Return to sports following discectomy: does a consensus exist?

INTRODUCTION: In the USA, lumbar discectomy is one of the most commonly performed spinal procedures. As certain sports are considered to be major risk factors for disc herniation, the question remains as to when highly active patients should return to their previous level of activity. This study aimed to analyze spine surgeons' opinions on when patients may return to activities following discectomy as well as their underlying rationale for their decision. METHODS: A questionnaire was designed by five different fellowship-trained spine surgeons for the 168 members of the Spine Society of Australia. Questions on the surgeons experience, decision making, preferred surgical technique, the postoperative rehabilitation and the response to patient expectations were included. RESULTS: In total, 83.9% of surgeons discuss the postoperative level of activity with their patients. Sport is considered as an important contributor for good functional outcome by 71.0% of surgeons. Surgeons recommend avoiding, often permanently, weightlifting (35.7%) of the time, rugby (21.4%), horseback riding (17.9%) as well as martial arts (14.3%) postoperatively even with previous training. The return to high levels of activity is considered as a major risk factor for disc herniation recurrence by 25.8% of surgeons. Return to high level of activity is typically recommended after 3 months by 48.4% of surgeons. CONCLUSION: So far no consensus on the rehabilitation protocol and return to level of activity exists. Recommendations depend on personal experience as well as the individuals' training, and typically, a period of avoidance of sport for up to 3 months is recommended. LEVEL OF EVIDENCE: Level III, therapeutic and prognostic study.

The clinical and radiographic degenerative spondylolisthesis classification and its predictive value.

INTRODUCTION: The clinical and radiographic degenerative spondylolisthesis (CARDS) classification is a new classification that has been introduced for degenerative spondylolisthesis (DS). It has four categories. Our study aimed to analyse the functional and radiographic outcome following DS surgery based on the preoperative CARDS classification. METHODS: A retrospective study of the prospectively collected Australian Spine Registry database was performed. Data on demographics, patient reported outcome measures including the Oswestry Disability Index (ODI) and EQ-5D-3 L scores, and changes in radiographic measurements were analysed. Based on the preoperative findings all x-rays were classified applying the CARDS classification. RESULTS: Between 2018 and 2021 a total of 54-patients were identified as having had surgery for DS at L4/5. The mean age was 65.3 ± 11.3years and females were predominantly affected (61%). Most cases were of CARDS type C (46%), followed by type B (29%). CARDS type A and D were observed in 18% and 6% respectively. Preoperatively, the L4/5 lordosis was 19.8 ± 6.3° and lumbar lordosis 43.9 ± 12.8°. Postoperatively the L4/5 lordosis alignment changed significantly to 23.5 ± 8.8° (p < 0.05). Preoperatively, the CARDS classification was 34.8 ± 17.4 (type A), 40.5 ± 11.0 (type B), 43.8 ± 12.9 and 50.0 ± 14.4 for type D (Pearson-coefficient 0.284, p = 0.041). Postoperatively this changed to 22.7 ± 16.1, 28.7 ± 21.2, 12.5 ± 13.1, and 6.5 ± 2.1 respectively. Similar improvements were observed for the EQ-5D-3 L. CONCLUSION: This study shows that the CARDS classification correlates with preoperative functional scores as well as helping to predict response to surgery. CARDS will likely assist in operative planning and prognostication. LEVEL OF EVIDENCE: III, therapeutic and prognostic study.

Spinal fractures in fused spines: nonoperative treatment is a reliable alternative.

INTRODUCTION: Spinal fractures in fused spines such as in ankylosing spondylitis or DISH are typically of type B or C fractures where operative treatment is recommended. The mortality rate in non-operatively treated patients is reported to be 51%. The purpose of this study was to investigate the mortality rate, complication rate and demographics of patients following non-operatively treatment in fused spine injuries. METHODS: Between 2019 and 2021, a retrospective study was conducted including all patients who presented to our trauma center with a spinal fracture of a fused spine. Radiology and patient charts were analyzed for fracture pattern, complications, neurological deficit, comorbidities, and mortality rate. RESULTS: A total of 49 patients were found at a mean age was 79.8 ± 10.9 years and primarily males were affected in 65.3%. All fractures were of type B and the thoracic spine was involved in 85.7%. The mean follow-up was 6.3 ± 8.2 months and fusion was obtained in all patients. No neurological deficit was observed in any. A total of 13 patients died at a mean age of 86.5 ± 10.0 years after 157.1 ± 158.1 days. 6 patients (10.2%) deceased within the first 6 weeks at a mean age of 91.8 ± 3.8 years. One patient each suffered from heart failure, an acute delirium, end stage colon cancer and subdural hemorrhage. CONCLUSION: This study shows that the mortality rate in the first 6 weeks following a fracture in a fused spine is 10.2% for patients above the age of 90 years. Therefore, non-operative treatment should be taken into consideration as the mortality rate in other studies may be overestimated. LEVEL OF EVIDENCE: III, retrospective study.

Kaposi's Sarcoma-associated Herpesvirus microRNA mutants modulate cancer hallmark phenotypic differences in human endothelial cells.

Kaposi's sarcoma (KS) results from the transformation of Kaposi's sarcoma-associated herpesvirus (KSHV)-infected endothelial cells. The contribution of the KSHV microRNAs (miRNAs) to the process of oncogenesis in endothelial cells has not been fully elucidated. To better understand the contributions of individual miRNAs to oncogenesis-related cellular phenotypes, we used KSHV miRNA knockout mutants, each one lacking one of the twelve miRNA genes. An additional mutant lacked all miRNAs. Since KSHV infection causes a variety of phenotypic changes in endothelial cells, we tested the mutants for their ability to effect such changes in Telomerase-Immortalized Vein Endothelial (TIVE) cells infected with each of the mutant viruses. Wild type- and mutant-infected as well as uninfected cells were evaluated for perturbations to proliferation, migration, tubule formation, and glycolysis. We found broad variation between the different viruses in these aspects. With respect to proliferation rate, ΔmiR-K12-3, ΔmiR-K12-8, and ΔmiR-K12-11 showed significant impairment. Cells infected with ΔmiR-K12-11 had reduced migration. In tubule formation, the ΔmiR-K12-5, -6, and -7 viruses were deficient. At the same time, cells infected with the ΔmiR-K12-10 virus showed dysregulated glycolysis. By combining these observations with previously published KSHV miRNA targetome lists from ribonomics data, we were able to functionally validate a number of new miRNA targets in specific pathways. As proof of concept, miR-K12-3 was shown to target Cathepsin D, a strong promoter of apoptosis. Taken together, the results demonstrate that KSHV miRNAs play different roles in inducing the phenotypic changes which are characteristic of transformed cells.Importance: Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma (KS). The contribution of KSHV microRNAs (miRNAs) to oncogenesis is not fully understood. This is particularly true for human endothelial cells, the cell type from which KS tumors are derived. Here we used a panel of KSHV miRNA knockout viruses in order to shed light on the roles of individual miRNAs in the process of transformation. Latently infected endothelial cells were studied for phenotypic changes related to cancer, including proliferation, migration, angiogenesis, glycolysis, and apoptosis. The mutant-infected cell lines displayed a wide range of phenotypes in these selected measures of oncogenesis which differed from wild type-infected cells and from each other. These results indicate that KSHV miRNAs contribute to different aspects of oncogenesis, and that each one has a unique role to play.

Juvenile muscular atrophy of the distal upper extremity (Hirayama syndrome): a systematic review.

INTRODUCTION: Hirayama syndrome is likely caused by a forward displacement of the posterior dura during cervical flexion leading to changes in the muscles of the fingers and wrist. The aim of this systematic review was to document the number of reported cases, the necessity of dynamic MRI of the cervical spine and the subsequent treatment. METHODS AND MATERIALS: A systematic review was conducted and the Pubmed/Medbase, Cochrane, Google, Embase and Ovid database were searched for (Hirayama) AND ((disease) OR (syndrome)). A total of 42 studies were included for analysis reporting 2311 patients. RESULTS: The mean age was 20.2 ± 2.26 years and predominantly males (92.8%) were identified. On MRI the "snake eyes" appearance of the spinal cord was present in 27.8% and the typical time between onset of symptoms and diagnosis was 41.5 ± 16.4 months. A variety of different treatments have been reported, although there is no substantial evidence that any of them are superior to observation. CONCLUSION: The delay in diagnosis from initial presentation of symptoms shows that this condition may be underdiagnosed in a variety of cases. Further, this study shows the necessity of either a dynamic MRI in flexion or a static MRI scan in neutral position and in flexion, to identify functional spinal and/or foraminal stenosis for a prompt diagnosis and subsequent treatment.

Cervical immobilization in trauma patients: soft collars better than rigid collars? A systematic review and meta-analysis.

INTRODUCTION: Rigid cervical spine following trauma immobilization is recommended to reduce neurological disability and provide spinal stability. Soft collars have been proposed as a good alternative because of the complications related to rigid collars. The purpose of this study was to perform a systematic review on soft and rigid collars in the prehospital management of cervical trauma. METHOD: A systematic review was performed following the PRISMA guidelines. Search terms were (immobilization) AND (collar) AND ((neck) OR (cervical)) to evaluate the range of motion (ROM) and evidence of clinical outcome for soft and rigid collars. RESULTS: A total of 18 studies met eligibility criteria including 2 clinical studies and 16 articles investigating the range of motion (ROM). Four hundred and ninety-six patients at a mean age of 32.5 years (SD 16.8) were included. Measurements were performed in a seated position in twelve studies. Eight articles reported the ROM without a collar, 7 with a soft collar, and 15 with a rigid collar. There was no significant difference in flexion/extension, bending and rotation following immobilization with soft collars compared to no collar. Rigid collars provided significantly higher stability compared to no collar (p < 0.005) and to soft collars in flexion/extension and rotation movements (p < 0.05). The retrospective clinical studies showed no significant differences in secondary spinal cord injuries for soft collar (0.5%) and for rigid collar (1.1%). One study, comparing immobilization without a collar compared to that with a rigid collar, found a significant difference in neurologic deficiency and supraclavicular nerve lesion. CONCLUSION: Although rigid collars provide significant higher stability to no collar and to soft collars in flexion/ extension and rotation movements, clinical studies could not confirm a difference in neurological outcome. LEVEL OF EVIDENCE: II, Systematic Review.

Near-term deployment of carbon capture and sequestration from biorefineries in the United States.

Capture and permanent geologic sequestration of biogenic CO2 emissions may provide critical flexibility in ambitious climate change mitigation. However, most bioenergy with carbon capture and sequestration (BECCS) technologies are technically immature or commercially unavailable. Here, we evaluate low-cost, commercially ready CO2 capture opportunities for existing ethanol biorefineries in the United States. The analysis combines process engineering, spatial optimization, and lifecycle assessment to consider the technical, economic, and institutional feasibility of near-term carbon capture and sequestration (CCS). Our modeling framework evaluates least cost source-sink relationships and aggregation opportunities for pipeline transport, which can cost-effectively transport small CO2 volumes to suitable sequestration sites; 216 existing US biorefineries emit 45 Mt CO2 annually from fermentation, of which 60% could be captured and compressed for pipeline transport for under $25/tCO2 A sequestration credit, analogous to existing CCS tax credits, of $60/tCO2 could incent 30 Mt of sequestration and 6,900 km of pipeline infrastructure across the United States. Similarly, a carbon abatement credit, analogous to existing tradeable CO2 credits, of $90/tCO2 can incent 38 Mt of abatement. Aggregation of CO2 sources enables cost-effective long-distance pipeline transport to distant sequestration sites. Financial incentives under the low-carbon fuel standard in California and recent revisions to existing federal tax credits suggest a substantial near-term opportunity to permanently sequester biogenic CO2 This financial opportunity could catalyze the growth of carbon capture, transport, and sequestration; improve the lifecycle impacts of conventional biofuels; support development of carbon-negative fuels; and help fulfill the mandates of low-carbon fuel policies across the United States.

Geospatial analysis of near-term potential for carbon-negative bioenergy in the United States.

Bioenergy with carbon capture and storage (BECCS) is a negative-emissions technology that may play a crucial role in climate change mitigation. BECCS relies on the capture and sequestration of carbon dioxide (CO2) following bioenergy production to remove and reliably sequester atmospheric CO2 Previous BECCS deployment assessments have largely overlooked the potential lack of spatial colocation of suitable storage basins and biomass availability, in the absence of long-distance biomass and CO2 transport. These conditions could constrain the near-term technical deployment potential of BECCS due to social and economic barriers that exist for biomass and CO2 transport. This study leverages biomass production data and site-specific injection and storage capacity estimates at high spatial resolution to assess the near-term deployment opportunities for BECCS in the United States. If the total biomass resource available in the United States was mobilized for BECCS, an estimated 370 Mt CO2⋅y-1 of negative emissions could be supplied in 2020. However, the absence of long-distance biomass and CO2 transport, as well as limitations imposed by unsuitable regional storage and injection capacities, collectively decrease the technical potential of negative emissions to 100 Mt CO2⋅y-1 Meeting this technical potential may require large-scale deployment of BECCS technology in more than 1,000 counties, as well as widespread deployment of dedicated energy crops. Specifically, the Illinois basin, Gulf region, and western North Dakota have the greatest potential for near-term BECCS deployment. High-resolution spatial assessment as conducted in this study can inform near-term opportunities that minimize social and economic barriers to BECCS deployment.

Promising Anticancer Activity of [Bis(1,8-quinolato)palladium (II)] Alone and in Combination.

Due to similar coordination chemistry of palladium and platinum, a large number of palladium compounds as well have been investigated for their anticancer activity. In the present study, we describe synthesis, characterization, and anticancer activity of palladium complex [Bis(1,8-quinolato)palladium (II)], coded as NH3 against seven different cancer cell lines. NH3 is found to have higher antitumor activity than cisplatin against both parent ovarian A2780 cell line and cisplatin-resistant cell lines. Also, NH3 has the lower IC50 value in HT-29 colorectal cancer cell line. The higher antitumor activity of NH3 is due to the presence of bulky 8-Hydroxyquinoline ligand, thus reducing its reactivity. Proteomic study has identified significantly expressed proteins which have been validated through bioinformatics. NH3 has been found to be less toxic than cisplatin at 2.5 mg/kg and 5 mg/kg dosages on mice models. Binary combinations of NH3 with curcumin and epigallocatechin gallate (EGCG) have demonstrated dose and sequence-dependent synergism in ovarian and colorectal cancer models. All of the preclinical studies indicate promising therapeutic potential of NH3 [Bis(1,8-quinolato)palladium (II)] as an anticancer drug.

Structural and Magnetic Studies of ABO4-Type Ruthenium and Osmium Oxides.

Oxides of the form ABO4 with A = K, Rb, Cs and B = Ru and Os have been synthesized and characterized by diffraction and magnetic techniques. For A = K the oxides adopted the tetragonal (I41/a) scheelite structure. RbOsO4, which crystallizes as a scheelite at room temperature, underwent a continuous phase transition to I41/amd near 550 K. RbRuO4 and CsOsO4 were found to crystallize in the orthorhombic (Pnma) pseudoscheelite structure, and both displayed discontinuous phase transitions to I41/a at high temperatures. CsOsO4 was determined to undergo a phase transition to a P21/c structure below 140 K. CsRuO4 crystallizes with a baryte-type structure at room temperature. Upon heating CsRuO4 a first order phase transition to the scheelite structure in I41/a is observed at 400 K. A continuous phase transition is observed to P212121 below 140 K. DC magnetic susceptibility data is consistent with long-range antiferromagnetic ordering at low temperatures for all compounds except for CsOsO4, which is paramagnetic to 2 K. The effective magnetic moments are in agreement with the spin only values for an S = 1/2 quantum magnet. Effective magnetic moments calculated for Os compounds were lower than their Ru counterparts, reflective of an enhanced spin orbit coupling effect. A magnetic structure is proposed for RbRuO4 consisting of predominately antiferromagnetic (AFM) ordering along the 001 direction, with canting of spins in the 100 plane. A small ordered magnetic moment of 0.77 µB was determined.

Nitrous oxide emissions are enhanced in a warmer and wetter world.

Nitrous oxide (N2O) has a global warming potential that is 300 times that of carbon dioxide on a 100-y timescale, and is of major importance for stratospheric ozone depletion. The climate sensitivity of N2O emissions is poorly known, which makes it difficult to project how changing fertilizer use and climate will impact radiative forcing and the ozone layer. Analysis of 6 y of hourly N2O mixing ratios from a very tall tower within the US Corn Belt-one of the most intensive agricultural regions of the world-combined with inverse modeling, shows large interannual variability in N2O emissions (316 Gg N2O-N⋅y-1 to 585 Gg N2O-N⋅y-1). This implies that the regional emission factor is highly sensitive to climate. In the warmest year and spring (2012) of the observational period, the emission factor was 7.5%, nearly double that of previous reports. Indirect emissions associated with runoff and leaching dominated the interannual variability of total emissions. Under current trends in climate and anthropogenic N use, we project a strong positive feedback to warmer and wetter conditions and unabated growth of regional N2O emissions that will exceed 600 Gg N2O-N⋅y-1, on average, by 2050. This increasing emission trend in the US Corn Belt may represent a harbinger of intensifying N2O emissions from other agricultural regions. Such feedbacks will pose a major challenge to the Paris Agreement, which requires large N2O emission mitigation efforts to achieve its goals.

Downregulation of the human peripheral myelin protein 22 gene by miR-29a in cellular models of Charcot-Marie-Tooth disease.

The majority of hereditary neuropathies are caused by duplication of the peripheral myelin protein 22 (PMP22) gene. Therefore, mechanisms to suppress the expression of the PMP22 gene have high therapeutic significance. Here we asked whether the human PMP22 gene is a target for regulation by microRNA 29a (miR-29a). Using bioinformatics, we determined that the human PMP22 gene contains the conserved seed sequence of the miR-29a binding site and this regulatory motif is included in the duplicated region in neuropathic patients. Using luciferase reporter assays in HEK293 cells, we demonstrated that transient transfection of a miR-29a mimic is associated with reduction in PMP22 3'UTR reporter activity. Transfecting normal and humanized transgenic neuropathic mouse Schwann cells with a miR-29a expression plasmid effectively lowered both the endogenous mouse and the transgenic human PMP22 transcripts compared with control vector. In dermal fibroblasts derived from neuropathic patients, ectopic expression of miR-29a led to ~50% reduction in PMP22 mRNA, which corresponded to ~20% decrease in PMP22 protein levels. Significantly, miR-29a-mediated reduction in PMP22 mitigated the reduced mitotic capacity of the neuropathic cells. Together, these results support further testing of miR-29a and/or PMP22-targeting siRNAs as therapeutic agents for correcting the aberrant expression of PMP22 in neuropathic patients.

Modified Cross-Linking, Ligation, and Sequencing of Hybrids (qCLASH) Identifies Kaposi's Sarcoma-Associated Herpesvirus MicroRNA Targets in Endothelial Cells.

Kaposi's sarcoma (KS) tumors are derived from endothelial cells and express Kaposi's sarcoma-associated herpesvirus (KSHV) microRNAs (miRNAs). Although miRNA targets have been identified in B cell lymphoma-derived cells and epithelial cells, little has been done to characterize the KSHV miRNA targetome in endothelial cells. A recent innovation in the identification of miRNA targetomes, cross-linking, ligation, and sequencing of hybrids (CLASH), unambiguously identifies miRNAs and their targets by ligating the two species while both species are still bound within the RNA-induced silencing complex (RISC). We developed a streamlined quick CLASH (qCLASH) protocol that requires a lower cell input than the original method and therefore has the potential to be used on patient biopsy samples. Additionally, we developed a fast-growing, KSHV-negative endothelial cell line derived from telomerase-immortalized vein endothelial long-term culture (TIVE-LTC) cells. qCLASH was performed on uninfected cells and cells infected with either wild-type KSHV or a mutant virus lacking miR-K12-11/11*. More than 1,400 cellular targets of KSHV miRNAs were identified. Many of the targets identified by qCLASH lacked a canonical seed sequence match. Additionally, most target regions in mRNAs originated from the coding DNA sequence (CDS) rather than the 3' untranslated region (UTR). This set of genes includes some that were previously identified in B cells and some new genes that warrant further study. Pathway analysis of endothelial cell targets showed enrichment in cell cycle control, apoptosis, and glycolysis pathways, among others. Characterization of these new targets and the functional consequences of their repression will be important in furthering our understanding of the role of KSHV miRNAs in oncogenesis.IMPORTANCE KS lesions consist of endothelial cells latently infected with KSHV. Cells that make up these lesions express KSHV miRNAs. Identification of the targets of KSHV miRNAs will help us understand their role in viral oncogenesis. The cross-linking and sequencing of hybrids (CLASH) protocol is a method for unambiguously identifying miRNA targetomes. We developed a streamlined version of CLASH, called quick CLASH (qCLASH). qCLASH requires a lower initial input of cells than for its parent protocol. Additionally, a new fast-growing KSHV-negative endothelial cell line, named TIVE-EX-LTC cells, was established. qCLASH was performed on TIVE-EX-LTC cells latently infected with wild-type (WT) KSHV or a mutant virus lacking miR-K12-11/11*. A number of novel targets of KSHV miRNAs were identified, including targets of miR-K12-11, the ortholog of the cellular oncogenic miRNA (oncomiR) miR-155. Many of the miRNA targets were involved in processes related to oncogenesis, such as glycolysis, apoptosis, and cell cycle control.

Voltage-Switchable HCl Transport Enabled by Lipid Headgroup-Transporter Interactions.

Synthetic anion transporters that facilitate transmembrane H+ /Cl- symport (cotransport) have anti-cancer potential due to their ability to neutralize pH gradients and inhibit autophagy in cells. However, compared to the natural product prodigiosin, synthetic anion transporters have low-to-modest H+ /Cl- symport activity and their mechanism of action remains less well understood. We report a chloride-selective tetraurea macrocycle that has a record-high H+ /Cl- symport activity similar to that of prodigiosin and most importantly demonstrates unprecedented voltage-switchable transport properties that are linked to the lack of uniport activity. By studying the anion binding affinity and transport mechanisms of four other anion transporters, we show that the lack of uniport and voltage-dependent H+ /Cl- symport originate from strong binding to phospholipid headgroups that hampers the diffusion of the free transporters through the membrane, leading to an unusual H+ /Cl- symport mechanism that involves only charged species. Our work provides important mechanistic insights into different classes of anion transporters and a new approach to achieve voltage-switchability in artificial membrane transport systems.

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis.

Chemical investigation of an undescribed Australian fungus, Aspergillus nanangensis, led to the identification of the nanangenines - a family of seven new and three previously reported drimane sesquiterpenoids. The structures of the nanangenines were elucidated by detailed spectroscopic analysis supported by single crystal X-ray diffraction studies. The compounds were assayed for in vitro activity against bacteria, fungi, mammalian cells and plants. Bioinformatics analysis, including comparative analysis with other acyl drimenol-producing Aspergilli, led to the identification of a putative nanangenine biosynthetic gene cluster that corresponds to the proposed biosynthetic pathway for nanangenines.

Deltamides and Croconamides: Expanding the Range of Dual H-bond Donors for Selective Anion Recognition.

Dual H-bond donors are widely used as recognition motifs in anion receptors. We report the synthesis of a library of dual H-bond receptors, incorporating the deltic and croconic acid derivatives, termed deltamides and croconamides, respectively, and a comparison of their anion binding affinities (for monovalent species) and Brønsted acidities to those of the well-established urea and squaramide dual H-bond donor motifs. For dual H-bonding cores with identical substituents, the trend in Brønsted acidity is croconamides>squaramides>deltamides>ureas, with the croconamides found to be 10-15 pKa units more acidic than the corresponding ureas. In contrast to the trends displayed by ureas, deltamides and squaramides, N,N'-dialkyl croconamides displayed higher binding affinity to chloride than the N,N'-diaryl derivatives, which was attributed to partial deprotonation of the N,N'-diaryl derivatives at neutral pH. A number of differences in anion binding selectivity were observed upon comparison of the dual H-bond cores. Whereas the squaramides display similar affinity for both chloride and acetate ions, the ureas have significantly higher affinity for acetate than chloride ions and the deltamides display higher affinity for dihydrogenphosphate ions than other oxoanions or halides. These inherent differences in binding affinity could be exploited in the design of anion receptors with improved ability to discriminate between monovalent anions.

Indirect nitrous oxide emissions from streams within the US Corn Belt scale with stream order.

N2O is an important greenhouse gas and the primary stratospheric ozone depleting substance. Its deleterious effects on the environment have prompted appeals to regulate emissions from agriculture, which represents the primary anthropogenic source in the global N2O budget. Successful implementation of mitigation strategies requires robust bottom-up inventories that are based on emission factors (EFs), simulation models, or a combination of the two. Top-down emission estimates, based on tall-tower and aircraft observations, indicate that bottom-up inventories severely underestimate regional and continental scale N2O emissions, implying that EFs may be biased low. Here, we measured N2O emissions from streams within the US Corn Belt using a chamber-based approach and analyzed the data as a function of Strahler stream order (S). N2O fluxes from headwater streams often exceeded 29 nmol N2O-N m(-2) ⋅ s(-1) and decreased exponentially as a function of S. This relation was used to scale up riverine emissions and to assess the differences between bottom-up and top-down emission inventories at the local to regional scale. We found that the Intergovernmental Panel on Climate Change (IPCC) indirect EF for rivers (EF5r) is underestimated up to ninefold in southern Minnesota, which translates to a total tier 1 agricultural underestimation of N2O emissions by 40%. We show that accounting for zero-order streams as potential N2O hotspots can more than double the agricultural budget. Applying the same analysis to the US Corn Belt demonstrates that the IPCC EF5r underestimation explains the large differences observed between top-down and bottom-up emission estimates.

A Fluorescent Ditopic Rotaxane Ion-Pair Host.

We report a rotaxane based on a simple urea motif that binds Cl- selectively as a separated ion pair with H+ and reports the anion binding event through a fluorescence switch-on response. The host selectively binds Cl- over more basic anions, which deprotonate the framework, and less basic anions, which bind more weakly. The mechanical bond also imparts size selectivity to the ditopic host.

Locking stand-alone cages versus anterior plate constructs in single-level fusion for degenerative cervical disease: a systematic review and meta-analysis.

PURPOSE: To conduct a meta-analysis to compare the clinical and radiological outcomes in single-level anterior cervical discectomy and fusion (ACDF) surgery for degenerative cervical disease performed by either single-level locking stand-alone cage (LSC) or anterior plate construct (APC). METHODS: We performed a comprehensive database search of Medline, PubMed, EMBASE and Cochrane Database of Systematic Reviews according to PRISMA guidelines and identified six articles that satisfied our inclusion criteria. We excluded all non-English language articles and articles which did not directly compare LSC and APC. Only papers which focussed on single-level ACDF were included in the study. RESULTS: There were no significant differences in blood loss, clinical outcomes (JOA, VAS, NDI scores) or radiological outcomes (cervical lordosis, segmental Cobb angle, subsidence and fusion) between the two groups. Operative time was significantly shorter in the LSC group (MD 7.2 min, 95% CI 0.3-14.1, p = 0.04). APC was associated with a statistically significant increase in dysphagia in the follow-up period (OR 6.2, 95% CI 1.0-36.6, p = 0.05). CONCLUSION: LSC and APC have similar clinical and radiological outcomes. Further blinded randomised trials are required to establish conclusive evidence in favour of LSC with regards to minimising post-operative dysphagia. We also encourage future studies to make use of formalised dysphagia outcome measures in reporting complications.

LANA binds to multiple active viral and cellular promoters and associates with the H3K4methyltransferase hSET1 complex.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a γ-herpesvirus associated with KS and two lymphoproliferative diseases. Recent studies characterized epigenetic modification of KSHV episomes during latency and determined that latency-associated genes are associated with H3K4me3 while most lytic genes are associated with the silencing mark H3K27me3. Since the latency-associated nuclear antigen (LANA) (i) is expressed very early after de novo infection, (ii) interacts with transcriptional regulators and chromatin remodelers, and (iii) regulates the LANA and RTA promoters, we hypothesized that LANA may contribute to the establishment of latency through epigenetic control. We performed a detailed ChIP-seq analysis in cells of lymphoid and endothelial origin and compared H3K4me3, H3K27me3, polII, and LANA occupancy. On viral episomes LANA binding was detected at numerous lytic and latent promoters, which were transactivated by LANA using reporter assays. LANA binding was highly enriched at H3K4me3 peaks and this co-occupancy was also detected on many host gene promoters. Bioinformatic analysis of enriched LANA binding sites in combination with biochemical binding studies revealed three distinct binding patterns. A small subset of LANA binding sites showed sequence homology to the characterized LBS1/2 sequence in the viral terminal repeat. A large number of sites contained a novel LANA binding motif (TCCAT)3 which was confirmed by gel shift analysis. Third, some viral and cellular promoters did not contain LANA binding sites and are likely enriched through protein/protein interaction. LANA was associated with H3K4me3 marks and in PEL cells 86% of all LANA bound promoters were transcriptionally active, leading to the hypothesis that LANA interacts with the machinery that methylates H3K4. Co-immunoprecipitation demonstrated LANA association with endogenous hSET1 complexes in both lymphoid and endothelial cells suggesting that LANA may contribute to the epigenetic profile of KSHV episomes.