Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age

Background: Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stem cells (MSCs) are used increasingly for autologous cell therapy in equine practice to treat musculoskeletal and other injuries. Current recommendations often call for 10–100 million MSCs per treatment, necessitating the expansion of primary cells in culture prior to therapeutic use. Of concern, human and rodent studies have shown a decline of both MSC recovery from sampled tissue and in vitro proliferative capacity with increasing donor age. This may be problematic for applications of autologous cell-based therapies in the important equine demographic of older patients. Objectives: To investigate the effect of donor age on the cellular proliferation of equine BM- and AT-MSCs. Study Design: In vitro study. Methods: BM- and AT-MSCs and dermal fibroblasts (biological control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15–17 months), adult (5–8 years), middle-aged (12–18 years), and geriatric (≥ 22 years). Proliferation of the cells was tested using an EdU incorporation assay and steady state mRNA levels measured for targeted proliferation, aging, and senescence biomarkers. Results: The cellular proliferation of equine BM- and AT-MSCs declined significantly in the geriatric cohort relative to the younger age groups. Proliferation levels in the two MSC types were equally affected by donor age. Analysis of steady state mRNA levels showed an up-regulation in tumor suppressors, apoptotic genes, and multiple growth factors in MSCs from old horses, and a down-regulation of some pro-cycling genes with a few differences between cell types. Main Limitations: Potential age-dependent differences in cell function parameters relevant to cell-therapy application were not investigated. Conclusions: The cellular proliferation of equine BM- and AT-MSCs declined at advanced donor ages. High levels of in vitro proliferation were observed in both MSC types from horses in the age groups below 18 years of age

Mood instability, mental illness and suicidal ideas : results from a household survey

Purpose: There is weak and inconsistent evidence that mood instability (MI) is associated with depression, post traumatic stress disorder (PTSD) and suicidality although the basis of this is unclear. Our objectives were first to test whether there is an association between depression and PTSD, and MI and secondly whether MI exerts an independent effect on suicidal thinking over and above that explained by common mental disorders. Methods: We used data from the Adult Psychiatric Morbidity Survey 2007 (N = 7,131). Chi-square tests were used to examine associations between depression and PTSD, and MI, followed by regression modelling to examine associations between MI and depression, and with PTSD. Multiple logistic regression analyses were used to assess the independent effect of MI on suicidal thinking, after adjustment for demographic factors and the effects of common mental disorder diagnoses. Results: There are high rates of MI in depression and PTSD and the presence of MI increases the odds of depression by 10.66 [95 % confidence interval (CI) 7.51–15.13] and PTSD by 8.69 (95 % CI 5.90–12.79), respectively, after adjusting for other factors. Mood instability independently explained suicidal thinking, multiplying the odds by nearly five (odds ratio 4.82; 95 % CI 3.39–6.85), and was individually by some way the most important single factor in explaining suicidal thoughts. Conclusions: MI is strongly associated with depression and PTSD. In people with common mental disorders MI is clinically significant as it acts as an additional factor exacerbating the risk of suicidal thinking. It is important to enquire about MI as part of clinical assessment and treatment studies are required

Factors affecting the use of biosecurity measures for the protection of ruminant livestock and farm workers against infectious diseases in central South Africa

Biosecurity measures have been introduced to limit economic losses and zoonotic exposures to humans by preventing and controlling animal diseases. However, they are implemented on individual farms with varying frequency. The goal of this study was to evaluate which biosecurity measures were used by farmers to prevent infectious diseases in ruminant livestock and to identify factors that influenced these decisions. We conducted a survey in 264 ruminant livestock farmers in a 40,000 km2 area in the Free State and Northern Cape provinces of South Africa. We used descriptive statistics, to characterize biosecurity measures and farm attributes, then multivariable binomial regression to assess the strength of the association between the attributes and the implementation of biosecurity measures including property fencing, separate equipment use on different species, separate rearing of species, isolation of sick animals, isolation of pregnant animals, quarantine of new animals, animal transport cleaning, vaccination, tick control and insect control. Ninety-nine percent of farmers reported using at least one of the 10 biosecurity measures investigated (median [M]: 6; range: 0–10). The most frequently used biosecurity measures were tick control (81%, 214 out of 264), vaccination (80%, 211 out of 264) and isolation of sick animals (72%, 190 out of 264). More biosecurity measures were used on farms with 65–282 animals (M: 6; odds ratio [OR]: 1.52) or farms with 283–12,030 animals (M: 7; OR: 1.87) than on farms with fewer than 65 animals (M: 4). Furthermore, farmers who kept two animal species (M: 7; OR: 1.41) or three or more species (M: 7) used more biosecurity measures than single-species operations (M: 4). Farmers with privately owned land used more biosecurity measures (M: 6; OR: 1.51) than those grazing their animals on communal land (M: 3.5). Farms that reported previous Rift Valley fever (RVF) outbreaks used more biosecurity measures (M: 7; OR: 1.25) compared with farms without RVF reports (M: 6) and those that purchased animals in the 12 months prior to the survey (M: 7; OR: 1.19) compared with those that did not (M: 6). When introducing new animals into their herds (n = 122), most farmers used fewer biosecurity measures than they did for their existing herd: 34% (41 out of 122) used multiple biosecurity measures like those of vaccination, tick control, quarantine or antibiotic use, whereas 36% (44 out of 122) used only one and 30% (37 out of 122) used none. Certain farm features, primarily those related to size and commercialization, were associated with more frequent use of biosecurity measures. Given the variation in the application of biosecurity measures, more awareness and technical assistance are needed to support the implementation of a biosecurity management plan appropriate for the type of farm operation and available resources.DATA AVAILABILITY STATEMENT : The data that support the study's findings and that can be disclosed per IRB protocol are available upon request from EcoHealth Alliance, 520 Eighth Ave Ste 1200, New York, NY 10018, from Melinda K. Rostal ([email protected]).The project depicted is sponsored by the U.S. Department of Defense, Defense Threat Reduction Agency.http://wileyonlinelibrary.com/journal/tbedhj2022Production Animal Studie

β-Lactam Resistance Response Triggered by Inactivation of a Nonessential Penicillin-Binding Protein

It has long been recognized that the modification of penicillin-binding proteins (PBPs) to reduce their affinity for β-lactams is an important mechanism (target modification) by which Gram-positive cocci acquire antibiotic resistance. Among Gram-negative rods (GNR), however, this mechanism has been considered unusual, and restricted to clinically irrelevant laboratory mutants for most species. Using as a model Pseudomonas aeruginosa, high up on the list of pathogens causing life-threatening infections in hospitalized patients worldwide, we show that PBPs may also play a major role in β-lactam resistance in GNR, but through a totally distinct mechanism. Through a detailed genetic investigation, including whole-genome analysis approaches, we demonstrate that high-level (clinical) β-lactam resistance in vitro, in vivo, and in the clinical setting is driven by the inactivation of the dacB-encoded nonessential PBP4, which behaves as a trap target for β-lactams. The inactivation of this PBP is shown to determine a highly efficient and complex β-lactam resistance response, triggering overproduction of the chromosomal β-lactamase AmpC and the specific activation of the CreBC (BlrAB) two-component regulator, which in turn plays a major role in resistance. These findings are a major step forward in our understanding of β-lactam resistance biology, and, more importantly, they open up new perspectives on potential antibiotic targets for the treatment of infectious diseases

Prevalence of self-reported finger deformations and occupational risk factors among professional cooks: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Previous studies have pointed out that the school lunch workers in Japan are suffering from work-related disorders including finger deformations. The purpose of this study was to investigate the prevalence of self-reported finger deformations and the association with job-related risk factors.</p> <p>Methods</p> <p>A cross-sectional questionnaire study of 5,719 subjects (response rate: 81%, 982 men and 4,737 women) was undertaken during September 2003 to February 2004.</p> <p>Results</p> <p>Finger deformations were found among 11.7% of the men and 35.6% of the women studied, with significant differences among sex, age and sex-age groups. For both men and women the pattern of finger deformations across the hand was similar for the right and the left hand. For women, the deformations were found in about 10% of the distal interphalangeal joints of all fingers. Based on multiple logistic regression analyses, the factors female sex, age, the number of cooked lunches per cook and cooking activities were independently associated with the prevalence of finger deformations. High prevalence odds ratios were found for those frequently carrying or using tools by hands such as delivering containers, distributing meals, preparing dishes, washing equipment, cutting and stirring foods.</p> <p>Conclusions</p> <p>Among the school lunch workers studied, women had a higher prevalence of finger deformations on all joints of both hands. Various cooking tasks were associated with the prevalence of finger deformations. The results suggest that improvements in working conditions are important for preventing work-related disorders such as finger deformations.</p

Identification and HLA-Tetramer-Validation of Human CD4(+) and CD8(+) T Cell Responses against HCMV Proteins IE1 and IE2

Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy