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Pathogenic species of Mycobacteria and Corynebacteria, including Mycobacterium tuberculosisand Corynebacterium diphtheriae, synthesize complex cell walls that are rich in very long-chain mycolic acids. These fatty acids are synthesized on the inner leaflet of the cell membrane and are subsequently transported to the periplasmic space as trehalose monomycolates (TMM), where they are conjugated to other cell wall components and to TMM to form trehalose dimycolates (TDM). Mycobacterial TMM, and the equivalent Corynebacterium glutamicumtrehalose corynomycolates (TMCM), are transported across the inner membrane by MmpL3, or NCgl0228 and NCgl2769, respectively, although little is known about how this process is regulated. Here, we show that transient acetylation of the mycolyl moiety of TMCM is required for periplasmic export. A bioinformatic search identified a gene in a cell wall biosynthesis locus encoding a putative acetyltransferase (M. tuberculosisRv0228/C. glutamicumNCgl2759) that was highly conserved in all sequenced Corynebacterineae. Deletion of C. glutamicumNCgl2759resulted in the accumulation of TMCM, with a concomitant reduction in surface transport of this glycolipid and syntheses of cell wall trehalose dicorynomycolates. Strikingly, loss of NCgl2759 was associated with a defect in the synthesis of a minor, and previously uncharacterized, glycolipid species. This lipid was identified as trehalose monoacetylcorynomycolate (AcTMCM) by mass spectrometry and chemical synthesis of the authentic standard. The in vitrosynthesis of AcTMCM was dependent on acetyl-CoA, whereas in vivo[14C]-acetate pulse–chase labeling showed that this lipid was rapidly synthesized and turned over in wild-type and genetically complemented bacterial strains. Significantly, the biochemical and TMCM/TDCM transport phenotype observed in the ΔNCgl2759mutant was phenocopied by inhibition of the activities of the two C. glutamicumMmpL3 homologues. Collectively, these data suggest that NCgl2759 is a novel TMCM mycolyl acetyltransferase (TmaT) that regulates transport of TMCM and is a potential drug target in pathogenic species.

Two experiments were conducted to develop a simplified dose–response technique to estimate the Lys requirement of individual, meal-fed growing pigs. In Exp. 1, we studied adaptation processes that occur during such a dose–response study in meal-fed pigs, and in Exp. 2, we studied the accuracy of this simplified technique to estimate changes in Lys requirement estimates of pigs following changes in energy intake. In Exp. 1, the effect of the Lys supply strategy on the Lys requirement was assessed in 14 barrows fed an increasing [low to high (LH)] or decreasing [high to low (HL)] total Lys supply, with total Lys levels varying from 0.36 to 1.06 g/MJ DE in 7 equidistant steps of 4 d each. Urinary urea and ammonia excretion and whole body N turnover were measured. In Exp. 2, the accuracy of the dose–response technique to determine a shift in Lys requirement was assessed in 20 barrows fed at either 2.2 [low energy (LE)] or 2.7 [high energy (HE)] times the energy requirements for maintenance, with total Lys supply decreasing from 1.10 to 0.37 g Lys/MJ DE in 9 equidistant steps of 3 d each. In Exp. 1, a lower increment in protein synthesis, breakdown, and whole body N turnover with increasing dietary Lys supply was observed in LH pigs than HL pigs (P< 0.01) and the estimated Lys requirement was 0.06 g/MJ DE greater (P= 0.01) in LH pigs than HL pigs. These results indicated that pigs at a decreasing Lys supply strategy require less time for metabolic adaptation to a change in Lys supply than those at an increasing Lys supply. In Exp. 2, the estimated Lys requirement was 2.6 g/d greater (P< 0.001) in HE pigs than LE pigs. The variation in AA requirement estimates between individual pigs was low (4.9% in LH pigs and 3.0% in HL pigs in Exp. 1 and 8.1% in LE pigs and 6.0% in HE pigs in Exp. 2). The present studies indicated that a dose–response technique with a decreasing Lys supply in time and a step length of 3 d with urinary N excretion as response criteria provides a simple, accurate technique to quantitatively estimate a change in AA requirements of individual meal-fed pigs.

Surgical resection is regarded as the only curative option for resectable oesophageal cancer, but pulmonary complications occurring in more than half of patients after open oesophagectomy are a great concern. We assessed whether minimally invasive oesophagectomy reduces morbidity compared with open oesophagectomy.

This study evaluated the effect of feeding level and protein content in feed in first- and second-parity sows during the first month of gestation on sow BW recovery, farrowing rate, and litter size during the first month of gestation. From d 3 to 32 after the first insemination, sows were fed either 2.5 kg/d of a standard gestation diet (control, n = 49), 3.25 kg/d (+30%) of a standard gestation diet (plus feed, n = 47), or 2.5 kg/d of a gestation diet with 30% greater ileal digestible AA (plus protein, n = 49). Feed intake during the experimental period was 29% greater for sows in the plus feed group compared with those in the control and plus protein groups (93 vs. 72 kg, P< 0.05). Sows in the plus feed group gained 10 kg more BW during the experimental period compared with those in the control and plus protein groups (24.2 ± 1.2 vs. 15.5 ± 1.2 and 16.9 ± 1.2 kg, respectively, P< 0.001). Backfat gain and loin muscle depth gain were not affected by treatment (P= 0.56 and P= 0.37, respectively). Farrowing rate was smaller, although not significantly, for sows in the plus feed group compared with those in the control and plus protein groups (76.6% vs. 89.8 and 89.8%, respectively, P= 0.16). Litter size, however, was larger for sows in the plus feed group (15.2 ± 0.5 total born) compared with those in the control and plus protein groups (13.2 ± 0.4 and 13.6 ± 0.4 total born, respectively, P= 0.006). Piglet birth weight was not different among treatments (P= 0.65). For both first- and second-parity sows, the plus feed treatment showed similar effects on BW gain, farrowing rate, and litter size. In conclusion, an increased feed intake (+30%) during the first month of gestation improved sow BW recovery and increased litter size, but did not significantly affect farrowing rate in the subsequent parity. Feeding a 30% greater level of ileal digestible AA during the same period did not improve sow recovery or reproductive performance in the subsequent parity.

AbstractObjective:Opioid users often experience constipation. In this study the impact of constipation on QoL was assessed in patients using opioids either for non-advanced illness or advanced illness.Methods:Patients using opioids, recruited via public pharmacies, were asked to complete questionnaires on opioid use, constipation and the EuroQol five-dimension questionnaire (EQ-5D). Patients with a severe non-curable disease and relatively short life-expectancy were classified as having an advanced illness; a disabling yet not directly life-threatening condition was defined as non-advanced illness. Constipation was assessed based on questions on opioid side-effects and laxative use. EQ-5D index scores were compared between patients with and without constipation using Wilcoxon two-samples test.Results:Questionnaires were returned by 588 patients with non-advanced illness, of whom 326 (55%) were classified as having constipation and by 113 patients with advanced illness, of whom 76 (67%) were classified as having constipation. The median EQ-5D index, a weighted health state index score with 1 full health, was lower in patients with constipation than in patients without constipation (0.31 vs. 0.65, p< 0.01 for non-advanced illness and 0.41 vs. 0.61, p0.12 for advanced illness).Conclusion:The results of this study suggest that, in patients using opioids either for non-advanced illness or advanced illness, constipation negatively influences QoL. By separately analysing patients with advanced illness and patients with non-advanced illness, possible selective non-response and confounding was accounted for, but not completely solved.

An experiment was conducted to determine the effects of yeast culture (YC) and modified yeast culture [YC + cell wall product (CWP) containing mannan oligosaccharides] in pig diets on the performance, gut integrity, and blood cell composition of weanling pigs and to determine whether these dietary supplements could replace antimicrobial growth promoters (AGP) in pig diets. A total of 480 weanling pigs (27 d old and 7.8 ± 0.1 kg of BW) were assigned to 1 of 4 experimental treatments: 1) diets without AGP or YC (control diet); 2) control + AGP; 3) control + 0.125% YC; and 4) control + 0.125% YC + 0.2% CWP. Piglets were fed experimental diets for 5 wk after weaning. Blood samples were collected from 8 piglets at weaning and from 8 piglets per treatment on d 14 and 35 after weaning for blood cell composition. These piglets were slaughtered for measurement of villous length and crypt depth in the jejunal mucosa and microbial profiling on the intestinal digesta. Average daily gain (P= 0.06) and G:F (P= 0.02) were improved for piglets that were fed the supplemented diets compared with piglets that were fed the control diet. Average daily feed intake was unaffected by dietary treatment. Performance was similar in piglets fed diets supplemented with AGP, YC, and YC + CWP. Blood cell composition, villous length, crypt depth, and microbial composition in the gut were unaffected by dietary treatment, but they were affected by time after weaning. Red blood cells, hemoglobin, hematocrit value, mean cell volume, mean cell hemoglobin, percentage of lymphocytes in the leukocyte population, villous length, and crypt depth were greater (P< 0.05) at 5 wk after weaning than at 2 wk after weaning. Eosinophils (P= 0.06) in the leukocyte population tended to be greater at 5 wk after weaning. Concentration of neutrophils in the leukocyte population and percentages of CD4 and CD8 cells were lower (P< 0.02) at 5 wk after weaning. The CD4:CD8 ratio (P= 0.07) tended to be lower at 5 wk after weaning. Results suggest that yeast culture could be an alternative to AGP in the diets of weanling pigs and that addition of CWP to diets containing YC would not improve the performance or health of weanling pigs above that of YC alone. Thus, more insight into the mode of action of YC is needed.

The objective of this study was to determine the effects of specific crystalline AA supplementation to a diet on odor emission, odor intensity, odor hedonic tone, and ammonia emission from pig manure, and on manure characteristics (pH; ammonia N; total nitrogen; sulfurous, indolic, and phenolic compounds; and VFA concentrations). An experiment was conducted with growing pigs (n = 18) in a randomized complete block design, with 3 treatments in 6 blocks. Treatment groups were (1) a 15%-CP basal diet with 3 times the requirement of sulfur-containing AA (14.2 g/kg of diet, as-fed basis); (2) the basal diet with 2 times the requirement of Trp and Phe+Tyr (2.9 and 20.4 g/kg of diet, respectively, as-fed basis); and (3) the basal diet with AA supplementation to levels sufficient for maximum protein gain. Pigs with an initial BW of 41.2 ± 0.8 kg were individually penned in partly slatted floor pens and offered a daily feed allowance of 2.8 times the maintenance requirement for NE (293 kJ/kg of BW0.75). Feed was mixed with water at 1:2.5 (wt/wt). Feces and urine of each pig was allowed to accumulate in separate manure pits under the slatted floor. After an adaptation period of 2 wk, and after cleaning the manure pits, manure was subsequently collected. In wk 5 of the collection period, separate samples were collected directly from each manure pit for odor, ammonia, and manure composition analyses. Air samples were analyzed for odor concentration and for hedonic tone and odor intensity above the odor detection threshold. Results showed that supplementing crystalline S-containing AA in surplus of the requirement increased odor emission (P< 0.001) and odor intensity (P< 0.05) and reduced odor hedonic tone (P< 0.05) from the air above the manure pits. Supplementing crystalline Trp, Tyr, and Phe in surplus of the recommended requirements did not affect odor emission, odor intensity, or odor hedonic tone. Regardless of dietary treatment, all pigs had similar performance levels. No differences were observed in ammonia emission from manure of pigs fed different levels of AA supplementation (P= 0.20). To reduce odor from pig manure, dietary S-containing AA should be minimized to just meet the recommended requirements.

The effects of feeding additional starch or fat from d 85 of gestation until parturition on litter performance and on glucose tolerance in sows that were fed a diet with a high level of fermentable nonstarch polysaccharides (NSP) were studied. The day after breeding, 141 multiparous sows were assigned to the experiment. At d 85 of gestation, sows were assigned to the treatments. Sows were fed 3.4 kg/d (as-fed basis) of a high-NSP diet or the same quantity of the high-NSP diet and an additional 360 g of starch (from wheat starch) daily, or the same quantity of the high-NSP diet and an additional 164 g of fat (from soybean oil) daily. During lactation, all sows were given free access to the same lactation diet. Approximately 1 wk before the expected time of parturition, an oral glucose tolerance test was performed in 38 randomly chosen sows by feeding pelleted glucose (3 g/kg BW0.75). Blood samples for glucose analyses were taken at −10, 10, 20, 30, 40, 50, 60, 70, 80, 90, 105, and 120 min after glucose was fed. The supply of additional dietary starch or fat did not increase piglet birth weight or total litter weight at birth. Sows that were fed the high-NSP diet had more (P= 0.097) live-born piglets and fewer (P= 0.084) stillborn piglets than did sows that were fed additional fat, whereas sows that were fed additional starch were intermediate for these variables. Piglet mortality after birth was not affected by dietary treatment. Body weight and backfat gains in the last month of gestation were higher for sows fed additional starch or fat than for sows fed the high-NSP diet (P< 0.001 and P= 0.017, respectively). Feed intake in lactation was greatest by sows fed the high-NSP diet, least by sows fed additional starch at the end of gestation, and intermediate by sows fed additional fat (P= 0.099). The differences in lactation feed intake did not result in differences in BW and backfat losses during lactation. Sows that were fed additional fat had the greatest glucose area under the curve (P= 0.044), indicating that these sows were less tolerant to glucose. In conclusion, feeding additional energy (starch or fat) in late-gestating sows that are fed a high-NSP diet did not increase litter weight at birth or piglet survival, but did increase maternal gain. Feeding sows additional energy from fat might induce glucose intolerance, whereas feeding sows additional energy from starch did not induce glucose intolerance.

Esophagus resection is the adequate treatment for some benign esophageal diseases, especially caustic and peptic stenosis and end-stage motility dysfunction. However, the most frequent indications for esophageal resection are the high-grade dysplasia of Barrett esophagus and nonmetasta-sized esophageal cancer. Different procedures have been developed to perform esophageal resection given the 5-year survival rate among operated patients of only 18%. The disadvantage of the conventional approach is the high morbidity rate, especially with pulmonary complications. Minimally invasive esophageal resections, which were first performed in 1991, may reduce this important morbidity and preserve the oncologic outcome. The first reports of morbidity and respiratory complications with this approach were discouraging and it seemed likely that the procedure would have to be abandoned. However, in the last 5 years, an important impetus for these techniques was given by Japanese groups and the group of Luketich in Pittsburgh. The outcomes of these new series are different than those of the beginning period, leading to an enormous expansion worldwide. Important factors for this change are the standardization of the operative technique, the experience of many surgeons with more advanced laparoscopic procedures, important improvements in instruments for dissection and division of tissues, a better anesthesia technique, and a better selection of patients for operation. Two minimally invasive techniques are being perfected: the three-stage operation by right thoracoscopy and laparoscopy, and the transhiatal laparoscopic approach. It seems that the first approach may be applied successfully for any tumor in the esophagus, whereas the transhiatal seems ideal for distal esophageal and esophagogastric junction tumors. This review paper discusses all these aspects, with special attention for indications and operative technique.

The objective of this experiment was to study the effects of feeding group-housed gestating sows a diet with a high level of fermentable nonstarch polysaccharides (NSP; approximately 45% sugar beet pulp as fed) ad libitum on the development in individual feed intake characteristics and reproductive performance during three successive reproduction cycles. Performance of the ad libitum-fed sows was compared to the performance of sows that were fed a conventional diet restrictedly. Feed intake characteristics during gestation were only measured in the ad libitum-fed sows. One hundred and nineteen sows were assigned to one of two gestation feeding regimens. Gestating sows were fed a conventional Dutch diet restrictedly or a diet with a high level of fermentable NSP ad libitum. During lactation, sows were given free access to a commercial lactation diet from d 6 after parturition onward. The ad libitum-fed sows ate 1.3 kg/d more during gestation than the restrictedly fed sows (P< 0.001), resulting in higher body weight and backfat gains during gestation (P< 0.05). Sows that were fed ad libitum during gestation lost more body weight and backfat during lactation (P< 0.001) than sows that were fed restrictedly during gestation. Feed intake during lactation, however, did not differ between sows that were fed restrictedly or ad libitum during gestation. The numbers of total piglets born, live-born and stillborn piglets, piglet birth weight, weaning-to-estrus interval, and percentage of sows that returned to estrus after first insemination were not affected by gestation feeding regimen. Mean daily voluntary feed intake (as-fed basis) over the three reproduction cycles in the ad libitum-fed gestating sows was 4.2 kg/d. Depending on the number of preceding reproduction cycles during which a sow was fed ad libitum, the maximum voluntary feed intake was reached in Parity 3, 4, or 5 and then remained stable in subsequent parities. Mean daily feed intake of the ad libitum-fed sows increased from wk 2 to 6 of gestation and then decreased to wk 15 of gestation. The mean number of daily visits with feed intake over the three reproduction cycles was 13.8. On average, ad libitum-fed sows spent 90 min/d on eating. This study shows that it is possible to feed gestating sows a diet with a high level of fermentable NSP ad libitum during three successive reproduction cycles without negative effects on reproductive performance.

In a 2-wk experiment, the effect of photoperiod on performance and energy metabolism of newly weaned pigs was studied. Forty 4-wk-old crossbred weanling barrows weighing 8.0 kg (SE = 0.13) were assigned to one of eight groups (five pigs per group) based on BW and litter. Groups were allotted to one of two lighting schedules: 8 h light:16 h darkness or 23 h light:1 h darkness. Each group was housed in a climate respiration chamber. Piglets had ad libitum access to feed and water. Energy and nitrogen balances, heat production, ADFI, and ADG were measured weekly. Heat production, energy metabolism, and performance were unaffected (P> 0.10) by photoperiod during wk 1. However, in the 2nd wk ADFI (418 vs 302 g/d) and ADG (381 vs 240 g/d) were higher (P< 0.05 and P= 0.05, respectively) for pigs on the 23:1 h lighting schedule than for those on the 8:16 h schedule. Furthermore, heat production (P< 0.10), total energy retention, and energy retained as protein and as fat were higher (P< 0.05) during wk 2 in pigs on the 23:1 h lighting schedule (8, 125, 41, and 350%, respectively) than in those on the 8:16 h schedule. Moreover, metabolizability of energy tended to be higher (P< 0.10) and energy requirements for maintenance were lower (P< 0.05) during wk 2 for pigs on the 23:1 h schedule compared with those on the 8:16 h schedule (P< 0.10). In conclusion, exposing pigs to a longer period of light after weaning stimulated ADFI and ADG. In addition to the feed intake, the high ADG is due to an improved metabolizability of energy and a reduced energy requirement for maintenance. This study suggests that lighting schedule can be used as a tool to stimulate feed intake after weaning.

To assess the effects of creep feed consumption on individual feed intake characteristics and performance of group-housed weaned pigs, 16 litters (149 piglets) were fed a commercial creep feed (3,040 kcal NE/kg, 15.2 g lysine/kg) supplemented with 1% chromic oxide. Another five litters (48 piglets) were not given access to creep feed (no-feed). Piglets were weaned at 28 d after birth. On d 18, 22, and 27 of age, fecal samples from all the piglets were taken using fecal loops. A green color of the feces indicated that the piglet had eaten creep feed. Piglets that had green-colored feces three times were considered as eaters. Piglets that never showed green-colored feces were considered as non-eaters. At weaning 22 piglets of each type (no-feed, non-eaters, and eaters) were selected based on BW, litter origin, and sex. These 66 pigs were assigned to six pens equipped with computerized feeding stations. Eaters, non-eaters, and no-feed pigs were equally divided over all six pens. After weaning a prestarter (d 0 to 13) and a starter diet (d 14 to 34) were offered for ad libitum consumption. The individual feed intake characteristics of latency time (interval between weaning and first feed intake) and initial feed intake (intake during the first 24 h following first feed intake) and performance traits were determined for all piglets. The pigs that were designated as eaters needed less time between weaning and first feed intake than the pigs that were designated as non-eaters and no-feed pigs (P = 0.04 and P = 0.06, respectively). Initial feed intake was not affected (P > 0.1) by feed intake prior to weaning. However, during d 0 to 8 the eaters had more visits per day during which feed was consumed than both the non-eaters and no-feed pigs. Averaged over the first 8 d after weaning, the ADFI and ADG of the eaters were higher than that of the non-eaters and no-feed pigs (P < 0.05). Averaged over the total 34-d period the effect of creep feed intake on postweaning ADFI was much less pronounced (P = 0.20), whereas ADG of the eaters was the highest (P < 0.05). Creep feed intake during the sucking period stimulates early postweaning feed intake as well as postweaning performance.

Effects of adding fermented wheat to liquid diets on gastrointestinal characteristics in weanling piglets were studied. Gastrointestinal characteristics of 40 28-d-old weanling piglets were measured at the day of weaning (d 0) and at d 4 and 8 after weaning. Piglets were group-housed and fed twice daily. Feeding level was based on the average metabolic BW of piglets per group. Groups were fed a liquid diet with either 45% unfermented wheat (FERM_0) or 45% fermented wheat (FERM_45). The other 55% of the diet was identical. To ferment wheat, water at 30 degrees C was added to milled wheat in a 1:2.2 ratio. The pH and contents of lactic acid, acetic acid, propionic acid, and butyric acid were measured in the digesta of the stomach, three parts of the small intestine, cecum, and large intestine. In addition, changes in microbial populations in the digesta were studied during the period after weaning. Moreover, villus height, crypt depth, and villus shape were studied in the small intestine. Piglets fed FERM_45 showed lower gastric pH (P < 0.05) at d 4 and higher gastric lactic acid content (P < 0.001) at both d 4 and 8. Piglets fed FERM_45 showed in the first part of the small intestine higher villus height (P < 0.01) at d 8 and higher villus:crypt ratio (P < 0.001) at both d 4 and 8. Villus shape tended (P < 0.10) to be favorable for piglets fed FERM_45. The present study indicates that feeding a partly fermented liquid diet to weanling piglets may be a concept to prevent undesirable changes in mucosal architecture after weaning.

Feed intake characteristics of 192, 27-d-old weanling pigs housed in groups and given ad libitum access to feed and water were measured individually with the use of computerized feeding stations. The groups were either homogeneous or heterogeneous as to BW distribution; pigs of three defined initial BW classes were used (mean BW of 6.7, 7.9, or 9.3 kg). The effects of BW distribution, BW class, and sex were studied with regard to average performance traits, latency time (interval between weaning and first feed intake), initial feed intake (intake during the first 24 h following first feed intake), and daily increase in feed intake during the interval between first feed intake and the day on which energy intake met or exceeded 1.5 times the maintenance requirement. Homogeneous and heterogeneous groups had similar latency times, initial feed intakes, and daily increases in feed intake. For the period 0 to 34 d after weaning, ADFI and ADG were also similar for homogeneous and heterogeneous groups, but gain:feed ratio was greater (P< 0.05) in the homogeneous groups. Gilts had higher (P< 0.05) initial feed intakes than barrows and also had greater (P< 0.05) ADFI and ADG during the period 0 to 13 d after weaning. Pigs with average BW of 6.7 kg had higher (P< 0.05) initial feed intakes than their counterparts with average BW of 7.9 kg and 9.3 kg, but the daily increase in feed intake was similar for the three groups. The lighter pigs had more daily visits and a lower feed intake per visit and tended to have a shorter postweaning latency to the onset of feeding than the heavier pigs. This study indicates that the high variability in early feeding behavior among group-housed weanling pigs may be related to BW and sex.

IMPORTANCE: The optimal staging for gastric cancer remains a matter of debate. OBJECTIVE: To evaluate the value of 18F-fludeoxyglucose–positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. DESIGN, SETTING, AND PARTICIPANTS: This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (≥cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020. EXPOSURES: All patients underwent an FDG-PET/CT and/or SL in addition to initial staging. MAIN OUTCOMES AND MEASURES: The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay. RESULTS: Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days. CONCLUSIONS AND RELEVANCE: This study’s findings suggest an apparently limited additional value of FDG-PET/CT; however, SL added considerably to the staging process of locally advanced gastric cancer by detection of peritoneal and nonresectable disease. Therefore, it may be useful to include SL in guidelines for staging advanced gastric cancer, but not FDG-PET/CT.

Large hiatal or paraesophageal hernias constitute between 5% and 10% of all hiatal hernias. This hernia is a potential threatening complication, and a timely operative correction should be performed in all patients with an acceptable risk. Based on the lessons learned from conventional approach, laparoscopic treatment has confirmed the initial good results with all advantages of laparoscopic surgery. Reduction of the hernia, excision of the sac, and approximation of the hiatus followed by selective use of an antireflux procedure and some form of gastropexy constitute the operative steps to obtain optimal postoperative results. Copyright © 1999 by W. B. Saunders Company

Crossbred barrows (n = 48) and gilts (n = 12) were used to examine the effectiveness of a pair-gain feeding strategy for individually fed, group-housed barrows. In a pair-gain feeding strategy, barrows were individually restricted to a feeding level at which their growth was similar to the mean growth of gilts with ad libitum access to feed. The purposes of this feeding strategy were to have barrows and gilts reach slaughter weight at the same time and to improve carcass traits of the barrows. At 29.8 ± .4 kg BW, barrows were assigned to either the pair-gain or the ad libitum treatment. All pigs had free access to feed until they reached 60 kg BW. The experimental period was from 60 to 110 kg BW. The 12 group-fed gilts and 24 individually fed barrows (12 per pen) were also given free access to feed throughout the experimental period. The remaining 24 barrows (12 per pen) were put on a pair-gain feeding strategy. In the pair-gain feeding strategy, the weekly feed allowance of each barrow was based on its measured BW and computed energy conversion ratio and on the mean growth of the gilts. The barrows in the pair-gain treatment grew at the same rate as gilts. The ad libitum intake barrows grew faster (P< .05) and had a poorer energy conversion ratio for production than the barrows in the pair-gain treatment. The total energy conversion ratio, backfat thickness, and lean meat percentage were similar (P> .10) for the two treatments. In conclusion, the pair-gain feeding strategy was effective in achieving similar growth between barrows and gilts. The total energy conversion ratio and carcass traits of the barrows, however, were not improved.

The effects of birth weight (BiW; low BiW [LBW] vs. high BiW [HBW]) and estimated breeding value (EBV) for protein deposition (low EBV [LBV]vs. high EBV [HBV]) on N retention, N efficiency, and concentrations of metabolites in plasma and urine related to N efficiency in growing pigs were studied. At an age of 14 wk, 10 LBW–LBV (BiW: 1.07 ± 0.09 [SD] kg; EBV: −2.52 ± 3.97 g/d, compared with an average crossbred pig with a protein deposition of 165 g/d), 10 LBW–HBV (BiW: 1.02 ± 0.13 kg; EBV: 10.47 ± 4.26 g/d), 10 HBW–LBV (BiW: 1.80 ± 0.13 kg; EBV: −2.15 ± 2.28 g/d), and 10 HBW–HBV (BiW: 1.80 ± 0.15 kg; EBV: 11.18 ± 3.68 g/d) male growing pigs were allotted to the experiment. The pigs were individually housed in metabolism cages and were subjected to an N balance study in two sequential periods of 5 d, after an 11-d dietary adaptation period. Pigs were assigned to a protein adequate (A) or protein restricted (R, 70% of A) regime in a change-over design. Pigs were fed 2.8 times the energy requirements for maintenance. Nontargeted metabolomics analyses were performed in urine and blood plasma samples. The N retention (in g/d) was higher in the HBW than in the LBW pigs (P< 0.001). The N retention (in g/[kg metabolic body weight (BW0.75) · d]) and N efficiency, however, were not affected by the BiW of the pigs. The N retention (P= 0.04) and N efficiency (P= 0.04) were higher in HBV than in LVB pigs on the A regime but were not affected by EBV in pigs on the R regime. Restricting the dietary protein supply with 30% decreased the N retention (P< 0.001) but increased the N efficiency (P= 0.003). Nontargeted metabolomics showed that a hexose, free amino acids (AA), and lysophosphatidylcholines were the most important metabolites in plasma for the discrimination between HBV and LBV pigs, whereas metabolites of microbial origin contributed to the discrimination between HBV and LBV pigs in urine. This study shows that BiW does not affect N efficiency in the later life of pigs. Nitrogen efficiency and N retention were higher in HBV than in LBV pigs on the A regime but similar in HBV and LBV pigs on the R regime. In precision feeding concepts aiming to further optimize protein and AA efficiency in pigs, the variation in EBV for protein deposition of pigs should be considered as a factor determining N retention, growth performance, and N efficiency.

Exploring factors that might affect nitrogen (N) efficiency in pigs could support the development of precision feeding concepts. Therefore, an experiment was conducted to determine the effects of birth weight (BiW) on N retention, N efficiency, and concentrations of metabolites in plasma and urine related to N efficiency in male pigs of 14 wk of age. BiW of the low BiW (LBW) and high BiW (HBW) pigs was 1.11 ± 0.14 and 1.79 ± 0.12 kg, respectively. Twenty LBW and 20 HBW pigs were individually housed in metabolism cages and were subjected to an N balance study in two sequential periods of 5 d, after an 11-d adaptation period. Pigs were assigned to a protein adequate (A) or protein restricted (R, 70% of A) regime in a change-over design and fed restrictedly 2.8 times the energy requirements for maintenance. Nontargeted metabolomics analyses were performed in urine and blood plasma samples. The N retention in g/d was higher in the HBW than in the LBW pigs (P < 0.001). The N retention in g/(kg BW0.75·d) and N efficiency (= 100% × N retention / N intake), however, were not affected by BiW of the pigs. Moreover, fecal digestibility of N and urinary concentration of N and urea were not affected by BiW of the pigs. The concentration of insulin (P = 0.08) and insulin-like growth factor-1 (IGF-1;P = 0.05) in blood plasma was higher in HBW pigs, whereas the concentration of a-amino N tended to be lower in HBW pigs (P = 0.06). The LBW and HBW pigs could not be discriminated based on the plasma and urinary metabolites retrieved by nontargeted metabolomics. Restricting dietary protein supply decreased N retention (P < 0.001), N efficiency (P = 0.07), fecal N digestibility (P < 0.001), urinary concentration of N and urea (P < 0.001), and concentration of urea (P < 0.001), IGF-1 (P < 0.001), and a-amino N (P < 0.001) in blood plasma. The plasma and urinary metabolites differing between dietary protein regime were mostly amino acids (AA) or their derivatives, metabolites of the tricarboxylic acid cycle, and glucuronidated compounds, almost all being higher in the pigs fed the A regime. This study shows that BiW affects absolute N retention but does not affect N efficiency in growing pigs. Therefore, in precision feeding concepts, BiW of pigs should be considered as a factor determining protein deposition capacity but less as a trait determining N efficiency.

The malaria parasite has a voracious appetite, requiring large amounts of glucose and nutrients for its rapid growth and proliferation inside human red blood cells. The host cell is resource rich, but this is a double-edged sword; nutrient excess can lead to undesirable metabolic reactions and harmful by-products. Here, we demonstrate that the parasite possesses a metabolite repair enzyme (PGP) that suppresses harmful metabolic by-products (via substrate dephosphorylation) and allows the parasite to maintain central carbon metabolism. Loss of PGP leads to the accumulation of two damaged metabolites and causes a domino effect of metabolic dysregulation. Accumulation of one damaged metabolite inhibits an essential enzyme in the pentose phosphate pathway, leading to substrate accumulation and secondary inhibition of glycolysis. This work highlights how the parasite coordinates metabolic flux by eliminating harmful metabolic by-products to ensure rapid proliferation in its resource-rich niche.

ObjectiveTo assess whether laparoscopic cholecystectomy is superior to percutaneous catheter drainage in high risk patients with acute calculous cholecystitis.DesignMulticentre, randomised controlled, superiority trial.Setting11 hospitals in the Netherlands, February 2011 to January 2016.Participants142 high risk patients with acute calculous cholecystitis were randomly allocated to laparoscopic cholecystectomy (n=66) or to percutaneous catheter drainage (n=68). High risk was defined as an acute physiological assessment and chronic health evaluation II (APACHE II) score of 7 or more.Main outcome measuresThe primary endpoints were death within one year and the occurrence of major complications, defined as infectious and cardiopulmonary complications within one month, need for reintervention (surgical, radiological, or endoscopic that had to be related to acute cholecystitis) within one year, or recurrent biliary disease within one year.ResultsThe trial was concluded early after a planned interim analysis. The rate of death did not differ between the laparoscopic cholecystectomy and percutaneous catheter drainage group (3% v9%, P=0.27), but major complications occurred in eight of 66 patients (12%) assigned to cholecystectomy and in 44 of 68 patients (65%) assigned to percutaneous drainage (risk ratio 0.19, 95% confidence interval 0.10 to 0.37; P<0.001). In the drainage group 45 patients (66%) required a reintervention compared with eight patients (12%) in the cholecystectomy group (P<0.001). Recurrent biliary disease occurred more often in the percutaneous drainage group (53% v5%, P<0.001), and the median length of hospital stay was longer (9 days v5 days, P<0.001).ConclusionLaparoscopic cholecystectomy compared with percutaneous catheter drainage reduced the rate of major complications in high risk patients with acute cholecystitis.Trial registrationDutch Trial Register NTR2666.