Comparative Response of Different Broiler Genotypes to Dietary Nutrient Levels

ABSTRACT Three studies were conducted to evaluate how the broiler has changed over the years due to intense genetic selection. Four different broiler genotypes, one unselected since the 1950\u27s (HER) representing the old meat-type bird and three current strains (Ross 308, Ross 708, and a test product (TY)) were studied. Differences in growth, morphometry, and response in performance and processing yield to different nutrient levels were studied. Experiment 1 evaluated growth and morphometric analysis. Birds of each strain were killed weekly from day 7 to day 56, necropsied and cut up parts and organs weighed. Measurement of small intestine segments was also done. Results show that current strains have significantly increased body weight (BW) and muscle accretion, especially breast meat. Jejunum and ileum segments are longer in the current genotypes but shorter when related to body weight. Heart and gizzard relative weight has reduced and tibia breaking strength has increased as a side effect of selection. Experiment 2 evaluated performance and processing yield at four different energy levels. Results show that the HER bird is able to regulate feed intake (FI) in order to regulate energy intake. Increasing energy levels did not affect its performance. The Ross 308 bird is not able to modify FI in order to regulate energy intake. Also, Ross 308 responded to increasing levels of energy by increasing BW while Ross 708 and TY did not. Current genotypes increased caloric conversion ratio with higher levels of energy. Experiment 3 evaluated performance and processing yield at six different amino acid (AA) levels (80, 85, 90, 95, 100, and 105% of the recommended levels). Results show that HER bird response to increasing levels of AA was moderate to absent while the response of the three current genotypes was similar increasing BW, FI, and breast meat yield, reducing feed conversion ratio. In conclusion, results show that a substantial change has occurred in the broiler due to selection, modifying anatomy, and its responses to different nutrient levels. These changes need to be considered when formulating diets for the different broiler genotypes used in the US industry in order to get the best economic return

Limestone Solubility: What Can You Do About It?

Calcium (Ca) is essential for bone development mineralisation, as well as for eggshell formation, muscle and neural functions. Depending on the type of diets (veggie vs. non-veggie), species (turkey, chicken, duck), and age of animal (young vs. adult), limestone can contribute up to 95% total Ca in the final diet, with more Ca from limestone for younger animals with veggie diet. Despite the significant contribution of limestone to total diet Ca levels, the bioavailability variation of limestone Ca is rarely considered. Phosphorus (P) is a limited resource and is the third most costly ingredient in poultry diets. Improving P utilization in poultry diets will decrease the amount of inorganic P needed, reduce P excretion and feed costs, as well as increase the sustainability of poultry production. Studies in the past two decades have clearly demonstrated that Ca can be detrimental to P utilization. Some recent studies suggested that phytase, if used correctly can partially or even completely alleviate such detrimental effect. In addition, recent evidences also showed that formulating on bioavailability of Ca, instead of total Ca, could be more favourable in regard to feed cost, animal performance, and sustainability. The global limestone survey started in 2018, primarily to understand the variation of: 1) Ca concentration from the most significant Ca source and probably the cheapest ingredient limestone; 2) solubility and potentially bioavailability of the Ca from limestone. In parallel, a series animal studies were carried out to determine: 1) correlation of in vitro limestone solubility and in vitro Ca digestibility; 2) the impact of solubility profile on P digestion and phytase efficacy. It has been four years since the survey started, with over 1500 samples collected globally. It is a good time to review the results from and learnings so far

Recent Findings on Phosphorus Digestibility of Feed Ingredients in Broilers

Accurately meeting the dietary P needs of broilers is critical to ensure optimal bird performance, health, and welfare without causing undue environmental burdens associated with excess dietary P excretion. Phosphorus is commonly supplied in broiler diets from inorganic phosphates derived from non-renewable sources, but it has been estimated that peak P production will occur between 2030-2040 and that the global supply of P could be depleted within this century (Cordell and Drangert, 2009; Nest and Cordell, 2012). To address these concerns, inorganic P use in agriculture, including use in broiler diet formulation, requires careful stewardship. To this end, the dietary inclusion of animal protein meals can help reduce or eliminate the need for inorganic phosphate use, especially when paired with phytase (van Harn et al., 2017). However, the proportion of P available to the bird within commonly used inorganic phosphate and animal protein sources is often not well-defined.With increasing adoption of ileal digestibility of P in feed formulation, additional data are needed to develop robust databases for commonly used and important sources of P. Therefore, the aim of this study was to generate values of AID and SID of P for different inorganic phosphates and meat and bone meal sources using the direct method. In addition, relative P digestibility of these sources was determined using monosodium phosphate as the reference ingredient to provide a basis for comparing quantitative digestibility results with relative values

Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients

Background: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients. Methods: In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA 6 months) cART. Results: Ninety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected. The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10). Discussion: Switching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms. Conclusion: Although still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials

One-pill once-a-day HAART: a simplification strategy that improves adherence and quality of life of HIV-infected subjects

OBJECTIVE: The aim of the ADONE (ADherence to ONE pill) study was to verify the effect of a reduced number of pills on adherence and quality of life (QoL) in HIV-infected patients on highly active antiretroviral therapy (HAART). DESIGN: Prospective, multicenter, study. METHODS: Patients chronically treated with emtricitabine (FTC) + tenofovir (TDF) + efavirenz (EFV) or lamivudine (3TC) +TDF +EFV and with a HIV-RNA < 50 copies/mL were switched to the single-pill fixed-dose regimen (FDR) of FTC +TDF +EFV. Data were collected with SF-36 using visual analog scales. Results of the final (6 months) primary as-treated analysis are reported. RESULTS: 212 patients (77.4% males) of mean age 45.8 years were enrolled; 202 completed the study. One month post switch to FDR the adherence rate increased significantly to 96.1% from a baseline value of 93.8% (P < 0.01). The increase was steadily maintained throughout the study (96.2% at 6 months). QoL improved over time from 68.8% to 72.7% (P = 0.042) as well, and was significantly associated with the perception of health status, presence of adverse events (AEs) and number of reported AEs (P < 0.0001). QoL significantly influenced adherence (P < 0.0001). During FDR use the mean CD4 count increased from 556 to 605 cells/muL (P < 0.0001). At the end of follow-up 98% of patients maintained HIV-RNA level < 50 copies/mL and 100% <400 copies/mL. Four patients stopped therapy because they were lost to follow-up and 6 because of AEs (insomnia/nervousness 4, allergy 1, difficulties swallowing pills 1). CONCLUSION: By substituting a one-pill once-a-day HAART, we observed an improvement of both adherence and QoL while maintaining high virologic and immunologic efficacy. HAART simplicity is an added value that favors adherence and may improve long-term success

Electrochemistry of inherently chiral molecular materials with bisindole atropisomeric cores: interacting equivalent redox sites, configurational stability, and enantioselection ability for different chiral probes

In "inherently chiral" molecules chirality and key functional properties originate from the same structural element, and are thus strictly linked together. In the case of poly(hetero)aromatic electroactive molecules, this can be achieved by inserting in the main conjugated backbone a tailored torsion with an energy barrier too high to be overcome at room temperature, while not entirely hampering conjugation. This strategy results in outstanding chirality manifestations. including e.g. circularly polarized luminescence as well as outstanding enantiorecognition ability in CV experiments. For instance, large peak potential differences were observed for the enantiomers of different chiral probes on electroactive surfaces obtained by electrooligomerization of inherently chiral monomers having atropisomeric (= with hindered rotation between two moieties) bibenzothiophene (Fig 1A) or bithiophene cores. [1-4]. An interesting option is also to change the thiophene-based atropisomeric cores with 2,2'-bisindole and 3,3'-bisindole ones (Fig 1B and 1C), on account of the easy functionalization of the core e.g. with long alkyl chains, modulating solubility and processability. A B C Figure 1 R = H or C1-C6 alkyl chains; Spacer = phenyl or nothing (oligothiophene wing attached to core) The change also leads to quite interesting modifications in the electrochemical activity. Since indole is electron richer than thiophene, the first two oxidations take place at significantly less positive potentials than in the former cases, and are localized on the two interacting moieties of the bisindole core rather than on the terminal wings; thus, they are chemically reversible (oligomerization can be achieved cycling around the third oxidation peak). A peculiar attractive feature concerns the interaction between the two equivalent redox centers in the biindole core, which can be evaluated from the potential difference between the corresponding oxidation peak: it can be shown that it can account for the atropisomeric energy barrier (depending on the 2,2' or 3,3' connectivity and on the N-alkyl substituents), and is also modulated by temperature and the solvent polarity. Thus electrochemistry can provide information on the torsional energy barrier and on the enantiomer stability, as confirmed by other approaches. Besides the intrinsic interest of these inherently chiral families, they are also quite attractive from the applicative point of view, since enantioselectivity test on films obtained by electrooligomerization of the more stable 2,2' monomers yield large potential differences for the antipodes of very different chiral probes, also of pharmaceutical interest. The current support of Fondazione Cariplo/Regione Lombardia "Avviso congiunto per l\u2019incremento dell\u2019attrattivit\ue0 del sistema di ricerca lombardo e della competitivit\ue0 dei ricercatori candidati su strumenti ERC - edizione 2016\u201d (Project 2016-0923) to our inherently chiral research is gratefully acknowledged. References: 1. Angew. Chem. Int. Ed. 2014, 53, 2623. 2. Chem. Eur. J. 2014, 20, 15298. 3. Chem. Sci. 2015, 6,1706. 4. Chem. Eur.2016 , 22,10839. 5. Anal. Bioanal. Chem. 2016, 408, 7243

Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings

Background: Virological response and resistance profile were evaluated in drug-naïve patients starting their first-line integrase inhibitors (INIs)-based regimen in a clinical setting. Study design: Virological success (VS) and virological rebound (VR) after therapy start were assessed by survival analyses. Drug-resistance was evaluated at baseline and at virological failure. Results: Among 798 patients analysed, 38.6 %, 27.1 % and 34.3 % received raltegravir, elvitegravir and dolutegravir, respectively. Baseline resistance to NRTIs, NNRTIs, PIs and INIs was: 3.9 %, 13.9 %, 1.6 % and 0.5 %, respectively. Overall, by 12 months of treatment, the probability of VS was 95 %, while the probability of VR by 36 months after VS was 13.1 %. No significant differences in the virological response were found according to the INI used. The higher pre-therapy viremia strata was (&lt;100,000 vs. 100,000-500,000 vs. &gt; 500,000 copies/mL), lower was the probability of VS (96.0 % vs. 95.2 % vs. 91.1 %, respectively, P &lt; 0.001), and higher the probability of VR (10.2 % vs. 15.8 % vs. 16.6 %, respectively, P = 0.010). CD4 cell count &lt;200 cell/mm3 was associated with the lowest probability of VS (91.5 %, P &lt; 0.001) and the highest probability of VR (20.7 %, P = 0.008) compared to higher CD4 levels. Multivariable Cox-regression confirmed the negative role of high pre-therapy viremia and low CD4 cell count on VS, but not on VR. Forty-three (5.3 %) patients experienced VF (raltegravir: 30; elvitegravir: 9; dolutegravir: 4). Patients failing dolutegravir did not harbor any resistance mutation either in integrase or reverse transcriptase. Conclusions: Our findings confirm that patients receiving an INI-based first-line regimen achieve and maintain very high rates of VS in clinical practice

Enhanced immunological recovery with early start of antiretroviral therapy during acute or early HIV infection–results of Italian Network of ACuTe HIV InfectiON (INACTION) retrospective study

ABSTRACT Background: Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation. Setting: Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers. Methods: This was an observational, retrospective, and multicenter study. We investigated the ef- fect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virolog- ical suppression, optimal immunological recovery (defined as CD4 count ≥ 500/μL, CD4 ≥ 30%, and CD4/CD8 ≥ 1), and first-line ART regimen discontinuation by Cox regression analysis. Results: There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log10 copies/mL and the median CD4 count was 456 cells/μL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥ 1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associ- ated with a shorter time to virological suppression. Early ART emerged as an independent predic- tor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percent- age count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including &gt; 3 drugs. Conclusions: In a large cohort of well-characterized patients with AEHI, we confirmed the ben- eficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunolog- ical markers associated with virological control

Search for Third Generation Vector Leptoquarks in p anti-p Collisions at sqrt(s) = 1.96 TeV

We describe a search for a third generation vector leptoquark (VLQ3) that decays to a b quark and tau lepton using the CDF II detector and 322 pb^(-1) of integrated luminosity from the Fermilab Tevatron. Vector leptoquarks have been proposed in many extensions of the standard model (SM). Observing a number of events in agreement with SM expectations, assuming Yang-Mills (minimal) couplings, we obtain the most stringent upper limit on the VLQ3 pair production cross section of 344 fb (493 fb) and lower limit on the VLQ3 mass of 317 GeV/c^2 (251 GeV/c^2) at 95% C.L.Comment: 7 pages, 2 figures, submitted to PR