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1.
J Pathol ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39022853

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver condition that often progresses to more advanced stages, such as metabolic dysfunction-associated steatohepatitis (MASH). MASH is characterized by inflammation and hepatocellular ballooning, in addition to hepatic steatosis. Despite the relatively high incidence of MASH in the population and its potential detrimental effects on human health, this liver disease is still not fully understood from a pathophysiological perspective. Deregulation of polyamine levels has been detected in various pathological conditions, including neurodegenerative diseases, inflammation, and cancer. However, the role of the polyamine pathway in chronic liver disorders such as MASLD has not been explored. In this study, we measured the expression of liver ornithine decarboxylase (ODC1), the rate-limiting enzyme responsible for the production of putrescine, and the hepatic levels of putrescine, in a preclinical model of MASH as well as in liver biopsies of patients with obesity undergoing bariatric surgery. Our findings reveal that expression of ODC1 and the levels of putrescine, but not spermidine nor spermine, are elevated in hepatic tissue of both diet-induced MASH mice and patients with biopsy-proven MASH compared with control mice and patients without MASH, respectively. Furthermore, we found that the levels of putrescine were positively associated with higher aspartate aminotransferase concentrations in serum and an increased SAF score (steatosis, activity, fibrosis). Additionally, in in vitro assays using human HepG2 cells, we demonstrate that elevated levels of putrescine exacerbate the cellular response to palmitic acid, leading to decreased cell viability and increased release of CK-18. Our results support an association between the expression of ODC1 and the progression of MASLD, which could have translational relevance in understanding the onset of this disease. © 2024 The Pathological Society of Great Britain and Ireland.

2.
Int J Geriatr Psychiatry ; 39(3): e6078, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38470426

ABSTRACT

OBJECTIVE: This study aimed to explore the interplay between frailty, physical function, physical activity, nutritional status, and their impact on the quality of life and depressive status in older adults with frailty. METHODS: A cross-sectional study involving 235 pre-frail/frail older adults residing in Spanish communities was conducted. Frailty was assessed using Fried's criteria, physical function was evaluated using the Short Physical Performance Battery, and physical activity levels were measured via wrist-worn accelerometers. Nutritional status was determined using the Mini-Nutritional Assessment alongside anthropometric measurements. Quality of life was gauged using the EuroQoL 5-Dimension 5-Level, while depressive status was assessed using the Yesavage 15-item Geriatric Depression Scale. Multivariate linear regression and logistic regression analyses were employed to elucidate the associations of these factors with quality of life and depression. RESULTS: Our findings revealed significant correlations between various factors and quality of life. Notably, reported fatigue (ß = -0.276, p = 0.002), performance in the 4-m gait test (ß = -0.242, p = 0.001), the score on the short version of the Mini-Nutritional Assessment (ß = 0.312, p = 0.002), and engagement in light physical activity (ß = 0.180, p = 0.023) were all found to be associated with quality of life. In terms of depressive symptoms, the Mini-Nutritional Assessment score emerged as a protective factor (Odds ratio, OR: 0.812, p < 0.001), as did participation in moderate physical activity (OR: 0.988, p = 0.028). Conversely, fatigue (OR: 3.277, p = 0.003) and a slow gait speed (OR: 1.136, p = 0.045) were identified as risk factors for depressive symptoms. CONCLUSIONS: This study underscores the detrimental association of fatigue and slow gait speed on both quality of life and depressive status among older adults with frailty. In contrast, engaging in physical activity and addressing malnutrition risk emerge as critical protective factors for enhancing quality of life and ameliorating depressive symptoms in this population. CLINICAL TRIAL REGISTRATION: This is a study that uses cross-sectional data from a trial registered at ClinicalTrials.gov (Identifier: NCT05610605).


Subject(s)
Frailty , Nutritional Status , Aged , Humans , Cross-Sectional Studies , Depression , Exercise , Fatigue , Phenotype , Quality of Life , Clinical Trials as Topic
3.
J Clin Nurs ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38932443

ABSTRACT

BACKGROUND: The coexistence of frailty and type 2 diabetes mellitus in the older population heightens the risk of adverse events. However, research on functional and wellness factors associated with frailty in this population is limited. PURPOSE: To investigate the associations of physical performance, functional dependency, physical activity, nutritional status, sleep, self-perceived health and depression with frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. DESIGN: Cross-sectional. METHODS: The study included 123 community-dwelling older adults (73.7 ± 6.0 years) with pre-frailty/frailty and type 2 diabetes mellitus. Physical performance (Short Physical Performance Battery), functional dependency (Barthel Index and Lawton & Brody), physical activity and inactivity (GeneActiv wrist-worn accelerometer), malnutrition risk (Mini Nutritional Assessment), sleep (Pittsburgh Sleep Quality Index), self-perceived health (EuroQoL 5-Dimension 3-Level) and depression (Yesavage 15-item-Geriatric-Depression-Scale) were evaluated through personal interviews. Principal component analysis (PCA) was performed to categorize the variables into components, and logistic regressions were used to propose the best-fitted model for each component. RESULTS: The PCA identified four components: (i) physical performance, with gait speed and leg mean velocity as the main variables associated with frailty; (ii) balance, showing significant associations with monopodal balance; (iii) daily activities, with moderate to vigorous physical activity and the Lawton and Brody score as the main variables associated with frailty within this component; and (iv) wellness factors, with nutritional status, self-perceived health and depression score as the primary variables associated with frailty. CONCLUSIONS: This research underscores the significance of physical function and daily activities as protective factors against frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. The health dimension contributes both protective and risk factors, emphasizing the need for comprehensive assessments in managing frailty in this population. REPORTING METHOD: The study adhered to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

4.
Acta Obstet Gynecol Scand ; 102(4): 480-485, 2023 04.
Article in English | MEDLINE | ID: mdl-36906815

ABSTRACT

INTRODUCTION: Nowadays, proinflammatory factors are considered to play an important role in the pathophysiology of threatened preterm labor or chorioamnionitis. The aim of this study was to establish the normal reference range for interleukin-6 (IL-6) levels in the amniotic fluid and to identify factors which may alter this value. MATERIAL AND METHODS: Prospective study in a tertiary-level center including asymptomatic pregnant women undergoing amniocentesis for genetic studies from October 2016 to September 2019. IL-6 measurements in amniotic fluid were performed using a fluorescence immunoassay with microfluidic technology (ELLA Proteinsimple, Bio Techne). Maternal history and pregnancy data were also recorded. RESULTS: This study included 140 pregnant women. Of those, women who underwent termination of pregnancy were excluded. Therefore, a total of 98 pregnancies were included in the final statistical analysis. The mean gestational age was 21.86 weeks (range: 15-38.7) at the time of amniocentesis, and 38.6 weeks (range: 30.9-41.4) at delivery. No cases of chorioamnionitis were reported. The log10 IL-6 values follow a normal distribution (W = 0.990, p = 0.692). The median, and the 5th, 10th, 90th, and 95th percentiles for IL-6 levels were 573, 105, 130, 1645, and 2260 pg/mL, respectively. The log10 IL-6 values were not affected by gestational age (p = 0.395), maternal age (p = 0.376), body mass index (p = 0.551), ethnicity (p = 0.467), smoking status (p = 0.933), parity (p = 0.557), method of conception (p = 0.322), or diabetes mellitus (p = 0.381). CONCLUSIONS: The log10 IL-6 values follow a normal distribution. IL-6 values are independent of gestational age, maternal age, body mass index, ethnicity, smoking status, parity and method of conception. Our study provides a normal reference range for IL-6 levels in the amniotic fluid that can be used in future studies. We also observed that normal IL-6 values were higher in the amniotic fluid than in serum.


Subject(s)
Amniotic Fluid , Chorioamnionitis , Infant, Newborn , Female , Pregnancy , Humans , Infant , Amniotic Fluid/chemistry , Interleukin-6 , Reference Values , Pregnant Women , Prospective Studies , Parity , Gestational Age
5.
J Nurs Scholarsh ; 55(1): 56-66, 2023 01.
Article in English | MEDLINE | ID: mdl-36102356

ABSTRACT

AIMS AND OBJECTIVES: The aim of the present study is to investigate the professional grief suffered by nurses in various medical units, after coping with the COVID-19 pandemic for the last 18 months. BACKGROUND: Addressing and acknowledging the reality of professional grief is of fundamental importance to nurses' mental health, as this condition has both professional and personal consequences. DESIGN: A qualitative, content analysis approach was taken. METHODS: Based on 25 interviews with nursing professionals working in different health centers units were performed. The following sampling schemes were used: first, convenience sampling, then nominated sampling, and finally theoretical sampling. RESULTS: From our analysis of the data obtained, three main themes were identified: the impact on nurses of COVID-19 outcomes; the symptoms of professional grief; and cognitive reactions. These core elements interacted with 12 subtopics, including symptoms of grief and the cognitive impact produced. CONCLUSIONS: A large proportion of the nurses consulted in this study have suffered and suffered professional grief and report many related symptoms. In response to the present pandemic and any future occurrence, the question of professional grief needs to be addressed. RELEVANCE TO CLINICAL PRACTICE: To help them cope better with this type of situation, nurses should receive appropriate training. Moreover, healthcare institutions should be made aware of the problem and be encouraged to offer assistance to address the impact produced on nurses by the deaths of their patients. CLINICAL RELEVANCE: This study shows the impact of professional grief on nurses in the context of the COVID-19 pandemic. Nurses are affected personally by the deaths of patients and by alterations to their working conditions. In many cases, this grief remains unresolved and its various symptoms persist.


Subject(s)
COVID-19 , Nurses , Humans , Pandemics , Public Health , Grief , Qualitative Research
6.
Int Nurs Rev ; 70(1): 43-49, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35879822

ABSTRACT

AIM: To analyse and validate a contextually adapted version of the Papadopoulos' Cultural Competence Assessment Tool (CCATool) for Spanish undergraduate nursing students. BACKGROUND: Globalization has driven and intensified international migration. Thus, nurses must treat patients of many different cultural origins. Accordingly, both cultural competence and an appropriate tool with which to evaluate it are required. METHODS: The CCATool questionnaire was adapted for use in a Spanish context and was evaluated through a questionnaire completed by 262 undergraduate nursing students. Seven days later, the same students completed the questionnaire, without any intervention, and a subgroup of 144 students completed the questionnaire for a third time after taking a course in Transcultural Care. The reliability, sensitivity and stability of the questionnaire were assessed. RESULTS: The reliability of the questionnaire obtained an adequate Cronbach's alpha of 0.81. Stability was assessed at seven days, using the intraclass correlation coefficient, which showed good/excellent results. Moreover, the questionnaire was able to detect the changes related to the nursing educative programme, thus highlighting a good sensitivity of the tool. CONCLUSION: Cultural competence is an essential element of nurses' education, and instruction in this area should begin as soon as possible. In addition, an appropriate evaluation system is required. For this purpose, the present study describes and analyses a valid, reliable tool for use with undergraduate nursing students in Spain. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Health and education policies must be sensitive to the ethnic and cultural differences of the patients who are cared for, and address the situations that cause difficulties in care. Hospitals and health centres must offer good care to patients from diverse cultures, so one of the necessary situations is the training and evaluation of the cultural competence of health professionals.


Subject(s)
Education, Nursing, Baccalaureate , Students, Nursing , Humans , Cultural Competency/education , Reproducibility of Results , Surveys and Questionnaires
7.
BMC Palliat Care ; 21(1): 27, 2022 Feb 28.
Article in English | MEDLINE | ID: mdl-35227246

ABSTRACT

BACKGROUND: This study anlyzed whether family caregivers of patients with advanced cancer suffer impaired sleep quality, increased strain, reduced quality of life or increased care burden due to the presence and heightened intensity of symptoms in the person being cared for. METHOD: A total of 41 patient-caregiver dyads (41 caregivers and 41 patients with advanced cancer) were recruited at six primary care centres in this cross-sectional study. Data were obtained over a seven-month period. Caregiver's quality of sleep (Pittsburgh Sleep Quality Index), caregiver's quality of life (Quality of Life Family Version), caregiver strain (Caregiver Strain Index), patients' symptoms and their intensity (Edmonton Symptom Assessment System), and sociodemographic, clinical and care-related data variables were assessed. The associations were determined using non-parametric Spearman correlation. RESULTS: Total Edmonton Symptom Assessment System was significantly related to overall score of the Pittsburgh Sleep Quality Index (r = 0.365, p = 0.028), the Caregiver Strain Index (r = 0.45, p = 0.005) and total Quality of Life Family Version (r = 0.432, p = 0.009), but not to the duration of daily care (r = -0.152, p = 0.377). CONCLUSIONS: Family caregivers for patients with advanced cancer suffer negative consequences from the presence and intensity of these patients' symptoms. Therefore, optimising the control of symptoms would benefit not only the patients but also their caregivers. Thus, interventions should be designed to improve the outcomes of patient-caregiver dyads in such cases.


Subject(s)
Caregivers , Hospice and Palliative Care Nursing , Cross-Sectional Studies , Humans , Palliative Care , Quality of Life
8.
Int J Mol Sci ; 23(9)2022 Apr 24.
Article in English | MEDLINE | ID: mdl-35563103

ABSTRACT

Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin's relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.


Subject(s)
Colorectal Neoplasms , Leptin , Adipokines/metabolism , Adipose Tissue/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Humans , Leptin/genetics , Leptin/metabolism , Obesity/complications , Obesity/genetics , Obesity/metabolism , Receptors, Leptin/metabolism
9.
Int J Mol Sci ; 23(21)2022 Nov 02.
Article in English | MEDLINE | ID: mdl-36362202

ABSTRACT

Acute myeloid leukemia (AML) is a cancer of the myeloid blood cells mainly treated with chemotherapy for cancer remission, but this non-selective treatment also induces numerous side effects. Investigations with bioactive compounds from plant-derived foods against cancer have increased in the last years because there is an urgent need to search for new anti-leukemic agents possessing higher efficacy and selectivity for AML cells and fewer negative side effects. In this study, we analyzed the anti-leukemic activity of several phytochemicals that are representative of the major classes of compounds present in cruciferous foods (glucosinolates, isothiocyanates, hydroxycinnamic acids, flavonols, and anthocyanins) in the human acute myeloid leukemia cell line HL-60. Our results revealed that among the different Brassica-derived compounds assayed, sulforaphane (SFN) (an aliphatic isothiocyanate) showed the most potent anti-leukemic activity with an IC50 value of 6 µM in dose-response MTT assays after 48 h of treatment. On the other hand, chlorogenic acid (a hydroxycinnamic acid) and cyanidin-3-glucoside (an anthocyanin) also displayed anti-leukemic potential, with IC50 values of 7 µM and 17 µM after 48 h of incubation, respectively. Importantly, these compounds did not show significant cell toxicity in macrophages-like differentiated cells at 10 and 25 µM, indicating that their cytotoxic effects were specific to AML cancer cells. Finally, we found that these three compounds were able to induce the NRF2/KEAP1 signaling pathway in a dose-dependent manner, highlighting SFN as the most potent NRF2 activator. Overall, the present evidence shed light on the potential for using foods and ingredients rich in anticancer bioactive phytochemicals from Brassica spp.


Subject(s)
Brassica , Leukemia, Myeloid, Acute , Humans , Brassica/metabolism , Anthocyanins/pharmacology , Anthocyanins/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , HL-60 Cells , Isothiocyanates/pharmacology , Isothiocyanates/metabolism , Phytochemicals/pharmacology , Leukemia, Myeloid, Acute/drug therapy
10.
BMC Palliat Care ; 19(1): 61, 2020 May 02.
Article in English | MEDLINE | ID: mdl-32359361

ABSTRACT

BACKGROUND: Patients with advanced cancer, receiving at-home palliative care, are subject to numerous symptoms that are changeable and often require attention, a stressful situation that also impacts on the family caregiver. It has been suggested that music therapy may benefit both the patient and the caregiver. We propose a study to analyse the efficacy and cost utility of a music intervention programme, applied as complementary therapy, for cancer patients in palliative care and for their at-home caregivers, compared to usual treatment. METHOD: A randomised, double-blind, multicentre clinical trial will be performed in cancer patients in at-home palliative care and their family caregivers. The study population will include two samples of 40 patients and two samples of 41 caregivers. Participants will be randomly assigned either to the intervention group or to the control group. The intervention group will receive a seven-day programme including music sessions, while the control group will receive seven sessions of (spoken word) therapeutic education. In this study, the primary outcome measure is the assessment of patients' symptoms, according to the Edmonton Symptom Assessment System, and of the overload experienced by family caregivers, measured by the Caregiver Strain Index. The secondary outcomes considered will be the participants' health-related quality of life, their satisfaction with the intervention, and an economic valuation. DISCUSSION: This study is expected to enhance our understanding of the efficacy and cost-utility of music therapy for cancer patients in palliative care and for their family caregivers. The results of this project are expected to be applicable and transferrable to usual clinical practice for patients in home palliative care and for their caregivers. The approach described can be incorporated as an additional therapeutic resource within comprehensive palliative care. To our knowledge, no previous high quality studies, based on a double-blind clinical trial, have been undertaken to evaluate the cost-effectiveness of music therapy. The cost-effectiveness of the project will provide information to support decision making, thereby improving the management of health resources and their use within the health system. TRIAL REGISTRATION: The COMTHECARE study is registered at Clinical Trials.gov, NCT04052074. Registered 9 August, 2019.


Subject(s)
Caregivers/psychology , Music Therapy/standards , Neoplasms/therapy , Adult , Clinical Protocols , Double-Blind Method , Female , Home Care Services/standards , Humans , Male , Music Therapy/methods , Neoplasms/psychology , Palliative Care/standards
11.
BMC Nurs ; 19(1): 107, 2020 Nov 16.
Article in English | MEDLINE | ID: mdl-33292183

ABSTRACT

BACKGROUND: Sleep disorders are commonly experienced by community caregivers for persons with cancer, with at least 72% reporting moderate to severe disorders. A consequence of this condition, which is associated with the presence of overload in the caregiver, is the increased risk of clinical depression. The aim of this study is to evaluate the effects of music on the sleep quality achieved by informal caregivers for cancer patients receiving home palliative care. In addition, we will assess the influence of specific variables that could modify these effects, analyse the correlates related to nocturnal wakefulness and consider the diurnal consequences according to the sleep characteristics identified. METHODS: This single-blind, multicentre, randomised clinical trial will focus on informal providers of care for cancer patients. Two samples of 40 caregivers will be recruited. The first, intervention, group will receive seven music-based sessions. The control group will be masked with seven sessions of therapeutic education (reinforcing previous sessions). Outcomes will be evaluated using the Pittsburgh Sleep Quality Index, a triaxial accelerometer, EuroQol-5D-5L, the Caregiver Strain Index, the Epworth Sleepiness Scale and the Client Satisfaction Questionnaire. The caregivers' satisfaction with the intervention performed will also be examined. DISCUSSION: This study is expected to extend our understanding of the efficacy of music therapy in enhancing the sleep quality of caregivers for patients receiving home palliative care. To our knowledge, no reliable scientific investigations of this subject have previously been undertaken. Music is believed to benefit certain aspects of sleep, but this has yet to be proven and, according to a Cochrane review, high-quality research in this field is necessary. One of the main strengths of our study, which heightens the quality of the randomised clinical trial design, is the objective assessment of physical activity by accelerometry and the use of both objective and subjective measures of sleep in caregivers. Music therapy for the caregivers addressed in this study is complementary, readily applicable, provokes no harmful side effects and may produce significant benefits. TRIAL REGISTRATION: The IMECA study is registered at Clinical Trials.gov, ClinicalTrials.gov Identifier: NCT04491110 . Registered 29 July, 2020.

12.
J Nurs Manag ; 28(8): 2007-2016, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32378748

ABSTRACT

AIM: To describe the frequency and types of near misses and the recovery strategies employed by nurses in primary health care. BACKGROUND: Insufficient data are available on the role of nurses in near miss events and related factors in primary health care. METHOD: A prospective descriptive study was carried out at one Urban Primary Health Care Centre, within the Málaga-Guadalhorce Health District (Malaga, Spain), from January to December 2018. Four of the ten nurses volunteered to take part. RESULTS: The nurses recovered 185 near misses, prevailing administrative or communication-related errors, followed by medication-related errors. No near misses were reported on the centre's anonymous error information platform. CONCLUSIONS: A significant number of near misses occurred which could have been avoided with better communication among health care personnel. A striking finding is the failure to inform the health centre, which suggests that improvements in safety culture are needed. IMPLICATIONS FOR NURSING MANAGEMENT: It is the responsibility and the duty of nursing management to be aware of the characteristics and frequency of near misses in primary health care, to implement strategies for improvement and to foster a culture in which the necessary information on actual or potential errors is supplied.


Subject(s)
Medication Errors , Safety Management , Humans , Medical Errors , Primary Health Care , Prospective Studies , Spain
13.
Eur J Nutr ; 56(2): 831-841, 2017 Mar.
Article in English | MEDLINE | ID: mdl-26680596

ABSTRACT

PURPOSE: Urolithins, metabolites produced by the gut microbiota from ellagic acid, have been acknowledged with cancer chemopreventive activity. Although urolithin A (Uro-A) has been reported to be the most active one, 10-50 % of humans can also produce the isomer isourolithin A (IsoUro-A). However, no biological activity for IsoUro-A has been reported so far. Herein, we describe for the first time the antiproliferative effect of IsoUro-A, compared to Uro-A, against both human colon cancer (Caco-2) and normal (CCD18-Co) cell lines. METHODS: Cell proliferation was evaluated by MTT and Trypan blue exclusion assays. Cell cycle was analyzed by flow cytometry and apoptosis measured by the Annexin V/PI method. Finally, urolithins metabolism was analyzed by HPLC-DAD-MS/MS. RESULTS: IsoUro-A inhibited the proliferation of Caco-2 cells in a time- and dose-dependent manner, though it was significantly lower than Uro-A (IC50 = 69.7 ± 4.5 and 49.2 ± 3.8 µM at 48 h, respectively). Both urolithins arrested Caco-2 cell cycle at S and G2/M phases and induced apoptosis at concentrations previously found in human colon tissues. Notably, Caco-2 cells glucuronidated more efficiently IsoUro-A than Uro-A (~50 vs. ~20 % of conversion after 48 h, respectively). Both Uro-A and IsoUro-A glucuronides did not exert antiproliferative effects. In addition, cell growth inhibition was higher in Caco-2 than in normal cells. CONCLUSIONS: IsoUro-A exerts strong antiproliferative activity, which is reduced by the extensive glucuronidation at 9-position in cancer cells. Further studies are needed to elucidate whether the in vitro structure-activity relationship found for Uro-A and IsoUro-A plays any role in humans.


Subject(s)
Anticarcinogenic Agents/metabolism , Apoptosis , Colon/metabolism , Colonic Neoplasms/metabolism , Coumarins/metabolism , Intestinal Mucosa/metabolism , Anticarcinogenic Agents/adverse effects , Anticarcinogenic Agents/chemistry , Biomarkers/metabolism , Cell Line , Cell Line, Tumor , Cell Proliferation , Cell Survival , Colon/cytology , Colon/pathology , Colonic Neoplasms/pathology , Coumarins/adverse effects , Coumarins/chemistry , G2 Phase , Glucuronides/chemistry , Glucuronides/metabolism , Humans , Intestinal Mucosa/cytology , Intestinal Mucosa/pathology , Isomerism , Kinetics , Molecular Structure , S Phase
15.
Eur J Nutr ; 53(3): 853-64, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24077694

ABSTRACT

PURPOSE: Urolithins, gut microbiota metabolites derived from ellagic acid and ellagitannins, reach micromolar concentrations in the colon lumen where can have anti-inflammatory and anticancer effects. The antiproliferative activity of urolithins (Uro-A, Uro-B, Uro-C and Uro-D) and their most relevant in vivo glucuronides were evaluated in three human colon cancer cell lines (Caco-2, SW480 and HT-29). METHODS: Cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and Trypan blue exclusion assays. Cell cycle was evaluated by flow cytometry and urolithins metabolism by HPLC­MS/MS. RESULTS: Urolithins inhibited cell proliferation and cell cycle progression in a time- and dose-dependent manner and arrested the cells at S and G2/M phases, depending on the urolithin. Uro-A exerted the highest antiproliferative activity, followed by Uro-C, Uro-D and Uro-B. Unlike Caco-2 and SW480 cells, HT-29 cells partially overcame the effects after 48 h, which was related to the complete glucuronidation of urolithins. Uro-A or Uro-B glucuronides did not affect cell cycle and showed lower antiproliferative activity than their aglycone counterparts. Uro-A or Uro-B plus inhibitors of drug efflux ABC transporters partially prevented the glucuronidation of urolithins in HT-29 cells which became more sensitive. CONCLUSIONS: Uro-A, Uro-B, Uro-C and Uro-D exerted different antiproliferative effects depending on the colon cancer cell line. We also report here, for the first time, the role of ABC transporters and Phase-II metabolism in HT-29 cells as a mechanism of cancer resistance against urolithins due to their conversion to glucuronide conjugates that exerted lower antiproliferative activity.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Colonic Neoplasms/drug therapy , Coumarins/pharmacology , Hydrolyzable Tannins/pharmacology , Metabolic Detoxication, Phase II , ATP-Binding Cassette Transporters/antagonists & inhibitors , ATP-Binding Cassette Transporters/metabolism , Anti-Inflammatory Agents, Non-Steroidal/antagonists & inhibitors , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Colon/drug effects , Colon/metabolism , Colonic Neoplasms/metabolism , Coumarins/antagonists & inhibitors , Coumarins/chemistry , Coumarins/metabolism , Drug Resistance, Neoplasm/drug effects , G2 Phase/drug effects , Glucuronides/chemistry , Glucuronides/metabolism , Humans , Hydrolyzable Tannins/antagonists & inhibitors , Hydrolyzable Tannins/chemistry , Hydrolyzable Tannins/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Kinetics , Membrane Transport Modulators/pharmacology , S Phase/drug effects
16.
Enferm Infecc Microbiol Clin ; 32(6): 359-62, 2014.
Article in Spanish | MEDLINE | ID: mdl-24054972

ABSTRACT

INTRODUCTION: An increase in cases of pertussis, mainly in young infants, has been reported in the last few years. The clinical presentation of this disease is very similar to that produced by respiratory syncytial virus (RSV), which makes the diagnosis difficult. OBJECTIVE: To compare the clinical and epidemiological characteristics between Bordetella pertussis and RSV infections in infants admitted to hospital. MATERIAL AND METHODS: An analytical matched case-control study was conducted during the period 2008-2011. Cases were defined as infants admitted with pertussis confirmed by PCR in nasopharyngeal aspirate. Each case was matched by age, sex and date of admission to two controls defined as patients with RSV infection detected by immunochromatography in nasal aspirate. Demographic, clinical, laboratory data were compared. RESULTS: Seventy eight patients (26 cases of pertussis and 52 controls RSV+) were included. Sociodemographic characteristics were similar in both groups. Cases had more days of symptoms prior to admission, longer hospital stays, and increased frequency of epidemic family environment. Apnoea and cyanosis were more frequent. Cases of pertussis were more likely to have apnoea, cyanosis, and lymphocytosis while RSV infections had more frequent fever, vomiting and respiratory distress. CONCLUSIONS: The clinical presentations of pertussis and RSV infection are similar, but there are some characteristics that can help to distinguish between them.


Subject(s)
Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus Infections/epidemiology , Whooping Cough/diagnosis , Whooping Cough/epidemiology , Case-Control Studies , Female , Humans , Infant , Male , Patient Admission , Retrospective Studies
17.
J Clin Med ; 13(14)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39064047

ABSTRACT

Background/Objectives: Non-Invasive prenatal test (NIPT) is used as a universal or contingent test after prior risk assessment. Screening is mainly performed for common trisomies (T21, T13, T18), although other chromosomal anomalies may be detected. Our objective was to study the performance of GWNIPT in the detection of chromosomal abnormalities in pregnancies in which an invasive prenatal study was performed and in early pregnancy losses, in comparison with the reference test. Method: VeriSeqTM NIPT Solution v2, a genome-wide NIPT (GWNIPT), was performed prior to invasive testing in fetal diagnostic study cases (FDS, n = 155) and in early pregnancy losses (EPL, n = 68). Results: In the FDS group, the diagnostic test (QFPCR, array and karyotype) detected anomalies in 32 pregnancies (21%), in twenty of them (61%) also detected by GWNIPT. Eleven of the twelve cases undetected by GWNIPT were balanced translocations (n = 4) or deletions/duplications <7 Mb (n = 7). In the EPL group, GWNIPT detected anomalies in 46% of cases (31/68) but comparison with reference test (QFPCR and karyotype) in products of conception (POC) was only possible in 18 cases. Concordant results between POC and GWNIPT test were obtained in 16 of the 18 cases. In EPL, with GWNIPT testing, common trisomies accounted for 25.8% of cases (8/31), rare trisomies 54.8% (17/31) and microdeletions/duplications 16.1% (5/31). Conclusions: The GWNIPT test may be useful in clinical practice in prenatal and in EPL's genetic diagnosis when the appropriate sample is not available.

18.
Trends Endocrinol Metab ; 35(7): 563-565, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38664153

ABSTRACT

Liver-targeted acetyl-coenzyme A (CoA) carboxylase (ACC) inhibitors in metabolic dysfunction-associated steatotic liver disease (MASLD) trials reveal notable secondary effects: hypertriglyceridemia and altered glucose metabolism, paradoxically with reduced hepatic steatosis. In their study, Deja et al. explored how hepatic ACC influences metabolism using different pharmacological and genetic methods, coupled with targeted metabolomics and stable isotope-based tracing techniques.


Subject(s)
Acetyl-CoA Carboxylase , Liver , Animals , Humans , Acetyl-CoA Carboxylase/antagonists & inhibitors , Acetyl-CoA Carboxylase/genetics , Acetyl-CoA Carboxylase/metabolism , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Fatty Liver/metabolism , Liver/metabolism
19.
Article in English | MEDLINE | ID: mdl-38436435

ABSTRACT

BACKGROUND: Frailty is associated with urinary and fecal incontinence, which are common geriatric syndromes. This study aims to identify health factors associated with incontinence in prefrail or frail older adults living in the community. METHODS: This multicenter cross-sectional study included 225 older adults (75.0 ±â€…6.4 years) with prefrailty or frailty based on the 5-component Fried phenotype. Physical function was assessed using the Short Physical Performance Battery (SPPB). Physical activity, inactivity, and sleep were estimated using a wrist-worn accelerometer. Urinary or fecal incontinence was registered using the Barthel scale (urine and bowel items). Multivariable logistic regression analyses, with age as a covariate, were conducted to identify associations of incontinence. RESULTS: In our participants, 27% presented urinary or fecal incontinence with no sex differences (p = .266). Our results showed that age, daily medication count, and number of falls in the previous year independently predicted incontinence in frail and prefrail older adults (p < .05). Some Fried's criteria, including self-reported exhaustion, gait speed, and handgrip strength, were associated with the presence of incontinence (p < .05), but not Fried's classification. The SPPB total score and its isolated variables were significantly associated with the urinary and fecal incontinence (p < .05). However, none of the accelerometer outcomes showed significant associations with incontinence status. CONCLUSIONS: According to this study, age, number of medications, and falls (but not sex) are linked to urinary and fecal incontinence in frail or prefrail older adults living in the community, recommending the assessment of physical function using the SPPB rather than estimating daily physical activity, inactivity, or sleep.


Subject(s)
Fecal Incontinence , Frail Elderly , Geriatric Assessment , Urinary Incontinence , Humans , Male , Aged , Female , Cross-Sectional Studies , Urinary Incontinence/epidemiology , Urinary Incontinence/physiopathology , Fecal Incontinence/epidemiology , Geriatric Assessment/methods , Aged, 80 and over , Risk Factors , Frailty/diagnosis , Frailty/physiopathology , Independent Living , Exercise/physiology
20.
Sleep Med ; 121: 196-202, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39002328

ABSTRACT

BACKGROUND: The prevalence of sleep-related issues among older adults is a significant concern, with half of the older population reporting these problems. Consequently, strategies to improve sleep are needed for this population. This study aims to assess the effects of a health educational program on sleep behaviour among pre-frail or frail older adults residing in the community and to explore possible associations with frailty. METHODS: This randomised controlled trial (NCT05610605) included a total of 197 community-dwelling older adults with frailty/pre-frailty, divided into control (n = 88) and educational (n = 109) groups, were assessed at baseline, after the 6-month educational program (6 months), and 6 months after the intervention (12 months). The intervention comprised four group sessions and six follow-up phone calls, focusing on frailty, physical activity, dietary habits, and cognitive training. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and wrist-worn accelerometry. RESULTS: At 6 months, a significant time-by-group interaction was found for self-reported [ß = -0.449, 95%CI (-0.844, -0.053), p = 0.026] and accelerometer-measured [ß = 0.505, 95%CI (0.085, 0.926), p = 0.019] sleep efficiency, showing improved sleep efficiency in the intervention group vs. controls. A significant time-by-group interaction at 6 months was noted for sleep awakenings [ß = -0.402, 95%CI (-0.825, -0.020), p = 0.047]. The educational program led to a significant decrease in awakenings, while the control group experienced an increase. The change in the number of awakenings (Rs = 0.183, p = 0.020) at 6 months was significantly associated with changes in frailty. Moreover, a significant time-by-group interaction was reported at the 12-month assessment [ß = -0.449, 95%CI (-0.844, -0.053), p = 0.026] for self-reported sleep quality, indicating better results in the intervention group compared to controls. CONCLUSION: The educational program improved sleep quality and sleep efficiency while reducing the number of awakenings per night among community-dwelling frail older adults, offering a practical approach to addressing sleep-related challenges in this demographic.

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