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Gastrointestinal (GI) toxicosis is a common side effect of cytotoxic chemotherapy treatment in humans and dogs. Measurement of cytokeratin 18 (CK18), an intracellular structural protein released during epithelial apoptosis, and Alpha1-Antitrypsin (A1AT) in faeces provides a mechanism for evaluating damage to the intestinal mucosa secondary to cytotoxic chemotherapy. Our goal was to evaluate the clinical utility of plasma CK18 and faecal A1-AT levels as non-invasive biomarkers of cytotoxic chemotherapy induced GI toxicity. We conducted a prospective cohort study in dogs (N = 10) with osteosarcoma undergoing amputation followed by carboplatin chemotherapy. #link# We hypothesized that plasma CK18 and faecal A1-AT levels would increase following carboplatin administration due to drug-induced GI epithelial damage/apoptosis, and that plasma CK18 and faecal A1-AT levels would correlate with severity of GI toxicity. Mean baseline plasma CK18 concentration was variable amongst patients; however, CK18 concentration prior to carboplatin chemotherapy treatment was not significantly different from CK18 levels after treatment. There was significant intra and inter-patient variability in mean faecal A1-AT levels at baseline. Mean A1-AT concentration did not change significantly from day 0 to day 21. link2 Gastrointestinal toxicity was minimal; therefore, we were unable to determine the association of plasma CK18 and faecal A1-AT concentrations with development of GI toxicosis. In this study population, plasma CK18 and faecal A1-AT concentration were not clinically useful biomarkers for the detection of GI toxicosis secondary to carboplatin administration. Further prospective evaluation of CK18 and A1-AT as biomarkers of drug-induced GI toxicity is warranted in a larger cohort of dogs receiving cytotoxic chemotherapy. AVMA clinical trial registration number AAHSD004827.A parameter uniform numerical method is presented for solving singularly perturbed parabolic differential-difference equations with small shift arguments in the reaction terms arising in computational neuroscience. To approximate the terms with the shift arguments, Taylor's series expansion is used. The resulting singularly perturbed parabolic differential equation is solved by applying the implicit Euler method in temporal direction and extended cubic B-spline basis functions consisting of a free parameter λ for the resulting system of ordinary differential equations in the spatial direction. The proposed method is shown to be accurate of order O Δ t + h 2 ε + h by preserving an ε- uniform convergence. To demonstrate the applicability of the proposed method, two test examples are solved by the method and the numerical results are compared with some existing results. The obtained numerical results agreed with the theoretical results.Almost 50 years ago, Michael Rosenzweig pointed out that nutrient addition can destabilise food webs, leading to loss of species and reduced ecosystem function through the paradox of enrichment. Around the same time, David Tilman demonstrated that increased nutrient loading would also be expected to cause competitive exclusion leading to deleterious changes in food web diversity. While both concepts have greatly illuminated general diversity-stability theory, we currently lack a coherent framework to predict how nutrients influence food web stability across a landscape. This is a vitally important gap in our understanding, given mounting evidence of serious ecological disruption arising from anthropogenic displacement of resources and organisms. Here, we combine contemporary theory on food webs and meta-ecosystems to show that nutrient additions are indeed expected to drive loss in stability and function in human-impacted regions. Our models suggest that destabilisation is more likely to be caused by the complete loss of an equilibrium due to edible plant species being competitively excluded. In highly modified landscapes, spatial nutrient transport theory suggests that such instabilities can be amplified over vast distances from the sites of nutrient addition. Consistent with this theoretical synthesis, the empirical frequency of these distant propagating ecosystem imbalances appears to be growing. This synthesis of theory and empirical data suggests that human modification of the Earth is strongly connecting distantly separated ecosystems, causing rapid, expansive and costly nutrient-driven instabilities over vast areas of the planet. Similar to existing food web theory, the corollary to this spatial nutrient theory is that slowing down spatial nutrient pathways can be a potent means of stabilising degraded ecosystems.
Renin-angiotensin-aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID-19). We investigated the association between use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID-19 hospitalization/death in a large nationwide population.
Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020. COVID-19 cases were defined based on hospitalization/death for COVID-19. Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID-19 in the overall population, and of all-cause mortality in COVID-19 cases. We performed consistency analysis to quantify the impact of potential unmeasured confounding. Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID-19. After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID-19 (odds ratio 0.86, 95% confidence interval 0.81-0.91) in the overall population, and with reduced mortality in COVID-19 cases (hazard ratio 0.89, 95% confidence interval 0.82-0.96). MRA use was not associated with risk of any outcome. Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use.
In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID-19.
In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID-19.Peste des petits ruminants (PPR) is a severe disease of goats and sheep that is widespread in Africa, the Middle East and Asia. The disease is caused by peste des petits ruminants virus (PPRV); cell culture-attenuated strains of PPRV have been shown, both experimentally and by extensive use in the field, to be effective vaccines and are widely used. We have previously demonstrated that these vaccines elicit both serological (PPRV-specific antibody) and cell-based (PPRV-specific CD4+ and CD8+ T cells) immune responses. However, it is not known which of these responses are required for protection from PPRV, information that would be useful in the evaluation of new vaccines that are being developed to provide the capability to differentiate infected and vaccinated animals (DIVA capability). To begin to address this issue, we have used a complement-fixing monoclonal antibody recognizing caprine CD8 to deplete >99.9% of circulating CD8+ T cells from vaccinated goats. Animals were then infected with wild-type PPRV. Despite the absence of the CD8+ T-cell component of the vaccine-induced immune response, the vaccinated animals were almost fully protected, showing no pyrexia or viraemia, and almost no clinical signs. These data suggest that a virus-specific CD8+ T-cell response is not critical for protection against PPRV and that virus-specific antibody and/or CD4+ T cells are the main mediators of protection. We have also shown that the leucopenia caused by infection with wild-type PPRV affects all major classes of circulating leucocytes.
Growing evidence indicates sex and gender differences exist in substance use. Framed by a lifecourse perspective, we explored prospectively by sex the effects of distal and proximal factors on the initiation of drug use in college.
College students without prior drug use (n=5,120 females; n=2,951 males) were followed longitudinally across 4years. Analyses were estimated as a multigroup survival analysis separately by sex within a latent variable SEM framework with illicit drug use (6 or more times in past year) as the latent factor.
More males initiated drug use (8.5%) than females (6.4%, χ2 (1)=10.351, p=.001), but less so for Black males (AOR 0.33, 95% CI [0.18, 0.60]) and females (0.35 [0.23, 0.54]). Students initiating drug use more likely included students smoking cigarettes at baseline (males 1.40 [1.23, 1.59]; females 1.43 [1.24, 1.64]), using alcohol (males 1.04 [1.02, 1.06]; females 1.04 [1.02, 1.06]), or having cannabis using peers (males 1.79 [1.52, 2.11]; females 1.70 [1.49, 1.93]). Impulsivity domain associations differed by sex [negative urgency females (1.23 [1.02, 1.49) and sensation seeking males (1.33 [1.01, 1.75])]. History of unwanted/uncomfortable sexual experience predicted drug use for males (1.60 [1.09, 2.35]) and females (1.95 [1.45, 2.62]) but physical assault only for females (1.45 [1.08, 1.94]). Mood symptoms predicted drug use only for males [depression (0.73 [0.56, 0.95]); anxiety (1.40 [1.04, 1.89])].
Risk factors for initiating drug use during college differ by sex. As substance use during early age predisposes one for addiction, sex- and gender-informed interventions for young adults are needed.
Risk factors for initiating drug use during college differ by sex. As substance use during early age predisposes one for addiction, sex- and gender-informed interventions for young adults are needed.
Continuous-wave cyclophotocoagulation (CW-CPC) is often preferred to medical and surgical treatments for managing refractory glaucoma. This review summarizes diode CW-CPC indications, history, histopathology, methods, efficacy and safety. It also provides an overview of the latest data available on micropulse transscleral laser treatment (MP-TLT) that uses repetitive micropulses of diode laser energy in an off-and-on cyclical fashion.
A literature review was conducted on transscleral CW-CPC (CW-TSCPC), endoscopic CPC (ECP) and MP-TLT. Relevant series of adult and paediatric patients were included for assessing the procedures.
Regarding CW-TCPC, highly variable success rates are reported in the literature, depending on the definition of success, type of underlying glaucoma, energy settings, follow-up duration and retreatment rates. CW-CPC often needs to be repeated, especially in paediatric patients. CW-CPC exposes to risks of inflammation and chronic ocular hypotony or phthisis with irreversible visual .
Approximately 6,000 people under the age of 65years reside in nursing homes each year in Australia. These young people in nursing homes are at risk of premature death and preventable morbidity from injuries. link3 Choking and falls are the leading causes of premature deaths in this cohort with reported rates of 44% and 33%, respectively.
To develop https://www.selleckchem.com/products/ap20187.html for young people in Australian nursing homes.
This mixed-methods study comprised two expert consultation panels and a follow-up survey. Two expert and stakeholder consultation panels used a modified nominal group technique to formulate recommendations. A short survey was subsequently given to participants to validate responses from the panels and to provide an opportunity to evaluate and rank recommendations.
Ten recommendations were formulated for consideration that focused on system-wide reforms. Four were ranked as most important for implementation education and training for nursing home staff; implementation of National Disability Insurance Scheme; support for coordinated care; and increasing residential housing stock that is appropriately designed.
