Anaesthesia-related morbidity associated with recumbent, low-field magnetic resonance imaging of horses.

CASE HISTORY: Medical records from 2009 to 2021 from a private equine referral hospital in Rochester, NH, USA were analysed for cases that underwent general anaesthesia for low-field MRI of the distal limb. These were used to determine peri-anaesthetic morbidity and mortality. CLINICAL FINDINGS AND OUTCOME: Two hundred and forty-three anaesthetic episodes were recorded in horses undergoing low-field MRI. The peri-anaesthetic complication rate prior to discharge was 6.2% (15/243). No patients experienced a fatal complication. Ninety two of the 243 patients had multiple sites imaged, 90/243 received pre-anaesthetic dantrolene, 134/243 received intra-anaesthetic dobutamine, and 15/243 were positioned in dorsal recumbency. Complications included: abdominal discomfort ("colic"; 9/243), myopathy (4/243), hyphaema (1/243) and carpal fracture (1/243). At the time of discharge, 14/15 complications had resolved. Of 135 horses for which data were available 55 became hypotensive during the procedure (lowest mean arterial pressure < 65 mmHg). Median body weight was 553 (min 363, max 771) kg. Horses were anaesthetised for a median of 150 (min 45, max 210) minutes. There was no evidence of an association between higher body weight (p = 0.051) or longer duration of anaesthesia (p = 0.421) and development of an anaesthetic complication. For categorical variables (dantrolene administration pre-anaesthesia, dobutamine administration during anaesthesia, hypotension (mean < 65 mmHg) during anaesthesia, dorsal vs. lateral recumbency, and imaging of single vs. multiple sites), the 95% CI for the OR included 1, indicating a lack of effect of the variable on the odds of complication. CLINICAL RELEVANCE: The cases included in this series suggest that low-field MRI under general anaesthesia is a viable option for diagnostic imaging in otherwise healthy horses. Complications occur, but most resolve before discharge.

Stereotactic Radiosurgery for Vestibular Schwannoma in Neurofibromatosis Type 2: An International Multicenter Case Series of Response and Malignant Transformation Risk.

BACKGROUND: Vestibular schwannomas (VSs) related to neurofibromatosis type 2 (NF2) are challenging tumors. The increasing use of stereotactic radiosurgery (SRS) necessitates further investigations of its role and safety. OBJECTIVE: To evaluate tumor control, freedom from additional treatment (FFAT), serviceable hearing preservation, and radiation-related risks of patients with NF2 after SRS for VS. METHODS: We performed a retrospective study of 267 patients with NF2 (328 VSs) who underwent single-session SRS at 12 centers participating in the International Radiosurgery Research Foundation. The median patient age was 31 years (IQR, 21-45 years), and 52% were male. RESULTS: A total of 328 tumors underwent SRS during a median follow-up time of 59 months (IQR, 23-112 months). At 10 and 15 years, the tumor control rates were 77% (95% CI: 69%-84%) and 52% (95% CI: 40%-64%), respectively, and the FFAT rate were 85% (95% CI: 79%-90%) and 75% (95% CI: 65%-86%), respectively. At 5 and 10 years, the serviceable hearing preservation rates were 64% (95% CI: 55%-75%) and 35% (95% CI: 25%-54%), respectively. In the multivariate analysis, age (hazards ratio: 1.03 [95% CI: 1.01-1.05]; P = .02) and bilateral VSs (hazards ratio: 4.56 [95% CI: 1.05-19.78]; P = .04) were predictors for serviceable hearing loss. Neither radiation-induced tumors nor malignant transformation were encountered in this cohort. CONCLUSION: Although the absolute volumetric tumor progression rate was 48% at 15 years, the rate of FFAT related to VS was 75% at 15 years after SRS. None of the patients with NF2-related VS developed a new radiation-related neoplasm or malignant transformation after SRS.

Effect of magnetized water on blood indices and histomorphometric parameters of intestinal sections of Japanese quail.

A two-way experimental design was used to demonstrate the physiological effects of magnetized water and sex on blood indices and histomorphometric parameters of Japanese quail intestine sections. Red blood cell count (RBCs), packed cell volume (PCV), hemoglobin concentration (Hb), thrombocytes, white blood cell count (WBCs), and WBC differentiation were investigated. A total of 450 unsexed Japanese quail were randomized into three groups (45/replicate; 3 replicates; 135/group). As a monitoring group, the first group was given untreated tap water to drink. The two others were consumed magnetized water that were subjected to an electrical magnetic field with a power of 1 Tesla (10,000 Gauss) and 2 Tesla (20,000 Gauss), respectively. The treatments had a significant (p ≤ 0.05) effect on thrombocytes and Hb. Sex showed significant (p ≤ 0.05) differences for RBCs and PCV at 42 days of age. At different ages, significant effects were observed on histomorphometric parameters of the Japanese quail intestinal tract. It may be inferred that the influence of magnetized water, up to 1 Tesla, was positive on the haematological and histomorphometric parameters of the Japanese quail intestinal tract by augmenting the haematological measurements, which were within a normal range and increasing the surface area of the villus.

Correction: Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection.

[This corrects the article DOI: 10.1371/journal.ppat.1010219.].

Fusarium and allied fusarioid taxa (FUSA). 1.

Seven Fusarium species complexes are treated, namely F. aywerte species complex (FASC) (two species), F. buharicum species complex (FBSC) (five species), F. burgessii species complex (FBURSC) (three species), F. camptoceras species complex (FCAMSC) (three species), F. chlamydosporum species complex (FCSC) (eight species), F. citricola species complex (FCCSC) (five species) and the F. concolor species complex (FCOSC) (four species). New species include Fusicolla elongata from soil (Zimbabwe), and Neocosmospora geoasparagicola from soil associated with Asparagus officinalis (Netherlands). New combinations include Neocosmospora akasia, N. awan, N. drepaniformis, N. duplosperma, N. geoasparagicola, N. mekan, N. papillata, N. variasi and N. warna. Newly validated taxa include Longinectria gen. nov., L. lagenoides, L. verticilliforme, Fusicolla gigas and Fusicolla guangxiensis. Furthermore, Fusarium rosicola is reduced to synonymy under N. brevis. Finally, the genome assemblies of Fusarium secorum (CBS 175.32), Microcera coccophila (CBS 310.34), Rectifusarium robinianum (CBS 430.91), Rugonectria rugulosa (CBS 126565), and Thelonectria blattea (CBS 952.68) are also announced here. Citation: Crous PW, Sandoval-Denis M, Costa MM, Groenewald JZ, van Iperen AL, Starink-Willemse M, Hernández-Restrepo M, Kandemir H, Ulaszewski B, de Boer W, Abdel-Azeem AM, Abdollahzadeh J, Akulov A, Bakhshi M, Bezerra JDP, Bhunjun CS, Câmara MPS, Chaverri P, Vieira WAS, Decock CA, Gaya E, Gené J, Guarro J, Gramaje D, Grube M, Gupta VK, Guarnaccia V, Hill R, Hirooka Y, Hyde KD, Jayawardena RS, Jeewon R, Jurjevic Z, Korsten L, Lamprecht SC, Lombard L, Maharachchikumbura SSN, Polizzi G, Rajeshkumar KC, Salgado-Salazar C, Shang Q-J, Shivas RG, Summerbell RC, Sun GY, Swart WJ, Tan YP, Vizzini A, Xia JW, Zare R, González CD, Iturriaga T, Savary O, Coton M, Coton E, Jany J-L, Liu C, Zeng Z-Q, Zhuang W-Y, Yu Z-H, Thines M (2022). Fusarium and allied fusarioid taxa (FUSA). 1. Fungal Systematics and Evolution 9: 161-200. doi: 10.3114/fuse.2022.09.08.

Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection.

Excessive inflammation is a major cause of morbidity and mortality in many viral infections including influenza. Therefore, there is a need for therapeutic interventions that dampen and redirect inflammatory responses and, ideally, exert antiviral effects. Itaconate is an immunomodulatory metabolite which also reprograms cell metabolism and inflammatory responses when applied exogenously. We evaluated effects of endogenous itaconate and exogenous application of itaconate and its variants dimethyl- and 4-octyl-itaconate (DI, 4OI) on host responses to influenza A virus (IAV). Infection induced expression of ACOD1, the enzyme catalyzing itaconate synthesis, in monocytes and macrophages, which correlated with viral replication and was abrogated by DI and 4OI treatment. In IAV-infected mice, pulmonary inflammation and weight loss were greater in Acod1-/- than in wild-type mice, and DI treatment reduced pulmonary inflammation and mortality. The compounds reversed infection-triggered interferon responses and modulated inflammation in human cells supporting non-productive and productive infection, in peripheral blood mononuclear cells, and in human lung tissue. All three itaconates reduced ROS levels and STAT1 phosphorylation, whereas AKT phosphorylation was reduced by 4OI and DI but increased by itaconate. Single-cell RNA sequencing identified monocytes as the main target of infection and the exclusive source of ACOD1 mRNA in peripheral blood. DI treatment silenced IFN-responses predominantly in monocytes, but also in lymphocytes and natural killer cells. Ectopic synthesis of itaconate in A549 cells, which do not physiologically express ACOD1, reduced infection-driven inflammation, and DI reduced IAV- and IFNγ-induced CXCL10 expression in murine macrophages independent of the presence of endogenous ACOD1. The compounds differed greatly in their effects on cellular gene homeostasis and released cytokines/chemokines, but all three markedly reduced release of the pro-inflammatory chemokines CXCL10 (IP-10) and CCL2 (MCP-1). Viral replication did not increase under treatment despite the dramatically repressed IFN responses. In fact, 4OI strongly inhibited viral transcription in peripheral blood mononuclear cells, and the compounds reduced viral titers (4OI>Ita>DI) in A549 cells whereas viral transcription was unaffected. Taken together, these results reveal itaconates as immunomodulatory and antiviral interventions for influenza virus infection.

Fusarium: more than a node or a foot-shaped basal cell.

Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org).

Assessment of microbial and heavy metal contamination in shallow hand-dug wells bordering Ona River, Southwest Nigeria.

Ona River is one of the three major rivers draining the city of Ibadan. Groundwater is the major source of drinking water in the metropolis; however, data on quality of shallow aquifers bordering Ona River is relatively scarce. This study aimed to evaluate bacteriological status, heavy metal content, and associated human and ecological health risks in hand-dug wells nearby Ona River. A total of 24 water samples from 12 sampling points were collected for chemical and microbial analyses. Heavy metals and microbial pathogens were analyzed using atomic absorption spectrometry and total plate count methods, respectively. Analyses of microbial and heavy metal (HMs) data showed that shallow hand-dug wells within the vicinity of Ona River were bacteriologically contaminated while most of analyzed heavy metals (except manganese) exceeded the drinking water quality standards. Interpretation of microbial and heavy metal (HMs) data identified predominance of anthropogenic activities as the major source of contamination in drinking water. Further scrutiny of HM data through integrated pollution indices identified two nearby wells (S7 and S8) exceed the safe limits and pose considerable risk to inhabitants. In terms of ecological risk index (ER), cadmium exhibited considerable to very high ER in all collected samples while manganese and zinc showed low ER in all analyzed water samples. Potential of non-carcinogenic risk through ingestion pathway in the study area was identified with the order of contributive ratios by HMs as Cd > Pb > Zn > Fe > Mn. The calculated target hazard quotient (THQ) due to ingested HMs for three human population categories exceeds the safe limit in the order of adult < children < infants. The study revealed the deteriorated state of waterside shallow hand-dug wells that need immediate actions by relevant stakeholders in water management. The study recommends improved hygienic practices, pretreatment of water before use, and most importantly, provision of potable pipe-borne water supply to the residents of the study area.

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA.

PURPOSE: This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial. METHODS AND MATERIALS: From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis. RESULTS: Two hundred thirty-three patients treated at 12 institutions were included. Patients presented at a median age of 60 years (range, 13-90), and many had at least 2 prior resections (30%) or radiation therapy (22%). Forty-eight percent of patients had prior gross total resection. At SRS, the median treatment volume was 6.1 cm3 (0.1-97.6). A median 15 Gy (10-30) was delivered to a median percent isodose of 50 (30-80), most commonly in 1 fraction (95%). A model was developed using recursive partitioning analysis, with one point attributed to age >50 years, treatment volume >11.5 cm3, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%). CONCLUSIONS: SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.

Stereotactic Radiosurgery for Atypical (World Health Organization II) and Anaplastic (World Health Organization III) Meningiomas: Results From a Multicenter, International Cohort Study.

BACKGROUND: Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described. OBJECTIVE: To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs. METHODS: An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model. RESULTS: A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively. CONCLUSION: AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.

Ameliorative effect of Nigella sativa oil and vitamin C on the thyroid gland and cerebellum of adult male albino rats exposed to Monosodium glutamate (histological, immunohistochemical and biochemical studies).

Monosodium glutamate (MSG) is a major taste enhancer that is used as a food additive. Vitamin C (Vit C) and Nigella sativa oil (NSO) are known for their potent antioxidant activities. OBJECTIVE: This study investigates the adverse effect of MSG on the thyroid gland and cerebellum of adult male albino rats and the protection against MSG-mediated toxicity provided by Vit C and NSO. DESIGN: Fifty rats were divided into five groups that were treated via oral gavage. Group I (control) rats received distilled water, Group II rats were treated with MSG (6 mg/gm body weight/day), Group III rats were treated with MSG and Vit C (100 mg/kg body weight /day), Group IV rats were treated with MSG and NSO (50 mg/kg body weight two times per week), and Group V rats were treated with MSG together with both Vit C and NSO with MSG. After 60 days of treatment, rats were euthanized and histological sections were prepared from the thyroid gland and the cerebellum for routine staining and immunohistochemical detection of glial fibrillar acidic protein (GFAP), Caspase-3 and proliferating cell nuclear antigen (PCNA), respectively. Cerebellar tissue was also evaluated to determine glutathione (GSH) and malondialdehyde (MDA) levels; GSH was also measured in thyroid tissue. Serum levels of fT3, fT4 and TSH (thyroid stimulating hormone) were also evaluated. RESULTS: Microscopic examination of cerebellar tissues revealed significant cerebellar injury and cellular apoptosis among the rats in Group II. The thyroid glands of Group II rats were notable for degenerating follicles, loss of colloid, sloughed follicular cells and congested blood vessels. The cerebellar and thyroid tissues from rats in treatment Groups III, IV and V revealed significantly less pathology. Cerebellar and thyroid tissues from Group II rats that were treated with MSG alone revealed intense GFAP and caspase-3 (cerebellar) and PCNA (thyroid) immunoreactivity. Furthermore, cerebellar tissues from rats received MSG alone (Group II) were notable for decreased levels of GSH and increased levels of MDA; thyroid tissue from rats in Group II also demonstrated decreased levels of GSH. Likewise, serum fT3 and fT4 levels were significantly decreased, while serum TSH was significantly increased among rats in Group II. Combined administration of Vit C and NSO together with MSG (Group V) revealed some variations in oxidative parameters compared to those in the Group I control rats. CONCLUSIONS: Oral intake of MSG resulted in degenerative changes in neurons and astrocytes in cerebellum and, also degeneration of the thyroid glands of albino rats. Concomitant administration of Vit C and NSO may limit MSG-induced damage to the cerebellum and thyroid glands and thereby provide significant protection against the oxidative damage induced by MSG.

An autopsy report of basilar artery aneurysm flow diversion complicated by postoperative day 3 hemorrhage from vessel rupture.

A middle-aged patient presented with posterior circulation symptoms attributable to a large eccentric basilar trunk aneurysm. The planned treatment was flow diversion with loose coil packing which was successfully performed using a Pipeline Flex device deployed from the basilar to the left posterior cerebral artery. The complete procedure including live biplane fluoroscopy was digitally recorded. The patient had symptomatic improvement postoperatively and was discharged on day 1. The patient suffered a cardiac arrest on postoperative day 3 secondary to massive intraventricular and subarachnoid hemorrhage. An aneurysm rupture was suspected; however, postmortem examination showed an intact aneurysm sac. The hemorrhage was attributed to a small focal rent in the distal basilar artery next to an atheromatous plaque. The Pipeline device was visible through the rent. This is an autopsy report documenting an injury to the parent artery and not the aneurysm as a source of fatal delayed subarachnoid hemorrhage following flow diversion.

Rapid Development of Spinal Epidural Lipomatosis after Treatment of Metastatic Castration-Resistant Prostate Cancer with Second-Generation Androgen Receptor Antagonists.

BACKGROUND: Previous studies have described the association of spinal epidural lipomatosis with several conditions including chronic steroid therapy, Cushing's syndrome, obesity, Paget disease, and hypothyroidism. We present a report of rapid development of spinal epidural lipomatosis after treatment with second-generation anti-androgen therapy, a new strategy for treatment of metastatic castration-resistant prostate cancer that has been increasingly employed in the past few years. A comprehensive discussion of the underlying molecular networks involving androgen receptor blockage and adipocyte differentiation, as well as the clinical implications of such a phenomenon, are provided. CASE DESCRIPTION: We describe the clinical and radiological evolution of a 58-year-old male patient with metastatic prostate cancer, who developed new onset of rapidly progressing lumbosacral epidural lipomatosis with significant compression of the nerve roots of the cauda equina a few months after initiation of treatment with second-generation androgen receptor antagonists. CONCLUSIONS: The underlying pathophysiology of adipose tissue growth following the administration of anti-androgen therapy is discussed, with emphasis on both the canonical Wnt/ß-catenin pathway as well as in the Wnt-independent pathway involving direct activation of downstream transcription factors from the T-cell factor family by the androgen receptor. As second-generation androgen receptor antagonists have been increasingly used for treatment of castration-resistant stage metastatic prostate cancer, new onset of symptomatic epidural lipomatosis should be considered as a possible differential diagnosis, especially because the urinary symptoms of cauda equina compression may be improperly attributed to the primary prostate neoplasm.

An autopsy report of basilar artery aneurysm flow diversion complicated by postoperative day 3 hemorrhage from vessel rupture.

A middle-aged patient presented with posterior circulation symptoms attributable to a large eccentric basilar trunk aneurysm. The planned treatment was flow diversion with loose coil packing which was successfully performed using a Pipeline Flex device deployed from the basilar to the left posterior cerebral artery. The complete procedure including live biplane fluoroscopy was digitally recorded. The patient had symptomatic improvement postoperatively and was discharged on day 1. The patient suffered a cardiac arrest on postoperative day 3 secondary to massive intraventricular and subarachnoid hemorrhage. An aneurysm rupture was suspected; however, postmortem examination showed an intact aneurysm sac. The hemorrhage was attributed to a small focal rent in the distal basilar artery next to an atheromatous plaque. The Pipeline device was visible through the rent. This is an autopsy report documenting an injury to the parent artery and not the aneurysm as a source of fatal delayed subarachnoid hemorrhage following flow diversion.

NS Segment of a 1918 Influenza A Virus-Descendent Enhances Replication of H1N1pdm09 and Virus-Induced Cellular Immune Response in Mammalian and Avian Systems.

The 2009 pandemic influenza A virus (IAV) H1N1 strain (H1N1pdm09) has widely spread and is circulating in humans and swine together with other human and avian IAVs. This fact raises the concern that reassortment between H1N1pdm09 and co-circulating viruses might lead to an increase of H1N1pdm09 pathogenicity in different susceptible host species. Herein, we explored the potential of different NS segments to enhance the replication dynamics, pathogenicity and host range of H1N1pdm09 strain A/Giessen/06/09 (Gi-wt). The NS segments were derived from (i) human H1N1- and H3N2 IAVs, (ii) highly pathogenic- (H5- or H7-subtypes) or (iii) low pathogenic avian influenza viruses (H7- or H9-subtypes). A significant increase of growth kinetics in A549 (human lung epithelia) and NPTr (porcine tracheal epithelia) cells was only noticed in vitro for the reassortant Gi-NS-PR8 carrying the NS segment of the 1918-descendent A/Puerto Rico/8/34 (PR8-wt, H1N1), whereas all other reassortants showed either reduced or comparable replication efficiencies. Analysis using ex vivo tracheal organ cultures of turkeys (TOC-Tu), a species susceptible to IAV H1N1 infection, demonstrated increased replication of Gi-NS-PR8 compared to Gi-wt. Also, Gi-NS-PR8 induced a markedly higher expression of immunoregulatory and pro-inflammatory cytokines, chemokines and interferon-stimulated genes in A549 cells, THP-1-derived macrophages (dHTP) and TOC-Tu. In vivo, Gi-NS-PR8 induced an earlier onset of mortality than Gi-wt in mice, whereas, 6-week-old chickens were found to be resistant to both viruses. These data suggest that the specific characteristics of the PR8 NS segments can impact on replication, virus induced cellular immune responses and pathogenicity of the H1N1pdm09 in different avian and mammalian host species.

Hypolipidemic and hepatoprotective activities of rosemary and thyme in gentamicin-treated rats.

Rosemary ( Rosmarinus officinalis; RM) and thyme ( Thymus vulgaris; TV) are used as remedies. We designed this work to investigate the preventive effect of aqueous extracts of RM or TV on the gentamicin (GM)-induced hepatotoxicity and abnormalities of lipid profile in rats. Both plant extracts exhibited an in vitro antioxidant activity as determined by the 1,1-diphenyl-2-picrylhydrazyl assay. Radical scavenging activity for TV extract was 48.7% and for RM extract was 25.6%. Polyphenolic determination by high-performance liquid chromatography for both extracts revealed that catechin, coumarin, cinnamic acid and rutin were detected in both extracts. RM extract had higher values than TV extract in all except rutin. Ferulic acid and quercetin were also detected in TV extract and sinapic acid and oleuropein were detected in RM extract. In rats given GM intraperitoneally for 10 days and coadministered either RM extract or TV extract orally, both aqueous extracts demonstrated similar hepatoprotective effects manifested by approximate normalization of plasma liver enzymes (AST and ALT), bilirubin level and total protein concentration compared with the group given GM only. Abnormal lipid parameters and raised hydrogen peroxide levels were ameliorated by both extracts. Pancreatic lipase activity was markedly reduced by RM extract. Also, the atherogenic index value was significantly reduced by both extracts as compared to that of GM group. DNA fragmentation analysis confirmed tissue damage by GM and its amelioration by the extracts. These findings suggest that RM and TV extracts could be helpful in ameliorating some aspects of gentamicin toxicity.

Clinical Outcomes of Total Disc Replacement Versus Anterior Lumbar Interbody Fusion for Surgical Treatment of Lumbar Degenerative Disc Disease.

STUDY DESIGN: The authors performed a retrospective controlled study of patients diagnosed with lumbar degenerative disc disease who received surgical intervention (either total disc replacement [TDR]/Activ-L or anterior lumbar interbody fusion [ALIF]) at a single tertiary-care hospital from 2007-2010. OBJECTIVES: To investigate the clinical outcomes after TDR in comparison with ALIF for surgical treatment of lumbar degenerative disc disease (DDD). METHODS: Analyzed data included intra-operative blood loss, time to return to work, and clinical outcomes as evaluated through the Oswestry Disability Index (ODI) and the Visual Analog Scale (VAS) pain questionnaires pre-operatively and at 6 weeks, 3 months, 6 months, and 1 year postoperative follow-up. RESULTS: At the univariate analysis, patients submitted to TDR presented significantly lower VAS pain scores than patients who received ALIF starting at 6 weeks (P < .001) and continuing through one year postoperatively (P = .007). Patients submitted to TDR also presented significantly lower ODI disability scores at all time points. There was a significant difference in the number of days to return to work, with TDR patients returning to work on average 65 days sooner than ALIF patients (P = .011). There was no significant difference in the total blood loss between both groups. CONCLUSIONS: The results of this retrospective controlled study suggest that, in comparison with patients submitted to ALIF, patients submitted to TDR present quicker return to work, less back pain, and lower disability scores at 1 year follow-up.

Preclinical biomarker associations with both incident rheumatoid arthritis and its subsequent mortality: sex effects in a 41-year, community-based, case-control cohort study.

OBJECTIVES: To identify sex effects and preclinical serum biomarker associations with both incident rheumatoid arthritis (RA) and its subsequent mortality, using a 41-year, community-based, case-control cohort. METHODS: After cohort entry in 1974, incident RA cases (n=54) had clinical onsets between 1977 and 1994. Cohort control (CN) subjects were individually matched on entry to cases (4 CN:1 RA, n=216). All subjects were followed for survival from 1995 through 2015. Ranks (1-5) of preclinical z-scores within each set of 1 RA and 4 matched CN were analysed for associations with incident RA and mortality. Survival was evaluated using Cox proportional hazards models. RESULTS: Preclinical serum IgG RF z-score ranks associated with incident RA in 90 males (18 RA, 72 CN). Cigarette smoking, androstenedione, pregnenolone, and sIL-2Rα ranks associated with incident RA in 180 females (36 RA, 144 CN). Total percentile mortality was greater (p=0.003) in RA (70.4) vs. CN (49.9) and equivalently increased in female RA (69.4) vs. CN (49.3) and in male RA (72.2) vs. CN (43.1) subjects. Percentile respiratory-related CODs were greater (p=0.009) only in the female RA cases (16.7) vs. CN (3.5). Ranks of preclinical hsCRP (p=0.028) and sIL-2Rα (p=0.030) independently associated with 140 total deaths, as did sTNF-R1 (p=0.003) and hsCRP (p=0.005) with 50 CVD deaths. Latter biomarker association were significant in females. Therapy responses in 1995 significantly associated with subsequent mortality. CONCLUSIONS: Sex effects were important in preclinical biomarker associations with incident RA, total and CVD mortality as well as occurrence of respiratory deaths.

Successful Treatment of Symptomatic Intracranial Carotid Artery Stenosis Using a 24-mm Long Bare Metal Coronary Stent.

BACKGROUND: Intracranial arterial atherosclerosis represents a common cause of stroke. Despite aggressive and optimal medical management, many patients will unfortunately suffer additional cerebrovascular events. The role of endovascular intervention for intracranial atherosclerotic disease continues to be uncertain, particularly in regard to extensive, symptomatic stenosis. CASE DESCRIPTION: We present a case of a 42-year-old man with a complex medical history who presented with recurrent ischemic stroke in the ipsilateral hemisphere despite optimal medical management. Given the length of stenosis and the luminal size of the intracranial cavernous and petrous segments of the internal carotid artery, we used a bare metal coronary stent (4.0 mm × 24 mm). This represents one of the longest stents deployed for intracranial disease reported in the literature. CONCLUSIONS: This case illustrates that a long coronary stent might be successfully used to manage extensive intracranial lesions. We also review the efficacy of using 1 very long stent versus multiple overlapping stents, with reference to the coronary angiography literature.

Analgesia after ACL reconstruction: Hamstring donor-site injection versus intra-articular local anaesthetic injection.

BACKGROUND: The purpose of this study was to compare hamstring donor-site injection versus intra-articular injection of a local anaesthetic for analgesia after anterior cruciate ligament (ACL) reconstruction. HYPOTHESIS: The two methods provide similar pain relief. MATERIAL AND METHODS: 158 consecutive patients undergoing ACL hamstring tendon graft reconstruction (semi-tendinosus/gracilis [STG] or four-stranded semi-tendinosus [ST4]) during two periods in 2015 were included. Peripheral nerve block was not performed. At the end of surgery, 20mL of ropivacaine 7.5mg/mL was injected, intra-articularly during the early period (n=79) and into the hamstring donor site during the second period (n=79). Post-operative pain was evaluated subjectively by the patients using a visual analogue scale (VAS). We recorded patient demographics, concomitant surgical procedures, VAS pain scores, rescue analgesic use, time to discharge, and patient satisfaction. VAS pain score, side effects, and patient satisfaction were also recorded during a phone interview on the day after surgery (D1). RESULTS: Mean VAS pain scores were not significantly different between the two groups immediately after surgery (D0) or on D1 (D0: intra-articular, 2.08 and donor site, 1.88; Mann-Whitney P=0.6). Neither were the groups significantly different for rescue analgesic use, patient satisfaction, or quadriceps activation. CONCLUSION: The same local anaesthetic provides similar pain relief when injected intra-articularly or into the hamstring donor site after hamstring tendon ACL reconstruction (STG or ST4). LEVEL OF EVIDENCE: III, prospective case-control study.