Association between low-carbohydrate-diet score, glycemia and cardiovascular risk factors in adults with type 1 diabetes.

BACKGROUND AND AIMS: Low-carbohydrate-diets (LCDs) are gaining popularity in individuals with type 1 diabetes (T1D). However, the impact of such diets on glycemia and cardiovascular risk factors is debated. This study aims to evaluate associations between low-carbohydrate intakes using LCD score with glycemia and cardiovascular risk factors (lipid profile) in adults with T1D or LADA in Québec, Canada. METHODS AND RESULTS: This is a cross-sectional study using data collected in the BETTER registry (02/2019 and 04/2021) including self-reported 24-h dietary recalls to calculate LCD scores, waist circumference, level-2 and level-3 hypoglycemic episodes and measured biochemical data (HbA1c, LDL-cholesterol and non-HDL-cholesterol). Participants were divided into quartiles (Q) based on LCD scores. Two hundred eighty-five adults (aged 48.2 ± 15.0 years; T1D duration 25.9 ± 16.2 years) were included. Categorical variables underwent Chi-squared/Fisher's Exact tests, while continuous variables underwent ANOVA tests. Mean carbohydrate intake ranged from 31.2 ± 6.9% (Q1) to 56.5 ± 6.8% (Q4) of total daily energy. Compared to Q4, more people in Q1 reported HbA1c ≤ 7% [≤53.0 mmol/mol] (Q1: 53.4% vs. Q4: 29.4%; P = 0.011). The same results were found in the models adjusted for age, sex and T1D duration. A greater proportion of participants in Q1 never experienced level-3 hypoglycemia compared to Q3 (Q1: 60.0% vs. Q3: 31.0%; P = 0.004). There were no differences across quartiles for frequency of level-2 hypoglycemia events and lipid profile (LDL-cholesterol and non-HDL-cholesterol). CONCLUSIONS: Low-carbohydrate intakes are associated with higher probabilities of reaching HbA1c target and of never having experienced level-3 hypoglycemia. No associations with level-2 hypoglycemia frequency, nor cardiovascular risk factors were observed.

Pain induced by investigations and procedures commonly administered to older adults in the emergency department: a prospective cohort study.

BACKGROUND: This study aimed to assess the level of pain induced by common interventions performed in older adults consulting to the ED. METHODS: We conducted a prospective multicentre observational cohort study in two academic EDs (Quebec City, Canada) between June 2018 and December 2019. A convenience sample of well-oriented and haemodynamically stable older adults (≥65 years old) who underwent at least two interventions during their ED stay was recruited. The level of pain was assessed using an 11-point Numerous Rating Scale (NRS) and is presented using median and IQR or categorised as no pain (0), mild (1-3), moderate (4-6) or severe pain (7-10). RESULTS: A total of 318 patients were included. The mean age was 77.8±8.0 years old and 54.4% were female . The number of pain assessments per intervention ranged between 22 (urinary catheterisation) and 240 (intravenous catheter). All imaging investigations (X-rays, CT and bedside ultrasound) were associated with a median level of pain of 0. The median level of pain for other interventions was as follows: blood samplings (n=231, NRS 1 (IQR 0-3)), intravenous catheters (n=240, NRS 2 (IQR 0-4)), urinary catheterisations (n=22, NRS 4.5 (IQR 2-6)), cervical collars (n=50, NRS 5 (IQR 0-8)) and immobilisation mattresses (n=34, NRS 5 (IQR 0-8)). Urinary catheterisations (63.8%), cervical collars (56.0%) and immobilisation mattresses (52.9%) frequently induced moderate or severe pain. CONCLUSIONS: Most interventions administered to older adults in the ED are associated with no or low pain intensity. However, urinary catheterisation and spinal motion restriction devices are frequently associated with moderate or severe pain.

Artificial Pancreas Systems and Physical Activity in Patients with Type 1 Diabetes: Challenges, Adopted Approaches, and Future Perspectives.

Physical activity is important for patients living with type 1 diabetes (T1D) but limited by the challenges associated with physical activity induced glucose variability. Optimizing glycemic control without increasing the risk of hypoglycemia is still a hurdle despite many advances in insulin formulations, delivery methods, and continuous glucose monitoring systems. In this respect, the artificial pancreas (AP) system is a promising therapeutic option for a safer practice of physical activity in the context of T1D. It is important that healthcare professionals as well as patients acquire the necessary knowledge about how the AP system works, its limits, and how glucose control is regulated during physical activity. This review aims to examine the current state of knowledge on exercise-related glucose variations especially hypoglycemic risk in T1D and to discuss their effects on the use and development of AP systems. Though effective and highly promising, these systems warrant further research for an optimized use around exercise.

IL-7 receptor blockade blunts antigen-specific memory T cell responses and chronic inflammation in primates.

Targeting the expansion of pathogenic memory immune cells is a promising therapeutic strategy to prevent chronic autoimmune attacks. Here we investigate the therapeutic efficacy and mechanism of new anti-human IL-7Rα monoclonal antibodies (mAb) in non-human primates and show that, depending on the target epitope, a single injection of antagonistic anti-IL-7Rα mAbs induces a long-term control of skin inflammation despite repeated antigen challenges in presensitized monkeys. No modification in T cell numbers, phenotype, function or metabolism is observed in the peripheral blood or in response to polyclonal stimulation ex vivo. However, long-term in vivo hyporesponsiveness is associated with a significant decrease in the frequency of antigen-specific T cells producing IFN-γ upon antigen restimulation ex vivo. These findings indicate that chronic antigen-specific memory T cell responses can be controlled by anti-IL-7Rα mAbs, promoting and maintaining remission in T-cell mediated chronic inflammatory diseases.

Changes in Ocular Subfoveal Choroidal Thickness After Carotid Endarterectomy Using Enhanced Depth Imaging Optical Coherence Tomography: A Pilot Study.

The influence of both severe chronic carotid stenosis and carotid endarterectomy (CEA) on ocular tissue has been poorly evaluated. The goal of this study was to measure subfoveal choroidal thickness (SFCT), before and after CEA, in patients with severe carotid stenosis. Consecutive patients (n = 36) with severe carotid stenosis were prospectively included. Patients (n = 19) were followed up at 1 and 3 months after CEA. The SFCT was measured bilaterally using enhanced depth imaging optical coherence tomography (EDI-OCT). Preoperatively, the median SFCT of the ipsilateral eye did not differ significantly from the contralateral eye (223 vs 236 µm; P = .75). In the ipsilateral eye, the mean SFCT was significantly higher at 1 month postsurgery and the effect was maintained at 3 months (226.3 ± 17.1 at 3 months vs 210.8 ± 16.5 µm at baseline; P < .001). For the contralateral eye, the increase in SFCT reached statistical significance at 3 months (220.1 ± 11.3 at 3 months vs 214.8 ± 11.5 µm at baseline; P = .04). The mean SFCT significantly increased bilaterally after CEA, with a more noticeable effect in the ipsilateral eye. Further studies are required to determine whether EDI-OCT could be useful as a potential marker of ophthalmologic outcomes.

Chimeric ß-lactamases: global conservation of parental function and fast time-scale dynamics with increased slow motions.

Enzyme engineering has been facilitated by recombination of close homologues, followed by functional screening. In one such effort, chimeras of two class-A ß-lactamases - TEM-1 and PSE-4 - were created according to structure-guided protein recombination and selected for their capacity to promote bacterial proliferation in the presence of ampicillin (Voigt et al., Nat. Struct. Biol. 2002 9:553). To provide a more detailed assessment of the effects of protein recombination on the structure and function of the resulting chimeric enzymes, we characterized a series of functional TEM-1/PSE-4 chimeras possessing between 17 and 92 substitutions relative to TEM-1 ß-lactamase. Circular dichroism and thermal scanning fluorimetry revealed that the chimeras were generally well folded. Despite harbouring important sequence variation relative to either of the two 'parental' ß-lactamases, the chimeric ß-lactamases displayed substrate recognition spectra and reactivity similar to their most closely-related parent. To gain further insight into the changes induced by chimerization, the chimera with 17 substitutions was investigated by NMR spin relaxation. While high order was conserved on the ps-ns timescale, a hallmark of class A ß-lactamases, evidence of additional slow motions on the µs-ms timescale was extracted from model-free calculations. This is consistent with the greater number of resonances that could not be assigned in this chimera relative to the parental ß-lactamases, and is consistent with this well-folded and functional chimeric ß-lactamase displaying increased slow time-scale motions.