Anesthetic management in a huge hydrocephalus.

The pediatric age group with massive hydrocephalus posted for ventriculoperitoneal (VP) shunt presents a lot of confrontation to anesthesiologists due to macrocephalus and associated congenital anomalies. Here, we presented a case report with massive hydrocephalus with aqueduct stenosis, posted for VP shunt placement, and retained a difficult airway.

RésumésLe grouped'âgepédiatrique avec unehydrocéphalie massive affichée pour un shunt ventriculopéritonéal (VP) présente beaucoup de confrontation à l'anesthésisteen raison de la macrocéphalieet des anomalies congénitalesassociées. Ici, nous avonsprésentéun rapport de casd'hydrocéphalie massive avec sténose de l'aqueduc, affiché pour la miseen place d'un shunt VP, et conservéunevoierespiratoire difficile. Mots-clés : Pédiatrique, Voiesrespiratoiresdifficiles, hydrocéphalie, dérivationventriculopéritonéale.

Preemptive Levetiracetam Decreases Postoperative Pain: A Double-Blind, Randomised, Control Trial.

Background Previously many studies have found the use of anti-epileptic drugs such as pregabalin, carbamazepine, and gabapentin in pain management. In addition, levetiracetam (LEV), an effective anti-epileptic drug, has shown analgesic effects in animal models. We aimed to evaluate the effect of oral LEV as pre-emptive analgesia in patients who underwent laparoscopic cholecystectomy under general anaesthesia and postoperative fentanyl requirements. Material and methods Forty-two patients of the American Society of Anaesthesiologists (ASA) grade I and II of either gender posted for elective laparoscopic cholecystectomy surgery were included in this double-blind, randomised, placebo-controlled study. Patients were divided into two equal groups of 21 each to receive either tablet LEV 500 mg or a matching placebo tablet, given 1 hour before surgery. Postoperative pain was assessed by a visual analogue scale (0-100 mm), where 0 meant no pain and 100, worst pain. In addition, patients received IV fentanyl as rescue analgesia during the first 24 hours of the postoperative period. Results Nineteen patients in the LEV group and 20 in the placebo group completed the study. Patients in the LEV group had significantly lower pain scores at all time intervals except 0 hours and reduced fentanyl consumption postoperatively in the first 24 hours (p<0.05). Side effects were comparable in both groups. Conclusion A single, preoperative dose of oral LEV 500 mg significantly decreases post-surgical pain and fentanyl demand as rescue analgesia in elective laparoscopic cholecystectomy.

Substrate Utilisation and Energy Metabolism in Non-Growing Campylobacter jejuni M1cam.

Campylobacter jejuni, the major cause of bacterial foodborne illness, is also a fastidious organism that requires strict growth requirements in the laboratory. Our aim was to study substrate utilisation and energy metabolism in non-growing C. jejuni to investigate the ability of these bacteria to survive so effectively in the food chain. We integrated phenotypic microarrays and genome-scale metabolic modelling (GSM) to investigate the survival of C. jejuni on 95 substrates. We further investigated the underlying metabolic re-adjustment associated with varying energy demands on each substrate. We identified amino acids, organic acids and H2, as single substrates supporting survival without growth. We identified several different mechanisms, which were used alone or in combination, for ATP production: substrate-level phosphorylation via acetate kinase, the TCA cycle, and oxidative phosphorylation via the electron transport chain that utilised alternative electron donors and acceptors. The benefit of ATP production through each of these mechanisms was associated with the cost of enzyme investment, nutrient availability and/or O2 utilisation. C. jejuni can utilise a wide range of substrates as energy sources, including organic acids commonly used for marination or preservation of ingredients, which might contribute to the success of their survival in changing environments.

Genome-Scale Metabolic Modelling Approach to Understand the Metabolism of the Opportunistic Human Pathogen Staphylococcus epidermidis RP62A.

Staphylococcus epidermidis is a common commensal of collagen-rich regions of the body, such as the skin, but also represents a threat to patients with medical implants (joints and heart), and to preterm babies. Far less studied than Staphylococcus aureus, the mechanisms behind this increasingly recognised pathogenicity are yet to be fully understood. Improving our knowledge of the metabolic processes that allow S. epidermidis to colonise different body sites is key to defining its pathogenic potential. Thus, we have constructed a fully curated, genome-scale metabolic model for S. epidermidis RP62A, and investigated its metabolic properties with a focus on substrate auxotrophies and its utilisation for energy and biomass production. Our results show that, although glucose is available in the medium, only a small portion of it enters the glycolytic pathways, whils most is utilised for the production of biofilm, storage and the structural components of biomass. Amino acids, proline, valine, alanine, glutamate and arginine, are preferred sources of energy and biomass production. In contrast to previous studies, we have shown that this strain has no real substrate auxotrophies, although removal of proline from the media has the highest impact on the model and the experimental growth characteristics. Further study is needed to determine the significance of proline, an abundant amino acid in collagen, in S. epidermidis colonisation.

MdaB and NfrA, Two Novel Reductases Important in the Survival and Persistence of the Major Enteropathogen Campylobacter jejuni.

The paralogues RrpA and RrpB, which are members of the MarR family of DNA binding proteins, are important for the survival of the global bacterial foodborne pathogen Campylobacter jejuni under redox stress. We report that RrpA is a positive regulator of mdaB, encoding a flavin-dependent quinone reductase that contributes to the protection from redox stress mediated by structurally diverse quinones, while RrpB negatively regulates the expression of cj1555c (renamed nfrA for NADPH-flavin reductase A), encoding a flavin reductase. NfrA reduces riboflavin at a greater rate than its derivatives, suggesting that exogenous free flavins are the natural substrate. MdaB and NfrA both prefer NADPH as an electron donor. Cysteine substitution and posttranslational modification analyses indicated that RrpA and RrpB employ a cysteine-based redox switch. Complete genome sequence analyses revealed that mdaB is frequently found in Campylobacter and related Helicobacter spp., while nfrA is predominant in C. jejuni strains. Quinones and flavins are redox cycling agents secreted by a wide range of cell types that can form damaging superoxide by one-electron reactions. We propose a model for stress adaptation where MdaB and NfrA facilitate a two-electron reduction mechanism to the less toxic hydroquinones, thus aiding survival and persistence of this major pathogen. IMPORTANCE Changes in cellular redox potential result in alteration in the oxidation state of intracellular metabolites and enzymes; consequently, cells make adjustments that favor growth and survival. The work we present here answers some of the many questions that have remained elusive over the years of investigation into the enigmatic microaerophile bacterium Campylobacter jejuni. We employed molecular approaches to understand the regulation mechanisms and functional analyses to reveal the roles of two novel quinone and flavin reductases; both serve as major pools of cellular redox-active molecules. This work extends our knowledge on bacterial redox sensing mechanisms and the significance of hemostasis.

Boosting Biomass Quantity and Quality by Improved Mixotrophic Culture of the Diatom Phaeodactylum tricornutum.

Diatoms are photoautotrophic unicellular algae and are among the most abundant, adaptable, and diverse marine phytoplankton. They are extremely interesting not only for their ecological role but also as potential feedstocks for sustainable biofuels and high-value commodities such as omega fatty acids, because of their capacity to accumulate lipids. However, the cultivation of microalgae on an industrial scale requires higher cell densities and lipid accumulation than those found in nature to make the process economically viable. One of the known ways to induce lipid accumulation in Phaeodactylum tricornutum is nitrogen deprivation, which comes at the expense of growth inhibition and lower cell density. Thus, alternative ways need to be explored to enhance the lipid production as well as biomass density to make them sustainable at industrial scale. In this study, we have used experimental and metabolic modeling approaches to optimize the media composition, in terms of elemental composition, organic and inorganic carbon sources, and light intensity, that boost both biomass quality and quantity of P. tricornutum. Eventually, the optimized conditions were scaled-up to 2 L photobioreactors, where a better system control (temperature, pH, light, aeration/mixing) allowed a further improvement of the biomass capacity of P. tricornutum to 12 g/L.

Ultrasound Guided Measurement of Anterior Neck Tissue for the Prediction of Difficult Airway: A Prospective Observational Study.

Objectives: To determine that ultrasound (US) measurements of anterior neck soft tissue thickness at hyoid bone, thyrohyoid membrane, and anterior commissure levels can be used to predict difficult laryngoscopy. Materials & Methods: The present study included 100 patients of age group 18-60 years undergoing elective surgery under general anaesthesia. It was a prospective observational study which included patients with ASA physical status I and II. Excluded patients were with facial and neck deformities, neck trauma, or those undergoing surgery of the larynx, epiglottis and pharynx. Comparison analysis was performed using t-test for continuous variables and chi-square or Fisher exact test for non-continuous variables. Correlation analysis performed using Pearson test. Results: There were 39 out of 100 patients categorised as difficult laryngoscopy. Thickness at hyoid bone (DSHB), thyrohyoid membrane (DSEM) and anterior commissure (DSAC), MMS (modified Mallampati score), and BMI (body mass index) were greater in the difficult laryngoscopy group (p < 0.001). TMD (thyromental distance) was less in the difficult laryngoscopy group (p < 0.001). There was a strong positive correlation between DSEM and DSAC (r = 0.784). Moderate positive correlation was between DSEM and DSHB (r = 0.559), DSEM and MMS(r=0.437). The area under curve (AUC) of DSHB, DSEM, DSAC, TMD and MMS is >0.7. The optimal cut-off values for DSEM, DSHB, DSAC and TMD were 1.34 cm, 0.98 cm, 1.68 cm and 6.59 cm, respectively, in predicting difficult airway. Conclusion: Ultrasound measurement of soft tissue thickness at hyoid bone, thyrohyoid membrane, and anterior commissure of vocal cord are good independent predictors for difficult laryngoscopy. When combined with traditional screening tests it improves the ability to predict difficult laryngoscopy.

Genome-Scale Metabolic Model Driven Design of a Defined Medium for Campylobacter jejuni M1cam.

Campylobacter jejuni, the most frequent cause of food-borne bacterial gastroenteritis, is a fastidious organism when grown in the laboratory. Oxygen is required for growth, despite the presence of the metabolic mechanism for anaerobic respiration. Amino acid auxotrophies are variably reported and energy metabolism can occur through several electron donor/acceptor combinations. Overall, the picture is one of a flexible, but vulnerable metabolism. To understand Campylobacter metabolism, we have constructed a fully curated, metabolic model for the reference organism M1 (our variant is M1cam) and validated it through laboratory experiments. Our results show that M1cam is auxotrophic for methionine, niacinamide, and pantothenate. There are complete biosynthesis pathways for all amino acids except methionine and it can produce energy, but not biomass, in the absence of oxygen. M1cam will grow in DMEM/F-12 defined media but not in the previously published Campylobacter specific defined media tested. Using the model, we identified potential auxotrophies and substrates that may improve growth. With this information, we designed simple defined media containing inorganic salts, the auxotrophic substrates, L-methionine, niacinamide, and pantothenate, pyruvate and additional amino acids L-cysteine, L-serine, and L-glutamine for growth enhancement. Our defined media supports a 1.75-fold higher growth rate than Brucella broth after 48 h at 37°C and sustains the growth of other Campylobacter jejuni strains. This media can be used to design reproducible assays that can help in better understanding the adaptation, stress resistance, and the virulence mechanisms of this pathogen. We have shown that with a well-curated metabolic model it is possible to design a media to grow this fastidious organism. This has implications for the investigation of new Campylobacter species defined through metagenomics, such as C. infans.

From bag-of-genes to bag-of-genomes: metabolic modelling of communities in the era of metagenome-assembled genomes.

Metagenomic sequencing of complete microbial communities has greatly enhanced our understanding of the taxonomic composition of microbiotas. This has led to breakthrough developments in bioinformatic disciplines such as assembly, gene clustering, metagenomic binning of species genomes and the discovery of an incredible, so far undiscovered, taxonomic diversity. However, functional annotations and estimating metabolic processes from single species - or communities - is still challenging. Earlier approaches relied mostly on inferring the presence of key enzymes for metabolic pathways in the whole metagenome, ignoring the genomic context of such enzymes, resulting in the 'bag-of-genes' approach to estimate functional capacities of microbiotas. Here, we review recent developments in metagenomic bioinformatics, with a special focus on emerging technologies to simulate and estimate metabolic information, that can be derived from metagenomic assembled genomes. Genome-scale metabolic models can be used to model the emergent properties of microbial consortia and whole communities, and the progress in this area is reviewed. While this subfield of metagenomics is still in its infancy, it is becoming evident that there is a dire need for further bioinformatic tools to address the complex combinatorial problems in modelling the metabolism of large communities as a 'bag-of-genomes'.

Network reduction methods for genome-scale metabolic models.

Genome-scale metabolic models (GSMs) provide a comprehensive representation of cellular metabolism. GSMs provide a mechanistic link between cellular genotypes and metabolic phenotypes, and are thus widely used to analyze metabolism at the systems level. GSMs consist of hundreds or thousands of reactions. They have thus largely been analyzed with computationally efficient constraint-based methods such as flux-balance analysis, limiting their scope and phenotype prediction accuracy. Computationally more demanding but potentially more informative methods, such as kinetic and dynamic modeling, are currently limited to small or medium-sized models. Thus, it is desirable to achieve unbiased stoichiometric reductions of large-scale metabolic models to small, coarse-grained model representations that capture significant metabolic modules. Here, we review published automated and semiautomated methods used for large-scale metabolic model reduction. The top-down methods discussed provide minimal networks that retain a set of user-protected phenotypes, but may reduce the model's metabolic and phenotypic versatility. In contrast, the two bottom-up approaches reviewed retain a more unbiased set of phenotypes; at the same time, these methods require the partitioning of the GSM into metabolic subsystems by the user, and make strong assumptions on the subsystems' connections and their states, respectively.

The comparison of dexmedetomidine, esmolol, and combination of dexmedetomidine with esmolol for attenuation of sympathomimetic response to laryngoscopy and intubation in patients undergoing coronary artery bypass grafting.

Background: The aim of this study was to compare the effects of dexmedetomidine, esmolol, and combination of both on control of sympathetic response to laryngoscopy and tracheal intubation in coronary artery disease patients. Material and Methods: A prospective, randomized, double-blinded clinical study included 90 patients scheduled for elective coronary artery bypass surgery. Patients were randomly allocated into three groups of 30 each: dexmedetomidine group (Group D) 1 µg/kg, esmolol group (Group E) 2 mg/kg, and group dexmedetomidine with esmolol (Group DE) 0.5 µg/kg of dexmedetomidine with 1 mg/kg of esmolol. Each drug was diluted with 0.9% normal saline to 20 ml volume and infused in 10 min before induction of anesthesia. Hemodynamic changes (heart rate [HR], arterial blood pressure, and pulmonary artery pressure) were compared at various time intervals as follows-baseline, after study drug, after induction, and 1, 3, and 5 min after intubation. Statistical analysis included analysis of variance, Chi-square, and Fisher's exact test. Results: In Group DE, there was no significant increase in HR at all-time intervals, and the HR was stable compared to Group D and Group E. Blood pressure values were comparable in all groups except in Group E at 5 min. The pulmonary arterial pressures were statistically less in DE group except at 3 and 5 min. Conclusions: The combination of dexmedetomidine and esmolol group has beneficial effect on HR and pulmonary arterial pressures but has no additional advantage with respect to arterial blood pressure when compared with dexmedetomidine and esmolol groups in patients undergoing elective coronary artery bypass grafting.

Modelling phosphorus uptake in microalgae.

Phosphorus (P) is an essential non-renewable nutrient that frequently limits plant growth. It is the foundation of modern agriculture and, to a large extent, demand for P is met from phosphate rock deposits which are limited and becoming increasingly scarce. Adding an extra stroke to this already desolate picture is the fact that a high percentage of P, through agricultural runoff and waste, makes its way into rivers and oceans leading to eutrophication and collapse of ecosystems. Therefore, there is a critical need to practise P recovery from waste and establish a circular economy applicable to P resources. The potential of microalgae to uptake large quantities of P and use of this P enriched algal biomass as biofertiliser has been regarded as a promising way to redirect P from wastewater to the field. This also makes the study of molecular mechanisms underlying P uptake and storage in microalgae of great interest. In the present paper, we review phosphate models, which express the growth rate as a function of intra- and extracellular phosphorus content for better understanding of phosphate uptake and dynamics of phosphate pools.

A systems-wide understanding of photosynthetic acclimation in algae and higher plants.

The ability of phototrophs to colonise different environments relies on robust protection against oxidative stress, a critical requirement for the successful evolutionary transition from water to land. Photosynthetic organisms have developed numerous strategies to adapt their photosynthetic apparatus to changing light conditions in order to optimise their photosynthetic yield, which is crucial for life on Earth to exist. Photosynthetic acclimation is an excellent example of the complexity of biological systems, where highly diverse processes, ranging from electron excitation over protein protonation to enzymatic processes coupling ion gradients with biosynthetic activity, interact on drastically different timescales from picoseconds to hours. Efficient functioning of the photosynthetic apparatus and its protection is paramount for efficient downstream processes, including metabolism and growth. Modern experimental techniques can be successfully integrated with theoretical and mathematical models to promote our understanding of underlying mechanisms and principles. This review aims to provide a retrospective analysis of multidisciplinary photosynthetic acclimation research carried out by members of the Marie Curie Initial Training Project, AccliPhot, placing the results in a wider context. The review also highlights the applicability of photosynthetic organisms for industry, particularly with regards to the cultivation of microalgae. It intends to demonstrate how theoretical concepts can successfully complement experimental studies broadening our knowledge of common principles in acclimation processes in photosynthetic organisms, as well as in the field of applied microalgal biotechnology.

Investigating mixotrophic metabolism in the model diatom Phaeodactylum tricornutum.

Diatoms are prominent marine microalgae, interesting not only from an ecological point of view, but also for their possible use in biotechnology applications. They can be cultivated in phototrophic conditions, using sunlight as the sole energy source. Some diatoms, however, can also grow in a mixotrophic mode, wherein both light and external reduced carbon contribute to biomass accumulation. In this study, we investigated the consequences of mixotrophy on the growth and metabolism of the pennate diatom Phaeodactylum tricornutum, using glycerol as the source of reduced carbon. Transcriptomics, metabolomics, metabolic modelling and physiological data combine to indicate that glycerol affects the central-carbon, carbon-storage and lipid metabolism of the diatom. In particular, provision of glycerol mimics typical responses of nitrogen limitation on lipid metabolism at the level of triacylglycerol accumulation and fatty acid composition. The presence of glycerol, despite provoking features reminiscent of nutrient limitation, neither diminishes photosynthetic activity nor cell growth, revealing essential aspects of the metabolic flexibility of these microalgae and suggesting possible biotechnological applications of mixotrophy.This article is part of the themed issue 'The peculiar carbon metabolism in diatoms'.

Efficacy of methylprednisolone and lignocaine on propofol injection pain: A randomised, double-blind, prospective study in adult cardiac surgical patients.

BACKGROUND AND AIMS: Propofol (2, 6-di-isopropylphenol) used for the induction of anaesthesia often causes mild to severe pain or discomfort on injection. We designed this double-blind study to compare the efficacy of methylprednisolone and lignocaine in reducing the pain of propofol injection in patients scheduled for cardiac surgery. METHODS: A total of 165 adult patients, scheduled for elective cardiac surgery, were divided into three groups: saline (group S, n = 55), lignocaine 20 mg (Group L, n = 55) and methylprednisolone 125 mg diluted into 2 ml of distilled water (Group MP, n = 55). Drugs were administered after tourniquet application and occlusion was released after 1 min and 1/4th of the total dose of propofol (2 mg/kg) was administered at the rate of 0.5 ml/s. Pain on propofol injection was evaluated by four-point verbal rating scale. Statistical methods used included Student's t-test and Chi-square test/Fisher's exact test. RESULTS: The overall incidence of pain was 70.9% in the saline group, 30.9% in the lignocaine group and 36.4% in the methylprednisolone group. The intensity of pain was significantly less in patients receiving methylprednisolone and lignocaine than those receiving saline (P < 0.012). CONCLUSION: Pre-treatment with intravenous methylprednisolone was found to be as effective as lignocaine in reducing propofol injection-induced pain.

Dexmedetomidine as an adjunct in postoperative analgesia following cardiac surgery: A randomized, double-blind study.

OBJECTIVES: The purpose of this study was to determine analgesic efficacy of dexmedetomidine used as a continuous infusion without loading dose in postcardiac surgery patients. SETTINGS AND DESIGN: A prospective, randomized, double-blind clinical study in a single tertiary care hospital on patients posted for elective cardiac surgery under cardiopulmonary bypass. INTERVENTIONS: Sixty-four patients who underwent elective cardiac surgery under general anesthesia were shifted to intensive care unit (ICU) and randomly divided into two groups. Group A (n = 32) received a 12 h infusion of normal saline and group B (n = 32) received a 12 h infusion of dexmedetomidine 0.4 µg/kg/h. Postoperative pain was managed with bolus intravenous fentanyl. Total fentanyl consumption, hemodynamic monitoring, Visual Analogue Scale (VAS) pain ratings, Ramsay Sedation Scale were charted every 6(th) hourly for 24 h postoperatively and followed-up till recovery from ICU. Student's t-test, Chi-square/Fisher's exact test has been used to find the significance of study parameters between the groups. RESULTS: Dexmedetomidine treated patients had significantly less VAS score at each level (P < 0.001). Total fentanyl consumption in dexmedetomidine group was 128.13 ± 35.78 µg versus 201.56 ± 36.99 µg in saline group (P < 0.001). A statistically significant but clinically unimportant sedation was noted at 6 and 12 h (P < 0.001, and P = 0.046 respectively). Incidence of delirium was less in dexmedetomidine group (P = 0.086+). Hemodynamic parameters were statistically insignificant. CONCLUSIONS: Dexmedetomidine infusion even without loading dose provides safe, effective adjunct analgesia, reduces narcotic consumption, and showed a reduced trend of delirium incidence without undesirable hemodynamic effects in the cardiac surgery patients.

Modelling metabolism of the diatom Phaeodactylum tricornutum.

Marine diatoms have potential as a biotechnological production platform, especially for lipid-derived products, including biofuels. Here we introduce some features of diatom metabolism, particularly with respect to photosynthesis, photorespiration and lipid synthesis and their differences relative to other photosynthetic eukaryotes. Since structural metabolic modelling of other photosynthetic organisms has been shown to be capable of representing their metabolic capabilities realistically, we briefly review the main approaches to this type of modelling. We then propose that genome-scale modelling of the diatom Phaeodactylum tricornutum, in response to varying light intensity, could uncover the novel aspects of the metabolic potential of this organism.

Prevention of propofol injection pain: Comparison between lidocaine and ramosetron.

BACKGROUND: Propofol causes a high incidence of pain during intravenous (IV) injection. The aim of this randomized, placebo-controlled, double-blinded study was to determine whether pre-treatment with IV ramosetron, used for prophylaxis of postoperative nausea and vomiting (PONV), would reduce propofol-induced pain as an equivalent to lidocaine. MATERIALS AND METHODS: Hundred and twenty American Society of Anesthesiologists grade (ASA) I and II patients were randomly assigned into three groups (40 in each). Group N received 2 ml of 0.9% saline, Group L received 2 ml of lidocaine, and Group R received 2 ml of ramosetron. Mid forearm was occluded manually before injection and released after 1 min and then propofol was injected over 5 s. Patients were observed and questioned 15 s later if they had pain in the arm and pain was scored on a four-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain. Unpaired Student's t-test and chi-square test/Fisher' exact test were used to analyze results. RESULTS: The incidence of pain in groups N, L, and R were 65, 35, and 30%, respectively. Pain was reduced significantly in the groups L and R (P < 0.05). Two patients each in Groups L and R (5% each) had moderate and severe pain. This difference in pain was statistically insignificant, but when compared to Group N (25 and 30%, respectively) it was statistically significant. CONCLUSION: Pretreatment with ramosetron 0.3 mg and lidocaine 40 mg are equally effective in preventing pain from propofol injection.