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The postprandial glucose response is an independent risk factor for type 2 diabetes. Observationally, early glucose response after an oral glucose challenge has been linked to intestinal glucose absorption, largely influenced by the expression of sodium–glucose cotransporter 1 (SGLT1). This study uses Mendelian randomization (MR) to estimate the causal effect of intestinal SGLT1 expression on early glucose response. Involving 1,547 subjects with class II/III obesity from the Atlas Biologique de l'Obésité Sévère cohort, the study uses SGLT1 genotyping, oral glucose tolerance tests, and jejunal biopsies to measure SGLT1 expression. A loss-of-function SGLT1 haplotype serves as the instrumental variable, with intestinal SGLT1 expression as the exposure and the change in 30-min postload glycemia from fasting glycemia (Δ30 glucose) as the outcome. Results show that 12.8% of the 1,342 genotyped patients carried the SGLT1 loss-of-function haplotype, associated with a mean Δ30 glucose reduction of −0.41 mmol/L and a significant decrease in intestinal SGLT1 expression. The observational study links a 1-SD decrease in SGLT1 expression to a Δ30 glucose reduction of −0.097 mmol/L. MR analysis parallels these findings, associating a statistically significant reduction in genetically instrumented intestinal SGLT1 expression with a Δ30 glucose decrease of −0.353. In conclusion, the MR analysis provides genetic evidence that reducing intestinal SGLT1 expression causally lowers early postload glucose response. This finding has a potential translational impact on managing early glucose response to prevent or treat type 2 diabetes Article Highlights: Loss-of-function variant of SGLT1 is associated with reduced intestinal SGLT1 expression and early postload glucose response. Mendelian randomization supports the causal relationship between intestinal glucose absorption and postprandial glucose. Modulating intestinal SGLT1 expression/function is a promising avenue for the prevention and treatment of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Cochlear implants (CIs) can restore binaural hearing in cases of single-sided deafness (SSD). However, studies with a high level of evidence in support of this phenomenon are lacking. The aim of this study is to analyze the effectiveness of CIs using several spatialized speech-in-noise tests and to identify potential predictors of successful surgery. Methods: Ten cases underwent standard CI surgery (MEDEL-Flex24). The speech-in-noise test was used in three different spatial configurations. The noise was presented from the front (N0), toward the CI (NCI), and toward the ear (Near), while the speech was always from the front (S0). For each test, the speech-to-noise ratio at 50% intelligibility (SNR50) was evaluated. Seven different effects were assessed (summation, head shadow [HS], speech released of masking [SRM], and squelch for the CI and for the ear). Results: A significant summation effect of 1.5 dB was observed. Contralateral PTA was positively correlated with S0N0-B and S0NCI-B (CIon and unplugged ear). S0N0-B results were positively correlated with S0N0-CIoff (p < 0.0001) and with S0Near-CIoff results (p = 0.004). A significant positive correlation was found between delay post-activation and HS gain for the CI (p = 0.005). Finally, the HS was negatively correlated with the squelch effect for the ear. Conclusion: CI benefits patients with SSD in noise and can improve the threshold for detecting low-level noise. Contralateral PTA could predict good postoperative results. Simple tests performed preoperatively can predict the likelihood of surgical success in reversing SSD. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare the originally applied frequency allocation of cochlear implant electrodes assigned by default at the time of activation with a more recent frequency allocation that is anatomy-based by a software called OTOPLAN®. Based on a computed tomography scan of the temporal bone, this software calculates the position of each electrode in the cochlea and its corresponding tonotopic frequency. We also evaluated whether patients with a significant mismatch between these two allocations present poorer speech intelligibility. Materials and Methods: Patients who underwent cochlear implantation from 2016 to 2021 at the University Hospital of Liege were included in this retrospective study. We used OTOPLAN® to calculate the tonotopic frequency allocation of each electrode according to its exact position in the cochlear duct. This anatomical frequency mapping was compared with the default frequency mapping at the time of cochlear implant activation. Finally, we compared the mismatch with the patients' auditory performance, represented by the Auditory Capacity Index (ACI). Results: Thirteen patients were included in the study. All patients had a mismatch between the two frequency maps, to a variable extent (200 Hz–1,100 Hz). Frequency shift was significantly inversely correlated with ACI and with the time needed to improve speech intelligibility. Conclusion: Our primary results show that patients with a larger mismatch between default frequency mapping and anatomically assigned frequency mapping experience poorer hearing performance and slower adaptation to a cochlear implant. [ABSTRACT FROM AUTHOR]

Circadian-paced biological processes are key to physiology and required for metabolic, immunologic, and cardiovascular homeostasis. Core circadian clock components are transcription factors whose half-life is precisely regulated, thereby controlling the intrinsic cellular circadian clock. Genetic disruption of molecular clock components generally leads to marked pathological events phenotypically affecting behavior and multiple aspects of physiology. Using a transcriptional signature similarity approach, we identified anti-cancer protein synthesis inhibitors as potent modulators of the cardiomyocyte molecular clock. Eukaryotic protein translation inhibitors, ranging from translation initiation (rocaglates, 4-EGI1, etc.) to ribosomal elongation inhibitors (homoharringtonine, puromycin, etc.), were found to potently ablate protein abundance of REV-ERBα, a repressive nuclear receptor and component of the molecular clock. These inhibitory effects were observed both in vitro and in vivo and could be extended to PER2, another component of the molecular clock. Taken together, our observations suggest that the activity spectrum of protein synthesis inhibitors, whose clinical use is contemplated not only in cancers but also in viral infections, must be extended to circadian rhythm disruption, with potential beneficial or iatrogenic effects upon acute or prolonged administration. [ABSTRACT FROM AUTHOR]

Introduction: Preservation of residual hearing, mainly the low frequencies, is the current main objective of cochlear implantation. New electrode arrays and the development of minimally invasive surgery have allowed electroacoustic stimulation. Over the past several years, robotic-assisted cochlear implant surgery aimed to improve the insertion process while respecting inner ear structures. However, the introduction of a foreign body inside the cochlea can lead to the development of fibrous tissue around the electrode array, or even induce osteogenesis. These histological changes disrupt the parameters of the cochlear implant, resulting in elevated impedance. In addition, long-term auditory performance can be affected, with a deterioration in word comprehension. We evaluated the potential impact of RobOtol® on impedance changes over time, leading to potentially positive functional outcomes. Methods: Cochlear implant surgery with a round window approach was performed under general anesthesia. Fifteen Med-El Flex24 electrode arrays were inserted manually and 24 using RobOtol®. All subjects underwent pure-tone audiometry tests before the surgery and at regular intervals up to 1 year after the surgery. Based on the pure-tone average at the low frequencies from 250 to 1,000 Hz, we divided the patients according to the degree of auditory preservation (full preservation ≤15 dB, partial preservation 15 dB–30 dB, significant loss >30 dB). These different groups were compared in terms of impedance changes and auditory performance, specifically word recognition score. Results: We found proportionally fewer patients who experienced significant low-frequency hearing loss after robotic insertion (53.33% in the manual group compared to 41.67% in the robot-assisted insertion group). Impedance changes at the apex of the electrode array, especially at the first electrode (p = 0.04), after robotic surgery, with less overall variability, a continuous decreasing trend without secondary elevation, and lower values in cases of complete residual hearing preservation (for the three first electrodes: p = 0.017, p = 0.04, p = 0.045). The speech intelligibility amelioration over time showed favorable evolution in patients with complete residual hearing preservation regardless of the insertion method. However, in the absence of auditory preservation, the positive evolution continued more than 6 months after robotic surgery but stagnated after manual insertion (difference at 1 year, p = 0.038; median auditory capacity index 83% vs. 57%). Conclusion: Atraumatic electrode array insertion with consistent, slow speed and the assistance of RobOtol® minimizes disturbances in the delicate neurosensory structures of the inner ear and leads to better auditory performance. [ABSTRACT FROM AUTHOR]

This prospective study investigates the impact of local anesthesia on ciliary function in nasal epithelium. The primary objective was to assess whether lidocaine 2% and naphazoline 0.5% nasal spray alter ciliary beat frequency and pattern in subjects undergoing nasal brushing, aiming to enhance primary ciliary dyskinesia (PCD) diagnosis., Hypothesis: It was hypothesized that local anesthesia administration would not significantly affect ciliary function in nasal epithelium., Study Design: A prospective, simple-blind randomized study was conducted between 2020 and 2023. The study employed digital high-speed videomicroscopy to analyze ciliary beat frequency and pattern., Patient/subject Selection: A cohort of 38 participants was recruited, consisting of 25 healthy volunteers and 13 referred individuals (including seven diagnosed with PCD). Selection criteria ensured the absence of chronic respiratory diseases, recent respiratory tract infections, or regular use of nasal medications., Methodology: Participants underwent nasal brushing with administration of lidocaine and naphazoline nasal spray in one nostril and saline in the contralateral nostril. Ciliary beat frequency and pattern were measured using digital high-speed video microscopy., Results: Nasal spray administration did not significantly alter ciliary beat frequency or pattern compared to saline (p = 0.841 and p = 0.125, respectively). Subgroup analysis revealed consistent results across healthy volunteers, referred patients, and PCD patients., Conclusion: Local anesthesia with lidocaine and naphazoline spray did not affect ciliary function outcomes. These findings support the safe use of these agents in clinical practice for PCD diagnostic procedures. Further research with larger cohorts is warranted for validation., (© 2024 Wiley Periodicals LLC.)