Pheochromocytomas

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors derived from chromaffin tissue of the adrenal medulla. Such tumors arising from the sympathetic ganglia of the thorax, abdomen, or pelvis are termed “paragangliomas” or “extra-adrenal pheochromocytomas.” The classic symptoms of these tumors are due to excess circulating levels of norepinephrine, epinephrine, or dopamine. Although 21% may be asymptomatic, the most common symptoms associated with pheochromocytomas include sweating, palpitations, and headaches in association with intermittent hypertension. If left untreated, excess catecholamines may result in hypertensive crisis leading to cardiac complications, cerebrovascular stroke, or ultimately sudden death. These catecholamine-secreting tumors are most commonly sporadic, but about 30% of patients have this disease as part of a familial disorder such as multiple endocrine neoplasia type 2 (MEN2) or von Hippel-Lindau (VHL) syndrome. Although most are benign, accurate recognition of pheochromocytomas with malignant potential and distant metastases remains a major diagnostic challenge. Advances in the field of molecular genetics have led to novel diagnostic and therapeutic strategies in an attempt to address this dilemma. Surgical excision of pheochromocytomas and paragangliomas is the mainstay of treatment and offers the only potential for cure. This chapter focuses on recent developments in the diagnosis of pheochromocytomas, encompassing biochemical, radiologic, histologic, and molecular analyzes. In addition, novel therapeutic strategies and advances in individualized targeted therapies for malignant pheochromocytomas will be discussed

Characterization of serine proteinase expression in agaricus bisporus and coprinopsis cinerea by using green fluorescent protein and the A. bisporus SPR1 Promoter

The Agaricus bisporus serine proteinase 1 (SPR1) appears to be significant in both mycelial nutrition and senescence of the fruiting body. We report on the construction of an SPR promoter::green fluorescent protein (GFP) fusion cassette, pGreen_hph1_SPR_GFP, for the investigation of temporal and developmental expression of SPR1 in homobasidiomycetes and to determine how expression is linked to physiological and environmental stimuli. Monitoring of A. bisporus pGreen_hph1_SPR_GFP transformants on media rich in ammonia or containing different nitrogen sources demonstrated that SPR1 is produced in response to available nitrogen. In A. bisporus fruiting bodies, GFP activity was localized to the stipe of postharvest senescing sporophores. pGreen_hph1_SPR_GFP was also transformed into the model basidiomycete Coprinopsis cinerea. Endogenous C. cinerea proteinase activity was profiled during liquid culture and fruiting body development. Maximum activity was observed in the mature cap, while activity dropped during autolysis. Analysis of the C. cinerea genome revealed seven genes showing significant homology to the A. bisporus SPR1 and SPR2 genes. These genes contain the aspartic acid, histidine, and serine residues common to serine proteinases. Analysis of the promoter regions revealed at least one CreA and several AreA regulatory motifs in all sequences. Fruiting was induced in C. cinerea dikaryons, and fluorescence was determined in different developmental stages. GFP expression was observed throughout the life cycle, demonstrating that serine proteinase can be active in all stages of C. cinerea fruiting body development. Serine proteinase expression (GFP fluorescence) was most concentrated during development of young tissue, which may be indicative of high protein turnover during cell differentiatio

Managing Fever in adults with possible or confirmed COVID-19 in Primary Care

The current evidence does not support routine antipyretic administration to treat fever in acute respiratory infections and COVID-19. Many protocols and professionals advise patients to self-medicate for Covid-19 using antipyretics (e.g. paracetamol and ibuprofen). The rapid and widespread purchase of antipyretic medication over-the-counter has led to temporary shortages

The Post-Romantic Way to God: Personal Agency and Self-Worship in Wuthering Heights

In considering spirituality in Emily Brontë’s Wuthering Heights (1847), the passionate intensity of Catherine and Heathcliff’s tumultuous relationship springs to mind, dwarfing the narrow and (to the modern reader) nearly indecipherable concerns of kirk muttered by the cantankerous Joseph. This article focuses on the effect of the novel’s context within the fragmenting Anglican Church and a cultural shift toward personal agency in worship, encouraged by revivalism, in representing the lives of its lovers. I interpret the Catherine-Heathcliff relationship in Wuthering Heights as self-worship, extending this view to consider how passion and suffering link the relationship to religious ecstasy, which then becomes a mechanism through which Brontë explores spirituality in a Post-Romantic world.

Accuracy of methods for detecting an irregular pulse and suspected atrial fibrillation: a systematic review and meta-analysis

Background: Pulse palpation has been recommended as the first step of screening to detect atrial fibrillation. We aimed to determine and compare the accuracy of different methods for detecting pulse irregularities caused by atrial fibrillation. Methods: We systematically searched MEDLINE, EMBASE, CINAHL and LILACS until 16 March 2015. Two reviewers identified eligible studies, extracted data and appraised quality using the QUADAS-2 instrument. Meta-analysis, using the bivariate hierarchical random effects method, determined average operating points for sensitivities, specificities, positive and negative likelihood ratios (PLR, NLR); we constructed summary receiver operating characteristic plots. Results: Twenty-one studies investigated 39 interventions (n = 15,129 pulse assessments) for detecting atrial fibrillation. Compared to 12-lead electrocardiography (ECG) diagnosed atrial fibrillation, blood pressure monitors (BPMs; seven interventions) and non-12-lead ECGs (20 interventions) had the greatest accuracy for detecting pulse irregularities attributable to atrial fibrillation (BPM: sensitivity 0.98 (95% confidence interval (CI) 0.92–1.00), specificity 0.92 (95% CI 0.88–0.95), PLR 12.1 (95% CI 8.2–17.8) and NLR 0.02 (95% CI 0.00–0.09); non-12-lead ECG: sensitivity 0.91 (95% CI 0.86–0.94), specificity 0.95 (95% CI 0.92–0.97), PLR 20.1 (95% CI 12–33.7), NLR 0.09 (95% CI 0.06–0.14)). There were similar findings for smartphone applications (six interventions) although these studies were small in size. The sensitivity and specificity of pulse palpation (six interventions) were 0.92 (95% CI 0.85–0.96) and 0.82 (95% CI 0.76–0.88), respectively (PLR 5.2 (95% CI 3.8–7.2), NLR 0.1 (95% CI 0.05–0.18)). Conclusions: BPMs and non-12-lead ECG were most accurate for detecting pulse irregularities caused by atrial fibrillation; other technologies may therefore be pragmatic alternatives to pulse palpation for the first step of atrial fibrillation screening

Addendum soils investigation -- Kuikahi Gardens, Kalihi Street, Kalihi-Uka, Honolulu, Hawaii

W.O. 344-10Sections: field exploration, soils, history of sliding, recommendations, grading plan, cross sections, boring logs, laboratory testing, and laboratory data.Mid-Pac Development, Ltd

ELECTRIC BREAKDOWN AS A PROBABILITY PROCESS

ImportanceRecent estimates suggest that more than 26 million people worldwide have heart failure. The syndrome is associated with major symptoms, significantly increased mortality, and extensive use of health care. Evidence-based treatments influence all these outcomes in a proportion of patients with heart failure. Current management also often includes advice to reduce dietary salt intake, although the benefits are uncertain. ObjectiveTo systematically review randomized clinical trials of reduced dietary salt in adult inpatients or outpatients with heart failure. Evidence ReviewSeveral bibliographic databases were systematically searched, including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and CINAHL. The methodologic quality of the studies was evaluated, and data associated with primary outcomes of interest (cardiovascular-associated mortality, all-cause mortality, and adverse events, such as stroke and myocardial infarction) and secondary outcomes (hospitalization, length of inpatient stay, change in New York Heart Association [NYHA] functional class, adherence to dietary low-salt intake, and changes in blood pressure) were extracted. FindingsOf 2655 retrieved references, 9 studies involving 479 unique participants were included in the analysis. None of the studies included more than 100 participants. The risks of bias in the 9 studies were variable. None of the included studies provided sufficient data on the primary outcomes of interest. For the secondary outcomes of interest, 2 outpatient-based studies reported that NYHA functional class was not improved by restriction of salt intake, whereas 2 studies reported significant improvements in NYHA functional class. Conclusions and RelevanceLimited evidence of clinical improvement was available among outpatients who reduced dietary salt intake, and evidence was inconclusive for inpatients. Overall, a paucity of robust high-quality evidence to support or refute current guidance was available. This review suggests that well-designed, adequately powered studies are needed to reduce uncertainty about the use of this intervention.</p

Functional analyses of <i>Agaricus bisporus </i>Serine Proteinase 1 (SPR1) reveals a role in utilisation of humic rich substrates and adaptation to the leaf-litter ecological niche

Agaricus bisporus is a secondary decomposer fungus and an excellent model for the adaptation, persistence and growth of fungi in humic‐rich environments such as soils of temperate woodland and pastures. The A. bisporus serine proteinase SPR1 is induced by humic acids and is highly expressed during growth on compost. Three Spr1 gene silencing cassettes were constructed around sense, antisense and non‐translatable‐stop strategies (pGRsensehph, pGRantihph and pGRstophph). Transformation of A. bisporus with these cassettes generated cultures showing a reduction in extracellular proteinase activity as demonstrated by the reduction, or abolition, of a clearing zone on plate‐based bioassays. These lines were then assessed by detailed enzyme assay, RT‐qPCR and fruiting. Serine proteinase activity in liquid cultures was reduced in 83% of transformants. RT‐qPCR showed reduced Spr1 mRNA levels in all transformants analysed, and these correlated with reduced enzyme activity. When fruiting was induced, highly‐silenced transformant AS5 failed to colonize the compost, whilst for those that did colonize the compost, 60% gave a reduction in mushroom yield. Transcriptional, biochemical and developmental observations, demonstrate that SPR1 has an important role in nutrient acquisition in compost and that SPR1 is a key enzyme in the adaptation of Agaricus to the humic‐rich ecological niche formed during biomass degradation

The Impact of Autoimmune Hepatitis and Its Treatment on Health Utility

Patient reporting suggests that the physical and psychological effects of autoimmune hepatitis (AIH) can be substantial. However, health‐related quality of life (HRQOL) in patients with AIH remains incompletely characterized, and health utility remains to be explored. Treatment for AIH often includes the use of corticosteroids, which are agents that can be associated with significant adverse effects. Here we explore the impact of AIH and its treatments on patient‐reported HRQOL and health utility in a large cohort of prevalent cases from the United Kingdom Autoimmune Hepatitis (UK‐AIH) national study. Data were collected from 990 adult participants with a clinical diagnosis of AIH using validated HRQOL tools including the European Quality‐of‐Life 5‐Dimension 5‐Level (EQ‐5D‐5L) and clinical data forms. The EQ‐5D‐5L dimension scores were compared with UK population norms and with a disease control cohort with primary biliary cholangitis (PBC). Within the AIH cohort, regression analysis was used to explore associations between HRQOL and demographic and clinical variables with a particular focus on the impact of AIH therapies including corticosteroid use. HRQOL, measured by the EQ‐5D‐5L utility index, is shown to be significantly impaired in our cohort of AIH patients compared with population norms. Within the AIH cohort, corticosteroid use was found to be significantly associated with impaired HRQOL, even when controlling for biochemical disease activity status. Conclusion: Our data show evidence of HRQOL impairment in a large cohort of AIH patients compared with the general population. Furthermore, corticosteroid use is strongly associated with decreased HRQOL, independent of remission status. This highlights the need for better corticosteroid‐free therapy approaches and it emphasizes the need for future novel therapeutic trials in AIH

Possibility between earthquake and explosion seismogram differentiation by discrete stochastic non-Markov processes and local Hurst exponent analysis

The basic purpose of the paper is to draw the attention of researchers to new possibilities of differentiation of similar signals having different nature. One of examples of such kind of signals is presented by seismograms containing recordings of earthquakes (EQ's) and technogenic explosions (TE's). We propose here a discrete stochastic model for possible solution of a problem of strong EQ's forecasting and differentiation of TE's from the weak EQ's. Theoretical analysis is performed by two independent methods: with the use of statistical theory of discrete non-Markov stochastic processes (Phys. Rev. E62,6178 (2000)) and the local Hurst exponent. Time recordings of seismic signals of the first four dynamic orthogonal collective variables, six various plane of phase portrait of four dimensional phase space of orthogonal variables and the local Hurst exponent have been calculated for the dynamic analysis of the earth states. The approaches, permitting to obtain an algorithm of strong EQ's forecasting and to differentiate TE's from weak EQ's, have been developed.Comment: REVTEX +12 ps and jpg figures. Accepted for publication in Phys. Rev. E, December 200