92 research outputs found
The Role of FoxO Transcription Factors in Alcohol-Induced Deficient Fracture Repair
Proper and complete repair of a bone fracture is essential in quality of life maintenance, but poor healing and fracture malunion are still medically and socially relevant problems. Alcohol abuse impairs normal fracture healing, leading to delayed or incomplete union. This dissertation aims to clarify mechanisms behind this alcohol-induced impaired healing, thereby elucidating potential methods of intervention.
Alcohol-induced oxidative stress has been linked to many morbidities associated with alcohol abuse. This dissertation elucidates a potential mechanism through which alcohol inhibits fracture healing by increasing oxidative stress. Using a rodent model, I found that alcohol exposure decreases fracture callus formation and endochondral ossification, and these changes are associated with markers of activation of FoxO transcription factors. FoxO transcription factors are known to be activated by oxidative stress and inhibit proper mesenchymal stem cell differentiation, which is crucial in callus formation. These deleterious effects of alcohol were prevented with the administration of an antioxidant. These results begin to illuminate how alcohol abuse can negatively affect fracture healing and bone health in general, while characterizing aspects of skeletal biology that are applicable beyond alcohol-associated pathologies
Multitasking by the OC lineage during bone infection: Bone resorption, immune modulation, and microbial niche
Bone infections, also known as infectious osteomyelitis, are accompanied by significant inflammation, osteolysis, and necrosis. Osteoclasts (OCs) are the bone-resorbing cells that work in concert with osteoblasts and osteocytes to properly maintain skeletal health and are well known to respond to inflammation by increasing their resorptive activity. OCs have typically been viewed merely as effectors of pathologic bone resorption, but recent evidence suggests they may play an active role in the progression of infections through direct effects on pathogens and via the immune system. This review discusses the host- and pathogen-derived factors involved in the in generation of OCs during infection, the crosstalk between OCs and immune cells, and the role of OC lineage cells in the growth and survival of pathogens, and highlights unanswered questions in the field
Estimating Increased Transient Water Storage With Increases in Beaver Dam Activity
Dam building by beaver (Castor spp.) slows water movement through montane valleys, increasing transient water storage and the diversity of residence times. In some cases, water storage created by beaver dam construction is correlated to changes in streamflow magnitude and timing. However, the total amount of additional surface and groundwater storage that beaver dams may create (and, thus, their maximum potential impact on streamflow) has not been contextualized in the water balance of larger river basins. We estimate the potential transient water storage increases that could be created at 5, 25, 50, and 100% of maximum modeled beaver dam capacity in the Bear River basin, USA, by adapting the height above nearest drainage (HAND) algorithm to spatially estimate surface water storage. Surface water storage estimates were combined with the MODFLOW groundwater model to estimate potential increases in groundwater storage throughout the basin. We tested four scenarios to estimate potential transient water storage increases resulting from the construction of 1179 to 34,897 beaver dams, and estimated surface water storage to range from 57.5 to 72.8 m3 per dam and groundwater storage to range from 182.2 to 313.3 m3 per dam. Overall, we estimate that beaver dam construction could increase transient water storage by up to 10.38 million m3 in the Bear River basin. We further contextualize beaver dam-related water storage increases with streamflow, reservoir, and snowpack volumes
Staphylococcus aureus infects osteoclasts and replicates intracellularly
Osteomyelitis (OM), or inflammation of bone tissue, occurs most frequently as a result of bacterial infection and severely perturbs bone structure. OM is predominantly caused b
Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer
PI3K inhibition in combination with other agents has not been studied in the context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of PIK3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer. Keywords: PI3K; MEK; KRAS; Colorectal cancer; Mouse model of cance
Why are family carers of people with dementia dissatisfied with general hospital care?: a qualitative study
Background
Families and other carers report widespread dissatisfaction with general hospital care for confused older people.
Methods
We undertook a qualitative interviews study of 35 family carers of 34 confused older patients to ascertain their experiences of care on geriatric and general medical, and orthopaedic wards of a large English hospital. Transcripts were analysed using a grounded theory approach. Themes identified in interviews were categorised, and used to build a model explaining dissatisfaction with care.
Results
The experience of hospital care was often negative. Key themes were events (illness leading to admission, experiences in the hospital, adverse occurrences including deterioration in health, or perceived poor care); expectations (which were sometimes unrealistic, usually unexplored by staff, and largely unmet from the carers’ perspective); and relationships with staff (poor communication and conflict over care). Expectations were influenced by prior experience. A cycle of discontent is proposed. Events (or ‘crises’) are associated with expectations. When these are unmet, carers become uncertain or suspicious, which leads to a period of ‘hyper vigilant monitoring’ during which carers seek out evidence of poor care, culminating in challenge, conflict with staff, or withdrawal, itself a crisis. The cycle could be completed early during the admission pathway, and multiple cycles within a single admission were seen.
Conclusion
People with dementia who have family carers should be considered together as a unit. Family carers are often stressed and tired, and need engaging and reassuring. They need to give and receive information about the care of the person with dementia, and offered the opportunity to participate in care whilst in hospital. Understanding the perspective of the family carer, and recognising elements of the ‘cycle of discontent’, could help ward staff anticipate carer needs, enable relationship building, to pre-empt or avoid dissatisfaction or conflict
Books in Arabic Script
The chapter approaches the book in Arabic script as the indispensable means for the transmission of knowledge across Eurasia and Africa, within cultures and across cultural boundaries, since the seventh century ad. The state of research can be divided into manuscript and print studies, but there is not yet a history of the book in Arabic script that captures its plurilinear development for over fourteen hundred years. The chapter explores the conceptual and practical challenges that impede the integration of the book in Arabic script into book history at large and includes an extensive reference list that reflects its diversity.
The final published version was slightly updated, and includes seven illustrations of six Qurans from the holdings of Columbia University Libraries, four manuscripts and two printed versions. Moreover, the illustrations are images of historical artifacts which are in the public domain - despite Wiley's copyright claim
Autosub Long Range 1500: A continuous 2000 km field trial
Long Range Autonomous Underwater Vehicles (LRAUVs) offer the potential to monitor the ocean at higher spatial and temporal resolutions compared to conventional ship-based techniques. The multi-week to multi-month endurance of LRAUVs enables them to operate independently of a support vessel, creating novel opportunities for ocean observation. The National Oceanography Centre’s Autosub Long Range is one of a small number of vehicles designed for a multi-month endurance. The latest iteration, Autosub Long Range 1500 (ALR1500), is a 1500 m depth-rated LRAUV developed for ocean science in coastal and shelf seas or in the epipelagic and meteorologic regions of the ocean. This paper presents the design of the ALR1500 and results from a five week continuous deployment from Plymouth, UK, to the continental shelf break and back again, a distance of approximately 2000km which consumed half of the installed energy. The LRAUV was unaccompanied throughout the mission and operated continuously beyond visual line of sight
High recombination rates and hotspots in a Plasmodium falciparum genetic cross
Using the universal P2/P8 primers, we were able to obtain the gene segments of chromo-helicase-DNA binding protein (CHD)-Z and CHD-W from ten species of ardeid birds including Chinese egret (Egretta eulophotes), little egret (E. garzetta), eastern reef egret (E. sacra), great egret (Ardea alba), grey heron (A. cinerea), Chinese pond-heron (Ardeola bacchus), cattle egret (Bubulcus ibis), black-crowned night-heron (Nycticorax nycticorax), cinnamon bittern (Ixobrychus cinnamomeus) and yellow bittern (I. sinensis). Based on conserved regions inside the P2/P8-derived sequences, we designed new PCR primers for sex identification in these ardeid species. Using agarose gel electrophoresis, the PCR products showed two bands for females (140 bp derived from CHD-W and the other 250 bp from CHD-ZW), whereas the males showed only the 250 bp band. The results indicated that our new primers could be used for accurate and convenient sex identification in ardeid species.National Natural Science Foundation of China[30970380, 40876077]; Fujian Natural Science Foundation of China[2008S0007, 2009J01195
Global Health Governance and the Commercial Sector: A Documentary Analysis of Tobacco Company Strategies to Influence the WHO Framework Convention on Tobacco Control
Heide Weishaar and colleagues did an analysis of internal tobacco industry documents together with other data and describe the industry's strategic response to the proposed World Health Organization Framework Convention on Tobacco Control
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