Context:
Cushing's syndrome (CS) is challenging to diagnose. Increased prevalence of CS in specific patient populations has been reported, but routine screening for CS remains questionable. To ...decrease the diagnostic delay and improve disease outcomes, simple new screening methods for CS in at-risk populations are needed.
Objective:
To develop and validate a simple scoring system to predict CS based on clinical signs and an easy-to-use biochemical test.
Design:
Observational, prospective, multicenter.
Setting:
Referral hospital.
Patients:
A cohort of 353 patients attending endocrinology units for outpatient visits.
Interventions:
All patients were evaluated with late-night salivary cortisol (LNSC) and a low-dose dexamethasone suppression test for CS.
Main Outcome Measures:
Diagnosis or exclusion of CS.
Results:
Twenty-six cases of CS were diagnosed in the cohort. A risk scoring system was developed by logistic regression analysis, and cutoff values were derived from a receiver operating characteristic curve. This risk score included clinical signs and symptoms (muscular atrophy, osteoporosis, and dorsocervical fat pad) and LNSC levels. The estimated area under the receiver operating characteristic curve was 0.93, with a sensitivity of 96.2% and specificity of 82.9%.
Conclusions:
We developed a risk score to predict CS in an at-risk population. This score may help to identify at-risk patients in non-endocrinological settings such as primary care, but external validation is warranted.
A prediction model for Cushing's syndrome diagnosis in at-risk populations was developed based on clinical variables and late night salivary cortisol levels.
Abstract
Context
Epigenetic alterations may play a role in the development and behavior of pituitary neuroendocrine tumors (PitNETs).
Objective
To evaluate the effect of methylation of tumor ...suppressor genes (TSGs) on their gene expression and on the behavior of PitNETs.
Material and Methods
We used methylation-specific multiplex ligation-dependent probe amplification and quantitative real-time PCR techniques to analyze the DNA-promoter hypermethylation and gene expression of 35 TSGs in 105 PitNETs. We defined functionality, size, and invasiveness of tumors according to their clinical manifestations, Hardy’s classification, and MRI invasiveness of the cavernous sinus, respectively.
Results
We observed different methylation patterns among PitNET subtypes. The methylation status of TP73 correlated negatively with its gene expression in the overall series (P = 0.013) and in some subtypes. MSH6 and CADM1 showed higher methylation frequency in macroadenomas than in microadenomas in the overall series and in corticotroph PitNETs (all P ≤ 0.053). ESR1 and RASSF1 were more highly methylated in noninvasive than in invasive tumors in the overall series (P = 0.054 and P = 0.031, respectively) and in the gonadotroph subtype (P = 0.055 and P = 0.050, respectively). ESR1 and CASP8 appeared more hypermethylated in functioning than in silent corticotroph tumors (P = 0.034 and P = 0.034, respectively).
Conclusions
DNA methylation of TSGs has a selective effect on their gene expression and on the growth and invasiveness of PitNETs. Its involvement in their functionality is biased because all silent operated tumors are macroadenomas, whereas all operated microadenomas are functioning ones. Therefore, the subtypes of PitNETs should be considered different entities.
The study of methylation status of 35 TSGs in a series of 105 PitNETs allowed us to show a selective effect on gene expression and on the clinical behavior and functionality of these tumors.
Background: Chagas disease is widely distributed in tropical and subtropical regions of the Americas, including more than 50% of the Mexican territory. The southern region of the State of Mexico (the ...Tejupilco Sanitary Jurisdiction) was recently reported as endemic; however the pathogenicity of the circulating strains has not been studied in depth. Recent studies have reported Trypanosoma cruzi seropositive dogs in the villages of Malinalco and Zumpahuacan in the central south of the State of Mexico. Dogs are epidemiologically important, because the evolution of symptoms and pathology of Chagas disease in this vertebrate mimics the human disease, and because dogs maintain the domestic cycle of parasite transmission. Objectives: To study the clinical and pathological findings of a dog showing serological evidence of T. cruzi infection. The study of the canine, identified in the Malinalco locality, is expected to contribute to the general characterization and behavior of the pathogen in the region. Methods: Clinical (electrocardiogram, echocardiogram and clinical exam), pathological (necropsy and histopathology) and serologic (indirect hemagglutination test and enzyme-linked immunoassay) analyses were conducted in a 4-year-old dog naturally infected with T. cruzi. Results: The canine was diagnosed with dilated cardiomyopathy and hepatomegaly associated with congestive cardiac insufficiency, presumably provoked by chronic myocarditis and derived from natural infection with T. cruzi. Conclusion: T. cruzi strains circulating in the village of Malinalco, State of Mexico are pathogenic for dogs, and could be affecting other domestic animals, and even infecting humans in the region.
By the end of October 2022, the US HL-LHC Accelerator Upgrade Project (AUP) had completed fabrication of ten MQXFA magnets and tested eight of them. The MQXFA magnets are the low-beta quadrupole ...magnets to be used in the Q1 and Q3 Inner Triplet elements of the High Luminosity LHC. This AUP effort is shared by BNL, Fermilab, and LBNL, with strand verification tests at NHMFL. An important step of the AUP QA plan is the testing of MQXFA magnets in a vertical cryostat at BNL. The acceptance criteria that could be tested at BNL were all met by the first four production magnets (MQXFA03-MQXFA06). Subsequently, two magnets (MQXFA07 and MQXFA08) did not meet some of the criteria and were disassembled. Lessons learned during the disassembly of MQXFA07 caused a revision to the assembly specifications that were used for MQXFA10 and subsequent magnets. In this article, we present a summary of: 1) the fabrication and test data for all the MQXFA magnets; 2) the analysis of MQXFA07/A08 test results with characterization of the limiting mechanism; 3) the outcome of the investigation, including the lessons learned during MQXFA07 disassembly; and 4) the finite element analysis correlating observations with test performance.
In the age of JWST, temperate terrestrial exoplanets transiting nearby late-type M dwarfs provide unique opportunities for characterising their atmospheres, as well as searching for biosignature ...gases. We report here the discovery and validation of two temperate super-Earths transiting LP 890-9 (TOI-4306, SPECULOOS-2), a relatively low-activity nearby (32 pc) M6V star. The inner planet, LP 890-9b, was first detected by TESS (and identified as TOI-4306.01) based on four sectors of data. Intensive photometric monitoring of the system with the SPECULOOS Southern Observatory then led to the discovery of a second outer transiting planet, LP 890-9c (also identified as SPECULOOS-2c), previously undetected by TESS. The orbital period of this second planet was later confirmed by MuSCAT3 follow-up observations. With a mass of 0.118\(\pm\)0.002 \(M_\odot\), a radius of 0.1556\(\pm\)0.0086 \(R_\odot\), and an effective temperature of 2850\(\pm\)75 K, LP 890-9 is the second-coolest star found to host planets, after TRAPPIST-1. The inner planet has an orbital period of 2.73 d, a radius of \(1.320_{-0.027}^{+0.053}\) \(R_\oplus\), and receives an incident stellar flux of 4.09\(\pm\)0.12 \(S_\oplus\). The outer planet has a similar size of \(1.367_{-0.039}^{+0.055}\) \(R_\oplus\) and an orbital period of 8.46 d. With an incident stellar flux of 0.906 \(\pm\) 0.026 \(S_\oplus\), it is located within the conservative habitable zone, very close to its inner limit. Although the masses of the two planets remain to be measured, we estimated their potential for atmospheric characterisation via transmission spectroscopy using a mass-radius relationship and found that, after the TRAPPIST-1 planets, LP 890-9c is the second-most favourable habitable-zone terrestrial planet known so far. The discovery of this remarkable system offers another rare opportunity to study temperate terrestrial planets around our smallest and coolest neighbours.
This work presents an experimentally validated theoretical model for Mg alloy dissolution that accounts for transport phenomena. The galvanic interaction between AZ31 Mg alloy and low carbon steels ...in a solid electrolyte was simulated. The use of a solid agar-based electrolyte allowed to neglect the strong convective effects that are normally present during Mg alloy dissolution caused by copious hydrogen evolution. Furthermore, it allowed for a constant electrolyte thickness to be fixed. The gelled-electrolyte contained a pH indicator to permit a reliable visual tracking of the transient propagation of H+ and OH− ions during the electrochemical reaction.
Antitumor efficacy of systemically administered oncolytic adenoviruses (OAdv) is limited due to diverse factors such as liver sequestration, neutralizing interactions in blood, elimination by the ...immune system, and physical barriers in tumors. It is therefore of clinical relevance to improve OAdv bioavailability and tumor delivery. Among the variety of tumor-targeting strategies, the use of stem cells and specifically bone marrow-derived mesenchymal stem cells (BM-MSCs) is of particular interest due to their tumor tropism and immunomodulatory properties. Nonetheless, the invasive methods to obtain these cells, the low number of MSCs present in the bone marrow, and their restricted in vitro expansion represent major obstacles for their use in cancer treatments, pointing out the necessity to identify an alternative source of MSCs. Here, we have evaluated the use of menstrual blood-derived mesenchymal stem cells (MenSCs) as cell carriers for regional delivery of an OAdv in the tumor. Our results indicate that MenSCs can be isolated without invasive methods, they have an increased proliferation rate compared to BM-MSCs, and they can be efficiently infected with different serotype 5-based capsid-modified adenoviruses, leading to viral replication and release. In addition, our in vivo studies confirmed the tumor-homing properties of MenSCs after regional administration.
The pecan nutshell contains phytochemicals with various biological activities that are potentially useful in the prevention or treatment of diseases, such as cancer, diabetes, and metabolic ...imbalances associated with heart diseases.
The aim of this study is to update this topic by means of a literature review and include those studies that contribute to the knowledge of the chemical composition and biological activities of pecan nutshell, particularly those related to the therapeutic potential against some chronic degenerative diseases associated with oxidative stress.
Exhaustive and detailed review of the existing literature was conducted using electronic databases.
The pecan nutshell is a promising natural product with pharmaceutical uses in various diseases. However, additional research related to the assessment of efficient extraction methods and characterization, particularly the evaluation of the mechanisms of action in new in vivo models, is necessary to confirm these findings and development of new drugs with therapeutic use.
Electrochemical water treatment is one of the key topics of environmental electrochemistry. Identifying electrocatalytic materials capable of electrogenerating high oxidant species in situ seems to ...have catalyzed researchers’ interest in these processes. While most studies have focused on ideal lab-made solutions, translation to higher technology readiness levels and commercialization requires reframing research questions in context of real water matrices. In this current opinion, we discuss disconnects that may occur when focusing on synthetic solution treatment rather than on real waters. Future research can fill the gaps identified herein, thus facilitating application of electrochemical water treatment technologies.
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