Gastrointestinal parasite infections in Nepalese Gurkha recruits arriving in the United Kingdom from 2012-2020.

BACKGROUND: Gastrointestinal parasite (GIP) infections are a major cause of global morbidity, infecting hundreds of millions of people each year and potentially leading to lifelong infection and serious complications. Few data exist on screening for GIP infections in migrants entering the UK or on the current performance of different traditional diagnostic approaches. This study aimed to describe the prevalence of GIP infections in Nepalese Gurkha recruits screened on arrival in the UK. METHODOLOGY/PRINCIPAL FINDINGS: We present a retrospective analysis of data from screening male adults (18-21 years) who arrived in the UK from Nepal between 2012 and 2020. Three separate faecal samples were obtained from participants at weekly intervals and processed for formalin-ethyl acetate (FEA) concentration/light microscopy and charcoal culture. Serum samples were analysed for IgG antibodies to Strongyloides stercoralis by ELISA. Results were available from 2,263 participants, of whom 463 (20.5%, 95% CI 18.8%-22.2%) had a positive diagnostic test for at least one GIP infection. A total of 525 potential infections were identified. Giardia duodenalis was most common (231/2263, 10.2%), followed by S. stercoralis (102/2263, 4.5%), and hookworm species (86/2263, 3.8%). Analysis (microscopy and culture) of the initial stool sample diagnosed only 244/427 (57.1%) faecally identified pathogens, including 41/86 (47.7%) hookworm infections. The proportion of participants infected with any GIP showed a downward trend over the study period. Log-binomial regression showed risk of infection decreasing by 6.1% year-on-year (95% CI 3.2% - 9.0%). This was driven predominantly by a fall in hookworm, S. stercoralis and Trichuris trichiura prevalence. CONCLUSIONS/SIGNIFICANCE: The level of potentially pathogenic GIP infection in young Nepalese men migrating to the UK is high (20.5%) and requires a combined diagnostic approach including serology and analysis of multiple stool samples incorporating specialised parasitological methods. Advances in molecular approaches may optimise and simplify the intensive screening strategy required.

Subduing the killer - sepsis; through simulation.

Few pathophysiological processes have a higher morbidity and mortality than sepsis. Implementing effective strategies to improve these poor outcomes remains a challenge. Previous work has shown improvements using single and multifaceted approaches, many with inclusion of sepsis training for doctors and nurses. However, previous work has not necessarily trained all those involved in the recognition and treatment of sepsis. After sepsis simulation training using cognitive-constructivist teaching methods, reaudit demonstrated highly significant improvement in 'sepsis-six' delivery. This study found inclusion of healthcare assistants in sepsis training is of great importance. This training should be tailored to personnel's current knowledge base and level of experience.

Rebalance between 7S and 11S globulins in soybean seeds of differing protein content and 11SA4.

Protein content and globulin subunit composition of soybean seeds affect the quality of soy foods. In this proteomic study, the protein profile of soybean seeds with high (∼45.5%) or low (∼38.6%) protein content and with or without the glycinin (11S) subunit 11SA4 was examined. 44 unique proteins and their homologues were identified and showed that both protein content and 11SA4 influenced the abundance of a number of proteins. The absence of 11SA4 exerted a greater impact than the protein content, and led to a decreased abundance of glycinin G2/A2B1 and G5/A5A4B3 subunits, which resulted in lower total 11S with a concomitant higher total ß-conglycinin (7S). Low protein content was associated with higher glycinin G3/A1aB1b and lower glycinin G4/A5A4B3. Using the proteomic approach, it was demonstrated that 11SA4 deficiency induced compensatory accumulation of 7S globulins and led to a similar total abundance for 7S+11S irrespective of protein content or 11SA4.

The effect of antenatal magnesium sulfate on left ventricular afterload and myocardial function measured using deformation and rotational mechanics imaging.

OBJECTIVE: Assess the effect of antenatal magnesium sulfate (MgSO4) on left ventricular function measured using deformation and rotational mechanics imaging. STUDY DESIGN: Infants who received MgSO4 were matched for gestation, birth weight and mode of delivery with controls. Echocardiography was carried out on days 1 and 2 to measure left ventricle longitudinal strain (LV LS), twist, untwist rate, ejection fraction (EF), and systemic vascular resistance (SVR). RESULTS: Thirty-eight infants with a median gestation and birth weight of 27.1 weeks and 923 g were included. On day 1, the MgSO4 group (n=19) had a lower SVR and higher LV LS, EF, twist and untwist rate than the Control group (n=19) (all P<0.05). There were no differences between the groups on day 2. CONCLUSION: Antenatal MgSO4 administration is associated with a lower SVR and higher myocardial function on day 1 in preterm infants <29 weeks gestation.

Treatment of premature infants with pulmonary hypertension and right ventricular dysfunction with milrinone: a case series.

OBJECTIVE: Milrinone has been proposed as an effective treatment for pulmonary hypertension (PH) and right ventricular (RV) dysfunction. We aimed to determine the effect of milrinone therapy on clinical and echocardiography parameters of PH in preterm infants with elevated pulmonary pressures. STUDY DESIGN: A retrospective case review was conducted on infants <32 weeks gestation who received milrinone for the treatment of PH and reduced RV function. Echocardiographic data were collected before and after treatment with milrinone, and serial clinical parameters were recorded over a 72h period. RESULT: Seven infants met the inclusion criteria with a median gestation and birth weight of 27.3 weeks and 1140 g, respectively. Four infants had a diagnosis of pulmonary hypoplasia with PH, and three infants were recipients in twin-to-twin transfusion syndrome who also developed PH. Nitric oxide was used in six infants before commencement of milrinone. Milrinone was commenced at a dose of 0.33 µg kg(-1) min(-1) to 0.5 µg kg(-1) min(-1) and continued for a median duration of 70 h. Use of milrinone was associated with a fall in oxygenation index and inhaled nitric oxide dose. Following an initial fall in blood pressure over the first 6 h, there was an increase in blood pressure over the subsequent 72 h. Echocardiographic data demonstrated an increase in indicators of myocardial performance and PH. One infant died before discharge. CONCLUSION: This case series suggests that milrinone may be a useful therapy for premature infants with echocardiography findings of PH and/or RH dysfunction. This data support the need for a randomised control trial to confirm its efficacy.

Scalable antifouling reverse osmosis membranes utilizing perfluorophenyl azide photochemistry.

We present a method to produce anti-fouling reverse osmosis (RO) membranes that maintains the process and scalability of current RO membrane manufacturing. Utilizing perfluorophenyl azide (PFPA) photochemistry, commercial reverse osmosis membranes were dipped into an aqueous solution containing PFPA-terminated poly(ethyleneglycol) species and then exposed to ultraviolet light under ambient conditions, a process that can easily be adapted to a roll-to-roll process. Successful covalent modification of commercial reverse osmosis membranes was confirmed with attenuated total reflectance infrared spectroscopy and contact angle measurements. By employing X-ray photoelectron spectroscopy, it was determined that PFPAs undergo UV-generated nitrene addition and bind to the membrane through an aziridine linkage. After modification with the PFPA-PEG derivatives, the reverse osmosis membranes exhibit high fouling-resistance.

Natural knowledge as a propaedeutic to self-betterment: Francis Bacon and the transformation of natural history.

This paper establishes the 'emblematic' use of natural history as a propaedeutic to self-betterment in the Renaissance; in particular, in the natural histories of Gessner and Topsell, but also in the works of Erasmus and Rabelais. Subsequently, it investigates how Francis Bacon's conception of natural history is envisaged in relation to them. The paper contends that, where humanist natural historians understood the use of natural knowledge as a preliminary to individual improvement, Bacon conceived self-betterment foremost as a means to Christian charity, or social-betterment. It thus examines the transformation of the moralizing aspect of Renaissance natural history in Bacon's conception of his Great Instauration.

Computational studies on the mechanism of the gold(I)-catalysed rearrangement of cyclopropenes.

Density functional theory calculations have been employed to investigate the mechanism of gold(I)-catalysed rearrangements of cyclopropenes. Product formation is controlled by the initial ring-opening step which results in the formation of a gold-stabilised carbocation/gold carbene intermediate. With 3-phenylcyclopropene-3-methylcarboxylate, the preferred intermediate allows cyclisation via nucleophilic attack of the carbonyl group and hence butenolide formation. Further calculations on simple model systems show that substituent effects can be rationalised by the charge distribution in the ring-opening transition state and, in particular, a loss of negative charge at what becomes the ß-position of the intermediate. With 1-C(3)H(3)R cyclopropenes (R = Me, vinyl, Ph), ring-opening therefore places the substituent at the ß-position.

Low prevalence of transmitted antiretroviral drug resistance in a large UK HIV-1 cohort.

OBJECTIVES: To describe current practice in testing for transmitted antiretroviral drug resistance (TDR) and the prevalence of TDR in a large UK HIV-1 cohort. METHODS: The study includes a retrospective analysis of newly diagnosed HIV-1-infected patients presenting to eight HIV clinics in the north of England between March 2005 and March 2007. Resistance mutations were defined by IAS-USA. Predicted phenotypes were calculated by the Stanford University database. RESULTS: Five hundred and fifty-eight patients were studied, of whom 394 (70.6%) had heterosexually acquired HIV and 377 (67.6%) were infected outside the UK. TDR testing was performed in 406 patients (72.8%). Thirteen of 392 viral resistance profiles (3.3%) showed genotypic TDR. There was no significant association between TDR and any demographic or risk factor or baseline CD4 count. In particular, rates of TDR were similar in white British (6/147, 4.1%) and black African (7/224, 3.1%) patients. The numbers of patients with TDR to individual drug classes were: nucleoside reverse transcriptase inhibitors, 2 (0.5%); non-nucleoside reverse transcriptase inhibitors, 7 (1.8%); and protease inhibitors, 4 (1.0%). No patients had multi-class resistance detected. Eleven patients (2.8%) were predicted to have significant phenotypic resistance to at least one drug. CONCLUSIONS: In a large unselected UK cohort, with high coverage of TDR testing, the prevalence of TDR was low and is in accordance with recent data, showing a decrease in the prevalence of TDR in the UK. Differences in population mix did not appear to explain this low rate.

Alterations in myofilament function contribute to left ventricular dysfunction in pigs early after myocardial infarction.

Myocardial infarction (MI) initiates cardiac remodeling, depresses pump function, and predisposes to heart failure. This study was designed to identify early alterations in Ca2+ handling and myofilament proteins, which may contribute to contractile dysfunction and reduced beta-adrenergic responsiveness in postinfarct remodeled myocardium. Protein composition and contractile function of skinned cardiomyocytes were studied in remote, noninfarcted left ventricular (LV) subendocardium from pigs 3 weeks after MI caused by permanent left circumflex artery (LCx) ligation and in sham-operated pigs. LCx ligation induced a 19% increase in LV weight, a 69% increase in LV end-diastolic area, and a decrease in ejection fraction from 54+/-5% to 35+/-4% (all P<0.05), whereas cardiac responsiveness to exercise-induced increases in circulating noradrenaline levels was blunted. Endogenous protein kinase A (PKA) was significantly reduced in remote myocardium of MI animals, and a negative correlation (R=0.62; P<0.05) was found between cAMP levels and LV weight-to-body weight ratio. Furthermore, SERCA2a expression was 23% lower after MI compared with sham. Maximal isometric force generated by isolated skinned myocytes was significantly lower after MI than in sham (15.4+/-1.5 versus 19.2+/-0.9 kN/m2; P<0.05), which might be attributable to a small degree of troponin I (TnI) degradation observed in remodeled postinfarct myocardium. An increase in Ca2+ sensitivity of force (pCa50) was observed after MI compared with sham (DeltapCa50=0.17), which was abolished by incubating myocytes with exogenous PKA, indicating that the increased Ca2+ sensitivity resulted from reduced TnI phosphorylation. In conclusion, remodeling of noninfarcted pig myocardium is associated with decreased SERCA2a and myofilament function, which may contribute to depressed LV function. The full text of this article is available online at http://circres.ahajournals.org.

Interpregnancy interval and disparity in term small for gestational age births between black and white women.

OBJECTIVE: To examine the influence of interpregnancy interval on the elevated risk of term small for gestational age (SGA) births to black women. METHODS: This study is a secondary analysis of data from the Delivery Interview Program, a hospital-based cohort study of 12,718 women conducted at the Boston Hospital for Women from 1977 to 1980. The current analysis was limited to black and white parous women who gave birth to term infants during the study and whose last previous pregnancies had also resulted in term, live births. There were 578 black and 3400 white women who met these criteria. The rates of term SGA births for black and white women were calculated according to six interpregnancy intervals (6 or less, 6-12, 12-24, 24-36, 36-60, or longer than 60 months). Multiple logistic regression was used to control for confounding. RESULTS: The overall rate of term SGA births was 6.4% for black women compared with 3.9% for white women (relative risk [RR] 1.7, 95% confidence interval [CI] 1.2, 2.4). Black women were also more likely than white women to have interpregnancy intervals of 6 months or less (9.2% black, 4.8% white; RR 1.9, 95% CI 1.4, 2.6). At every interpregnancy interval, black women had a higher rate of term SGA births than white women. After controlling for interpregnancy interval in a logistic regression analysis, the increased risk of SGA delivery among black women remained unchanged (odds ratio 1.7, 95% CI 1.1, 2.5). CONCLUSION: Although black women were more likely than white women to have SGA births and short interpregnancy intervals, differences in interpregnancy intervals between the races did not explain the disparity in term SGA births.

t-REML for robust heteroscedastic regression analysis of mitochondrial power.

The paper reports a long series of observations on two statistically independent variates which have different nonlinear regressions on the same parameter vector. In our analysis of the data, heteroscedasticity is handled by residual maximum likelihood, REML, but to cope with outliers as well, REML based on a t-specification, called t-REML, is introduced. The data are the results of factorial experiments designed to model the quantitative performance of mitochondria generating aerobic power. The response variates are flux, measured as respiration, and ATP potential as log(ATP/ADP). The background of metabolism and oxidative phosphorylation is briefly sketched.

A squared michaelis-menten function of substrate concentration for plant mitochondrial respiration.

Dry and Wiskich ([1987] Arch Biochem Biophys 257: 92-99) have published data showing the response of plant mitochondrial respiration to increasing additions of oxaloacetate or malate when these substrates have been depleted by inhibition of succinate dehydrogenase by malonate, and coenzyme A (CoA) has been sequestered as acetyl-CoA by pyruvate dehydrogenase. In the presence of 2-oxoglutarate, it is shown that the response is given by a Michaelis-Menten curve, but in its absence, when malate has to supply substrate for dehydrogenation as well as to liberate CoA via malate dehydrogenase and citrate synthase, the response is presumably the product of two Michaelis-Menten functions, which can be approximated by the square of a single function.

Statistical modelling of mitochondrial power supply.

By experiment and theory, formulae are derived to calculate the response of mitochondrial power supply, in flux and potential, to an ATP consuming enzyme load, incorporating effects of varying amounts of (i) enzyme, (ii) total circulating adenylate, and (iii) inhibition of the ATP/ADP translocase. The formulae, which apply between about 20% and 80% of maximum respiration, are the same as for the current and voltage of an electrical circuit in which a battery with potential, linear in the logarithm of the total adenylate, charges another battery whose opposing potential is also linear in the same logarithm, through three resistances. These resistances produce loss of potential due to dis-equilibrium of (i) intramitochondrial oxidative phosphorylation, (ii) the ATP/ADP translocase, and (iii) the ATP-consuming enzyme load. The model is represented geometrically by the following configuration: when potential is plotted against flux, the points lie on two pencils of lines each concurrent at zero respiration, the two pencils describing the respective characteristics of the mitochondrion and enzyme. Control coefficients and elasticities are calculated from the formulae.

Estimation of a derivative by a difference quotient: its application to hepatocyte lactate metabolism.

Values of the derivative of a convex function are estimated from data for the function by assigning the difference quotients of the observations to appropriate values of the determining variable. The procedure is illustrated for the time course of hepatocytes incubated with lactate, of amount l, for which pyruvate, of amount p, is also observed. An empirical linear relation between dp/dt and ln(l/p) is established.

The interaction of mammalian medium-chain hydrolase with yeast fatty acid synthetase.

The interaction of rat mammary gland medium-chain thioesterase with yeast fatty acid synthetase has been investigated. Medium-chain thioesterase interacts with yeast fatty acid synthetase causing premature chain termination of the fatty acids synthesized from acetyl-CoA and malonyl-CoA. This effect is most marked under conditions of rate-limiting malonyl-CoA availability. Immobilized yeast fatty acid synthetase specifically binds rat mammary gland medium-chain thioesterase. This interaction has been used to purify medium-chain thioesterase to near homogeneity from samples of rat mammary gland cytosol. The stoichiometry of binding of medium-chain thioesterase to yeast fatty acid synthetase has been investigated. Yeast fatty acid synthetase binds 5.7 +/- 1 mol medium-chain thioesterase/mol yeast fatty acid synthetase. It is concluded that yeast fatty acid synthetase has a medium-chain thioesterase binding site.

The delta 5 and delta 6 desaturation of fatty acids of varying chain length by rat liver: a preliminary report.

The delta 6 desaturase of rat liver can accommodate substrates with a wide range of chain length. delta 9-cis, 12-cis-Dienoic acids of chain lengths 14-22 carbon atoms were all desaturated at the delta 6 position by microsmal preparations from rat liver. By contrast, the delta 5 desaturase appeared much more chain-length sensitive. The percentage delta 5 desaturation of a series of delta 8-cis- and delta 9-trans-monoenoic acids increased with increasing chain length (from C16 to C20).