Clinical decision making: validation of the nursing anxiety and self-confidence with clinical decision making scale (NASC-CDM ©) into Spanish and comparative cross-sectional study in nursing students.

BACKGROUND: Decision making is a pivotal component of nursing education worldwide. This study aimed to accomplish objectives: (1) Cross-cultural adaptation and psychometric validation of the Nursing Anxiety and Self-Confidence with Clinical Decision Making (NASC-CDM©) scale from English to Spanish; (2) Comparison of nursing student groups by academic years; and (3) Analysis of the impact of work experience on decision making. METHODS: Cross-sectional comparative study. A convenience sample comprising 301 nursing students was included. Cultural adaptation and validation involved a rigorous process encompassing translation, back-translation, expert consultation, pilot testing, and psychometric evaluation of reliability and statistical validity. The NASC-CDM© scale consists of two subscales: self-confidence and anxiety, and 3 dimensions: D1 (Using resources to gather information and listening fully), D2 (Using information to see the big picture), and D3 (Knowing and acting). To assess variations in self-confidence and anxiety among students, the study employed the following tests: Analysis of Variance tests, homogeneity of variance, and Levene's correction with Tukey's post hoc analysis. RESULTS: Validation showed high internal consistency reliability for both scales: Cronbach's α = 0.920 and Guttman's λ2 = 0.923 (M = 111.32, SD = 17.07) for self-confidence, and α = 0.940 and λ2 = 0.942 (M = 80.44, SD = 21.67) for anxiety; and comparative fit index (CFI) of: 0.981 for self-confidence and 0.997 for anxiety. The results revealed a significant and gradual increase in students' self-confidence (p =.049) as they progressed through the courses, particularly in D2 and D3. Conversely, anxiety was high in the 1st year (M = 81.71, SD = 18.90) and increased in the 3rd year (M = 86.32, SD = 26.38), and significantly decreased only in D3. Work experience positively influenced self-confidence in D2 and D3 but had no effect on anxiety. CONCLUSION: The Spanish version (NASC-CDM-S©) was confirmed as a valid, sensitive, and reliable instrument, maintaining structural equivalence with the original English version. While the students' self-confidence increased throughout their training, their levels of anxiety varied. Nevertheless, these findings underscored shortcomings in assessing and identifying patient problems.

Saccharomyces cerevisiae wine strains show a wide range of competitive abilities and differential nutrient uptake behavior in co-culture with S. kudriavzevii.

The wine industry has implemented complex starters with multiple yeast species as an efficient method to improve certain wine properties. Strains' competitive fitness becomes essential for its use in such cases. In the present work, we studied this trait in 60 S. cerevisiae strains from different origins, co-inoculated with a S. kudriavzevii strain, and confirmed it to be associated with the strains' origin. To gather deeper knowledge about the characteristics of strains with highly competitive ability versus the rest, microfermentations using representative strains from each group were performed and the carbon and nitrogen sources uptake was analysed. Our results demonstrate that despite wine strains being the subclade with the highest competitive ability, they present a wide range of behaviors as well as nutrient uptake dynamics, which points to a heterogeneous nature of domestication processes. An interesting strategy was observed in the highly competitive strains (GRE and QA23), the nitrogen sources uptake in the competition was accelerated and the sugar fermentation was slowing despite the fermentation finish at the same time. Therefore, this competition study, using particular combinations of strains, expands the knowledge in the field of the usage of mixed starters in wine manufactured products.

Emotional experience of the diagnostic process of a rare disease and the perception of support systems: A scoping review.

AIMS AND OBJECTIVE: To explore the experience of adult patients and adult patients' families, and their perception of the support systems received during the diagnostic process of rare diseases. BACKGROUND: There are about 7,000 rare diseases that affect 7% of the world's population. Rare diseases are often underdiagnosed. This has been reported to have deleterious physical and psychological consequences in both the patients and their families, especially when institutional support during this process is low. DESIGN: A scoping review was carried out following the 6-phase model proposed by Arksey & O'Malley and Levac et al., including the consultation phase in which patients diagnosed with rare diseases were interviewed to seek their views on the bibliographic evidence reviewed and their experience during the diagnostic process. METHODS: The databases consulted were PubMed, CINAHL, Web of Science, SCOPUS, Cochrane Library, PsycINFO, OpenGrey, ProQuest Dissertations and Theses Global. They were explored from inception-July 2020, and qualitative, quantitative and mixed method studies were included. The Mixed Methods Appraisal Tool was used for the critical evaluation of the articles. The review was based on the guidance in the PRISMA-ScR statement. RESULTS: The initial search identified 2,350 articles, of which 20 fully met the inclusion criteria and were therefore reviewed. In this analysis appeared two dimensions: internal factors: emotional aspects, and external factors: resources and support systems. RELEVANCE TO CLINICAL: This review provides evidence on the emotional impact of the diagnostic process and during the communication phase of the definitive diagnosis. Health systems and professionals must be strengthened in order to improve the information, training and resources. Nurses can play a key role in coordinating communication and follow-up of those affected.

Lack of evidence for infectious SARS-CoV-2 in feces and sewage.

The SARS-CoV-2 can be excreted in feces and can reach sewage systems. Determining the presence of infective viral particles in feces and sewage is necessary to take adequate control measures and to elucidate new routes of transmission. Here, we have developed a sample concentration methodology that allows us to maintain viral infectivity. Feces of COVID-19 patients and wastewater samples have been analyzed both by molecular methods and cell culture. Our results show no evidence of infective viral particles, suggesting that fecal-oral transmission is not a primary route. However, larger-scale efforts are needed, especially with the emergence of new viral variants.

Usefulness of guideline recommendations for prognosis in patients with candidemia.

We aimed to analyze whether the lack of inclusion of specific recommendations for the management of candidemia is an independent risk factor for early and overall mortality. Multicenter study of adult patients with candidemia in 13 hospitals. We assessed the proportion of patients on whom nine specific ESCMID and IDSA guidelines recommendations had been applied, and analyzed its impact on mortality. 455 episodes of candidemia were documented. Patients who died within the first 48 hours were excluded. Sixty-two percent of patients received an appropriate antifungal treatment. Either echinocandin or amphotericin B therapy were administered in 43% of patients presenting septic shock and in 71% of those with neutropenia. Sixty-one percent of patients with breakthrough candidemia underwent a change in antifungal drug class. Venous catheters were removed in 79% of cases. Follow-up blood cultures were performed in 72% of cases. Ophthalmoscopy and echocardiogram were performed in 48% and 50% of patients, respectively. Length of treatment was appropriate in 78% of cases. Early (2-7 days) and overall (2-30 days) mortality were 8% and 27.7%, respectively. Inclusion of less than 50% of the specific recommendations was independently associated with a higher early (HR = 7.02, 95% CI: 2.97-16.57; P < .001) and overall mortality (HR = 3.55, 95% CI: 2.24-5.64; P < .001). In conclusion, ESCMID and IDSA guideline recommendations were not performed on a significant number of patients. Lack of inclusion of these recommendations proved to be an independent risk factor for early and overall mortality.

Are retailers "bagging" the carrier bag levy in England? An exploratory enquiry.

This paper examines the business impact of the legislation in England requiring retailers to charge consumers for single-use carrier bags. The legislation impacts three key stakeholders - Government, retailers, and consumers. The primary focus of this study is, however, from the perspective of retailers and how this group of stakeholders may have benefitted from the charge. Retailers are using the collected revenues to promote their image in the marketplace and presenting themselves as corporate social responsible entities. For retailers, the charge provides an avenue for bolstering their carbon footprint as consumers are expected to reuse their plastic bags - i.e. the "bag for life" as they now have to pay for them. At the same time, the proceeds are helping some retailers to top up their coffers which to some extent implies that there is some misuse or abuse of the policy by retailers.

Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+ T Cells.

UNLABELLED: Tripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type 1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two nonhuman TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8(+) T cells. We illustrate how TRIM5 restriction improves CD8(+) T-cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the nonimmunosuppressive analog of cyclosporine (CsA), sarcosine-3(4-methylbenzoate)-CsA (SmBz-CsA), we found a significant reduction in CD107a/MIP-1ß expression in HIV-1-specific CD8(+) T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8(+) T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8(+) T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for nonhuman TRIM5 variants in cellular immunity. We hypothesize that TRIM5 can couple innate viral sensing and CD8(+) T-cell activation to increase species barriers against retrovirus infection. IMPORTANCE: New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The nonhuman TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8(+) T-cell-mediated inhibition through the direct activation of HIV-1-specific CD8(+) T-cell responses. We found that the potency in CD8(+) activation was stronger for RhT5 variants and capsid-specific CD8(+) T cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection.

Skeletal involvement in Gaucher disease: An observational multicenter study of prognostic factors in the Argentine Gaucher disease patients.

Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0. 16% of patients showed new irreversible BL (bone infarcts and avascular osteonecrosis) despite ERT, suggesting that they appeared during ERT or were not detected at the moment of diagnosis. We observed 5 prognostic factors that predicted a higher probability of being free of bone disease: optimal ERT compliance; early diagnosis; timely initiation of therapy; ERT initiation dose ≥45 UI/kg/EOW; and the absence of history of splenectomy. Skeletal involvement was classified into 4 major phenotypic groups according to BL: group 1 (12.9%) without BL; group 2 (28.2%) with reversible BL; group 3 (41.9%) with reversible BL and irreversible chronic BL; and group 4 (16.9%) with acute irreversible BL. Our study identifies prognostic factors for achieving best therapeutic outcomes, introduces new risk stratification for patients and suggests the need for a redefinition of bone TG. Am. J. Hematol. 91:E448-E453, 2016. © 2016 Wiley Periodicals, Inc.

Cell cycle control and HIV-1 susceptibility are linked by CDK6-dependent CDK2 phosphorylation of SAMHD1 in myeloid and lymphoid cells.

Proliferating cells are preferentially susceptible to infection by retroviruses. Sterile α motif and HD domain-containing protein-1 (SAMHD1) is a recently described deoxynucleotide phosphohydrolase controlling the size of the intracellular deoxynucleotide triphosphate (dNTP) pool, a limiting factor for retroviral reverse transcription in noncycling cells. Proliferating (Ki67(+)) primary CD4(+) T cells or macrophages express a phosphorylated form of SAMHD1 that corresponds with susceptibility to infection in cell culture. We identified cyclin-dependent kinase (CDK) 6 as an upstream regulator of CDK2 controlling SAMHD1 phosphorylation in primary T cells and macrophages susceptible to infection by HIV-1. In turn, CDK2 was strongly linked to cell cycle progression and coordinated SAMHD1 phosphorylation and inactivation. CDK inhibitors specifically blocked HIV-1 infection at the reverse transcription step in a SAMHD1-dependent manner, reducing the intracellular dNTP pool. Our findings identify a direct relationship between control of the cell cycle by CDK6 and SAMHD1 activity, which is important for replication of lentiviruses, as well as other viruses whose replication may be regulated by intracellular dNTP availability.

Characterization of the influence of mediator complex in HIV-1 transcription.

HIV-1 exploits multiple host proteins during infection. siRNA-based screenings have identified new proteins implicated in different pathways of the viral cycle that participate in a broad range of cellular functions. The human Mediator complex (MED) is composed of 28 elements and represents a fundamental component of the transcription machinery, interacting with the RNA polymerase II enzyme and regulating its ability to express genes. Here, we provide an evaluation of the MED activity on HIV replication. Knockdown of 9 out of 28 human MED proteins significantly impaired viral replication without affecting cell viability, including MED6, MED7, MED11, MED14, MED21, MED26, MED27, MED28, and MED30. Impairment of viral replication by MED subunits was at a post-integration step. Inhibition of early HIV transcripts was observed by siRNA-mediated knockdown of MED6, MED7, MED11, MED14, and MED28, specifically affecting the transcription of the nascent viral mRNA transactivation-responsive element. In addition, MED14 and MED30 were shown to have special relevance during the formation of unspliced viral transcripts (p < 0.0005). Knockdown of the selected MED factors compromised HIV transcription induced by Tat, with the strongest inhibitory effect shown by siMED6 and siMED14 cells. Co-immunoprecipitation experiments suggested physical interaction between MED14 and HIV-1 Tat protein. A better understanding of the mechanisms and factors controlling HIV-1 transcription is key to addressing the development of new strategies required to inhibit HIV replication or reactivate HIV-1 from the latent reservoirs.

Restriction of HIV-1 replication in primary macrophages by IL-12 and IL-18 through the upregulation of SAMHD1.

Monocyte-derived macrophages (MDM) can polarize into different subsets depending on the environment and the activation signal to which they are submitted. Differentiation into macrophages allows HIV-1 strains to infect cells of the monocytic lineage. In this study, we show that culture of monocytes with a combination of IL-12 and IL-18 led to macrophage differentiation that was resistant to HIV-1 infection. In contrast, M-CSF-derived MDM were readily infected by HIV-1. When monocytes were differentiated in the presence of M-CSF and then further treated with IL-12/IL-18, cells became resistant to infection. The restriction on HIV-1 replication was not dependent on virus entry or coreceptor expression, as vesicular stomatitis virus-pseudotyped HIV-1 replication was also blocked by IL-12/IL-18. The HIV-1 restriction factor sterile α motif and HD domain-containing protein-1 (SAMHD1) was significantly overexpressed in IL-12/IL-18 MDM compared with M-CSF MDM, and degradation of SAMHD1 by RNA interference or viral-like particles carrying the lentiviral protein Vpx restored HIV-1 infectivity of IL-12/IL-18 MDM. SAMHD1 overexpression induced by IL-12/IL-18 was not dependent on IFN-γ. Thus, we conclude that IL-12 and IL-18 may contribute to the response against HIV-1 infection through the induction of restriction factors such as SAMHD1.

SAMHD1 specifically affects the antiviral potency of thymidine analog HIV reverse transcriptase inhibitors.

Sterile alpha motif and histidine-aspartic domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase recently recognized as an antiviral factor that acts by depleting dNTP availability for viral reverse transcriptase (RT). SAMHD1 restriction is counteracted by the human immunodeficiency virus type 2 (HIV-2) accessory protein Vpx, which targets SAMHD1 for proteosomal degradation, resulting in an increased availability of dNTPs and consequently enhanced viral replication. Nucleoside reverse transcriptase inhibitors (NRTI), one of the most common agents used in antiretroviral therapy, compete with intracellular dNTPs as the substrate for viral RT. Consequently, SAMHD1 activity may be influencing NRTI efficacy in inhibiting viral replication. Here, a panel of different RT inhibitors was analyzed for their different antiviral efficacy depending on SAMHD1. Antiviral potency was measured for all the inhibitors in transformed cell lines and primary monocyte-derived macrophages and CD4(+) T cells infected with HIV-1 with or without Vpx. No changes in sensitivity to non-NRTI or the integrase inhibitor raltegravir were observed, but for NRTI, sensitivity significantly changed only in the case of the thymidine analogs (AZT and d4T). The addition of exogenous thymidine mimicked the change in viral sensitivity observed after Vpx-mediated SAMHD1 degradation, pointing toward a differential effect of SAMHD1 activity on thymidine. Accordingly, sensitivity to AZT was also reduced in CD4(+) T cells infected with HIV-2 compared to infection with the HIV-2ΔVpx strain. In conclusion, reduction of SAMHD1 levels significantly decreases HIV sensitivity to thymidine but not other nucleotide RT analog inhibitors in both macrophages and lymphocytes.

Increased expression of SAMHD1 in a subset of HIV-1 elite controllers.

OBJECTIVES: SAMHD1 and the CDKN1A (p21) cyclin-dependent kinase inhibitor have been postulated to mediate HIV-1 restriction in CD4+ cells. We have shown that p21 affects HIV replication through its effect on SAMHD1. Thus, we aimed at evaluating the expression of SAMHD1 and p21 in different HIV+ phenotypic groups. PATIENTS AND METHODS: We evaluated SAMHD1 and CDKN1A mRNA expression in CD4+ T cells from HIV+ individuals including elite controllers (n = 12), individuals who control HIV without the need for antiretroviral treatment, viraemic progressors (n = 10) and HIV-1 seronegative healthy donors (n = 14). Immunological variables were measured by flow cytometry. RESULTS: We show that a subset of HIV+ elite controllers with lower T cell proliferation levels (Ki67+ cells) expressed higher SAMHD1 compared with healthy donors or viraemic progressors. Conversely, there was no difference in p21 expression before or after T cell activation with a bispecific CD3/CD8 antibody. CONCLUSIONS: Our results suggest that SAMHD1 may play a role in controlling virus replication in HIV+ individuals and slow the rate of disease progression.

Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

INTRODUCTION: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. METHODS: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. RESULTS: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. CONCLUSIONS: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Management from a multidisciplinary perspective of phlebitis related to peripheral venous catheter insertion: An international Delphi study.

AIM: To determine the consensus and importance of care practices related to the management of peripheral venous catheter (PVC)-related phlebitis in hospitalized patients through the views of experts from different disciplines. BACKGROUND: PVCs are commonly used in hospitals but are associated with complications such as phlebitis. Their management differs widely, and studies are heterogeneous. DESIGN: Delphi method. METHODS: Four stages: problem area (with Web of Science bibliometric review in July 2022), panel members, two Delphi rounds and closing criteria. In the Delphi survey, experts answered an online questionnaire based on assessment, treatment and follow-up dimensions (September 2022-February 2023). Statistical analyses were conducted of frequencies, percentages, measures of central tendency and levels of dispersion (QD). A space for comments was created, and a thematic analysis conducted of them. RESULTS: Eighteen experts (nurses, doctors and pharmacists) participated in the Delphi rounds. Forty-five activities were identified: 19 in assessment, 15 in treatment and 11 in follow-up. A high consensus level (QD ≤ 0.6) was found in five activities (11.12%), moderate level (0.6 < QD < 1.0) in 19 (42.22%) and low level (QD > 1.0) in 21 (46.66%). Seven themes were determined (patient perspective, lack of consensus, low evidence-based practices, stage-based treatments, prevention activities, high variability in practice and specialist teams and interdisciplinary work). CONCLUSION: The importance of systematic assessment scales is highlighted together with consensus on signs and symptoms (pain, redness, inflammation, palpable cord and induration). Treatment according to severity and daily visual recording and monitoring are emphasized along with the need for patient participation and healthcare literacy. A high level of consensus was obtained in 11% of the activities, showing the large variability of criteria and interventions for phlebitis management. Highlighted needs include working in a team, the use of specialist teams and promoting evidence- and prevention-based activities. RELEVANCE TO CLINICAL PRACTICE: Clinical variability is noted and, therefore, the importance of consensus on standardized care for PVC phlebitis and evidence-based practice. REPORTING METHOD: Delphi studies (CREDES). PATIENT OR PUBLIC CONTRIBUTION: Experts contribution.

Assessment, Treatment, and Follow-Up of Phlebitis Related to Peripheral Venous Catheterisation: A Delphi Study in Spain.

BACKGROUND: Phlebitis related to peripheral venous catheters (PVCs) is a common complication in patients who require these devices and can have important consequences for the patients and the healthcare system. The management and control of the PVC-associated complications is related to nursing competency. The present study aims to determine, at the national level in Spain, the consensus on the assessment, treatment, and follow-up of PVC-related phlebitis and the importance of the actions taken. METHOD: A three-round Delphi technique was used with clinical care nurses who are experts in the field of in-hospital intravenous treatment in Spain. For this, an online questionnaire was developed with three open-ended questions on the dimensions of phlebitis assessment, treatment, and follow-up. For the statistical analysis of the results, frequencies and percentages were used to determine consensus, and the measures of central tendency (mean, standard deviation, and the coefficient of variation) were used to rank importance. The coefficient of variation was set as acceptable at ≤30%. RESULTS: The final sample was 27 expert nurses. At the conclusion of round 3, actions were ranked according to their importance, with six items included in the PVC-related phlebitis assessment (symptomatology/observation, redness, the Maddox scale, induration, temperature, and pain), two in treatment (catheter removal, pentosan polysulphate sodium ointment + application of cold), and just one in follow-up (general monitoring + temperature control). CONCLUSIONS: There is a major disparity in relation to the PVC-related phlebitis assessment, treatment, and follow-up actions. More clinical studies are therefore needed to minimise the complications associated with the use of PVCs, given their impact on the quality of care and patient safety and their economic cost.

Differences in metabolism among Saccharomyces species and their hybrids during wine fermentation.

This study aimed to investigate how parental genomes contribute to yeast hybrid metabolism using a metabolomic approach. Previous studies have explored central carbon and nitrogen metabolism in Saccharomyces species during wine fermentation, but this study analyses the metabolomes of Saccharomyces hybrids for the first time. We evaluated the oenological performance and intra- and extracellular metabolomes, and we compared the strains according to nutrient consumption and production of the main fermentative by-products. Surprisingly, no common pattern was observed for hybrid genome influence; each strain behaved differently during wine fermentation. However, this study suggests that the genome of the S. cerevisiae species may play a more relevant role in fermentative metabolism. Variations in biomass/nitrogen ratios were also noted, potentially linked to S. kudriavzevii and S. uvarum genome contributions. These results open up possibilities for further research using different "omics" approaches to comprehend better metabolic regulation in hybrid strains with genomes from different species.

Optimization of [(11)C]raclopride positron emission tomographic rat studies: comparison of methods for image quantification.

The goal of this study was to compare different quantification approaches and reconstruction methods to estimate the binding potential in [11C]raclopride studies in rats. The final aim was to determine if the results obtained with short-acquisition scanning were comparable to the results obtained with long-acquistion (conventional) scanning. We analyzed two rat data sets: a baseline versus a pretreatment study (with cold raclopride) and a young versus an old animal group comparison. The study results support the contention that optimization of [11C]raclopride positron emission tomographic studies in rats by shortening the acquisition time is feasible. In addition, filtered backprojection is recommended as a reconstruction algorithm, although iterative methods may be more sensitive to detect within-group differences.

Antiretroviral agents effectively block HIV replication after cell-to-cell transfer.

Cell-to-cell transmission of HIV has been proposed as a mechanism contributing to virus escape to the action of antiretrovirals and a mode of HIV persistence during antiretroviral therapy. Here, cocultures of infected HIV-1 cells with primary CD4(+) T cells or lymphoid cells were used to evaluate virus transmission and the effect of known antiretrovirals. Transfer of HIV antigen from infected to uninfected cells was resistant to the reverse transcriptase inhibitors (RTIs) zidovudine (AZT) and tenofovir, but was blocked by the attachment inhibitor IgGb12. However, quantitative measurement of viral DNA production demonstrated that all anti-HIV agents blocked virus replication with similar potency to cell-free virus infections. Cell-free and cell-associated infections were equally sensitive to inhibition of viral replication when HIV-1 long terminal repeat (LTR)-driven green fluorescent protein (GFP) expression in target cells was measured. However, detection of GFP by flow cytometry may incorrectly estimate the efficacy of antiretrovirals in cell-associated virus transmission, due to replication-independent Tat-mediated LTR transactivation as a consequence of cell-to-cell events that did not occur in short-term (48-h) cell-free virus infections. In conclusion, common markers of virus replication may not accurately correlate and measure infectivity or drug efficacy in cell-to-cell virus transmission. When accurately quantified, active drugs blocked proviral DNA and virus replication in cell-to-cell transmission, recapitulating the efficacy of antiretrovirals in cell-free virus infections and in vivo.