Horizontally transferred mitochondrial DNA tracts become circular by microhomology-mediated repair pathways.

The holoparasitic plant Lophophytum mirabile exhibits remarkable levels of mitochondrial horizontal gene transfer (HGT). Gathering comparative data from other individuals and host plants can provide insights into the HGT process. We sequenced the mitochondrial genome (mtDNA) from individuals of two species of Lophophytum and from mimosoid hosts. We applied a stringent phylogenomic approach to elucidate the origin of the whole mtDNAs, estimate the timing of the transfers, and understand the molecular mechanisms involved. Ancestral and recent HGT events replaced and enlarged the multichromosomal mtDNA of Lophophytum spp., with the foreign DNA ascending to 74%. A total of 14 foreign mitochondrial chromosomes originated from continuous regions in the host mtDNA flanked by short direct repeats. These foreign tracts are circularized by microhomology-mediated repair pathways and replicate independently until they are lost or they eventually recombine with other chromosomes. The foreign noncoding chromosomes are variably present in the population and likely evolve by genetic drift. We present the 'circle-mediated HGT' model in which foreign mitochondrial DNA tracts become circular and are maintained as plasmid-like molecules. This model challenges the conventional belief that foreign DNA must be integrated into the recipient genome for successful HGT.

Invited Review Beyond parasitic convergence: unravelling the evolution of the organellar genomes in holoparasites.

BACKGROUND: The molecular evolution of organellar genomes in angiosperms has been studied extensively, with some lineages, such as parasitic ones, displaying unique characteristics. Parasitism has emerged 12 times independently in angiosperm evolution. Holoparasitism is the most severe form of parasitism, and is found in ~10 % of parasitic angiosperms. Although a few holoparasitic species have been examined at the molecular level, most reports involve plastomes instead of mitogenomes. Parasitic plants establish vascular connections with their hosts through haustoria to obtain water and nutrients, which facilitates the exchange of genetic information, making them more susceptible to horizontal gene transfer (HGT). HGT is more prevalent in the mitochondria than in the chloroplast or nuclear compartments. SCOPE: This review summarizes current knowledge on the plastid and mitochondrial genomes of holoparasitic angiosperms, compares the genomic features across the different lineages, and discusses their convergent evolutionary trajectories and distinctive features. We focused on Balanophoraceae (Santalales), which exhibits extraordinary traits in both their organelles. CONCLUSIONS: Apart from morphological similarities, plastid genomes of holoparasitic plants also display other convergent features, such as rampant gene loss, biased nucleotide composition and accelerated evolutionary rates. In addition, the plastomes of Balanophoraceae have extremely low GC and gene content, and two unexpected changes in the genetic code. Limited data on the mitochondrial genomes of holoparasitic plants preclude thorough comparisons. Nonetheless, no obvious genomic features distinguish them from the mitochondria of free-living angiosperms, except for a higher incidence of HGT. HGT appears to be predominant in holoparasitic angiosperms with a long-lasting endophytic stage. Among the Balanophoraceae, mitochondrial genomes exhibit disparate evolutionary paths with notable levels of heteroplasmy in Rhopalocnemis and unprecedented levels of HGT in Lophophytum. Despite their differences, these Balanophoraceae share a multichromosomal mitogenome, a feature also found in a few free-living angiosperms.

Plastomes in the holoparasitic family Balanophoraceae: Extremely high AT content, severe gene content reduction, and two independent genetic code changes.

The transition to a heterotrophic lifestyle in angiosperms is characterized by convergent evolutionary changes. Plastid genome remodeling includes dramatic functional and physical reductions with the highest degrees observed in fully heterotrophic plants. Genes related to photosynthesis are generally absent or pseudogenized, while a few genes related to other metabolic processes that take place within the plastid are almost invariably maintained. The family Balanophoraceae consists of root holoparasites that present reduced plastid genomes with an extraordinarily elevated AT content and the single genetic code change ever documented in land plant plastomes (the stop codon TAG now codes for tryptophan). Here, we studied the plastomes of Lophophytum leandri and Ombrophytum subterraneum (Balanophoraceae) that showed the remarkable absence of the gene trnE, a highly biased nucleotide composition, and an independent genetic code change (the standard stop codon TGA codes for tryptophan). This is the second genetic code change identified in land plant plastomes. Analysis of the transcriptome of Lophophytum indicated that the entire C5 pathway typical of plants is conserved despite the lack of trnE in its plastome. A hypothetical model of plastome evolution in the Balanophoraceae is presented.

Multichromosomal structure and foreign tracts in the Ombrophytum subterraneum (Balanophoraceae) mitochondrial genome.

Horizontal gene transfer (HGT) is frequent in parasitic plant mitochondria as a result of vascular connections established in host-parasite relationships. Recent studies of the holoparasitic plant Lophophytum mirabile (Balanophoraceae) revealed the unprecedented acquisition of a large amount of mitochondrial sequences from its legume host. We focused on a close relative, the generalist holoparasite Ombrophytum subterraneum, to examine the incidence of HGT events in the mitochondrial genome (mtDNA). The mtDNA of O. subterraneum assembles into 54 circular chromosomes, only 34 of which contain the 51 full-length coding regions. Numerous foreign tracts (totaling almost 100 kb, ~ 14% of the mtDNA), including 12 intact genes, were acquired by HGT from the Asteraceae hosts. Nine chromosomes concentrate most of those regions and eight are almost entirely foreign. Native homologs of each foreign gene coexist in the mtDNA and are potentially functional. A large proportion of shorter regions were related to the Fabaceae (a total of ~ 110 kb, 15.4%), some of which were shared with L. mirabile. We also found evidence of foreign sequences donated by angiosperm lineages not reported as hosts (Apocynaceae, Euphorbiaceae, Lamiaceae, and Malvales). We propose an evolutionary hypothesis that involves ancient transfers from legume hosts in the common ancestor of Ombrophytum and Lophophytum followed by more recent transfer events in L. mirabile. Besides, the O. subterraneum mtDNA was also subjected to additional HGT events from diverse angiosperm lineages, including large and recent transfers from the Asteraceae, and also from Lamiaceae.

Urine drainage management in colorectal surgery.

INTRODUCTION: Enhanced recovery programs (ERP) is aimed at reducing a patient's surgical stress response, specifically by reducing the duration of catheterization. In cases of colorectal surgery, there is pronounced heterogeneity in urinary catheterization, which is largely explained by fear of acute urinary retention (AUR). OBJECTIVE: The objective of the work is to report on the current literature on postoperative urinary catheterization following colorectal surgery, particularly with regard to the risk of AUR, and thereby contribute to the standardization of perioperative practices. RESULTS: In colon surgery without preoperative urinary disorders, catheterization must not exceed 24h. In rectal surgery, catheter removal starting on postoperative D2 seems reasonable in the absence of AUR risk factor (RF). Male sex, past history of lower urinary tract obstruction, abdomino-perineal amputation (APA) and low rectal anastomosis are AUR risk factors that must be taken into account when deciding to withdraw the urinary catheter. While the role of a suprapubic catheter is not clearly defined, it may be of use following APA. The epidural catheter is another AUR risk factor, but it seems possible to withdraw the urinary catheter on postoperative D1, before the epidural catheter, provided that the other risk factors have been taken into full account. Lastly, up until now no satisfactorily conducted study has assessed the prophylactic value of systematic perioperative alpha-blocker treatment in colorectal surgery.

[Prevalence of undernutrition in 143 patients before liver transplantation. The Lausanne experience between 1997 and 2005]. / Prévalence de la dénutrition chez 143 adultes en bilan prétransplantation hépatique. Experience lausannoise de 1997 a 2005.

The prevalence of undernutrition was prospectively studied in 143 patients before liver transplantation between 1997 and 2005. Nutritional assessment is a particularly tricky problem in cirrhosis and mid-arm muscle circumference is considered as the best reliable anthropometric tool. In this prospective study, prevalence rate is very high (61%) and undernutrition is more frequent in alcoholic cirrhotic patients. In conclusion, these patients should benefit from an early dietician intervention before liver transplantation.

Ambulatory unicompartmental knee arthroplasty: Short outcome of 50 first cases.

INTRODUCTION: The reduction in length of stay (LOS) in orthopedic surgery has been steady for several years. For the past 3 or 4 years in France, the trend toward outpatient surgery has been growing upwards, as it is a goal for hospital administration. MATERIALS AND METHODS: This is a prospective, continuous, mono-centric, single operator study on 56 UKAs. Included were all UKAs carried out between January 2014 and December 2015, meeting the following criteria: voluntary patients, supportive family environment, absence of comorbidity (oral anticoagulants, diabetes, obesity), ASA score≤3. Preoperatively, patients received: Dexamethasone 2mg/10kg, Tranexamic acid 2g, Cefazolin 2g IV. All patients were operated on under general anesthesia with the same technique: Alpina® (Zimmer-Biomet) uni-prosthesis without tourniquet. The arthrotomy was closed after a capsular injection of a solution of 150mg Ropivacaine+30mg Bi-Profenid®. Patient discharge on the same day evening was authorized by both surgeon and anesthesiologist. Three criteria were quantified: number of patients seen before the date of the first consultation for the removal of stitches (around day 12), Visual Pain Scale (10 points scale) on the first 12 days, and the level of satisfaction at the one-month postoperative visit. RESULTS: Six patients (11%) were not included in the ambulatory program during the initial consultation. Three patients were not able to be discharged on the same day evening due to nausea and therefore remained hospitalized for one night. Eighteen patients (38%) were reviewed before D10: 13 patients were reviewed between D1 and D4 for bleeding through the dressing and 5 for pain not controlled by level 1 and 2 analgesics. The Visual Pain Scale (VPS) reached level 6±2 by the 2nd day and then dropped to 1±1 by the 12th day. At 1 month, 85% of the patients were satisfied or very satisfied with their care. There were no general or localized complications. DISCUSSION: Ambulatory UKA surgery is possible for most patients. The inclusion rate for ambulatory UKA was 88% for Berger RA in 2010, therefore very close to this study rate of 89%. Ambulatory care is not only a change in surgical and anesthetic practice but a totally new management process involving all medical and non-medical actors. Ambulatory UKA surgery is feasible and safe for most patients. LEVEL OF EVIDENCE: IV, retrospective cohort study.

[Hospital undernutrition: how not to ignore it any more?]. / Dénutrition: quelles stratégies pour une pathotogie que l'on ne peut plus négliger à l'hôpital?

About 1/5 of patients are undernourished in Swiss hospitals. Despite of a high morbidity and mortality associated with this pathology, nearly 1/3 of them do not receive an appropriate nutritional support which can be even indicated at an obese patient. This paper approaches the key points of early nutritional care. NRS-2002 is presented like a simple tool able to identify patients nutritionally at-risk who are likely to benefit from nutritional support. Moreover, the major role of a diet adapted to the specific needs of the patient points out the need for an institutional policy coordinated around diet-nutrition.

[Short bowel syndrome: nutritional guidelines for the adult patient]. / Approche nutritionnelle pratique d'un patient adulte avec intestin court.

The short bowel is defined by the extended resection of the small intestine, leaving a maximum of 100 cm of healthy organ beyond the ligament of Treitz, with or without preservation of the colon. Nutritional management must be quick in order to optimize adaptation of the remaining intestine, therefore avoiding intestinal insufficiency. Consequent nutrition support such as long term enteral or parental nutrition is some times indispensable. Home enteral nutrition is relatively comfortable. Home parental nutrition somewhat complex, necessitates the creation of a strong home support group. This article addresses practitioners unfamiliar with clinical nutrition, directly faced with problems due to the short bowel in hospital (short and mean term phases) and in home settings (mean and long term phases).

[Chronic renal failure: what diet?]. / Insuffisance rénale chronique: quel régime?

A low protein diet has been traditionally advocated in patients with chronic renal failure (CRF), in order to slow its progression. However, CRF is often associated with malnutrition, aggravating its prognosis, especially in elderly patients. In severe CRF, the spontaneous reduction of appetite coupled with additional restrictions regarding sodium, potassium and phophates may further impact on nutrition status. The potential benefit of a low protein diet is therefore questionable. We only recommend a moderately restricted protein diet (0,8 g/kg/day) in selected patients with no sign of malnutrition. This strategy, if applied, must be supported by a multidisciplinary approach involving a nephrologist and a specialised dietician. Additional dietary restrictions are not justified, except in particular situations.

[Malnutrition on dialysis: the end of a fatality]. / Dénutrition en diatlyse: vers la fin d'une fatalité.

Protein-energy malnutrition in patients treated with haemodialysis (HD) is a complex, multifactorial and prevalent problem, starting well ahead of the dialysis program. It is associated with an increased morbidity and mortality. Uraemic patients are relatively resistant to nutrients because of metabolism abnormalities. Prevention of malnutrition is therefore more efficient than treatment per se. Classical supplementation including oral nutritional supplements, intradialytic parenteral nutrition and enteral nutrition remain efficient, if applied for a sufficient time. A global approach coupling supplementation and strategies designed to optimise metabolism abnormalities should increase treatment efficacy and improve the outcome and quality of life of these patients.

[Detection and management of early Pseudomonas aeruginosa infection in patients with cystic fibrosis]. / Détection et prise en charge précoce de la primo-infection à Pseudomonas aeruginosa chez les patients avec mucoviscidose.

Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis is a key step in pulmonary evolution of the disease. This first infection is most of the time early in life and gives some practical problems to the clinicians. It is important to look for colonisation with Pseudomonas aeruginosa as often as possible, at least every 3 month, by sputum culture when the child is able to or with induced sputum by hypertonic saline nebulisation. Treatment with inhalation of an antibiotic, preferably tobramycin for a 28 days course. Efficacy of the treatment as to be assessed by new culture.

Chronic ethanol ingestion increases efficiency of oxidative phosphorylation in rat liver mitochondria.

The efficiency of oxidative phosphorylation was compared between rats chronically fed with ethanol and controls. (i) Results showed that the liver mitochondria state 4 respiratory rate was strongly inhibited, while the corresponding proton-motive force was not affected; (ii) the cytochrome oxidase content and activity were decreased and (iii) the oxidative-phosphorylation yield was increased in the ethanol exposed group. Furthermore, oxidative phosphorylation at coupling site II was not affected by ethanol. Cytochrome oxidase inhibition by sodium-azide mimicked the effects of ethanol intoxication in control mitochondria. This indicates that the decrease in cytochrome oxidase activity induced by ethanol intoxication directly increases the efficiency of oxidative phosphorylation.

Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization.

Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.

Vasoactivity of trimetazidine on guinea-pig isolated ductus arteriosus.

The effect of trimetazidine (TMZ), an anti-anginal drug, on the mechanical response of the guinea-pig ductus arteriosus placed under conditions of mild hypoxia (PO2 approximately equal to 75 mmHg) was investigated. When the PO2 of the bathing solution was 75 mmHg, TMZ caused a dose-dependent increase in tension. The median effective dose (ED50) for the drug was 8 X 10(-5)M. TMZ-induced increase in tension was not significantly affected by pretreatment of the preparation with adrenoceptor blocking agents, or indomethacin. The amplitude of the PO2-dependent tension was significantly augmented by exposure of the strip to TMZ 10(-4)M, whereas neither the resting tone (low PO2), nor the oxygen-induced contraction (high PO2) were altered. This ability of TMZ to increase the tension response during hypoxia was dependent on the external calcium concentration. Under low PO2 conditions, a contractile activity of 10(-4)M TMZ was unmasked in preparations perfused with 18 mM K+-PSS medium. This response to TMZ disappeared after the removal of calcium from the bath. At the maximally effective dose of 10(-3)M, and during low PO2, the TMZ-induced contractile response changed to a relaxation response when the external K+ concentration was raised more than five fold. The possibility that TMZ stimulates the mechanism by which oxygen normally controls the concentration of free intracellular calcium in the ductus arteriosus is proposed.

Muscle carnitine pools in cancer patients.

Muscle and plasma concentrations of free and acylated carnitine (short-chain acylcarnitine and long-chain acylcarnitine) were determined by employing an optimized radiochemical-enzymatic assay in 14 healthy volunteers and in 10 patients with oesophageal carcinoma prior to elective operation. No significant correlations between total carnitine and its subfractions in muscle and plasma were observed and no sex differences were apparent. The estimated total carnitine pool in the patients (75.0 +/- 27 mmol) was significantly reduced compared to controls (130 +/- 24.3 mmol). The reduction was still present when expressed per kg muscle tissue (3.5 +/- 1.0 mmol versus 4.5 +/- 0.7 mmol) in order to consider age related decreased muscle mass in the patients. The muscular ratio of acylcarnitines to free carnitine was higher in the patients (0.23 +/- 0.10) than in healthy subjects (0.15 +/- 0.07), whereas the corresponding plasma quotient in the patients (0.22 +/- 0.09) was lowered compared to controls (0.30 +/- 0.10), indicating that instead of glucose, oxidation of fatty acids can be maintained, resulting in a preservation of the glycogen stores and thus an energy-conserving metabolic adaptation as a response to prolonged energy deficit.

Adverse effects of high dose carnitine supplementation of total parenteral nutrition on protein and fat oxidation in the critically ill.

The aim of the present study was to investigate the effects of continuous and acute L-carnitine supplementation of total parenteral nutrition (TPN) on protein and fat oxidation in severe catabolism. A critically ill and severely malnourished male patient received TPN (non protein energy = 41 kcal/kg/day, provided equally as fat and glucose) over 38 days, without L-carnitine for 23 days and with carnitine supplements (15 mg/kg/day) for the following 15 days. Subsequently, he was given carnitine-free enteral nutrition for 60 more days. A four-hour infusion of 100 mg L-carnitine was given on day 11 of each TPN period. Indirect calorimetry was carried out after 11 days of either carnitine-free or supplemented TPN and at the initiation of enteral nutrition. Additional measurements were performed 4 hours and 24 hours after the acute infusions of carnitine. The rate of protein oxidation and the respiratory quotient were found to be higher, and the rate of fat oxidation to be lower, with carnitine-supplemented TPN, than with either carnitine-free TPN or enteral nutrition. Acute infusion of carnitine resulted in an increased rate of protein oxidation and a reduced rate of fat oxidation on both TPN-regimens. These unfavourable effects on protein metabolism may be due to an impairment of fat oxidation by excess amounts of carnitine.

A controlled trial of the effect of parenteral nutritional support on patients with respiratory failure and sepsis.

Energy and protein metabolism was studied in 11 septic patients receiving ventilatory support while on three different intravenous regimens. They received 5% dextrose in water (D5W), and one of two different regimens of parenteral nutritional support (PNS); either amino acid and dextrose (PNA) or amino acid and dextrose and lipid (PNB). All patients were given D5W and PNS in random order. The energy intake was targetted to exceed by 50% the measured metabolic rate. On D5W the mean measured energy expenditure was only 15.2% above the expected energy expenditure (p<0.02). A respiratory quotient of 0.75 while on D5W showed that in the absence of PNS the major part of energy requirements came from fat oxidation. In addition, on D5W these patients were in negative nitrogen and protein (synthesis-catabolism) balance. With PNS the metabolic rate rose significantly (p<0.02). While on PNA, the CO2 production was significantly higher than with PNB, and despite receiving all non-protein energy as glucose, the patients continued to oxidise fat to meet about 30% of their energy requirements. Continued fat oxidation was found to be associated with insulin resistance and high catecholamine levels, suggesting a cause and effect relationship. PNS caused an increase in protein (synthesis - catabolism) and nitrogen balances, and reduced leucine oxidation. The fall in leucine oxidation was greater on PNB than on PNA. Protein and nitrogen balances, expressed per gram of amino acid infused, were significantly better with PNB than PNA. It was concluded that insulin resistance may make fat an efficient source of energy.

Body composition by X-ray absorptiometry and bioelectrical impedance in chronic respiratory insufficiency patients.

Nutrition assessment is important during chronic respiratory insufficiency to evaluate the level of malnutrition or obesity and should include body composition measurements. The appreciation of fat-free and fat reserves in patients with chronic respiratory insufficiency can aid in designing an adapted nutritional support, e.g., nutritional support in malnutrition and food restriction in obesity. The purpose of the present study was to cross-validate fat-free and fat mass obtained by various bioelectric impedance (BIA) formulas with the fat-free and fat mass measured by dual-energy X-ray absorptiometry (DXA) and determine the formulas that are best suited to predict the fat-free and fat mass for a group of patients with severe chronic respiratory insufficiency. Seventy-five patients (15 women and 60 men) with chronic obstructive and restrictive respiratory insufficiency aged 45-86 y were included in this study. Body composition was calculated according to 13 different BIA formulas for women and 12 for men and compared with DXA. Because of the variability, calculated as 2 standard deviations, of +/- 5.0 kg fat-free mass for women and +/- 6.4 kg for men for the best predictive formula, the use of the various existing BIA formulas was considered not clinically relevant. Therefore disease-specific formulas for patients with chronic respiratory insufficiency should be developed to improve the prediction of fat-free and fat mass by BIA in these patients.

Effects of intravenously infused fish oil on platelet fatty acid phospholipid composition and on platelet function in postoperative trauma.

BACKGROUND: The aim of this study was to assess the short-term effect of IV infusion of fish oil emulsion on the fatty acid profiles of platelet phosphatidylcholine and phosphatidylethanolamine and on platelet function in postoperative patients. METHODS: Over a 7-day period, 10 patients received a 20% soybean fat emulsion with an added 10% marine fish oil emulsion, whereas 9 controls received only 20% soybean fat emulsion. RESULTS: By comparison with controls, in patients receiving fish oil, (1) a large increase in eicosapentaenoic acid (20:5n-3) was observed in both platelet phosphatidylcholine (1.55% +/- 0.17% vs 0.38% +/- 0.06% by weight, p < .01) and phosphatidylethanolamine 2.21% +/- 0.18% vs 0.66% +/- 0.08% by weight, p < .01); (2) eicosapentaenoic acid (20:5n-3)/arachidonic acid (20:4n-6) ratios doubled in both platelet phosphatidylcholine (p < .01) and phosphatidylethanolamine (p < .05); (3) with collagen as aggregating factor, maximal reaction speed decreased (p < .02) and latency increased (p < .002); and (4) no toxic effect, in particular no increase of postoperative bleeding and no perturbation of hepatic and renal function, was observed during the fish oil infusion. CONCLUSIONS: A short-term IV infusion of fish oil clearly modifies the platelet composition and changes some parameters of platelet function.