Butanetriol and pentanetriol dialkyl glycerol tetraethers (BDGTs and PDGTs)
are membrane lipids, recently discovered in sedimentary environments and in
the methanogenic archaeon Methanomassiliicoccus ...luminyensis. They
possess an unusual structure, which challenges fundamental assumptions in
lipid biochemistry. Indeed, they bear a butanetriol or a pentanetriol
backbone instead of a glycerol at one end of their core structure. In this
study, we unambiguously located the additional methyl group of the BDGT
compound on the C3 carbon of the lipid backbone via high-field nuclear
magnetic resonance (NMR) experiments. We further systematically explored the
abundance, distribution and isotopic composition of BDGTs and PDGTs as both
intact polar and core lipid forms in marine sediments collected in
contrasting environments of the Mediterranean Sea and Black Sea. High
proportions of intact polar BDGTs and PDGTs in the deeper methane-laden
sedimentary layers and relatively 13C-depleted BDGTs, especially in
the Rhone Delta and in the Black Sea, are in agreement with a probable
methanogenic source for these lipids. However, contributions from
heterotrophic Archaea to BDGTs (and PDGTs) cannot be excluded, particularly
in the eastern Mediterranean Sea, and contrasting BDGT and PDGT headgroup
distribution patterns were observed between the different sites studied. This
points to additional, non-methanogenic, archaeal sources for these lipids.
Diabetes affects 10-15% of the surgical population and patients with diabetes undergoing surgery have greater complication rates, mortality rates and length of hospital stay. Modern management of the ...surgical patient with diabetes focuses on: thorough pre-operative assessment and optimisation of their diabetes (as defined by a HbA1c < 69 mmol.mol(-1) ); deciding if the patient can be managed by simple manipulation of pre-existing treatment during a short starvation period (maximum of one missed meal) rather than use of a variable-rate intravenous insulin infusion; and safe use of the latter when it is the only option, for example in emergency patients, patients expected not to return to a normal diet immediately postoperatively, and patients with poorly controlled diabetes. In addition, it is imperative that communication amongst healthcare professionals and between them and the patient is accurate and well informed at all times. Most patients with diabetes have many years of experience of managing their own care. The purpose of this guideline is to provide detailed guidance on the peri-operative management of the surgical patient with diabetes that is specific to anaesthetists and to ensure that all current national guidance is concordant.
Pseudomonas aeruginosa and Staphylococcus aureus are thought to cause the majority of lung infections in patients with cystic fibrosis (CF). However, other bacterial pathogens may contribute to the ...pathophysiology of lung disease. Here, obligate anaerobes were identified in a cross-sectional study, and cell numbers and antibiotic susceptibilities of facultative and obligate anaerobes from 114 sputum samples from nine children and 36 adults with CF were determined. Furthermore, in 12 CF patients, we investigated whether conventional intravenous antibiotic therapy, administered during acute exacerbations, would affect the numbers of obligate anaerobes. Fifteen genera of obligate anaerobes were identified in 91% of the CF patients. Cell numbers (mean: 2.2 × 107 ± standard deviation 6.9 × 107 CFU/mL of sputum sample) were comparable to those of P. aeruginosa and S. aureus. Staphylococcus saccharolyticus and Peptostreptococcus prevotii were most prevalent. Infection with P. aeruginosa did not increase the likelihood that obligate anaerobes are present in sputum specimens. Single obligate anaerobic species persisted for up to 11 months in sputum plugs in vivo. Patients with and without obligate anaerobes in sputum specimens did not differ in lung function. Intravenous therapy directed against P. aeruginosa during acute exacerbations increased lung function, but did not reduce the numbers of obligate anaerobes. Obligate anaerobic species differed widely in their patterns of resistance against meropenem, piperacillin–tazobactam, clindamycin, metronidazole and ceftazidime. In 58% of patients with acute exacerbations, obligate anaerobes were detected that were resistant to the antibiotics used for treatment. Antibiotic therapy, optimized to target anaerobes in addition to P. aeruginosa, may improve the management of CF lung disease.
The geochemistry of river sediments is routinely used to obtain information about geologic and environmental processes occurring upstream. For example, downstream samples are used to constrain ...chemical weathering and physical erosion rates upstream, as well as the locations of mineral deposits or contaminant sources. Previous work has shown that, by assuming conservative mixing, the geochemistry of downstream samples can be reliably predicted given a known source region geochemistry. In this study, we tackle the inverse problem and “unmix” the composition of downstream river sediments to produce geochemical maps of drainage basins (i.e., source regions). The scheme is tested in a case study of rivers draining the Cairngorms, UK. The elemental geochemistry of the <150 μm fraction of 67 samples gathered from the beds of channels in this region is used to invert for concentrations of major and trace elements upstream. A smoothed inverse problem is solved using the Nelder‐Mead optimization algorithm. Predictions of source region geochemistry are assessed by comparing the spatial distribution of 22 elements of different affinities (e.g., Be, Li, Mg, Ca, Rb, U, V) using independent geochemical survey data. The inverse approach makes reliable predictions of the major and trace element concentration in first order river sediments. We suggest this scheme could be a novel means to generate geochemical baselines across drainage basins and within river channels.
Key Points
Maps of drainage basin geochemistry are generated by unmixing the elemental composition of downstream sediment samples
A small number of downstream samples are inverted for continuous upstream composition using a smoothed model
Favorable comparison to independent data emphasizes the importance of drainage basin topology and source composition for setting composition of fluvial sediments
Lymphocytes travel throughout the body to carry out immune surveillance and participate in inflammatory reactions. Their path takes them from blood through tissues into lymph and back to blood. ...Molecules that control lymphocyte recruitment into extralymphoid tissues are well characterized, but exit is assumed to be random. Here, we showed that lymphocyte emigration from the skin was regulated and was sensitive to pertussis toxin. CD4(+) lymphocytes emigrated more efficiently than CD8(+) or B lymphocytes. T lymphocytes in the afferent lymph expressed functional chemokine receptor CCR7, and CCR7 was required for T lymphocyte exit from the skin. The regulated expression of CCR7 by tissue T lymphocytes may control their exit, acting with recruitment mechanisms to regulate lymphocyte transit and accumulation during immune surveillance and inflammation.
Bevacizumab improves outcome for most recurrent glioblastoma patients, but the duration of benefit is limited and survival after initial bevacizumab progression is poor. We evaluated bevacizumab ...continuation beyond initial progression among recurrent glioblastoma patients as it is a common, yet unsupported practice in some countries.
We analysed outcome among all patients (n=99) who received subsequent therapy after progression on one of five consecutive, single-arm, phase II clinical trials evaluating bevacizumab regimens for recurrent glioblastoma. Of note, the five trials contained similar eligibility, treatment and assessment criteria, and achieved comparable outcome.
The median overall survival (OS) and OS at 6 months for patients who continued bevacizumab therapy (n=55) were 5.9 months (95% confidence interval (CI): 4.4, 7.6) and 49.2% (95% CI: 35.2, 61.8), compared with 4.0 months (95% CI: 2.1, 5.4) and 29.5% (95% CI: 17.0, 43.2) for patients treated with a non-bevacizumab regimen (n=44; P=0.014). Bevacizumab continuation was an independent predictor of improved OS (hazard ratio=0.64; P=0.04).
The results of our retrospective pooled analysis suggest that bevacizumab continuation beyond initial progression modestly improves survival compared with available non-bevacizumab therapy for recurrent glioblastoma patients require evaluation in an appropriately randomised, prospective trial.
The human startle response is a sensitive, noninvasive measure of central nervous system activity that is currently used in a wide variety of research and clinical settings. In this article, we raise ...methodological issues and present recommendations for optimal methods of startle blink electromyographic (EMG) response elicitation, recording, quantification, and reporting. It is hoped that this report will foster more methodological validity and reliability in research using the startle response, as well as increase the detail with which relevant methodology is reported in publications using this measure.
These Joint British Diabetes Societies guidelines, commissioned by NHS Diabetes, for the perioperative management of the adult patient undergoing surgery are available in full in the Supporting ...Information. This document goes through the seven stages of the patient journey when having surgery. These are: primary care referral; surgical outpatients; preoperative assessment; hospital admission; surgery; post-operative care; discharge. Each stage is given its own considerations, outlining the roles and responsibilities of each group of healthcare professionals. The evidence base for the recommendations made at each stage, discussion of controversial areas and references are provided in the report. This document has two key recommendations. Firstly, that the management of the elective adult surgery patients should be with modification to their usual diabetes treatment if the fasting is minimized because the routine use of a variable rate intravenous insulin infusion is not recommended. Secondly, that poor preoperative glycaemic control leads to post-outcomes and thus, where appropriate, needs to be addressed prior to referral for surgery.
Venous thromboembolism (VTE) is a life-threating condition that is common in patients with adult-type diffuse gliomas, yet thromboprophylaxis is controversial because of possible intracerebral ...hemorrhage. Effective VTE prediction models exist for other cancers, but not glioma. Our objective was to develop a VTE prediction tool to improve glioma patient care, incorporating clinical, blood-based, histologic, and molecular markers. We analyzed preoperative arterial blood, tumor tissue, and clinical-pathologic data (including next-generation sequencing data) from 258 patients with newly diagnosed World Health Organization (WHO) grade 2 to 4 adult-type diffuse gliomas. Forty-six (17.8%) experienced VTE. Tumor expression of tissue factor (TF) and podoplanin (PDPN) each positively correlated with VTE, although only circulating TF and D-dimers, not circulating PDPN, correlated with VTE risk. Gliomas with mutations in isocitrate dehydrogenase 1 (IDH1) or IDH2 (IDHmut) caused fewer VTEs; multivariable analysis suggested that this is due to IDHmut suppression of TF, not PDPN. In a predictive time-to-event model, the following predicted increased VTE risk in newly diagnosed patients with glioma: (1) history of VTE; (2) hypertension; (3) asthma; (4) white blood cell count; (5) WHO tumor grade; (6) patient age; and (7) body mass index. Conversely, IDHmut, hypothyroidism, and MGMT promoter methylation predicted reduced VTE risk. These 10 variables were used to create a web-based VTE prediction tool that was validated in 2 separate cohorts of patients with adult-type diffuse glioma from other institutions. This study extends our understanding of the VTE landscape in these tumors and provides evidence-based guidance for clinicians to mitigate VTE risk in patients with glioma.
The hydrothermal sediments of Guaymas Basin, an active spreading center in the Gulf of California (Mexico), are rich in porewater methane, short-chain alkanes, sulfate and sulfide, and provide a ...model system to explore habitat preferences of microorganisms, including sulfate-dependent, methane- and short chain alkane-oxidizing microbial communities. In this study, hot sediments (above 60°C) covered with sulfur-oxidizing microbial mats surrounding a hydrothermal mound (termed "Mat Mound") were characterized by porewater geochemistry of methane, C2-C6 short-chain alkanes, sulfate, sulfide, sulfate reduction rate measurements, in situ temperature gradients, bacterial and archaeal 16S rRNA gene clone libraries and V6 tag pyrosequencing. The most abundantly detected groups in the Mat mound sediments include anaerobic methane-oxidizing archaea of the ANME-1 lineage and its sister clade ANME-1Guaymas, the uncultured bacterial groups SEEP-SRB2 within the Deltaproteobacteria and the separately branching HotSeep-1 Group; these uncultured bacteria are candidates for sulfate-reducing alkane oxidation and for sulfate-reducing syntrophy with ANME archaea. The archaeal dataset indicates distinct habitat preferences for ANME-1, ANME-1-Guaymas, and ANME-2 archaea in Guaymas Basin hydrothermal sediments. The bacterial groups SEEP-SRB2 and HotSeep-1 co-occur with ANME-1 and ANME-1Guaymas in hydrothermally active sediments underneath microbial mats in Guaymas Basin. We propose the working hypothesis that this mixed bacterial and archaeal community catalyzes the oxidation of both methane and short-chain alkanes, and constitutes a microbial community signature that is characteristic for hydrothermal and/or cold seep sediments containing both substrates.
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