Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved cerebral perfusion pressures and 24-hr neurological survival in a porcine model of cardiac arrest with active compression-decompression cardiopulmonary resuscitation and augmentation of negative intrathoracic pressure*

Objective:Generation of negative intrathoracic pressure during the decompression phase of cardiopulmonary resuscitation enhances the refilling of the heart. We tested the hypothesis that when compared with closed-chest manual compressions at 80 chest compressions per min, treatment with active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min combined with augmentation of negative intrathoracic pressure would lower intracranial pressure and increase cerebral perfusion, thereby improving neurologically intact survival rates following prolonged untreated cardiac arrest. Design:Prospective, randomized animal study. Setting:Animal laboratory facilities. Subjects:A total of 26 female farm pigs in two different protocols (n = 17 and n = 9). Interventions, Measurements, and Main Results:Seventeen pigs were subjected to 8.5 mins of untreated ventricular fibrillation and prospectively randomized to cardiopulmonary resuscitation at 80 chest compressions/min or active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min plus an impedance threshold device. Coronary perfusion pressures (29.5 ± 2.7 mm Hg vs. 22.4 ± 1.6 mm Hg, p = .03), carotid blood flow (44.0 ± 12.2 vs. 30.9 ± 10.4, p = .03), and 24-hr neurological survival (88% vs. 22%, p = .015) were higher with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device. Cerebral perfusion pressures, measured in nine additional pigs, were improved with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device (21.9 ± 1.2 mm Hg vs. 8.9 ± 0.8 mm Hg, p < .0001). With active compression-decompression cardiopulmonary resuscitation + impedance threshold device, mean diastolic intracranial pressure during decompression was lower (12.2 ± 0.2 mm Hg vs. 16.6 ± 1.2 mm Hg, p = .02) and the downward slope of the decompression phase intracranial pressure curve was steeper (−60.3 ± 12.9 mm Hg vs. −46.7 ± 11.1 mm Hg/sec, p < .001). Conclusions:Active compression-decompression cardiopulmonary resuscitation + an impedance threshold device increased cerebral perfusion pressures and lowered diastolic intracranial pressure and intracranial pressure rate during the decompression phase. These mechanisms may underlie the observed increase in cerebral perfusion pressure, carotid blood flow, and survival rates with favorable neurologic outcomes in this pig model of cardiac arrest.
Transgenic Overexpression of Gremlin Results in Developmental Defects in Enamel and Dentin in Mice

Bone morphogenetic proteins (BMPs) and BMP antagonists play a crucial role in the regulation of tooth development. One of the BMP extracellular antagonists, gremlin, is a highly conserved 20.7-kDa glycoprotein. Previously, researchers reported that transgenic mice overexpressing gremlin under the control of the osteocalcin promoter (gremlin OE) exhibit a skeletal phenotype and tooth fragility. To further define the tooth phenotype, teeth and surrounding supporting tissues, obtained from gremlin OE at ages of 4 weeks, 2 months, and 4 months, were examined. The histological results demonstrate that gremlin OE exhibit an enlarged pulp chamber with ectopic calcification and thinner dentin and enamel compared with wild-type control. In vitro studies using murine pulp cells revealed that gremlin inhibited BMP-4 mediated induction of Dspp. These data provide evidence that balanced interactions between BMP agonists/antagonists are required for proper development of teeth and surrounding tissues. It is clear that these interactions require further investigation to better define the mechanisms controlling tooth root formation (pulp, dentin, cementum, and surrounding tissue) to provide the information needed to successfully regenerate these tissues.
Gene expression in human meniscal tears has limited association with early degenerative changes in knee articular cartilage

ABSTRACT Purpose/Aim: Meniscus tears are a common injury to the knee associated with the development of osteoarthritis. Gene expression in the injured meniscus may be associated with early degeneration in the articular cartilage. The purpose of this study was to test the hypothesis that gene expression in meniscus tears is associated with early degenerative changes in the articular cartilage at the time of partial meniscectomy. Materials and Methods: Torn meniscus was removed at the time of partial meniscectomy in 68 patients without radiographic osteoarthritis. Meniscal mRNA expression was measured by quantitative PCR for multiple molecular markers of osteoarthritis and cartilage homeostasis. The presence of early degenerative changes in the knee was recorded by X-ray (N = 63), magnetic resonance imaging (MRI, N = 48), and arthroscopy (N = 63). Gene expression was tested for correlation with the presence/absence of degenerative changes after adjusting for age, sex, and body mass index. Results: Overall gene expression varied significantly with degenerative changes based on X-ray (P = 0.047) and MRI (P = 0.018). The linear combination of gene variation was also significant. However, only adiponectin (ADIPOQ) (P = 0.015) was expressed at a significantly lower level in patients with chondrosis on MRI, while the expression of ADIPOQ (P = 0.035) and resistin (RETN) (P = 0.017) was higher in patients with early degenerative changes on X-ray. None of the genes varied significantly with presence/absence of chondrosis as measured by arthroscopy. Conclusions: There is an overall association of gene expression in meniscal tears to early degenerative changes in the knee, but only a limited number of specific genes demonstrate this relationship. The roles of adiponectin and resistin in knee injury and osteoarthritis deserve further study.
Persistent peripheral and microcirculatory perfusion alterations after out-of-hospital cardiac arrest are associated with poor survival*

Objective: To evaluate sublingual microcirculatory and peripheral tissue perfusion parameters in relation to systemic hemodynamics during and after therapeutic hypothermia following out-of-hospital cardiac arrest. Design: Prospective observational study. Setting: Intensive cardiac care unit at a university teaching hospital. Subjects: We followed 80 patients, of whom 25 were included after out-of-hospital cardiac arrest. Intervention: In all patients, we induced therapeutic hypothermia to 33°C during the first 24 hrs of admission. Measurements and Main Results: Complete hemodynamic measurements were obtained directly on intensive cardiac care unit admission (baseline), during induced hypothermia (T1), directly after rewarming (T2), and another 24 hrs later (T3). In addition, the sublingual microcirculation was observed using sidestream dark-field imaging, and peripheral tissue perfusion was monitored with the peripheral perfusion index, capillary refill time, tissue oxygen saturation, and forearm-to-fingertip skin temperature gradient. During hypothermia, all sublingual microcirculatory parameters decreased significantly together with peripheral capillary refill time and the peripheral perfusion index, followed by a significant increase at T2. Changes in sublingual and peripheral tissue perfusion parameters were significantly related to changes in central body temperature, but not to changes in systemic hemodynamic variables such as cardiac index or mean arterial pressure. Surprisingly, these parameters were significantly lower in nonsurvivors (n = 6) at admission and after rewarming. Persistent alterations in these parameters were related with the prevalence of organ dysfunction and were highly predictive of mortality. Conclusions: Following out-of-hospital cardiac arrest, the early postresuscitation phase is characterized by abnormalities in sublingual microcirculation and peripheral tissue perfusion, which are caused by vasoconstriction due to induced systemic hypothermia and not by impaired systemic blood flow. Persistence of these alterations is associated with organ failure and death, independent of systemic hemodynamics.
Generalized sunbed lentigines in a patient with systemic lupus erythematosus

Sir, The development of melanocytic lesions following treatment with psoralen and ultraviolet A (PUVA therapy) is well documented. The first case of lentigines induced by cosmetic UVA tanning was reported in the 1980s (1), and another three cases have been published since then (2 – 5). We report the case of a woman with systemic lupus erythematosus (SLE) who developed generalized persistent melanocytic lesions while using UVA tanning beds.
A multicenter, phased, cluster-randomized controlled trial to reduce central line-associated bloodstream infections in intensive care units*

Objectives:To determine the causal effects of an intervention proven effective in pre-post studies in reducing central line-associated bloodstream infections in the intensive care unit. Design:We conducted a multicenter, phased, cluster-randomized controlled trial in which hospitals were randomized into two groups. The intervention group started in March 2007 and the control group started in October 2007; the study period ended September 2008. Baseline data for both groups are from 2006. Setting:Forty-five intensive care units from 35 hospitals in two Adventist healthcare systems. Interventions:A multifaceted intervention involving evidence-based practices to prevent central line-associated bloodstream infections and the Comprehensive Unit–based Safety Program to improve safety, teamwork, and communication. Measurements and Results:We measured central line-associated bloodstream infections per 1,000 central line days and reported quarterly rates. Baseline average central line-associated bloodstream infections per 1,000 central line days was 4.48 and 2.71, for the intervention and control groups (p = .28), respectively. By October to December 2007, the infection rate declined to 1.33 in the intervention group compared to 2.16 in the control group (adjusted incidence rate ratio 0.19; p = .003; 95% confidence interval 0.06–0.57). The intervention group sustained rates <1/1,000 central line days at 19 months (an 81% reduction). The control group also reduced infection rates to <1/1,000 central line days (a 69% reduction) at 12 months. Conclusions:This study demonstrated a causal relationship between the multifaceted intervention and the reduced central line-associated bloodstream infections. Both groups decreased infection rates after implementation and sustained these results over time, replicating the results found in previous, pre-post studies of this multifaceted intervention and providing further evidence that most central line-associated bloodstream infections are preventable.
Automatic reconstruction of personalized avatars from 3D face scans

We present a simple algorithm for computing a high‐quality personalized avatar from a single color image and the corresponding depth map which have been captured by Microsoft's Kinect sensor. Due to the low market price of our hardware setup, 3D face scanning becomes feasible for home use. The proposed algorithm combines the advantages of robust non‐rigid registration and fitting of a morphable face model. We obtain a high‐quality reconstruction of the facial geometry and texture along with one‐to‐one correspondences with our generic face model. This representation allows for a wide range of further applications such as facial animation or manipulation. Our algorithm has proven to be very robust. Since it does not require any user interaction, even non‐expert users can easily create their own personalized avatars. Copyright © 2011 John Wiley & Sons, Ltd.
Charting the possible impact of national guidelines on the management of rheumatoid arthritis

Objective: To identify temporal trends in the prescription of disease‐modifying antirheumatic drugs (DMARDs) in patients with early rheumatoid arthritis (RA). Methods: Using data from the Swedish RA register (n = 2584), we analysed the proportion of RA patients prescribed DMARDs at their first consultation between 1997 and 2001. Statistical process control (SPC) was used to chart and analyse major changes in prescription behaviour, while more traditional time series analysis methods (i.e. regression) were used to corroborate the nature of any trend. Results: The SPC method identified an upward shift in the prescription of DMARDs in July 1998 and a change in the process by October 1998. Time series analysis confirmed an increasing trend in DMARD prescription over the period as a whole and the trend was statistically significant (p⩽0.0001). Further analysis showed that the trend was driven by a single shift in the data in July 1998 (p⩽0.0095), and once this shift was accounted for, no remaining trends within the periods (i.e. before and after the jump) could be detected (p = 0.5934 and 0.7497, respectively). Conclusion: The formulation and promulgation of Swedish guidelines in 1998 may have influenced the prescription of DMARDs for this patient group. Prospectively analysing data derived from clinical registers in real time using SPC shows promise as a means to evaluate interventions designed to have an impact on a national level.
Osteoprotegerin/RANKL system imbalance in active polyarticular‐onset juvenile idiopathic arthritis: a bone damage biomarker?

Objective: To evaluate the importance of receptor activator of nuclear factor κB (RANK)/receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) modulation in active polyarticular juvenile idiopathic arthritis (pJIA) patients with and without bone erosions. Methods: Thirty female patients (mean age 11.07±3.77 years, range 4–17 years) with active pJIA and 30 healthy gender‐ and age‐matched controls were consecutively selected for this study. All involved articulations were assessed by X‐ray and examined for the presence of bone erosions. The serum levels of RANKL and OPG were measured using an enzyme‐linked immunosorbent assay (ELISA). Results: Patients with active pJIA had higher levels of serum RANKL than controls [2.90 (0.1–37.4) vs. 0.25 (0.1–5.7) pg/mL, p = 0.007] and a lower OPG/RANKL ratio [21.25 (1.8–897.6) vs. 347.5 (9–947.8), p = 0.005]. However, levels of OPG were comparable in both groups [55.24 (28.34–89.76) vs. 64.42 (30.68–111.28) pg/mL, p = 0.255]. Higher levels of serum RANKL and a lower OPG/RANKL ratio were also observed in active pJIA patients with bone erosions compared to controls [3.49 (0.1–37.4) vs. 0.25 (0.1–5.7) pg/mL, p = 0.0115 and 14.3 (1.8–897.6) vs. 347.5 (9–947.8), p = 0.016]. However, RANKL levels and OPG/RANKL ratio were similar in pJIA patients without bone erosion and controls [1.75 (0.1–10.9) vs. 0.25 (0.1–5.7) pg/mL, p = 0.055 and 29.2 (3.3–756.8) vs. 347.5 (9–947.8), p = 0.281]. Conclusion: These data suggest that active pJIA with bone erosions is associated with high serum levels of RANKL and a low OPG/RANKL ratio, indicating that these alterations may reflect bone damage in this disease.
Imaging the Interaction of Atelectasis and Overdistension in Surfactant-Depleted Lungs*

Objective:Atelectasis and surfactant depletion may contribute to greater distension—and thereby injury—of aerated lung regions; recruitment of atelectatic lung may protect these regions by attenuating such overdistension. However, the effects of atelectasis (and recruitment) on aerated airspaces remain elusive. We tested the hypothesis that during mechanical ventilation, surfactant depletion increases the dimensions of aerated airspaces and that lung recruitment reverses these changes. Design:Prospective imaging study in an animal model. Setting:Research imaging facility. Subjects:Twenty-seven healthy Sprague Dawley rats. InterventionsSurfactant depletion was obtained by saline lavage in anesthetized, ventilated rats. Alveolar recruitment was accomplished using positive end-expiratory pressure and exogenous surfactant administration. Measurements and Main Results:Airspace dimensions were estimated by measuring the apparent diffusion coefficient of 3He, using diffusion-weighted hyperpolarized gas magnetic resonance imaging. Atelectasis was demonstrated using computerized tomography and by measuring oxygenation. Saline lavage increased atelectasis (increase in nonaerated tissue from 1.2% to 13.8% of imaged area, p < 0.001), and produced a concomitant increase in mean apparent diffusion coefficient (~33%, p < 0.001) vs. baseline; the heterogeneity of the computerized tomography signal and the variance of apparent diffusion coefficient were also increased. Application of positive end-expiratory pressure and surfactant reduced the mean apparent diffusion coefficient (~23%, p < 0.001), and its variance, in parallel to alveolar recruitment (i.e., less computerized tomography densities and heterogeneity, increased oxygenation). Conclusions:Overdistension of aerated lung occurs during atelectasis is detectable using clinically relevant magnetic resonance imaging technology, and could be a key factor in the generation of lung injury during mechanical ventilation. Lung recruitment by higher positive end-expiratory pressure and surfactant administration reduces airspace distension.
Long-Term Effect of Colestimide on Glycemic Control in Patients with Type 2 Diabetes with Elevated Low-Density Lipoprotein Cholesterol Levels

Objective. Bile acid sequestrants (BASs) have been shown to improve both low-density lipoprotein-(LDL-) cholesterol and hemoglobin (Hb) A1c levels in patients with type 2 diabetes with elevated LDL levels. However, the longitudinal effect on glycemic control in these patients has not been fully examined. In the current study, the effect of colestimide (a BAS used in Japan, called also as colestilan) over a mean period of 18 months was investigated in patients with type 2 diabetes with elevated LDL levels. Methods. The study was performed prospectively in 34 patients with type 2 diabetes with elevated LDL levels who started colestimide (3.0 g a day) between April 2007 and March 2008. Results. HbA1c was significantly decreased after 3 months of colestimide therapy and at the end point of treatment (a mean period of 18 months) compared with baseline values (8.1%±1.1% at baseline, 7.1%±0.7% at 3 months, and 7.2%±0.9% at the end point; both P .05, 3 months versus end point). Colestimide also significantly reduced LDL-C at 3 months and at the end point (both P .05, 3 months versus end point). However, fasting plasma glucose, triglycerides, systolic and diastolic blood pressure, and body weight did not differ significantly after 3 months and at the end point compared with the respective baseline values. Conclusion. Colestimide significantly decreased HbA1c over a relatively long-term period in patients with type 2 diabetes with elevated LDL levels.
A Phase 2 Randomized, Double-Blind, Placebo–Controlled Study of the Safety and Efficacy of Talactoferrin in Patients With Severe Sepsis*

Objectives:Lactoferrin is a glycoprotein with anti-infective and anti-inflammatory properties found in secretions and immune cells. Talactoferrin alfa, a recombinant form of human lactoferrin, has similar properties and plays an important role in maintaining the gastrointestinal mucosal barrier integrity. In experimental animal models, administration of talactoferrin reduces translocation of bacteria from the gut into the systemic circulation and mortality from sepsis. Our objective was to determine if talactoferrin could reduce 28-day all-cause mortality in patients with severe sepsis and to assess its safety. Design:Prospective, randomized, double-blind, placebo-controlled, multicenter phase 2 trial. Setting:Adult ICUs and emergency departments in the United States. Patients:One hundred ninety-four adults within 24 hrs of the onset of severe sepsis. Interventions:Enterally administered talactoferrin 1.5g or placebo every 8 hrs for up to 28 days or until discharge from the ICU. Measurements and Main Results:Modified intention-to-treat analysis was used to assess the primary (28-day all-cause mortality) and secondary endpoints. The all-cause mortality at 28 days was 26.9% in the placebo group and 14.4% in the talactoferrin group (two-sided p = 0.052), representing a 12.5% absolute and a 46.5% relative reduction in mortality, meeting the protocol-specified primary endpoint. Reduction in all cause mortality was sustained at 6 months (p = 0.039). These reductions in mortality were observed across a wide spectrum of subgroups. The drug was well tolerated with a safety profile similar to that of placebo. Conclusions:Enteral administration of talactoferrin reduced 28-day all-cause mortality in patients with severe sepsis. This reduction in mortality was sustained at 6 months. Talactoferrin was very well tolerated.
THREE STRATEGIES FOR DELIVERING CONTINUING MEDICAL EDUCATION IN GERIATRICS TO GENERAL PRACTITIONERS

General practitioners (GPs) need advanced skills in geriatric assessment to be competent to treat the increasing number of elderly patients. Continuing medical education in geriatrics for GPs is heterogeneous, and not assessed for effectiveness. In this study we compared the educational effects of three geriatric post-graduate training methods on GPs. GPs in the health district of the Nijmegen University Medical Centre (The Netherlands) were offered a variety of training options in geriatric assessment: (1) a formal one-day teacher centered conference (TCC), (2) an interactive GP-centered day of workshops (GCW), and (3) participation in a project of knowledge translation, linked to a research project of geriatric intermediate care (GKT). Pre-post measures were taken of the attitudes of GPs towards the elderly (Aging Semantic Differential, 1969), attitudes towards geriatric patients (Maxwell & Sullivan, 1980; Rosencranz & McNevin, 1969) and geriatric competencies (Robinson, Barry, Renick, et al., 2001). After training, neither the attitudes towards the elderly nor geriatric patients changed in any of the three groups. The TCC did not show a significant change in perceived competencies, while the GCW and GKT group improved. A formal large group conference is ineffective in improving GPs' geriatric assessment skills, while small interactive workshops and participation in a project of knowledge translation are equally effective. None of the three training methods improved or worsened attitudes toward the elderly in general or the geriatric patients in particular.
Special Interest Group for Neuroscience in Psychiatry

Neuroscience is an emergent discipline which lies naturally at the heart of reliable knowledge in many aspects of general psychiatry. It is a preclinical development with origins in shared problems in neuroanatomy, neurophysiology, neuropharmacology, genetics and psychology. It is necessarily a multidisciplinary enterprise and it takes as its central questions how the brain works and how it goes wrong in disease. It is unlike the traditional subject groups in basic medical science by having as its focus the brain, not a set of related techniques. There are important parallels between basic neuroscience and the multidisciplinary structure of medicine itself which will be recognisable to clinicians. However, neuroscience has its own tensions. The creation of a whole unified from historically separate techniques or strands of scholarship is difficult. The priorities within neuroscience are fluid and the creation of courses or departments often follows existing strengths in traditional subjects like physiology or pharmaco logy. We should be prepared to argue that psychiatry poses neuroscience's most challenging