Biomass formation represents one of the most basic aspects of bacterial metabolism. While there is an abundance of information concerning individual reactions that result in cell duplication, there ...has been surprisingly little information on the bioenergetics of growth. For many years, it was assumed that biomass production (anabolism) was proportional to the amount of ATP which could be derived from energy-yielding pathways (catabolism), but later work showed that the ATP yield (YATP) was not necessarily a constant. Continuous-culture experiments indicated that bacteria utilized ATP for metabolic reactions that were not directly related to growth (maintenance functions). Mathematical derivations showed that maintenance energy appeared to be a growth rate-independent function of the cell mass and time. Later work, however, showed that maintenance energy alone could not account for all the variations in yield. Because only some of the discrepancy could be explained by the secretion of metabolites (overflow metabolism) or the diversion of catabolism to metabolic pathways which produced less ATP, it appeared that energy-excess cultures had mechanisms of spilling energy. Bacteria have the potential to spill excess ATP in futile enzyme cycles, but there has been little proof that such cycles are significant. Recent work indicated that bacteria can also use futile cycles of potassium, ammonia, and protons through the cell membrane to dissipate ATP either directly or indirectly. The utility of energy spilling in bacteria has been a curiosity. The deprivation of energy from potential competitors is at best a teleological explanation that cannot be easily supported by standard theories of natural selection. The priming of intracellular intermediates for future growth or protection of cells from potentially toxic end products (e.g., methylglyoxal) seems a more plausible explanation.
Meta-analysis and systematic reviews of epidural compared with paravertebral blockade analgesia techniques for thoracotomy conclude that although the analgesia is comparable, paravertebral blockade ...has a better short-term side-effect profile. However, reduction in major complications including mortality has not been proven.
The UK pneumonectomy study was a prospective observational cohort study in which all UK thoracic surgical centres were invited to participate. Data presented here relate to the mode of analgesia and outcome. Data were analysed for 312 patients having pneumonectomy at 24 UK thoracic surgical centres in 2005. The primary endpoint was a major complication.
The most common type of analgesia used was epidural (61.1%) followed by paravertebral infusion (31%). Epidural catheter use was associated with major complications (odds ratio 2.2, 95% confidence interval 1.1–3.8; P=0.02) by stepwise logistic regression analysis.
An increased incidence of clinically important major post-pneumonectomy complications was associated with thoracic epidural compared with paravertebral blockade analgesia. However, this study is unable to provide robust evidence to change clinical practice for a better clinical outcome. A large multicentre randomized controlled trial is now needed to compare the efficacy, complications, and cost-effectiveness of epidural and paravertebral blockade analgesia after major lung resection with the primary outcome of clinically important major morbidity.
Background
Approximately 30 000 emergency laparotomies are performed each year in England and Wales. Patients with pathology of the gastrointestinal tract requiring emergency laparotomy are managed ...by general surgeons with an elective special interest focused on either the upper or lower gastrointestinal tract. This study investigated the impact of special interest on mortality after emergency laparotomy.
Methods
Adult patients having emergency laparotomy with either colorectal or gastroduodenal pathology were identified from the National Emergency Laparotomy Audit database and grouped according to operative procedure. Outcomes included all‐cause 30‐day mortality, length of hospital stay and return to theatre. Logistic and Poisson regression were used to analyse the association between consultant special interest and the three outcomes.
Results
A total of 33 819 patients (28 546 colorectal, 5273 upper gastrointestinal (UGI)) were included. Patients who had colorectal procedures performed by a consultant without a special interest in colorectal surgery had an increased adjusted 30‐day mortality risk (odds ratio (OR) 1·23, 95 per cent c.i. 1·13 to 1·33). Return to theatre also increased in this group (OR 1·13, 1·05 to 1·20). UGI procedures performed by non‐UGI special interest surgeons carried an increased adjusted risk of 30‐day mortality (OR 1·24, 1·02 to 1·53). The risk of return to theatre was not increased (OR 0·89, 0·70 to 1·12).
Conclusion
Emergency laparotomy performed by a surgeon whose special interest is not in the area of the pathology carries an increased risk of death at 30 days. This finding potentially has significant implications for emergency service configuration, training and workforce provision, and should stimulate discussion among all stakeholders.
Mortality after emergency laparotomy is increased at 30 days if the operation is not performed by a consultant with a special interest in the area of pathology (colorectal or gastroduodenal).
Specialist interest affects outcome
The effect of altered oxygen transport potential on behavioural responses to environmental hypoxia was tested experimentally in snapper, Pagrus auratus, treated with a haemolytic agent ...(phenylhydrazine) or a sham protocol. Standard metabolic rate was not different between anaemic and normocythaemic snapper (Hct=6.7 and 25.7 g dl(-1), respectively), whereas maximum metabolic rate, and hence aerobic scope (AS), was consistently reduced in anaemic groups at all levels of water P(O(2)) investigated (P<0.01). This reduction of AS conferred a higher critical oxygen limit (P(crit)) to anaemic fish (8.6±0.6 kPa) compared with normocythaemic fish (5.3±0.4 kPa), thus demonstrating reduced hypoxic tolerance in anaemic groups. In behavioural choice experiments, the critical avoidance P(O(2)) in anaemic fish was 6.6±2.5 kPa compared with 2.9±0.5 kPa for controls (P<0.01). Behavioural avoidance was not associated with modulation of swimming speed. Despite differences in physiological and behavioural parameters, both groups avoided low P(O(2)) just below their P(crit), indicating that avoidance was triggered consistently when AS limits were reached and anaerobic metabolism was unavoidable. This was confirmed by high levels of plasma lactate in both treatments at the point of avoidance. This is the first experimental demonstration of avoidance behaviour being modulated by internal physiological state. From an ecological perspective, fish with disturbed oxygen delivery potential arising from anaemia, pollution or stress are likely to avoid environmental hypoxia at a higher P(O(2)) than normal fish.
The common non-coding single nucleotide polymorphism (SNP)
in
is associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II ...(MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD.
For immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD.
Homozygosity for
at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses.
In sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression.
Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor ...injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.
The IMPACT (In situ Measurements of Particles And CME Transients) investigation on the STEREO mission was designed and developed to provide multipoint solar wind and suprathermal electron, ...interplanetary magnetic field, and solar energetic particle information required to unravel the nature of coronal mass ejections and their heliospheric consequences. IMPACT consists of seven individual sensors which are packaged into a boom suite, and a SEP suite. This review summarizes the science objectives of IMPACT, the instruments that comprise the IMPACT investigation, the accommodation of IMPACT on the STEREO twin spacecraft, and the overall data products that will flow from the IMPACT measurements. Accompanying papers in this volume of Space Science Reviews highlight the individual sensor technical details and capabilities, STEREO project plans for the use of IMPACT data, and modeling activities for IMPACT (and other STEREO) data interpretation.
Objective: Rifampicin (RIF)-resistance, a surrogate marker for multidrug-resistant tuberculosis (TB), is mediated by mutations in the rpoB gene. We aimed to investigate the prevalence of mutations ...pattern in the entire rpoB gene of Mycobacterium tuberculosis clinical isolates and their association with resistance level to RIF. Methods: Among 465 clinical isolates collected from the Guangzhou Chest Hospital, drug-susceptibility of 175 confirmed Mtb strains was performed via the proportion method and Bactec MGIT 960 system. GeneXpert MTB/RIF and sanger sequencing facilitated in genetic characterization, whereas the MICs of RIF were determined by Alamar blue assay. Results: We found 150/175 (85.71%) RIF-resistant strains (MIC: 4 to >64 microg/mL) of which 57 were MDR and 81 pre- XDR TB. Genetic analysis identified 17 types of mutations 146/150 (97.33%) within RRDR (codons 426-452) of rpoB, mainly at L430 (P), D435 (V, E, G, N), H445 (N, D, Y, R, L), S450 (L, F) and L452 (P). D435V 12/146 (8.2%), H445N 16/146 (10.9%), and S450L 70/146 (47.94%) were the most frequently encountered mutations. Mutations Q432K, M434V, and N437D are rarely identified in RRDR. Deletions at (1284- 1289 CCAGCT,1295-1303 AATTCATGG), and insertion at (1300-1302 TTC) were detected within RRDR of three RIFr strains for the first time. We detected 47 types of mutations and insertions/deletions (indels) outside the RRDR. Four RIFr strains were detected with only novel mutations/indels outside the RRDR. Two of the four had (K274Q + C897 del + I491M) and (A286V + L494P), respectively. The other two had (G1687del + P454L) and (TT1835-6 ins + I491L) individually. Compared with phenotypic characterization, diagnostic sensitivities of GeneXpert MTB/RIF and sequencing analysis were 95.33% (143/150), and 100% (150/150) respectively. Conclusion: Our findings underscore the key role of RRDR mutations and the contribution of non-RRDR mutations in rapid molecular diagnosis of RIFr clinical isolates. Such insights will support early detection of disease and recommend the appropriate anti-TB regimens in high-burden settings. Keywords: rifampicin-resistance, Mycobacterium tuberculosis, rpoB, GeneXpert MTB/RIF, resistance-determining region
Summary
The i‐gel, a novel supraglottic airway, has been proposed for use during cardiopulmonary resuscitation. We evaluated the performance of this device in manikins and anaesthetised patients when ...used by novices: medical students, non‐anaesthetist physicians and allied health professionals all unfamiliar with the i‐gel. Fifty i‐gels were placed in manikins. Eighty‐eight percent (44/50) were placed on the first attempt with a median insertion time of 14 s (range 7–45). I‐gels were placed in 40 healthy anaesthetised patients. Success on the first attempt was 82.5% (33/40) and on the second attempt 15% (6/40). After three attempts there were no failures. Median insertion time was 17.5 s (range 7–197). Median airway seal was 20 cmH2O (range 13–40). One case of regurgitation and partial aspiration occurred. Our results suggest the i‐gel is rapidly inserted in both manikins and patients by novice users and compares favourably to other supraglottic airways available. Further work determining safety and efficacy during cardiopulmonary resuscitation is required.
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