Integrating metabolic expenditure information from wearable fitness sensors into an AI-augmented automated insulin delivery system: a randomised clinical trial.

BACKGROUND: Exercise can rapidly drop glucose in people with type 1 diabetes. Ubiquitous wearable fitness sensors are not integrated into automated insulin delivery (AID) systems. We hypothesised that an AID can automate insulin adjustments using real-time wearable fitness data to reduce hypoglycaemia during exercise and free-living conditions compared with an AID not automating use of fitness data. METHODS: Our study population comprised of individuals (aged 21-50 years) with type 1 diabetes from from the Harold Schnitzer Diabetes Health Center clinic at Oregon Health and Science University, OR, USA, who were enrolled into a 76 h single-centre, two-arm randomised (4-block randomisation), non-blinded crossover study to use (1) an AID that detects exercise, prompts the user, and shuts off insulin during exercise using an exercise-aware adaptive proportional derivative (exAPD) algorithm or (2) an AID that automates insulin adjustments using fitness data in real-time through an exercise-aware model predictive control (exMPC) algorithm. Both algorithms ran on iPancreas comprising commercial glucose sensors, insulin pumps, and smartwatches. Participants executed 1 week run-in on usual therapy followed by exAPD or exMPC for one 12 h primary in-clinic session involving meals, exercise, and activities of daily living, and 2 free-living out-patient days. Primary outcome was time below range (<3·9 mmol/L) during the primary in-clinic session. Secondary outcome measures included mean glucose and time in range (3·9-10 mmol/L). This trial is registered with ClinicalTrials.gov, NCT04771403. FINDINGS: Between April 13, 2021, and Oct 3, 2022, 27 participants (18 females) were enrolled into the study. There was no significant difference between exMPC (n=24) versus exAPD (n=22) in time below range (mean [SD] 1·3% [2·9] vs 2·5% [7·0]) or time in range (63·2% [23·9] vs 59·4% [23·1]) during the primary in-clinic session. In the 2 h period after start of in-clinic exercise, exMPC had significantly lower mean glucose (7·3 [1·6] vs 8·0 [1·7] mmol/L, p=0·023) and comparable time below range (1·4% [4·2] vs 4·9% [14·4]). Across the 76 h study, both algorithms achieved clinical time in range targets (71·2% [16] and 75·5% [11]) and time below range (1·0% [1·2] and 1·3% [2·2]), significantly lower than run-in period (2·4% [2·4], p=0·0004 vs exMPC; p=0·012 vs exAPD). No adverse events occurred. INTERPRETATION: AIDs can integrate exercise data from smartwatches to inform insulin dosing and limit hypoglycaemia while improving glucose outcomes. Future AID systems that integrate exercise metrics from wearable fitness sensors may help people living with type 1 diabetes exercise safely by limiting hypoglycaemia. FUNDING: JDRF Foundation and the Leona M and Harry B Helmsley Charitable Trust, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

Enabling fully automated insulin delivery through meal detection and size estimation using Artificial Intelligence.

We present a robust insulin delivery system that includes automated meal detection and carbohydrate content estimation using machine learning for meal insulin dosing called robust artificial pancreas (RAP). We conducted a randomized, single-center crossover trial to compare postprandial glucose control in the four hours following unannounced meals using a hybrid model predictive control (MPC) algorithm and the RAP system. The RAP system includes a neural network model to automatically detect meals and deliver a recommended meal insulin dose. The meal detection algorithm has a sensitivity of 83.3%, false discovery rate of 16.6%, and mean detection time of 25.9 minutes. While there is no significant difference in incremental area under the curve of glucose, RAP significantly reduces time above range (glucose >180 mg/dL) by 10.8% (P = 0.04) and trends toward increasing time in range (70-180 mg/dL) by 9.1% compared with MPC. Time below range (glucose <70 mg/dL) is not significantly different between RAP and MPC.

The Inhibition of Zinc Excitotoxicity and AMPK Phosphorylation by a Novel Zinc Chelator, 2G11, Ameliorates Neuronal Death Induced by Global Cerebral Ischemia.

AMP-activated protein kinase (AMPK) is necessary for maintaining a positive energy balance and essential cellular processes such as glycolysis, gene transcription, glucose uptake, and several other biological functions. However, brain injury-induced energy and metabolic stressors, such as cerebral ischemia, increase AMPK phosphorylation. Phosphorylated AMPK contributes to excitotoxicity, oxidative, and metabolic problems. Furthermore, brain disease-induced release of zinc from synaptic vesicles contributes to neuronal damage via mechanisms including ROS production, apoptotic cell death, and DNA damage. For this reason, we hypothesized that regulating zinc accumulation and AMPK phosphorylation is critical for protection against global cerebral ischemia (GCI). Through virtual screening based on the structure of AMPK subunit alpha 2, we identified a novel compound, 2G11. In this study, we verified that 2G11 administration has neuroprotective effects via the blocking of zinc translocation and AMPK phosphorylation after GCI. As a result, we demonstrated that 2G11 protected hippocampal neurons against GCI and OGD/R-derived cellular damage. In conclusion, we propose that AMPK inhibition and zinc chelation by 2G11 may be a promising tool for preventing GCI-induced hippocampal neuronal death.

Assessment of a Decision Support System for Adults with Type 1 Diabetes on Multiple Daily Insulin Injections.

Introduction: DailyDose is a decision support system designed to provide real-time dosing advice and weekly insulin dose adjustments for adults living with type 1 diabetes using multiple daily insulin injections. Materials and Methods: Twenty-five adults were enrolled in this single-arm study. All participants used Dexcom G6 for continuous glucose monitoring, InPen for short-acting insulin doses, and Clipsulin to track long-acting insulin doses. Participants used DailyDose on an iPhone for 8 weeks. The primary endpoint was % time in range (TIR) comparing the 2-week baseline to the final 2-week period of DailyDose use. Results: There were no significant differences between TIR or other glycemic metrics between the baseline period compared to final 2-week period of DailyDose use. TIR significantly improved by 6.3% when more than half of recommendations were accepted and followed compared with 50% or fewer recommendations (95% CI 2.5%-10.1%, P = 0.001). Conclusions: Use of DailyDose did not improve glycemic outcomes compared to the baseline period. In a post hoc analysis, accepting and following recommendations from DailyDose was associated with improved TIR. Clinical Trial Registration Number: NCT04428645.

S-Nitrosylation of cathepsin B affects autophagic flux and accumulation of protein aggregates in neurodegenerative disorders.

Protein S-nitrosylation is known to regulate enzymatic function. Here, we report that nitric oxide (NO)-related species can contribute to Alzheimer's disease (AD) by S-nitrosylating the lysosomal protease cathepsin B (forming SNO-CTSB), thereby inhibiting CTSB activity. This posttranslational modification inhibited autophagic flux, increased autolysosomal vesicles, and led to accumulation of protein aggregates. CA-074Me, a CTSB chemical inhibitor, also inhibited autophagic flux and resulted in accumulation of protein aggregates similar to the effect of SNO-CTSB. Inhibition of CTSB activity also induced caspase-dependent neuronal apoptosis in mouse cerebrocortical cultures. To examine which cysteine residue(s) in CTSB are S-nitrosylated, we mutated candidate cysteines and found that three cysteines were susceptible to S-nitrosylation. Finally, we observed an increase in SNO-CTSB in both 5XFAD transgenic mouse and flash-frozen postmortem human AD brains. These results suggest that S-nitrosylation of CTSB inhibits enzymatic activity, blocks autophagic flux, and thus contributes to AD pathogenesis.

Programmed hierarchical radial association of anisotropic foldamer assemblies.

Herein, we report the first example of a programmed radial assembly of anisotropic microparticles derived from a helical foldamer with a C-terminal cysteine residue. Surface-exposed thiols played a crucial role in facilitating the interparticle hydrogen bonding to form higher-order structures in an aqueous solution.

Apixaban use in an atrial fibrillation patient with double mechanical heart valves: a case report.

BACKGROUND: Warfarin is the only approved oral anticoagulant for long-term prophylaxis against valve thrombosis and thromboembolism in patients with mechanical heart valves. To date, apixaban for patients with double (aortic and mitral) mechanical heart valves has not been reported in the literature. CASE SUMMARY: We report the case of a 50-year-old female who underwent double (aortic and mitral) mechanical valve replacement in February 2017. Warfarin was prescribed after mechanical valve replacement. However, she complained of side effects of warfarin, including tingling sensation and numbness of legs, urticaria, skin rash, and nausea and voluntarily stopped taking medication. In December 2018, she was admitted to the emergency room due to ongoing chest pain. Coronary angiogram revealed embolic myocardial infarction at the left circumflex coronary artery. Nevertheless, she continued to refuse to take warfarin after anticoagulant therapy for coronary artery embolism. Given the patient's objection, we prescribed apixaban 5 mg b.i.d. since February 2019. When she was diagnosed with atrial fibrillation in April 2020, no intracardiac thrombosis was confirmed on computed tomography and electrical cardioversion was performed safely. While on apixaban, no evidence of prosthetic valve thrombosis or thrombo-embolic events was observed during a 24-month period. CONCLUSION: We report the efficacy and safety of apixaban in a patient with atrial fibrillation and double mechanical heart valves for preventing prosthetic valve thrombus and systemic embolism.

Conductive GelMA-Collagen-AgNW Blended Hydrogel for Smart Actuator.

Blended hydrogels play an important role in enhancing the properties (e.g., mechanical properties and conductivity) of hydrogels. In this study, we generated a conductive blended hydrogel, which was achieved by mixing gelatin methacrylate (GelMA) with collagen, and silver nanowire (AgNW). The ratio of GelMA, collagen and AgNW was optimized and was subsequently gelated by ultraviolet light (UV) and heat. The scanning electron microscope (SEM) image of the conductive blended hydrogels showed that collagen and AgNW were present in the GelMA hydrogel. Additionally, rheological analysis indicated that the mechanical properties of the conductive GelMA-collagen-AgNW blended hydrogels improved. Biocompatibility analysis confirmed that the human umbilical vein endothelial cells (HUVECs) encapsulated within the three-dimensional (3D), conductive blended hydrogels were highly viable. Furthermore, we confirmed that the molecule in the conductive blended hydrogel was released by electrical stimuli-mediated structural deformation. Therefore, this conductive GelMA-collagen-AgNW blended hydrogel could be potentially used as a smart actuator for drug delivery applications.

A New Methodology for Predicting Brittle Fracture of Plastically Deformable Materials: Application to a Cold Shell Nosing Process.

The traditional theory of ductile fracture has limitations for predicting crack generation during a cold shell nosing process. Various damage criteria are employed to explain fracture and failure in the nose part of a cold shell. In this study, differences in microstructure among fractured materials and analysis of their surfaces indicated the occurrence of brittle fractures. The degree of "plastic deformation-induced embrittlement" (PDIE) of plastically deformable materials affects the likelihood of brittle fractures; PDIE can also decrease the strength in tension due to the Bauschinger effect. Two indicators of brittle fracture are presented, i.e., the critical value of PDIE and the allowable tensile strength (which in turn depends on the degree of PDIE or embrittlement-effective strain). When the maximum principal stress is greater than the latter and the PDIE is greater than the former, our method determines the likelihood of brittle fracture. This approach was applied to an actual cold shell nosing process, and the predictions were in good quantitative agreement with the experimental results.

Optical properties and 14C ages of stream DOM from agricultural and forest watersheds during storms.

Forest and agricultural land use affects the concentration and composition of dissolved organic carbon (DOC) in streams and rivers. To elucidate the impacts of forest and agricultural land use on stream DOC during storm events, we investigated DOC concentration ([DOC]), optical properties of dissolved organic matter (DOM), and Δ14C-DOC in both forest- and agriculture-dominated headwater streams in South Korea in the summer of 2012. One forested and five agricultural streams were investigated. During storms, the peak [DOC] of forest stream increased to 5.8 mg L-1, approximately two times larger than that of the most agricultural stream (3.2 mg L-1), demonstrating the weaker storm responses of the [DOC] of agricultural streams to hydrological change. Five PARAFAC components were identified, including three terrestrial humic-like substances (C1, C2, C3), one microbial humic substance (C4), and one microbial protein-like substances (C5). The mean (C4+C5)/(C1+C2+C3) of all storm events at the most agricultural stream was 1.5 times larger than that of the most forested stream, suggesting that more protein-like DOM is exported from agricultural watersheds. Whereas a forest stream was primarily composed of terrestrially derived and 14C-enriched modern DOC, the 14C-age of the most agricultural stream was up to ∼1000 years old. The results suggest that agricultural practices could decrease the old organic carbon pools from soils. However, how quickly the aged DOC can be degraded to CO2 in streams is unknown, warranting future investigation on lability of the aged DOC and their effects on CO2 evasion from rivers and estuaries downstream.

Mechanism of Zinc Excitotoxicity: A Focus on AMPK.

Over the last 20 years, it has been shown that complex signaling cascades are involved in zinc excitotoxicity. Free zinc rapidly induces PKC activation, which causes reactive oxygen species (ROS) production at least in part through NADPH oxidase. It also promotes neuronal nitric oxide synthase, thereby increasing nitric oxide (NO) production. Extracellular signal-regulated kinase activation and Egr-1 transcription factor activity were quickly induced by zinc, too. These concurrent actions of kinases consequently produce oxygen free radical, ROS, and NO, which may cause severe DNA damage. Following the excessive activity of poly(ADP-ribose) polymerase-1 depletes NAD+/ATP in the cells. Zinc excitotoxicity exhibits distinct characteristics of apoptosis, too. Activation of caspase-3 is induced by liver kinase B1 (LKB1)-AMP-activated kinase (AMPK)-Bim cascade signaling and induction of p75NTR receptors and p75NTR-associated Death Executor. Thus, zinc excitotoxicity is a mechanism of neuronal cell death showing various cell death patterns. In addition to the above signaling cascades, individual intracellular organelles also play a crucial role in zinc excitotoxicity. Mitochondria and lysosomes function as zinc reservoirs, and as such, are capable of regulating zinc concentration in the cytoplasm. However, when loaded with too much zinc, they may undergo mitochondrial permeability transition pore (mPTP) opening, and lysosomal membrane permeabilization (LMP), both of which are well-established mechanisms of cell death. Since zinc excitotoxicity has been reported to be associated with acute brain injuries, including stroke, trauma, and epilepsy, we performed to find the novel AMPK inhibitors as therapeutic agents for these diseases. Since we thought acute brain injury has complicated neuronal death pathways, we tried to see the neuroprotection against zinc excitotoxicity, calcium-overload excitotoxicity, oxidative damage, and apoptosis. We found that two chemicals showed significant neuroprotection against all cellular neurotoxic models we tested. Finally, we observed the reduction of infarct volume in a rat model of brain injury after middle cerebral artery occlusion (MCAO). In this review, we introduced the AMPK-mediated cell death mechanism and novel strategy for the development of stroke therapeutics. The hope is that this understanding would provide a rationale for acute brain injury and eventually find new therapeutics.

A Novel Zinc Chelator, 1H10, Ameliorates Experimental Autoimmune Encephalomyelitis by Modulating Zinc Toxicity and AMPK Activation.

Previous studies in our lab revealed that chemical zinc chelation or zinc transporter 3 (ZnT3) gene deletion suppresses the clinical features and neuropathological changes associated with experimental autoimmune encephalomyelitis (EAE). In addition, although protective functions are well documented for AMP-activated protein kinase (AMPK), paradoxically, disease-promoting effects have also been demonstrated for this enzyme. Recent studies have demonstrated that AMPK contributes to zinc-induced neurotoxicity and that 1H10, an inhibitor of AMPK, reduces zinc-induced neuronal death and protects against oxidative stress, excitotoxicity, and apoptosis. Here, we sought to evaluate the therapeutic efficacy of 1H10 against myelin oligodendrocyte glycoprotein 35-55-induced EAE. 1H10 (5 µg/kg) was intraperitoneally injected once per day for the entire experimental course. Histological evaluation was performed three weeks after the initial immunization. We found that 1H10 profoundly reduced the severity of the induced EAE and that there was a remarkable suppression of demyelination, microglial activation, and immune cell infiltration. 1H10 also remarkably inhibited EAE-associated blood-brain barrier (BBB) disruption, MMP-9 activation, and aberrant synaptic zinc patch formation. Furthermore, the present study showed that long-term treatment with 1H10 also reduced the clinical course of EAE. Therefore, the present study suggests that zinc chelation and AMPK inhibition with 1H10 may have great therapeutic potential for the treatment of multiple sclerosis.

Identifying New AMP-Activated Protein Kinase Inhibitors That Protect against Ischemic Brain Injury.

We recently reported that AMP-activated protein kinase (AMPK) contributes to zinc-induced neuronal death by inducing Bim, a pro-apoptotic Bcl-2 homology domain 3-only protein, in a liver kinase B1 (LKB1)-dependent manner. Current data suggest AMPK plays key roles in excitotoxicity and ischemic brain injury, with zinc neurotoxicity representing at least one mechanism of ischemic neuronal death. Inhibition of AMPK could be a viable therapeutic strategy to prevent ischemic brain injury following stroke. This prompted our search for novel inhibitors of AMPK activity and zinc-induced neuronal death using cultured mouse cortex and a rat model of brain injury after middle cerebral artery occlusion (MCAO). In structure-based virtual screening, 118 compounds were predicted to bind the active site of AMPK α2, and 40 showed in vitro AMPK α2 inhibitory activity comparable to compound C (a well-known, potent AMPK inhibitor). In mouse cortical neuronal cultures, 7 of 40 compound reduced zinc-induced neuronal death at levels comparable to compound C. Ultimately, only agents 2G11 and 1H10 significantly attenuated various types of neuronal death, including oxidative stress, excitotoxicity, and apoptosis. When administered as intracerebroventricular injections prior to permanent MCAO in rats, 2G11 and 1H10 reduced brain infarct volumes, whereas compound C did not. Therefore, these novel AMPK inhibitors could be drug development candidates to treat stroke.

Directing Foldamer Self-Assembly with a Cyclopropanoyl Cap.

The rational design of self-assembling organic materials is extremely challenging due to the difficulty in precisely predicting solid-state architectures from first principles, especially if synthons are conformationally flexible. A tractable model system to study self-assembly was constructed by appending cyclopropanoyl caps to the N termini of helical α/ß-peptide foldamers, designed to form both N-H⋅⋅⋅O and Cα -H⋅⋅⋅O hydrogen bonds, which then rapidly self-assembled to form foldectures (foldamer architectures). Through a combined analytical and computational investigation, cyclopropanoyl capping was observed to markedly enhance self-assembly in recalcitrant substrates and direct the formation of a single intermolecular N-H⋅⋅⋅O/Cα -H⋅⋅⋅O bonding motif in single crystals, regardless of peptide sequence or foldamer conformation. In contrast to previous studies, foldamer constituents of single crystals and foldectures assumed different secondary structures and different molecular packing modes, despite a conserved N-H⋅⋅⋅O/Cα -H⋅⋅⋅O bonding motif. DFT calculations validated the experimental results by showing that the N-H⋅⋅⋅O/Cα -H⋅⋅⋅O interaction created by the cap was sufficiently attractive to influence self-assembly. This versatile strategy to harness secondary noncovalent interactions in the rational design of self-assembling organic materials will allow for the exploration of new substrates and speed up the development of novel applications within this increasingly important class of materials.

Application of Lateral Approach for the Removal of Migrated Interbody Cage: Taphole and Fixing Technique.

When a revision surgery related with removal of failed interbody cage is required, going through the previous passage can lead to a higher risk of neurological deficits or incidental dural injuries. Recently, the lateral approach has become a popular method instead of the conventional anterior or posterior approaches. The lateral approach is also useful method to remove failed interbody cage previously placed and re-do interbody fusion with lower risks compared to revision surgery via previous passage. However, there is still some difficulty in retrieving the interbody cage from the intervertebral space because of no spacious passage, subsidence, and uncontrolled movable cage. In this study, we introduce our experience that we removed failed interbody cage more easily with only the simple additional steps of making a taphole and fixing the cage using a thread-tipped stick.

Connecting two proteins using a fusion alpha helix stabilized by a chemical cross linker.

Building a sophisticated protein nano-assembly requires a method for linking protein components in a predictable and stable structure. Most of the cross linkers available have flexible spacers. Because of this, the linked hybrids have significant structural flexibility and the relative structure between their two components is largely unpredictable. Here we describe a method of connecting two proteins via a 'fusion α helix' formed by joining two pre-existing helices into a single extended helix. Because simple ligation of two helices does not guarantee the formation of a continuous helix, we used EY-CBS, a synthetic cross linker that has been shown to react selectively with cysteines in α-helices, to stabilize the connecting helix. Formation and stabilization of the fusion helix was confirmed by determining the crystal structures of the fusion proteins with and without bound EY-CBS. Our method should be widely applicable for linking protein building blocks to generate predictable structures.

AMP-activated protein kinase contributes to zinc-induced neuronal death via activation by LKB1 and induction of Bim in mouse cortical cultures.

BACKGROUND: We reported that zinc neurotoxicity, a key mechanism of ischemic neuronal death, was mediated by poly ADP-ribose polymerase (PARP) over-activation following NAD(+)/ATP depletion in cortical cultures. Because AMP-activated protein kinase (AMPK) can be activated by ATP depletion, and AMPK plays a key role in excitotoxicity and ischemic neuronal death, we examined whether AMPK could be involved in zinc neurotoxicity in mouse cortical neuronal cultures. RESULTS: Compound C, an AMPK inhibitor, significantly attenuated zinc-induced neuronal death. Activation of AMPK was detected beginning 2 h after a 10-min exposure of mouse cortical neurons to 300 µM zinc, although a significant change in AMP level was not detected until 4 h after zinc treatment. Thus, AMPK activation might not have been induced by an increase in intracellular AMP in zinc neurotoxicity. Furthermore, we observed that liver kinase B1 (LKB1) but not Ca(2+)/calmodulin-dependent protein kinase kinase ß (CaMKKß), was involved in AMPK activation. Although STO-609, a chemical inhibitor of CaMKKß, significantly attenuated zinc neurotoxicity, zinc-induced AMPK activation was not affected, which suggested that CaMKKß was not involved in AMPK activation. Knockdown of LKB1 by siRNA significantly reduced zinc neurotoxicity, as well as zinc-induced AMPK activation, which indicated a possible role for LKB1 as an upstream kinase for AMPK activation. In addition, mRNA and protein levels of Bim, a pro-apoptotic Bcl-2 family member, were noticeably increased by zinc in an AMPK-dependent manner. Finally, caspase-3 activation in zinc-induced neuronal death was mediated by LKB1 and AMPK activation. CONCLUSIONS: The results suggested that AMPK mediated zinc-induced neuronal death via up-regulation of Bim and activation of caspase-3. Rapid activation of AMPK was detected after exposure of cortical neuronal cultures to zinc, which was induced by LKB1 activation but not increased intracellular AMP levels or CaMKKß activation. Hence, blockade of AMPK in the brain may protect against zinc neurotoxicity, which is likely to occur after acute brain injury.

A Hollow Foldecture with Truncated Trigonal Bipyramid Shape from the Self-Assembly of an 11-Helical Foldamer.

The creation of self-assembling microscale architectures that possess new and useful physical properties remains a significant challenge. Herein we report that an 11-helical foldamer self-assembles in a controlled manner to form a series of 3D foldectures with unusual three-fold symmetrical shapes that are distinct from those generated from 12-helical foldamers. The foldamer packing motif was revealed by powder X-ray diffraction technique, and provides an important link between the molecular-level symmetry and the microscale morphologies. The utility of foldectures with hollow interiors as robust and well-defined supramolecular hosts was demonstrated for inorganic, organic, and even protein guests. This work will pave the way for the design of functional foldectures with greater 3D shape diversity and for the development of biocompatible delivery vehicles and containment vessels.

Consensus scoring approach to identify the inhibitors of AMP-activated protein kinase α2 with virtual screening.

Due to the involvement in the ischemic damage in the brain, 5'-adenosine monophosphate-activated protein kinase subunit α2 (AMPK2) serves as a promising target for the development of new medicines for stroke. Despite such a pharmaceutical importance, only a few small-molecule inhibitors have been reported so far. We aim in this study to identify a new class of AMPK2 inhibitors based on the structure-based virtual screening with docking simulations. To take advantage of and supplement the deficiencies of force field-based and empirical scoring functions, a consensus scoring method is employed to select the putative inhibitors by the combined use of AutoDock and FlexX programs. Prior to the virtual screening with docking simulations, both scoring functions are modified by implementing the molecular solvation free energy term to enhance the accuracy in estimating the protein-ligand binding affinity. As a consequence of the consensus virtual screening with the two modified scoring functions, we find seven structurally diverse AMPK2 inhibitors with micromolar inhibitory activity. Detailed binding mode analyses indicate that all these inhibitors can be stabilized in the ATP-binding pocket through the simultaneous establishment of the multiple hydrogen bonds and hydrophobic interactions. It is also found that a high inhibitory activity can be achieved by the reduction of desolvation cost for the inhibitor as well as by the strengthening of the enzyme-inhibitor interactions. Thus, the results of the present study demonstrate the outperformance of consensus scoring with the force field-based and empirical scoring functions that are modified to include the effects of ligand solvation on protein-ligand docking.

Sonographic features of cervical lymph nodes after thyroidectomy for papillary thyroid carcinoma.

OBJECTIVES: Unlike the preoperative findings in patients with papillary thyroid carcinoma, the postoperative sonographic features of cervical lymph nodes have not been established. This study aimed to assess the sonographic features of metastatic lymph nodes after thyroidectomy for papillary thyroid carcinoma. METHODS: The study population consisted of 104 consecutively registered patients who had undergone thyroidectomy for papillary thyroid carcinoma and underwent sonographically guided fine-needle aspiration of lymph nodes in the neck. The sonographic features of each lymph node were retrospectively evaluated by a single radiologist. The confirmation methods for the 115 lymph nodes included surgery (n = 35), measurement of thyroglobulin levels in the aspirates (n = 2), malignant cytologic analysis (n = 10), and benign cytologic analysis with sonographic follow-up over 12 months (n = 68). We determined the diagnostic indices of individual sonographic features for differentiating between metastatic and benign lymph nodes by comparing these features with the final diagnoses. RESULTS: Of the 104 patients, 67 underwent at least 1 cycle of radioisotope therapy after thyroidectomy. The malignancy rate for the lymph nodes was 42.6% (49 of 115). A significant relationship was found between malignancy and the presence of an intranodal cystic component, intranodal microcalcifications, diffusely increased echogenicity, a microlobulated margin, a round shape, loss of echogenic hila, and mixed or central vascularity on color Doppler sonography (P < .05). CONCLUSIONS: The sonographic features of metastatic cervical lymph nodes in postoperative patients with papillary thyroid carcinoma were similar to those in preoperative patients.