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Background Context: Gut microbiome alterations resulting in inflammatory responses have been implicated in many distant effects on different organs. However, its influence on disc health is still not fully investigated., Purpose: Our objective was to document the gut biome in healthy volunteers and patients with disc degeneration and to understand the role of gut dysbiosis on human disc health., Study Design: Experimental case-control study., Patient Sample: We included 40 patients with disc degeneration (DG) and 20 healthy volunteers (HV). HV comprised of age groups 30 to 60 years with no known record of back pain and no clinical comorbidities, with normal MRI. Diseased group (DG) were patients in the same age group undergoing surgery for disc disease (disc herniation-25; discogenic stenosis-15) and without instability (with Modic-20; and non-Modic-20)., Outcome Measures: N/A., Methods: We analyzed 16S V3-V4 rDNA gut metagenome from 20 healthy volunteers (HV) and compared the top signature genera from 40 patients with disc degeneration (DG) across Modic and non-Modic groups. Norgen Stool DNA Kit was used for DNA extraction from ∼200 mg of each faecal sample collected using the Norgen Stool Collection Kit.16S V3-V4 rDNA amplicons were generated with universal bacterial primers 341F and 806R and amplified with Q5 High-Fidelity DNA Polymerase. Libraries were sequenced with 250×2 PE to an average of 0.1 million raw reads per sample (Illumina Novaseq 6000). Demultiplexed raw data was assessed with FastQC, and adapter trimmed reads >Q30 reads were processed in the QIME2 pipeline. Serum C-reactive protein (CRP) was measured by the immunoturbimetry method and Fatty acid-binding protein 5 (FABP5) was measured in albumin-globulin-depleted plasma through global proteome analysis., Results: We observed significant gut dysbiosis between HV and DG and also between the Modic and non-Modic groups. In the Modic group, commensals Bifidobacterium and Ruminococcus were significantly depleted, while pathobionts Streptococcus, Prevotella, and Butryvibrio were enriched. Firmicutes/Bacteroidetes ratio was decreased in DG (Modic-0.62, non-Modic-0.43) compared to HV (0.70). Bacteria-producing beneficial short-chain fatty acids were also depleted in DG. Elevated serum CRP and increased FABP5 were observed in DG., Conclusion: The study revealed gut dysbiosis, an altered Firmicutes/Bacteroidetes ratio, reduced SCFA-producing bacteria, and increased systemic and local inflammation in association with disc disease, especially in Modic changes. The findings have considerable importance for our understanding and prevention of disc degeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Context: Patients with modic changes (MC) form a distinct clinical subset with reports of higher intensity of pain, poor clinical and surgical outcomes and higher incidence of recurrence. MC also is an independent risk factor for increased post-operative surgical site infection., Purpose: This study aimed to investigate the biological changes at molecular level, in discs with MCs. We also aim to identify biological biomarkers and potential targets for molecular therapy., Study Design: Experimental analysis MATERIALS AND METHODS: Nucleus pulposus (NP) from 24 patients undergoing microdiscectomy for disc herniation [14 discs with MC and 10 without modic changes (NMC)] were procured. The overall expression of proteins, biological processes, protein-protein and metabolite interactions were analysed and compared. Host defense response proteins (HDRPs) and immunological pathways activated in patients with MC were documented and analysed., Results: Label-free proteomic approach with stringent filters revealed a total of 208 proteins in MC and 193 in NMC groups. 45 proteins were specific to MC; 30 to NMC and 163 common to both. Downregulated proteins in MC belonged to components of extracellular matrix such as collagens (COL- 6A1, 6A2, 6A3, 11A1, 12A1, and 20A1), and proteoglycans (versican (VCAN), and biglycan (BGN)). Inflammatory molecules [plasminogen (PLG), angiogenin (ANG), fibroblast growth factor-binding protein 2 (FGFBP2), tetranectin (CLEC3B), cartilage acidic protein 1(CRTAC1), kininogen (KNG-1), chitinase-3-like protein 2 (CHI3L2), and ferritin (FTL) were expressed only in the MC group. The significantly altered pathways in MC included Fc Fragment of IgG Receptor IIIa (FCGR3A)-mediated phagocytosis, regulation of Toll-like receptors (TLR) by endogenous ligand, neutrophil and platelet degranulation. 50 HDRPs were identified in the study, 14 of which were specific to MC and included acute phase reactants, antimicrobial peptides, complement cascade proteins, inflammatory molecule and stress response proteins. Metabolite-protein interaction analysis revealed a significant interaction between 19 proteins, specifically involving ubiquitin mediating proteasome degradative pathway and an association with the metabolite-glutamic acid in the MC group. Accumulation of glutamic acid in MC discs was confirmed by quantitative amino acid analysis using High-performance liquid chromatography., Conclusion: Our study confirms that MC represents an intense inflammatory status and activation of host defense response and immunological pathways. Downstream effects leading to ubiquitin mediated proteasomal degradation of ECM proteins and the resulting metabolites such as glutamic acid could cause excessive pain and needs further investigation., Clinical Significance: We have documented the expression of inflammatory molecules, immune mechanisms and host defense response proteins which throw molecular insights into the pathological mechanisms of MC. Further, ubiquitin mediated proteasomal degradation and accumulation of glutamate in discs with MC might serve as targets for molecular therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Study Design: This is a retrospective study., Purpose: Recent advances in intraoperative imaging and closed reduction techniques have led to a shifting trend toward surgical management in every unstable sacral fracture. This study aimed to evaluate the clinicoradiological outcome of the sacroiliac (SI) screw and lumbopelvic fixation (LPF) techniques and thereby delineate the indications for each., Overview of Literature: Optimal management guidelines for unstable sacral fractures are still lacking probably due to the rarity of these injuries and varying fixation trends., Methods: Out of the 67 patients, 40 and 27 were in the SI and LPF groups, respectively. The electronic medical record for each patient was reviewed, including patient demographic data, mode of trauma, coexisting injuries, neurological status (Gibbon's four-grade system), Injury Severity Score, time from admission to operative stabilization, type of surgical stabilization, complications, return to the operating room, and treatment outcome measures using Majeed's functional grading system and Matta's radiological criteria. The minimum follow-up period was 2 years., Results: Noncomminuted longitudinal injuries with normal neurology and acceptable closed reduction have undergone SI screw fixation (n=40). Irreducible, comminuted, or high transverse fractures associated with dysmorphic anatomy or neurodeficit were managed by LPF (n=27). Excellent and good Majeed and Matta scores at 86.57% and 92.54% of the patients, respectively, were postoperatively achieved., Conclusions: Unstable sacral fractures can be effectively managed with percutaneous SI screw including vertically unstable injuries by paying strict attention to preoperative patient selection whereas LPF can be reserved for comminuted fractures, unacceptable closed reduction, associated neurodeficit, lumbosacral dysmorphism, and high transverse fractures.

Background-One year has passed since the first COVID-19 case in Singapore. This scoping review commemorates Singaporean researchers that have expanded the knowledge on this novel virus. We aim to provide an overview of healthcare-related articles published in peer-reviewed journals, authored by the Singapore research community about COVID-19 during the first year of the pandemic. Methods-This was reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) protocol. It included healthcare-related articles about COVID-19 published between 23 January 2020 and 22 January 2021 with a Singapore-affiliated author. MEDLINE, Embase, Scopus, Web of Science, CINAHL, PsycINFO, Google Scholar, and local journals were searched. The articles were screened independently by two reviewers. Results-The review included 504 articles. Most of the articles narrated the changes to hospital practice (210), while articles on COVID-19 pathology (94) formed most of the non-narrative papers. Publications on public health (61) and the indirect impacts to clinical outcomes (45) were other major themes explored by the research community. The remaining articles detailed the psychological impact of the pandemic (35), adaptations of medical education (30), and narratives of events (14). Conclusion-Amidst a resurgence of community cases involving variant COVID-19 strains, the resources from the research community will provide valuable guidance to navigate these uncertain times.

Cancer cells respond to matrix mechanical stiffness in a complex manner using a coordinated, hierarchical mechano-chemical system composed of adhesion receptors and associated signal transduction membrane proteins, the cytoskeletal architecture, and molecular motors. Mechanosensitivity of different cancer cells in vitro are investigated primarily with immortalized cell lines or murine derived primary cells, not with primary human cancer cells. Hence, little is known about the mechanosensitivity of primary human colon cancer cells in vitro. Here, an optimized protocol is developed that describes the isolation of primary human colon cells from healthy and cancerous surgical human tissue samples. Isolated colon cells are then successfully cultured on soft (2 kPa stiffness) and stiff (10 kPa stiffness) polyacrylamide hydrogels and rigid polystyrene (~3.6 GPa stiffness) substrates functionalized by an extracellular matrix (fibronectin in this case). Fluorescent microbeads are embedded in soft gels near the cell culture surface, and traction assay is performed to assess cellular contractile stresses using free open access software. In addition, immunofluorescence microscopy on different stiffness substrates provides useful information about primary cell morphology, cytoskeleton organization and vinculin containing focal adhesions as a function of substrate rigidity.

Here, we present the development, characterization and quantification of a novel 1D/2D like polymeric platform for cell culture. The platform consists of a 2D surface anchoring a long (few millimeters) narrow filament (1D) with a single cell scale (micro scale) cross section. We plate C2C12 cells on the platform and characterize their migration, proliferation, and differentiation patterns in contrast to 2D culture. We find that the cells land on the 2D surface, and then migrate to the filament only when the 2D surface has become nearly confluent. Individual and isolated cells randomly approaching the filament always retract away towards the 2D surface. Once on the filament, their differentiation to myotubes is expedited compared to that on 2D substrate. The myotubes generate periodic twitching forces that deform the filament producing more than 17 μm displacement at the tip. Such flagellar motion can be used to develop autonomous micro scale bio-bots.

Cerebral hyperperfusion syndrome (CHS) describes a syndrome of sudden onset focal neurological features, unilateral headache, and systemic hypertension. Recurrent CHS in the same patient has not been described to date. We describe a 55-year-old woman who first developed CHS post intracranial stenting with sudden-onset right focal seizures and associated acute focal edema on imaging. After one and half years, the patient developed symptomatic in-stent restenosis and underwent repeat angioplasty with stenting. Postprocedure, the patient had another episode of CHS in the form of acute bleed in the basal ganglia and died. A review of literature of patients for CHS postintracranial angioplasty and stenting also was performed. The present case describes a rare clinical scenario where the patient had recurrent CHS with different clinical and imaging features.

Traction forces exerted by adherent cells on their microenvironment can mediate many critical cellular functions. Accurate quantification of these forces is essential for mechanistic understanding of mechanotransduction. However, most existing methods of quantifying cellular forces are limited to single cells in isolation, whereas most physiological processes are inherently multi-cellular in nature where cell-cell and cell-microenvironment interactions determine the emergent properties of cell clusters. In the present study, a robust finite-element-method-based cell traction force microscopy technique is developed to estimate the traction forces produced by multiple isolated cells as well as cell clusters on soft substrates. The method accounts for the finite thickness of the substrate. Hence, cell cluster size can be larger than substrate thickness. The method allows computing the traction field from the substrate displacements within the cells' and clusters' boundaries. The displacement data outside these boundaries are not necessary. The utility of the method is demonstrated by computing the traction generated by multiple monkey kidney fibroblasts (MKF) and human colon cancerous (HCT-8) cells in close proximity, as well as by large clusters. It is found that cells act as individual contractile groups within clusters for generating traction. There may be multiple of such groups in the cluster, or the entire cluster may behave a single group. Individual cells do not form dipoles, but serve as a conduit of force (transmission lines) over long distances in the cluster. The cell-cell force can be either tensile or compressive depending on the cell-microenvironment interactions.

Many microorganisms, including spermatozoa and forms of bacteria, oscillate or twist a hair-like flagella to swim. At this small scale, where locomotion is challenged by large viscous drag, organisms must generate time-irreversible deformations of their flagella to produce thrust. To date, there is no demonstration of a self propelled, synthetic flagellar swimmer operating at low Reynolds number. Here we report a microscale, biohybrid swimmer enabled by a unique fabrication process and a supporting slender-body hydrodynamics model. The swimmer consists of a polydimethylsiloxane filament with a short, rigid head and a long, slender tail on which cardiomyocytes are selectively cultured. The cardiomyocytes contract and deform the filament to propel the swimmer at 5-10 μm s(-1), consistent with model predictions. We then demonstrate a two-tailed swimmer swimming at 81 μm s(-1). This small-scale, elementary biohybrid swimmer can serve as a platform for more complex biological machines.

Polymerized carbon nanotubes (CNTs) are promising materials for polymer-based electronics and electro-mechanical sensors. The advantage of having a polymer nanolayer on CNTs widens the scope for functionalizing it in various ways for polymer electronic devices. However, in this paper, we show for the first time experimentally that, due to a resistive polymer layer having carbon nanoparticle inclusions and polymerized carbon nanotubes, an interesting dynamics can be exploited. We first show analytically that the relative change in the resistance of a single isolated semiconductive nanotube is directly proportional to the axial and torsional dynamic strains, when the strains are small, whereas, in polymerized CNTs, the viscoelasticity of the polymer and its effective electrical polarization give rise to nonlinear effects as a function of frequency and bias voltage. A simplified formula is derived to account for these effects and validated in the light of experimental results. CNT-polymer-based channels have been fabricated on a PZT substrate. Strain sensing performance of such a one-dimensional channel structure is reported. For a single frequency modulated sine pulse as input, which is common in elastic and acoustic wave-based diagnostics, imaging, microwave devices, energy harvesting, etc, the performance of the fabricated channel has been found to be promising.