Development and validation of a robotic system for milling individualized jawbone cavities in oral and maxillofacial surgery.

OBJECTIVES: This study aimed to develop and validate a robotic system capable of performing accurate and minimally invasive jawbone milling procedures in oral and maxillofacial surgery. METHODS: The robotic hardware system mainly includes a UR5E arm (Universal Robots, Denmark) and the binocular positioning system (FusionTrack 250, Atracsys LLC, Switzerland). The robotic software (Dental Navi 3.0.0, Yakebot Technology Ltd., China) is capable of generating cutting tool paths based on three-dimensional shape description files, typically in the stereolithography format, and selected cutting tool parameters, as well as designing surgical accessories. Fully impacted supernumerary tooth models in the maxilla were fabricated using software and three-dimensional printing. Following the planning of a customized cavity to fully expose the tooth, maxillary bone milling was performed on both the robot and static guide groups (n = 8). After milling, all models underwent scanning for assessment. RESULTS: In the experiment with fully buried supernumerary tooth models in the maxilla, the root mean square, translation error, over-removal rate, and maximum distance were significantly smaller in the robot group compared to the static guide group. Moreover, the overlap ratio and Dice coefficient were significantly greater in the robot group. No statistically significant differences were observed between the two groups in terms of the rotation error (P = 0.80) or under-removal rate (P = 0.92). CONCLUSIONS: This study has developed a robotic system for milling individualized jawbone cavities in oral and maxillofacial surgery, and its accuracy has been preliminarily verified to meet clinical requirements. CLINICAL SIGNIFICANCE: The robotic system can achieve precise, minimally invasive, individualized jawbone milling in a variety of oral and maxillofacial surgeries, including tooth autotransplantation, surgical reshaping for zygomatic fibrous dysplasia, removal of fully impacted supernumerary or impacted teeth, and endodontic microsurgery, among other relevant clinical applications.

Theoretical study of adsorption of gas (CO, CO2, NH3) by metal (Au, Ag, Cu)-doped single-layer WS2.

CONTEXT: The adsorptions of gas (CO, CO2, NH3) by metal (Au, Ag, Cu)-doped single layer WS2 are studied by density functional theory. The doping of metal atoms makes WS2 behave as n-type semiconductors. The final adsorption sites for CO, CO2, and NH3 are close to the atomic sites of the doped metal. The adsorptions of CO and NH3 gases on Cu/WS2, Ag/WS2, and Au/WS2 are dominated by chemisorption. The doped metal atoms enhance the hybridization of the substrate with the gas molecular orbitals, which contributes to the charge transfer and enhances the adsorption of the gas with the material surface. The adsorptions of CO and NH3 on Cu/WS2 and Ag/WS2 allow favorable desorption in a short time after heating. The single-layer Cu/WS2 is proved to have the potential to be used as a reliable recyclable sensor for CO. This work provides a theoretical basis for developing high-performance WS2-based gas sensors. METHODS: In this paper, the adsorption energy, electronic structure, charge transfer, and recovery time of CO, CO2, and NH3 in the doped system have been investigated based on the CASTEP code of density functional theory. The exchange correlation function used is the Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation (GGA). The TS (Tkatchenko-Scheffler) dispersion correction method was used to involve the effects of van der Waals interaction on the adsorption energies for all adsorption system. The ultrasoft pseudopotentials are chosen and the plane-wave cut-off energies are set to 500 eV. The k-point mesh generated by the Monkhorst package scheme is used to perform the numerical integration of the Brillouin zone and 5 × 5 × 1 k-point grid is used. The tolerances of total energy convergence, maximum ionic force, ionic displacement, and stress component are 1.0 × 10-5 eV/atom, 0.03 eV/Å, 0.001 Å, and 0.05 GPa, respectively.

Polyetheretherketone split post and core for restoration of multirooted molar with insufficient dental tissue remnants by digital techniques: a case report and 3-year follow up.

BACKGROUND: Multi-rooted teeth with extensive dental defects often face challenges in stability and biomechanical failure. High-performance polymer PEEK materials, with properties closer to dentin, show promise in reducing stress concentration and preserving tooth structure. This report aimed to explore the use of a highly retentive polyetheretherketone (PEEK) for manufacturing custom-made split post and core for the restoration of grossly destroyed endodontically treated molars. CLINICAL CONSIDERATIONS: A 40-year-old female patient presented with complaints of loss of tooth substance in the posterior mandibular tooth. This case involved the digital design and fabrication of PEEK split post and core to restore multirooted molar with insufficient dental tissue remnants. The restorations were evaluated over a 3-year follow-up using the World Federation criteria (FDI). The restoration was clinically evaluated through intraoral examination, radiographic assessment, and subjective patient satisfaction, and was deemed clinically good according to FDI criteria. CONCLUSION: The outstanding mechanical properties of PEEK, coupled with the structure of the split post, provide an effective treatment option for weakened multirooted teeth. Simultaneously, the restoration configuration effectively addressed the challenge of varying postinsertion directions, and the interlocking mechanism between the primary and auxiliary posts enhanced the stability of the post and core.

Fetal/maternal-determined birth weight and adulthood type 2 diabetes and its subtypes: a Mendelian randomization study.

BACKGROUND: Lower birth weight (BW) might increase the risk of adulthood type 2 diabetes, but its associations with the highly heterogeneous type 2 diabetes subtypes remain to be studied. In addition, whether the associations between lower BW and adulthood type 2 diabetes risks depend on fetal or maternal effect is largely unknown. METHODS: In this study, we performed a two-sample Mendelian Randomization analysis to study the associations between overall, fetal-determined, and maternal-determined BW and the risks of type 2 diabetes and its subtypes, namely mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), and severe insulin-resistant diabetes (SIRD). RESULTS: Lower BW was genetically associated with increased risks of type 2 diabetes (odds ratio (OR): 1.86; 95% confidence interval (CI): 1.53, 2.26), MARD (OR: 2.15; 95%CI: 1.43, 3.23), MOD (OR: 1.75; 95%CI: 1.10, 2.77), SIDD (OR: 1.86; 95%CI: 1.11, 3.10), and SIRD (OR: 1.66; 95%CI: 1.06, 2.60). When examining the fetal-determined genetic effects independently, lower BW remained associated with type 2 diabetes and its subtypes, except for MOD. Using maternal-determined BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it raised offspring risks of type 2 diabetes. CONCLUSIONS: Fetal-determined but not maternal-determined lower BW were associated with increased risks of adulthood type 2 diabetes and its subtypes. Our results underscored the importance of early targeted management among people with a low BW in the prevention of type 2 diabetes.

SARS-CoV-2 spike protein potentiates platelet aggregation via upregulating integrin αIIbß3 outside-in signaling pathway.

Platelet hyperreactivity is one of the crucial causes of coagulative disorders in patients with COVID-19. Few studies have indicated that integrin αIIbß3 may be a potential target for spike protein binding to platelets. This study aims to investigate whether spike protein interacts with platelet integrin αIIbß3 and upregulates outside-in signaling to potentiate platelet aggregation. In this study, we found that spike protein significantly potentiated platelet aggregation induced by different agonists and platelet spreading in vitro. Mechanism studies revealed that spike protein upregulated the outside-in signaling, such as increased thrombin-induced phosphorylation of ß3, c-Src. Moreover, using tirofiban to inhibit spike protein binding to αIIbß3 or using PP2 to block outside-in signaling, we found that the potentiating effect of spike protein on platelet aggregation was abolished. These results demonstrate that SARS-CoV-2 spike protein directly enhances platelet aggregation via integrin αIIbß3 outside-in signaling, and suggest a potential target for platelet hyperreactivity in patients with COVID-19. HIGHLIGHTS: • Spike protein potentiates platelet aggregation and upregulates αIIbß3 outside-in signaling. • Spike protein interacts with integrin αIIbß3 to potentiate platelet aggregation. • Blocking outside-in signaling abolishes the effect of spike protein on platelets.

Effects of genetically proxied lipid-lowering drugs on acute myocardial infarction: a drug-target mendelian randomization study.

OBJECTIVE: High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. METHODS: Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. RESULTS: Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004-1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002-1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995-0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994-0.999 and 0.986, 0.975-0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993-0.996). CONCLUSIONS: The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.

Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images.

Accurate segmentation of oral surgery-related tissues from cone beam computed tomography (CBCT) images can significantly accelerate treatment planning and improve surgical accuracy. In this paper, we propose a fully automated tissue segmentation system for dental implant surgery. Specifically, we propose an image preprocessing method based on data distribution histograms, which can adaptively process CBCT images with different parameters. Based on this, we use the bone segmentation network to obtain the segmentation results of alveolar bone, teeth, and maxillary sinus. We use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding tasks. The tooth segmentation results can obtain the order information of the dentition. The corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing methods. Its average Dice scores on the tooth, alveolar bone, maxillary sinus, and mandibular canal segmentation tasks were 96.5%, 95.4%, 93.6%, and 94.8%, respectively. These results demonstrate that it can accelerate the development of digital dentistry.

Women's reproductive risk score and healthy lifestyle modification in cardiovascular disease: Findings from the UK Biobank.

BACKGROUND AND AIMS: Reproductive risk factors are associated with increased risk of cardiovascular disease (CVD) in women. However, the combined effects of the composite reproductive risk factors on CVD are unknown. This study was performed to construct a reproductive risk score (RRS) to measure reproductive status, examine the association between RRS and CVD, and explore the modification effect of healthy lifestyle on the association in women in the UK Biobank cohort. METHODS: The RRS was constructed in 74,141 female participants with data about the items derived for the RRS in the UK Biobank. The RRS was derived from 17 baseline variables, all of which indicated women's reproductive health status. We defined four categories of RRS status: low-risk group (score 0-1); low-intermediate group (score 2-3); high-intermediate group (score 4-5); and high-risk group (score 6-13). We also constructed a healthy lifestyle score (HLS) with five related factors, and categorized into unhealthy lifestyle group (score: 0-1), intermediate lifestyle group (score: 2-3) and healthy lifestyle group (score: 4-5). RESULTS: Each point increase in the RRS was associated with a 22 % higher risk of CVD (adjusted hazard ratio (aHR): 1.22; 95 % confidence interval (CI): 1.16 to 1.28), 23 % higher risk of IHD (1.23; 1.17 to 1.31) and 19 % higher risk of stroke (1.19; 1.07 to 1.32). The percentage population-attribution risks (PAR%) were 16 % (95 % CI: 8 to 24) for CVD, 15 % (95 % CI: 6 to 24) for IHD and 18 % (95 % CI: 1 to 33) for stroke. A healthy lifestyle significantly attenuated RRS associations with the incidence of CVD and IHD. The attributable proportions due to additive interaction (p < 0.001) between RRS and HLS were 0.14 (95 % CI: 0.07 to 0.22) for CVD and 0.15 (95 % CI: 0.09 to 0.23) for IHD, respectively. CONCLUSIONS: High RRS was associated with increased risks of CVD, IHD and stroke in female participants in the UK Biobank. The early-stage identification of women with reproductive risk using synthesised indicators and appropriate healthy lifestyle interventions could be useful for the prevention of early CVD and the extension of healthy active life expectancy.

Genetically determined blood pressure, antihypertensive drug classes, and frailty: A Mendelian randomization study.

Observational studies have suggested that the use of antihypertensive drugs was associated with the risk of frailty; however, these findings may be biased by confounding and reverse causality. This study aimed to explore the effect of genetically predicted lifelong lowering blood pressure (BP) through different antihypertensive medications on frailty. One-sample Mendelian randomization (MR) and summary data-based MR (SMR) were applied. We utilized two kinds of genetic instruments to proxy the antihypertensive medications, including genetic variants within or nearby drugs target genes associated with systolic/diastolic BP, and expression level of the corresponding gene. Among 298,618 UK Biobank participants, one-sample MR analysis observed that genetically proxied BB use (relative risk ratios, 0.76; 95% CI, 0.65-0.90; p = 0.001) and CCB use (0.83; 0.72-0.95; p = 0.007), equivalent to a 10-mm Hg reduction in systolic BP, was significantly associated with lower risk of pre-frailty. In addition, although not statistically significant, the effect directions of systolic BP through ACEi variants (0.72; 0.39-1.33; p = 0.296) or thiazides variants (0.74; 0.53-1.03; p = 0.072) on pre-frailty were also protective. Similar results were obtained in analyses for diastolic BP. SMR of expression in artery showed that decreased expression level of KCNH2, a target gene of BBs, was associated with lower frailty index (beta -0.02, p = 2.87 × 10-4). This MR analysis found evidence that the use of BBs and CCBs was potentially associated with reduced frailty risk in the general population, and identified KCNH2 as a promising target for further clinical trials to prevent manifestations of frailty.

A digital workflow for designing and manufacturing metal frameworks and removable partial dentures: A novel dental technique.

The purpose of this technical report is to demonstrate a fully digital workflow for designing and fabricating metal frameworks and removable partial dentures. After obtaining a digital cast of the dental arch with bilateral distal extension defect, computer-aided design software and 3D printing technology are used for the design and fabrication of the removable partial denture frameworks, denture teeth, and denture bases, instead of the traditional workflow. The assembly of the three components is facilitated through a meticulously structured framework. The technology, which prints metal frameworks, denture bases, and denture teeth through different processes with different materials, achieves full 3D printing technology for making removable partial dentures.

Four Parallel Pathways in T4 Ligase-Catalyzed Repair of Nicked DNA with Diverse Bending Angles.

The structural diversity of biological macromolecules in different environments contributes complexity to enzymological processes vital for cellular functions. Fluorescence resonance energy transfer and electron microscopy are used to investigate the enzymatic reaction of T4 DNA ligase catalyzing the ligation of nicked DNA. The data show that both the ligase-AMP complex and the ligase-AMP-DNA complex can have four conformations. This finding suggests the parallel occurrence of four ligation reaction pathways, each characterized by specific conformations of the ligase-AMP complex that persist in the ligase-AMP-DNA complex. Notably, these complexes have DNA bending angles of ≈0°, 20°, 60°, or 100°. The mechanism of parallel reactions challenges the conventional notion of simple sequential reaction steps occurring among multiple conformations. The results provide insights into the dynamic conformational changes and the versatile attributes of T4 DNA ligase and suggest that the parallel multiple reaction pathways may correspond to diverse T4 DNA ligase functions. This mechanism may potentially have evolved as an adaptive strategy across evolutionary history to navigate complex environments.

The evolution of robotics: research and application progress of dental implant robotic systems.

The use of robots to augment human capabilities and assist in work has long been an aspiration. Robotics has been developing since the 1960s when the first industrial robot was introduced. As technology has advanced, robotic-assisted surgery has shown numerous advantages, including more precision, efficiency, minimal invasiveness, and safety than is possible with conventional techniques, which are research hotspots and cutting-edge trends. This article reviewed the history of medical robot development and seminal research papers about current research progress. Taking the autonomous dental implant robotic system as an example, the advantages and prospects of medical robotic systems would be discussed which would provide a reference for future research.

Associations of birth weight, plasma metabolome in adulthood and risk of type 2 diabetes.

AIMS: We aimed to examine the longitudinal associations of birth weight with plasma metabolites in adulthood, and further quantify the proportions of the links between birth weight and incident adult type 2 diabetes (T2D) that were mediated by plasma metabolites. MATERIALS AND METHODS: A total of 62,033 participants with complete nuclear magnetic resonance metabolomics and birth weight data from the UK Biobank were included in this study. Linear regression was used to assess the associations between birth weight and metabolites. Cox regression was used to estimate hazard ratios for T2D associated with metabolites. We further performed mediation analyses to estimate the extent to which metabolites might mediate the association between birth weight and T2D risk. RESULTS: Low birth weight was associated with the adverse metabolic responses across multiple metabolic pathways, including lipoprotein subclasses, amino acids, fatty acids (FA), and inflammation. Metabolites associated with higher birth weight tended to be associated with a lower risk of T2D (Pearson correlation coefficient: -0.85). A total of 62 metabolites showed statistically significant mediation effects in the protective association of higher birth weight and T2D risk, including large-sized very low-density lipoprotein particles and triglyceride concentrations as well as saturated, and monounsaturated FA and glycoprotein acetyls. CONCLUSIONS: We identified a range of metabolites that reflect the adult metabolic response to birth weight, some of which might lie on the pathway between birth weight and adult T2D risk.

Autonomous robotic system for the assisted immediate placement of a maxillary anterior implant: A clinical report.

Precise reproduction of the preoperatively designed 3-dimensional (3D) implant position is key to seating a prefabricated restoration and restoring esthetics. Static and dynamic computer-aided implant surgery (CAIS) based on the fusion of 3D imaging files have been used to improve implant accuracy. However, both techniques have shortcomings that can be remedied by a robotic system. This clinical report describes the immediate placement of an implant in the anterior esthetic zone by using an autonomous dental implant robotic system (ADIR).

Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity.

The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.

Endodontic Microsurgery With an Autonomous Robotic System: A Clinical Report.

INTRODUCTION: Endodontic microsurgery (EMS) requires minimally invasive osteotomy and accurate root-end resection, which can be challenging in many instances. Evidence suggests that autonomous robotic systems can significantly enhance the precision of dental implantation. The aim of this case report is to introduce a novel EMS technique that employs robot-guided osteotomy and root resection procedures. METHODS: A 59-year-old man was diagnosed with previously treated, symptomatic apical periodontitis in the mandibular left first molar. Patient data were used to integrate a digital model into preoperative planning software to design the surgical plan. The robotic system utilizes spatial alignment techniques for registration, guiding the robotic arm to autonomously perform a 3-mm osteotomy and root-end resection, based on the surgical plan. After completing the resection, the clinician confirmed the absence of cracks or root fractures and subsequently performed root-end preparation and filling under a microscope. RESULTS: To the best of our knowledge, this case marks the first use of autonomous robotic assistance in EMS. CONCLUSIONS: Utilizing an autonomous robotic system could enable precise apicoectomy in patients with intact cortical plates, thus facilitating successful EMS procedures. This has the potential to minimize errors caused by operator inexperience and mitigate the risks associated with excessive bone removal.

Plant size-dependent influence of foliar fungal pathogens promotes diversity through allometric growth.

The effect of pathogens on host diversity has attracted much attention in recent years, yet how the influence of pathogens on individual plants scales up to affect community-level host diversity remains unclear. Here, we assessed the effects of foliar fungal pathogens on plant growth and species richness using allometric growth theory in population-level and community-level foliar fungal pathogen exclusion experiments. We calculated growth scaling exponents of 24 species to reveal the intraspecific size-dependent effects of foliar fungal pathogens on plant growth. We also calculated the intercepts to infer the growth rates of relatively larger conspecific individuals. We found that foliar fungal pathogens inhibited the growth of small conspecific individuals more than large individuals, resulting in a positive allometric growth. After foliar fungal pathogen exclusion, species-specific growth scaling exponents and intercepts decreased, but became positively related to species' relative abundance, providing a growth advantage for individuals of abundant species with a higher growth scaling exponent and intercept compared with rare species, and thus reduced species diversity. By adopting allometric growth theory, we elucidate the size-dependent mechanisms through which pathogens regulate species diversity and provide a powerful framework to incorporate antagonistic size-dependent processes in understanding species coexistence.

Clinical evaluation of autonomous robotic-assisted full-arch implant surgery: A 1-year prospective clinical study.

OBJECTIVES: This prospective clinical study aimed to evaluate the accuracy and 1-year clinical follow-up performance of dental implant placement with an autonomous dental implant robot (ADIR) system in full-arch implant surgery. MATERIALS AND METHODS: Twelve patients with edentulous arches or final dentition received 102 implants using the ADIR system. Global platform deviation, global apex deviation, and global angular deviation between the planned and actual implants were calculated after surgery. Data were statistically analyzed for factors including jaws, implant positions, patient sequences, implant systems, and implant length. Surgery duration was recorded. Patients were followed for 3 months and 1 year after surgery. Periodontal parameters, buccal bone thickness (BBT), and facial vertical bone wall peak (IP-FC) were recorded. RESULTS: Among the 102 implants, the mean (SD) global platform deviation, global apex deviation, and global angular deviation were 0.53 (0.19) mm, 0.58 (0.17) mm, and 1.83 (0.82)°, respectively. The deviation differences between the mandible and maxilla did not show statistical significance (p > .05). No statistically significant differences were found for the jaws, implant positions, patient sequences, implant systems, and implant length to the deviations (p > .05). The periodontal parameters, the BBT, and IP-FC remained stable during 1-year follow-up. CONCLUSION: The ADIR system showed excellent positional accuracy. The 1-year follow-up after full-arch implant surgery indicated that the ADIR system could achieve promising clinical performance. Additional clinical evidence is requisite to furnish guidelines for the implementation of the ADIR system in full-arch implant surgery.

Sleep patterns, genetic predisposition, and risk of chronic liver disease: A prospective study of 408,560 UK Biobank participants.

BACKGROUND: Little is known about the role that combined sleep behaviors play in the association with chronic liver disease (CLD) risk. METHODS: We included 408,560 participants initially free of CLD from the UK Biobank. A healthy sleep pattern was defined by early chronotype, sleep duration of 7-8 h/day, no insomnia, no snoring, and no excessive daytime sleepiness. Cox regression models were used to examine the association of healthy sleep pattern with incident CLD and their interaction with PNPLA3 genetic risk. RESULTS: During a median 12.5 years of follow-up, we documented 10,915 incident all-cause CLD cases, including 388 viral hepatitis, 4782 non-alcoholic fatty liver disease (NAFLD), 1356 cirrhosis, 973 alcoholic liver disease, and 725 liver cancer cases. Compared to participants with a healthy sleep score of 0-1, the hazard ratio (HR) (95 % confidence interval [CI]) for those with a sleep score of 5 was 0.54 (0.49, 0.60) for CLD, 0.52 (0.30, 0.90) for viral hepatitis, 0.47 (0.41, 0.55) for NAFLD, 0.57 (0.43, 0.75) for cirrhosis, 0.32 (0.23, 0.44) for alcoholic liver disease, and 0.53 (0.37, 0.77) for liver cancer. Healthy sleep pattern and PNPLA3 genetic risk exerted significant additive effects on CLD risk (relative excess risk due to the interaction: 0.05; attributable proportion due to the interaction: 13 %). LIMITATIONS: Measurement error was unavoidable for self-reported data on sleep behaviors. CONCLUSIONS: Our analyses provide evidence that healthy sleep pattern was inversely associated with the development of CLD, and participants with higher genetic risk were more likely to develop CLD when exposed to the unhealthy sleep pattern.

Frequency of Adding Salt to Foods, Genetic Susceptibility, and Incident Type 2 Diabetes: A Prospective Cohort Study.

CONTEXT: Excessive salt consumption is known to increase the risk of hypertension and cardiovascular disease, but the association between salt intake and incident type 2 diabetes has not been extensively researched. OBJECTIVE: In this study, we aimed to investigate the relationships between the frequency of adding salt to foods and incident type 2 diabetes, as well as any potential interactions with genetic predisposition. METHODS: We included 368 137 eligible participants, aged 37 to 73 years, from the UK Biobank. The frequency of adding salt to foods was assessed via a food frequency questionnaire. RESULTS: During a median follow-up of 12.6 years, we documented 10 981 incident type 2 diabetes cases. After adjustment for major confounders, participants who sometimes, usually, and always added salt to foods had 7% (hazard ratio [HR]: 1.07; 95% CI, 1.03-1.12), 9% (HR: 1.09; 95% CI, 1.03-1.16), 28% (HR: 1.28; 95% CI, 1.19-1.38) higher risks of developing type 2 diabetes, respectively, than those that never/rarely added salt to foods (P for trend < .001). We found these associations to be consistent across stratified and sensitivity analyses. However, we did not observe any statistically significant multiplicative or additive interactions between the frequency of adding salt to foods and genetic predisposition regarding incident type 2 diabetes. CONCLUSION: Our findings suggest that consuming salt regularly, regardless of genetic susceptibility, may increase the risk of type 2 diabetes. Therefore, public health interventions aimed at reducing excessive salt consumption may help prevent the onset of type 2 diabetes.