HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III.

Molecular chaperones are critical for protein homeostasis and are implicated in several human pathologies such as neurodegeneration and cancer. While the binding of chaperones to nascent and misfolded proteins has been studied in great detail, the direct interaction between chaperones and RNA has not been systematically investigated. Here, we provide the evidence for widespread interaction between chaperones and RNA in human cells. We show that the major chaperone heat shock protein 70 (HSP70) binds to non-coding RNA transcribed by RNA polymerase III (RNA Pol III) such as tRNA and 5S rRNA. Global chromatin profiling revealed that HSP70 binds genomic sites of transcription by RNA Pol III. Detailed biochemical analyses showed that HSP70 alleviates the inhibitory effect of cognate tRNA transcript on tRNA gene transcription. Thus, our study uncovers an unexpected role of HSP70-RNA interaction in the biogenesis of a specific class of non-coding RNA with wider implications in cancer therapeutics.

Early cement augmentation may be a good treatment option for pain relief for osteoporotic compression fractures: a systematic review and meta-analysis.

PURPOSE: The incidence of osteoporotic compression fractures (VCFs) have been rising over the past decades. Presently, vertebral cement augmentation procedures such as balloon kyphoplasty and vertebroplasty are common treatments allowing pain relief and functional recovery. However, there is controversy on whether different timeframes for cement augmentation affects clinical outcomes. Hence, this study aimed to compare pain relief and complication rates between early versus late cement augmentation. METHODS: A comprehensive systematic review of PubMed, EMBASE, Scopus and Cochrane Library was conducted, identifying studies that compared early versus late cement augmentation for VCFs. As the definitions of "early" and "late" phases across studies are heterogenous, we established the cut-off between early and late phase as intervals to accommodate as many studies as possible for analysis. We conducted two separate analyses with different cut-off intervals and included studies that reported interventions within these respective time intervals. In analysis 1, we included studies which grouped patients into "early" and "late" group based on a cut-off time frame of 2-4 weeks. On the other hand, in analysis 2, we included studies which grouped patients into "early" and "late" groups based on a cut-off time frame of 6-8 weeks. Meta-analysis was conducted via random-effect models, comparing outcomes of interest between early and late groups. RESULTS: Eleven studies were included. The total cohort size was 712 and 775 patients in analysis 1 and 2 respectively. Mean follow-up was 12.9 ± 3.7 months and 11 ± 0.6 months respectively. VAS change at final follow-up was significantly greater in the early group for both analyses. (MD = - 0.66, p = 0.01; and MD = - 1.18, p < 0.005 respectively). There was no significant difference in post-operative absolute VAS score, number of cement leakage, number of adjacent compression fractures and local kyphotic angle, for both analyses. Patients in both groups experienced reductions in VAS score that exceeded the minimum clinically important difference. CONCLUSION: Both early and late timeframes for cement augmentation offered significant improvement in pain relief, with similar post-operative absolute pain score, kyphotic angle, cement leakage and adjacent vertebral fractures. Early surgery may offer substantial pain relief in patients presenting with pain as early as < 2-4 weeks of VCFs.

Titanium (Ti) cages may be superior to polyetheretherketone (PEEK) cages in lumbar interbody fusion: a systematic review and meta-analysis of clinical and radiological outcomes of spinal interbody fusions using Ti versus PEEK cages.

AIM: Interbody cages are commonly used to augment interbody fusion. Commonly used materials include titanium (Ti) and polyetheretherketone (PEEK), with their inherent differences. The aim of this study is to perform a systematic review and meta-analysis to compare between the various clinical and radiological outcomes of Ti and PEEK interbody spinal cages. METHODS: A systematic review and meta-analysis comparing clinical and radiological outcomes between Ti and PEEK interbody cages in patients undergoing spinal fusion was performed. PubMed, Scopus, Web of Science, Embase, and Cochrane Central Register of Controlled Trials database were searched. All studies that compared the clinical and radiological outcomes of patients who underwent Ti and PEEK cages were included. Subgroup analyses was performed to differentiate between patients who had cervical and lumbar interbody fusion. RESULTS: A total of 11 articles were identified, with a total of 743 patients. Spinal fusion rates at final follow-up did not differ between Ti and PEEK cages (OR 1.50, 95% CI 0.57-3.94, P = 0.41), although in patients undergoing lumbar fusion, Ti cages demonstrated superior fusion (OR 2.12, 95% CI 1.05-4.28, P = 0.04). In patients with non-infective etiologies, Ti cages had a higher rate of cage subsidence (RR 2.17, 95% CI 1.13-4.16, P = 0.02). Both types of cages had similar operating time, postoperative hematoma formation, neuropathic pain, segmental angle correction and postoperative clinical outcome improvement. CONCLUSION: In non-infective lumbar spine conditions, Ti cage may be the superior option due to the higher fusion rate. LEVEL OF EVIDENCE: III.

A novel hospital capacity versus clinical justification triage score (CCTS) for prioritization of spinal surgeries in the "new normal state" of the COVID-19 pandemic.

INTRODUCTION: During the Coronavirus disease 2019 outbreak, while healthcare systems and hospitals are diverting their resources to combat the pandemic, patients who require spinal surgeries continue to accumulate. The aim of this study is to describe a novel hospital capacity versus clinical justification triage score (CCTS) to prioritize patients who require surgery during the "new normal state" of the COVID-19 pandemic. METHODOLOGY: A consensus study using the Delphi technique was carried out among clinicians from the Orthopaedic Surgery, Neurosurgery, and Anaesthesia departments. Three rounds of consensus were carried out via survey and Webinar discussions. RESULTS: A 50-points score system consisting of 4 domains with 4 subdomains was formed. The CCTS were categorized into the hospital capacity, patient factors, disease severity, and surgery complexity domains. A score between 30 and 50 points indicated that the proposed operation should proceed without delay. A score of less than 20 indicates that the proposed operation should be postponed. A score between 20 and 29 indicates that the surgery falls within a grey area where further discussion should be undertaken to make a joint justification for approval of surgery. CONCLUSION: This study is a proof of concept for the novel CCTS scoring system to prioritize surgeries to meet the rapidly changing demands of the COVID-19 pandemic. It offers a simple and objective method to stratify patients who require surgery and allows these complex and difficult decisions to be unbiased and made transparently among surgeons and hospital administrators.

Optical steering of electron beam in laser plasma accelerators.

Using a Dazzler system and tilting a compressor grating, we provide an effective way of using the laser group delay dispersion to continuously steer the electron beam accelerated by an asymmetric laser wakefield. The deviation angle of the electron beam was the same as that of the angularly chirped laser pulse from its initial optical axis, which is determined by the laser pulse-front-tilt (PFT). This method can be utilized to continuously control over the pointing direction of electron bunches to the requisite trajectories, especially for practical applications in highly sensitive alignment devices such as electron-positron colliders or undulators. Additionally, we investigate the effect of PFT on the properties of the electron beam.

Detection and characterization of a novel bat-borne coronavirus in Singapore using multiple molecular approaches.

Bats are important reservoirs and vectors in the transmission of emerging infectious diseases. Many highly pathogenic viruses such as SARS-CoV and rabies-related lyssaviruses have crossed species barriers to infect humans and other animals. In this study we monitored the major roost sites of bats in Singapore, and performed surveillance for zoonotic pathogens in these bats. Screening of guano samples collected during the survey uncovered a bat coronavirus (Betacoronavirus) in Cynopterus brachyotis, commonly known as the lesser dog-faced fruit bat. Using a capture-enrichment sequencing platform, the full-length genome of the bat CoV was sequenced and found to be closely related to the bat coronavirus HKU9 species found in Leschenault's rousette discovered in the Guangdong and Yunnan provinces.

Short-period high-strength helical undulator by laser-driven bifilar capacitor coil.

Laser wakefield accelerators have emerged as a promising candidate for compact synchrotron radiation and even x-ray free electron lasers. Today, to make the electrons emit electromagnetic radiation, the trajectories of laser wakefield accelerated electrons are deflected by transverse wakefield, counter-propagating laser field or external permanent magnet insertion device. Here, we propose a novel type of undulator that has a period of a few hundred microns and a magnetic field of tens of Tesla. The undulator consists of a bifilar capacitor-coil target that sustains a strong discharge current that generates a helical magnetic field around the coil axis when irradiated by a high-energy laser. Coupling this undulator with state-of-the-art laser wakefield accelerators can, simultaneously, produce ultra-bright quasi-monochromatic x-rays with tunable energy ranging 5-250 keV and optimize the free electron laser parameter and gain length compared with a permanent magnet-based undulator. This concept may pave a path toward ultra-compact synchrotron radiation and even x-ray free electron lasers.

Is MIS-TLIF superior to open TLIF in obese patients?: A systematic review and meta-analysis.

PURPOSE: Obesity is a global health problem. It increases the risk of surgical complications and re-operations. While both MIS-TLIF and O-TLIF are reported to have comparably good long-term outcomes for non-obese patients, no consensus has been reached for obese patients. METHODS: A comprehensive search of the published literature was performed: PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials database in accordance to the PRISMA 2009 checklist. Data were collected with attention to baseline demographics, intra-operative blood loss, duration of surgery, surgical complications, hospitalization stay, VAS and Oswestry disability index (ODI) pre- and postoperatively. RESULTS: A total of 863 abstracts were identified from the databases, of which 4 articles were included in the meta-analysis. A total of 430 patients were identified, of which 217(50.5%) underwent the O-TLIF, while 213(49.5%) underwent MIS-TLIF. One hundred and ninety-four (45.1%) patients were males, while 236(54.9%) were females. The average age was 54.8 ± 12.0 years. The pooled BMI was 33.4 ± 4.7 for the open-TLIF group, and 32.7 ± 3.9 for MIS-TLIF group (p = 0.22). When comparing O-TLIF to MIS-TLIF: Patients who underwent O-TLIF had 383 mls more blood loss (95% CI: 329.5-437.4, p < 0.00001), 1.2-day longer hospitalization stay (95% CI: 0.80-1.62, p < 0.00001) and 3.8 times higher risk of dural tear (95% CI: 1.61-9.87, p = 0.003) when compared to MIS-TLIF patients. A trend toward higher postoperative wound infection rates (O-TLIF: 4.5%, MIS-TLIF: 2.4%) and an inferior improvement in ODI score (O-TLIF: 39.3, MIS-TLIF: 44.1) was found in O-TLIF patients when compared to MIS-TLIF patients. However, these were not statistically significant. CONCLUSION: MIS-TLIF is safe and may be a better option for lumbar fusion in obese patients. These slides can be retrieved under Electronic Supplementary Material.

In silico region of difference (RD) analysis of Mycobacterium tuberculosis complex from sequence reads using RD-Analyzer.

BACKGROUND: Whole-genome sequencing is increasingly used in clinical diagnosis of tuberculosis and study of Mycobacterium tuberculosis complex (MTC). MTC consists of several genetically homogenous mycobacteria species which can cause tuberculosis in humans and animals. Regions of difference (RDs) are commonly regarded as gold standard genetic markers for MTC classification. RESULTS: We develop RD-Analyzer, a tool that can accurately infer the species and lineage of MTC isolates from sequence reads based on the presence and absence of a set of 31 RDs. Applied on a publicly available diverse set of 377 sequenced MTC isolates from known major species and lineages, RD-Analyzer achieved an accuracy of 98.14 % (370/377) in species prediction and a concordance of 98.47 % (257/261) in Mycobacterium tuberculosis lineage prediction compared to predictions based on single nucleotide polymorphism markers. By comparing respective sequencing read depths on each genomic position between isolates of different sublineages, we were able to identify the known RD markers in different sublineages of Lineage 4 and provide support for six potential delineating markers having high sensitivities and specificities for sublineage prediction. An extended version of RD-Analyzer was thus developed to allow user-defined RDs for lineage prediction. CONCLUSIONS: RD-Analyzer is a useful and accurate tool for species, lineage and sublineage prediction using known RDs of MTC from sequence reads and is extendable to accepting user-defined RDs for analysis. RD-Analyzer is written in Python and is freely available at https://github.com/xiaeryu/RD-Analyzer .

Outcome of Single-Bundle Hamstring Anterior Cruciate Ligament Reconstruction Using the Anteromedial Versus the Transtibial Technique: A Systematic Review and Meta-analysis.

PURPOSE: To compare the clinical outcomes of single-bundle hamstring anterior cruciate ligament (ACL) reconstruction between the anteromedial (AM) and transtibial (TT) techniques. METHODS: We performed a comprehensive systematic review and meta-analysis of the English-language literature in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases for articles that compared clinical outcomes of AM versus TT ACL reconstruction. The outcome measures analyzed included postoperative Lachman test, pivot-shift test, International Knee Documentation Committee (IKDC), and Lysholm scores. RESULTS: We included 10 articles from an initial 308 abstracts for the systematic review and included 6 studies for the meta-analysis. The study population consisted of a total of 733 patients, of whom 366 (49.9%) underwent the AM technique and 367 (50.1%) underwent the TT technique for ACL reconstruction. For postoperative knee stability, the AM technique yielded superior results in terms of the proportion of negative Lachman test results (n = 243; odds ratio [OR], 2.98 [95% confidence interval (CI), 1.29 to 6.88]) and proportion of negative pivot-shift test results (n = 238; OR, 3.67 [95% CI, 1.80 to 7.52]). For postoperative functional status, the AM technique yielded superior results in terms of objective IKDC grading (proportion with IKDC grade A) (n = 269; OR, 2.19 [95% CI, 1.23 to 3.88]) but had comparable Lysholm scores (n = 478; mean difference, 1.43 [95% CI, 0.01 to 2.84]). CONCLUSIONS: Single-bundle hamstring ACL reconstruction using the AM technique showed superior surgeon-recorded stability according to the IKDC knee score, Lachman test, and pivot-shift test. However, there was no difference in patient-reported functional outcome (Lysholm score). LEVEL OF EVIDENCE: Level III, systematic review and meta-analysis of Level I, II, and III studies.

Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes.

CXCL14 is a chemokine that has previously been implicated in insulin resistance in mice. In humans, the role of CXCL14 in metabolic processes is not well established, and we sought to determine whether CXCL14 is a risk susceptibility gene important in fetal programming of metabolic disease. For this purpose, we investigated whether CXCL14 is differentially regulated in human umbilical cords of infants with varying birth weights. We found an elevated expression of CXCL14 in human low birth weight (LBW) cords, as well as in cords from nutritionally restricted Macaca fascicularis macaques. To further analyze the regulatory mechanisms underlying the expression of CXCL14, we examined CXCL14 in umbilical cord-derived mesenchymal stem cells (MSCs) that provide an in vitro cell-based system amenable to experimental manipulation. Using both whole frozen cords and MSCs, we determined that site-specific CpG methylation in the CXCL14 promoter is associated with altered expression, and that changes in methylation are evident in LBW infant-derived umbilical cords that may indicate future metabolic compromise through CXCL14.

Molecular pathways reflecting poor intrauterine growth are found in Wharton's jelly-derived mesenchymal stem cells.

STUDY QUESTION: Are molecular pathways reflecting the biology of small for gestational age (SGA) neonates preserved in umbilical cord-derived mesenchymal stem cells (MSCs)? SUMMARY ANSWER: MSCs from SGA newborns were found to express an altered EGR-1-dependent gene network involved in the regulation of cell proliferation and oxidative stress. WHAT IS KNOWN ALREADY: Individuals with suboptimal intrauterine development are at greater risk of metabolic diseases such as type II diabetes, obesity and cardiovascular disease. STUDY DESIGN, SIZE, DURATION: Umbilical cords (n = 283) from the GUSTO (growing up in Singapore towards healthy outcomes) birth cohort study, and primary MSC isolates established from SGA and matched control cases (n = 6 per group), were subjected to gene expression analysis and candidate genes were studied for functional validation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Umbilical cord specimens were derived from babies born at the National University Hospital (NUH) in Singapore. Local ethical approval was obtained. MSC isolates were established in Wharton's jelly and molecular analysis was conducted by gene expression microarrays and RT-PCR. Cells from SGA and control groups were compared in the presence and absence of insulin and candidate gene function was studied via siRNA-mediated gene knockdown and over-expression experiments in MSCs. MAIN RESULTS AND THE ROLE OF CHANCE: Using repeated measure ANOVAs, proliferation rates of MSCs isolated from SGA neonates were found to be significantly increased (P < 0.01). In the absence of insulin, EGR-1 levels were found to be significantly reduced in the group of SGA-derived MSCs, whereas EGR-1 expression was found to be up-regulated in the same group in the presence of insulin (P < 0.01). EGR-1 was found to induce expression of COX-2 in the SGA group (P < 0.01) and both, EGR-1 and COX-2 stimulated glucose uptake in MSCs (P < 0.01). EGR-1 and COX-2 levels were associated in whole umbilical cords (n = 283, P < 0.01) and EGR-1 positively correlated with abdominal circumference and birthweight (n = 91, P < 0.01 and n = 91, P < 0.01). LIMITATIONS, REASONS FOR CAUTION: Cell models may not entirely reflect the physiology of the host and patient follow-up studies will be necessary for further clinical validation. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that Wharton's jelly-derived MSCs are useful in identifying pathways specific for fetal growth restriction. STUDY FUNDING/COMPETING INTERESTS: This work is supported by the Translational Clinical Research (TCR) Flagship Program on Developmental Pathways to Metabolic Disease funded by the National Research Foundation (NRF) and administered by the National Medical Research Council (NMRC), Singapore- NMRC/TCR/004-NUS/2008'. SICS Investigators are supported through the Agency for Science Technology and Research (A*STAR) funding. No potential conflicts of interest relevant to this article were reported.

Changes in Spinopelvic Parameters Between Standing and Sitting Postures: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To report the ratio-of-differences between standing and sitting. To understand how sex and age influence these differences. SUMMARY OF BACKGROUND DATA: Currently, spinal deformity surgery aims to realign the sagittal profile of the spine with-reference-to the standing posture resulting in overcorrection. New studies report significant disparities between standing and sitting spinal alignment. METHODS: A comprehensive search and review of the published literature was performed on 4 platforms in accordance with the PRISMA 2009 checklist by 2 authors independently. RESULTS: From 753 abstracts extracted from the databases, 38 papers involving 5423 patients were identified. sagittal vertical axis was more positive in sitting, with a pooled mean difference of 29.5 mm (95% CI: 17.9-41.0). Pelvic tilt (PT) was larger in sitting, with a pooled mean difference of 16.7 degrees (95% CI: 12.5-20.9), and a pooled odds ratio of 1.2(95% CI:1.1-1.3. P =0.001). Sacral Slope (SS) was smaller and lumbar lordosis (LL) was less lordotic in sitting, with a pooled mean difference of 15.0 degrees (95% CI: 11.918.1) and 21.1 degrees (95% CI:14.5-27.8), respectively, and a pooled odds ratio of 0.7 (95% CI: 0.6-0.8. P <0.001) and 0.7 (95% CI:0.6-0.7, P <0.001), respectively. Pelvic incidence and thoracic kyphosis was similar in sitting. Subgroup meta-analysis comparing odd ratio of standing to sitting showed: Among younger patients (age younger than 50), the PT and LL pooled odds-ratios were 1.4 and 0.7, respectively. Among older patients (age older than or equal to 50), the PT and LL pooled odds-ratios were 1.1 and 0.8, respectively. Among female patients, the SS pooled odds ratio was 0.6. Among male patients, the SS pooled odds ratio was 0.7. CONCLUSION: When comparing sitting to standing, it gives a more positive sagittal vertical axis, a smaller SS and LL, and a larger PT. pelvic incidence and thoracic kyphosis remained similar. Younger and female patients have pronounced differences in SS, PT, and LL, suggesting the existence of age and sex variations, and its role to be considered when planning for spinal realignment surgeries. Clinical outcome studies are required to ascertain the impact of these findings.

A Comparison between Structural Allografts and Polyetheretherketone Interbody Spacers Used in Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-analysis.

Among interbody implants used during anterior cervical discectomy and fusion (ACDF), structural allografts and polyetheretherketone (PEEK) are the most used spacers. Currently, no consensus has been established regarding the superiority of either implant, with US surgeons preferring structural allografts, whereas UK surgeons preferring PEEK. The purpose of this systematic review (level of evidence, 4) was to compare postoperative and patient-reported outcomes between the use of structural allografts PEEK interbody spacers during ACDF. Five electronic databases (PubMed, Embase, Scopus, Web of Science, and Cochrane) were searched for articles comparing the usage of structural allograft and PEEK interbody spacers during ACDF procedures from inception to April 10, 2023. The searches were conducted using the keywords "Spine," "Allograft," and "PEEK" and were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Subsequent quality and sensitivity analyses were performed on the included studies. Nine studies involving 1,074 patients were included. Compared with the PEEK group, the structural allograft group had comparable rates of postoperative pseudoarthrosis (p=0.58). However, when stratified according to the number of levels treated, the 3-level ACDF PEEK group was 3.45 times more likely to have postoperative pseudoarthrosis than the structural allograft group (p=0.01). Subsequent postoperative outcomes (rate of subsidence and change in the preoperative and postoperative segmental disc heights) were comparable between the PEEK and structural allograft groups. Patient-reported outcomes (Visual Analog Scale [VAS] of neck pain and Neck Disability Index [NDI]) were comparable. This study showed that for 3-level ACDFs, the use of structural allografts may confer higher fusion rates. However, VAS neck pain, NDI, and subsidence rates were comparable between structural allografts and PEEK cages. In addition, no significant difference in pseudoarthrosis rates was found between PEEK cages and structural allografts in patients undergoing 1- and 2-level ACDFs.

A Risk Quantification Reference Table for Progressed Adolescent Idiopathic Scoliosis Surgery: An Exact Case Matched Outcomes Analysis.

STUDY DESIGN: Retrospective Exact Matched case-control study. OBJECTIVES: Surgical treatment delay in AIS due to family preferences is common. This study aims to quantify the increase in risks as the Cobb angle increases and provide a Quantifiable Risk Reference Table that can be utilized for counseling. METHODOLOGY: AIS patients were divided into 3 groups: Group A: Cobb angle 50-60°, Group 61-70°, and Group CFinal ≥80°. Each patient in Group CFinal who had curve progression were then traced-back-in-time (TBIT) to review the clinical data at earlier presentations at 50-60° (C1), and 61-70° (C2). Patient demographics, radiological, operative, and outcomes data were compared between Group A vs C1 and Group B vs Group C2. RESULTS: A total of 614 AIS surgeries were reviewed. Utilizing the EM technique, a total of 302 AIS patients were recruited. There were 147, 111, 31, and 32 patients matched in Groups A, B, C1, and C2, respectively. C2 Final patients had 34% curve pattern change, 23.2% higher incidence of requiring two surgeries, and 17.3% increase in complications. There was a statistically significant increase of 2.4 spinal levels fused, 12% increase in implant density, 35% increase in operative time, 97% increase in intra-operative blood loss, 10% loss of scoliosis correction, 40% longer hospitalization stay, and 36% increase in costs for patients who had curve progression. CONCLUSION: This study is the first to use a homogenously matched AIS cohort to provide a Quantifiable Risk Reference Table. The Risk Table provides essential knowledge for treating physicians when counseling AIS patients.

Prevalence and Risk Factors of Degenerative Spondylolisthesis and Retrolisthesis in the Thoracolumbar and Lumbar Spine - An EOS Study Using Updated Radiographic Parameters.

STUDY DESIGN: Single centre, cross-sectional study. OBJECTIVES: The objective is to report the prevalence of spondylolisthesis and retrolisthesis, analyse both conditions in terms of the affected levels and severity, as well as identify their risk factors. METHODS: A review of clinical data and radiographic images of consecutive spine patients seen in outpatient clinics over a 1-month period is performed. Images are obtained using the EOS® technology under standardised protocol, and radiographic measurements were performed by 2 independent, blinded spine surgeons. The prevalence of both conditions were shown and categorised based on the spinal level involvement and severity. Associated risk factors were identified. RESULTS: A total of 256 subjects (46.1% males) with 2304 discs from T9/10 to L5/S1 were studied. Their mean age was 52.2(± 18.7) years. The overall prevalence of spondylolisthesis and retrolisthesis was 25.9% and 17.1% respectively. Spondylolisthesis occurs frequently at L4/5(16.3%), and retrolisthesis at L3/4(6.8%). Majority of the patients with spondylolisthesis had a Grade I slip (84.3%), while those with retrolisthesis had a Grade I slip. The presence of spondylolisthesis was found associated with increased age (P < .001), female gender (OR: 2.310; P = .005), predominantly sitting occupations (OR:2.421; P = .008), higher American Society of Anaesthesiology grades (P = .001), and lower limb radiculopathy (OR: 2.175; P = .007). Patients with spondylolisthesis had larger Pelvic Incidence (P < .001), Pelvic Tilt (P < .001) and Knee alignment angle (P = .011), but smaller Thoracolumbar junctional angle (P = .008), Spinocoxa angle (P = .007). Retrolisthesis was associated with a larger Thoracolumbar junctional angle (P =.039). CONCLUSION: This is the first study that details the prevalence of spondylolisthesis and retrolisthesis simultaneously, using the EOS technology and updated sagittal radiographic parameters. It allows better understanding of both conditions, their mutual relationship, and associated clinical and radiographic risk factors.

Risk and protective factors associated with adolescent depression in Singapore: a systematic review.

Introduction: Adolescent depression is prevalent, and teen suicide rates are on the rise locally. A systemic review to understand associated risk and protective factors is important to strengthen measures for the prevention and early detection of adolescent depression and suicide in Singapore. This systematic review aims to identify the factors associated with adolescent depression in Singapore. Methods: A systematic search on the following databases was performed on 21 May 2020: PubMed, EMBASE and PsycINFO. Full texts were reviewed for eligibility, and the included studies were appraised for quality using the Newcastle Ottawa Scale. Narrative synthesis of the finalised articles was performed through thematic analysis. Results: In total, eight studies were included in this review. The four factors associated with adolescent depression identified were: (1) sociodemographic factors (gender, ethnicity); (2) psychological factors, including childhood maltreatment exposure and psychological constructs (hope, optimism); (3) coexisting chronic medical conditions (asthma); and (4) lifestyle factors (sleep inadequacy, excessive internet use and pathological gaming). Conclusion: The identified factors were largely similar to those reported in the global literature, except for sleep inadequacy along with conspicuously absent factors such as academic stress and strict parenting, which should prompt further research in these areas. Further research should focus on current and prospective interventions to improve mental health literacy, targeting sleep duration, internet use and gaming, and mitigating the risk of depression in patients with chronic disease in the primary care and community setting.

Lin28a maintains a subset of adult muscle stem cells in an embryonic-like state.

During homeostasis and after injury, adult muscle stem cells (MuSCs) activate to mediate muscle regeneration. However, much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and regeneration. Here, we show that Lin28a is expressed in embryonic limb bud muscle progenitors, and that a rare reserve subset of Lin28a+Pax7- skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7+ MuSC pool to drive muscle regeneration. Compared with adult Pax7+ MuSCs, Lin28a+ MuSCs displayed enhanced myogenic potency in vitro and in vivo upon transplantation. The epigenome of adult Lin28a+ MuSCs showed resemblance to embryonic muscle progenitors. In addition, RNA-sequencing revealed that Lin28a+ MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors, telomerase components and the p53 inhibitor Mdm4, and lower levels of myogenic differentiation markers compared to adult Pax7+ MuSCs, resulting in enhanced self-renewal and stress-response signatures. Functionally, conditional ablation and induction of Lin28a+ MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle regeneration. Together, our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration.

Outcomes of operatively treated calcaneal tuberosity avulsion fractures.

BACKGROUND: Calcaneal tuberosity avulsion fractures are uncommon but when present should be treated emergently due to the high risk of skin compromise. Multiple fixation techniques have been reported in the literature but there are little data regarding the ideal fixation construct and outcomes. We aimed to characterize the clinical presentation, focussing on soft tissue compromise and outcomes of operatively treated calcaneal tuberosity avulsion fractures with its associated complications. METHODS: A retrospective review of all surgically treated calcaneus fracture in our institution from Jun 2008 to Jun 2017 was done. We reviewed patients' demographics, types of avulsion fracture, presence of preoperative skin compromise, age of fracture, time to operation, types of fixation construct, postoperative weight bearing regime, union rates, complications and revision surgeries if present. RESULTS: We found 9 patients from our database who met the inclusion criteria. They had an average age of 55.6 (range: 43 - 90) years with 5 (55.6%) of them aged 60 years and older. Seven (77.8%) patients were female. Four out of 9 patients (44.4%) presented with soft tissue compromise (3 cases of skin tenting and 1 case of blistering). None of them required soft tissue reconstructive surgery for skin defects postoperatively. However, 2 patients (22.2%) had wound complications after surgery requiring prolonged wound care for up to 4 months. There were 2 patients with fixation failure whereby both were allowed weight bearing prematurely. All of them were able to ambulate independently at their last review. CONCLUSION: Calcaneal tuberosity avulsion fractures have a high prevalence of soft tissue compromise and warrant early attention. This condition should be treated as both a bony and soft tissue injury rather than just a bony fracture alone. Management of this injury should take into account fracture reduction and stable fixation with neutralization of the Achilles tendon forces.