Auraptene Boosts the Efficacy of the Tamoxifen Metabolites Endoxifen and 4-OH-Tamoxifen in a Chemoresistant ER+ Breast Cancer Model.

Approximately 80% of breast cancer (BC) cases are estrogen receptor positive (ER+) and sensitive to hormone treatment; Tamoxifen is a prodrug, and its main plasmatic active metabolites are 4-hydroxytamoxifen (4-OH Tam) and endoxifen. Despite the effectiveness of tamoxifen therapy, resistance can be developed. An increment in eukaryotic initiation factor-4A complex (eIF4A) activity can result in tamoxifen-resistant tumor cells. For this work, we developed a cell variant resistant to 4-OH Tam and endoxifen, denominated MCF-7Var E; then, the aim of this research was to reverse the acquired resistance of this variant to tamoxifen metabolites by incorporating the natural compound auraptene. Combination treatments of tamoxifen derivatives and auraptene successfully sensitized the chemoresistant MCF-7Var E. Our data suggest a dual regulation of eIF4A and ER by auraptene. Joint treatments of 4-OH Tam and endoxifen with auraptene identified a novel focus for chemoresistance disruption. Synergy was observed using the auraptene molecule and tamoxifen-derived metabolites, which induced a sensitization in MCF-7Var E cells and ERα parental cells that was not observed in triple-negative breast cancer cells (TNBC). Our results suggest a synergistic effect between auraptene and tamoxifen metabolites in a resistant ER+ breast cancer model, which could represent the first step to achieving a pharmacologic strategy.

Can Improving Postoperative Sleep Speed Up Surgical Recovery?

Sleep disturbance is common during recovery after surgical procedures and may have an important effect on mortality, and quality of life. Sleep restriction/deprivation, including decreased quantity and continuity, is common in patients who are patients and persons with acute and chronic illnesses. Age, gender, illness, primary sleep disorders, environment, and medical treatment factors are thought to influence sleep throughout the preoperative period, hospitalization, and recovery. Resulting sleep pattern disturbances include decreases in circadian patterning, continuity, duration, and perceived (subjective) sleep quality. This article synthesizes sleep disturbance in patients who have undergone surgery and highlights sleep strategies to improve faster surgical recovery.

The association between sleep and Alzheimer's disease: a systematic review.

It is estimated that 45% of individuals with cognitive impairment experience sleep disturbances prior to the onset of cognitive symptoms. Assessing sleeping problems and enhancing sleep quality are critical first steps to reduce the risk of cognitive impairment. Objective: To review existing literature based on predefined eligibility criteria to understand the connection between sleep disturbance and Alzheimer's disease. Methods: A thorough and systematic evaluation of numerous studies was carried out to assess one or more of the following epidemiological factors: (1) sleep disorders, (2) cognitive impairment, and (3) risk estimates for cognitive impairment due to sleep. Results: Studies suggest that individuals who experience memory loss may encounter sleep disturbances before noticing other symptoms. Numerous sleep disorders, such as excessive and inadequate sleep duration, poor sleep quality, circadian rhythm abnormalities, insomnia, and obstructive sleep apnea were found to increase the risk of cognitive dysfunction and dementia. Additionally, lower sleep quality and shorter sleep duration have been linked to higher cerebral-ß-amyloid levels. Objective evidence for the development of cognitive impairment is provided by the architecture of sleep stages. Patients experiencing sleep problems may benefit from specific types of sleep medicine as a preventative measure against cognitive decline. Conclusion: Sleep disorders can have adverse effects on cognitive health. The duration and quality of sleep are fundamental factors for maintaining a healthy brain as we age. Proper sleep can aid prevent cognitive impairment, particularly Alzheimer's disease and dementia.

Acredita-se que 45% dos indivíduos com comprometimento cognitivo experimentem distúrbios do sono antes do início dos sintomas cognitivos. Avaliar problemas de sono e melhorar a qualidade do sono são passos críticos iniciais para reduzir o risco de comprometimento cognitivo. Objetivo: Revisar a literatura existente com base em critérios de elegibilidade predefinidos para entender a conexão entre distúrbios do sono e a Doença de Alzheimer. Métodos: Uma avaliação completa e sistemática de vários estudos foi realizada para avaliar um ou mais dos seguintes fatores epidemiológicos: (1) distúrbios do sono, (2) comprometimento cognitivo e (3) estimativas de risco de comprometimento cognitivo decorrente do sono. Resultados: Os estudos sugerem que indivíduos que experimentam perda de memória podem enfrentar distúrbios do sono antes de notarem outros sintomas. Foi constatado que vários distúrbios do sono, como duração excessiva e inadequada do sono, má qualidade do sono, anormalidades no ritmo circadiano, insônia e apneia obstrutiva do sono, podem aumentar o risco de disfunção cognitiva e demência. Além disso, menor qualidade do sono e duração mais curta do sono têm sido associadas a níveis mais altos de ß-amiloide cerebral. Evidências objetivas para o desenvolvimento de comprometimento cognitivo são fornecidas pela arquitetura dos estágios do sono. Pacientes que experimentam problemas de sono podem se beneficiar de tipos específicos de medicamentos para o sono como medida preventiva contra o declínio cognitivo. Conclusão: Os distúrbios do sono podem ter efeitos adversos na saúde cognitiva. A duração e a qualidade do sono são fatores fundamentais para manter um cérebro saudável à medida que envelhecemos. Um sono adequado pode ajudar a prevenir o comprometimento cognitivo, especialmente a Doença de Alzheimer e a demência.

Predictors of Clinical Outcomes among People with HIV and Tuberculosis Symptoms after Rapid Treatment Initiation in Haiti.

Introduction: Few studies have evaluated baseline predictors of clinical outcomes among people with HIV starting antiretroviral therapy (ART) in the modern era of rapid ART initiation. Methods: We conducted a secondary analysis of a randomized controlled trial of two rapid treatment initiation strategies for people with treatment-naïve HIV and tuberculosis symptoms at an urban clinic in Haiti. We used logistic regression models to assess associations between baseline characteristics and (1) retention in care at 48 weeks, (2) HIV viral load suppression at 48 weeks (among participants who underwent viral load testing), and (3) all-cause mortality. Results: 500 participants were enrolled in the study 11/2017-1/2020. Eighty-eight (18%) participants were diagnosed with tuberculosis, and ART was started in 494 (99%). After adjustment, less than secondary education (adjusted odds ratio [AOR] 0.21, 95% CI 0.10-0.46), dolutegravir initiation (AOR 2.57, 95% CI 1.22-5.43), age (AOR 1.42 per 10-year increase, 95% CI 1.01-1.99), and tuberculosis diagnosis (AOR 3.92, 95% CI 1.36-11.28) were significantly associated with retention. Age (AOR 1.36, 95% CI 1.05-1.75), dolutegravir initiation (AOR 1.75, 95% CI 1.07-2.85), and tuberculosis diagnosis (AOR 0.50, 95% CI 0.28-0.89) were associated with viral suppression. Higher CD4 cell count at enrollment (unadjusted odds ratio [OR] 0.69, 95% CI 0.55-0.87) and anemia (OR 4.86, 95% CI 1.71-13.81) were associated with mortality. Conclusions: We identified sociodemographic, treatment-related, clinical, and laboratory-based predictors of clinical outcomes. These characteristics may serve as markers of sub-populations that could benefit from additional interventions to support treatment success after rapid treatment initiation.

Evaluation of rapid antiretroviral initiation strategy in a cohort of newly diagnosed people living with HIV in Panama, 2018-2019.

Antiretroviral therapy (ART) has been adopted as a form of HIV treatment and prevention. This study assesses rapid ART initiation using clinical outcomes such as viral load (VL) and CD4+ T lymphocytes count. Over the course of one year, the progress of newly diagnosed people living with HIV who started ART early in a hospital in Panama City was followed. The evaluation of early initiation of ART in achieving viral suppression (VL <200 copies/ml) was analyzed using descriptive statistics. Additionally, the cost difference between early (first 7 days) and late initiation of ART was evaluated from the perspective of the service provider. In total, 209 people were followed up during the study; 85% were male, 70% started ART on same day from hospital arrival, 80% had suppressed viral load at 6 months, and the median count of CD4 increased from 285 (IQR: 166-429) to 509 (IQR: 373-696) over 12 months. Starting ART early led to a 42% increase for the provider in terms of staffing costs; however, the clients had the opportunity to decrease absenteeism in daily activities. The results reveal that early initiation of ART generates clinical and economic benefits for the person in treatment.

Accelerometer approach for anticipatory postural adjustments assessment during step initiation in patients with leprosy.

Anticipatory postural adjustments (APAs) involve a complex coordination of sensorimotor information that can be impaired in diseases that affect nerve conduction. Assessing APAs typically requires costly video recording technology, posing a challenge to the study of postural changes. This hurdle is compounded in impoverished communities affected by diseases such as leprosy, which often receive limited government support. Recent years have seen the validation of inertial sensors in wearable devices and smartphones for APA analysis in diverse populations, including adults, the elderly and people with Parkinson's disease. This progress offers economically efficient alternatives for the study of APA in leprosy. Do patterns of activation of anticipatory postural adjustment differ between leprosy patients and healthy controls? We also investigated the validity and replicability of APAs recorded in leprosy patients using inertial measurements and video capture recordings. Thirty healthy individuals in the control group and 30 individuals with leprosy in the leprosy group performed ten gait initiation trials. To record the APA for gait initiation, the participants stood on a 2 m platform. Each participant was informed that the experimenter would give an signal, after which the participant would initiate a two-step walk on the platform. Inertial recordings (low-cost method) and video capture recordings (gold-standard method) from center of mass displacements were used to extract the APA before gait initiation. The results show that APAs are similar between groups (control and leprosy), but leprosy patients have less consistent APAs. In addition, this study highlights the reproducibility and high correlation between the values of variables obtained from both instruments, the video recording as gold standard method and portable digital inertial sensor as a low-cost alternative method. These promising findings support the use of affordable inertial sensors to track and record APAs in underserved populations that lack easy access to gold standard methods such as video recording. This approach has the potential to improve the therapeutic care and rehabilitation of these patients. Although not currently part of official protocols for leprosy patients, this assessment method could prove particularly valuable in situations where significant sensorimotor impairments are suspected or documented.

Brief Psychoeducational and Cognitive Therapy for Nightmare Disorder (BPCT-ND).

In adults, nightmare disorder is related to sleep deprivation, drug consumption or abuse, or other comorbid sleep disorders such as insomnia or insufficient sleep syndrome. Behavioral treatment has solid scientific evidence in disorders such as insomnia and, more recently, parasomnias. The aim of the present study was to investigate the clinical effectiveness of a Brief Behavioral Telemedicine Therapy in Nightmare Disorder in a 23-year-old female patient. The procedure consisted of the case study, with pre and posttreatment measures as well as follow-up after 1 month; and the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Paris Arousal Disorders Severity Scale, and a sleep diary were applied. In parallel with changes recorded in the sleep diary, a decrease in nightmares, sleepiness, and insomnia symptoms was observed when the intervention was finished. The behavioral intervention was clinically effective; therefore, the present case report provides information on behavioral treatments for nightmare disorder.

The Mytilus chilensis Steamer-like Element-1 Retrotransposon Antisense mRNA Harbors an Internal Ribosome Entry Site That Is Modulated by hnRNPK.

LTR-retrotransposons are transposable elements characterized by the presence of long terminal repeats (LTRs) directly flanking an internal coding region. They share genome organization and replication strategies with retroviruses. Steamer-like Element-1 (MchSLE-1) is an LTR-retrotransposon identified in the genome of the Chilean blue mussel Mytilus chilensis. MchSLE-1 is transcribed; however, whether its RNA is also translated and the mechanism underlying such translation remain to be elucidated. Here, we characterize the MchSLE-1 translation mechanism. We found that the MchSLE-1 5' and 3'LTRs command transcription of sense and antisense RNAs, respectively. Using luciferase reporters commanded by the untranslated regions (UTRs) of MchSLE-1, we found that in vitro 5'UTR sense is unable to initiate translation, whereas the antisense 5'UTR initiates translation even when the eIF4E-eIF4G interaction was disrupted, suggesting the presence of an internal ribosomal entry site (IRES). The antisense 5'UTR IRES activity was tested using bicistronic reporters. The antisense 5'UTR has IRES activity only when the mRNA is transcribed in the nucleus, suggesting that nuclear RNA-binding proteins are required to modulate its activity. Indeed, heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as an IRES trans-acting factor (ITAF) of the MchSLE-1 IRES. To our knowledge, this is the first report describing an IRES in an antisense mRNA derived from a mussel LTR-retrotransposon.

Activity of the Di-Substituted Urea-Derived Compound I-17 in Leishmania In Vitro Infections.

Protein synthesis has been a very rich target for developing drugs to control prokaryotic and eukaryotic pathogens. Despite the development of new drug formulations, treating human cutaneous and visceral Leishmaniasis still needs significant improvements due to the considerable side effects and low adherence associated with the current treatment regimen. In this work, we show that the di-substituted urea-derived compounds I-17 and 3m are effective in inhibiting the promastigote growth of different Leishmania species and reducing the macrophage intracellular load of amastigotes of the Leishmania (L.) amazonensis and L. major species, in addition to exhibiting low macrophage cytotoxicity. We also show a potential immunomodulatory effect of I-17 and 3m in infected macrophages, which exhibited increased expression of inducible Nitric Oxide Synthase (NOS2) and production of Nitric Oxide (NO). Our data indicate that I-17, 3m, and their analogs may be helpful in developing new drugs for treating leishmaniasis.

Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease.

Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2 = 0.32, p = 0.0006) and APA amplitude (R2 = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

Factors associated with delayed initiation of breast cancer treatment at an oncology referral center in Juiz de Fora, Minas Gerais state, from 2010 to 2019: a cohort study / Factores asociados al retraso en el inicio del tratamiento del cáncer de mama en un centro oncológico de referencia en Juiz de Fora, de 2010 a 2019: estudio de cohorte / Fatores associados ao atraso para o início do tratamento para câncer de mama em um centro oncológico de referência em Juiz de Fora, de 2010 a 2019: estudo de coorte

ABSTRACT Objectives To analyze factors associated with delayed initiation of breast cancer treatment at an oncology referral center in Juiz de Fora, Minas Gerais state, between 2010 and 2019. Methods This was a cohort study using data from the Hospital-based Cancer Registry. The probability of not starting treatment within 60 days, in accordance with Brazilian law, was estimated using Kaplan-Meier, method and its association with the factors studied was assessed using the Cox model, presenting hazard ratios (HR) and respective 95% confidence intervals (95%CI). Results Among the 911 participants, the probability of delayed treatment initiation was 18.8% (95%CI 16.4;21.5). Those who underwent treatment at a health service other than the one where the cancer was diagnosed had a significantly higher risk (HR: 3.49; 95%CI 3.00;4.07). Conclusion Receiving a diagnosis and treatment at the same institution may help reduce waiting time to initiate cancer treatment.

RESUMEN Objetivos Determinar los retrasos en el inicio del tratamiento de cáncer de mama en un centro de referencia en oncología de Juiz de Fora, MG, entre 2010 y 2019. Métodos Se trata de una cohorte con datos del Registro Hospitalario de Cáncer. La probabilidad de no iniciar tratamiento dentro de los 60 días, según la legislación brasileña, fue estimada mediante el método de Kaplan-Meier, y su asociación con los factores estudiados mediante el modelo de Cox, con la presentación del Hazard Ratios (HR) y los respectivos intervalos de confianza de 95% (IC95%). Resultados Se evaluaron 911 participantes, la probabilidad de iniciar el tratamiento con retraso fue del 18,8% (IC95% 16,4;21,5). Quienes se sometieron a tratamiento en un servicio de salud distinto al que estableció el diagnóstico de cáncer tuvieron un riesgo significativamente mayor (HR: 3,49; IC95% 3,00;4,07). Conclusión La realización del diagnóstico y tratamiento en una misma institución puede contribuir a reducir el tiempo de espera para el inicio del tratamiento.

RESUMO Objetivos Analisar fatores associados ao atraso para o início do tratamento do câncer de mama em um centro de referência em oncologia em Juiz de Fora, MG, entre 2010 e 2019. Métodos Trata-se de coorte com dados do Registro Hospitalar de Câncer. A probabilidade de não iniciar o tratamento em até 60 dias, conforme legislação brasileira, foi estimada pelo método de Kaplan-Meier, e sua associação com os fatores estudados pelo modelo de Cox, com apresentação das hazard ratios (HR) e respectivos intervalos de confiança de 95% (IC95%). Resultados Entre as 911 participantes, a probabilidade de iniciar o tratamento com atraso foi de 18,8% (IC95% 16,4;21,5). Aquelas que realizaram o tratamento em um serviço de saúde diferente do que estabeleceu o diagnóstico de câncer apresentaram risco significativamente maior (HR: 3,49; IC95% 3,00;4,07). Conclusão Realizar diagnóstico e tratamento na mesma instituição pode contribuir para a redução do tempo de espera para o início do tratamento.

Influence of the mRNA initial region on protein production: a case study using recombinant detoxified pneumolysin as a model

Recombinant proteins are of great importance in modern society, mostly as biopharmaceutical products. However, challenging and complex processes with low production yield are major drawbacks. Normally, the optimization to overcome these obstacles is focused on bioreactor and purification processes, and the biomolecular aspects are neglected, seen as less important. In this work, we present how the 5′ mRNA secondary structure region can be relevant for translation and, therefore, protein production. For this, Escherichia coli BL21(DE3) clones, producing recombinant detoxified pneumolysin (PdT) with and without the N-terminal His-tag, were cultivated in 10-L bioreactors. Another version of the pdt gene (version 2) with synonymous changes in the 5′-end nucleotide sequence was also obtained. Protein production, plasmid stability, carbon sources, and acetic acid were quantified during the cultures. Furthermore, in silico mRNA analyses were performed using TIsigner and RNAfold. The results showed that the His-tag presence at the N-terminus generated a minimum 1.5-fold increase in target protein synthesis, which was explained by the in silico mRNA analyses that returned an mRNA secondary structure easier to translate and, therefore, higher protein production than without the His-tag. The pdt gene version 2 showed lower 5′ mRNA opening energy than version 1, allowing higher PdT production even without a tag. This work reveals that simple mRNA analyses during heterologous gene design and production steps can help reach high-recombinant protein titers in a shorter time than using only traditional bioprocess optimization strategies.

Maternal and perinatal outcomes of women with vaginal birth after cesarean section compared to repeat cesarean birth in select South Asian and Latin American settings of the global network for women's and children's health research.

OBJECTIVE: Our objective was to analyze a prospective population-based registry including five sites in four low- and middle-income countries to observe characteristics associated with vaginal birth after cesarean versus repeat cesarean birth, as well as maternal and newborn outcomes associated with the mode of birth among women with a history of prior cesarean. HYPOTHESIS: Maternal and perinatal outcomes among vaginal birth after cesarean section will be similar to those among recurrent cesarean birth. METHODS: A prospective population-based study, including home and facility births among women enrolled from 2017 to 2020, was performed in communities in Guatemala, India (Belagavi and Nagpur), Pakistan, and Bangladesh. Women were enrolled during pregnancy, and delivery outcome data were collected within 42 days after birth. RESULTS: We analyzed 8267 women with a history of prior cesarean birth; 1389 (16.8%) experienced vaginal birth after cesarean, and 6878 (83.2%) delivered by a repeat cesarean birth. Having a repeat cesarean birth was negatively associated with a need for curettage (ARR 0.12 [0.06, 0.25]) but was positively associated with having a blood transfusion (ARR 3.74 [2.48, 5.63]). Having a repeat cesarean birth was negatively associated with stillbirth (ARR 0.24 [0.15, 0.49]) and, breast-feeding within an hour of birth (ARR 0.39 [0.30, 0.50]), but positively associated with use of antibiotics (ARR 1.51 [1.20, 1.91]). CONCLUSIONS: In select South Asian and Latin American low- and middle-income sites, women with a history of prior cesarean birth were 5 times more likely to deliver by cesarean birth in the hospital setting. Those who delivered vaginally had less complicated pregnancy and labor courses compared to those who delivered by repeat cesarean birth, but they had an increased risk of stillbirth. More large scale studies are needed in Low Income Country settings to give stronger recommendations. TRIAL REGISTRATION: NCT01073475, Registered February 21, 2010, https://clinicaltrials.gov/ct2/show/record/NCT01073475 .

[Factors associated with benzodiazepines dependence in insomnia patients]. / Factores asociados a la dependencia a benzodiacepinas en pacientes con insomnio.

Background: The use of benzodiazepines as a treatment for insomnia can have side effects such as impaired coordination causing falls in adults and even dependence. Objective: To assess the factors associated with dependence on benzodiazepines in patients with insomnia. Methods: Observational, cross-sectional, prospective, and analytical study, at the first level of care. Patients older than 18 years with a diagnosis of insomnia and a benzodiazepine prescription were selected. The dependency was measured with the International Neuropsychiatric Interview. Results: 107 patients were included. Median age 67 years, predominantly female (72%), 74% attended secondary school or more, 71% had more than 3 years of diagnosis, 84% used clonazepam. The 54% presented dependency. In the bivariate analysis, schooling RM 0.392 (95%CI: 0.15-0.96) p = 0.038, moderate and severe clinical insomnia RM 3.618 (95%CI: 1.44-9.08) p = 0.005 and more than 3 years of diagnosis RM 2.428 (95%CI: 1.03-5.71) p = 0.040. In the multivariate model, schooling (p = 0.084), years of diagnosis (p = 0.062) and frequency of consumption (p = 0.065) obtained an R2 of 0.13. Conclusions: Primary schooling showed a lower risk of presenting dependence on benzodiazepines. The risk was increased in those with more than 3 years of diagnosis, and in those with moderate and severe insomnia.

Introducción: el uso de benzodiacepinas como tratamiento para el insomnio puede tener efectos secundarios, como el deterioro de la coordinación que puede provocar caídas en adultos e, incluso, dependencia. Objetivo: evaluar los factores asociados a la dependencia a benzodiacepinas en pacientes con insomnio. Material y métodos: estudio observacional, transversal, prospectivo y analítico, llevado a cabo en el primer nivel de atención. Se seleccionaron pacientes mayores de 18 años con diagnóstico de insomnio y prescripción de benzodiacepina. La dependencia se midió con la Entrevista Neuropsiquiátrica Internacional. Resultados: se incluyeron 107 pacientes, la mediana de edad fue de 67 años, con predominio del sexo femenino (72%), el 74% cursó educación secundaria o más, el 71% tenía más de tres años con diagnóstico de insomnio, el 84% usaba clonazepan. El 54% presentó dependencia. En el análisis bivariado, la escolaridad primaria mostró una razón de momios (RM) de 0.392 (IC95%: 0.15-0.96), p = 0.038; el insomnio clínico moderado y grave RM de 3.618 (IC95%: 1.44-9.08) p = 0.005, y más de tres años de diagnóstico con una RM de 2.428 (IC95%: 1.03-5.71) p = 0.040. En el modelo multivariado, la escolaridad (p = 0.084), los años de diagnóstico (p = 0.062) y la frecuencia de consumo (p = 0.065) obtuvieron una R2 de 0.13. Conclusiones: los pacientes con escolaridad primaria mostraron un menor riesgo de presentar dependencia a benzodiacepinas. El riesgo se incrementó en los pacientes con más de tres años de diagnóstico y en aquellos con insomnio moderado y grave.

Structural validity of nursing diagnosis insomnia in older adults of a community center.

PURPOSE: Insomnia is an important sleep disorder in older persons. Conceptual analysis studies on this nursing diagnosis have been developed, but the diagnostic accuracy has not been verified. This study aimed to verify the diagnostic accuracy of the nursing diagnosis of Insomnia (00095) in older adults in a community center in Brazil. METHODS: A validation study for diagnostic accuracy of the defining characteristics of the nursing diagnosis Insomnia. Data were collected through telephone interviews with 90 participants. Latent class analysis was used to verify the sensitivity and specificity of the defining characteristics. Poisson regression was used to assess the prevalence of the association of factors related to the nursing diagnosis of insomnia. FINDINGS: A 47.42% prevalence of insomnia in the sample was identified. Defining characteristics such as expresses dissatisfaction with sleep and nonrestorative sleep-wake cycle showed the best accuracy values for insomnia, with a specificity of 0.92 (0.78-1.00) and 0.89 (0.74-1.00), respectively. Related factors such as stressors and frequent naps during the day were more likely to develop insomnia in individuals. CONCLUSIONS: This study indicates diagnostic accuracy of nursing diagnosis of insomnia in community-dwelling older people from a community center. The findings highlighted the importance of the defining characteristics of nursing diagnosis insomnia and its main related factors contributing to accurate diagnostic identification. IMPLICATIONS FOR NURSING PRACTICE: This study can contribute to providing objective clinical indicators of insomnia in the older population to guide nurses in early diagnostic confirmation for the selection of health interventions. In addition, it can be a consistent contribution to theoretical and conceptual reviews of this diagnosis.

OBJETIVO: A insônia é um importante distúrbio do sono em pessoas idosas. Foram desenvolvidos estudos de análise conceitual sobre esse diagnóstico de enfermagem, mas a precisão diagnóstica não foi verificada. Este estudo teve como objetivo verificar a acurácia diagnóstica do diagnóstico de enfermagem Insônia (00095) em idosos frequentadores de um centro de convivência no Brasil. MÉTODOS: Um estudo de validação de acurácia diagnóstica das características definidoras do diagnóstico de enfermagem Insônia. Os dados foram coletados por meio de entrevistas telefônicas com 90 participantes. Foi utilizada a Análise de Classe Latente para verificar a sensibilidade e especificidade das características definidoras. A regressão de Poisson foi usada para avaliar a prevalência da associação dos fatores relacionados ao diagnóstico de enfermagem insônia. RESULTADOS: Foi identificada uma prevalência de 47,42% de insônia na amostra. Características definidoras, como expressa insatisfação com o sono e ciclo sono-vigília não restaurador, apresentaram os melhores valores de precisão para a insônia, com especificidade de 0,92 (0,78-1,00) e 0,89 (0,74-1,00), respectivamente. Fatores relacionados, como estressores e cochilos frequentes durante o dia, aumentaram a probabilidade de desenvolver insônia em idosos do centro de convivência. CONCLUSÕES: Este estudo indica a precisão diagnóstica do diagnóstico de enfermagem de insônia em idosos que vivem em comunidade, frequentadores de um centro comunitário. Os resultados destacaram a importância das características definidoras do diagnóstico de enfermagem de insônia e seus principais fatores relacionados que contribuem para a identificação precisa do diagnóstico. IMPLICAÇÕES PARA A PRÁTICA DE ENFERMAGEM: Este estudo pode contribuir fornecendo indicadores clínicos objetivos da insônia na população idosa para orientar os enfermeiros na confirmação precoce do diagnóstico para a seleção de intervenções de saúde. Além disso, pode ser uma contribuição consistente para revisões teóricas e conceituais desse diagnóstico. DESCRITORES: Distúrbios do Início e da Manutenção do Sono; Idoso; Estudo de Validação; Diagnóstico de Enfermagem; Transtornos Cronobiológicos.

Back To Basics: Theory of Thrombus Formation and Potential Implications for Therapies?

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially fatal condition. Despite existing treatments, recurrence rates and complications remain high. Understanding the pathophysiology of thrombus formation is crucial for developing effective therapies. This narrative review provides an overview of the critical elements of acute and chronic DVT, presents a theoretical framework for understanding thrombus formation, and discusses potential implications for therapeutic interventions. In addition, a hypothesis of thrombus formation is formulated, encompassing all elements described in this work.

eIF4E as a molecular wildcard in metazoans RNA metabolism.

The evolutionary origin of eukaryotes spurred the transition from prokaryotic-like translation to a more sophisticated, eukaryotic translation. During this process, successive gene duplication of a single, primordial eIF4E gene encoding the mRNA cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) gave rise to a plethora of paralog genes across eukaryotes that underwent further functional diversification in RNA metabolism. The ability to take different roles is due to eIF4E promiscuity in binding many partner proteins, rendering eIF4E a highly versatile and multifunctional player that functions as a molecular wildcard. Thus, in metazoans, eIF4E paralogs are involved in various processes, including messenger RNA (mRNA) processing, export, translation, storage, and decay. Moreover, some paralogs display differential expression in tissues and developmental stages and show variable biochemical properties. In this review, we discuss recent advances shedding light on the functional diversification of eIF4E in metazoans. We emphasise humans and two phylogenetically distant species which have become paradigms for studies on development, namely the fruit fly Drosophila melanogaster and the roundworm Caenorhabditis elegans.

Comparison of inertial records during anticipatory postural adjustments obtained with devices of different masses.

Background: Step initiation involves anticipatory postural adjustments (APAs) that can be measured using inertial measurement units (IMUs) such as accelerometers. However, previous research has shown heterogeneity in terms of the population studied, sensors used, and methods employed. Validity against gold standard measurements was only found in some studies, and the weight of the sensors varied from 10 to 110 g. The weight of the device is a crucial factor to consider when assessing APAs, as APAs exhibit significantly lower magnitudes and are characterized by discrete oscillations in acceleration paths. Objective: This study aims to validate the performance of a commercially available ultra-light sensor weighing only 5.6 g compared to a 168-g smartphone for measuring APAs during step initiation, using a video capture kinematics system as the gold standard. The hypothesis is that APA oscillation measurements obtained with the ultra-light sensor will exhibit greater similarity to those acquired using video capture than those obtained using a smartphone. Materials and Methods: Twenty subjects were evaluated using a commercial lightweight MetaMotionC accelerometer, a smartphone and a system of cameras-kinematics with a reflective marker on lumbar vertebrae. The subjects initiated 10 trials of gait after a randomized command from the experimenter and APA variables were extracted: APAonset, APAamp, PEAKtime. A repeated measures ANOVA with post-hoc test analyzed the effect of device on APA measurements. Bland-Altman plots were used to evaluate agreement between MetaMotionC, smartphone, and kinematics measurements. Pearson's correlation coefficients were used to assess device correlation. Percentage error was calculated for each inertial sensor against kinematics. A paired Student's t-test compared th devices percentage error. Results: The study found no significant difference in temporal variables APAonset and PEAKtime between MetaMotionC, smartphone, and kinematic instruments, but a significant difference for variable APAamp, with MetaMotionC yielding smaller measurements. The MetaMotionC had a near-perfect correlation with kinematic data in APAonset and APAamp, while the smartphone had a very large correlation in APAamp and a near-perfect correlation in APAonset and PEAKtime. Bland-Altman plots showed non-significant bias between smartphone and kinematics for all variables, while there was a significant bias between MetaMotionC and kinematics for APAamp. The percentage of relative error was not significantly different between the smartphone and MetaMotionC. Conclusions: The temporal analysis can be assessed using ultralight sensors and smartphones, as MetaMotionC and smartphone-based measurements have been found to be valid compared to kinematics. However, caution should be exercised when using ultralight sensors for amplitude measurements, as additional research is necessary to determine their effectiveness in this regard.

Hsa_circ_0102899 promotes epithelial-mesenchymal transition in non-small cell lung cancer.

OBJECTIVE: The significance of circular RNAs (circRNAs) has been identified in the progression of non-small cell lung cancer (NSCLC). Consistently, our study probed the functional actions of hsa_circ_0102899 (circ_0102899) in NSCLC cells. METHODS: circ_0102899 expression was checked in NSCLC tissues, as well as its correlation with clinical characteristics of patients, Using A459 cells, transfection to alter gene expression was performed, thus measuring the changes of proliferation, apoptosis, migration, and apoptosis, as well as epithelial-mesenchymal transition (EMT)-related proteins. circ_0102899's effects in vivo were validated by tumor xenograft assay. Finally, the regulatory mechanism of circ_0102899 was investigated. RESULTS: circ_0102899 indicated a high-expression level in NSCLC tissues which was associated with NSCLC tumor characteristics. Functionally, circ_0102899 knockdown not only inhibited the growth and EMT process of NSCLC cells, but also inhibited tumor formation in vivo. In terms of the regulatory mechanism, circ_0102899 had a binding to miR-885-5p to target eukaryotic translation initiation factor 4γ2 (EIF4G2). circ_0102899 mediated miR-885-5/EIF4G2 axis to accelerate the process of cell malignant behavior in NSCLC. CONCLUSION: circ_0102899 promotes EMT and metastasis in NSCLC by regulating the miR-885-5p/EIF4G2 axis.

Deciphering the hormone regulatory mechanisms of storage root initiation in sweet potato: challenges and future prospects.

Sweet potato (Ipomoea batatas) is an economically important food crop that is grown primarily for its edible storage roots. Several researchers have consequently been conducting studies to increase sweet potato yield, and an important aspect of this research involves understanding how storage root initiation occurs. Although significant progress has been made, several challenges associated with studying this crop have resulted in lagging progress compared to other crops and thus sweet potato storage root initiation is not clearly understood. This article highlights the most important aspects of the hormone signalling processes during storage root initiation that needs to be investigated further and suggests candidate genes that should be prioritized for further study, based on their importance in storage organ formation in other crops. Lastly, ways of overcoming the challenges associated with studying this crop are suggested.