Trace gas oxidation sustains energy needs of a thermophilic archaeon at suboptimal temperatures.

Diverse aerobic bacteria use atmospheric hydrogen (H2) and carbon monoxide (CO) as energy sources to support growth and survival. Such trace gas oxidation is recognised as a globally significant process that serves as the main sink in the biogeochemical H2 cycle and sustains microbial biodiversity in oligotrophic ecosystems. However, it is unclear whether archaea can also use atmospheric H2. Here we show that a thermoacidophilic archaeon, Acidianus brierleyi (Thermoproteota), constitutively consumes H2 and CO to sub-atmospheric levels. Oxidation occurs across a wide range of temperatures (10 to 70 °C) and enhances ATP production during starvation-induced persistence under temperate conditions. The genome of A. brierleyi encodes a canonical CO dehydrogenase and four distinct [NiFe]-hydrogenases, which are differentially produced in response to electron donor and acceptor availability. Another archaeon, Metallosphaera sedula, can also oxidize atmospheric H2. Our results suggest that trace gas oxidation is a common trait of Sulfolobales archaea and may play a role in their survival and niche expansion, including during dispersal through temperate environments.

Transforaminal Unilateral Biportal Endoscopic Spinal Surgery for Extraforaminal Lumbar Disc Herniation: A Retrospective Observational Study.

OBJECTIVE: Biportal endoscopic spinal surgery (BESS) is recommended as a safer and less destructive option for lumbar disc herniations. However, limited data exist on clinical outcomes for extraforaminal lumbar disc herniation (ELDH) surgery. This retrospective study presents our preliminary experience with transforaminal unilateral BESS for ELDH. METHODS: Patients with lumbar radiculopathy refractory to conservative treatment, diagnosed with ELDH by magnetic resonance imaging, and treated with transforaminal unilateral BESS in 2021-2023 in 2 institutions in Taiwan were eligible for inclusion. Those with lumbar spondylolisthesis grade 2 or more with segmental instability, history of drug abuse or psychiatric diseases, or with a follow-up duration <1 year were excluded. Primary outcomes included visual analog scale for pain, assessed at 1 week, 1 month, 6 months, and 1 year using generalized estimating equations analysis; success and satisfaction of BESS graded by the Macnab criteria; and perioperative complications. Secondary outcomes were operative time and hospital length of stay. RESULTS: Seventeen patients were included in the analysis, with a mean age of 65.8 years; 11 (64.7%) were males and 15 (88.2%) had no prior lumbar spine surgery. mean operative time was 107.9 minutes, and length of stay was 3.5 days. Graded by Macnab criteria, 16 (94.1%) of patients had good to excellent outcomes. Only 1 patient experienced complications. No recurrence/reoperation was observed. Generalized estimating equations analysis showed that postoperative visual analog scale scores decreased significantly at 1 week (adjusted Beta [aBeta] = -5.47, standard error: 0.29, P < 0.001), 1 month (aBeta = -5.82), 6 months (aBeta = -5.88), and 1 year (aBeta = -6.29). CONCLUSIONS: Transforaminal unilateral BESS is an alternative and feasible method for treating ELDH, producing good surgical outcomes with few complications and sustaining pain improvement. Future studies with larger patient numbers and comparisons between BESS and other minimally invasive techniques for ELDH are warranted.

The Medicago SymCEP7 hormone increases nodule number via shoots without compromising lateral root number.

Legumes acquire soil nutrients through nitrogen-fixing root nodules and lateral roots. To balance the costs and benefits of nodulation, legumes negatively control root nodule number by autoregulatory and hormonal pathways. How legumes simultaneously coordinate root nodule and lateral root development to procure nutrients remains poorly understood. In Medicago (Medicago truncatula), a subset of mature C-TERMINALLY ENCODED PEPTIDE (CEP) hormones can systemically promote nodule number, but all CEP hormones tested to date negatively regulate lateral root number. Here we showed that Medicago CEP7 produces a mature peptide, SymCEP7, that promotes nodulation from the shoot without compromising lateral root number. Rhizobial inoculation induced CEP7 in the susceptible root nodulation zone in a Nod factor-dependent manner, and, in contrast to other CEP genes, its transcription level was elevated in the ethylene signaling mutant sickle. Using mass spectrometry, fluorescence microscopy and expression analysis, we demonstrated that SymCEP7 activity requires the COMPACT ROOT ARCHITECTURE 2 receptor and activates the shoot-to-root systemic effector, miR2111. Shoot-applied SymCEP7 rapidly promoted nodule number in the pM to nM range at concentrations up to five orders of magnitude lower than effects mediated by root-applied SymCEP7. Shoot-applied SymCEP7 also promoted nodule number in White Clover (Trifolium repens) and Lotus (Lotus japonicus), which suggests that this biological function may be evolutionarily conserved. We propose that SymCEP7 acts in the Medicago shoot to counter balance the autoregulation pathways induced rapidly by rhizobia to enable nodulation without compromising lateral root growth, thus promoting the acquisition of nutrients other than nitrogen to support their growth.

Mitochondrial Dysfunction in Down Syndrome: From Pathology to Therapy.

Mitochondrial dysfunctions have been described in Down syndrome (DS) caused by either partial or full trisomy of chromosome 21 (HSA21). Mitochondria play a crucial role in various vital functions in eukaryotic cells, especially in energy production, calcium homeostasis and programmed cell death. The function of mitochondria is primarily regulated by genes encoded in the mitochondrion and nucleus. Many genes on HSA21 are involved in oxidative phosphorylation (OXPHOS) and regulation of mitochondrial functions. This review highlights the HSA21 dosage-sensitive nuclear-encoded mitochondrial genes associated with overexpression-related phenotypes seen in DS. This includes impaired mitochondrial dynamics, structural defects and dysregulated bioenergetic profiles such as OXPHOS deficiency and reduced ATP production. Various therapeutic approaches for modulating energy deficits in DS, effects and molecular mechanism of gene therapy and drugs that exert protective effects through modulation of mitochondrial function and attenuation of oxidative stress in DS cells were discussed. It is prudent that improving DS pathophysiological conditions or quality of life may be feasible by targeting something as simple as cellular mitochondrial biogenesis and function.

Incidence of Screw Loosening in Cortical Bone Trajectory Fixation Technique between Single- and Dual-Threaded Screws.

Purpose: This study aims to elucidate the radiological outcome after Cortical bone trajectory (CBT) screw fixation and whether dual-threaded (DT) screws should be used in the fusion surgery. Methods: 159 patients with degenerative lumbar disorder who had undergone midline lumbar inter-body fusion surgery by CBT screw-fixation technique (2014 to 2018). Patient subgroups were based on single-threaded (ST) or DT screw, fixation length, as well as whether fixation involved to sacrum level (S1). Serial dynamic plain films were reviewed and an appearance of a halo phenomenon between screw-bone interfaces was identified as a case of screw loosening. Results: 29 patients (39.7%) in ST group and 10 patients (11.6%) in DT group demonstrated a halo phenomenon (p < 0.0001 ****). After subgrouping with fixation length, the incidence rates of a halo phenomenon in each group were 11.1%:3% (ST-1L vs. DT-1L), 37%:13.8% (ST-2L vs. DT-2L), and 84.2%:23.5% (ST-3L vs. DT-3L). Among the 85 patients with a fixation involved in S1, 26 patients (52%) with single-threaded screw (STS group) and 8 patients (22.8%) with dual-threaded screw (DTS group) demonstrated a halo appearance (p = 0.0078 **). After subgrouping the fixation level, the incidence of a halo appearance in each group was 25%:0% (STS-1L vs. DTS-1L), 40.9%:26.3% (STS-2L vs. DTS-2L), and 87.5%: 30% (STS-3L vs. DTS-3L). Conclusion: Both fixation length and whether fixation involved to S1 contribute to the incidence of screw loosening, the data supports clinical evidence that DT screws had greater fixation strength with an increased fixative stability and lower incidence of screw loosening in CBT screw fixation compared with ST screws. Level of evidence: 2.

Selected Kefir Water from Malaysia Attenuates Hydrogen Peroxide-Induced Oxidative Stress by Upregulating Endogenous Antioxidant Levels in SH-SY5Y Neuroblastoma Cells.

Kefir, a fermented probiotic drink was tested for its potential anti-oxidative, anti-apoptotic, and neuroprotective effects to attenuate cellular oxidative stress on human SH-SY5Y neuroblastoma cells. Here, the antioxidant potentials of the six different kefir water samples were analysed by total phenolic content (TPC), total flavonoid content (TFC), ferric reducing antioxidant power (FRAP), and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) assays, whereas the anti-apoptotic activity on hydrogen peroxide (H2O2) induced SH-SY5Y cells was examined using MTT, AO/PI double staining, and PI/Annexin V-FITC assays. The surface and internal morphological features of SH-SY5Y cells were studied using scanning and transmission electron microscopy. The results indicate that Kefir B showed the higher TPC (1.96 ± 0.54 µg GAE/µL), TFC (1.09 ± 0.02 µg CAT eq/µL), FRAP (19.68 ± 0.11 mM FRAP eq/50 µL), and DPPH (0.45 ± 0.06 mg/mL) activities compared to the other kefir samples. The MTT and PI/Annexin V-FITC assays showed that Kefir B pre-treatment at 10 mg/mL for 48 h resulted in greater cytoprotection (97.04%), and a significantly lower percentage of necrotic cells (7.79%), respectively. The Kefir B pre-treatment also resulted in greater protection to cytoplasmic and cytoskeleton inclusion, along with the conservation of the surface morphological features and the overall integrity of SH-SY5Y cells. Our findings indicate that the anti-oxidative, anti-apoptosis, and neuroprotective effects of kefir were mediated via the upregulation of SOD and catalase, as well as the modulation of apoptotic genes (Tp73, Bax, and Bcl-2).

A new method to visualize CEP hormone-CEP receptor interactions in vascular tissue in vivo.

C-TERMINALLY ENCODED PEPTIDEs (CEPs) control diverse responses in plants including root development, root system architecture, nitrogen demand signalling, and nutrient allocation that influences yield, and there is evidence that different ligands impart different phenotypic responses. Thus, there is a need for a simple method that identifies bona fide CEP hormone-receptor pairings in vivo and examines whether different CEP family peptides bind the same receptor. We used formaldehyde or photoactivation to cross-link fluorescently tagged group 1 or group 2 CEPs to receptors in semi-purified Medicago truncatula or Arabidopsis thaliana leaf vascular tissues to verify that COMPACT ROOT ARCHITECTURE 2 (CRA2) is the Medicago CEP receptor, and to investigate whether sequence diversity within the CEP family influences receptor binding. Formaldehyde cross-linked the fluorescein isothiocyanate (FITC)-tagged Medicago group 1 CEP (MtCEP1) to wild-type Medicago or Arabidopsis vascular tissue cells, but not to the CEP receptor mutants, cra2 or cepr1. Binding competition showed that unlabelled MtCEP1 displaces FITC-MtCEP1 from CRA2. In contrast, the group 2 CEP, FITC-AtCEP14, bound to vascular tissue independently of CEPR1 or CRA2, and AtCEP14 did not complete with FITC-MtCEP1 to bind CEP receptors. The binding of a photoactivatable FITC-MtCEP1 to the periphery of Medicago vascular cells suggested that CRA2 localizes to the plasma membrane. We separated and visualized a fluorescent 105 kDa protein corresponding to the photo-cross-linked FITC-MtCEP1-CRA2 complex using SDS-PAGE. Mass spectrometry identified CRA2-specific peptides in this protein band. The results indicate that FITC-MtCEP1 binds to CRA2, MtCRA2 and AtCEPR1 are functionally equivalent, and the binding specificities of group 1 and group 2 CEPs are distinct. Using formaldehyde or photoactivated cross-linking of biologically active, fluorescently tagged ligands may find wider utility by identifying CEP-CEP receptor pairings in diverse plants.

Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice.

Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0-30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100ß mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.

Level-based analysis of screw loosening with cortical bone trajectory screws in patients with lumbar degenerative disease.

This study aimed to verify the relationship between the number of fusion level and the risk of screw loosening by using cortical bone trajectory (CBT) screws in patients with lumbar degenerative disease.We retrospectively reviewed the serial plain radiograph images of lumbar degenerative disease patients who had undergone posterior fixation and fusion surgery with CBT from 2014. All included patients should have been followed-up with computed tomography scan or plain radiograph for at least 6 months after operation. We individually evaluated the prevalence of screw loosening according to each vertebral level. We also determined whether the number of screw fixation affected the prevalence of screw loosening and whether S1 fixation increased the risk of screw loosening.The screw-loosening rates were high at the S1 level. Moreover, although fixation involved to S1, the loosening rates evidently increased (Fisher exact test, P = .002). The screw-loosening rate was 6.56% in 2 level fusion. However, it increased with the number of fusion levels (3 level: 25.00%, 4 level: 51.16%, and 5 level: 62.50%). To investigate if the number of fusion level affected the S1 screw loosening, we classified the cohort of patients into either involving S1 (S1+ group) or not (S1- group) according to different fusion levels (). The screw loosening between 2 group in 2 (5.56% vs 6.98%) and 3 fusion level (26.32% vs 22.73%) did not exhibit any significant difference. Interestingly, significantly high screw loosening was found in 4 fusion level (60.00% vs 15.38%), indicating that the higher fusion level (4 level) can directly increase the risk of S1 screw loosening.Our data confirmed that the screw-loosening rate increases rate when long segment CBT fixation involves to S1. Therefore, in case of long-segment fixation by using CBT screw, surgeons should be aware of the fusion level of S1.

Water-Extracted Ganoderma lucidum Induces Apoptosis and S-Phase Arrest via Cyclin-CDK2 Pathway in Glioblastoma Cells.

Glioblastoma is one of the most common and most aggressive brain cancers. The current treatment is mainly surgery, chemotherapy, and radiation therapy, but the results are not satisfactory. Ganoderma lucidum (G. lucidum), also called "Lingzhi", is a medicinal mushroom that has been used as a therapeutic agent for the treatment of numerous diseases, including cancer. However, whether it is effective for treating cancer is still unclear. In the present study, the anti-tumor effect of a water extract of G. lucidum was investigated using brain tumor cells. We used an analysis of cell viability, flow cytometry, the IncuCyte live-cell analysis system, and Western blotting to study its effects. The water extract from G. lucidum inhibited cell proliferation in a dose- and time-dependent manner, and it induced mitochondria-mediated apoptosis and cell cycle arrest at S phase via the cyclin-CDK2 pathway in human brain tumor cells. In addition, the G. lucidum extract significantly inhibited cell migration and mesenchymal marker expression based on the IncuCyte live-cell assay and qRT-PCR analysis. In summary, these anti-tumor effects in brain tumor cells suggest that G. lucidum may be useful for treating brain tumors.

Epigenetic Silencing of miR-9 Promotes Migration and Invasion by EZH2 in Glioblastoma Cells.

Glioblastoma (GBM) is the most common primary brain tumor in adults. Tumor invasion is the major reason for treatment failure and poor prognosis in GBM. Inhibiting migration and invasion has become an important therapeutic strategy for GBM treatment. Enhancer of zeste homolog 2 (EZH2) and C-X-C motif chemokine receptor 4 (CXCR4) have been determined to have important roles in the occurrence and development of tumors, but the specific relationship between EZH2 and CXCR4 expression in GBM is less well characterized. In this study, we report that EZH2 and CXCR4 were overexpressed in glioma patients. Furthermore, elevated EZH2 and CXCR4 were correlated with shorter disease-free survival. In three human GBM cell lines, EZH2 modulated the expression of miR-9, which directly targeted the oncogenic signaling of CXCR4 in GBM. The ectopic expression of miR-9 dramatically inhibited the migratory capacity of GBM cells in vitro. Taken together, our results indicate that miR-9, functioning as a tumor-suppressive miRNA in GBM, is suppressed through epigenetic silencing by EZH2. Thus, miR-9 may be an attractive target for therapeutic intervention in GBM.

Phenotype microarrays reveal metabolic dysregulations of neurospheres derived from embryonic Ts1Cje mouse model of Down syndrome.

Down syndrome (DS), is the most common cause of intellectual disability, and is characterized by defective neurogenesis during perinatal development. To identify metabolic aberrations in early neurogenesis, we profiled neurospheres derived from the embryonic brain of Ts1Cje, a mouse model of Down syndrome. High-throughput phenotypic microarray revealed a significant decrease in utilisation of 17 out of 367 substrates and significantly higher utilisation of 6 substrates in the Ts1Cje neurospheres compared to controls. Specifically, Ts1Cje neurospheres were less efficient in the utilisation of glucose-6-phosphate suggesting a dysregulation in the energy-producing pathway. T Cje neurospheres were significantly smaller in diameter than the controls. Subsequent preliminary study on supplementation with 6-phosphogluconic acid, an intermediate of glucose-6-phosphate metabolism, was able to rescue the Ts1Cje neurosphere size. This study confirmed the perturbed pentose phosphate pathway, contributing to defects observed in Ts1Cje neurospheres. We show for the first time that this comprehensive energetic assay platform facilitates the metabolic characterisation of Ts1Cje cells and confirmed their distinguishable metabolic profiles compared to the controls.

Cortical Bone Trajectory Instrumentation with Vertebroplasty for Osteoporotic Thoracolumbar Compression Fracture.

BACKGROUND: Osteoporotic spinal fractures commonly occur in elderly patients with low bone mineral density. In these cases, percutaneous vertebroplasty or percutaneous kyphoplasty can provide significant pain relief and improve mobility. However, studies have reported both the recurrence of vertebral compression fractures at the index level after vertebroplasty and the development of new vertebral fractures at the adjacent level that occur without any additional trauma. Pedicle screw fixation combined with percutaneous vertebroplasty has been proposed as an effective procedure for addressing osteoporotic thoracolumbar fractures. However, in osteoporotic populations, pedicle screws can loosen, pullout, or migrate. Currently, the efficacy of cortical bone trajectory screw fixation for osteoporotic fractures remains unclear. Thus, we assessed the effects of using cortical bone trajectory instrumentation with vertebroplasty on patient outcomes. METHOD: We retrospectively reviewed data from 12 consecutively sampled osteoporotic thoracolumbar fracture patients who underwent cortical bone trajectory instrumentation with vertebroplasty. Patients were enrolled beginning in October 2015 and were followed for >24 months. RESULT: The average age was 74 years, and the average dual-energy x-ray absorptiometry T-score was -3.6. The average visual analog scale pain scores improved from 8 to 2.5 after surgery. The average blood loss was 36.25 mL. All patients regained ambulation and experienced reduced pain post-surgery. No recurrent fractures or instrument failures were recorded during follow-up. CONCLUSIONS: Our findings suggest that cortical bone trajectory instrumentation combined with percutaneous vertebroplasty may be a good option for treating osteoporotic thoracolumbar fractures, as it can prevent recurrent vertebral fractures or related kyphosis in sagittal alignment.

Improving the Identification and Coverage of Plant Transmembrane Proteins in Medicago Using Bottom-Up Proteomics.

Plant transmembrane proteins (TMPs) are essential for normal cellular homeostasis, nutrient exchange, and responses to environmental cues. Commonly used bottom-up proteomic approaches fail to identify a broad coverage of peptide fragments derived from TMPs. Here, we used mass spectrometry (MS) to compare the effectiveness of two solubilization and protein cleavage methods to identify shoot-derived TMPs from the legume Medicago. We compared a urea solubilization, trypsin Lys-C (UR-TLC) cleavage method to a formic acid solubilization, cyanogen bromide and trypsin Lys-C (FA-CTLC) cleavage method. We assessed the effectiveness of these methods by (i) comparing total protein identifications, (ii) determining how many TMPs were identified, and (iii) defining how many peptides incorporate all, or part, of transmembrane domains (TMD) sequences. The results show that the FA-CTLC method identified nine-fold more TMDs, and enriched more hydrophobic TMPs than the UR-TLC method. FA-CTLC identified more TMPs, particularly transporters, whereas UR-TLC preferentially identified TMPs with one TMD, particularly signaling proteins. The results suggest that combining plant membrane purification techniques with both the FA-CTLC and UR-TLC methods will achieve a more complete identification and coverage of TMPs.

Gene and protein expression profiles of JAK-STAT signalling pathway in the developing brain of the Ts1Cje down syndrome mouse model.

Aims: The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Therefore, we aimed to profile the expression of Jak1, Jak2, Stat1, Stat3 and Stat6 at different stages of brain development in the Ts1Cje mouse model of DS. Methods: Whole brain samples from Ts1Cje and wild-type mice at embryonic day (E)10.5, E15, postnatal day (P)1.5; and embryonic cortex-derived neurospheres were collected for gene and protein expression analysis. Gene expression profiles of three brain regions (cerebral cortex, cerebellum and hippocampus) from Ts1Cje and wild-type mice across four time-points (P1.5, P15, P30 and P84) were also analysed. Results: In the developing mouse brain, none of the Jak/Stat genes were differentially expressed in the Ts1Cje model compared to wild-type mice. However, Western blot analyses indicated that phosphorylated (p)-Jak2, p-Stat3 and p-Stat6 were downregulated in the Ts1Cje model. During the postnatal brain development, Jak/Stat genes showed complex expression patterns, as most of the members were downregulated at different selected time-points. Notably, embryonic cortex-derived neurospheres from Ts1Cje mouse brain expressed lower Stat3 and Stat6 protein compared to the wild-type group. Conclusion: The comprehensive expression profiling of Jak/Stat candidates provides insights on the potential role of the JAK-STAT signalling pathway during abnormal development of the Ts1Cje mouse brains.

Comparison of radiological outcomes and complications between single-level and multilevel anterior cervical discectomy and fusion (ACDF) by using a polyetheretherketone (PEEK) cage-plate fusion system.

This study aimed to compare the differences in radiological outcomes and complications between single- and multilevel anterior cervical discectomy and fusion (ACDF) by using a polyetheretherketone (PEEK) cage-plate fusion system.Fifty-seven patients who underwent ACDF via the PEEK cage-plate fusion system were enrolled and subjected to ≥6 months of follow-up. The patients were divided into 4 groups according to different cage-plate implantation levels: 1-level group (n = 17), 2-level group (n = 24), 3-level group (n = 12), and 4-level group (n = 4). Fusion time, changes in segment and global lordotic angle, subsidence rate, and changes in disc and adjacent segmental disc height were subjected to radiological evaluation.The fusion period of multilevel ACDF was longer than that of single-level ACDF. The fusion period of the 3-level (4.09 ±â€Š0.94, P = .004) and 4-level (5.25 ±â€Š0.89, P = .004) group was also significantly longer than that of the 1-level group. The mean lordotic angle in all of the groups was changed in the immediate postoperative period and in the final follow-up. The cage subsidence rates were 11.76% (2/17) in the 1-level group, 20.83% (5/24) in the 2-level group, and 2/12 (16.67%) in the 3-level group. No subsidence occurred in the 4-level groups. Changes in the lower adjacent segmental disc height were significantly increased in multilevel ACDF compared with those in single-level ACDF.Despite the longer fusion time, the outcomes of the proposed system were even better with the greater number of treatment levels by using PEEK cage-plate fusion system. Changes in the lower adjacent segmental disc height should also prolong follow-up duration to investigate the symptomatic adjacent segment degeneration in multilevel ACDF.

Expression Profiling of Notch Signalling Pathway and Gamma-Secretase Activity in the Brain of Ts1Cje Mouse Model of Down Syndrome.

Notch signalling pathway is involved in the proliferation of neural progenitor cells (NPCs), to inhibit neuronal cell commitment and to promote glial cell fate. Notch protein is cleaved by gamma-secretase, a multisubunit transmembrane protein complex that releases the Notch intracellular domain (NICD) and subsequently activates the downstream targets. Down syndrome (DS) individuals exhibit an increased number of glial cells (particularly astrocytes), and reduced number of neurons suggesting the involvement of Notch signalling pathway in the neurogenic-to-gliogenic shift in DS brain. Ts1Cje is a DS mouse model that exhibit similar neuropathology to human DS individuals. To date, the spatiotemporal gene expression of the Notch and gamma-secretase genes have not been characterised in Ts1Cje mouse brain. Understanding the expression pattern of Notch and gamma-secretase genes may provide a better understanding of the underlying mechanism that leads to the shift. Gene expression analysis using RT-qPCR was performed on early embryonic and postnatal development of DS brain. In the developing mouse brain, mRNA expression analysis showed that gamma-secretase members (Psen1, Pen-2, Aph-1b, and Ncstn) were not differentially expressed. Notch2 was found to be downregulated in the developing Ts1Cje brain samples. Postnatal gene expression study showed complex expression patterns and Notch1 and Notch2 genes were found to be significantly downregulated in the hippocampus at postnatal day 30. Results from RT-qPCR analysis from E15.5 neurosphere culture showed an increase of expression of Psen1, and Aph-1b but downregulation of Pen-2 and Ncstn genes. Gamma-secretase activity in Ts1Cje E15.5 neurospheres was significantly increased by fivefold. In summary, the association and the role of Notch and gamma-secretase gene expression throughout development with neurogenic-to-gliogenic shift in Ts1Cje remain undefined and warrant further validation.

Minimal invasive surgical technique in midline lumbar inter-body fusion: A technique note.

Midline lumbar inter-body fusion (MIDLF) surgery with cortical bone trajectory (CBT) screw insertion is a modern fusion technique for spinal surgery. The difference in entry point of this trajectory from conventional pedicle screw surgery offers the potential benefits of less soft tissue dissection and reduced blood loss, post-operative wound pain, and infection risks. Because this is a newly developed technique first announced by Santoni in 2009, most surgeons perform this surgery in a mini-open fashion and require more intra-operative fluoroscopy and ionizing radiation exposure during screw placement. In this article, we demonstrate a minimally invasive midline lumbar interbody fusion (MIS-MIDLF) technique with percutaneous CBT screw placement. Using a designed cannulated awl, we only need a single dimensional fluoroscopy view from anterior to posterior (AP view) to achieve an accurate trajectory and therefore reduce radiation exposure. We report our first ten consecutive patients with degenerative spondylolithesis who underwent MISS-MIDLF and were followed up for more than 18 months. The procedure required a single wound of about 3 cm in length in one to two level fusion surgery and only three to four shots of fluoroscopy were needed for each screw placement. There were no screws malpositioned in subsequent plain films or computer tomography scans. We demonstrate a case with detailed surgical procedures and provide this technique as an alternative approach for surgeons performing MILDF surgery.

Risk of posterior circulation stroke in patients with cervical spondylosis: A nationwide, population-based study.

BACKGROUND AND AIMS: Cervical spondylosis (CS) is reported to be associated with vertebrobasilar insufficiency. However, few cohort studies have investigated the association between CS and posterior circulation ischemic stroke. METHODS: The study cohort comprised 27,990 patients aged ≥18 years with a first diagnosis of CS. The controls consisted of patients with propensity score matched for age, sex, and comorbidities at a ratio of 1:1. We investigated the relationships of CS with ischemic stroke and all-cause mortality. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The average follow-up duration was 6.13 (SD = 3.18) and 6.07 (SD = 3.19) years in the CS and non-CS cohorts, respectively. RESULTS: The mean age of CS patients and non-CS patients was 54.9 ±â€¯13.4 and 55.1 ±â€¯14.9 years. Fifty-eight point five percent of CS patients and 59.2% of non-CS patients were women. CS patients were 1.46 folds more likely to develop a posterior circulation ischemic stroke (95% CI, 1.23-1.72) than non-CS patients. CS patients with myelopathy exhibited a 1.50-fold risk (95% CI, 1.21-1.86) of posterior circulation ischemic stroke compared with non-CS patients; CS patients without myelopathy were at a 1.43-fold risk (95% CI, 1.18-1.73) of posterior ischemic stroke compared with non-CS patients. The risk of posterior ischemic stroke was non-significant between non-CS patients and CS patients who had received spinal anterior decompression (adjusted HR, 1.66; 95% CI, 0.78-3.52), while receiving posterior decompression was associated with a 4.23-fold risk of posterior ischemic stroke (95% CI, 1.05-17.0). CONCLUSIONS: This population-based study showed that CS is associated with an increased risk of posterior circulation ischemic stroke. Surgical posterior decompression was associated with the highest risk of posterior ischemic stroke.

Risk of acute coronary syndrome in patients with cervical spondylosis.

BACKGROUND AND AIMS: Cervical spondylosis (CS) is reported to be associated with increased sympathetic activity and hypertension. However, the cardiovascular (CV) outcomes of patients with CS are largely unknown. METHODS: A national insurance claims dataset of 22 million enrollees in Taiwan during 1999-2010 was used as the research database. We identified 27,948 patients with CS and age-, sex-, and comorbidity-matched controls. By using multivariate logistic regression analysis after adjustment for potential cardiovascular (CV) confounders, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) to quantify the association between CS and acute coronary syndrome (ACS). RESULTS: A total of 744 ACS events were identified among the 27,948 patients with CS. The overall incidence of ACS was 4.27 per 1000 person-years in the CS cohort and 3.90 per 1000 person-years in the non-CS cohort, with an adjusted hazard ratio (aHR) of 1.13 (95% CI = 1.08-1.18). The aHRs of ACS were 1.08 (95% CI = 1.03-1.15) in the CS cohort without myelopathy and 1.20 (95% CI = 1.13-1.28) in the CS cohort with myelopathy, compared with the non-CS cohort. Compared with patients with CS without neurological signs, patients with CS receiving rehabilitation exhibited a 0.67 aHRs of ACS (95% CI = 0.59-0.76), whereas those with neurological signs receiving spinal decompression exhibited 0.73 aHRs of ACS (95% CI = 0.63-0.84). CONCLUSIONS: CS is associated with an increased risk of ACS. Receiving treatment for CS, either rehabilitation or spinal decompression, is associated with less risk of ACS.