Reversed-phase ultrahigh-performance liquid chromatography-mass spectrometry (RP-UHPLC/MS) method is optimized for the quantitation of a large number of lipid species in biological samples, primarily in human plasma and serum. The method uses a C18 bridged ethylene hybrid (BEH) column (150 × 2.1 mm; 1.7 μm) for the separation of lipids from 23 subclasses with a total run time of 25 min. Lipid species separation allows the resolution of isobaric and isomeric lipid forms. A triple quadrupole mass spectrometer is used for targeted lipidomic analysis using multiple reaction monitoring (MRM) in the positive ion mode. Data are evaluated by Skyline software, and the concentrations of analytes are determined using internal standards per each individual lipid class.

• Keywords
• High-throughput lipidomics, Mass spectrometry, Plasma, Quantitation, Reversed-phase, Serum, Ultrahigh-performance liquid chromatography,
• MeSH
• Chromatography, Reverse-Phase * methods   MeSH
• Mass Spectrometry methods   MeSH
• Liquid Chromatography-Mass Spectrometry MeSH
• Humans MeSH
• Lipidomics * methods   MeSH
• Lipids * analysis   MeSH
• High-Throughput Screening Assays methods   MeSH
• Software MeSH
• Tandem Mass Spectrometry methods   MeSH
• Chromatography, High Pressure Liquid methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Lipids * MeSH

PURPOSE: To evaluate treatment outcomes and toxicity in patients with stage T1-3N0M0 oral cancer treated with surgery followed by high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Retrospective study of 50 patients with stage T1-T3N0 tongue and floor-of-mouth cancer who underwent tumour excision (+ elective neck dissection) followed by postoperative HDR-BT due to the presence of negative prognostic factors (close or positive resection margins, lymphovascular and/or perineural invasion, deep invasion). The plastic tube technique (dose: 18 x 3 Gy b.i.d.) was used. Survival outcomes, toxicity, and prognostic factors were evaluated. RESULTS: At a median follow-up of 81 months (range, 4-121), actuarial 5-year local control (LC), nodal control (NC) and progression-free survival (PFS) rates were 79%, 69%, and 64%. After salvage treatment (surgery + external beam radiotherapy), LC, NC, and PFS increased to 87%, 77%, and 72.3%, respectively. Five-year overall survival and cancer-specific survival (CSS) rates were 73% and 77%. Treatmentrelated toxicity included two cases of mandibular osteoradionecrosis and five cases of small soft tissue necrosis. T stage was significantly correlated with nodal control (p=0.02) and CSS (p=0.04). Tumour grade correlated with DFS (p=0.01). CONCLUSION: Postoperative HDR-BT 18 x 3 Gy b.i.d. seems to be an effective method in patients with T1-3N0M0 oral cancer with negative prognostic factors after tumour resection.

• Keywords
• Brachytherapy, Early oral cancer, Postoperative treatment,
• MeSH
• Brachytherapy * methods   adverse effects   MeSH
• Radiotherapy Dosage MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Mouth Neoplasms * radiotherapy   surgery   pathology   mortality   MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

In esophageal squamous cell carcinoma, genetic activation of NRF2 increases resistance to chemotherapy and radiotherapy, which results in a significantly worse prognosis for patients. Therefore NRF2-activated cancers create an urgent clinical need to identify new therapeutic options. In this context, we previously identified the geldanamycin family of HSP90 inhibitors, which includes 17DMAG, to be synthetic lethal with NRF2 activity. As the first-generation of geldanamycin-derivative drugs were withdrawn from clinical trials due to hepatotoxicity, we designed second-generation compounds with C19-substituted structures in order to inhibit glutathione conjugation-mediated hepatotoxicity. In this study, using a variety of in vitro and in vivo cancer models, we found that C19-substituted 17DMAG compounds maintain their enhanced toxicity profile and synthetic lethal interaction with NRF2-NQO1-activated cancer cells. Importantly, using a xenograft mouse tumor model, we found that C19-substituted 17DMAG displayed significant anticancer efficacy against NRF2-NQO1-activated cancer cells without causing hepatotoxicity. These results clearly demonstrate the improved clinical potential for this new class of HSP90 inhibitor anticancer drugs, and suggest that patients with NRF2-NQO1-activated esophageal carcinoma may benefit from this novel therapeutic approach.

• Keywords
• C19-position substituted geldanamycin derivatives, ESCC, HSP90, NQO1, NRF2-NQO1-activated cancer,
• MeSH
• Benzoquinones * pharmacology   chemistry   MeSH
• NF-E2-Related Factor 2 * metabolism   genetics   MeSH
• Humans MeSH
• Lactams, Macrocyclic * pharmacology   chemistry   MeSH
• Mice, Nude MeSH
• Mice MeSH
• NAD(P)H Dehydrogenase (Quinone) * metabolism   genetics   MeSH
• Cell Line, Tumor MeSH
• Esophageal Neoplasms * drug therapy   metabolism   pathology   MeSH
• HSP90 Heat-Shock Proteins antagonists & inhibitors   metabolism   MeSH
• Antineoplastic Agents * pharmacology   chemistry   MeSH
• Esophageal Squamous Cell Carcinoma * drug therapy   metabolism   MeSH
• Xenograft Model Antitumor Assays MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Benzoquinones * MeSH
• NF-E2-Related Factor 2 * MeSH
• geldanamycin MeSH Browser
• Lactams, Macrocyclic * MeSH
• NAD(P)H Dehydrogenase (Quinone) * MeSH
• NFE2L2 protein, human MeSH Browser
• NQO1 protein, human MeSH Browser
• HSP90 Heat-Shock Proteins MeSH
• Antineoplastic Agents * MeSH

BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.

• MeSH
• Aortic Valve Stenosis * surgery   complications   MeSH
• Heart Valve Prosthesis Implantation methods   MeSH
• Fractional Flow Reserve, Myocardial * MeSH
• Percutaneous Coronary Intervention * methods   MeSH
• Coronary Artery Bypass * methods   MeSH
• Humans MeSH
• Coronary Artery Disease * surgery   complications   therapy   MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Transcatheter Aortic Valve Replacement * methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Equivalence Trial MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

INTRODUCTION AND OBJECTIVES: With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. MATERIALS AND METHODS: This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. RESULTS: Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). CONCLUSIONS: Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. GOV REGISTRATION: NCT04895943.

• Keywords
• Elastography, Intragastric balloon, Liver fibrosis, Non-alcoholic fatty liver disease, Obesity,
• MeSH
• Bariatric Surgery * MeSH
• Time Factors MeSH
• Equipment Design MeSH
• Adult MeSH
• Elasticity Imaging Techniques MeSH
• Weight Loss MeSH
• Liver Cirrhosis * etiology   diagnostic imaging   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Non-alcoholic Fatty Liver Disease * diagnostic imaging   diagnosis   etiology   MeSH
• Obesity * complications   surgery   diagnosis   MeSH
• Pilot Projects MeSH
• Prospective Studies MeSH
• Treatment Outcome MeSH
• Gastric Balloon * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH

INTRODUCTION: This study aimed to assess the impact of midline lumbar fusion with cortical bone trajectory screws (MIDLF/CBT) on the multifidus muscles, focusing on the evaluation of their postoperative atrophy. CLINICAL RATIONALE FOR THE STUDY: MIDLF/CBT is a relatively new technique increasingly used to treat spinal instability. Despite its reduced invasiveness compared to traditional posterior lumbar interbody fusion with traditional pedicle screws (PLIF/TP), concerns remain about potential damage to the multifidus muscles that are crucial for spinal stability. Understanding the extent of muscular atrophy post-MIDLF/CBT is vital for improving surgical outcomes, and potentially patient rehabilitation strategies. MATERIAL AND METHODS: This study retrospectively analysed preoperative and postoperative MRI scans of patients who underwent MIDLF/CBT for degenerative segmental spondylolisthesis. The bilateral width of the multifidus muscles at the operated segment and adjacent segments was measured using axial T2-weighted MRI scans. Statistical comparisons were made using a paired t test, with significance set at p < 0.05. RESULTS: The study included 16 patients with an average age of 57 ± 10 years, 10 of whom (62.5%) were women, and featured a mean follow-up period of 37 ± 25 months. Postoperative measurements showed a significant reduction in the width of the multifidus muscles at the operated segment (mean difference -3.3mm, p = 0.02) and the inferior adjacent segment (-7.4 mm, p < 0.01). A decrease in muscle width at the superior adjacent segment was also observed, although this was not statistically significant. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study concluded that MIDLF/CBT results in significant multifidus muscle atrophy at and below the operated segment, potentially impacting postoperative rehabilitation and recovery. These findings highlight the need for further research comparing MIDLF/CBT to other spinal stabilisation techniques. Additionally, incorporating functional electromyographic assessments of paraspinal muscles could provide deeper insights into the long-term consequences of spinal surgeries and helpdevelop new approaches and strategies to mitigate paravertebral muscles atrophy, thus enhancing patient outcomes.

• Keywords
• cortical bone trajectory, midline lumbar fusion, multifidus muscles, spinal fusion, spinal instability, spinal stabilisation,
• MeSH
• Lumbar Vertebrae * surgery   MeSH
• Adult MeSH
• Spinal Fusion * adverse effects   methods   MeSH
• Paraspinal Muscles * diagnostic imaging   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Pedicle Screws adverse effects   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Spondylolisthesis * surgery   MeSH
• Muscular Atrophy * etiology   diagnostic imaging   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Spices are a rich source of vitamins, polyphenols, proteins, dietary fiber, and minerals such as calcium, magnesium, iron, and zinc, all of which play an important role in biological functions. Since ancient times, spices have been used in our kitchen as a food coloring agent. Spices like cinnamon and turmeric allegedly contain various functional ingredients, such as phenolic and volatile compounds. Therefore, this review aims to summarize the current knowledge about the nutritional profiles of cinnamon and turmeric, as well as to analyze the clinical studies on their extracts and essential oils in animals and humans. Furthermore, their enrichment applications for food products and animal feed have also been investigated in terms of safety and toxicity. Numerous studies have shown that cinnamon and turmeric have various health benefits, including the reduction of insulin resistance and insulin signaling pathways in diabetic patients, the reduction of inflammatory biomarkers, and the maintenance of gut microflora in both animals and humans. The food and animal feed industries have taken notice of these health benefits and have begun to promote cinnamon and turmeric as healthy foods. This has resulted in the development of new food products and animal feeds that contain cinnamon and turmeric as primary ingredients, which have been deemed an effective means of promoting cinnamon and turmeric's health benefits.

• Keywords
• Cinnamon, enrichment, functional feed, functional food, turmeric,
• MeSH
• Curcuma * chemistry   MeSH
• Food, Fortified * MeSH
• Functional Food * analysis   MeSH
• Spices analysis   MeSH
• Animal Feed * analysis   MeSH
• Humans MeSH
• Nutritive Value MeSH
• Oils, Volatile analysis   MeSH
• Plant Extracts MeSH
• Cinnamomum zeylanicum * chemistry   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Oils, Volatile MeSH
• Plant Extracts MeSH

The endorsement of conspiracy theories may be increased by subjectively perceived stress. Yet, it is not known whether this correlation is caused by the effects of the acute stress reaction on the brain or other psychological, social, or methodological factors. The effect of an experimentally induced acute stress reaction on conspiracy thinking was tested on a sample (n = 115) of students of medicine. Although the stress procedure caused a substantial increase in salivary cortisol, there was no significant effect on endorsing conspiracy theories or adopting conspiracy interpretations of novel information. The results confirmed no effect of the acute stress reaction on conspiracy thinking, suggesting it may be absent or weaker than expected. The study demonstrated the viability of psychophysiological experimental design in conspiracy research and may inspire further examination of the physiological mechanisms underlying susceptibility to conspiracy theories.

• Keywords
• Conspiracy theories, Maastricht Acute Stress Test, cortisol, stress,
• MeSH
• Adult MeSH
• Hydrocortisone analysis   metabolism   MeSH
• Humans MeSH
• Young Adult MeSH
• Stress, Psychological * psychology   MeSH
• Saliva chemistry   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Hydrocortisone MeSH

PURPOSE: MRI-only adaptive brachytherapy (MRI-ABT) is the state-of-the-art for treating locally advanced cervical cancer (LACC) in combination with concurrent chemoradiotherapy. We aimed to evaluate the pattern of pelvic recurrence after the treatment. MATERIAL AND METHODS: A total of one hundred LACC patients were treated between January 2017 and December 2023 with concurrent chemoradiotherapy of 45 Gy in 25 fractions ± boost to lymphadenopathy (up to a maximum dose of 60 Gy in 25 fractions) with concurrent weekly cisplatin chemotherapy at the dose of 40 mg/m2/week, and MR-ABT. RESULTS: At a median follow-up of 30.2 months, there were 2 local recurrences (2%) and 9 regional pelvic recurrences (9%). The median time to local/regional recurrence was 11 months (range 6-21). For all stages, the 3-year local control was 97.66%, and the 3-year pelvic control was 89.45%. Twenty-four patients died during follow-up; the 3-year overall survival was 75.11%, and the 3-year disease-free survival was 70.97%. CONCLUSION: MRI-ABT combined with external beam radiotherapy and concurrent chemotherapy for LACC demonstrates excellent local and regional pelvic control. Most local/regional recurrences occur inside or at the edge of the external-beam irradiated field. Recurrences inside the field of brachytherapy are rare. Distant recurrences are the predominant cause of death in LACC patients treated with definitive CRT and MRI-ABT.

• Keywords
• Adaptive brachytherapy, Cervical cancer, MRI-only brachytherapy, Recurrence,
• MeSH
• Brachytherapy * methods   MeSH
• Chemoradiotherapy methods   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Uterine Cervical Neoplasms * pathology   radiotherapy   diagnostic imaging   therapy   mortality   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The global trend of transferring responsibility for dignified aging from the state to individuals is conducive to a variability of alternative attitudes and strategies. Despite having important implications for both the state and individuals, the variability of old age risk management has not been fully appreciated by social policy. Social policy cannot adapt to every individual, but it can reflect various categories of citizens and their patterns of old age risk management. In this article, we navigate the plethora of individual choices by identifying patterns of strategic behavior in old age risk management in society. Based on our data from the original 2018 survey, representative for the Czech population, we identify four distinctive strategies: risk taking, risk avoiding, risk neglecting, and risk preventing. We conclude by discussing how the data gathered and analyzed through our research may help social policy actors better understand sources of variability and design more effective policy interventions.

• Keywords
• Ageing, individual old age risk management, risk assessment, risk coping, risk management,
• MeSH
• Individuality * MeSH
• Humans MeSH
• Cross-Sectional Studies MeSH
• Risk Management * classification   statistics & numerical data   MeSH
• Aging in Place * psychology   MeSH
• Aging * psychology   MeSH
• Public Policy * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH