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Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1ß), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.
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Compuestos de Bencidrilo , Pollos , Estrés del Retículo Endoplásmico , Ferroptosis , Fenoles , Piroptosis , Especies Reactivas de Oxígeno , Selenio , Animales , Compuestos de Bencidrilo/toxicidad , Ferroptosis/efectos de los fármacos , Piroptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Selenio/deficiencia , Fenoles/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Timo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
ABSTRACT Introduction: Acute kidney injury (AKI) is an abrupt deterioration of kidney function. The incidence of pediatric AKI is increasing worldwide, both in critically and non-critically ill settings. We aimed to characterize the presentation, etiology, evolution, and outcome of AKI in pediatric patients admitted to a tertiary care center. Methods: We performed a retrospective observational single-center study of patients aged 29 days to 17 years and 365 days admitted to our Pediatric Nephrology Unit from January 2012 to December 2021, with the diagnosis of AKI. AKI severity was categorized according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The outcomes considered were death or sequelae (proteinuria, hypertension, or changes in renal function at 3 to 6 months follow-up assessments). Results: Forty-six patients with a median age of 13.0 (3.5-15.5) years were included. About half of the patients (n = 24, 52.2%) had an identifiable risk factor for the development of AKI. Thirteen patients (28.3%) were anuric, and all of those were categorized as AKI KDIGO stage 3 (p < 0.001). Almost one quarter (n = 10, 21.7%) of patients required renal replacement therapy. Approximately 60% of patients (n = 26) had at least one sequelae, with proteinuria being the most common (n = 15, 38.5%; median (P25-75) urinary protein-to-creatinine ratio 0.30 (0.27-0.44) mg/mg), followed by reduced glomerular filtration rate (GFR) (n = 11, 27.5%; median (P25-75) GFR 75 (62-83) mL/min/1.73 m2). Conclusions: Pediatric AKI is associated with substantial morbidity, with potential for proteinuria development and renal function impairment and a relevant impact on long-term prognosis.
RESUMO Introdução: Insuficiência renal aguda (IRA) é uma deterioração abrupta da função renal. A incidência de IRA pediátrica está aumentando em todo o mundo, em ambientes críticos e não críticos. Nosso objetivo foi caracterizar apresentação, etiologia, evolução e desfechos da IRA em pacientes pediátricos internados em um centro de atendimento terciário. Métodos: Realizamos estudo retrospectivo observacional de centro único de pacientes com idade entre 29 dias a 17 anos e 365 dias internados em nossa Unidade de Nefrologia Pediátrica, de janeiro de 2012 a dezembro de 2021, com diagnóstico de IRA. A gravidade da IRA foi categorizada de acordo com os critérios do Kidney Disease Improving Global Outcomes (KDIGO). Os desfechos considerados foram óbito ou sequelas (proteinúria, hipertensão ou alterações na função renal em avaliações de acompanhamento de 3 a 6 meses). Resultados: Incluímos 46 pacientes com idade mediana de 13,0 (3,5-15,5) anos. Cerca de metade (n = 24; 52,2%) apresentou um fator de risco identificável para o desenvolvimento de IRA. Treze pacientes (28,3%) eram anúricos; todos foram classificados como IRA KDIGO 3 (p < 0,001). Quase um quarto (n = 10; 21,7%) dos pacientes necessitaram de terapia renal substitutiva. Aproximadamente 60% (n = 26) apresentou pelo menos uma sequela, sendo proteinúria a mais comum (n = 15; 38,5%; mediana (P25-75) da relação proteína/creatinina urinária 0,30 (0,27-0,44) mg/mg), seguida de taxa de filtração glomerular (TFG) reduzida (n = 11; 27,5%; mediana (P25-75) da TFG 75 (62-83) mL/min/1,73 m2). Conclusões: A IRA pediátrica está associada à morbidade substancial, com potencial para desenvolvimento de proteinúria e comprometimento da função renal e impacto relevante no prognóstico de longo prazo.
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Abstract Introduction: Nonagenarians constitute a rising percentage of inpatients, with acute kidney injury (AKI) being frequent in this population. Thus, it is important to analyze the clinical characteristics of this demographic and their impact on mortality. Methods: Retrospective study of nonagenarian patients with AKI at a tertiary hospital between 2013 and 2022. Only the latest hospital admission was considered, and patients with incomplete data were excluded. A logistic regression analysis was conducted to define risk factors for mortality. A p-value < 0.05 was considered statistically significant. Results: A total of 150 patients were included, with a median age of 93.0 years (91.2-95.0), and males accounting for 42.7% of the sample. Sepsis was the most common cause of AKI (53.3%), followed by dehydration/hypovolemia (17.7%), and heart failure (17.7%). ICU admission occurred in 39.3% of patients, mechanical ventilation in 14.7%, vasopressors use in 22.7% and renal replacement therapy (RRT) in 6.7%. Death occurred in 56.7% of patients. Dehydration/hypovolemia as an etiology of AKI was associated with a lower risk of mortality (OR 0.18; 95% CI 0.04-0.77, p = 0.020). KDIGO stage 3 (OR 3.15; 95% CI 1.17-8.47, p = 0.023), ICU admission (OR 12.27; 95% CI 3.03-49.74, p < 0.001), and oliguria (OR 5.77; 95% CI 1.98-16.85, p = 0.001) were associated with mortality. Conclusion: AKI nonagenarians had a high mortality rate, with AKI KDIGO stage 3, oliguria, and ICU admission being associated with death.
Resumo Introdução: Nonagenários constituem um percentual de pacientes internados em ascensão, sendo a injúria renal aguda (IRA) frequente nesses pacientes. Sendo assim, é importante analisar as características clínicas dessa população e seu impacto na mortalidade. Métodos: Estudo retrospectivo de pacientes nonagenários com IRA entre 2013 e 2022 em um hospital terciário. Apenas o último internamento foi considerado e pacientes com dados incompletos foram excluídos. Uma análise por regressão logística foi realizada para definir fatores de risco para mortalidade. Um valor de p < 0,05 foi considerado significativo. Resultados: Foram incluídos 150 pacientes com mediana de idade 93,0 anos (91,2-95,0) e sexo masculino em 42,7%. Sepse foi a causa mais comum de IRA (53,3%), seguida de desidratação/hipovolemia (17,7%) e insuficiência cardíaca (17,7%). Admissão na UTI ocorreu em 39,3% dos pacientes, ventilação mecânica em 14,7%, uso de vasopressores em 22,7% e realização de terapia renal substitutiva (TRS) em 6,7%. Óbito ocorreu em 56,7% dos pacientes. Desidratação/hipovolemia como etiologia da IRA foi associado a menor risco de mortalidade (OR 0,18; IC 95% 0,04-0,77, p = 0,020). Estágio KDIGO 3 (OR 3,15; IC 95% 1,17-8,47, p = 0,023), admissão na UTI (OR 12,27; IC 95% 3,03-49,74, p < 0,001) e oligúria (OR 5,77; IC 95% 1,98-16,85, p = 0,001) foram associados à mortalidade. Conclusão: Nonagenários com IRA apresentaram alta mortalidade e IRA KDIGO 3, oligúria e admissão na UTI foram associadas ao óbito.
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Introduction: The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. Methods: We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9 g/g, and median serum creatinine was 3.2 mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. Conclusion: The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.
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Background: Continuous renal replacement therapy (CRRT) is the most frequently used modality of renal replacement therapy (RRT) in critical care patients with acute kidney injury (AKI). Adequate CRRT delivery can be challenging, due to problems with circuit patency. To improve circuit patency, we developed a new CRRT protocol using continuous veno-venous hemodiafiltration (CVVHDF) with 3.0 mmol/l regional citrate anticoagulation (CVVHDF/RCA3.0) as our first choice RRT modality. Methods: Retrospective comparison of efficacy and safety of a CVVHDF/RCA3.0 protocol with our former continuous veno-venous hemofiltration protocol with 2.2 regional citrate anticoagulation (CVVH/RCA2.2) in adult critically ill patients with AKI requiring CRRT between 25 April 2020 and 24 October 2021. Results: In total, 56 patients (257 circuits) and 66 patients (290 circuits) were included in the CVVH/RCA2.2 and CVVHDF/RCA3.0 groups, respectively. Median circuit survival was significantly higher in patients treated with CVVHDF/RCA3.0 (39.6 (IQR 19.5-67.3) hours) compared to patients treated with CVVH/RCA2.2 (22.9 (IQR 11.3-48.6) hours) (P < .001). Higher body weight and higher convective flow were associated with a lower circuit survival. Metabolic control was similar, except for metabolic alkalosis that occurred less frequently during CVVHDF/RCA3.0 (19% of patients) compared to CVVH/RCA2.2 (46% of patients) (P = .006). Conclusions: CRRT circuit survival was longer with CVVHDF/RCA3.0 compared to CVVH/RCA2.2. CRRT circuit survival was negatively associated with higher body weight and higher convective flow.
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Introduction: Girls and boys presenting disruptive behavior disorders (DBDs) display differences in white matter microstructure (WMM) relative to typically developing (TD) sex-matched peers. Boys with DBDs are at increased risk for traumatic brain injuries (TBIs), which are also known to impact WMM. This study aimed to disentangle associations of WMM with DBDs and TBIs. Methods: The sample included 673 children with DBDs and 836 TD children, aged 9-10, from the Adolescent Brain Cognitive Development Study. Thirteen white matter bundles previously associated with DBDs were the focus of study. Analyses were undertaken separately by sex, adjusting for callous-unemotional traits (CU), attention-deficit hyperactivity disorder (ADHD), age, pubertal stage, IQ, ethnicity, and family income. Results: Among children without TBIs, those with DBDs showed sex-specific differences in WMM of several tracts relative to TD. Most differences were associated with ADHD, CU, or both. Greater proportions of girls and boys with DBDs than sex-matched TD children had sustained TBIs. Among girls and boys with DBDs, those who had sustained TBIs compared to those not injured, displayed WMM alterations that were robust to adjustment for all covariates. Across most DBD/TD comparisons, axonal density scores were higher among children presenting DBDs. Discussion: In conclusion, in this community sample of children, those with DBDs were more likely to have sustained TBIs that were associated with additional, sex-specific, alterations of WMM. These additional alterations further compromise the future development of children with DBDs.
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Hexavalent chromium (Cr(VI)) is a hazardous metallic compound commonly used in industrial processes. The liver, responsible for metabolism and detoxification, is the main target organ of Cr(VI). Toxicity experiments were performed to investigate the impacts of low-dose exposure to Cr(VI) on rat livers. It was revealed that exposure of 0.05 mg/kg potassium dichromate (K2Cr2O7) and 0.25 mg/kg K2Cr2O7 notably increased malondialdehyde (MDA) levels and the expressions of P-AMPK, P-ULK, PINK1, P-Parkin, and LC3II/LC3I, and significantly reduced SOD activity and P-mTOR and P62 expression levels in liver. Electron microscopy showed that CR(VI) exposure significantly increased mitophagy and the destruction of mitochondrial structure. This study simulates the respiratory exposure mode of CR(VI) workers through intratracheal instillation of CR(VI) in rats. It confirms that autophagy in hepatocytes is induced by low concentrations of CR(VI) and suggest that the liver damage caused by CR(VI) may be associated with the AMPK-related PINK/Parkin signaling pathway.
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Cromo , Hígado , Mitofagia , Proteínas Quinasas , Transducción de Señal , Ubiquitina-Proteína Ligasas , Animales , Cromo/toxicidad , Mitofagia/efectos de los fármacos , Proteínas Quinasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Transducción de Señal/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Ratas , Masculino , Dicromato de Potasio/toxicidad , Proteínas Quinasas Activadas por AMP/metabolismo , Ratas Sprague-Dawley , Malondialdehído/metabolismoRESUMEN
Iatrogenic injury of the bladder is a rare incidence during inguinal hernia repair in children, with serious consequences for such patients. Due to the scarcity of information on this matter, it is our goal to share our experience regarding the therapeutic approach to such a rare occurrence. Specifically, a 22-month-old male was admitted to our department with the complaint of vomiting, abdominal pain and anuria, two days after inguinal hernia repair. The child had distention of the inguinal hernia region and was lethargic. The diagnostic investigation did not reveal any significant findings. During surgical exploration, we discovered an injury to the bladder, while a large part of the dome of the bladder was ligated and subsequently became necrotic. After a reoperation and an enduring postoperative course, the patient finally recovered. Currently, the child is under observation. Therefore, it is of paramount importance for pediatric surgeons to be acquainted with the potential for bladder injury during inguinal hernia repair, ways to manage this complication, and various issues that may emerge during the therapeutic process.
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Background In the pediatric population, acute post-streptococcal glomerulonephritis (PSGN) is a common glomerular etiology of hematuria and acute hypertension leading to hospitalization. We conducted this study to know the clinical profile and occurrence of acute PSGN in patients presenting with features of acute nephritic syndrome. Methods This prospective observational study was conducted on children aged between two and 18 years, presenting with clinical features of acute glomerular nephritis (AGN). After due ethical considerations, all eligible patients were enrolled and underwent detailed clinical assessment, laboratory, and imaging evaluation, followed by protocolized treatment. Relevant data were collected and analyzed to reach valid results. Results Out of 60 patients with AGN, PSGN was found in 83.3% of the patients (50/60). The age group under five years was the most commonly involved, with a male/female ratio of 1.6:1. Around half of the studied patients were from the lower middle class, and 40 (80%) were from rural backgrounds. Facial puffiness was the most common clinical presentation, seen in 45 (90%) patients. Hypocomplementemia and proteinuria were seen in all PSGN patients. Pyoderma was the most common preceding infection, seen in 38 (76%) patients, followed by pharyngitis. Acute kidney injury (AKI) was the most common complication, seen in 12 (24%) patients. Complete resolution of the signs and symptoms was seen in 37 (74%) patients at the time of discharge, which increased to 47 (94%) patients at six months post discharge. Conclusion PSGN stands to be the most common cause of pediatric AGN. The population under five years of age, with a past history of pyoderma, is more predisposed to PSGN. The potential for the occurrence of AKI and other life-threatening complications is high, for which early diagnosis and institution of proper treatment would be very beneficial.
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Traumatic brain injury (TBI) is a significant global health issue, contributing substantially to mortality and disability. Serum biomarkers, such as homocysteine (Hcy), play a critical role in the prognosis of brain injuries, with hyperhomocysteinemia (HHcy) potentially leading to neurological disorders. We present the case of a 64-year-old patient admitted to the emergency department following a road traffic accident (RTA). Magnetic resonance imaging (MRI) revealed parietal subdural hematoma (SDH), right frontal contusion, and left subarachnoid hemorrhage (SAH). The patient underwent a craniotomy to address SAH and SDH. Initial Hcy levels were markedly elevated compared to post-operative levels. Hcy represents a rapid, non-invasive, and cost-effective diagnostic tool for assessing brain injury severity and guiding medical intervention. Early detection of HHcy could potentially mitigate vascular and neurological complications, thereby improving patient outcomes.
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Background: Concussions are an ever present risk for many sports. Underlying emotional disturbances and drowsiness are associated with worse post-concussion symptom scores. Yet, not study has examined associations of both emotional disturbances and drowsiness on concussion severity and symptomology. Objectives: Examine the associations between baseline sleepiness, emotional complaints, and concussion risk and symptom severity in adolescent athletes. Methods: A cohort of 626 adolescent athletes underwent baseline/pre-season concussion screening. Those who experienced a physician diagnosed concussion underwent follow up concussion symptomology assessment. Over 90% of players were seen within two weeks of the concussion incident. Linear regression examined for associations between concussion symptom scores and baseline drowsiness and baseline emotional symptoms. Logistic regression examined for association between each symptom and baseline drowsiness and baseline emotional symptoms. Results: Of the 626 athletes that underwent baseline testing, 292 experienced a concussion. Of those 292 athletes, 174 (59.6%) reported baseline drowsiness and 183 (62.7%) baseline emotional symptoms. Baseline drowsiness and emotional complaints were associated with a 2.6 (95% confidence interval = 1.9 to 3.6) and 2.8 (95% confidence interval = 2.0 to 3.9) times greater odds of sustaining a concussion respectively. Increased symptomology after concussion was associated with both baseline drowsiness (unstandardised b = 4.6, p < 0.01) and baseline emotional complaints (unstandardised b = 6.0, p < 0.01). Conclusion: Preseason drowsiness and emotional complaints in adolescent athletes are associated with higher risk of adverse clinical outcomes following concussion. Therefore, clinicians and coaches should be aware, and properly screen, for sleep and emotional problems as part of pre-season/baseline health screening.
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Wounding occurs across multicellular organisms. Wounds can affect host mobility and reproduction, with ecological consequences for competitive interactions and predator-prey dynamics. Wounds are also entry points for pathogens. An immune response is activated upon injury, resulting in the deposition of the brown-black pigment melanin in insects. Despite the abundance of immunity studies in the laboratory and the potential ecological and evolutionary implications of wounding, the prevalence of wounding in wild-collected insects is rarely systematically explored. We investigated the prevalence and potential causes of wounds in wild-collected Drosophilidae flies. We found that 31% of Drosophila melanogaster were wounded or damaged. The abdomen was the most frequently wounded body part, and females were more likely to have melanized patches on the ventral abdomen, compared with males. Encapsulated parasitoid egg frequency was approximately 10%, and just under 1% of Drosophilidae species had attached mites, which also caused wounds. Wounding is prevalent in D. melanogaster, likely exerting selection pressure on host immunity for two reasons: on a rapid and efficient wound repair and on responding efficiently to opportunistic infections. Wounding is thus expected to be an important driver of immune system evolution and to affect individual fitness and population dynamics.
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Background: Injuries in professional baseball players have become exceedingly common. Efforts to mitigate injury risk have focused on the kinetic chain, shoulder motion, and so forth. It is unclear whether grip strength is related to injury risk in professional baseball pitchers. Purpose/Hypothesis: The purpose of this study was to determine if grip strength was a risk factor for injury. It was hypothesized that pitchers with weaker grip strength would have a higher likelihood of sustaining a shoulder or elbow injury compared with pitchers with stronger grip strength. Study Design: Case-control study; Level of evidence, 3. Methods: All professional pitchers from a single Major League Baseball organization were included. Dominant and nondominant grip strength were measured after each pitching outing throughout the 2022 season. Injuries over the course of the season were recorded, and data were compared between pitchers who sustained a shoulder or elbow injury and those who did not. Results: Overall, 213 pitchers were included, of whom 53 (24.9%) sustained a shoulder or elbow injury during the season. The mean grip strength for all pitchers was 144.0 ± 20.8 lb (65.3 ± 9.4 kg). The mean dominant-arm grip strength was 142.6 ± 20.8 lb (64.7 ± 9.4 kg) for pitchers who did not sustain a shoulder or elbow injury and 148.2 ± 20.9 lb (67.2 ± 9.5 kg) for pitchers who did sustain an injury, with no significant group difference in grip strength (P > .05). Furthermore, there were no significant differences in change in grip strength over the course of the season between the groups. Conclusion: There was no significant difference in mean grip strength or change in grip strength over the course of a single season between professional baseball pitchers who sustained a shoulder or elbow injury and those who did not.
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Objective: To (1) estimate the lifetime prevalence of suspected and diagnosed traumatic brain injury (TBI) based on parent report overall and select sociodemographic characteristics; and (2) describe differences in prevalence of health conditions and health-related risk factors by whether a child had a lifetime history of diagnosed TBI. Study design: We analyzed data from the 2020 National Survey of Children's Health, a cross-sectional address-based survey of US households. A categorical variable was created on the basis of parent responses to 3 questions inquiring about their suspicion of their child having a brain injury, if they sought medical care, and if the health care provider provided a diagnosis. Parents also were asked to report on their child's additional health conditions, functional indicators, school and social factors, and health care access and service use. Results: The prevalence of lifetime diagnosed TBI was 4.2% (95% CI 3.8-4.5). Children with a parent-reported lifetime history of diagnosed TBI were more likely to have a variety of health conditions, special health care needs, disabilities, activity limitations, missed days of school, and unmet care coordination needs, compared with those without a history. However, they were more likely to have a usual source of sick care and to receive more health-related services. Conclusions: For school-aged children, a history of TBI is associated with parent-reported health needs and conditions, as well as missed days from school. It is particularly important for parents to seek care when they suspect their child has experienced a TBI to receive a diagnosis and monitor the impacts of the TBI.
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Introduction: The prevention and mitigation of intestinal immune challenge is crucial for poultry production. This study investigated the effects of dietary Macleaya cordata extract (MCE) supplementation on the prevention of intestinal injury in broiler chickens challenged with lipopolysaccharide (LPS). Methods: A total of 256 one-day-old male Arbor Acres broilers were randomly divided into 4 treatment groups using a 2×2 factorial design with 2 MCE supplemental levels (0 and 400 mg/kg) and 2 LPS challenge levels (0 and 1 mg/kg body weight). The experiment lasted for 21 d. Results and discussion: The results showed that MCE supplementation increased the average daily feed intake during days 0-14. MCE supplementation and LPS challenge have an interaction on the average daily gain during days 15-21. MCE supplementation significantly alleviated the decreased average daily gain of broiler chickens induced by LPS. MCE supplementation increased the total antioxidant capacity and the activity of catalase and reduced the level of malondialdehyde in jejunal mucosa. MCE addition elevated the villus height and the ratio of villus height to crypt depth of the ileum. MCE supplementation decreased the mRNA expression of pro-inflammatory cytokines interleukin (IL)-6 and IL-8 in the jejunum. MCE addition mitigated LPS-induced mRNA up-expression of pro-inflammatory factors IL-1ß and IL-17 in the jejunum. MCE supplementation increased the abundance of probiotic bacteria (such as Lactobacillus and Blautia) and reduced the abundance of pathogenic bacteria (such as Actinobacteriota, Peptostretococcaceae, and Rhodococcus), leading to alterations in gut microbiota composition. MCE addition altered several metabolic pathways such as Amino acid metabolism, Nucleotide metabolism, Energy metabolism, Carbohydrate metabolism, and Lipid metabolism in broilers. In these pathways, MCE supplementation increased the levels of L-aspartic acid, L-Glutamate, L-serine, etc., and reduced the levels of phosphatidylcholine, phosphatidylethanolamine, thromboxane B2, 13-(S)-HODPE, etc. In conclusion, dietary supplementation of 400 mg/kg MCE effectively improved the growth performance and intestinal function in LPS-challenged broiler chickens, probably due to the modulation of gut microbiota and plasma metabolites.
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Pollos , Suplementos Dietéticos , Microbioma Gastrointestinal , Lipopolisacáridos , Extractos Vegetales , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Masculino , Papaveraceae/química , Alimentación Animal , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/inmunología , Citocinas/metabolismo , Citocinas/sangre , Intestinos/efectos de los fármacos , Intestinos/microbiología , Intestinos/inmunologíaRESUMEN
Background: The anti-inflammatory effects of budesonide (BUN) and N-acetylcysteine (NAC) attenuate acute lung injury (ALI). The aim of this study was to investigate the effects of combination therapy consisting of BUN and NAC on ALI and the underlying mechanisms. Methods: In vitro and in vivo models of ALI were generated by LPS induction. Western blotting was used to detect the expression levels of pyroptosis-related proteins and inflammation-related factors, and RT-qPCR was used to detect the expression of miR-381. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. ELISA was used to detect the levels of inflammation-related factors. HE staining was used to detect lung injury. Results: The results showed that LPS effectively induced pyroptosis in cells and promoted the expression of pyroptosis-related proteins (Caspase1, Gasdermin D and NLRP3) and inflammatory cytokines (TNF-α, IL-6 and IL-1ß). The combination of BUN and NAC significantly alleviated LPS-induced pyroptosis and inflammation. In addition, the combination of BUN and NAC effectively promoted miR-381 expression. Transfection of miR-381 mimics effectively alleviated LPS-induced pyroptosis and inflammation, while transfection of miR-381 inhibitors had the opposite effect. miR-381 negatively regulates NLRP3 expression. Treatment with a miR-381 inhibitor or pc-NLRP3 reversed the effects of the combination of BUN and NAC. In a mouse model of ALI, the combination of BUN and NAC effectively improved lung injury, while treatment with a miR-381 inhibitor or pc-NLRP3 effectively reversed this effect. Conclusion: Overall, this study revealed that BUN + NAC inhibits the activation of NLRP3 by regulating miR-381, thereby alleviating ALI caused by pyroptosis-mediated inflammation.
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Mortality rates are significantly affected by severe cardiac trauma in both adult and pediatric patients. Although rare in children, cardiac injuries of significant magnitude can lead to fatal outcomes. We report the rare case of a 5-year-old girl who sustained a penetrating cardiac injury from a sharp palm tree frond in a home accident. Immediately, the patient was transferred to a tertiary care center, and life-saving measures were initiated. To ensure prompt optimal care, the pediatric emergency medicine team leader delegated team tasks 1 hour before arrival. The patient underwent immediate surgical repair and experienced a smooth recovery with appropriate management.
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To examine the feasibility, utility and safety of superimposed lower body negative pressure (LBNP) and tilt during supine cycling in individuals suffering from persisting post-concussive symptoms (PPCS). Eleven individuals aged 17-31 (6 females/5 males) participated in two randomized separate visits, 1 week apart. A ramp-incremental test was performed during both visits until volitional failure. Visits included no pressure (control) or LBNP at -40 Torr (experimental) with head-up tilt at 15 degrees (females) or 30 degrees (males). Transcranial Doppler ultrasound was utilized to quantify middle cerebral artery velocity (MCAv), while symptom reports were filled out before and 0, 10, and 60 min post-exertion. Ratings of exertion and overall condition followed similar trends for participants across both tests. The relative increase in MCAv was blunted during the experimental condition (8%) compared to control (24%), while a greater heart rate (17 beats/min) was achieved during the LBNP condition (P = 0.047). Symptom severity at the 0 and 10 min post-exertion time points displayed negligible-to-small effect sizes between conditions (Wilcoxon's r < 0.11). Symptom reporting was lower at the 60 min post-exertion time point with these displaying a moderate effect size (Wilcoxon's r = 0.31). The combination of LBNP and tilt during supine cycling did not change the participants' subjective interpretation of the exertional test but attenuated the hyperpnia-induced vasodilatory MCAv response, while also enabling participants to achieve a higher heart rate during exercise and reduced symptoms 1 h later. As this protocol is safe and feasible, further research is warranted in this area for developing PPCS treatment options. HIGHLIGHTS: What is the central question of this study? What are the feasibility, safety and utility of combining head-up tilt with lower body negative pressure during supine cycling for blunting the increase in cerebral blood velocity seen during moderate-intensity exercise in individuals experiencing persisting post-concussion symptoms? What is the main finding and its importance? Although no differences were found in symptoms between conditions within the first 10 min following exertion, symptom severity scores showed a clinically meaningful reduction 60 min following the experimental condition compared to the non-experimental control condition.
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BACKGROUND: Coronoid fractures are often part of a complex fracture-dislocation of the elbow. For an optimum prognosis, it is important to understand the characteristics of coronoid fractures in different elbow injury patterns. Significant differences in these characteristics have been observed in various studies, but these previous studies have suffered from limitations, such as insufficient quantification and unknown prognostic differences among different injury patterns. Therefore, we aimed to quantitatively analyze coronoid fracture characteristics and functional outcomes in different elbow injury patterns using 3D-CT. METHODS: All patients with coronoid fractures surgically treated at our hospital between January and December 2017 were categorized into three groups according to elbow injury pattern: PLRI, VPMRI and OFD. 3D models were reconstructed using Mimics 17.0, and the total volume (TV) and number of coronoid fragments (NCF) were measured. The coronoid process edge was classified into different anatomical regions, and each region was assigned a number to quantify the distribution of fracture lines. At the last follow-up, the ROM, VAS, MEPS, complications and reoperations were recorded. RESULTS: The ninety-two patients enrolled had an average age of 42±15 years and a male-to-female ratio of 66:26. The median TV in PLRI patients was less than that in VPMRI patients [431 (132, 818)mm3 vs. 1125 (746,1421)mm3,adjusted P<0.001] and OFD patients [431 (132, 818) mm3 vs. 2565 (381, 4076)mm3, adjusted P =0.001]. The median NCF in PLRI patients was also less than that in VPMRI patients [1 (1, 2) vs. 2 (1, 3), adjusted P=0.043]. Most of the PCFL-Rs (79%) were located around the volar edge of the lesser sigmoid notch. Compared with that of PLRI, the PCFL-Us of the VPMRI and OFD tended to be located on the more ulnodorsal side of the coronoid process edge. The median ROM [110 (90, 133), P=0.001] and the median MEPS [85 (68, 95), P=0.038] of patients with OFD were significantly less than those of patients with the other two patterns. The incidence of elbow stiffness (56%, 5/9, P=0.001) and implant-related irritation (44%, 4/9, P<0.001) in the OFD group was significantly higher than that in the other two groups. CONCLUSION: Coronoid fractures differ significantly in fragment volume, comminution severity and fracture line distribution among different elbow injury patterns. OFD has the worst functional outcomes among complex elbow injury patterns.
RESUMEN
The treatment of thoracic tumors with ionizing radiation can cause radiation-induced lung injury (RILI), which includes radiation pneumonitis and radiation-induced pulmonary fibrosis. Preventing RILI is crucial for controlling tumor growth and improving quality of life. However, the serious adverse effects of traditional RILI treatment methods remain a major obstacle, necessitating the development of novel treatment options that are both safe and effective. This review summarizes the molecular mechanisms of RILI and explores novel treatment options, including natural compounds, gene therapy, nanomaterials, and mesenchymal stem cells. These recent experimental approaches show potential as effective prevention and treatment options for RILI in clinical practice.