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Article ; Online: Conserving Brazil's free-flowing rivers.

Fernandes, Stephannie / Couto, Thiago B A / Ferreira, Manuel / Pompeu, Paulo S / Athayde, Simone / Anderson, Elizabeth P / Fernandes, Geraldo W

Science (New York, N.Y.)

2023 Volume 379, Issue 6635, Page(s) 887

Language	English
Publishing date	2023-03-02
Publishing country	United States
Document type	Letter
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adg9858
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Zs.MG 77: Show issues

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Article ; Online: Binding studies of synthetic cathinones to human serum albumin by high-performance affinity chromatography.

Sofia Almeida, Ana / Cardoso, Tony / Cravo, Sara / Elizabeth Tiritan, Maria / Remião, Fernando / Fernandes, Carla

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2023 Volume 1227, Page(s) 123836

Abstract: ... on HSA, namely (S)-ibuprofen and warfarin. Competition was observed between the tested drugs and ...

Abstract	The binding affinity to human serum albumin (HSA) of a series of fourteen synthetic cathinones, new psychoactive substances widely abused, was investigated by high-performance affinity chromatography (HPAC). Zonal elution experiments were conducted to measure the retention times of each synthetic cathinone on an HSA column, which enabled the calculation of the percentage of the drug bound. For some synthetic cathinones, enantioselectivity on HSA was found. To gather information on the HSA binding sites and better understand the chiral recognition mechanisms, enantioresolution of selected cathinones was carried out at a milligram scale through liquid chromatography (LC) with carbamate polysaccharide-based columns. This work was followed by zonal displacement chromatography using known competitors with specific binding sites on HSA, namely (S)-ibuprofen and warfarin. Competition was observed between the tested drugs and both competitors (except for pentedrone with warfarin), which is consistent with an allosteric competition involving a non-cooperative binding mechanism.
MeSH term(s)	Humans ; Serum Albumin, Human/metabolism ; Warfarin/chemistry ; Serum Albumin/chemistry ; Synthetic Cathinone ; Chromatography, Affinity/methods ; Protein Binding
Chemical Substances	Serum Albumin, Human (ZIF514RVZR) ; Warfarin (5Q7ZVV76EI) ; Serum Albumin ; Synthetic Cathinone
Language	English
Publishing date	2023-07-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2023.123836
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Article: Antimicrobial and Anti-Infective Activity of Natural Products-Gaining Knowledge from Novel Studies.

Fernandes, Elizabeth S / da Silva Figueiredo, Isabella F / Monteiro, Cinara R A V / Monteiro-Neto, Valério

Antibiotics (Basel, Switzerland)

2023 Volume 12, Issue 6

Abstract: Despite advances in the development of antimicrobial drugs in the last centuries, antimicrobial resistance has consistently raised in the last decades, compromising their effectiveness. Novel antimicrobial compounds, especially from natural sources, ... ...

Abstract	Despite advances in the development of antimicrobial drugs in the last centuries, antimicrobial resistance has consistently raised in the last decades, compromising their effectiveness. Novel antimicrobial compounds, especially from natural sources, including plants, microorganisms, and animals, have since become a growing area of research. In this context, studies covering the investigation of their ability to combat resistant microorganisms, either by neutralization or inactivation of pathogen resistance mechanisms and virulence properties, have gained attention. Herein, a collection of 19 manuscripts focused on the antimicrobial and anti-infective activity of natural products, including their mechanisms of action, in silico evidence of antimicrobial activity, synergistic associations with antibiotics, and other aspects, will be discussed.
Language	English
Publishing date	2023-06-15
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics12061051
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Article ; Online: Evaluation of the type of silo associated or not with additives on the nutritional value, aerobic stability, and microbiology of pearl millet silage.

Camilo, Michele Gabriel / Fernandes, Alberto M / Processi, Elizabeth F / Motta, Olney V DA / Roseira, João Paulo S / Oliveira, Tadeu S DE

Anais da Academia Brasileira de Ciencias

2023 Volume 95, Issue 2, Page(s) e20210421

Abstract: The objective of this study was to evaluate the effect of the silo type with the use or not of additives on chemical composition, in vitro gas production, fermentative losses, aerobic stability, fermentative profile, and microbial population of the pearl ...

Abstract	The objective of this study was to evaluate the effect of the silo type with the use or not of additives on chemical composition, in vitro gas production, fermentative losses, aerobic stability, fermentative profile, and microbial population of the pearl millet silage. We used a randomized block design in a 2 × 3 factorial scheme, with two types of silos (plastic bags and PVC silos) and three additives ([CON] without additive; 50 g of ground corn [GC], and Lactobacillus plantarum and Propionibacterium acidipropionici, with five replicates per treatment. We evaluated the chemical analyses, in vitro gas production, losses, aerobic stability, pH, ammoniacal nitrogen, and microbial population of the silages. The use of GC in the ensiling process improved the chemical composition of the silages. The additives and the type of silo did not affect (p > 0.05) the gas production kinetics, ammoniacal nitrogen, and population of lactic acid bacteria and fungi. Thus, the use of ground corn improved the nutritional value of the pearl millet silage. In turn, the inoculant provided better aerobic stability for the pearl millet silage. The plastic bag silos without vacuum were not efficient in the ensiling process like the PVC silos, which resulted in low-quality silage.
MeSH term(s)	Silage/analysis ; Lactobacillus ; Pennisetum ; Zea mays/chemistry ; Fermentation ; Nutritive Value ; Plastics
Chemical Substances	Plastics
Language	English
Publishing date	2023-04-03
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2046885-4
ISSN	1678-2690 ; 0001-3765
ISSN (online)	1678-2690
ISSN	0001-3765
DOI	10.1590/0002-3765202320210421
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Article: Performance of a Norfentanyl Immunoassay in Specimens with Low Concentrations of Fentanyl and/or Norfentanyl.

Uljon, Sacha / Tolan, Nicole V / Mahowald, Grace K / Khaliq, Tahira / Urwiller, Elizabeth D / Fernandes, Maria Daluz / Basu, Sankha S / Kang, Phillip / Erickson, Timothy B / Hayes, Bryan D / Chai, Peter R / Melanson, Stacy E F

The journal of applied laboratory medicine

2024

Abstract: Background: Many fentanyl immunoassays are limited in their ability to detect norfentanyl. Urine specimens collected from individuals who have been exposed to fentanyl frequently have detectable concentrations of norfentanyl (≥2 ng/mL) but low ... ...

Abstract	Background: Many fentanyl immunoassays are limited in their ability to detect norfentanyl. Urine specimens collected from individuals who have been exposed to fentanyl frequently have detectable concentrations of norfentanyl (≥2 ng/mL) but low concentrations of fentanyl (<2 ng/mL) by LC-MS/MS. The Lin-Zhi Fentanyl II Immunoassay (Lin-Zhi) claims 100% cross-reactivity with norfentanyl and therefore may detect exposure missed by other assays. Methods: In addition to verifying the manufacturer's analytical sensitivity claims, we selected 92 urine specimens with low-positive Lin-Zhi results (1-99 absorbance units, lowest 10%) for analysis by the Immunalysis Health Equity Impact Assessment and ARK II fentanyl methods. The accuracy of the 3 immunoassays was compared to LC-MS/MS as the reference method. Results: Spiking studies using purified fentanyl and norfentanyl and a set of 100 consecutive specimens confirmed the manufacturer's claims of limit of detection for fentanyl (3.8 ng/mL) and norfentanyl (5.0 ng/mL). However, the 92 low-positive patient specimens demonstrated concentrations of norfentanyl and fentanyl below 2.0 ng/mL by LC-MS/MS, with 47 (51%) having only norfentanyl detected. When comparing Lin-Zhi to the Immunalysis and ARK II immunoassays, only 27 (29%) of the 92 specimens were concordant. Fifty-two (57%) of the specimens were positive by LC-MS/MS and Lin-Zhi but false negative by one or both other immunoassays. Seven specimens (8%) were positive by Lin-Zhi but negative by the other immunoassays and had undetectable concentrations (<2 ng/mL) of fentanyl and norfentanyl by LC-MS/MS. Conclusions: The clinical sensitivity of the Lin-Zhi exceeds the manufacturer's claims, providing results comparable to LC-MS/MS methods.
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article
ISSN	2576-9456
ISSN	2576-9456
DOI	10.1093/jalm/jfae036
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Article ; Online: Transient Receptor Potential Canonical 5 (TRPC5): Regulation of Heart Rate and Protection against Pathological Cardiac Hypertrophy.

Thakore, Pratish / Clark, James E / Aubdool, Aisah A / Thapa, Dibesh / Starr, Anna / Fraser, Paul A / Farrell-Dillon, Keith / Fernandes, Elizabeth S / McFadzean, Ian / Brain, Susan D

Biomolecules

2024 Volume 14, Issue 4

Abstract: TRPC5 is a non-selective cation channel that is expressed in cardiomyocytes, but there is a lack of knowledge of its (patho)physiological role in vivo. Here, we examine the role of TRPC5 on cardiac function under basal conditions and during cardiac ... ...

Abstract	TRPC5 is a non-selective cation channel that is expressed in cardiomyocytes, but there is a lack of knowledge of its (patho)physiological role in vivo. Here, we examine the role of TRPC5 on cardiac function under basal conditions and during cardiac hypertrophy. Cardiovascular parameters were assessed in wild-type (WT) and global TRPC5 knockout (KO) mice. Despite no difference in blood pressure or activity, heart rate was significantly reduced in TRPC5 KO mice. Echocardiography imaging revealed an increase in stroke volume, but cardiac contractility was unaffected. The reduced heart rate persisted in isolated TRPC5 KO hearts, suggesting changes in basal cardiac pacing. Heart rate was further investigated by evaluating the reflex change following drug-induced pressure changes. The reflex bradycardic response following phenylephrine was greater in TRPC5 KO mice but the tachycardic response to SNP was unchanged, indicating an enhancement in the parasympathetic control of the heart rate. Moreover, the reduction in heart rate to carbachol was greater in isolated TRPC5 KO hearts. To evaluate the role of TRPC5 in cardiac pathology, mice were subjected to abdominal aortic banding (AAB). An exaggerated cardiac hypertrophy response to AAB was observed in TRPC5 KO mice, with an increased expression of hypertrophy markers, fibrosis, reactive oxygen species, and angiogenesis. This study provides novel evidence for a direct effect of TRPC5 on cardiac function. We propose that (1) TRPC5 is required for maintaining heart rate by regulating basal cardiac pacing and in response to pressure lowering, and (2) TRPC5 protects against pathological cardiac hypertrophy.
MeSH term(s)	Animals ; TRPC Cation Channels/metabolism ; TRPC Cation Channels/genetics ; Cardiomegaly/metabolism ; Mice, Knockout ; Mice ; Heart Rate ; Male ; Myocytes, Cardiac/metabolism ; Mice, Inbred C57BL ; Blood Pressure
Chemical Substances	TRPC Cation Channels ; Trpc5 protein, mouse
Language	English
Publishing date	2024-04-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom14040442
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Article ; Online: Predictors of germline genetic testing referral and completion in ovarian cancer patients at a Comprehensive Cancer Center.

Saylor, Katherine W / Fernandes, Elizabeth Q / Adams, Michael / Paraghamian, Sarah / Shalowitz, David I

Gynecologic oncology

2024 Volume 186, Page(s) 53–60

Abstract: Objectives: To identify predictors of referral and completion of germline genetic testing among newly diagnosed ovarian cancer patients, with a focus on geographic social deprivation, oncologist-level practices, and time between diagnosis and completion ...

Abstract	Objectives: To identify predictors of referral and completion of germline genetic testing among newly diagnosed ovarian cancer patients, with a focus on geographic social deprivation, oncologist-level practices, and time between diagnosis and completion of testing. Methods: Clinical and sociodemographic data were abstracted from medical records of patients newly diagnosed with ovarian cancer between 2014 and 2019 in the University of North Carolina Health System. Factors associated with referral for genetic counseling, completion of germline testing, and time between diagnosis and test results were identified using multivariable regression. Results: 307/459 (67%) patients were referred for genetic counseling and 285/459 (62%) completed testing. The predicted probability of test completion was 0.83 (95% CI: 0.77-0.88) for patients with a referral compared to 0.27 (95% CI: 0.18-0.35) for patients without a referral. The predicted probability of referral was 0.75 (95% CI: 0.69-0.82) for patients at the 25th percentile of ZIP code-level Social Deprivation Index (SDI) and 0.67 (0.60-0.74) for patients at the 75th percentile of SDI. Referral varied by oncologist, with predicted probabilities ranging from 0.47 (95% CI: 0.32-0.62) to 0.93 (95% CI: 0.85-1.00) across oncologists. The median time between diagnosis and test results was 137 days (IQR: 55-248 days). This interval decreased by a predicted 24.46 days per year (95% CI: 37.75-11.16). Conclusions: We report relatively high germline testing and a promising trend in time from diagnosis to results, with variation by oncologist and patient factors. Automated referral, remote genetic counseling and sample collection, reduced out-of-pocket costs, and educational interventions should be explored.
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2024.03.028
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Article ; Online: Photothermal therapies to improve immune checkpoint blockade for cancer.

Balakrishnan, Preethi B / Sweeney, Elizabeth E / Ramanujam, Anvitha S / Fernandes, Rohan

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

2020 Volume 37, Issue 3, Page(s) 34–49

Abstract: Immune checkpoint blockade (ICB) comprising monoclonal antibodies (mAbs) against immune 'checkpoints', such as CTLA-4 and the PD1/PDL1 axis have dramatically improved clinical outcomes for patients with cancer. However, ICB by itself has failed to ... ...

Abstract	Immune checkpoint blockade (ICB) comprising monoclonal antibodies (mAbs) against immune 'checkpoints', such as CTLA-4 and the PD1/PDL1 axis have dramatically improved clinical outcomes for patients with cancer. However, ICB by itself has failed to provide benefit in a wide range of solid tumors, where recurrence still occurs with high incidence. These poor response rates may be due to the therapeutic shortcomings of ICB; namely, a lack of cancer-specific cytotoxicity and ability to debulk tumors. To overcome these limitations, effective ICB therapy may require the combination with other complementary therapeutic platforms. Here, we propose that photothermal therapy (PTT) is an ideal therapeutic modality for combination with ICB because it can generate both tumor-specific cytotoxicity and immunogenicity. PTT elicits these specific effects because it is a localized thermal ablation technique that utilizes light-responsive nanoparticles activated by a wavelength-matched laser. While ICB immunotherapy alone improves cancer immunogenicity but does not generate robust antitumor cytotoxicity, nanoparticle-based PTT elicits targeted and controlled cytotoxicity but sub-optimal long-term immunogenicity. Thus, the two platforms offer complementary and potentially synergistic antitumor effects, which will be detailed in this review. We highlight three classes of nanoparticles used as agents of PTT (i.e., metallic inorganic nanoparticles, carbon-based nanoparticles and organic dyes), and illustrate the potential for nanoparticle-based PTT to potentiate the effects of ICB in preclinical models. Through this discussion, we aim to present PTT combined with ICB as a potent synergistic combination treatment for diverse cancer types currently refractory to ICB as well as PTT monotherapies.
MeSH term(s)	Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Neoplasms/drug therapy ; Photothermal Therapy
Chemical Substances	Antineoplastic Agents, Immunological ; Immune Checkpoint Inhibitors
Language	English
Publishing date	2020-01-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632526-9
ISSN	1464-5157 ; 0265-6736
ISSN (online)	1464-5157
ISSN	0265-6736
DOI	10.1080/02656736.2020.1797190
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Article: Analysis of the Effect of the TRPC4/TRPC5 Blocker, ML204, in Sucrose-Induced Metabolic Imbalance.

Araújo, Mizael C / Soczek, Suzany H S / Pontes, Jaqueline P / Pinto, Bruno A S / França, Lucas M / Soley, Bruna da Silva / Santos, Gabriela S / Saminez, Warlison F de Silva / Fernandes, Fernanda K M / Lima, João L do Carmo / Maria-Ferreira, Daniele / Rodrigues, João F S / Quintão, Nara L M / Monteiro-Neto, Valério / Paes, Antônio M A / Fernandes, Elizabeth S

Pharmaceuticals (Basel, Switzerland)

2023 Volume 16, Issue 8

Abstract: Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in ... ...

Abstract	Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast, restaurant, and processed foods. Herein, we investigated the effects of a TRPC4/TRPC5 blocker, ML204, in the metabolic imbalances triggered by early exposure to sucrose-enriched diet in mice. TRPC4 and TRPC5 belong to the family of non-selective Ca
Language	English
Publishing date	2023-08-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16081100
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Article ; Online: Evaluation of junior doctors' knowledge of corneal donation and the new opt-out system in England.

Gopal, Bhavesh P / Titi-Lartey, Owuraku Asiedu / Fernandes, Princeton / Noubani, Nur-Emel / Blatherwick, Elizabeth / Said, Dalia / Dua, Harminder Singh / Ting, Darren S J

Postgraduate medical journal

2021 Volume 98, Issue e3, Page(s) e174–e176

MeSH term(s)	Attitude of Health Personnel ; England ; Humans ; Medical Staff, Hospital
Language	English
Publishing date	2021-05-26
Publishing country	England
Document type	Letter
ZDB-ID	80325-x
ISSN	1469-0756 ; 0032-5473
ISSN (online)	1469-0756
ISSN	0032-5473
DOI	10.1136/postgradmedj-2021-140108
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