Medications for the treatment of obesity.

After several years with no real therapeutic alternatives, the management of obesity is entering a new era with the development of new surgical and endoscopic bariatric techniques, digital therapeutics and the arrival of new classes of drugs. New medication treatments aim to reduce food intake, targeting the hypothalamic regulation of food intake and satiety. The mechanism of their action remains poorly understood but, combines weight reduction and amelioration of cardiometabolic risk factors with a favorable benefit-risk balance and known side effects, mainly digestive. The future will tell us how these drugs will find their place in the management of this chronic disease that is obesity.

Microalgae supplementation to late gestation sows and its effects on the health status of weaned piglets fed diets containing high- or low-quality protein sources.

Maternal stress, such as a bacterial infection occurring in late gestation, may predispose offspring to a variety of diseases later in life. It may also alter programming of developing systems within the fetus, such as the hypothalamic-pituitary-adrenal (HPA) axis and immune system. Dietary supplementation during the last trimester of pregnancy with immune-modulating compounds may be a means of reducing potential adverse effects of maternal stress on the developing fetus. Essential omega-3 polyunsaturated fatty acids (n-3 PUFA) such as docosahexanoic acid (DHA) and eicosapentanoic acid are well-known for their immune-modulating and anti-inflammatory properties. Sources of these n-3 PUFA include fish products such as fish oil and microalgae, which may be a suitable alternative to fish-based products. The aim of this study was to determine the effect of supplementing gestating sow diets with n-3 PUFA and inducing an immune stress challenge in late gestation on piglet growth and immune responsiveness when placed on either a high- or low-quality protein diet after weaning. Forty-eight sows were fed gestation diets containing either 3.12% microalgae, 3.1% fish oil or a corn oil control diet containing 1.89% corn oil starting on gestation day (gd) 75. On gd112, half the sows in each treatment were immune stress challenged with bacterial lipopolysaccharide (LPS) endotoxin (10 µg/kg administered i.m). After farrowing, piglet BW gain was monitored weekly during lactation and pigs were weaned at 21 days of age. One week after weaning, four piglets per sow were immune stress challenged with LPS (40 µg/kg administered i.m.). At the same time, four piglets per sow were vaccinated with the novel antigens chicken ovalbumin (OVA) and Candida cellular antigen (CAA) and received booster vaccinations two weeks later. Four weeks after the initial vaccination, a transdermal hypersensitivity immune challenge was performed using the same antigens. Blood samples were also collected to quantify IgG antibody responses to both antigens. PUFA enrichment in sow blood and piglet brain was detected after sows were on feed for 40 days. Piglet growth was increased in pigs fed a high-quality diet in nursery phase 1. Concentrations of the cytokines IL-1ra, IL-6 and IL-10 were elevated in pigs fed a high-quality protein diet following LPS immune challenge. Overall, it appears that in the current study piglet nursery diet quality was more important for determining piglet health and growth than maternal diet and immune stress.

Management of patients with multidrug-resistant tuberculosis.

The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.

Treatment responses in multidrug-resistant tuberculosis in Germany.

BACKGROUND: Excellent treatment outcomes have recently been reported for patients with multi/extensively drug-resistant tuberculosis (M/XDR-TB) in settings where optimal resources for individualised therapy are available. OBJECTIVE: To ascertain whether differences remain in treatment responses between patients with M/XDR-TB and those with non-M/XDR-TB. METHOD: Patients with TB were prospectively enrolled between March 2013 and March 2016 at five hospitals in Germany. Treatment was conducted following current guidelines and individualised on the basis of drug susceptibility testing. Two-month and 6-month sputum smear and sputum culture conversion rates were assessed. A clinical and radiological score were used to assess response to anti-tuberculosis treatment. RESULTS: Non-M/XDR-TB (n = 29) and M/XDR-TB (n = 46) patients showed similar rates of microbiological conversion: 2-month smear conversion rate, 90% vs. 78%; culture conversion rate, 67% vs. 61%; time to smear conversion, 19 days (IQR 10-32) vs. 31 days (IQR 14-56) (P = 0.066); time to culture conversion, 39 days (IQR 17-67) vs. 39 days (IQR 6-85) (P = 0.191). Both clinical and radiological scores decreased after the introduction of anti-tuberculosis treatment. CONCLUSION: There were no significant differences in scores between the two groups until 6 months of treatment. Under optimal clinical conditions, with the availability of novel diagnostics and a wide range of therapeutic options for individualised treatment, patients with M/XDR-TB achieved 6-month culture conversion rates that were compatible with those in patients with non-M/XDR-TB.

Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.

Replacing dietary nonessential amino acids with ammonia nitrogen does not alter amino acid profile of deposited protein in the carcass of growing pigs fed a diet deficient in nonessential amino acid nitrogen.

Amino acid usage for protein retention, and, consequently, the AA profile of retained protein, is the main factor for determining AA requirements in growing animals. The objective of the present study was to determine the effect of supplementing ammonia N on whole-body N retention and the AA profile of retained protein in growing pigs fed a diet deficient in nonessential AA (NEAA) N. In total, 48 barrows with a mean initial BW of 13.6 kg (SD 0.7) were used. At the beginning of the study, 8 pigs were euthanized for determination of initial protein mass. The remaining animals were individually housed and fed 1 of 5 dietary treatments. A common basal diet (95% of experimental diets) was formulated to meet the requirements for all essential AA (EAA) but to be deficient in NEAA N (CP = 8.01%). The basal diet was supplemented (5%) with cornstarch (negative control) or 2 N sources (ammonia or NEAA) at 2 levels each to supply 1.35 or 2.70% extra CP. The final standardized ileal digestible (SID) NEAA content in the high-NEAA-supplemented diet (positive control) was based on the NEAA profile of whole-body protein of 20-kg pigs, and it was expected to reduce the endogenous synthesis of NEAA. Pigs were fed at 3.0 times maintenance energy requirements for ME in 3 equal meals daily. At the end of a 3-wk period, pigs were euthanized and the carcass and visceral organs were weighed, frozen, and ground for determination of protein mass. From pigs in the initial, negative control, high-ammonia, and high-NEAA groups, AA contents in the carcass and pooled visceral organs were analyzed to determine the total and deposited protein AA profile, dietary EAA efficiencies, and minimal de novo synthesis of NEAA. Carcass weight and whole-body N retention linearly increased ( < 0.05) with N supplementation. The AA profile of protein and deposited protein in the carcass was not different ( > 0.10) between N sources, but Cys content increased ( < 0.05) with NEAA compared with ammonia in visceral organ protein and deposited protein. The dietary SID EAA efficiency for increasing EAA deposition in whole-body protein increased ( < 0.05) with N supplementation, but it was not different ( > 0.10) between N sources. The de novo synthesis of NEAA increased ( < 0.05) for ammonia compared with NEAA supplementation. In conclusion, adding ammonia as a N source to diets deficient in NEAA N increases whole-body N retention without affecting the carcass AA profile.

Effects of diet complexity and multicarbohydrase supplementation on growth performance, nutrient digestibility, blood profile, intestinal morphology, and fecal score in newly weaned pigs.

To study the effects of diet complexity and multicarbohydrase (MC) supplementation, 144 piglets (6.70 ± 0.81 kg of BW) weaned at 21 ± 2 d of age (1:1 male to female ratio) were assigned to 1 of 6 dietary treatments in a 3 × 2 factorial arrangement based on diet complexity (complex1, complex2, and simple) and MC addition (0 vs. 0.1% of MC). Diets were provided in a 2-phase feeding program with phase I (d 1 to 14) and phase II diets (d 15 to 28). Complex1 was formulated to mimic a conventional weaner diet with blood plasma, fish meal, dried whey, and skim milk powder, whereas complex2 partially or totally replaced these ingredients with various plant-based ingredients. The simple diet primarily comprised corn, wheat, and soybean meal. No interactions were found between diet complexity and MC supplementation ( > 0.10), except for apparent total tract digestibility (ATTD) of ash and globulin concentration on d 28 ( < 0.05). Pigs fed the complex1 diet had greater ( < 0.01) ADG, ADFI, and G:F than those fed the other diets during the first week after weaning. However, no differences in ADG or ADFI were observed for pigs fed the complex1 and simple diets throughout the 28-d experimental period ( > 0.10), whereas the complex2 diet led to lower ADG and ADFI compared with the complex1 diet ( < 0.05). Overall, G:F was greater for pigs fed the simple diet compared with those fed the complex1 diet ( < 0.01). Pigs fed the simple diet showed ATTD of DM, OM, GE, and ash comparable to those fed the complex1 diet on d 14 ( > 0.10). In contrast, greater ATTD of DM, OM, NDF, GE, and ash was observed ( < 0.05) in pigs fed the complex1 diet than in those fed the complex2 diet or the simple diet on d 28. The simple diet increased the lymphocyte proportion in serum compared with the complex1 diet ( < 0.01) on d 14. Pigs fed the complex1 diet had a greater ( < 0.05) ratio of villus height (VH) to crypt depth (CD) in the ileum compared with the other diets. The complex2 diet decreased ( < 0.05) the fecal score during 3 wk of the postweaning period compared with the complex1 diet. Dietary MC supplementation increased ( < 0.05) G:F during the overall experimental period, VH in the ileum, VH:CD ratio in the duodenum, and ATTD of DM and GE but it reduced fecal score ( < 0.05). In conclusion, feeding a simple diet resulted in BW comparable to feeding the complex1 diet, but it led to inferior intestinal morphology and ATTD of nutrients on d 28. Also, MC supplementation could be beneficial regardless of diet complexity.

Nitrogen from ammonia is as efficient as that from free amino acids or protein for improving growth performance of pigs fed diets deficient in nonessential amino acid nitrogen.

Inclusion of NPN in diets may compensate the deficient supply of nonessential AA (NEAA) in very low CP levels. To assess this, 2 studies were conducted to determine the effect of supplementing NPN and specific NEAA to diets severely deficient in NEAA nitrogen (NEAA-N) on growth performance of pigs. In Exp. 1, 48 gilts (initial BW 15.2 ± 1.3 kg; 2 pigs per pen; 6 pens per treatment) were randomly assigned to 1 of the 4 dietary treatments: 1) positive control (Pos Ctrl), not deficient in essential AA (EAA) and total N, with all N supplied from intact protein (casein and soybean meal) or crystalline EAA, (2) negative control (Neg Ctrl), supplying the same amount of potentially limiting EAA as Pos Ctrl but deficient in NEAA-N, 3) Neg Ctrl plus 1.45% CP from ammonia-N (low NPN), and 4) Neg Ctrl plus 2.90% CP from ammonia-N (high NPN), supplying the same amount of digestible N as the Pos Ctrl diet. Pigs were fed ad libitum, and ADG and ADFI were monitored weekly during a 3-wk period. Gain:feed improved linearly ( < 0.05) with supplementation of ammonia-N in diets. Gain:feed for high NPN was similar ( = 0.496) to that for Pos Crtl (0.51 and 0.52, respectively). In the Exp. 2, 72 individually housed barrows (initial BW 13.5 ± 0.6 kg; 8 pigs per treatment) were assigned to 9 dietary treatments. A basal diet was formulated to be deficient in NEAA-N with a ratio of EAA-N to total N (EAA-N:TN) of 0.74. The basal diet was supplemented with 1 of 4 different N sources (urea, ammonia, glutamic acid, and a mixture of NEAA) at 2 levels each, decreasing the final EAA-N:TN to 0.63 and 0.55, respectively. Pigs were fed at 3.0 times maintenance energy requirements during 9 d of adaptation and 3 wk of observations. Body weight was monitored weekly. At the end of the experiment, blood samples from the portal vein and abdominal aorta were collected to determine ammonia- and urea-N concentrations. Final BW, ADG, and G:F increased ( < 0.05) with supplemented ammonia, glutamate, and the NEAA mix but not (> 0.10) with urea. Final BW, ADG, and G:F were not different ( > 0.05) between pigs fed the ammonia, glutamate, and NEAA mix supplemented diets. Urea concentration in portal and arterial blood plasma increased linearly ( < 0.05) with urea intake. In conclusion, growing pigs can utilize N from ammonia as efficiently as intact protein or NEAA as a source of extra N when diets are severely deficient in NEAA-N.

Early factors related to carbohydrate and fat intake at 8 and 12 months: results from the EDEN mother-child cohort.

BACKGROUND/OBJECTIVES: Few studies have examined the factors explaining the variability in fat and carbohydrate intake during infancy. We aimed to describe infants' fat and carbohydrate intake and analyse the associations with infant and maternal characteristics and feeding practices. SUBJECTS/METHODS: This study included 1275 infants aged 8 months from the French EDEN mother-child cohort. Carbohydrate intake, fat intake, added fat (vegetable oils and animal fats) and added sugar (honey, white sugar, brown sugar, jam and sweetened beverages) consumption were calculated at 8 and 12 months. Associations between these variables and infant and maternal characteristics as well as maternal dietary patterns during pregnancy, breast-feeding duration and age at complementary feeding introduction were analysed using multivariable linear and logistic regressions. RESULTS: Less than 5% of non-breast-fed infants reached the recommendation of consuming at least 40% of total energy from fat, whereas more than 95% of them reached 45% of energy from carbohydrates. Overall, infant and maternal characteristics and maternal diet during pregnancy were marginally associated with both carbohydrate/added sugar and fat/added fat intake. Nevertheless, age at complementary feeding introduction was associated with all outcomes. CONCLUSIONS: Our results suggest that only a small proportion of non-breast-fed infants at 8 and 12 months reached the recommendations for fat intake, whereas a majority of them reached the recommendations for carbohydrate intake. As subgroups of infants with a higher risk of inadequate diet were not identified, the present results call for an improved dissemination of information regarding infant-specific dietary fat needs in the entire population.

Impact of improving dietary amino acid balance for lactating sows on efficiency of dietary amino acid utilization and transcript abundance of genes encoding lysine transporters in mammary tissue.

Lactating multiparous Yorkshire sows ( = 64) were used in 2 experiments to test the hypothesis that reducing dietary CP intake and improving AA balance through crystalline AA (CAA) supplementation improves apparent dietary AA utilization efficiency for milk production and increases transcript abundance of genes encoding Lys transporter proteins in mammary tissue. In Exp. 1, 40 sows were assigned to 1 of 4 diets: 1) high CP (HCP; 16.0% CP, as-fed basis; analyzed concentration), 2) medium-high CP (MHCP; 15.7% CP), 3) medium-low CP (MLCP; 14.3% CP), and 4) low CP (LCP; 13.2% CP). The HCP diet was formulated using soybean meal and corn as the only Lys sources. The reduced-CP diets contained CAA to meet estimated requirements for essential AA that became progressively limiting with reduction in CP concentration, that is, Lys, Ile, Met + Cys, Thr, Trp, and Val. Dietary standardized ileal digestible (SID) Lys concentration was 80% of the estimated requirement. In Exp. 2, 24 sows were assigned to the HCP or LCP diets. In Exp. 1, blood samples were postprandially collected 15 h on d 3, 7, 14, and 18 of lactation and utilization efficiency of dietary AA for milk production was calculated during early (d 3 to 7) and peak (d 14 to 18) lactation. Efficiency values were estimated from daily SID AA intakes and milk AA yield, with corrections for maternal AA requirement for maintenance and AA contribution from body protein losses. In Exp. 2, mammary tissue was biopsied on d 4 and 14 of lactation to determine the mRNA abundance of genes encoding Lys transporter proteins. In peak lactation, Lys, Thr, Trp, and Val utilization efficiency increased with decreasing dietary CP (linear for Trp and Val, < 0.05; in sows fed the MHCP diet vs. sows fed the HCP diet for Lys and Thr, < 0.05). Total essential and nonessential 15-h postprandial serum AA concentrations increased with decreasing dietary CP (linear, = 0.09 and < 0.05, respectively), suggesting increased maternal body protein mobilization. Transcript abundance of several genes involved in Lys transport in mammary tissue did not differ between sows fed the LCP and HCP diets. Feeding lactating sows low-CP diets supplemented with CAA increases the efficiency of utilizing dietary Lys, Thr, Trp, and Val for milk protein production but is unrelated to abundance in mRNA of genes encoding Lys transport proteins in the mammary gland. Dietary Lys utilization for milk protein production in lactating sows appears to be optimized when crystalline Lys is included at a minimum of 0.10% in a diet containing 15.70% CP.

Effect of supplemental dietary leucine and immune system stimulation on whole-body nitrogen utilization in starter pigs.

The increase in circulating pro-inflammatory cytokines following an immune challenge (e.g., with bacterial lipopolysaccharide [LPS]) causes a disruption in normal AA metabolism and increases visceral protein synthesis at the expense of muscle protein synthesis. The objective of this study was to determine the effect of supplemental dietary Leu on the dynamics of whole body nitrogen (N) retention in starter pigs before and after immune system stimulation (ISS) induced by LPS. A total of 28 starter pigs (14.46 ± 0.73 kg BW) were assigned to isoenergetic and isonitrogenous diets formulated to supply essential AA 10% above estimated requirements for maximum whole-body protein deposition (PD) and to contain increasing amounts of Leu: CON (1.36% SID Leu); LEU-M (2.04% SID Leu); and LEU-H (2.72% SID Leu). Pigs were housed in metabolic crates, scale-fed every 4 h based on BW, and adjusted to dietary treatments for 5 d. The 108-h N-balance experiment was divided into two periods: prechallenge (before LPS challenge; six 12-h collections) and challenge (after LPS challenge; three 12-h collections) periods. In both periods, blood was collected to determine plasma AA and urea N concentrations. At the start of the challenge period, one-half of the pigs fed CON and all pigs fed LEU-M and LEU-H were challenged with LPS (ISS+; 30 µg/kg injected intramuscularly); the remaining pigs fed CON were injected with saline (ISS-). Whole-body N retention was determined during subsequent 12-h collections. Plasma free Leu concentration increased linearly with increasing Leu content in the diet before LPS was administered (CON, 124 µmol/L; LEU-M, 185 µmol/L; LEU-H, 227 µmol/L; < 0.01). During the prechallenge period, N retention was lower in pigs fed LEU-M ( < 0.01) and there was no difference between pigs fed CON and LEU-H (7.91, 7.18, and 7.71 g/12 h for CON, LEU-M, and LEU-H, respectively). During the challenge period, N retention in pigs fed CON was higher in ISS- than ISS+ (5.37 vs. 3.83 g/12 h; < 0.01) but was not affected by diet in ISS+ pigs (3.83, 3.21, and 3.45 g/12 h for CON, LEU-M, and LEU-H, respectively; > 0.10). In healthy pigs, feeding a high excess of dietary Leu induced an anabolic response to compensate for reduced N retention that occurred in pigs fed an intermediate excess of dietary Leu. There was no effect of supplemental Leu on N retention in pigs after an LPS challenge.

Enzyme supplementation to improve the nutritional value of fibrous feed ingredients in swine diets fed in dry or liquid form.

This study evaluated the effect of xylanase supplementation (with or without), feeding method (dry or liquid), and feedstuff (corn distiller's dried grains with solubles [DDGS] or wheat middlings) on apparent total tract digestibility (ATTD) and apparent ileal digestibility (AID) of GE and nutrients, intestinal morphology, ileal and cecal pH, and VFA concentrations. Sixty-four growing pigs (25.87 ± 0.38kg initial BW) were blocked by BW and sex and randomly assigned to 8 dietary treatments. Within each feedstuff, diets were fed either liquid or dry, without or with xylanase (24,000 birch xylan units/kg feed), for 16 d. Diets contained 3.32 and 3.19 Mcal/kg ME for DDGS- and wheat middlings-based diets, respectively. Pigs were fed restricted at 3 times maintenance ME requirements. Liquid diets were prepared by steeping DDGS or wheat middlings with water (1:3, wt/vol) with or without xylanase for 24 h followed by mixing with a basal ingredient mixture and water to achieve a final ratio of 1:2.5 (wt/vol). During steeping of wheat middlings, some fiber degradation occurred. When xylanase was added in dry wheat middlings diets, AID of GE ( < 0.10) and NDF ( < 0.05) increased compared with dry wheat middlings diets without xylanase (64.50 vs. 54.67% and 52.88 vs. 31.69%, respectively), but supplementation of xylanase did not impact AID of GE and NDF when liquid wheat middlings diets were fed. Xylanase in liquid DDGS diets increased ( < 0.05) the AID of NDF compared with liquid DDGS diets without xylanase, but xylanase did not affect AID of NDF in dry DDGS diets. Xylanase in wheat middlings diets improved ( < 0.05) ATTD of GE and N compared with wheat middlings diets without xylanase (80.37 vs. 78.07% and 80.23 vs. 77.94%, respectively). However, there was no effect of xylanase in DDGS diets. Pigs fed DDGS diets had greater concentrations of butyrate in the cecum ( = 0.001) than pigs fed wheat middlings diets (27.6 vs. 20.4 mmol/L). Pigs fed DDGS diets with xylanase had deeper crypts ( < 0.05) in the jejunum than pigs fed DDGS diets without xylanase (98.20 vs. 86.16 µm), but xylanase had no effect in pigs fed wheat middlings diets. Results suggest that liquid feeding and xylanase supplementation had limited potential to enhance nutrient digestibility in pigs fed DDGS-based diets. However, xylanase supplementation in dry wheat middlings-based diets improved the AID of NDF and ATTD of GE and N, but liquid feeding as pretreatment did not further enhance the nutritional value of wheat middlings-based diets.

Impact of feeding reduced crude protein diets to lactating sows on nitrogen utilization.

Forty lactating multiparous Yorkshire sows were used to test the hypothesis that reducing dietary CP and supplementing with crystalline amino acids (CAA) increases dietary N utilization for milk production during early and peak lactation. Sows were assigned to 1 of 4 diets: 1) 16.0% CP (as-fed; analyzed contents; HCP); 2) 15.7% CP (MHCP); 3) 14.3% CP (MLCP); 4) 13.2% CP (LCP); diet HCP was formulated using soybean meal and corn as the only Lys sources. The reduced CP diets contained CAA to meet requirements of the limiting AA. Sow and piglet BW were measured on d 1, 3, 7, 14, 18, and 21 of lactation. Nitrogen retention was measured on sows between d 3 and 7 (early) and d 14 and 18 (peak) of lactation. Milk true protein output was calculated from estimated milk yield and analyzed true protein concentration. Sow BW change (overall mean: -4.2 ± 3.37 kg over the 21-d lactation period) and average daily DM intake (overall mean: 4.05 ± 0.18 and 6.12 ± 0.20 kg/d, early and peak lactation, respectively) did not differ between diets. Nitrogen intake decreased as dietary CP concentration decreased (114.3, 106.0, 107.4, and 99.0 ± 5.29 g/d and 169.5, 168.3, 161.2, and 145.1 ± 5.29 g/d for HCP, MHCP, MLCP, and LCP in early and peak lactation, respectively; L: < 0.05). Sow loin eye area loss tended to increase as dietary CP concentration decreased (Linear (): = 0.082). Litter growth rate (LGR) over the 21-d lactation period tended to increase with decreasing dietary CP concentration (L: = 0.084). In early lactation, N retention (N intake- fecal and urinary N) and milk true protein and casein output were not affected by dietary treatment. In early lactation, as dietary CP decreased, N retained as percentage of N intake tended to increase (L: = 0.093) and estimated efficiency of using retained N for milk N output was not influenced by dietary CP concentration. In peak lactation, N retention (122.5, 123.8, 121.2, and 109.0 ± 4.88 g/d for HCP, MHCP, MLCP, and LCP, respectively) decreased (L: < 0.05), N retained as percentage of N absorbed (N intake - fecal N) increased (L: < 0.05), milk casein yield increased ( = 0.051), and estimated efficiency of using retained N for milk N output (44.5, 51.0, 54.9, and 62.9 ± 5.9% for HCP, MHCP, MLCP, and LCP, respectively) increased (L: < 0.05). Feeding lactating diets reduced in CP from 16.0% to 14.3% with CAA inclusion as partial replacement for limiting AA improved N retention and N utilization efficiency for milk protein production in peak lactation, while these effects were less pronounced in early lactation.

Beyond multidrug-resistant tuberculosis in Europe: a TBNET study.

The emergence of drug-resistant tuberculosis (TB) is a challenge to TB control in Europe. We evaluated second-line drug susceptibility testing in Mycobacterium tuberculosis isolates from patients with multidrug-resistant, pre-extensively drug-resistant (pre-XDR-TB) and XDR-TB at 23 TBNET sites in 16 European countries. Over 30% of bacilli from patients with pre-XDR-TB showed resistance to any fluoroquinolone and almost 70% to any second-line injectable drug. Respectively >90% and >80% of the XDR-TB strains tested showed phenotypic resistance to pyrazinamide and ethambutol. Resistance to prothionamide/ethionamide was high in bacilli from pre-XDR-TB patients (43%) and XDR-TB patients (49%).

Influence of a flooding dose of valine on key indicators of metabolic status in the growing pig.

A key concern with the flooding dose technique for measuring protein synthesis is that a large dose of amino acid (AA) can potentially change the animals' hormonal and nutritional status, which in turn can influence protein synthesis. Among stable isotope tracers, 1-[(13)C]-valine is the preferred AA for measuring protein synthesis in gut tissue and mucins. A study was conducted to determine the impact of a flooding dose of valine on the metabolic status of pigs. Six barrows [16.5 kg body weight (BW)] were randomly assigned to intravenous infusions of either 150 mM valine (1.5 mmol/kg BW) or physiological saline, following a crossover design. Blood samples were taken 10 min prior to infusion, at the end of infusion, at 10-min intervals for 60 min post-infusion, and at 90 and 120 min post-infusion. Plasma concentrations of insulin, glucose, AA, urea nitrogen and packed cell volume (PCV) were measured. Infusion of valine increased plasma valine concentrations (4129 vs. 582 µM; P < 0.05) but had no influence on PCV (26.4% vs. 27.2%) and plasma concentrations of glucose (6.0 vs. 5.8 mM) and insulin (8.2 vs. 8.5 µU/ml; P > 0.10). Plasma urea nitrogen concentration was reduced with valine infusion (8.5 vs. 7.8 mg/dl; P < 0.05). A flooding dose of valine had no impact on plasma concentrations of AA, and specifically branched-chain AA such as leucine (240 vs. 231 µM) and isoleucine (310 vs. 331 µM; P > 0.10). There was, however, a slight increase in the plasma concentrations of threonine (224 vs. 263 µM; P < 0.05) and a tendency towards reduced glycine (1387 vs. 1313 µM; P < 0.10). The results indicate that a flooding dose of valine does not cause a substantial change in the metabolic status of growing pigs and is therefore suitable for measuring protein synthesis rates.

Rapid detection of antibiotic resistance based on mass spectrometry and stable isotopes.

With the emergence and growing complexity of bacterial drug resistance, rapid and reliable susceptibility testing has become a topical issue. Therefore, new technologies that assist in predicting the effectiveness of empiric antibiotic therapy are of great interest. Although the use of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) for the rapid detection of antibiotic resistance is an attractive option, the current methods for MALDI-TOF MS susceptibility testing are restricted to very limited conditions. Here, we describe a technique that may allow for rapid susceptibility testing to an extent that is comparable to phenotypic methods. The test was based on a stable isotope labelling by amino acids in cell culture (SILAC)-like approach. This technique was used to visualise the growth of bacteria in the presence of an antibiotic. Pseudomonas aeruginosa was chosen as the model organism, and strains were incubated in normal medium, medium supplemented with (13)C6-(15) N2-labelled lysine and medium supplemented with labelled lysine and antibiotic. Peak shifts occurring due to the incorporation of the labelled amino acids were detected by MALDI-TOF MS. Three antibiotics with different mechanisms of action, meropenem, tobramycin and ciprofloxacin, were tested. A semi-automated algorithm was created to enable rapid and unbiased data evaluation. With the proposed test, a clear distinction between resistant and susceptible isolates was possible for all three antibiotics. The application of SILAC technology for the detection of antibiotic resistance may contribute to accelerated and reliable susceptibility testing.

Epidermal growth factor-expressing Lactococcus lactis enhances growth performance of early-weaned pigs fed diets devoid of blood plasma.

The effect of supplementing Lactococcus lactis (L. lactis) that was engineered to express epidermal growth factor (EGF-LL) to early-weaned pigs fed diets with typical levels of blood plasma (5%) or diets without blood plasma [blood plasma was substituted with soybean (Glycine max) meal and fish meal, based on amino acid supply] was examined. A total of 108 weaned piglets (19-26 d of age; mean initial BW 6.58 kg; 9 pigs per pen) were fed ad libitum according to a 2-phase feeding program without growth promoters. Three pens were assigned to each of 4 treatments: i) blood plasma-containing diet with blank bacterial growth medium (BP-Con), ii) blood plasma-containing diet with fermented EGF-LL (BP-EGF), iii) blood plasma-free diet with blank bacterial growth medium (BPF-Con), and iv) blood plasma-free diet with fermented EGF-LL (BPF-EGF). The amount of epidermal growth factor (EGF) was determined in the fermentation product and pigs were allotted 60 µg EGF/kg BW/d for 3 wk postweaning. There were no differences in overall growth performance between BP-Con and BP-EGF pigs and no differences in overall growth performance between LoCon and BPF-EGF pigs. Pigs fed BPF-EGF showed increased daily BW gain (410 vs. 260 g/d; P < 0.01) and gain:feed (0.67 vs. 0.58; P < 0.05) compared to BPF-Con pigs in wk 3 postweaning; this was comparable to values for the BP-Con group (400 g/d and 0.64). These results indicate that supplementation with EGF-LL can be effective in enhancing the performance of early-weaned piglets fed a low complexity diet and reduces the need for feeding high-quality animal proteins and antibiotics.

Plantas medicinais utilizadas por idosos com diagnóstico de Diabetes mellitus no tratamento dos sintomas da doença / Medicinal plants used by elderly people with Diabetes mellitus in the treatment of the disease symptoms

Este trabalho teve como objetivo investigar as plantas medicinais utilizadas por idosos assistidos em uma Unidade Básica de Saúde de Pelotas-RS, com diagnóstico de Diabetes mellitus, como terapia complementar no tratamento dos sintomas da doença. Caracterizou-se por pesquisa qualitativa, realizada em julho de 2009, no município de Pelotas-RS. Foram entrevistados 18 idosos com idade entre 60 e 77 anos, sendo 14 do sexo feminino. Os participantes citaram 20 plantas medicinais utilizadas como terapia complementar no tratamento do Diabetes mellitus. Entre estas, as mais citadas utilizadas para diminuir os níveis de glicose no sangue foram Sphagneticola trilobata, Bauhinia spp. e Syzygium cumini, sendo que para as duas últimas há comprovação científica do efeito hipoglicemiante. A infusão foi a forma de preparo predominante. Considera-se importante a realização de estudos farmacológicos que investiguem os efeitos das plantas utilizadas pela população, a fim de que o uso proporcione os benefícios desejados e não cause danos à saúde.

This study aimed to investigate medicinal plants used as complementary therapy by the elderly with diabetes mellitus, assisted by a Health Basic Unit in Pelotas (RS, Brazil). This qualitative research was conducted in July 2009. Eighteen 60 to 77 years old elderly (14 of them female) were interviewed. The participants identified 20 medicinal plants used as complementary therapies in the treatment of diabetes mellitus. Among these, the most used ones to reduce the levels of glucose in the blood were Sphagneticola trilobata, Bauhinia spp. and Syzygium cumini. For the last two plants, there are scientific proofs of hypoglycemic effects. The infusion was the predominant form of preparation. Studies to investigate the pharmacological effects of plants used by the population have become very important, for providing scientific information on their possible health benefits and side effects.

Treatment of tuberculosis: update 2010.

Currently, the standard short-course chemotherapy for tuberculosis comprises a 6-month regimen, with a four-drug intensive phase and a two-drug continuation phase. Alternative chemotherapy using more costly and toxic drugs, often for prolonged durations generally >18 months, is required for multidrug-resistant and extensively drug-resistant tuberculosis. Directly observed treatment, as part of a holistic care programme, is a cost-effective strategy to ensure high treatment success and curtail development of drug resistance in tuberculosis. New antituberculosis drugs are urgently needed to improve the present standard short-course and alternative chemotherapies, by shortening administration durations and increasing cure rates, through the greater potency of these agents. At the same time, the role of adjunctive surgery for drug-resistant tuberculosis has to be better defined. Immunotherapy might improve treatment outcomes of both drug-susceptible and -resistant tuberculosis, and warrants further exploration.