Neutrophil to lymphocyte ratio predicts short- and long-term mortality following revascularization therapy for ST elevation myocardial infarction

Background: Several inflammation biomarkers have been implicated in the pathogenesis and prognosis of acute coronary syndromes. However, the prognostic role of the neutrophil-lymphocyte white cell interactive response to myocardial injury in predicting short- and long-term mortality after ST elevation myocardial infarction (STEMI) remains poorly defined.Methods: We evaluated 250 consecutive STEMI patients presenting acutely for revascularization to our tertiary care center over 1 year. Patients with acute sepsis, trauma, recent surgery, autoimmune diseases, or underlying malignancy were excluded. Data gathered included demographics, clinical presentation, leukocyte markers, electrocardiograms, evaluations, therapy,major adverse cardiac events, and all-cause mortality.Results: Mean age was 62 ± 15 years, 70.4% of subjects were males while majority (49.4%) were Caucasians. Mean duration of follow-up was 571 ± 291 days (median 730 days). Univariate analysis of several inflammatory biomarkers including C-reactive protein, revealed white cell count (OR = 1.09, p < 0.001) and neutrophil to lymphocyte ratio (NLR) (OR = 1.05, p = 0.011) as predictors of short- and long-term mortality; but not mean neutrophil count (OR = 1.04, p = 0.055) or lymphocyte count alone (OR = 0.96, p = 0.551). Multivariate analysis using backward stepwise regression revealed NLR (OR = 2.64, p = 0.026), female gender (OR = 5.35, p < 0.001), cerebrovascular accident history (OR = 3.36, p = 0.023), low glomerular filtration rate (OR = 0.98, p = 0.012) and cardiac arrest on admission (OR = 17.43, p < 0.001) as robust independent predictors of long-term mortality. NLR was divided into two sub-groups based on an optimal cut off value of 7.4. This provided the best discriminatory cut off point for predicting adverse mortality outcome. Both short-term (≤ 30 days) and long-term (≤ 2 years) mortality were predicted with Kaplan-Meier survival curve separation best stratified by a NLR cut off value of 7.4.Conclusions: NLR based on an optimal cut off value of 7.4, was an excellent predictor of short- and long-term survival in patients with revascularized STEMI and warrants larger scale multi-center prospective evaluation, as a prognostic indicator. NLR offers improved prognostic capacity when combined with conventional clinical scoring systems, such as the Thrombolysis In Myocardial Infarction risk score.

Case report on renal failure reversal in lambda chain multiple myeloma with bortezomib and dexamethasone

Renal failure (RF) reversal in multiple myeloma (MM) is associated with an improved prognosis. Light chain myeloma, serum creatinine (SCr) \u3e 4 mg/dL, extensive proteinuria, early infections, and certain renal biopsy findings are associated with lower rates of RF reversal. Our patient is a 67-year-old female with multiple poor prognostic factors for RF reversal who demonstrated a rapid renal response with bortezomib and dexamethasone (BD) regimen. She presented initially with altered mental status. On exam, she appeared lethargic and dehydrated and had generalized tenderness. She had been taking ibuprofen as needed for pain for a few weeks. Labs showed a white cell count-18,900/muL with no bandemia, hemoglobin 10.8 gm/dL, potassium-6.7 mEq/L, bicarbonate-15 mEq/L, blood urea nitrogen-62 mg/dL, SCr-5.6 mg/dL (baseline: 1.10), and corrected calcium-11.8 mg/dL. A rapid flu test was positive. Imaging studies were unremarkable. Her EKG showed sinus tachycardia and her urinalysis was unremarkable. The unexplained RF in an elderly individual in conjunction with hypercalcemia and anemia prompted a MM work-up; eventually, lambda variant MM was diagnosed. An immediate (4 days) renal response defined as 50% reduction in SCr was noticed after initiation of the BD regimen

Role of Bradykinin Type 2 Receptors in Human Sweat Secretion: Translational Evidence Does Not Support a Functional Relationship

Bradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and nonhuman paw pad studies into in vivo human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46–48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer’s) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79 ± 0.12 and vehicle = +0.64 ± 0.10 mg/cm2/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/mL) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38 ± 0.16 and vehicle = +0.32 ± 0.12 mg/cm2/min); again no differences were observed with B2R antagonism. Last, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically or pharmacologically induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted

Prokaryote genome fluidity is dependent on effective population size

Many prokaryote species are known to have fluid genomes, with different strains varying markedly in accessory gene content through the combined action of gene loss, gene gain via lateral transfer, as well as gene duplication. However, the evolutionary forces determining genome fluidity are not yet well understood. We here for the first time systematically analyse the degree to which this distinctive genomic feature differs between bacterial species. We find that genome fluidity is positively correlated with synonymous nucleotide diversity of the core genome, a measure of effective population size Ne. No effects of genome size, phylogeny or homologous recombination rate on genome fluidity were found. Our findings are consistent with a scenario where accessory gene content turnover is for a large part dictated by neutral evolution

Calibration of VELC detectors on-board Aditya-L1 mission

Aditya-L1 is the first Indian space mission to explore the Sun and solar atmosphere with seven multi-wavelength payloads, with Visible Emission Line Coronagraph (VELC) being the prime payload. It is an internally occulted coronagraph with four channels to image the Sun at 5000 \AA~ in the field of view 1.05 - 3 \rsun, and to pursue spectroscopy at 5303 \AA, 7892 \AA~ and 10747 \AA~ channels in the FOV (1.05 - 1.5 \rsun). In addition, spectropolarimetry is planned at 10747 \AA~ channel. Therefore, VELC has three sCMOS detectors and one InGaAs detector. In this article, we aim to describe the technical details and specifications of the detectors achieved by way of thermo-vacuum calibration at the CREST campus of the Indian Institute of Astrophysics, Bangalore, India. Furthermore, we report the estimated conversion gain, full-well capacity, and readout noise at different temperatures. Based on the numbers, it is thus concluded that it is essential to operate the sCMOS detectors and InGaAs detectors at $-5^{\circ}$ and $-17^{\circ}$ C, respectively, at the spacecraft level.Comment: Accepted for publication in Experimental Astronomy; 13 Pages, 5 Figures and 8 Table

MRI characterization of 124 CT-indeterminate focal hepatic lesions: evaluation of clinical utility

Objective. To evaluate the diagnostic yield of MRI performed for characterization of focal hepatic lesions that are interpreted as indeterminate on CT. Patients and methods. In a retrospective investigation, 124 indeterminate focal hepatic lesions in 96 patients were identified on CT examinations over 5 years from 1997 to 2001. All patients had MRI performed for the liver within 6 weeks of their CT examination. CT and MR images were reviewed independently by two separate groups of two radiologists. The value of MRI in characterizing these lesions was assessed. Diagnoses were confirmed based on histology, characteristic imaging features, and clinical follow-up . Results. MRI definitely characterized 73 lesions (58%) that were indeterminate on CT. MRI was accurate in 72/73 of these lesions. MRI could not definitely characterize 51 lesions (42%). Ten lesions were not visualized on MRI, and follow-up imaging confirmed that no lesion was present in eight of these cases (pseudolesions). Conclusion. MRI is valuable for the characterization of indeterminate focal hepatic lesions detected on CT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75168/1/13651820701216950.pd

The Orphan Gene ybjN Conveys Pleiotropic Effects on Multicellular Behavior and Survival of Escherichia coli

YbjN, encoding an enterobacteria-specific protein, is a multicopy suppressor of temperature sensitivity in the ts9 mutant strain of Escherichia coli. In this study, we further explored the role(s) of ybjN. First, we demonstrated that the ybjN transcript was about 10-fold lower in the ts9 strain compared to that of E. coli strain BW25113 (BW). Introduction of multiple copies of ybjN in the ts9 strain resulted in over-expression of ybjN by about 10-fold as compared to that of BW. These results suggested that temperature sensitivity of the ts9 mutant of E. coli may be related to expression levels of ybjN. Characterization of E. coli ybjN mutant revealed that ybjN mutation resulted in pleiotropic phenotypes, including increased motility, fimbriation (auto-aggregation), exopolysaccharide production, and biofilm formation. In contrast, over-expression of ybjN (in terms of multiple copies) resulted in reduced motility, fimbriation, exopolysaccharide production, biofilm formation and acid resistance. In addition, our results indicate that a ybjN-homolog gene from Erwinia amylovora, a plant enterobacterial pathogen, is functionally conserved with that of E. coli, suggesting similar evolution of the YbjN family proteins in enterobacteria. A microarray study revealed that the expression level of ybjN was inversely correlated with the expression of flagellar, fimbrial and acid resistance genes. Over-expression of ybjN significantly down-regulated genes involved in citric acid cycle, glycolysis, the glyoxylate shunt, oxidative phosphorylation, amino acid and nucleotide metabolism. Furthermore, over-expression of ybjN up-regulated toxin-antitoxin modules, the SOS response pathway, cold shock and starvation induced transporter genes. Collectively, these results suggest that YbjN may play important roles in regulating bacterial multicellular behavior, metabolism, and survival under stress conditions in E. coli. These results also suggest that ybjN over-expression-related temperature rescue of the ts9 mutant may be due to down-regulation of metabolic activity and activation of stress response genes in the ts9 mutant