Alien Registration- Foley, Julia (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/23763/thumbnail.jp

A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea

Background: Irritable bowel syndrome with diarrhoea (IBS-D) is particularly debilitating due to urgency and episodic incontinence. Some 5-hydroxytryptamine 3 (5-HT3) receptor antagonists (5-HT3RAs) have proven effective but have serious side effects. Ondansetron, also a 5-HT3RA, has been widely used as an antiemetic with an excellent safety record for over two decades. Our aim was to assess its effectiveness in IBS-D. Methods: 120 patients meeting Rome III criteria for IBS-D entered a randomised, double-blind, placebo-controlled crossover study of 5 weeks of ondansetron 4 mg versus placebo with dose titration allowed, up to two tablets three times daily in the first 3 weeks. Patients completed daily diaries documenting stool consistency using the Bristol Stool Form score. Gut transit was measured in the last week of each treatment. The primary endpoint was average stool consistency in the last 2 weeks of treatment. Results: Ondansetron significantly improved stool consistency (mean difference in stool form between ondansetron and placebo −0.9, 95% CI −1.1 to −0.6, p<0.001). Compared with placebo, patients on ondansetron experienced fewer days with urgency (p<0.001), lower urgency scores (p<0.001), reduced frequency of defaecation (p=0.002) and less bloating (p=0.002), although pain scores did not change significantly. IBS symptom severity score fell more with ondansetron than placebo (83±9.8 vs 37±9.7, p=0.001). 65% reported adequate relief with ondansetron but not placebo compared with 14% reporting relief with placebo but not ondansetron, relative risk 4.7, 95% CI 2.6 to 8.5, p<0.001. Conclusions: Ondansetron relieves some of the most intrusive symptoms of IBS-D, namely loose stools, frequency and urgency

Cost-effectiveness of trans-abdominal ultrasound for gallbladder cancer surveillance in patients with gallbladder polyps less than 10mm in the United Kingdom

Objective Gallbladder polyps (GBPs) are commonly detected with trans-abdominal ultrasound (TAUS). Gallbladder cancer (GBC) is associated with GBPs but the risk of malignancy is low. International guidelines recommend ultrasound surveillance (USS) in selected cases of GBPs <10mm, with cholecystectomy advised if polyp size increases. USS (including potential surgeries) is resource intense. We evaluated the costs and potential cost-effectiveness of USS in a theoretical UK patient cohort with GBPs. Methods A health economic model mapped expected management pathways over 2-years for 1,000 GBP patients with and without USS, stratified by initial size of GBP (<6mm and 6-9mm). We estimated USS resource and costs under alternate thresholds for surgery. Clinical data were extracted from a large-scale cohort study. TAUS and surgery costs were based on NHS tariffs. GBC costs were estimated from the literature. Outcomes included USS costs, expected numbers of GBC and incremental cost for each case of GBC avoided. Results The 2-year additional cohort costs of USS (n=number of additional surgeries) were estimated between £213,441 (n = 50) and £750,045 (n = 253) in GBPs <6mm, and between £420,275 (n = 165) and £531,297 (n = 207) in GBPs 6-9mm, balanced against avoidance of 1.3 (<6mm) and 8.7 (6-9mm) cases of GBC. Model findings were robust to plausible changes in inputs. Conclusions Using published data, we demonstrated that, in patients with GBPs <10mm, the costs of USS to avoid GBC outweigh potential GBC cost offsets, and would result in high rates of cholecystectomy. Additional evidence is needed to establish the formal cost-effectiveness of GBP USS in the UK

Quantitative Factors Proposed to Influence the Prevalence of Canine Tick-Borne Disease Agents in the United States

The Companion Animal Parasite Council hosted a meeting to identify quantifiable factors that can influence the prevalence of tick-borne disease agents among dogs in North America. This report summarizes the approach used and the factors identified for further analysis with mathematical models of canine exposure to tick-borne pathogens

Antimalarial Activity of Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase Enzyme Selected by Docking Studies

The Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH) has been considered as a potential molecular target for antimalarials due to this parasite's dependence on glycolysis for energy production. Because the LDH enzymes found in P. vivax, P. malariae and P. ovale (pLDH) all exhibit ∼90% identity to PfLDH, it would be desirable to have new anti-pLDH drugs, particularly ones that are effective against P. falciparum, the most virulent species of human malaria. Our present work used docking studies to select potential inhibitors of pLDH, which were then tested for antimalarial activity against P. falciparum in vitro and P. berghei malaria in mice. A virtual screening in DrugBank for analogs of NADH (an essential cofactor to pLDH) and computational studies were undertaken, and the potential binding of the selected compounds to the PfLDH active site was analyzed using Molegro Virtual Docker software. Fifty compounds were selected based on their similarity to NADH. The compounds with the best binding energies (itraconazole, atorvastatin and posaconazole) were tested against P. falciparum chloroquine-resistant blood parasites. All three compounds proved to be active in two immunoenzymatic assays performed in parallel using monoclonals specific to PfLDH or a histidine rich protein (HRP2). The IC50 values for each drug in both tests were similar, were lowest for posaconazole (<5 µM) and were 40- and 100-fold less active than chloroquine. The compounds reduced P. berghei parasitemia in treated mice, in comparison to untreated controls; itraconazole was the least active compound. The results of these activity trials confirmed that molecular docking studies are an important strategy for discovering new antimalarial drugs. This approach is more practical and less expensive than discovering novel compounds that require studies on human toxicology, since these compounds are already commercially available and thus approved for human use

The Lantern, 2021-2022

No More Buses through El Paso • A Woman\u27s World • The Angel of Tragedy • A Victim of Circumstance • Ace of Hearts • Ghost Light • Missing Diamonds • The Upside-Down House: A Dialogue with the Self • What is Chronic Pain? • A Sunny Day in Sinkhole • Extra Marshmallows • Fourth Wall Broken • Hemlock • In the Comfort of Others • Lasting Impressions • Let\u27s Do the Time Warp Again • One Last Afternoon • Space Invaders • The Dogwood Tree • An Ode to Poppies • Charlotte\u27s Web • Crab • Crossing • Dandelions • Dandelion Sandwich • Grizzly Hood • Help Wanted • I Gave Way • I\u27m not who you wanted but maybe one day I can be • Kneeling • Lemon Cookies • Lies • Method Acting • Moment of Tranquility • Our Home • Overthinking • Sea Glass • Seasonal • Thirty-Two (No Spares) • The Autumn Beast • The Miller\u27s Daughter • Theodore • To the Earring I Left Behind in Your Carpet • Virginia • Waltzing • Yellow House • 1/25 British Monarch • Cracked • In the Shadows • Jewelwing • Life on the Wing • O\u27 Captain my Captain • Stars Above the Bay • The Common Fall • Tom • Cats + Crowshttps://digitalcommons.ursinus.edu/lantern/1190/thumbnail.jp

Severe Airway Epithelial Injury, Aberrant Repair and Bronchiolitis Obliterans Develops after Diacetyl Instillation in Rats

Bronchiolitis obliterans (BO) is a fibrotic lung disease that occurs in a variety of clinical settings, including toxin exposures, autoimmunity and lung or bone marrow transplant. Despite its increasing clinical importance, little is known regarding the underlying disease mechanisms due to a lack of adequate small animal BO models. Recent epidemiological studies have implicated exposure to diacetyl (DA), a volatile component of artificial butter flavoring, as a cause of BO in otherwise healthy factory workers. Our overall hypothesis is that DA induces severe epithelial injury and aberrant repair that leads to the development of BO. Therefore, the objectives of this study were 1) to determine if DA, delivered by intratracheal instillation (ITI), would lead to the development of BO in rats and 2) to characterize epithelial regeneration and matrix repair after ITI of DA.Male Sprague-Dawley rats were treated with a single dose of DA (125 mg/kg) or sterile water (vehicle control) by ITI. Instilled DA resulted in airway specific injury, followed by rapid epithelial regeneration, and extensive intraluminal airway fibrosis characteristic of BO. Increased airway resistance and lung fluid neutrophilia occurred with the development of BO, similar to human disease. Despite rapid epithelial regeneration after DA treatment, expression of the normal phenotypic markers, Clara cell secretory protein and acetylated tubulin, were diminished. In contrast, expression of the matrix component Tenascin C was significantly increased, particularly evident within the BO lesions.We have established that ITI of DA results in BO, creating a novel chemical-induced animal model that replicates histological, biological and physiological features of the human disease. Furthermore, we demonstrate that dysregulated epithelial repair and excessive matrix Tenacin C deposition occur in BO, providing new insights into potential disease mechanisms and therapeutic targets

The Lantern, 2019-2020

Cochlea, Greek for Snail • That Light in the Sky • Overview Effect • The Running Man • Sunset • Rabbits • What Happened While You Were Drunk Last Saturday Night • 21st Century Frankenstein • Passing • I Saw the Veil • Star Crossed • Subtle Hints • Hungry • Basement High • The Night Who Lost Its Stars • Remnants • Nostalgia • I Want to Go to Bed • Wooden Car Blues • Silver Honey • The Breakup • Here\u27s to Losing You • Marfa • Cold Wind Blows • Last Week • 6/12/2019 • These Feather Earrings • Every Piece of White Trash Comes from Somewhere • Color Motion Blur • Song of the Kauai O\u27o • You/Me/Him • Girl in Three Parts • With Anxiety • Foreigner • Eating Your Own Field • Mary Cassatt Sits for a Self Portrait • Thanatourism • Lost in Transportation • Chicken Pot Pie Picture Show • Curses, Foiled Again • From Amelia Goldstein\u27s Movement in Your Words 2019 • At the Altar • More Than Words • Show Me Your Eyes • Ears • The Deflowering • Space • The Tea Bags • Make No Mistake • What Does He Do With the Body?: Four Possibilities • The Story of How I Died, or What the Witches Gave Me • Fortune-Teller • No Thanks • Winter Words • Fluorescent Adolescent • Etiquettical Triptych • Curls and Flower Petals • Being or Falling • Fond Memories • You • All to My City • The Shoreline • Tranquility • Eggs • Burnt • Anthony • Targets • Looking Up • Nebula • Eastern State • Beachhttps://digitalcommons.ursinus.edu/lantern/1188/thumbnail.jp

Redefining palliative care-a new consensus-based definition

Context: The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. Objective: The main objective of this article is to present the research behind the new definition. Methods: The three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. Results: The consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. Conclusion: Participants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span