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1.
Dev Biol ; 512: 1-10, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38657748

RESUMEN

Precise regulation of gene expression is of utmost importance during cell fate specification. DNA methylation is a key epigenetic mechanism that plays a significant role in the regulation of cell fate by recruiting repression proteins or inhibiting the binding of transcription factors to DNA to regulate gene expression. Limb development is a well-established model for understanding cell fate decisions, and the formation of skeletal elements is coordinated through a sequence of events that control chondrogenesis spatiotemporally. It has been established that epigenetic control participates in cartilage maturation. However, further investigation is required to determine its role in the earliest stages of chondrocyte differentiation. This study investigates how the DNA methylation environment affects cell fate divergence during the early chondrogenic events. Our research has shown for the first time that inhibiting DNA methylation in interdigital tissue with 5-azacytidine results in the formation of an ectopic digit. This discovery suggested that DNA methylation dynamics could regulate the fate of cells between chondrogenesis and cell death during autopod development. Our in vitro findings indicate that DNA methylation at the early stages of chondrogenesis is integral in regulating condensation by controlling cell adhesion and proapoptotic genes. As a result, the dynamics of methylation and demethylation are crucial in governing chondrogenesis and cell death during different stages of limb chondrogenesis.


Asunto(s)
Diferenciación Celular , Condrocitos , Condrogénesis , Metilación de ADN , Extremidades , Metilación de ADN/genética , Condrogénesis/genética , Animales , Extremidades/embriología , Diferenciación Celular/genética , Condrocitos/metabolismo , Condrocitos/citología , Azacitidina/farmacología , Regulación del Desarrollo de la Expresión Génica , Embrión de Pollo , Epigénesis Genética , Apoptosis/genética
2.
J Am Pharm Assoc (2003) ; 64(5): 102140, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38825153

RESUMEN

BACKGROUND: The Medicare Medication Therapy Management (MTM) program has been available to eligible Medicare Part D beneficiaries since 2006, but research regarding program utilization and characterization is limited. OBJECTIVE: To describe enrollee and MTM program characteristics in a national sample of Medicare fee-for-service (FFS) beneficiaries (2013 to 2016). METHODS: Using a 5% random sample of Medicare FFS beneficiaries, we conducted a descriptive time series analysis to examine annual MTM enrollment and describe the type of MTM criteria at enrollment (Center for Medicare and Medicaid Services [CMS] vs. expanded). We investigated the offer of Comprehensive Medication Review (CMR) along with CMR receipt status, and delivery characteristics, as well as frequencies of Target Medication Reviews (TMRs). RESULT: Beneficiaries who met CMS enrollment criteria, compared to those eligible under expanded criteria, were significantly older, more likely to be of white race, more likely to be female, and had a significantly higher number of comorbidities. Of those meeting CMS criteria, the proportion receiving TMR increased from 95% in 2013% to 98.1% in 2016, and over 97% were offered a CMR. Although the proportion of beneficiaries offered a CMR was stable over the study period, the proportion who received a CMR increased from 17% in 2013% to 35.4% in 2016. Telephone CMR delivery was the most common method used (87.8% to 89.1% of CMRs over the study period). Over 95% of the CMRs were delivered by a pharmacist. CONCLUSION: During the years 2013 to 2016, enrollment in the MTM program increased, as did the proportion of enrollees receiving TMRs and CMRs. However, uptake remained low and the main factors driving participation remain unclear. Significant differences in demographic characteristics between beneficiaries enrolled under the CMS MTM enrollment criteria and the expanded criteria suggest the need to further investigate the optimal provision of such programs.


Asunto(s)
Planes de Aranceles por Servicios , Medicare Part D , Administración del Tratamiento Farmacológico , Humanos , Estados Unidos , Administración del Tratamiento Farmacológico/estadística & datos numéricos , Femenino , Masculino , Anciano , Planes de Aranceles por Servicios/estadística & datos numéricos , Anciano de 80 o más Años , Medicare Part D/estadística & datos numéricos , Centers for Medicare and Medicaid Services, U.S. , Medicare/estadística & datos numéricos , Farmacéuticos/estadística & datos numéricos
3.
Pharmacoepidemiol Drug Saf ; 29(3): 306-315, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32043303

RESUMEN

PURPOSE: Although polypharmacy in younger populations is a growing public health concern, most studies addressing polypharmacy focus on elderly populations. Thus, polypharmacy is not yet well understood in younger populations. METHODS: Baseline data from the Maule Cohort (MAUCO) (adults aged 38-74 years) were used to study the prevalence of polypharmacy and associated participant characteristics using logistic and zero-inflated negative binomial regressions. Factors studied include age, sex, self-rated health, education, smoking, obesity, diabetes, hypertension, and other chronic conditions. RESULTS: Polypharmacy was reported by 10% of participants overall, with higher prevalence among older (≥60 years) vs middle aged (<60 years) participants (overall: 20.9% vs 6.0%, P < .0001; for those reporting any medication use: 30.2% vs 15.9%, P < .0001). Middle-aged adults reported different patterns of medication use by polypharmacy status, while older adults reported similar medication use patterns regardless of polypharmacy. Diabetes, hypertension, dyslipidemia, cardiovascular diseases, hypothyroidism, and osteomuscular diseases were significantly associated with polypharmacy. Analyses also revealed that there are MAUCO participants who are potentially being undertreated for conditions like depression. CONCLUSIONS: Research into medication use among younger and middle-aged adults and development of possible tools to deprescribe medications in this population are warranted. However, it is important that patients who need treatment receive it, and so both potential overtreatment and undertreatment need further study in this population.


Asunto(s)
Polifarmacia , Población Rural/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Chile/epidemiología , Enfermedad Crónica , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia
4.
Can J Anaesth ; 67(8): 942-948, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32152885

RESUMEN

PURPOSE: Despite the popularity of the erector spinae plane (ESP) block, both the mechanism of the block and the extent of injectate spread is unclear. This study used magnetic resonance imaging (MRI) to evaluate the spread of local anesthetic injectate following ESP blocks in six patients with pain. METHODS: Six patients received a left-sided ultrasound-guided ESP block at the T10 level. The injectate contained 29.7 mL of 0.25% bupivacaine and 0.3 mL of gadolinium in the first patient, with an additional 5 mL (50 mg) of triamcinolone in the subsequent five patients. Sensory block to pinprick and cold as well as pain score (with 0 indicating no pain and 10 being maximum pain) were assessed 20 and 30 min respectively following the ESP block. MRI was performed one hour after the block. RESULT: The injectate spread into the intercostal space and neural foramina in all six patients, but the extent of cephalocaudal spread was variable, with a median [interquartile range] spread of 9 [5-11] and 3 [2-6] levels for the intercostal space and neural foramina, respectively. The injectate also spread extensively within the erector spinae muscles. Spread to the epidural space was seen in two patients. Sensory block was achieved in both ventral and dorsal dermatomes in all patients, though the extent was variable. CONCLUSIONS: Our study showed that the ESP block injectate consistently spread to the erector spinae muscles, neural foramina, and intercostal space. It was associated with sensory changes and pain relief in the dorsal and ventral thoracic and abdominal walls. Nevertheless, the extent of spread to the neural foramina and intercostal space, and the sensory block itself, was highly variable.


RéSUMé: OBJECTIF: Malgré la popularité du bloc plan des érecteurs du rachis (PER), le mécanisme du bloc et l'ampleur de la diffusion du produit injecté ne sont pas clairement connus. Cette étude a utilisé l'imagerie par résonance magnétique (IRM) pour évaluer la diffusion de l'anesthésique local injecté après des blocs du PER chez six patients présentant des douleurs. MéTHODES: Six patients ont reçu un bloc du PER guidé par échographie du côté gauche au niveau T10. Le produit injecté contenait 29,7 mL de bupivacaïne 0,25 % et 0,3 mL de gadolinium pour le premier patient avec un supplément de 5 mL (50 mg) de triamcinolone pour les cinq patients suivants. Le bloc sensitif au toucher/piquer et au froid, ainsi que le score de douleur (où 0 indique une absence de douleur et 10, une douleur maximum) ont été évalués respectivement 20 et 30 minutes après le bloc du PER. Une IRM a été réalisée une heure après le bloc. RéSULTAT: Le produit injecté a diffusé dans l'espace intercostal et les foramens intervertébraux chez les six patients, mais l'étendue de la diffusion céphalocaudale a été variable avec une diffusion médiane [plage interquartile] de 9 [5 à 11] niveaux pour les espaces intercostaux et 3 [2 à 6] niveaux pour les foramens intervertébraux. Le produit injecté a également largement diffusé dans les muscles érecteurs du rachis. Une diffusion vers l'espace épidural a été observée chez deux patients. Un bloc sensitif des dermatomes ventraux et dorsaux a été obtenu chez tous les patients, bien que son étendue ait été variable. CONCLUSIONS: Notre étude a montré que le produit injecté dans un bloc du PER diffusait constamment dans les muscles érecteurs du rachis, les foramens intervertébraux et les espaces intercostaux. Il a été associé à des modifications sensorielles et à un soulagement de la douleur dans les parois thoraciques et abdominales, ventrales et dorsales. Néanmoins, l'étendue de la diffusion vers les foramens intervertébraux et les espaces intercostaux, ainsi que le bloc sensitif proprement dit ont été très variables.


Asunto(s)
Anestésicos Locales , Bloqueo Nervioso , Cadáver , Humanos , Imagen por Resonancia Magnética , Vértebras Torácicas/diagnóstico por imagen
5.
Rev Med Chil ; 148(3): 393-398, 2020 Mar.
Artículo en Español | MEDLINE | ID: mdl-32730385

RESUMEN

The catastrophic emergency experienced by many countries with the COVID-19 pandemic emphasized the importance of bioethics for decision-making, both at the public health (equitable and effective policies) and at the clinical level. At the clinical level, the issues are the fulfillment of medical care demand with adequate health care teams, infrastructure, and supplies, and to cover critical care demands that surpass the available resources. Therefore, ethically correct approaches are required for the allocation of life sustaining resources. There are recommendations for the allocating life support during disasters based on multiple considerations, including ethical ones. However, the ethical criteria of existing guidelines are variable. Ethical principles usually considered are saving the greatest number of lives, saving the greatest number of years of life and the principle of the life cycle or the goal to give each individual equal opportunity to live through the various phases of life. However, the centrality of the human being and the search for the common good should be considered. Knowledge of public perspectives and moral benchmarks on these issues is essential. A successful assignment effort will require everyone's trust and cooperation. Decision making should be planned and discussed in advance, since in-depth deliberation will be extremely complex during the disaster. Our goal is to help the health care teams to wisely allocate resources in shortage periods.


Asunto(s)
Toma de Decisiones Clínicas/ética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Asignación de Recursos para la Atención de Salud/ética , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/terapia , COVID-19 , Chile/epidemiología , Humanos , Guías de Práctica Clínica como Asunto
6.
Pharmacol Res ; 114: 175-184, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27818231

RESUMEN

Epigenetic silencing of tumor suppressor genes is a phenomenon frequently observed in multiple cancers. Ras-association domain family 1 isoform A (RASSF1A) is a well-characterized tumor suppressor that belongs to the Ras-association domain family. Several studies have demonstrated that hypermethylation of the RASSF1A promoter is frequently observed in lung, prostate, and breast cancers. Phenethyl isothiocyanate (PEITC), a phytochemical abundant in cruciferous vegetables, possesses chemopreventive activities; however, its potential involvement in epigenetic mechanisms remains elusive. The present study aimed to examine the role of PEITC in the epigenetic reactivation of RASSF1A and the induction of apoptosis in LNCaP cells. LNCaP cells were treated for 5days with 0.01% DMSO, 2.5 or 5µM PETIC or 2.5µM azadeoxycytidine (5-Aza) with 0.5µM trichostatin A (TSA). We evaluated the effects of these treatments on CpG demethylation using methylation-specific polymerase chain reaction (MSP) and bisulfite genomic sequencing (BGS). CpG demethylation was significantly enhanced in cells treated with 5µM PEITC and 5-Aza+TSA; therefore, the latter treatment was used as a positive control in subsequent experiments. The decrease in RASSF1A promoter methylation correlated with an increase in expression of the RASSF1A gene in a dose-dependent manner. To confirm that promoter demethylation was mediated by DNA methyltransferases (DNMTs), we analyzed the expression levels of DNMTs and histone deacetylases (HDACs) at the gene and protein levels. PEITC reduced DNMT1, 3A and 3B protein levels in a dose-dependent manner, and 5µM PEITC significantly reduced DNMT3A and 3B protein levels. HDAC1, 2, 4 and 6 protein expression was also inhibited by 5µM PEITC. The combination of 5-Aza and TSA, a DNMT inhibitor and a HDAC inhibitor, respectively, was used as a positive control as this treatment significantly inhibited both HDACs and DNMTs. The function of RASSF1A reactivation in promoting apoptosis and inducing G2/M cell cycle arrest was analyzed using flow-cytometry analysis with Annexin V and propidium iodide (PI). Growth inhibition effect on LNCaP cells were investigated by colony formation assay. In addition, we analyzed p21, caspase-3 and 7, Bax, and Cyclin B1 protein levels. Flow-cytometry analysis of cells stained with PI alone demonstrated that 5µM PEITC promotes early apoptosis and G2/M cell cycle arrest. Flow cytometry analysis of cells stained with Annexin V and PI also demonstrated an increased proportion of cells in early apoptosis in cells treated with 5µM PEITC or 5-Aza with TSA. PEITC and efficiently inhibit colony numbers and total area. In addition, 5µM PEITC significantly enhanced p21, caspase-3, 7 and Bax levels and reduced Cyclin B1 expression compared with the control group. Collectively, the results of our study suggest that PEITC induces apoptosis in LNCaP cells potentially by reactivating RASSF1A via epigenetic mechanisms.


Asunto(s)
Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Isotiocianatos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas Supresoras de Tumor/genética , Línea Celular Tumoral , Metilación de ADN/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Regiones Promotoras Genéticas/efectos de los fármacos , Neoplasias de la Próstata/genética
7.
Biopharm Drug Dispos ; 36(7): 440-51, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25904312

RESUMEN

Apigenin (API) and luteolin (LUT) have been used as therapeutic agents in folk medicine for thousands of years. These compounds exert a variety of biological activities, including anticancer, antioxidant and antiinflammatory activities. This study investigated whether API and LUT could activate Nrf2-antioxidant response element (ARE)-mediated gene expression and induce antiinflammatory activities in human hepatoma HepG2 cells. The compounds did not exhibit any substantial toxicity at low doses (1.56-6.25 µm). The induction of ARE activity was assessed in HepG2-C8 cells after treatment with low doses of API and LUT for 6 and 12 h. It was found that the induction of ARE activity by these compounds at the higher doses was comparable to the effects of the positive control, SFN at a dose of 6.25 µm. Exposure to the PI3K inhibitor LY294002 abolished ARE activation by both API and LUT, whereas the ERK-1/2 inhibitor PD98059 only decreased ARE activity induced by API. Both compounds significantly increased the endogenous mRNA and protein levels of Nrf2 and Nrf2 target genes with important effects on heme oxygenase-1 (HO-1) expression. API and LUT significantly and dose-dependently decreased the production of nitric oxide (NO), nitric oxide synthase (iNOS) and cytosolic phospholipase A2 (cPLA2), which were induced by the treatment of HepG2 cells with 1 µg/ml of lipopolysaccharide (LPS) for 24 h. The results indicate that API and LUT significantly activate the PI3K/Nrf2/ARE system, and this activation may be responsible for their antiinflammatory effects, as demonstrated by the suppression of LPS-induced NO, iNOS and cPLA2.


Asunto(s)
Apigenina/farmacología , Flavonas/farmacología , Luteolina/farmacología , Factor 2 Relacionado con NF-E2/biosíntesis , Fitoquímicos/farmacología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica , Células Hep G2 , Humanos , Factor 2 Relacionado con NF-E2/agonistas , Factor 2 Relacionado con NF-E2/genética
8.
Chem Res Toxicol ; 27(12): 2036-43, 2014 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-25387343

RESUMEN

The role of phytochemicals in preventive and therapeutic medicine is a major area of scientific research. Several studies have illustrated the mechanistic roles of phytochemicals in Nrf2 transcriptional activation. The present study aims to examine the importance of the transcription factor Nrf2 by treating peritoneal macrophages from Nrf2(+/+) and Nrf2(-/-) mice ex vivo with phenethyl isothiocyanate (PEITC) and curcumin (CUR). The peritoneal macrophages were pretreated with the drugs and challenged with lipopolysaccharides (LPSs) alone and in combination with PEITC or CUR to assess their anti-inflammatory and antioxidative effects based on gene and protein expression in the treated cells. LPS treatment resulted in an increase in the expression of inflammatory markers such as cycloxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in both Nrf2(+/+) and Nrf2(-/-) macrophages, detected by quantitative polymerase chain reaction (qPCR). Nrf2(+/+) macrophages treated with PEITC and CUR exhibited a significant decrease in the expression of these anti-inflammatory genes along with an increase in the expression of hemeoxygenase-1 (HO-1), which is an antioxidative stress gene downstream of the Nrf2 transcription factor battery. Although there was no significant decrease in the expression of the anti-inflammatory genes or an increase in HO-1 expression in Nrf2(-/-) macrophages treated with either PEITC or CUR, there was a significant decrease in the protein expression of COX-2 and an increase in the expression of HO-1 in Nrf2(+/+) macrophages treated with PEITC compared to that with CUR treatment. No significant changes were observed in the macrophages from knockout animals. Additionally, there was a significant decrease in LPS-induced IL-6 and TNF-α production following PEITC treatment compared with that following CUR in Nrf2(+/+) macrophages, whereas no change was observed in the macrophages from knockout animals. The results from qPCR, western blot, and ELISA analyses in macrophages from Nrf2(+/+) and Nrf2 (-/-) mice indicate that Nrf2 plays an important role in the anti-inflammatory and antioxidative effects of PEITC and CUR, as observed by their decreased activities in Nrf2(-/-) macrophages.


Asunto(s)
Antiinflamatorios/farmacología , Curcumina/farmacología , Isotiocianatos/farmacología , Factor 2 Relacionado con NF-E2/fisiología , Animales , Secuencia de Bases , Cartilla de ADN , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 2 Relacionado con NF-E2/genética , Nitritos/antagonistas & inhibidores , Nitritos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
9.
Ecancermedicalscience ; 18: 1661, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38425770

RESUMEN

Research is an essential element in the practice of healthcare, and hospitals play a fundamental role in its promotion. Research in hospitals can improve the quality of care, knowledge of diseases and the discovery of new therapies. Hospitals can conduct research in various fields, including basic research, clinical research, population-based research and even hospital management research. The findings of hospital research can be directly applied to clinical practice and management, thereby enhancing the quality of patient care, a central paradigm in translational health. This article details the experience of the National Cancer Institute of Chile over the past 8 years in its role as a high-complexity public hospital, specialised institute, healthcare centre, teaching institution, and research facility. It reviews the work of generating and strengthening its institutional research model since its redesign in 2018, the key elements that underpin it, and discusses the challenges the institute faces in its growth amidst the increasing cancer epidemiology in Chile, the recent enactment of a National Cancer Law, the post-pandemic scenario that has left a significant waiting list of oncology patients, and the initiation of the design and construction process for the new institute building.

10.
JAMA Netw Open ; 7(2): e2356619, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38393731

RESUMEN

Importance: Nonadherence to antihypertensive medications is associated with uncontrolled blood pressure, higher mortality rates, and increased health care costs, and food insecurity is one of the modifiable medication nonadherence risk factors. The Supplemental Nutrition Assistance Program (SNAP), a social intervention program for addressing food insecurity, may help improve adherence to antihypertensive medications. Objective: To evaluate whether receipt of SNAP benefits can modify the consequences of food insecurity on nonadherence to antihypertensive medications. Design, Setting, and Participants: A retrospective cohort study design was used to assemble a cohort of antihypertensive medication users from the linked Medical Expenditure Panel Survey (MEPS)-National Health Interview Survey (NHIS) dataset for 2016 to 2017. The MEPS is a national longitudinal survey on verified self-reported prescribed medication use and health care access measures, and the NHIS is an annual cross-sectional survey of US households that collects comprehensive health information, health behavior, and sociodemographic data, including receipt of SNAP benefits. Receipt of SNAP benefits in the past 12 months and food insecurity status in the past 30 days were assessed through standard questionnaires during the study period. Data analysis was performed from March to December 2021. Exposure: Status of SNAP benefit receipt. Main Outcomes and Measures: The main outcome, nonadherence to antihypertensive medication refill adherence (MRA), was defined using the MEPS data as the total days' supply divided by 365 days for each antihypertensive medication class. Patients were considered nonadherent if their overall MRA was less than 80%. Food insecurity status in the 30 days prior to the survey was modeled as the effect modifier. Inverse probability of treatment (IPT) weighting was used to control for measured confounding effects of baseline covariates. A probit model was used, weighted by the product of the computed IPT weights and MEPS weights, to estimate the population average treatment effects (PATEs) of SNAP benefit receipt on nonadherence. A stratified analysis approach was used to assess for potential effect modification by food insecurity status. Results: This analysis involved 6692 antihypertensive medication users, of whom 1203 (12.8%) reported receiving SNAP benefits and 1338 (14.8%) were considered as food insecure. The mean (SD) age was 63.0 (13.3) years; 3632 (51.3%) of the participants were women and 3060 (45.7%) were men. Although SNAP was not associated with nonadherence to antihypertensive medications in the overall population, it was associated with a 13.6-percentage point reduction in nonadherence (PATE, -13.6 [95% CI, -25.0 to -2.3]) among the food-insecure subgroup but not among their food-secure counterparts. Conclusions and Relevance: This analysis of a national observational dataset suggests that patients with hypertension who receive SNAP benefits may be less likely to become nonadherent to antihypertensive medication, especially if they are experiencing food insecurity. Further examination of the role of SNAP as a potential intervention for preventing nonadherence to antihypertensive medications through prospectively designed interventional studies or natural experiment study designs is needed.


Asunto(s)
Asistencia Alimentaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antihipertensivos/uso terapéutico , Estudios Transversales , Pobreza , Estudios Retrospectivos , Anciano , Conjuntos de Datos como Asunto
11.
Anat Rec (Hoboken) ; 307(9): 3166-3186, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38323748

RESUMEN

Annual killifishes have active and voracious rates in acquisition of food resources with display of behaviors that allow them to maintain high metabolic rates to deal with the harsh and unpredictable conditions prevalent in temporary pools where they inhabit. The objective of this research was to describe histologically and ultrastructurally, the digestive system of the annual killifish Millerichthys robustus to identify morphological traits related to its annual life history and digestive physiology. Also, we quantify food items along the intestine as a proxy for rates of digestion. Millerichthys has a short digestive system, associated with a carnivorous diet, with no evidence of a stomach. Instead, the presence of pharyngeal jaws with caniform teeth was documented, related to the breakdown of invertebrate exoskeletons, allowing prey fluids to be tasted by taste corpuscles related to selection of food items, and that digestive enzymes penetrate once in the intestine. The histological morphology of the intestine showed four different regions, associated with its digestive rates: (i) reception of food from the esophagus with intact pray; (ii) digestion with enzymes from the pancreas and liver/gallbladder of simple exoskeleton prey (Entognatha), and beginning of absorption; (iii) absorption of nutrients, and digestion of large-complex exoskeleton prey (Hexanauplia, Brachiopoda, and Ostracoda); and (iv) probable absorption of intact macromolecules. The second region of the intestine presented two anatomical loops and the highest thickness that may be related to reducing the speed of food transit, allowing for more efficient digestion given the large amount of food ingested by this species.


Asunto(s)
Tracto Gastrointestinal , Animales , Tracto Gastrointestinal/anatomía & histología , Tracto Gastrointestinal/fisiología , Fundulidae/fisiología , Fundulidae/anatomía & histología , Digestión/fisiología , Conducta Alimentaria/fisiología
12.
Drug Saf ; 47(1): 93-102, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37935996

RESUMEN

INTRODUCTION: Polypharmacy is common and is associated with higher risk of adverse drug event (ADE) among older adults. Knowledge on the ADE risk level of exposure to different drug combinations is critical for safe polypharmacy practice, while approaches for this type of knowledge discovery are limited. The objective of this study was to apply an innovative data mining approach to discover high-risk and alternative low-risk high-order drug combinations (e.g., three- and four-drug combinations). METHODS: A cohort of older adults (≥ 65 years) who visited an emergency department (ED) were identified from Medicare fee-for-service and MarketScan Medicare supplemental data. We used International Classification of Diseases (ICD) codes to identify ADE cases potentially induced by anticoagulants, antidiabetic drugs, and opioids from ED visit records. We assessed drug exposure data during a 30-day window prior to the ED visit dates. We investigated relationships between exposure of drug combinations and ADEs under the case-control setting. We applied the mixture drug-count response model to identify high-order drug combinations associated with an increased risk of ADE. We conducted therapeutic class-based mining to reveal low-risk alternative drug combinations for high-order drug combinations associated with an increased risk of ADE. RESULTS: We investigated frequent high-order drug combinations from 8.4 million ED visit records (5.1 million from Medicare data and 3.3 million from MarketScan data). We identified 5213 high-order drug combinations associated with an increased risk of ADE by controlling the false discovery rate at 0.01. We identified 1904 high-order, high-risk drug combinations had potential low-risk alternative drug combinations, where each high-order, high-risk drug combination and its corresponding low-risk alternative drug combination(s) have similar therapeutic classes. CONCLUSIONS: We demonstrated the application of a data mining technique to discover high-order drug combinations associated with an increased risk of ADE. We identified high-risk, high-order drug combinations often have low-risk alternative drug combinations in similar therapeutic classes.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Polifarmacia , Anciano , Humanos , Estados Unidos , Medicare , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Combinación de Medicamentos , Minería de Datos
13.
J Alzheimers Dis ; 95(3): 1221-1231, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37661887

RESUMEN

BACKGROUND: Subjective memory complaints (SMC) are commonly studied in older adults and have been identified as potentially prodromal to dementia and Alzheimer's disease. Studies among younger adults from South America are lacking. OBJECTIVE: To estimate the prevalence of SMC and the factors associated with it among Maule Cohort (MAUCO) participants. METHODS: We performed a cross-sectional analysis to estimate the prevalence of SMC and investigated its associated factors from MAUCO baseline data (N = 6,687). Within groups defined by age (38-59, 60-74) and global cognition (Mini-Mental State Examination: ≥26, 25-22, ≤21), multinomial logistic regression models evaluated risk factors for SMC (Yes, Sometimes, No). RESULTS: Overall, SMC prevalence was 16.4%; 15.9% (95% CI 14.9-16.9%) among younger and 17.6% (15.8-19.4%) among older participants. Female sex, comorbidities, and bad/fair self-reported health status (SRHS) were generally associated with higher odds of SMC. CONCLUSION: Overall prevalence of SMC was 16%. Different factors were associated with the odds of SMC depending on age and global cognitive status. Future SMC studies should include sex-specific assessments, evaluate SRHS as a moderator of SMC reporting, and the influence of the SARS-CoV-2 pandemic on SMC reporting.


Asunto(s)
COVID-19 , Trastornos de la Memoria , Masculino , Humanos , Femenino , Anciano , Trastornos de la Memoria/etiología , Chile/epidemiología , Prevalencia , Población Rural , Estudios Transversales , COVID-19/epidemiología , COVID-19/complicaciones , SARS-CoV-2 , Pruebas Neuropsicológicas
14.
Theriogenology ; 202: 93-102, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36933286

RESUMEN

Lectin-like molecules play a key role in mammalian sperm functionality. These multifunctional proteins have been proven to be involved in sperm capacitation, sperm motility, and viability, formation of the oviductal sperm reservoir, and in sperm-oocyte interaction. In a previous study, we reported the presence of a novel seminal plasma lectin, sperm lectin 15 kDa (SL15), adsorbed to the llama sperm. In order to gain knowledge in the understanding of SL15 and its functions, the aims of this study were to (a) elucidate the presence and localization of SL15 in the llama male reproductive tract and sperm, and (b) determine whether the sperm cryopreservation process of cooling and freeze-thawing affects the SL15 levels and distribution on llama sperm. We found that SL15 protein was expressed along the male reproductive system: testis, epididymis, prostate, and bulbourethral glands, being the prostate the main site of SL15 secretion. SL15 was localized on the sperm head, following different localization patterns. In order to understand if sperm cryopreservation induces modifications in the SL15 adsorption pattern, immunocytochemistry and flow cytometry analysis were carried out on fresh, 24 h cooled, and frozen-thawed sperm. Both cooled and frozen sperm showed particular SL15 patterns, that were not observed in the freshly ejaculated, indicating loss of SL15. Flow cytometry analysis also exhibited a decrease of SL15 in the cooled sperm (P < 0.05), whereas a tendency to decrease was found in frozen-thawed sperm (P < 0.1) when compared with freshly ejaculated sperm. This study extends the knowledge about the SL15 in the llama male physiology and provides evidence that cryopreservation-related techniques disrupt SL15 adsorption to the sperm membrane, possibly affecting sperm functionality and fertility.


Asunto(s)
Camélidos del Nuevo Mundo , Preservación de Semen , Masculino , Animales , Semen/metabolismo , Próstata , Lectinas/metabolismo , Motilidad Espermática , Espermatozoides/fisiología , Criopreservación/veterinaria , Criopreservación/métodos , Preservación de Semen/veterinaria , Preservación de Semen/métodos
15.
Int J Breast Cancer ; 2021: 5691584, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34707910

RESUMEN

BACKGROUND: With treatment for breast cancer, women treated may present significant sensory abnormalities in the upper extremity. However, there are no conclusive studies that have evaluated pressure pain thresholds (PPT) in the shoulder of postoperated women for breast cancer. The aim of this study was to compare PPT in the shoulder, stress, anxiety, depression symptoms, and quality of sleep among postoperated women for breast cancer (PO group) and asymptomatic women of shoulder pain (control group). METHODS: 40 women participated (n = 20, PO group, age: average ± standard deviation, 49.2 ± 8.3 years; body mass index (BMI): 27.5 ± 3.0 kg/cm2; surgery time: 22.2 ± 34.4 months; n = 20, control group, 46.9 ± 8.1 years; BMI: 26.8 ± 3.5 kg/cm2). The PPT was evaluated with a digital algometer at 32 points in the shoulder region and one control point in the tibialis anterior. Stress, anxiety, and depression were evaluated with the Depression, Anxiety and Stress Scale 21 (DASS-21) and the quality of sleep by the Pittsburgh Sleep Quality Index. RESULTS: Significant differences were observed over 1.5 kgf/cm2 in 33 points evaluated (p < 0.01) with a small to high effect size (Cliff's delta range = 0.16; 0.92) and higher levels of anxiety and stress in the PO group (anxiety: median [first; third quartile], 5[3; 12.5]; stress: 9.7 ± 4.7 (7.8; 11.8)) in comparison with the control group (anxiety: 2.5[1; 4.8]; stress: 6.7 ± 3.31 (5.2; 8.3), (p < 0.05)). No significant differences were found between the groups in depression and sleep quality (p > 0.05). CONCLUSION: Postoperated women for breast cancer present hyperalgesia in the shoulder anterior and posterior region, low PPT in the tibialis anterior, and higher levels of stress and anxiety compared to the control group.

16.
Front Vet Sci ; 7: 587596, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33195617

RESUMEN

Semen cryopreservation in South American camelids has a low efficiency. Post-thaw viability of sperm is low, and poor results are obtained when artificial insemination is performed with cryopreserved semen, impeding advances both in accelerated genetic progress and selection. This study aimed to describe the effect of a conventional method of camelid semen cryopreservation on the llama sperm ultrastructure during cooling and freezing, using transmission and scanning electron microscopy (TEM, SEM). Sperm motility, vigor, viability, and DNA integrity during those steps were also examined. Ejaculates from five fertile adult llama males were obtained by electroejaculation. For cooling, semen samples were washed with Hepes-balanced salt solution (HBSS), diluted in Tris-citric acid-fructose egg yolk extender (TCF-EY), and then cooled until 5°C for 24 h. For freezing, sperm samples were washed with HBSS, diluted in TCF-EY and cooled until 5°C for 2.5 h. Samples were equilibrated with TCF-EY, supplemented with 6% glycerol at 5°C for 20 min, and then stored in liquid nitrogen for a month before thawing. TEM and SEM analyses were carried out on sperm samples prior to cryopreservation, after cooling down until 5°C for 2.5 and 24 h, and after the freeze-thaw process. Ultrastructural injury was noticed during cooling, even though sperm motility, vigor, viability, and DNA integrity were not significantly affected. Analysis revealed plasma membrane and acrosome damage, loss of mitochondria, and axoneme and periaxonemal structure disorganization after 2.5 h of cooling. During freezing, a significant decrease in sperm motility and viability was observed after thawing. TEM and SEM revealed prominent signs of post-thawing damage. The plasma membrane was lost or exhibited various degrees of swelling, undulation, and perforations. Besides, the sperm presented vacuoles in the nucleus and broken acrosomes. Mitochondria in the midpiece showed vacuolization and structural disorganization. In conclusion, SEM and TEM revealed that cryopreservation induced ultrastructural damages in llama sperm that initiated during cooling and intensified during freezing. These details provide valuable data for further studies to minimize cryodamage in camelid sperm.

17.
Mol Oncol ; 14(11): 2834-2852, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33326125

RESUMEN

Gallbladder stones (cholecystolithiasis) are the main risk factor for gallbladder cancer (GBC), a lethal biliary malignancy with poor survival rates worldwide. Gallbladder stones are thought to damage the gallbladder epithelium and trigger chronic inflammation. Preneoplastic lesions that arise in such an inflammatory microenvironment can eventually develop into invasive carcinoma, through mechanisms that are not fully understood. Here, we developed a novel gallbladder preneoplasia mouse model through the administration of two lithogenic diets (a low- or a high-cholesterol diet) in wild-type C57BL/6 mice over a period of 9 months. Additionally, we evaluated the chemopreventive potentials of the anti-inflammatory drug aspirin and the cholesterol absorption inhibitor ezetimibe. Both lithogenic diets induced early formation of gallbladder stones, together with extensive inflammatory changes and widespread induction of metaplasia, an epithelial adaptation to tissue injury. Dysplastic lesions were presented only in mice fed with high-cholesterol diet (62.5%) in late stages (9th month), and no invasive carcinoma was observed at any stage. The cholesterol absorption inhibitor ezetimibe inhibited gallbladder stone formation and completely prevented the onset of metaplasia and dysplasia in both lithogenic diets, whereas aspirin partially reduced metaplasia development only in the low-cholesterol diet setting. This model recapitulates several of the structural and inflammatory findings observed in human cholecystolithiasic gallbladders, making it relevant for the study of gallbladder carcinogenesis. In addition, our results suggest that the use of cholesterol absorption inhibitors and anti-inflammatory drugs can be evaluated as chemopreventive strategies to reduce the burden of GBC among high-risk populations.


Asunto(s)
Aspirina/uso terapéutico , Quimioprevención , Ezetimiba/uso terapéutico , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/prevención & control , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/prevención & control , Animales , Colecistolitiasis/complicaciones , Colesterol/metabolismo , Colesterol en la Dieta , Enfermedad Crónica , Dieta , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Hígado Graso/patología , Conducta Alimentaria , Neoplasias de la Vesícula Biliar/patología , Cálculos Biliares/etiología , Cálculos Biliares/patología , Inflamación/patología , Masculino , Metaplasia , Ratones Endogámicos C57BL , Lesiones Precancerosas/patología , Bazo/patología
18.
Cell Biosci ; 8: 3, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29344347

RESUMEN

PURPOSE: We investigated the genomic DNA methylation profile of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to analyze the crosstalk among targeted genes and the related functional pathways. METHODS: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were isolated. The DNA methylation profiles were analyzed by methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq). Canonical pathways, diseases and function and network analyses of the different samples were then performed using the Ingenuity® Pathway Analysis (IPA) software. Some target genes with significant difference in methylation were selected for validation using methylation specific primers (MSP) and qPCR. RESULTS: TRAMP mice undergo extensive aberrant CpG hyper- and hypo-methylation. There were 2147 genes with a significant (log2-change ≥ 2) change in CpG methylation between the two groups, as mapped by the IPA software. Among these genes, the methylation of 1105 and 1042 genes was significantly decreased and increased, respectively, in TRAMP prostate tumors. The top associated disease identified by IPA was adenocarcinoma; however, the cAMP response element-binding protein (CREB)-, histone deacetylase 2 (HDAC2)-, glutathione S-transferase pi (GSTP1)- and polyubiquitin-C (UBC)-related pathways showed significantly altered methylation profiles based on the canonical pathway and network analyses. MSP and qPCR results of genes of interests corroborated with MeDIP-seq findings. CONCLUSIONS: This is the first MeDIP-seq with IPA analysis of the TRAMP model to provide novel insight into the genome-wide methylation profile of prostate cancer. Studies on epigenetics, such as DNA methylation, will potentially provide novel avenues and strategies for further development of biomarkers targeted for treatment and prevention approaches for prostate cancer.

19.
Curr Pharmacol Rep ; 1(3): 179-196, 2015 05.
Artículo en Inglés | MEDLINE | ID: mdl-26457242

RESUMEN

Glucosinolates are a group of sulfur-containing glycosides found in many plant species, including cruciferous vegetables such as broccoli, cabbage, brussels sprouts, and cauliflower. Accumulating evidence increasingly supports the beneficial effects of dietary glucosinolates on overall health, including as potential anti-cancer agents, because of their role in the prevention of the initiation of carcinogenesis via the induction of cellular defense detoxifying/antioxidant enzymes and their epigenetic mechanisms, including modification of the CpG methylation of cancer-related genes, histone modification regulation and changes in the expression of miRNAs. In this context, the defense mechanism mediated by Nrf2-antioxidative stress and anti-inflammatory signaling pathways can contribute to cellular protection against oxidative stress and reactive metabolites of carcinogens. In this review, we summarize the cancer chemopreventive role of naturally occurring glucosinolate derivatives as inhibitors of carcinogenesis, with particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo human cancer animal models.

20.
Rev. méd. Chile ; 148(3): 393-398, mar. 2020.
Artículo en Español | LILACS | ID: biblio-1115804

RESUMEN

The catastrophic emergency experienced by many countries with the COVID-19 pandemic emphasized the importance of bioethics for decision-making, both at the public health (equitable and effective policies) and at the clinical level. At the clinical level, the issues are the fulfillment of medical care demand with adequate health care teams, infrastructure, and supplies, and to cover critical care demands that surpass the available resources. Therefore, ethically correct approaches are required for the allocation of life sustaining resources. There are recommendations for the allocating life support during disasters based on multiple considerations, including ethical ones. However, the ethical criteria of existing guidelines are variable. Ethical principles usually considered are saving the greatest number of lives, saving the greatest number of years of life and the principle of the life cycle or the goal to give each individual equal opportunity to live through the various phases of life. However, the centrality of the human being and the search for the common good should be considered. Knowledge of public perspectives and moral benchmarks on these issues is essential. A successful assignment effort will require everyone's trust and cooperation. Decision making should be planned and discussed in advance, since in-depth deliberation will be extremely complex during the disaster. Our goal is to help the health care teams to wisely allocate resources in shortage periods.


Asunto(s)
Humanos , Neumonía Viral/terapia , Neumonía Viral/epidemiología , Asignación de Recursos para la Atención de Salud/ética , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/epidemiología , Pandemias , Toma de Decisiones Clínicas/ética , Chile/epidemiología , Guías de Práctica Clínica como Asunto
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