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Women are born with all of their oocytes. The oocyte proteome must be maintained with minimal damage throughout the woman's reproductive life, and hence for decades. Here we report that oocyte and ovarian proteostasis involves extreme protein longevity. Mouse ovaries had more extremely long-lived proteins than other tissues, including brain. These long-lived proteins had diverse functions, including in mitochondria, the cytoskeleton, chromatin and proteostasis. The stable proteins resided not only in oocytes but also in long-lived ovarian somatic cells. Our data suggest that mammals increase protein longevity and enhance proteostasis by chaperones and cellular antioxidants to maintain the female germline for long periods. Indeed, protein aggregation in oocytes did not increase with age and proteasome activity did not decay. However, increasing protein longevity cannot fully block female germline senescence. Large-scale proteome profiling of ~8,890 proteins revealed a decline in many long-lived proteins of the proteostasis network in the aging ovary, accompanied by massive proteome remodeling, which eventually leads to female fertility decline.
Subject(s)
Oocytes , Ovary , Proteome , Proteostasis , Female , Animals , Oocytes/metabolism , Ovary/metabolism , Proteome/metabolism , Mice , Mice, Inbred C57BL , Aging/metabolism , Aging/genetics , Proteasome Endopeptidase Complex/metabolism , Cellular Senescence , Fertility , Proteomics/methods , Longevity/physiologyABSTRACT
Introduction: Currently the use of prohibited performance-enhancing substances (PES) in fitness and gym settings is a public health concern as adverse health consequences are emerging. Understanding the characteristics of gym-goers who do not use these substances could lead to an important complement to the ongoing research about risk factors for PES use. The aim of this study was to identify the profile of PES non-use in gym-goers. Methods: In total, 453 gym-goers (mean age = 35.64 years; SD = 13.08 - measure of central tendency location and measure of absolute dispersion, respectively) completed an online survey assessing sociodemographic factors, exercise characteristics, gym modalities, peers, social influence, attitudes, subjective norms, beliefs, intentions, and self-reported use of PES. Results: Decision Trees showed that being a woman, training less frequently, not practicing bodybuilding and having a negative intention to consume PES were identified as characteristics of non-users of PES. Discussion: These results may support evidence-based anti-doping interventions to prevent abusive use of PES in the fitness context.
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Enzyme immobilization can offer a range of significant advantages, including reusability, and increased selectivity, stability, and activity. In this work, a central composite design (CCD) of experiments and response surface methodology (RSM) were used to study, for the first time, the L-asparaginase (ASNase) immobilization onto functionalized carbon xerogels (CXs). The best results were achieved using CXs obtained by hydrothermal oxidation with nitric acid and subsequent heat treatment in a nitrogen flow at 600 °C (CX-OX-600). Under the optimal conditions (81â min of contact time, pHâ 6.2 and 0.36â g/L of ASNase), an immobilization yield (IY) of 100 % and relative recovered activity (RRA) of 103 % were achieved. The kinetic parameters obtained also indicate a 1.25-fold increase in the affinity of ASNase towards the substrate after immobilization. Moreover, the immobilized enzyme retained 97 % of its initial activity after 6 consecutive reaction cycles. All these outcomes confirm the promising properties of functionalized CXs as support for ASNase, bringing new insights into the development of an efficient and stable immobilization platform for use in the pharmaceutical industry, food industry, and biosensors.
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Nitrogen-doped graphene-based materials are of utmost importance in sensing and energy conversion devices due to their unique physicochemical properties. However, the presence of defects such as pyrrolic nitrogen and oxygenated functional groups reduces their electrical conductivity. Herein, a two-step approach based on the electrochemical exfoliation of graphite foils in aqueous mixed electrolytes followed by thermal reduction at 900 °C is used to prepare high-quality few layers of N-doped graphene-based materials. The exfoliations were conducted in 0.1 M (NH4)2SO4 or H2SO4 and HNO3 (5 mM or 0.1 M) electrolytes mixtures and the HNO3 vol% varied. Chemical analysis demonstrated that the as-prepared graphene oxides contain nitro and amine groups. Thermal reduction is needed for substitutional N-doping. Nitrogen and oxygen surface concentrations vary between 0.23-0.96% and 3-8%, respectively. Exfoliation in (NH4)2SO4 and/or 5 mM HNO3 favors the formation of pyridinic-N (10-40% of the total N), whereas 1 M HNO3 favors the formation of graphitic-N (≈60%). The electrical conductivity ranges between 166-2705 Scm-1. Raman spectroscopy revealed a low density of defects (ID/IG ratio between 0.1 and 0.7) and that most samples are composed of mono-to-bilayer graphene-based materials (IG/I2D integrated intensities ratio). Structural and compositional stability of selected samples after storage in air for three months is demonstrated. These results confirm the high quality of the synthesized undoped and N-doped graphene-type materials.
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Purpose: In the last decades we have seen an increase in sedentary behaviors and a decrease in physical activity in children when compared to past generations. This lifestyle is commonly associated with the development of clustering risk factors that define metabolic syndrome (MetS). Knowing that motor competence (MC) development can influence lifelong physical activity habits, it is reasonable to assume that children's MC will directly link to clustered cardiometabolic health outcomes. The aim of this study was to analyze the role of MC in MetS risk factors. Methods: Seventy children with a mean age of 7.49 (SD = 1.28) years were evaluated on motor competence (MCA-Motor Competence Assessment instrument), cardiovascular fitness (PACER test), upper body strength (UBS; handgrip), and the components of MetS, hypertriglyceridemia, hypertension, abdominal obesity, low concentration of high-density lipoprotein cholesterol, and high fasting blood glucose. The composite value of MetS was calculated according to Burns et al. (2017). Multiple standard regressions were performed to explore the effect of different variables on MetS. Motor competence and health-related fitness (cardiovascular fitness and relative upper body strength) were used as independent variables (predictors) and MetS as dependent variable. Results: Overall, the results showed that motor competence (ß = -.072; p < .05) is a significant predictor and this model explained 7,1% of the variance in MetS. Conclusion: Although more studies are needed, our results indicate that MC seems to have a positive role in children's health markers.
This study aimed to analyze the role of MC, cardiorespiratory fitness, and upper body strength in MetS risk factors.The results suggest that upper body strength is the strongest predictor for MetS (negative association), followed by MC (positive association).When the different MC components were entered independently instead of total MC, the upper body strength and locomotor MC were found to be significant predictors of the MetS behavior.Considering our results and the fact that MC levels during childhood positively influence PA levels along lifespan, this study suggests a pathway to follow in future research.
Subject(s)
Metabolic Syndrome , Child , Humans , Hand Strength , Risk Factors , Obesity , ExerciseABSTRACT
The non-human primate (NHP) Leontopithecus rosalia is an endangered species native of Brazil and lives in forest fragments with different levels of contact with humans (natural, private and urban). Other NHPs - Callithrix spp. - were introduced by humans and co-exist and interact with the native species in these forests. To evaluate if living in or close to human-modified environments could constitute a risk for L. rosalia, we compared the prevalence, genetic background, antibiotic susceptibility and virulence gene content of staphylococci collected from the native and the introduced species from different forest fragments. We found that presence in human-dominated environments increased the colonization rate of L. rosalia with Mammaliicoccus sciuri (former Staphylococcus sciuri) from 18 % to 85 % (p = 0.0001) and of Callithrix spp with Staphylococcus aureus from 6 % to 100 % (p = 0.0001). According to molecular typing data obtained differences probably resulted from dissemination of these bacterial species from the invader NHP species and from humans. Changes in microbiota were paralleled by an increase in the prevalence of Panton-Valentine Leukocidin gene and in resistance to beta-lactams, macrolides and/or lincosamides as exposure to human environment increased. In particular, erythromycin resistance in S. aureus from Callithrix spp. increased from 0 % to 50 % and resistance rate to at least one antibiotic in coagulase-negative staphylococci species from L. rosalia increased from 13 % to 56 % (p = 0.0003). Our results showed that contact of native animal species with human-created environments increased the content of antimicrobial resistant and pathogenic bacteria on their commensal microbiota, which ultimately can impact on their health. IMPORTANCE: Endangered animal species are vulnerable to environmental alterations and human activities have been repeatedly identified as factors driving drastic changes in the natural landscape. It is extremely important to monitor changes in the environment surrounding protected species, because this could lead to early detection of any potential threats. In this study, we found that the contact of L. rosalia - a protected non-human primate from Brazil - with human environments is related to changes in their commensal microbiota. These included an increase in the number of pathogenic and antibiotic resistant bacteria, which have a higher potential to cause infections that are more difficult to treat. We provided evidence for the harmful impact human contact has on L. rosalia. Also, our results suggest that monitoring of commensal microbiota of protected animal species might be a useful way of sensing the risks of protected species to human exposure.
Subject(s)
Anti-Bacterial Agents , Staphylococcal Infections , Animals , Humans , Anti-Bacterial Agents/pharmacology , Staphylococcus aureus/genetics , Brazil/epidemiology , Callithrix , Drug Resistance, Bacterial , Staphylococcal Infections/epidemiology , Staphylococcal Infections/veterinary , Staphylococcal Infections/microbiology , Microbial Sensitivity Tests/veterinaryABSTRACT
Resumo Objetivo Analisar as evidências disponíveis sobre a transição alimentar de sonda orogástrica para aleitamento materno diretamente na mama com prematuros internados em unidades hospitalares. Métodos Revisão sistemática da literatura com busca nas bases de dados PubMed/MEDLINE, Web of Science, EMBASE, Scopus, Cochrane CENTRAL, CINAHL, com os critérios de inclusão: estudos experimentais, sem restrição temporal e nos idiomas português, espanhol e inglês. A avaliação metodológica foi realizada por meio das ferramentas Grading of Recommendations Assessment, Development and Evaluation (GRADE) e Revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) e consistiu em duas etapas: qualidade metodológica e o risco de viés dos estudos. Resultados Foram identificados 10 artigos, todos ensaios clínicos randomizados. As técnicas utilizadas na transição da dieta dos prematuros encontradas foram: sonda-dedo e seringa, copo e sonda-dedo, copo e mamadeira, colher e sucção não-nutritiva, sucção não-nutritiva, sucção não-nutritiva e estimulação oral, comportamento dos prematuros, cheiro do leite materno. Conclusão As técnicas evidenciadas permitiram a transição da dieta, em um período mais curto, reduzindo o tempo de internação, aumentando o ganho de peso e se mostraram seguras, desde que o prematuro tenha maturidade para ser realizada. Contudo, a mamadeira foi desaconselhada, pela ocorrência de episódios de dessaturação, aumento da frequência cardíaca e confusão de bico.
Resumen Objetivo Analizar las evidencias disponibles sobre la transición alimentaria de sonda orogástrica a lactancia materna directamente de la mama con prematuros internados en unidades hospitalarias. Métodos Revisión sistemática de la literatura con búsqueda en las bases de datos PubMed/MEDLINE, Web of Science, EMBASE, Scopus, Cochrane CENTRAL, CINAHL, con los siguientes criterios de inclusión: estudios experimentales, sin restricción temporal y en idioma portugués, español e inglés. La evaluación metodológica se realizó por medio de las herramientas Grading of Recommendations Assessment, Development and Evaluation (GRADE) y Revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) y consistió en dos etapas: calidad metodológica y riesgo de sesgo de los estudios. Resultados Se identificaron 10 artículos, todos ensayos clínicos aleatorizados. Las técnicas utilizadas para la transición de la dieta de prematuros fueron: dedo-jeringa y jeringa, vaso y dedo-jeringa, vaso y mamadera, cuchara y succión no nutritiva, succión no nutritiva, succión no nutritiva y estimulación oral, comportamiento de los prematuros, olor de la leche materna. Conclusión Las técnicas observadas permitieron realizar la transición de la dieta en un período más corto, con reducción del tiempo de internación y mejor aumento de peso y demostraron ser seguras, siempre que el prematuro tenga madurez para realizarlas. No obstante, se desaconseja la mamadera por la presencia de episodios de desaturación, aumento de la frecuencia cardíaca y confusión tetina-pezón. Número de registro da revisão sistemática: CRD42021240725 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=240725)
Abstract Objective To analyze the available evidence on the transition from orogastric tube feeding to breastfeeding directly from the breast with premature infants admitted to hospital units. Methods Systematic literature review with search in the following databases: PubMed/MEDLINE, Web of Science, EMBASE, Scopus, Cochrane CENTRAL, CINAHL, with the inclusion criteria: experimental studies, without temporal restrictions and in Portuguese, Spanish and English. The methodological assessment was carried out using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) tools and consisted of two stages: methodological quality and the risk of bias of the studies. Results 10 papers were identified, all randomized clinical trials. The techniques used in transitioning the premature babies' diet were: finger tube and syringe, cup and finger tube, cup and bottle, spoon and non-nutritive sucking, non-nutritive sucking, non-nutritive sucking and oral stimulation, behavior of premature babies, and smell of breast milk. Conclusion The demonstrated techniques allowed the transition of the diet in a shorter period, reducing the length of hospital stay, increasing weight gain 1and proved to be safe, as long as the premature baby is mature enough to undergo the procedure. However, bottle feeding was not recommended due to the occurrence of episodes of desaturation, increased heart rate and nipple confusion. Systematic review registration number: CRD42021240725 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=240725)
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ABSTRACT Objective: to construct and validate the content of a bundle for nutrition transition for premature newborns admitted to a Kangaroo Intermediate Care Unit based on Interactive Theory of Breastfeeding. Method: this is a multiple method research, carried out in five steps: systematic review; situational diagnosis; interview with Kangaroo Unit nurses; methodological step - (bundle construction with Interactive Theory of Breastfeeding application, pre-test); and content validity with expert judges and clinical nurses. The methodological step was carried out from January to July 2022 with Kangaroo Unit nurses of a public maternity hospital in Fortaleza-CE. Experts were invited by email using the snowball method. Validity occurred using a Content Validity Index >0.80. Results: the bundle was constructed using 13 items, distributed and organized into corrected age groups: corrected age of ≤32 weeks; from 32 to 34 weeks; and ≥ 34 weeks. In the validity step, the judges, three experts and seven clinical nurses, judged the bundle to be adequate, presenting a Content Validity Index of 1.0. Conclusion: given the lack of standardization for feeding transition in clinical practice, there is difficulty in recognizing the ideal moment to transition from orogastric tube feeding to mothers' breast. The food transition bundle, anchored by the Interactive Theory of Breastfeeding, allows nurses to assess the mother-child dyad, their particularities, time for both, maternal role, involving organizational systems to protect, promote and support breastfeeding. Brazilian Clinical Trials Registry (REBEC) under UTN number: U1111-1285-3181.
RESUMEN Objetivo: construir y validar el contenido de un bundle de transición dietética para bebés prematuros admitidos en la Unidad de Cuidados Intermedios Canguro basado en la Teoría de la Lactancia Materna Interactiva. Métodos: se trata de una investigación de métodos múltiples realizada en cinco steps: revisión sistemática; diagnóstico situacional; entrevista con enfermeras de la Unidad Canguro; etapa metodológica - (construcción de bundle con aplicación de la Teoría de Lactancia Interactiva, pretest); y validez de contenido con jueces expertos y enfermeras clínicas. La etapa metodológica se realizó de enero a julio de 2022 con enfermeras de la Unidad Canguro de una maternidad pública de Fortaleza-CE. Se invitó a los expertos por correo electrónico utilizando el método de bola de nieve. La validación se produjo mediante el índice de validez de contenido >0,80. Resultados: el bundle se construyó utilizando 13 ítems, distribuidos y organizados en grupos de edad corregidos: edad corregida de ≤32 weeks; entre 32 a 34 semanas y ≥ 34 semanas. En la etapa de validez, los jueces, tres expertos y siete enfermeras clínicas, juzgaron adecuado el bundle, presentando un Índice de Validez de Contenido de 1,0. Conclusión: dada la falta de estandarización para la transición alimentaria en la práctica clínica, existe dificultad en reconocer el momento ideal para la transición de la alimentación por sonda orogástrica al pecho materno. El bundle de transición alimentaria, anclado en la Teoría Interactiva de la Lactancia Materna, permite a las enfermeras evaluar el binomio madre-hijo, sus particularidades, el tiempo de ambos, el rol materno, involucrando los sistemas organizacionales de protección, promoción y apoyo a la lactancia materna. Registro Brasileño de Ensayos Clínicos (REBEC) con el número UTN: U1111-1285-3181.
RESUMO Objetivo: construir e validar o conteúdo de um Bundle para transição alimentar para prematuros internados na Unidade de Cuidados Intermediários Canguru baseada na Teoria Interativa de Amamentação. Método: Pesquisa do tipo método múltiplos realizada em cinco etapas: Revisão Sistemática; Diagnóstico Situacional; Entrevista com Enfermeiras da Unidade Canguru; Etapa Metodológica - (Construção do Bundle com aplicação da Teoria Interativa de Amamentação, Pré-teste) e por última, a validação de conteúdo com juízes expertises e enfermeiras assistenciais. A etapa metodológica, foi realizada de janeiro a julho de 2022, com enfermeiras da Unidade Canguru, de uma Maternidade pública de Fortaleza-CE, já os expertises foram convidados por e-mail, pelo método de bola de neve. A validação ocorreu mediante Índice de Validade de Conteúdo >0,80. Resultados: A construção do Bundle ocorreu partindo de 13 itens, distribuídos e organizados em grupos de idade corrigida: idade corrigida de ≤32 semanas; entre 32 a 34 semanas e ≥ 34 semanas. Na etapa de validação, os juízes, três expertises e sete enfermeiras assistenciais, julgaram adequado o Bundle, apresentando Índice de Validade de Conteúdo de 1,0. Conclusão: diante da inexistência de padronização para transição alimentar na prática clínica, existe uma dificuldade para o reconhecimento do momento ideal em realizar a transição da alimentação da sonda orogástrica para o peito materno. O Bundle de Transição Alimentar, ancorado pela Teoria Interativa de Amamentação, possibilita que o enfermeiro avalie o binômio mãe-filho, suas particularidades, tempo de ambos, protagonismo materno, envolvendo os sistemas organizacionais de proteção, promoção e apoio a amamentação. Registro Brasileiro de Ensaios Clínicos (REBEC) sob número UTN: U1111-1285-3181.
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Objetivo: compreender os impactos para os profissionais de enfermagem como segunda vítima de incidentes de segurança do paciente. Método: estudo qualitativo aprovado pelo comitê de ética em pesquisa, do tipo exploratório-descritivo, realizado com 20 profissionais de enfermagem em hospital universitário do Sul do Brasil, entre novembro de 2021 e janeiro de 2022, por meio de entrevistas semiestruturadas analisadas a partir da análise textual discursiva. Resultados: as categorias sentimentos das segundas vítimas, demonstrando a presença de sentimentos negativos, sendo o medo o mais recorrente; e, impacto na trajetória profissional e no ambiente de trabalho, questionando sua habilidade como um bom profissional e a escolha da profissão como sendo adequada permitiram compreender o impacto no profissional de enfermagem. Considerações finais: os impactos relacionaram-se ao sentimento de culpa pelo fato ocorrido, autojulgamento, julgamento pelos pares e pelo paciente, medo do desfecho ao paciente e das consequências para si e dúvidas quanto à sua habilidade e desempenho no trabalho(AU)
Objective: to understand the impacts on nursing professionals as the second victim of patient safety incidents. Method: qualitative exploratory-descriptive study approved by the research ethics committee, carried out with 20 nursing professionals at a university hospital in southern Brazil, between November 2021 and January 2022, through semi-structured interviews analyzed from the discursive textual analysis. Results: the second victims' feelings categories, demonstrating the presence of negative feelings, with fear being the most recurrent; and impact on the professional path and on the work environment, questioning their ability as a good professional and the choice of profession as being adequate, allowed understanding the impact on the nursing professional. Final considerations: the impacts were related to the feeling of guilt for the fact that occurred, self-judgment, judgment by peers and by the patient, fear of the outcome for the patient and the consequences for himself, and doubts about his ability and performance at work(AU)
Objetivo: comprender los impactos sobre los profesionales de enfermería como segunda víctima de los incidentes de seguridad del paciente. Método: estudio cualitativo, de tipo exploratorio-descriptivo, aprobado por el comité de ética en investigación, y realizado junto a 20 profesionales de enfermería de un hospital universitario del sur de Brasil, entre noviembre de 2021 y enero de 2022, a través de entrevistas semiestructuradas analizadas a partir del análisis textual discursivo. Resultados: las categorías de sentimientos de las segundas víctimas han permitido comprender el impacto sobre el profesional de enfermería: indican la presencia de sentimientos negativos, el miedo siendo el más recurrente; el impacto en la trayectoria profesional y en el ambiente de trabajo, ya que los enfermeros cuestionan su habilidad de buen profesional y si ha sido adecuada la elección de la profesión. Consideraciones finales: los impactos se relacionaron con el sentimiento de culpa por el hecho ocurrido, el juicio propio, el juicio de los pares y del paciente, el miedo al desenlace para el paciente y las consecuencias para él mismo, y las dudas sobre su capacidad y desempeño en el trabajo(AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Emotions , Patient Safety , Patient Harm/nursing , Licensed Practical Nurses/psychology , Nurses/psychology , Qualitative Research , Near Miss, Healthcare , Guilt , Hospitals, UniversityABSTRACT
Recurrent miscarriage (RM) affects up to 2.5% of couples of reproductive age. Up to 10% of couples using assisted reproductive technology experience recurrent implantation failure (RIF). Immunosuppressive drugs, such as calcineurin inhibitors (CNIs), has been proposed for RM and RIF management. This systematic review and meta-analysis (SRMA) aimed to evaluate the efficacy and safety of CNIs in RM and RIF treatment. We searched in the three databases. Review Manager 5.4.1 was used for statistical analysis. This review included 8 studies involving 1042 women (485 women in the CNIs group and 557 women in the control group). CNI treatment (cyclosporine [CsA] and tacrolimus [TAC]) increases live birth rate (LBR, odds ratio [OR]: 2.52; 95% confidence interval [CI]: 1.93-3.28, p < 0.00001) and clinical pregnancy rate (OR: 2.25; 95% CI: 1.54-4.40, p < 0.0001) and decreases miscarriage rate (OR: 0.45 95% CI: 0.32-0.63, p < 0.00001) when compared to the control. Side effects and obstetric and neonatal complications was similar in both groups. In conclusion, CNIs increased LBR in women with RM and RIF but there is a moderate risk of bias. Subgroup analysis revealed that CNIs improved LBR in women with RM with a low risk of bias. However, in women with RIF, with moderate to high risk of bias. The use of CsA and TAC, in low doses and for a short period, for managing reproductive failures in women seems to be safe, not causing serious side effects nor increasing the risk of obstetric and neonatal complications.
Subject(s)
Abortion, Habitual , Calcineurin Inhibitors , Pregnancy , Infant, Newborn , Female , Humans , Calcineurin Inhibitors/therapeutic use , Pregnancy Rate , Immunosuppressive Agents/therapeutic use , Birth Rate , Tacrolimus/therapeutic useABSTRACT
Tobacco misuse as a comorbidity of schizophrenia is frequently established during adolescence. However, comorbidity markers are still missing. Here, the method of label-free proteomics was used to identify deregulated proteins in the medial prefrontal cortex (prelimbic and infralimbic) of male and female mice modelled to schizophrenia with a history of nicotine exposure during adolescence. Phencyclidine (PCP), used to model schizophrenia (SCHZ), was combined with an established model of nicotine minipump infusions (NIC). The combined insults led to worse outcomes than each insult separately when considering the absolute number of deregulated proteins and that of exclusively deregulated ones. Partially shared Reactome pathways between sexes and between PCP, NIC and PCPNIC groups indicate functional overlaps. Distinctively, proteins differentially expressed exclusively in PCPNIC mice reveal unique effects associated with the comorbidity model. Interactome maps of these proteins identified sex-selective subnetworks, within which some proteins stood out: for females, peptidyl-prolyl cis-trans isomerase (Fkbp1a) and heat shock 70 kDa protein 1B (Hspa1b), both components of the oxidative stress subnetwork, and gamma-enolase (Eno2), a component of the energy metabolism subnetwork; and for males, amphiphysin (Amph), a component of the synaptic transmission subnetwork. These are proposed to be further investigated and validated as markers of the combined insult during adolescence.
Subject(s)
Phencyclidine , Schizophrenia , Mice , Animals , Male , Female , Phencyclidine/metabolism , Schizophrenia/metabolism , Nicotine/pharmacology , Prefrontal Cortex/metabolism , Synaptic Transmission , Disease Models, AnimalABSTRACT
Background: A growing interest in long-term sequelae of COVID-19 has prompted several systematic literature reviews (SLRs) to evaluate long-COVID-19 effects. However, many of these reviews lack in-depth information on the timing, duration, and severity of these conditions. Objectives: Our aim was to synthesize both qualitative and quantitative evidence on prevalence and outcomes of long-term effect of COVID-19 through an umbrella review. Design: Umbrella review of relevant SLRs on long-COVID-19 in terms of prolonged symptoms and clinical conditions, and comprehensively synthesized the latest existing evidence. Data Sources and Methods: We systematically identified and appraised prior systematic reviews/meta-analyses using MEDLINE, Embase, and Cochrane database of systematic review from 2020 to 2021 following the preferred reporting items for systematic reviews and meta-analyses guidance. We summarized and categorized all relevant clinical symptoms and outcomes in adults with COVID-19 using the Medical Dictionary for Regulatory Activities System Organ Class (MedDRA SOC). Results: We identified 967 systematic reviews/meta-analyses; 36 were retained for final data extraction. The most prevalent SOC were social circumstances (40%), blood and lymphatic system disorders (39%), and metabolism and nutrition disorder (38%). The most frequently reported SOC outcomes within each MedDRA category were poor quality of life (59%), wheezing and dyspnea (19-49%), fatigue (30-64%), chest pain (16%), decreased or loss of appetite (14-17%), abdominal discomfort or digestive disorder (12-18%), arthralgia with or without myalgia (16-24%), paresthesia (27%) and hair loss (14-25%), and hearing loss or tinnitus (15%). Conclusion: This study confirmed a high prevalence of several long COVID-19 outcomes according to the MedDRA categories and indicated that the majority of evidence was rated as moderate to low. Registration: The review was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022303557).
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The Iberian harbour porpoise population is small and fisheries bycatch has been described as one of its most important threats. Data on harbour porpoise strandings collected by the Portuguese and Galician stranding networks between 2000 and 2020 are indicative of a recent mortality increase in the western Iberian coast (particularly in northern Portugal). Overall, in Portugal and Galicia, individuals stranded due to confirmed fishery interaction represented 46.98% of all analysed porpoises, and individuals stranded due to probable fishery interaction represented another 10.99% of all analysed porpoises. Considering the Portuguese annual abundance estimates available between 2011 and 2015, it was possible to calculate that an annual average of 207 individuals was removed from the population in Portuguese waters alone, which largely surpasses the potential biological removal (PBR) estimates (22 porpoises, CI: 12-43) for the same period. These results are conservative and bycatch values from strandings are likely underestimated. A structured action plan accounting for new activities at sea is needed to limit the Iberian porpoise population decline. Meanwhile, there is an urgent need for a fishing effort reorganization to directly decrease porpoise mortality.
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Sex-biased differences in schizophrenia are evident in several features of the disease, including symptomatology and response to pharmacological treatments. As a neurodevelopmental disorder, these differences might originate early in life and emerge later during adolescence. Considering that the disruption of the glutamatergic system during development is known to contribute to schizophrenia, we hypothesized that the neonatal phencyclidine model could induce sex-dependent behavioral and neurochemical changes associated with this disorder during adolescence. C57BL/6 mice received either saline or phencyclidine (5, 10, or 20 mg/kg) on postnatal days (PN) 7, 9, and 11. Behavioral assessment occurred in late adolescence (PN48-50), when mice were submitted to the open field, social interaction, and prepulse inhibition tests. Either olanzapine or saline was administered before each test. The NMDAR obligatory GluN1 subunit and the postsynaptic density protein 95 (PSD-95) were evaluated in the frontal cortex and hippocampus at early (PN30) and late (PN50) adolescence. Neonatal phencyclidine evoked dose-dependent deficits in all analyzed behaviors and males were more susceptible. Males also had reduced GluN1 expression in the frontal cortex at PN30. There were late-emergent effects at PN50. Cortical GluN1 was increased in both sexes, while phencyclidine increased cortical and decreased hippocampal PSD-95 in females. Olanzapine failed to mitigate most phencyclidine-evoked alterations. In some instances, this antipsychotic aggravated the deficits or potentiated subthreshold effects. These results lend support to the use of neonatal phencyclidine as a sex-biased neurodevelopmental preclinical model of schizophrenia. Olanzapine null effects and deleterious outcomes suggest that its use during adolescence should be further evaluated.
Subject(s)
Antipsychotic Agents , Schizophrenia , Male , Female , Animals , Mice , Phencyclidine/pharmacology , Schizophrenia/chemically induced , Schizophrenia/drug therapy , Olanzapine/therapeutic use , Mice, Inbred C57BL , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Disease Models, AnimalABSTRACT
BACKGROUND: Current clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication 'single autosomal recessive mutation in rare disease'. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing. Whole genome sequencing (WGS) aimed to identify cryptic 'second-hit' variants. METHODS: To investigate the 31 families with available data that remained unsolved following formal review within the 100kGP, SVRare was used to aggregate structural variants present in <1% of 100kGP participants. Small variants were assessed using population allele frequency data and SpliceAI. Literature searches and publicly available online tools were used for further annotation of pathogenicity. RESULTS: Using these strategies, 8/31 cases were solved, increasing the overall diagnostic yield of this cohort from 10/41 (24.4%) to 18/41 (43.9%). Exemplar cases include a patient with cystic fibrosis harbouring a novel exonic LINE1 insertion in CFTR and a patient with generalised arterial calcification of infancy with complex interlinked duplications involving exons 2-6 of ENPP1. Although ambiguous by short-read WGS, the ENPP1 variant structure was resolved using optical genome mapping and RNA analysis. CONCLUSION: Systematic examination of cryptic variants across a multi-disease cohort successfully identifies additional pathogenic variants. WGS data analysis in autosomal recessive rare disease should consider complex structural and small intronic variants as potentially pathogenic second hits.
Subject(s)
Rare Diseases , Humans , Mutation/genetics , Base Sequence , Exons , Chromosome MappingABSTRACT
Transducers made from graphene-type materials are widely used in sensing applications. However, utilization of graphene oxide obtained from electrochemical exfoliation of graphite (EGO) has remained relatively unexplored. In this study, electrochemical cocaine aptasensors based on large-size EGO flakes were investigated. In particular, the influence of the following parameters on the sensor performance was examined: (i) aptamer's terminal group (-NH2 vs -OH), (ii) functionalization of EGO with the aptamer via physical adsorption and covalent immobilization, and (iii) intrinsic electrochemical properties of EGO such as the electrochemical surface area (ESA) and standard rate constant of electron transfer (k0). The results demonstrate that EGO-based electrochemical aptasensors fabricated by physical adsorption with an NH2-modified aptamer have very good reproducibility, shelf-life stability, and high sensitivity for detecting cocaine with a detection limit of 50 nM. Their performance is comparable to that of the aptasensors prepared using the covalent immobilization. Additionally, it is shown that EGO materials with high ESA and k0 can enhance the sensing performance. The fast (less than 10 min) and strong adsorption of the NH2-modified cocaine aptamer on the surface of large EGO flakes makes the fabrication of the sensing platform simple and rapid. This simple approach has the potential to simplify the fabrication of sensors.
ABSTRACT
OVERVIEW: In recent years, there has been increasing clinical and empirical interest in the concept of pediatric loss of control over eating, particularly about its link with the executive functions related to the concept of impulsivity, such as inhibitory control and reward sensitivity. However, there has yet to be a comprehensive literature synthesis about the associations between these variables. A comprehensive literature synthesis would help identify future research directions to advance the field in this area. Therefore, this systematic review aimed to synthesize evidence concerning the associations between loss of control over eating, inhibitory control, and reward sensitivity in children and adolescents. METHODS: The systematic review was conducted according to the guidelines proposed by PRISMA in Web of Science, Scopus, PubMed, and PsycINFO. The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the risk of bias. RESULTS: Twelve studies met the selection criteria and were included in the final review. Overall, methodological heterogeneity, variability in assessment methods, and the age of participants make it difficult to draw general conclusions. Nevertheless, most studies with community samples of adolescents indicate that inhibitory control difficulties are linked to the concept of loss of control eating. The presence of obesity seems to be associated with inhibitory control difficulties, regardless of the presence of loss of control eating. Studies on reward sensitivity are scarcer. However, it has been suggested that higher reward sensitivity is related to loss of control eating behaviors in young people, particularly binge eating. CONCLUSIONS: The literature on the link between loss of control eating and trait-level facets of impulsivity (low inhibitory control and higher reward sensitivity) among young people remains limited, and more studies on children are needed. Findings from this review may make healthcare professionals more aware of the potential clinical importance of targeting the trait-level facets of impulsivity and help to inform existing and future weight-loss/maintenance interventions in childhood and adolescence.
Subject(s)
Feeding Behavior , Hyperphagia , Humans , Child , Adolescent , Cross-Sectional Studies , Obesity , RewardABSTRACT
Patient Reported Outcomes (PROs) are an evidenced way of adding value to routine clinical care. As a source of unique information on the effect of a medical condition and its treatment from the patients' perspective (Mercieca-Bebber et al. in Patient Relat Outcome Meas 9: 353-367, https://doi.org/10.2147/PROM.S156279 , 2018), PROs allow for an improved assessment in routine clinical care of symptoms, side effects, functional outcomes (physical, sexual, social, emotional, cognitive functioning), and health-related quality of life (HRQoL). By helping to align healthcare providers' interventions with what matters most to the patient, PROs contribute to the individualized choice of Anti-Retroviral Therapy (Carfora et al. in PLoS ONE 17(4): e0267030, https://doi.org/10.1371/journal.pone.0267030 , 2022) as a paramount component of tailored and person-centred care management, in routine clinical practice. This article outlines a practical framework and process tested in Portugal to raise awareness of PROs' added value, and to help guide first steps in the implementation and seamless integration of PROs, in routine HIV care.