Hypothalamic action of atrial natriuretic factor to inhibit vasopressin secretion

The ability of synthetic atrial natriuretic factor (ANF) to inhibit vasopressin (AVP) release, as well as its action to inhibit water intake and salt preference in the rat, suggest a role for the peptide in the hypothalamic control of fluid volume in addition to its established actions in the kidney. We report here evidence for a direct, hypothalamic site of action of ANF to inhibit, specifically, AVP secretion. Third cerebroventricular infusion of 1.0 (p less than 0.05) and 2.0 (p less than 0.025) nmoles ANF significantly inhibited AVP release in euvolemic, normally hydrated rats while IV doses of ANF failed to significantly alter AVP release except when 5 nmoles (p less than 0.05) were infused. No significant effects on oxytocin (OT) release were observed. Vasopressin release from median eminence or pituitary, neural lobe explants during static, in vitro incubations was not significantly altered by doses of ANF ranging from 10(-12) to 10(-7) molar. Release of AVP during perifusion of neural lobe explants in the presence of ANF was similarly unaffected. However, AVP and not OT release from hypothalamo-neurohypophysial system explants was significantly inhibited in the presence of 10(-8) and 10(-7) M ANF, suggesting an action of the peptide at the levels of the AVP-producing cell bodies in the included supraoptic nucleus either directly or via an action on an interneuron, and not at the AVP-containing terminal fields in the median eminence or neural lobe.     

Obestatin acts in brain to inhibit thirst

Derived from the same prohormone, obestatin has been reported to exert effects on food intake that oppose those of ghrelin. The obestatin receptor GPR39 is present in brain and pituitary gland. Since the gene encoding those two peptides is expressed also in those tissues, we examined further the possible actions of obestatin in vivo and in vitro. Intracerebroventricular administration of obestatin inhibited water drinking in ad libitum-fed and -watered rats, and in food-and water-deprived animals. The effects on water drinking preceded and were more pronounced than any effect on food intake, and did not appear to be the result of altered locomotor/behavioral activity. In addition, obestatin inhibited ANG II-induced water drinking in animals provided free access to water and food. Current-clamp recordings from cultured, subfornical organ neurons revealed significant effects of the peptide on membrane potential, suggesting this as a potential site of action. In pituitary cell cultures, log molar concentrations of obestatin ranging from 1.0 pM to 100 nM failed to alter basal growth hormone (GH) secretion. In addition, 100 nM obestatin failed to interfere with the stimulation of GH secretion by GH-releasing hormone or ghrelin and did not alter the inhibition by somatostatin in vitro. We conclude that obestatin does not act in pituitary gland to regulate GH secretion but may act in brain to alter thirst mechanisms. Importantly, in rats the effects of obestatin on food intake may be secondary to an action of the peptide to inhibit water drinking.     

Choice of Allocations and Constructs for Attributional or Consequential Life Cycle Assessment and Input‐Output Analysis

The divide between attributional and consequential research perspectives partly overlaps with the long‐standing methodological discussions in the life cycle assessment (LCA) and input‐output analysis (IO) research communities on the choice of techniques and models for dealing with situations of coproduction. The recent harmonization of LCA allocations and IO constructs revealed a more diverse set of coproduction models than had previously been understood. This increased flexibility and transparency in inventory modeling warrants a re‐evaluation of the treatment of coproduction in analyses with attributional and consequential perspectives. In the present article, the main types of coproductions situations and of coproduction models are reviewed, along with key desirable characteristics of attributional and consequential studies. A concordance analysis leads to clear recommendations, which call for important refinements to current guidelines for both LCA/IO practitioners and database developers. We notably challenge the simple association between, on the one hand, attributional LCA and partition allocation, and on the one hand, consequential LCA and substitution modeling.     

Galanin: evidence for a hypothalamic site of action to release growth hormone

Galanin is a 29 amino acid peptide that was isolated and characterized from porcine intestinal extracts. The presence of galanin-like immunoreactivity in neuronal elements in the hypothalamus and median eminence suggested a role for it in the hypothalamic control of anterior pituitary function. A hypothalamic site of action of galanin to stimulate growth hormone (GH) release is suggested by our observation that doses as low as 50 picomoles when infused into the third cerebroventricle of conscious, unrestrained ovariectomized rats resulted in significantly elevated plasma levels of GH. This effect was specific for GH and was dose-related. The failure of galanin to alter GH release from dispersed, cultured anterior pituitary cells in vitro further suggests that endogenous galanin plays a neuromodulatory role at the level of the median eminence, possibly affecting the release of known GH-releasing and/or inhibiting factors.     

French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides)

Systemic necrotizing vasculitis comprises a group of diseases resembling polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA): granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. The definitive diagnosis is made in cooperation with a reference center for autoimmune diseases and rare systemic diseases or a competency center. The management goals are: to obtain remission and, in the long term, healing; to reduce the risk of relapses; to limit and reduce the sequelae linked to the disease; to limit the side effects and the sequelae linked to the treatments; to improve or at least maintain the best possible quality of life; and to maintain socio-professional integration and/or allow a rapid return to school and/or professional activity. Information and therapeutic education of the patients and those around them are an integral part of the care. All health professionals and patients should be informed of the existence of patient associations. The treatment of vasculitis is based on variable combinations of glucocorticoids and immunosuppressants, chosen and adapted according to the disease concerned, the severity and/or extent of the disease, and the underlying factors (age, kidney function, etc.). Follow-up clinical and paraclinical examinations must be carried out regularly to clarify the progression of the disease, detect and manage treatment failures and possible relapses early on, and limit sequelae and complications (early then late) related to the disease or treatment. A distinction is made between the induction therapy, lasting approximately 3–6 months and aimed at putting the disease into remission, and the maintenance treatment, lasting 12–48 months, or even longer. The role of the increase or testing positive again for ANCA as a predictor of a relapse, which has long been controversial, now seems to have greater consensus: Anti-myeloperoxidase ANCAs are less often associated with a relapse of vasculitis than anti-PR3 ANCA.

     

Lifting the veil on the correction of double counting incidents in hybrid life cycle assessment

Life cycle assessment (LCA) and environmentally extended input–output analyses (EEIOA) are two techniques commonly used to assess environmental impacts of an activity/product. Their strengths and weaknesses are complementary, and they are thus regularly combined to obtain hybrid LCAs. A number of approaches in hybrid LCA exist, which leads to different results. One of the differences is the method used to ensure that mixed LCA and EEIOA data do not overlap, which is referred to as correction for double counting. This aspect of hybrid LCA is often ignored in reports of hybrid assessments and no comprehensive study has been carried out on it. This article strives to list, compare, and analyze the different existing methods for the correction of double counting. We first harmonize the definitions of the existing correction methods and express them in a common notation, before introducing a streamlined variant. We then compare their respective assumptions and limitations. We discuss the loss of specific information regarding the studied activity/product and the loss of coherent financial representation caused by some of the correction methods. This analysis clarifies which techniques are most applicable to different tasks, from hybridizing individual LCA processes to integrating complete databases. We finally conclude by giving recommendations for future hybrid analyses.     

Allocation of scarce resources in Africa during COVID‐19: Utility and justice for the bottom of the pyramid?

The COVID‐19 pandemic has raised important universal public health challenges. Conceiving ethical responses to these challenges is a public health imperative but must take context into account. This is particularly important in sub‐Saharan Africa (SSA). In this paper, we examine how some of the ethical recommendations offered so far in high‐income countries might appear from a SSA perspective. We also reflect on some of the key ethical challenges raised by the COVID‐19 pandemic in low‐income countries suffering from chronic shortages in health care resources, and chronic high morbidity and mortality from non‐COVID‐19 causes. A parallel is drawn between the distribution of severity of COVID‐19 disease and the classic “Fortune at the bottom of the pyramid” model that is relevant in SSA. Focusing allocation of resources during COVID‐19 on the ‘thick’ part of the pyramid in Low‐to‐Middle Income Countries (LMICs) could be ethically justified on utilitarian and social justice grounds, since it prioritizes a large number of persons who have been economically and socially marginalized. During the pandemic, importing allocation frameworks focused on the apex of the pyramid from the global north may therefore not always be appropriate. In a post‐COVID‐19 world, we need to think strategically about how health care systems can be financed and structured to ensure broad access to adequate health care for all who need it. The root problems underlying health inequity, exposed by COVID‐19, must be addressed, not just to prepare for the next pandemic, but to care for people in resource poor settings in non‐pandemic times.     

Identification of novel dysregulated circular RNAs in early-stage breast cancer

Breast cancer is a major cause of cancer-related death in women worldwide. Non-coding RNAs are a potential resource to be used as an early diagnostic biomarker for breast cancer. Circular RNAs are a recently identified group of non-coding RNA with a significant role in disease development with potential utility in diagnosis/prognosis in cancer. In this study, we identified 26 differentially expressed circular RNAs associated with early-stage breast cancer. RNA sequencing and two circRNA detection tools (find_circ and DCC) were used to understand the circRNA expression signature in breast cancer. We identified hsa_circ_0006743 (circJMJD1C) and hsa_circ_0002496 (circAPPBP1) to be significantly up-regulated in early-stage breast cancer tissues. Co-expression analysis identified four pairs of circRNA-miRNA (hsa_circ_0023990 : hsa-miR-548b-3p, hsa_circ_0016601 : hsa_miR-1246, hsa_circ_0001946 : hsa-miR-1299 and hsa_circ_0000117:hsa-miR-502-5p) having potential interaction. The miRNA target prediction and network analysis revealed mRNA possibly regulated by circRNAs. We have thus identified circRNAs of diagnostic implications in breast cancer and also observed circRNA-miRNA interaction which could be involved in breast cancer development.