Brain Natriuretic Peptide is a Predictor of Cardiac Thrombus in Critically Ill Acute Ischemic Stroke Patients

CONTEXT: Plasma brain natriuretic peptide (BNP) levels are elevated in patients with acute ischemic stroke, particularly when accompanied by atrial fibrillation (AF). Plasma BNP might be a useful marker of vulnerability to thromboembolism in non-valvular AF patients. AIM: The aim of the present study was to assess whether the BNP level can serve as a biomarker of the left atrial (LA) thrombus in AF patients with acute ischemic stroke. SETTINGS AND DESIGN: This was a multicenter prospective cohort study. PATIENTS AND METHODS: Thirty AF patients with acute ischemic stroke were included in the study. Their transesophageal echocardiography (TEE) and BNP were assessed. RESULTS: There was a positive significant relation between serum BNP levels and LA thrombus detection by TEE. BNP with a cutoff value >498 pg/l can be used as a diagnostic biomarker for the presence of the LA thrombus. A significant positive correlation existed between serum BNP and LA diameter. Furthermore, a statistically significant positive correlation between serum BNP and AF rate and duration was found in all patients. In addition, a statistically significant inverse correlation was detected between serum BNP and direct bilirubin, international normalized ratio, and albumin. A statistically significant positive correlation existed between serum BNP and prothrombin concentration. CONCLUSION: BNP can be a good diagnostic biomarker for the detection of the LA thrombus in chronic AF patients with acute ischemic stroke

POTENTIAL ROLE OF MILK THISTLE SEED AND ITS OIL EXTRACTS AGAINST HEART AND BRAIN INJURIES INDUCED BY γ-RADIATION EXPOSURE

Objective: This study aimed to investigate the protective effect of Silybum marianum (S. marianum) seeds extract its oil fraction against damage effect of γ-radiation in female albino rats.Methods: Ultrasonic-assisted extraction was used for the extraction of S. marianum seeds. Lipid patterns of S. marianum seeds oil were elucidated using gas chromatography-mass spectrometry (GC-MS). S. marianum seeds extract was analyzed using high-performance liquid chromatography (HPLC). Malondialdehyde (MDA), reduced glutathione (GSH) and metallothionein (MT) were estimated in heart and brain tissues of the examined rats. Lactate dehydrogenase (LDH) and creatine kinase-MB (CKMB) were measured in the serum of the examined rats, and the brain biomarkers; dopamine and serotonin were also measured.Results: The oil was found to be rich in linoleic acid (58.20%) and arachidic acid (23.38%). S. marianum seeds extract revealed the presence of taxifolin and six main active constituents of silymarin, including silydianin, silychristin, silybin A, silybin B, isosilybin A and isosilybin B. Treatment of γ-radiation damage effect using S. marianum seeds extract and its oil fraction led to a significant reduction of MDA levels in heart (139.6 and 165.5 nmol/g, respectively) and brain (158.5 and 135.2 nmol/g, respectively) tissues, however, significant increase of GSH levels in heart (316.4 and 293 mg/g, respectively) and brain (210.4 and 227 mg/g, respectively) tissues was observed, also a significant increase of dopamine levels (85.27 and 65.74 ng/g, respectively) and MT levels of heart tissues (108.5 and 70.52 mg/g, respectively) was observed.Conclusion: S. marianum seeds extract and its oil fraction showed a protective effect against γ-radiation-induced damage in heart and brain.Â

Safety of Transcatheter Aortic Valve Replacement in Patients with Aortic Aneurysm: A Propensity-Matched Analysis

Introduction There is a paucity of data regarding the outcomes of transcatheter aortic valve replacement (TAVR) among patients with thoracic or abdominal aortic aneurysms (AA). Using the Nationwide Inpatient Sample (NIS) database, we explored the safety of TAVR among patients with a diagnosis of AA. Methods We queried the National Inpatient Sample database (2012–2017) for hospitalized patients undergoing TAVR, using ICD-9 and ICD-10 codes for endovascular TAVR. Reports show that \u3e 95% of endovascular TAVR in the US is via transfemoral access, so our population are mostly patients undergoing transfemoral TAVR. Using propensity score matching, we compared the trends and outcomes of TAVR procedures among patients with versus without AA. Results From a total sample of 29,517 individuals who had TAVR procedures between January 2012 and December 2017, 910 had a diagnosis of AA. In 774 matched-pair analysis, all-cause in-hospital mortality was similar in patients with and without AA OR 0.63 [(95% CI 0.28–1.43), p = 0.20]. The median length of stay was higher in patients with AA: 4 days (IQR 2.0–7.0) versus 3 days (IQR 2.0–6.0) p = 0.01. Risk of AKI [OR 1.01 (0.73–1.39), p = 0.87], heart block requiring pacemaker placement [OR 1.17 (0.81–1.69), p = 0.40], aortic dissection [OR 2.38 (0.41–13.75), p = 0.25], acute limb ischemia [OR 0.46 (0.18–1.16), p = 0.09], vascular complications [OR 0.80 (0.34–1.89), p = 0.53], post-op bleeding [OR 1.12 (0.81–1.57), p = 0.42], blood transfusion [OR 1.20 (0.84–1.70), p = 0.26], and stroke [OR 0.58 (0.24–1.39), p = 0.25] were similar in those with and without AA. Conclusions Data from a large nationwide database demonstrated that patients with AA undergoing TAVR are associated with similar in-hospital outcomes compared with patients without AA. Key Summary Points Patients with a diagnosis aortic aneurysm (thoracic or abdominal) undergoing transcatheter aortic valve replacement (TAVR) have same risk of periprocedural complications as those without a diagnosis of aortic aneurysms (AA). Patients with a diagnosis of aortic aneurysm had a longer length of hospital stay. Further studies are needed to determine how specific features of aortic aneurysm such as size, shape, thrombus burden, or calcifications affect the safety of TAVR

Herbimycins D-F, Ansamycin Analogues from \u3cem\u3eStreptomyces\u3c/em\u3e sp. RM-7-15

Bacterial strains belonging to the class actinomycetes were isolated from the soil near a thermal vent of the Ruth Mullins coal fire (Appalachian mountains of Eastern Kentucky). High resolution electrospray ionization mass spectrometry (HR-ESI-MS) and ultraviolet (UV) absorption profiles of metabolites from one of the isolates (Streptomyces sp. RM-7-15) revealed the presence of a unique set of metabolites ultimately determined to be herbimycins D-F (1–3). In addition, herbimycin A (4), dihydroherbimycin A (TAN 420E) (7), and the structurally distinct antibiotic bicycylomycin were isolated from the crude extract of Streptomyces sp. RM-7-15. Herbimycins A, D-F (1–3) displayed comparable binding affinities to the Hsp90α. While the new analogues were found to be inactive in cancer cell cytotoxicity and antimicrobial assays, they may offer new insights in the context of non-toxic ansamycin-based Hsp90 inhibitors for the treatment of neurodegenerative disease

Structure and Specificity of a Permissive Bacterial C-prenyltransferase

This study highlights the biochemical and structural characterization of the L-tryptophan C6 C-prenyltransferase (C-PT) PriB from Streptomyces sp. RM-5-8. PriB was found to be uniquely permissive to a diverse array of prenyl donors and acceptors including daptomycin. Two additional PTs also produced novel prenylated daptomycins with improved antibacterial activities over the parent drug

Structure and Specificity of a Permissive Bacterial C-Prenyltransferase

This study highlights the biochemical and structural characterization of the L-tryptophan C6 C-prenyltransferase (C-PT) PriB from Streptomyces sp. RM-5-8. PriB was found to be uniquely permissive to a diverse array of prenyl donors and acceptors including daptomycin. Two additional PTs also produced novel prenylated daptomycins with improved antibacterial activities over the parent drug

The Native Production of the Sesquiterpene Isopterocarpolone by \u3cem\u3eStreptomyces\u3c/em\u3e sp. RM-14-6

We report the production, isolation and structure elucidation of the sesquiterpene isopterocarpolone from an Appalachian isolate Streptomyces species RM-14-6. While isopterocarpolone was previously put forth as a putative plant metabolite, this study highlights the first native bacterial production of isopterocarpolone and the first full characterisation of isopterocarpolone using 1D and 2D NMR spectroscopy and HR-ESI mass spectrometry. Considering the biosynthesis of closely related metabolites (geosmin or 5-epiaristolochene), the structure of isopterocarpolone also suggests the potential participation of one or more unique enzymatic transformations. In this context, this work also sets the stage for the elucidation of potentially novel bacterial biosynthetic machinery

Far-Lateral Cervical Approach as a Minimally Invasive Technique for Excision of Upper Cervical Anterolateral and Anterior Meningiomas and Dumbbell Schwannomas: Technical Report and Case Series

Objective To demonstrate the details of the far-lateral approach (FLA) as a minimally invasive technique for the excision of the upper cervical anterolateral and anterior meningiomas and dumbbell schwannomas, and to assess the clinical and radiological outcomes. Methods In this technical report and case series we report the FLA technique and patients who underwent the FLA for C1-C4 anterolateral and anterior meningiomas and dumbbell schwannomas between June 2007 and June 2020. All patients’ relative preoperative demographic, clinical, radiographic, operative, histopathological, and perioperative complications and follow-up clinical and radiographic data were reported. Results A total of 19 patients including 12 females and 7 males with a mean age 56.7±17.6 years and mean duration of symptoms 12.8±12.3 months were reported. 9 patients with anterolateral meningiomas, 5 with anterior meningiomas, and 5 with dumbbell schwannomas underwent uneventful FLA procedures. Gross total resection of tumors was reported in 17 patients (89.5%). Preoperative JOA score was normal in ten, grade-I in five, and grade-II in 4 patients, while at the last follow-up it improved to normal in seventeen and grade-I in two patients. Reported postoperative JOA scores at 6 months and at the last follow-up showed that all patients improved at least one grade on JOA scores. There was CSF leak in three patients and superficial wound infection in one. Conclusion Our results advocate the far-lateral cervical approach as a minimally invasive technique in the resection of the upper cervical anterolateral and anterior meningiomas and dumbbell schwannomas as a safe and effective technique

Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate \u3cem\u3eStreptomyces\u3c/em\u3e sp. RM-14- 6

The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6–8] and 11 previously reported bacterial metabolites (1, 3, 9–12a, and 14–18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time. Comparative analysis also provided the basis for structural revision of several previously reported putative aziridine-containing compounds [exemplified by madurastatins A1, B1, C1 (also known as MBJ-0034), and MBJ-0035] as phenol-dihydrooxazoles. Bioactivity analysis [including antibacterial, antifungal, cancer cell line cytotoxicity, unfolded protein response (UPR) modulation, and EtOH damage neuroprotection] revealed 2 and 5 as potent neuroprotectives and lenoremycin (9) and its sodium salt (10) as potent UPR modulators, highlighting new functions for phenol-oxazolines/salicylates and polyether pharmacophores

Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated \u3cem\u3eStreptomyces\u3c/em\u3e

We report the isolation and characterization of three new nybomycins (nybomycins B–D, 1–3) and six known compounds (nybomycin, 4; deoxynyboquinone, 5; α-rubromycin, 6; β-rubromycin, 7; γ-rubromycin, 8; and [2α(1E,3E),4β]-2-(1,3-pentadienyl)-4-piperidinol, 9) from the Rock Creek (McCreary County, KY) underground coal mine acid reclamation site isolate Streptomyces sp. AD-3-6. Nybomycin D (3) and deoxynyboquinone (5) displayed moderate (3) to potent (5) cancer cell line cytotoxicity and displayed weak to moderate anti-Gram-(+) bacterial activity, whereas rubromycins 6–8 displayed little to no cancer cell line cytotoxicity but moderate to potent anti-Gram-(+) bacterial and antifungal activity. Assessment of the impact of 3 or 5 cancer cell line treatment on 4E-BP1 phosphorylation, a predictive marker of ROS-mediated control of cap-dependent translation, also revealed deoxynyboquinone (5)-mediated downstream inhibition of 4E-BP1p. Evaluation of 1–9 in a recently established axolotl embryo tail regeneration assay also highlighted the prototypical telomerase inhibitor γ-rubromycin (8) as a new inhibitor of tail regeneration. Cumulatively, this work highlights an alternative nybomycin production strain, a small set of new nybomycin metabolites, and previously unknown functions of rubromycins (antifungal activity and inhibition of tail regeneration) and also provides a basis for revision of the previously proposed nybomycin biosynthetic pathway