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1.
Enferm Clin (Engl Ed) ; 34(2): 130-140, 2024.
Article in English | MEDLINE | ID: mdl-38484935

ABSTRACT

AIM: To examine and map alcohol consumption in children and adolescents with chronic pain (CP). METHOD: A scoping review of international databases (CINAHL, WOS, PubMed, PsycINFO, Scopus, Embase, and MEDLINE) and grey literature was conducted between September 2022 and February 2023. Documents addressing the relationship between alcohol consumption and CP in children and adolescents, published in English and Spanish between 2012 and 2023, were included. Those papers with a population suffering from CP derived from neurodegenerative diseases, chronic infectious diseases or cognitive impairment were excluded. We assessed the level of evidence (LE) and the degree of recommendation (DR) of the studies included in accordance with the Scottish Intercollegiate Guidelines Network. Finally, 11 documents were considered out of the 479 reviewed. RESULTS: The relationship between substance consumption and CP in adolescents is a scarcely investigated topic. While there is a trend towards lower rates of alcohol consumption in youth with pain, there is evidence suggesting an association, particularly in cases of intense pain. The use of various substances, both legal and illegal, for pain management underscores the importance of comprehensively addressing this phenomenon in this population. CONCLUSIONS: Further research is needed to assess the relationship between alcohol consumption in children and adolescents with CP.


Subject(s)
Alcohol Drinking , Chronic Pain , Humans , Chronic Pain/epidemiology , Adolescent , Child , Alcohol Drinking/epidemiology
2.
Kidney Blood Press Res ; 49(1): 114-123, 2024.
Article in English | MEDLINE | ID: mdl-38246148

ABSTRACT

INTRODUCTION: A comprehensive pathophysiological mechanism to explain the relationship between high-salt intake and hypertension remains undefined. Evidence suggests that chloride, as the accompanying anion of sodium in dietary salt, is necessary to develop hypertension. We evaluated whether reducing dietary Cl- while keeping a standard Na+ intake modified blood pressure, cardiac hypertrophy, renal function, and vascular contractility after angiotensin II (AngII) infusion. METHODS: C56BL/6J mice fed with standard Cl- diet or a low-Cl- diet (equimolar substitution of Cl- by a mixture of Na+ salts, both diets with standard Na+ content) received AngII (infusion of 1.5 mg/kg/day) or vehicle for 14 days. We measured systolic blood pressure (SBP), glomerular filtration rate (GFR), natriuretic response to acute saline load, and contractility of aortic rings from mice infused with vehicle and AngII, in standard and low-Cl- diet. RESULTS: The mice fed the standard diet presented increased SBP and cardiac hypertrophy after AngII infusion. In contrast, low-Cl- diet prevented the increase of SBP and cardiac hypertrophy. AngII-infused mice fed a standard diet presented hampered natriuretic response to saline load, meanwhile the low-Cl- diet preserved natriuretic response in AngII-infused mice, without change in GFR. Aortic rings from mice fed with standard diet or low-Cl- diet and infused with AngII presented a similar contractile response. CONCLUSION: We conclude that the reduction in dietary Cl- as the accompanying anion of sodium in salt is protective from AngII pro-hypertensive actions due to a beneficial effect on kidney function and preserved natriuresis.


Subject(s)
Angiotensin II , Blood Pressure , Hypertension , Kidney , Animals , Mice , Angiotensin II/pharmacology , Blood Pressure/drug effects , Cardiomegaly/prevention & control , Cardiomegaly/chemically induced , Chlorides/administration & dosage , Chlorides/pharmacology , Glomerular Filtration Rate/drug effects , Hypertension/chemically induced , Hypertension/prevention & control , Kidney/drug effects , Mice, Inbred C57BL , Sodium Chloride, Dietary/adverse effects , Sodium Chloride, Dietary/administration & dosage
3.
ACS Med Chem Lett ; 14(12): 1760-1766, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38116421

ABSTRACT

A high-throughput fragment-based screen has been employed to discover a series of quinazolinone inositol hexakisphosphate kinase (IP6K) inhibitors. IP6Ks have been studied for their role in glucose homeostasis, metabolic disease, fatty liver disease, chronic kidney disease, blood coagulation, neurological development, and psychiatric disease. IP6Ks phosphorylate inositol hexakisphosphate (IP6) to form pyrophosphate 5-diphospho-1,2,3,4,6-pentakisphosphate (IP7). Molecular docking studies and investigation of structure-activity relationships around the quinazolinone core resulted in compounds with submicromolar potency and interesting selectivity for IP6K1 versus the closely related IP6K2 and IP6K3 isoforms.

4.
ACS Med Chem Lett ; 14(8): 1088-1094, 2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37583812

ABSTRACT

Glutamate plays a key role in cognition and mood, and it has been shown that inhibiting ionotropic glutamate receptors disrupts cognition, while enhancing ionotropic receptor activity is pro-cognitive. One approach to elevating glutamatergic tone has been to antagonize presynaptic metabotropic glutamate receptor 2 (mGluR2). A desire for selectivity over the largely homologous mGluR3 motivated a strategy to achieve selectivity through the identification of mGluR2 negative allosteric modulators (NAMs). Extensive screening and optimization efforts led to the identification of a novel series of 4-arylquinoline-2-carboxamides. This series was optimized for mGluR2 NAM potency, clean off-target activity, and desirable physical properties, which resulted in the identification of improved C4 and C7 substituents. The initial lead compound from this series was Ames-positive in a single strain with metabolic activation, indicating that a reactive metabolite was likely responsible for the genetic toxicity. Metabolic profiling and Ames assessment across multiple analogs identified key structure-activity relationships associated with Ames positivity. Further optimization led to the Ames-negative mGluR2 negative allosteric modulator MK-8768.

5.
Life Sci Space Res (Amst) ; 38: 59-66, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37481309

ABSTRACT

Humans have stepped on the Lunar surface for less than 80 h of Extravehicular Activity, providing a narrow understanding of Lunar gait patterns. NASA's Human-crewed Artemis missions are quickly approaching; understanding how fractional gravity affects gait patterns will be critical for the Moon's and Mars' long-term habitation. This study examined gait patterns under 1.0 g (Earth), simulated 0.38 g (Martian), and 0.17 g (Lunar). Participants walked and ran on a treadmill supported by ARGOS (Active Response Gravity Offload System), simulating fractional gravity. Vicon motion capture data and principal component analysis software were used to capture and quantify coordinated gait structures. There were found to be significant differences (p < 0.05) in the coordinative gait structures for ambulation between fractional gravity conditions. Additionally, there were significantly higher asymmetric gait components for Lunar conditions. Finally, a skipping coordinative structure was identified within Lunar and Martian running.


Subject(s)
Extraterrestrial Environment , Mars , Humans , Gait , Earth, Planet , Hypogravity
6.
J Am Chem Soc ; 145(29): 16200-16209, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37459594

ABSTRACT

Solid polymer electrolytes have the potential to enable safer and more energy-dense batteries; however, a deeper understanding of their ion conduction mechanisms, and how they can be optimized by molecular design, is needed to realize this goal. Here, we investigate the impact of anion dissociation energy on ion conduction in solid polymer electrolytes via a novel class of ionenes prepared using acyclic diene metathesis (ADMET) polymerization of highly dissociative, liquid crystalline fluorinated aryl sulfonimide-tagged ("FAST") anion monomers. These ionenes with various cations (Li+, Na+, K+, and Cs+) form well-ordered lamellae that are thermally stable up to 180 °C and feature domain spacings that correlate with cation size, providing channels lined with dissociative FAST anions. Electrochemical impedance spectroscopy (EIS) and differential scanning calorimetry (DSC) experiments, along with nudged elastic band (NEB) calculations, suggest that cation motion in these materials operates via an ion-hopping mechanism. The activation energy for Li+ conduction is 59 kJ/mol, which is among the lowest for systems that are proposed to operate via an ion conduction mechanism that is decoupled from polymer segmental motion. Moreover, the addition of a cation-coordinating solvent to these materials led to a >1000-fold increase in ionic conductivity without detectable disruption of the lamellar structure, suggesting selective solvation of the lamellar ion channels. This work demonstrates that molecular design can facilitate controlled formation of dissociative anionic channels that translate to significant enhancements in ion conduction in solid polymer electrolytes.

7.
Microb Ecol ; 86(1): 127-143, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35624343

ABSTRACT

The coccolithophore Emiliania huxleyi shows a variety of responses to ocean acidification (OA) and to high-CO2 concentrations, but there is still controversy on differentiating between these two factors when using different strains and culture methods. A heavily calcified type A strain isolated from the Norwegian Sea was selected and batch cultured in order to understand whether acclimation to OA was mediated mainly by CO2 or H+, and how it impacted cell growth performance, calcification, and physiological stress management. Emiliania huxleyi responded differently to each acidification method. CO2-enriched aeration (1200 µatm, pH 7.62) induced a negative effect on the cells when compared to acidification caused by decreasing pH alone (pH 7.60). The growth rates of the coccolithophore were more negatively affected by high pCO2 than by low pH without CO2 enrichment with respect to the control (400 µatm, pH 8.1). High CO2 also affected cell viability and promoted the accumulation of reactive oxygen species (ROS), which was not observed under low pH. This suggests a possible metabolic imbalance induced by high CO2 alone. In contrast, the affinity for carbon uptake was negatively affected by both low pH and high CO2. Photochemistry was only marginally affected by either acidification method when analysed by PAM fluorometry. The POC and PIC cellular quotas and the PIC:POC ratio shifted along the different phases of the cultures; consequently, calcification did not follow the same pattern observed in cell stress and growth performance. Specifically, acidification by HCl addition caused a higher proportion of severely deformed coccoliths, than CO2 enrichment. These results highlight the capacity of CO2 rather than acidification itself to generate metabolic stress, not reducing calcification.


Subject(s)
Haptophyta , Seawater , Haptophyta/physiology , Carbon Dioxide/metabolism , Hydrogen-Ion Concentration , Photosynthesis
8.
J Geophys Res Planets ; 127(11): e2022JE007194, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36582809

ABSTRACT

Nearly half a century ago, two papers postulated the likelihood of lunar lava tube caves using mathematical models. Today, armed with an array of orbiting and fly-by satellites and survey instrumentation, we have now acquired cave data across our solar system-including the identification of potential cave entrances on the Moon, Mars, and at least nine other planetary bodies. These discoveries gave rise to the study of planetary caves. To help advance this field, we leveraged the expertise of an interdisciplinary group to identify a strategy to explore caves beyond Earth. Focusing primarily on astrobiology, the cave environment, geology, robotics, instrumentation, and human exploration, our goal was to produce a framework to guide this subdiscipline through at least the next decade. To do this, we first assembled a list of 198 science and engineering questions. Then, through a series of social surveys, 114 scientists and engineers winnowed down the list to the top 53 highest priority questions. This exercise resulted in identifying emerging and crucial research areas that require robust development to ultimately support a robotic mission to a planetary cave-principally the Moon and/or Mars. With the necessary financial investment and institutional support, the research and technological development required to achieve these necessary advancements over the next decade are attainable. Subsequently, we will be positioned to robotically examine lunar caves and search for evidence of life within Martian caves; in turn, this will set the stage for human exploration and potential habitation of both the lunar and Martian subsurface.

9.
ACS Med Chem Lett ; 13(4): 608-614, 2022 Apr 14.
Article in English | MEDLINE | ID: mdl-35450366

ABSTRACT

RNA polymerase I (Pol I) transcribes ribosomal DNA (rDNA) into the 47S ribosomal RNA (rRNA) precursor. Further processing produces the 28S, 5.8S, and 18S rRNAs that are assembled into mature ribosomes. Many cancers exhibit higher Pol I transcriptional activity, reflecting a need for increased ribosome biogenesis and protein synthesis and making the inhibition of this process an attractive therapeutic strategy. Lead molecule BMH-21 (1) has been established as a Pol I inhibitor by affecting the destruction of RPA194, the Pol I large catalytic subunit. A previous structure-activity relationship (SAR) study uncovered key pharmacophores, but activity was constrained within a tight chemical space. This work details further SAR efforts that have yielded new scaffolds and improved off-target activity while retaining the desired RPA194 degradation potency. Pharmacokinetic profiling was obtained and provides a starting point for further optimization. New compounds present additional opportunities for the development of Pol I inhibitory cancer therapies.

10.
Article in English | MEDLINE | ID: mdl-34639280

ABSTRACT

The purpose of this paper is to describe the protocol for the design, implementation, and evaluation of an animation- versus text-based computer tailoring game intervention aimed at preventing alcohol consumption and binge drinking (BD) in adolescents. A cluster-randomized controlled trial (CRCT) is carried out in students aged 14-19 enrolled in 24 high schools from Andalusia (Spain), which are randomized either to experimental (EC-1, EC-2) or waiting-list control conditions (CC). EC-1 receives an online intervention (Alerta Alcohol) with personalized health advice, using textual feedback and several gamification techniques. EC-2 receives an improved version (Alerta Alcohol 2.0) using animated videos and new gamification strategies. Both programs consist of nine sessions (seven taking place at high school and two at home): session 1 or baseline, sessions 2 and 3 that provide tailored advice based on the I-Change Model; sessions 4, 5, 7, and 8 are booster sessions, and sessions 6 and 9 are follow-up questionnaires at six and twelve months. The CC completes the baseline and the evaluation questionnaires. The primary outcome is BD within 30 days before post-test evaluations, and as secondary outcomes we assess other patterns of alcohol use. The findings should help the development of future alcohol drinking prevention interventions in adolescents.


Subject(s)
Binge Drinking , Text Messaging , Adolescent , Alcohol Drinking/prevention & control , Binge Drinking/prevention & control , Computers , Ethanol , Humans , Randomized Controlled Trials as Topic
13.
Rev Assoc Med Bras (1992) ; 66(11): 1473-1475, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33295393

ABSTRACT

Atrial fibrillation (AF) is the most common arrhythmia in the postoperative period of cardiac surgery, with a prevalence between 15-40% after coronary artery bypass surgery (CABG). Several strategies have been tested for the prevention and management of AF postoperatively. Previous studies and analysis of records have shown higher rates of hospitalization and clinical outcomes associated with this entity, including increased mortality in the short- and long-term. This perspective reviews the topic, and offers recommendations for the management of this arrhythmia in the postoperative period of CABG, with a special focus on anticoagulation strategies.


Subject(s)
Atrial Fibrillation , Cardiac Surgical Procedures , Atrial Fibrillation/epidemiology , Atrial Fibrillation/etiology , Coronary Artery Bypass/adverse effects , Humans , Postoperative Complications , Postoperative Period
14.
Einstein (Sao Paulo) ; 18: eAO6106, 2020.
Article in English, Portuguese | MEDLINE | ID: mdl-33295428

ABSTRACT

OBJECTIVE: To characterize variables associated with referral to the emergency department following Telemedicine consultation during the COVID-19 pandemic. METHODS: Cross-sectional retrospective study conducted between March and May 2020, with a sample of 500 adult patients. The inclusion criterion was the manifestation of respiratory symptoms, regardless of type. RESULTS: The mean age of patients was 34.7±10.5 years, and 59% were women. Most patients (62.6%) perceived their own health status as malaise and some (41.4%) self-diagnosed COVID-19. Cough (74.4%), rhinorrhea (65.6%), sore throat (38.6%) and sneezing (20.6%) were the most common infection-related symptoms. Overall, 29.4% and 16% of patients reported dyspnea and chest pain, respectively. The Roth score was calculated for a sizeable number of patients (67.6%) and was normal, moderately altered or severely altered in 83.5%, 10.7% and 5.6% of patients, respectively. The percentage of suspected COVID-19 cases was 67.6%. Of these, 75% were managed remotely and only one quarter referred for emergency assessment. CONCLUSION: Telemedicine assessment is associated with reclassification of patient's subjective impression, better inspection of coronavirus disease 2019 and identification of risk patients. Referral is therefore optimized to avoid inappropriate in-person assessment, and low-risk patients can be properly guided. Telemedicine should be implemented in the health care system as a cost-effective strategy for initial assessment of acute patients.


Subject(s)
COVID-19 Drug Treatment , Telemedicine , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pandemics , Referral and Consultation , Retrospective Studies , SARS-CoV-2 , Young Adult
15.
Rev. Assoc. Med. Bras. (1992) ; 66(11): 1473-1475, Nov. 2020.
Article in English | Sec. Est. Saúde SP, LILACS | ID: biblio-1143643

ABSTRACT

SUMMARY Atrial fibrillation (AF) is the most common arrhythmia in the postoperative period of cardiac surgery, with a prevalence between 15-40% after coronary artery bypass surgery (CABG). Several strategies have been tested for the prevention and management of AF postoperatively. Previous studies and analysis of records have shown higher rates of hospitalization and clinical outcomes associated with this entity, including increased mortality in the short- and long-term. This perspective reviews the topic, and offers recommendations for the management of this arrhythmia in the postoperative period of CABG, with a special focus on anticoagulation strategies.


Subject(s)
Humans , Atrial Fibrillation/etiology , Atrial Fibrillation/epidemiology , Cardiac Surgical Procedures , Postoperative Complications , Postoperative Period , Coronary Artery Bypass/adverse effects
16.
Mar Environ Res ; 162: 105195, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33129167

ABSTRACT

The Alborán Sea sardine (Sardina pilchardus) is the most abundant small pelagic fish in the Mediterranean Sea. Along the northern coast of the Alborán Sea, Málaga and Almería Bay are two important nursery grounds with contrasting oceanographic characteristics. Post-larval stages of S. pilchardus were collected during the late autumn and late winter along with the mesozooplankton community. We examined the influence of feeding behavior on larval growth using environmental variables, daily growth metrics, otolith biometry, stable isotope analysis and trophodynamics. Trophic positions were calculated using mesoozooplankton as potential prey for S. pilchardus. During both seasons, we observed faster growth in larger otoliths that also corresponded to higher trophic positions. Our results indicate that the isotopic signature of larvae is highly influenced by the mesozooplankton community structure. Moreover, the trophic variables showed a significant linear relationship with the estimated ages for all larvae indicating dietary changes throughout ontogenic development.


Subject(s)
Bays , Fishes , Animals , Ecosystem , Mediterranean Sea , Seafood
17.
Rev. Col. méd. cir ; 159(1): 23-25, abr 2020. tab
Article in Spanish | LIGCSA, LILACS | ID: biblio-1247543

ABSTRACT

Objetivo: determinar la presencia de proteinuria en habitantes de una aldea de la región costera de Santa Rosa, Guatemala, julio del año 2019. Material y métodos: estudio descriptivo y transversal, en una muestra de 575 habitantes de la aldea Casas Viejas, captada por durante cuatro jornadas médicas. Las muestras de orina fueron analizadas con tiras reactivas. Resultados: de los habitantes que participaron, 55.48 % (319) fueron de sexo femenino, la mediana de edad fue de 24 años, el 39.820% (229) estudiante y el 85.2 % (490) sin antecedentes patológicos. De los factores predisponentes de enfermedad renal, el 56.170% (323) consume antiinflamatorios no esteroideo -AINES-, el 82.26 % (473) bebidas carbonatadas, el 13.570% (78) bebidas alcohólicas; la mediana de consumo de agua fue de 6 vasos diarios y 13.22 % (76) han estado expuestos a agroquímicos. Proteinuria se documentó en 8.87 % (51) de los habitantes. Conclusiones: más de la mitad de los sujeto de estudio son de sexo femenino y sin antecedentes patológicos; de los factores predisponentes a enfermedad renal los más frecuentes son el consumo de -AINES-, bebidas carbonatadas y la hidratación inadecuada. Nueve de cada cien sujetos de estudio presentan proteinuria.


Objetive: to establish urine protein presence in inhabitants of a small village of the coastal region in Santa Rosa, Guatemala. July 2019. Material y methods: Descriptive and transversal study performed on 575 persons from Casas Viejas village, using a nonprobabilistic sampling. Proteinuria was determined by urine test strips. Results: Of the persons studied, 55.48% (319) were female, mean age was 24 years old, 39.82% (229) were students and 85.25% had no pathological background. Predisposing factors of kidney disease were noted, 56.17% (323) consumed Non-steroidal Anti-inflammatory Drugs (NSAIDs), 82.26% (473) consumed carbonated drinks, 13.57% (78) alcoholic beverages, the mean water consumption was 6 glasses per day, and 13.22% (76), were exposed to agrochemical pesticides. Proteinuria was found in 8.87% (51) of the sample. Conclutions: more than half of population were female and didn´t showed pathological signs. Predisposing factors to kidney disease were, frequent NSAIDs use, carbonated drinks consumption a no adequate hydration. Nine of each one hundred people studied presented urine protein.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Proteinuria/epidemiology , Pesticides/adverse effects , Proteinuria/diagnosis , Proteinuria/urine , Alcohol Drinking/adverse effects , Carbonated Beverages/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Prevalence , Cross-Sectional Studies , Risk Factors , Drinking , Guatemala/epidemiology , Kidney Diseases/diagnosis , Kidney Diseases/urine , Kidney Diseases/epidemiology
18.
Einstein (Säo Paulo) ; 18: eAO6106, 2020. tab
Article in English | LILACS | ID: biblio-1142872

ABSTRACT

ABSTRACT Objective: To characterize variables associated with referral to the emergency department following Telemedicine consultation during the COVID-19 pandemic. Methods: Cross-sectional retrospective study conducted between March and May 2020, with a sample of 500 adult patients. The inclusion criterion was the manifestation of respiratory symptoms, regardless of type. Results: The mean age of patients was 34.7±10.5 years, and 59% were women. Most patients (62.6%) perceived their own health status as malaise and some (41.4%) self-diagnosed COVID-19. Cough (74.4%), rhinorrhea (65.6%), sore throat (38.6%) and sneezing (20.6%) were the most common infection-related symptoms. Overall, 29.4% and 16% of patients reported dyspnea and chest pain, respectively. The Roth score was calculated for a sizeable number of patients (67.6%) and was normal, moderately altered or severely altered in 83.5%, 10.7% and 5.6% of patients, respectively. The percentage of suspected COVID-19 cases was 67.6%. Of these, 75% were managed remotely and only one quarter referred for emergency assessment. Conclusion: Telemedicine assessment is associated with reclassification of patient's subjective impression, better inspection of coronavirus disease 2019 and identification of risk patients. Referral is therefore optimized to avoid inappropriate in-person assessment, and low-risk patients can be properly guided. Telemedicine should be implemented in the health care system as a cost-effective strategy for initial assessment of acute patients.


RESUMO Objetivo: Caracterizar as variáveis associadas ao encaminhamento à emergência após consulta de Telemedicina durante a pandemia de COVID-19. Métodos: Estudo transversal e retrospectivo, realizado entre março e maio de 2020, com amostra de 500 pacientes adultos. O critério de inclusão foi apresentação de sintomas respiratórios, independente do tipo. Resultados: A média de idade dos pacientes foi de 34,7±10,5 anos, e 59% eram do sexo feminino. A maioria dos pacientes (62,6%) se classificou subjetivamente como tendo um mal-estar, e alguns (41,4%) autodiagnosticaram COVID-19. Tosse (74,4%), rinorreia (65,6%), dor de garganta (38,6%) e espirros (20,6%) foram os sintomas mais comuns relacionados à infecção. Dispneia e dor torácica foram relatados por 29,4% e 16% dos pacientes, respectivamente. Foi calculado o escore de Roth de um número considerável de pacientes (67,6%), obtendo resultado normal em 83,5%, moderadamente alterado em 10,7% e grave em 5,6%. A percentagem de casos suspeitos de COVID-19 foi de 67,6%, e 75% desses foram gerenciados remotamente, com apenas um quarto sendo encaminhado para avaliação imediata na emergência. Conclusão: A avaliação da Telemedicina está associada à reclassificação da impressão subjetiva do paciente, melhor inspeção da COVI-19 e identificação de pacientes de risco. O encaminhamento é otimizado, para evitar avaliação presencial inadequada, e permite que os pacientes de baixo risco sejam orientados de forma apropriada. A Telemedicina deve ser implementada no sistema de saúde como estratégia com boa relação custo-efetividade para a avaliação inicial de pacientes agudos.


Subject(s)
Humans , Male , Female , Adult , Young Adult , Telemedicine , COVID-19/drug therapy , Referral and Consultation , Cross-Sectional Studies , Retrospective Studies , Pandemics , SARS-CoV-2 , Middle Aged
19.
J Phycol ; 55(4): 775-788, 2019 08.
Article in English | MEDLINE | ID: mdl-31090939

ABSTRACT

We studied the effects of elevated CO2 concentrations on cell growth, calcification, and spectral variation in the sensitivity of photosynthesis to inhibition by solar radiation in the globally important coccolithophore Emiliania huxleyi. Growth rates and chlorophyll a content per cell showed no significant differences between elevated (800 ppmv) and ambient (400 ppmv) CO2 conditions. However, the production of organic carbon and the cell quotas for both carbon and nitrogen, increased under elevated CO2 conditions, whilst particulate inorganic carbon production rates decreased under the same conditions. Biometric analyses of cells showed that coccoliths only presented significant differences due to treatments in the central area width. Most importantly, the size of the coccosphere decreased under elevated CO2 conditions. The susceptibility of photosynthesis to inhibition by ultraviolet radiation (UVR) was estimated using biological weighting functions (BWFs) and a model that predicts photosynthesis under photosynthetically active radiation and UVR exposures. BWF results demonstrated that the sensitivity of photosynthesis to UVR was not significantly different between E. huxleyi cells grown under elevated and present CO2 concentrations. We propose that the acclimation to elevated CO2 conditions involves a physiological mechanism of regulation and allocation of energy and metabolites in the cell, which is also responsible for altering the sensitivity to UVR. In coccolithophores, this mechanism might be affected by the decrease in the calcification rates.


Subject(s)
Haptophyta , Calcification, Physiologic , Carbon Dioxide , Chlorophyll A , Photosynthesis , Ultraviolet Rays
20.
J Bone Miner Res ; 34(10): 1851-1861, 2019 10.
Article in English | MEDLINE | ID: mdl-31099911

ABSTRACT

Renal transplantation (RTx) is an effective therapy to improve clinical outcomes in pediatric patients with terminal chronic kidney disease. However, chronic immunosuppression with glucocorticoids (GCs) reduces bone growth and BMD. The mechanisms causing GC-induced growth impairment have not been fully clarified. Fibroblast growth factor 23 (FGF23) is a peptide hormone that regulates phosphate homeostasis and bone growth. In pathological conditions, FGF23 excess or abnormal FGF receptors (FGFR) activity leads to bone growth impairment. Experimental data indicate that FGF23 expression is induced by chronic GC exposure. Therefore, we hypothesize that GCs impair bone growth by increasing FGF23 expression, which has direct effects on bone growth plate. In a post hoc analysis of a multicentric randomized clinical trial of prepubertal RTx children treated with early GC withdrawal or chronic GC treatment, we observed that GC withdrawal was associated with improvement in longitudinal growth and BMD, and lower plasma FGF23 levels as compared with a chronic GC group. In prepubertal rats, GC-induced bone growth retardation correlated with increased plasma FGF23 and bone FGF23 expression. Additionally, GC treatment decreased FGFR1 expression whereas it increased FGFR3 expression in mouse tibia explants. The GC-induced bone growth impairment in tibiae explants was prevented by blockade of FGF23 receptors using either a pan-FGFR antagonist (PD173074), a C-terminal FGF23 peptide (FGF23180-205) which blocks the binding of FGF23 to the FGFR-Klotho complex or a specific FGFR3 antagonist (P3). Finally, local administration of PD173074 into the tibia growth plate ameliorated cartilage growth impairment in GC-treated rats. These results show that GC treatment partially reduces longitudinal bone growth via upregulation of FGF23 and FGFR3 expression, thus suggesting that the FGF23/Klotho/FGFR3 axis at the growth plate could be a potential therapeutic target for the management of GC-induced growth impairment in children.


Subject(s)
Bone Development/drug effects , Bone and Bones/metabolism , Fibroblast Growth Factors/metabolism , Glucocorticoids/administration & dosage , Kidney Transplantation , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Signal Transduction/drug effects , Animals , Bone Density/drug effects , Bone and Bones/pathology , Child , Female , Fibroblast Growth Factor-23 , Follow-Up Studies , Glucocorticoids/adverse effects , Humans , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/surgery , Klotho Proteins , Male , Membrane Proteins , Mice , Rats , Rats, Sprague-Dawley
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