Delayed-Onset Malignant Hyperthermia in Association with Rocuronium Use

Purpose Two cases of malignant hyperthermia suspected to be related to the use of a nondepolarizing neuromuscular blocker are reported. Summary A pharmacogenetic disorder that may occur in as many as 1 in 3000 anesthesia procedures, malignant hyperthermia has been linked to the use of certain anesthetic gases and depolarizing neuromuscular blocking agents (e.g., succinylcholine). Although nondepolarizing neuromuscular blockers were cited as contributing to the development of malignant hyperthermia in a small number of published reports, the agents are generally considered safe for use in at-risk patients. Here investigators report two cases in which the nondepolarizing agent rocuronium is thought to have triggered malignant hyperthermia in patients with no known history of the disorder. In one case, a critically ill 27-year-old man undergoing an induced-hypothermia protocol developed a fever about 4 days after receiving rocuronium infusions, with temperatures rising over 11 days to a maximum of 105.2 °F. In the other case, a 63-year-old man being treated for serious complications of elective surgery developed extreme fever (maximum temperature of 107.1 °F) about 4 days after receiving two bolus doses and a continuous infusion of rocuronium. In both cases, the discontinuation of rocuronium therapy was followed by the rapid diminution of fever over 12–36 hours. After consultations with medical staff and consideration of other potential causal and contributory factors (e.g., neurologic injury, antimicrobial-induced fever), rocuronium was deemed the most likely trigger of the severe febrile response experienced by these two patients. Conclusion A 27-year-old man and a 63-year-old man received rocuronium and subsequently developed delayed-onset malignant hyperthermia, which resolved after the rocuronium was discontinued

Peptide based amphiphiles

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High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks.

During 2015 to 2016, Brazil reported more Zika virus (ZIKV) cases than any other country, yet population exposure remains unknown. Serological studies of ZIKV are hampered by cross-reactive immune responses against heterologous viruses. We conducted serosurveys for ZIKV, dengue virus (DENV), and Chikungunya virus (CHIKV) in 633 individuals prospectively sampled during 2015 to 2016, including microcephaly and non-microcephaly pregnancies, HIV-infected patients, tuberculosis patients, and university staff in Salvador in northeastern Brazil using enzyme-linked immunosorbent assays (ELISAs) and plaque reduction neutralization tests. Sera sampled retrospectively during 2013 to 2015 from 277 HIV-infected patients were used to assess the spread of ZIKV over time. Individuals were georeferenced, and sociodemographic indicators were compared between ZIKV-positive and -negative areas and areas with and without microcephaly cases. Epidemiological key parameters were modeled in a Bayesian framework. ZIKV seroprevalence increased rapidly during 2015 to 2016, reaching 63.3% by 2016 (95% confidence interval [CI], 59.4 to 66.8%), comparable to the seroprevalence of DENV (75.7%; CI, 69.4 to 81.1%) and higher than that of CHIKV (7.4%; CI, 5.6 to 9.8%). Of 19 microcephaly pregnancies, 94.7% showed ZIKV IgG antibodies, compared to 69.3% of 257 non-microcephaly pregnancies (P = 0.017). Analyses of sociodemographic data revealed a higher ZIKV burden in low socioeconomic status (SES) areas. High seroprevalence, combined with case data dynamics allowed estimates of the basic reproduction number R0 of 2.1 (CI, 1.8 to 2.5) at the onset of the outbreak and an effective reproductive number Reff of <1 in subsequent years. Our data corroborate ZIKV-associated congenital disease and an association of low SES and ZIKV infection and suggest that population immunity caused cessation of the outbreak. Similar studies from other areas will be required to determine the fate of the American ZIKV outbreak.IMPORTANCE The ongoing American Zika virus (ZIKV) outbreak involves millions of cases and has a major impact on maternal and child health. Knowledge of infection rates is crucial to project future epidemic patterns and determine the absolute risk of microcephaly upon maternal ZIKV infection during pregnancy. For unknown reasons, the vast majority of ZIKV-associated microcephaly cases are concentrated in northeastern Brazil. We analyzed different subpopulations from Salvador, a Brazilian metropolis representing one of the most affected areas during the American ZIKV outbreak. We demonstrate rapid spread of ZIKV in Salvador, Brazil, and infection rates exceeding 60%. We provide evidence for the link between ZIKV and microcephaly, report that ZIKV predominantly affects geographic areas with low socioeconomic status, and show that population immunity likely caused cessation of the outbreak. Our results enable stakeholders to identify target populations for vaccination and for trials on vaccine efficacy and allow refocusing of research efforts and intervention strategies

Prediction of hybrid biomass in Arabidopsis thaliana by selected parental SNP and metabolic markers

A recombinant inbred line (RIL) population, derived from two Arabidopsis thaliana accessions, and the corresponding testcrosses with these two original accessions were used for the development and validation of machine learning models to predict the biomass of hybrids. Genetic and metabolic information of the RILs served as predictors. Feature selection reduced the number of variables (genetic and metabolic markers) in the models by more than 80% without impairing the predictive power. Thus, potential biomarkers have been revealed. Metabolites were shown to bear information on inherited macroscopic phenotypes. This proof of concept could be interesting for breeders. The example population exhibits substantial mid-parent biomass heterosis. The results of feature selection could therefore be used to shed light on the origin of heterosis. In this respect, mainly dominance effects were detected

Symptom increase following a functional capacity evaluation in patients with chronic low back pain:An explorative study of safety

Introduction: This study was performed to study intensity and duration of symptom increase following an FCE and to explore safety of an FCE. Methods: Included were 92 patients with chronic low back pain (CLBP), mean age 38.5 years, mean self-reported disability 12.5 (Roland Morris Disability Questionnaire). All patients underwent an FCE. Symptom increase was measured with a 2-item questionnaire. Operational definition for safety: no formal complaint filed and symptom increase to occur only temporarily. Results: No formal complaints were filed (n=92). In total, 54 patients returned the questionnaire (59%; 'responders'). Of the responders, 76% reported increased symptom intensity after an FCE, ranging from 'little increase' to 'severe increase'. Symptoms of all responders returned to pre-FCE level. Duration of symptom increase of the responders ranged from 1 day to 3 weeks. Symptom increase resided to pre-FCE level within 1 week in 93% of the responders. Symptom increase was weakly related to self-reported disability (r=0.38, p <0.05). Except for gender, differences between responders and non-responders were non-significant. Conclusion: A temporary increase in symptom intensity following an FCE is common. Within the operational definitions of safety used in this study, assessment of functional capacity of patients with CLBP appears safe

Hyperglycemia in bacterial meningitis: a prospective cohort study

ABSTRACT: BACKGROUND: Hyperglycemia has been associated with unfavorable outcome in several disorders, but few data are available in bacterial meningitis. We assessed the incidence and significance of hyperglycemia in adults with bacterial meningitis. METHODS: We collected data prospectively between October 1998 and April 2002, on 696 episodes of community-acquired bacterial meningitis, confirmed by culture of CSF in patients >16 years. Patients were dichotomized according to blood glucose level on admission. A cutoff random non-fasting blood glucose level of 7.8 mmol/L (140 mg/dL) was used to define hyperglycemia, and a cutoff random non-fasting blood glucose level of 11.1 mmol/L (200 mg/dL) was used to define severe hyperglycemia. Unfavorable outcome was defined on the Glasgow outcome scale as a score <5. We also evaluated characteristics of patients with a preadmission diagnosis of diabetes mellitus. RESULTS: 69% of patients were hyperglycemic and 25% severely hyperglycemic on admission. Compared with non-hyperglycemic patients, hyperglycemia was related with advanced age (median, 55 yrs vs. 44 yrs, P<0.0001), preadmission diagnosis of diabetes (9% vs. 3%, P=0.005), and distant focus of infection (37% vs. 28%, P=0.02). They were more often admitted in coma (16% vs. 8%; P=0.004) and with pneumococcal meningitis (55% vs. 42%, P=0.007). These differences remained significant after exclusion of patients with known diabetes. Hyperglycemia was related with unfavorable outcome (in a hockey stick-shaped curve) but this relation did not remain robust in a multivariate analysis. Factors predictive for neurologic compromise were related with higher blood glucose levels, whereas factors predictive for systemic compromise were related with lower blood glucose levels. Only a minority of severely hyperglycemic patients were known diabetics (19%). The vast majority of these known diabetic patients had meningitis due to Streptococcus pneumoniae (67%) or Listeria monocytogenes (13%) and they were at high risk for unfavorable outcome (52%). CONCLUSIONS: The majority of patients with bacterial meningitis have hyperglycemic blood glucose levels on admission. Hyperglycemia can be explained by a physical stress reaction, the central nervous system insult leading to disturbed blood-glucose regulation mechanisms, and preponderance of diabetics for pneumococcal meningitis. Patients with diabetes and bacterial meningitis are at high risk for unfavorable outcom

Highly Selective End-Tagged Antimicrobial Peptides Derived from PRELP

Background: Antimicrobial peptides (AMPs) are receiving increasing attention due to resistance development against conventional antibiotics. Pseudomonas aeruginosa and Staphylococcus aureus are two major pathogens involved in an array of infections such as ocular infections, cystic fibrosis, wound and post-surgery infections, and sepsis. The goal of the study was to design novel AMPs against these pathogens. Methodology and Principal Findings: Antibacterial activity was determined by radial diffusion, viable count, and minimal inhibitory concentration assays, while toxicity was evaluated by hemolysis and effects on human epithelial cells. Liposome and fluorescence studies provided mechanistic information. Protease sensitivity was evaluated after subjection to human leukocyte elastase, staphylococcal aureolysin and V8 proteinase, as well as P. aeruginosa elastase. Highly active peptides were evaluated in ex vivo skin infection models. C-terminal end-tagging by W and F amino acid residues increased antimicrobial potency of the peptide sequences GRRPRPRPRP and RRPRPRPRP, derived from proline arginine-rich and leucine-rich repeat protein (PRELP). The optimized peptides were antimicrobial against a range of Gram-positive S. aureus and Gram-negative P. aeruginosa clinical isolates, also in the presence of human plasma and blood. Simultaneously, they showed low toxicity against mammalian cells. Particularly W-tagged peptides displayed stability against P. aeruginosa elastase, and S. aureus V8 proteinase and aureolysin, and the peptide RRPRPRPRPWWWW-NH2 was effective against various "superbugs'' including vancomycin-resistant enterococci, multi-drug resistant P. aeruginosa, and methicillin-resistant S. aureus, as well as demonstrated efficiency in an ex vivo skin wound model of S. aureus and P. aeruginosa infection. Conclusions/Significance: Hydrophobic C-terminal end-tagging of the cationic sequence RRPRPRPRP generates highly selective AMPs with potent activity against multiresistant bacteria and efficiency in ex vivo wound infection models. A precise "tuning'' of toxicity and proteolytic stability may be achieved by changing tag-length and adding W-or F-amino acid tags