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.

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.

Simultaneous measurements of volume, pressure, optical images, and crystal structure with a dynamic diamond anvil cell: A real-time event monitoring system.

The dynamic diamond anvil cell (dDAC) technique has attracted great interest because it possibly provides a bridge between static and dynamic compression studies with fast, repeatable, and controllable compression rates. The dDAC can be a particularly useful tool to study the pathways and kinetics of phase transitions under dynamic pressurization if simultaneous measurements of physical quantities are possible as a function of time. We here report the development of a real-time event monitoring (RTEM) system with dDAC, which can simultaneously record the volume, pressure, optical image, and structure of materials during dynamic compression runs. In particular, the volume measurement using both Fabry-Pérot interferogram and optical images facilitates the construction of an equation of state (EoS) using the dDAC in a home-laboratory. We also developed an in-line ruby pressure measurement (IRPM) system to be deployed at a synchrotron x-ray facility. This system provides simultaneous measurements of pressure and x-ray diffraction in low and narrow pressure ranges. The EoSs of ice VI obtained from the RTEM and the x-ray diffraction data with the IRPM are consistent with each other. The complementarity of both RTEM and IRPM systems will provide a great opportunity to scrutinize the detailed kinetic pathways of phase transitions using dDAC.

Implantable device with magnetically rotating disk for needle-free administrations of emergency drug.

Prompt administration of first-aid drugs can save lives during medical emergencies such as anaphylaxis and hypoglycemia. However, this is often performed by needle self-injection, which is not easy for patients under emergency conditions. Therefore, we propose an implantable device capable of on-demand administration of first-aid drugs (i.e., the implantable device with a magnetically rotating disk [iMRD]), such as epinephrine and glucagon, via a noninvasive simple application of the magnet from the outside skin (i.e., the external magnet). The iMRD contained a disk embedded with a magnet, as well as multiple drug reservoirs that were sealed with a membrane, which was designed to rotate at a precise angle only when the external magnet was applied. During this rotation, the membrane on a designated single-drug reservoir was aligned and torn to expose the drug to the outside. When implanted in living animals, the iMRD, actuated by an external magnet, delivers epinephrine and glucagon, similar to conventional subcutaneous needle injections.

Implantable device actuated by manual button clicks for noninvasive self-drug administration.

Self-injectable therapy has several advantages in the treatment of metabolic disorders. However, frequent injections with needles impair patient compliance and medication adherence. Therefore, we develop a fully implantable device capable of on-demand administration of self-injection drugs via noninvasive manual button clicks on the outer skin. The device is designed to infuse the drug only at the moment of click actuation, which allows for an accurate and reproducible drug infusion, and also prevents unwanted drug leakage. Using a mechanical means of drug infusion, this implantable device does not contain any electronic compartments or batteries, making it compact, and semi-permanent. When tested in animals, the device can achieve subcutaneous injection-like pharmacokinetic and pharmacodynamic effects for self-injection drugs such as exenatide, insulin, and glucagon.

Site-specific temporal variation of population dynamics in subalpine endemic plant species.

Endemic plants in high mountains are projected to be at high risk because of climate change. Temporal demographic variation is a major factor affecting population viability because plants often occur in small, isolated populations. Because isolated populations tend to exhibit genetic differentiation, analyzing temporal demographic variation in multiple populations is required for the management of high mountain endemic species. We examined the population dynamics of an endemic plant species, Primula farinosa subsp. modesta, in four subalpine sites over six years. Stage-based transition matrices were constructed, and temporal variation in the projected population growth rate (λ) was analyzed using life table response experiments (LTREs). The variation in λ was primarily explained by the site × year interaction rather than the main effects of the site and year. The testing sites exhibited inconsistent patterns in the LTRE contributions of the vital rates to the temporal deviation of λ. However, within sites, growth or stasis had significant negative correlations with temporal λ deviation. Negative correlations among the contributions of vital rates were also detected within the two testing sites, and the removal of the correlations alleviated temporal fluctuations in λ. The response of vital rates to yearly environmental fluctuations reduced the temporal variation of λ. Such effects manifested especially at two sites where plants exhibited higher plasticity than plants at other sites. Site-specific temporal variation implies that populations of high mountain species likely exhibit asynchronous temporal changes, and multiple sites need to be evaluated for their conservation.

Magnetically actuating implantable pump for the on-demand and needle-free administration of human growth hormone.

A bolus of human growth hormone (hGH) is often prescribed for the treatment of growth hormone deficiency, which requires frequent injections in current clinical settings. This painful needle-involved delivery often results in poor patient compliance, leading to low medication adherence and poor clinical outcomes. Therefore, we propose a magnetically actuating implantable pump (MAP) that can infuse an accurate dose of hGH only at the time of non-invasive magnet application from the skin. The MAP herein could reproducibly infuse 20.6 ±â€¯0.9 µg hGH per actuation without any leak at times without actuation. The infused amount increased proportionally with an increase in the number of actuations. When the MAP was implanted and actuated with a magnet in animals with growth hormone deficiency for 21 days, the profiles of plasma hGH concentration and insulin-like growth factor (IGF)-1, as well as changes in body weight, were similar to those observed in animals treated with conventional subcutaneous hGH injections. Therefore, we anticipate that the MAP fabricated in this study can be a non-invasive alternative to administer hGH without repeated and frequent needle 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.

Differential plastic responses to temperature and nitrogen deposition in the subalpine plant species, Primula farinosa subsp. modesta.

Future environmental changes are projected to threaten plant populations near mountaintops, but plastic responses of plant traits that are related to demographic parameters may reduce the detrimental effects of altered environments. Despite its ecological significance, little is known about the intraspecific variation of plasticity in alpine plant species such as Primula farinosa subsp. modesta. In this study, we investigated the plastic responses of plants at the early developmental stage from four P. farinosa natural populations in response to temperature and nitrogen deposition under laboratory conditions. Measured traits included plant survival, leaf number, rosette diameter, carbon assimilation rate and leaf chlorophyll content. In addition, we conducted a demographic survey of the natural populations to assess the plant's performance at the early developmental stage in the field and evaluate the ecological implications of our experimental treatments. The seedling stage contributed to the projected population growth rate in natural conditions, and the growth and survival of seedlings in the field were comparable to those grown in the control treatment. In response to high temperature, plants exhibited lower survival but produced larger rosettes with more leaves. Nitrogen deposition had little effect on plant survival and plant size; however, it increased plant survival in one population and altered the effect of temperature on the carbon assimilation rate. Populations exhibited differential plasticity indexes of measured traits in response to environmental treatments. These results suggest that even though the plants suffer from high early mortality under increasing temperature, stimulated growth at a high temperature potentially contributes to the persistence of P. farinosa natural populations. Natural populations might face differential extinction risks due to distinctive plastic responses to altered environments.

Differential responses to fertilization and competition among invasive, noninvasive alien, and native Bidens species.

Comparative studies of invasive, noninvasive alien, and native congenic plant species can identify plant traits that drive invasiveness. In particular, functional traits associated with rapid growth rate and high fecundity likely facilitate invasive success. As such traits often exhibit high phenotypic plasticity, characterizing plastic responses to anthropogenic environmental changes such as eutrophication and disturbance is important for predicting the invasive success of alien plant species in the future. Here, we compared trait expression and phenotypic plasticity at the species level among invasive, noninvasive alien, and native Bidens species. Plants were grown under nutrient addition and competition treatments, and their functional, morphological, and seed traits were examined. Invasive B. frondosa exhibited higher phenotypic plasticity in most measured traits than did the alien noninvasive B. pilosa or native B. bipinnata. However, differential plastic responses to environmental treatments rarely altered the rank of trait values among the three Bidens species, except for the number of inflorescences. The achene size of B. frondosa was larger, but its pappus length was shorter than that of B. pilosa. Two species demonstrated opposite plastic responses of pappus length to fertilization. These results suggest that the plasticity of functional traits does not significantly contribute to the invasive success of B. frondosa. The dispersal efficiency of B. frondosa is expected to be lower than that of B. pilosa, suggesting that long-distance dispersal is likely not a critical factor in determining invasive success.

Redefining floristic zones in the Korean Peninsula using high-resolution georeferenced specimen data and self-organizing maps.

The use of biota to analyze the distribution pattern of biogeographic regions is essential to gain a better understanding of the ecological processes that cause biotic differentiation and biodiversity at multiple spatiotemporal scales. Recently, the collection of high-resolution biological distribution data (e.g., specimens) and advances in analytical theory have led to the quantitative analysis and more refined spatial delineation of biogeographic regions. This study was conducted to redefine floristic zones in the southern part of the Korean Peninsula and to better understand the eco-evolutionary significance of the spatial distribution patterns. Based on 309,333 distribution data of 2,954 vascular plant species in the Korean Peninsula, we derived floristic zones using self-organizing maps. We compared the characteristics of the derived regions with those of historical floristic zones and ecologically important environmental factors (climate, geology, and geography). In the clustering analysis of the floristic assemblages, four distinct regions were identified, namely, the cold floristic zone (Zone I) in high-altitude regions at the center of the Korean Peninsula, cool floristic zone (Zone II) in high-altitude regions in the south of the Korean Peninsula, warm floristic zone (Zone III) in low-altitude regions in the central and southern parts of the Korean Peninsula, and maritime warm floristic zone (Zone IV) including the volcanic islands Jejudo and Ulleungdo. Totally, 1,099 taxa were common to the four floristic zones. Zone IV showed the highest abundance of specific plants (those found in only one zone), with 404 taxa. Our study improves floristic zone definitions using high-resolution regional biological distribution data. It will help better understand and re-establish regional species diversity. In addition, our study provides key data for hotspot analysis required for the conservation of plant diversity.

Preocular sensor system for concurrent monitoring of glucose levels and dry eye syndrome using tear fluids.

The present study demonstrated a noninvasive preocular sensor system for the concurrent monitoring of diabetes and one of its prevalent complications, dry eye syndrome (DES), using tear fluids. Two distinct sensors, i.e., the glucose and DES sensors, were prepared and encased together in a single housing unit to produce the sensor system, and the tip was designed to be in contact with the eye surface noninvasively to collect and deliver tear fluid to the sensors. The glucose sensor was modified from a commercially available electrochemical sensor to allow for the measurement of glucose concentrations, even in a small amount of collected tear fluid. The DES sensor was equipped with a microchannel spaced with two parallel electrodes to determine the amount of collected tear fluid. In vivo experimental results revealed that with the collected tear fluid of about 0.6-1.0 µl, the sensor system estimated the blood glucose concentrations with acceptable accuracy compared with that of the glucometer in clinical use. The DES condition in animals was diagnosed with high sensitivity (91.7%) and specificity (83.3%).

Magnetically-driven implantable pump for on-demand bolus infusion of short-acting glucagon-like peptide-1 receptor agonist.

For type 2 diabetic patients, short acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) is often prescribed with frequent needled injections. Long-acting GLP-1 RA for less frequent injections do not mimic physiologic secretion of GLP-1. Therefore, an implantable pump is proposed in this work, which can deliver a short-acting GLP-1 RA, exenatide, without needles and batteries. The implanted pump can infuse an accurate amount of exenatide bolus only when a noninvasive magnetic force is applied from outside the body. The pump includes a safety feature of patterned magnets for actuation to prevent accidental infusion possibly caused by a general household magnet. The reservoir for exenatide is made of a flexible biomaterial and thus, a negative pressure build-up in the reservoir can be prevented even after multiple actuations and almost all drug consumption (~ 94%). This allows a reproducible drug dose for a longer period after implantation, hence less frequent replenishment procedures. The pump is also equipped with an intermediate container with two distinct check-valves and thus, the reservoir of exenatide can be further separated and better prevented from infiltration of the bodily fluid surrounding the implanted pump. When tested in Goto-Kakizaki rats, the pump demonstrates the efficacy of exenatide similar to conventional subcutaneous injections. Therefore, the pump can be promising for patient-friendly, optimal delivery of short-acting GLP-1 RA that better follows the physiologic secretion profile of GLP-1.

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.

Hydration breaking and chemical ordering in a levitated NaCl solution droplet beyond the metastable zone width limit: evidence for the early stage of two-step nucleation.

For over two decades, NaCl nucleation from a supersaturated aqueous solution has been predicted to occur via a two-step nucleation (TSN) mechanism, i.e., two sequential events, the formation of locally dense liquid regions followed by structural ordering. However, the formation of dense liquid regions in the very early stage of TSN has never been experimentally observed. By using a state-of-the-art technique, a combination of electrostatic levitation (ESL) and in situ synchrotron X-ray and Raman scatterings, we find experimental evidence that indicates the formation of dense liquid regions in NaCl bulk solution at an unprecedentedly high level of supersaturation (S = 2.31). As supersaturation increases, evolution of ion clusters leads to chemical ordering, but no topological ordering, which is a precursor for forming the dense disordered regions of ion clusters at the early stage of TSN. Moreover, as the ion clusters proceed to evolve under highly supersaturated conditions, we observe the breakage of the water hydration structure indicating the stability limit of the dense liquid regions, and thus leading to nucleation. The evolution of solute clusters and breakage of hydration in highly supersaturated NaCl bulk solution will provide new insights into the detailed mechanism of TSN for many other aqueous solutions.

Soft implantable device with drug-diffusion channels for the controlled release of diclofenac.

We propose the use of an implantable device with multiple embedded drug diffusion channels, each of which is connected to a drug reservoir, for the controlled release of diclofenac. To minimize the size of the incision needed during device implantation, the device used herein was made of the soft biocompatible material polydimethylsiloxane (PDMS), thereby allowing for folding during device implantation. We aimed to achieve a profile of diclofenac release that was reproducible even after folding, and thus the channel was filled with cross-linked gelatin, which could be swollen via the infiltration of a bodily fluid to compensate for any possible defects formed during folding. We first assessed the use of individual channels of varying lengths of 1-12 mm, and the onset time and average rate varied from 1 to 14 days and from 0.31-4.3%/day, respectively. According to these results, we prepared a device with multiple integrated pairs of drug reservoirs and channels of different lengths (i.e., the SDD_I), in which the channel combination was selected to achieve the long-term, zero-order release of the largest amount of drug. Thus, the SDD_I used herein exhibited almost zero-order drug release for 55 days at a release rate of 1.19%/day (179.8 µg/day), which did not vary even after the device was folded multiple times due to the presence of gelatin in the channel. When tested in living rats, the SDD_I device could be folded and inserted subcutaneously through an incision less than half the size of that needed for the implantation of the unfolded, intact SDD_I. For both the unfolded and folded SDD_I devices, the drug concentration in blood was observed to be maintained within a similar range due to the almost zero-order, reproducible release of diclofenac.

Author Correction: Noninvasive Self-diagnostic Device for Tear Collection and Glucose Measurement.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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.

Wirelessly Controlled Implantable System for On-demand and Pulsatile Insulin Administration.

We propose a wirelessly controlled implantable system for on-demand and pulsatile insulin delivery with a more convenient and safer strategy than currently available strategies. The system is a combined entity of a magnetically driven pump (i.e., an MDP), external control device (i.e., an ECD) and mobile app. The MDP for implantation consists of a plunger, barrel and drug reservoir, where an accurate amount of insulin can be infused in a pulsatile manner only at the time when a magnetic force is applied to actuate the plunger in the barrel. The ECD at the outside body can modulate the MDP actuation with an electromagnet and its control circuit, and this modulation can be wirelessly controlled by the mobile app. As a safety feature, the mobile app is programmed to pre-set the restrictions for the insulin dose and administration schedule to avoid overdose. The system is shown to infuse insulin in a highly reproducible manner, but it does not allow for insulin infusion when the pre-set restrictions are violated. When tested with diabetic rats, the profiles of insulin plasma concentration and blood glucose level are similar to those of animals treated with a subcutaneous injection of the same dose of insulin.