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1.
J Am Chem Soc ; 145(48): 26279-26286, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37984498

RESUMO

Living organisms are replete with rhythmic and oscillatory behavior at all levels, to the extent that oscillations have been termed as a defining attribute of life. Recent studies of synthetic oscillators that mimic such functions have shown decayed cycles in batch-mode reactions or sustained oscillatory kinetics under flow conditions. Considering the hypothesized functionality of peptides in early chemical evolution and their central role in current bio-nanotechnology, we now reveal a peptide-based oscillator. Oscillatory behavior was achieved by coupling coiled-coil-based replication processes as positive feedback to controlled initiation and inhibition pathways in a continuously stirred tank reactor (CSTR). Our results stress that assembly into the supramolecular structure and specific interactions with the replication substrates are crucial for oscillations. The replication-inhibition processes were first studied in batch mode, which produced a single damped cycle. Thereafter, combined experimental and theoretical characterization of the replication process in a CSTR under different flow and environmental (pH, redox) conditions demonstrated reasonably sustained oscillations. We propose that studies in this direction might pave the way to the design of robust oscillation networks that mimic the autonomous behavior of proteins in cells (e.g., in the cyanobacterial circadian clock) and hence hint at feasible pathways that accelerated the transition from simple peptides to extant enzymes.


Assuntos
Relógios Circadianos , Peptídeos , Retroalimentação
2.
Langenbecks Arch Surg ; 408(1): 428, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932463

RESUMO

INTRODUCTION: Fournier's gangrene (FG) is a necrotizing fasciitis affecting the perineum and urogenital tissue. The mortality rate is high although early detection and aggressive debridement can reduce mortality by up to 16%. The prevalence of sequelae is very high and a colostomy is often necessary to control the perineal wound. MATERIAL AND METHODS: A retrospective study was carried out to recruit all patients operated on by the General Surgery and Urology Departments with a diagnosis of GF at the University Hospital over 22 years. Mortality, the Fournier gangrene severity index (FGSI), and fecal diversion (either surgical (colostomy) or straight (Flexi-seal)) are collected. RESULTS: A total of 149 patients met the inclusion criteria. FG's most frequent cause was a perianal abscess (107 patients-72%). Eighteen patients (12%) died of a specific cause of FG. Age (p = 0.014) and patients with an oncological history (p = 0.038) both were the only mortality risk factors for mortality according to logistic regression. Fifty patients required some form of fecal diversion in the postoperative period (32 colostomies and 18 Flexi-seal). Neither the use of postoperative fecal diversion (surgical or Flexi-seal) nor the timing of its use had any effect on postoperative mortality. CONCLUSIONS: One in eight patients died in the immediate postoperative period secondary to FG. Despite improved outcomes, 22% required a colostomy during admission. However, neither the performance of a colostomy nor the timing was associated with decreased FG-associated mortality. Non-invasive methods should be used first and surgical bowel diversion should be postponed as long as possible.


Assuntos
Doenças do Ânus , Gangrena de Fournier , Masculino , Humanos , Gangrena de Fournier/diagnóstico , Gangrena de Fournier/etiologia , Gangrena de Fournier/cirurgia , Estudos Retrospectivos , Períneo , Doenças do Ânus/complicações , Colostomia/efeitos adversos , Desbridamento/efeitos adversos
3.
Am J Trop Med Hyg ; 109(5): 1118-1121, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37722664

RESUMO

There is a knowledge gap in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) causing bloodstream infections (BSIs) in Peru. Through a surveillance study in 13 hospitals of 10 Peruvian regions (2017-2019), we assessed the proportion of MRSA among S. aureus BSIs as well as the molecular typing of the isolates. A total of 166 S. aureus isolates were collected, and 36.1% of them were MRSA. Of note, MRSA isolates with phenotypic and genetic characteristics of the hospital-associated Chilean-Cordobes clone (multidrug-resistant SCCmec I, non-Panton-Valentine leukocidin [PVL] producers) were most commonly found (70%), five isolates with genetic characteristics of community-associated MRSA (CA-MRSA)-SCCmec IV, PVL-producer-(8.3%) were seen in three separate regions. These results demonstrate that hospital-associated MRSA is the most frequent MRSA found in patients with BSIs in Peru. They also show the emergence of S. aureus with genetic characteristics of CA-MRSA. Further studies are needed to evaluate the extension of CA-MRSA dissemination in Peru.


Assuntos
Infecções Comunitárias Adquiridas , Staphylococcus aureus Resistente à Meticilina , Sepse , Infecções Estafilocócicas , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus/genética , Peru/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Exotoxinas/genética , Leucocidinas/genética , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
4.
Am J Trop Med Hyg ; 109(5): 1095-1106, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37722663

RESUMO

Surveillance of antimicrobial resistance among gram-negative bacteria (GNB) is of critical importance, but data for Peru are not available. To fill this gap, a non-interventional hospital-based surveillance study was conducted in 15 hospitals across Peru from July 2017 to October 2019. Consecutive unique blood culture isolates of key GNB (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp.) recovered from hospitalized patients were collected for centralized antimicrobial susceptibility testing, along with linked epidemiological and clinical data. A total of 449 isolates were included in the analysis. Resistance to third-generation cephalosporins (3GCs) was present in 266 (59.2%) GNB isolates. Among E. coli (n = 199), 68.3% showed 3GC resistance (i.e., above the median ratio for low- and middle-income countries in 2020 for this sustainable development goal indicator). Carbapenem resistance was present in 74 (16.5%) GNB isolates, with wide variation among species (0% in E. coli, 11.0% in K. pneumoniae, 37.0% in P. aeruginosa, and 60.8% in Acinetobacter spp. isolates). Co-resistance to carbapenems and colistin was found in seven (1.6%) GNB isolates. Empiric treatment covered the causative GNB in 63.3% of 215 cases. The in-hospital case fatality ratio was 33.3% (92/276). Pseudomonas aeruginosa species and carbapenem resistance were associated with higher risk of in-hospital death. In conclusion, an important proportion of bloodstream infections in Peru are caused by highly resistant GNB and are associated with high in-hospital mortality.


Assuntos
Infecções por Bactérias Gram-Negativas , Sepse , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli , Prevalência , Peru/epidemiologia , Mortalidade Hospitalar , Farmacorresistência Bacteriana , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Carbapenêmicos , Bactérias Gram-Negativas , Klebsiella pneumoniae , Pseudomonas aeruginosa , Sepse/tratamento farmacológico , Testes de Sensibilidade Microbiana
5.
Int J Gen Med ; 16: 2753-2770, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37408844

RESUMO

The Starling principle is a model that explains the transvascular distribution of fluids essentially governed by hydrostatic and oncotic forces, which dynamically allow vascular refilling according to the characteristics of the blood vessel. However, careful analysis of fluid physiology has shown that the principle, while correct, is not complete. The revised Starling principle (Michel-Weinbaum model) provides relevant information on fluid kinetics. Special emphasis has been placed on the endothelial glycocalyx, whose subendothelial area allows a restricted oncotic pressure that limits the reabsorption of fluid from the interstitial space, so that transvascular refilling occurs mainly from the lymphatic vessels. The close correlation between pathological states of the endothelium (eg: sepsis, acute inflammation, or chronic kidney disease) and the prescription of fluids forces the physician to understand the dynamics of fluids in the organism; this will allow rational fluid prescriptions. A theory that integrates the physiology of exchange and transvascular refilling is the "microconstant model", whose variables include dynamic mechanisms that can explain edematous states, management of acute resuscitation, and type of fluids for common clinical conditions. The clinical-physiological integration of the concepts will be the hinges that allow a rational and dynamic prescription of fluids.

7.
Toxicon X ; 19: 100159, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37251689

RESUMO

Tarantula venoms may be a natural source of new vasodilator components useful in pharmacological research. Moreover, biological function data of the venoms are important to enhance the knowledge about the biodiversity and evolution of these species. The present study aims to describe the vasodilatory activity induced by the venom of Poecilotheria ornata on isolated rat aortic rings. This venom induced a vasodilator activity that was significantly reduced after incubation with L-NAME or ODQ. Measurements of nitrite concentrations on rat aorta homogenates showed that the venom significantly increased the basal levels. Moreover, the venom attenuates the contraction induced by calcium. These results suggest that P. ornata venom contains a mixture of vasodilator components that act through the activation of the nitric oxide/cGMP pathway, as well as, through an endothelium-independent mechanism that involves the calcium influx into vascular smooth muscle cells.

8.
Front Public Health ; 11: 1089565, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181727

RESUMO

Introduction: The COVID-19 pandemic highlighted the lack of a government contingency plan for an effective response to an unexpected health crisis. This study uses a phenomenological approach to explore the experience of healthcare professionals during the first three waves of the COVID-19 pandemic in a public health hospital in the Valencia region, Spain. It assesses the impact on their health, coping strategies, institutional support, organizational changes, quality of care, and lessons learned. Methods: We carried out a qualitative study with semi-structured interviews with doctors and nurses from the Preventive Medicine, Emergency, and Internal Medicine Services and the Intensive Care Unit, using the Colaizzi's 7-step data analysis method. Results: During the first wave, lack of information and leadership led to feelings of uncertainty, fear of infection, and transmission to family members. Continuous organizational changes and lack of material and human resources brought limited results. The lack of space to accommodate patients, along with insufficient training in treating critical patients, and the frequent moving around of healthcare workers, reduced the quality of care. Despite the high levels of emotional stress reported, no sick leave was taken; the high levels of commitment and professional vocation helped in adapting to the intense work rhythms. Healthcare professionals in the medical services and support units reported higher levels of stress, and a greater sense of neglect by their institution than their colleagues in managerial roles. Family, social support, and camaraderie at work were effective coping strategies. Health professionals showed a strong collective spirit and sense of solidarity. This helped them cope with the additional stress and workload that accompanied the pandemic. Conclusion: In the wake of this experience, they highlight the need for a contingency plan adapted to each organizational context. Such a plan should include psychological counseling and continuous training in critical patient care. Above all, it needs to take advantage of the hard-won knowledge born of the COVID-19 pandemic.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias/prevenção & controle , Espanha/epidemiologia , Pessoal de Saúde/psicologia , Hospitais Públicos
9.
Rev. iberoam. fertil. reprod. hum ; 40(1): 27-36, enero-febrero-marzo-abril 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-220191

RESUMO

Introducción: En los últimos años, los tratamientos de FIV en ciclo natural y la FIV con estimulación ovárica “suave” están resurgiendo como una opción más segura, económica y cómoda para las pacien-tes. Definimos FIV en ciclo natural como el tratamiento en el que los ovocitos son obtenidos de un ciclo ovulatorio espontáneo. Cuando añadimos fármacos orales (citrato de clomifeno o letrozol), hablamos de estimulación “mínima”. El objetivo de este estudio es clarificar si la introducción de esta medicación es beneficiosa para las pacientes. Materials y métodos: Analizamos retrospectivamente los tratamientos de FIV en ciclo natural o con estimulación mínima llevados realizados en nuestro centro de enero 2016 a diciembre 2020.Resultados: Encontramos diferencias significativas entre los dos protocolos en el número de ovocitos obtenidos después de la punción folicular (1.03 vs 1.63, p<0.001), número de ovocitos maduros (0.9 vs 1.3, p < 0.01), ovocitos fecundados (0.7 vs 1.1, p < 0.01), y número de embriones disponibles para trans-ferencia (0.5 vs 0.7, p < 0.01). Sin embargo, no encontramos diferencias en la tasa de embarazo (26,3% vs 19,6%, p=0.251) ni en la tasa de recién nacido vivo (16.3% vs 14,3%, p=0.7806).Discusión: Añadir medicación oral a la FIV en ciclo natural no parece tener ningún impacto sobre los resultados clínicos del ciclo. Son necesarios más estudios, pero podríamos reconsiderar la necesidad de añadir esta medicación, ya que supone un mayor coste para los pacientes. (AU)


Introduction: In recent years, natural cycle IVF and minimal ovarian stimulation IVF had been under-going a revival, gaining recognition as safer, cheaper, and more comfortable options for patients. We define natural cicle IVF as the treatment in which oocytes are obtained from a spontaneous ovulatory cycle. When oral drugs are used (usually clomiphene citrate or letrozole), the process is referred to as minimal ovarian stimulation cycle IVF. The aim of this study is to clarify whether the introduction of oral medication is beneficial for patients.Methods: We retrospectively analysed all natural or minimal ovarian stimulation IVF treatments that took place in our clinic during the studied period (January 2016 - December 2020). Descriptive variables were analysed with a t-test, and a chi-square test was performed on result variables. Results: We found significant differences, between both protocols, in the number of oocytes obtained after oocyte retrieval (1.03 vs 1.63, p<0.001), number of mature oocytes (0.9 vs 1.3, p < 0.01), fertilized oocytes (0.7 vs 1.1, p < 0.01), and number of embryos available for transfer (0.5 vs 0.7, p < 0.01).Howe-ver, we did not found signficant differences in terms of pregnancy rate (26,3% vs 19,6%, p=0.251) or live birth rate (16.3% vs 14,3%, p=0.7806). (AU)


Assuntos
Humanos , Esquema de Medicação , Terapêutica , Oócitos
10.
Humanidad. med ; 23(1)abr. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1506383

RESUMO

El envejecimiento poblacional es uno de los problemas más latentes en la realidad actual cubana. Según cifras de la ONEI la población de más de 60 años asciende a más de dos millones de personas. Este es un fenómeno presente a lo largo del ciclo vital desde el mismo proceso de la concepción hasta la muerte; el que, a pesar de ser un fenómeno natural conocido por todos, ha resultado a muchos difícil aceptarlo como una realidad innata a todo ser. Dada la gran complejidad de los cambios que se producen durante el mismo, no ha de sorprender la existencia de más de 300 teorías a los fines de explicar el dónde, el cómo y el porqué de estos cambios. En el presente artículo se caracteriza doctrinalmente el fenómeno del envejecimiento poblacional en Cuba como proceso irreversible, único, individual, universal de cambio que involucra todas las dimensiones del ser humano y disminuye la velocidad de los procesos del cuerpo; sustentado su análisis en los fundamentos teóricos del mismo, así como en la visión totalizadora, que permite asumirlo como totalidad dialéctica, por ello se asume como objetivo Sistematizar una concepción teórica y metodológica que sustente el carácter polisémico del proceso de envejecimiento de la población. El estudio se desarrolla en el momento actual, como parte de un proceso de investigación que se acomete en el Tribunal Provincial de La Habana.


Population aging is one of the most latent problems in the current Cuban reality. According to ONEI figures, the population over 60 years of age amounts to more than two million people. This is a phenomenon present throughout the life cycle from the very process of conception until death; which, despite being a natural phenomenon known to all, has been difficult for many to accept as an innate reality to all beings. Given the great complexity of the changes that occur during it, it is not surprising that there are more than 300 theories in order to explain the where, how and why of these changes. In this article, the phenomenon of population aging in Cuba is doctrinally characterized as an irreversible, unique, individual, universal process of change that involves all dimensions of the human being, and slows down the processes of the body; Supporting its analysis on its theoretical foundations, as well as on the totalizing vision, which allows it to be assumed as a dialectical totality, for this reason it is assumed as an objective to Systematize a theoretical and methodological conception that supports the polysemic nature of the aging process of the population. The study is being carried out at the present time, as part of an investigation process that is being undertaken in the Provincial Court of Havana.

11.
Cell Death Dis ; 14(1): 61, 2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702816

RESUMO

LKB1 and KRAS are the third most frequent co-mutations detected in non-small cell lung cancer (NSCLC) and cause aggressive tumor growth. Unfortunately, treatment with RAS-RAF-MEK-ERK pathway inhibitors has minimal therapeutic efficacy in LKB1-mutant KRAS-driven NSCLC. Autophagy, an intracellular nutrient scavenging pathway, compensates for Lkb1 loss to support Kras-driven lung tumor growth. Here we preclinically evaluate the possibility of autophagy inhibition together with MEK inhibition as a treatment for Kras-driven lung tumors. We found that the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and the MEK inhibitor Trametinib displays synergistic anti-proliferative activity in KrasG12D/+;Lkb1-/- (KL) lung cancer cells, but not in KrasG12D/+;p53-/- (KP) lung cancer cells. In vivo studies using tumor allografts, genetically engineered mouse models (GEMMs) and patient-derived xenografts (PDXs) showed anti-tumor activity of the combination of HCQ and Trametinib on KL but not KP tumors. We further found that the combination treatment significantly reduced mitochondrial membrane potential, basal respiration, and ATP production, while also increasing lipid peroxidation, indicative of ferroptosis, in KL tumor-derived cell lines (TDCLs) and KL tumors compared to treatment with single agents. Moreover, the reduced tumor growth by the combination treatment was rescued by ferroptosis inhibitor. Taken together, we demonstrate that autophagy upregulation in KL tumors causes resistance to Trametinib by inhibiting ferroptosis. Therefore, a combination of autophagy and MEK inhibition could be a novel therapeutic strategy to specifically treat NSCLC bearing co-mutations of LKB1 and KRAS.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ferroptose/genética , Proteínas Serina-Treonina Quinases/metabolismo , Antineoplásicos/uso terapêutico , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Autofagia , Linhagem Celular Tumoral , Mutação
12.
J Chem Phys ; 157(22): 225101, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36546800

RESUMO

In this paper, we report an open system consisting of three self-replicating peptides, in which peptide 1 inhibits the duplex template of peptide 2, peptide 2 inhibits duplex 3, and peptide 3 inhibits duplex 1 to complete the negative feedback loop. This interacting chemical network yields oscillations in the concentrations of all species over time and establishes a possible mechanism for pre-biotic chemical systems organization. The first focus of our analysis is the effect of altering rates of duplex formation and inhibition on oscillations. We then examine the autocatalytic rate constant in the symmetric and asymmetric cases.


Assuntos
Peptídeos , Peptídeos/química
13.
Commun Med (Lond) ; 2(1): 158, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482179

RESUMO

BACKGROUND: New technologies with novel and ambitious approaches are being developed to diagnose or screen for SARS-CoV-2, including breath tests. The US FDA approved the first breath test for COVID-19 under emergency use authorization in April 2022. Most breath-based assays measure volatile metabolites exhaled by persons to identify a host response to infection. We hypothesized that the breathprint of COVID-19 fluctuated after Omicron became the primary variant of transmission over the Delta variant. METHODS: We collected breath samples from 142 persons with and without a confirmed COVID-19 infection during the Delta and Omicron waves. Breath samples were analyzed by gas chromatography-mass spectrometry. RESULTS: Here we show that based on 63 exhaled compounds, a general COVID-19 model had an accuracy of 0.73 ± 0.06, which improved to 0.82 ± 0.12 when modeling only the Delta wave, and 0.84 ± 0.06 for the Omicron wave. The specificity improved for the Delta and Omicron models (0.79 ± 0.21 and 0.74 ± 0.12, respectively) relative to the general model (0.61 ± 0.13). CONCLUSIONS: We report that the volatile signature of COVID-19 in breath differs between the Delta-predominant and Omicron-predominant variant waves, and accuracies improve when samples from these waves are modeled separately rather than as one universal approach. Our findings have important implications for groups developing breath-based assays for COVID-19 and other respiratory pathogens, as the host response to infection may significantly differ depending on variants or subtypes.


In recent decades, scientists have found we exhale thousands of compounds that reveal much about our health, including whether we are sick with COVID-19. Our team asked whether the breath profile of someone infected with the Delta variant of COVID-19 would match the breath profile caused by the Omicron variant­a version of the virus that is more transmissible. We analyzed breath samples from 142 people, some sick with either the Delta or Omicron variant of COVID-19, and others who were negative for COVID-19. Our results indicate that the Delta variant altered the contents of our breath in a different way than the Omicron variant, and breath-based tests improved when optimized to detect only one of the variants. These findings might impact the design of future breath-based tests for COVID-19.

14.
An. pediatr. (2003. Ed. impr.) ; 97(4): 270-279, Oct. 2022. graf, ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-210026

RESUMO

Introducción: No existe consenso sobre qué gráfica neonatal es mejor utilizar en niños con muy bajo peso al nacer (MBPN). El objetivo del estudio fue comparar las gráficas de Fenton 2013 e Intergrowth-21st (IW-21) con base en su capacidad predictora de la somatometría a los dos años, así como analizar factores relacionados con talla baja a los dos años. Material y métodos: Cohorte de niños con MBPN nacidos entre 2002-2017. Se analizó la asociación entre la somatometría neonatal (z-score por Fenton e IW-21) y el riesgo de talla baja (< -2 desviación estándar [DS]), perímetro craneal < -2 DS y desnutrición a los 2 años (IMC < -2 DS) (gráficas OMS). Resultados: Se incluyeron 513 niños con una edad gestacional media de 30,05 ± 2,5 semanas. El z-score del peso al nacimiento y al alta por Fenton y por IW-21 resultaron útiles para predecir riesgo de talla baja y desnutrición a los dos años (sin diferencias en el AUC de las curvas ROC), siendo el z-score al alta útil además para predecir perímetro craneal < -2D. A los dos años, la prevalencia de talla baja, perímetro craneal < -2 DS, y desnutrición fue del 17,2, 4,1 y 6,1%, respectivamente. El bajo peso para la edad gestacional y la duración del ingreso neonatal se identificaron como factores de riesgo independientes para talla baja a los dos años. Conclusiones: El z-score peso al alta resulta útil para predecir riesgo de talla baja, desnutrición y perímetro craneal < -2 DS a los dos años en niños con muy bajo peso al nacer, sin diferencias estadísticas entre utilizar las gráficas de Fenton o IW-21. (AU)


Introduction: There is no consensus on which neonatal chart is best to use in very low birth weight (VLBW) infants. The aim of the study was to compare the Fenton 2013 and Intergrowth-21st (IW-21) charts based on their predictive ability for somatometry at 2 years, as well as to analyze factors related to short stature at 2 years. Material and methods: Cohort of children with VLBW born in 2002–2017. Association between neonatal somatometry (z-score by Fenton and IW-21) and risk of short stature (< −2 DS), head circumference < −2 DS and malnutrition at 2 years (BMI < −2 DS) was analyzed (WHO charts). Results: 513 children with a mean gestational age of 30.05 ± 2.5 weeks were included. Birth and discharge weight z-score by Fenton and IW-21 were useful for predicting risk of short stature and malnutrition at 2 years (without differences in the AUC of the ROC curves). Weight z-score at discharge was also useful for predicting head circumference < −2 DS. At 2 years, prevalence of short stature, head circumference < −2 DS, and malnutrition was 17.2, 4.1, and 6.1%, respectively. Low weight for gestational age and length of stay were identified as independent risk factors for short stature at 2 years. Conclusions: Discharge weight z-score is useful for predicting risk of short stature, malnutrition and head circumference < −2 DS at 2 years in very low birth weight children, with no statistical difference between using Fenton or IW-21 charts. (AU)


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , História do Século XXI , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Gráficos de Crescimento , Recém-Nascido Prematuro , Epidemiologia Descritiva , Estudos Retrospectivos , Desnutrição
15.
Cancer Res ; 82(23): 4429-4443, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36156071

RESUMO

Autophagy is a conserved catabolic process that maintains cellular homeostasis. Autophagy supports lung tumorigenesis and is a potential therapeutic target in lung cancer. A better understanding of the importance of tumor cell-autonomous versus systemic autophagy in lung cancer could facilitate clinical translation of autophagy inhibition. Here, we exploited inducible expression of Atg5 shRNA to temporally control Atg5 levels and to generate reversible tumor-specific and systemic autophagy loss mouse models of KrasG12D/+;p53-/- (KP) non-small cell lung cancer (NSCLC). Transient suppression of systemic but not tumor Atg5 expression significantly reduced established KP lung tumor growth without damaging normal tissues. In vivo13C isotope tracing and metabolic flux analyses demonstrated that systemic Atg5 knockdown specifically led to reduced glucose and lactate uptake. As a result, carbon flux from glucose and lactate to major metabolic pathways, including the tricarboxylic acid cycle, glycolysis, and serine biosynthesis, was significantly reduced in KP NSCLC following systemic autophagy loss. Furthermore, systemic Atg5 knockdown increased tumor T-cell infiltration, leading to T-cell-mediated tumor killing. Importantly, intermittent transient systemic Atg5 knockdown, which resembles what would occur during autophagy inhibition for cancer therapy, significantly prolonged lifespan of KP lung tumor-bearing mice, resulting in recovery of normal tissues but not tumors. Thus, systemic autophagy supports the growth of established lung tumors by promoting immune evasion and sustaining cancer cell metabolism for energy production and biosynthesis, and the inability of tumors to recover from loss of autophagy provides further proof of concept that inhibition of autophagy is a valid approach to cancer therapy. SIGNIFICANCE: Transient loss of systemic autophagy causes irreversible damage to tumors by suppressing cancer cell metabolism and promoting antitumor immunity, supporting autophagy inhibition as a rational strategy for treating lung cancer. See related commentary by Gan, p. 4322.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Autofagia/fisiologia , Glucose/metabolismo , Lactatos
16.
An Pediatr (Engl Ed) ; 97(4): 270-279, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35953382

RESUMO

INTRODUCTION: There is no consensus on which neonatal chart is best to use in very low birth weight (VLBW) infants. The aim of the study was to compare the Fenton 2013 and Intergrowth-21st (IW-21) charts based on their predictive ability for somatometry at 2 years, as well as to analyze factors related to short stature at 2 years. MATERIAL AND METHODS: Cohort of children with VLBW born between 2002 and 2017. Association between neonatal somatometry (z-score by Fenton and IW-21) and risk of short stature (<-2 DS), head circumference <-2 DS and malnutrition at 2 years (BMI < -2 DS) was analyzed (WHO charts). RESULTS: 513 children with a mean gestational age of 30.05 ± 2.5 weeks were included. Birth and discharge weight z-score by Fenton and IW-21 were useful for predicting risk of short stature and malnutrition at 2 years (without differences in the AUC of the ROC curves). Weight z-score at discharge was also useful for predicting head circumference < -2 DS. At 2 years, prevalence of short stature, head circumference < -2 DS, and malnutrition was 17.2, 4.1, and 6.1%, respectively. Low weight for gestational age and length of stay were identified as independent risk factors for short stature at 2 years. CONCLUSIONS: Discharge weight z-score is useful for predicting risk of short stature, malnutrition and head circumference < -2 DS at 2 years in very low birth weight children, with no statistical difference between using Fenton or IW-21 charts.


Assuntos
Nanismo , Desnutrição , Peso ao Nascer , Criança , Feminino , Idade Gestacional , Gráficos de Crescimento , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional
17.
J Contin Educ Health Prof ; 42(2): 78-80, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35439765

RESUMO

INTRODUCTION: Different organizations have recommended changes in life support in the COVID-19 pandemic, just when maintaining the competence in cardiopulmonary resuscitation is compromised because on-site training must be avoided. We developed a pilot teaching-learning experience to promote cardiopulmonary resuscitation skills acquisition in this situation. The aim of this study was to describe that tool and to analyze its usefulness. METHODS: The experience consisted of three phases: first, reviewing the scientific literature; second, defining written local recommendations and recording a short video simulating the initial attention to a cardiac arrest in this COVID-19 context; third, creating a test to be answered by hospital health professionals. RESULTS: The final sample was 121 subjects; 66.1% were women; the mean age was 45.8 years (SD = 10.24). Among them, 43% were doctors, 43% nurses, 4.1% nursing assistants, and 9.9% others. 89.3% participants had received prior training in life support. In the test, questions 1, 2, 5, 6, 7, and 8 were answered correctly by more than 80%; questions 3 and 4 were answered correctly by 57.9% and 41.3%, respectively. All participants expressed that the video helped them to refresh their knowledge and skills in life support. DISCUSSION: When on-site training is not possible, distance learning-as in our teaching-learning innovation because of the COVID-19 pandemic-may be a valid option to acquire/refresh cardiopulmonary resuscitation skills.


Assuntos
COVID-19 , Reanimação Cardiopulmonar , Parada Cardíaca , COVID-19/epidemiologia , Reanimação Cardiopulmonar/educação , Competência Clínica , Feminino , Parada Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
18.
Mol Genet Genomic Med ; 10(6): e1950, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35411715

RESUMO

BACKGROUND: The increased expression of B cell-activating factor (BAFF) has been linked to autoantibody production in autoimmune diseases (ADs). The aim of this study was to investigate the association among TNFSF13B gene (OMIM: 603969) single nucleotide polymorphisms (SNPs), TNFSF13B mRNA, and soluble BAFF (sBAFF) expression in patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). The diagnostic value of sBAFF also was evaluated by the area under the curve (AUC) of receiver operating characteristic or receptor (ROC) curves. METHODS: Genotypes of the TNFSF13B rs9514827 (-2841 T > C), rs1041569 (-2701 A > T) and rs9514828 (-871 C > T) SNPs were determined by PCR-RFLP assay. TNFSF13B mRNA and sBAFF expression were performed by RT-qPCR and ELISA, respectively. The study included 320 RA patients, 101 pSS patients, and 309 healthy subjects (HS). RESULTS: The rs9514828 T allele and the TAT haplotype were associated with an increased risk to develop RA. In both ADs, the TNFSF13B mRNA levels were increased in comparison with HS. The rs9514828 (-871 C > T) polymorphism was associated with increased gene expression in RA patients. Also, sBAFF levels were higher in both ADs, however pSS patients showed the highest sBAFF levels. sBAFF showed higher diagnostic performance for pSS with an AUC of 0.968, with a similar accuracy of anti-SSA/Ro antibody diagnosis (AUC = 0.974). CONCLUSIONS: Our findings demonstrate that the TNFSF13B rs9514828 (-871 C > T) polymorphism is a risk factor for RA in the western Mexican population. sBAFF levels may be a potential diagnosis biomarker in pSS.


Assuntos
Artrite Reumatoide , Síndrome de Sjogren , Artrite Reumatoide/genética , Fator Ativador de Células B/genética , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/genética
19.
J Adolesc Health ; 70(3S): S22-S27, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35184826

RESUMO

PURPOSE: This study explores links among marianismo, girls' mobility and sexuality, and child marriage among adolescent girls in rural areas of Honduras. METHODS: We analyze quantitative and qualitative data collected in 2008-2016 for a longitudinal cohort study of rural Honduran adolescent girls. These data include interviews (n = 10 married before age 18) and surveys (n = 563; 155 married early). We also use qualitative data from focus groups in 2016 that included students, parents, teachers, and community members (n = 120). RESULTS: We find that girls who scored higher on a scale of traditional gender norms were more likely to marry early. Furthermore, our qualitative findings indicate that girls experienced control over their mobility and their sexuality because of rigid gender norms prevalent in their communities. The control girls experience clashes with undergoing psychosocial changes that are associated with increased desire for autonomy and intimacy as well as increased awareness of their sexuality. In some cases, girls believed that marriage was better than staying in their restrictive households, and/or they viewed marriage as the only way to have a romantic relationship. DISCUSSION: Rigid gender norms that promote excessive regulation of girls' behavior and sexuality influence girls' decision-making processes to enter child marriage. Educational initiatives that challenge sexist gender norms and explain and normalize attraction and intimacy during adolescence should be a central component of child marriage prevention programming for adolescents, parents, and community members.


Assuntos
Casamento , Comportamento Sexual , Adolescente , Criança , Feminino , Identidade de Gênero , Humanos , Estudos Longitudinais , Sexualidade
20.
Chaos ; 32(1): 013119, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35105110

RESUMO

In our search to understand complex oscillation in discrete dynamic systems, we modify the Ricker map, where one parameter is also a dynamic variable. Using the bistable behavior of the fixed point solution, we analyze two response functions that characterize the change of the dynamic parameter. The 2D map sustains different types of burst oscillations that depend on the response functions. In either case, the parameter values yield a slow dynamic variable required to observe bursting-type oscillations.


Assuntos
Potenciais de Ação
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