Review of electrospun microtube array membrane (MTAM)-a novel new class of hollow fiber for encapsulated cell therapy (ECT) in clinical applications.

Encapsulated cell therapy (ECT) shows significant potential for treating neurodegenerative disorders including Alzheimer's and Parkinson's, which currently lack curative medicines and must be managed symptomatically. This novel technique encapsulates functional cells with a semi-permeable membrane, providing protection while enabling critical nutrients and therapeutic substances to pass through. Traditional ECT procedures, on the other hand, pose difficulties in terms of cell survival and retrieval. We introduce the Microtube Array Membrane (MTAM), a revolutionary technology that solves these constraints, in this comprehensive overview. Microtube Array Membrane has distinct microstructures that improve encapsulated cells' long-term viability by combining the advantages of macro and micron scales. Importantly, the MTAM platform improves biosafety by allowing the entire encapsulated unit to be retrieved in the event of an adverse reaction. Our findings show that MTAM-based ECT has a great potential in a variety of illness situations. For cancer treatment, hybridoma cells secreting anti-CEACAM 6 antibodies inhibit triple-negative breast cancer cell lines for an extended period of time. In animal brain models of Alzheimer's disease, hybridoma cells secreting anti-pTau antibodies successfully reduce pTau buildup, accompanied by improvements in memory performance. In mouse models, MTAM-encapsulated primary cardiac mesenchymal stem cells dramatically improve overall survival and heart function. These findings illustrate the efficacy and adaptability of MTAM-based ECT in addressing major issues such as immunological isolation, cell viability, and patient safety. We provide new possibilities for the treatment of neurodegenerative illnesses and other conditions by combining the potential of ECT with MTAM. Continued research and development in this subject has a lot of promise for developing cell therapy and giving hope to people suffering from chronic diseases.

Unveiling the Power of Anticancer Drug Screening: A Clinical Case Study Comparing the Effectiveness of Hollow Fiber Assay Microtube Array Membrane (MTAM-HFA) in Breast Cancer Patients.

Breast cancer is a severe public health problem, and early treatment with powerful anticancer drugs is critical for success. The researchers investigated the clinical results of a novel screening tool termed Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA) in breast cancer patients in this clinical investigation. In all trial participants, the MTAM-HFA was utilized to identify active medicines for the treatment of breast cancer. The MTAM-HFA was shown to be extremely useful in predicting patient response to anticancer medication therapy in this study. Furthermore, the substantial association between the MTAM-HFA screening outcome and the clinical outcome of the respective patients emphasizes the promise of this unique screening technology in discovering effective anticancer medication combinations for the treatment of breast cancer. These findings indicate that the MTAM-HFA has clinical significance and might be a valuable tool in the development of tailored therapy for cancer care. This study provides helpful information for physicians and scientists working on breast cancer therapy research. The potential benefits of employing MTAM-HFA to find accurate therapies for breast cancer patients might lead to enhanced personalized medicine approaches to cancer care, resulting in better patient outcomes. Overall, the MTAM-HFA screening approach has the potential to revolutionize customized cancer therapy, providing hope to both patients and physicians.

Traversability analysis with vision and terrain probing for safe legged robot navigation.

Inspired by human behavior when traveling over unknown terrain, this study proposes the use of probing strategies and integrates them into a traversability analysis framework to address safe navigation on unknown rough terrain. Our framework integrates collapsibility information into our existing traversability analysis, as vision and geometric information alone could be misled by unpredictable non-rigid terrains such as soft soil, bush area, or water puddles. With the new traversability analysis framework, our robot has a more comprehensive assessment of unpredictable terrain, which is critical for its safety in outdoor environments. The pipeline first identifies the terrain's geometric and semantic properties using an RGB-D camera and desired probing locations on questionable terrains. These regions are probed using a force sensor to determine the risk of terrain collapsing when the robot steps over it. This risk is formulated as a collapsibility metric, which estimates an unpredictable region's ground collapsibility. Thereafter, the collapsibility metric, together with geometric and semantic spatial data, is combined and analyzed to produce global and local traversability grid maps. These traversability grid maps tell the robot whether it is safe to step over different regions of the map. The grid maps are then utilized to generate optimal paths for the robot to safely navigate to its goal. Our approach has been successfully verified on a quadrupedal robot in both simulation and real-world experiments.

Microtube Array Membrane Encapsulated Cell Therapy: A Novel Platform Technology Solution for Treatment of Alzheimer's Disease.

Alzheimer's disease is the most frequent form of dementia in aging population and is presently the world's sixth largest cause of mortality. With the advancement of therapies, several solutions have been developed such as passive immunotherapy against these misfolded proteins, thereby resulting in the clearance. Within this segment, encapsulated cell therapy (ECT) solutions that utilize antibody releasing cells have been proposed with a multitude of techniques under development. Hence, in this study, we utilized our novel and patented Microtube Array Membranes (MTAMs) as an encapsulating platform system with anti-pTau antibody-secreting hybridoma cells to study the impact of it on Alzheimer's disease. In vivo results revealed that in the water maze, the mice implanted with hybridoma cell MTAMs intracranially (IN) and subcutaneously (SC) showed improvement in the time spent the goal quadrant and escape latency. In passive avoidance, hybridoma cell loaded MTAMs (IN and SC) performed significantly well in step-through latency. At the end of treatment, animals with hybridoma cell loaded MTAMs had lower phosphorylated tau (pTau) expression than empty MTAMs had. Combining both experimental results unveiled that the clearance of phosphorylated tau might rescue the cognitive impairment associated with AD.

Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA)-An Accurate and Rapid Potential Companion Diagnostic and Pharmacological Interrogation Solution for Cancer Immunotherapy (PD-1/PD-L1).

Immunotherapy is one of the most promising forms of cancer treatment. In particular, immune checkpoint blockers (ICBs) represent some of the leading candidates which many drug developers have heavily invested in. During pre-clinical development and prior to human clinical trials, animal tests are a critical component for determining the safety and efficacy of newly developed ICBs for cancer treatment. In this study, we strive to demonstrate the feasibility of using hollow fiber assay microtube array membrane (MTAM-HFA) in the screening of anti-cancer ICBs. The MTAM-HFA process was carried out by encapsulating peripheral blood mononuclear cells (PBMCs) and the target cancer cells (cell lines or primary cells) and subcutaneously implanting them into Balb/C mice. At predetermined time points combination regimens of PD-1/PD-L1+ were administered accordingly and at a predetermined time point, the MTAMs were retrieved, and cell viability assays were carried out. The outcomes of the MTAM-HFA were compared against the clinical outcome of patients. Clinical comparison demonstrated excellent correlation between the screening outcome of MTAM-HFA of PD-1/PD-L1+ combination therapy and the clinical outcome of the lung cancer patients. Basic cell studies revealed that the utilization of MTAM-HFA in PD-1/PD-L1+ combination therapy revealed enhanced T-cell activity upon the administration of the PD-1/PD-L1 drug; thereby resulting in the reduction of tumor cell viability by up to 70%, and the cytotoxic effects by 82%. The outcome was echoed in the in vivo cell studies. This suggested that the MTAM-HFA system is suitable for use in PD-1/PD-L1+ screening and the accuracy, rapidity and cost effectiveness made it extremely suitable for application as a companion diagnostic system in both personalized medicine for cancer treatment and could potentially be applied to screen for candidate compounds in the development of next generation PD-1/PD-L1+ combination therapies.

Tissue-Engineered Vascular Graft with Co-Culture of Smooth Muscle Cells and Human Endothelial Vein Cells on an Electrospun Poly(lactic-co-glycolic acid) Microtube Array Membrane.

Coronary artery disease is one of the major diseases that plagues today's modern society. Conventional treatments utilize synthetic vascular grafts such as Dacron® and Teflon® in bypass graft surgery. Despite the wide adaptation, these synthetic grafts are often plagued with weaknesses such as low hemocompatibility, thrombosis, intimal hyperplasia, and risks of graft infection. More importantly, these synthetic grafts are not available at diameters of less than 6 mm. In view of these challenges, we strived to develop and adapt the electrospun Poly Lactic-co-Glycolic Acid (PLGA) Microtube Array Membrane (MTAM) vascular graft for applications smaller than 6 mm in diameter. Homogenously porous PLGA MTAMs were successfully electrospun at 5.5-8.5 kV under ambient conditions. Mechanically, the PLGA MTAMs registered a maximum tensile strength of 5.57 ± 0.85 MPa and Young's modulus value of 1.134 ± 0.01 MPa; while MTT assay revealed that seven-day Smooth Muscle Cells (SMCs) and Human Umbilical Vein Endothelial Cells (HUVECs) registered a 6 times and 2.4 times higher cell viability when cultured in a co-culture setting in medium containing α-1 haptaglobulin. When rolled into a vascular graft, the PLGA MTAMs registered an overall degradation of 82% after 60 days of cell co-culture. After eight weeks of culturing, immunohistochemistry staining revealed the formation of a monolayer of HUVECs with tight junctions on the surface of the PLGA MTAM, and as for the SMCs housed within the lumens of the PLGA MTAMs, a monolayer with high degree of orientation was observed. The PLGA MTAM registered a burst pressure of 1092.2 ± 175.3 mmHg, which was sufficient for applications such as small diameter blood vessels. Potentially, the PLGA MTAM could be used as a suitable substrate for vascular engineering.

Metabolic effects of brown fat in transitioning from hyperthyroidism to euthyroidism.

OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

Ultra-High Packing Density Next Generation Microtube Array Membrane for Absorption Based Applications.

Previously, we successfully developed an extracorporeal endotoxin removal device (EERD) that is based on the novel next generation alternating microtube array membrane (MTAM-A) that was superior to the commercial equivalent. In this article, we demonstrated multiple different parameter modifications that led to multiple different types of novel new MTAM structures, which ultimately led to the formation of the MTAM-A. Contrary to the single layered MTAM, the MTAM-A series consisted of a superior packing density fiber connected in a double layered, alternating position which allowed for the greater fiber count to be packed per unit area. The respective MTAM variants were electrospun by utilizing our internally developed tri-axial electrospinning set up to produce the novel microstructures as seen in the respective MTAM variants. A key uniqueness of this study is the ability to produce self-arranged fibers into the respective MTAM variants by utilizing a single spinneret, which has not been demonstrated before. Of the MTAM variants, we observed a change in the microstructure from a single layered MTAM to the MTAM-A series when the ratio of surfactant to shell flow rate approaches 1:1.92. MTAM-A registered the greatest surface area of 2.2 times compared to the traditional single layered MTAM, with the greatest tensile strength at 1.02 ± 0.13 MPa and a maximum elongation of 57.70 ± 9.42%. The MTAM-A was selected for downstream immobilization of polymyxin B (PMB) and assembly into our own internally developed and fabricated dialyzer housing. Subsequently, the entire setup was tested with whole blood spiked with endotoxin; and benchmarked against commercial Toraymyxin fibers of the same size. The results demonstrated that the EERD based on the MTAM-A performed superior to that of the commercial equivalent, registering a rapid reduction of 73.18% of endotoxin (vs. Toraymyxin at 38.78%) at time point 15 min and a final total endotoxin removal of 89.43% (vs. Toraymyxin at 65.03%).

Effects of root chord movement on thrust generation of oscillatory pectoral fins.

Fin kinematics is the key to thrust generation of oscillatory pectoral fins of manta rays. This could be one of the main reasons that fin designs of robotic manta rays are becoming more complex to simulate the fin kinematics more closely so as to generate high thrusts. However, as the trend suggests, the extent of improvement to thrust generation might not be worth the complexities added to the designs. Out-of-the-box design changes that favour the simplicity and yet improve the fin performance can be a sound replicate for the complicated fin design features. One aspect of manta rays' pectoral fins that influences the fin kinematics is the constraint imposed on the movement of their particularly long root chord that is entirely attached to the body of manta rays. Hypothetically, reducing such a constraint can promote the angle-of-attack during flapping, which can improve thrust generation. This paper aims to study if the simple idea of disengagement of the fin root chord from the body, which is obviously a deviation from the nature, can improve thrust generation. An experiment was conducted on thrust generation of four basic fin designs, where different portions of their chord was disengaged from the body step-by-step. The disengagement occurred for each quarter of the chord, starting from the trailing edge towards the leading edge. It was found that the fins with free root chord (minimal attachment to the body) could generate thrust slightly less than the fully constrained fins (full attachment). In addition, it was shown that thrust generation efficiency kept increasing while disengaging the chord further, and reached the maximum for free root chord. This may show that a powerful and yet more efficient fin can be produced with such a deviation from the nature.

Ultrahigh packing density next generation microtube array membrane: A novel solution for absorption-based extracorporeal endotoxin removal device.

Sepsis is a deadly disease that is widely attributed to endotoxin released by gram-negative bacterial infections often plague emergency care facilities. Conventionally antibiotics and vasopressors are used to treat this disease. Recent treatment protocol shifted to a membrane to remove the offending endotoxin monomer. Despite this shift, membrane-based devices are often extremely costly, hindering accessibility to this life saving medical device. In view of this challenges, we adopted the internally developed polysulfone (PSF) microtube array membrane alternating (MTAM-A) for use in blood sepsis treatment. PSF MTAM-A were with polymyxin B (PMB) molecules immobilized were assembled into an internally developed cartridge housing and subjected to endotoxin removal models with water and blood spiked with 100 EU/ml of endotoxin as the feed solution. Samples were derived at 15, 30, 60, and 120 min and endotoxin levels were determined with limulus amebocyte lysate assay and benchmarked against the commercially available Toraymyxin device. The PSF MTAM-A with 2.3 times the surface area was successfully fabricated and with PMB molecules immobilized, and assembled into a hemoperfusion device. Dynamic endotoxin removal test revealed and overall endotoxin removal capacity of 90% and a superior endotoxin removal efficiency that was significantly higher than that of Toraymyxin (internally conducted and reported). The data suggested that PSF MTAM-A PMB membranes could potentially be applied in future hemoperfusion devices which would be significantly more efficient, compact, and affordable; potentially making such a life-saving medical device widely available to the general public.

Microtube Array Membrane (MTAM)-Based Encapsulated Cell Therapy for Cancer Treatment.

The treatment of cancer has evolved significantly in recent years with a strong focus on immunotherapy. Encapsulated Cell Therapy (ECT) for immunotherapy-based anti-cancer treatment is a unique niche within this landscape, where molecules such as signaling factors and antibodies produced from cells are encapsulated within a vehicle, with a host amount of benefits in terms of treatment efficacy and reduced side effects. However, traditional ECTs generally lie in two extremes; either a macro scale vehicle is utilized, resulting in a retrievable system but with limited diffusion and surface area, or a micro scale vehicle is utilized, resulting in a system that has excellent diffusion and surface area but is unretrievable in the event of side effects occurring, which greatly compromises the biosafety of patients. In this study we adapted our patented and novel electrospun Polysulfone (PSF) Microtube Array Membranes (MTAMs) as a 'middle' approach to the above dilemma, which possess excellent diffusion and surface area while being retrievable. Hybridoma cells were encapsulated within the PSF MTAMs, where they produced CEACAM6 antibodies to be used in the suppression of cancer cell line A549, MDA-MB-468 and PC 3 (control). In vitro and in vivo studies revealed excellent cell viability of hybridoma cells with continuous secretion of CEACAM6 antibodies which suppressed the MDA-MB-468 throughout the entire 21 days of experiment. Such outcome suggested that the PSF MTAMs were not only an excellent three-dimensional (3D) cell culture substrate but potentially also an excellent vehicle for the application in ECT systems. Future research needs to include a long term in vivo >6 months study before it can be used in clinical applications.

Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism.

Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further demonstrate that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group, and also that type 2 diabetic patients treated with DMAb show significant reductions in HbA1c as compared to patients treated either with bisphosphonates or calcium and vitamin D. Thus, our results identify several coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link between bone remodeling and energy metabolism.

Effect of Periosteal Flap Augmentation on Outcomes of Modified Broström-Gould Procedure for Chronic Lateral Ankle Instability.

BACKGROUND: Chronic lateral ankle instability is relatively common after ankle sprains. The modified Broström-Gould procedure (MBG) is the gold standard operative treatment but has a known failure rate of up to 10%, or even more in high-risk groups. Periosteal flap augmentation (PFA) has been proposed to strengthen the repair. This study aimed to compare the outcomes of MBG with and without PFA. METHODS: A matched-pair study was performed based on prospectively collected registry data for all patients undergoing lateral ankle ligament reconstruction in a tertiary institution. Patients who underwent the MBG with PFA were matched in a 1:1 ratio with patients undergoing MBG alone, based on age, gender, and body mass index (BMI). Patients with generalized ligamentous laxity or obesity were excluded. Clinical outcome scores were compared preoperatively and 2 years postoperatively. A total of 48 patients were included in the study (24 in each group). The mean age was 24.1 years, mean BMI was 23.1, and all patients were male. The baseline demographics and clinical scores in both groups were similar. RESULTS: At 2 years postoperatively, both groups demonstrated significantly improved AOFAS Ankle-Hindfoot scores (P < .001), but there were no between-group differences in total AOFAS scores (PFA score 90, MBG score 88, P = .79). There were no recurrences of instability or revision surgeries. CONCLUSION: Routine PFA did not improve the outcomes of MBG for chronic lateral ankle instability in the absence of risk factors for failure. Further studies are warranted to determine if there is a long-term benefit for augmentation in this population. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Solvent Fractionation and Acetone Precipitation for Crude Saponins from Eurycoma longifolia Extract.

Eurycoma longifolia is a popular folk medicine in South East Asia. This study was focused on saccharide-containing compounds including saponins, mainly because of their medical potentials. Different organic solvents such as ethyl acetate, butanol, and chloroform were used to fractionate the phytochemical groups, which were consequently precipitated in cold acetone. Solvent fractionation was found to increase the total saponin content based on colorimetric assay using vanillin and sulfuric acid. Ethyl acetate fraction and its precipitate were showed to have the highest crude saponins after acetone precipitation. The samples were shown to have anti-proliferative activity comparable with tamoxifen (IC50 = 110.6 µg/mL) against human breast cancer cells. The anti-proliferative activities of the samples were significantly improved from crude extract (IC50 = 616.3 µg/mL) to ethyl acetate fraction (IC50 = 185.4 µg/mL) and its precipitate (IC50 = 153.4 µg/mL). LC-DAD-MS/MS analysis revealed that the saccharide-containing compounds such as m/z 497, 610, 723, 836, and 949 were abundant in the samples, and they could be ionized in negative ion mode. The compounds consisted of 226 amu monomers with UV-absorbing property at 254 nm, and were tentatively identified as formylated hexoses. To conclude, solvent fractionation and acetone precipitation could produce saccharide-containing compounds including saponins with higher anti-proliferative activity than crude extract against MCF-7 cells. This is the first study to use non-toxic solvents for fractionation of bioactive compounds from highly complex plant extract of E. longifolia.

Electrospun Polylactic Acid (PLLA) Microtube Array Membrane (MTAM)-An Advanced Substrate for Anticancer Drug Screening.

The advent of personalized cancer treatment resulted in the shift from the administration of cytotoxic drugs with broad activity spectrum to a targeted tumor-specific therapy. Aligned to this development, the focus of this study revolved around the application of our novel and patented microtube array membrane (MTAM) in the US National Cancer Institute (NCI) developed an HFA (hollow fiber assay) assay; hereinafter known as MTAM/HFA. Electrospun poly-L-lactic acid (PLLA) MTAM was sterilized and loaded with cell lines/patient derived tumor cells (PDTC) and subcutaneously implanted into the backs of BALB/C mice. Anticancer drugs were administered at the respective time points and the respective MTAMs were retrieved and the viability tumor cells within were quantified with the MTT assay. Results revealed that the MTAMs were excellent culture substrate for various cancer cell lines and PDTCs (patient derived tumor cells). Compared to traditional HFA systems that utilize traditional hollow fibers, MTAM/HFA revealed superior drug sensitivity for a wide range of anticancer drug classes. Additionally, the duration for each test was <14 days; all this while capable of producing similar trend outcome to the current gold-standard xenograft models. These benefits were observed in both the in vitro and in vivo stages, making it a highly practical phenotypic-based solution that could potentially be applied in personalized medicine.

Extracellular Microvesicles as New Industrial Therapeutic Frontiers.

Microvesicles (MVs) are subcellular physiological vehicles present in all body fluids that mediate the transfer of intercellular information within biological systems and contribute to healthy conditions. MVs have lipid bilayer membranes decorated with multiple ligands that can interact with receptors on target cells, rendering them as promising candidates for targeted delivery. The biotechnology and cell therapy industries are developing MV-based preparations that use this subcellular therapeutic machinery (in a naïve or modified state) for regenerative medicine, as substitutes for intact cell therapy, and as intelligent targeted drug delivery carriers. However, significant production challenges must be overcome before MVs scale-up development, clinical translation, and routine therapeutic application can be realized. The unique expertise developed in the biotechnology industry should facilitate market access to MV-based therapeutics. In this review, the roles of biotechnology and cell therapy industries to manufacture MVs as inherent therapeutic agents or drug delivery systems are summarized. The manufacturing, development, characterization, and regulatory challenges for successful translation are discussed.

Case Report of a Rare Pipkin Type III Femoral Head Fracture.

INTRODUCTION: Femoral head fractures are rare injury compared to other hip pathologies and often associated with posterior hip dislocation. Such fractures are often fraught with complications even after successful surgical fixation. Pipkin described a classification system for such fractures, dividing them into four types, of which Type III (31C.3) fractures are associated with femoral neck fractures. These fractures are the least common and often associated with the worst outcomes. CASE REPORT: We report a rare case of Pipkin Type III fracture after attempted hip relocation and review literature on this topic. A 35-year-old female sustained a right posterior hip dislocation with femoral head fracture following a fall. After attempts of manipulation and reduction, she sustained an iatrogenic right femoral neck fracture resulting in a Pipkin III femoral head fracture. Open reduction and reduction of fracture achieved through headless compression screw of femoral head and cortical screws of femoral neck. Four months after surgery, the patient under osteonecrosis of the femoral head and subsequently required conversion to a right total hip arthroplasty. CONCLUSION: Femoral head fractures have serious sequelae and should be treated with caution. A high index of suspicion is required; hence, if clinically suspicious, proper imaging is paramount to prevent iatrogenic injury to the femoral neck resulting in subsequent avascular necrosis.

A Microtube Array Membrane (MTAM) Encapsulated Live Fermenting Staphylococcus epidermidis as a Skin Probiotic Patch against Cutibacterium acnes.

Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. epidermidis) onto the open acne lesions may run the risk of bloodstream infections. Here, we fabricated the polysulfone microtube array membranes (PSF MTAM) to encapsulate probiotic S. epidermidis. We demonstrate that the application of the encapsulation of S. epidermidis in PSF MTAM enhanced the glycerol fermentation activities of S. epidermidis. To mimic the granulomatous type of acne inflammatory acne vulgaris, the ears of mice were injected intradermally with C. acnes to induce the secretion of macrophage inflammatory protein-2 (MIP-2), a murine counterpart of human interleukin (IL)-8. The C. acnes-injected mouse ears were covered with a PST MTAM encapsulated with or without S. epidermidis in the presence of glycerol. The application of S. epidermidis-encapsulated PST MTAM plus glycerol onto the C. acnes-injected mouse ears considerably reduced the growth of C. acnes and the production of MIP-2. Furthermore, no S. epidermidis leaked from PSF MTAM into mouse skin. The S. epidermidis-encapsulated PST MTAM functions as a probiotic acne patch.

Imaging and Quantification of Secreted Peroxynitrite at the Cell Surface by a Streptavidin-Biotin-Controlled Binding Probe.

The ability to detect and image secreted peroxynitrite (ONOO- ) along the extracellular surface of a single cell is biologically significant, as ONOO- generally exerts its function for host defense and signal transductions at the plasma membrane. However, as a result of the short lifetime and fast diffusion rate of small ONOO- , precise determination of the ONOO- level at the cell surface remains a challenging task. In this paper, the use of a membrane-anchored streptavidin-biotin-controlled binding probe (CBP), ONOO-CBP, to determine quantitatively the ONOO- level at the cell surface and to investigate the effect of different stimulants on the production of ONOO- along the plasma membrane of macrophages is reported. Our results revealed that the combination of NO synthase (iNOS) and NADPH oxidase (NOX) activators was highly effective in inducing ONOO- secretion, achieving more than a 25-fold increase in ONOO- relative to untreated cells. After 1 h of phorbol-12-myristate-13-acetate (PMA) stimulation, the amount of ONOO- secreted by RAW264.7 macrophages was similar to the condition treated with 25 µm 3-morpholinosydnonimine hydrochloride (SIN-1), which was estimated to release about 20 µm of ONOO- into Dulbecco's modified Eagle's medium (DMEM) in 1 h. This novel approach should open up new opportunities to image various reactive oxygen and nitrogen species secreted at the plasma membrane that cannot be simply achieved by conventional analytical methods.