Perioperative management of patients with anaemia: a new guideline.

Anaemia is common before major surgery and increases complications. A new guideline aims to help with early diagnosis of the type and cause of anaemia and initiate effective treatment. The guideline includes clear education for all staff and patients about the biology of iron homeostasis and patient blood management.

Management of Critically Ill Patients With Spinal Muscular Atrophy Admitted With Acute Respiratory Failure.

BACKGROUND: Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in progressive muscular atrophy and weakness. The primary cause of morbidity and mortality in these children is pulmonary disease due to poor airway clearance that leads to acute respiratory failure. There is a paucity of literature on the treatment of children with SMA and acute respiratory failure. METHODS: We performed a retrospective chart review of pediatric patients with SMA type I or II admitted to the PICU in a tertiary-care children's hospital with acute respiratory failure who required mechanical ventilation and/or aggressive airway clearance. RESULTS: The study included 300 unique encounters among 137 unique subjects. All the subjects received airway clearance at home before admission, and 257 encounters (85.7%) were supported with noninvasive ventilation (NIV) before admission. Sixty-eight subjects (49.6%) required endotracheal intubation on admission or at some point during their PICU stay. The median (interquartile range [IQR]) time to intubation was 0 (0-20) h, and the median (IQR) duration of mechanical ventilation was 2 (1-5) d on invasive mechanical ventilation with no statistical difference between type I and type II (P = .89). Of those, 65 (91.1%) were successfully extubated to NIV on the first attempt, whereas 4 subjects (5.8%) required multiple extubation attempts and 3 subjects (4.4%) required subsequent tracheostomy. For the subjects who were intubated, both PICU and hospital length of stay were longer (P < .001) when compared with the subjects managed by NIV alone. The subjects with SMA type I had a longer PICU length of stay, with a median (IQR) of 5 (3-11) d versus 4 (2-7) d (P = .002). The hospital length of stay and duration of invasive mechanical ventilation were not statistically different (P = .055 and P = .068, respectively). CONCLUSIONS: The subjects with SMA types I or II can be treated successfully with NIV and aggressive airway clearance during acute respiratory failure. Similarly, when intubation is required, successful extubation can be achieved with NIV transitional support combined with aggressive airway clearance maneuvers.

Understanding the Contributions of Trait Autism and Anxiety to Extreme Demand Avoidance in the Adult General Population.

Autism and anxiety are thought to be related to extreme demand avoidance (EDA), which is characterised by intense avoidance of everyday demands. However, the relative importance of autism and anxiety to EDA has yet to be investigated, and little is known about EDA in adulthood. We conducted two online survey studies (Ns = 267 and 549) with adults in the general population to establish the relative importance of autistic traits and anxiety as predictors of demand avoidance, using dominance analysis. Both autistic traits and anxiety were unique and equally important predictors of demand avoidance. These findings suggest EDA is linked to autism and are consistent with the theory that demand avoidance behaviours are potentially anxiety-driven in adults.

Preoperative assessment and optimisation: the key to good outcomes after the pandemic.

Complications following surgery are common, predictable and often preventable. New preoperative assessment and optimisation guidance recommends clear pathways with triggers for interventions, patient involvement, shared decision making and team education, to help both patients and service efficiency.

A multiplex RT-PCR method to detect papaya meleira virus complex in adult pre-flowering plants.

Papaya sticky disease (PSD), which can destroy orchards, was first attributed to papaya meleira virus (PMeV). However, the discovery of papaya meleira virus 2 (PMeV2) associated with PSD plants impose the need to detect this viral complex. We developed a multiplex RT-PCR (mPCR) technique capable of detecting two viruses in a single assay from pre-flowering plant samples, which is a useful tool for early diagnosis of PSD. We also determined the limit of detection (LOD) using asymmetric plasmid dilutions of both PMeV and PMeV2, which revealed that a higher titer of one virus prevents detection of the other. Thus, this technique is an alternative method for detecting PMeV and PMeV2 in a single reaction.

Encoding canonical DNA quadruplex structure.

The main challenge in DNA quadruplex design is to encode a three-dimensional structure into the primary sequence, despite its multiple, repetitive guanine segments. We identify and detail structural elements describing all 14 feasible canonical quadruplex scaffolds and demonstrate their use in control of design. This work outlines a new roadmap for implementation of targeted design of quadruplexes for material, biotechnological, and therapeutic applications.

Comprehensive two-dimensional gas chromatography-mass spectrometry of complex mixtures of anaerobic bacterial metabolites of petroleum hydrocarbons.

Anaerobic biotransformation of petroleum hydrocarbons is an important alteration mechanism, both subsurface in geological reservoirs, in aquifers and in anoxic deep sea environments. Here we report the resolution and identification, by comprehensive two-dimensional gas chromatography-mass spectrometry (GC×GC-MS), of complex mixtures of aromatic acid and diacid metabolites of the anaerobic biodegradation of many crude oil hydrocarbons. An extended range of metabolites, including alkylbenzyl, alkylindanyl, alkyltetralinyl, alkylnaphthyl succinic acids and alkyltetralin, alkylnaphthoic and phenanthrene carboxylic acids, is reported in samples from experiments conducted under sulfate-reducing conditions in a microcosm over two years. The range of metabolites identified shows that the fumarate addition mechanism applies to the alteration of hydrocarbons with up to C8 alkylation in monoaromatics and that functionalisation of up to three ring aromatic hydrocarbons with at least C1 alkylation occurs. The GC×GC-MS method might now be applied to the identification of complex mixtures of metabolites in samples from real environmental oil spills.

Spirometry interpretation feasibility among pre-school children according to the European Respiratory Society and American Thoracic Society Guidelines / Factibilidad de la interpretación de espirometrías en preescolares según criterios ATS/ERS.

INTRODUCTION: Spirometry is the most used test to evaluate pulmonary function. Guidelines that defined acceptability and repeatability criteria for its implementation and interpretation among preschoolers were published in 2007. Our objective was to quantify the actual compliance with these criteria among pre-school patients. METHODS: A review was performed on the baseline spirometry measured in patients aged 2 to 5 years in the Pediatric Respiratory Laboratory of the Pontificia Universidad Católica de Chile, who were admitted due to recurrent or persistent coughing or wheezing. Only those results obtained in patients who took the test for the first time were considered. They were analyzed by international standards. RESULTS: A total of 93 spirometry results (mean age 57.4 ± 8.6 months, 48 males) were obtained, of which 44 (47%) met all acceptable criteria, 87 (93%) obtained expiratory time of ≥ 0.5seconds, and 67 (72%) of the patients had an end-expiratory flow of ≤10% from peak flow. The variation in the measurement of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) was very low (intraclass correlation coefficient > 0.9). CONCLUSION: It was possible to meet the acceptability and repeatability criteria for spirometry among pre-school children in our Center, which was similar to previous reports. As in older children, this test is fully recommended for pre-school children who require lung function studies.

An assessment of Trinidad & Tobago’s health information system readiness

OBJECTIVES: (i). The establishment of a baseline of Trinidad & Tobago’s Health Information System (HIS) status; (ii). The promotion of a common and comprehensive understanding of the HIS among all stakeholders; (iii). The identification of existing strengths and weaknesses of the HIS; and (iv). The identification of priority areas for improvement. DESIGN AND METHODS: Using the Version 4.0 of the WHO’s Health Metrics Network Assessment Tool three (3) Regional Health Authorities (RHAs) were evaluated. The scoring scheme was based on a system of “0” to “3”. “0” meaning “not prepared at all” and “3” meaning “fully prepared”. Interviews were conducted with County Medical Officers of Health, Medical Chiefs of Staff, Executive Medical Directors, Information and Communications Technology (ICT) Managers and Public Health Observatory Heads. RESULTS AND FINDINGS: The results indicated that the lowest scores were assigned to data management (48%) and resources (49%), both classified as present but not adequate. Dissemination and use (53%), information products (58%) and data sources (61%) were found to be adequate. HIS indicators were found to be highly adequate (76%). CONCLUSION: The main areas of weakness in Trinidad and Tobago’s current HIS readiness were Data Management and Resources, while Indicator status was its greatest attribute.

Mass spectral characterisation of a polar, esterified fraction of an organic extract of an oil sands process water.

RATIONALE: Characterising complex mixtures of organic compounds in polar fractions of heavy petroleum is challenging, but is important for pollution studies and for exploration and production geochemistry. Oil sands process-affected water (OSPW) stored in large tailings ponds by Canadian oil sands industries contains such mixtures. METHODS: A polar OSPW fraction was obtained by silver ion solid-phase extraction with methanol elution. This was examined by numerous methods, including electrospray ionisation (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) and ultra-high-pressure liquid chromatography (uHPLC)/Orbitrap MS, in multiple ionisation and MS/MS modes. Compounds were also synthesised for comparison. RESULTS: The major ESI ionisable compounds detected (+ion mode) were C15-28 SO3 species with 3-7 double bond equivalents (DBE) and C27-28 SO5 species with 5 DBE. ESI-MS/MS collision-induced losses were due to water, methanol, water plus methanol and water plus methyl formate, typical of methyl esters of hydroxy acids. Once the fraction was re-saponified, species originally detected by positive ion MS, could be detected only by negative ion MS, consistent with their assignment as sulphur-containing hydroxy carboxylic acids. The free acid of a keto dibenzothiophene alkanoic acid was added to an unesterified acid extract of OSPW in known concentrations as a putative internal standard, but attempted quantification in this way proved unreliable. CONCLUSIONS: The results suggest the more polar acidic organic SO3 constituents of OSPW include C15-28 S-containing, alicyclic and aromatic hydroxy carboxylic acids. SO5 species are possibly sulphone analogues of these. The origin of such compounds is probably via further biotransformation (hydroxylation) of the related S-containing carboxylic acids identified previously in a less polar OSPW fraction. The environmental risks, corrosivity and oil flow assurance effects should be easier to assess, given that partial structures are now known, although further identification is still needed.

Elemental and spectroscopic characterization of fractions of an acidic extract of oil sands process water.

'Naphthenic acids' (NAs) in petroleum produced water and oil sands process water (OSPW), have been implicated in toxicological effects. However, many are not well characterized. A method for fractionation of NAs of an OSPW was used herein and a multi-method characterization of the fractions conducted. The unfractionated OSPW acidic extract was characterized by elemental analysis, electrospray ionization-Orbitrap-mass spectrometry (ESI-MS), and an esterified extract by Fourier Transform infrared (FTIR) and ultraviolet-visible (UV) absorption spectroscopy and by comprehensive multidimensional gas chromatography-MS (GCxGC-MS). Methyl esters were fractionated by argentation solid phase extraction (Ag(+) SPE) and fractions eluting with: hexane; diethyl ether: hexane and diethyl ether, examined. Each was weighed, examined by elemental analysis, FTIR, UV, GC-MS and GCxGC-MS (both nominal and high resolution MS). The ether fraction, containing sulfur, was also examined by GCxGC-sulfur chemiluminescence detection (GCxGC-SCD). The major ions detected by ESI-MS in the OSPW extract were assigned to alicyclic and aromatic 'O2' acids; sulfur was also present. Components recovered by Ag(+) SPE were also methyl esters of alicyclic and aromatic acids; these contained little sulfur or nitrogen. FTIR spectra showed that hydroxy acids and sulfoxides were absent or minor. UV spectra, along with the C/H ratio, further confirmed the aromaticity of the hexane:ether eluate. The more minor ether eluate contained further aromatics and 1.5% sulfur. FTIR spectra indicated free carboxylic acids, in addition to esters. Four major sulfur compounds were detected by GCxGC-SCD. GCxGC-high resolution MS indicated these were methyl esters of C18 S-containing, diaromatics with ≥C3 carboxylic acid side chains.

Acute toxicity of aromatic and non-aromatic fractions of naphthenic acids extracted from oil sands process-affected water to larval zebrafish.

The toxicity of oil sands process-affected water (OSPW) has regularly been attributed to naphthenic acids, which exist in complex mixtures. If on remediation treatment (e.g., ozonation) or on entering the environment, the mixtures of these acids all behave in the same way, then they can be studied as a whole. If, however, some acids are resistant to change, whilst others are not, or are less resistant, it is important to establish which sub-classes of acids are the most toxic. In the present study we therefore assayed the acute toxicity to larval fish, of a whole acidified OSPW extract and an esterifiable naphthenic acids fraction, de-esterified with alkali: both fractions were toxic (LC50 ∼5-8mgL(-1)). We then fractionated the acids by argentation solid phase extraction of the esters and examined the acute toxicity of two fractions: a de-esterified alicyclic acids fraction, which contained, for example, adamantane and diamantane carboxylic acids, and an aromatic acids fraction. The alicyclic acids were toxic (LC50 13mgL(-1)) but the higher molecular weight aromatic acids fraction was somewhat more toxic, at least on a weight per volume basis (LC50 8mgL(-1); P<0.05) (for comparison, the monoaromatic dehydroabietic acid had a LC50 of ∼1mgL(-1)). These results show how toxic naphthenic acids of OSPW are to these larval fish and that on a weight per volume basis, the aromatic acids are at least as toxic as the 'classical' alicyclic acids. The environmental fates and other toxic effects, if any, of the fractions remain to be established.

Synthesis and toxicity of some metabolites of the microbial degradation of synthetic naphthenic acids.

Some ill-defined carboxylic acids, termed 'naphthenic acids' (NA), are best known as important constituents of the >720billionlitres of process-affected water associated with the expanding oil sands industries. Other NA are components of some immature and biodegraded crude oils and these may enter the environment via produced water discharges from oil production platforms. Yet others are used as biocides and in the manufacture of steel radial tyres and these may also enter the environment through disposal and/or weathering. The environmental fate of NA, including the mechanisms of biodegradation, therefore needs to be better understood. In order to better elucidate such mechanisms, previously we studied the biodegradation in the laboratory of some alkylcyclohexylbutanoic synthetic NA. However, we could only tentatively identify the metabolites produced. In the present study we report the synthesis and characterisation of six alkylcyclohexylethanoic NA. Each was characterised by gas chromatography-mass spectrometry (GC-MS; trimethylsilyl esters) and we show by co-chromatography that these were indeed the metabolites. Also, a preferential degradation of the trans- isomers was revealed. Assessment of the toxicity of the synthetic NA (Microtox assay), revealed that the relative toxicity of the alkylcyclohexylbutanoic acids was reduced by biotransformation to the alkylcyclohexylethanoic acids, as observed recently for the corresponding aromatic acids. Very recent studies have shown that at least one commercial NA mixture contains cyclohexylbutanoic and alkylcyclohexylethanoic acids, suggesting that the biotransformation of the acids studied herein may be quite relevant to the environmental fate of such acids. A similar study of the acid extractables of one oil sands process-affected water sample suggests that the synthetic acids may be less good 'models' for oil sands NA. The consortia of microbes present in oil sands process-affected water may also be different to those used herein. However, the heterogeneity of oil sands process water is well-known and further detailed studies will need to be made in order to establish whether degradation of oil sands NA proceeds by beta oxidation as observed for the acids herein, or whether the oil sands acids are more resistant to bioremediation.

Combined effects of single nucleotide polymorphisms TP53 R72P and MDM2 SNP309, and p53 expression on survival of breast cancer patients.

INTRODUCTION: Somatic inactivation of the TP53 gene in breast tumors is a marker for poor outcome, and breast cancer outcome might also be affected by germ-line variation in the TP53 gene or its regulators. We investigated the effects of the germ-line single nucleotide polymorphisms TP53 R72P (215G>C) and MDM2 SNP309 (-410T>G), and p53 protein expression in breast tumors on survival. METHODS: We pooled data from four breast cancer cohorts within the Breast Cancer Association Consortium for which both TP53 R72P and MDM2 SNP309 were genotyped and follow-up was available (n = 3,749). Overall and breast cancer-specific survival analyses were performed using Kaplan-Meier analysis and multivariate Cox's proportional hazards regression models. RESULTS: Survival of patients did not differ by carriership of either germ-line variant, R72P (215G>C) or SNP309 (-410G>T) alone. Immunohistochemical p53 staining of the tumor was available for two cohorts (n = 1,109 patients). Survival was worse in patients with p53-positive tumors (n = 301) compared to patients with p53-negative tumors (n = 808); breast cancer-specific survival: HR 1.6 (95% CI 1.2 to 2.1), P = 0.001. Within the patient group with p53-negative tumors, TP53 rare homozygous (CC) carriers had a worse survival than G-allele (GG/GC) carriers; actuarial breast cancer-specific survival 71% versus 80%, P = 0.07; HR 1.8 (1.1 to 3.1), P = 0.03. We also found a differential effect of combinations of the two germ-line variants on overall survival; homozygous carriers of the G-allele in MDM2 had worse survival only within the group of TP53 C-allele carriers; actuarial overall survival (GG versus TT/TG) 64% versus 75%, P = 0.001; HR (GG versus TT) 1.5 (1.1 to 2.0), P = 0.01. We found no evidence for a differential effect of MDM2 SNP309 by p53 protein expression on survival. CONCLUSIONS: The TP53 R72P variant may be an independent predictor for survival of patients with p53-negative tumors. The combined effect of TP53 R72P and MDM2 SNP309 on survival is in line with our a priori biologically-supported hypothesis, that is, the role of enhanced DNA repair function of the TP53 Pro-variant, combined with increased expression of the Mdm2 protein, and thus overall attenuation of the p53 pathway in the tumor cells.

Thyroid hormone stimulation of extracellular signal-regulated kinase and cell proliferation in human osteoblast-like cells is initiated at integrin alphaVbeta3.

The aim of the present study was to examine whether triiodo-l-thyronine (T(3)) or l-thyroxine (T(4)) rapidly activated the mitogen-activated protein kinase (MAPK) intracellular signalling cascade in osteoblast-like cells and investigate whether this activation was initiated at the integrin alpha(V)beta(3) cell surface receptor. Using PCR and western blotting, the expression of integrin alpha(V)beta(3) mRNA and protein was demonstrated in the human osteoblast-like cell lines MG-63 and SaOS-2. The treatment of MG-63 cells with T(3) (10 nM) or T(4) (100 nM) for 10 min stimulated extracellular signal-regulated kinase activity (ERK, a component of the MAPK pathway) as determined by fluorescent immunocytochemistry and an immunocomplex activity assay (T(3) by 10.7-fold, P<0.01 and T(4) by 10.4-fold, P<0.01 compared with control). T(3) (10 nM) and T(4) (100 nM) also significantly stimulated thymidine incorporation into MG-63 cells by 2.3+/-0.7-fold (P<0.01) and 2.1+/-0.1-fold (P<0.05) respectively. To establish whether transient ERK activation via the integrin alpha(V)beta(3) cell surface receptor mediated these effects, MG-63 cells were pretreated for 30 min with the specific MAPK kinase inhibitor, U0126 (1 microM), or an anti-integrin alpha(V)beta(3)-blocking antibody. Both pretreatments significantly inhibited T(3)- and T(4)-stimulated ERK activation and abolished T(3)-stimulated thymidine incorporation (P<0.01). T(4)-stimulated incorporation was significantly inhibited from 2.1- to 1.3-fold above control (P<0.05). Thus, our results suggest that T(3) and T(4) rapidly stimulate ERK activation in MG-63 cells via integrin alpha(V)beta(3) and that one functional effect of this ERK activation is increased DNA synthesis.

Method for assessing the chronic toxicity of marine and estuarine sediment-associated contaminants using the amphipod Corophium volutator.

Acute sediment toxicity tests do not test key life stage events such as moulting and reproduction and therefore do not reveal the longer-term effects of contaminant exposure. A laboratory method is described for determining the chronic toxicity of contaminants associated with whole sediments. The test is conducted using neonates of the estuarine amphipod Corophium volutator at 15 degrees C, salinity 25 psu and a 12 h light:12 h dark photoperiod. The endpoints are survival and growth after 28 days and survival, growth and reproduction of amphipods upon termination of test i.e. reproduction within all control vessels (ca 75 days). The sediment chronic toxicity test was used to investigate the effects of sediments spiked with environmentally relevant preparations of slightly weathered Alaskan North Slope crude oil, including a water-accommodated-fraction (WAF) and a chemically-dispersed (Corexit 9527) WAF. Sediment oil concentrations were quantified using ultra-violet fluorescence. The amphipods exposed to chemically dispersed oil had higher mortality and lower growth rates than control-, Corexit 9527- and WAF-exposed organisms, resulting in reduced reproduction. The described method supplements the standard acute sediment test and would be particularly useful when long-term ecological effects are suspected but acute tests reveal no significant mortality. The sediment chronic test reported herein has shown that sediment that was not evidently toxic during 10-day acute tests could have population-level effects on sediment-dwelling amphipods.

Dislocation after revision of hemiarthroplasty to total hip replacement.

Over a 3-year period, nine hemiarthroplasties were revised to total hip arthroplasty. The hemiarthroplasties were all performed for an original diagnosis of subcapital fracture, and the revisions were for a variety of indications including instability, loosening and acetabular erosion. Four of the revised prostheses subsequently dislocated, and one has recurrent subluxation. This dislocation rate of 50% is higher than previously reported. Factors contributing to this are discussed. These include: previous strokes, advanced age, difficulty complying with instructions, and a hip capsule not contracted by osteoarthritis. Preventative factors are discussed. It is imperative to treat this group of patients differently from those having other hip arthroplasties, and to consider prophylactic bracing post-operatively. The capsule or pseudo-capsule should be preserved wherever possible.