Pressure Thresholds and Stiffness on the Plantar Surface of the Human Foot

The objective was to develop a methodology to assess Pressure Discomfort Thresholds (PDT), Pressure Pain Thresholds (PPT), and tissue stiffness on the plantar surface of the foot. Ten male and ten female participants volunteered for the study. Foot landmarks were used to create a standardized grid-type template of 95 points. For each test point, PPT and PDT values were obtained, and stiffness was calculated for each of the twenty participants. Cluster analyses were performed to determine the regions of similarity for the three dependent variables, PPT, PDT and stiffness. Moran’s-I-index was used to determine the spatial auto correlations. The use of k-means clustering showed five distinct clusters while the three dependent variables showed strong correlations to each other. Morisita’s similarity index was used to check the similarity of the grid among all participants. Both male and female participants showed a Morisita’s index greater than 0.7 confirming the reliability of the foot template

Lipoxygenase in wheat: Genetic control and impact on stability of lutein and lutein esters

Published: 20 May 2021Preservation of lutein concentrations in wheat-based end-products during processing is important both for product quality and nutritional value. A key constituent involved in lutein degradation is endogenous lipoxygenase. Lutein and lutein ester concentrations were compared at intervals during storage of noodle sheets prepared from flour of wheat varieties representing a range in lipoxygenase activity, as well as in different mill streams and in different grain tissues. Higher lipoxygenase concentration was associated with an increased loss of free lutein and lutein mono-esters whereas lutein diesters appeared to be more resistant to degradation. Lutein degradation was reduced in the presence of a lipoxygenase inhibitor, when noodle sheets were heated to destroy enzyme activity or when pH was increased. In addition, three populations were used to investigate the genetic control of lipoxygenase. A previously reported mutation of Lpx-B1.1 was associated with a reduction in activity from high to intermediate whilst a new locus on chromosome 4D was associated with variation between intermediate and near-zero. The gene underlying the 4D locus is a putative lipoxygenase. Stability of lutein could be improved by deployment of the mutations at the 4B and 4D loci and/or by post-harvest storage of grain under conditions that promote esterification.Daryl J. Mares, Judy Cheong, Shashi N. Goonetilleke and Diane E. Mathe

Prevalence and occurrence of zoonotic bacterial pathogens in surface waters determined by quantitative PCR

The prevalence and concentrations of Campylobacter jejuni, Salmonella spp. and enterohaemorrhagic E. coli (EHEC) were investigated in surface waters in Brisbane, Australia using quantitative PCR (qPCR) based methodologies. Water samples were collected from Brisbane City Botanic Gardens (CBG) Pond, and two urban tidal creeks (i.e., Oxley Creek and Blunder Creek). Of the 32 water samples collected, 8 (25%), 1 (3%), 9 (28%), 14 (44%), and 15 (47%) were positive for C. jejuni mapA, Salmonella invA, EHEC O157 LPS, EHEC VT1, and EHEC VT2 genes, respectively. The presence/absence of the potential pathogens did not correlate with either E. coli or enterococci concentrations as determined by binary logistic regression. In conclusion, the high prevalence, and concentrations of potential zoonotic pathogens along with the concentrations of one or more fecal indicators in surface water samples indicate a poor level of microbial quality of surface water, and could represent a significant health risk to users. The results from the current study would provide valuable information to the water quality managers in terms of minimizing the risk from pathogens in surface waters

Cohort Profile: The Flu Watch Study

Influenza is a common, highly contagious respiratory virus which infects all age groups, causing a range of outcomes from asymptomatic infection and mild respiratory disease to severe respiratory disease and death.1 If infected, the adaptive immune system produces a humoral (antibody) and cell-mediated (T cell) immune response to fight the infection.2 Influenza viruses continually evolve through antigenic drift, resulting in slightly different ‘seasonal’ influenza strains circulating each year. Population-level antibody immunity to these seasonal viruses builds up over time, so in any given season only a proportion of the population is susceptible to the circulating strains. Occasionally, influenza A viruses evolve rapidly through antigenic shift by swapping genes with influenza viruses usually circulating in animals. This process creates an immunologically distinct virus to which the population may have little to no antibody immunity. The virus can result in a pandemic if a large portion of the population is susceptible and the virus is easily spread

MVA.85A Boosting of BCG and an Attenuated, phoP Deficient M. tuberculosis Vaccine Both Show Protective Efficacy Against Tuberculosis in Rhesus Macaques

BACKGROUND: Continuous high global tuberculosis (TB) mortality rates and variable vaccine efficacy of Mycobacterium bovis Bacille Calmette-Guérin (BCG) motivate the search for better vaccine regimes. Relevant models are required to downselect the most promising vaccines entering clinical efficacy testing and to identify correlates of protection. METHODS AND FINDINGS: Here, we evaluated immunogenicity and protection against Mycobacterium tuberculosis in rhesus monkeys with two novel strategies: BCG boosted by modified vaccinia virus Ankara expressing antigen 85A (MVA.85A), and attenuated M. tuberculosis with a disrupted phoP gene (SO2) as a single-dose vaccine. Both strategies were well tolerated, and immunogenic as evidenced by induction of specific IFNgamma responses. Antigen 85A-specific IFNgamma secretion was specifically increased by MVA.85A boosting. Importantly, both MVA.85A and SO2 treatment significantly reduced pathology and chest X-ray scores upon infectious challenge with M. tuberculosis Erdman strain. MVA.85A and SO2 treatment also showed reduced average lung bacterial counts (1.0 and 1.2 log respectively, compared with 0.4 log for BCG) and significant protective effect by reduction in C-reactive protein levels, body weight loss, and decrease of erythrocyte-associated hematologic parameters (MCV, MCH, Hb, Ht) as markers of inflammatory infection, all relative to non-vaccinated controls. Lymphocyte stimulation revealed Ag85A-induced IFNgamma levels post-infection as the strongest immunocorrelate for protection (spearman's rho: -0.60). CONCLUSIONS: Both the BCG/MVA.85A prime-boost regime and the novel live attenuated, phoP deficient TB vaccine candidate SO2 showed significant protective efficacy by various parameters in rhesus macaques. Considering the phylogenetic relationship between macaque and man and the similarity in manifestations of TB disease, these data support further development of these primary and combination TB vaccine candidates

Curing HIV: Seeking to Target and Clear Persistent Infection

Margolis and colleagues review progress and prospects toward developing a true cure for HIV-1 infection, focusing on the biological underpinnings of the “kick and kill” approach to curing HIV-1 infection, which couples reactivation of the latent, integrated provirus with immunotherapies to recognize and kill infected cells. © 2020 Elsevier Inc.Human immunodeficiency virus type 1 (HIV-1) infection persists despite years of antiretroviral therapy (ART). To remove the stigma and burden of chronic infection, approaches to eradicate or cure HIV infection are desired. Attempts to augment ART with therapies that reverse viral latency, paired with immunotherapies to clear infection, have advanced into the clinic, but the field is still in its infancy. We review foundational studies and highlight new insights in HIV cure research. Together with advances in ART delivery and HIV prevention strategies, future therapies that clear HIV infection may relieve society of the affliction of the HIV pandemic

Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer Detection

BACKGROUND: To discover novel markers for improving the efficacy of pancreatic cancer (PC) diagnosis, the secretome of two PC cell lines (BxPC-3 and MIA PaCa-2) was profiled. UL16 binding protein 2 (ULBP2), one of the proteins identified in the PC cell secretome, was selected for evaluation as a biomarker for PC detection because its mRNA level was also found to be significantly elevated in PC tissues. METHODS: ULBP2 expression in PC tissues from 67 patients was studied by immunohistochemistry. ULBP2 serum levels in 154 PC patients and 142 healthy controls were measured by bead-based immunoassay, and the efficacy of serum ULBP2 for PC detection was compared with the widely used serological PC marker carbohydrate antigen 19-9 (CA 19-9). RESULTS: Immunohistochemical analyses revealed an elevated expression of ULPB2 in PC tissues compared with adjacent non-cancerous tissues. Meanwhile, the serum levels of ULBP2 among all PC patients (n = 154) and in early-stage cancer patients were significantly higher than those in healthy controls (p<0.0001). The combination of ULBP2 and CA 19-9 outperformed each marker alone in distinguishing PC patients from healthy individuals. Importantly, an analysis of the area under receiver operating characteristic curves showed that ULBP2 was superior to CA 19-9 in discriminating patients with early-stage PC from healthy controls. CONCLUSIONS: Collectively, our results indicate that ULBP2 may represent a novel and useful serum biomarker for pancreatic cancer primary screening

Dual Neonate Vaccine Platform against HIV-1 and M. tuberculosis

Acquired immunodeficiency syndrome and tuberculosis (TB) are two of the world's most devastating diseases. The first vaccine the majority of infants born in Africa receive is Mycobacterium bovis bacillus Calmette-Guérin (BCG) as a prevention against TB. BCG protects against disseminated disease in the first 10 years of life, but provides a variable protection against pulmonary TB and enhancing boost delivered by recombinant modified vaccinia virus Ankara (rMVA) expressing antigen 85A (Ag85A) of M. tuberculosis is currently in phase IIb evaluation in African neonates. If the newborn's mother is positive for human immunodeficiency virus type 1 (HIV-1), the baby is at high risk of acquiring HIV-1 through breastfeeding. We suggested that a vaccination consisting of recombinant BCG expressing HIV-1 immunogen administered at birth followed by a boost with rMVA sharing the same immunogen could serve as a strategy for prevention of mother-to-child transmission of HIV-1 and rMVA expressing an African HIV-1-derived immunogen HIVA is currently in phase I trials in African neonates. Here, we aim to develop a dual neonate vaccine platform against HIV-1 and TB consisting of BCG.HIVA administered at birth followed by a boost with MVA.HIVA.85A. Thus, mMVA.HIVA.85A and sMVA.HIVA.85A vaccines were constructed, in which the transgene transcription is driven by either modified H5 or short synthetic promoters, respectively, and tested for immunogenicity alone and in combination with BCG.HIVA222. mMVA.HIVA.85A was produced markerless and thus suitable for clinical manufacture. While sMVA.HIVA.85A expressed higher levels of the immunogens, it was less immunogenic than mMVA.HIVA.85A in BALB/c mice. A BCG.HIVA222–mMVA.HIVA.85A prime-boost regimen induced robust T cell responses to both HIV-1 and M. tuberculosis. Therefore, proof-of-principle for a dual anti-HIV-1/M. tuberculosis infant vaccine platform is established. Induction of immune responses against these pathogens soon after birth is highly desirable and may provide a basis for lifetime protection maintained by boosts later in life

Implications of CTL-Mediated Killing of HIV-Infected Cells during the Non-Productive Stage of Infection

Patients infected with HIV exhibit orders of magnitude differences in their set-point levels of the plasma viral load. As to what extent this variation is due to differences in the efficacy of the cytotoxic T lymphocyte (CTL) response in these patients is unclear. Several studies have shown that HIV-infected CD4+ T cells also present viral epitopes that are recognized by CTLs before the productive stage of infection, i.e., during the intracellular eclipse phase before the infected cell starts to produce new viral particles. Here, we use mathematical modeling to investigate the potential impact of early killing of HIV-infected cells on viral replication. We suggest that the majority of CTL-mediated killing could occur during the viral eclipse phase, and that the killing of virus-producing cells could be substantially lower at later stages due to MHC-I-down-regulation. Such a mechanism is in agreement with several experimental observations that include CD8+ T cell depletion and antiretroviral drug treatment. This indicates a potentially important role of CTL-mediated killing during the non-productive stage of HIV-infected cells