Escala de alerta precoce na identificação de pacientes com risco de deterioração clínica / Early warning scale for identifying patients at risk of clinical deterioration / Escala de alerta temprana en la identificación de pacientes con riesgo de deterioro clínico

Objetivo: avaliar pontuação da National Early Warning Score (NEWS) em relação ao tipo de desfecho e perfil dos pacientes da enfermaria clínica médica de um hospital em Teresina, Piauí, Brasil. Método: estudo quantitativo realizado num hospital público, em Teresina, com 150 prontuários de pacientes internados no setor clínica médica de fevereiro de 2022 a dezembro de 2022, a partir de registros demográficos, clínicos e valores da escala na admissão e desfecho. Resultados: houve associação dos valores da escala com a faixa etária (p=0,029), tempo de internação (p=0,023) e tipo de desfecho (p < 0,001). Alto risco clínico prevaleceu entre pacientes do sexo masculino (13%), na faixa etária de 60 a 94 anos (13%), com permanência de 21 a 57 dias (19,2%) e óbito como desfecho (100%). Conclusão: implementação da referida escala evidenciou ser fundamental para prever agravos clínicos e melhorar qualidade da assistência.

Objective: to evaluate the National Early Warning Score (NEWS) in relation to the type of outcome and profile of patients in the medical clinical ward of a hospital in Teresina, Piauí, Brazil. Method: a quantitative study conducted in a public hospital in Teresina, with 150 medical records of patients admitted to the medical clinic sector from February 2022 to December 2022, based on demographic and clinical records and scale values at admission and outcome. Results: there was an association between the scale values and the age group (p=0.029), length of stay (p=0.023) and type of outcome (p < 0.001). High clinical risk prevailed among male patients (13%), aged between 60 and 94 years (13%), with a stay of 21 to 57 days (19.2%), and death as an outcome (100%). Conclusion: implementation of the aforementioned scale proved to be fundamental for predicting clinical problems and improving care quality.

Objetivo: evaluar el puntaje de la National Early Warning Score (NEWS) con respecto al tipo de desenlace y el perfil de los pacientes de la enfermería clínica médica de un hospital en Teresina, Piauí, Brasil. Método: estudio cuantitativo realizado en un hospital público en Teresina, con 150 historiales médicos de pacientes internados en el sector de clínica médica desde febrero de 2022 hasta diciembre de 2022, a partir de registros demográficos, clínicos y valores de la escala en la admisión y desenlace. Resultados: hubo asociación de los valores de la escala con la edad (p=0,029), tiempo de internación (p=0,023) y tipo de desenlace (p < 0,001). El alto riesgo clínico prevaleció entre los pacientes del sexo masculino (13%), en la franja de edad entre 60 y 94 años (13%), con una estancia de 21 a 57 días (19,2%) y fallecimiento como desenlace (100%). Conclusión: la implementación de dicha escala demostró ser fundamental para prever agravios clínicos y mejorar la calidad de la asistencia.

Occupational risks associated with chronic kidney disease of non-traditional origin (CKDnt) in Brazil: it is time to dig deeper into a neglected problem / Riscos ocupacionais associados à doença renal crônica de origem não tradicional (DRCnt) no Brasil: é hora de nos aprofundarmos em um problema negligenciado

Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.

Resumo Nas últimas décadas, uma epidemia de doença renal crônica (DRC) tem sido associada a fatores ambientais e ocupacionais (estresse térmico decorrente de cargas de trabalho elevadas em altas temperaturas e exposição a produtos químicos, como agrotóxicos e metais), denominada DRC de origem não tradicional (DRCnt). Esta revisão descritiva tem como objetivo apresentar evidências recentes sobre estresse térmico, agrotóxicos e metais como possíveis causas de DRCnt e fornecer uma visão geral das estratégias brasileiras de regulamentação, fiscalização e vigilância sanitária relacionadas. Os trabalhadores brasileiros são comumente expostos a condições extremas de calor e outros fatores de risco de DRCnt, incluindo o aumento da exposição a agrotóxicos e metais. Além disso, há uma falta de regulamentação e fiscalização, políticas públicas e estratégias adequadas para proteger a saúde renal dos trabalhadores em relação aos principais fatores de risco. É provável que a DRCnt seja uma causa significativa de DRC no Brasil, uma vez que a etiologia da doença é desconhecida em muitos pacientes e diversas condições para seu desenvolvimento estão presentes no país. Estudos epidemiológicos devem ser realizados para explorar associações causais e estimar o impacto do calor, dos agrotóxicos e dos metais na DRCnt no Brasil. Além disso, as políticas públicas devem priorizar a redução da exposição dos trabalhadores e a promoção de sua saúde e segurança.

Lobaplatin-based concurrent chemoradiotherapy in elderly nasopharyngeal carcinoma.

BACKGROUND: The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC. METHODS: We included stage II-IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan-Meier's analysis was performed to calculate survival rates. RESULTS: A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3-4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively. CONCLUSIONS: Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.

Nutritional and metabolic modulation of inflammation in critically ill patients: a narrative review of rationale, evidence and grey areas.

BACKGROUND: Inflammation is the hallmark of critical illness and triggers the neuro-endocrine stress response and an oxidative stress. Acute inflammation is initially essential for patient's survival. However, ongoing or exaggerated inflammation, due to persistent organ dysfunction, immune dysfunction or poor inflammation resolution, is associated to subsequent hypermetabolism and hypercatabolism that severely impact short and long-term functional status, autonomy, as well as health-related costs. Modulation of inflammation is thus tempting, with the goal to improve the short- and long-term outcomes of critically ill patients. FINDINGS: Inflammation can be modulated by nutritional strategies (including the timing of enteral nutrition initiation, the provision of some specific macronutrients or micronutrients, the use of probiotics) and metabolic treatments. The most interesting strategies seem to be n-3 polyunsaturated fatty acids, vitamin D, antioxidant micronutrients and propranolol, given their safety, their accessibility for clinical use, and their benefits in clinical studies in the specific context of critical care. However, the optimal doses, timing and route of administration are still unknown for most of them. Furthermore, their use in the recovery phase is not well studied and defined. CONCLUSION: The rationale to use strategies of inflammation modulation is obvious, based on critical illness pathophysiology and based on the increasingly described effects of some nutritional and pharmacological strategies. Regretfully, there isn't always substantial proof from clinical research regarding the positive impacts directly brought about by inflammation modulation. Some arguments come from studies performed in severe burn patients, but such results should be transposed to non-burn patients with caution. Further studies are needed to explore how the modulation of inflammation can improve the long-term outcomes after a critical illness.

Targeted therapies in children with renal cell carcinoma (RCC): An International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG)-related retrospective descriptive study.

INTRODUCTION: Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC. METHODS: This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti-programmed cell death 1 (PD-(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced-stage and relapsed pediatric RCC. RESULTS: Of the 31 identified patients (0-18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT-RCC) (21/31) and the remaining patients mainly presented with papillary or clear-cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono- or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis. CONCLUSION: This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies.

Understanding the secondary outcomes of international travel measures during the covid-19 pandemic: a scoping review of social impact evidence.

BACKGROUND: Assessment of the effective use of international travel measures during the COVID-19 pandemic has focused on public health goals, namely limiting virus introduction and onward transmission. However, risk-based approaches includes the weighing of public health goals against potential social, economic and other secondary impacts. Advancing risk-based approaches thus requires fuller understanding of available evidence on such impacts. METHODS: We conducted a scoping review of existing studies of the social impacts of international travel measures during the COVID-19 pandemic. Applying a standardized typology of travel measures, and five categories of social impact, we searched 9 databases across multiple disciplines spanning public health and the social sciences. We identified 26 studies for inclusion and reviewed their scope, methods, type of travel measure, and social impacts analysed. RESULTS: The studies cover a diverse range of national settings with a strong focus on high-income countries. A broad range of populations are studied, hindered in their outbound or inbound travel. Most studies focus on 2020 when travel restrictions were widely introduced, but limited attention is given to the broader effects of their prolonged use. Studies primarily used qualitative or mixed methods, with adaptations to comply with public health measures. Most studies focused on travel restrictions, as one type of travel measure, often combined with domestic public health measures, making it difficult to determine their specific social impacts. All five categories of social impacts were observed although there was a strong emphasis on negative social impacts including family separation, decreased work opportunities, reduced quality of life, and inability to meet cultural needs. A small number of countries identified positive social impacts such as restored work-life balance and an increase in perceptions of safety and security. CONCLUSIONS: While international travel measures were among the most controversial interventions applied during the COVID-19 pandemic, given their prolonged use and widespread impacts on individuals and populations, there remains limited study of their secondary impacts. If risk-based approaches are to be advanced, involving informed choices between public health and other policy goals, there is a need to better understand such impacts, including their differential impacts across diverse populations and settings.

Displacement and functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice.

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in situ targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS while fUS imaging revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We report a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with a brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV responses with peak CBV, activated area, and correlation coefficient increasing with the ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalized and linearly correlated with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths while the evoked hemodynamic responses colocalize and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as shedding light on one of the mechanisms behind FUS modulation, i.e., how FUS mechanically displaces brain tissue affecting cerebral hemodynamics and thereby its associated connectivity.

Immune Response and Risk of Decompensation following SARS-CoV-2 Infection in Outpatients with Advanced Chronic Liver Disease.

Advanced chronic liver disease (ACLD) is associated with a wide spectrum of immune dysfunction. The clinical impact of SARS-CoV-2 on the development of decompensation and immune response in unvaccinated outpatients has not as yet been clearly defined. This study aimed to evaluate the clinical and immunological impact of SARS-CoV-2 on outpatients with ACLD. This is an observational case-control study, in which ACLD outpatients were included prospectively and consecutively and classified into two groups: SARS-CoV-2 infected and non-infected. Patients' baseline characteristics and infection data were collected and analyzed. Immunoglobulin G (IgG) levels against Spike 1 were evaluated. The primary endpoint was risk of liver decompensation during follow-up, assessed after propensity score matching and adjusted by Cox regression. Between October 2020 and July 2021, ACLD outpatients (n = 580) were identified, and 174 patients with clinical follow-up were included. SARS-CoV-2 infection incidence was 7.6% (n = 44). Risk of liver decompensation was significantly higher after infection (HR = 2.43 [1.01-5.86], p = 0.048) vs. non-infection. The time of IgG evaluation was similar in all patients (n = 74); IgG concentrations were significantly higher in compensated vs. decompensated patients (1.02 ± 0.35 pg/mL vs. 0.34 ± 0.16 pg/mL, p < 0.0001) and correlated with hemoglobin levels. The dysregulation of the innate immune response in patients with decompensated liver disease increased the risk of further decompensation following SARS-CoV-2, mainly due to a worsening of ascites.

The Association of Genetic Markers Involved in Muscle Performance Responding to Lactate Levels during Physical Exercise Therapy by Nordic Walking in Patients with Long COVID Syndrome: A Nonrandomized Controlled Pilot Study.

Several genetic markers have shown associations with muscle performance and physical abilities, but the response to exercise therapy is still unknown. The aim of this study was to test the response of patients with long COVID through an aerobic physical therapy strategy by the Nordic walking program and how several genetic polymorphisms involved in muscle performance influence physical capabilities. Using a nonrandomized controlled pilot study, 29 patients who previously suffered from COVID-19 (long COVID = 13, COVID-19 = 16) performed a Nordic walking exercise therapy program for 12 sessions. The influence of the ACE (rs4646994), ACTN3 (rs1815739), AMPD1 (rs17602729), CKM (rs8111989), and MLCK (rs2849757 and rs2700352) polymorphisms, genotyped by using single nucleotide primer extension (SNPE) in lactic acid concentration was established with a three-way ANOVA (group × genotype × sessions). For ACE polymorphism, the main effect was lactic acid (p = 0.019). In ACTN3 polymorphism, there were no main effects of lactic acid, group, or genotype. However, the posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CT and TT genotypes (all p < 0.05). For AMPD1 polymorphism, there were main effects of lactic acid, group, or genotype and lactic acid × genotype or lactic acid × group × genotype interactions (all p < 0.05). The posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CC and CT genotypes (all p < 0.05). Physical therapy strategy through Nordic walking enhanced physical capabilities during aerobic exercise in post-COVID19 patients with different genotypes in ACTN3 c.1729C>T and AMPD1 c.34C>T polymorphisms. These findings suggest that individuals who reported long COVID who presumably exercised less beforehand appeared to be less able to exercise, based on lactate levels, and the effect of aerobic physical exercise enhanced physical capabilities conditioned by several genetic markers in long COVID patients.

Genome-Wide Identification, Expression, and Interaction Analysis of the Auxin Response Factor and AUX/IAA Gene Families in Vaccinium bracteatum.

BACKGROUND: Auxin, a plant hormone, plays diverse roles in the modulation of plant growth and development. The transport and signal transduction of auxin are regulated by various factors involved in shaping plant morphology and responding to external environmental conditions. The auxin signal transduction is primarily governed by the following two gene families: the auxin response factor (ARF) and auxin/indole-3-acetic acid (AUX/IAA). However, a comprehensive genomic analysis involving the expression profiles, structures, and functional features of the ARF and AUX/IAA gene families in Vaccinium bracteatum has not been carried out to date. RESULTS: Through the acquisition of genomic and expression data, coupled with an analysis using online tools, two gene family members were identified. This groundwork provides a distinguishing characterization of the chosen gene families in terms of expression, interaction, and response in the growth and development of plant fruits. In our genome-wide search of the VaARF and VaIAA genes in Vaccinium bracteatum, we identified 26 VaARF and 17 VaIAA genes. We analyzed the sequence and structural characteristics of these VaARF and VaIAA genes. We found that 26 VaARF and 17 VaIAA genes were divided into six subfamilies. Based on protein interaction predictions, VaIAA1 and VaIAA20 were designated core members of VaIAA gene families. Moreover, an analysis of expression patterns showed that 14 ARF genes and 12 IAA genes exhibited significantly varied expressions during fruit development. CONCLUSION: Two key genes, namely, VaIAA1 and VaIAA20, belonging to a gene family, play a potentially crucial role in fruit development through 26 VaARF-IAAs. This study provides a valuable reference for investigating the molecular mechanism of fruit development and lays the foundation for further research on Vaccinium bracteatum.

How does orthodontic tooth movement influence the dental pulp? RNA-sequencing on human premolars.

OBJECTIVES: The objective of this study is to analyse the gene expression profile of the dental pulp (DP) of human premolars subjected to 7 and 28 days of orthodontic force (OF) in vivo by using RNA sequencing. The maxillary and mandibular DP were additionally compared. METHODS: Healthy patients requiring orthodontic premolar extractions were randomly assigned to one of the three groups: control (CG) where no OF was applied, 7 and 28 days, where premolars were extracted either 7 or 28 days after the application of a 50-100 g OF. Total RNA was extracted from the DP and analysed via RNA-seq. Differentially expressed genes (DEGs) were identified using a false discovery rate and fold change threshold of <0.05 and ≥1.5, respectively. Functional analysis was performed. RESULTS: After 7 days of OF, pulp reaction indicates immune response, hypoxia, DNA damage and epigenetic regulation. After 28 days, cell adhesion, migration, organization and tissue repair are evident. The maxillary and mandibular pulp tissues react differently to OF. The maxilla exhibits minimal alterations, mostly related to immune response at 7 days and tissue repair at 28 days, whereas the mandible shows mostly DNA damage and epigenetic regulation at 7 days and return to the original state at 28 days. CONCLUSIONS: This study demonstrates that the early reaction of the DP to OF is marked by immune response, hypoxia and DNA damage. In contrast, after 28 days, cell adhesion, migration, organization, tissue repair and dentine formation are observed. Maxillary and mandibular premolars react differently to OF: although the maxilla exhibits minimal alterations at both time points, the mandible mostly shows DNA damage, epigenetic regulation, and immune response at 7 days. These disparities could stem from different blood supplies or the lower maxillary bone density, potentially triggering faster biological changes. Our findings provide insights into the gene regulatory networks modulating DP response to OF.

Vaccinia virus F1L blocks the ribotoxic stress response to subvert ZAKα-dependent NLRP1 inflammasome activation.

Inflammasomes are essential for host defense, recognizing foreign or stress signals to trigger immune responses, including maturation of IL-1 family cytokines and pyroptosis. Here, NLRP1 is emerging as an important sensor of viral infection in barrier tissues. NLRP1 is activated by various stimuli, including viral double-stranded (ds) RNA, ribotoxic stress, and inhibition of dipeptidyl peptidases 8 and 9 (DPP8/9). However, certain viruses, most notably the vaccinia virus, have evolved strategies to subvert inflammasome activation or effector functions. Using the modified vaccinia virus Ankara (MVA) as a model, we investigated how the vaccinia virus inhibits inflammasome activation. We confirmed that the early gene F1L plays a critical role in inhibiting NLRP1 inflammasome activation. Interestingly, it blocks dsRNA and ribotoxic stress-dependent NLRP1 activation without affecting its DPP9-inhibition-mediated activation. Complementation and loss-of-function experiments demonstrated the sufficiency and necessity of F1L in blocking NLRP1 activation. Furthermore, we found that F1L-deficient, but not wild-type MVA, induced ZAKα activation. Indeed, an F1L-deficient virus was found to disrupt protein translation more prominently than an unmodified virus, suggesting that F1L acts in part upstream of ZAKα. These findings underscore the inhibitory role of F1L on NLRP1 inflammasome activation and provide insight into viral evasion of host defenses and the intricate mechanisms of inflammasome activation.

Strategies of invasive snail Pomacea canaliculata during hibernation in rice fields of south China: effects of body size, sex, and soil depth.

BACKGROUND: The invasive freshwater snail Pomacea canaliculata is an agricultural pest with a certain level of tolerance to abiotic stress. After the harvest of late rice, the snails usually burrow themselves into the soil surface layers to overwinter and pose a renewed threat to rice production in the following year. Revealing the response of snails to environmental stresses is crucial for developing countermeasures to control their damage and spread. RESULTS: In this study, we conducted a 120-day in situ experiment during the winter to investigate the survival and physiological changes of hibernating snails in 0-5 and 5-10 cm soil depths, aiming to explore their overwintering strategies. Our results showed that 73.61%, 87.50%, and 90.28% of male, female, and juvenile snails survived after hibernation for 120 days in 0-10 cm soil depth, respectively. The differences in survival rates based on sex and size of snails potentially reflect the countermeasures of snails to rapidly reproduce after hibernation. Simultaneously, the hibernating snails exhibited the ability to maintain a certain level of body weight. During this period, the snails increased their antioxidant enzyme activities to cope with oxidative stress, and enhanced their lipid storage. The hibernation survival of snails was not significantly affected by different soil depths, indicating that they have the potential to hibernate into deeper soils. Furthermore, snails were capable of increasing their contents of bound water and glycerol to cope with sudden cold spells during hibernation. CONCLUSION: Our findings emphasize the adaptive changes of P. canaliculata snails overwintering in paddy soils. In future studies, the vulnerabilities of P. canaliculata during hibernation (e.g. shell characteristics, nutrient reserves, and dehydration tolerance, etc.,) should be investigated to develop effective control methods for this period. © 2024 Society of Chemical Industry.

Screening significance of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) in coronary heart disease of symptomatic youth.

BACKGROUND: The incidence of coronary heart disease (CHD) in youth is rapidly increasing but difficultly recognized in the early stage. METHODS AND RESULTS: In this retrospective study, 194 CHD patients under the age of 45 who previously experienced chest pain symptoms and 170 non-CHD patients were included and demographic data were collected. Systemic inflammation index (SII) and systemic inflammation response index (SIRI) were increased in young CHD patients (p < 001). Spearman's correlation analysis showed that both SII and SIRI were negatively correlated with HDL and positively correlated with hypertension, Gensini score, and hsTnI. Logistic regression analysis indicated that SII and SIRI were independently associated with the presence of CHD in youth with chest pain symptoms. The area under the ROC curve (AUC) of the SII model for young CHD patients was 0.805 (0.728-0.869), and the sensitivity and specificity were 0.65 and 0.823, respectively. Meanwhile, the AUC for the SIRI model was 0.812 (0.739-0.872), and the sensitivity and specificity were 0.673 and 0.8022. The calibration curves of both SII and SIRI models are in good agreement with the actual curves. And the decision curves of both models indicated their clinical practicality. CONCLUSION: SII and SIRI are independent risk factors for CHD in young adults, which can quickly and effectively identify CHD patients among young adults who have previously experienced chest pain symptoms.

Chitosan/agarose hydrogel dressing: pH response real-time monitoring and chemo-/photodynamic therapy synergistic treatment of infected wounds.

The early diagnosis and real-time monitoring of bacterial infections are of great significance for the establishment of integrated diagnosis and treatment systems. In this study, a pH-responsive smart hydrogel patch system, named CABP, was developed to monitor and treat wound infections. CABP has a sandwich structure, with non-woven fabric/chitosan (NF/CS) as the intermediate skeleton layer, Agarose/chitosan/Bromothymol Blue (AG/CS/BTB) hydrogel as the detection layer, and Agarose/chitosan/phthalocyanine (AG/CS/Pc) hydrogel as the treatment layer. When Staphylococcus aureus (S. aureus) infection occurs, the pH of the environment decreases, which triggers the CABP to change from its original blue color to yellow, achieving an intuitive visual transformation. Moreover, the hydrogel patch showed a significant inhibition rate of up to 99.99971 % against S. aureus under 660 nm light radiation, showing a good photodynamic therapy (PDT)/ chemotherapy (CT) synergistic effect. In addition, CABP showed excellent antibacterial and wound healing effects on S. aureus infection in a full-layer skin defect experiment. In short, the patch system is simple to prepare and easy to use, and can provide important research value for the integrated diagnosis and treatment system in biomedical applications.

Genetic modules for α-factor pheromone controlled growth regulation of Saccharomyces cerevisiae.

Saccharomyces cerevisiae is a commonly used microorganism in the biotechnological industry. For the industrial heterologous production of compounds, it is of great advantage to work with growth-controllable yeast strains. In our work, we utilized the natural pheromone system of S. cerevisiae and generated a set of different strains possessing an α-pheromone controllable growth behavior. Naturally, the α-factor pheromone is involved in communication between haploid S. cerevisiae cells. Perception of the pheromone initiates several cellular changes, enabling the cells to prepare for an upcoming mating event. We exploited this natural pheromone response system and developed two different plasmid-based modules, in which the target genes, MET15 and FAR1, are under control of the α-factor sensitive FIG1 promoter for a controlled expression in S. cerevisiae. Whereas expression of MET15 led to a growth induction, FAR1 expression inhibited growth. The utilization of low copy number or high copy number plasmids for target gene expression and different concentrations of α-factor allow a finely adjustable control of yeast growth rate.

Effects of N-acetylcysteine on hepatocellular carcinoma in chronic hepatitis C.

Hepatitis C virus (HCV) infection significantly contributes to global hepatocellular carcinoma (HCC) incidence. N-Acetylcysteine (NAC), known for its antioxidant properties, is a potential therapeutic agent. However, evidence on its efficacy in reducing HCC risk among HCV patients is limited. A retrospective cohort analysis using Taiwan's National Health Insurance Research Database (2008-2018) included ≥18-year-old HCV patients. NAC usage (≥28 cumulative defined daily doses [cDDDs]) was assessed for its association with HCC risk using Cox regression models and propensity score matching. The study comprised 269,647 HCV patients, with detailed NAC dosage characterization and hazard ratios (HRs) for HCC risk. Post-matching, NAC usage emerged as the significant predictor of reduced HCC risk (adjusted HR: 0.39, 95% CI: 0.37-0.41, P<0.0001). Dose-response analysis showed reduced HCC risk with increasing cDDDs of NAC (P<0.0001). Higher daily NAC dosage (≥1 DDD) was associated with significantly lower HCC risk (adjusted HR: 0.33, 95% CI: 0.31-0.36, P<0.0001). The study provides compelling evidence for NAC's potential in reducing HCC risk among HCV patients. Insights into dose-dependent effects and optimal daily intensity thresholds offer valuable directions for future therapeutic strategies and clinical trials targeting HCC burden in HCV-infected individuals.

The speed of completion of the decremental responses on repetitive nerve stimulation.

Objective: It is generally believed that the decremental response in repetitive nerve stimulation (RNS) stabilizes at the fourth or fifth response. We have a preliminary impression that the decremental response approaches a plateau earlier in proximal muscles than in distal muscles. We investigated the speed of the completion of the decremental response in different muscles. Methods: The "decrement completion ratio (DCR)" in the second or third response (DCR2 or DCR3) was defined as the ratio of the decremental percentage of the second or third response to that of the fourth response. Patients showing more than 10% decremental response both in the abductor pollicis (APB) and deltoid muscles were retrospectively extracted from our EMG database. The DCR2 and DCR3 were compared between two muscles in patients with myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS). Results: Identified subjects consisted of 11patients with MG and 11 patients with ALS. Multiple regression analysis revealed that only the difference of muscle influenced on DCR2 and DCR3, with no contribution from the different disorder (MG or ALS) or the initial amplitude of the compound muscle action potential (CMAP). Both DCR2 and DCR3 were significantly higher in deltoid than in APB. In ALS, the normalized CMAP amplitude was not different between APB and deltoid whereas the decremental percentage was significantly higher in deltoid, suggesting a lower safety factor of the neuromuscular transmission in proximal muscles. Conclusions: The decremental response completed more rapidly in deltoid than in APB which may be related to the lower safety factor also documented by this study. Significance: Unexpected early completion of the decrement such as at the second response in RNS is not a technical error but may be an extreme of the rapid completion in deltoid, a proximal muscle.

Sustainable biosynthesis of lycopene by using evolutionary adaptive recombinant Escherichia coli from orange peel waste.

This study aimed to evaluate the hydrolysates from orange peel waste (OPW) as the low-cost carbon source for lycopene production. Initially, the dilute acid pretreatment combined with enzymatic hydrolysis of OPW resulted in a total sugar concentration of 62.18 g/L. Meanwhile, a four-month adaptive laboratory evolution (ALE) experiment using a d-galacturonic acid minimal medium resulted in an improvement in the growth rate of our previously engineered Escherichia coli strain for lycopene production. After evolutionary adaptation, response surface methodology (RSM) was adapted to optimize the medium composition in fermentation. The results obtained from RSM analysis revealed that the 5.53 % carbon source of orange peel hydrolysate (OPH), 6.57 g/L nitrogen source, and 30 °C temperature boosted lycopene production in the final strain. Subsequently, the optimized treatment for lycopene fermentation was then conducted in a 5 L batch fermenter under the surveillance of a kinetic model that uses the Logistic equation for strain growth (µm = 0.441 h-1), and Luedeking-Piret equations for lycopene production (Pm = 1043 mgL-1) with growth rate constant (α = 0.1491). At last, lycopene biosynthesized from OPH was extracted and analyzed for qualitative validation. Likewise, its data on phytic acid (between 1.01 % and 0.86 %) and DPPH radical scavenging (between 38.06 % and 29.08 %) highlighted the better antioxidant capacity of lycopene. In conclusion, the OPH can be used as a fermentation feedstock which opens new possibilities of exploiting fruit crop residues for food and pharmaceutical applications.

The hypoxic respiratory response of the pre-Bötzinger complex.

Since the discovery of the pre-Bötzinger Complex (preBötC) as a crucial region for generating the main respiratory rhythm, our understanding of its cellular and molecular aspects has rapidly increased within the last few decades. It is now apparent that preBötC is a highly flexible neuronal network that reconfigures state-dependently to produce the most appropriate respiratory output in response to various metabolic challenges, such as hypoxia. However, the responses of the preBötC to hypoxic conditions can be varied based on the intensity, pattern, and duration of the hypoxic challenge. This review discusses the preBötC response to hypoxic challenges at the cellular and network level. Particularly, the involvement of preBötC in the classical biphasic response of the respiratory network to acute hypoxia is illuminated. Furthermore, the article discusses the functional and structural changes of preBötC neurons following intermittent and sustained hypoxic challenges. Accumulating evidence shows that the preBötC neural circuits undergo substantial changes following hypoxia and contribute to several types of the respiratory system's hypoxic ventilatory responses.