Engineering Low Volume Resuscitants for the Prehospital Care of Severe Hemorrhagic Shock.

Globally, traumatic injury is a leading cause of suffering and death. The ability to curtail damage and ensure survival after major injury requires a time-sensitive response balancing organ perfusion, blood loss, and portability, underscoring the need for novel therapies for the prehospital environment. Currently, there are few options available for damage control resuscitation (DCR) of trauma victims. We hypothesize that synthetic polymers, which are tunable, portable, and stable under austere conditions, can be developed as effective injectable therapies for trauma medicine. In this work, we design injectable polymers for use as low volume resuscitants (LVRs). Using RAFT polymerization, we evaluate the effect of polymer size, architecture, and chemical composition upon both blood coagulation and resuscitation in a rat hemorrhagic shock model. Our therapy is evaluated against a clinically used colloid resuscitant, Hextend. We demonstrate that a radiant star poly(glycerol monomethacrylate) polymer did not interfere with coagulation while successfully correcting metabolic deficit and resuscitating animals from hemorrhagic shock to the desired mean arterial pressure range for DCR - correcting a 60 % total blood volume (TBV) loss when given at only 10 % TBV. This highly portable and non-coagulopathic resuscitant has profound potential for application in trauma medicine.

Description of a new moray eel (Anguilliformes: Muraenidae) from the Philippines, with a preliminary assessment of genetic and morphological variations of the Uropterygius concolor species complex.

Uropterygius concolor Rüppell, the type species of the genus Uropterygius, is a small, uniformly brown moray considered to be widely distributed in the Indo-Pacific region. However, a recent study indicated that the real U. concolor is currently known only from the type locality in the Red Sea, and species recorded outside the Red Sea may represent a species complex that comprises several species. In this study, we assess the genetic and morphological variations of this species complex based on available data. Analyses of cytochrome c oxidase subunit I sequences revealed at least six distinct genetic lineages recognized under 'U. concolor'. After carefully comparing the morphologies, one of the lineages is described herein as a new species, Uropterygius mactanensis sp. nov., based on 21 specimens collected from Mactan Island, Cebu, Philippines. Another distinct lineage is considered to be a possibly undescribed species based on diagnostic morphological characters. Although the taxonomic status of junior synonyms of U. concolor and some lineages still remain unresolved, this study provides informative morphological characters (i.e., tail length, trunk length, vertebrae number, and arrangement of teeth) that can be used in future studies on this species complex.

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions.

Artificially performing chemical reactions in living biosystems to attain various physiological aims remains an intriguing but very challenging task. In this study, the Schiff base reaction was conducted in cells using Sc(OTf)3 as a catalyst, enabling the in situ synthesis of a hollow covalent organic polymer (HCOP) without external stimuli. The reversible Schiff base reaction mediated intracellular Oswald ripening endows the HCOP with a spherical, hollow porous structure and a large specific surface area. The intracellularly generated HCOP reduced cellular motility by restraining actin polymerization, which consequently induced mitochondrial deactivation, apoptosis, and necroptosis. The presented intracellular synthesis system inspired by the Schiff base reaction has strong potential to regulate cell fate and biological functions, opening up a new strategic possibility for intervening in cellular behavior.

A Biodegradable Multifunctional Film as a Tissue Adhesive for Instant Hemostasis and Wound Closure.

Here, a multifunctional film (MFF) as an alternative tissue adhesive in the form of an interpenetrating network consisting of self-crosslinked aldehyde-functionalized chitosan (AC) and crosslinked poly(acrylic acid) (PAA) further coordinated with Ag+ is reported. The MFF combines enhanced toughness and stretchability, which is attributed to the synergistic effects of the double-network design. Covalent crosslinking maintains the overall integrity of the MFF matrix, while noncovalent crosslinking dissipates energy under deformation. Upon contact, the MFF quickly dries the tissue surface followed by instant physical crosslinking to the tissue. Subsequent covalent crosslinking between the aldehyde groups of the MFF and the primary amine groups on the surface of the tissue further stabilizes the adhesion. Meanwhile, Ag+ provides strong antibacterial properties to the MFF. Notably, in vivo studies demonstrate that the MFF allows facile and tough attachment to the wet and dynamic surface of rabbit liver and presents superior hemostasis and sealing properties. Furthermore, the MFF can be safely degraded without causing abnormal defects in vivo. The outstanding physicochemical properties of the MFF can potentially be a good alternative to existing sutures or staples and has potential for use in clinical practice.

The Efficacy of Senna Bowel Preparation for Colonoscopy: A Systematic Review and Meta-analysis.

The quality of bowel preparation is an extremely important determinant of colonoscopy results. However, the efficacy of senna regimens in improving bowel cleanliness is uncertain. We conducted a systematic review and meta-analysis to synthesize data on whether using a senna bowel preparation regimen enhances the bowel cleanliness. We searched Web of Science Core Collection, MEDLINE, PubMed, Embase, Cochrane Library, and Scopus databases (from the inception to August 2021). The primary efficacy outcome was bowel cleanliness. Secondary outcomes included patient compliance, tolerance, and adverse events. Eleven trials fulfilled the inclusion criteria (3,343 patients. Overall, we found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% confidence interval]: 1.02 [0.63, 1.67], p = 0.93). There was significant difference in tolerance (odds ratio [95% confidence interval]: 1.66 [1.08, 2.54], p = .02) and compliance (odds ratio [95% confidence interval]: 3.05 [1.42, 6.55], p = .004). The senna regimen yielded a significantly greater proportion of no nausea (odds ratio [95% confidence interval]: 1.84 [1.45, 2.32]) and vomiting (odds ratio [95% confidence interval]: 1.65 [0.81, 3.35]). Compared with other bowel preparation regimens, the senna regimen may be effective and safe in bowel cleaning before colonoscopy, with superior compliance and tolerance.

Assessment of pegylated arginine deiminase and modified FOLFOX6 in patients with advanced hepatocellular carcinoma: Results of an international, single-arm, phase 2 study.

BACKGROUND: Arginine starvation depletes the micronutrients required for DNA synthesis and interferes with both thymidylate synthetase activity and DNA repair pathways in preclinical models of hepatocellular carcinoma (HCC). Pegylated arginine deiminase (ADI-PEG 20), an arginine degrader, potentiates the cytotoxic activity of platinum and pyrimidine antimetabolites in HCC cellular and murine models. METHODS: This was a global, multicenter, open-label, single-arm, phase 2 trial of ADI-PEG 20 and modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients who had HCC with Child-Pugh A cirrhosis and disease progression on ≥2 prior lines of treatment. The primary objective was the objective response rate assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary objectives were to estimate progression-free survival, overall survival, safety, and tolerability. Eligible patients were treated with mFOLFOX6 intravenously biweekly at standard doses and ADI-PEG-20 intramuscularly weekly at 36 mg/m2 . RESULTS: In total, 140 patients with advanced HCC were enrolled. The median patient age was 62 years (range, 30-85 years), 83% of patients were male, 76% were of Asian race, 56% had hepatitis B viremia, 10% had hepatitis C viremia, 100% had received ≥2 prior lines of systemic therapy, and 39% had received ≥3 prior lines of systemic therapy. The objective response rate was 9.3% (95% confidence interval [CI], 5.0%-15.4%), with a median response duration of 10.2 months (95% CI, 5.8 months to not reached). The median progression-free survival was 3.8 months (95% CI, 1.8-6.3 months), and the median overall survival was 14.5 months (95% CI, 13.6-20.9 months). The most common grade ≥3 treatment-related events were neutropenia (32.9%), white blood cell count decrease (20%), platelet count decrease (19.3%), and anemia (9.3%). CONCLUSIONS: Concurrent mFOLFOX6 plus ADI-PEG 20 exhibited limited antitumor activity in patients with treatment-refractory HCC. The study was terminated early, and no further evaluation of the combination will be pursued. LAY SUMMARY: Arginine is an important nutrient for hepatocellular carcinoma (HCC). The depletion of arginine with pegylated arginine deiminase (ADI-PEG 20), an arginine degrader, appeared to make chemotherapy (FOLFOX) work better in animal models of HCC and in patients with HCC on an early phase clinical trial. To formally test this hypothesis in the clinical setting, a large, global, phase 2 clinical trial was conducted of ADI-PEG 20 and FOLFOX in the treatment of patients with refractory HCC. The study showed limited activity of ADI-PEG 20 and FOLFOX in advanced HCC and was stopped early.

Oral tegafur-uracil as a metronomic therapy in stage IVa and IVb cancer of the oral cavity.

PURPOSE: This study aimed to evaluate the impact of accumulated oral tegafur-uracil (UFUR) as maintenance chemotherapy on overall survival (OS) and disease-free survival (DFS) rates after definitive treatment for non-distant metastatic stage IV cancer of the oral cavity. MATERIALS AND METHODS: This retrospective, hospital center-based study analyzed data of patients diagnosed with stage IVa and IVb cancer of the oral cavity who underwent surgical resection and concurrent chemoradiotherapy (CCRT) obtained from a database between October 2008 and December 2014. RESULTS: Forty-two patients were treated with CCRT (non-UFUR group); the remaining 51 patients received the same regimen, followed by additional oral UFUR (UFUR group). For all study patients, the 3-year DFS rates were 53.05% and 35.41% in the UFUR and non-UFUR groups, respectively (p = 0.011), while the 3-year OS rates were 74.96% and 48.47%, respectively (p = 0.001). CONCLUSIONS: Adding UFUR to CCRT significantly improved the DFS and OS rates in patients with non-distant metastatic stage IV cancer of the oral cavity.

Anti-Inflammatory Effect of Charantadiol A, Isolated from Wild Bitter Melon Leaf, on Heat-Inactivated Porphyromonas gingivalis-Stimulated THP-1 Monocytes and a Periodontitis Mouse Model.

Porphyromonas gingivalis has been identified as one of the major periodontal pathogens. Activity-directed fractionation and purification processes were employed to identify bioactive compounds from bitter melon leaf. Ethanolic extract of bitter melon leaf was separated into five subfractions by open column chromatography. Subfraction-5-3 significantly inhibited P. gingivalis-induced interleukin (IL)-8 and IL-6 productions in human monocytic THP-1 cells and then was subjected to separation and purification by using different chromatographic methods. Consequently, 5ß,19-epoxycucurbita-6,23(E),25(26)-triene-3ß,19(R)-diol (charantadiol A) was identified and isolated from the subfraction-5-3. Charantadiol A effectively reduced P. gingivalis-induced IL-6 and IL-8 productions and triggered receptors expressed on myeloid cells (TREM)-1 mRNA level of THP-1 cells. In a separate study, charantadiol A significantly suppressed P. gingivalis-stimulated IL-6 and tumor necrosis factor-α mRNA levels in gingival tissues of mice, confirming the inhibitory effect against P. gingivalis-induced periodontal inflammation. Thus, charantadiol A is a potential anti-inflammatory agent for modulating P. gingivalis-induced inflammation.

A review of the genus Strophidon (Anguilliformes: Muraenidae), with description of a new species.

Strophidon McClelland is a muraenid genus with characteristic appearance of a very elongated body, a large mouth cleft and anteriorly placed eyes. The nomenclature and taxonomic history of species within Strophidon are contentious and its members are easily misidentified. In the present study, species of the genus Strophidon are revised based on morphological and molecular data, and five species are considered valid, including S. dawydoffi Prokofiev, S. dorsalis (Seale), S. sathete (Hamilton), S. ui Tanaka and a new species, S. tetraporus. Strophidon tetraporus sp. nov. is described based on 15 specimens from Indonesia, the Philippines, Taiwan and Vietnam with the unique characteristic of the constant presence of the fourth infraorbital pore among species of Strophidon. The intraspecific variation of vertebral formula within S. dorsalis is discussed based on molecular data. Muraena macrurus Bleeker and Thyrsoidea longissima Kaup are synonyms of S. sathete that can be distinguished from the most similar congener S. ui by a longer tail, smaller eyes and more inner maxillary and inner dentary teeth. A key to identify species of Strophidon is provided. The distribution and maximum size of each species are also re-evaluated.

Enterovirus Inhibition by Hinged Aromatic Compounds with Polynuclei.

The modern world has no available drugs for the treatment of enteroviruses (EV), which affect millions of people worldwide each year. The EV71 is a major causative disease for hand, foot, and mouth disease; sometimes it is associated with severe central nervous system diseases. Treatment for enteroviral infection is mainly supportive; treatment for aseptic meningitis caused by enteroviruses is also generally symptomatic. Upon the urgent request of new anti-enterovirus drugs, a series of hinged aromatic compounds with polynulei were synthesized through two different chemical pathways. Among these morpholine-furan/thiophene/pyrrole-benzene-pyrazole conjugates, three new agents exhibited inhibitory activity with EC50 = 2.29-6.16 µM toward EV71 strain BrCr in RD cells. Their selectivity index values were reached as high as 33.4. Their structure-activity relationship was deduced that a thiophene derivative with morpholine and trifluorobenzene rings showed the greatest antiviral activity, with EC50 = 2.29 µM.

A novel autolysis system for extracellular production and direct immobilization of a phospholipase D fused with cellulose binding domain.

BACKGROUND: Several types of phospholipases have been described in phospholipids modification. The majority of phospholipase D (PLD) superfamily members can catalyze two separate reactions: the hydrolysis of phospholipids to produce phosphatidic acid (PA) and the transphosphatidylation of phosphatidyl groups into various phosphatidyl alcohols to produce modified phospholipids. Transphosphatidylation is a useful biocatalytic method for the synthesis of functional phospholipids from lecithin or phosphatidylcholine (PC), which are both easily accessible. Different PLD coding genes have been cloned from various sources from viral, prokaryotic, and eukaryotic organisms. Despite the catalytic potential of PLD, their low productivity has hampered their practical applications, probably because PLD, which is highly toxic to the host cells, when transformation of the PLD genes into the host cells, degrade PLs in the cell membrane. In this study, we designed a novel two-step expression system to produce and secrete recombinant PLD in extracellular medium, cellulose-binding domains as an affinity fused with PLD for immobilization and purification proteins. RESULTS: The engineered BL21 (DE3) host strain, which harbored the final expression vector pET28a-PLD-CBD-araC-ESN, was induced by IPTG and L-arabinose, the cell density decreased rapidly over a 2 h period and the enzymes released into the extracellular medium accounts owned 81.75% hydrolytic activity. Scanning electron microscopy results showed that there were obvious structural changes on the cell surface. The extracellularly secreted PLD-CBD powder was used to catalyze the transphosphatidylation reaction synthesis of phosphatidylserine, 2.3 U enzymes reacted for 12 h, during which the conversion rate reached 99% with very few by-products being produced. When the fused protein PLD-CBD immobilized on microcrystalline cellulose, the enzymes can be cycle used five times with 26% conversion rate was preserved. CONCLUSIONS: This study introduced an effective method for use in the expression of recombinant proteins and their extracellular secretion that simplifies the steps of sonication and purification and demonstrates great potential in the industrial application of enzymes. Cellulose as the most abundant renewable biomass resources in nature, and the cost is low, used for PLD immobilization make it more simple, effective and sustainable.

Recurrent episodes of reversible posterior leukoencephalopathy in three Chinese families with GJB1 mutations in X-linked Charcot-Marie-tooth type 1 disease: cases report.

BACKGROUND: The X-linked form of Charcot-Marie-Tooth disease type 1 (CMTX1) is an inherited peripheral neuropathy that arises in patients with mutations in the gap-junction beta-1 gene (GJB1). CASE PRESENTATION: Three young male patients from Southern China with pes cavus experienced multiple episodes of transient central nervous system (CNS) dysfunction. Three patients all had reversible posterior leukoencephalopathy as detected by brain diffusion-weighted magnetic resonance imaging (MRI-DWI). Nerve conduction velocity (NCV) showed sensorimotor polyneuropathy with mixed demyelinating and axonal features. Genetic testing indicated a c.425G > A (p.Arg142Glu) or c.563 C > T (p.Thr188Ile) or c.103G > C (p.Val35Leu) mutation in GJB1. The unique feature of this report is the identification of two novel mutations: c.563 C > T and sc.103G > C of the GJB1 gene detected in two families respectively. Another unique feature is that peripheral neuropathy symptoms in the three patients were insidious and found at the onset of CNS symptoms. CONCLUSIONS: Posterior leukoencephalopathy is involved in CMTX1 patients. The white matter changes in MRI of CMTX1 patients are reversible and recover later than CNS symptoms.

Priming effect of root-applied silicon on the enhancement of induced resistance to the root-knot nematode Meloidogyne graminicola in rice.

BACKGROUND: Silicon (Si) can confer plant resistance to both abiotic and biotic stress. In the present study, the priming effect of Si on rice (Oryza sativa cv Nipponbare) against the root-knot nematode Meloidogyne graminicola and its histochemical and molecular impact on plant defense mechanisms were evaluated. RESULTS: Si amendment significantly reduced nematodes in rice roots and delayed their development, while no obvious negative effect on giant cells was observed. Increased resistance in rice was correlated with higher transcript levels of defense-related genes (OsERF1, OsEIN2 and OsACS1) in the ethylene (ET) pathway. Si amendment significantly reduced nematode numbers in rice plants with enhanced ET signaling but had no effect in plants deficient in ET signaling, indicating that the priming effects of Si were dependent on the ET pathway. A higher deposition of callose and accumulation of phenolic compounds were observed in rice roots after nematode attack in Si-amended plants than in the controls. CONCLUSION: These findings indicate that the priming effect may partially depend on the production of phenolic compounds and hydrogen peroxide. Further research is required to model the ethylene signal transduction pathway that occurs in the Si-plant-nematode interaction system and gain a better understanding of Si-induced defense in rice.

Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

Magnetic Nanoparticle-Based Lateral Flow Immunochromatographic Strip as a Reporter for Rapid Detection of Melamine.

Magnetite nanoparticles (MNPs) Fe3O4 and r-Fe2O3 were surface-modified with poly(ethylene glycol) (PEG) in order to improve their specificity and bioactivity. PEG and the anti-MEL monoclonal antibody (mAb) were successfully immobilized on the surface of MNPs and characterized using FTIR, UV-Vis and TEM analyses. Surface modification of MNPs-PEG-mAb conjugates of a variety of sizes and magnetite types was employed to design and prepare labels for use in a lateral flow immunoassay (LFIA) to test whether the size of the conjugate can affect the performance of the assay. The results showed that the detection limit was mainly determined by the size of the MNPs-PEG-mAb conjugate. Under optimized conditions, a detection limit of 0.4 ppm for melamine was achieved using Fe2O3-PEG-mAb, which was almost 5-fold lower than that of the Fe3O4-PEG-mAb conjugate (2.2 ppm).

Clinical outcomes for primary molars treated by different types of pulpotomy: A retrospective cohort study.

BACKGROUND/PURPOSE: Pulpotomy is the amputation of coronally infected pulp tissue to maintain the vitality and function of the radicular pulp. This study was designed to assess the clinical and radiographic success rates of primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication after a follow-up period of 24 months. METHODS: A retrospective study was conducted by evaluating the success rates of primary molars treated by pulpotomy with diode laser, sodium hypochlorite, or no medication according to the clinical symptoms and signs and radiographic features. RESULTS: There were 145 primary molars included in the study. No significant differences in clinical and radiographic success rates were found among primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication, when the teeth were treated by experienced pedodontists and restored with stainless steel crowns. The 2-year clinical success rates for primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication were all 100%. The 2-year radiographic success rates were 90.9%, 100%, and 87.5% for primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication, respectively. However, when the pulpotomy for primary molars was performed by less-experienced residents, a reduced overall success rate from 94% for attending doctors to 58% for residents was found. CONCLUSION: Operators and final restorations are confounding factors for determining the success rate of primary molars treated by pulpotomy. Pulpotomy with diode laser, sodium hypochlorite, or no medication are all acceptable treatments of choice for coronally infected primary molars.

Mechanically-Guided Deterministic Assembly of 3D Mesostructures Assisted by Residual Stresses.

Formation of 3D mesostructures in advanced functional materials is of growing interest due to the widespread envisioned applications of devices that exploit 3D architectures. Mechanically guided assembly based on compressive buckling of 2D precursors represents a promising method, with applicability to a diverse set of geometries and materials, including inorganic semiconductors, metals, polymers, and their heterogeneous combinations. This paper introduces ideas that extend the levels of control and the range of 3D layouts that are achievable in this manner. Here, thin, patterned layers with well-defined residual stresses influence the process of 2D to 3D geometric transformation. Systematic studies through combined analytical modeling, numerical simulations, and experimental observations demonstrate the effectiveness of the proposed strategy through ≈20 example cases with a broad range of complex 3D topologies. The results elucidate the ability of these stressed layers to alter the energy landscape associated with the transformation process and, specifically, the energy barriers that separate different stable modes in the final 3D configurations. A demonstration in a mechanically tunable microbalance illustrates the utility of these ideas in a simple structure designed for mass measurement.

Whey Protein Improves Marathon-Induced Injury and Exercise Performance in Elite Track Runners.

Whey protein has been widely applied to athletes and the fitness field for muscle growth and performance improvement. Limited studies focused on the beneficial effects of whey on aerobic exercise according to biochemical assessments. In the current study, 12 elite male track runners were randomly assigned to whey and maltodextrin groups for 5 weeks' supplementation. The aim of this study was to investigate the effect of whey protein on physiological adaptions and exercise performance. During this period, three time points (pre-, post-, and end-test) were used to evaluate related biochemical parameters, body composition, and performance. The post-test was set 1 day after a marathon for injury status evaluation and the end-test was also assessed after 1-week recovery from endurance test. The results showed that the whey group exhibited significantly lower aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase indicators after the marathon (post-test), as well as at the end-test (p<0.016). The endurance performance in twelve-minute walk/run was also significantly elevated (p<0.012) possibly due to an increase in the muscle mass and amelioration of exercise injuries. In the current study, we demonstrated that whey protein can also be used for aerobic exercise for better physiological adaptation, in addition to resistance training. Whey protein could be also a potential nutrient supplement with a variety of benefits for amateur runners.

Stepwise illustration of teeth-fixation semi-constrained cervical disc arthroplasty.

There are many kinds of artificial discs available for cervical disc arthroplasty (CDA), with various designs of fixation and articulation mechanisms. Each of these designs has different features and theoretically fits most optimally in selected types of patients. However, there has been insufficient literature to guide individualized selection among these CDA devices. Since CDA aims to restore the joint function rather than arthrodesis, tailor-made size, shape, and mechanical properties should be taken into account for each candidate's target disc. Despite several large-scale prospective randomized control trials that have demonstrated the effectiveness and durability of CDA for up to 8 years, none of them involved more than one kind of artificial disc. In this video the authors present detailed steps and technical aspects of the newly introduced ProDisc-C Vivo (DePuy Synthes Spine), which has the same ball-and-socket design for controlled, predictable motion as the ProDisc-C. The newly derived teeth fixation provides high primary stability and multilevel capability by avoidance of previous keel-related limitations and complications (e.g., split vertebral fracture). Please note that the ProDisc-C Vivo is currently not available on the US market. The authors present the case of a 53-year-old woman who had symptoms of both radiculopathy and myelopathy caused by a large, calcified disc herniation at C4-5. There was no improvement after 4 months of medical treatment and rehabilitation. A single-level CDA was successfully performed with the ProDisc-C Vivo, and her symptoms were completely ameliorated afterward. The follow-up images demonstrated preservation of motion at the indexed level. The video can be found here: https://youtu.be/4DSES1xgvQU .

188Re-Liposome Can Induce Mitochondrial Autophagy and Reverse Drug Resistance for Ovarian Cancer: From Bench Evidence to Preliminary Clinical Proof-of-Concept.

Despite standard treatment, about 70% of ovarian cancer will recur. Cancer stem cells (CSCs) have been implicated in the drug-resistance mechanism. Several drug resistance mechanisms have been proposed, and among these, autophagy plays a crucial role for the maintenance and tumorigenicity of CSCs. Compared to their differentiated counterparts, CSCs have been demonstrated to display a significantly higher level of autophagy flux. Moreover, mitophagy, a specific type of autophagy that selectively degrades excessive or damaged mitochondria, is shown to contribute to cancer progression and recurrence in several types of tumors. Nanomedicine has been shown to tackle the CSCs problem by overcoming drug resistance. In this work, we developed a nanomedicine, 188Re-liposome, which was demonstrated to target autophagy and mitophagy in the tumor microenvironment. Of note, the inhibition of autophagy and mitophagy could lead to significant tumor inhibition in two xenograft animal models. Lastly, we presented two cases of recurrent ovarian cancer, both in drug resistance status that received a level I dose from a phase I clinical trial. Both cases developing drug resistance showed drug sensitivity to 188Re-liposome. These results suggest that inhibition of autophagy and mitophagy by a nanomedicine may be a novel strategy to overcome drug resistance in ovarian cancer.