Cerebrospinal fluid proteins in idiopathic intracranial hypertension: An exploratory SWATH proteomics analysis.

PURPOSE: The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases compared to controls using SWATH-MS proteomics approach. EXPERIMENTAL DESIGN: CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change > 1.5 or < 0.67 and p-value < 0.05 were considered significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD027751. Statistical analysis was conducted in R version 3.6.2. RESULTS: We included CSF samples from 33 subjects, consisting of 13 IIH cases and 20 controls. A total of 262 proteins were identified in Proteinpilot search. Through SWATH analysis, we quantified 232 proteins. We observed 37 differentially expressed proteins between the two groups with 24 upregulated and 13 downregulated proteins. There were two differential proteins among overweight versus non-overweight IIH cases. Network for 23 proteins was highly connected in the interaction analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Neurosecretory, neuroendocrine, and inflammatory proteins were predominantly involved in causing IIH. This exploratory study served as a platform to identify 37 differentially expressed proteins in IIH and also showed significant differences between overweight and non-overweight IIH patients.

Sacral ESP for pain management in transforaminal lumbar interbody fusion cases: A case series.

Lumbar erector spinae plane block (ESPB) is effective for spine surgeries but is deep and technically demanding. Sacral ESPB is a novel approach for sacrococcygeal procedures and can potentially cover lumbar dermatomes by the cranial drug spread. This is the first reported case series demonstrating the potential analgesic efficacy of sacral ESPB for lumbar spine surgeries. Five patients with radiculopathy at the lumbosacral area level were scheduled for transforaminal lumbar interbody fusion (TLIF). General anaesthesia was induced as per standard practice. All patients received sacral ESP in a prone position under ultrasound guidance with a needle inserted in-plane while targeting the fascial plane between the S2 median crest and overlying muscles. All the included patients had good analgesia in the postoperative period and required minimal opioid analgesic doses. Sacral ESPB is an easy, effective, and safe technique in the scheme of multimodal analgesia for TLIF surgeries as a component of pre-emptive analgesia, where the main goal is an opioid-sparing effect.

"Vitamin D supplementation and COVID-19 treatment: A systematic review and meta-analysis".

BACKGROUND: Vitamin-D is an immune-modulator which might be linked to disease severity by SARS-CoV-2. METHODS: Meta-analysis of RCTs and quasi-experimental studies, evaluating the role of vitamin-D supplementation in COVID patients was done. RESULTS: Total 5 studies (3 RCTs and 2 Quasi-experimental) including n = 467 patients were included. Vitamin D didn't reduce mortality (RR 0.55, 95%CI 0.22 to 1.39, p = 0.21), ICU admission rates (RR 0.20, 95% CI 0.01-4.26, p = 0.3) and need for invasive ventilation (RR 0.24, 95% CI 0.01-7.89, p = 0.42). CONCLUSION: No significant difference with vitamin-D supplementation on major health related outcomes in COVID-19. Well-designed RCTs are required addressing this topic.

Bilateral Kienböck's disease concomitant with gouty arthritis.

A 38-year-old man presented with a 2-month history of pain and stiffness in the bilateral wrist. The pain in right wrist was disabling and severe enough to restrict the daily life activities. After the evaluation of clinical and radiological features, the patient was diagnosed with Kienböck's disease Lichtman stage IIIB in the right wrist and stage IIIA in the left wrist. Routine laboratory investigations revealed a serum uric acid 9.27 mg/dL. Lunate excision and scaphocapitate fusion were done in the right wrist after discussing with the patient. The histopathological examinations of tophi in synovial tissue were negatively birefringent under polarised light microscopy. It confirmed the diagnoses of gout. Febuxostat was started postoperatively. The patient returned to work at the end of 5 months. There was no recurrence of symptoms and radiological signs of arthritis at the end of 1 year.

A Comparison of Bacterial Adhesion and Biofilm Formation on Commonly Used Orthopaedic Metal Implant Materials: An In vitro Study.

BACKGROUND: Bacterial adherence and biofilm formation on the surface of biomaterials can often lead to implant-related infections, which may vary depending on the species of microorganisms, type of biomaterial used, and physical characteristics of implant surfaces. However, there are limited studies specifically comparing biofilm formation between commonly used metallic orthopaedic implant materials and different bacterial strains. This in vitro study is to evaluate the ability of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa to adhere to and to form biofilms on the surface of five orthopaedic biomaterials, viz., cobalt and chromium, highly cross-linked polyethylene, stainless steel, trabecular metal, and titanium alloy. MATERIALS AND METHODS: Bacterial adherence and bacterial biofilm-formation assays were performed by culturing S. aureus ATCC 29213, S. epidermidis ATCC 35984, E. coli ATCC 35218, K. pneumoniae ATCC 700603, and P. aeruginosa ATCC 27853 for 48 h on five different biomaterials. Quantitative bacterial adherence and biofilm formation were analyzed with a scanning electron microscope. RESULTS: The highest level of adherence was observed on highly cross-linked polyethylene, followed by titanium, stainless steel, and trabecular metal, with the lowest occurring on the cobalt-chromium alloy. Among the bacterial strains tested, the ability for high adherence was observed with S. epidermidis and K. pneumoniae followed by P. aeruginosa and E. coli, whereas S. aureus showed the least adherence. CONCLUSION: Cobalt-chromium was observed to have the lowest proclivity towards bacterial adherence compared to the other biomaterials tested. However, bacterial adhesion occurred with all the materials. Hence, it is necessary to further evaluate newer biomaterials that are resistant to bacterial adherence.

Popliteal neurovascular bundle is safe during inside-out repair of medial meniscus without a safety incision.

PURPOSE: There is a theoretical risk of injury to neurovascular structures during inside-out meniscal repair without a safety incision, although there are limited studies assessing this risk. This simulation study on archival MRI films was performed to assess the risk for the popliteal neurovascular bundle and the peroneal nerve during passage of needles for inside-out meniscus repair without a "safety incision", thereby defining a "safe zone" of the menisci that can be safely repaired using this technique. METHODS: Archival MRI scans (n = 50) were retrieved and axial sections through the menisci were used for simulation. The needle passage was simulated for different points on the posterior horn and body of lateral and medial menisci at "half-hour" intervals using clock method (15° intervals) with three different portals and two different needle cannulas, resulting in six different scenarios of needle passage for each point on the meniscus. The distance of the needle in each scenario was measured from popliteal vessels (n = 50) and peroneal nerve (n = 10). The value "mean-3SD" was calculated for positive means and "Mean + 3SD" was calculated if the mean was negative. An additional 2 mm was defined as "safe distance". Thus, simulation models in which the mean - 3SD was less than 2 mm (or mean + 3SD was greater than - 2 mm for negative means) were labelled as "unsafe". RESULTS: Needle passage through medial meniscus at and medial to 1 o'clock position for a right knee (or 11 o'clock position for a left knee) was safe, irrespective of the portal and needle type. For the lateral meniscus, only the equatorial region was found to be safe with this method. CONCLUSIONS: The popliteal neurovascular bundle is safe during the inside-out medial meniscal repair without a safety incision. For the terminal-most part of the posterior horn, the AM portal and the straight cannula should be avoided. However, this method without safety incision cannot be recommended for lateral meniscus because of the risk to the popliteal vessels and the peroneal nerve. Instead, the inside-out method with a safety incision, or an all-inside method should be used for lateral meniscus. LEVEL OF EVIDENCE: III.

Patellar inversion: 180 degree rotation of the patella around its vertical axis within the intercondylar notch.

BACKGROUND: Dislocation of the patella can occur around its vertical as well as horizontal axis. However, near 180 degree rotation of the patella around its vertical axis within the intercondylar notch without its complete dislocation has never been previously reported to the best of our knowledge. We report one such neglected case along with its management. METHODS: The patient underwent open reduction and de-rotation of patella with repair of the medial and lateral patellar retinacula. The orientation of the patellar tendon intra-operatively was used as a guide for the reduction manoeuvre required. RESULTS: The patient had a good functional result at more than one year of follow-up. CONCLUSIONS: A skyline view of the knee in symptomatic patients with normal AP and lateral radiographs of the knee can be useful in diagnosing a rare intra-articular dislocation of the patella around its vertical axis. Neglected cases of such injuries can be easily treated with open reduction with the orientation of the patellar tendon guiding the manoeuvre to de-rotate the patella. Careful repair of lateral and medial retinacula in such cases is important in preventing future patellar instability.

Effectiveness of arthroscopic elbow synovectomy in rheumatoid arthritis patients: Long-term follow-up of clinical and functional outcomes.

OBJECTIVE: To determine the long-term clinical and functional results of arthroscopic elbow synovectomy in rheumatoid arthritis patients with refractory elbow synovitis in terms of improvement in pain, function, and active range of motion (AROM) or arc of motion. METHOD: Fifteen rheumatoid elbows in 13 patients, not responding to DMARD therapy and with radiological changes not more than Larsen grade 3 were taken, who underwent arthroscopic elbow synovectomy. The main outcome measured in forms of Mayo Elbow Performance Scale (MEPS) score, measurement of pain using a Visual Analogue Scale (VAS), radiological angles of elbow, disease activity score (DAS-28), arc of motions (AOM) and complications, which were assessed at follow-up periods of 6 months, 24 months, and 30 months. Statistical analysis was done both qualitatively and quantitatively. Mann-Whitney U test, chi-square test, and Student t test were used as the statistical test for determining significance. RESULTS: In the study group, the improvement was sustained and significant as compared to baseline (VAS 1.28, MEPS 81.07 and mean flexion range 85°) (p value <0.001). No significant complications were encountered postoperatively after elbow synovectomy. CONCLUSION: The study assesses the long-term results of arthroscopic synovectomy in elbow synovitis secondary to rheumatoid arthritis with significant results favoring arthroscopic synovectomy.

Baastrup's disease: The kissing spine.

A 67-year-old male presented with a gradually progressive low back pain of 2 years duration. The patient was leading a retired life and there was no history of chronic fever or significant trauma. There was no radiation of pain or any features suggestive of claudication. There was no history of any comorbidity. The pain was aggravated with extension of the spine and relieved with flexion. There was no swelling or neurological deficit, but muscle spasm was present. Radiographs of the spine revealed degenerative changes in the lumbosacral spine, along with articulation of spinous processes at in lumbar spine at all levels level suggestive of Baastrup's disease, commonly known as "kissing spine". Routine blood investigations were within normal limits. The patient was managed conservatively. He was given a week's course of analgesics and muscle relaxants and then started on spinal flexion exercises, with significant improvement being noted at 6 months follow up.

Weismann-Netter-Stuhl syndrome: report of two cases and treatment.

Weismann-Netter-Stuhl syndrome is a rarely reported cause of bowed legs; hence a thorough clinical and radiological examination is needed for its diagnosis. In view of the paucity of reports guiding the treatment of the deformity, we propose a one-level/two-level osteotomy with intramedullary nail fixation as a treatment modality for the tibial bowing.

Can comprehensive background knowledge be incorporated into substitution models to improve phylogenetic analyses? A case study on major arthropod relationships.

BACKGROUND: Whenever different data sets arrive at conflicting phylogenetic hypotheses, only testable causal explanations of sources of errors in at least one of the data sets allow us to critically choose among the conflicting hypotheses of relationships. The large (28S) and small (18S) subunit rRNAs are among the most popular markers for studies of deep phylogenies. However, some nodes supported by this data are suspected of being artifacts caused by peculiarities of the evolution of these molecules. Arthropod phylogeny is an especially controversial subject dotted with conflicting hypotheses which are dependent on data set and method of reconstruction. We assume that phylogenetic analyses based on these genes can be improved further i) by enlarging the taxon sample and ii) employing more realistic models of sequence evolution incorporating non-stationary substitution processes and iii) considering covariation and pairing of sites in rRNA-genes. RESULTS: We analyzed a large set of arthropod sequences, applied new tools for quality control of data prior to tree reconstruction, and increased the biological realism of substitution models. Although the split-decomposition network indicated a high noise content in the data set, our measures were able to both improve the analyses and give causal explanations for some incongruities mentioned from analyses of rRNA sequences. However, misleading effects did not completely disappear. CONCLUSION: Analyses of data sets that result in ambiguous phylogenetic hypotheses demand for methods, which do not only filter stochastic noise, but likewise allow to differentiate phylogenetic signal from systematic biases. Such methods can only rely on our findings regarding the evolution of the analyzed data. Analyses on independent data sets then are crucial to test the plausibility of the results. Our approach can easily be extended to genomic data, as well, whereby layers of quality assessment are set up applicable to phylogenetic reconstructions in general.

A reversible jump method for Bayesian phylogenetic inference with a nonhomogeneous substitution model.

Nonhomogeneous substitution models have been introduced for phylogenetic inference when the substitution process is nonstationary, for example, when sequence composition differs between lineages. Existing models can have many parameters, and it is then difficult and computationally expensive to learn the parameters and to select the optimal model complexity. We extend an existing nonhomogeneous substitution model by introducing a reversible jump Markov chain Monte Carlo method for efficient Bayesian inference of the model order along with other phylogenetic parameters of interest. We also introduce a new hierarchical prior which leads to more reasonable results when only a small number of lineages share a particular substitution process. The method is implemented in the PHASE software, which includes specialized substitution models for RNA genes with conserved secondary structure. We apply an RNA-specific nonhomogeneous model to a structure-based alignment of rRNA sequences spanning the entire tree of life. A previous study of the same genes from a similar set of species found robust evidence for a mesophilic last universal common ancestor (LUCA) by inference of the G+C composition at the root of the tree. In the present study, we find that the helical GC composition at the root is strongly dependent on the root position. With a bacterial rooting, we find that there is no longer strong support for either a mesophile or a thermophile LUCA, although a hyperthermophile LUCA remains unlikely. We discuss reasons why results using only RNA helices may differ from results using all aligned sites when applying nonhomogeneous models to RNA genes.

On the correlation between composition and site-specific evolutionary rate: implications for phylogenetic inference.

Model-based phylogenetic reconstruction methods traditionally assume homogeneity of nucleotide frequencies among sequence sites and lineages. Yet, heterogeneity in base composition is a characteristic shared by most biological sequences. Compositional variation in time, reflected in the compositional biases among contemporary sequences, has already been extensively studied, and its detrimental effects on phylogenetic estimates are known. However, fewer studies have focused on the effects of spatial compositional heterogeneity within genes. We show here that different sites in an alignment do not always share a unique compositional pattern, and we provide examples where nucleotide frequency trends are correlated with the site-specific rate of evolution in RNA genes. Spatial compositional heterogeneity is shown to affect the estimation of evolutionary parameters. With standard phylogenetic methods, estimates of equilibrium frequencies are found to be biased towards the composition observed at fast-evolving sites. Conversely, the ancestral composition estimates of some time-heterogeneous but spatially homogeneous methods are found to be biased towards frequencies observed at invariant and slow-evolving sites. The latter finding challenges the result of a previous study arguing against a hyperthermophilic last universal ancestor from the low apparent G + C content of its rRNA sequences. We propose a new model to account for compositional variation across sites. A Gaussian process prior is used to allow for a smooth change in composition with evolutionary rate. The model has been implemented in the phylogenetic inference software PHASE, and Bayesian methods can be used to obtain the model parameters. The results suggest that this model can accurately capture the observed trends in present-day RNA sequences.

Consideration of RNA secondary structure significantly improves likelihood-based estimates of phylogeny: examples from the bilateria.

Sequences from ribosomal RNA (rRNA) genes have made a huge contribution to our current understanding of metazoan phylogeny and indeed the phylogeny of all of life. That said, some parts of this rRNA-based phylogeny remain unresolved. One approach to increase the resolution of these trees would be to use more appropriate models of sequence evolution in phylogenetic analysis. RNAs transcribed from rRNA genes have a complex secondary structure mediated by base pairing between sometimes distant regions of the rRNA molecule. The pairing between the stem nucleotides has important consequences for their evolution which differs from that of unpaired loop nucleotides. These differences in evolution should ideally be accounted for when using rRNA sequences for phylogeny estimation. We use a novel permutation approach to demonstrate the significant superiority of models of sequence evolution that allow stem and loop regions to evolve according to separate models and, in common with previous studies, we show that 16-state models that take base pairing of stems into account are significantly better than simpler, 4-state, single-nucleotide models. One of these 16-state models has been applied to the phylogeny of the Bilateria using small subunit rRNA (SSU) sequences. Our optimal tree largely echoes previous results based on SSU in particular supporting the tripartite Bilaterian tree of deuterostomes, lophotrochozoans, and ecdysozoans. There are also a number of differences, however, perhaps most important of which is the observation of a clade consisting of the gastrotrichs plus platyheminthes that is basal to all other lophotrochozoan taxa. Use of 16-state models also appears to reduce the Bayesian support given to certain biologically improbable groups found using standard 4-state models.

A comprehensive analysis of mammalian mitochondrial genome base composition and improved phylogenetic methods.

Phylogenetic analysis of mammalian species using mitochondrial protein genes has proved to be problematic in many previous studies. The high mutation rate of mitochondrial DNA and unusual base composition of several species has prompted us to conduct a detailed study of the composition of 69 mammalian mitochondrial genomes. Most major changes in base composition between lineages can be attributed to shifts between the proportions of C and T on the L-strand. These changes are significant at all codon positions and are shown to affect amino acid composition. Correlated changes in the base composition of the RNA loops and stems are also observed. Following up from previous studies, we investigate changes in the base composition of all 12 H-strand proteins and find that variability in proportions of C and T is correlated with location on the genome. Variation in base composition across genes and species is known to adversely affect the performance of phylogenetic inference methods. We have, therefore, developed a customized three-state general time-reversible DNA substitution model, implemented in the PHASE phylogenetic inference package, which lumps C and T into a composite pyrimidine state. We compare the phylogenetic tree obtained using the new three-state model with that obtained using a standard four-state model. Results using the three-state model are more congruent with recent studies using large sets of nuclear genes and help resolve some of the apparent conflicts between studies using nuclear and mitochondrial proteins.

RNA-based phylogenetic methods: application to mammalian mitochondrial RNA sequences.

The PHASE software package allows phylogenetic tree construction with a number of evolutionary models designed specifically for use with RNA sequences that have conserved secondary structure. Evolution in the paired regions of RNAs occurs via compensatory substitutions, hence changes on either side of a pair are correlated. Accounting for this correlation is important for phylogenetic inference because it affects the likelihood calculation. In the present study we use the complete set of tRNA and rRNA sequences from 69 complete mammalian mitochondrial genomes. The likelihood calculation uses two evolutionary models simultaneously for different parts of the sequence: a paired-site model for the paired sites and a single-site model for the unpaired sites. We use Bayesian phylogenetic methods and a Markov chain Monte Carlo algorithm is used to obtain the most probable trees and posterior probabilities of clades. The results are well resolved for almost all the important branches on the mammalian tree. They support the arrangement of mammalian orders within the four supra-ordinal clades that have been identified by studies of much larger data sets mainly comprising nuclear genes. Groups such as the hedgehogs and the murid rodents, which have been problematic in previous studies with mitochondrial proteins, appear in their expected position with the other members of their order. Our choice of genes and evolutionary model appears to be more reliable and less subject to biases caused by variation in base composition than previous studies with mitochondrial genomes.