in rice production between sub-districts is an important problem that affects rice harvests in Indramayu, so improvements need to be made, including clustering, namely grouping sub-districts based on harvest potential using K-Means clustering by looking at historical harvest data for the past 5 years between 2019–2023. Then compared using the orange data mining application. K-Means clustering either manually or using orange3 produces three clusters with the same sub-district cluster results. This data is also used to predict future harvest results using the random forest algorithm in Orange3. Analysis of K-Means clustering results and prediction results shows that sub-districts in the lower cluster have the potential for a greater percentage reduction in harvest than clusters with a higher harvest category.

Antimicrobial Efficacy of Chemomechanical Carie Removal Agents-A Systematic Integrative Review.

Dental caries is the most common oral disease in the world. When treatable, the drilling method continues to be used. This technique has its disadvantages because it is invasive and nonspecific. Chemomechanical carious tissue removal agents (CCRAs) such as Carisolv™ or Papacarie® are non-invasive products that allow for the specific elimination of infected dentin. On the other hand, cariogenic bacteria are largely responsible for the initiation and development of lesions. The aim is to analyze whether CCRAs have a relevant antimicrobial effect on cariogenic bacteria. A bibliographic search strategy was carried out in online databases using PRISMA 2020. The evaluation of the antibacterial efficacy of CCRAs was carried out through the analysis of the reduction in CFUs of cariogenic bacteria, and the presence of bacterial deposits, TVC, SVC and LVC by comparison with conventional drilling methods. The results showed that the percentage of reduction in TVC, SVC and LVC for each agent is mostly high, but not significantly different from mechanical methods. The best results were found with CCRAs when compared to polymeric drills. The results also showed that there is a lack of methodological standardization. CCRAs have been shown to have a relevant antimicrobial effect on cariogenic bacteria; however, more studies need to be carried out using standardized methodologies.

Efficacy and safety of azathioprine versus mycophenolate mofetil in chronic actinic dermatitis in skin of color: results of a randomized controlled trial.

Chronic actinic dermatitis (CAD) is an immunologically mediated photodermatosis that has been effectively treated with azathioprine and mycophenolate mofetil (MMF) in uncontrolled studies. We conducted a prospective randomized controlled trial to compare the efficacy and safety of azathioprine and MMF in CAD treatment, aiming to address existing evidence gaps. Consecutive CAD patients were randomized into two groups: azathioprine (Group A) or MMF (Group B) for 12 weeks. Primary outcomes included Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) at baseline and Week 12. Secondary outcomes included various clinicodemographic factors predictive of treatment response, defined at least a 75% reduction in EASI score (EASI75) by Week 12. The median (IQR) percentage reduction in EASI at 12 weeks was higher in Group B than in Group A [78.3% (75.0-83.30%) vs. 68.3% (31.2-80.10%), P = 0.034]. Baseline DLQI scores indicated a moderate impact on quality of life, with significant reductions by Week 12 in both groups and no intergroup differences at baseline (P = 0.291) or Week 12 (P = 0.599). Overall, 23 patients were classified as non-responders, with more extended illness duration (P = 0.026) and outdoor occupations (P = 0.042) associated with poorer responses. Adverse effects were consistent with known profiles, with one patient discontinuing azathioprine due to hypersensitivity. Our study highlights the efficacy and safety of azathioprine and MMF in CAD treatment, with MMF showing superior outcomes. However, further research is warranted to explore emerging therapies and prognostic factors in CAD management.

In vitro assessment of the Kirpa Kit™ modified manual single lumen alternating micro-batch (mSLAMB) dialysis device.

Access to pediatric dialysis is challenged in low-resource settings due to high costs, scarcity of equipment, and the lack of qualified personnel availability. We demonstrated the manual single lumen alternating micro-batch (mSLAMB) device can remove small solutes in vitro without the need for electricity, batteries, or pumps. We developed a new version (Kirpa Kit™) to address some of the technical limitations of mSLAMB. Here, we compare the in vitro clearance performance and ease of use of the Kirpa Kit™ with that of prior mSLAMB configurations. A mixture of expired packed red blood cells, 0.9% NaCl, urea, and heparin was used to test the efficiency of two mSLAMB configurations and the Kirpa Kit™ in removing potassium and urea. Clearance was evaluated by measuring percent reduction after 25-min sessions with each device. A survey was used to evaluate the ease of use of each configuration. The Kirpa Kit™ achieved a median urea reduction of 82.4% and potassium reduction of 82.1%, which were higher than those achieved with the best-performing mSLAMB configuration (urea 71.9%, potassium 75.4%). The Kirpa Kit™ was easier to use with a shorter perceived time of use than the mSLAMB. The Kirpa Kit™, evolution of mSLAMB, is easy to use and may have improved efficacy, making it an optimal candidate for in vivo testing.

Dupilumab treatment in paediatric atopic dermatitis (2 to 18 years): Spanish multicentre retrospective real-life study.

Moderate-to-severe atopic dermatitis (AD) can be difficult to manage in paediatric patients, with few licensed treatments in this age group. Dupilumab is approved for AD in children older than 6 months. To assess the effectiveness and safety of dupilumab in a real-life cohort of paediatric AD patients in Spain. A multicentre, retrospective real-life study on the effectiveness and safety of dupilumab in patients aged 2 to 18 years old with moderate-to-severe AD was conducted. Demographic and clinical characteristics were analysed, and effectiveness (EASI, IGA, DLQI, NRS itch), safety, and drug survival measures were assessed. A comparison of our results with other real-world outcomes and with clinical trials was made. Data from 243 patients from 19 centres was collected, with a mean follow-up of 85 weeks. Dupilumab exhibited significant effectiveness, with marked reductions in severity scores from week 4. By week 16, 79.4% of patients reached EASI75 and 40.5% reached EASI90. Mean percentage reduction in EASI was 79.7%. Increasing improvements were observed until week 52, with 85.8% and 49.6% achieving EASI75 and EASI90, respectively. Forty-three patients developed adverse events (AE) (43/243, 17.7%), being the most frequent ocular surface diseases (20/243, 8.2%), injection site reactions (8/243, 3.3%) and facial redness (7/243, 2.9%). Drug survival was high (96.9% and 93.1% after 1 and 2 years of follow-up, respectively), with only 19 (19/243, 7.8%) patients interrupting treatment: 7 (7/243, 2.9%) due to AE, 2 (2/243, 0.82%) due to secondary failure, 5 (5/243, 2.1%) were lost to follow-up and 5 (5/243, 2.1%) entered remission and stopped treatment. Real-life use of dupilumab in paediatric AD showcased sustained effectiveness, high drug survival, and acceptable safety profiles. Longer-term studies are crucial for AE surveillance and how to manage disease remission.

Statistical considerations when estimating time-saving treatment effects in Alzheimer's disease clinical trials.

Estimating treatment effects as time savings in disease progression may be more easily interpretable than assessing the absolute difference or a percentage reduction. In this study, we investigate the statistical considerations of the existing method for estimating time savings and propose alternative complementary methods. We propose five alternative methods to estimate the time savings from different perspectives. These methods are applied to simulated clinical trial data that mimic or modify the Clinical Dementia Rating Sum of Boxes progression trajectories observed in the Clarity AD lecanemab trial. Our study demonstrates that the proposed methods can generate more precise estimates by considering two crucial factors: (1) the absolute difference between treatment arms, and (2) the observed progression rate in the treatment arm. Quantifying treatment effects as time savings in disease progression offers distinct advantages. To provide comprehensive estimations, it is important to use various methods. We explore the statistical considerations of the current method for estimating time savings. We proposed alternative methods that provide time savings estimations based on the observed absolute differences. By using various methods, a more comprehensive estimation of time savings can be achieved.

Dupilumab reduces inflammatory biomarkers in pediatric patients with moderate-to-severe atopic dermatitis

BackgroundPatients with atopic dermatitis (AD) often have elevated type 2 inflammatory serum biomarkers. ObjectiveTo report changes in thymus- and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17), total immunoglobulin E (IgE), lactate dehydrogenase (LDH), and eosinophils in pediatric patients treated with dupilumab or placebo. MethodsBiomarker data were analyzed from three randomized, double-blind, placebo-controlled, phase 3 studies of patients with moderate-to-severe AD. Patients aged 6 months–5 years were randomized to weight-dependent dupilumab 200/300mg every 4 weeks (q4w) or placebo; aged 6–11 years to dupilumab 100/200mg every 2 weeks (q2w), dupilumab 300mg q4w, or placebo; aged 12–17 years to dupilumab 200/300mg q2w, dupilumab 300mg q4w, or placebo. The youngest two groups also applied topical corticosteroids. Median percent changes from baseline to week 16 reported using last observation carried forward method, censoring after rescue treatment. ResultsPediatric patients who received dupilumab vs placebo achieved significantly greater median percent reductions at week 16 in: TARC/CCL17 (−83.3% to −72.4% vs −14.9% to −1.8%), total IgE (−71.2% to −58.4% vs −21.0% to +28.1%), and LDH (−26.2% to −9.8% vs −1.5% to +1.5%). All comparisons were significantly different (P < .0001) between each dupilumab dosing group and respective placebo groups. In contrast, absolute changes in eosinophils were small in all groups. ConclusionsDupilumab treatment for pediatric patients with moderate-to-severe AD significantly reduced levels of TARC/CCL17, total IgE, and LDH to levels comparable to those of healthy controls, reflecting a reduction in systemic type 2 and general inflammation.

Comprehensive scoping review of fenfluramine's role in managing generalized tonic-clonic seizures in developmental and epileptic encephalopathies.

Developmental and epileptic encephalopathies (DEEs) are characterized by pharmacoresistant seizures and developmental delay. Patients with DEEs experience multiple seizure types, including tonic-clonic seizures (TCS) that can be generalized tonic-clonic (GTCS) or focal evolving to bilateral tonic-clonic (FBTCS). Fenfluramine (FFA) has demonstrated efficacy in reduction of TCS in patients with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and other DEEs. Using the PRISMA-ScR (Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Review) guidelines, we performed a scoping review to describe changes in TCS in patients treated with FFA. A comprehensive search of five literature databases was conducted up to February 14, 2023. Studies were included if they reported change in GTCS or TCS (but not FBTCS) after treatment with FFA in patients with DEEs. Duplicate patients and studies with unclear efficacy data were excluded. Fourteen of 422 studies met the eligibility criteria. Data extracted and evaluated by expert clinicians identified 421 unique patients with DS (in nine studies), CDKL5 deficiency disorder, SCN8A-related disorder, LGS, SCN1B-related disorder, and other DEEs. The median percent reduction in GTCS or TCS from baseline was available in 10 studies (n = 328) and ranged from 47.2% to 100%. Following FFA treatment, 10 studies (n = 144) reported ≥50% reduction in GTCS or TCS from baseline in 72% of patients; in nine of those (n = 112), 54% and 29% of patients achieved ≥75% and 100% reduction in GTCS or TCS from baseline, respectively. Overall, this analysis highlighted improvements in GTCS or TCS frequency when patients were treated with FFA regardless of the DEE evaluated. Future studies may confirm the impact of FFA on TCS reduction and on decreased premature mortality risk (including sudden unexpected death in epilepsy), improvement in comorbidities and everyday executive function, decreased health care costs, and improvement in quality of life.

Novel polybenzoxazine-based arylidene moiety modified cellulose acetate for enhanced antifouling properties

Marine fouling is a widespread problem in the maritime industry, causing significant damage to equipment and vessels. Polybenzoxazine (PBz) is a resin that is both remarkable and captivating, and it has a wide range of sophisticated uses. Due to their distinctive characteristics, benzoxazines have sparked the interest of scholars globally. However, most benzoxazine resin production and processing depend on petroleum resources, particularly those based on bisphenol A. This study aimed to create new benzoxazine monomers using bio-based raw materials, primarily motivated by the environmental ramifications. The main goal of this study is to synthesize a benzoxazine molecule, specifically (2E,6E)-2,6-bis(3-(2-hydroxyethyl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-yl)methylene) cyclohexane-1-one, abbreviated as (CHPE), by employing an arylidene base. Later, the chemical was used as a modifier for the cellulose acetate (CA) matrix to create film samples. The primary objective is to evaluate the effectiveness of these film samples in preventing fouling. The CHPE molecule was produced using a bis(arylidene) cyclohexanone diol and analyzed using Fourier transform infrared (FTIR) and Nuclear magnetic resonance (NMR) spectroscopic techniques, respectively. The films were fabricated by blending various weight proportions. The composition of the (CHPE-CA) films was determined by FTIR analysis, while their morphology was examined using scanning electron microscopy (SEM). The thermal stability of the films was studied using Thermal Gravimetric Analysis (TGA). This study investigated the antifouling properties of polymer sheet compositions containing varying amounts of CA at two different processing temperatures, 180 °C and 200 °C and without curing. The results demonstrated the potential of incorporating CA into the polymer matrix to enhance antifouling performance. Among the polymer compositions tested, the 20% CA composition exhibited the highest percentage reduction in fouling at both processing temperatures, suggesting that a small amount of CA can contribute to effective antifouling properties.

A novel chlorin derivative Shengtaibufen (STBF) mediated photodynamic therapy combined with iodophor for the treatment of chronic superficial leg wounds infected with methicillin-resistant Staphylococcus aureus: A retrospective clinical study

ObjectiveChronic wounds are costly and difficult to treat, resulting in morbidity and even mortality in some cases due to a high methicillin-resistant Staphylococcus aureus (MRSA) burden contributing to chronicity. We aimed to observe the antimicrobial activity and healing-promoting effect of a novel photosensitizer Shengtaibufen (STBF)-mediated antibacterial photodynamic therapy (PDT) on MRSA-infected chronic leg ulcers. Patients and methodsThis was a retrospective, comparative, single-center clinical study. A total of 32 patients with chronic lower limb wounds infected with MRSA from January 2022 to December 2023 were finally included in this study by searching the electronic medical records of the dermatology department of Huadong Hospital, including a group of red light combined with iodophor (control+iodophor, n=16, receiving red light once a week for 8 weeks and routine dressing change with iodophor once a day) and a group of STBF-mediated PDT (STBF-PDT) combined with iodophor (STBF-PDT+iodophor, n=16, receiving STBF-PDT and routine dressing change with iodophor once a day). STBF-PDT was performed once a week (1 mg/ml STBF, 1 h incubation, 630 nm red light, 80 J/cm2) for 8 weeks. The primary endpoints included wound clinical signs, wound size, wound-related pain, re-epithelialization score, MRSA load and wound-related quality of life (wound-QoL). Any adverse events were also recorded. ResultsWe found that STBF-PDT+iodophor could effectively alleviate clinical infection symptoms, accelerate wound closure, reduce average biological burden and improve wound-QoL without severe adverse events in comparison to the control+iodophor group. The STBF-PDT+iodophor group obtained a mean percentage reduction of 65.22% in wound size (from 18.96±11.18 cm2 to 6.59±7.94 cm2) and excellent re-epithelialization scores, as compared with a decrease of 30.17% (from 19.23±9.80 cm2 to 13.43±9.32 cm2) for the control+iodophor group. Significant differences in wound area were observed at week 6 (p=0.028*) and week 8 (p=0.002**). The bacterial load decreased by 99.86% (from 6.45 × 107±2.69 × 107 to 8.94 × 104±1.92 × 105 CFU/cm2, p<0.0001) in the STBF-PDT+iodophor group and 1.82% (from 6.61 × 107±2.13 × 107 to 6.49 × 107±2.01 × 107 CFU/cm2, p=0.029) in the control+iodophor group. The wound-QoL in STBF-PDT+iodophor group had a 51.62% decrease in overall score (from 29.65±9.33 at the initial to 14.34±5.17 at week 8, p<0.0001) compared to those receiving red light and routine wound care (from 30.73±17.16 to 29.32±15.89 at week 8, p=0.003). Moreover, patients undergoing STBF-PDT+iodophor exhibited great improvements in all domains of wound-QoL (physical, psychological and everyday-life), whereas the control+iodophor group ameliorated in only one field (everyday-life). ConclusionOur data confirmed that a novel photosensitizer, STBF-mediated PDT, when combined with iodophor, served as a potential modality for MRSA infection and a possible therapy for other drug-resistant microorganisms, and as a promising alternative for chronic cutaneous infectious diseases.