Emergency intubation in trauma in KwaZulu-Natal Province, South Africa.

BACKGROUND: Advanced airway management is a research priority in prehospital care. There is a high burden of major trauma in KwaZulu-Natal (KZN) Province, South Africa (SA), and transfer times to trauma units are often prolonged. OBJECTIVES: To examine emergency intubation practice in trauma and burns patients in Pietermaritzburg, KZN, and its environs. METHODS: This was a prospective consecutive case series, conducted from 11 May to 17 July 2016. Data were collected from urban emergency department (ED), rural hospital and roadside procedures in Pietermaritzburg and its drainage area. Patients with emergency intubation following trauma were eligible for inclusion. The primary outcome was successful airway management. Secondary outcomes included first-pass success and adverse events. RESULTS: Forty-one cases were recorded in patients aged 1 - 60 years. No instances of unsuccessful airway management were reported. Recorded first-pass intubation success rates were higher in receiving EDs than rural hospitals (19/22 v. 2/7; p=0.003). Use of a formal preintubation checklist was associated with a higher first-pass success rate (21/23 v. 6/15; p=0.001) and fewer adverse events (0/23 v. 7/16; p<0.001). Identified adverse event rates were 1/22 (EDs), 5/8 (rural hospitals) and 2/9 (roadside). Unmedicated intubation was more common in rural hospitals than EDs (3/8 v. 1/22; p=0.019), despite absence of cardiac arrest in these cases. Minimum standards of anaesthetic monitoring were not consistently met in any setting. CONCLUSIONS: The use of a preprocedural checklist was associated with improved intubation outcomes and may improve practice in SA trauma care and the prehospital environment, including in rural hospitals. Standardised rapid sequence induction protocols, routine use of introducers and end-tidal carbon dioxide monitoring, and increased availability of intraosseous devices also merit consideration. Key performance indicators should be monitored routinely.

Sexual behaviour of backpackers who visit Koh Tao and Koh Phangan, Thailand: a cross-sectional study.

OBJECTIVES: To measure the proportion of backpackers engaging in unprotected sex while travelling in Thailand and to identify predictors of unsafe sexual behaviour. METHODS: A cross-sectional study using an anonymous questionnaire was performed. English-speaking backpackers, excluding US and Thai citizens, were recruited while travelling through the piers of Koh Tao and Koh Phangan between 25 January and 13 March 2013. RESULTS: 61.5% (1238/2013) respondents were travelling without a long-term sexual partner, of whom 39.1% (29.4% females; 51.9% males) reported intercourse with a new partner. 36.8% of these reported inconsistent/no condom use. Inconsistent condom use was independently associated with age <25 years, UK (vs Canadian) nationality and not bringing condoms from home. Backpackers who brought condoms from home were more likely to have sex with a new partner. Male gender and longer trip length increased the likelihood of new partner acquisition and overall risk of unsafe sex but were not associated with inconsistent condom use. New partners were most commonly backpackers from other countries. Men were more likely than women to have sex with a local person. CONCLUSIONS: Backpackers visiting Thailand frequently report unsafe sex. Partner demographics demonstrate a mechanism of international sexually transmitted infection (STI) transfer. In an era of growing antibiotic resistance and continuing HIV transmission, targeting unsafe sex in backpackers has the potential to reduce STI incidence internationally. These data highlight the need for innovative public health intervention. To focus such measures, future research may elucidate why certain groups are at higher risk.

One fungus, which genes? Development and assessment of universal primers for potential secondary fungal DNA barcodes.

The aim of this study was to assess potential candidate gene regions and corresponding universal primer pairs as secondary DNA barcodes for the fungal kingdom, additional to ITS rDNA as primary barcode. Amplification efficiencies of 14 (partially) universal primer pairs targeting eight genetic markers were tested across > 1 500 species (1 931 strains or specimens) and the outcomes of almost twenty thousand (19 577) polymerase chain reactions were evaluated. We tested several well-known primer pairs that amplify: i) sections of the nuclear ribosomal RNA gene large subunit (D1-D2 domains of 26/28S); ii) the complete internal transcribed spacer region (ITS1/2); iii) partial ß -tubulin II (TUB2); iv) γ-actin (ACT); v) translation elongation factor 1-α (TEF1α); and vi) the second largest subunit of RNA-polymerase II (partial RPB2, section 5-6). Their PCR efficiencies were compared with novel candidate primers corresponding to: i) the fungal-specific translation elongation factor 3 (TEF3); ii) a small ribosomal protein necessary for t-RNA docking; iii) the 60S L10 (L1) RP; iv) DNA topoisomerase I (TOPI); v) phosphoglycerate kinase (PGK); vi) hypothetical protein LNS2; and vii) alternative sections of TEF1α. Results showed that several gene sections are accessible to universal primers (or primers universal for phyla) yielding a single PCR-product. Barcode gap and multi-dimensional scaling analyses revealed that some of the tested candidate markers have universal properties providing adequate infra- and inter-specific variation that make them attractive barcodes for species identification. Among these gene sections, a novel high fidelity primer pair for TEF1α, already widely used as a phylogenetic marker in mycology, has potential as a supplementary DNA barcode with superior resolution to ITS. Both TOPI and PGK show promise for the Ascomycota, while TOPI and LNS2 are attractive for the Pucciniomycotina, for which universal primers for ribosomal subunits often fail.

Gut ischaemia following cardiac surgery.

Gut ischaemia following cardiac surgery carries a high mortality and is usually due to non-occlusive mesenteric ischaemia. We reviewed 4464 patients undergoing cardiac surgery over a 5-year period. Sixteen of them developed gut ischaemia post-operatively, 13 of whom were discovered at laparotomies while the remaining 3 were post-mortem diagnoses. Eleven patients were found to have extensive ischaemia and all 11 died irrespective of the treatment and the delay in diagnosis. In five patients ischaemia was localized, involving the caecum in three and terminal ileum in two. They all underwent local resections and survived. The differences in the groups were analysed and the average time between onset of symptoms and laparotomies was longer in the localized ischaemia group compared to the extensive ischaemia group. Our experience illustrates the continuing difficulty in diagnosis of mesenteric ischaemia before gut infarction has occurred. We conclude that different pathologies might be involved in post-cardiac surgery gut ischaemia and although early diagnosis and treatment is considered to be crucial, early laparotomies do not necessarily equate to survival in cases of extensive ischaemia. There is a need to evaluate aggressive strategies for early diagnosis if prognosis is to be improved in these cases.

New insights into onset mechanisms of atrial fibrillation and flutter after coronary artery bypass graft surgery.

OBJECTIVE: To determine by means of a monitoring study the onset mechanisms of atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG). PATIENTS AND DESIGN: During elective CABG, 81 patients had one bipolar atrial and one ventricular epicardial electrode attached. These were connected to a Vitatron 900E external pacing device, which monitored the patients for four consecutive days. 12 lead ECGs were obtained if AF was clinically detected and Holter ECGs were obtained in 8 (33%) of these patients. RESULTS: 24 patients (30%) developed paroxysmal AF (50%), atrial flutter (17%), or both (33%). The number of AF episodes varied from 1-169 a day (median 5) and were usually of short duration (median 2.25 minutes). Pacemaker diagnostics showed much intrapatient and interpatient variability in onset mechanisms but the majority of AF onsets (71%) were preceded by either short runs of AF or multiple atrial extrasystoles. The final trigger was a conducted atrial extrasystole in 72% of cases. There were no bradycardic triggers. The Holter ECGs confirmed the device's data. CONCLUSIONS: The onset mechanisms of post-CABG AF are dominated by atrial extrasystoles with multiple atrial extrasystoles and short runs of AF preceding the main AF onset in the majority of cases. These results have major implications for the development of new preventive pacing algorithms.

Churg-Strauss syndrome with critical endomyocardial fibrosis: 10 year survival after combined surgical and medical management.

A case is presented of the Churg-Strauss syndrome with hypereosinophilia and severe cardiac involvement, namely biventricular endomyocardial fibrosis and gross encroachment of the right ventricular cavity. The clinical picture was similar to Loeffler's syndrome and the idiopathic hypereosinophilic syndrome. Combined aggressive surgical and medical management led to full recovery and survival at 10 years. The good long term outcome is attributed to strict control of peripheral eosinophil count by oral corticosteroids. This case illustrates the damaging effects of hypereosinophilia on the heart.

Multivalued mappings in generalized chaos synchronization.

The onset of generalized synchronization of chaos in directionally coupled systems corresponds to the formation of a continuous mapping that enables one to persistently define the state of the response system from the trajectory of the drive system. A recently developed theory of generalized synchronization of chaos deals only with the case where this synchronization mapping is a single-valued function. In this paper, we explore generalized synchronization in a regime where the synchronization mapping can become a multivalued function. Specifically, we study the properties of the multivalued mapping that occurs between the drive and response systems when the systems are synchronized with a frequency ratio other than one-to-one, and address the issues of the existence and continuity of such mappings. The basic theoretical framework underlying the considered synchronization regimes is then developed.

Subharmonic destruction of generalized chaos synchronization.

A bifurcation of transition that destroys generalized chaos synchronization is considered. This transition frequently occurs in regimes of subharmonic chaos entrainment where synchronization can be abruptly terminated due only to an almost unnoticeable change in the shape of the driving attractor. We explore the main cause of this sensitivity and ascertain the mechanism behind this transition.

Synchronization of chaotic oscillations in doped fiber ring lasers.

The synchronization of chaotic rare-earth-doped fiber ring lasers is analyzed. The lasers are first coupled by transmitting a fraction c of the circulating electric field in the transmitter and injecting it into the optical cavity of the receiver. A coupling strategy which relies on modulation of the intensity of the light alone is also examined. Synchronization is studied as a function of the coupling strength, and we see excellent synchronization, even with very small c. We prove that in an open loop configuration (c=1) synchronization is guaranteed due to the particular structure of our equations and of the injection method we use. The generalized synchronization of these model lasers is examined when there is parameter mismatch between the transmitter and receiver lasers. The synchronization is found to be insensitive to a wide range of mismatch in laser parameters, but it is sensitive to other parameters, in particular those associated with the phase and the polarization of the circulating electric field. Communicating information between the transmitter and receiver lasers is also addressed. We investigate a scheme for modulating information onto the chaotic electric field and then demodulating and detecting the information embedded in the chaotic signal passed down the communications channel. We show full recovery with very low error for a wide range of coupling strengths.

Prenatal care in the United States, 1980-94.

OBJECTIVES: This report examines trends in timing of prenatal care in the United States from 1980 to 1994. Demographic characteristics examined include age, race, Hispanic origin, marital status, place of birth of mother, educational attainment of mother, and live-birth order. Social characteristics discussed include barriers to care and pregnancy wantedness. METHODS: The source of data for trends and demographic analysis is the certificate of live birth filed for each child born in the United States. Data for social characteristics are from the 1988 National Maternal and Infant Health Survey (NMIHS). Data from the NMIHS are based on 9,953 responses. RESULTS: Very few groups of women have yet to achieve the goal of 90 percent initiating prenatal care in the first trimester as set by Healthy People 2000. In 1994, 80 percent of all mothers initiated care in the first trimester. Cuban mothers were the only mothers to reach the objective of 90 percent with Japanese mothers close behind at 89 percent. Mothers with the lowest percent initiating early prenatal care were non-Hispanic black (68 percent), Puerto Rican (67 percent), and American Indian mother (65 percent). Mothers who have problems getting prenatal care due to financial, scheduling, transportation, or other problems have lower rates of initiating early care. Mothers who wanted to be pregnant when they did were more inclined to initiate early care than mothers who did not want to become pregnant or whose pregnancies were mistimed. CONCLUSIONS: Prenatal care use in the United States did not improve in the 1980's but has been improving since 1990. Variations in use by demographic characteristics persist. There are wide gaps between mothers with easier access to prenatal care and those who encounter barriers to care. Mothers who want to become pregnant also tend to seek help in understanding their pregnancy and its risks earlier than those who did not intend to get pregnant or cared to become pregnant at another time.

Structure-based design of novel, urea-containing FKBP12 inhibitors.

The structure-based design and subsequent chemical synthesis of novel, urea-containing FKBP12 inhibitors are described. These compounds are shown to disrupt the cis-trans peptidylprolyl isomerase activity of FKBP12 with inhibition constants (Ki,app) approaching 0.10 microM. Analyses of several X-ray crystal structures of FKBP12-urea complexes demonstrate that the urea-containing inhibitors associate with FKBP12 in a manner that is similar to, but significantly different from, that observed for the natural product FK506.

Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex.

Calcineurin (CaN) is a calcium- and calmodulin-dependent protein serine/threonine phosphate which is critical for several important cellular processes, including T-cell activation. CaN is the target of the immunosuppressive drugs cyclosporin A and FK506, which inhibit CaN after forming complexes with cytoplasmic binding proteins (cyclophilin and FKBP12, respectively). We report here the crystal structures of full-length human CaN at 2.1 A resolution and of the complex of human CaN with FKBP12-FK506 at 3.5 A resolution. In the native CaN structure, an auto-inhibitory element binds at the Zn/Fe-containing active site. The metal-site geometry and active-site water structure suggest a catalytic mechanism involving nucleophilic attack on the substrate phosphate by a metal-activated water molecule. In the FKBP12-FK506-CaN complex, the auto-inhibitory element is displaced from the active site. The site of binding of FKBP12-FK506 appears to be shared by other non-competitive inhibitors of calcineurin, including a natural anchoring protein.

Right ventricular failure in patients requiring left ventricular assistance.

Right ventricular failure may complicate isolated left ventricular assistance. In a series of 8 patients undergoing left ventricular assistance in postcardiotomy cardiogenic shock, right ventricular failure developed in 5, directly contributing to death in all cases despite initially satisfactory support. Difficulty in grafting a dominant right coronary artery was a common factor in all cases. Early consideration should be given to biventricular support under these circumstances.

Hepatic portal venous flow in patients undergoing tricuspid valve surgery.

OBJECTIVE: To determine the changes of flow in the hepatic artery and portal vein of patients undergoing tricuspid valve repair together with mitral valve replacement. DESIGN: Non-randomised parallel group study. SETTING: Tertiary referral centre. PATIENTS: 18 patients with mitral valve disease with or without tricuspid regurgitation (age range 46-73; six men) and six patients with coronary artery disease and normal left ventricular function (women age range 39-78; four men). INTERVENTIONS: Mitral valve replacement with or without modified De Vega repair of the tricuspid valve or coronary artery bypass surgery. MAIN OUTCOME MEASURES: Flow in the hepatic artery and portal vein as measured by duplex Doppler flowmetry before and two to four weeks after operation. RESULTS: Preoperative hepatic artery flow was less in patients with mitral valve disease than in patients with coronary artery disease (162.7(13.1) ml.min-1 v 242.5(6.6) ml.min-1, p < 0.05). Portal vein perfusion was significantly reduced only in patients with associated tricuspid regurgitation compared with (844(83) ml.min-1 v 1422(64) ml.min-1 p < 0.05). Hepatic perfusion was unaltered after operation in patients undergoing coronary artery bypass surgery (p > 0.05). Flow in the hepatic artery and portal vein was improved only in patients undergoing mitral valve replacement with associated tricuspid valve repair (p < 0.05). CONCLUSION: Abnormalities of hepatic perfusion can be measured non-invasively in all patients with mitral valve disease but especially in those with associated tricuspid regurgitation needing valve repair. These abnormalities improved two to four weeks after mitral valve surgery and tricuspid valve repair, suggesting that measurement of portal flow might be a useful means of assessing the severity of tricuspid regurgitation.

Effect of vascular clamp on endothelial integrity of the internal mammary artery.

The preservation of endothelial integrity is essential for maintaining patency of vascular grafts. The internal mammary artery flow is often interrupted with the application of a soft vascular clamp to achieve a bloodless field during the anastomosis. We investigated the effect of the vascular clamp on the internal mammary artery endothelium using the scanning electron and light microscope. The endothelium was examined before and at 15 and 30 minutes after clamping in both the pedicled and the skeletonized arteries. Endothelial integrity was breached by clamping with early evidence of platelet adhesion to the damaged areas. The severity of the endothelial damage was related to the clamp time, but there was no difference in the degree of damage between the pedicled and the skeletonized arteries. We conclude that the vascular clamp causes injury to the internal mammary artery endothelium and may be implicated in early postoperative graft failure.

Identification of vicinal thiols of phosphoenolpyruvate carboxykinase (GTP).

Phosphoenolpyruvate carboxykinase (PEPCK) from the cytosol of rat liver has 13 cysteines, at least one of which (Cys288) is known to be very reactive and critical for catalytic activity (Lewis, C. T., Seyer, J. M., and Carlson, G. M. (1989) J. Biol. Chem. 264, 27-33). Previous results provided evidence for the existence of at least 1 pair of vicinal cysteines within or near the active site of PEPCK (Lewis, C. T., Haley, B. E., and Carlson, G. M. (1989) Biochemistry 28, 9248-9255). An intramolecular cystine disulfide is induced to form upon treatment of PEPCK with equimolar 5,5'-dithiobis(2-nitrobenzoate) (Nbs2) or upon irradiation of the enzyme in the presence of the photoaffinity probe 8-azidoGTP. In each case, modification is accompanied by a substantial loss in catalytic activity, and substrates protect against inactivation and modification. We now report the identification of these modified thiols by differential alkylation of cysteines and half-cystines with radioactive iodoacetate, followed by isolation and sequencing of the modified tryptic peptides. The results indicate that the disulfide formed by equimolar Nbs2 lies within a 15-residue region of the PEPCK sequence that includes Cys399, Cys407, and Cys413. In addition, Cys407 and/or Cys413 also appear to participate in formation of the disulfide induced by 8-azidoGTP. These thiols lie very near a consensus sequence that has been suggested to represent the binding site for the guanine ring of GTP.

Photochemical cross-linking of guanosine 5'-triphosphate to phosphoenolpyruvate carboxykinase (GTP).

Mammalian phosphoenolpyruvate carboxykinase (PEPCK) specifically requires a guanosine or inosine nucleotide as a substrate; however, the structural basis for this nucleotide specificity is not yet known. Because affinity labels derived from guanosine have not yielded a stable, modified peptide in quantities sufficient for sequence analysis, we have investigated the utility of direct photochemical cross-linking of GTP to PEPCK in order to identify the nucleotide binding site. UV irradiation at a distance of 2 cm by a Mineralight lamp (330 microW/cm2) results in the attachment of [alpha-32P]GTP to PEPCK via a stable, covalent linkage in a reaction that is dependent upon GTP concentration and duration of irradiation. After 10 min of irradiation, more than 0.2 mol of [alpha-32P] GTP is incorporated per mole of PEPCK; under these conditions the GTP concentration required for half-maximal labeling is 69 microM. The substrates phosphoenolpyruvate, ITP, and GDP provide protection against photolabeling, as do Mn2+ and Mg2+. One major and one minor radioactive peptide derived from proteolytic digests of photolabeled PEPCK have been isolated and identified. The major modified peptide has been provisionally assigned to an acidic region near the C-terminus, and the minor peptide has been identified as Ser462-Lys471.