High vs low CPAP strategy with aerosolized calfactant in preterm infants with respiratory distress syndrome.

BACKGROUND: Optimal CPAP strategy to prevent CPAP failure defined as need for endotracheal intubation is unknown. OBJECTIVE: To evaluate the risk of CPAP failure in infants treated with high vs low CPAP strategy while receiving aerosolized calfactant in the AERO-02 clinical trial and AERO-03 expanded access program. METHODS: Infants born between 29 0/7 to 36 6/7 weeks were included. Comparisons were made between low and high CPAP groups (Low, 4-7 cm H2O; High, 8-10 cm H2O). RESULTS: CPAP failure and pneumothorax were not different between the groups. Odds of CPAP failure were not different after adjustment for baseline characteristics (OR = 0.61; 95% CI: 0.29, 1.24). CONCLUSION: We found no difference in CPAP failure among infants who received aerosolized calfactant that were treated with high vs low CPAP strategy. Efficacy of high CPAP strategy with aerosolized surfactant treatment needs to be evaluated in future studies.

Sarcopenia and outcomes in ventral hernia repair: a preliminary review.

PURPOSE: Sarcopenia, or loss of muscle mass, is associated with increased morbidity and mortality in oncologic resections and several other major surgeries. Complex ventral hernia repairs (VHRs) and abdominal wall reconstruction are often performed in patients at high risk for morbidity and recurrence, though limited data exist on outcomes related to sarcopenia. We aimed to determine if sarcopenia is associated with worse outcomes in patients undergoing VHR. METHODS: We reviewed patients undergoing VHRs from 2014 to 2015. Preoperative CT images were analyzed for cross-sectional muscle mass. Patients with and without sarcopenia underwent statistical analysis to evaluate differences in perioperative morbidity and hernia recurrence. Muscle indices were analyzed independently for outcomes. RESULTS: 135 patients underwent VHR with/without fistula takedown, staged repairs or other concomitant procedures. 27% had sarcopenia (age 34-84, BMI 27-33, 62% male). Postoperative complications occurred in 43% of sarcopenic patients and 47% of non-sarcopenic patients (p = 0.70). Surgical site infections (SSI) were seen in 16% of sarcopenic patients compared to 29% without sarcopenia (p = 0.14). There was no difference in hernia recurrence between groups (p = 0.90). However, after adjusting for diabetes and BMI, a 10 cm2/m2 decrease in muscle index had 1.44 OR of postoperative complications (p < 0.05). CONCLUSIONS: Though prevalent in our population, sarcopenia was not associated with an increase in postoperative complications, surgical site occurences/infections,  or hernia recurrence when previously published oncologic sarcopenia cutoffs were utilized. Previously established sarcopenia outcomes in malignancy may be attributable to an altered metabolic state that is not present in hernia repair patients. Larger-scale studies are recommended to establish new sarcopenia cutoffs for VHRs.

Lower sulfurtransferase detoxification rates of cyanide in konzo-A tropical spastic paralysis linked to cassava cyanogenic poisoning.

Using a matched case-control design, we sought to determine whether the odds of konzo, a distinct spastic paraparesis associated with food (cassava) cyanogenic exposure in the tropics, were associated with lower cyanide detoxification rates (CDR) and malnutrition. Children with konzo (N=122, 5-17 years of age) were age- and sex-matched with presumably healthy controls (N=87) and assessed for motor and cognition performances, cyanogenic exposure, nutritional status, and cyanide detoxification rates (CDR). Cyanogenic exposure was ascertained by thiocyanate (SCN) concentrations in plasma (P-SCN) and urine (U-SCN). Children with a height-for-age z-score (HAZNCHS)<-2 were classified as nutritionally stunted. CDR was measured as time required to convert cyanide to SCN, and expressed as ms/µmol SCN/mg protein or as mmolSCN/ml plasma/min. Mean (SD) U-SCN in children with konzo was 521.9 (353.6) µmol/l and was, significantly higher than 384.6 (223.7) µmol/l in those without konzo. Conditional regression analysis of data for age- and sex- matched case-control pairs showed that konzo was associated with stunting (OR: 5.8; 95% CI: 2.7-12.8; p<0.01; N=83 paired groups) and higher U-SCN (OR: 1.1; 95% CI: 1.02-1.20 per 50-µmol increase in U-SCN; p=0.02; N=47 paired groups). After adjusting for stunting and U-SCN, the odds of developing konzo was reduced by 63% (95% CI: 11-85%, p=0.03; N=41 paired groups) for each 5mmol SCN/(ml plasma/min)-increase in CDR. Linear regression analysis indicated a significant association between BOT-2 or KABC-II scores and both the HAZNCHS z-score and the U-SCN concentration, but not the CDR. Our findings provide evidence in support of interventions to remove cyanogenic compounds from cassava prior to human consumption or, peharps, enhance the detoxification of cyanide in those relying on the cassava as the main source of food.

Factors affecting the success of glucagon delivered during an automated closed-loop system in type 1 diabetes.

BACKGROUND: In bi-hormonal closed-loop systems for treatment of diabetes, glucagon sometimes fails to prevent hypoglycemia. We evaluated glucagon responses during several closed-loop studies to determine factors, such as gain factors, responsible for glucagon success and failure. METHODS: We extracted data from four closed-loop studies, examining blood glucose excursions over the 50min after each glucagon dose and defining hypoglycemic failure as glucose values<60 mg/dl. Secondly, we evaluated hyperglycemic excursions within the same period, where glucose was>180 mg/dl. We evaluated several factors for association with rates of hypoglycemic failure or hyperglycemic excursion. These factors included age, weight, HbA1c, duration of diabetes, gender, automation of glucagon delivery, glucagon dose, proportional and derivative errors (PE and DE), insulin on board (IOB), night vs. day delivery, and point sensor accuracy. RESULTS: We analyzed a total of 251 glucagon deliveries during 59 closed-loop experiments performed on 48 subjects. Glucagon successfully maintained glucose within target (60-180 mg/dl) in 195 (78%) of instances with 40 (16%) hypoglycemic failures and 16 (6%) hyperglycemic excursions. A multivariate logistic regression model identified PE (p<0.001), DE (p<0.001), and IOB (p<0.001) as significant determinants of success in terms of avoiding hypoglycemia. Using a model of glucagon absorption and action, simulations suggested that the success rate for glucagon would be improved by giving an additional 0.8µg/kg. CONCLUSION: We conclude that glucagon fails to prevent hypoglycemia when it is given at a low glucose threshold and when glucose is falling steeply. We also confirm that high IOB significantly increases the risk for glucagon failures. Tuning of glucagon subsystem parameters may help reduce this risk.

Determinants of cognitive performance in children relying on cyanogenic cassava as staple food.

While risk factors for konzo are known, determinants of cognitive impairment in konzo-affected children remain unknown. We anchored cognitive performance (KABC-II scores) to serum levels of free-thyroxine (free-T4), thyroid-stimulating hormone (TSH), albumin, and motor proficiency (BOT-2 scores) in 40 children including 21 with konzo (median age: 9 years) and 19 without konzo (median age: 8 years). A multiple regression model was used to determine variables associated with changes in KABC-II scores. Age (ß: -0.818, 95% CI: -1.48, -0.152) (p = 0.018), gender (ß: -5.72; 95% CI: -9.87, -1.57 for females) (p = 0.009), BOT-2 score (ß: 0.390; 95% CI: 0.113, 0.667) (p = 0.008), and free-T4 (ß: 1.88; 95% CI: 0.009, 3.74) (p = 0.049) explained 61.1 % of variation in KABC-II scores. Subclinical hypothyroidism was not associated with poor cognition. A crude association was found between serum albumin and KABC-II scores (ß: 1.26; 95 % CI: 0.136, 2.39) (p = 0.029). On spot urinary thiocyanate reached 688 µmol/l in children without konzo and 1,032 µmol/L in those with konzo. Female gender and low serum albumin are risk factors common to cognitive and proportionally associated motor deficits in children exposed to cassava cyanogens. The two types of deficits may share common mechanisms.

Expression of kinesin superfamily genes in cultured hippocampal neurons.

The nature of the different kinesin family members that function in a single, specific neuron type has not been systematically investigated. Here, we used quantitative real-time PCR to analyze the developmental expression patterns of kinesin family genes in cultured mouse hippocampal neurons, a highly homogeneous population of nerve cells. For purposes of comparison, we also determined the set of kinesins expressed in embryonic and adult hippocampal tissue. Twenty kinesins are expressed at moderate-to-high levels in mature hippocampal cultures. These include 9 plus-end directed kinesins from the Kinesin-1, -2, and -3 families that are known to mediate organelle transport and 6 other members of the Kinesin-3 and -4 families that are candidate organelle motors. Hippocampal cultures express high levels of a Kinesin-13, which regulates microtubule depolymerization, and moderate-to-high levels of Kinesin-9 and -14 family members, whose functions are not understood. Twelve additional kinesins, including 10 known mitotic kinesins, are expressed at moderate levels in embryonic hippocampus but at very low levels in mature cultures and the adult hippocampus. Collectively, our findings suggest that kinesins subserve diverse functions within a single type of neuron.

Assessing pesticide safety knowledge among Hispanic migrant farmworkers in Oregon.

The purpose of this article is to report on the development and initial use of a pesticide knowledge test (PKT) specifically designed to evaluate agricultural workers' knowledge of the content mandated by the federal Worker Protection Standard (WPS). The PKT is a 20-item, true-false test, used in a sample of 414 adult and adolescent migrant farmworkers in Oregon. The overall mean score, i.e., number correct, was 15.67(78.4%), with both adults and adolescents demonstrating the most difficulty with questions related to the overall health effects of pesticides. The internal consistency was 0.73, when estimated using a method to correct for small sample sizes. Only six items had less than 70% correct answers. Content validity was achieved by basing the items directly on the Worker Protection Standard; face validity was obtained by having the final version of the test reviewed by a bilingual (English-Spanish) educator familiar with the requirements of the WPS. Overall, adult participants scored better than adolescents, and those with previous pesticide training scored better than those without. There were no differences in scores based on gender or whether the test was taken in English or Spanish; however, participants who spoke indigenous languages scored significantly lower than those who did not. These results indicate that the PKT is a valid, reliable measure of worker knowledge of the content of the WPS, although it does not measure the extent to which that knowledge is actually used in the work setting.

Pesticide knowledge and risk perception among adolescent Latino farmworkers.

A substantial proportion of the agricultural production in the U.S. is dependent on the labor of Latino farmworkers. While exact figures are not known, it is estimated that adolescents make up 7% of this valuable workforce. These young workers may be at increased risk for the toxic effects of environmental exposures encountered during their work. Furthermore, language barriers and health beliefs may influence the risk perceptions of this population. We conducted a cross-sectional survey of migrant adolescent farmworkers in 1998 to investigate their work practices, health beliefs, and pesticide knowledge. The large majority of the adolescents in our sample were from Mexico, and 36.3% spoke primarily indigenous languages. Many of the adolescents (64.7%) were traveling and working in the U.S. independent of their parents. Few of the adolescents reported having received pesticide training; however, 21.6% of the sample reported that their current work involved mixing and/or applying agricultural chemicals. The scores on the pesticide knowledge questionnaire were found to significantly predict self-reported use of protection for adolescent farmworkers. The results of this study point to a need for improved pesticide training in youth agricultural workers and specialized education efforts directed toward minorities who speak indigenous dialects. Special attention is merited toward adolescent farmworkers who report that their work includes mixing or applying agricultural chemicals. As the number of adolescent farmworkers increases in the U.S. and the characteristics of the migrant stream continue to change, culturally and developmentally appropriate instruments are needed to adequately assess the health beliefs and protective practices of this population.

Two resting potential levels regulated by the inward-rectifier potassium channel in the guinea-pig spiral modiolar artery.

1. Intracellular in vitro recordings were made from 771 cells from the spiral modiolar artery (SMA). The initial resting potentials (RPs) displayed a bimodal distribution that was well modelled as a mixture of two Gaussian distributions. About half of the cells had an average RP of -74 mV, and were termed high-RP cells, whereas the other half had an average RP around -41 mV, and were termed low-RP cells. Preparations that were incubated for longer than 24 h contained significantly more high-RP cells than those incubated for less than 8 h. 2. When labelled with the fluorescent dye propidium iodide, 68 and 36 cells were identified as smooth muscle cells (SMC) and endothelial cells (EC), respectively. The RP and input resistance were not significantly different between these two types of cell. Dye coupling was observed only in ECs. Dual cell recordings with 0.2-1.0 mm separation demonstrated the simultaneous existence of high- and low-RP cells and a heterogeneous low-strength electrical coupling. 3. The high-RP cells were depolarized by ACh and by high extracellular potassium concentration (high K(+)). The low-RP cells were usually hyperpolarized by moderately high K(+) (7.5-20 mM) and by ACh. The high K(+)-induced hyperpolarization was suppressed by barium (Ba(2+), 10-50 microM). The putative gap junction blocker 18 beta-glycyrrhetinic acid suppressed the ACh-induced responses in SMCs, but not in ECs. 4. Low-RP cells could rapidly shift the membrane potential to a permanent high-RP state spontaneously or, more often, after a brief application of hyperpolarizing agents including high K(+), ACh, nitric oxide and pinacidil. Once shifted to a high-RP state, the responses of these cells to high K(+) and ACh became similar to those of the original high-RP cells. 5. High-RP cells occasionally shifted their potentials to a low-RP state either spontaneously or after a brief application of 10-50 microM Ba(2+) or 100 microM ouabain. Once shifted to the low-RP state, the response of these cells to high K(+) and ACh became a hyperpolarization. The shift between high- and low-RP states was largely mimicked by wash-in and wash-out of low concentrations of Ba(2+). The shift often showed a regenerative process as a fast phase in its middle course. 6. It is concluded that the cochlear SMA in vitro is composed of poorly and heterogeneously coupled SMCs and ECs, simultaneously resting in one of two distinct states, one a high-RP state and the other a low-RP state. The two RP states are exchangeable mainly due to all-or-none-like conductance changes of the inward-rectifier K(+) channel.

Work characteristics and pesticide exposures among migrant agricultural families: a community-based research approach.

There are few data on pesticide exposures of migrant Latino farmworker children, and access to this vulnerable population is often difficult. In this paper we describe a community-based approach to implement culturally appropriate research methods with a migrant Latino farmworker community in Oregon. Assessments were conducted in 96 farmworker homes and 24 grower homes in two agricultural communities in Oregon. Measurements included surveys of pesticide use and work protection practices and analyses of home-dust samples for pesticide residues of major organophosphates used in area crops. Results indicate that migrant farmworker housing is diverse, and the amounts and types of pesticide residues found in homes differ. Azinphos-methyl (AZM) was the pesticide residue found most often in both farmworker and grower homes. The median level of AZM in farmworker homes was 1.45 ppm compared to 1.64 ppm in the entry area of grower homes. The median level of AZM in the play areas of grower homes was 0.71 ppm. The levels of AZM in migrant farmworker homes were most associated with the distance from fields and the number of agricultural workers in the home. Although the levels of AZM in growers and farmworker homes were comparable in certain areas, potential for disproportionate exposures occur in areas of the homes where children are most likely to play. The relationship between home resident density, levels of pesticide residues, and play behaviors of children merit further attention.

Gulf War unexplained illnesses: persistence and unexplained nature of self-reported symptoms.

Most published reports of health symptoms among Gulf War (GW) veterans have been based on self-reported questionnaire data. The presence of these symptoms at the time of a clinical evaluation and the unexplained nature of the symptoms have not been described. We report the findings of a sample of symptomatic veterans that were examined as part of a population-based case-control study of GW unexplained illnesses. Participants in the case-control study were selected from responders to a cross-sectional survey of a random sample of GW veterans residing in the northwestern United States. The initial survey questionnaire solicited information on the presence of fatigue and psychological/cognitive, gastrointestinal, musculoskeletal, and dermatological problems. The persistence of the symptoms and possible explanatory diagnoses were explored at the time of the clinical evaluation. Findings from the first 225 participants who completed clinical examinations indicate significant differences between self-reported symptoms on the survey questionnaire and those confirmed at the time of clinical exam. The agreement between symptoms reported both on the survey and at the time of examination varies across the symptom groups. While self-reported unexplained fatigue was confirmed at the time of clinical encounter in 79% of participants, self-reported gastrointestinal symptoms were confirmed at the clinical encounter in only 20% of participants. Differences between symptoms reported on the survey questionnaire and those confirmed at the time of clinical encounter were attributable to finding a clinical diagnosis for the symptom, resolution of symptom(s) between time of questionnaire and clinical exam, and inadvertent endorsement of the symptom on the questionnaire. These findings suggest that due to the possibility of outcome misclassification, inappropriate conclusions may be drawn about the association between exposures and unexplained illnesses in GW veterans from data derived solely from self-administered questionnaires.

Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava.

Neurological disorders have been reported from parts of Africa with protein-deficient populations and attributed to cyanide (CN-) exposure from prolonged dietary use of cassava, a cyanophoric plant. Cyanide is normally metabolized to thiocyanate (SCN-) by the sulfur-dependent enzyme rhodanese. However, in protein-deficient subjects where sulfur amino acids (SAA) are low, CN may conceivably be converted to cyanate (OCN-), which is known to cause neurodegenerative disease in humans and animals. This study investigates the fate of potassium cyanide administered orally to rats maintained for up to 4 weeks on either a balanced diet (BD) or a diet lacking the SAAs, L-cystine and L-methionine. In both groups, there was a time-dependent increase in plasma cyanate, with exponential OCN- increases in SAA-deficient rats. A strongly positive linear relationship between blood CN- and plasma OCN- concentrations was observed in these animals. These data are consistent with the hypothesis that cyanate is an important mediator of chronic cyanide neurotoxicity during protein-calorie deficiency. The potential role of thiocyanate in cassava-associated konzo is discussed in relationship to the etiology of the comparable pattern of motor-system disease (spastic paraparesis) seen in lathyrism.

U.S. Gulf War Veterans: service periods in theater, differential exposures, and persistent unexplained illness. Portland Environmental Hazards Research Centre.

Approximately 80,000 of the 697,000 American men and women who were stationed in SW Asia during the Gulf War (GW) report unexplained illness consisting of symptoms of persistent fatigue, cognitive difficulties, such as mild memory loss, diffuse muscle and joint pain, gastrointestinal symptoms, skin lesions, and respiratory problems, among others. Associations between major symptom groups and periods of deployment in the theater of operations have been sought in a population-based, clinical case-control study of GW veterans resident in the north-western region of the United States. No statistically significant differences were evident in the proportion of cases with unexplained fatigue, cognitive/psychological or musculoskeletal symptoms among veterans present in SW Asia in 3 specific time periods: (a) 8/1/1990-12/31/1990 (which includes Desert Shield), (b) the period surrounding Desert Storm (1/1/1991-3/31/1991), and (c) the (post-combat) period immediately following hostilities (4/1/1991-7/31/1991). There was a trend for all 3 case symptoms to be more common among GW veterans who served in the post-combat period. As numbers in these deployment groups were small, and power to detect differences low, the apparent absence of significant differences in the frequency of major symptom groups among these veterans requires confirmation in a larger study. Deployment for discrete periods in SW Asia is a method to separate distinct constellations of environmental factors; these are useful for analyses of associations among symptoms and exposures given the near-total absence of objective data on chemical and other possible exposures in the theater of operations.