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Head trauma is a common reason for emergency department (ED) visits. Delayed intracranial hemorrhage (ICH) in patients with minor head trauma is a major concern, but controversies exist regarding the incidence of delayed ICH and discharge planning at the ED. This study aimed to determine the incidence of delayed ICH in adults who developed ICH after a negative initial brain computed tomography (CT) at the ED and investigate the clinical outcomes for delayed ICH. This nationwide population cohort study used data from the National Health Insurance Service of Korea from 2013 to 2019. Adult patients who presented to an ED due to trauma and were discharged after a negative brain CT examination were selected. The main outcomes were the incidence of ICH within 14 days after a negative brain CT at initial ED visit and the clinical outcomes of patients with and without delayed ICH. The study patients were followed up to 1 year after the initial ED discharge. Cox proportional hazard regression analysis was used to estimate the hazard ratio for all-cause 1-year mortality of delayed ICH. During the 7-year study period, we identified 626,695 adult patients aged 20 years or older who underwent brain CT at the ED due to minor head trauma, and 2666 (0.4%) were diagnosed with delayed ICH within 14 days after the first visit. Approximately two-thirds of patients (64.3%) were diagnosed with delayed ICH within 3 days, and 84.5% were diagnosed within 7 days. Among the patients with delayed ICH, 71 (2.7%) underwent neurosurgical intervention. After adjustment for age, sex, Charlson Comorbidity Index, and insurance type, delayed ICH (adjusted hazard ratio, 2.15; 95% confidence interval, 1.86-2.48; p < 0.001) was significantly associated with 1-year mortality. The incidence of delayed ICH was 0.4% in the general population, with the majority diagnosed within 7 days. These findings suggest that patient discharge education for close observation for a week may be a feasible strategy for the general population.
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Hemorragias Intracraneales , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/mortalidad , Hemorragias Intracraneales/etiología , Incidencia , Adulto , Anciano , República de Corea/epidemiología , Estudios de Cohortes , Servicio de Urgencia en Hospital/estadística & datos numéricos , Traumatismos Craneocerebrales/complicaciones , Traumatismos Craneocerebrales/epidemiología , Adulto Joven , Alta del Paciente/estadística & datos numéricos , Factores de TiempoRESUMEN
STUDY OBJECTIVE: Asystole is the most common initial rhythm in out-of-hospital cardiac arrest (OHCA) but indicates a low likelihood of neurologic recovery. This study aimed to develop a novel scoring system to be easily applied at the time of emergency department arrival for identifying favorable neurologic outcomes in OHCA survivors with an asystole rhythm. METHODS: This study is a secondary analysis based on a previously collected nationwide database, targeting nontraumatic adult OHCA patients aged ≥18 years with an asystole rhythm who achieved return of spontaneous circulation (ROSC) between January 2016 and December 2020. The primary outcome was a favorable neurologic outcome defined as Cerebral Performance Categories scores of 1 or 2 at hospital discharge. A prediction model was developed through multivariable logistic regression analysis in a derivation cohort in the form of a scoring system (WBC-ASystole). The performance and calibration of the model were tested using an internal validation cohort. RESULTS: Among 19,803 OHCA patients with survival to hospital admission, 6,322 had asystole, and 285 (4.5%) achieved good neurologic outcomes. Factors associated with favorable outcomes included age, witness arrest, bystander cardiopulmonary resuscitation, time from call to hospital arrival, and out-of-hospital ROSC achievement. The WBC-ASystole score, totaling 11 points, exhibited a predictive performance with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval [CI] 0.76 to 0.83) and 0.79 (95% CI 0.74 to 0.83) in the derivation and validation cohorts, respectively. After categorizing patients into 3 groups based on probability for good neurologic outcomes, the sensitivity and specificity were as follows: 0.98 (95% CI 0.97 to 0.99) and 0.09 (95% CI 0.09 to 0.10) for the very low predicted probability group (WBC-ASystole ≤2), 0.85 (95% CI 0.82 to 0.89) and 0.54 (95% CI 0.53 to 0.55) for the low predicted probability group (WBC-ASystole 3 to 4), and 0.36 (95% CI 0.34 to 0.39) and 0.93 (95% CI 0.92 to 0.93) for fair predicted probability group (WBC-ASystole≥5), respectively. CONCLUSIONS: Although external validation studies must be performed, among OHCA patients with asystole, the WBC-ASystole scoring system may identify those patients who are likely to have a favorable neurologic outcome.
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Research on prognostic factors for good outcomes in out-of-hospital cardiac arrest (OHCA) survivors is lacking. We assessed whether normal levels of normal neuron-specific enolase (NSE) value would be useful for predicting good neurological outcomes in comatose OHCA survivors treated with targeted temperature management (TTM). This registry-based observational study with consecutive adult (≥18 years) OHCA survivors with TTM who underwent NSE measurement 48 hours after cardiac arrest was conducted from October 2015 to November 2022. Normal NSE values defined as the upper limit of the normal range by the manufacturer (NSE <16.3 µg/L) and guideline-suggested (NSE < 60 µg/L) were examined for good neurologic outcomes, defined as Cerebral Performance Categories ≤2, at 6 months post-survival. Among 226 OHCA survivors with TTM, 200 patients who underwent NSE measurement were enrolled. The manufacturer-suggested normal NSE values (<16.3 µg/L) had a specificity of 99.17% for good neurological outcomes with a very low sensitivity of 12.66%. NSE <60 µg/L predicted good outcomes with a sensitivity of 87.34% and specificity of 72.73%. However, excluding 14 poor-outcome patients who died from multi-organ dysfunction excluding hypoxic brain injury, the sensitivity and specificity of normal NSE values were 12.66% and 99.07% of NSE < 16.3 µg/L, and 87.34% and 82.24% of NSE < 60 µg/L. The manufacturer-suggested normal NSE had high specificity with low sensitivity, but the guideline-suggested normal NSE value had a comparatively low specificity for good outcome prediction in OHCA survivors. Our data demonstrate normal NSE levels can be useful as a tool for multimodal appropriation of good outcome prediction.
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Coma , Paro Cardíaco Extrahospitalario , Fosfopiruvato Hidratasa , Humanos , Fosfopiruvato Hidratasa/sangre , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Coma/etiología , Anciano , Sobrevivientes , Pronóstico , Hipotermia Inducida , AdultoRESUMEN
The likelihood of neurological recovery after out-of-hospital cardiac arrest (OHCA) may be influenced by advanced age. This study aims to evaluate the impact of advanced age on neurological recovery in elderly OHCA survivors treated with targeted temperature management (TTM). This retrospective observational study, using a nationwide population-based OHCA registry, was conducted from January 2016 to December 2020. Non-traumatic elderly (≥ 65 years) comatose OHCA survivors treated with TTM were categorized according to age (65-69, 70-74, 75-79, and ≥ 80 years). Among 23,336 admitted OHCA patients, 3,398 were treated with TTM. Excluding 2,033 non-elderly patients, 1,365 were analyzed. Among the four groups, the rate of good neurological outcomes decreased by advanced age (24.2%, 16.1%, 11.4%, and 5.9%, respectively), which was also observed after subgroup analysis based on the initial shockable (40.6%, 31.5%, 28.6%, and 14.9%, respectively) and non-shockable rhythm (10.6%, 7.2%, 4.1%, and 3.4%, respectively). Multivariate analysis showed the adjusted odds ratio (aOR) for good neurological outcome decreased as age increased (65-69: reference, 70-74: aOR 0.70, 75-79: aOR 0.49, and ≥ 80 years: aOR 0.25). The optimal age cutoffs for good outcomes in elderly OHCA survivors with shockable and non-shockable rhythm were 77 and 72 years, respectively. The neurologic recovery rate in OHCA survivors treated with TTM gradually decreased with increasing age. However, even patients aged ≥ 80 years with shockable rhythm had a good neurologic outcome of 14.9% compared with patients aged 65-69 years with non-shockable rhythm (10.6%).
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BACKGROUND: This study aimed to evaluate the association between initial fibrinogen levels and massive transfusion (MT) in emergency department (ED) patients with primary postpartum hemorrhage (PPH). METHODS: This retrospective study was conducted in the ED of a university-affiliated, tertiary referral center from January 2004 to August 2023. Patients were divided into two groups: the MT group, which included those who received a transfusion of 10 or more units of packed red blood cells within the first 24 h, and the Non-MT group. RESULTS: Out of the 364 patients included in the study, 97 (26.6%) required MT. Fibrinogen, shock index, and lactate were independently associated with MT (odds ratio [OR] 0.987; 95% confidence interval [CI] 0.983-0.991; p < 0.001, OR 7.277; 95% CI 1.856-28.535; p = 0.004, and OR 1.261; 95% CI 1.021-1.557; p = 0.031, respectively). The area under the receiver operating characteristic curve for fibrinogen, shock index, and lactate in predicting MT was 0.871 (95% CI 0.832-0.904; p < 0.001), 0.821 (95% CI 0.778-0.859; p < 0.001), and 0.784 (95% CI 0.738-0.825; p < 0.001), respectively. When the cutoff value of fibrinogen was 400 mg/dL, both the sensitivity and negative predictive values for predicting MT were 100.0%. When the cutoff value of fibrinogen was 100 mg/dL, the specificity and positive predictive values were 91.8% and 70.7%, respectively. CONCLUSION: The initial fibrinogen levels were independently associated with the need for MT in ED patients with primary PPH.
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BACKGROUND: The early prediction of the need for massive transfusions (MTs) and the preparation of blood products are essential for managing patients with primary postpartum hemorrhage (PPH). Thromboelastography (TEG) enables a thorough evaluation of coagulation status and is useful for guiding the treatment of hemorrhagic events in various diseases. We investigated the role of TEG in predicting the need for MT in patients with primary PPH. METHODS: A retrospective observational study was conducted in the emergency department (ED) of a university-affiliated, tertiary referral center between November 2015 and August 2023. TEG was performed upon admission. We defined MT as the requirement for transfusion of more than 10 units of packed red blood cells within the first 24 h. The primary outcome was the need for MT. RESULTS: Among the 184 patients with initial TEG, 34 (18.5%) required MT. Except for lysis after 30 min, the MT and non-MT groups had significantly different TEG values. Based on multivariate analysis, an angle < 60 was an independent predictor of MT (odds ratio (OR) 7.769; 95% confidence interval (CI), 2.736-22.062), along with lactate (OR, 1.674; 95% CI, 1.218-2.300) and shock index > 0.9 (OR, 4.638; 95% CI, 1.784-12.056). Alpha angle < 60 degrees indicated the need for MT with 73.5% sensitivity, 72.0% specificity, and 92.3% negative predictive value. CONCLUSIONS: Point-of-care testing of TEG has the potential to be a useful tool in accurately predicting the necessity for MT in ED patients with primary PPH at an early stage.
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BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.
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Hemorragia Posparto , Embarazo , Humanos , Femenino , Estudios Retrospectivos , Hemorragia Posparto/terapia , Transfusión Sanguínea , Servicio de Urgencia en Hospital , Frecuencia CardíacaRESUMEN
BACKGROUND: The predictive value of the respiratory rateoxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits. METHODS: We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure. RESULTS: Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively. CONCLUSIONS: The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.
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COVID-19 , Ventilación no Invasiva , Insuficiencia Respiratoria , Humanos , Cánula , COVID-19/terapia , Frecuencia Respiratoria , Estudios Retrospectivos , Insuficiencia Respiratoria/terapia , Terapia por Inhalación de OxígenoRESUMEN
The ion shift index (ISI) is a suggested marker to reflect the magnitude of ischemic damage. This study aimed to investigate the prognostic value of the ISI for predicting poor neurological outcomes at 6 months in comatose out-of-hospital cardiac arrest (OHCA) survivors by comparing it with the OHCA and Cardiac Arrest Hospital Prognosis (CAHP) scores. This observational registry-based cohort study included adult comatose OHCA survivors admitted to a tertiary care hospital in Korea between 2015 and 2021. The ISI was calculated using the serum electrolyte levels obtained within one hour of resuscitation. The primary outcome was poor neurological function (Cerebral Performance Category score of 3−5) at 6 months. Of the 250 OHCA survivors, 164 (65.6%) had poor neurological outcomes. These patients had a higher median ISI than those with good neurological outcomes (4.95 vs. 3.26, p < 0.001). ISI (adjusted odds ratio, 2.107; 95% confidence interval, 1.350−3.288, p = 0.001) was associated with poor neurological outcomes. The prognostic performance of ISI (area under the curve [AUC], 0.859) was similar to that of the OHCA score (AUC, 0.858; p = 0.968) and the CAHP score (AUC, 0.894; p = 0.183). ISI would be a prognostic biomarker for comatose OHCA survivors that is available during the immediate post-cardiac arrest period.
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Recent guidelines for diagnosing acute pulmonary embolism (PE) are based on clinical decision rules and D-dimer. D-dimer measurement is recommended only for patients who are 'PE-unlikely'. We aimed to assess the current guidelines for cancer patients and to determine an optimal D-dimer cut-off level. This retrospective observational study was conducted in the emergency department of Asan Medical Center (Seoul, Korea) between 02/2017 and 09/2017 for the development cohort and between 06/2018 and 02/2019 for the validation cohort. Among adult active cancer patients with suspected PE, we included those who were 'PE-unlikely' according to Wells' criteria and who underwent D-dimer testing and computed tomographic pulmonary angiography (CTPA). A total of 498 patients (227 in the development cohort and 271 in the validation cohort) were included, and PE was diagnosed in 8.8% and 18.5% of patients, respectively. The optimal D-dimer cut-off level was 2.0 µg/mL. This elevated cut-off level showed a much higher specificity of 21.3% (95% confidence interval [CI] 16.2-27.3%) and 21.7% (95% CI 16.8-7.6%) in the development and validation sets, respectively, compared with the specificity of 4.4% (95% CI 2.3-8.1%) and 4.1% (95% CI 2.2-7.6%) using the age-adjusted cut-off. The new D-dimer cut-off value identified unnecessary CTPA for 21.3% of patients (absolute difference, 16.9%, 35 of 207) in the development cohort and 21.7% (absolute difference, 17.6%, 39 of 221) of patients in the validation cohort compared to using the standard age-adjusted cut-off. The elevated D-dimer cut-off value combined with Wells' criteria might reduce unnecessary CTPA in active cancer patients with a 'PE-unlikely' classification. Further clinical trials are warranted to improve the PE diagnostic strategy in cancer patients.
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Neoplasias , Embolia Pulmonar , Adulto , Servicio de Urgencia en Hospital , Productos de Degradación de Fibrina-Fibrinógeno , Humanos , Neoplasias/complicaciones , Embolia Pulmonar/diagnóstico , Estudios RetrospectivosRESUMEN
When ejaculated sperm travels through the vagina to the uterus, mucus secreted by the cervical canal generally filters out sperm having low motility and poor morphology. To investigate this selection principle in vivo, we developed a microfluidic sperm-sorting chip with a viscous medium (polyvinylpyrrolidone: PVP) to imitate the biophysical environment mimic system of the human cervical canal. The material property of the PVP solution was tuned to the range of viscosities of cervical mucus using micro-viscometry. The selection of high-quality human sperm was experimentally evaluated in vitro and theoretically analyzed by the convection-diffusion mechanism. The convection flow is shown to be dominant at low viscosity of the medium used in the sperm-sorting chip when seeded with raw semen; hence, the raw semen containing sperm and debris convectively flow together with suppressed relative dispersions. Also, it was observed that the sperm selected via the chip not only had high motilities but also normal morphologies and high DNA integrity. Therefore, the biomimetic sperm-sorting chip with PVP medium is expected to improve male fertility by enabling the selection of high-quality sperm as well as uncovering pathways and regulatory mechanisms involved in sperm transport through the female reproductive tract for egg fertilization.
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Total motile sperm count is an important parameter for predicting the probability of natural pregnancy. We have externally validated the Samplaski's post-varicocele repair semen analysis nomogram to confirm the predictive accuracy of total motile sperm count. A total of 300 patients who had undergone varicocelectomy between July 2016 and July 2019 from 4 treatment centres were included in this validation cohort study. The predictive performance of the externally validated nomogram was revealed by applying the Pearson correlation coefficient (R = 0.328; 95% confidence interval (CI) 0.220-0.435; p < .001). Compared to Samplaski's nomogram result (R = 0.581; 95% CI 0.186-0.729), our study also revealed a statistically significant rate. However, it had a relatively lower correlation coefficient rate. Notably, the predicted total motile sperm count was lower than the observed post-varicocelectomy total motile sperm count. The calibration plot revealed that the discrepancy between the predicted and observed total motile sperm count was plausible. However, it had low explanatory power in this nomogram model. This validation study demonstrates that the post-varicocele repair Samplaski's nomogram predicts a relatively lower total motile sperm count than the observed count.
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Infertilidad Masculina , Nomogramas , Motilidad Espermática , Varicocele , Estudios de Cohortes , Femenino , Humanos , Masculino , Embarazo , Análisis de Semen , Recuento de Espermatozoides , EspermatozoidesRESUMEN
Benign prostate hyperplasia (BPH) is a common disease in old-age males, accounting for approximately 77% of morbidity within the age range of 40 to 70 years. It has been shown that morbidity increases with social graying. Quisqualis indica linn (QI) has been used to treat inflammation, stomach pain, and digestion problems. In this study, we evaluated the symptom-regulating effects of QI extract on a testosterone-induced BPH rat model. After inducing BPH in rats using testosterone propionate (TP) injection, we assessed basal intraurethral pressure (IUP) and increments of IUP elicited by electrical field stimulation (5 V, 5, 10, or 20 Hz) or phenylephrine (Phe) (0.01, 0.03, 0.1 mg/kg IV). To induce BPH, 8-week-old rats were subjected to a daily subcutaneous TP (3 mg/kg) injection for 4 weeks. Finasteride (Fina) (10 mg/kg PO) was administered to the rats in the first treatment, while QI (150 mg/kg PO) was administered to those in the second group. Blood pressure was measured together with IUP, after which low urinary tract (LUT), ventral prostate (VP), testicle, and corpus spongiosum were isolated and weighed. Basal IUPs for the Fina- and QI-treated groups were 87.6 and 86.8%, respectively. LUT and VP organ weights in the QI group were lower than those in the Fina group. However, the QI group showed significantly reduced electrical stimulated or Phe-induced IUP increment compared to the Fina and BPH groups. These results proved that QI can be beneficial for BPH symptoms by inhibiting 5α-reductase and consequently decreasing prostate and releasing urinary pressure.
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Sperm motility is a crucial factor for normal fertilisation that is partly supported by mitochondrial activity. Enzymatic biofuel cells (EBFCs) generate electric currents by an electron grade from anodic to cathodic electrodes in a culture media. We demonstrate that electrical stimulation by EBFC at the nano-Ampere range enhances sperm motility that can potentially allow the development of a new therapeutic tool for male infertility, including poor motility. EBFC was set up with three different electrical currents (112 nA/cm2 and 250 nA/cm2) at two different times (1 h, 2 h). Each sample was evaluated for its motility by computer-assisted sperm analyses and sperm viability testing. In the expanded study, we used the optimal electrical current of the EBFC system to treat asthenozoospermia and sperm with 0% motility. Results showed that optimal electrical stimulation schemes with EBFCs enhanced sperm motility by 30-40% compared with controls. Activated spermatozoa led to tyrosine phosphorylation in the tail area of the sperm following the electrical stimulation in the nano-Ampere range. However, the electrically stimulated group did not exhibit increased acrosomal reaction rates compared with the control group. In cases related to asthenozoospermia, 40% of motility was recovered following the electrical stimulation at the nano-Ampere range. However, motility is not recovered in sperm with 0% motility. In conclusion, we found that sperm motility was enhanced by exposure to electrical currents in the nano-Ampere range induced by optimal EBFCs. Electrical stimulation enhanced the motility of the sperm though tyrosine phosphorylation in spermatozoa. Therefore, our results show that electrical currents in the nano-Ampere range can be potentially applied to male infertility therapy as enhancers of sperm motility in assisted reproductive technology.
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Fuentes de Energía Bioeléctrica , Estimulación Eléctrica , Enzimas/metabolismo , Motilidad Espermática , Espermatozoides/citología , Humanos , Masculino , Fosforilación , Tirosina/metabolismoRESUMEN
[Purpose] This study was conducted to assess the physical fitness of children with juvenile rheumatoid arthritis (JRA). [Subjects and Methods] In total, 26 children with juvenile rheumatoid arthritis (JRA) and 25 healthy controls participated in this study. Using the physical fitness measurement instruments, the Inbody 720 and Quark b2, the elements of physical fitness that were assessed included muscular strength, muscular endurance, flexibility, lung capacity, and body composition. [Results] The results revealed significant differences in muscular strength, muscular endurance, lung capacity, body composition, functional ability, and health-related quality of life between the children with juvenile rheumatoid arthritis (JRA) and the control group. [Conclusion] These results suggested that children with juvenile rheumatoid arthritis (JRA) have inferior physical fitness when compared to healthy children. The present study was conducted to develop an accurate evaluation standard to assess the physical fitness of children with juvenile rheumatoid arthritis (JRA).
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Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.
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Major peripheral arterial graft infection is a potentially devastating complication of vascular surgery, associated with significant mortality and high amputation rates. Autologous saphenous veins are considered optimal arterial conduits for lower extremity revascularization in infected fields, but they are often unavailable or unsuitable in these patients. This study describes two patients with major peripheral graft infection, but without available autologous veins, who underwent graft excision and cryopreserved cadaveric arterial allograft reconstruction. Although long-term graft durability is unclear because of gradual deterioration and degeneration, these findings suggest that cadaveric allografts may be good options for patients with major peripheral graft infection.
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[Purpose] The aim of this study was to assess patients' health-related quality of life, compare it with a healthy age-matched population, and examine associations between functional ability and quality of life among juvenile rheumatoid arthritis (JRA) patients. [Subjects and Methods] The study participants were 26 JRA patients and 25 controls. The Childhood Health Assessment Questionnaire and the Pediatric Quality of Life Inventory 4.0 Generic Core Scales were used to evaluate functional ability and health-related quality of life, respectively. [Results] Functional ability scores averaged 0.37 in the JRA group and 0.08 in the control group. There were significant between-group differences in functional ability scores in the overall cohort and in the subgroup of participants aged 14-16â years. Health-related quality of life scores were significantly lower in the JRA group than in the control group (68.39 vs. 85.17). In the JRA group, functional ability was statistically positively correlated with health-related quality of life. [Conclusion] We conclude that the mental state of adolescents with JRA affects their particular functional abilities. Subjects in the 14-16 age group who had a longer disease duration and higher difficulty scores showed a lower health-related quality of life than children in the other age groups.
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Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but its overall biological and pathogenic regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs). Here, we report the construction of a high-quality library of 322 signature-tagged gene-deletion strains for 155 putative TF genes previously predicted using the DNA-binding domain TF database, and examine their in vitro and in vivo phenotypic traits under 32 distinct growth conditions. At least one phenotypic trait is exhibited by 145 out of 155 TF mutants (93%) and â¼85% of them (132/155) are functionally characterized for the first time in this study. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and human fungal pathogens.
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Criptococosis , Cryptococcus neoformans/genética , Proteínas Fúngicas/genética , Factores de Transcripción/genética , Animales , Cryptococcus neoformans/fisiología , Bases de Datos de Compuestos Químicos , Proteínas Fúngicas/fisiología , Perfilación de la Expresión Génica , Ratones , Mariposas Nocturnas/microbiología , Factores de Transcripción/fisiología , Factores de Virulencia/genética , Factores de Virulencia/fisiologíaRESUMEN
In this study we explored the mode of action of KR-72, a 9-O-butyl-13-(4-isopropylbenzyl)berberine derivative previously shown to exhibit potent antifungal activity against a variety of human fungal pathogens. The DNA microarray data revealed that KR-72 treatment significantly changed the transcription profiles of C. neoformans, affecting the expression of more than 2,000 genes. Genes involved in translation and transcription were mostly upregulated, whereas those involved in the cytoskeleton, intracellular trafficking, and lipid metabolism were downregulated. KR-72 also exhibited a strong synergistic effect with the antifungal agent FK506. KR-72 treatment regulated the expression of several essential genes, including ECM16, NOP14, HSP10 and MGE1, which are required for C. neoformans growth. The KR-72-mediated induction of MGE1 also likely reduced the viability of C. neoformans by impairing cell cycle or the DNA repair system. In conclusion, KR-72 showed antifungal activity by modulating diverse biological processes through a mode of action distinct from those of clinically available antifungal drugs such as polyene and azole drugs.