Rapid and efficient stable gene transfer to mesenchymal stromal cells using a modified foamy virus vector

Mesenchymal stromal cells (MSCs) hold great promise for regenerative medicine. Stable ex vivo gene transfer to MSCs could improve the outcome and scope of MSC therapy, but current vectors require multiple rounds of transduction, involve genotoxic viral promoters and/or the addition of cytotoxic cationic polymers in order to achieve efficient transduction. We describe a self-inactivating foamy virus vector (FVV), incorporating the simian macaque foamy virus envelope and using physiological promoters, which efficiently transduces murine MSCs (mMSCs) in a single-round. High and sustained expression of the transgene, whether GFP or the lysosomal enzyme, arylsulphatase A (ARSA), was achieved. Defining MSC characteristics (surface marker expression and differentiation potential), as well as long-term engraftment and distribution in the murine brain following intracerebroventricular delivery, are unaffected by FVV transduction. Similarly, greater than 95% of human MSCs (hMSCs) were stably transduced using the same vector, facilitating human application. This work describes the best stable gene transfer vector available for mMSCs and hMSCs

PCR clonality detection in Hodgkin lymphoma

B-cell clonality detection in whole tissue is considered indicative of B-cell non-Hodgkin lymphoma (NHL). We tested frozen tissue of 24 classical Hodgkin lymphomas (cHL) with a varying tumor cell load with the multiplex polymerase chain reaction (PCR) primer sets for IGH and IGK gene rearrangement (BIOMED-2). A clonal population was found in 13 cases with the IGH FR1 and/or FR2/FR3 PCRs. Using the IGK-VJ and IGK-DE PCRs, an additional six cases had a dominant clonal cell population, resulting in a detection rate of 79% in frozen tissue. Of 12 cases, also the formalin-fixed and paraffin-embedded (FFPE) tissue was tested. Surprisingly, in eight of the 12 FFPE cases with acceptable DNA quality (allowing PCR amplification of >200 nt fragments), the IGK multiplex PCRs performed better in detecting clonality (six out of eight clonal IGK rearrangements) than the IGH PCRs (four out of nine clonal rearrangements), despite a rather large amplicon size. There was no evidence of B-cell lymphoma during follow-up of 1 to 6 years and no correlation was found between the presence of a clonal result and Epstein–Barr virus in the tumor cells. Our results indicate that the present routine PCR methods are sensitive enough to detect small numbers of malignant cells in cHL. Therefore, the presence of a clonal B-cell population does not differentiate between cHL and NHL

Bayesian Based Comment Spam Defending Tool

Spam messes up user's inbox, consumes network resources and spread worms and viruses. Spam is flooding of unsolicited, unwanted e mail. Spam in blogs is called blog spam or comment spam.It is done by posting comments or flooding spams to the services such as blogs, forums,news,email archives and guestbooks. Blog spams generally appears on guestbooks or comment pages where spammers fill a comment box with spam words. In addition to wasting user's time with unwanted comments, spam also consumes a lot of bandwidth. In this paper, we propose a software tool to prevent such blog spams by using Bayesian Algorithm based technique. It is derived from Bayes' Theorem. It gives an output which has a probability that any comment is spam, given that it has certain words in it. With using our past entries and a comment entry, this value is obtained and compared with a threshold value to find if it exceeds the threshold value or not. By using this concept, we developed a software tool to block comment spam. The experimental results show that the Bayesian based tool is working well. This paper has the major findings and their significance of blog spam filter.Comment: 14 Pages,4 Figures, International Journal of Network Security & Its Applications (IJNSA), Vol.2, No.4, October 201

The Red Sea, Coastal Landscapes, and Hominin Dispersals

This chapter provides a critical assessment of environment, landscape and resources in the Red Sea region over the past five million years in relation to archaeological evidence of hominin settlement, and of current hypotheses about the role of the region as a pathway or obstacle to population dispersals between Africa and Asia and the possible significance of coastal colonization. The discussion assesses the impact of factors such as topography and the distribution of resources on land and on the seacoast, taking account of geographical variation and changes in geology, sea levels and palaeoclimate. The merits of northern and southern routes of movement at either end of the Red Sea are compared. All the evidence indicates that there has been no land connection at the southern end since the beginning of the Pliocene period, but that short sea crossings would have been possible at lowest sea-level stands with little or no technical aids. More important than the possibilities of crossing the southern channel is the nature of the resources available in the adjacent coastal zones. There were many climatic episodes wetter than today, and during these periods water draining from the Arabian escarpment provided productive conditions for large mammals and human populations in coastal regions and eastwards into the desert. During drier episodes the coastal region would have provided important refugia both in upland areas and on the emerged shelves exposed by lowered sea level, especially in the southern sector and on both sides of the Red Sea. Marine resources may have offered an added advantage in coastal areas, but evidence for their exploitation is very limited, and their role has been over-exaggerated in hypotheses of coastal colonization

Socioeconomic status and prostate cancer incidence and mortality rates among the diverse population of California

The racial/ethnic disparities in prostate cancer rates are well documented, with the highest incidence and mortality rates observed among African-Americans followed by non-Hispanic Whites, Hispanics, and Asian/Pacific Islanders. Whether socioeconomic status (SES) can account for these differences in risk has been investigated in previous studies, but with conflicting results. Furthermore, previous studies have focused primarily on the differences between African-Americans and non-Hispanic Whites, and little is known for Hispanics and Asian/Pacific Islanders. To further investigate the relationship between SES and prostate cancer among African-Americans, non-Hispanic Whites, Hispanics, and Asian/Pacific Islanders, we conducted a large population-based cross-sectional study of 98,484 incident prostate cancer cases and 8,997 prostate cancer deaths from California. Data were abstracted from the California Cancer Registry, a population-based surveillance, epidemiology, and end results (SEER) registry. Each prostate cancer case and death was assigned a multidimensional neighborhood-SES index using the 2000 US Census data. SES quintile-specific prostate cancer incidence and mortality rates and rate ratios were estimated using SEER*Stat for each race/ethnicity categorized into 10-year age groups. For prostate cancer incidence, we observed higher levels of SES to be significantly associated with increased risk of disease [SES Q1 vs. Q5: relative risk (RR) = 1.28; 95% confidence interval (CI): 1.25–1.30]. Among younger men (45–64 years), African-Americans had the highest incidence rates followed by non-Hispanic Whites, Hispanics, and Asian/Pacific Islanders for all SES levels. Yet, among older men (75–84 years) Hispanics, following African-Americans, displayed the second highest incidence rates of prostate cancer. For prostate cancer deaths, higher levels of SES were associated with lower mortality rates of prostate cancer deaths (SES Q1 vs. Q5: RR = 0.88; 95% CI: 0.92–0.94). African-Americans had a twofold to fivefold increased risk of prostate cancer deaths in comparison to non-Hispanic Whites across all levels of SES. Our findings suggest that SES alone cannot account for the greater burden of prostate cancer among African-American men. In addition, incidence and mortality rates of prostate cancer display different age and racial/ethnic patterns across gradients of SES

The Sound of Interconnectivity; The European Vasculitis Society 2022 Report

The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer -term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among bio-markers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale

Mental health: A cause or consequence of injury? A population-based matched cohort study

BACKGROUND: While a number of studies report high prevalence of mental health problems among injured people, the temporal relationship between injury and mental health service use has not been established. This study aimed to quantify this relationship using 10 years of follow-up on a population-based cohort of hospitalised injured adults. METHODS: The Manitoba Injury Outcome Study is a retrospective population-based matched cohort study that utilised linked administrative data from Manitoba, Canada, to identify an inception cohort (1988–1991) of hospitalised injured cases (ICD-9-CM 800–995) aged 18–64 years (n = 21,032), which was matched to a non-injured population-based comparison group (n = 21,032). Pre-injury comorbidity and post-injury mental health data were obtained from hospital and physician claims records. Negative Binomial regression was used to estimate adjusted rate ratios (RRs) to measure associations between injury and mental health service use. RESULTS: Statistically significant differences in the rates of mental health service use were observed between the injured and non-injured, for the pre-injury year and every year of the follow-up period. The injured cohort had 6.56 times the rate of post-injury mental health hospitalisations (95% CI 5.87, 7.34) and 2.65 times the rate of post-injury mental health physician claims (95% CI 2.53, 2.77). Adjusting for comorbidities and pre-existing mental health service use reduced the hospitalisations RR to 3.24 (95% CI 2.92, 3.60) and the physician claims RR to 1.53 (95% CI 1.47, 1.59). CONCLUSION: These findings indicate the presence of pre-existing mental health conditions is a potential confounder when investigating injury as a risk factor for subsequent mental health problems. Collaboration with mental health professionals is important for injury prevention and care, with ongoing mental health support being a clearly indicated service need by injured people and their families. Public health policy relating to injury prevention and control needs to consider mental health strategies at the primary, secondary and tertiary level

Interventions aimed at improving the nursing work environment: a systematic review

<p>Abstract</p> <p>Background</p> <p>Nursing work environments (NWEs) in Canada and other Western countries have increasingly received attention following years of restructuring and reported high workloads, high absenteeism, and shortages of nursing staff. Despite numerous efforts to improve NWEs, little is known about the effectiveness of interventions to improve NWEs. The aim of this study was to review systematically the scientific literature on implemented interventions aimed at improving the NWE and their effectiveness.</p> <p>Methods</p> <p>An online search of the databases CINAHL, Medline, Scopus, ABI, Academic Search Complete, HEALTHstar, ERIC, Psychinfo, and Embase, and a manual search of Emerald and Longwoods was conducted. (Quasi-) experimental studies with pre/post measures of interventions aimed at improving the NWE, study populations of nurses, and quantitative outcome measures of the nursing work environment were required for inclusion. Each study was assessed for methodological strength using a quality assessment and validity tool for intervention studies. A taxonomy of NWE characteristics was developed that would allow us to identify on which part of the NWE an intervention targeted for improvement, after which the effects of the interventions were examined.</p> <p>Results</p> <p>Over 9,000 titles and abstracts were screened. Eleven controlled intervention studies met the inclusion criteria, of which eight used a quasi-experimental design and three an experimental design. In total, nine different interventions were reported in the included studies. The most effective interventions at improving the NWE were: primary nursing (two studies), the educational toolbox (one study), the individualized care and clinical supervision (one study), and the violence prevention intervention (one study).</p> <p>Conclusions</p> <p>Little is known about the effectiveness of interventions aimed at improving the NWE, and published studies on this topic show weaknesses in their design. To advance the field, we recommend that investigators use controlled studies with pre/post measures to evaluate interventions that are aimed at improving the NWE. Thereby, more evidence-based knowledge about the implementation of interventions will become available for healthcare leaders to use in rebuilding nursing work environments.</p