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Information about amino acids and carbohydrate absorption in fish is important to formulate an adequate diet to obtain optimal growth. Therefore, the objective of this study was to investigate if Na+-dependent transporters are involved on the absorption of glycine, L-glutamine, L-leucine, L-lysine, L-proline, L-alanine, and the carbohydrates fructose and glucose in the pyloric ceca of Hoplias malabaricus. The pyloric ceca were mounted in a system of continuous perfusion "in vitro". Amino acids and carbohydrates were placed on the mucosal side at concentrations of 10, 20, and 40mM. The serosal side of the pyloric ceca was positive in relation to the mucosal side. The addition of glycine, L-glutamine, L-leucine, L-lysine, L-proline (all tested concentrations), and glucose (at concentrations of 20 and 40mM) increased the positivity of the serosal side, indicating the presence of Na+-dependent transporters in the absorption of these substances. L-alanine and fructose did not change the positivity of the serosal side. The pyloric ceca seem to be the main site of nutrient absorption in the digestive tract of H. malabaricus.

Background: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg., Methods: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUC tau ) and concentration at the end of the dosing interval (C tau ) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320., Findings: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUC tau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); C tau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48., Interpretation: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg., Funding: Gilead Sciences., Competing Interests: Declaration of interests CAR received grant support to their institution from Gilead, GSK, and ViiV Healthcare during the study and outside the submitted work; and support for meeting travel from Gilead outside the submitted work. RS reports grant support to their institution from Gilead, GSK, Merck, and Penta outside the submitted work; and support for meeting travel from Gilead outside the submitted work. CKC and PK report grant support to their institution from Gilead for the conduct of this study. MK, RL, JTH, VAV, and KK are employed by Gilead and hold stocks in Gilead. MFC reports grant support to their institution from Gilead for the conduct of this study. AHG reports clinical trial agreement to their institution from Gilead for the conduct of this study; and is Chair of the Data Safety and Monitoring Board for a study sponsored by the National Institute of Dental and Craniofacial Research. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The objective of this study was to examine the effect of replacing soybean meal (SBM) with detoxified castor seed meal (DCM) on the intake, digestibility, feeding behavior, and performance of pasture-finished (rainy season) steers supplemented with concentrate at 0.4% of their body weight. Forty ½ Holstein + ½ Zebu steers (initial weight: 283.3 ± 36.3 kg) were allocated to four treatments in a completely randomized experimental design. Treatments consisted of diets in which DCM replaced 0, 30, 60, and 90% of SBM in the supplement dry matter (DM). The steers were finished on an Urochloa brizantha pasture and the experiment lasted 112 days. Replacing SBM with DCM did not influence (P > 0.05) the intake or apparent digestibility of DM, crude protein, or neutral detergent insoluble fiber of the animals. Grazing time increased (P < 005), whereas the intake and rumination efficiencies of the steers did not change (P > 0.05) with the substitution. The replacement of SBM with DCM in the supplement fed to the steers also did not influence (P > 0.05) their final weight, average daily gain, or feed conversion (P > 0.05). We recommend replacing up to 90% (DM basis) of SBM with DCM in the concentrate supplement of steers grazing on Urochloa brizantha pasture during rainy season while supplemented with concentrate at 0.4% of their body weight., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The aim of this study was to evaluate the effect of increasing inclusion levels of palm kernel cake (PKC) in the supplement of steers finished on a Urochloa brizantha cv. Marandu pasture on intake, digestibility, feeding behavior, weight gain, and carcass traits. Forty 1/2 Holstein × 1/2 Zebu crossbred steers with an average body weight of 352.80 ± 3.32 kg, at 36 months of age, were supplemented with concentrate at 0.4% of their body weight. Four treatments were formulated (supplement containing 0, 15, 30, or 45% PKC, dry matter [DM] basis) and the animals were monitored for 240 days, weighed, and slaughtered. The inclusion of PKC in the supplement did not influence the intakes of total DM, crude protein, or neutral detergent fiber, but increased (P < 0.05) ether extract intake and reduced (P < 0.05) non-fibrous carbohydrate intake. The apparent digestibility of DM, crude protein, and neutral detergent fiber decreased (P < 0.05), whereas intake and rumination efficiencies by the dietary treatments. Average daily gain, carcass weight, and backfat thickness did not change in response to the inclusion of PKC in the supplement. We recommend the inclusion of 45% palm kernel cake in the concentrate of steers supplemented at 0.4% of their body weight and finished on Urochloa brizantha cv. Marandu pasture., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Only three well-characterised cases of functional cure have been described in paediatric HIV infection over the past decade. This underlines the fact that early initiation of combination antiretroviral therapy (cART), whilst minimising the size of the viral reservoir, is insufficient to achieve cure, unless other factors contribute. In this review, we consider these additional factors that may facilitate functional cure in paediatric infection. Among the early life immune activity, these include HIV-specific cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell responses. The former have less potent antiviral efficacy in paediatric compared with adult infection, and indeed, in early life, NK responses have greater impact in suppressing viral replication than CTL. This fact may contribute to a greater potential for functional cure to be achieved in paediatric versus adult infection, since post-treatment control in adults is associated less with highly potent CTL activity, and more with effective antiviral NK cell responses. Nonetheless, antiviral CTL responses can play an increasingly effective role through childhood, especially in individuals expressing then 'protective' HLA-I molecules HLA-B*27/57/58:01/8101. The role of the innate system on preventing infection, in shaping the particular viruses transmitted, and influencing outcome is discussed. The susceptibility of female fetuses to in utero mother-to-child transmission, especially in the setting of recent maternal infection, is a curiosity that also provides clues to mechanisms by which cure may be achieved, since initial findings are that viral rebound is less frequent among males who interrupt cART. The potential of broadly neutralising antibody therapy to facilitate cure in children who have received early cART is discussed. Finally, we draw attention to the impact of the changing face of the paediatric HIV epidemic on cure potential. The effect of cART is not limited to preventing AIDS and reducing the risk of transmission. cART also affects which mothers transmit. No longer are mothers who transmit those who carry genes associated with poor immune control of HIV. In the cART era, a high proportion (>70% in our South African study) of transmitting mothers are those who seroconvert in pregnancy or who for social reasons are diagnosed late in pregnancy. As a result, now, genes associated with poor immune control of HIV are not enriched in mothers who transmit HIV to their child. These changes will likely influence the effectiveness of HLA-associated immune responses and therefore cure potential among children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vieira, Herbert, Cromhout, Adland and Goulder.)

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants., (© 2022. The Author(s).)

HIV-specific CD8 + T cells play a central role in immune control of adult HIV, but their contribution in pediatric infection is less well characterized. Previously, we identified a group of ART-naive children with persistently undetectable plasma viremia, termed "elite controllers," and a second group who achieved aviremia only transiently. To investigate the mechanisms of failure to maintain aviremia, we characterized in three transient aviremic individuals (TAs), each of whom expressed the disease-protective HLA-B*81:01, longitudinal HIV-specific T-cell activity, and viral sequences. In two TAs, a CD8 + T-cell response targeting the immunodominant epitope TPQDLNTML (Gag-TL9) was associated with viral control, followed by viral rebound and the emergence of escape variants with lower replicative capacity. Both TAs mounted variant-specific responses, but only at low functional avidity, resulting in immunological progression. In contrast, in TA-3, intermittent viremic episodes followed aviremia without virus escape or a diminished CD4 + T-cell count. High quality and magnitude of the CD8 + T-cell response were associated with aviremia. We therefore identify two distinct mechanisms of loss of viral control. In one scenario, CD8 + T-cell responses initially cornered low-replicative-capacity escape variants, but with insufficient avidity to prevent viremia and disease progression. In the other, loss of viral control was associated with neither virus escape nor progression but with a decrease in the quality of the CD8 + T-cell response, followed by recovery of viral control in association with improved antiviral response. These data suggest the potential for a consistently strong and polyfunctional antiviral response to achieve long-term viral control without escape. IMPORTANCE Very early initiation of antiretroviral therapy (ART) in pediatric HIV infection offers a unique opportunity to limit the size and diversity of the viral reservoir. However, only rarely is ART alone sufficient to achieve remission. Additional interventions that likely include contributions from host immunity are therefore required. The HIV-specific T-cell response plays a central role in immune control of adult HIV, often mediated through protective alleles such as HLA-B*57/58:01/81:01. However, due to the tolerogenic and type 2 biased immune response in early life, HLA-I-mediated immune suppression of viremia is seldom observed in children. We assessed a rare group of HLA-B*81:01-positive, ART-naive children who achieved aviremia, albeit only transiently, and investigated the role of the CD8 + T-cell response in the establishment and loss of viral control. We identified a mechanism by which the HIV-specific response can achieve viremic control without viral escape that can be explored in strategies to achieve remission.

Humans often respond to sensory impulses provided by aromas, and current trends have generated interest in natural sources of fragrances rather than the commonly used synthetic additives. For the first time, the resulting aroma of a selected culture of Thymus mastichina L. was studied as a potential food ingredient. In this context, dried (DR) and fresh (FR) samples were submitted to carbon dioxide (CO 2 ) supercritical extraction (SFE) and hydrodistillation (HD) methods. The extracts were characterised according to their volatile composition by GC-MS, cytotoxicity against a non-tumour cell culture, and sensory attributes (odour threshold and olfactive descriptors). The most abundant aromas were quantified, and the analysis performed by GC-MS revealed an abundance of terpenoids such as thymol chemotype, followed by the precursors α-terpinene and p -cymene. DR and FR extracts (EX) obtained from SFE-CO 2 show the highest content of thymol, achieving 52.7% and 72.5% of the isolated volatile fraction. The DR essential oil (EO) contained the highest amount of terpenoids, but it was also the most cytotoxic extract. In contrast, SFE-CO 2 products showed the lowest cytotoxic potential. Regarding FR-OE, it had the lowest extraction yield and composition in aroma volatiles. Additionally, all samples were described as having green, fresh and floral sensory notes, with no significant statistical differences regarding the odour detection threshold (ODT) values. Finally, FR-EX of T. mastichina obtained by SFE-CO 2 presented the most promising results regarding food application.

Background: Elite controllers are therapy-naive individuals living with HIV capable of spontaneous control of plasma viraemia for at least a year. Although viremic nonprogressors are more common in vertical HIV-infection than in adults' infection, elite control has been rarely characterized in the pediatric population., Design: We analyzed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four pediatric elite controllers (PECs) compared with age-matched nonprogressors (PNPs), progressors and HIV-exposed uninfected (HEUs) adolescents., Results: PECs T-cell populations had lower immune activation and exhaustion levels when compared with progressors, reflected by a more sustained and preserved effector function. The HIV-specific T-cell responses among PECs were characterized by high-frequency Gag-specific CD4+ T-cell activity, and markedly more polyfunctional Gag-specific CD8+ activity, compared with PNPs and progressors. These findings were consistently observed even in the absence of protective HLA-I molecules such as HLA-B∗27/57/81., Conclusion: Pediatric elite control is normally achieved after years of infection, and low immune activation in PNPs precedes the increasing ability of CD8+ T-cell responses to achieve immune control of viraemia over the course of childhood, whereas in adults, high immune activation in acute infection predicts subsequent CD8+ T-cell mediated immune control of viremia, and in adult elite controllers, low immune activation is therefore the consequence of the rapid CD8+ T-cell mediated immune control generated after acute infection. This distinct strategy adopted by PECs may help identify pathways that facilitate remission in posttreatment controllers, in whom protective HLA-I molecules are not the main factor., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Early HIV diagnosis allows combination antiretroviral therapy (cART) initiation in the first days of life following in utero (IU) infection. The impact of early cART initiation on infant viral reservoir size in the setting of high-frequency cART nonadherence is unknown., Methods: Peripheral blood total HIV DNA from 164 early treated (day 0-21 of life) IU HIV-infected South African infants was measured using droplet digital PCR at birth and following suppressive cART. We evaluated the impact of cART initiation timing on HIV reservoir size and decay, and on the risk of subsequent plasma viremia in cART-suppressed infants., Results: Baseline HIV DNA (median 2.8 log10 copies/million peripheral blood mononuclear cells, range 0.7-4.8) did not correlate with age at cART initiation (0-21 days) but instead with maternal antenatal cART use. In 98 infants with plasma viral suppression on cART, HIV DNA half-life was 28 days. However, the probability of maintenance of plasma aviremia was low (0.46 at 12 months) and not influenced by HIV DNA load. Unexpectedly, longer time to viral suppression was associated with protection against subsequent viral rebound., Conclusions: With effective prophylaxis against mother-to-child transmission, cART initiation timing in the first 3 weeks of life is not critical to reservoir size., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Natural Killer (NK) cells contribute to HIV control in adults, but HLA-B-mediated T-cell activity has a more substantial impact on disease outcome. However, the HLA-B molecules influencing immune control in adults have less impact on paediatric infection. To investigate the contribution NK cells make to immune control, we studied >300 children living with HIV followed over two decades in South Africa. In children, HLA-B alleles associated with adult protection or disease-susceptibility did not have significant effects, whereas Bw4 (p = 0.003) and low HLA-A expression (p = 0.002) alleles were strongly associated with immunological and viral control. In a comparator adult cohort, Bw4 and HLA-A expression contributions to HIV disease outcome were dwarfed by those of protective and disease-susceptible HLA-B molecules. We next investigated the immunophenotype and effector functions of NK cells in a subset of these children using flow cytometry. Slow progression and better plasma viraemic control were also associated with high frequencies of less terminally differentiated NKG2A+NKp46+CD56dim NK cells strongly responsive to cytokine stimulation and linked with the immunogenetic signature identified. Future studies are indicated to determine whether this signature associated with immune control in early life directly facilitates functional cure in children., Competing Interests: The authors have declared that no competing interests exist.

Background: We have previously described CxxCpep, a peptide with anti-platelet properties that inhibits peri/epicellular protein disulphide isomerase (pecPDI) by forming a mixed disulfide bond with Cys400 within the pecPDI active site., Objectives: Here we sought to determine if pecPDI targeted by CxxCpep is relevant to redox mechanisms downstream of the collagen receptor GPVI in platelets., Methods and Results: Restriction of effects of CxxCpep to the platelet surface was confirmed by LC-MS/MS following cell fractionation. Platelet aggregation was measured in platelet-rich plasma (PRP) incubated with 30 μM CxxCpep or vehicle. CxxCpep inhibited collagen-induced platelet aggregation but exerted no effect in TRAP-6-stimulated platelets. PRP was incubated with DCFDA to measure oxidative burst upon platelet adhesion to collagen. Results showed that CxxCpep decreased oxidative burst in platelets adhered to immobilized collagen while the number of adherent cells was unaffected. Furthermore, flow cytometry studies using a FITC-maleimide showed that the GPVI agonist CRP stimulated an increase in free thiols on the platelet outer membrane, which was inhibited by CxxCpep. Finally, CxxCpep inhibited platelet mitochondrial respiration upon activation with collagen, but not with thrombin., Conclusions: Our data suggest that pecPDI is a potential modulator of GPVI-mediated redox regulation mechanisms and that CxxCpep can be further exploited as a template for new antiplatelet compounds., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.

Background: Early combination antiretroviral therapy (cART) reduces the size of the viral reservoir in paediatric and adult HIV infection. Very early-treated children may have higher cure/remission potential., Methods: In an observational study of 151 in utero (IU)-infected infants in KwaZulu-Natal, South Africa, whose treatment adhered strictly to national guidelines, 76 infants diagnosed via point-of-care (PoC) testing initiated cART at a median of 26 h (IQR 18-38) and 75 infants diagnosed via standard-of-care (SoC) laboratory-based testing initiated cART at 10 days (IQR 8-13). We analysed mortality, time to suppression of viraemia, and maintenance of aviraemia over the first 2 years of life., Findings: Baseline plasma viral loads were low (median 8000 copies per mL), with 12% of infants having undetectable viraemia pre-cART initiation. However, barely one-third (37%) of children achieved suppression of viraemia by 6 months that was maintained to >12 months. 24% had died or were lost to follow up by 6 months. Infant mortality was 9.3%. The high-frequency virological failure in IU-infected infants was associated not with transmitted or acquired drug-resistant mutations but with cART non-adherence (plasma cART undetectable/subtherapeutic, p <0.0001) and with concurrent maternal cART failure (OR 15.0, 95%CI 5.6-39.6; p <0.0001). High-frequency virological failure was observed in PoC- and SoC-tested groups of children., Interpretation: The success of early infant testing and cART initiation strategies is severely limited by subsequent cART non-adherence in HIV-infected children. Although there are practical challenges to administering paediatric cART formulations, these are overcome by mothers who themselves are cART-adherent. These findings point to the ongoing obligation to address the unmet needs of the mothers. Eliminating the particular barriers preventing adequate treatment for these vulnerable women and infants need to be prioritised in order to achieve durable suppression of viraemia on cART, let alone HIV cure/remission, in HIV-infected children., Funding: Wellcome Trust, National Institutes of Health., Competing Interests: Dr. Martinez-Picado reports institutional grants and educational/consultancy fees outside the submitted work from AbiVax, Astra-Zeneca, Gilead Sciences, Grifols, Janssen, Merck and ViiV Healthcare. Dr. Millar reports personal fees from Cepheid, outside the submitted work., (© 2020 The Author(s).)

Background: Reports of posttreatment control following antiretroviral therapy (ART) have prompted the question of how common immune control of HIV infection is in the absence of ART. In contrast to adult infection, where elite controllers have been very well characterized and constitute approximately 0.5% of infections, very few data exist to address this question in paediatric infection., Methods: We describe 11 ART-naive elite controllers from 10 cohorts of HIV-infected children being followed in South Africa, Brazil, Thailand, and Europe., Results: All but one of the elite controllers (91%) are females. The median age at which control of viraemia was achieved was 6.5 years. Five of these 11 (46%) children lost control of viraemia at a median age of 12.9 years. Children who maintained control of viraemia had significantly higher absolute CD4 cell counts in the period of elite control than those who lost viraemic control. On the basis of data available from these cohorts, the prevalence of elite controllers in paediatric infection is estimated to be 5-10-fold lower than in adults., Conclusion: Although conclusions are limited by the study design, these data suggest that, whilst paediatric elite control can be achieved, compared with adult elite controllers, this occurs rarely, and takes some years after infection to achieve. Also, loss of immune control arises in a high proportion of children and often relatively rapidly. These findings are consistent with the more potent antiviral immune responses observed in adults and in females.

Background: Oral preexposure prophylaxis (PrEP) has been established as a pivotal strategy in HIV prevention. However, bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis and Neisseria gonorrhoeae, are also highly prevalent. Although the presence of STI-related mucosal lesions is a known risk factor for HIV acquisition, the potential increase in risk associated with asymptomatic STIs is not completely understood. Recent data demonstrated higher T-cell activation is a risk factor for sexually acquired HIV-1 infection. We examined the effect of asymptomatic C. trachomatis and N. gonorrhoeae anorectal infection on systemic immune activation, potentially increasing the risk of HIV acquisition., Methods: We analyzed samples from participants of PrEP Brasil, a demonstration study of daily oral emtricitabine/tenofovir disoproxil fumarate HIV PrEP among healthy MSM, for T-cell activation by flow cytometry. We included 34 asymptomatic participants with anorectal swab for C. trachomatis and/or N. gonorrhoeae infection, whereas negative for other STIs, and 35 controls., Results: We found a higher frequency of human leukocyte antigen DRCD38 CD8 T cells (1.5 vs. 0.9%, P < 0.005) and with memory phenotype in the group with asymptomatic C. trachomatis and/or N. gonorrhoeae infection. Exhaustion and senescence markers were also significant higher in this group. No difference was observed in the soluble CD14 levels., Conclusion: Our findings suggest asymptomatic anorectal C. trachomatis and/or N. gonorrhoeae increase systemic immune activation, potentially increasing the risk of HIV acquisition. Regular screening and treatment of asymptomatic STIs should be explored as adjuvant tools for HIV prevention.

Although the breadth of the human immunodeficiency virus type 1 (HIV-1)-specific cellular immune response and its impact on the control of viral replication have already been addressed, reported data have proven controversial. We hypothesize that the nature of targeted epitopes, rather than the simple breadth or magnitude of responses, correlates with disease outcome. In this study, we explore the occurrence of patterns of Gag p24 recognition among untreated HIV-1-infected patients by identifying the epitopes that compose such patterns and how they distinctly associate with disease progression. Utilizing enzyme-linked immunospot (ELISPOT) interferon gamma (IFN-γ), we screened cellular responses of 27 HIV-1-infected subjects against 15-mer peptides encompassing the whole Gag p24 protein. Obtained data were used to develop a clustering analysis that allowed definition of two groups of individuals with totally distinct patterns of recognition. Although targeted Gag p24 peptides were completely different between the two groups, the breadth and magnitude of the responses were not. Interestingly, viral control and preservation of CD4 + T cells were increased in one group. In addition, we compared genetic conservation of amino acid sequences of the recognized peptides, as well as of the human leucocyte antigen class I (HLA-I)-restricted epitopes within them. Subjects presenting higher control of HIV-1 replication targeted more conserved epitopes, and higher genetic variation was present mainly in anchor residues for HLA-I molecules. We strengthen the existing evidence from cases of HIV-1 infection in humans that, cellular immune responses targeting conserved epitopes, rather than the magnitude and breadth of responses, associate with a better control of viral replication and maintenance of peripheral CD4 + T cell counts.

Objectives: To identify the profile of nursing diagnoses in people with hypertension and diabetes in primary health care., Methods: A cross-sectional study involving 175 individuals followed up in eight primary health units of Minas Gerais, Brazil. Data collection was made through interview and physical examination, and diagnostic inference was made according with NANDA-I Taxonomy II., Results: The average age of the users was 62.1 years and the female gender predominated (66.9%). A total of 26 diagnoses were identified, an average of 16 per client (standard deviation=3.9). The most frequent problem-focused diagnosis were: Ineffective Health Management (98.9%), Ineffective Peripheral Tissue Perfusion (78.3%), Sedentary lifestyle (74.3%), Obesity (54.3%) and Insomnia (51.4%). With respect to the defining characteristics and related factors, the average per person was 24 and 28, respectively., Conclusions: In this group of clients, the most frequent diagnoses were in the domain activity/rest. These diagnoses are the basis for planning nursing interventions and provide improved quality of life for these clients., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Universidad de Antioquia.)

This study evaluated the effect of storage temperature (4, 25 and 40°C) and time on the color and contents of 3-deoxyanthocyanins, total anthocyanins, total phenols and tannins of sorghum stored for 180days. Two genotypes SC319 (grain and flour) and TX430 (bran and flour) were analyzed. The SC319 flour showed luteolinidin and apigeninidin contents higher than the grain and the TX430 bran had the levels of all compounds higher than the flour. The storage temperature did not affect most of the analyzed variables. The content of most of the compounds reduced during the first 60days when they became stable. At day 180, the retention of the compounds in the genotypes SC319 and TX430 ranged from 56.1-77.9% and 67.3-80.1% (3-deoxyanthocyanins), 88.4-93.8% and 84.6-96.8% (total anthocyanins) and 86.7-86.8 and 89.4-100% (phenols) respectively. The retention of tannins ranged from 56.6 to 85.3%. The color of samples remained stable for 120days., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Moulds and arthroconidial yeasts are potential life-threatening agents of fungemia in immunocompromised patients. Fast and accurate identification (ID) of these pathogens hastens initiation of targeted antifungal therapy, thereby improving the patients' prognosis. We describe a new strategy that enabled the identification of moulds and arthroconidial yeasts directly from positive blood cultures by MALDI-TOF mass spectrometry (MS). Positive blood cultures (BCs) with Gram staining showing hyphae and/or arthroconidia were prospectively selected and submitted to an in-house protein extraction protocol. Mass spectra were obtained by Vitek MS™ system, and identifications were carried out with in the research use only (RUO) mode with an extended database (SARAMIS™ [v.4.12] plus in-house database). Fusarium solani, Fusarium verticillioides, Exophiala dermatitidis, Saprochaete clavata, and Trichosporon asahii had correct species ID by MALDI-TOF MS analysis of positive BCs. All cases were related to critically ill patients with high mortality fungemia and direct ID from positive BCs was helpful for rapid administration of targeted antifungal therapy., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The resistant starch (RS) contents in 49 sorghum genotypes and the effects of heat treatment using dry and wet heat on the grain and flour from two sorghum genotypes were investigated. The results showed a wide variation in the RS contents of the genotypes analyzed. The RS mean values were grouped into six distinct groups and ranged from 0.31±0.33 g/100 g to 65.66±5.46 g/100 g sorghum flour on dry basis. Dry heat causes minor losses in the RS content with retentions of up to 97.19±1.92% of this compound, whereas wet heat retained at most 6.98±0.43% of the RS. The SC 59 and (SSN76)FC6608 RED KAFIR BAZINE (ASA N23) cultivars, which have an average RS content of 65.51 g/100 g, were appropriate for human consumption, and the use of dry heat is presented as a better alternative for the preservation of RS in heat-treated grains., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The profile and levels of bioactive amines in different sorghum lines were reported for the first time. The amines were quantified by ion-pair HPLC, post-column derivatisation with o-phthalaldehyde and fluorimetric detection. The extraction procedure was optimised: 420 μm particle size, extraction with 5% trichloroacetic acid and three extractions. The screening of 22 sorghum lines showed that four of the ten amines investigated were detected. Spermine and spermidine were the prevalent amines (100%), followed by putrescine (77%) and cadaverine (14%). Total amines ranged from 5.8 to 41.4 mg/100 g, and the polyamines represented 60-100% of the total. Sorghum without tannin had higher amines levels compared to sorghum with tannin and cadaverine was specific to samples without tannin. Hydric stress caused accumulation of spermidine in the grains and affected the levels of other amines at rates depending on the presence or not of tannin. Sorghum is a significant source of polyamines., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The content and stability (retention) to dry heat in a conventional oven (DHCO) and extrusion of tocochromanols and carotenoids in sorghum genotypes were evaluated. One hundred sorghum genotypes showed high variability in tocochromanol content (280.7-2962.4 μg/100g in wet basis) and 23% of the genotypes were classified as source of vitamin E. The total carotenoid varied from 2.12 to 85.46 μg/100g in one hundred sorghum genotypes. According to the genetic variability for carotenoids and tocochromanols, the 100 genotypes were grouped into 7 groups. The retention of the total tocochromanols and α-tocopherol equivalent decreased after extrusion (69.1-84.8% and 52.4-85.0%, respectively) but increased after DHCO (106.8-114.7% and 109.9-115.8%, respectively). Sorghum carotenoids were sensitive to extrusion (30.7-37.1%) and DHCO (58.6-79.2%). In conclusion, the tocochromanols profile in sorghum varied widely and the genotypes presented high genetic variability for carotenoids and tocochromanols. Sorghum was a source of tocochromanols, which increased after DHCO and decreased after extrusion. The carotenoid content in sorghum decreased after DHCO and extrusion., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The effects of domestic processing with dry heat (F2-oven/milling; F3-milling/oven; F4-microwave oven/milling; F5-milling/microwave oven; F6-popped grains/milling) and wet heat (F7-cooking in water/drying/milling) on the antioxidant profile of sorghum flours (F1-raw flour) were evaluated. 3-Deoxyanthocyanidins and total phenolic compounds were stable to dry heat (retention between 96.1% and 106.3%) and reduced with wet heat. All processing with dry heat increased the vitamin E content (2,201.9-3,112.1 μg/100 g) and its retention, and reduced the carotenoids (4.78-17.27 μg/100 g). The antioxidant activity in processed flours with dry heat remained constant (F3 and F6) or increased (F2, F4 and F5) and decreased after processing with wet heat. Overall, the grains milled before processing in oven and in microwave oven retained more vitamin E and less carotenoids than those milled after these processing. In conclusion, dry heat did not affect the phenolic compounds and 3-deoxyanthocyanidins of sorghum, but increased the vitamin E and antioxidant activity, and reduced the carotenoids. The wet heat processing reduced all antioxidant compounds except carotenoids, which increased., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We investigated the effects of acidic pH and acute aluminum (Al) exposure on the metabolic substrates of Astyanax bimaculatus, and on the ability of these animals to recover in clean water. After an acclimation period, sexually mature A. bimaculatus females were sorted into six glass aquaria with three experimental groups: control in neutral pH (7.0), acidic pH (5.5), and Al (0.5 mg·L(-1)) in acidic pH (5.5). After a 96 h treatment, 10 animals from each experimental group were sampled and the rest were returned to clean water in neutral pH without Al for a recovery period of 96 h. The acidic pH, either alone or combined with Al, decreased T4 levels, whereas Al exposure increased T3 levels. Recovery of T3 levels occurred after 96 h. Al exposure decreased ovary and plasma proteins, muscle glycogen contents, and hepatic lipids due to lipoperoxidation. In the recovery phase, lipids decreased in most tissues, probably to re-establish ovary protein and hepatic glycogen. A. bimaculatus prioritized the use of energetic resources during acclimatization to Al instead of prioritizing reproduction, thereby avoiding the ovulation of impaired eggs., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The in vivo protein qualities were evaluated in flours from raw sorghum grains (RF) and flours from sorghum grains subjected to heat treatment in an oven (HTF) from the hybrids BRS 305, BRS 309 and BRS 310, developed by the Brazilian Agricultural Research Corporation (Embrapa). There were no differences in feed efficiency ratios among experimental groups. Heat-treated flour from BRS 309 and BRS 310 genotypes had higher protein efficiency ratios and net protein ratio values; however, they did not differ from those of flour from raw grain of BRS 310 genotype. Effects of heat treatment were observed in the BRS 309 genotype. Heat treatment did not affect true digestibility observed for the RF and HTF of the three genotypes. Lysine was the first limiting amino acid of the three sorghum genotypes. The HTF BRS 305 showed the lowest protein digestibility-corrected amino acid score value. Heat treatment improved the protein quality of genotype BRS 309; however, no differences were observed among the other genotypes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The objective of this study was to evaluate iron bioavailability of maize genotypes, and analyze the correlation between in vitro and in vivo methods. Dialysable iron was analyzed in 13 genotypes from which 5 were selected for the biological assay. Mean iron content of the genotypes (n = 13) was 17.93 +/- 2.93 mg kg(-1). Phytate varied from 0.77% to 1.03%; phytate: iron molar ratio from 30.64 to 55.41; and soluble iron from 13.17 to 39.63%. The highest value for dialysable iron was 19.14%. In the biological assay, the control group, that received ferrous sulphate, did not present significant difference between the genotypes for Hb gain, Hb gain per gram of iron consumed and HRE. Hb gain did not present a significant correlation with in vitro assay. However, there were positive correlations varying from 0.653 to 0.809. The maize genotypes evaluated presented a good bioavailability since the genotypes showed the same result in hemoglobin gain than control group.

Human endogenous retrovirus (HERV)-specific T cell responses in HIV-1-infected adults have been reported. Whether HERV-specific immunity exists in vertically HIV-1-infected children is unknown. We performed a cross-sectional analysis of HERV-specific T cell responses in 42 vertically HIV-1-infected children. HERV (-H, -K, and -L family)-specific T cell responses were identified in 26 of 42 subjects, with the greatest magnitude observed for the responses to HERV-L. These HERV-specific T cell responses were inversely correlated with the HIV-1 plasma viral load and positively correlated with CD4(+) T cell counts. These data indicate that HERV-specific T cells may participate in controlling HIV-1 replication and that certain highly conserved HERV-derived proteins may serve as promising therapeutic vaccine targets in HIV-1-infected children.