Cultured meat with enriched organoleptic properties by regulating cell differentiation.

Research on cultured meat has primarily focused on the mass proliferation or differentiation of muscle cells; thus, the food characteristics of cultured meat remain relatively underexplored. As the quality of meat is determined by its organoleptic properties, cultured meat with similar sensory characteristics to animal-derived meat is highly desirable. In this study, we control the organoleptic and nutritional properties of cultured meat by tailoring the 2D differentiation of primary bovine myoblasts and primary bovine adipose-derived mesenchymal stem cells on gelatin/alginate scaffolds with varying stiffness. We assess the effect of muscle and adipose differentiation quality on the sensory properties of cultured meat. Thereafter, we fabricate cultured meat with similar sensory profiles to that of conventional beef by assembling the muscle and adipose constructs composed of highly differentiated cells. We introduce a strategy to produce cultured meat with enriched food characteristics by regulating cell differentiation with scaffold engineering.

Zwitterionic Inhaler with Synergistic Therapeutics for Reprogramming of M2 Macrophage to Pro-Inflammatory Phenotype.

Myriad lung diseases are life threatening and macrophages play a key role in both physiological and pathological processes. Macrophages have each pro-/anti-inflammatory phenotype, and each lung disease can be aggravated by over-polarized macrophage. Therefore, development of a method capable of mediating the macrophage phenotype is one of the solutions for lung disease treatment. For mediating the phenotype of macrophages, the pulmonary delivery system (PDS) is widely used due to its advantages, such as high efficiency and accessibility of the lungs. However, it has a low drug delivery efficiency ironically because of the perfect lung defense system consisting of the mucus layer and airway macrophages. In this study, zwitterion-functionalized poly(lactide-co-glycolide) (PLGA) inhalable microparticles (ZwPG) are synthesized to increase the efficiency of the PDS. The thin layer of zwitterions formed on PLGA surface has high nebulizing stability and show high anti-mucus adhesion and evasion of macrophages. As a reprogramming agent for macrophages, ZwPG containing dexamethasone (Dex) and pirfenidone (Pir) are treated to over-polarized M2 macrophages. As a result, a synergistic effect of Dex/Pir induces reprogramming of M2 macrophage to pro-inflammatory phenotypes.

Whole-genome sequencing of 20 cholangiocarcinoma cases reveals unique profiles in patients with cirrhosis and primary sclerosing cholangitis.

Background: Cholangiocarcinoma (CCA) is a molecularly heterogenous disease that is often fatal. Whole genome sequencing (WGS) can provide additional knowledge of mutational spectra compared with panel sequencing. We describe the molecular landscape of CCA using whole-genome sequencing and compare the mutational landscape between short-term and long-term survivors. Methods: We explored molecular differences between short-term and long-term survivors by performing WGS on 20 patient samples from our biliary tract cancer database. Short-term survivors were enriched for cases with underlying primary sclerosing cholangitis (PSC) and patients with cirrhosis. All samples underwent tumour epithelial enrichment using laser capture microdissection (LCM). Results: Dominant single base substitution (SBS) signatures across the cohort included SBS1 and SBS5, with the latter more prevalent in long-term survivors. SBS17 was evident in 3 cases, all of whom had underlying ulcerative colitis (UC) with PSC. Additional rare signatures included SBS3 in a patient treated for prior mantle cell lymphoma and SBS26/SBS6 in a patient with a tumor mutational burden of 33 mutations/Mb and a pathogenic MLH1 germline mutation. Somatic TP53 inactivating mutations were present in 8/10 (80%) short-term survivors and in none of the long-term survivors. Additional mutations occurred in KRAS, SMAD4, CDKN2A, and chromatin remodelling genes. The long-term survivor group harboured predicted fusions in FGFR (n=2) and pathogenic mutations in BRAF and IDH1 (n=2). Conclusions: TP53 alterations are associated with poor outcomes in patients with CCA. Patients with underlying inflammatory/autoimmune conditions may be enriched for unique tumour mutational signatures.

Unraveling the Structured Solvation Shell of Zwitterion Nanoparticles for Controlled Release of Nitric Oxide.

Zwitterions have been attracting emerging attention as an anti-fouling polymer. However, the relationship between structured solvation shells and controlled drug release induced by deceleration of water molecule's translational and vibrational motions of zwitterions is an uncharted territory. Herein, sulfobetaine zwitterion nanoparticles (ZWNPs) were designed as a stable nitric oxide (NO)-delivering carrier. The condensed water structure of the solvation shell at its isoelectric point (PI) and the loose structure of water under different pH conditions were investigated through rheological and thermodynamical analyses. The ZWNPs showed a sustained-release profile at the PI, which presented a structured solvation barrier. On the other hand, NO-loaded ZWNPs showed different release profiles with the burst release at pH 5.5. Notably, an increased cell proliferation rate and a decreased antibacterial effect were observed at the same concentration depending on solvation shell's characteristics.

Stand-Alone Posterior Expandable Cage Technique for Adjacent Segment Degeneration with Lumbar Spinal Canal Stenosis: A Retrospective Case Series.

Background and Objectives: Symptomatic adjacent segment degeneration (ASD) with lumbar spinal canal stenosis (LSCS) is a common complication after spinal intervention, particularly interbody fusion. Stand-alone posterior expandable cages enable interbody fusion with preservation of the previous operation site, and screw-related complications are avoided. Thus, the aim of this study was to investigate the clinicoradiologic outcomes of stand-alone posterior expandable cages for ASD with LSCS. Materials and Methods: Patients with persistent neurologic symptoms and radiologically confirmed ASD with LSCS were evaluated between January 2011 and December 2016. The five-year follow-up data were used to evaluate the long-term outcomes. The radiologic parameters for sagittal balance, pain control (visual analogue scale), disability (Oswestry Disability Index), and early (peri-operative) and late (implant) complications were evaluated. Results: The data of 19 patients with stand-alone posterior expandable cages were evaluated. Local factors, such as intervertebral and foraminal heights, were significantly corrected (p < 0.01 and p < 0.01, respectively), and revision was not reported. The pain level (p < 0.01) and disability rate (p < 0.01) significantly improved, and the early complication rate was low (n = 2, 10.52%). However, lumbar lordosis (p = 0.62) and sagittal balance (p = 0.80) did not significantly improve. Furthermore, the rates of subsidence (n = 4, 21.05%) and retropulsion (n = 3, 15.79%) were high. Conclusions: A stand-alone expandable cage technique should only be considered for older adults and patients with previous extensive fusion. Although this technique is less invasive, improves the local radiologic factors, and yields favorable clinical outcomes with low revision rates, it does not improve the sagittal balance. For more widespread application, the strength of the cage material and high subsidence rates should be improved.

Can posterior stand-alone expandable cages safely restore lumbar lordosis? A minimum 5-year follow-up study.

BACKGROUND: Lumbar lordosis (LL) can be restored, and screw-related complications may be avoided with the stand-alone expandable cage method. However, the long-term spinopelvic changes and safety remain unknown. We aimed to elucidate the long-term radiologic outcomes and safety of this technique. METHODS: Data from patients who underwent multi-level stand-alone expandable cage fusion and 80 patients who underwent screw-assisted fusion between February 2007 and December 2012, with at least 5 years of follow-up, were retrospectively analyzed. Segmental angle and translation, short and whole LL, pelvic incidence, pelvic tilt, sacral slope (SS), sagittal vertical axis, thoracic kyphosis, and presence of subsidence, pseudoarthrosis, retropulsion, cage breakage, proximal junctional kyphosis (PJK), and screw malposition were assessed. The relationship between local, lumbar, and spinopelvic effects was investigated. The implant failure rate was considered a measure of procedure effectiveness and safety. RESULTS: In total, 69 cases were included in the stand-alone expandable cage group and 150 cases in the control group. The stand-alone group showed shorter operative time (58.48 ± 11.10 vs 81.43 ± 13.75, P = .00028), lower rate of PJK (10.1% vs 22.5%, P = .03), and restoration of local angle (4.66 ± 3.76 vs 2.03 ± 1.16, P = .000079) than the control group. However, sagittal balance (0.01 ± 2.57 vs 0.50 ± 2.10, P = .07) was not restored, and weakness showed higher rate of subsidence (16.31% vs 4.85%, P = .0018), pseudoarthrosis (9.92% vs 2.42%, P = .02), cage, and retropulsion (3.55% vs 0, P = .01) than the control group. CONCLUSIONS: Stand-alone expandable cage fusion can restore local lordosis; however, global sagittal balance was not restored. Furthermore, implant safety has not yet been proven.

Searching for consensus in the approach to patients with chronic lateral ankle instability: ask the expert.

PURPOSE: The purpose of this study is to propose recommendations for the treatment of patients with chronic lateral ankle instability (CAI) based on expert opinions. METHODS: A questionnaire was sent to 32 orthopaedic surgeons with clinical and scientific experience in the treatment of CAI. The questions were related to preoperative imaging, indications and timing of surgery, technical choices, and the influence of patient-related aspects. RESULTS: Thirty of the 32 invited surgeons (94%) responded. Consensus was found on several aspects of treatment. Preoperative MRI was routinely recommended. Surgery was considered in patients with functional ankle instability after 3-6 months of non-surgical treatment. Ligament repair is still the treatment of choice in patients with mechanical instability; however, in patients with generalized laxity or poor ligament quality, lateral ligament reconstruction (with grafting) of both the ATFL and CFL should be considered. CONCLUSIONS: Most surgeons request an MRI during the preoperative planning. There is a trend towards earlier surgical treatment (after failure of non-surgical treatment) in patients with mechanical ligament laxity (compared with functional instability) and in high-level athletes. This study proposes an assessment and a treatment algorithm that may be used as a recommendation in the treatment of patients with CAI. LEVEL OF EVIDENCE: V.

Impaired pre-attentive auditory processing in fibromyalgia: A mismatch negativity (MMN) study.

OBJECTIVE: Fibromyalgia (FM) patients often show deficits in cognitive functions such as attention and working memory. We assumed that pre-attentive information processing, a crucial element in human perception and cognition, would be altered in FM patients. Thus, the objective of this study was to determine whether FM patients exhibit alterations in pre-attentive processing as assessed by auditory mismatch negativity (MMN). METHODS: Auditory evoked magnetic fields were recorded in FM patients (n=18) and healthy control subjects (n=21) during a duration-deviant auditory oddball paradigm. The magnetic mismatch negativity (MMNm) was obtained by subtracting responses to standard tones from responses to deviant tones. Pressure pain thresholds over the thenar and trapezius muscles were determined using an algometer. RESULTS: MMNm peak amplitudes in right hemispheres were attenuated, and the directional asymmetry coefficient of the MMNm amplitude was lower in FM patients, indicating a more leftward asymmetry than in healthy control subjects. Smaller right MMNm amplitude was associated with lower pressure pain thresholds of thenar muscles in FM patients. CONCLUSIONS: Our results suggested that pre-attentive processing of auditory information is impaired in FM patients. SIGNIFICANCE: This study provided neurophysiological evidence of impaired pre-attentive sensory change detection in FM.

Effects of gamichunggantang on hyperlipidemia.

AIM: To evaluate the therapeutic effects of gamichunggantang (GCT) on hyperlipidemia through high cholesterol diet model. GCT is an Oriental herbal medication, which has been used for the treatment of fatty liver, hyperlipidemia or alcoholic liver disease in Daejeon University Oriental Hospital, Korea since 1999. METHODS: Rats were fed with high cholesterol diet for 4 weeks and GCT was administrated for 2 weeks from 2 weeks later in experimental days. The levels of serum total cholesterol, HDL-cholesterol, and triglyceride were analyzed every week. Absolute and relative liver weight to body, and histopathological changes were determined at last day. And, lipid metabolism-related gene expressions (ACAT and DGAT) in liver tissue were analyzed by using RT-PCR. RESULTS: In GCT group, TG levels were reduced at 3 and 4 weeks after GCT administration (39.4 %, P < 0.05 and 36.3 %, P < 0.01 respectively). Total cholesterol levels also were reduced at 3 weeks (20.5 %, P < 0.05) and 4 weeks (35.86 %, P < 0.01) after GCT administration, but HDL-cholesterol levels were increased significantly (P < 0.05) at 3 weeks (14.7 %) and 4 weeks (25.5 %) compared with hyperlipidemia-induced group without GCT. In the GCT treated group, liver weight was lower and lipid accumulation was decreased in histological finding. ACAT gene expression was suppressed compared with hyperlipidemia-induced group but not DGAT. CONCLUSION: GCT possesses preventive or therapeutic effects on diet-induced hyperlipidemia by inhibiting the intestinal absorption and storage of exogenous and endogenous cholesterol.