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Aims: To determine the relationship between exposure and weight‐loss trajectories for the glucagon‐like peptide‐1 analogue semaglutide for weight management. Materials and Methods: Data from one 52‐week, phase 2, dose‐ranging trial (once‐daily subcutaneous semaglutide 0.05–0.4 mg) and two 68‐week phase 3 trials (once‐weekly subcutaneous semaglutide 2.4 mg) for weight management in people with overweight or obesity with or without type 2 diabetes were used to develop a population pharmacokinetic (PK) model describing semaglutide exposure. An exposure‐response model describing weight change was then developed using baseline demographics, glycated haemoglobin and PK data during treatment. The ability of the exposure‐response model to predict 1‐year weight loss based on weight data collected at baseline and after up to 28 weeks of treatment, was assessed using three independent phase 3 trials. Results: Based on population PK, exposure levels over time consistently explained the weight‐loss trajectories across trials and dosing regimens. The exposure‐response model had high precision and limited bias for predicting body weight loss at 1 year in independent datasets, with increased precision when data from later time points were included in the prediction. Conclusion: An exposure‐response model has been established that quantitatively describes the relationship between systemic semaglutide exposure and weight loss and predicts weight‐loss trajectories for people with overweight or obesity who are receiving semaglutide doses up to 2.4 mg once weekly. [ABSTRACT FROM AUTHOR]

Malabsorption is a consequence of gastric bypass (GB). GB increases the risk of kidney stone formation. This study aimed to evaluate the accuracy of a screening questionnaire for assessing the risk of lithiasis in this population. We performed a monocentric retrospective study to evaluate a screening questionnaire administered to patients who underwent gastric bypass surgery between 2014 and 2015. Patients were asked to answer a questionnaire that included 22 questions divided into four parts: medical history, episodes of renal colic before and after bypass surgery, and eating habits. A total of 143 patients were included in the study, and the mean age of the patients was 49.1 ± 10.8 years. The time between gastric bypass surgery and the completion of the questionnaire was 50.75 ± 4.95 months. The prevalence of kidney stones in the study population was 19.6%. We found that with a score of ≥6, the sensitivity and specificity were 92.9% and 76.5%, respectively. Positive and negative predictive values were 49.1% and 97.8%, respectively. The ROC curve showed an Area Under the Curve (AUC) of 0.932 ± 0.029 (p < 0.001). We developed a reliable and short questionnaire to identify patients at a high risk of kidney stones after gastric bypass. When the results of the questionnaire were equal to or greater than six, the patient was at a high risk of kidney stone formation. With a good predictive negative value, it could be used in daily practice to screen patients who have undergone gastric bypass and are at a high risk of renal lithiasis. [ABSTRACT FROM AUTHOR]

Experiments and molecular mechanics computations were performed to examine the electronic and structural factors that determine the Diels-Alder reactivity and regiochemistry of N-phenyl-2-cyano-1-azadienes. N-phenyl-1-aza-2-cyano-1,3-butadiene was subjected to (4 + 2) cycloadditions with dienophiles such as methyl vinyl ketone, styrene and ethyl(methyl)vinyl ether at 90-120 degrees Celsius. The results showed that the 1-azadienes undergo an endo cycloaddition.

Evaluating genetically heat stress (HS) of cattle is still a major challenge, also because of the need to have access to HS sensitive phenotypes relating their reaction to temperature and humidity as described by the temperature-humidity index (THI). A solution could be to add the information of data from sensors. However, activity (ACT) and rumination (RUM) sensors reflect no "production" [i.e., milk yields (MY), milk composition, but also intake or growth] related aspects which is suboptimal. Therefore, the objectives of this study were thus to assess the possible usefulness for adding sensors data for HS genetic evaluation based on a dairy situation. But the context described can be easily enlarged and include beef cattle and pigs. Strategy was illustrated using daily SenseHub collar records that were obtained from October 2019 to July 2022 in six dairy herds in Wallonia in Southern Belgium. A total of 453 Walloon Holstein cows were followed during this period for activity time. Meteorological data and a HS sensitive "production" trait (here MY) were also obtained from 2015 to 2022 for 1,740 cows from the same herds. In total 32,154 MY, 130,867 ACT and 130,848 RUM records were available. The thresholds at which the different traits start to be affected by HS were estimated at a THI of 63, 64 and 66, respectively, for MY, ACT and RUM. A three-trait random regression reaction norm model was fitted with these different thresholds. Estimated heritability values were 0.19 ± 0.03, 0.14 ± 0.06 and 0.21 ± 0.05 respectively for MY, ACT and RUM using AIREML. Ratios of variance associated to THI and constant genetic effect were 0.002, 0.02 and 0.04 indicating a stronger reaction by RUM but also ACT than MY to THI. However, it is uncertain if the reactions of these sensor traits are reflected in the production traits. Estimated genetic correlations of regressions on THI for ACT and RUM showed values of 0.51 ± 0.70 and 0.08 ± 0.54 with MY and 0.77 ± 0.69 between ACT and RUM. The first eigenvector of the correlation matrix explained 65% of the total variability and standardized coefficients of this eigenvector were 0.42, 0.69 and 0.59 for MY, ACT and RUM. A total of 50% of the variance associated with the regression on THI for MY could be explained by the regressions on THI for ACT and RUM. Adding the constant genetic effects for ACT and RUM only marginally increased to 51% the ability to explain the effect of THI on MY. Based on these results, reactions of different indicator traits, here sensor data, may reflect a different reaction than production and therefore economically important traits. Additional research, also beyond dairy cattle, should continue to address this topic that is very important for the validation of sensor data detecting HS. [ABSTRACT FROM AUTHOR]

The food preparation conditions essential for killing contaminating blow fly eggs and larvae are discussed. Freezing, refrigeration, balding, baking, boiling, frying and microwaving methods were successful in killing most or all of the eggs and larvae.

Background: Multiple chemical sensitivity (MCS) is a chronic condition of unknown etiology. MCS is characterized by recurrent nonspecific symptoms from multiple organ systems in response to chemical exposures in concentrations that are normally tolerated by the majority of the population. The symptoms may have severe impact on patients' lives, but an evidence-based treatment for the condition is nonexisting. The pathophysiology is unclarified, but several indicators point towards abnormal processing of sensory signals in the central nervous system. Pulsed electromagnetic fields (PEMF) offer a promising new treatment for refractory depression and can be targeted at the brain, thereby activating biochemical cell processes.Methods/design: In a parallel, randomized, double-blind, placebo-controlled trial conducted at the Danish Research Centre for Chemical Sensitivities, the effects of PEMF in MCS patients will be assessed using the Re5 Independent System. Based on sample size estimation, 40 participants will be randomized to either PEMF therapy or placebo. The allocation sequence will be generated by computer. All involved parties (that is, participants, investigators, the research nurse, and the statistician) will be blinded to group allocation. The participants will receive PEMF therapy or placebo applied transcranially 30 minutes twice a day for 7 days a week over 6 consecutive weeks. Outcomes will be measured at baseline, once weekly during treatment, post treatment, and at 2.5-month and 4.5-month follow-up according to a predefined timetable. The primary outcome will be a measurement of the impact of MCS on everyday life. The secondary outcomes will be measurements of MCS symptoms, psychological distress (stress, anxiety or depressive symptoms), capsaicin-induced secondary punctate hyperalgesia, immunological markers in serum, and quality of life.Discussion: This trial will assess the effects of PEMF therapy for MCS. Currently, there is no treatment with a documented effect on MCS, and in terms of healthcare there is very little to offer these patients. There is thus a great need for well-conducted randomized trials aimed at assessing possible treatment effects. A positive outcome will pave the way for improved healthcare and understanding of this very disabling and overlooked condition.Trial Registration: ClinicalTrials.gov, NCT01834781. [ABSTRACT FROM AUTHOR]