Market Needs and Methodologies Associated with Patient Lipidomic Diagnoses and Analyses.

This chapter conducts an in-depth exploration of the impact of musculoskeletal (MSK) disorders and injuries, with a specific emphasis on their consequences within the older population demographic. It underscores the escalating demand for innovative interventions in MSK tissue engineering. The chapter also highlights the fundamental role played by lipid signaling mediators (LSMs) in tissue regeneration, with relevance to bone and muscle recovery. Remarkably, Prostaglandin E2 (PGE2) emerges as a central orchestrator in these regenerative processes. Furthermore, the chapter investigates the complex interplay between bone and muscle tissues, explaining the important influence exerted by LSMs on their growth and differentiation. The targeted modulation of LSM pathways holds substantial promise as a beneficial way for addressing muscle disorders. In addition to these conceptual understandings, the chapter provides a comprehensive overview of methodologies employed in the identification of LSMs, with a specific focus on the Liquid Chromatography-Mass Spectrometry (LC-MS). Furthermore, it introduces a detailed LC MS/MS-based protocol tailored for the detection of PGE2, serving as an invaluable resource for researchers immersed in this dynamic field of study.

Monitoring and evaluation of childhood stunting reduction program based on fish supplement product in North Sumatera, Indonesia.

The government of Serdang Bedagai Regency initiated a supplementation program to reduce the high prevalence of stunting in the area by delivering extra supplementation, which were nutritious biscuits from national government and fish-based supplement produced from local resources. A 6-month study from April 2022 to September 2022 was conducted to monitor and evaluate the government program that involved 219 under-5-year-old children with height-for-age Z-score (HAZ-score) below - 2. We observed the stunting prevalence reduction by 37.00%, where 81 children recovered from stunting (HAZ-score ≥ - 2). Furthermore, the mean HAZ-score and WHZ-score (Weight-for-Height Z-score) were monitored to significantly improve by 0.97 ± 1.45 (P-value = 1.74e-14) and 1.00 ± 2.18 (P-value = and 2.40e-8), subsequently. The most significant improvement in HAZ-score was monitored among children receiving fish-based supplements with 1.04 ± 1.44 improvement (P-value = 6.59e-17). Then, a significant WHZ-score improvement was reported from children consuming fish-based supplements and a combination of fish-based supplements with nutritious biscuits (P-value = 2.32e-8 and 5.48e-5) by 1.04 ± 2.29 and 0.83 ± 1.84, respectively. The results of the observation become evidence that the program could effectively reduce the prevalence of stunting in children below five years old, especially among children who received locally produced fish-based supplements.

Global tuberculosis disease and infection in systemic lupus erythematosus patients: A systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) is one of the most common infections among systemic lupus erythematosus (SLE) patients. We aimed to evaluate the global prevalence of TB infection and disease, its type, and medication risk factors in SLE patients. METHODS: We searched PubMed, Science Direct, EBSCO, and Web of Science databases from inception to April 30, 2023, and included studies assessing TB among SLE patients. We estimated the prevalence of TB disease (including type of TB disease), TB infection, and SLE medication as TB risk factors. Meta-analysis was performed using Stata 14.2 and Review Manager 5.3. RESULTS: Twenty-seven studies met the eligibility criteria. The global prevalence of TB disease was 4% (95% confidence interval (CI): 3-4%, n = 25) and TB infection was 18% (95% CI: 10-26%, n = 3). The pooled prevalence of pulmonary TB, extrapulmonary TB, and disseminated TB were 2% (95% CI: 2-3%, n = 20), 1% (95% CI: 1-2%, n = 17), and 1% (95% CI: 0-1%, n = 6), respectively. The 1-year cumulative glucocorticoid (GC) dose in SLE patients contracting TB was higher than in those without TB, having a mean difference of 2.56 (95% CI: 0.22-4.91, p < .00001, n = 3). The odd ratio of TB was 2.11 (95% CI: 1.01-4.41, p = .05, n = 3) in SLE patients receiving methylprednisolone (MP) pulse therapy as compared to those without MP pulse therapy. Other immunosuppressive agents were not significantly associated with TB. CONCLUSION: TB prevalence in SLE was relatively high and associated with GC. Awareness of TB and lowering GC dose are warranted to alleviate the TB burden in SLE.

Detection Rate of PSMA PET Using Different Ligands in Men with Biochemical Recurrent Prostate Cancer Following Radical Treatment: A Systematic Review and Meta-analysis of Prospective Studies.

BACKGROUND: Despite the acknowledged diagnostic detection rate of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging in prostate cancer, little is known about the quality of evidence, particularly focusing on prospective studies. Most systematic reviews are based on retrospective reports. RATIONALE AND OBJECTIVES: To conduct systematic review and meta-analysis of prospective studies reporting the diagnostic detection rate of PSMA PET (computed tomography (CT) and MR) for the detection of biochemically recurrent metastatic prostate cancer. MATERIALS AND METHODS: We systematically searched PubMed, MEDLINE, Embase, and Scopus, from database until March 1, 2023 for randomized controlled trials and prospective studies using PSMA PET imaging in prostate cancer. The primary endpoint was to assess diagnostic detection rate of PSMA PET imaging in the detection of recurrent prostate cancer in men with biochemical relapse following radical treatment. We calculated the pooled overall diagnostic detection rate with 95% CI using a random-effects model and assessed the heterogeneity between the studies including risk of biases estimation. RESULTS: A total of 6800 patients from 32 articles were included in this study. The overall detection rate of PSMA PET for prostate cancer was 0.67 (95% CI, 0.63, 0.71). For histologically confirmed lymph nodes, the PPV from 13 prospective studies containing 1496 patients was 0.96 (95% CI, 0.93, 0.99). We performed a subgroup analysis of PSMA PET detection rates according to categorically grouped Prostate Specific Antigen (PSA) values of 0-0.5, 0.5-1.0, 1.0-2.0, and >2.0 ng/ml and obtained detection rates of 0.44, 0.63, 0.82, and 0.94, respectively. The detection rate of 18F PSMA was better in men with a PSA between 1 ng/ml and 2 ng/ml in comparison to 68Ga PSMA (0.91 with 95% CI 0.81-0.99 vs. 0.79 with 95% CI 0.73, 0.85). CONCLUSION: PSMA PET imaging provides a good detection rate for the metastatic recurrence of prostate cancer in men with biochemical relapse following radical treatment. The detection rate improves significantly above a serum PSA value of 1 ng/ml. The diagnostic detection rate of 18F-PSMA is best at PSA values between 1 and 2 ng/ml, in comparison to 68Ga PSMA. This conclusion is heavily biased, further research needs to focus on better methodology to minimize the risk of biases.

ZFH-2 is required for Drosophila ovarian follicle development and is expressed at the band/interband boundaries of polytene chromosomes.

The transcription factor ZFH-2 has well-documented roles in Drosophila neurogenesis and other developmental processes. Here we provide the first evidence that ZFH-2 has a role in oogenesis. We demonstrate that ZFH-2 is expressed in the wild-type ovary and that a loss of zfh-2 function produces a mutant ovary phenotype where egg chambers are reduced in number and fused. We also show that a loss of zfh-2 function can suppress a daughterless loss-of-function ovary phenotype suggesting a possible genetic relationship between these two genes in the ovary. We also show that ZFH-2 is located at the boundary between bands and interbands on polytene chromosomes and that at a subset of these sites ZFH-2 colocalizes with the insulator/promoter cofactor CP190.

Purification of functional mouse skeletal muscle mitochondria using percoll density gradient centrifugation.

OBJECTIVE: Our goal was to isolate purified mitochondria from mouse skeletal muscle using a Percoll density gradient and to assess bioenergetic function and purity via Seahorse Extracellular Flux (XF) Analyses and mass spectrometry. RESULTS: Mitochondria isolated from murine quadriceps femoris skeletal muscle using a Percoll density gradient method allowed for minimally contaminated preparations with time from tissue harvest to mitochondrial isolation and quantification in about 3-4 h. Percoll purification from 100 to 200 mg fresh tissue yielded ~ 200-400 ug protein. Mitochondrial bioenergetics evaluated using the Seahorse XFe96 analyzer, a high-throughput respirometry platform, showed optimum mitochondrial input at 500 ng with respiratory control ratio ranging from 3.9 to 7.1 using various substrates demonstrating a high degree of functionality. Furthermore, proteomic analysis of Percoll-enriched mitochondria isolated from skeletal muscle using this method showed significant enrichment of mitochondrial proteins indicating high sample purity. This study established a methodology that ensures sufficient high quality mitochondria for downstream analyses such as mitochondrial bioenergetics and proteomics.

Genetic variation among elite inbred lines suggests potential to breed for BNI-capacity in maize.

Biological nitrification inhibition (BNI) is a plant function where root systems release antibiotic compounds (BNIs) specifically aimed at suppressing nitrifiers to limit soil-nitrate formation in the root zone. Little is known about BNI-activity in maize (Zea mays L.), the most important food, feed, and energy crop. Two categories of BNIs are released from maize roots; hydrophobic and hydrophilic BNIs, that determine BNI-capacity in root systems. Zeanone is a recently discovered hydrophobic compound with BNI-activity, released from maize roots. The objectives of this study were to understand/quantify the relationship between zeanone activity and hydrophobic BNI-capacity. We assessed genetic variability among 250 CIMMYT maize lines (CMLs) characterized for hydrophobic BNI-capacity and zeanone activity, towards developing genetic markers linked to this trait in maize. CMLs with high BNI-capacity and ability to release zeanone from roots were identified. GWAS was performed using 27,085 SNPs (with unique positions on the B73v.4 reference genome, and false discovery rate = 10), and phenotypic information for BNI-capacity and zeanone production from root systems. Eighteen significant markers were identified; three associated with specific BNI-activity (SBNI), four with BNI-activity per plant (BNIPP), another ten were common between SBNI and BNIPP, and one with zeanone release. Further, 30 annotated genes were associated with the significant SNPs; most of these genes are involved in pathways of "biological process", and one (AMT5) in ammonium regulation in maize roots. Although the inbred lines in this study were not developed for BNI-traits, the identification of markers associated with BNI-capacity suggests the possibility of using these genomic tools in marker-assisted selection to improve hydrophobic BNI-capacity in maize.

Suture suspension sling arthroplasty in thumb carpometacarpal joint arthritis: A case series.

INTRODUCTION AND IMPORTANCE: Thumb carpometacarpal (CMC) joint arthritis is the most common condition in older adults and an upper-extremity surgical reconstruction site. Multiple treatments for CMC arthritis have been developed. Among them, suspension sling arthroplasty provides great results without requiring a tendon graft or advanced implants. However, it is rarely used in Indonesia. CASE PRESENTATION: The modified suture suspension sling arthroplasty technique developed by Arnold Peter C Weiss was performed on three patients with CMC joint arthritis. In this procedure, after trapeziectomy, a nonabsorbable suture is performed to create a hammock between the abductor pollicis longus and flexor carpi radialis tendon to rest the thumb base metacarpal. The rehabilitation protocol was then continued, and the postoperative clinical condition was observed. Three weeks postoperatively, none of the three patients complained of pain. At 3 months postoperatively, there were no signs of infection, and all patients continued the rehabilitation protocol. At 6 months postoperatively, thumb range of motion was excellent, with no sign of infection and an increased DASH score of <5. CLINICAL DISCUSSION: Multiple treatments for CMC joint arthritis have been described in the literature but the indications and which treatment provides the best results were unclear. Among the various suspension sling methods, trapeziectomy is important for treating CMC joint arthritis. CONCLUSION: Suture suspension arthroplasty for treating thumb CMC joint arthritis achieved excellent clinical results and has several advantages, including shorter surgical time, no additional incision, reduced cost, no tendon harvesting, and implant fixation.

Evaluating Radiation Exposure in Patients with Stable Chest Pain in the SCOT-HEART Trial.

Background In the Scottish Computed Tomography of the Heart (SCOT-HEART) trial in individuals with stable chest pain, a treatment strategy based on coronary CT angiography (CTA) led to improved outcomes. Purpose To assess 5-year cumulative radiation doses of participants undergoing investigation for suspected angina due to coronary artery disease with or without coronary CTA. Materials and Methods This secondary analysis of the SCOT-HEART trial included data from six of 12 recruiting sites and two of three imaging sites. Participants were recruited between November 18, 2010, and September 24, 2014, with follow-up through January 31, 2018. Study participants had been randomized (at a one-to-one ratio) to standard care with CT (n = 1466) or standard care alone (n = 1428). Imaging was performed on a 64-detector (n = 223) or 320-detector row scanner (n = 1466). Radiation dose from CT (dose-length product), SPECT (injected activity), and invasive coronary angiography (ICA; kerma-area product) was assessed for 5 years after enrollment. Effective dose was calculated using conversion factors appropriate for the imaging modality and body region imaged (using 0.026 mSv/mGy · cm for cardiac CT). Results Cumulative radiation dose was assessed in 2894 participants. Median effective dose was 3.0 mSv (IQR, 2.6-3.3 mSv) for coronary calcium scoring, 4.1 mSv (IQR, 2.6-6.1 mSv) for coronary CTA, 7.4 mSv (IQR, 6.2-8.5 mSv) for SPECT, and 4.1 mSv (IQR, 2.5-6.8 mSv) for ICA. After 5 years, total per-participant cumulative dose was higher in the CT group (median, 8.1 mSv; IQR, 5.5-12.4 mSv) compared with standard-care group (median, 0 mSv; IQR, 0-4.5 mSv; P < .001). In participants who underwent any imaging, cumulative radiation exposure was higher in the CT group (n = 1345; median, 8.6 mSv; IQR, 6.1-13.3 mSv) compared with standard-care group (n = 549; median, 6.4 mSv; IQR, 3.4-9.2 mSv; P < .001). Conclusion In the SCOT-HEART trial, the 5-year cumulative radiation dose from cardiac imaging was higher in the coronary CT angiography group compared with the standard-care group, largely because of the radiation exposure from CT. Clinical trial registration no. NCT01149590 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Dodd and Bosserdt in this issue.

Effects of PTH on osteoblast bioenergetics in response to glucose.

Parathyroid hormone acts through its receptor, PTHR1, expressed on osteoblasts, to control bone remodeling. Metabolic flexibility for energy generation has been demonstrated in several cell types dependent on substrate availability. Recent studies have identified a critical role for PTH in regulating glucose, fatty acid and amino acid metabolism thus stimulating both glycolysis and oxidative phosphorylation. Therefore, we postulated that PTH stimulates increased energetic output by osteoblasts either by increasing glycolysis or oxidative phosphorylation depending on substrate availability. To test this hypothesis, undifferentiated and differentiated MC3T3E1C4 calvarial pre-osteoblasts were treated with PTH to study osteoblast bioenergetics in the presence of exogenous glucose. Significant increases in glycolysis with acute ∼1 h PTH treatment with minimal effects on oxidative phosphorylation in undifferentiated MC3T3E1C4 in the presence of exogenous glucose were observed. In differentiated cells, the increased glycolysis observed with acute PTH was completely blocked by pretreatment with a Glut1 inhibitor (BAY-876) resulting in a compensatory increase in oxidative phosphorylation. We then tested the effect of PTH on the function of complexes I and II of the mitochondrial electron transport chain in the absence of glycolysis. Utilizing a novel cell plasma membrane permeability mitochondrial (PMP) assay, in combination with complex I and II specific substrates, slight but significant increases in basal and maximal oxygen consumption rates with 24 h PTH treatment in undifferentiated MC3T3E1C4 cells were noted. Taken together, our data demonstrate for the first time that PTH stimulates both increases in glycolysis and the function of the electron transport chain, particularly complexes I and II, during high energy demands in osteoblasts.

A Novel ENU-Induced Mfn2 Mutation Causes Motor Deficits in Mice without Causing Peripheral Neuropathy.

Mitochondrial fission and fusion are required for maintaining functional mitochondria. The mitofusins (MFN1 and MFN2) are known for their roles in mediating mitochondrial fusion. Recently, MFN2 has been implicated in other important cellular functions, such as mitophagy, mitochondrial motility, and coordinating endoplasmic reticulum-mitochondria communication. In humans, over 100 MFN2 mutations are associated with a form of inherited peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Here we describe an ENU-induced mutant mouse line with a recessive neuromuscular phenotype. Behavioral screening showed progressive weight loss and rapid deterioration of motor function beginning at 8 weeks. Mapping and sequencing revealed a missense mutation in exon 18 of Mfn2 (T1928C; Leu643Pro), within the transmembrane domain. Compared to wild-type and heterozygous littermates, Mfn2L643P/L643P mice exhibited diminished rotarod performance and decreases in activity in the open field test, muscular endurance, mean mitochondrial diameter, sensory tests, mitochondrial DNA content, and MFN2 protein levels. However, tests of peripheral nerve physiology and histology were largely normal. Mutant leg bones had reduced cortical bone thickness and bone area fraction. Together, our data indicate that Mfn2L643P causes a recessive motor phenotype with mild bone and mitochondrial defects in mice. Lack of apparent nerve pathology notwithstanding, this is the first reported mouse model with a mutation in the transmembrane domain of the protein, which may be valuable for researchers studying MFN2 biology.

Purification of functional mouse skeletal muscle mitochondria using Percoll density gradient centrifugation.

Objective: Our goal was to isolate purified mitochondria from mouse skeletal muscle using a Percoll density gradient and to assess bioenergetic function and purity via Seahorse Extracellular Flux (XF) Analyses and mass spectrometry. Results: Mitochondria isolated from murine quadriceps femoris skeletal muscle using a Percoll density gradient method allowed for minimally contaminated preparations with time from tissue harvest to mitochondrial isolation and quantification in about 3-4 hours. Percoll purification from 100-200 mg fresh tissue yielded ∼200-400 ug protein. Mitochondrial bioenergetics evaluated using the Seahorse XFe96 analyzer, a high-throughput respirometry platform, showed optimum mitochondrial input at 500 ng with respiratory control ratio ranging from 3.9-7.1 using various substrates demonstrating a high degree of functionality. Furthermore, proteomic analysis of Percoll-enriched mitochondria isolated from skeletal muscle using this method showed significant enrichment of mitochondrial proteins indicating high sample purity. This study established a methodology that ensures sufficient high quality mitochondria for downstream analyses such as mitochondrial bioenergetics and proteomics.

Potent pan huACE2-dependent sarbecovirus neutralizing monoclonal antibodies isolated from a BNT162b2-vaccinated SARS survivor.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to their ability to escape neutralizing antibodies induced by vaccination or prior infection, highlighting the need to develop broad-spectrum vaccines and therapeutics. Most human monoclonal antibodies (mAbs) reported to date have not demonstrated true pan-sarbecovirus neutralizing breadth especially against animal sarbecoviruses. Here, we report the isolation and characterization of highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus from a SARS-CoV survivor vaccinated with BNT162b2. Among the six mAbs identified, one (E7) showed better huACE2-dependent sarbecovirus neutralizing potency and breadth than any other mAbs reported to date. Mutagenesis and cryo-electron microscopy studies indicate that these mAbs have a unique RBD contact footprint and that E7 binds to a quaternary structure-dependent epitope.

Peptide derived C. striata albumin as a natural angiotensin-converting enzyme inhibitor.

As one of the most popular sources for fish albumin, Channa striata has been considered as a promising substitute for human albumin. However, scientific information regarding its genomic and proteomic is very limited, making its identification rather complicated. In this study, we aimed to isolate, characterize, and examine the bioactivity of protein and peptide derivatives of C. striata albumin. Fractionation of albumin from C. striata extract was conducted using Cohn Process and the yield was evaluated. The peptides were further produced by enzymatic hydrolysis. All these proteins were studied using tricine-SDS PAGE and tested for in vitro ACE inhibition. Dry weights of the Fraction-5, where the albumin was more abundant and purer, was 3.8 ± 2.1%. Based on tricine-SDS PAGE analysis, two bands of protein, e.g., approximately 10 and 13 kDa, were detected with highest intensity found in Fraction-5, which might be albumin of C. striata. An increasing trend of ACE inhibition by the fractions was observed, ranging from 7.09 to 22.99%. The highest ACEI activity was found in peptides from alcalase hydrolysis with molecular size <3 kDa (56.65 ± 2.32%, IC50 36.93 µg/mL). This value was also statistically significant compared with the non-hydrolyzed Fraction-5 and Parental Fraction, which were 23.48 ± 3.11% (P < 0.05) and 13.02 ± 0.68% (P < 0.01), respectively. Taken together, these findings suggest a promising potential of peptide-derived C. striata albumin for natural antihypertensive agents.

Comparison of interferon-gamma production between TB1 and TB2 tubes of QuantiFERON-TB Gold Plus: a meta-analysis.

OBJECTIVES: CD8 T-cells play an important role in interferon-gamma (IFN-γ) production as a host defense against tuberculosis (TB) infection. Therefore, QuantiFERON-TB Gold Plus (QFT-Plus) was developed by adding a TB2 tube beside the TB1 tube. This study aimed to compare and analyze the difference in IFN-γ production between the two tubes in general and specific populations. CONTENT: PubMed, Web of Science, and EBSCO were searched for studies reporting IFN-γ production levels in the TB1 and TB2 tubes. Statistical analysis was performed using RevMan 5.3. SUMMARY: A total of 17 studies met the inclusion criteria. The IFN-γ production in the TB2 tube was statistically higher than that in the TB1 tube (mean difference (MD)=0.02, 95 % confidence interval (95 % CI): 0.01-0.03). Further subgroup analysis in specific populations revealed that the MD of IFN-γ production between the TB2 and TB1 tubes was significantly higher in active TB subjects than in latent TB infection (LTBI) subjects (MD=1.13, 95 % CI: 0.49-1.77, and MD=0.30, 95 % CI: 0.00-0.60, respectively). A similar finding was found in immune-mediated inflammatory disease subjects, but not statistically significant. Interestingly, IFN-γ production capacity was lower in active TB subjects than in LTBI subjects in each of the TB1 and TB2 tubes. OUTLOOK: This study is the first to systematically compare IFN-γ production between the TB1 and TB2 tubes. The IFN-γ production was higher in the TB2 tube than in the TB1 tube, representing the host's CD8 T-cell response magnitude to TB infection.

Transcarotid artery revascularization in blunt carotid injury.

Introduction: Transcarotid artery revascularization (TCAR) with flow reversal has substantially changed the management of carotid artery stenosis, enabling an endovascular approach with a periprocedural stroke rate as low as or lower than that of open carotid surgery. The use of TCAR for blunt carotid artery injury has not yet been described. Methods: A review of the use of TCAR for blunt carotid artery injury was performed at a single center from October 2020 to August 2021. The patient demographics, mechanism of injury, and outcomes were collected and compared. Results: Ten carotid stents were placed via TCAR in eight patients for hemodynamically significant blunt carotid artery injuries. No periprocedural neurologic events occurred, and all stents remained patent during short-term follow-up. Conclusions: TCAR is feasible and safe in the management of significant blunt carotid artery injuries. More data are needed regarding the long-term outcomes and ideal surveillance intervals.

The mitophagy receptor BNIP3 is critical for the regulation of metabolic homeostasis and mitochondrial function in the nucleus pulposus cells of the intervertebral disc.

The contribution of mitochondria to the metabolic function of hypoxic NP cells has been overlooked. We have shown that NP cells contain networked mitochondria and that mitochondrial translocation of BNIP3 mediates hypoxia-induced mitophagy. However, whether BNIP3 also plays a role in governing mitochondrial function and metabolism in hypoxic NP cells is not known. BNIP3 knockdown altered mitochondrial morphology, and number, and increased mitophagy. Interestingly, BNIP3 deficiency in NP cells reduced glycolytic capacity reflected by lower production of lactate/H+ and lower ATP production rate. Widely targeted metabolic profiling and flux analysis using 1-2-13C-glucose showed that the BNIP3 loss resulted in redirection of glycolytic flux into pentose phosphate and hexosamine biosynthesis as well as pyruvate resulting in increased TCA flux. An overall reduction in one-carbon metabolism was noted suggesting reduced biosynthesis. U13C-glutamine flux analysis showed preservation of glutamine utilization to maintain TCA intermediates. The transcriptomic analysis of the BNIP3-deficient cells showed dysregulation of cellular functions including membrane and cytoskeletal integrity, ECM-growth factor signaling, and protein quality control with an overall increase in themes related to angiogenesis and innate immune response. Importantly, we observed strong thematic similarities with the transcriptome of a subset of human degenerative samples. Last, we noted increased autophagic flux, decreased disc height index and aberrant COL10A1/collagen X expression, signs of early disc degeneration in young adult bnip3 knockout mice. These results suggested that in addition to mitophagy regulation, BNIP3 plays a role in maintaining mitochondrial function and metabolism, and dysregulation of mitochondrial homeostasis could promote disc degeneration.Abbreviations: ECAR extracellular acidification rate; HIF hypoxia inducible factor; MFA metabolic flux analysis; NP nucleus pulposus; OCR oxygen consumption rate; ShBnip3 short-hairpin Bnip3.

Depiction of detailed surgical anatomy and CSF flow information using a single MRI technique.

We describe a novel MRI sequence (T2 SPACE) capable of demonstrating detailed structural anatomy and functional CSF flow information simultaneously. While traditionally, a variety of sequences are utilised for this purpose, we have highlighted the advantages of this technique over traditional approaches, using example of a patient with CSF loculation in prepontine/suprasellar cistern, causing third ventricular compression and hydrocephalus. The sequence depicted the surgical anatomy by showing the web/cyst wall as well as CSF flow entering the cyst potentially causing increased pressure.