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For newly graduated nurses (NGNs), the characteristically challenging and dynamic period of transition from student to professional practitioner is being further strained by global crises and the uncertainty and insecurity they motivate, health care systems and institutional restructuring, and extreme workload burdens. A novel approach to aiding the transition of NGNs is detailed in this article, culminating in the offering of an inclusive framework of potential strategies aimed at supporting NGNs and those who lead, manage, and educate them. This approach outlines strategies of support deliverable by both centralized and local means and acknowledging contemporary needs such as workload burdens and generationally-sensitive employee needs. Nursing The Future is a platform that uniquely situates an evidence-based, grassroots-driven response to the needs of NGNs, while encouraging collaborative partnering of health care institutions with governmental, professional, and regional advanced education bodies. This is the second article in a 2-part series that builds on the historical and developmental intents of Nursing The Future as an organization and outlines how evidence-informed, creative, and affordable grassroots-driven supports may be offered to NGNs for the purpose of sustaining and advancing our future nurse professionals.

The transition from student to practitioner for newly graduated nurses is impacted by their physical, social, professional, and practice environments. COVID-19, global insecurity, institutional restructuring, and “acute on chronic” staffing shortages have increased the immediate burden experienced by emerging nurses. As detailed through the historical development of Duchscher's Stages of Transition Theory and Transition Shock Model, theorization of the transition process offers graduates, their educators, and workplace managers key areas of support opportunities for these new practitioners. In part 1 of a 2-part article series, this article explores how novel new graduate supports have been developed and delivered in partnership with nonprofit groups, government bodies, and employers across much of Canada. For nurse stakeholders, theorists, and beyond, support for the transition period of new nurses remains anecdotally, evidentially, and fiscally advisable, with an increasing urgency due to rising human capital pressures.

Administration of azithromycin after allogeneic hematopoietic stem cell transplantation for hematologic malignancies has been associated with relapse in a randomized phase 3 controlled clinical trial. Studying 240 samples from patients randomized in this trial is a unique opportunity to better understand the mechanisms underlying relapse, the first cause of mortality after transplantation. We used multi-omics on patients’ samples to decipher immune alterations associated with azithromycin intake and post-transplantation relapsed malignancies. Azithromycin was associated with a network of altered energy metabolism pathways and immune subsets, including T cells biased toward immunomodulatory and exhausted profiles. In vitro, azithromycin exposure inhibited T-cell cytotoxicity against tumor cells and impaired T-cell metabolism through glycolysis inhibition, down-regulation of mitochondrial genes, and up-regulation of immunomodulatory genes, notably SOCS1. These results highlight that azithromycin directly affects immune cells that favor relapse, which raises caution about long-term use of azithromycin treatment in patients at high risk of malignancies. The ALLOZITHRO trial was registered at www.clinicaltrials.gov as #NCT01959100.

•Azithromycin after allogeneic hematopoietic stem cell transplantation increases relapse of malignancies in a randomized-placebo trial.•Azithromycin dampens antitumor immune response by disrupting T-cell functions through inhibition of energy metabolism in immune cells.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective treatment for selected patients with acute myeloid leukemia (AML) and relies on a “graft-versus-leukemia” effect (GVL) where donor T lymphocytes mediate control of malignant cell growth. However, relapse remains the major cause of death after allo-HSCT. In various malignancies, several immunoregulatory mechanisms have been shown to restrain antitumor immunity, including ligand-mediated engagement of inhibitory receptors (IRs) on effector cells, and induction of immunosuppressive cell subsets, such as regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs). Relapse after HSCT remains a major therapeutic challenge, but immunoregulatory mechanisms involved in restraining the GVL effect must be better deciphered in humans. We used mass cytometry to comprehensively characterize circulating leukocytes in 2 cohorts of patients after allo-HSCT. We first longitudinally assessed various immunoregulatory parameters highlighting specific trends, such as opposite dynamics between MDSCs and Tregs. More generally, the immune landscape was stable from months 3 to 6, whereas many variations occurred from months 6 to 12 after HSCT. Comparison with healthy individuals revealed that profound alterations in the immune equilibrium persisted 1 year after HSCT. Importantly, we found that high levels of TIGIT and CD161 expression on CD4 T cells at month 3 after HSCT were distinct features significantly associated with subsequent AML relapse in a second cross-sectional cohort. Altogether, these data provide global insights into the reconstitution of the immunoregulatory landscape after HSCT and highlight non-canonical IRs associated with relapse, which could open the path to new prognostic tools or therapeutic targets to restore subverted anti-AML immunity.

Fibrosis is defined as an excessive accumulation of extracellular matrix (ECM) components. Many organs are subjected to fibrosis including the lung, liver, heart, skin, kidney, and muscle. Muscle fibrosis occurs in response to trauma, aging, or dystrophies and impairs muscle function. Fibrosis represents a hurdle for the treatment of human muscular dystrophies. While data on the mechanisms of fibrosis have mostly been investigated in mice, dystrophic mouse models often do not recapitulate fibrosis as observed in human patients. Consequently, the cellular and molecular mechanisms that lead to fibrosis in human muscle still need to be identified. Combining mass cytometry, transcriptome profiling, in vitroco‐culture experiments, and in vivotransplantation in immunodeficient mice, we investigated the role and nature of nonmyogenic cells (fibroadipogenic progenitors, FAPs) from human fibrotic muscles of healthy individuals (FibMCT) and individuals with oculopharyngeal muscular dystrophy (OPMD; FibMOP), as compared with nonmyogenic cells from human nonfibrotic muscle (MCT). We found that the proliferation rate of FAPs from fibrotic muscle is 3–4 times higher than those of FAPs from nonfibrotic muscle (population doubling per day: MCT0.2 ± 0.1, FibMCT0.7 ± 0.1, and FibMOP0.8 ± 0.3). When cocultured with muscle cells, FAPs from fibrotic muscle impair the fusion index unlike MCTFAPs (myoblasts alone 57.3 ± 11.1%, coculture with MCT43.1 ± 8.9%, with FibMCT31.7 ± 8.2%, and with FibMOP36.06 ± 10.29%). We also observed an increased proliferation of FAPs from fibrotic muscles in these co‐cultures in differentiation conditions (FibMCT+17.4%, P <0.01 and FibMOP+15.1%, P <0.01). This effect is likely linked to the increased activation of the canonical TGFβ‐SMAD pathway in FAPs from fibrotic muscles evidenced by pSMAD3 immunostaining (P< 0.05). In addition to the profibrogenic TGFβ pathway, we identified endothelin as a new actor implicated in the altered cross‐talk between muscle cells and fibrotic FAPs, confirmed by an improvement of the fusion index in the presence of bosentan, an endothelin receptor antagonist (from 33.8 ± 10.9% to 52.9 ± 10.1%, P< 0.05). Our data demonstrate the key role of FAPs and their cross‐talk with muscle cells through a paracrine signalling pathway in fibrosis of human skeletal muscle and identify endothelin as a new druggable target to counteract human muscle fibrosis.

Purpose: To assess how nutrition knowledge is associated with global diet quality and to investigate whether sociodemographic characteristics (ie, sex, age, education, income, marital status, and living with children or not) moderate this association.Design: Cross-sectional web-based study.Participants: The PREDISE study aims at identifying correlates of adherence to healthy eating guidelines in French-speaking adults from the Province of Quebec, Canada.Subjects: A probability sample of 1092 participants (50% female).Measures: The Nutrition Knowledge Questionnaire and 24-hour food recalls from which the Canadian Healthy Eating Index (C-HEI) was calculated.Analysis: Multiple linear regressions performed to assess how nutrition knowledge is associated with the C-HEI. Interaction terms tested to evaluate whether sociodemographic characteristics moderate the association between nutrition knowledge and the C-HEI.Results: Nutrition knowledge (B = 0.141 [95% CI: 0.075-0.208], P< .0001) was identified as a significant correlate of the C-HEI. Education significantly moderated the association between nutrition knowledge and the C-HEI (Pinteraction = .0038), with a significative association among participants with a lower education level (B = 0.295 [95% CI: 0.170-0.421], P< .0001) but not among participants with a higher education level (B = 0.077 [95% CI: −0.004 to 0.157], P= .06). Whether participants lived with or without children also significantly moderated the association (Pinteraction = 0.0043); nutrition knowledge was associated with the C-HEI only in participants who were not living with children (B = 0.261 [95% CI: 0.167 to 0.355], P< .0001).Conclusion: This study suggests that the association between nutrition knowledge and adherence to healthy eating guidelines is not the same in different subgroups of the population. Interventions aiming at increasing nutrition knowledge may be a promising approach to improve diet quality, especially among individuals with a lower education.

Hematopoietic stem cells (HSCs) sustain blood cell homeostasis throughout life and can regenerate all blood lineages after transplantation. Despite this clear functional definition, highly enriched isolation of human HSCs can currently only be achieved through combinatorial assessment of multiple surface antigens. Although several transgenic HSC reporter mouse strains have been described, no analogous approach to prospectively isolate human HSCs has been reported. To identify genes with the most selective expression in human HSCs, we profiled population and single-cell transcriptomes of unexpanded and ex vivo cultured cord blood–derived hematopoietic stem and progenitor cells as well as peripheral blood, adult bone marrow, and fetal liver. On the basis of these analyses, we propose the master transcription factor HLF (hepatic leukemia factor) as one of the most specific HSC marker genes. To directly track its expression in human hematopoietic cells, we developed a genomic HLF reporter strategy, capable of selectively labeling the most immature blood cells on the basis of a single engineered parameter. Most importantly, HLF-expressing cells comprise all stem cell activity in culture and in vivo during serial transplantation. Taken together, these results experimentally establish HLF as a defining gene of the human HSC state and outline a new approach to continuously mark these cells with high fidelity.

Hematopoietic stem cells (HSCs) sustain blood cell homeostasis throughout life and can regenerate all blood lineages after transplantation. Despite this clear functional definition, highly enriched isolation of human HSCs can currently only be achieved through combinatorial assessment of multiple surface antigens. Although several transgenic HSC reporter mouse strains have been described, no analogous approach to prospectively isolate human HSCs has been reported. To identify genes with the most selective expression in human HSCs, we profiled population and single-cell transcriptomes of unexpanded and ex vivo cultured cord blood–derived hematopoietic stem and progenitor cells as well as peripheral blood, adult bone marrow, and fetal liver. On the basis of these analyses, we propose the master transcription factor HLF(hepatic leukemia factor) as one of the most specific HSC marker genes. To directly track its expression in human hematopoietic cells, we developed a genomic HLFreporter strategy, capable of selectively labeling the most immature blood cells on the basis of a single engineered parameter. Most importantly, HLF-expressing cells comprise all stem cell activity in culture and in vivo during serial transplantation. Taken together, these results experimentally establish HLFas a defining gene of the human HSC state and outline a new approach to continuously mark these cells with high fidelity.

We describe the use of periodic micropillar arrays, produced from cyclic olefin copolymer using high-fidelity microfabrication, as templates for colorimetric DNA detection. The assay involves PCR-amplified gene markers for E. coliO157:H7 (rfbO157, eae, vt1, and vt2) incorporating a detectable digoxigenin label, which is revealed through an immunoenzymatic process following hybridization with target-specific oligonucleotide capture probes. The capacity of micropillar arrays to induce wicking is used to distribute and confine capture probes with spatial control, making it possible to achieve a uniform signal while allowing multiple, independent probes to be arranged in close proximity on the same substrate. The kinetic profile of color pigment formation on the surface was followed using absorbance measurements, showing maximum signal increase between 20 and 60 min of reaction time. The relationship between microstructure and colorimetric signal was investigated through variation of geometric parameters, such as pitch (10–50 μm), pillar diameter (5–40 μm), and height (16–48 μm). Our findings suggest that signal intensity is largely influenced by the edges of the pillars and less by their height such that it deviates from a linear relationship when both aspect ratio and pillar density become very high. A theoretical model used to simulate the changes in surface composition at the molecular level suggests that differences in the temporal and spatial accumulation of assay components account for this observation.

Foodborne viruses such as norovirus and hepatitis A virus (HAV) are highly transmissible, persistent in the environment, and resistant to many conventional inactivation methods. Foods can become contaminated with these viruses either at the source of harvest or during food handling and processing. Multiple lines of evidence suggest that foodborne viruses can survive desiccation and dry conditions. Several foodborne virus outbreaks have been linked to low-moisture foods (LMFs), indicating that these foods can be vehicles of virus transmission. However, the efficiencies of common virus extraction methodologies have not been examined with LMFs. We adapted the International Organization for Standardization (ISO) 15216-1:2017 method for virus recovery for use with chocolate, pistachios, and cornflakes. We also developed a magnetic bead assay for the recovery of HAV from LMFs and used the porcine gastric mucin–coated magnetic beads (PGM-MBs) to extract norovirus surrogates, feline calicivirus (FCV), and murine norovirus (MNV) from the same LMFs. The efficiency of virus recovery using the bead-based assay was then compared with that of the ISO 15216-1:2017 method. In chocolate and pistachios, the recovery rates with the PGM-MB method were 5.6- and 21.3-fold higher, respectively, for FCV and 1.65- and 18-fold higher, respectively, for MNV than those with the ISO 15216-1:2017 method. However, the PGM-MB method failed to recover MNV and FCV from cornflakes. The recovery rates for HAV in chocolate, pistachios, and corn flakes with the magnetic bead method were 11.5-, 3-, and 5.6-fold higher, respectively, than those with the ISO 15216-1:2017 method. Thus, depending upon the food matrix and the target virus, the bead-based assays can be used to efficiently and rapidly extract viruses from LMFs.

Benefits of cord blood transplantation include low rates of relapse and chronic graft-versus-host disease (GVHD). However, the use of cord blood is rapidly declining because of the high incidence of infections, severe acute GVHD, and transplant-related mortality. UM171, a haematopoietic stem cell self-renewal agonist, has been shown to expand cord blood stem cells and enhance multilineage blood cell reconstitution in mice. We aimed to investigate the safety and feasibility of single UM171-expanded cord blood transplantation in patients with haematological malignancies who do not have a suitable HLA-matched donor.

IMPORTANCE: Medicare hospice beneficiaries discontinue disease-modifying treatments because the hospice benefit limits access. While veterans have concurrent access to hospice care and Veterans Affairs (VA) Medical Center (VAMC)-provided treatments, the association of this with changes in treatment and costs of veterans’ end-of-life care is unknown. OBJECTIVE: To determine whether increasing availability of hospice care, without restrictions on disease-modifying treatments, is associated with reduced aggressive treatments and medical care costs at the end of life. DESIGN, SETTING, AND PARTICIPANTS: A modified difference-in-differences study design, using facility fixed effects, compared patient outcomes during years with relatively high vs lower hospice use. This study evaluated 13 085 veterans newly diagnosed with stage IV non–small cell lung cancer (NSCLC) from 113 VAMCs with a minimum of 5 veterans diagnosed with stage IV NSCLC per year, between 2006 and 2012. Data analyses were conducted between January 2017 and July 2018. EXPOSURES: Using VA inpatient, outpatient, pharmacy claims, and similar Medicare data, we created VAMC-level annual aggregates of all patients who died of cancer for hospice use, cancer treatment, and/or concurrent receipt of both in the last month of life, dividing all VAMC years into quintiles of exposure to hospice availability. MAIN OUTCOMES AND MEASURES: Receipt of aggressive treatments (2 or more hospital admissions within 30 days, tube feeding, mechanical ventilation, intensive care unit [ICU] admission) and total costs in the first 6 months after diagnosis. RESULTS: Of the 13 085 veterans included in the study, 12 858 (98%) were men; 10 531 (81%) were white, and 5949 (46%) were older than 65 years. Veterans with NSCLC treated in a VAMC in the top hospice quintile (79% hospice users), relative to the bottom quintile (55% hospice users), were more than twice as likely to have concurrent cancer treatment after initiating hospice care (adjusted odds ratio [AOR], 2.28; 95% CI, 1.67-3.31). Nonetheless, for veterans with NSCLC seen in VAMCs in the top hospice quintile, the AOR of receiving aggressive treatment in the 6 months after diagnosis was 0.66 (95% CI, 0.53-0.81), and the AOR of ICU use was 0.78 (95% CI, 0.62-0.99) relative to patients seen in VAMCs in the bottom hospice quintile. The 6-month costs were lower by an estimated $266 (95% CI, −$358 to −$164) per day for the high-quintile group vs the low-quintile group. There was no survival difference. CONCLUSIONS AND RELEVANCE: Increasing the availability of hospice care without restricting treatment access for veterans with advanced lung cancer was associated with less aggressive medical treatment and significantly lower costs while still providing cancer treatment.

Patients diagnosed with acute myeloid leukemia with complex karyotype (CK AML) have an adverse prognosis using current therapies, especially when accompanied by TP53 alterations. We hereby report the RNA-sequencing analysis of the 68 CK AML samples included in the Leucegene 415 patient cohort. We confirm the frequent occurrence of TP53 alterations in this subgroup and further characterize the allele expression profile and transcript alterations of this gene. We also document that the RAS pathway (N/KRAS, NF1, PTPN11, BRAF) is frequently altered in this disease. Targeted chemical interrogation of genetically characterized primary CK AML samples identifies polo-like kinase 1 (PLK1) inhibitors as the most selective agents for this disease subgroup. TP53 status did not alter sensitivity to PLK1 inhibitors. Interestingly, CK AML specimens display a G2/M transcriptomic signature that includes higher expression levels of PLK1 and correlates with PLK1 inhibition sensitivity. Together, our results highlight vulnerability in CK AML. In line with these in vitro data, volasertib shows a strong anti-AML activity in xenotransplantation mouse models of human adverse AML. Considering that PLK1 inhibitors are currently being investigated clinically in AML and myelodysplastic syndromes, our results provide a new rationale for PLK1-directed therapy in patients with adverse cytogenetic AML.

Patients diagnosed with acute myeloid leukemia with complex karyotype (CK AML) have an adverse prognosis using current therapies, especially when accompanied by TP53alterations. We hereby report the RNA-sequencing analysis of the 68 CK AML samples included in the Leucegene 415 patient cohort. We confirm the frequent occurrence of TP53alterations in this subgroup and further characterize the allele expression profile and transcript alterations of this gene. We also document that the RAS pathway (N/KRAS, NF1, PTPN11, BRAF) is frequently altered in this disease. Targeted chemical interrogation of genetically characterized primary CK AML samples identifies polo-like kinase 1 (PLK1) inhibitors as the most selective agents for this disease subgroup. TP53status did not alter sensitivity to PLK1 inhibitors. Interestingly, CK AML specimens display a G2/M transcriptomic signature that includes higher expression levels of PLK1and correlates with PLK1 inhibition sensitivity. Together, our results highlight vulnerability in CK AML. In line with these in vitro data, volasertib shows a strong anti-AML activity in xenotransplantation mouse models of human adverse AML. Considering that PLK1 inhibitors are currently being investigated clinically in AML and myelodysplastic syndromes, our results provide a new rationale for PLK1-directed therapy in patients with adverse cytogenetic AML.

Background:The impact of care delays and outcome among HF patients during the COVID-19 pandemic and role of virtual video or telephone visits has not been well studied. We studied changes in outpatient care patterns and associated mortality among HF patients during the pandemic.Methods:Retrospective analysis of HF patients using Veterans Affairs data, with exposure period 2/2020-9/2020 and outcome period 10/2020-4/2021. Veterans were diagnosed with HF prior to 2/2020 and had at least 1 cardiology/primary care visit in 2019. We compared volume/type of outpatient visit (in-person, virtual video, telephone, none) and yearly mortality rates 2 years before and 1 year after 2/2020. We related type of outpatient encounter to mortality during the outcome period. Hazard ratios and 95% confidence intervals were estimated using multivariable Cox-models adjusted for potential confounders.Results:290,789 Veterans with HF were included, with mean age 73 years, 96% male. Compared to the prior 2 years, in-person encounter days were lower (224.3/100 in 2018, 2019 vs 180.4/100 after 2/2020 P<0.01), while video encounter days increased (3.4/100 in 2018, 2019 vs 9.8/100 after 2/2020 P<0.01). Mortality rates were 12.7/1000 in 2018, 2019 and 12.9/1000 after 2/2020 P<0.01. Compared to those with no outpatient visits after 2/2020, mortality risk was lowest for Veterans with at least one in-person visit (HR 0.66, 95% CI 0.61-0.71), followed by video-only (HR 0.71, 95% CI 0.66-0.77) and lastly by telephone-only (HR 0.78, 95% CI 0.71-0.86) (Figure 1).Conclusions:During the COVID-19 pandemic, a decrease in outpatient visits and increase in mortality was seen among Veterans with HF compared to prior years. Veterans engaged in any outpatient care (evidenced by visits) had lower mortality compared to those with none. Patients with in-person visits had slightly lower mortality risk than those with virtual video only visits, whom had lower mortality risk than those with telephone-only visits.

The mechanisms underlying operational tolerance after hematopoietic stem cell transplantation in humans are poorly understood. We studied two independent cohorts of patients who underwent allogeneic hematopoietic stem cell transplantation from human leukocyte antigen–identical siblings. Primary tolerance was associated with long-lasting reshaping of the recipients’ immune system compared to their healthy donors with an increased proportion of regulatory T cell subsets and decreased T cell activation, proliferation, and migration. Transcriptomics profiles also identified a role for nicotinamide adenine dinucleotide biosynthesis in the regulation of immune cell functions. We then compared individuals with operational tolerance and nontolerant recipients at the phenotypic, transcriptomic, and metabolomic level. We observed alterations centered on CD38+-activated T and B cells in nontolerant patients. In tolerant patients, cell subsets with regulatory functions were prominent. RNA sequencing analyses highlighted modifications in the tolerant patients’ transcriptomic profiles, particularly with overexpression of the ectoenzyme NT5E(encoding CD73), which could counterbalance CD38 enzymatic functions by producing adenosine. Further, metabolomic analyses suggested a central role of androgens in establishing operational tolerance. These data were confirmed using an integrative approach to evaluating the immune landscape associated with operational tolerance. Thus, balance between a CD38-activated immune state and CD73-related production of adenosine may be a key regulator of operational tolerance.

The article presents information on the views of candidates to the city council in Vancouver, British Columbia on gay issues. David Cadman, Ellen Woodsworth, George Chow and Heather Deal all agree on the city proclamation of Davie Village as a gay neighborhood. They alsp presented their opinions on the prevention of the displacement of the community from the West End.

Current methods for detecting and genotyping noroviruses focus on the use of reverse transcriptase (RT)–mediated PCR. A major drawback of this approach is that short target RT-PCR products do not always encompass sequences that can be compared among research laboratories, resulting in difficulties for molecular epidemiology. We describe the use of a microarray-based system for simultaneous detection and molecular characterization of noroviruses. The protocol generates a 917-bp RT-PCR product that encompasses two major regions currently used for detection and analysis of norovirus genomes. The PCR products are then hybridized to an oligonucleotide array (NoroChip) based on 50-mer features, which allows for both confirmation of reaction specificity and molecular characterization of the amplified genome. Parallel sequence analyses of amplicons revealed that our microarray data were robust in separating genogroups I and II, and further subtyping to the cluster level was possible. This approach, combining detection and characterization, overcomes the need for expensive and time-consuming sequence analysis of amplified genome targets for molecular epidemiology.

Background: The aim of this study was to examine the metabolic risk profile in postmenopausal women characterized by either the metabolic syndrome (MS) as defined by the World Health Organization (WHO) or the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII).Methods: One hundred and eight postmenopausal women (56.9 ± 4.2 years; 28.5 ± 5.9 kg/m2) were examined. Each underwent an oral glucose tolerance test, an euglycemic-hyperinsulinemic clamp, an assessment of body fat distribution by computed tomography, a complete plasma lipid-lipoprotein profile, and standard measurements of inflammatory markers.Results: The prevalence of the MS-WHO was 29.6% in our women. Type 2 diabetes was found in 28.1% of women with the MS-WHO. Thirty-one percent of women had the MS-ATP, from which 36.4% had type 2 diabetes. Among the 32 women identified as having MS-WHO, 25 (78.1 %) were also identified as having the MS-ATP. On the other hand, among the 34 women identified as having MS-ATP, 24 (70.0 %) also had MS-WHO (kappa = 0.60). When we subdivided our sample of women as having either isolated MS-WHO, isolated MS-ATP, or combined MS-WHO and MS-ATP, we observed a more deteriorated metabolic risk profile (higher values for visceral adipose tissue, 2-h plasma glucose, and lower HDL-cholesterol concentrations) in women characterized by isolated MS-ATP compared to women with isolated MS-WHO.Conclusions: These results suggest that, in postmenopausal women, the concordance in the identification of subjects with the MS using each of the proposed definitions is only moderate.

The purpose of this study was to assess the contribution of the apolipoprotein E (apoE) polymorphism and factors, such as age and waist circumference, to variations in plasma low-density lipoprotein-cholesterol (LDL-C) response following ad libitum consumption of a diet rich in complex carbohydrates (high-CHO: 58% of energy as CHO) versus a diet rich in fat and monounsaturated fatty acids (high-MUFA: fat, 40% of energy and 22% as MUFA). Sixty-five men participated in this parallel 6- to 7-week study involving either a high-CHO or a high-MUFA diet. Fasting plasma lipid profile and anthropometry were determined at the beginning and at the end of the dietary period. The high-CHO and high-MUFA diets both induced significant (P< .01) and comparable reductions in body weight and waist circumference. These changes were associated with a significant (P< .01) and comparable decrease in LDL-C (−19% and −16%, respectively). Stepwise multiple regression analyses showed that 32% of the variation in the LDL-C response to the high-CHO diet was attributable to the apoE polymorphism (18.5%, P= .04) and waist circumference (13.5%, P= .03) indicating that men with a waist circumference greater than100 cm and the E2 allele had the greatest reduction in plasma LDL-C after the high-CHO diet. On the other hand, in the high-MUFA group, waist circumference was the only significant contributing factor to the LDL-C response and accounted for 44.5% of its variance. In conclusion, the plasma LDL-C response to ad libitum comsumption of a high-CHO and a high-MUFA diets are not modulated to the same extent by the apoE polymorphism and waist circumference.

Oncostatin M (OM) transforms the lymph node (LN) into a “super lymphoid organ” with 2 striking features: massive thymus-independent T-cell development and major expansion of the memory T-cell pool. We report that T-cell development in the LckOM LN is regulated by a cyclooxygenase-2 (COX-2)–dependent neoangiogenesis involving high endothelial venules (HEVs). That LN HEVs are particularlyrich in OM-receptor β-chain provides aplausible explanation for the fact that extrathymic T-cell development in LckOM mice is limited to the LN. Moreover, we found that increased production of the CCL20 chemokine by LN stromal cells was instrumental in the expansion of the memory phenotype CD4 T-cell pool in LckOM mice. The generality of the latter finding was demonstrated by the fact that CCL20/CCR6 interactions increase the basal proliferation rate of CD62Llo CD4 T cells irrespective of their thymic (in non–OM-transgenic mice) or extrathymic (in LckOM mice) origin. To our knowledge, CCL20 is the first molecule found to increase the proliferation of memory phenotype CD4 T cells. These findings identify potential targets for the creation of thymic substitutes (LN HEVs) and for expansion of the CD4 memory T-cell compartment (CCL20).

Oncostatin M (OM) transforms the lymph node (LN) into a “super lymphoid organ” with 2 striking features: massive thymus-independent T-cell development and major expansion of the memory T-cell pool. We report that T-cell development in the LckOM LN is regulated by a cyclooxygenase-2 (COX-2)–dependent neoangiogenesis involving high endothelial venules (HEVs). That LN HEVs are particularlyrich in OM-receptor β-chain provides aplausible explanation for the fact that extrathymic T-cell development in LckOM mice is limited to the LN. Moreover, we found that increased production of the CCL20 chemokine by LN stromal cells was instrumental in the expansion of the memory phenotype CD4 T-cell pool in LckOM mice. The generality of the latter finding was demonstrated by the fact that CCL20/CCR6 interactions increase the basal proliferation rate of CD62LloCD4 T cells irrespective of their thymic (in non–OM-transgenic mice) or extrathymic (in LckOM mice) origin. To our knowledge, CCL20 is the first molecule found to increase the proliferation of memory phenotype CD4 T cells. These findings identify potential targets for the creation of thymic substitutes (LN HEVs) and for expansion of the CD4 memory T-cell compartment (CCL20).

Objective: To examine the extent to which variations in body composition modulate changes in the lipid profile in response to the ad libitum consumption of a diet rich in carbohydrates (CHOs) (high‐CHO diet: 58% of energy as CHOs) or high in fat and in monounsaturated fatty acids (MUFAs) (high‐MUFA diet: 40% of energy as fat, 23% as MUFAs). Research Methods and Procedures: Sixty‐three men were randomly assigned to one of the two diets that they consumed for 6 to 7 weeks. Body composition and fasting plasma lipid levels were measured at the beginning and the end of the dietary intervention. Results: The high‐CHO and high‐MUFA diets induced significant and comparable reductions in body weight and waist circumference. These changes were accompanied by significant and comparable (p< 0.01) reductions in total plasma cholesterol and low‐density lipoprotein cholesterol levels. However, the high‐MUFA diet had more beneficial effects on plasma triglyceride concentrations (p< 0.01) and on plasma high‐density lipoprotein cholesterol levels (p= 0.02) compared with the high‐CHO diet. Diet‐induced changes in waist circumference were significantly associated with changes in low‐density lipoprotein cholesterol levels in the high‐CHO group (r= 0.39, p= 0.03) but not in the high‐MUFA group (r= 0.16, p= 0.38). Discussion: Improvements in plasma lipids induced by the ad libitum consumption of a high‐CHO diet seem to be partly mediated by changes in body weight, whereas lipid changes induced by the high‐MUFA diet seem to be independent of changes in body weight.

Conjugated linoleic acids (CLA) found in ruminant milk fat are a byproduct of incomplete biohydrogenation of lipids by ruminal bacteria. We examined the effect of different dietary fat supplements and processing methods on CLA. In trial 1, dietary supplements of Ca salts of fatty acids from canola oil, soybean oil, and linseed oil increased CLA content of milk fat by three-to fivefold over the control diet. Trials 2 and 3 examined the effect of processing methods for heat treatment of full fat soybeans. In trial 2, extrusion, micronizing, and roasting resulted in two- to threefold greater concentrations of CLA in milk fat than the control diet (raw ground soybeans). In trial 3, different temperatures of extrusion (120, 130, and 14°C) increased the CLA content of milk fat to a similar extent; CLA averaged 19.9 mg/g of fatty acids for the extrusion treatments compared with 4.2 mg/g of fatty acids for the control diet (raw ground soybeans). Fish oil (200 and 400 ml/d) was examined in trial 4 and both levels resulted in CLA concentrations in milk fat that were about threefold greater than the control diet. In trial 5, grain and silage from a high oil corn hybrid increased the CLA content of milk fat; however, responses were modest with the CLA concentration (mg/g of fatty acids) averaging 4.6 and 2.8 for diets with high oil hybrid and normal hybrid, respectively. Similarly, dietary supplements of animal fat byproducts (tallow plus yellow grease; trial 6) resulted in modest increases in the CLA content of milk fat. Overall, several dietary manipulations involving lipid sources and processing methods were identified that allow for a marked increase in the conjugated linoleic acid content of milk fat.

This article studies palatalization gestures in the production of /t/ and /d/ in standard Belgium French through the use of electropalatography. The articulatory results are compared with an acoustic study of the affricated realization of these consonants when followed by /i/, /y/, /j/, and /[inverted h]/ in Quebec French (Bento, 1993). The study examines regional and individual differences in palatalization gestures to show how affrication can be ascribed to palatalization. Results are analyzed with regard to temporal, articulatory (electropalatography), and voicing aspects to compare production strategies across French variants, speakers, and phonetic contexts. The aim is to understand coordination processes, which are explained in terms of biomechanical constraints resulting from the coordination of adjacent gestures. These processes are used to show how palatalization traces in a variant with no recognized affrication (Belgium French) are similar in nature to the affrication in Quebec French, because palatalization is due to the coarticulation of the stop with a following high front vowel or a palatal approximant. Results are also compared with diachronic data to propose explanations for some patterns in the development from Latin to French.

Protozoan parasites in food or water samples are generally detected using microscopy or PCR followed by Sanger sequencing. However, microscopy is subjective, requires a high degree of expertise and has limited sensitivity, while DNA sequencing requires expensive and specialized equipment and facilities. This study describes a cloth-based hybridization array system (CHAS) that is an alternative to Sanger sequencing to confirm PCR-positive samples. CHAS is an inexpensive, rapid and reliable method for the simultaneous detection of multiple protozoan parasite species based on the colorimetric detection of PCR amplicons on a polyester cloth. PCR primers and CHAS hybridization probes were developed to detect the protozoan parasites Giardia duodenalis, Cryptosporidiumspp. and Toxoplasma gondii. In addition, CHAS probes were designed for the differentiation of G. duodenalisAssemblages A and B. In artificially contaminated fresh produce (lettuce, parsley) and water samples (river water, wastewater), this CHAS assay allowed for the successful detection of G. duodenalis, Cryptosporidiumspp., and T. gondii. The present study demonstrates that the CHAS detection method is a simple and inexpensive alternative to DNA sequencing for the confirmation of PCR-positive results in laboratories testing for parasites in food or water samples. This assay may also be beneficial in developing countries, where DNA sequencing facilities may not be readily available.