Changes in murine anorectum signaling across the life course

Background: Increasing age is associated with an increase in the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to these conditions is not fully understood. This study examined the effects of increasing age on the function of the murine anorectum.Methods: The effects of increasing age on cholinergic, nitrergic, and purinergic signaling pathways in the murine anorectum were examined using classical organ bath assays to examine tissue function and electrochemical sensing to determine age‐related changes in nitric oxide and acetylcholine release.Key Results: Nitrergic relaxation increased between 3 and 6 months, peaked at 12 months and declined in the 18 and 24 months groups. These changes were in part explained by an age‐related decrease in nitric oxide (NO) release. Cholinergic signaling was maintained with age by an increase in acetylcholine (ACh) release and a compensatory decrease in cholinesterase activity. Age‐related changes in purinergic relaxation were qualitatively similar to nitrergic relaxation although the relaxations were much smaller. Increasing age did not alter the response of the anorectum smooth muscle to exogenously applied ACh, ATP, sodium nitroprusside or KCl. Similarly, there was no change in basal tension developed by the anorectum.Conclusions and Inferences: The decrease in nitrergic signaling with increasing age may contribute to the age‐related fecal impaction and constipation previously described in this model by partially obstructing defecation

A population-based cohort study

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Techno-economic analysis of biofuel production via bio-oil zeolite upgrading: An evaluation of two catalyst regeneration systems

Biofuels have been identified as a mid-term greenhouse gas (GHG) emissions abatement solution for decarbonising the transport sector. This study examines the techno-economic analysis of biofuel production via biomass fast pyrolysis and subsequent bio-oil upgrading via zeolite cracking. The aim of this study is to compare the techno-economic feasibility of two conceptual catalyst regeneration configurations for the zeolite cracking process: (i) a two-stage regenerator operating sequentially in partial and complete combustion modes (P-2RG) and (ii) a single stage regenerator operating in complete combustion mode coupled with a catalyst cooler (P-1RGC). The designs were implemented in Aspen Plus® based on a hypothetical 72 t/day pine wood fast pyrolysis and zeolite cracking plant and compared in terms of energy efficiency and profitability. The energy efficiencies of P-2RG and P-1RGC were estimated at 54% and 52%, respectively with corresponding minimum fuel selling prices (MFSPs) of £7.48/GGE and £7.20/GGE. Sensitivity analysis revealed that the MFSPs of both designs are mainly sensitive to variations in fuel yield, operating cost and income tax. Furthermore, uncertainty analysis indicated that the likely range of the MFSPs of P-1RGC (£5.81/GGE − £11.63/GGE) at 95% probability was more economically favourable compared with P-2RG, along with a penalty of 2% reduction in energy efficiency. The results provide evidence to support the economic viability of biofuel production via zeolite cracking of pyrolysis-derived bio-oil

Patch Tests Under Systemic Immunossupression - An Absolute Contra-Indication?

Introdução: As provas epicutâneas (PE) são o exame complementar de diagnóstico indicado para avaliação de suspeita de dermite de contacto alérgica. Idealmente, devem ser realizadas sem que o doente se encontre sob imunossupressores. Existem contudo situações clínicas em que tal não é possível, não havendo informação disponível acerca de como realizar e valorizar os resultados das PE nestes doentes. O objectivo do presente trabalho é rever a literatura no que concerne à realização de PE sob imunossupressão iatrogénica. Material e Métodos: Revisão da literatura relevante para o tema publicada até Janeiro de 2015 e indexada à Medline. Resultados: De acordo com o reportado na literatura, foram realizadas PE em 77 doentes sob corticóide sistémico, 78 doentes sob ciclosporina (CyA), 6 sob azatioprina, 10 sob metotrexato (MTX), 4 sob micofenolato de mofetil (MMF), 11 sob fármacos anti-factor de necrose tumoral e 7 sob fármaco anti-IL-12/23. Foram ainda descritos 15 casos de realização de PE sob associação de imunossupressores. Verificaram-se reacções positivas em todos os grupos. Conclusão: O tratamento concomitante com imunossupressores não deve ser uma contra-indicação para realização de PE, estando descritas reacções positivas em doentes sob prednisolona, azatioprina, CyA, MTX, MMF, infliximab, etanercept, adalimumab e ustecinumab. Os resultados negativos ou duvidosos devem, contudo, ser interpretados de forma cautelosa

Phototherapy in Childhood: a 17-Year Retrospective Study Regarding Effectiveness and Safety

Introduction: Skin diseases in paediatric age are often distressing conditions with significant impact in children’s psychosocial development. Additionally, systemic therapeutic options are often limited in childhood, due to its potential toxicity in this vulnerable group. Phototherapy is therefore an endorsed option for photo-responsive dermatological conditions. Objective and Methods:This observational retrospective study aims to access efficacy and safety of Phototherapy in our paediatric population. Relevant clinical data from 1996 to present concerning patients aged 18 years or less was collected. Results: 78 patients were included, of which64,1%was female. Mean age was 12,9 years (range 2-18). Distribution according to diagnosis was:47,4%psoriasis, 34,6% alopecia areata, 9,0% vitiligo, 9,0% other diagnosis. Mean number of cycles was 1,5 (range 1-7), with an average of 16,3 treatments per cycle and mean cumulative dose 134 J/cm2. 70,5% was treated with one single cycle. Topic and systemic PUVA were the first choice in 37,2% and 39,7%, respectively, while UVB TL01 and broadband UVB were used in 11,5% each. On the first cycle 67,5% improved, 14,3% showed no sustained clinical response and 19,5% were lost to follow-up. Psoriasis patients had the best response rates (81,8%), followed by alopecia areata (59,3%). Side effects occurred in 21%, being erythema the most common (12%). None led to therapeutic interruption. Discussion: Phototherapy is a safe and effective option in childhood, yet the withdraw rate might be an important limitation

What every Intensivist should know about the role of ammonia in liver failure

Publisher Copyright: © 2023 The AuthorsPurpose: Acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) patients have high short-term mortality and morbidity. In the context of liver failure, increased serum ammonia is associated with worse neurological outcomes, including high-grade hepatic encephalopathy (HE), cerebral edema, and intracranial hypertension. Besides its neurotoxicity, hyperammonemia may contribute to immune dysfunction and the risk of infection, a frequent trigger for multi-organ failure in these patients. Material and methods: We performed a literature-based narrative review. Publications available in PubMed® up to June 2023 were considered. Results: In the ICU management of liver failure patients, serum ammonia may play an important role. Accordingly, in this review, we focus on recent insights about ammonia metabolism, serum ammonia measurement strategies, hyperammonemia prognostic value, and ammonia-targeted therapeutic strategies. Conclusions: Serum ammonia may have prognostic value in liver failure. Effective ammonia targeted therapeutic strategies are available, such as laxatives, rifaximin, L-ornithine-L-aspartate, and continuous renal replacement therapy.proofepub_ahead_of_prin

Limitations and perceived delays for diagnosis and staging of lung cancer in Portugal: A nationwide survey analysis

Background We aimed to identify the perception of physicians on the limitations and delays for diagnosing, staging and treatment of lung cancer in Portugal. Methods Portuguese physicians were invited to participate an electronic survey (Feb-Apr-2020). Descriptive statistical analyses were performed, with categorical variables reported as absolute and relative frequencies, and continuous variables with non-normal distribution as median and interquartile range (IQR). The association between categorical variables was assessed through Pearson’s chi-square test. Mann-Whitney test was used to compare categorical and continuous variables (Stata v.15.0). Results Sixty-one physicians participated in the study (45 pulmonologists, 16 oncologists), with n = 26 exclusively assisting lung cancer patients. Most experts work in public hospitals (90.16%) in Lisbon (36.07%). During the last semester of 2019, responders performed a median of 85 (IQR 55–140) diagnoses of lung cancer. Factors preventing faster referral to the specialty included poor articulation between services (60.0%) and patients low economic/cultural level (44.26%). Obtaining National Drugs Authority authorization was one of the main reasons (75.41%) for delaying the begin of treatment. The cumulative lag-time from patients’ admission until treatment ranged from 42–61 days. Experts believe that the time to diagnosis could be optimized in around 11.05 days [IQR 9.61–12.50]. Most physicians (88.52%) started treatment before biomarkers results motivated by performance status deterioration (65.57%) or high tumor burden (52.46%). Clinicians exclusively assisting lung cancer cases reported fewer delays for obtaining authorization for biomarkers analysis (p = 0.023). Higher waiting times for surgery (p = 0.001), radiotherapy (p = 0.004), immunotherapy (p = 0.003) were reported by professionals from public hospitals. Conclusions Physicians believe that is possible to reduce delays in all stages of lung cancer diagnosis with further efforts from multidisciplinary teams and hospital administration.This work was supported by AstraZeneca. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript