Miracle-dz/UniFAR-FTUs huggingface dataset:
Family factors in end-of-life decision-making: family conflict and proxy relationship.

BACKGROUND Few studies have examined proxy decision-making regarding end-of-life treatment decisions. Proxy accuracy is defined as whether proxy treatment choices are consistent with the expressed wishes of their index elder. The purpose of this study was to examine proxy accuracy in relation to two family factors that may influence proxy accuracy: perceived family conflict and type of elder-proxy relationship. METHODS Telephone interviews with 202 community-dwelling elders and their proxy decision makers were conducted including the Life-Support Preferences Questionnaire (LSPQ), and a measure of family conflict, and sociodemographic characteristics, including type of relationship. RESULTS Elder-proxy accuracy was associated with the type of elder-proxy relationship. Adult children demonstrated the lowest elder-proxy accuracy and spousal proxies the highest elder-proxy accuracy. Elder-proxy accuracy was associated with family conflict. Proxies reporting higher family conflict had lower elder-proxy accuracy. No interaction between family conflict and relationship type was revealed. CONCLUSIONS Spousal proxies were more accurate in their substituted judgment than adult children, and proxies who perceive higher degree of family conflict tended to be less accurate than those with lower family conflict. Health care providers should be aware of these family factors when discussing advance care planning.
Puffed-Up But Shaky Selves: State Self-Esteem Level and Variability in Narcissists

Different theoretical conceptualizations characterize grandiose narcissists by high, yet fragile self-esteem. Empirical evidence, however, has been inconsistent, particularly regarding the relationship between narcissism and self-esteem fragility (i.e., self-esteem variability). Here, we aim at unraveling this inconsistency by disentangling the effects of two theoretically distinct facets of narcissism (i.e., admiration and rivalry) on the two aspects of state self-esteem (i.e., level and variability). We report on data from a laboratory-based and two field-based studies (total N = 596) in realistic social contexts, capturing momentary, daily, and weekly fluctuations of state self-esteem. To estimate unbiased effects of narcissism on the level and variability of self-esteem within one model, we applied mixed-effects location scale models. Results of the three studies and their meta-analytical integration indicated that narcissism is positively linked to self-esteem level and variability. When distinguishing between admiration and rivalry, however, an important dissociation was identified: Admiration was related to high (and rather stable) levels of state self-esteem, whereas rivalry was related to (rather low and) fragile self-esteem. Analyses on underlying processes suggest that effects of rivalry on self-esteem variability are based on stronger decreases in self-esteem from one assessment to the next, particularly after a perceived lack of social inclusion. The revealed differentiated effects of admiration and rivalry explain why the analysis of narcissism as a unitary concept has led to the inconsistent past findings and provide deeper insights into the intrapersonal dynamics of grandiose narcissism governing state self-esteem.
Mixed brain pathologies account for most dementia cases in community-dwelling older persons

Objective: To examine the spectrum of neuropathology in persons from the Rush Memory and Aging Project, a longitudinal community-based clinical-pathologic cohort study. Methods: The study includes older persons who agreed to annual clinical evaluation and brain donation. We examined the neuropathologic diagnoses, including Alzheimer disease (AD) (NIA-Reagan Criteria), cerebral infarctions, and Parkinson disease/Lewy body disease (PD/LBD), in the first 141 autopsies. We calculated the frequency of each diagnosis alone and mixed diagnoses. We used logistic regression to compare one to multiple diagnoses on the odds of dementia. Results: Twenty persons (14.2%) had no acute or chronic brain abnormalities. The most common chronic neuropathologic diagnoses were AD (n = 80), cerebral infarctions (n = 52), and PD/LBD (n = 24). In persons with dementia (n = 50), 38.0% (n = 19) had AD and infarcts, 30.0% (n = 15) had pure AD, and 12% each had vascular dementia (n = 6) and AD with PD/LBD (n = 6). In those without dementia (n = 91), 28.6% (n = 26) had no chronic diagnostic abnormalities, 24.2% (n = 22) had pure AD, and 17.6% (n = 16) had infarctions. In persons with dementia, over 50% had multiple diagnoses (AD, PD/LBD, or infarcts), whereas, in persons without dementia, over 80% had one or no diagnosis. After accounting for age, persons with multiple diagnoses were almost three times (OR = 2.8; 95% CI = 1.2, 6.7) more likely to exhibit dementia compared to those with one pathologic diagnosis. Conclusion: The majority of community-dwelling older persons have brain pathology. Those with dementia most often have multiple brain pathologies, which greatly increases the odds of dementia.
Analytical evaluation of blocking probability in optical burst switching networks

In this paper we present a new analytical model for evaluating the blocking probability in Just-Enough-Time-based optical burst switching networks. The proposed analytical model takes into consideration the effects of the burst offset time and the burst length on the blocking probability. We use a (M+1)-state nonhomogenous Markov chain to describe the state of an output link carrying M wavelength channels. In addition, we model each wavelength channel by a 2-state Markov chain. The offset time is drawn from a specified distribution so that wavelength reservation requests, made before a given time, build up to be a workload whose mean value declines with the reservation starting time. Furthermore, we express the blocking probability in terms of first passage time distributions to account for the burst length. To verify its accuracy, the model results are compared with the results of a sophisticated discrete-event simulation model. The model results were found to be in satisfactory agreement with simulation results.
Pattern of Bone Markers during Pregnancy and Their Changes after Delivery

Objective: To investigate whether bone resorption markers change during pregnancy and lactation, and how they are correlated with human placental lactogen (hPL) and PRL. Subjects: Young women before pregnancy, during pregnancy and during a 12-month post-delivery period (study group; n = 22); and age- and weight-matched normal cycling women (control group; n = 22) for a 20-month-period participated in the study. Results: In the study group, women both during pregnancy (from the 8th up to the 38th week) and during a 6-month period of lactation, pyridinoline and deoxypyridinoline urinary levels were significantly higher than those of pre-pregnancy and control women. They returned to basal values at the 12th post-delivery month. During pregnancy there were early and late peak increases, at the 8th and 32nd week, respectively. At the 32nd, 34th, 36th and 38th week of pregnancy, pyridinoline and deoxypyridinoline urinary values were significantly correlated with hPL serum levels. Conclusions: During pregnancy the maternal bone resorption seems to vary critically at early and late stages. A complete reversal of these variations seems to occur after lactation. Further studies could evaluate if changes in placental function are capable of differently interfering with maternal bone resorption.
Interaction Between Surgical Procedure for Repairing Retinal Detachment and Clinical Risk Factors for Proliferative Vitreoretinopathy

Purpose: To asses risk factors of proliferative vitreoretinopathy (PVR) and a model for predicting it. Methods: Observational, case-control. 335 patients with non-complicated retinal detachment (RD) were included: 134 developed PVR (Cases); 201 patients did not (Controls). Risk factors for PVR were identified by multivariate analysis. Influence of variables was assayed according to the surgical approach. By logistic regression analysis a model to predict the risk of developing PVR and odds ratio (OR) values for each clinical factor were estimated. Results: Risk was higher in patients > 70 years and with intraocular pressure lower than 14 (OR: 3.84; CI 95%: 2.04–7.30) and in retinal breaks larger than “1 clock hour” (OR: 2.54; CI: 1.28–5.05), extended retinal detachments (OR: 4.01; CI: 1.98–8.10) and reinterventions (OR: 1.55; CI: 1.14–9.22). Scleral surgery also was a risk factor (OR: 3.89; CI: 2.12–7.14) and aphakia/pseudophakia when scleral surgery is performed (OR: 3.33; CI: 1.54–7.22). A model to predict PVR was proposed with these results. Conclusions: Surgical approach modifies risk factors of PVR, and should be taken into account to improve the models for predicting it.
Expression of telomerase mRNA component (hTR) in transitional cell carcinoma of the upper urinary tract

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric repeats onto chromosomal ends using a segment of its RNA component as a template. Its activity has become an established indicator of the diagnosis, biologic behavior, and prognosis of several tumors. However, to the authors' knowledge, no previous study has investigated the diagnostic and prognostic importance of the expression of telomerase RNA component (hTR) in transitional cell carcinoma of the upper urinary tract (TCC‐UUT).
Retinoic Acid Receptor and Retinoid X Receptor Alterations in Lung Cancer Precursor Lesions 1

Smoking prevention will decrease lung cancer incidence in time. However , early detection would improve lung cancer prognosis in subjects at risk provided that specific markers could be identified. We previously reported that retinoic acid receptor (RAR) and retinoid X receptor (RXR) expression was altered in lung tumors. RAR-␤ gene status could be derived from corresponding allelotyping and immunohistochemistry data. We now report the continued study on lung cancer precursor lesions. Fluorescence PCR-based assays were used for allelotyping at the RAR/ RXR loci of: (a) 66 lung precursor lesions found at the free resection margins of 41 patients undergoing surgery for lung cancer (؉ 31 paired tumors); and (b) bronchial cells also found at the free resection margins from 16 current and 8 never smokers operated on for noncancerous diseases. Three microsatellites located at 3p14 –21 and 9p21 were also used for interwork comparison. Immunohistochemistry was additionally performed to evaluate P53 and RAR-␤ expression in precursor lesions. ␹ 2 tests showed significant differences (P < 0.05) when comparing the results obtained from never smokers, smokers, squamous metaplasia, dyspla-sia ؉ in situ carcinoma, and tumors. Microsatellite changes occurred frequently in all samples, but without specificity for any group (P < 0.08 – 0.52). They were globally correlated with tobacco exposure (P < 0.04), for which the RAR-␥ marker appeared as a preferential target (P < 0.004). Few reparation error phenotypes were observed, mostly at the RXR-␣ and RXR-␥ markers for which combined changes were also linearly increasing from never smokers to dysplasia ؉ in situ carcinoma (P < 0.05 and P < 0.03). RAR-␤ marker losses also increased from the first to the last group studied (P < 0.01), with a concomitant decrease in RAR-␤ protein expression and correlated p53 increased immunoreactivity (P < 0.02). Losses at 3p14, 3p21, and P16 were frequent, but no significant differences between groups could be found. Unexpectedly, high constitutive homozy-gosity was observed near the RAR-␣ locus in squamous cell lung cancer cases. RARs/RXRs form homodimers or heterodimers involved in ligand binding. Their added alterations could result in a state of functional vitamin A deficiency in the affected bronchial cells. Further deletion events drawn from a limited repertoire of specific regions such as 3p14 –21 and 9p21 could subsequently drive the deficient cells to invasive carci-noma.
Trypanosoma cruzi infection in mice induces a polyisotypic hypergammaglobulinaemia and parasite‐specific response involving high lgG2a concentrations and highly avid lgG1 antibodies

Trypanosoma cruzi infection in BALB/c mice induced a reversible polyisotypic hypergammaglobulinaemia, with particularly high levels of IgG2a, IgM and IgE. Hypergammaglobulinaemia started during the acute phase of infection and persisted during chronic disease until 11–13 weeks post‐infection (w.p.i.), when immunoglobulin levels, with the exception of IgE, returned near normal values. Parasite‐specific antibodies counted for 14 to 23% of gammaglobulinaemia, in acute and chronic infection respectively. The titres of IgM antibodies rose from two w.p.i. IgA, IgE and IgG subclass antibodies built up gradually over the time of parasite clearance (i.e., between three and six w.p.i.). All antibody isotypes, including IgM reached significant and stable titres throughout chronic infection. IgG2a, IgG1 and IgM antibodies had constantly higher titres than the other antibody isotypes. The dominance of IgG2a antibodies was due to their high plasma concentrations, around 70% of all antibodies available in the chronic infection. IgG1 had the highest functional avidity, whereas its concentration corresponded to only 10% of the whole antibody fraction. These results indicate that T. cruzi infection in mice induces a polyisotypic humoral immune response, dominated by some antibody isotypes, with major differences in concentrations and functional avidities. This could be of crucial importance in determining the outcome of infection.
Premature mortality in health regions with high aboriginal populations.

OBJECTIVES Potential years of life lost (PYLL) before age 75 in health regions with a relatively high proportion of Aboriginal residents is compared, by cause of death, with all other health regions. DATA SOURCES The findings are based on mortality data for 1995 through 1997 from the Canadian Vital Statistics Database, and on population estimates for 1995, 1996 and 1997 at the health region level. ANALYTICAL TECHNIQUES PYLL was calculated by age and sex for two groups of health regions: the 18 with a high proportion (19% or more) of Aboriginal residents and the remaining 120, which had smaller proportions of Aboriginal residents. PYLL rate differences and rate ratios were used to compare the two groups. MAIN RESULTS The PYLL rate per 1,000 person-years at risk for all causes of death was about 50% greater in the high-Aboriginal health regions than in the other group. Almost 40% of total PYLL in high-Aboriginal health regions was attributable to injuries, notably, suicide and motor vehicles accidents.
Post‐transplant lymphoproliferative disease in children

Abstract: Epstein–Barr virus (EBV)‐driven post‐transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following transplantation, and it occurs more frequently in children than in adults. Of 22 (5%) children at our institution who developed tissue‐proven PTLD 1–60 months (mean 16.5 months) following organ transplant, 11 died: nine of these 22 patients developed PTLD between 1989 and 1993, and seven (78%) died; the remaining 13 developed PTLD between 1994 and 1998, and four (31%) died (p = 0.08). All nine patients who developed PTLD < 6 months after transplant died, but 11 of 13 patients who manifested disease ≥ 6 months after transplant survived (p = 0.0002). Ten of 11 (91%) survivors, but only two of eight (25%) children who died, had serologic evidence of EBV infection at the time of PTLD diagnosis (p = 0.04). EBV seroconversion identified patients at risk for developing PTLD, but also characterized patients with sufficient immune function to survive EBV‐related lymphoid proliferation. In situ hybridization for EBER1 mRNA was diagnostically helpful because it detected EBV in tissue sections of all 20 patients with B‐cell PTLD, including those with negative serology.
The Exonuclease Domain of Lassa Virus Nucleoprotein Is Involved in Antigen-Presenting-Cell-Mediated NK Cell Responses

ABSTRACT Lassa virus is an Old World Arenavirus which causes Lassa hemorrhagic fever in humans, mostly in West Africa. Lassa fever is an important public health problem, and a safe and effective vaccine is urgently needed. The infection causes immunosuppression, probably due to the absence of activation of antigen-presenting cells (dendritic cells and macrophages), low type I interferon (IFN) production, and deficient NK cell function. However, a recombinant Lassa virus carrying D389A and G392A substitutions in the nucleoprotein that abolish the exonuclease activity and IFN activation loses its inhibitory activity and induces strong type I IFN production by dendritic cells and macrophages. We show here that during infection by this mutant Lassa virus, antigen-presenting cells trigger efficient human NK cell responses in vitro, including production of IFN-γ and cytotoxicity. NK cell activation involves close contact with both antigen-presenting cells and soluble factors. We report that infected dendritic cells and macrophages express the NKG2D ligands major histocompatibility complex (MHC) class I-related chains A and B and that they may produce interleukin-12 (IL-12), IL-15, and IL-18, all involved in NK cell functions. NK cell degranulation is significantly increased in cocultures, suggesting that NK cells seem to kill infected dendritic cells and macrophages. This work confirms the inhibitory function of Lassa virus nucleoprotein. Importantly, we demonstrate for the first time that Lassa virus nucleoprotein is involved in the inhibition of antigen-presenting cell-mediated NK cell responses. IMPORTANCE The pathogenesis and immune responses induced by Lassa virus are poorly known. Recently, an exonuclease domain contained in the viral nucleoprotein has been shown to be able to inhibit the type I IFN response by avoiding the recognition of viral RNA by cell sensors. Here, we studied the responses of NK cells to dendritic cells and macrophages infected with a recombinant Lassa virus in which the exonuclease functions have been abolished and demonstrated that NK cells are strongly activated and presented effective functions. These results show that the strategy developed by Lassa virus to evade innate immunity is also effective on NK cells, explaining the weak NK cell activation observed with the wild-type virus. By providing a better understanding of the interactions between Lassa virus and the host immune system, these results are important for the field of arenavirus biology and may be useful for a vaccine approach against Lassa fever.
Nek11, a New Member of the NIMA Family of Kinases, Involved in DNA Replication and Genotoxic Stress Responses*

DNA replication and genotoxic stresses activate various checkpoint-associated protein kinases, and checkpoint dysfunction often leads to cell lethality. Here, we have identified new members of the mammalian NIMA family of kinases, termed Nek11L and Nek11S (NIMA-related kinase11 Long and Short isoform) as novel DNA replication/damage stresses-responsive kinases. Molecular cloning and biochemical studies showed that the catalytic domain of Nek11 is most similar to Nek4 and Nek3, and substrate specificity of Nek11L is distinguishable from those of NIMA and Nek2. The expression ofnek11L mRNA increased through S to G2/M phase, and subcellular localization of Nek11 protein altered between interphase and prometaphase, suggesting multiple roles of Nek11. We found an activation of Nek11 kinase activity when cells were treated with various DNA-damaging agents and replication inhibitors, and this activation of Nek11 was suppressed by caffeine in HeLaS3 cells. The transient expression of wild-type Nek11L enhanced the aphidicolin-induced S-phase arrest, whereas the aphidicolin-induced S-phase arrest was reduced in the U2OS cell lines expressing kinase-negative Nek11L (K61R), and these cells were more sensitive to aphidicolin-induced cell lethality. Collectively, these results suggest that Nek11 has a role in the S-phase checkpoint downstream of the caffeine-sensitive pathway.
Neonatal Short-Term Outcomes of Gestational Diabetes Mellitus in Saudi Mothers: A Retrospective Cohort Study

Background: Gestational diabetes mellitus (GDM) affects up to 10% of all pregnancies and results in significant maternal and neonatal morbidities. Objectives: Our main objective was to investigate retrospectively the rate of neonatal intensive care unit (NICU) admissions and significant neonatal complications in pregnant mothers with gestational diabetes. Materials and Methods: A retrospective cohort study was conducted. The medical records of King Khalid University Hospital (KKUH) were reviewed from January till December 2007. All pregnant women with GDM along with their offsprings were included and matched with healthy pregnant women. The primary outcome was the rate of NICU admission, hypoglycemia, birth weight and length of hospital stay. Results: A total of 766 mothers (419 GDM mothers and 347 controls) with their term babies were included. Infants born to GDM mothers had significantly higher risk of NICU admissions [OR 2.7 (95% CI 1.5, 4.9), P value 0.0004], longer hospital stay and higher rates of hypoglycemia. Newborns of GDM mothers had higher rates of perinatal distress and macrosomia; however, the difference did not reach statistical significance. Conclusion: GDM remains a significant morbidity to newborns resulting in increased intensive care admission, prolongation of hospital stay and higher rates of neonatal hypoglycemia. More efforts to assure early recognition and strict sugar control during pregnancy are still needed.
The effect of genistein supplementation on performance and antioxidant status of Japanese Quail under heat stress

Genistein, a phytoestrogen found in soybeans, is a powerful antioxidant. We evaluated the effects of genistein supplementation on performance, carcass characteristics, levels of malondialdehyde (MDA), homocysteine, vitamins C, E, A in Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature of 34°C. Two hundred and forty Japanese quails (10 d old) were randomly assigned to eight treatment groups consisting of 10 replicates of three birds. The birds were kept in an environmental controlled room either for 24 h/d at 22°C with (thermoneutral, TN groups) or for 16 h/d at 22°C and for 8 h/d (09.00 am to 05.00 pm) at 34°C (heat stress, HS groups). Birds were fed either a basal (control) diet (TN and HS) or the basal diet supplemented with 200, 400 or 800 mg of genistein per kg of diet. Heat exposure decreased birds' performance when basal diet was fed. Increase in feed intake and body weight, and improvement of feed efficiency and carcass traits were found in genistein-supplemented quails reared under heat stress conditions. Growth rate and feed efficiency improved in quails reared under thermo-neutral conditions as well. Concentration of serum vitamins C, E, and A increased in supplemented birds reared at high temperature, while non-significant changes occurred in TN groups. With genistein supplementation homocysteine levels in serum and MDA levels in serum and liver decreased in all birds of both TN and HS groups. Effects of genistein were relatively greater in heat-stressed quails than in quails kept under thermo-neutral conditions. Results of the present study suggest that supplementation with genistein can be considered to be protective by reducing the negative effects of oxidative stress induced by heat stress in quail.
Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high‐risk cohort: A prospective study of allergy‐prone children from birth to six years

Thomson JA, Widjaja C, Darmaputra AAP, Lowe A, Matheson MC, Bennett CM, Allen K, Abramson MJ, Hosking C, Hill D, Dharmage SC. Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high‐risk cohort: a prospective study of allergy‐prone children from birth to six years. Pediatr Allergy Immunol 2010: 21: 1076–1085. © 2010 John Wiley & Sons A/S