Batteryless implantable device with built-in mechanical clock for automated and precisely timed drug administration.

Adherence to medication plays a crucial role in the effective management of chronic diseases. However, patients often miss their scheduled drug administrations, resulting in suboptimal disease control. Therefore, we propose an implantable device enabled with automated and precisely timed drug administration. Our device incorporates a built-in mechanical clock movement to utilize a clockwork mechanism, i.e., a periodic turn of the hour axis, enabling automatic drug infusion at precise 12-h intervals. The actuation principle relies on the sophisticated design of the device, where the rotational movement of the hour axis is converted into potential mechanical energy and is abruptly released at the exact moment for drug administration. The clock movement can be charged either automatically by mechanical agitations or manually by winding the crown, while the device remains implanted, thereby enabling the device to be used permanently without the need for batteries. When tested using metoprolol, an antihypertensive drug, in a spontaneously hypertensive animal model, the implanted device can deliver drug automatically at precise 12-h intervals without the need for further attention, leading to similarly effective blood pressure control and ultimately, prevention of ventricular hypertrophy as compared with scheduled drug administrations. These findings suggest that our device is a promising alternative to conventional methods for complex drug administration.

Recurrent Spinal Canal Stenosis after Decompression and Fusion Surgery Due to Bone Overgrowth: Case Report.

Bone regrowth commonly occurs following lumbar decompression surgery. Although it is rare for neurological symptoms to occur due to bone regrowth, this study describes two patients who underwent both decompression and fusion surgeries but experienced spinal canal restenosisthat was severe enough to induce neurological symptoms. A 32-year-old man underwent posterior decompression and posterior lumbar interbody fusion for lumbar canal stenosis at the L4/L5 level 5 years prior. However, the sudden onset of lower back pain occurred 5 years later. Bone overgrowth on the left side was observed at the L4/L5 level. A second surgery was performed, and the patient's symptoms improved significantly. In the second case, a 56-year-old man underwent posterior decompression and posterior lumbar fusion at the L3/L4 and L4/L5 levels for an L4 burst fracture. One month later, he complained of lower back pain and underwent a second posterior decompression surgery. One year later, he presented to an outpatient clinic with lower back pain and neurological symptoms. Bone overgrowth was observed on both sides at the L4/L5 level. Thus, screw removal and laminectomy at the L3, L4, and L5 levels were performed as a third surgery. This study discusses the factors affecting bone regrowth and the methods that can be used to prevent it.

Implantable multireservoir device with stimulus-responsive membrane for on-demand and pulsatile delivery of growth hormone.

Implantable devices for on-demand and pulsatile drug delivery have attracted considerable attention; however, many devices in clinical use are embedded with the electronic units and battery inside, hence making them large and heavy for implantation. Therefore, we propose an implantable device with multiple drug reservoirs capped with a stimulus-responsive membrane (SRM) for on-demand and pulsatile drug delivery. The SRM is made of thermosensitive POSS(MEO2MA-co-OEGMA) and photothermal nanoparticles of reduced graphene oxide (rGO), and each of the drug reservoirs is filled with the same amount of human growth hormone (hGH). Therefore, with noninvasive near-infrared (NIR) irradiation from the outside skin, the rGO nanoparticles generate heat to rupture the SRM in the implanted device, which can open a single selected drug reservoir to release hGH. Therefore, the device herein is shown to release hGH reproducibly only at the times of NIR irradiation without drug leakage during no irradiation. When implanted in rats with growth hormone deficiency and irradiated with an NIR light from the outside skin, the device exhibits profiles of hGH and IGF1 plasma concentrations, as well as body weight change, similar to those in animals treated with conventional s.c. hGH injections.

Establishment of geochemical thresholds for vanadium throughout Korea and at potential development sites using geochemical map data.

Geochemical maps can be used for a variety of purposes, one of which is to establish regional or local geochemical thresholds for the analyzed elements. In the case of vanadium, as industrial demand and use increase, it is necessary to expand the development of vanadium in Korea. However, the environmental management standards are insufficient. Therefore, in this study, using geochemical data, we derived geochemical threshold values for the entire country and areas with potential for the development of vanadium deposits. The regional (country-wide) threshold value was derived using logarithmic transformation of raw data (N = 23,548) of the first- and second-order stream sediments collected across the country in the late 1990s and the early 2000s. The median + 2 median absolute deviation (MAD) and Tukey inner fence (TIF) values were 116 mg/kg and 200 mg/kg, respectively. Of these, the TIF standard, which showed 0.6% of data exceeding the threshold, was judged to be appropriate for distinguishing clear enrichment or contamination of vanadium. In the case of the Geumsan and Pocheon, areas with potential for vanadium development, the TIF and median + 2 MAD values of 259 mg/kg and 218 mg/kg, respectively, can be used as the criteria for evaluating the impact of environmental pollution before and after deposit development. Likewise, by deriving threshold values of the target elements using geochemical map data, it is possible to provide basic environmental information for geochemical evaluation and follow-up management in advance during large-scale site development.

Real-Time Monitoring of Colloidal Crystallization in Electrostatically-Levitated Drops.

Colloidal crystallization is analogous to the crystallization in bulk atomic systems in various aspects, which has been explored as a model system. However, a real-time probing of the phenomenon still remains challenging. Here, a levitation system for a study of colloidal crystallization is demonstrated. Colloidal particles in a levitated droplet are gradually concentrated by isotropic evaporation of water from the surface of the droplet, resulting in crystallization. The structural change of the colloidal array during crystallization is investigated by simultaneously measuring the volume and reflectance spectra of the droplet. The crystal nucleates from the surface of the droplet at which the volume fraction exceeds the threshold and then the growth proceeds. The crystal growth behavior depends on the initial concentrations of colloidal particles and salts which determine the overall direction of crystal growth and interparticle spacing, respectively. The results show that a levitating bulk droplet has a great potential as a tool for in situ investigation of colloidal crystallization.

Multiple pathways of crystal nucleation in an extremely supersaturated aqueous potassium dihydrogen phosphate (KDP) solution droplet.

Solution studies have proposed that crystal nucleation can take more complex pathways than previously expected in classical nucleation theory, such as formation of prenucleation clusters or densified amorphous/liquid phases. These findings show that it is possible to separate fluctuations in the different order parameters governing crystal nucleation, that is, density and structure. However, a direct observation of the multipathways from aqueous solutions remains a great challenge because heterogeneous nucleation sites, such as container walls, can prevent these paths. Here, we demonstrate the existence of multiple pathways of nucleation in highly supersaturated aqueous KH2PO4 (KDP) solution using the combination of a containerless device (electrostatic levitation), and in situ micro-Raman and synchrotron X-ray scattering. Specifically, we find that, at an unprecedentedly deep level of supersaturation, a high-concentration KDP solution first transforms into a metastable crystal before reaching stability at room temperature. However, a low-concentration solution, with different local structures, directly transforms into the stable crystal phase. These apparent multiple pathways of crystallization depend on the degree of supersaturation.

Adapter-based Safety Injection System for Prevention of Wrong Route and Wrong Patient Medication Errors.

Wrong-route or -patient medication errors due to human mistakes have been considered difficult to resolve in clinical settings. In this study, we suggest a safety injection system that can help to prevent an injection when a mismatch exists between the drug and route or patient. For this, we prepared two distinct adapters with key and keyhole patterns specifically assigned to a pair of drug and route or patient. When connected to a syringe tip and its counterpart, a catheter injection-port, respectively, the adapters allowed for a seamless connection only with their matching patterns. In this study, each of the adapters possessed a specific key and keyhole pattern at one end and the other end was shaped to be a universal fit for syringe tips or catheter injection-ports in clinical use. With the scheme proposed herein, we could generate 27,000 patterns, depending on the location and shape of the key tooth in the adapters. With a rapid prototyping technique, multiple distinct pairs of adapters could be prepared in a relatively short period of time and thus, we envision that a specific adapter pair can be produced on-site after patient hospitalization, much like patient identification barcodes.

Climate-induced distribution dynamics and niche adaptation of South Korean endemic plants across the Korean Peninsula.

As climate change intensifies, endemic plants native to South Korea, especially those in specialized ecological niches, confront heightened risks of distribution shifts and habitat degradation. To provide a comprehensive understanding of these impacts, this study evaluates the climate-induced distribution dynamics and niche adaptation of these endemic species across the entire Korean Peninsula. Utilizing species distribution models (SDMs) for 179 plant species and incorporating environmental variables under projected future climate scenarios, our analysis identified unique distribution and niche adaptation patterns. Findings demonstrate that specialized endemic species are likely to migrate to higher altitudes and latitudes, highlighting their distinct vulnerability due to limited ecological niches. Our comparative approach underscores the necessity for refined conservation strategies that address the specific requirements of these endemic species, as opposed to those with wider distributions. This research offers valuable insights into biodiversity conservation amid climate change, proposing targeted actions such as the establishment of protected areas, habitat restoration, and the implementation of assisted migration strategies to safeguard these vital endemic plant species throughout the Korean Peninsula.

Arthroscopic repair of large and massive rotator cuff tears-"sandwich augmentation" with the long head of the biceps tendon: a technical note.

For most shoulder surgeons, addressing massive rotator cuff tears that have retracted ends poses a significant challenge. This study introduces a technique, termed the "sandwich augmentation technique," which incorporates the long head of the biceps tendon (LHBT) into a single-row rotator cuff repair. The procedure, performed arthroscopically with the patient in the lateral decubitus position, involves attaching the LHBT and rotator cuff tissues together to the greater tuberosity. This effectively sandwiches them within the rotator cuff footprint. The goal of this technique is to enhance the thickness of the fully interposed cuff margin, thereby providing better support for the repair. The sandwich augmentation technique, which integrates the biceps into the rotator cuff repair, has demonstrated positive clinical outcomes and moderate anatomical results. It also prevents superior migration of the humeral head in cases of large or massive rotator cuff tears. Further research is required to assess the long-term effectiveness of this procedure.

Impact of molecular symmetry on crystallization pathways in highly supersaturated KH2PO4 solutions.

Solute structure and its evolution in supersaturated aqueous solutions are key clues to understand Ostwald's step rule. Here, we measure the structural evolution of solute molecules in highly supersaturated solutions of KH2PO4 (KDP) and NH4H2PO4 (ADP) using a combination of electrostatic levitation and synchrotron X-ray scattering. The measurement reveals the existence of a solution-solution transition in KDP solution, caused by changing molecular symmetries and structural evolution of the solution with supersaturation. Moreover, we find that the molecular symmetry of H2PO4- impacts on phase selection. These findings manifest that molecular symmetry and its structural evolution can govern the crystallization pathways in aqueous solutions, explaining the microscopic origin of Ostwald's step rule.