Tremor arises from mechanical, reflex, or central oscillatory mechanisms. Transcranial magnetic stimulation (TMS) can transiently perturb ongoing tremor and enables the quantitative assessment of phase resetting, offering circuit-level insight into tremor types. Although numerous studies have applied TMS-induced resetting, the findings have not been systematically reviewed. This study systematically reviews human studies evaluating TMS-induced tremor resetting across tremor types. A systematic search of PubMed and Google Scholar identified human studies using TMS to perturb tremor or rhythmic movement. Search terms included "tremor resetting," "resetting of tremor," "tremor phase shift," "tremor phase reset," "transcranial magnetic stimulation," and "central oscillator." Inclusion criteria were human participants, experimental TMS perturbation, and quantitative tremor phase/resetting outcomes. Exclusion criteria were animal studies, therapeutic repetitive TMS trials without resetting analyses, and isolated case reports. Two researchers independently screened and extracted data. The PRISMA 2020 guidelines were followed. Twenty-one studies were identified, three of which were excluded from the primary synthesis (two case reports and one qualitative-only design). Eighteen studies remained, which addressed essential tremor (ET) (n = 6), Parkinson's disease tremor (PDT) (n = 7), orthostatic tremor (OT) (n = 4), palatal tremor (n = 1), dystonic tremor (DT) (n = 1), and voluntary rhythmic movement (n = 4). M1 stimulation reset ET, postural PDT, OT, palatal tremor, DT, and voluntary rhythmic movements. Rest PDT had inconsistent resetting by M1 stimulation and no resetting by cerebellar stimulation. Cerebellar stimulation reset postural PDT but not ET. The resetting index was associated with the stimulus intensity and duration of the silent period. TMS-induced resetting is a strong physiological tool for differentiating tremor circuits. M1 acts as a major convergence node, while cerebellar involvement is tremor-specific. Methodological heterogeneity and small samples limit the comparability of study results. Advances in targeting technologies and closed-loop and phase-locked protocols could enhance the diagnostic and therapeutic utility of resetting paradigms.
Unravelling a reliable timing of past earthquakes through luminescence dating of fault gouge depends on sufficient frictional heat during a co-seismic event to fully reset the luminescence signal. Laboratory fault-gouge production using a rotary shear apparatus has attracted interest as a method for probing the degree of signal resetting in quartz during friction experiments. However, natural fault gouges are complex, exhibiting a mixture of minerals that are specific to the host rocks. Here, we employed a host rock sample from the Alborz Mountains (Iran) and subjected it to a friction experiment without any chemical treatment, after being reset and irradiated with a known gamma dose. We performed a medium-slip velocity friction experiment with a slip velocity of 0.05 m/s and a normal stress of 12 MPa, while the temperature evolution of the gouge zone was recorded using an infrared camera. The thermographic images show a transient temperature of approximately 296 °C, with the luminescence signal resetting at a small, extremely localised slip patch, confirming the challenges involved in identifying the best spot for signal resetting. However, we identified a high-temperature signal enhancement in the thermoluminescence (TL) curves that might serve as a marker for fault-gouge formation.
The first hitting times of a stochastic process, i.e., the first time a process reaches a particular level, are of significant interest across various scientific disciplines, including biology, chemistry, and economics. We modify the standard setup by allowing the target to spontaneously switch between two states, either active or inactive, and investigate the distribution of first hitting times accrued while the target is active. For this setup, we provide closed formulas for the distribution of the first hitting time. Additionally, we can introduce stochastic resetting to the underlying process and, utilizing our results, derive the formulas for the first time the active target is hit by the process under stochastic resetting. Interestingly, we show that resetting in this setup still leaves some memory; the system is no longer Markovian, which prevents a straightforward application of standard techniques. The analytical results are accompanied by computer simulations of Langevin dynamics.
Sensorimotor transformation, the process of converting sensory input signals into a movement command, is essential for mediating goal-directed movements. Neural correlates of sensorimotor transformation were assessed in the delay period activity of superior colliculus (SC) neurons recorded simultaneously in three male monkeys generating saccades to visual targets. We applied dimensionality reduction on the SC population response and used a proximity index to quantify the relative, probabilistic closeness of the evolving delay period activity to the visual- and motor-dominant subspaces associated with the sensation and action states. Here, we show that sensorimotor transformation is achieved through a drift in population activity from a visual-like to a motor-like representation during the delay period, with transient visual resets following microsaccades. Also, the proximity index was correlated to reaction time throughout the delay period, suggesting a similar movement preparation mechanism is conserved across the skeletomotor and oculomotor systems.
As ubiquitous features of every natural environment, microbes have profoundly shaped eukaryotic biology throughout evolution. Circadian clocks evolved in all domains of life as central regulators that align physiology with environmental cycles, yet whether they respond directly to microbial signals remains unknown. Here, we demonstrate that evolutionarily diverse microbes potently reset mammalian cellular clocks and can drive phase shifts in plants and algae, indicating cross-kingdom effects of microbes on circadian rhythms. In mammals, exposure to soluble bacterial components distinct from canonical innate immune ligands induces acute PER2 upregulation independently of Bmal1 or nascent transcription. A targeted inhibitor screen and biochemical assays implicate p38 MAPK as a modulator of this response. Taken together, this positions bacterial exposure as a previously unrecognized circadian clock input, revealing a new axis of host-microbe interaction that modulates biological timing at the cellular level.
Mismatch repair-deficient (dMMR) tumours are highly sensitive to immune checkpoint blockade in the metastatic setting. Previous trials showed near-universal pathological responses after short-course dual immune checkpoint inhibition in patients with early-stage dMMR colon cancer, and high clinical complete response rates after 6 months of single-agent PD-1 blockade in patients with dMMR rectal cancer. We aimed to evaluate the activity and safety of a short duration of preoperative nivolumab and ipilimumab in patients with early or locally advanced dMMR rectal cancer. In the RESET-R trial, a multicentre, single-arm, phase 2 trial conducted in two hospitals in Denmark, we enrolled patients aged 18 years or older with histologically confirmed stage I-III dMMR rectal adenocarcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no previous systemic or local therapy for rectal cancer. Patients received one cycle of nivolumab (3 mg/kg intravenously on days 1 and 15) and ipilimumab (1 mg/kg intravenously on day 1). Patients with definite tumour regression but without clinical complete response at day 43 received a second cycle (nivolumab 3 mg/kg intravenously on days 50 and 65 and ipilimumab 1 mg/kg intravenously on day 50). The primary endpoint was the proportion of patients with a clinical complete response at day 93, defined as no visible or palpable tumour on rectal digital examination, endoscopy, and MRI. In patients with digital and endoscopic complete response, and with non-complete response on MRI, the absence of viable tumour cells in a representative biopsy was also classified as clinical complete response. Patients who had a clinical complete response were recommended to proceed with a watch-and-wait strategy without surgery. Analyses were done in the intention-to-treat population. The study was designed as a Simon two-stage trial, with an analysis for futility after enrolment of 19 participants. The study was to continue to enrol an additional 20 participants if six or more of the initial 19 participants had a clinical complete response, and the regimen would be deemed worthy of further investigation if 16 participants of the total 39 had a clinical complete response. An early interim analysis (and dissemination of the findings) was approved by the trial protocol committee when it became apparent that this measure of success had been met after enrolment of the first 16 participants. The trial is registered with EU Clinical Trials (2022-500646-14-00); the study is ongoing and continues to enrol patients. Between Feb 1, 2023, and Oct 28, 2025, 16 patients (nine [56%] male, seven [44%] female) were enrolled. Four (25%) patients had stage I tumours, two (13%) had stage II tumours, and ten (63%) had stage III tumours. All patients received at least one cycle of nivolumab and ipilimumab. By day 93, all 16 patients (100·0% [95% CI 79·4-100·0]) had a clinical complete response: 11 (68·7% [41·3-89·0]) patients after one cycle and five (31·3% [11·0-58·7]) after two cycles. No patient received chemoradiotherapy or underwent surgery, and no patients had progression or recurrence during follow-up (median 16 months [IQR 9-18]). Grade 3 immune-related adverse events occurred in three (19%) patients (infusion-related reaction, hypophysitis, and serous retinal detachment). No grade 4 or grade 5 toxicities, serious treatment-related adverse events, treatment discontinuations, or treatment-related deaths were reported. All participants in this trial of short-course dual immune checkpoint blockade for dMMR rectal cancer had a clinical complete response with manageable toxicity, allowing them to proceed to a watch-and-wait strategy without surgery. Longer follow-up and completion of enrolment are needed to confirm the durability of these effects and the safety of an organ-preserving strategy. The Danish Comprehensive Cancer Center-ctDNA Research Center, the NEYE Foundation, the Aage and Johanne Louis-Hansen Foundation, and the Eva and Henry Frænkel Memorial Foundation.
The aim of this exploratory analysis was to investigate effects of time-restricted eating (TRE) on glycemic control and variability in adults with prediabetes. This study utilized data from the Restricted Eating Time (RESET) randomized controlled trial. A subset of 46 participants with prediabetes, allocated to either a 10-hour TRE intervention (n = 20) or the control group (n = 26), was analyzed. Changes in continuous glucose monitoring derived outcomes, fasting glucose and glycosylated hemoglobin (HbA1c), at 6 weeks and 3 months were assessed using a linear mixed-effects model. There were no between-group differences in fasting glucose or HbA1c after 6 weeks and 3 months. The 24-hour and daytime coefficient of variation was reduced within the TRE group after 6 weeks but not after 3 months. Nighttime average sensor glucose was lower in the TRE compared with the control group after 6 weeks [-0.3 mmol/L (-0.6 to -0.1)], but this effect was not maintained after 3 months [-0.1 mmol/L (-0.4 to 0.2)]. TRE may have a small short-term beneficial effect on nighttime glucose levels in adults with prediabetes. Larger long-term TRE studies are warranted.
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Fatigue, insomnia, and depression are persistent, burdensome symptoms for patients recovering from hematopoietic cell transplantation (HCT). Restoring Sleep and Energy after Transplant (ReSET) is a novel behavioral intervention designed to alleviate these symptoms by optimizing patients' 24-hr rest-activity patterns. The primary aim was to evaluate feasibility and acceptability of ReSET. An exploratory aim was to determine preliminary effect sizes. This pilot randomized controlled trial compared ReSET to usual care. Participants randomized to ReSET completed three in-person intervention sessions at approximately 3-4, 8 and 12 weeks post-HCT that focused on strategies to improve nighttime sleep and increase non-sedentary daytime activity. All participants wore an actigraphy device (Philips) and completed patient-reported outcome measures (PROMIS sleep disturbance, fatigue, depression) pre-HCT (T0), 9 (T1), and 18 weeks post-HCT (T2). Interviews were conducted at T2. Ability to recruit, retain, and collect complete data from participants and participant engagement with the intervention were the primary measures of feasibility and Y acceptability. Interviews were conducted at T2 to provide supplementary insight regarding participant satisfaction and barriers to completion. Thirty-nine patients were randomized and most (n = 35; 89.7%) completed the study. Most ReSET participants (85%) completed all intervention sessions. PROMs of sleep (η2 = .033) and depression (η2 = .015) improved over time for participants in ReSET compared to usual care. Those randomized to ReSET also showed improved rest-activity rhythms relative to usual care, including mesor (η2 = .044), amplitude (η2 = .087) and R-squared (η2 = .073) actigraphy indices. ReSET demonstrated feasibility, acceptability, and preliminary promise for intervention efficacy.
Posttraumatic stress symptoms (PTSS) affect nearly 50% of children experiencing physical trauma. PTSS often persists after physical recovery and is associated with reduced health-related quality of life. To evaluate efficacy of the online therapist-assisted, trauma-focused Reducing Stress After Trauma (ReSeT) program in reducing PTSS in children after hospitalization for physical injury. A 2-arm randomized clinical trial with 1:1 assignment to the ReSeT program or usual care (UC) was conducted between 2021 and 2024 at 4 sites with level 1 trauma centers. Injured children ages 8 to 17 years were recruited from inpatient and short-stay units. Exclusion criteria included moderate to severe traumatic brain injury, preexisting severe psychiatric problems, current psychotherapy, developmental disorders preventing participation, interpersonal violence, hospitalization for more than 30 days, and injury-related death of friend or family. The ReSeT program has 8 online psychoeducational modules containing 3 to 4 short interactive videos that children completed independently. Modules are followed by an electronic health session with a therapist to practice cognitive behavioral skills and desensitization using trauma narrative techniques. Parents received optional psychoeducational resources. Generalized linear regression, controlling for baseline scores, was used to examine group differences on the Child Posttraumatic Stress Disorder Scale (CPSS) scores obtained 10 weeks (primary outcome) and 6 months (secondary outcome) after randomization. A total of 638 of 722 children screened positive at 1 week, and 271 children and caregivers completed the CPSS at 4 weeks. The highest value from each respondent on each item was summed, and 130 children (48%) had CPSS scores of 11 or greater, indicating potential eligibility for enrollment. A total of 93 children (72%; mean [SD] age, 11.7 [2.4] years; 56 male [60.2%]) were included in the study; 47 were randomized to the ReSeT cohort and 46 were randomized to the UC cohort. Intention-to-treat analyses indicated significant reduction in combined CPSS scores in the ReSeT vs UC cohorts, -4.2 points (95% CI, -7.6 to -0.8 points) at 10 weeks, which was maintained at the 6-month follow-up, -5.5 points (95% CI, -8.9 to -2.1 points). Findings of this randomized clinical trial show that the ReSeT program was an effective, brief, trauma-focused intervention for reducing PTSS after physical injury. It offers a potentially cost-effective, scalable program to address American College of Surgeons standards for psychological screening and treatment for children sustaining PTSS. ClinicalTrials.gov Identifier: NCT04838977.
Ferroptosis has emerged as a viable approach to enhance therapeutic efficacy in triple-negative breast cancer (TNBC), making monitoring essential for prognostic evaluation. However, conventional MR imaging cannot characterize ferroptosis-related biomarkers. Herein, we propose a Relaxation Suppressed Exchange Tuning (ReSET) MRI strategy for ferroptosis modulation and monitoring, which relies on T1 relaxation and chemical exchange saturation transfer (CEST). ReSET was achieved by a tumor-microenvironment-responsive nanoprobe (SiO2@FUDR@MnO2, SiFM), consisting of a mesoporous silica core loaded with chemotherapeutic floxuridine and the MnO2 shell with nanozyme activities. This structure promotes robust ROS generation, which induces lipid peroxidation and ultimately facilitates chemodynamic therapy (CDT)-sensitized ferroptosis. Notably, ReSET takes advantage of the tumor-responsive release of Mn2+ from SiFM, which shortens T1 relaxation and suppresses the saturation transfer efficiency between water and exchangeable endogenous protons reducing magnetization transfer ratio asymmetry (MTRasym). The inverse correlation between the T1 intensity and MTRasym provides a sensitive and specific indicator for visualizing glutathione peroxidase 4 (GPX4) expression, thereby enabling cross-modal monitoring of ferroptosis. Meanwhile, we revealed that the ReSET strategy enables sensitive detection of small lesions in liver micrometastasis models. Overall, we establish a ReSET MRI-guided strategy using a manganese-based nanoplatform, which represents a promising ferroptosis-related theranostic approach for TNBC.
To properly reflect the dynamic environment, the online representations in visual working memory (VWM) must be constantly accessed and modified when the corresponding items change. Such updating depends on a continuous mapping between each VWM representation and a subset of the external environment, instantiated by a "pointer system." If this mapping is disrupted, the representations cannot be updated, and instead VWM removes the unmapped representations and starts anew. During this "resetting" process, people are blind to salient changes in the items whose representations are inaccessible, creating a behavioral cost. The goal of this study was to test whether VWM's pointers are governed by spatiotemporal information or objecthood. In two preregistered studies, participants performed an "online change detection" task, reporting visible changes in items' shapes, which happened during their (task-irrelevant) movement. Experiment 1 showed that when an intact object abruptly changes its spatiotemporal trajectory, the mapping is sustained, with no resetting cost. Experiment 2 showed that when only half the object changes its trajectory, which effectively splits the object in two, the mapping no longer survives, with diminished performance indicating a resetting process. Critically, a behavioral cost was found even for the half that continued in the same spatiotemporal trajectory, pinpointing objecthood as the driving factor. Together, the results demonstrate that resetting does not reflect mere pointer reassignment, but a specific invalidation of the mapping between representations and the environment. In sustaining this mapping, VWM's pointer system relies not on spatiotemporal information per se, but on physical objecthood.
This article aimed to articulate the most important unmet scientific needs in rheumatology. At the 25th Advances in Targeted Therapies (ATT) meeting, over 100 investigators joined 6 disease-focused breakout groups (rheumatoid arthritis [RA], psoriatic arthritis [PsA], axial spondyloarthritis [axSpA], systemic lupus erythematous [SLE], systemic sclerosis [SSc], and osteoarthritis [OA]). Each group, led by a facilitator and rapporteur, mapped (i) key unmet needs, (ii) promising mechanistic or therapeutic approaches, and (iii) near-term priorities for research and trials. This report synthesises the consensus highlights. Six disease-focused groups (RA, PsA, axSpA, SLE, SSc, and OA) identified convergent priorities: earlier detection and interception; validated molecular and clinical endotypes to guide therapy; strategies for immune reset and short-course induction combinations with strict safety oversight; metabolic modifiers; precision targets in axSpA and fibroblast-directed approaches in RA; phenotype-driven therapeutic development and intra-articular options in OA; and pragmatic trial designs that include pregnant persons and very early disease. Across immune-mediated diseases, progress will hinge on validated endotypes, practical interception strategies, and trials that reflect real-world populations. The immediate agenda is to de-risk immune reset and induction approaches, standardise tissue and digital biomarkers, and close evidence gaps for refractory disease. Prevention-and ultimately cure-remains the horizon.
Perceptual processing may rhythmically alternate. There is a line of evidence from dense sampling psychophysics supporting this claim: In such studies, performance in visual target detection or discrimination is repeatedly tested at various fine-grained time intervals relative to a reference event. This reference event is presented at the beginning of each trial, and it is thought to reset some internal oscillation. Performance time courses following the reset often show rhythmic oscillations in the sub-second range. The interpretation has been that several quickly alternating peaks and troughs of perceptual efficiency exist. Here, we propose an alternative. Instead of being rhythmic, the perceptual processing efficiency time course might exhibit only a single peak in each trial. If the temporal location of this peak is constrained to co-occur with one of the peaks of the internal continuing oscillation, rhythmicity in overall performance time courses can be explained when performance is computed across many trials. Applying this perspective to three published datasets (N = 44, N = 34, N = 11) and running simulations, we confirm the possible existence of such phase-aligned peaks in perceptual efficiency. We show that foreperiod priming (behavioural advantage of repeating the same time interval between reference and target from one trial to the next) alternates across time. This is predicted if peaks in perceptual efficiency are consistently allocated to those time intervals that coincide with a peak in the underlying oscillation. Priming therefore works best at these intervals, which coincide with a peak in the underlying oscillation.
The importance of precise timing of neuronal activity, relative to ongoing slower oscillations, is reshaping the engram theory and our understanding of how memories are encoded and stored. The hippocampal theta-wave phase-encoding of neuronal firing predicts behavioral outcomes and cognitive performance in memory tasks. A single external stimulus or a sensory/cognitive cue may induce Phase-Resetting shift of theta waves, without changing their frequency or power. This phenomenon seems to be a core mechanism for temporal coordination, information encoding, and memory formation. We hypothesize that not only Phase-Resetting, but temporally coded neuromodulation packaged around an averaged theta cycle of 140 ms, plays a role in engram formation. Inter-pulse microstimulation patterns (MS) consisting of six stimuli within a 140 ms period were applied to the intermedial CA3 hippocampal area of C57/BL6 mice. Each MS-pattern consisted of a 10-bit word (each bit representing a 14-ms bin), indicating the phase at which MS was applied. The randomized (MSr) or fixed pattern (MSf) stimulus was applied during a 30 s presentation of a pure tone (CS) that terminated with a 2 s/0.4 mA footshock (US). Sham animals underwent surgery and cued fear conditioning, but no MS. Cued fear memory was tested by presenting the CS (without MS) in a different context. The group of mice that received the MSf during conditioning showed higher levels of freezing compared to the Sham group; the MSr group did not. We measured c-Fos/NeuN labeling as a proxy for neuronal activity 90 min after memory retrieval. As expected, since cued-fear memory is predominantly amygdala-dependent, all groups showed an increase in c-Fos expression in the amygdala. However, only the MSf group had higher hippocampal activation after retrieval, suggesting that fixed pattern stimulation framed around an averaged theta cycle led to neuronal integration into the memory trace. Our findings indicate that temporal organization plays a crucial role in how memories are stored and accessed.
In stochastic processes with absorbing states, the quasi-stationary distribution provides valuable insights into the long-term behavior prior to absorption. In this work, we revisit two well-established numerical methods for its computation. The first is an iterative algorithm for solving the nonlinear equation that defines the quasi-stationary distribution. We generalize this technique to accommodate general Markov stochastic processes, either with discrete or continuous state space, and with multiple absorbing states. The second is a Monte Carlo method with resetting, for which we propose a single-trajectory approach that uses the trajectory's own history to perform resets after absorption. In addition to these methodological contributions, we provide a detailed analysis of implementation aspects for both methods. We also compare their accuracy and efficiency across a range of examples. The results indicate that the iterative algorithm is generally the preferred choice for problems with simple boundaries, while the Monte Carlo approach is more suitable for problems with complex boundaries, where the implementation of the iterative algorithm is a challenging task.
Seeds are resilient to genetic and envirxonmental perturbation. For example, they can compensate for the loss of highly abundant seed storage proteins (SSPs) while maintaining amino acid levels and composition, a process known as proteome rebalancing. This buffering involves large-scale adjustments in translational capacity and metabolic networks, yet it remains unclear whether such plasticity persists under environmental stress or eventually reaches a physiological limit. To address this, we examined Arabidopsis Col-0 (wild type, WT) and cruabc (a triple SSP-deficient mutant) dry seeds produced under no nitrogen supplementation, weekly nitrogen supplementation, or drought (water-deficit) treatment imposed during the seed-filling stage. Analyses of physiological traits, metabolic profiles, and proteomes revealed substantial treatment-dependent changes; however, cruabc seeds consistently remained comparable to Col-0 within each environment, indicating that rebalancing represents a robust, hard-coded plasticity operating downstream of primary stress responses. Nevertheless, the molecular routes used to achieve metabolic and proteomic homeostasis differ across environments in rebalanced seeds. Under drought during seed filling, both genotypes upregulated photosynthetic and pentose phosphate pathway components to mitigate carbon limitation and energy stress, yet cruabc maintained a more oxidative redox state. Under low nitrogen, the cruabc dry seed proteome exhibited minimal reprogramming, whereas under high nitrogen, it underwent extensive remodeling, including enhanced translation-related activity compared to WT. These findings suggest that proteome rebalancing represents a stable homeostatic endpoint that can be reset by environmental cues. However, the metabolic pathways and energetic costs required to achieve this state differ markedly between genotypes, revealing how SSP loss reshapes stress adaptation during seed maturation and desiccation. Collectively, our results refine the mechanistic framework underlying proteome rebalancing and establish a foundation for leveraging this process to enhance amino acid biofortification.
Roux-en-Y gastric bypass (RYGB) improves glucose homeostasis beyond weight loss, but the underlying mechanisms remain incompletely understood. Counter-regulatory hormones such as glucagon, ACTH, and cortisol are key components of glucose regulation. The aim of this study was to characterize alterations in glucagon, ACTH, and cortisol regulation before and after RYGB using nonlinear mixed-effects (NLME) population modeling, and to explore potential mediators of these changes. Post-hoc analysis of one cross-sectional and two prospective cohort studies. Clinical research unit. In total, 62 individuals without diabetes from three previous clamp studies were included: 39 from a cross-sectional cohort covering a wide range of BMI and insulin sensitivity (cohort 1, utilized for model development only), and 23 participants examined both before and approximately four months after RYGB (cohort 2). Hyperinsulinemic-euglycemic-hypoglycemic (both cohorts) and hyperglycemic (cohort 1 only) clamps. Glucose-dependent secretion dynamics of glucagon, ACTH, and cortisol quantified through NLME modeling and the impact of RYGB and metabolic characteristics on corresponding model parameters. According to models developed using presurgical data from both cohorts, glucagon and ACTH turnover rates and baseline concentrations decreased post-RYGB in cohort 2. Insulin-mediated glucagon suppression and the glucose deficit required for ACTH stimulation increased, while cortisol dynamics remained stable. Higher insulin sensitivity was associated with lower baseline glucagon levels. RYGB induces reductions in glucagon and ACTH responsiveness to hypoglycemia, partially indicative of central nervous system-mediated resetting of glucose regulation. These adaptations may contribute to improved metabolic control following bariatric surgery.
To evaluate the clinical and radiographic outcomes at 3 years following immediate loading of tapered implants (TI) versus straight implants (SI) from a randomized controlled trial (RCT). Of the 41 patients who received 93 implants in the original RCT (TI group: 23 patients, 50 implants; SI group: 18 patients, 43 implants), those who completed 3-year follow-up were included in this analysis. Implant survival and success rates, as well as changes in marginal bone loss (MBL), were assessed and compared using Kaplan-Meier curves, Cox proportional hazards models, and linear mixed-effects models. A total of 28 patients with 61 implants were evaluated (TI group: 15 patients, 32 implants; SI group: 13 patients, 29 implants). At 3 years post-immediate loading, cumulative survival rates at the patient level were 95.8% for the TI group and 78.3% for the SI group (intergroup p = 0.109). At the implant level, survival rates were 96.2% for TI and 90.0% for SI (intergroup p = 0.351). All implant failures occurred within the first year (1 implant in TI; 5 implants in SI), and no further losses were recorded thereafter. However, two TI implants in a single patient exhibited progressive peri-implantitis during follow-up. Mean MBL values were 0.61 ± 1.70 mm for the TI group and 0.53 ± 0.53 mm for the SI group, with no statistically significant differences between groups (intergroup p = 0.428). It could be cautiously concluded that the TI rather than the SI might be a more predictable option in terms of achieving an optimized initial stability for immediate loading in the posterior region. Once osseointegration was successfully achieved, however, the macro-design of the implant might not have an influence on the clinical and radiographic outcomes including the osseointegrated state during the 3 years of observational period. KCT0002489; https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=L&pageSize=10&page=undefined&seq=19032&status=5&seq_group=8332.