Miracle-dz/UniFAR-FTUs huggingface dataset:
Fetal Intervention Increases Maternal T Cell Awareness of the Foreign Conceptus and Can Lead to Immune-Mediated Fetal Demise

Fetal interventions to diagnose and treat congenital anomalies are growing in popularity but often lead to preterm labor. The possible contribution of the maternal adaptive immune system to postsurgical pregnancy complications has not been explored. We recently showed that fetal intervention in mice increases maternal T cell trafficking into the fetus and hypothesized that this process also may lead to increased maternal T cell recognition of the foreign conceptus and subsequent breakdown in maternal–fetal tolerance. In this study, we show that fetal intervention in mice results in accumulation of maternal T cells in the uterus and that these activated cells can produce effector cytokines. In adoptive transfer experiments, maternal T cells specific for a fetal alloantigen proliferate after fetal intervention, escape apoptosis, and become enriched compared with endogenous T cells in the uterus and uterine-draining lymph nodes. Finally, we demonstrate that such activation and accumulation can have a functional consequence: in utero transplantation of hematopoietic cells carrying the fetal alloantigen leads to enhanced demise of semiallogeneic fetuses within a litter. We further show that maternal T cells are necessary for this phenomenon. These results suggest that fetal intervention enhances maternal T cell recognition of the fetus and that T cell activation may be a culprit in postsurgical pregnancy complications. Our results have clinical implications for understanding and preventing complications associated with fetal surgery such as preterm labor.
Multiple pathways control cell growth and transformation: overlapping and independent activities of p53 and p21Cip1/WAF1/Sdi1

Many tumour therapies act by inducing a cellular damage response pathway mediated by the tumour suppressor protein p53. Alternative outcomes of p53 induction include apoptosis or transient cell‐cycle arrest, both thought to require the transcriptional activity of wild‐type p53. Current research highlights the action of a p53‐activated gene, p21Cip1/WAF1/Sdi1, which encodes a cyclin‐kinase inhibitor important in mediating p53‐dependent cell‐cycle arrest, while programmed cell death in response to DNA damage requires transcriptionally active p53 but not activation of p21Cip1/WAF1/Sdi1. This review examines the roles of p53 and p21Cip1/WAF1/Sdi1 in controlling cell proliferation, in the light of a new study on expression of p53 and p21 Cip1/WAF1/Sdi1 in squamous cell carcinoma of the larynx. © 1997 John Wiley & Sons, Ltd.
Challenging the Other: Exploring the Role of Opponent Gender in Digital Game Competition for Female Players

Abstract The present study investigated the effect of opponent gender on the game experience of female players. Concretely, it looked into skill perception and player emotions of women in same gender and cross-gender game competition. We set up a 2×2×2 (male vs. female opponent×low vs. high competitive women×lost vs. won game) experimental design in which women were instructed to play against a proclaimed male and female competitor. Unknowingly, however, participants played against an AI, which was configured to produce a winning and a losing condition for each opponent by manipulating difficulty. Results indicated that opponent gender only had an effect on perceived stress, which was higher with male opponents. Moreover, players evaluated their own gaming skills as lower and the skills of presumed male opponents as higher when they thought they were playing against men. Importantly, our results also showed that the above described pattern for self-perceived skills and perceived opponent skills was modulated by trait competitiveness with a larger effect size for low competitive women. Overall, this study illustrates that gender dynamics affect the play experience of women in cross-gender gaming competition. Implications and suggestions for future research are discussed.
Psychosocial Status and Cognitive Achievement in Peru

This paper assesses the importance of psychosocial status in the accumulation of cognitive skills during the transition from mid to late childhood. We use longitudinal data from a cohort of 700 Peruvian children drawn from a very rich dataset, the Young Lives Survey, to test the impact of children's perception of respect at the age of 8 on cognitive achievement 4 years later, controlling for cognitive skills at the age of 8, lagged child and household characteristics, and community fixed effects. This empirical specification is akin to estimating a conditional demand function for cognitive skills, which deals with some of the main pitfalls of skill endogeneity. We find that poorly respected children are linked to a lower rate of cognitive accumulation than their better‐respected counterparts. As expected, we also find that previously accumulated cognitive skills enable higher subsequent cognitive skill accumulation. We go one step further by testing and finding evidence of complementarities across skills. We show that cognitive differences amplify over time between children with low and high psychosocial skills. Overall, our results suggest that psychosocial status, an aspect little studied in the context of developing countries, plays an important role in the acquisition of cognitive skills during childhood.
The influence of social networks and social support on violence by persons with serious mental illness.

OBJECTIVE The authors examined the relationship between violent acts and threats by persons with serious mental illness, the size and composition of their social networks, and characteristics of the social support they received. METHODS A group of 169 respondents with serious mental illness and 59 of their significant others were interviewed using structured and semi-structured protocols to elicit data on demographic characteristics, clinical characteristics, characteristics of respondents' social networks and of the social support they received, and perceptions of threat within the social network. Data on acts and threats of violence by respondents over an 18-month period were collected from self-reports by respondents and significant others and from hospital and court records. RESULTS Fifty-six respondents either threatened violence or committed a violent act during the study period. Respondents with a diagnosis of schizophrenia were more likely to commit violent acts but were not more likely to threaten violence than were respondents with other diagnoses. Respondents in larger networks, those with networks composed primarily of relatives, and those who lived with unrelated persons were more likely to threaten violence. Financial dependence on family was associated with more violent threats and acts. Respondents who perceived hostility from others were more likely to engage in violent threats and acts, and those with confused thinking were less likely to act or threaten violence. More than half of the targets of violence were respondents' relatives, particularly mothers living with a respondent. Respondents who were violent perceived their significant others as threatening but did not perceive themselves as being threatening in return. CONCLUSIONS The interpersonal and social contexts of respondents and their perceptions of these contexts are important considerations in assessing risk for violence by persons with mental illness. Mothers who live with an adult offspring with schizophrenia may be at increased risk for being a target of violence. Violence by persons with psychiatric disorders may be linked to their perceptions and experience of being threatened by others.
Efficacy of intermittent sub-glottic suctioning in prevention of ventilator-associated pneumonia- A preliminary study of 100 patients

Background and Aims: Oropharyngeal colonisation followed by aspiration of contaminated secretions is the major cause for ventilator-associated pneumonia (VAP). Pooled secretions present in the sub-glottic area above inflated endotracheal tube cuff may be aspirated into the lower airways. It was hypothesised that intermittent suctioning of sub-glottic secretions would prevent VAP. Methods: Group I (n = 50) patients were intubated with HiLo Evac™ endotracheal (ET) tube with facility for sub-glottic suctioning, and Group II (n = 50) patients were intubated with HiLo Contour™ ET tube without such facility. In the Group I, sub-glottic suctioning was performed every 2 h. Incidence of VAP, mean ventilator days, Intensive Care Unit (ICU) stay and mortality were compared. Qualitative variables were reported as percentages and were compared by Chi-square test or unpaired two-tailed, Fisher′s exact test, as appropriate, to analyse the significance of difference between the two groups. Results: The two groups were similar with respect to demographic characteristics. VAP was seen in 6% of patients in Group I and 22% of patients in Group II (P = 0.021). Both early- and late-onset VAPs were significantly reduced in Group I. Both ventilator days (8.0 vs. 6.45; P = 0.001) and ICU stay (8.33 vs. 6.33; P = 0.001) on the day of onset of VAP were significantly more in the Group I. Total ventilator days were significantly less (6.52 vs. 8.32; P = 0.006) with lower incidence of mortality (36% vs. 48%; P = 0.224) in the Group I. Conclusion: Intermittent sub-glottic suctioning reduces the incidence of VAP including late-onset VAP.
Impact of Human Growth Hormone on Plasma Lipoprotein Concentrations

To evaluate whether the moderately elevated human growth hormone concentration, seen in insulin dependent diabetic patients, has any impact on lipoproteins, human growth hormone was given to nondiabetic persons in doses which would bring their plasma human growth hormone concentration up in the same level as seen in insulin dependent diabetic patients. After one week of treatment with human growth hormone we found total plasma triglyceride to be significantly raised (0.98 mmol/l +/- 0.28 mmol/l (mean +/- SD) before versus 1.27 mmol/l +/- 0.38 mmol/l (mean +/- SD) after treatment). Very low density lipoprotein (VLDL) was separated into two fractions (VLDL-1 and VLDL-2) of which VLDL-2 is regarded as a VLDL-remnant which is suggested to be of importance for development of atherosclerosis. After one week of human growth hormone treatment there were no changes in VLDL-1 concentrations whereas a significant raise in VLDL-2 triglyceride and VLDL-2 cholesterol was seen.
Tracer coupling between fish rod horizontal cells: Modulation by light and dopamine but not the retinal circadian clock

Horizontal cells are second order neurons that receive direct synaptic input from photoreceptors. In teleosts horizontal cells can be divided into two categories, cone-connected and rod-connected. Although the anatomy and physiology of fish cone horizontal cells have been extensively investigated, less is known about rod horizontal cells. This study was undertaken to determine whether light and/or the circadian clock regulate gap junctional coupling between goldfish rod horizontal cells. We used fine-tipped, microelectrode intracellular recording to monitor rod horizontal cells under various visual stimulation conditions, and tracer (biocytin) iontophoresis to visualize their morphology and evaluate the extent of coupling. Under dark-adapted conditions, rod horizontal cells were extensively coupled to cells of like-type (homologous coupling) with an average of ∼120 cells coupled. Under these conditions, no differences were observed between day, night, the subjective day, and subjective night. In addition, under dark-adapted conditions, application of the dopamine D2-like agonist quinpirole (1 μM), the D2-like antagonist spiperone (10 μM), or the D1-like antagonist SCH23390 (10 μM) had no effect on rod horizontal cell tracer coupling. In contrast, the extent of tracer coupling was reduced by ∼90% following repetitive light (photopic range) stimulation of the retina or application of the D1-agonist SKF38393 (10 μM) during the subjective day and night. We conclude that similarly to cone horizontal cells, rod horizontal cells are extensively coupled to one another in darkness and that the extent of coupling is dramatically reduced by bright light stimulation or dopamine D1-receptor activation. However, in contrast to cone horizontal cells whose light responses are under the control of the retinal clock, the light responses of rod horizontal cells under dark-adapted conditions were similar during the day, night, subjective day, and subjective night thus demonstrating that they are not under the influence of the circadian clock.
Defective calcium influx factor activity in neutrophils from patients with localized juvenile periodontitis.

BACKGROUND Localized juvenile periodontitis (LJP) is an early-onset periodontal disease associated with neutrophil dysfunction, including defective chemotaxis, reduced protein kinase C (PKC) activity, and reduced calcium entry. These observations are important because reduced availability of cytosolic-free calcium concentration in the cell will have detrimental consequences for the numerous cytosolic calcium concentration-dependent pathways. In particular, there is a direct relationship between Ca2+ flux and the cell activation enzyme PKC. In this report, we focused on the mechanism of calcium entry, investigating a newly described molecule, calcium influx factor (CIF). CIF is thought to be a second messenger for the opening of membrane calcium channels when intracellular calcium stores are depleted. We examined CIF activity in neutrophils from normal subjects and LJP patients. METHODS Neutrophils from 11 LJP patients, 3 adult periodontitis (AP) patients, and 12 normal subjects were isolated from peripheral venous blood. CIF was extracted with thapsigargin, a Ca2+-ATPase inhibitor, from isolated neutrophils and CIF activity measured using a 45CaCl2 uptake assay. RESULTS The CIF activity in neutrophils from LJP patients ranged from 98.9 to 281.5 units/mg protein (mean = 180.2 +/- 56.3) and from 291.9 to 755.5 units/mg protein (mean = 528.8 +/- 153.8) in non-periodontal disease controls. CIF activity in AP patients was also measured and found to be similar to controls. The CIF activity in LJP patients was statistically significantly reduced compared to that in normal subjects (P <0.001). CONCLUSIONS This study suggests that CIF activity may be an important determinant in neutrophil abnormalities in LJP.
Relationship between five common viruses and febrile seizure in children

Objectives: To examine the role of viruses in febrile seizures (FS) by comparing the relative risk (RR) of developing FS with common viral infections and subsequent risk of recurrence. Methods: We matched the medical records of all children admitted with FS over 5 years and the contemporary records for all admissions for febrile illnesses associated with influenza, adenovirus, parainfluenza, respiratory syncytial virus (RSV) and rotavirus to calculate the RR of FS following these viral infections. For patients admitted for a first FS, we carried multivariate analysis for type of viral infection, age of onset, family history, complex FS features and maximum temperature during the episode, to identify the risk factors for recurrence. Results: There were 923 admissions for FS, of which 565 were for first seizures. The five most common viruses in FS were influenza (163/923, 17.6%), adenovirus (63/923, 6.8%), parainfluenza (55/923, 6%), RSV (25/923, 2.7%) and rotavirus (12/923, 1.3%). Incidences of FS in febrile illnesses due to these viruses were 20.8% (163/785) for influenza, 20.6% (55/267) for parainfluenza, 18.4% (63/343) for adenovirus, 5.3% (25/468) for RSV and 4.3% (12/280) for rotavirus. Complex FS occurred in 20.6% (n = 191) and the risk of developing complex FS was similar for the five viruses. Overall recurrence rate was 20.5% and was not predicted by type of viral infection. Conclusion: The risk of developing FS is similar with influenza, adenovirus or parainfluenza and is higher than with RSV or rotavirus. Type of viral infection is not important in predicting complex features or future recurrences.
Mesenchymal Stem Cells Alter Migratory Property of T and Dendritic Cells to Delay the Development of Murine Lethal Acute Graft‐Versus‐Host Disease

Due to the potent immunoregulatory capacity, mesenchymal stem cells (MSCs) have been used in clinical trials to treat acute graft‐versus‐host disease (aGvHD), although the detailed in vivo mechanisms remain elusive. In a murine lethal aGvHD model, MSCs delayed the development of the disease. Interestingly, we found that MSC infusion increased the number of T lymphocytes in the secondary lymphoid organs (SLOs). Since the expression of CD62L and CCR7 is prerequisite for lymphocyte migration into SLOs, the in vitro experiments revealed that in the presence of MSCs, T lymphocytes (including CD4+CD25+ regulatory T cells) preferred to take the naive‐like phenotype (CD62L+/CCR7+) in mixed lymphocyte reaction and maintained the migratory activity elicited by secondary lymphoid tissue chemokine (SLC). Dendritic cells (DCs) are the initiator of immune response. CCR7 expression is pivotal for their maturation and migration into SLOs. However, CCR7 expression and SLC‐driven migratory activity of DCs were remarkably suppressed by MSC coculture. The processes above were realized mainly through secretory mechanism. Consistently, MSC infusion maintained T lymphocytes to take CD62L+/CCR7+ phenotype and decreased the CCR7 expression and proportion of DCs in SLOs of aGvHD mice. In conclusion, the altered migratory properties of T cells and DCs might contribute to the immunosuppressive activity of transplanted MSCs in the setting of aGvHD.
The Times of Ira Hirsh: Multiple Ranges of Auditory Temporal Perception.

Ira Hirsh was among the first to recognize that the auditory system does not deal with temporal information in a unitary way across the continuum of time intervals involved in speech processing. He identified the short range (extending from 1 to 20 milliseconds) as that of phase perception, the range between 20 and 100 milliseconds as that in which auditory patterns emerge, and the long range from 100 milliseconds and longer as that of separate auditory events. Furthermore, he also was among the first to recognize that auditory time perception heavily depended on spectral context. A study of the perception of sequences representing different temporal orders of three tones, by Hirsh and the author (e.g., Divenyi and Hirsh, 1978) demonstrated the dependence of auditory sequence perception on both time range and spectral context, and provided a bridge between Hirsh's view of auditory time and Bregman's view of stream segregation. A subsequent search by the author for psychophysical underpinnings of the cocktail-party phenomenon (e.g., Divenyi and Haupt, 1997) suggests that segregation of simultaneous streams of speech might rely on the ability to follow spectral changes in the demisyllabic-to-syllabic (100 to 200 milliseconds) range (i.e., Hirsh's long range). Learning Outcomes: As a result of this activity, the participant will be able to (1) describe the importance of temporal processing in hearing; and (2) identify time ranges where the auditory system will spontaneously adopt different analysis techniques.
CTGF enhances the motility of breast cancer cells via an integrin-αvβ3–ERK1/2-dependent S100A4-upregulated pathway

Connective tissue growth factor (CTGF) expression is elevated in advanced stages of breast cancer, but the regulatory role of CTGF in invasive breast cancer cell phenotypes is unclear. Presently, overexpression of CTGF in MCF-7 cells (MCF-7/CTGF cells) enhanced cellular migratory ability and spindle-like morphological alterations, as evidenced by actin polymerization and focal-adhesion-complex aggregation. Reducing the CTGF level in MDA-MB-231 (MDA231) cells by antisense CTGF cDNA (MDA231/AS cells) impaired cellular migration and promoted a change to an epithelial-like morphology. A neutralizing antibody against integrin αvβ3 significantly attenuated CTGF-mediated ERK1/2 activation and cellular migration, indicating that the integrin-αvβ3–ERK1/2 signaling pathway is crucial in mediating CTGF function. Moreover, the cDNA microarray analysis revealed CTGF-mediated regulation of the prometastatic gene S100A4. Transfection of MCF-7/CTGF cells with AS-S100A4 reversed the CTGF-induced cellular migratory ability, whereas overexpression of S100A4 in MDA231/AS cells restored their high migratory ability. Genetic and pharmacological manipulations suggested that the CTGF-mediated S100A4 upregulation was dependent on ERK1/2 activation, with expression levels of CTGF and S100A4 being closely correlated with human breast tumors. We conclude that CTGF plays a crucial role in migratory/invasive processes in human breast cancer by a mechanism involving activation of the integrin-αvβ3–ERK1/2–S100A4 pathway.
Pharmacological treatment in moderate-to-severe Alzheimer's disease.

BACKGROUND Moderate-to-severe stage Alzheimer's disease (AD) is a clinically diagnosable entity that represents a substantial burden to our healthcare system in terms of its prevalence, symptomatology, caregiver stress and economics. OBJECTIVE In this paper, we review the data from currently available clinical trials aimed at treatment of this later stage of the disease. METHODS A literature search was performed and published randomized controlled trials (RCTs) in which the majority of the study population consisted of Alzheimer patients in the moderate-to-severe stage were selected for review. RESULTS A total of nine RCTs were identified in which the study population consisted of mainly moderate-to-severe AD patients. The results from these studies suggest that memantine and donepezil, individually or in combination, provide measurable global, cognitive and behavioral benefits in AD patients. CONCLUSION Pharmacological treatment of moderate-to-severe AD patients can be beneficial. However, cost-benefit data are limited, and the long-term effects and the optimal duration of treatment as patients continue to progress to more severe stages are unknown and require further investigation.
Video-Assisted Thoracic Surgery Lobectomy for Non-small Cell Lung Cancer in Patients with a Charlson Comorbidity Index Score of Two or More

Introduction: We evaluated the feasibility and safety of the video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) in patients with comorbidity. Methods: Between April 2000 and December 2006, a prospective database of 58 consecutive patients undergoing a VATS lobectomy for NSCLC, who had a Charlson comorbidity index score of 2 or more, was retrospectively analyzed. The demographic, perioperative, histopathologic, and outcome variables, including the recurrence and survival, were assessed. Results: The VATS lobectomy was successfully performed in 57 patients (16 women and 41 men; median age, 70 years). Twenty-three patients (40.4%) were aged 75 years or older. The total score of the Charlson comorbidity index was as follows: 2 in 26 patients, 3 in 13 patients, 4 in 12 patients, 5 in five patients, and 6 in one patient. None of the patients required a blood transfusion during surgery or during the postoperative course. We observed no intraoperative or in-hospital deaths, and no complications occurred in the 45 patients (78.9%). At a median follow-up of 34 months, a recurrence was observed in five patients who had advanced stages: a local recurrence in one and a distant recurrence in four. The overall 5-year survival rates for postoperative stage IA (n = 25) and IB (n = 16) were 100% and 94%, respectively. Conclusions: We believe that a VATS lobectomy is a feasible and safe procedure for NSCLC in patients with comorbidity because this modality demonstrates an acceptable morbidity and a favorable oncologic outcome.