Community sharing: Contextualizing Western research notions of contamination within an Indigenous research paradigm.

Báa nnilah is a chronic illness self-management program designed by and for the Apsáalooke (Crow) community. Arising from a collaboration between an Indigenous nonprofit organization and a university-based research team, Báa nnilah's development, implementation, and evaluation have been influenced by both Indigenous and Western research paradigms (WRPs). Báa nnilah was evaluated using a randomized wait-list control group design. In a WRP, contamination, or intervention information shared by the intervention group with the control group, is actively discouraged as it makes ascertaining causality difficult, if not impossible. This approach is not consonant with Apsáalooke cultural values that include the encouragement of sharing helpful information with others, supporting an Indigenous research paradigm's (IRP) goal of benefiting the community. The purpose of this paper is to address contamination and sharing as an area of tension between WRP and IRP. We describe how the concepts of contamination and sharing within Báa nnilah's implementation and evaluation are interpreted differently when viewed from these contrasting paradigms, and set forth a call for greater exploration of Indigenous research approaches for developing, implementing, and evaluating intervention programs in Indigenous communities. (Improving Chronic Illness Management with the Apsáalooke Nation: The Báa nnilah Project.: NCT03036189), ClinicalTrials. gov: NCT03036189).

High-frequency oscillatory ventilation in a tertiary paediatric intensive care unit in an academic hospital in Johannesburg, South Africa.

Background: High-frequency oscillatory ventilation (HFOV) remains an option for the management of critically ill children when conventional mechanical ventilation fails. However, its use is not widespread, and there is wide variability reported with respect to how it is used. Objectives: To describe the frequency, indications, settings and outcomes of HFOV use among paediatric patients with a primary respiratory disorder admitted to a tertiary paediatric intensive care unit (PICU). Methods: The study was a 2-year, single-centre, retrospective chart review. Results: Thirty-four (32.7%) patients were managed with HFOV in the PICU during the study period. Thirty-three of the 34 patients had paediatric acute respiratory distress syndrome. Indications for HFOV were inadequate oxygenation in 17 patients (50%), and refractory respiratory acidosis in 15 patients (44.1%) (2 patients did not fit into either category). Approaches to the setting of HFOV varied considerably, particularly with respect to initial pressure around the airways. HFOV was effective at improving both oxygenation, with a median (interquartile range (IQR)) decrease in oxygenation index of 6.34 (5.0 - 9.5), and ventilation with a the median decrease in PaCO2 of 67.6 (46.2 - 105.7) mmHg after 24 hours. Overall mortality was 29.4% in the HFOV group, which is consistent with other studies. Conclusion: HFOV remains an effective rescue ventilatory strategy, which resulted in rapid and sustained improvement in gas exchange in patients with severe hypoxaemia and/or severe respiratory acidosis, particularly in the absence of extracorporeal support. However, the variability in practice and the adverse effects described highlight the need for future high-quality randomised controlled trials to allow for development of meaningful guidelines to optimise HFOV use. Contributions of the study: This study describes the use and outcomes of high-frequency oscillatory ventilation (HFOV) in a South African paediatric intensive care unit, thus addressing a local knowledge gap and providing evidence of the continued efficacy of HFOV for severe hypoxaemia and refractory respiratory acidosis in settings without access to extracorporeal technologies.

High-frequency oscillatory ventilation in a tertiary paediatric intensive care unit in an academic hospital in Johannesburg, South Africa

Background. High-frequency oscillatory ventilation (HFOV) remains an option for the management of critically ill children when conventional mechanical ventilation fails. However, its use is not widespread, and there is wide variability reported with respect to how it is used. Objectives. To describe the frequency, indications, settings and outcomes of HFOV use among paediatric patients with a primary respiratory disorder admitted to a tertiary paediatric intensive care unit (PICU). Methods. The study was a 2-year, single-centre, retrospective chart review. Results. Thirty-four (32.7%) patients were managed with HFOV in the PICU during the study period. Thirty-three of the 34 patients had paediatric acute respiratory distress syndrome. Indications for HFOV were inadequate oxygenation in 17 patients (50%), and refractory respiratory acidosis in 15 patients (44.1%) (2 patients did not fit into either category). Approaches to the setting of HFOV varied considerably, particularly with respect to initial pressure around the airways. HFOV was effective at improving both oxygenation, with a median (interquartile range (IQR)) decrease in oxygenation index of 6.34 (5.0 - 9.5), and ventilation with a the median decrease in PaCO2 of 67.6 (46.2 - 105.7) mmHg after 24 hours. Overall mortality was 29.4% in the HFOV group, which is consistent with other studies. Conclusion. HFOV remains an effective rescue ventilatory strategy, which resulted in rapid and sustained improvement in gas exchange in patients with severe hypoxaemia and/or severe respiratory acidosis, particularly in the absence of extracorporeal support. However, the variability in practice and the adverse effects described highlight the need for future high-quality randomised controlled trials to allow for development of meaningful guidelines to optimise HFOV use

An implementation of a spike-response model with escape noise using an avalanche diode.

This paper introduces a novel probabilistic spike-response model through the combination of avalanche diode-generated Poisson distributed noise, and a standard exponential decay-based spike-response curve. The noise source, which is derived from a 0.35-µm single-photon avalanche diode (kept in the dark), was tested experimentally to verify its characteristics, before being combined with a field-programmable gate-array implementation of a spike-response model. This simple model was then analyzed, and shown to reproduce seven of eight behaviors recorded during an extensive study of the ventral medial hypothalamic (VMH) region of the brain. It is thought that many of the cell types found within the VMH are fed from a tonic noise synaptic input, where the patterns generated are a product of their spike response and not their interconnection. This paper shows how this tonic noise source can be modelled, and due to the independent nature of the noise sources, provides an avenue for the exploration of networks of noise-fueled neurons, which play a significant role in pattern generation within the brain.

Glutamine in critical illness: the time has come, the time is now.

Glutamine (GLN) has been shown to be a key pharmaconutrient in the body's response to stress and injury. It exerts its protective effects via multiple mechanisms, including direct protection of cells and tissue from injury, attenuation inflammation, and preservation of metabolic function. Data support GLN as an ideal pharmacologic intervention to prevent or treat multiple organ dysfunction syndrome after sepsis or other injuries in the intensive care unit population. A large and growing body of clinical data shows that in well-defined critically ill patient groups GLN can be a life-saving intervention.

Discovery and verification of protein differences between Er positive/Her2/neu negative breast tumor tissue and matched adjacent normal breast tissue.

This study was designed to quantify and identify differences in protein levels between tumor and adjacent normal breast tissue from the same breast in 18 women with stage I/II ER positive/Her2/neu negative invasive breast cancer. Eighteen separate difference gel electrophoresis (DIGE) gels were run (1 gel per patient). Relative quantification was based on DIGE analysis. After excision and tryptic digestion, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and peptide mass mapping were used to identify protein spots. Two hundred and forty-three spots were differentially abundant between normal and cancer tissues. Fifty spots were identified: 41 were over abundant and nine were less abundant in cancers than in normal breast tissue. Western blotting provided independent confirmation for three of the most biologically and statistically interesting proteins. All 18 gels were replicated by another technician and 32% of the differentially abundant proteins were verified by the duplicate analysis. Follow-up studies are now examining these proteins as biomarkers in blood.

Effects of pharmaconutrients on cellular dysfunction and the microcirculation in critical illness.

PURPOSE OF REVIEW: A growing body of data has revealed that specific nutrient deficiencies contribute to microvascular and cellular dysfunction following critical illness. Further, targeted administration of these 'pharmaconutrients' may reverse or improve this dysfunction and improve clinical outcome. RECENT FINDINGS: Specific nutrient therapy with glutamine protects cellular metabolism and vascular function via induction of heat shock proteins, which are key proteins found to be deficient following acute illness. Arginine becomes rapidly deficient following trauma and surgery. This leads to significant immunosuppression, which when treated by arginine administration significantly reduces postoperative infection. Omega-3 fatty acids attenuate the inflammatory response and provide for resolution of ongoing inflammatory injury via production of resolvins/protectins. Antioxidants (vitamin C and selenium) and trace elements (zinc) become rapidly depleted in critical illness and replacement appears vital to ensure optimal cellular and microvascular function. Data on targeted metabolic (mitochondrial) therapies (i.e. co-enzyme Q10) show promise to improve myocardial function following cardiac surgery. SUMMARY: These specific nutrients have newly discovered vital mechanistic roles in the optimization of cellular and microcirculatory function in critical illness and injury. A growing body of literature is demonstrating that correction of key nutrient deficiencies via therapeutic administration of these pharmaconutrients can improve clinical outcome in critically ill patients.

Performance-enhancing sports supplements: role in critical care.

Many performance-enhancing supplements and/or drugs are increasing in popularity among professional and amateur athletes alike. Although the uncontrolled use of these agents can pose health risks in the general population, their clearly demonstrated benefits could prove helpful to the critically ill population in whom preservation and restoration of lean body mass and neuromuscular function are crucial. Post-intensive care unit weakness not only impairs post-intensive care unit quality of life but also correlates with intensive care unit mortality. This review covers a number of the agents known to enhance athletic performance, and their possible role in preservation of muscle function and prevention/treatment of post-intensive care unit weakness in critically ill patients. These agents include testosterone analogues, growth hormone, branched chain amino acid, glutamine, arginine, creatine, and beta-hydryoxy-beta-methylbutyrate. Three of the safest and most effective agents in enhancing athletic performance in this group are creatine, branched-chain amino acid, and beta-hydryoxy-beta-methylbutyrate. However, these agents have received very little study in the recovering critically ill patient suffering from post-intensive care unit weakness. More placebo-controlled studies are needed in this area to determine efficacy and optimal dosing. It is very possible that, under the supervision of a physician, many of these agents may prove beneficial in the prevention and treatment of post-intensive care unit weakness.

Mask-less ultraviolet photolithography based on CMOS-driven micro-pixel light emitting diodes.

We report on an approach to ultraviolet (UV) photolithography and direct writing where both the exposure pattern and dose are determined by a complementary metal oxide semiconductor (CMOS) controlled micro-pixellated light emitting diode array. The 370 nm UV light from a demonstrator 8 x 8 gallium nitride micro-pixel LED is projected onto photoresist covered substrates using two back-to-back microscope objectives, allowing controlled demagnification. In the present setup, the system is capable of delivering up to 8.8 W/cm2 per imaged pixel in circular spots of diameter approximately 8 microm. We show example structures written in positive as well as in negative photoresist.

Relationships of dietary fat, body composition, and bone mineral density in inbred mouse strain panels.

Laboratory inbred mouse strains show a broad range of variation in phenotypes, such as body composition, bone mineral density (BMD), plasma leptin, and insulin-like growth factor I (IGF-I), and thus provide a basis for the study of associations among them. We analyzed these phenotypes in male and female mice from 43 inbred strains fed on a high-fat (30% caloric content) diet and from 30 inbred strains fed on a low-fat (6%) diet. Structural equation modeling of these data reveals that the relationship of body fat content and areal BMD is altered by dietary factors and genotypes. Sex has no net effect on areal BMD, but after accounting for body mass difference females have higher areal BMD. Leptin is affected by relative fat mass and has no net effect on areal BMD. IGF-I has a direct effect on areal BMD.

Genome scan linkage results for longitudinal systolic blood pressure phenotypes in subjects from the Framingham Heart Study.

The relationship between elevated blood pressure and cardiovascular and cerebrovascular disease risk is well accepted. Both systolic and diastolic hypertension are associated with this risk increase, but systolic blood pressure appears to be a more important determinant of cardiovascular risk than diastolic blood pressure. Subjects for this study are derived from the Framingham Heart Study data set. Each subject had five records of clinical data of which systolic blood pressure, age, height, gender, weight, and hypertension treatment were selected to characterize the phenotype in this analysis. We modeled systolic blood pressure as a function of age using a mixed modeling methodology that enabled us to characterize the phenotype for each individual as the individual's deviation from the population average rate of change in systolic blood pressure for each year of age while controlling for gender, body mass index, and hypertension treatment. Significant (p = 0.00002) evidence for linkage was found between this normalized phenotype and a region on chromosome 1. Similar linkage results were obtained when we estimated the phenotype while excluding values obtained during hypertension treatment. The use of linear mixed models to define phenotypes is a methodology that allows for the adjustment of the main factor by covariates. Future work should be done in the area of combining this phenotype estimation directly with the linkage analysis so that the error in estimating the phenotype can be properly incorporated into the genetic analysis, which, at present, assumes that the phenotype is measured (or estimated) without error.

Rocuronium versus succinylcholine: are they equally effective during rapid-sequence induction of anesthesia?

UNLABELLED: The purpose of our study was to assess the onset and quality of muscle paralysis and intubation conditions with succinylcholine (Sch) or rocuronium (Roc) during rapid-sequence induction. Patients were randomly assigned to receive thiopental (5 mg/kg) and Sch (1.5 mg/kg) or thiopental (5 mg/kg) and Roc (1.2 mg/kg). The anesthesiologists performing the endotracheal intubation were blinded by standing with their back to the patient. Thirty seconds after drug administration, laryngoscopy was performed. Intubating conditions were scored, the clinical onset of apnea was noted, and a train-of-four monitor recorded data. All patients were ASA physical status I-III and scheduled for emergency procedures; both groups were demographically similar. Thirteen patients received Roc and 13 received Sch. There was no significant difference between the two groups in the number of patients receiving excellent intubating scores (P = 0.41) or in the combined number of patients receiving good and excellent scores (P = 1.0). There was no significant difference in time of onset of apnea for Sch (22+/-13 s) versus Roc (16+/-8s). The return of the first twitch response was significantly faster with Sch (5.05+/-2.5 min) compared with Roc (17.3+/-21.7 min) (P = 0.0001). IMPLICATIONS: In pediatric patients scheduled for emergency surgery, thiopental 5 mg/kg and rocuronium 1.2 mg/kg provided conditions for the completion of intubation in <60 s comparable to those provided by thiopental 5 mg/kg and succinylcholine 1.5 mg/kg. We conclude that rocuronium is a reasonable substitute for succinylcholine in children for rapid-sequence intubation when a rapid return to spontaneous respiration is not desired.

A bronchoscopic, computer-assisted examination of the changes in dimension of the infant tracheal lumen with changes in head position: implications for emergency airway management.

BACKGROUND: Resuscitation guidelines caution against extreme extension or flexion of an infant's head because tracheal obstruction may occur. No data support this recommendation. The authors therefore examined the dimensions of the tracheal lumen in neutral, extended, and flexed head positions in infants undergoing general endotracheal anesthesia for elective surgery. METHODS: Eighteen healthy full-term infants were studied. A flexible fiberoptic bronchoscope was passed through a previously inserted endotracheal tube and positioned above the cricoid cartilage. Video recordings were taken in each of three head positions. Recordings were analyzed by an investigator blinded to head position. A computer-digitized technique was used to measure anterior-posterior and lateral dimensions and cross-sectional area. Data were analyzed using paired t tests and sign tests. RESULTS: No significant differences in mean tracheal dimensions with changes in head position were found. No infant had complete tracheal obstruction. Infants were equally as likely to have a small increase as they were to have a small decrease in tracheal dimension with changes in head position. CONCLUSIONS: Despite the belief that infants and neonates have obstruction at the level of the trachea with extreme positions of the head, the authors were unable to demonstrate this phenomenon.

Molecular analysis and overexpression of the gene encoding endothiapepsin, an aspartic protease from Cryphonectria parasitica.

The gene, epn-1, encoding endothiapepsin (Epn), an aspartic protease (AspP) synthesized and secreted by the ascomycete fungus responsible for chestnut blight, Cryphonectria (Endothia) parasitica, was identified and characterized. Inspection of the nucleotide and deduced amino acid (aa) sequences revealed perfect agreement with the experimentally derived 330-aa sequence of mature Epn [Barkholt, Eur. J. Biochem. 167 (1987) 327-338] and an additional 89 aa of putative preprosequence. Of the nine fungal AspP characterized to date, Epn was found to be most closely related to aspergillopepsin and penicillopepsin (52% and 55% identity, respectively), proteases produced by the ascomycetes Aspergillus awamori and Penicillium janthinellum, and least related to proteases produced by the yeasts Candida albicans and Saccharomyces cerevisiae (27% and 26% identity, respectively). Epn production was found to be the same in isogenic virus-free and virus-containing strains, indicating that this AspP is not down-regulated by the presence of a hypovirulence-associated viral double-stranded RNA, as has been reported for several other secreted C. parasitica gene products. Strains containing multiple copies of epn-1 were obtained by transformation with a plasmid vector containing the cloned epn-1. One of these strains was shown to produce seven to ten times more Epn than the parental wild-type strain.

Fasting urinary calcium/creatinine and hydroxyproline/creatinine values in young women with amenorrhoea and in matched eumenorrhoeic controls.

The present study was undertaken to compare fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (HP/Cr) values in young amenorrhoeic women with those of age and weight-matched menstruating women and to see whether restoration of menstruation would influence values. Thirty amenorrhoeic patients were matched with 30 controls. Higher Ca/Cr (0.393 (SD 0.213) vs 0.142 (0.89), p less than 0.001) and HP/Cr (0.025 (0.005) vs 0.020 (0.007), p less than 0.005) values were found in patients with hyperprolactinaemia or hypothalamic dysfunction associated with weight loss, anorexia nervosa or excessive exercise (n = 20), suggesting excessive bone loss in these amenorrhoeic patients, who are frequently oestrogen deficient. Furthermore when 9 amenorrhoeic patients with hypothalamic dysfunction became eumenorrhoeic their urinary Ca/Cr values fell (p less than 0.02). However, amenorrhoeic patients with polycystic ovaries (n = 10) had similar Ca/Cr and HP/Cr values as their controls. It is therefore probable that amenorrhoeic patients with polycystic ovaries are not at risk of osteopenia. The present findings suggest measurements of fasting urinary Ca/Cr and HP/Cr values are likely to prove useful in identifying patients with amenorrhoea who are rapidly losing bone, and in assessing their responses to therapy.

Characterization of double-stranded RNA genetic elements associated with biological control of chestnut blight: organization of terminal domains and identification of gene products.

We have determined the organization within the terminal domains of the major large double-stranded RNA genetic elements associated with the hypovirulent strain EP713 of the chestnut blight pathogen Cryphonectria (Endothia) parasitica. Only the polyadenylated strand contained long open reading frames. Furthermore, only RNA of the same polarity as the polyadenylated strand was detectable in a single-stranded form, indicating that the polyadenylated strand is the coding or plus strand. The organization of the 5'-proximal portion of the plus strand consisted of a 495 nucleotide non-coding leader sequence followed by two overlapping open reading frames. The first, ORF1, extended 957 nucleotides while the second, ORF2, began 68 nucleotides upstream of the ORF1 termination codon and extended at least 1412 nucleotides. No open reading frames of significant size were detected within 0.8 kb of the poly(A) tail. In vitro translation of synthetic transcripts containing ORF1 yielded a polypeptide of Mr 29 kd. The ORF1 product was also detected in lysates of the hypovirulent strain but was absent in lysates of the isogenic virulent strain. It represents the first protein to be identified as a gene product encoded by a hypovirulence-associated double-stranded RNA genetic element.

Characterization of the mutations responsible for the electrophoretic mobility differences in the NS proteins of vesicular stomatitis virus New Jersey complementation group E mutants.

Temperature-sensitive (ts) mutants of vesicular stomatitis virus, New Jersey serotype, classified in complementation group E contain lesions in the NS gene, which manifest as marked electrophoretic mobility differences of the mutant NS proteins in SDS-polyacrylamide gels. We have cloned full-length cDNA copies of the mutant NS mRNAs, and have determined their nucleotide sequences. tsE1 and tsE3 had single nucleotide changes, and tsE2 had two nucleotide changes, compared to the wild-type NS gene. Three of the mutations were clustered in a region of 18 nucleotides. All the nucleotide differences resulted in amino acid substitutions, which in each case changed the charge of the amino acid concerned. Analysis of the wild-type and mutant NS protein sequences by the method of Chou & Fasman indicated that single amino acid substitutions can radically alter the predicted secondary structure, and these data are discussed in relation to the observed electrophoretic mobility differences.

Conservation of potential phosphorylation sites in the NS proteins of the New Jersey and Indiana serotypes of vesicular stomatitis virus.

A full length cDNA copy of the NS mRNA of the Missouri strain (Hazelhurst subtype, New Jersey serotype) of vesicular stomatitis virus (VSV) has been cloned and sequenced. The mRNA is 856 nucleotides long (excluding polyadenylic acid) and encodes a protein of 274 amino acids (mol. wt. 31 000). Comparison with the NS gene of the Ogden strain (Concan subtype, New Jersey serotype) showed 15% difference at the nucleotide level and 10% difference at the amino acid level; the majority of the changes were located in the 3' half of the mRNA. Comparison with the NS genes of two strains representing the Indiana serotype showed about 50% nucleotide and 33% amino acid sequence homology between the serotypes. In a four-way comparison of the proteins, two regions of higher homology were noted which may be of functional importance. Eighteen potential phosphorylation sites (Ser or Thr) were conserved between the four proteins; five of these sites correspond to the residues which have been suggested to be constitutively phosphorylated and may be essential for NS activity.