Cabergoline treatment in acromegaly: pros

Cabergoline is an ergot-derived dopamine D2 receptor agonist which may be effective for the medical management of acromegaly. Its efficacy in reducing growth hormone and IGF-I levels, as well as its antiproliferative and pro-apoptotic effects on pituitary tumor cells, has been observed in several studies. Cabergoline may be used alone or as an add-on therapy to patients who are partially resistant to somatostatin analogs (SSA), or who do not achieve complete control with maximum doses of pegvisomant (PEG). Additionally, the convenience of its oral administration, allowing better compliance, and its lower economic cost, in comparison with SSA and PEG, favor cabergoline as an attractive option for acromegalic patients, who frequently require long-life medical treatment to achieve disease control. The few adverse events observed with prolonged DA therapy, mainly regarding cardiac valve disease, are not frequent at the doses generally used in acromegaly

New upper limits on low-frequency radio emission from isolated neutron stars with LOFAR

Neutron stars that show X-ray and $\gamma$-ray pulsed emission must, somewhere in the magnetosphere, generate electron-positron pairs. Such pairs are also required for radio emission, but then why do a number of these sources appear radio quiet? Here, we carried out a deep radio search towards four such neutron stars that are isolated X-ray/$\gamma$-ray pulsars but for which no radio pulsations have been detected yet. These sources are 1RXS J141256.0+792204 (Calvera), PSR J1958+2846, PSR J1932+1916 and SGR J1907+0919. Searching at lower radio frequencies, where the radio beam is thought to be wider, increases the chances of detecting these sources, compared to the earlier higher-frequency searches. We thus carried a search for periodic and single-pulse radio emission with the LOFAR radio telescope at 150 MHz. We used the known periods, and searched a wide range of dispersion measures, as the distances are not well constrained. We did not detect pulsed emission from any of the four sources. However, we put very constraining upper limits on the radio flux density at 150 MHz, of $\lesssim$1.4 mJy.Comment: 7 pages, 2 figures, 1 table. Accepted for publication in Astronomy & Astrophysic

Bringing Cardiovascular Comorbidities in Acromegaly to an Update. How Should We Diagnose and Manage Them?

Patients with acromegaly frequently develop cardiovascular comorbidities, which significantly affect their morbidity and contribute to an increased all-cause mortality. In this regard, the most frequent complications that these patients may encounter include hypertension, cardiomyopathy, heart valve disease, arrhythmias, atherosclerosis, and coronary artery disease. The specific underlying mechanisms involved in the pathophysiology of these comorbidities are not always fully understood, but uncontrolled GH/IGF-I excess, age, prolonged disease duration, and coexistence of other cardio-vascular risk factors have been identified as significant influencing predisposing factors. It is important that clinicians bear in mind the potential development of cardiovascular comorbidities in acromegalic patients, in order to promptly tackle them, and avoid the progression of cardiac abnormalities. In many cases, this approach may be performed using straightforward screening tools, which will guide us for further diagnosis and management of cardiovascular complications. This article focuses on those cardiovascular comorbidities that are most frequently encountered in acromegalic patients, describes their pathophysiology, and suggests some recommendations for an early and optimal diagnosis, management and treatment

Sustainability indicator for the prevention of potential thermal interferences between groundwater heat pump systems in urban aquifers

The steady increase of geothermal systems using groundwater is compromising the renewability of the geothermal resources in shallow urban aquifers. To ensure sustainability, scientifically-based criteria are required to prevent potential thermal interferences between geothermal systems. In this work, a management indicator (balanced sustainability index, BSI) applicable to groundwater heat pump systems is defined to assign a quantitative value of sustainability to each system, based on their intrinsic potential to produce thermal interference. The BSI indicator relies on the net heat balance transferred to the terrain throughout the year and the maximum seasonal thermal load associated. To define this indicator, 75 heating-cooling scenarios based in 23 real systems were established to cover all possible different operational conditions. The scenarios were simulated in a standard numerical model, adopted as a reference framework, and thermal impacts were evaluated. Two polynomial regression models were used for the interpolation of thermal impacts, thus allowing the direct calculation of the sustainability indicator developed as a function of heating-cooling ratios and maximum seasonal thermal loads. The BSI indicator could provide authorities and technicians with scientifically-based criteria to establish geothermal monitoring programs, which are critical to maintain the implementation rates and renewability of these systems in the cities

Finding answers in lipid profile in COVID-19 patients

Introduction: A small percentage of patients will develop a severe form of COVID-19 caused by SARS-CoV-2 infection. Thus, it is important to predict the potential outcomes identifying early markers of poor prognosis. In this context, we evaluated the association of SARS-CoV-2 infection with lipid abnormalities and their role in prognosis. Methods: Single-center, retrospective, observational study of COVID-19 patients admitted from March to October 2020. Clinical and laboratory data, comorbidities, and treatments for COVID-19 were evaluated. Main outcomes including intensive care unit (ICU) admission and mortality were analyzed with a multivariable Cox proportional hazards regression model. Results: We selected 1489 from a total of 2038 consecutive patients with confirmed COVID-19, who had a complete lipid profile before ICU admission. During the follow-up performed in 1109 patients, we observed a decrease in T-c, HDL-c, and LDL-c in 28.6%, 42.9%, and 30.4% of patients, respectively, and an increase in TG in 76.8%. The decrease of both T-c and HDL- c was correlated with a decrease in albumin levels (r = 0.39 and r = 0.37, respectively). Kaplan–Meier survival curves found an increased ICU admission in patients with lower T-c (HR 0.55, CI 0.36–0.86), HDL-c (HR 0.61, CI 0.45–0.84), and LDL-c (HR 0.85, CI 0.74–0.97). Higher values of T-c (HR 0.45, CI 0.36–0.57), HDL-c (HR 0.66, CI 0.54–0.81), and LDL-c (HR 0.86, CI 0.78–0.94) showed a protective effect on mortality. Conclusions: Abnormalities in lipid profile are a frequent complication of SARS-CoV-2 infection and might be related to morbidity and mortalityThis work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PI16-02091 and PI19-00584 (funded by Instituto de Salud Carlos III), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid) and cofinanced by FEDER funds to M.M

Vasoactive intestinal peptide axis is dysfunctional in patients with Graves’ disease

Vasoactive intestinal peptide (VIP) is a neuropeptide with potent immunoregulatory properties. Reduced serum VIP levels and alterations in VIP receptors/signaling on immune cells have been associated with different inflammatory/autoimmune diseases. However, its role in autoimmune thyroid diseases (AITD) remains unknown. This study examined the interrelationship between VIP system, autoimmune background and thyroid hormones in peripheral immune cells in patients with AITD. Only Graves’ disease (GD) patients showed significantly lower serum VIP levels when compared to healthy subjects and to Hashimoto’s thyroiditis patients. Serum VIP levels were lower at the onset of GD, showing a significant negative correlation with thyroid hormone levels. The expression of VIP receptors, VPAC1 and VPAC2, was significantly upregulated in peripheral blood mononuclear cells (PBMC) from GD patients. There was an impairment of VIP signalling in these patients, probably attributable to a dysfunction of VPAC1 with preservation of VPAC2. The correlation between VPAC1 and thyroid hormone receptor expression in PBMC from healthy subjects was lost in GD patients. In summary, the VIP system is altered in peripheral immune cells of GD patients and this finding is associated with different thyroid hormone receptor patterns, showing a dynamic inter-regulation and a prominent role of VIP in this setting.This work has been supported by Instituto de Salud Carlos III, Spain, cofinanced by FEDER, European Union: RETICS program, Red de Investigación en Inflamación y Enfermedades Reumáticas (RD16/0012/0008, PI17/00027, PI16-02091, PIE13-0004) and from Consejería de Educación, Juventud y Deporte, Comunidad de Madrid: B2017/BMD372

Combined biological and chemical assessment of estrogenic activities in wastewater treatment plant effluents

Five wastewater treatment plant effluents were analyzed for known endocrine disrupters and estrogenicity. Estrogenicity was determined by using the yeast estrogen screen (YES) and by measuring the blood plasma vitellogenin (VTG) concentrations in exposed male rainbow trout (Oncorhynchus mykiss). While all wastewater treatment plant effluents contained measurable concentrations of estrogens and gave a positive response with the YES, only at two sites did the male fish have significantly increased VTG blood plasma concentrations after the exposure, compared to pre-exposure concentrations. Estrone (E1) concentrations ranged up to 51ngL−1, estradiol (E2) up to 6ngL−1, and ethinylestradiol (EE2) up to 2ngL−1 in the 90samples analyzed. Alkylphenols, alkylphenolmonoethoxylates and alkylphenoldiethoxylates, even though found at µgL−1 concentrations in effluents from wastewater treatment plants with a significant industrial content, did not contribute much to the overall estrogenicity of the samples taken due to their low relative potency. Expected estrogenicities were calculated from the chemical data for each sample by using the principle of concentration additivity and relative potencies of the various chemicals as determined with the yeast estrogen screen. Measured and calculated estradiol equivalents gave the same order of magnitude and correlated rather well (R 2=0.6

Fluorescent carbon dioxide indicators

Over the last decade, fluorescence has become the dominant tool in biotechnology and medical imaging. These exciting advances have been underpinned by the advances in time-resolved techniques and instrumentation, probe design, chemical / biochemical sensing, coupled with our furthered knowledge in biology. Complementary volumes 9 and 10, Advanced Concepts of Fluorescence Sensing: Small Molecule Sensing and Advanced Concepts of Fluorescence Sensing: Macromolecular Sensing, aim to summarize the current state of the art in fluorescent sensing. For this reason, Drs. Geddes and Lakowicz have invited chapters, encompassing a broad range of fluorescence sensing techniques. Some chapters deal with small molecule sensors, such as for anions, cations, and CO2, while others summarize recent advances in protein-based and macromolecular sensors. The Editors have, however, not included DNA or RNA based sensing in this volume, as this were reviewed in Volume 7 and is to be the subject of a more detailed volume in the near future

Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors

Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors, and their biological behavior is not well known. We studied the presence and potential functional roles of somatostatin receptors (sst1-5), focusing particularly on the truncated variants (sst5TMD4, sst5TMD5) and on their relationships with the angiogenic system (Ang/Tie-2 and VEGF) in human GEP-NETs. Experimental Design: We evaluated 42 tumor tissue samples (26 primary/16 metastatic) from 26 patients with GEP-NETs, and 30 non-tumoral tissues (26 from adjacent non-tumor regions and 4 from normal controls) from a single center. Expression of sst1-5, sst5TMD4, sst5TMD5, Ang1-2, Tie-2 and VEGF was analyzed using real-time qPCR, immunofluorescence and immunohistochemistry. Expression levels were associated with tumor characteristics and clinical outcomes. Functional role of sst5TMD4 was analyzed in GEP-NET cell lines. Results: sst1 exhibited the highest expression in GEP-NET, whilst sst2 was the most frequently observed sst-subtype (90.2%). Expression levels of sst1, sst2, sst3, sst5TMD4, and sst5TMD5 were significantly higher in tumor tissues compared to their adjacent non-tumoral tissue. Lymph-node metastases expressed higher levels of sst5TMD4 than in its corresponding primary tumor tissue. sst5TMD4 was also significantly higher in intestinal tumor tissues from patients with residual disease of intestinal origin compared to those with non-residual disease. Functional assays demonstrated that the presence of sst5TMD4 was associated to enhanced malignant features in GEP-NET cells. Angiogenic markers correlated positively with sst5TMD4, which was confirmed by immunohistochemical/fluorescence studies. Conclusions: sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs.This work has received the following grants: Proyectos de Investigación en Salud (FIS) PI13-01414, and PIE-0041 (funded by Instituto de Salud Carlos III) and S2011/BMD-2328 TIRONET (funded by Comunidad de Madrid) (to MM). BIO-0139, CTS-5051, CTS-1406, PI-0369-2012, BFU2010-19300, BFU2013-43282-R, PI13/00651, CIBERobn and Ayuda Merck Serono 2013 (to RML and JPC). Fellowship CTS-5051 (to AIC). “Sara Borrell” program CD11/00276 (to MDG