Publications by authors named "Carlos Martinez"

429 Publications

A prospective clinical and transcriptomic feasibility study of oral-only hormonal therapy with radiation for unfavorable prostate cancer in men 70 years of age and older or with comorbidity.

Cancer 2021 Apr 21. Epub 2021 Apr 21.

Department of Radiation and Cellular Oncology, University of Chicago Medicine, Chicago, Illinois.

Background: Androgen deprivation therapy (ADT) improves outcomes in unfavorable-risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone-releasing hormone (LHRH) agonists with a 5-α-reductase inhibitor (5-ARI) would improve hormonal health-related quality of life (HRQOL) without differentially suppressing androgen-responsive (AR) gene expression.

Methods: Patients with localized unfavorable-risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5-ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long-term LHRH agonist with RT. RNA sequencing was performed from matched pre-/post-ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment.

Results: Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow-up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6-month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4-year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold-change = 2; false-discovery rate-adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling.

Conclusions: For men with PCa undergoing RT, oral versus standard ADT may improve 6-month QOL and appears to have a similar impact on androgen-responsive gene expression.
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http://dx.doi.org/10.1002/cncr.33556DOI Listing
April 2021

Gender differences in the renal changes induced by a prolonged high-fat diet in rats with altered renal development.

J Physiol Biochem 2021 Apr 14. Epub 2021 Apr 14.

Department of Physiology, School of Medicine, University of Murcia, 30100, Murcia, Spain.

The mechanisms involved in renal dysfunction induced by high-fat diet (HFD) in subjects with altered renal development (ARDev) are understudied. The objective of this study is to examine whether there are sex-dependent differences in the mechanisms involved in the hypertension and deterioration of renal function in SD rats with prolonged HFD and ARDev. The role of angiotensin II (Ang II) in the arterial pressure (AP) increments, the renal hemodynamic sensitivity to Ang II, glomerular damage and changes in fat abdominal volume, plasma adipokine levels, renal NADPHp67phox expression, and renal infiltration of immune cells were examined. Hypertension and deterioration of renal function were enhanced (P < 0.05) in both sexes of rats with HFD and ARDev. The decrease (P < 0.05) of AP elicited by candesartan in hypertensive rats was similar to that induced by the simultaneous administration of candesartan and apocynin. The greater (P < 0.05) renal vasoconstriction induced by Ang II in both sexes of rats with HFD and ARDev was accompanied by an enhanced (P < 0.05) infiltration of CD-3 cells and macrophages in the renal cortex and renal medulla. The increments (P < 0.05) in the renal expression of NADPHp67phox and glomeruloesclerosis were greater (P < 0.05) in males than in females with HFD and ARDev. Our results suggest that the hypertension and deterioration of renal function induced by HFD in rats with ARDev are Ang II-dependent and mediated by increments in oxidative stress and immune system activation. Sex-dependent increments in oxidative stress and glomerular damage may contribute to the deterioration of renal function in these rats.
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http://dx.doi.org/10.1007/s13105-021-00815-yDOI Listing
April 2021

Structural vulnerability: migration and health in social context.

BMJ Glob Health 2021 Apr;6(Suppl 1)

Department of Anthropology, University of California San Francisco, San Francisco, California, USA.

Based on the authors' work in Latin America and Africa, this article describes and applies the concept 'structural vulnerability' to the challenges of clinical care and healthcare advocacy for migrants. This concept helps consider how specific social, economic and political hierarchies and policies produce and pattern poor health in two case studies: one at the USA-Mexico border and another in Djibouti. Migrants' and providers' various entanglements within inequitable and sometimes violent global migration systems can produce shared structural vulnerabilities that then differentially affect health and other outcomes. In response, we argue providers require specialised training and support; professional associations, healthcare institutions, universities and humanitarian organisations should work to end the criminalisation of medical and humanitarian assistance to migrants; migrants should help lead efforts to reform medical and humanitarian interventions; and alternative care models in Global South to address the structural vulnerabilities inherent to migration and asylum should be supported.
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http://dx.doi.org/10.1136/bmjgh-2021-005109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031011PMC
April 2021

Efficiency of Machine Learning Algorithms for the Determination of Macrovesicular Steatosis in Frozen Sections Stained with Sudan to Evaluate the Quality of the Graft in Liver Transplantation.

Sensors (Basel) 2021 Mar 12;21(6). Epub 2021 Mar 12.

Experimental Pathology Service, Institute for Biomedical Research of Murcia (IMIB), 30120 Murcia, Spain.

Liver transplantation is the only curative treatment option in patients diagnosed with end-stage liver disease. The low availability of organs demands an accurate selection procedure based on histological analysis, in order to evaluate the allograft. This assessment, traditionally carried out by a pathologist, is not exempt from subjectivity. In this sense, new tools based on machine learning and artificial vision are continuously being developed for the analysis of medical images of different typologies. Accordingly, in this work, we develop a computer vision-based application for the fast and automatic objective quantification of macrovesicular steatosis in histopathological liver section slides stained with Sudan stain. For this purpose, digital microscopy images were used to obtain thousands of feature vectors based on the RGB and CIE L*a*b* pixel values. These vectors, under a supervised process, were labelled as fat vacuole or non-fat vacuole, and a set of classifiers based on different algorithms were trained, accordingly. The results obtained showed an overall high accuracy for all classifiers (>0.99) with a sensitivity between 0.844 and 1, together with a specificity >0.99. In relation to their speed when classifying images, KNN and Naïve Bayes were substantially faster than other classification algorithms. Sudan stain is a convenient technique for evaluating ME in pre-transplant liver biopsies, providing reliable contrast and facilitating fast and accurate quantification through the machine learning algorithms tested.
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http://dx.doi.org/10.3390/s21061993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001362PMC
March 2021

COVID-19 and the political geography of racialisation: Ethnographic cases in San Francisco, Los Angeles and Detroit.

Glob Public Health 2021 Mar 30:1-15. Epub 2021 Mar 30.

Joint Program in Medical Anthropology, University of California Berkeley, Berkeley, CA, USA.

The COVID-19 pandemic has overwhelmed health systems around the globe, and intensified the lethality of social and political inequality. In the United States, where public health departments have been severely defunded, Black, Native, Latinx communities and those experiencing poverty in the country's largest cities are disproportionately infected and disproportionately dying. Based on our collective ethnographic work in three global cities in the U.S. (San Francisco, Los Angeles, and Detroit), we identify how the political geography of racialisation potentiated the COVID-19 crisis, exacerbating the social and economic toll of the pandemic for non-white communities, and undercut the public health response. Our analysis is specific to the current COVID19 crisis in the U.S, however the lessons from these cases are important for understanding and responding to the corrosive political processes that have entrenched inequality in pandemics around the world.
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http://dx.doi.org/10.1080/17441692.2021.1908395DOI Listing
March 2021

Photobiomodulation therapy increases collagen II after tendon experimental injury.

Histol Histopathol 2021 Mar 23:18330. Epub 2021 Mar 23.

Department of Surgery, Laboratory of Medical Research - Division of Human Structural Topography, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo-SP, Brazil.

A tendon is a mechanosensitive tissue that transmits muscle-derived forces to bones. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), has been used in therapeutic approaches in tendon lesions, but uncertainties regarding its mechanisms of action have prevented its widespread use. We investigated the response of PBM therapy in experimental lesions of the Achilles tendon in rats. Thirty adult male Wistar rats weighing 250 to 300 g were surgically submitted to bilateral partial transverse section of the Achilles tendon. The right tendon was treated with PBM, whereas the left tendon served as a control. On the third postoperative day, the rats were divided into three experimental groups consisting of ten rats each, which were treated with PBM (Konf, Aculas - HB 750), 780 nm and 80 mW for 20 seconds, three times/week for 7, 14 and 28 days. The rats were sacrificed at the end of the therapeutic time period. The Sca-1 was examined by immunohistochemistry and histomorphometry, and COLA1, COLA2 and COLA3 gene expression was examined by qRT-PCR. COLA2 gene expression was higher in PBM treated tendons than in the control group. The histomorphometric analysis coincided with increased number of mesenchymal cells, characterized by Sca-1 expression in the lesion region (p<0.001). PBM effectively interferes in tendon tissue repair after injury by stimulating mesenchymal cell proliferation and the synthesis of collagen type II, which is suggested to provide structural support to the interstitial tissues during the healing process of the Achilles tendon. Further studies are needed to confirm the role of PBM in tendon healing.
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http://dx.doi.org/10.14670/HH-18-330DOI Listing
March 2021

Warming and elevated CO induces changes in the reproductive dynamics of a tropical plant species.

Sci Total Environ 2021 May 29;768:144899. Epub 2021 Jan 29.

Department of Biology, Ribeirão Preto School of Philosophy, Science and Literature, University of São Paulo, Av. Bandeirantes 3900, 14040-901 Ribeirão Preto, SP, Brazil. Electronic address:

Tropical plant species are vulnerable to climate change and global warming. Since flowering is a critical factor for plant reproduction and seed-set, warming and elevated atmospheric carbon dioxide concentrations (eCO) are crucial climate change factors that can affect plant reproductive dynamics and flowering related events in the tropics. Using a combined free-air CO enrichment and a free-air temperature-controlled enhancement system, we investigate how warming (+2 °C above ambient, eT) and elevated [CO] (~600 ppm, eCO) affect the phenological pattern, plant-insect interactions, and outcrossing rates in the tropical legume forage species Stylosanthes capitata Vogel (Fabaceae). In comparison to the control, a significantly greater number of flowers (NF) per plot (+62%) were observed in eT. Furthermore, in warmed plots flowers began opening approximately 1 h earlier (~09:05), with a canopy temperature of ~23 °C, than the control (~09:59) and eCO (~09:55) treatments. Flower closure occurred about 3 h later in eT (~11:57) and control (~13:13), with a canopy temperature of ~27 °C. These changes in flower phenology increased the availability of floral resources and attractiveness for pollinators such as Apis mellifera L. and visitors such as Paratrigona lineata L., with significant interactions between eT treatments and insect visitation per hour/day, especially between 09:00-10:40. In comparison to the control, the additive effects of combined eCO + eT enhanced the NF by 137%, while the number of A. mellifera floral visits per plot/week increased by 83% during the period of greatest flower production. Although we found no significant effect of treatments on mating system parameters, the overall mean multilocus outcrossing rate (tm = 0.53 ± 0.03) did confirm that S. capitata has a mixed mating system. The effects of elevated [CO] and warming on plant-pollinator relationships observed here may have important implications for seed production of tropical forage species in future climate scenarios.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144899DOI Listing
May 2021

Phase-unwrapping method based on local polynomial models and a maximum a posteriori model correction.

Appl Opt 2021 Feb;60(5):1121-1131

Recently, a theory on local polynomial approximations for phase-unwrapping algorithms, considering a state space analysis, has been proposed in Appl. Opt.56, 29 (2017)APOPAI0003-693510.1364/AO.56.000029. Although this work is a suitable methodology to deal with relatively low signal to noise ratios observed in the wrapped phase, the methodology has been developed only for local-polynomial phase models of order 1. The resultant proposal is an interesting Kalman filter approach for estimating the coefficient or state vectors of these local plane models. Thus, motivated by this approach and simple Bayesian theory, and considering our previous research on local polynomial models up to the third order [Appl. Opt.58, 436 (2019)APOPAI0003-693510.1364/AO.58.000436], we propose an equivalent methodology based on a simple maximum a posteriori estimation, but considering a different state space: difference vectors of coefficients for the current high-order polynomial models. Specific estimations of the covariance matrices for difference vectors, as well as noise covariance matrices involved with the correct estimation of coefficient vectors, are proposed and reconstructions with synthetic and real data are provided.
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http://dx.doi.org/10.1364/AO.411238DOI Listing
February 2021

Tumor immunogenomic signatures improve a prognostic model of melanoma survival.

J Transl Med 2021 02 17;19(1):78. Epub 2021 Feb 17.

Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, 522 First Avenue, New York City, NY, 10016, USA.

Background: Tumor mutation burden (TMB) has been associated with melanoma immunotherapy (IT) outcomes, including survival. We explored whether combining TMB with immunogenomic signatures recently identified by The Cancer Genome Atlas (TCGA) can refine melanoma prognostic models of overall survival (OS) in patients not treated by IT.

Methods: Cox proportional-hazards (Cox PH) analysis was performed on 278 metastatic melanomas from TCGA not treated by IT. In a discovery and two validation cohorts Cox PH models assessed the interaction between TMB and 53 melanoma immunogenomic features to refine prediction of melanoma OS.

Results: Interferon-γ response (IFNγRes) and macrophage regulation gene signatures (MacReg) combined with TMB significantly associated with OS (p = 8.80E-14). We observed that patients with high TMB, high IFNγRes and high MacReg had significantly better OS compared to high TMB, low IFNγRes and low MacReg (HR = 2.8, p = 3.55E-08). This association was not observed in low TMB patients.

Conclusions: We report a model combining TMB and tumor immune features that significantly improves prediction of melanoma OS, independent of IT. Our analysis revealed that patients with high TMB, high levels of IFNγRes and MacReg had significantly more favorable OS compared to high TMB patients with low IFNγRes and low MacReg. These findings may substantially improve current melanoma prognostic models.
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http://dx.doi.org/10.1186/s12967-021-02738-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888085PMC
February 2021

Global dynamics of the chemostat with overflow metabolism.

J Math Biol 2021 02 2;82(3):13. Epub 2021 Feb 2.

Biocore Team, Université Côte d'Azur, Inria, INRAE, CNRS, Sorbonne Université, Sophia Antipolis, France.

Fast growing E. coli cells, in glucose-aerobic conditions, excrete fermentation by-products such as acetate. This phenomenon is known as overflow metabolism and has been observed in a diverse range of microorganisms. In this paper, we study a chemostat model subject to overflow metabolism: if the substrate uptake rate (or the specific growth rate) is above a threshold rate (different from zero), then secretion of a by-product happens. We assume that the presence of the by-product has an inhibitory effect on the growth of the microorganism. The model is described by a non-smooth differential system of dimension three. We prove the existence of at most one equilibrium (or steady-state) with presence of microorganism, which is globally stable. We use these results to discuss the performance of chemostat-type systems to produce biomass or recombinant proteins.
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http://dx.doi.org/10.1007/s00285-021-01566-6DOI Listing
February 2021

PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease.

J Med Chem 2021 01 24;64(1):326-342. Epub 2020 Dec 24.

Pfizer Medicine Design, Pfizer Worldwide Research and Development, Groton, Connecticut 06340, United States.

Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu → Val) on the β-chain of adult hemoglobin (HbA) that results in sickled hemoglobin (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke. We report the design of a noncovalent modulator of HbS, clinical candidate PF-07059013 (). The seminal hit molecule was discovered by virtual screening and confirmed through a series of biochemical and biophysical studies. After a significant optimization effort, we arrived at , a compound that specifically binds to Hb with nanomolar affinity and displays strong partitioning into RBCs. In a 2-week multiple dose study using Townes SCD mice, showed a 37.8% (±9.0%) reduction in sickling compared to vehicle treated mice. (PF-07059013) has advanced to phase 1 clinical trials.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01518DOI Listing
January 2021

Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis.

Gastroenterology 2021 Apr 10;160(5):1725-1740.e2. Epub 2020 Dec 10.

Daniel Baugh Institute, Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.

Background & Aims: We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism.

Methods: We performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells.

Results: Patients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes.

Conclusions: Altered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH.
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http://dx.doi.org/10.1053/j.gastro.2020.12.008DOI Listing
April 2021

Origen anómalo de la coronaria izquierda corregido con maniobra modificada de Lecompte.

Arch Cardiol Mex 2020 Dec 1. Epub 2020 Dec 1.

Servicio de Cardiología y Falla Cardiaca, Clínica Cardio VID. Medellín, Colombia.

La irrigación cardiaca normal viene dada por el origen de las arterias coronarias derecha e izquierda a nivel de los senos coronarianos derecho e izquierdo; sin embargo, pueden presentarse modificaciones de la anatomía descrita, algunas de las cuales corresponden a variantes inocuas, mientras que otras pueden asociarse con alto riesgo de morbimortalidad1,2.
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http://dx.doi.org/10.24875/ACM.20000169DOI Listing
December 2020

How does leaf physiological acclimation impact forage production and quality of a warmed managed pasture of Stylosanthes capitata under different conditions of soil water availability?

Sci Total Environ 2021 Mar 13;759:143505. Epub 2020 Nov 13.

Department of Biology, FFCLRP, University of Sao Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address:

Tropical pastures play a significant role in the global carbon cycle and are crucial for world livestock production. Despite its importance, there is a paucity of field studies that clarify how tropical pasture species will be affected by environmental changes predicted for tropical regions. Using a temperature-free air-controlled enhancement (T-FACE) system, we increased canopy temperature (+2 °C over ambient) and evaluated the effects of warming under two soil moisture conditions in a factorial design over the physiology, forage production, and forage quality of a tropical forage legume, Stylosanthes capitata. Under well-watered conditions, warming increased the PSII efficiency, net photosynthesis, and aboveground biomass accumulation, but reduced forage quality and digestibility by decreasing crude protein content and increasing lignin content. Non-irrigated conditions under ambient temperature reduced leaf water status presumably promoting the reduction in net photosynthesis, forage production, and forage quality and digestibility. Under the combination of canopy warming and non-irrigated conditions, warming mitigated the effects of reduced soil moisture on leaf photosynthesis and biomass production, but a significant interaction reduced forage quality and digestibility more than under isolated treatments of warming or non-irrigated conditions. We found a potential physiological acclimation of the tropical forage species to moderate warming when grown under rainfed or well-watered conditions. However, this acclimation was achieved due to a trade-off that reduced forage nutritional value and digestibility that may impact future animal feeding, livestock production, and would contribute to methane emissions.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143505DOI Listing
March 2021

Platelet Apoptotic Response May Be Associated With the Capacity of Aspirin to Inhibit Platelets.

J Cardiovasc Pharmacol 2020 11;76(5):584-591

Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain.

An inadequate platelet response to aspirin (ASA) has been identified in some patients under chronic ASA treatment. The aim of this study was to analyze if ASA-sensitive and ASA-resistant platelets have differences in their apoptotic capability. Clinically stable ischemic coronary patients who had been taking ASA (100 mg/d) for at least 9 months before inclusion were divided into ASA-resistant (n = 11) and ASA-sensitive (n = 13) groups as defined by the PFA-100 test. Platelets from ASA-sensitive patients showed higher expression of the proapoptotic proteins Bak and Bax than those from ASA-resistant patients, although only Bak protein remained different when the results were adjusted by age. In resting platelets, neither caspase-3 activity nor cytosolic cytochrome C levels were different between both experimental groups. Stimulation of platelets with calcium ionophore (10 nmol/L, A23187) increased caspase-3 activity (1.91-fold higher; P < 0.05) and cytosolic cytochrome C levels (1.84-fold higher; P < 0.05) to a higher degree in ASA-sensitive than in ASA-resistant platelets. In conclusion, ASA-sensitive platelets seem to be better prepared to undergo apoptosis during robust platelet activation.
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http://dx.doi.org/10.1097/FJC.0000000000000908DOI Listing
November 2020

CD14 release induced by P2X7 receptor restricts inflammation and increases survival during sepsis.

Elife 2020 11 2;9. Epub 2020 Nov 2.

Línea de Inflamación Molecular, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.

P2X7 receptor activation induces the release of different cellular proteins, such as CD14, a glycosylphosphatidylinositol (GPI)-anchored protein to the plasma membrane important for LPS signaling via TLR4. Circulating CD14 has been found at elevated levels in sepsis, but the exact mechanism of CD14 release in sepsis has not been established. Here, we show for first time that P2X7 receptor induces the release of CD14 in extracellular vesicles, resulting in a net reduction in macrophage plasma membrane CD14 that functionally affects LPS, but not monophosphoryl lipid A, pro-inflammatory cytokine production. Also, we found that during a murine model of sepsis, P2X7 receptor activity is important for maintaining elevated levels of CD14 in biological fluids and a decrease in its activity results in higher bacterial load and exacerbated organ damage, ultimately leading to premature deaths. Our data reveal that P2X7 is a key receptor for helping to clear sepsis because it maintains elevated concentrations of circulating CD14 during infection.
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http://dx.doi.org/10.7554/eLife.60849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690950PMC
November 2020

Outpatient Microsurgical Breast Reconstruction.

Plast Reconstr Surg Glob Open 2020 Sep 23;8(9):e3109. Epub 2020 Sep 23.

Houston Plastic Craniofacial and Sinus Surgery, Houston, Tex.

Background: The extensive nature of perforator-based breast reconstructions, combined with the need for postoperative flap monitoring, often leads to long hospitalizations. We present an early report demonstrating the feasibility and advantages of a modified operative technique and recovery protocol, allowing us to perform outpatient breast reconstructions with the DIEP flap. This follow-up comprises the experience gained, which is expanded to other perforator-based flaps and not limited to DIEP breast reconstructions.

Methods: We have implemented a general protocol in patients undergoing breast reconstruction with autologous flaps, promoting early mobilization and discharge by improving postoperative pain and decreasing opioid requirements. This protocol includes intraoperative local anesthesia, a microfascial incision for DIEP harvest with rib preservation, along with prophylactic anticoagulation.

Results: Ninety-two consecutive patients underwent autologous tissue-based breast reconstruction with DIEP, IGAP, and PAP flaps. No intraoperative complications were reported. All patients were discharged within 23 hours, without evidence of flap compromise. One patient required operative takeback for evacuation of a hematoma on postoperative day 4. No partial or total flap losses were documented. The aim of any procedure should be to get to the patient back to the preoperative status as quickly as possible, as prolonged hospitalizations are associated with higher incidences of infection, deep venous thrombosis, overall dissatisfaction, and higher overall costs of care.

Conclusions: By using a modified operative technique, multimodal pain control, and postoperative anticoagulant therapy, outpatient perforator-flap-based breast reconstructions can be performed with high success and low complication rates.
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http://dx.doi.org/10.1097/GOX.0000000000003109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544295PMC
September 2020

Changes in soil water availability and air-temperature impact biomass allocation and C:N:P stoichiometry in different organs of Stylosanthes capitata Vogel.

J Environ Manage 2021 Jan 27;278(Pt 1):111540. Epub 2020 Oct 27.

São Paulo State University (UNESP), School of Agricultural and Veterinarian Sciences, Jaboticabal, São Paulo, Brazil.

Temperature and soil water availability play important roles in the biogeochemical cycles of essential elements for plant growth, such as carbon (C), nitrogen (N), and phosphorus (P). In this study, we investigated how drought and warming impact C:N:P stoichiometric ratios of different plant organs (leaves, inflorescences, and stems), and biomass allocation and production of a field-grown pasture of Stylosanthes capitata, a tropical forage legume. We evaluated the effects of elevated temperature (+2 °C above ambient temperature) under two conditions of soil water availability, irrigated, and non-irrigated. In general, we observed that different functional plant organs showed distinct responses to drought and warming demonstrating how important is to evaluate different functional plant organs to unravel crop nutrient dynamics. In addition, interactive effects between warming and drought were observed in many situations, highlighting the importance of multifactorial studies. Our data showed that warming produced plants with more inflorescences, decreasing leaf:inflorescence ratio. However, only warming under well-watered conditions improved biomass production (in 38%). Warmed and irrigated plants showed higher stoichiometric homeostasis compared to other treatments. In an opposite direction, drought decreased P concentration and increased N:P ratios in different organs, reducing the stoichiometric homeostasis under both conditions of temperature. We have concluded that warm and well-watered conditions without restrictions in soil nutrient availability can enhance plant production, presumably due to a higher level of stoichiometric homeostasis.
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http://dx.doi.org/10.1016/j.jenvman.2020.111540DOI Listing
January 2021

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial.

Clin Cancer Res 2020 Dec 7;26(24):6437-6444. Epub 2020 Oct 7.

University of Chicago Medicine, Chicago, Illinois.

Purpose: Multisite stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) has demonstrated safety in advanced solid tumors (ASTs). However, no studies have examined the relationships between irradiated tumor response, SBRT-induced tumor gene expression, and overall survival (OS).

Patients And Methods: Patients with AST received SBRT (30-50 Gy in 3-5 fractions) to two to four metastases followed by pembrolizumab (200 mg i.v. every 3 weeks). SBRT was prescribed to a maximum tumor volume of 65 mL. Small metastases received the complete prescribed coverage (complete-Rx), while larger metastases received partial coverage (partial-Rx). Treated metastasis control (TMC) was defined as a lack of progression for an irradiated metastasis. Landmark analysis was used to assess the relationship between TMC and OS. Thirty-five biopsies were obtained from 24 patients: 19 pre-SBRT and 16 post-SBRT (11 matched) prior to pembrolizumab and were analyzed via RNA microarray.

Results: Sixty-eight patients (139 metastases) were enrolled with a median follow-up of 10.4 months. One-year TMC was 89.5% with no difference between complete-Rx or partial-Rx. On multivariable analysis, TMC was independently associated with a reduced risk for death (HR, 0.36; 95% confidence interval, 0.17-0.75; = 0.006). SBRT increased expression of innate and adaptive immune genes and concomitantly decreased expression of cell cycle and DNA repair genes in the irradiated tumors. Elevated post-SBRT expression of correlated with increased expression of cytolytic T-cell genes and irradiated tumor response.

Conclusions: In the context of SBRT+P, TMC independently correlates with OS. SBRT impacts intratumoral immune gene expression associated with TMC. Randomized trials are needed to validate these findings.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1790DOI Listing
December 2020

Mixed-type intraductal papillary mucinous neoplasm: Tailored surgical planning - case report.

Int J Surg Case Rep 2020 24;76:111-115. Epub 2020 Sep 24.

Post Graduate Program in Health of Sciences, São Francisco University Medical School (USF), Bragança Paulista-SP, Brazil; Department of Surgery, University of Campinas, Campinas, SP, Brazil. Electronic address:

Introduction: With the greater availability of imaging exams, the diagnosis of intraductal papillary mucinous neoplasms (IPMNs) has increased recently. However, there are still questions about adequate management approaches for this disease, especially regarding the best therapeutic strategy. The objective is to describe the case of a patient with mixed-type (MT) IPMN successfully treated by a tailored surgical plan that adopted duodenopancreatectomy and imaging to monitor the remaining lesions of the tail and body of the pancreas.

Presentation Of Case: A 65-year-old asymptomatic man underwent ultrasonography of the abdomen and was diagnosed with a cystic tumor, measuring 3.0 × 2.5 cm, located on the head of the pancreas. Magnetic resonance cholangiopancreatography (MRCP) showed dilation of the main pancreatic duct and multiple cystic lesions scattered throughout the entire parenchyma. The patient underwent duodenopancreatectomy; postoperatively, he did not have complications and was discharged on the 6th postoperative day. The histopathological panel confirmed the presence of MT-IPMN of the intestinal pattern. The patient is currently well four years after surgery and is undergoing semiannual MRCP examinations to follow up the remaining lesions.

Discussion: MT-IPMNs represent 28-41% of all IPMNs. Among all subtypes, MT-IPMNs are the most challenging in terms of choosing the ideal therapeutic strategy. These lesions are the most difficult to treat because they can be multifocal and compromise different locations of the pancreatic parenchyma.

Conclusion: MRI findings, Ca19.9 serum level and negative family history of pancreatic neoplasia were indications for the surgical choice for the MT- IPMN presented in this case.
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http://dx.doi.org/10.1016/j.ijscr.2020.09.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548937PMC
September 2020

An oral presentation of dermatofibromasarcoma protuberans with literature review: A case report.

Int J Surg Case Rep 2020 28;76:98-102. Epub 2020 Sep 28.

South Carolina ENT, Allergy and Sleep Medicine, 3 Medical Park Rd. Suite 100, Columbia, SC 20203, United States.

Introduction: Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally invasive soft tissue tumor with a high rate of recurrence after surgical intervention. DFSP primarily occurs on the trunk and proximal extremities, with reported 10-15% occurring in the head and neck region. DFSP presenting within the oral cavity is a rare entity with few descriptions in the literature. Standard of care involves resection, either by Mohs micrographic surgery or wide local excision with careful evaluation of the surgical margins. Due to the invasive nature of this tumor, complete excision in sensitive areas such as the head and neck pose unique challenges.

Case Presentation: We present a case of DFSP presenting from within the oral cavity, along with its management, in a 50-year-old male. In addition, we review the published literature. The patient neglected a 3-month history of a rapidly enlarging mass of the left cheek. A buccal mucosal biopsy revealed the diagnosis of DFSP. The patient underwent wide local excision of the tumor resulting in a full thickness defect which required reconstruction utilizing a radial forearm free flap. The final pathology report demonstrated positive margins that necessitated additional excision.

Discussion: There are few reported cases of an intraoral presentation of dermatofibrosarcoma. Due to the sensitive location of the tumor, there are challenges associated with obtaining clear margins after resection and ultimately reconstruction.

Conclusion: This case and literature review highlight the rarity of an oral cavity presentation DFSP, and the associated surgical challenges.
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http://dx.doi.org/10.1016/j.ijscr.2020.09.172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533289PMC
September 2020

Contribution of Individual and Neighborhood Factors to Racial Disparities in Respiratory Outcomes.

Am J Respir Crit Care Med 2021 04;203(8):987-997

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.

Black adults have worse health outcomes compared with white adults in certain chronic diseases, including chronic obstructive pulmonary disease (COPD). To determine to what degree disadvantage by individual and neighborhood socioeconomic status (SES) may contribute to racial disparities in COPD outcomes. Individual and neighborhood-scale sociodemographic characteristics were determined in 2,649 current or former adult smokers with and without COPD at recruitment into SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). We assessed whether racial differences in symptom, functional, and imaging outcomes (St. George's Respiratory Questionnaire, COPD Assessment Test score, modified Medical Research Council dyspnea scale, 6-minute-walk test distance, and computed tomography [CT] scan metrics) and severe exacerbation risk were explained by individual or neighborhood SES. Using generalized linear mixed model regression, we compared respiratory outcomes by race, adjusting for confounders and individual-level and neighborhood-level descriptors of SES both separately and sequentially. After adjusting for COPD risk factors, Black participants had significantly worse respiratory symptoms and quality of life (modified Medical Research Council scale, COPD Assessment Test, and St. George's Respiratory Questionnaire), higher risk of severe exacerbations and higher percentage of emphysema, thicker airways (internal perimeter of 10 mm), and more air trapping on CT metrics compared with white participants. In addition, the association between Black race and respiratory outcomes was attenuated but remained statistically significant after adjusting for individual-level SES, which explained up to 12-35% of racial disparities. Further adjustment showed that neighborhood-level SES explained another 26-54% of the racial disparities in respiratory outcomes. Even after accounting for both individual and neighborhood SES factors, Black individuals continued to have increased severe exacerbation risk and persistently worse CT outcomes (emphysema, air trapping, and airway wall thickness). Disadvantages by individual- and neighborhood-level SES each partly explain disparities in respiratory outcomes between Black individuals and white individuals. Strategies to narrow the gap in SES disadvantages may help to reduce race-related health disparities in COPD; however, further work is needed to identify additional risk factors contributing to persistent disparities.
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http://dx.doi.org/10.1164/rccm.202002-0253OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048743PMC
April 2021

Recognizing postoperative nutritional complications of bariatric surgery in the primary care patient: a narrative review.

J Osteopath Med 2021 Jan;121(1):105-112

Arnot Ogden Medical Cente , Elmira , NY , USA.

Bariatric surgery is an effective treatment for patients with morbid obesity. However, as safe and common as bariatric procedures have become, multiple complications can still result. These complications vary depending on the type of procedure performed (malabsorptive or restrictive) and are often nutritional derangements from the altered malabsorptive surface of the gastrointestinal tract and decreased capacity of the stomach. Deficiencies in vitamin D after malabsorptive procedures such as the Roux-en-Y gastric bypass can result in subsequent hypocalcemia and bone demineralization, and anemias can also present after surgery from inadequate vitamin B12 and iron absorption. Because of the prevalence of these deficiencies, baseline micronutrient testing and postoperative screening are recommended in many cases. Additionally, supplemental treatment often requires higher doses than those recommended for healthy adults. The purpose of this narrative review is to outline the various nutrient deficiencies that can result from bariatric procedures and report previously-published recommendations for screening and medical treatment of patients with these deficiencies. This review is directed toward primary care practitioners because of their unique position in delivering continuity of care and the frequency with which they will encounter patients who have undergone bariatric surgery and are seeking counseling regarding weight loss modalities.
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http://dx.doi.org/10.7556/jaoa.2020.135DOI Listing
January 2021

Cerebral venous thrombosis in Argentina: clinical presentation, predisposing factors, outcomes and  literature review.

J Stroke Cerebrovasc Dis 2020 Oct 28;29(10):105145. Epub 2020 Jul 28.

Stroke Outcomes and Decision Neuroscience Research Unit, Department of Medicine, St. Michael's Hospital, University of Toronto, Canada.

Background: Cerebral venous thrombosis (CVT) is a rare medical condition that primarily affects young adults. The clinical spectrum is broad and its recognition remains a challenge for clinicians. Limited information is available on CVT in Argentina. Our goal was to report the results of the first National registry on CVT in Argentina and to compare clinical presentation, predisposing factors and outcomes with other international registries.

Material And Method: The Argentinian National Registry on CVT (ANR-CVT) is a multicenter retrospective cohort study comprising patients aged 18 and older with a diagnosis of CVT from January 2015 to January 2019. We evaluated demographics, predisposing factors, clinical presentation, and radiological characteristics (e.g. number of involved sinuses, venous infarction or hemorrhage on CT and MRI scans at admission), therapeutic interventions and functional outcomes at discharge and at 90 days. Our results were compared to a literature review of CVT registries.

Results: Overall, one hundred and sixty-two patients met the inclusion criteria. The mean age was 42 (±17) years; 72% were women. Seventy percent of patients were younger than 50 years. The most common presenting symptom was headache (82%). The transverse sinus was the most common site of thrombosis (70%) followed by the sigmoid sinus (46%). The main predisposing factor in women was contraceptive use (44%), 3% of the events occurred during pregnancy and 9% during the puerperium. Participants 50 years and older had a higher frequency on malignancy related (7.5% vs. 30%, p = 0.0001) and infections (2% vs. 11%, p = 0.001). The modified Rankin Scale (mRS) ≤2 at discharge was 81% and the rate of mortality at discharge was 4%. At 90 days, the mRS≤2 was 93%. When the ANR-CVT was compared with larger registries from Europe and Asia, the prevalence of cancer among patients with CVT was two to five-fold higher (15% vs. 7% and 3%, respectively; p = 0.002 and p < 0.001). Anticoagulation rates at discharge were also higher (94%) compared to registries from Asia (ASCVT - 68%) or Turkey (VENOST - 67%).

Conclusion: Participants in the first ANR-CVT had a low mortality and disability at 90 days. Clinical and radiological characteristics were similar to CVT from other international registries with a higher prevalence of cancer. There was a high variability in treatment adherence to guidelines as reflected by anticoagulation rates (range 54.5%-100%) at discharge.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105145DOI Listing
October 2020

Novel Respiratory Disability Score Predicts COPD Exacerbations and Mortality in the SPIROMICS Cohort.

Int J Chron Obstruct Pulmon Dis 2020 4;15:1887-1898. Epub 2020 Aug 4.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Rationale: Some COPD patients develop extreme breathlessness, decreased exercise capacity and poor health status yet respiratory disability is poorly characterized as a distinct phenotype.

Objective: To define respiratory disability in COPD based on available functional measures and to determine associations with risk for exacerbations and death.

Methods: We analyzed baseline data from a multi-center observational study (SPIROMICS). This analysis includes 2332 participants (472 with severe COPD, 991 with mild/moderate COPD, 726 smokers without airflow obstruction and 143 non-smoking controls).

Measurements: We defined respiratory disability by ≥4 of 7 criteria: mMRC dyspnea scale ≥3; Veterans Specific Activity Questionnaire <5; 6-minute walking distance <250 m; St George's Respiratory Questionnaire activity domain >60; COPD Assessment Test >20; fatigue (FACIT-F Trial Outcome Index) <50; SF-12 <20.

Results: Using these criteria, respiratory disability was identified in 315 (13.5%) participants (52.1% female). Frequencies were severe COPD 34.5%; mild-moderate COPD 11.2%; smokers without obstruction 5.2% and never-smokers 2.1%. Compared with others, participants with disability had more emphysema (13.2 vs. 6.6%) and air-trapping (37.0 vs. 21.6%) on HRCT (P<0.0001). Using principal components analysis to derive a disability score, two factors explained 71% of variance, and a cut point -1.0 reliably identified disability. This disability score independently predicted future exacerbations (ß=0.34; CI 0.12, 0.64; P=0.003) and death (HR 2.97; CI 1.54, 5.75; P=0.001). Thus, participants with disability by this criterion had almost three times greater mortality compared to those without disability.

Conclusion: Our novel SPIROMICS respiratory disability score in COPD was associated with worse airflow obstruction as well as airway wall thickening, lung parenchymal destruction and certain inflammatory biomarkers. The disability score also proved to be an independent predictor of future exacerbations and death. These findings validate disability as an important phenotype in the spectrum of COPD.
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http://dx.doi.org/10.2147/COPD.S250191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417644PMC
August 2020

Use of Single-recipient Vessels for Cross-chest Abdominal Flap-based Breast Augmentation as an Outpatient.

Plast Reconstr Surg Glob Open 2020 Jul 15;8(7):e2978. Epub 2020 Jul 15.

Houston Plastic Craniofacial and Sinus Surgery, Houston, Tex.

Breast reconstruction with autologous tissue following mastectomy for breast cancer has become the standard of care. Microvascular breast augmentation is an alternative for patients with failed breast prostheses, including painful capsular contractures or poor cosmetic outcomes. We present a series of 4 patients who underwent microvascular breast augmentation with cross-chest flap recipient vessels.

Methods: We perform a bilateral DIEP flap reconstruction in an outpatient setting following a modified recovery protocol, focused on decreasing postoperative pain and narcotic requirements, allowing early ambulation and discharge. This includes harvest of the flap via abdominal microfascial incisions and rib-sparing vessel dissection. Cosmetic microvascular augmentation of the contralateral breast was performed via cross-chest flap recipient vessel anastomoses, where the pedicle was tunneled across the chest and anastomosed to the primary flap.

Results: Four patients underwent flap-based breast augmentation with cross-chest recipient vessels. Two patients underwent immediate DIEP flap breast reconstruction of the affected side and contralateral flap-based augmentation, while 2 patients underwent bilateral breast augmentation with DIEP flaps for cosmetic purposes due to undesired cosmetic results following implant-based augmentations. No intraoperative complications were reported, and all patients were discharged within 23 hours without signs of flap compromise or need for operative take-backs. Mean follow-up was 23 weeks.

Conclusions: The DIEP flap is recognized as an option for breast augmentation, although its limitations are several, including the pain and recovery associated with autologous tissue-based breast reconstruction. Enhanced recovery protocols help reduce this burden, making it more acceptable and feasible.
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http://dx.doi.org/10.1097/GOX.0000000000002978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413810PMC
July 2020

Comprehensive Telestroke Network to Optimize Health Care Delivery for Cerebrovascular Diseases: Algorithm Development.

J Med Internet Res 2020 07 27;22(7):e18058. Epub 2020 Jul 27.

Department of Diagnostic Imaging, University Hospital Fundación Santa Fe de Bogotá, Bogotá DC, Colombia.

Background: Health care delivery for cerebrovascular diseases is a complex process, which may be improved using telestroke networks.

Objective: The purpose of this work was to establish and implement a protocol for the management of patients with acute stroke symptoms according to the available treatment alternatives at the initial point of care and the transfer possibilities.

Methods: The review board of our institutions approved this work. The protocol was based on the latest guidelines of the American Heart Association and American Stroke Association. Stroke care requires human and technological resources, which may differ according to the patient's point of entry into the health care system. Three health care settings were identified to define the appropriate protocols: primary health care setting, intermediate health care setting, and advanced health care setting.

Results: A user-friendly web-based telestroke solution was developed. The predictors, scales, and scores implemented in this system allowed the assessment of the vascular insult severity and neurological status of the patient. The total number of possible pathways implemented was as follows: 10 in the primary health care setting, 39 in the intermediate health care setting, and 1162 in the advanced health care setting.

Conclusions: The developed comprehensive telestroke platform is the first stage in optimizing health care delivery for patients with stroke symptoms, regardless of the entry point into the emergency network, in both urban and rural regions. This system supports health care personnel by providing adequate inpatient stroke care and facilitating the prompt transfer of patients to a more appropriate health care setting if necessary, especially for patients with acute ischemic stroke within the therapeutic window who are candidates for reperfusion therapies, ultimately contributing to mitigating the mortality and morbidity associated with stroke.
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http://dx.doi.org/10.2196/18058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418009PMC
July 2020

Plasma Lipid Profile Reveals Plasmalogens as Potential Biomarkers for Colon Cancer Screening.

Metabolites 2020 Jun 25;10(6). Epub 2020 Jun 25.

Laboratory of Multidisciplinary Research, São Francisco University, Bragança Paulista, São Paulo 12916-900, Brazil.

In this era of precision medicine, there is an increasingly urgent need for highly sensitive tests for detecting tumors such as colon cancer (CC), a silent disease where the first symptoms may take 10-15 years to appear. Mass spectrometry-based lipidomics is an emerging tool for such clinical diagnosis. We used ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry operating in high energy collision spectral acquisition mode (MS) mode (UPLC-QTOF-MS) and gas chromatography (GC) to investigate differences between the plasmatic lipidic composition of CC patients and control (CTR) subjects. Key enzymes in lipidic metabolism were investigated using immuno-based detection assays. Our partial least squares discriminant analysis (PLS-DA) resulted in a suitable discrimination between CTR and CC plasma samples. Forty-two statistically significant discriminating lipids were putatively identified. Ether lipids showed a prominent presence and accordingly, a decrease in glyceronephosphate O-acyltransferase (GNPAT) enzyme activity was found. A receiver operating characteristic (ROC) curve built for three plasmalogens of phosphatidylserine (PS), named PS(P-36:1), PS(P-38:3) and PS(P-40:5), presented an area under the curve (AUC) of 0.998, and sensitivity and specificity of 100 and 85.7% respectively. These results show significant differences in CC patients' plasma lipid composition that may be useful in discriminating them from CTR individuals with a special role for plasmalogens.
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http://dx.doi.org/10.3390/metabo10060262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345851PMC
June 2020