Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevation of C-reactive protein and interleukin-6 in plasma of patients with aggressive periodontitis.

BACKGROUND AND OBJECTIVE Systemic levels of C-reactive protein and interleukin-6 have been reported to be elevated in patients with periodontitis compared with periodontally healthy individuals. Most studies included patients with chronic periodontitis and comprised predominantly Caucasians. The aim of this study was to determine the relative levels of C-reactive protein and interleukin-6 in plasma of patients with aggressive periodontitis in China and to examine the relationships between these two inflammatory mediators and clinical parameters, peripheral blood cells and protein variables. MATERIAL AND METHODS Plasma samples were collected from 84 patients with aggressive periodontitis and from 65 control subjects. Periodontal examination consisted of taking probing depth and attachment loss measurements. The levels of plasma C-reactive protein and interleukin-6 were determined using enzyme-linked immunosorbent assays. RESULTS The levels of plasma C-reactive protein in patients with aggressive periodontitis were significantly higher than those in control subjects (1.87 vs. 0.52 mg/L). The level of plasma interleukin-6 in patients with aggressive periodontitis was 1.20 pg/mL, higher than that in control subjects (0.08 pg/mL). Multiple linear regression analysis showed that log C-reactive protein was significantly related to severe sites percentage and albumin following correction for age, gender, body mass index and smoking (p = 0.000, p = 0.008, respectively). Log interleukin-6 was found to be significantly correlated with periodontal diagnosis, leukocyte count and level of fasting blood glucose after adjusting for the confounders (p = 0.000, p = 0.009 and p = 0.013, respectively). CONCLUSION Patients with aggressive periodontitis have significantly elevated levels of plasma C-reactive protein and interleukin-6. These elevated inflammatory factors might potentially increase the risk for cardiovascular events and glucose dysregulation in relatively young individuals.
Newly Developed Endotoxin Measurement Method (the Endotoxin Activity Assay) May Reflect the Severity of Sepsis

Objectives: Endotoxin (ET) is a structural molecule of the Gram-negative bacilli extracellular membrance, which activates targeted cells including macrophages and neutrophils, and causes septic shock. But it is known that the conventional ET measurement method has many problems; for example, a discrepancy between plasma ET concentration and clinical manifestation in the septic patients has been reported. The purpose of this study was to evaluate the usefulness of a newly developed method (Endotoxin Activity Assay (EAA)) to measure the ET activity (EA) in patients under sepsis compared with the prior method of the limulus amebocyte lysate (LAL) assay and explore the association between EA levels and patients’ severity. Method: We measured the EA levels in 40 patients (aged 63.5 +/－ 17.7 years) admitted to the ICU. EA level was measured using a chemiluminometer (Autolumat LB953; EG & Berthold). Patients were divided into 5 groups: 1) control group; 2) systemic inflammatory response syndrome (SIRS) group; 3) sepsis (SIRS and infection) group; 4) severe sepsis group and 5) septic shock group. We then compared the EA level between each group and control group. We made the statistical evaluation by unpaired t test and significant difference was p Results: The EA levels were significantly increased as sepsis severity rises. The measured EA levels were (0.18 +/－ 0.09), (0.33 +/－ 0.19), (0.39 +/－ 0.16), (0.65 +/－ 0.25) and (0.78 +/－ 0.34) in control, SIRS, sepsis, severe sepsis and septic shock groups, respectively. In the EA level measured by EAA, severe patients had a tendency to exceed the cutoff value. Conclusion: The EA levels were significantly correlated as patients’ severity rise. Measuring EA levels on admission to ICU may provide a mechanism to identify and target severe septic patients.
Long‐term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke

Neural stem cells (NSCs) in the adult rat subventricular zone (SVZ) generate new striatal neurons during several months after ischemic stroke. Whether the microglial response associated with ischemic injury extends into SVZ and influences neuroblast production is unknown. Here, we demonstrate increased numbers of activated microglia in ipsilateral SVZ concomitant with neuroblast migration into the striatum at 2, 6, and 16 weeks, with maximum at 6 weeks, following 2 h middle cerebral artery occlusion in rats. In the peri‐infarct striatum, numbers of activated microglia peaked already at 2 weeks and declined thereafter. Microglia in SVZ were resident or originated from bone marrow, with maximum proliferation during the first 2 weeks postinsult. In SVZ, microglia exhibited ramified or intermediate morphology, signifying a downregulated inflammatory profile, whereas amoeboid or round phagocytic microglia were frequent in the peri‐infarct striatum. Numbers of microglia expressing markers of antigen‐presenting cells (MHC‐II, CD86) increased in SVZ but very few lymphocytes were detected. Using quantitative PCR, strong short‐ and long‐term increase (at 1 and 6 weeks postinfarct) of insulin‐like growth factor‐1 (IGF‐1) gene expression was detected in SVZ tissue. Elevated numbers of IGF‐1‐expressing microglia were found in SVZ at 2, 6, and 16 weeks after stroke. At 16 weeks, 5% of microglia but no other cells in SVZ expressed the IGF‐1 protein, which mitigates apoptosis and promotes proliferation and differentiation of NSCs. The long‐term accumulation of microglia with proneurogenic phenotype in the SVZ implies a supportive role of these cells for the continuous neurogenesis after stroke. © 2008 Wiley‐Liss, Inc.
Defining neonatal sepsis

Purpose of review Although infection rates have modestly decreased in the neonatal intensive care unit (NICU) as a result of ongoing quality improvement measures, neonatal sepsis remains a frequent and devastating problem among hospitalized preterm neonates. Despite multiple attempts to address this unmet need, there have been minimal advances in clinical management, outcomes, and accuracy of diagnostic testing options over the last 3 decades. One strong contributor to a lack of medical progress is a variable case definition of disease. The inability to agree on a precise definition greatly reduces the likelihood of aligning findings from epidemiologists, clinicians, and researchers, which, in turn, severely hinders progress toward improving outcomes. Recent findings Pediatric consensus definitions for sepsis are not accurate in term infants and are not appropriate for preterm infants. In contrast to the defined multistage criteria for other devastating diseases encountered in the NICU (e.g., bronchopulmonary dysplasia), there is significant variability in the criteria used by investigators to substantiate the diagnosis of neonatal sepsis. Summary The lack of an accepted consensus definition for neonatal sepsis impedes our efforts toward improved diagnostic and prognostic options, and accurate outcomes information for this vulnerable population.
Prediction of neonatal respiratory distress syndrome via pulmonary artery Doppler examination

Abstract Objective: We aimed with this study to evaluate the role of pulmonary artery acceleration time to ejection time ratio (PATET) in the prediction of respiratory distress syndrome (RDS) in preterm neonates. Materials and methods: In this prospective cohort study, 105 singleton pregnant women with no congenital abnormalities and pregnancy complications who delivered before 37 weeks of gestational age were included. All the patients underwent ultrasound examination to obtain fetal pulmonary artery Doppler. 15 patients were excluded from the study as they did not give birth within 3 days subsequent to ultrasound examination, or inadequate Doppler measurements. After delivery the neonates were grouped according to diagnosis of RDS as RDS + and RDS−. Results: One hundred five women met the inclusion criteria. Regarding the Doppler findings; only the PATET ratio was significantly different between the groups (0.2965 ± 0.042 versus 0.386 ± 0.068 p < .001, Z = −5.206). There was an inverse correlation between the diagnosis of RDS in the neonates and the PATET values, even after adjusted for gestational age estimated fetal weight and fetal gender (r = −0.52 and p = .0017). A cut-off value of 0.327 provided optimal specificity of 77.1%, a sensitivity of 90.9%, a negative predictive value of 95.4%, and a positive predictive value 52.7%. Conclusions: In consideration of these results fetal PATET ratio is a promising noninvasive tool to predict RDS in cases of preterm deliveries.
Wnt/β-catenin Signaling Regulates Cranial Base Development and Growth

Wnt proteins and β-catenin signaling regulate major processes during embryonic development, and we hypothesized that they regulate cranial base synchondrosis development and growth. To address this issue, we analyzed cartilage-specific β-catenin-deficient mice. Mutant synchondroses lacked typical growth plate zones, and endochondral ossification was delayed. In reciprocal transgenic experiments, cartilage overexpression of a constitutive active Lef1, a transcriptional mediator of Wnt/β-catenin signaling, caused precocious chondrocyte hypertrophy and intermingling of immature and mature chondrocytes. The developmental changes seen in β-catenin-deficient synchondroses were accompanied by marked reductions in Ihh and PTHrP as well as sFRP-1, an endogenous Wnt signaling antagonist and a potential Ihh signaling target. Thus, Wnt/β-catenin signaling is essential for cranial base development and synchondrosis growth plate function. This pathway promotes chondrocyte maturation and ossification events, and may exert this important role by dampening the effects of Ihh-PTHrP together with sFRP-1.
Topical application of Aggregatibacter actinomycetemcomitans cytolethal distending toxin induces cell cycle arrest in the rat gingival epithelium in vivo.

BACKGROUND Aggregatibacter actinomycetemcomitans is one of the etiological pathogens implicated in the onset of periodontal disease. This pathogen produces cytolethal distending toxin (CDT) that acts as a genotoxin to induce cell cycle arrest and cellular distension in cultured cell lines. Therefore, CDT is a possible virulence factor; however, the in vivo activity of CDT on periodontal tissue has not been explored. Here, CDT was topically applied into the rat molar gingival sulcus; and the periodontal tissue was histologically and immunohistochemically examined. MATERIALS AND METHODS Recombinant purified A. actinomycetemcomitans CDT was applied to gingival sulcus of male Wistar rats and tissue samples were immunohistochemmically examined. RESULTS One day after application, infiltration of neutrophils and dilation of blood vessels in the gingival connective tissue were found. At day three, desquamation and detachment of cells in the junctional epithelium was observed. This abrasion of junctional epithelium was not observed in rats treated with mutated CDT, in which a His274Ala mutation is present in the CdtB subunit. This indicates the tissue abrasion may be caused by the genotoxicity of CdtB. Expression of the proliferating cell nuclear antigen (PCNA), a marker for proliferating cells, was significantly suppressed using CDT treatment in the junctional epithelium and gingival epithelium. CONCLUSION Using the rat model, these data suggest CDT intoxication induces cell cycle arrest and damage in periodontal epithelial cells in vivo.
Sepsis: etiología, manifestaciones clínicas y diagnóstico

La infeccion bacteriana es la causa mas comun de sepsis y shock septico, siendo los germenes gram-negativos los mas frecuentemente involucrados, seguidos muy de cerca por los microorganismos grampositivos (1). Los virus tambien pueden verse involucrados como causa de sepsis, sobre todo en individuos con inmunocompromiso grave existe amplia evidencia de que un cuadro de shock septico florido puede ser causado por virus del herpes y la infeccion mas grave puede ser por citomegalovirus en receptores de transplante de medula osea. En el paciente inmunocomprometido tambien es habitual el herpes zoster diseminado con sindrome infeccioso acompanado de erupcion cutanea vesicular, a menudo de neumonia difusa y con menor frecuencia afeccion del sistema nervioso central o hepatica. El virus del herpes simple tambien llega a causar sindrome infeccioso evidente en estas personas, raras veces afeccion visceral; con menor frecuencia este virus ocasiona tambien un cuadro septico con CID y hepatitis fulminante en mujeres embarazadas por lo demas inmunocompetentes. El virus del dengue y los enterovirus suelen verse tambien generando cuadros de shock septico. Otras causas no bacterianas son los parasitos de los cuales el Plasmodium falciparum , las rickettsiosis (2) y los hongos.
Clinical genetics of craniosynostosis

Purpose of review When providing accurate clinical diagnosis and genetic counseling in craniosynostosis, the challenge is heightened by knowledge that etiology in any individual case may be entirely genetic, entirely environmental, or anything in between. This review will scope out how recent genetic discoveries from next-generation sequencing have impacted on the clinical genetic evaluation of craniosynostosis. Recent findings Survey of a 13-year birth cohort of patients treated at a single craniofacial unit demonstrates that a genetic cause of craniosynostosis can be identified in one quarter of cases. The substantial contributions of mutations in two genes, TCF12 and ERF, is confirmed. Important recent discoveries are mutations of CDC45 and SMO in specific craniosynostosis syndromes, and of SMAD6 in nonsyndromic midline synostosis. The added value of exome or whole genome sequencing in the diagnosis of difficult cases is highlighted. Summary Strategies to optimize clinical genetic diagnostic pathways by combining both targeted and next-generation sequencing are discussed. In addition to improved genetic counseling, recent discoveries spotlight the important roles of signaling through the bone morphogenetic protein and hedgehog pathways in cranial suture biogenesis, as well as a key requirement for adequate cell division in suture maintenance.
Effects of herpes simplex virus type 1 infection on immune functions of human neutrophils.

BACKGROUND AND OBJECTIVE Herpesviruses may play roles in the development of periodontal diseases. This study analyzed the effects of herpes simplex virus type 1 (HSV-1) infection on neutrophil function. The effects of lipopolysaccharide (LPS) from the periodontal pathogen, Porphyromonas gingivalis, during HSV-1 infection were also determined. MATERIAL AND METHODS Purified HSV-1 was pretreated with buffer containing no serum, with HSV-1 immunoglobulin G (IgG)-positive serum (HSV-1 antiserum) or with control serum. Neutrophils were mock-infected or infected with the pretreated HSV-1. Viral binding and phagosome formation were detected using immunostaining. Intracellular reactive oxygen species (ROS) were determined using 2',7'-dichlorofluorescin diacetate and fluorometry. Leukotriene B(4) (LTB(4)) and interleukin-8 (IL-8) were detected using enzyme immunoassays. Release of matrix metalloproteinase-9 (MMP-9) was examined using gelatin zymography. Phosphorylation of Akt/glycogen synthase kinase-3 (GSK-3) was determined using western blotting. RESULTS HSV-1 bound directly to neutrophils and enhanced the release of MMP-9. HSV-1 immune complexes, formed in the HSV-1 antiserum, bound neutrophils and induced the formation of early phagosome more effectively than did HSV-1 alone. The relative levels of ROS and phosphorylation of Akt/GSK-3 were increased significantly in neutrophils after infection with HSV-1 immune complexes. Infection with HSV-1 and HSV-1 immune complexes also stimulated the production of inflammatory mediators, LTB(4) and IL-8. Moreover, LPS enhanced the HSV-1-stimulatory production of IL-8. CONCLUSION This study demonstrated differences in neutrophils infected with HSV-1 alone or with HSV-1 immune complexes, suggesting that opsonization of HSV-1 might enhance its effects on neutrophils. The in vitro findings suggest that HSV-1 infection may induce the inflammatory response and affect periodontal health.
Pediatric traumatic brain injury: an update of research to understand and improve outcomes

Purpose of review Traumatic brain injury is the leading cause of death in the pediatric population. The purpose of this review is to highlight recent contributions in evaluation, management, and predictors of outcome in pediatric traumatic brain injury. Recent findings Advances have been made in defining the critical Glasgow Coma Score for predicting poor outcome and in developing the Relative Head Injury Severity Score, which can assess severity of traumatic brain injury from administrative datasets. More information regarding the radiation risks of head computed tomography imaging and guidelines for the appropriate use of imaging have recently been evaluated. Important steps have also been taken to reduce secondary brain injury through the use of hypertonic saline and induced hypothermia. There continues to be long-term neurodevelopmental deficits among survivors and new tools to assess these deficits have been developed and tested. Finally, increased investigation into understanding the impact of minority race and socioeconomic status has on outcome following traumatic brain injury has determined the existence of disturbing disparities. Summary Traumatic brain injury is the leading cause of mortality and is a major public health issue in the pediatric population. There have been many recent contributions in the diagnosis, treatment, and long-term morbidity of traumatic brain injury. Ongoing work is needed to improve outcomes of traumatic brain injury equitably for all patients.
Emerging Issues in Demographic Research in the United States.

Chastened by the unanticipated scale and duration of the American baby boom, U.S. demographers have tended to keep rather close to their data. This Chapter abandons that tradition, and speculates about the processes underlying recent trends in U.S. families. The discussion then briefly overviews emerging data and research styles relating to family transitions, and then concludes by describing the design and scope of our National Survey of Families and Households.
Pain as a Human Right

On October 11, 2004, the International Association for the Study of Pain (IASP), the World Health Organization (WHO), and the European Federation of IASP Chapters (EFIC) held a Global Day against Pain campaign to promote pain relief as a human right. International leaders in pain management and public health participated in the full day program that took place in Geneva Switzerland and was simultaneously broadcast around the world through the Word Wide Web. The declaration and statements that were released and announced, and selected contents of the program are summarized in this report.
Refractory angina: new drugs on the block

Refractory angina constitutes an advanced form of stable angina and refers to patients with symptomatic myocardial ischemia refractory to standard medical treatment. Surgical or percutaneous coronary revascularization is not considered a vital option for those patients due to the anatomical complexity of coronary artery disease (CAD) and/or pertinent comorbidities [1]. This subgroup of CAD patients represents a continuously growing population. Recent epidemiological data estimate that approximately up to 15% of the stable CAD population fall into this category [2,3]. Traditional treatment approaches include increasing coronary blood oxygen supply and decreasing oxygen consumption while novel new treatments target myocyte metabolism modulation and coronary flow redistribution. Current multidisciplinary management of refractory angina patients combines intensified traditional and newer medical agents with novel non-pharmacological interventional and noninterventional techniques [4]. These include among others, enhanced external counterpulsation, spinal cord stimulation, reduction of coronary sinus, gene therapy, and embolization/ intermittent occlusion of internal thoracic arteries aiming to improve non-coronary collateral myocardial blood flow [4–6]. Pharmacotherapy constitutes the basis of refractory angina management [7]. While standard antianginal therapy, i.e. betablockers, calcium channel blockers, and nitrates, fails to provide adequate symptoms relief, a number of newer agents have emerged and are currently in use. Ivabradine, ranolazine, and trimetazidine are the most frequently utilized amongst the ‘non-traditional’ antianginal regimens. These agents target either well-established mechanisms of ischemia, i.e. the imbalance between myocardial oxygen supply/demand or metabolic routes in the ischemic myocardium promoting more efficient energy utilization. Their safety and efficacy have been evaluated in large clinical studies and some of those drugs have been already implemented in clinical practice guidelines of European and American cardiovascular societies for the treatment of patients with stable CAD [8,9].
Low antigenicity of hematopoietic progenitor cells derived from human ES cells

correspondence: nicholas Zavazava University of iowa hospitals and clinics, Department of internal Medicine, 200 hawkins Drive, c51-F, iowa city, iowa 52242, UsA Tel +1 319 384 6577 Fax +1 319 356 8280 email nicholas-zavazava@uiowa.edu Abstract: Human embryonic stem (hES) cells are essential for improved understanding of diseases and our ability to probe new therapies for use in humans. Currently, bone marrow cells and cord blood cells are used for transplantation into patients with hematopoietic malignancies, immunodeficiencies and in some cases for the treatment of autoimmune diseases. However, due to the high immunogenicity of these hematopoietic cells, toxic regimens of drugs are required for preconditioning and prevention of rejection. Here, we investigated the efficiency of deriving hematopoietic progenitor cells (HPCs) from the hES cell line H13, after co-culturing with the murine stromal cell line OP9. We show that HPCs derived from the H13 ES cells poorly express major histocompatibility complex (MHC) class I and no detectable class II antigens (HLA-DR). These characteristics make hES cell-derived hematopoietic cells (HPCs) ideal candidates for transplantation across MHC barriers under minimal immunosuppression.