S�der�kra, Sweden

Postprandial Metabolome and Metabolic Flexibility

Enrolled subjects are followed every week for one month. At each visit, a questionnaire assesses daily time activity patterns relevant to energy expenditure, general health status, including infectious symptoms, and confirmation of basic social and demographic characteristics. Dietary intake is assessed by a food frequency questionnaire and a multi-step 24-hour dietary recall for quantitative analysis. If symptoms of infection are present, participants are treated with ad-hoc broad antibiotics. Anthropometrics are obtained. Subjects will then be randomized to receive the metabolic challenges in a different order. The procedures will be performed before (fasting; 8-10 hours) and after (postprandial) consumption of the metabolic challenges. Capillary blood samples (40µ) are obtained in the morning after an 8-hour fasting and after test meal consumption. To obtain the capillary blood sample, sterilize the ring finger with alcohol and allow it to dry. Then, puncture the area with a sterile 2 mm long lancet. Once the drop of blood is formed, it is placed directly into the CardioCheck Plus® cassette to determine glucose triglyceride, LDL-cholesterol, HDL-cholesterol, and total cholesterol. A second drop of capillary blood shall be placed on a filter paper (S&S 903) until a circle of filter paper is filled with blood to saturate the paper throughout its thickness. Insulin concentration shall be determined following the protocol for dried blood, which is standardized in the laboratory. Indirect fasting calorimetry is also performed. After the indirect calorimetry, the metabolic and hormonal response to the test meal is performed. Each challenge should be consumed within 15 minutes. After 5 minutes of rest, indirect calorimetry will be postprandially, lasting 30 minutes. Capillary blood shall be obtained at the following times: 15-30-45-60-90 and 120 min after ingestion of food. Nutrient composition of standardized meal and meal example. - High carbohydrate challenge: Energy, 479.6 kcal; Carbohydrate, 83.6%; Lipids, 12.4% and Protein, 4.0% (70 g of hot-Cake, 100 g of mango, 270 ml of peach nectar, and 40 g of strawberry jam) - High lipid challenge: Energy, 1043.4 kcal; Carbohydrate, 4.9%; Lipids, 86.8%, and Protein, 8.3% (60 g of manchego cheese, 25 g of egg, white, dried, 24 g of bacon, 5 ml of oil, 65 g of cream cheese, 70 g of cream, and 16 g of poblano pepper) - High protein challenge: Energy, 441.3 kcal; Carbohydrate, 1.6%; Lipids, 5.1%, and Protein, 93.3% (2 scoop Isopure Zero Carb, 180 g of chicken breast, 20 g of lettuce and 24 g of ham turkey breast) Determination of metabolites in dried blood To determine the concentration of metabolites (amino acids and acyl-carnitines), a circle of 3 mm diameter shall be punched out of the filter paper and placed in a 96-well plate. Add 100 µl of the acyl-carnitine and amino acid standards from the NeoBase PerkinElmer kit. Subsequently, follow the manufacturer's instructions for determining metabolites by liquid chromatography coupled to mass spectrometry (LC-MS). Determination of the respiratory quotient (RQ) To determine the respiratory quotient (RQ= VmaxCO2/ VmaxO2) and lipid and carbohydrate oxidation examinations, the Cardio Coach CO2 Vmax Encore 29 System calorimeter software (Korr, Inc, UT, USA) will be used according to the instructions of the supplier. Examinations are invariably performed in the morning (8:00-9:00 am) in a thermoneutral environment with controlled pressure, humidity, and temperature, with the patient supine but awake. The investigators examine a maximum of two subjects per day. Oxygen consumption and carbon dioxide production were obtained using a canopy and were monitored continuously for 30 minutes. The initial 10 minutes of the measurement are discarded for the calculation to ensure greater data homogeneity. O2 consumption and CO2 production will be recorded continuously for 30 min. VO2 and VCO2 values will be used in the equation proposed by Weir (Energy Expenditure = [3.941(VO2) + 1.11(VCO2)] x 1440 min/day), considered as the standard method [34]. Additionally, one day before the test, subjects are instructed to fast for 8 hours and not engage in physical activity or consume caffeine the day before the exam. All participants will be asked to eat the same dinner the night before each test. Dinner provides 15% of the daily energy intake; 20 g of protein, 7 g of lipids, and 34 g of carbohydrates)

Efficacy Anda Safety of Etoricoxib With Betamethasone for the Treatment of Acute Gout Arthritis

Researchers will compare the fixed-dose combination of Etoricoxib/Betamethasone versus Etoricoxib in acute gouty arthritis by comparing the level of pain in the affected joint during the 8 days of follow up. The adverse events related to the interventions will be registered during follow up. Participants will: - Be randomized into one of the 2 intervention groups (A or B) - Visit the clinic in 3 occasions (day 0, day 5 of follow up and day 8 of follow up) - In case needed the patient could take 500 mg of acetaminophen, as a rescue medication, previous authorization of de principal investigator

Efficacy and Safety of Etoricoxib/Tizanidine Versus Etoricoxib for Acute Low Back Pain Associated to Muscle Spasm

Researchers will compare the efficacy of a fixed-dose combination of etoricoxib and tizanidine versus etoricoxib alone in the treatment of acute low back pain associated with muscle spasms. Efficacy will be assessed by evaluating the average change in pain among patients who report improvement over the 7-day follow-up period. Adverse events related to the interventions will be recorded throughout the study. Participants will: - Be randomized into one of two intervention groups (Group A or Group B). - Attend three in-person clinic visits: Day 0 (baseline), Day 3, and Day 7 of follow-up. - Receive follow-up phone calls on Days 1 and 5. - Be allowed to take 500 mg of acetaminophen as rescue medication if needed, with prior authorization from the Principal Investigator.

Efficacy and Safety of Celecoxib/Acetaminophen Versus Celecoxib for Diagnosed Osteoarthritis in Acute Exacerbation

Researchers will evaluate the efficacy and safety of a fixed-dose combination of celecoxib and acetaminophen compared to celecoxib monotherapy for the treatment of pain in patients with osteoarthritis experiencing an acute exacerbation over a 6-week follow-up period. Adverse events related to the study interventions will be recorded throughout the follow-up phase. Participants will: Be randomized into one of three intervention groups (A, B, or C). Attend five scheduled clinic visits (Day 0, and Weeks 1, 2, 4, and 6 of follow-up). Be permitted to take 500 mg of naproxen as rescue medication, if needed, with prior authorization from the principal investigator.

Evaluation of Maralixibat in Pruritus Associated With General Cholestatic Liver Disease (EXPAND)

This study will be conducted in multiple sites in North America, Europe, Middle East and South America.

Automation of the In Vitro Fertilization Laboratory

Confirmatory Study on the Efficacy and Safety of the Fixed-dose Combination of Desloratadine/Betamethasone Versus Desloratadine

Nasal symptom changes will be assessed daily over a 10-day intervention period using the Total Nasal Symptom Score (TNSS) for allergic rhinitis. Patients will complete the first questionnaire during the randomization visit, followed by daily entries each night before bedtime using a patient diary. The final assessment will be completed during the study's end-of-treatment visit. Quality of life, global clinical impression, and patient global assessment will be evaluated during in-person visits conducted at baseline, Day 5, and Day 10. The incidence of adverse events throughout the study will be analyzed by treatment group and reported as frequencies and percentages. Events will be classified according to frequency, seriousness, severity, and their relationship to the investigational product.

A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)

Metabolic Impact on the Mitochondria-gut Microbiota Axis of Failure to Follow Restrictive Dietary Interventions in Subjects Living with Obesity

The study consists of an open-label randomized controlled clinical trial. The selected subjects will be men or women over 18 years of age with a body mass index (BMI) greater than or equal to 30 kg/m2, who meet the selection criteria, the subjects who will be randomly assigned to one of 3 dietary intervention groups. The study consisted of a dietary intervention with a duration of 8 weeks and a follow-up of 24 weeks after dietary intervention. The intervention groups will be as follows: 1. Calorie-restricted diet: Dietary recommendations will be given restricting 30% in energy (kcal) according to their usual diet with normal macronutrient distribution (20-30% protein, 50-60% carbohydrates, 20-30% fats). 2. Intermittent fasting diet: Dietary recommendations will be given according to the energy expenditure determined by indirect calorimetry with normal macronutrient distribution. Intermittent fasting will be used with a time-restricted model of 16:8. For 16 hours, they will not be able to eat or drink calories. In the other 8 hours, they need to adhere to the energy-restricted diet. 3. Ketogenic diet: Recommendation will be given according to the energy expenditure determined by indirect calorimetry, with the following distribution of macronutrients: 20-25% protein, 5-10% carbohydrates, 70-80% fat. Participants with calorie-restriction, intermittent fasting, or ketogenic diet dietary intervention will be provided with a food menu guide for fifteen days. After 8 weeks of the assigned intervention, patients will be provided with general dietary recommendations and will be invited to three more follow-up visits at 8, 16 and 24 weeks post-intervention. In addition, all participants will be provided with general recommendations for a physical activity plan for people living with obesity. To evaluate adherence to treatment, participants will be asked to fill out 2 logbooks every two weeks (1 during the week and 1 for the weekend) in which they must record the type, amount and place where they consumed the food at each feeding time. They will also be called once a week for a 24-hour reminder. Participants on the ketogenic diet will be given test strips to measure ketones in urine.

Intraoperative Hypotension in Pancreatoduodenectomy: A Randomized Trial of General Versus Combined Anesthesia

Pancreatoduodenectomy is a major surgical procedure associated with significant hemodynamic challenges. Thoracic epidural anesthesia provides effective analgesia and may attenuate the surgical stress response, its intraoperative use has been associated with increased risk of hypotension and higher vasopressor requirements. This randomized clinical trial aims to evaluate intraoperative hemodynamic changes in patients undergoing elective pancreatoduodenectomy managed with either general anesthesia or combined general anesthesia (thoracic epidural). A total of 206 patients will be enrolled at the "National Institute of Medical Sciences and Nutrition Salvador Zubirán". Patients will be randomized into two groups: one receiving general anesthesia and the other receiving combined general anesthesia (thoracic epidural). Randomization will be performed using the REDCap platform with a simple 1:1 allocation ratio. Each patient's group assignment will be generated automatically by REDCap at the time of enrollment to ensure allocation concealment. An independent observer, blinded to the anesthetic technique, will monitor and record episodes of hypotension throughout the perioperative period. The principal investigator will be blinded to group assignment. Secondary outcomes include intraoperative vasopressor use, estimated blood loss, transfusion requirements, postoperative complications (such as pancreatic fistula, anastomotic leak, hemorrhage, surgical site infection, and acute kidney injury), admission to the intensive care unit, length of stay in the ICU and hospital, and mortality. A planned interim analysis will be conducted after the enrollment of the first 66 patients to assess the safety and feasibility of the study protocol. Based on this analysis, modifications to improve patient safety may be recommended by the research team or ethics committee. This study will help determine the optimal anesthetic strategy to minimize hemodynamic instability and postoperative morbidity in patients undergoing pancreatoduodenectomy.