Strengthening Research Articles

Celiac Disease, Gluten-Free Diet and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Celiac disease (CD) is a chronic autoimmune disorder triggered by the ingestion of gluten-containing food by genetically predisposed individuals. Hence, treatment of CD consists of permanent avoidance of wheat, rye, barley, and other gluten-containing foods. Lifelong adherence to a gluten-free diet (GFD) improves the symptoms of CD, but recent evidence suggests it is also associated with a higher risk for hepatic steatosis and the coexistence or emergence of other cardiometabolic risk factors. Moreover, a higher risk for liver steatosis is also reported by some authors as a potential extraintestinal complication of the CD itself. Recent nomenclature changes designate the association between hepatic steatosis and at least one of five cardiometabolic risk factors as metabolic dysfunction-associated steatotic liver disease (MASLD). An extended network of potentially causative factors underlying the association between MAFLD and CD, before and after dietary therapy is implemented, was recently described. The individualized treatment of these patients is less supported by evidence, with most of the current recommendations relying on empiric clinical judgment. This review focuses on the causative associations between CD and hepatic injury, either as an extraintestinal manifestation of CD or a side effect of GFD, also referring to potential therapeutic strategies for these individuals.

Persian Medicine Standard Terminology

Persian Medicine (PM) is an ancient and holistic healthcare approach that has been practiced for thousands of years. While PM is often considered to be a traditional or alternative form of medicine, it has a rich history and a wealth of knowledge that can be of great value in contemporary medical practice. It encompasses a wide range of medical practices, including herbal medicine, dietary therapy, manual intervention, and lifestyle modification. Despite its long history and widespread use, there is a lack of standardized terminology in PM, which can lead to confusion and miscommunication among practitioners and patients. The Persian Medicine standard terminology provides a framework for understanding Persian medical concepts and terminology and can serve as a bridge between traditional and modern medicine. Therefore, to systematize the use of Persian medicine standard terminology, a working group was formed in the Persian Medicine Office of the Iranian Ministry of Health. After gathering opinions from experts in Persian medicine and the English language, a set of commonly used words was identified for the project. The first step of the project includes 100 standardized terms which are presented in this paper.

Dietary ellagic acid therapy for CNS autoimmunity: Targeting on Alloprevotella rava and propionate metabolism

BackgroundMediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS.ResultsWe found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells.ConclusionsOur study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis.7AEBLBqRMMqqUZLLsSi8h5Video

Sequential Treatment with Modified Atkins Diet and Low Glycemic Index Treatment for Drug-Resistant Epilepsy in Children.

The present study was designed to study the efficacy of sequential dietary therapy with a modified Atkins diet (mAD) followed by low glycemic index treatment (LGIT) in treating drug-resistant epilepsy in children. This interventional study was conducted from February 2021 to February 2022 among children aged 6 months to 5 years who had failed to respond to more than two conventional and correctly chosen antiseizure medications. The primary endpoint was the proportion of good responders, that is, children with more than 50% seizure reduction. Secondary outcome measures were the proportion of children with seizure freedom, > 90% seizure reduction, and the nature of parent-reported adverse events. A total of 45 children were recruited for the study, with 6 children being lost to follow-up at 12 weeks. At 12 weeks, 30 of 39 (76.9%) children were good responders with more than 50% seizure reduction. Of these 30 children, 11 (24.4%) had more than 90% seizure reduction, with 9 (20%) achieving complete spasm freedom. Constipation was the most common side effect of the diet among the enrolled subjects. Clinicians can consider sequential dietary therapy with a mAD in the first month followed by LGIT in the next 2 months for treating children who could not tolerate mAD beyond 1 month.

The Safety and Efficacy of Baked Egg and Milk Dietary Advancement Therapy: A Systematic Review and Meta-Analysis

BackgroundCow’s milk and egg allergy affect approximately 1.9% and 0.9% of children, respectively. Dietary advancement therapies (DAT), including milk (ML) and egg (EL) ladders, baked milk (BM-OIT) and baked egg (BE-OIT) oral immunotherapy are potential therapeutic options for these patients. ObjectiveTo perform systematic review and meta-analysis of the safety and efficacy of DAT in children with IgE-mediated milk or egg allergy. MethodsA systematic literature review was conducted, exploring 22 potential outcomes, with meta-analysis performed where >3 studies reported data. The GRADE approach was used to determine the certainty of evidence for each outcome, and the Johanna Briggs Institute tools for determining risk of bias. ResultsTwenty-nine studies met inclusion criteria among 9946 titles screened. Tolerance occurred in 69% of EL, 58% of ML, 49% of BE-OIT and 29% of BM-OIT patients. All-severity allergic reactions occurred in 21% of EL, 25% of ML, 20% of BE-OIT and 61% of BM-OIT patients, with epinephrine use in 3% of EL, 2% of ML, and 9% of BM-OIT patients. At-home reactions occurred in 19% of BE-OIT and 10% of BM-OIT patients. Discontinuation occurred in 14% of EL, 17% of ML, 17% of BE-OIT and 20% of BM-OIT patients. Mean time to BE egg and BE-OIT tolerance was 13.25 months (4 studies) and 19.1 months (3 studies). Certainty of evidence was very low, and risk of bias high. Study heterogeneity was high, attributable to multiple factors. ConclusionsThere is very low certainty of evidence supporting DAT safety and efficacy. We cannot conclude DAT accelerates tolerance development.

The Multidisciplinary Approach in the Management of Patients with Kidney Stone Disease-A State-of-the-Art Review.

Kidney stone disease has a multifactorial etiology, and evolving dietary habits necessitate continuous updates on the impact of dietary components on lithogenesis. The relationship between diseases influenced by lifestyle, such as obesity and diabetes, and kidney stone risk underscores the need for comprehensive lifestyle analysis. Effective management of kidney stones requires a multidisciplinary approach, involving collaboration among nutritionists, urologists, nephrologists, and other healthcare professionals to address the complex interactions between diet, lifestyle, and individual susceptibility. Personalized dietary therapy, based on each patient's unique biochemical and dietary profile, is essential and necessitates comprehensive nutritional assessments. Accurate dietary intake evaluation is best achieved through seven-day, real-time dietary records. Key factors influencing urinary risk include fluid intake, dietary protein, carbohydrates, oxalate, calcium, and sodium chloride. Personalized interventions, such as customized dietary changes based on gut microbiota, may improve stone prevention and recurrence. Current research suggests individualized guidance on alcohol intake and indicates that tea and coffee consumption might protect against urolithiasis. There is potential evidence linking tobacco use and secondhand smoke to increased kidney stone risk. The effects of vitamins and physical activity on kidney stone risk remain unresolved due to mixed evidence. For diseases influenced by lifestyle, conclusive evidence on targeted interventions for nephrolithiasis prevention is lacking, though preliminary research suggests potential benefits. Management strategies emphasize lifestyle modifications to reduce recurrence risks, support rapid recovery, and identify predisposing conditions, highlighting the importance of these changes despite inconclusive data.

Adult Inception of Ketogenic Diet Therapy Increases Sleep during the Dark Cycle in C57BL/6J Wild Type and Fragile X Mice.

Sleep problems are a significant phenotype in children with fragile X syndrome. Our prior work assessed sleep-wake cycles in Fmr1KO male mice and wild type (WT) littermate controls in response to ketogenic diet therapy where mice were treated from weaning (postnatal day 18) through study completion (5-6 months of age). A potentially confounding issue with commencing treatment during an active period of growth is the significant reduction in weight gain in response to the ketogenic diet. The aim here was to employ sleep electroencephalography (EEG) to assess sleep-wake cycles in mice in response to the Fmr1 genotype and a ketogenic diet, with treatment starting at postnatal day 95. EEG results were compared with prior sleep outcomes to determine if the later intervention was efficacious, as well as with published rest-activity patterns to determine if actigraphy is a viable surrogate for sleep EEG. The data replicated findings that Fmr1KO mice exhibit sleep-wake patterns similar to wild type littermates during the dark cycle when maintained on a control purified-ingredient diet but revealed a genotype-specific difference during hours 4-6 of the light cycle of the increased wake (decreased sleep and NREM) state in Fmr1KO mice. Treatment with a high-fat, low-carbohydrate ketogenic diet increased the percentage of NREM sleep in both wild type and Fmr1KO mice during the dark cycle. Differences in sleep microstructure (length of wake bouts) supported the altered sleep states in response to ketogenic diet. Commencing ketogenic diet treatment in adulthood resulted in a 15% (WT) and 8.6% (Fmr1KO) decrease in body weight after 28 days of treatment, but not the severe reduction in body weight associated with starting treatment at weaning. We conclude that the lack of evidence for improved sleep during the light cycle (mouse sleep time) in Fmr1KO mice in response to ketogenic diet therapy in two studies suggests that ketogenic diet may not be beneficial in treating sleep problems associated with fragile X and that actigraphy is not a reliable surrogate for sleep EEG in mice.

Resmetirom: The First Food and Drug Administration-Approved Medication for Nonalcoholic Steatohepatitis (NASH).

To review the literature leading to the Food and Drug Administration (FDA) approval of the first medication, resmetirom, for the treatment of nonalcoholic steatohepatitis (NASH), including the pharmacology, pharmacokinetics, clinical studies, dosing, and adverse effects. Relevant data will be used to discuss how resmetirom impacts clinical practice. A literature search was conducted using MEDLINE from database inception to May 12, 2024. Keywords included non-alcoholic steatohepatitis, nonalcoholic fatty liver disease, and resmetirom. Study selection, data extraction and all English-language studies involving the use of resmetirom for nonalcoholic fatty liver disease (NAFLD)/NASH were included. Resmetirom, a thyroid hormone receptor agonist, is administered at daily doses of either 80 mg or 100 mg. The drug was shown to provide NASH resolution as assessed by the NAFLD activity score, 80 mg-24.2%, 100 mg-25.9% compared to 14.2% with the placebo group (P < 0.001). Resmetirom, improved liver fibrosis, 80 mg-25.9%, 100 mg-29.9% compared to 9.7% with the placebo group (P < 0.001). Resmetirom's ability to improve fibrosis in patients with F2-F3 fibrosis offers valuable benefit for patients at risk of progressing to cirrhosis. Resmetirom expands the medication options available to treat patients with NASH which can be given alongside other medications to optimize metabolic factors such as glucagon-like peptide-1 and hydroxymethylglutaryl-coenzyme A reductase inhibitors. Resmetirom was well tolerated in studies. Resmetirom serves as an attractive option in patients diagnosed with NASH with evidence of advanced fibrosis (F2-F3) in combination with exercise, diet, and other multimodal therapies targeting metabolic risk factors.

Battle of the strategies: diet versus drug therapy for gout

The best results in combating gout are achieved through a combination of diet and drug therapy. Urate-lowering therapy, which includes febuxostat, has been shown to be more effective and convenient than diet when it comes to achieving and maintaining target uric acid (UA) levels in gout patients. Febuxostat, a xanthine oxidase inhibitor, helps to reduce UA levels in the blood by blocking its formation. This helps prevent the deposition of urate crystals in joints and tissues and reduces the frequency and severity of gout attacks. At the same time, a diet of low purine foods may also have some effect on UA levels. Diet can improve the results of drug treatment by reducing the need for medications and minimizing the risk of side effects. However, without adequate drug therapy, diet will not produce the desired results. Therefore, febuxostat remains the preferred urate-lowering treatment option for gout, especially given its proven efficacy in these patients.

Role of Ayurveda medicine in the management of Carcinoma of Breast

The incidence of malignant disorders is increasing in modern India. Due to altered lifestyle, faulty food habits intake of carcinogenic drugs, alcohol and tobacco and derangements in hormonal activities, cancers are seen common. Carcinoma of stomach, carcinoma of head of pancreas, carcinoma of breasts, carcinoma of prostate, squamous cells carcinoma of the mouth and tongue, skin carcinoma, osteosarcoma, carcinoma of rectum, Bronchogenic carcinoma are few malignant conditions seen commonly in the society. Surgical excision, Radiotherapy and chemotherapy are practiced in the management of cancer. In Ayurveda, Nidana Parivarjana, use of Vyadhi Pratyanika Aushadhi, Panchakarma therapy, practice of Yogasanas and Pranayama, Pyramid therapy, Pathapathya Prayoga and diet therapies are advocated. Ayurveda provides palliative treatment in this disease. It often improves the quality of life and body strength in these patients. In the review paper, the role of Ayurveda medicine in the management of Carcinoma of breast is discussed elaborately.

Diallyl disulfide, the bioactive component of Allium species, ameliorates pulmonary fibrosis by mediating the crosstalk of farnesoid X receptor and yes-associated protein 1 signaling pathway.

Environmental pollution, virus infection, allergens, and other factors may cause respiratory disease, which could be improved by dietary therapy. Allium species are common daily food seasoning and have high nutritional and medical value. Diallyl disulfide (DADS) is the major volatile oil compound of Allium species. The present study aims to explore the preventive effect and potential mechanism of DADS on pulmonary fibrosis. C57BL/6J mice were intratracheally injected with bleomycin (BLM) to establish pulmonary fibrosis and then administrated with DADS. Primary lung fibroblasts or A549 were stimulated with BLM, followed by DADS, farnesoid X receptor (FXR) agonist (GW4064), yes-associated protein 1 (YAP1) inhibitor (verteporfin), or silencing of FXR and YAP1. In BLM-stimulated mice, DADS significantly ameliorated histopathological changes and interleukin-1β levels in bronchoalveolar lavage fluid. DADS decreased fibrosis markers, HIF-1α, inflammatory cytokines, and epithelial-mesenchymal transition in pulmonary mice and activated fibroblasts. DADS significantly enhanced FXR expression and inhibited YAP1 activation, which functions as GW4064 and verteporfin. A deficiency of FXR or YAP1 could result in the increase of these two protein expressions, respectively. DADS ameliorated extracellular matrix deposition, hypoxia, epithelial-mesenchymal transition, and inflammation in FXR or YAP1 knockdown A549. Taken together, targeting the crosstalk of FXR and YAP1 might be the potential mechanism for DADS against pulmonary fibrosis. DADS can serve as a potential candidate or dietary nutraceutical supplement for the treatment of pulmonary fibrosis.

Dietary Therapy in Eosinophilic Esophagitis

Dietary Therapy in Eosinophilic Esophagitis

Anorexia nervosa – A New Look at an Old Problem

In Russia, according to Rosstat, about 2.5% of adolescents suffer from anorexia, in Moscow, according to 2015 data, at least 5% of young women suffered from anorexia, but most experts believe the true figures are much higher, since only advanced cases are recorded. The relevance of the problem of anorexia nervosa is associated with the potential threat to the lives of patients, eating disorders, concomitant mental diseases and, in general, the deterioration of the mental status of the patient. Despite the seeming simplicity of diagnosis, patients with advanced stages that require long-term therapy are more likely to turn to the doctor. Treatment of anorexia requires a comprehensive approach, including psychopharmacotherapy, psychological influence, diet therapy, therapy of somatic pathology and concomitant complications. It is important that all these aspects of treatment are carried out at the same time. The key to success is the constant monitoring of therapy by a psychiatrist. As a result of the patient's malnutrition, there is a deterioration in the general somatic state of health, as a result of which specifically in girls there are menstrual disorders, complications associated with conception and gestation, and a difficult pregnancy. In this regard, it is especially important to consider this disease from the point of view of psychiatry, obstetrics and gynecology.

Biological basis and treatment of frailty and sarcopenia.

In an ageing society, the importance of maintaining healthy life expectancy has been emphasized. As a result of age-related decline in functional reserve, frailty is a state of increased vulnerability and susceptibility to adverse health outcomes with a serious impact on healthy life expectancy. The decline in skeletal muscle mass and function, also known as sarcopenia, is key in the development of physical frailty. Both frailty and sarcopenia are highly prevalent in patients not only with advanced age but also in patients with illnesses that exacerbate their progression like heart failure (HF), cancer, or dementia, with the prevalence of frailty and sarcopenia in HF patients reaching up to 50-75% and 19.5-47.3%, respectively, resulting in 1.5-3 times higher 1-year mortality. The biological mechanisms of frailty and sarcopenia are multifactorial, complex, and not yet fully elucidated, ranging from DNA damage, proteostasis impairment, and epigenetic changes to mitochondrial dysfunction, cellular senescence, and environmental factors, many of which are further linked to cardiac disease. Currently, there is no gold standard for the treatment of frailty and sarcopenia, however, growing evidence supports that a combination of exercise training and nutritional supplement improves skeletal muscle function and frailty, with a variety of other therapies being devised based on the underlying pathophysiology. In this review, we address the involvement of frailty and sarcopenia in cardiac disease and describe the latest insights into their biological mechanisms as well as the potential for intervention through exercise, diet, and specific therapies.

High-calorie refeeding in adolescents with anorexia nervosa: a narrative review.

Recent studies about refeeding in anorexia nervosa (AN) suggest starting with a high calorie diet. This narrative review aims to understand the initial refeeding management in hospitalized children and adolescents with AN and to develop a practical protocol. We performed a comprehensive database search in June 2023 for abstracts published between January 2010 and May 2023 in different databases: Pubmed, The Cochrane Library and Embase with the terms refeeding syndrome, energy intake, diet therapy, weight restoration, hypophosphatemia, nutritional rehabilitation, anorexia nervosa, restrictive eating disorders, child, adolescent and young adult. Fifteen papers were included in this review. Twelve studies were retrospective or observational. Only 3 randomized controlled trials were found. Initial energy intake varies within a wide range between 500 and 2800 kcal per day but generally begins with higher calories than current recommendations. Only hypophosphatemia was often described without clinical refeeding syndrome. Initial weight restoration was better with high calorie refeeding (HCR). Length of stay was shorter with HCR in some studies. Long term outcomes were unknown. Only two studied severely malnourished patients (< 70 % mBMI). In adolescents with AN and with a low risk of RS, high calorie refeeding is possible under close medical monitoring and with prompt electrolyte correction. Robust studies with a unified protocol are needed to confirm the safety of high calorie refeeding especially in severely malnourished adolescents with AN.

Effects of plant-based diet (PBD) and exercise therapy (Ex) on weight and body composition in patients with primary hormone receptor (HR) positive breast cancer: A phase 2 randomized controlled trial.

548 Background: Obesity increases breast cancer recurrence and mortality. Strategies that induce weight loss may improve clinical outcomes. We investigated the feasibility and efficacy of personalized energy restricted PBD plus Ex on weight and body composition in primary HR-positive breast cancer (NCT04298086). Methods: Postmenopausal women with body mass index (BMI) ≥ 27 kg/m2 on adjuvant endocrine therapy were randomized (1:1) to PBD plus Ex or attention control for 24 weeks. PBD plus Ex received individualized caloric goals adjusted weekly to target 1.5 lbs/week weight loss. PBD targeted 500 kcal/day goal deficit achieved via nutrition coaching and meal delivery. Ex sessions targeted 250 kcal goal expenditure via remotely delivered treadmill walking 3-5 days/week with real-time monitoring. Attention control received a home treadmill and monthly check-in calls. Baseline to post-intervention changes in weight and body composition, measured by dual energy X-ray absorptiometry (DXA), were compared between arms using linear mixed models. Results: 43 women were randomized between 8/2020 and 4/2023. Weight data was available for all participants (35 measured at follow-up, 8 abstracted from clinical documentation); 37 completed post-intervention DXA. At baseline, mean BMI was 34 (SD 4) kg/m2. Intention-to-treat results are presented in the Table. Mean weight loss in PBD plus Ex was –13% (SD 6%) compared with –5% (SD 6%) in attention control (mean between group difference –8 kg, 95% CI –11, –4). Mean fat loss in PBD plus Ex was –6 kg compared with –2 kg in attention control (mean between group difference –4 kg, 95% CI –6, –2). Lean mass increases were greater in PBD plus Ex (P&lt;0.001). Weekly energy deficit goal compliance was 95% in month 1 and 64% in month 6. No serious adverse events were observed. Baseline and post-intervention tissue samples were available on 37 (86%) patients, which will undergo biologic correlative analysis. Conclusions: Personalized PBD plus Ex led to substantial weight loss and favorable changes in body composition during endocrine therapy for HR-positive breast cancer. Clinical trial information: NCT04298086 . [Table: see text]

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70–145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient’s age, and patients’ origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders.What is Known:• Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness.What is New:• Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy.• PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

A rare case report: multiple intrahepatic masses in a pediatric patient with citrin deficiency

Deficiency of citrin, the liver-type aspartate-glutamate carrier, arises from biallelic mutations of the gene SLC25A13. Although citrin deficiency (CD) is associated with higher risk of hepatocellular carcinoma (HCC) in adult patients, this association remains inconclusive in pediatric cases. The patient in this paper had been diagnosed to have CD by SLC25A13 analysis at the age 10 months, and then in response to dietary therapy, her prolonged jaundice and marked hepatosplenomegaly resolved gradually. However, she was referred to the hospital once again due to recurrent abdominal distention for 2 weeks at her age 4 years and 9 months, when prominently enlarged liver and spleen were palpated, along with a strikingly elevated serum alpha-fetoprotein (AFP) level of 27605 ng/mL as well as a large mass in the right liver lobe and a suspected tumor thrombus within the portal vein on enhanced computed tomography. After 4 rounds of adjuvant chemotherapy, right hepatic lobectomy and portal venous embolectomy were performed at her age 5 years and 3 months, and metastatic hepatoblastoma was confirmed by histopathological analysis. Afterwards, the patient underwent 5 additional cycles of chemotherapy and her condition remained stable for 7 months after surgery. Unfortunately, hepatoblastoma recurred in the left lobe at the age 5 years and 10 months, which progressed rapidly into liver failure, and led to death at the age 6 years and 1 month. As far as we know, this is the the first case of hepatoblastoma in a patient with CD, raising the possibility of an association between these two conditions.

Antioxidant, anti-amylase, anti-lipase, and efficiency of Satureja fatty acid on the anti-inflammatory parameters in lipopolysaccharide-stimulated macrophage through Nrf2/NF-kB/NADH oxidase pathway

Satureja is an aromatic plant that is used for flavoring, perfume, and food manufacturing due to its pleasant essential oil. Modern medicine research revealed several biological activities of Satureja essential oil, including antifungal, antibacterial, antiviral, antioxidant, anticancer, and anti-inflammatory. However, the functional properties of Satureja fatty acid have not been explored. This study examined the fatty acid profile, lipid nutritional quality, antioxidant, anti-amylase, and anti-lipase capacities of Satureja. The efficiency of Satureja fatty acid on the anti-oxidative and anti-inflammatory parameters in LPS-induced macrophage through the Nrf2/NF-kB/NADH oxidase pathway was examined. The whole lipid extract was prepared with chloroform/methanol/water solution. Fatty acids methyl ester from whole lipid extract were prepared with methanol/sulfuric acid reagent. The fatty acid profile was analyzed using gas chromatography-mass spectrometry. Total antioxidant was determined by ABTS decolorization. Lipase and amylase activities were determined by monitoring the decomposition of p-nitrophenyl butyrate and starch. The macrophage cell line was grown in DMEM media in the presence of fatty acid. The hydrogen peroxide production in treated cells was monitored using the FOX reagent. NADH oxidase activity was measured by monitoring NADH breakdown. The expression of NOX, NF-kB, and NRF2, were tested in the treated cells by real-time PCR. The main components of the Satureja fatty acid were linolenic acid (24.67–37.32%), palmitic acid (10.65–20.29%), linoleic acid (8.31–13.39%), oleic acid (4.42–14.35%), stearic acid (2.76–8.77%) and palmitoleic acid (1.77–4.95%). Given the nutritional quality, omega-3 PUFA (23.58–37.32%), SFA (21.53–26.70%), omega-6 PUFA (10.86–16.14%), omega-9 MUFA (4.42–14.35%), and omega-7 MUFA (1.77–4.95%) comprise the majority of fatty acids. Satureja fatty acid has a promising unsaturation index (120.77–164.27), PUFA/MUFA (2.07–6.41), hypocholesterolemic index (2.44–3.47), health-promoting index (2.03–2.42), PUFA/SFA (1.37–1.94), nutritive value index (0.53–1.71), MUFA/SFA (0.30–0.80) omega-6/omega-3 (0.34–0.65), atherogenicity index (0.41–0.49), and thrombogenicity index (0.17–0.27). Satureja fatty acid displayed strong antioxidant capacity (with IC50 ranging from 354 to 428 µg/mL), anti-lipase capacity (with IC50 ranging from 354 to 428 µg/mL), and anti-amylase capacity (with IC50 ranging from 370 to 390 µg/mL). LPS induced the expression of NOX, NRF2, and NF-kB and the synthesis of hydrogen peroxide in macrophage cells. In LPS-stimulated macrophages, Satureja fatty acid reduced NOX expression, hydrogen peroxide, and NF-kB expression and increased NRF2 at 0.04 mg/mL. In conclusion, Satureja fatty acids have potent antioxidant, anti-amylase, anti-lipase, and anti-inflammatory activities. The mechanisms in lowering oxidative stress markers depended on down-regulating superoxide-producing enzymes at gene and protein levels. Satureja polyunsaturated omega-3 fatty acids could be recommended for healthy products combined with dietary therapy to treat obesity, diabetes, and oxidative stress.

Dravet Syndrome: An Electroclinical, Genetic, Treatment, and Outcome Study of 35 Patients in Argentina

AbstractWe analyzed the electroclinical features, molecular findings, treatment, disease course, and outcomes of patients with Dravet syndrome (DS) with positive genetic markers seen at a public hospital in Argentina. A retrospective study was conducted assessing the clinical records of 44 patients who met the diagnostic criteria for DS according to the 2022 classification of epilepsy of the International League Against Epilepsy seen at our center between March 2018 and June 2023. Of 44 patients, 35 (18 males and 17 females), in whom genetic studies yielded positive results, were included. Median age was 9 years (range 4 to 16 years), and the median time of follow-up was 10 years (range 3 to 14 years). The mean age at onset was 7 months. The first seizure was associated with febrile illness in all patients, and in 11 (31.4%), seizures were immediately preceded by either infectious disease or vaccination. Heterozygous pathogenic/likely pathogenic SCN1A variants were detected in 32 of the original 44 patients (73%), of which 47% were novel. Variants in other genes related to DS (HCN1, STXB1, and SCN1B) were identified in three patients. Cognitive delay and motor impairment were found to be more severe in patients that had multiple and drug-resistant seizures and in those who had the complete phenotype with myoclonic seizures. Novel SCN1A gene variants were identified in nearly half of the patients. The prognosis for cognitive development is unfavorable. Seizures are not well controlled with antiseizure medications and early treatment with ketogenic dietary therapy as well as cannabidiol should be considered.