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Tests of both corollaries of social identity theory's self-esteem hypothesis in real group settings.

The present study tests both corollaries of the self-esteem hypothesis from social identity theory derived by Abrams and Hogg (1988). Greek students completed a pre-test collective self-esteem (CSE) measure and then rated Greek students and either American or Turkish students. They then completed a post-test collective self-esteem measure. Inconsistent with Corollary 2, higher prior CSE was associated both with higher in-group ratings and higher out-group ratings, but not with bias. Consistent with Corollary 1, change in CSE was positively associated with bias, positively associated with in-group ratings and negatively associated with out-group ratings. There were no differences due to type of out-group. The findings are consistent with the idea that, for specific comparisons between real groups, individual differences in self-esteem may affect the zone within which bias occurs rather than the amount of bias. However, achieving increases in self-esteem depends on establishing positive distinctiveness for the in-group in the context of a specific intergroup comparison.

Adult↗

Birth month, school graduation, and the timing of births and marriages.

We investigated the timing of fertility and marriage in Sweden using exogenous variation in the age at school graduation that results from differences in birth month. Our analysis found that the difference of 11 months in the age at leaving school between women who were born in two consecutive months, December and January, implies a delay in the age at first birth of 4.9 months. This effect of delayed graduation also persists for the timing of second births and first marriages, but it does not affect completed fertility or the overall probability of marriage before age 45. These results suggest the existence of a relatively rigid sequencing of demographic events in early adulthood, and the age at graduation from school emerges as an important factor in determining the timing--but not the quantum--of familyformation. In addition, these effects point to a potentially important influence of social age, defined by an individual's school cohort, instead of biological age. The relevance of social age is likely due to social interactions and peer-group influences exerted by individuals who are in the same school cohort but are not necessarily of the same age.

Adult↗

The community-acquired pneumonia symptom questionnaire: a new, patient-based outcome measure to evaluate symptoms in patients with community-acquired pneumonia.

STUDY OBJECTIVE: s: To develop and validate a patient-based outcome measure to evaluate symptoms in patients with community-acquired pneumonia (CAP). DESIGN: A psychometric study within an international, prospective, randomized, double-blind study. The CAP-symptom questionnaire (CAP-Sym) is a new, 18-item, patient-reported outcome measure that evaluates the bothersomeness of CAP-related symptoms during the past 24 h using a 6-point Likert scale. We used "gold standard" psychometric methods to comprehensively evaluate the acceptability, reliability, validity, and responsiveness of the CAP-Sym. SETTING: Sixty-four centers in 13 countries (France, Germany, Hungary, Israel, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, United Kingdom). PATIENTS: Five hundred fifty-six patients with CAP, recruited from outpatient clinics, general practice, and hospital centers. INTERVENTIONS: Randomization 1:1 to moxifloxacin (400 mg once daily), oral or standard oral treatment (amoxicillin, 1 g tid, or clarithromycin, 500 mg bid), alone or in combination, for up to 14 days. RESULTS: Standard psychometric tests confirmed the acceptability (item nonresponse, item-endorsement frequencies, item/scale floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest reliability), validity (content, construct, convergent, discriminant, known groups), and responsiveness of the CAP-Sym. CONCLUSIONS: The CAP-Sym is a practical and scientifically sound patient-based outcome measure of CAP-related symptoms that has been developed using "gold standard" methods. As the only fully validated measure of symptoms in patients with CAP, which is quick and easy to administer and is more responsive than the generic Medical Outcomes Study 36-Item Short-Form Health Survey, the CAP-Sym provides a practical and rigorous method for improving the evaluation of outcomes in clinical trials and audit.

Adult↗

Efficacy of congenital hypothyroidism neonatal screening in preterms less than 32 weeks of gestational age: more evidence.

OBJECTIVE: To evaluate the double screening performed for congenital hypothyroidism (CH) to preterm infants <32 weeks of gestational age (GA) between 1994 and 2003. INFANTS AND METHODS: TSH was assessed by IFMA. Infants were classified as: term (T) (>37 weeks GA); preterm (PT) (33-37 weeks GA); and very preterm (VPT) (< or =32 weeks GA). RESULTS: In 585,221 screened infants, CH was confirmed in 228 T, 23 PT and seven VPT. An increasing incidence of CH was found with decreasing GA, affecting 1:1,603 PT and 1:585 VPT. PT infants had 1.5 times more risk than full-term infants of suffering CH, and VPT 4 times more. Only 4/7 affected VPT had an adequate double screening as requested. Three had elevated TSH values in the first sample and in one a normal TSH (10.3 mIU/l) at 3 days rose to 240 mIU/l after day 15. In the remaining three VPT, TSH in the unique filter paper sample (21 to 34 days) was markedly elevated. CONCLUSIONS: Our findings reinforce the need for awareness in neonatal settings for adequate screening of VPT infants. Screening in the first week of life was effective in detection of most but not all affected VPT. Larger studies are needed in order to establish accurate screening recommendations for VPT newborns. Until this step is reached, repeated screening is advised in these infants.

Congenital Hypothyroidism↗

R-type calcium channels contribute to afterdepolarization and bursting in hippocampal CA1 pyramidal neurons.

Action potentials in pyramidal neurons are typically followed by an afterdepolarization (ADP), which in many cells contributes to intrinsic burst firing. Despite the ubiquity of this common excitable property, the responsible ion channels have not been identified. Using current-clamp recordings in hippocampal slices, we find that the ADP in CA1 pyramidal neurons is mediated by an Ni2+-sensitive calcium tail current. Voltage-clamp experiments indicate that the Ni2+-sensitive current has a pharmacological and biophysical profile consistent with R-type calcium channels. These channels are available at the resting potential, are activated by the action potential, and remain open long enough to drive the ADP. Because the ADP correlates directly with burst firing in CA1 neurons, R-type calcium channels are crucial to this important cellular behavior, which is known to encode hippocampal place fields and enhance synaptic plasticity.

Action Potentials↗

Differential expression of TASK channels between horizontal interneurons and pyramidal cells of rat hippocampus.

Among the electrophysiological properties differentiating stratum oriens horizontal interneurons from pyramidal neurons of the CA1 hippocampal subfield are the more depolarized resting potential and the higher input resistance; additionally, these interneurons are also less sensitive to ischemic damage than pyramidal cells. A differential expression of pH-sensitive leakage potassium channels (TASK) could contribute to all of these differences. To test this hypothesis, we studied the expression and properties of TASK channels in the two cell types. Electrophysiological recordings from acute slices showed that barium- and bupivacaine-sensitive TASK currents were detectable in pyramidal cells but not in interneurons and that extracellular acidification caused a much stronger depolarization in pyramidal cells than in interneurons. This pyramidal cell depolarization was paralleled by an increase of the input resistance, suggesting the blockade of a background conductance. Single-cell reverse transcription-PCR experiments showed that the expression profile of TASK channels differ between the two cell types and suggested that these channels mediate an important share of the leakage current of pyramidal cells. We suggest that the different expression of TASK channels in these cell types contribute to their electrophysiological differences and may result in cell-specific sensitivity to extracellular acidification in conditions such as epilepsy and ischemia.

Anesthetics, Local↗

Membrane lateral diffusion and capture of CFTR within transient confinement zones.

The cystic fibrosis transmembrane conductance regulator (CFTR) channel interacts with scaffolding and other proteins that are expected to restrict its lateral movement, yet previous studies have reported predominantly free diffusion. We examined the lateral mobility of CFTR channels on live baby hamster kidney cells using three complementary methods. Channels bearing an extracellular biotinylation target sequence were labeled with streptavidin conjugated with fluorescent dyes (Alexa Fluor 488 or 568) or quantum dots (qDot605). Fluorescence recovery after photobleaching and image correlation spectroscopy of the dye-labeled channels revealed a significant immobile population ( approximately 50%), which was confirmed by direct single particle tracking (SPT) of qDot605-labeled CFTR. Adding 10 histidine residues at the C-terminus of CFTR to mask the postsynaptic density 95, Discs large, ZO-1 (PDZ) binding motif abolished its association with EBP50/NHERF1, reduced the immobile fraction, and increased mobility. Other interactions that are not normally detected on this timescale became apparent when binding of PDZ domain proteins was disrupted. SPT revealed that CFTR(His-10) channels diffuse randomly, become immobilized for periods lasting up to 1 min, and in some instances are recaptured at the same location. The impact of transient confinement on the measured diffusion using the three fluorescence techniques were assessed using computer simulations of the biological experiments. Finally, the impact of endosomal CFTR on mobility measurements was assessed by fluorescence correlation spectroscopy. These results reveal unexpected features of CFTR dynamics which may influence its ion channel activity.

Animals↗

Developmental origins of pregnancy loss in cattle.

Pregnancy losses constitute a major economic burden in cattle farming and are caused by developmental failures occurring mostly during the first month of gestation. This review integrates knowledge gathered from direct and indirect estimations of embryo survival at critical developmental periods with knowledge obtained from functional in vivo and in vitro studies to elucidate the developmental origins of pregnancy loss in cattle. Fertilization failures and embryonic arrest prior to the blastocyst stage, estimated based on morphological observation of flushed structures, average 10 to 20 and 10 to 30%, respectively. Reduced oocyte competence arises as the major driver of the underlying developmental failures, including impaired embryonic genome activation, loss of totipotency and defective first lineage differentiation. To estimate embryonic losses from blastocyst to implantation, direct observation of embryo development and indirect proxies of pregnancy have been employed. Indirect proxies such as nonreturn to oestrus or biochemical markers such as Interferon Stimulated Genes or Pregnancy Associated Glycoproteins inform on the development of extra-embryonic membranes, but do not distinguish between viable pregnancies and anembryonic pregnancies, where embryo-devoid structures formed by extra-embryonic membranes are able to maintain the corpus luteus to day 37. Merging data from recovery rates of early elongated structures and incidence of embryo-devoid structures, embryonic mortality from blastocyst hatching to pregnancy recognition oscillates between 12-79% for in vivo derived and 40-86% for in vitro produced embryos. The exclusion of anembryonic pregnancies diminishes embryonic mortality between day 16 and the time when the embryo proper is clearly identifiable by ultrasound (days 31-42) to less than 10%. The manuscript also provides an update on novel tools used to elucidate embryonic metabolic and signalling requirements, as well as on the molecular regulation of key developmental landmarks that must be achieved during developmental windows most susceptible to pregnancy loss.

cattle↗

Having a sibling with schizophrenia: a phenomenological study.

Limited attention has been paid to experiences of individuals with siblings diagnosed with schizophrenia. The purpose of this article is to address this gap by exploring the impact of having a brother or sister with schizophrenia. The lived experience of 6 individuals with a sibling with schizophrenia was explored using van Manen's (1997) Hermeneutic Phenomenology. Four themes were identified: struggling to understand, struggling with the system, caring for the sibling, and seeing beyond the illness. Health care providers need to re-evaluate current approaches for assisting individuals to cope with having a sibling with schizophrenia. Inclusion in the plan of care and recognition of their struggle is essential for individuals having a sibling with schizophrenia.

Adaptation, Psychological↗

Causes of syncope in patients with Alzheimer's disease treated with donepezil.

INTRODUCTION: Treatment of Alzheimer's disease (AD) with cholinesterase inhibitors carries a theoretical risk of precipitating bradycardia. Though syncope occurs in patients with AD, its aetiology is unclear. The aim of this study was to determine the causes of syncope in patients with AD who were treated with donepezil and hospitalised for evaluation of syncope. METHODS: We studied 16 consecutive patients (12 women, 4 men) with AD aged 80 +/- 4 years who were hospitalised for evaluation of syncope. All patients underwent staged evaluation, ranging from physical examination to electrophysiological testing. RESULTS: The mean dose of donepezil administered was 7.8 mg/day, and the mean duration of donepezil treatment at the time of syncope was 12 +/- 8 months. A cause of syncope was identified in 69% of patients. Carotid sinus syndrome was observed in three patients, complete atrioventricular block in two patients, sinus node dysfunction in two patients, severe orthostatic hypotension in two patients and paroxysmal atrial fibrillation in one patient. A brain tumour was discovered in one patient. No cause of syncope was found in 31% of patients despite comprehensive investigation. Repetition of the investigations after discontinuation of donepezil was noncontributory. CONCLUSION: In patients with AD treated with donepezil, a noninvasive evaluation identified a probable cause of syncope in over two-thirds of patients. Cardiovascular abnormalities were predominant. Noninvasive evaluation is recommended before discontinuing treatment with cholinesterase inhibitors in patients with AD and unexplained syncope.

Aged↗

Compliance-guided therapy : a new insight into the potential role of clinical pharmacologists.

BACKGROUND AND OBJECTIVE: In the field of drug noncompliance, we investigated an original approach that could give the prescribing physician, in collaboration with a clinical pharmacologist, an active role. The aim here is for the prescribing physician to take compliance into account so as to provide an optimised prescription (choice of molecule prescribed and its rhythm of administration) adapted to each patient. The example considered is that of oral anticoagulant treatment prescribed long-term. METHODS: In order to investigate the choice of the best molecule and treatment regimen for a given noncompliance pattern, we performed an in silico study with two oral anticoagulant agents, warfarin and acenocoumarol, each taken in one or two daily doses. Three linked models were used: the first model generated specific noncompliance patterns, the second model described the pharmacokinetics of oral anticoagulant agents and the third model summarised the pharmacokinetic-pharmacodynamic relations. RESULTS: Considering different patterns of noncompliance (including timing errors in drug intake and the phenomenon of drug holidays) and comparing warfarin with acenocoumarol, we identified different situations in which one agent (prescribed once or twice daily) could clearly minimise both the thromboembolic and haemorrhagic risks. However, for some specific noncompliance patterns, the choice of the optimal therapy should also be guided by the basal individual thromboembolic and haemorrhagic risks. CONCLUSION: Individualisation of drug therapy involves both drug dose and drug choice. In addition to the classical approach (i.e. drug level measurements, enzyme assays and even genetic sequence data), our study suggests that compliance-guided therapy may represent a potential, evolving way for the individualisation of prescriptions.

Humans↗

Cardiovascular effects and risk of syncope related to donepezil in patients with Alzheimer's disease.

BACKGROUND: When otherwise unexplained, syncope in patients with Alzheimer's disease may be attributed to bradycardia caused by cholinesterase inhibitors. We studied prospectively the clinical events and cardiovascular changes occurring during treatment with donepezil in patients with Alzheimer's disease. METHODS: Consecutive patients presenting with mild-to-moderate Alzheimer's disease were included in the study. Their clinical characteristics, blood pressure, heart rate and electrocardiogram were recorded before (baseline) and during treatment with donepezil. The drug was administered at a dosage of 5 mg/day for 1 month and 10 mg/day for the following 7 months, as tolerated. We compared the baseline observations with those made at 1, 2 and 8 months of donepezil treatment. We also examined the effects of negatively chronotropic or dromotropic drugs concomitantly administered with donepezil. RESULTS: Thirty patients were included in the study, of whom 43% were taking negatively chronotropic or dromotropic drugs. The first month of therapy (donepezil 5 mg/day) was completed by 26 patients. During the 7-month high-dosage phase (10 mg/day), four patients dropped out of the study; thus, 22 patients completed the full 8 months of the study. The mean heart rate was 66 +/- 8 beats/min at baseline in the overall study population. This decreased significantly to 62 +/- 9, 61 +/- 7 and 62 +/- 8 beats/min at the 1, 2 and 8 month timepoints, respectively (all p = 0.002 vs baseline). Among patients not receiving negatively chronotropic or dromotropic drugs, heart rate decreased significantly over the course of the study (from 67 +/- 8 beats/min at baseline to 62 +/- 8 beats/min at 1 month, 62 +/- 7 beats/min at 2 months and 62 +/- 8 beats/min at 8 months [all p = 0.005 vs baseline]). There was no significant change in heart rate in patients who were receiving negatively chronotropic or dromotropic drugs. The PR interval increased over the course of the study in all patient groups, but these changes were only statistically significant in the group of patients who were not taking negatively chronotropic or dromotropic drugs (155 +/- 23ms at baseline vs 158 +/- 21, 160 +/- 22 and 163 +/- 24ms at the 1, 2 and 8 month timepoints; all p = 0.02 vs baseline). One patient developed syncope due to orthostatic hypotension; there were no cases of bradycardia-induced syncope. Gastrointestinal manifestations were reported in ten of the study patients. Abdominal pain and vomiting were the reasons for study termination in five of the eight patients who did not complete the trial. CONCLUSION: A donepezil-induced decrease in heart rate and increase in PR interval were observed only in patients with Alzheimer's disease who were not treated with negatively chronotropic or dromotropic drugs. These changes were not associated with bradycardia-induced syncope.

Aged↗

MR elastography of breast cancer: preliminary results.

OBJECTIVE: Motivated by the long-recognized value of palpation in detecting breast cancer, we tested the feasibility of a technique for quantitatively evaluating the mechanical properties of breast tissues on the basis of direct MR imaging visualization of acoustic waves. SUBJECTS AND METHODS: The prototypic elasticity imaging technique consists of a device for generating acoustic shear waves in tissue, an MR imaging-based method for imaging the propagation of these waves, and an algorithm for processing the wave images to generate quantitative images depicting tissue stiffness. After tests with tissue-simulating phantom materials and breast cancer specimens, we used the prototypic breast MR elastography technique to image six healthy women and six patients with known breast cancer. RESULTS: Acoustic shear waves were clearly visualized in phantoms, breast cancer specimens, healthy volunteers, and patients with breast cancer. The elastograms of the tumor specimens showed focal areas of high shear stiffness. MR elastograms of healthy volunteers revealed moderately heterogeneous mechanical properties, with the shear stiffness of fibroglandular tissue measuring slightly higher than that of adipose tissue. The elastograms of patients with breast cancer showed focal areas of high shear stiffness corresponding to the locations of the known tumors. The mean shear stiffness of breast carcinoma was 418% higher than the mean value of surrounding breast tissues. CONCLUSION: The results confirm the hypothesis that the prototypic breast MR elastographic technique can quantitatively depict the elastic properties of breast tissues in vivo and reveal high shear elasticity in known breast tumors. Further research is needed to evaluate the potential applications of MR elastography, such as detecting breast carcinoma and characterizing suspicious breast lesions.

Adult↗

Endothelial dysfunction relates to folate status in children and adolescents with type 1 diabetes.

Endothelial dysfunction occurs early in the development of vascular disease in diabetes. Total plasma homocyst(e)ine (tHcy) is associated with endothelial dysfunction. We therefore aimed to assess endothelial function in children with type 1 diabetes in relation to tHcy and its determinants. Endothelial function was assessed in 36 children with type 1 diabetes aged 13.7 +/- 2.2 years and 20 age- and sex-matched control subjects using ultrasound assessment of flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)-dependent brachial artery responses. von Willebrand factor (vWF) and thrombomodulin, markers of endothelial activation, were measured in 64 children with type 1 diabetes and 52 control subjects. Fasting glucose, tHcy, serum and red cell folate, vitamin B12, HbA(1c), creatinine, and lipids were also measured. FMD (5.2 +/- 4.7 vs. 9.1 +/- 4.0%, P = 0.002) and the ratio of FMD:GTN-induced dilatation (0.22 +/- 0.39 vs. 0.41 +/- 0.29%, P = 0.008) were significantly lower in diabetic subjects, indicating endothelial dysfunction. In diabetic subjects, red cell folate correlated independently with FMD (beta = 0.42, P = 0.028) and the ratio of FMD:GTN-induced dilatation (beta = 0.59, P < 0.001). Resting vessel diameter correlated independently with tHcy (beta = -0.51, P < 0.001) and height (beta = 0.65, P < 0.001). vWF correlated independently with HbA(1c) (beta = 0.38, P = 0.003), and thrombomodulin correlated independently with red cell folate (beta = -0.38, P = 0.005), tHcy (beta = -0.37, P = 0.004), diastolic blood pressure (beta = -0.28, P = 0.025), and creatinine clearance (beta = 0.26, P = 0.033). Children with type 1 diabetes have early endothelial dysfunction. Better folate status is associated with better endothelial function, as measured by higher FMD, higher FMD:GTN ratio, and lower thrombomodulin. Folate may therefore protect against endothelial dysfunction in children with diabetes.

Adolescent↗

Repair and regeneration across the lifespan: an ontogenetic perspective.

The capacity for tissue repair and regeneration undergoes a profound and progressive decline across the human lifespan, representing a fundamental driver of aging and chronic disease. This review establishes a comprehensive ontogenetic framework by mapping the continuous biological transition from the flawless, scarless regenerative plasticity of embryonic development to the irreversible fibrotic scarring and organ failure characteristic of senescence. We synthesize the hierarchical collapse of reparative networks across multiple biological scales. Importantly, this ontogenetic decline should not be interpreted as a purely degenerative trajectory but rather as a dynamic systems-level reprogramming in which evolutionary trade-offs prioritize tumor suppression, immune surveillance, and reproductive fitness over long-term regenerative fidelity. Recognizing this adaptive reallocation of biological resources reframes aging not simply as failure but as a predictable recalibration of repair hierarchies. At the molecular and cellular levels, the accumulation of genomic instability, unresolvable DNA damage, and mitochondrial dysfunction gradually overwhelms intracellular quality-control mechanisms. Concurrently, epigenetic drift and chronic, low-grade systemic inflammation ("inflammaging") dismantle the stem cell niche, driving adult stem cell exhaustion and shifting wound healing away from functional tissue replacement toward maladaptive fibrosis. Furthermore, we examine divergent, organ-specific repair trajectories. By contrasting the severe regenerative restrictions of the adult central nervous system and myocardium with the persistent, yet exhaustible, resilience of the liver, we elucidate the unique intrinsic and microenvironmental barriers that impede structural and functional recovery. Finally, we evaluate the clinical paradigm shift from passive management of age-related degeneration to active restoration of tissue integrity. By integrating systemic geroscience-which addresses the global hallmarks of aging-with targeted bioengineering and in vivo epigenetic modulation, contemporary regenerative medicine seeks to recreate permissive, youthful microenvironments. Ultimately, mastering these ontogenetic principles holds unprecedented potential to reactivate endogenous repair pathways, mitigate multi-organ collapse, and significantly extend human functional healthspan.

DNA repair↗

Shaping a career trajectory in academic administration: leadership development for the deanship.

The nursing profession continues to face many challenges, one of which is an insufficient number of aspiring leaders. The role of an academic leader, specifically that of dean, brings with it unique challenges and opportunities. Shaping a career in academic administration requires careful consideration of the leadership skills necessary to perform in this complex and challenging role. However, it is critical to the future of nursing as a profession that ample numbers of aspiring leaders can successfully make this transition. One can be better prepared to take on this exciting and rewarding leadership opportunity when one understands the challenges deans face, asks questions such as "Do I really want a deanship?," identifies the required leadership skills, defines a career trajectory and pathway, and develops the leadership skills necessary for deans.

Education, Nursing↗