Understanding Human Astrovirus from Pathogenesis to Treatment

While human astroviruses (HAstV) were discovered nearly 45 years ago, these small positive-sense RNA viruses remain critically understudied. These studies provide fundamental new research on astrovirus pathogenesis and disruption of the gut epithelium by induction of epithelial-mesenchymal transition (EMT) following astrovirus infection. Here we characterize HAstV-induced EMT as an upregulation of SNAI1 and VIM with a down regulation of CDH1 and OCLN, loss of cell-cell junctions most notably at 18 hours post-infection (hpi), and loss of cellular polarity by 24 hpi. While active transforming growth factor- (TGF-) increases during HAstV infection, inhibition of TGF- signaling does not hinder EMT induction. However, HAstV-induced EMT does require active viral replication. These are among the first studies describing the induction of EMT by a non-oncogenic virus and provides an exciting opportunity to understand EMT induction independent of cancer. Our findings likely extend beyond astrovirus to other viruses and may shed light on novel ways pathogens can circumvent the barriers meant to protect against them. Crossing these barriers can lead to systemic and even fatal infections. Astroviruses can be especially problematic in immunocompromised individuals and infants where the virus has been associated with necrotizing enterocolitis, severe and persistent diarrhea, and even encephalitis and meningitis. Using our novel tools and models, we demonstrate that the FDA-approved broad-spectrum anti-infective drug nitazoxanide (NTZ) blocks astrovirus replication in vitro with a 50% effective concentration (EC50) of approximately 1.47μM. It can be administered up to 8 hours post-infection and is effective against multiple human astrovirus serotypes including clinical isolates. Most importantly, NTZ reduces viral shed in vivo, exhibiting its potential as a future clinical therapeutic. Overall, these studies will further our understanding of astrovirus pathogenesis leading to the development of therapeutic options for vulnerable populations

Changing concepts of accounting for treasury stock as reflected by the published reports of 391 selected industrial corporations for the years 1939 through 1945

Thesis (M.B.A.)--Boston University, 1947. This item was digitized by the Internet Archive

Desegregation\u27s Effect on Job Opportunities for Negro Teachers

The 1954 Supreme Court decision declaring segregated public education to be in violation of the equal protection clause of the Fourteenth Amendment broke the job monopoly of Negro teachers. While integrated student bodies were becoming commonplace, the integration of faculties lagged. Faced with the new job market that discriminates against him rather than for him, the Negro teacher, in many states, found himself forced out of teaching jobs in direct proportion to the rate and extent of integration. In the absence of integration, Negro teachers would be hired in proportion to the number of students of their race. The number of Negro students, therefore, establishes an a priori standard for hiring Negro teachers. For this reason, the comparison of job opportunities, over time, is feasible. If a substantial number of Negro students attend integrated schools and are taught by white teachers, the need for Negro teachers declines. The difference between the a priori standard and the actual number of Negro teachers yields an aggregate job disadvantage. Several states show a high correlation between increases in aggregate job disadvantage for Negro teachers and the extent of integration. Seventeen southern and border states are classified according to this criterion. Although federal legislation will undoubtedly invalidate the results of this study over time, it is apparent that the short run effect of school integration has been to relegate the Negro teacher into a disadvantaged employment position

A physiotherapist facilitated walking intervention using an activity tracker to improve daily step counts in people with stroke

Background Globally, stroke is a leading cause of long-term disability in adults. Participating in regular physical activity such as walking has multiple health benefits for stroke survivors and can reduce the risk of recurrent stroke. Despite this, physical activity levels are known to be low in people living with stroke. Activity trackers are increasingly being used to motivate individuals to increase physical activity and may be an effective strategy to increase participation in physical activity for people living with stroke. Objectives The objectives of this study were a) to investigate whether an eight-week walking intervention using a commercially available activity tracker and a behavioural change intervention could increase daily step counts in people living with chronic stroke; b) to investigate the acceptability of the intervention. Methods This study used a mixed methods design using an embedded approach with an experimental design. The quantitative method was quasi-experimental using a single group, pre-test, post-test design. Qualitative data was collected from a self-administered survey to investigate the acceptability of the intervention, and to provide context to the quantitative data. Participants were community dwelling, chronic stroke survivors (median time since stroke = 13.5 months). The intervention involved an individually, tailored eight-week walking programme monitored by a Fitbit™ Zip activity tracker. The intervention contained weekly face-to-face consultations for the first four weeks, to establish a progressive walking programme and promote exercise self-efficacy by incorporating strategies such as barrier identification, problem-solving, goal setting, self-monitoring and action planning. The primary outcome was the change in mean daily step counts. Secondary outcomes were resting systolic and diastolic blood pressure, walking endurance, stroke specific self-efficacy, health-related quality of life, adherence and acceptability of the intervention. Results Eight participants completed the study. The mean daily step count increased by 1343 (SD = 2467) steps or by a mean change of 52% compared to baseline steps. There was no statistically significant change in the secondary outcome measures except for health-related quality of life measured on the EuroQol-5D-5L VAS which increased by a mean of 14 points (SD=13.7). Participants were positive about the intervention and it appeared acceptable, although many barriers to completing the intervention were reported. Common barriers identified were lack of motivation, lack of time, fatigue, pain and environmental barriers such as unfavourable weather. There were no difficulties reported with regards to using the Fitbit™ Zip activity tracker. Conclusion This study used a low-cost commercially available activity tracker device alongside a behavioural change intervention delivered by a physiotherapist. The results show it is possible to increase daily step counts in a population of chronic stroke participants and that the intervention was acceptable. More research with larger sample sizes, a comparison group and longer follow-up time is warranted to determine whether the increase in daily step count can be maintained

Five thousand years of minimal access surgery: 1850 to 1990: Technological developments

This is the second of a three-part series that charts the history of minimal access surgery from antiquity to current times. Although rapid developments in laparoscopic and robotic surgery have transformed surgical care over the last 30 years, our predecessors made significant advances in their time which set the principles for modern practice. Part I of this series described how ancient medical practitioners developed simple instruments, from metal or wood, for viewing body cavities. Improvements in the use of metal, glass and lighting allowed for inspection of deeper parts of the body. This second part of the series will show how advances in electrical technology allowed the development of improved lighting for endoscopy and laparoscopy along with the use of electrocautery for a wide range of therapeutic procedures

Gene therapy for pyoderma gangrenosum: optimal transfection conditions and effect of drugs on gene delivery in the HaCaT cell line using cationic liposomes

Background/Aims: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, currently treated empirically with immunosuppression. PG is a good target for gene therapy since the skin is easily accessible. This study used the FDA-approved vector Lipofectamine® 2000 to investigate in vitro transfection of skin keratinocytes. The aim was to determine an optimum transfection protocol, including the effect of drugs currently used to treat PG on the efficiency of gene transfer, since gene therapy is unlikely to be used as monotherapy. Methods: Cells of the HaCaT line were transfected with the lacZ reporter gene, and transgene expression was measured after a given time period. Conditions tested were: relative concentrations of DNA and Lipofectamine®, time from transfection to measurement of expression, pH, and exposure to clinically relevant drugs (hydrocortisone, methotrexate, infliximab). Results: The greatest levels of β-galactosidase expression were observed using a DNA:Lipofectamine® ratio of 1:5 (μg/μl) on day 3 after transfection, using culture medium at pH 7, and in the presence of hydrocortisone. Transfection efficiency was reduced by the presence of methotrexate and not significantly affected by infliximab. Conclusion: Gene therapy is a potential future strategy for the management of PG; this study is a step towards the development of a topical gene-based agent

Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for regulation of foetal development, tissue differentiation and homeostasis, and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease specific bone metastasis

A case-control study of risk factors for wound infection in a colorectal unit

INTRODUCTION Postoperative wound infections have been responsible for increasing morbidity and are associated with an increased use of hospital resources. Previous studies have identified several risk factors. However, most studies are outdated, and few relate to the era of enhanced recovery and laparoscopic surgery. This study investigated the association between patient and operative factors and the development of postoperative wound infections in colorectal surgery. METHODS Patients with documented wound infections or dehiscences were identified from a database of elective and emergency colorectal surgery. Patients with wound infections were matched by operation type to a control group of colorectal patients. Differences in patient and operative factors between case and control group were analysed using conditional logistic regression. RESULTS A total of 56 patients with wound infection were identified from 647 operations (8.6%). Fifty-seven per cent were emergency operations and eighty-eight per cent were performed as open surgery or as laparoscopic surgery converted to open. Forty per cent of patients had high ASA (American Society of Anesthesiologists) grades (3 or 4). Multivariate logistical regression showed that obese patients and those having open surgery had the highest risk of infections. The median postoperative hospital stay for patients with wound infections was twice as long as for those patients without wound infections. CONCLUSIONS Open surgery and obesity are independent risk factor for wound infections. An increase in laparoscopically performed operations and new strategies for managing wounds in obese patients may help to reduce the rate of wound infection