Search

Background: Sedentary lifestyles, poor nutritional choices, inadequate sleep, risky substance use, limited social connections, and high stress contribute to the growing prevalence of chronic diseases. Lifestyle medicine, emphasizing therapeutic lifestyle changes for prevention and treatment, has demonstrated effectiveness but remains underutilized in clinical settings. The Complete Lifestyle Medicine Intervention Program-Ontario (CLIP-ON) was developed to educate the rural population of Northern Ontario in lifestyle medicine to improve health outcomes and engagement., Objective: This study evaluates the implementation and effectiveness of the CLIP-ON program for patients with chronic diseases in the Parry Sound area, focusing on lifestyle behaviors, health outcomes, enrollment, retention rates, and interdisciplinary team engagement., Methods: This observational cohort study guided by the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance) includes pre- and postintervention assessments from participants and health care providers. A hybrid type II mixed methods design evaluates the intervention's effectiveness and implementation process in real-world settings through quantitative and qualitative data collection. CLIP-ON is tailored to the residents of the Parry Sound catchment area in Northern Ontario. Participants (≥18 years old) with chronic conditions such as prediabetes, type II diabetes, systemic hypertension, cardiovascular vascular disease, dyslipidemia, or high BMI (≥25) will be recruited through self-referral or provider referral. Approximately 10 participants per cohort will be enrolled in the CLIP-ON program, consisting of 22 weeks of weekly group sessions and monthly individual consultations with physicians, health coaches, kinesiologists, and registered dieticians either in person or through a web-based platform. CLIP-ON will cover the 6 pillars of lifestyle medicine through 14 group sessions followed by an 8-week supervised exercise program. Anthropometric and cardiometabolic variables will be measured before and after the program. Participants will be surveyed on lifestyle habits, wellness, perceived barriers, and program satisfaction at 3 and 6 months. Focus groups and dropout interviews with participants (n=10 per cohort) and providers (n=6 per cohort) will guide program adaptations. Quantitative and qualitative data collected at baseline and follow-up will assess the program's implementation and identify barriers and opportunities for improvement., Results: This study was approved by the Laurentian University Research Ethics Board (6021397) on July 6, 2023. The first cohort was enrolled in late 2023 and is still under evaluation. The second cohort began in mid-2024, and data collection is currently underway. A mixed methods analysis will be used at enrollment, program completion (22 weeks), and follow-up (6 months after program completion). Focus groups assessing the program's effectiveness and implementation will take place after the 22-week intervention. Data will be analyzed in early 2025., Conclusions: This protocol provides insights into the implementation of this lifestyle medicine program and its impact on participants' health. The findings will guide future advancements and establish a scalable model for other communities., Trial Registration: ClinicalTrials.gov NCT06192251; https://clinicaltrials.gov/study/NCT06192251., International Registered Report Identifier (irrid): DERR1-10.2196/59179., (©Kush Patel, Lisa Allen, Karine Boucher, Michelle Fedele, Debbie Fong, Sangeeta Kumar, Deanna Lavigne, Elisa Marin-Couture, Magdalena Partyka-Sitnik, Nicole Rietze, Jenna Smith-Turchyn, Mylene Juneau, Caroline Rhéaume. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 31.12.2024.)

Ultra-tight binding is usually observed for proteins associating with rigidified molecules. Previously, we demonstrated that femtomolar binders derived from the Armadillo repeat proteins (ArmRPs) can be designed to interact very tightly with fully flexible peptides. Here we show for ArmRPs with four and seven sequence-identical internal repeats that the peptide-ArmRP complexes display conformational dynamics. These dynamics stem from transient breakages of individual protein-residue contacts that are unrelated to overall unbinding. The labile contacts involve electrostatic interactions. We speculate that these dynamics allow attaining very high binding affinities, since they reduce entropic losses. Importantly, only NMR techniques can pick up these local events by directly detecting conformational exchange processes without complications from changes in solvent entropy. Furthermore, we demonstrate that the interaction surface of the repeat protein regularizes upon peptide binding to become more compatible with the peptide geometry. These results provide novel design principles for ultra-tight binders., (© 2023. The Author(s).)

Protocatechuate 3,4-dioxygenases (P34Os) catalyze the reaction of the ring cleavage of aromatic acid derivatives. It is a key reaction in many xenobiotic metabolic pathways. P34Os characterize narrow substrate specificity. This property is an unfavorable feature in the biodegradation process because one type of pollution is rarely present in the environment. Thus, the following study aimed at the characterization of a P34O from Stenotrophomonas maltophilia KB2, being able to utilize a wide spectrum of aromatic carboxylic acids. A total of 3 mM vanillic acid and 4-hydroxybenzoate were completely degraded during 8 and 4.5 h, respectively. When cells of strain KB2 were grown on 9 mM 4-hydroxybenzoate, P34O was induced. Biochemical analysis revealed that the examined enzyme was similar to other known P34Os, but showed untypical wide substrate specificity. A high activity of P34O against 2,4- and 3,5-dihydroxybenzoate was observed. As these substrates do not possess ortho configuration hydroxyl groups, it is postulated that their cleavage could be connected with their monodentate binding of substrate to the active site. Since this enzyme characterizes untypical wide substrate specificity it makes it a useful tool in applications for environmental clean-up purposes., (© 2014 S. Karger AG, Basel.)

This is the first report of a catechol 1,2-dioxygenase from Stenotrophomonas maltophilia strain KB2 with high activity against catechol and its methyl derivatives. This enzyme was maximally active at pH 8.0 and 40 °C and the half-life of the enzyme at this temperature was 3 h. Kinetic studies showed that the value of K m and V max was 12.8 μM and 1,218.8 U/mg of protein, respectively. During our studies on kinetic properties of the catechol 1,2-dioxygenase we observed substrate inhibition at >80 μM. The nucleotide sequence of the gene encoding the S. maltophilia strain KB2 catechol 1,2-dioxygenase has high identity with other catA genes from members of the genus Pseudomonas. The deduced 314-residue sequence of the enzyme corresponds to a protein of molecular mass 34.5 kDa. This enzyme was inhibited by competitive inhibitors (phenol derivatives) only by ca. 30 %. High tolerance against condition changes is desirable in industrial processes. Our data suggest that this enzyme could be of use as a tool in production of cis,cis-muconic acid and its derivatives.