25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1.

Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case-control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive protein (CRP, marker of inflammation). Logistic regression was used to test for associations between study variables and the risk of invasive breast cancer. Two hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and 49% were premenopausal. There were negative correlations for 25OHD with body mass index (BMI), insulin, CRP, and leptin. BMI ≥ 25 kg/m(2) was associated with higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen treatment was associated with lower risk (OR = 0.44, p < 0.001). Suboptimal 25OHD (<72 nmol/l) did not influence breast cancer risk (OR = 1.06, p = 0.76). When evaluated as continuous variables, 25OHD, insulin, CRP, and leptin levels were not associated with breast cancer risk (all p > 0.34). In this high risk population, higher BMI was associated with a greater breast cancer risk. Serum levels of 25OHD, insulin, CRP, and leptin were not independent predictors of either breast cancer risk or tamoxifen benefit

Guidance for laboratories performing molecular pathology for cancer patients

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here

LinTT1 peptide-functionalized liposomes for targeted breast cancer therapy

Breast cancer, with around 2 million new cases in 2019, is the second most common cancer worldwide and the second leading cause of cancer death among females. The aim of this work is to prepare a targeting nanoparticle through the conjugation of LinTT1 peptide, a specific molecule targeting p32 protein overexpressed by breast cancer and cancer associated cells, on liposomes' surface. This approach increases the cytotoxic effects of doxorubicin (DOX) and sorafenib (SRF) co-loaded in therapeutic liposomes on both 2D and 3D breast cancer cellular models. The liposome functionalization leads to a higher interaction with 3D breast cancer spheroids than bare ones. Moreover, interaction studies between LinTT1-functionalized liposomes and M2 primary human macrophages show an internalization of 50% of the total nanovesicles that interact with these cells, while the other 50% results only associated to cell surface. This finding suggests the possibility to use the amount of associated liposomes to enrich the hypoxic tumor area, exploiting the ability of M2 macrophages to accumulate in the central core of tumor mass. These promising results highlight the potential use of DOX and SRF co-loaded LinTT1-functionalized liposomes as nanomedicines for the treatment of breast cancer, especially in triple negative cancer cells.Peer reviewe

On the design of mesostructured acidic catalysts for the one-pot dimethyl ether production from CO2

Dimethyl ether (DME) production from hydrogenation of CO2 based on two-function (redox and acidic) catalysts is receiving increasing attention due to the high demand for alternative and green fuels. In this work, we propose different mesostructured acidic metal oxides as methanol dehydration catalysts to be used as physical mixtures in combination with a commercial Cu-based redox catalyst (CZA) for the CO2-to-DME one-pot production. Al-MCM41, TiO2 and TiO2-ZrO2 mixed oxides, obtained through Sol-Gel methods, either in a conventional or Evaporation-Induced Self-Assembly approach were selected as mesostructured acidic systems and compared with a commercial zeolite (ferrierite). The regular mesoporous structure should render the active sites of the acidic catalyst easily accessible for CO2 and H2 and allow a homogeneous dispersion of the redox phase inside the mesopores in view of a possible development of bifunctional catalysts (redox + acidic). With the aim of understanding how the textural and acidic properties can be correlated with the performances and eventually design efficient dehydration catalysts, a careful study on the acidic sites was performed by both adsorption microcalorimetry with ammonia and FTIR-monitored adsorption of pyridine. The results of the performances highlighted a higher activity toward methanol dehydration for catalysts featured by Bronsted sites (zeolite and Al-MCM-41); as for catalysts with Lewis sites only (TiO2, Ti0.77Zr0.23O2) better performances were shown in case of systems presenting sites of moderate strength (Ti0.77Zr0.23O2). In the light of the above, Al-MCM-41 and TiO2ZrO2 demonstrated to be the most promising mesostructured dehydration catalysts in terms of selectivity to DME

Leveraging a Rapid, Round-the-Clock HIV Testing System to Screen for Acute HIV Infection in a Large Urban Public Medical Center

Methods The hospital laboratory performed round-the-clock rapid HIV antibody testing on venipuncture specimens from patients undergoing HIV testing in hospital and community clinics, inpatient settings, and the emergency department. For patients with negative results, a public health laboratory conducted pooled HIV RNA testing for acute HIV infection. The laboratories communicated positive results from the hospital campus to a linkage team. Linkage was defined as one outpatient HIV-related visit. Results Among 7,927 patients, 8,550 rapid tests resulted in 137 cases of HIV infection (1.7%, 95% CI 1.5%–2.0%), of whom 46 were new HIV diagnoses (0.58%, 95% CI 0.43%–0.77%). Pooled HIV RNA testing of 6,704 specimens (78.4%) resulted in 3 cases of acute HIV infection (0.05%, 95% CI 0.01%–0.14) and increased HIV case detection by 3.5%. Half of new HIV diagnoses and 2/3 of acute infections were detected in the emergency department and urgent care clinic. Rapid test sensitivity was 98.9% (95% CI 93.8%– 99.8%); specificity was 99.9% (95% CI 99.7%–99.9%). Over 95% of newly diagnosed and out-of-care HIV-infected patients were linked to care. Conclusions Patients undergoing HIV testing in emergency departments and urgent care clinics may benefit from being simultaneously screened for acute HIV infection

Reflections and Experiences of a Co-Researcher involved in a Renal Research Study

Background Patient and Public Involvement (PPI) is seen as a prerequisite for health research. However, current Patient and public involvement literature has noted a paucity of recording of patient and public involvement within research studies. There have been calls for more recordings and reflections, specifically on impact. Renal medicine has also had similar criticisms and any reflections on patient and public involvement has usually been from the viewpoint of the researcher. Roles of patient and public involvement can vary greatly from sitting on an Advisory Group to analysing data. Different PPI roles have been described within studies; one being a co-researcher. However, the role of the co-researcher is largely undefined and appears to vary from study to study. Methods The aims of this paper are to share one first time co-researcher's reflections on the impact of PPI within a mixed methods (non-clinical trial) renal research study. A retrospective, reflective approach was taken using data available to the co-researcher as part of the day-to-day research activity. Electronic correspondence and documents such as meeting notes, minutes, interview thematic analysis and comments on documents were re-examined. The co-researcher led on writing this paper. Results This paper offers a broad definition of the role of the co-researcher. The co-researcher reflects on undertaking and leading on the thematic analysis of interview transcripts, something she had not previously done before. The co-researcher identified a number of key themes; the differences in time and responsibility between being a coresearcher and an Advisory Group member; how the role evolved and involvement activities could match the co-researchers strengths (and the need for flexibility); the need for training and support and lastly, the time commitment. It was also noted that it is preferable that a co-researcher needs to be involved from the very beginning of the grant application. Conclusions The reflections, voices and views of those undertaking PPI has been largely underrepresented in the literature. The role of co-researcher was seen to be rewarding but demanding, requiring a large time commitment. It is hoped that the learning from sharing this experience will encourage others to undertake this role, and encourage researchers to reflect on the needs of those involved.Peer reviewedFinal Published versio

Tuning the activity of cobalt 2-hydroxyphosphonoacetates-derived electrocatalysts for water splitting and oxygen reduction: insights into the local order by pair distribution function analysis

Pyrophosphate- or phosphide-based iron/cobalt electrocatalysts were prepared from the metal (R,S)−2-hydroxyphosphonoacetates to evaluate the effects of metal composition, N-doping and P-enrichment on the electrocatalytic activity. Rietveld and Pair Distribution Function analysis were used to determine phase composition. Irrespectively of the amorphous or crystalline nature, all pyrolyzed solids transformed under OER operation into biphasic Fe/CoO(OH), composed of discrete clusters (size ≤ 20 Å). Carbon paper-supported Fe0.2Co0.8O(OH) electrocatalysts displayed the best OER performances (overpotentials of 270–279 mV at 10 mA·cm−2), attributable to the formation of highly active bimetallic intermediate species. For HER, increased concentration of o-CoP in phosphide-based electrocatalysts resulted in improved performance, up to an overpotential of 140 mV. Employed as anode in alkaline water splitting, amorphous Fe-doped cobalt pyrophosphate and phosphide-derived electrocatalysts showed a cell voltage of 1.58 V at 10 mA·cm−2, with comparable stability to that of RuO2 and requiring lower voltage demand at high current densities.This work was funded by the PID2019-110249RB-I00/AEI/10.13039/501100011033; TED2021–129836B-I00/AEI/10.13039/501100011033/Unión Europea NextGenerationEU/PRTR (MICIU, Spain) and P20-00416 (Junta de Andalucia, Spain/FEDER) research projects. Synchrotron X-ray powder diffraction studies were performed at MSPD04 beamline at ALBA Synchrotron Light with the collaboration of ALBA staff. A.V.C. thanks MICIU for PRE2020-094459 student grant. R.M.P.C. acknowledges funding by project acknowledges B1_2022-23 (Plan Propio UMA). M.B.G. thanks PAIDI2020-DOC_00272 research grant (Junta de Andalucia, Spain). Funding for open access charge: Universidad de Málaga / CBUA

Reactive hyperemia is associated with adverse clinical outcomes in heart failure

© 2016 Elsevier Inc. All rights reserved. Introduction Impaired endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), is an established risk factor for cardiovascular events. FMD is impaired in heart failure (HF) patients, but less is known about hyperemic brachial artery flow. We investigated the relationship between FMD and hyperemic flow with adverse clinical outcomes in HF patients. Methods Brachial artery FMD and hyperemic flow were assessed in 156 patients (70.5 % Male; 45.5% Caucasian; mean age (± SD) = 56.2 (±12.4) years) with HF and reduced left ventricular ejection fraction (LVEF). Cox proportional hazard models were used to assess the potential explanatory association of FMD and hyperemic flow with the composite outcome of death or cardiovascular hospitalization over a median 5-year follow-up period. Results Both FMD and hyperemic flow were negatively correlated with age, but unrelated to sex, race, body mass index, LVEF or N-terminal pro-B-Type natriuretic peptide (NT-ProBNP). Reduced hyperemic flow, but not FMD, was associated with an increased risk of death or cardiac hospitalization after controlling for traditional risk factors. Conclusion The association of reduced hyperemic flow with increased risk of adverse clinical outcomes suggests that micro-vascular function may be an important prognostic marker in patients with HF