Growth hormone stimulation of normal and leukemic human T-lymphocyte proliferation in vitro.
In order to investigate the effect of human growth hormone on T lymphocytes, we utilized a clonogenic assay for mitogen-responsive human peripheral blood T lymphocytes. Lymphocytes were purified by density gradient centrifugation and incubated in the presence of phytohemagglutinin using a two-layer agar technique for CFU- T-lymphocyte culture. Nanogram concentrations of human growth hormone, ovine prolactin, human chorionic somatomammotropin, or growth hormone fragment were added to cell cultures. Growth hormone potentiated normal T-cell colony formation in a species-specific manner. Cells from a homogeneous T-lymphoblast line derived from a patient with a T-cell variant of hairy cell leukemia also showed augmentation of colony growth in the presence of human growth hormone. These studies provide evidence for a direct effect of growth hormone on normal and some neoplastic human T cells.


Keratinocytes can differentiate into eccrine sweat ducts in vitro: involvement of epidermal growth factor and fetal bovine serum.
in addition to formation of an epidermal sheet and dermal substitution, reconstruction of skin that possesses functionality is an important goal for dermatologists. we attempted to regenerate eccrine sweat glands in vitro. we constructed skin equivalent models with various combination of normal human keratinocytes and fibroblasts and also examined the effect of various growth factors. we found that keratinocytes invaded the collagen gels and formed eccrine duct-like structures, only when (i) the culture media contained at least 15 ng/ml of epidermal growth factor (EGF) and fetal bovine serum (FBS), (ii) the keratinocytes were derived from young donors, and (iii) fibroblasts were present in the gel. Interestingly, when cultured under the same conditions eccrine gland duct cells were unable to invade the gel. Immunohistochemical analyses revealed induction of carcinoembryonic antigen by EGF at the inner part of the eccrine duct-like structures. Proliferating cell nuclear antigen was expressed mainly in basal layers of the epithelia but was not observed in the deeply invaded part. Cytokeratin profiles of the reconstructed epithelia were consistent with those of the regenerating epidermis and partly with the eccrine sweat duct. although not perfect model, these results indicate that 'young' keratinocytes could differentiate into/toward eccrine sweat ducts in vitro in the presence of EGF and FBS in cooperation with dermal fibroblasts.


Burns and military clothing.
Burn injury is a ubiquitous threat in the military environment. The risks during combat are well recognised, but the handling of fuel, oil, munitions and other hot or flammable materials during peacetime deployment and training also imposes an inherent risk of accidental burn injury. Over the last hundred years, the burn threat in combat has ranged from nuclear weapons to small shoulder-launched missiles. Materials such as napalm and white phosphorus plainly present a risk of burn, but the threat extends to encompass personnel in vehicles attacked by anti-armour weapons, large missiles, fuel-air explosives and detonations/conflagrations on weapons platforms such as ships. Large numbers of burn casualties were caused at Pearl Harbor, in Hiroshima and Nagasaki, Vietnam, during the Arab/Israeli Wars and in the Falkland Islands conflict. The threat from burns is unlikely to diminish, indeed new developments in weapons seek to exploit the vulnerability of the serviceman and servicewoman to burns. Clothing can be a barrier to some types of burn--both inherently in the properties of the material, but also by trapping air between clothing layers. Conversely, ignition of the clothing may exacerbate a burn. There is hearsay that burnt clothing products within a wound may complicate the clinical management, or that materials that melt (thermoplastic materials) should not be worn if there is a burn threat. This paper explores the incidence of burn injury, the mechanisms of heat transfer to bare skin and skin covered by materials, and the published evidence for the complication of wound management by materials. Even light-weight combat clothing can offer significant protection to skin from short duration flash burns; the most vulnerable areas are the parts of the body not covered--face and hands. Multilayered combat clothing can offer significant protection for short periods from engulfment by flames; lightweight tropical wear with few layers offers little protection. Under high heat loads in the laboratory, combat clothing can ignite, but there is little evidence that clothing ignition is a common occurrence in military burn casualties. Thermoplastic materials have many benefits in civil and military clothing. There is little objective evidence that they exacerbate burns, or complicate burn management. Their use in military clothing must be based on objective evidence, not hearsay.


In vivo activities of simulated human doses of cefepime and cefepime-AAI101 against multidrug-resistant Gram-negative Enterobacteriaceae.
The combination of cefepime with AAI101, a novel extended-spectrum β-lactamase inhibitor, possesses potent in vitro activity against many resistant Gram-negative pathogens. Against a panel of 20 mostly carbapenemase-producing cefepime-nonsusceptible strains of the family Enterobacteriaceae, we evaluated the MICs of cefepime in the presence of various fixed AAI101 concentrations (1, 2, 4, 8, and 16 mg/liter) and the in vivo efficacy of simulated human doses of cefepime and cefepime-AAI101 in a neutropenic murine thigh infection model. At 2 h after inoculation, mice were dosed with regimens that provided a profile mimicking the free drug concentration-time profile observed in humans given cefepime at 2 g every 8 h (q8h; as a 30-min infusion) or cefepime-AAI101 at 2 g/0.5 g q8h (as a 30-min infusion). Efficacy was determined by calculation of the change in thigh bacterial density (log10 number of CFU) after 24 h relative to the starting inoculum (0 h). After 24 h, bacterial growth of 2.7 ± 0.1 log10 CFU (mean ± standard error) was observed in control animals. Efficacy for cefepime monotherapy was observed against only 3 isolates, whereas increases in bacterial density similar to that in the control animals were noted for the remaining 17 strains (all with cefepime MICs of ≥ 64 mg/liter). The humanized cefepime-AAI101 dosing regimen resulted in bacterial reductions of ≥ 0.5 log10 CFU for 12 of the 20 strains. Evaluation of efficacy as a function of the fraction of the dosing interval during which free drug concentrations were above the MIC determined with different fixed concentrations of AAI101 suggested that a fixed concentration of 8 mg/liter AAI101 is most predictive of in vivo activity for the studied regimen.


WNK4 kinase inhibits Maxi K channel activity by a kinase-dependent mechanism.
WNK [with no lysine (k)] kinase is a serine/threonine kinase subfamily. Mutations in two of the WNK kinases result in pseudohypoaldosteronism type II (PHA II) characterized by hypertension, hyperkalemia, and metabolic acidosis. Recent studies showed that both WNK1 and WNK4 inhibit ROMK activity. However, little is known about the effect of WNK kinases on Maxi K, a large-conductance Ca(2+) and voltage-activated potassium (K) channel. Here, we report that WNK4 wild-type (WT) significantly inhibits Maxi K channel activity in HEK αBK stable cell lines compared with the control group. However, a WNK4 dead-kinase mutant, D321A, has no inhibitory effect on Maxi K activity. We further found that WNK4 inhibits total and cell surface protein expression of Maxi K equally compared with control groups. A dominant-negative dynamin mutant, K44A, did not alter the WNK4-mediated inhibitory effect on Maxi K surface expression. Treatment with bafilomycin A1 (a proton pump inhibitor) and leupeptin (a lysosomal inhibitor) reversed WNK4 WT-mediated inhibition of Maxi K total protein expression. These findings suggest that WNK4 WT inhibits Maxi K activity by reducing Maxi K protein at the membrane, but that the inhibition is not due to an increase in clathrin-mediated endocytosis of Maxi K, but likely due to enhancing its lysosomal degradation. Also, WNK4's inhibitory effect on Maxi K activity is dependent on its kinase activity.


[A simple method for tricuspid annuloplasty (author's transl)].
A new operative method for tricuspid annuloplasty is reported. In this method the antero-posterior portion of the tricuspid annulus is sutured to a semi-circular nonelastic strip of teflon by double needle sutures. Since the radius of this strip is shorter than the radius of the valve ring, the tricuspid annulus will be narrowed after the sutures are tied. Because of its simplicity, firmness and maintenance of the valvular ring elasticity, this method seems to be advantageous to all similar procedures. The results of the method in 5 patients with severe tricuspid incompetence have been excellent. This method can also be used for annuloplasty of the mitral valve.


Pilot Study Evaluating the Use of Typodonts (Dental Models) for Teaching Veterinary Dentistry as Part of the Core Veterinary Curriculum.
Periodontal disease is one the most common disease pathologies in small animal medicine, yet new graduates report they feel unprepared to perform dentistry in general practice. Novel methodologies to close the knowledge gap in veterinary dentistry need to be identified. Typodonts (dental models) are commonly used in human dental schools to teach basic principles prior to practice on clinical patients and have been shown to be an effective teaching tool. The study aimed to determine if independent study and self-guided practice on a veterinary typodont prior to a structured, in-person cadaver laboratory with feedback increases students' perceived dentistry clinical skills in performing periodontal techniques. We calculated the knowledge gap before and after the cadaver laboratory by comparing the students' perceived and desired skill levels in performing periodontal charting, ultrasonic cleaning, hand scaling, and root planing. Ninety-six percent of students reported that practice with the dental typodont prior to the cadaver laboratory increased their comfort level in performing periodontal skills. However, practice did not result in a significant decrease in knowledge gap compared with participation in the cadaver laboratory alone. Although students perceived a benefit to practicing with the typodont, self-guided practice was not effective in decreasing the knowledge gap, most likely due to a lack of structured feedback with typodont use. Further investigation into the use of typodonts with direct feedback prior to structured laboratory or, alternatively, as an additional practice tool following a structured laboratory would further define if there is a benefit to typodont practice in veterinary dentistry.


[Pleuropneumonectomy with the trans-sternal approach].
The trans-sternal access to the lung and its root was used in 31 operations of pleuropulmonectomy. The access made it possible to separate without difficulty and almost without blood loss and to treat the elements of the lung root without its preliminary isolation from the adhesion with the thoracic wall. Before the removal of the lung the author proposes to transfuse the remaining blood from the pulmonary vessels into the vein of the patients. This measure helps preserve about 500 ml of the patient's blood. By means of using the trans-sternal access and inverse blood transfusion the total blood loss during the operation was found to be 5--6 times less which in its turn resulted in 2,5--3 times less postoperative lethality.


Chemists gather in denver to get the big picture.
The Rockies were hidden by clouds, but "Welcome ACS" signs were visible all over the Mile High City from 28 March to 2 April. No wonder the city's boosters were cheering: More than 10,000 scientists, purveyors of laboratory equipment, and other chemophiles had flooded into Denver to take in a vision of chemistry's intellectual scope that was wide enough to compensate for the missing scenic grandeur. In just a tiny sampling of the roughly 4800 presentations, chemistry appears in guises ranging from the most basic molecule making, through cleanup strategies for major environmental challenges, to forensic methods for unraveling a historical mystery.


The role of endplate poromechanical properties on the nutrient availability in the intervertebral disc.
To investigate the relevance of the human vertebral endplate poromechanics on the fluid and metabolic transport from and to the intervertebral disc (IVD) based on educated estimations of the poromechanical parameter values of the bony endplate (BEP). 50 micro-models of different BEP samples were generated from μCTs of lumbar vertebrae and allowed direct determination of porosity values. Permeability values were calculated by using the micro-models, through the simulation of permeation via computational fluid dynamics. These educated ranges of porosity and permeability values were used as inputs for mechano-transport simulations to assess their effect on both the distributions of metabolites within an IVD model and the poromechanical calculations within the cartilaginous part of the endplate i.e., the cartilage endplate (CEP). BEP effective permeability was highly correlated to local variations of porosity (R(2) ≈ 0.88). Universal patterns between bone volume fraction and permeability arose from these results and from other experimental data in the literature. These variations in BEP permeability and porosity had negligible effects on the distributions of metabolites within the disc. In the CEP, the variability of the poromechanical properties of the BEP did not affect the predicted consolidation but induced higher fluid velocities. The present paper provides the first sets of thoroughly identified BEP parameter values that can be further used in patient-specific poromechanical studies. Representing BEP structural changes through variations in poromechanical properties did not affect the diffusion of metabolites. However, attention might be paid to alterations in fluid velocities and cell mechano-sensing within the CEP.


Neutrophil depletion in the pre-implantation phase impairs pregnancy index, placenta and fetus development.
Maternal neutrophils cells are players in gestational tolerance and fetus delivery. Nonetheless, their actions in each phase of the pregnancy are unknown. We here investigated the role of maternal neutrophil depletion before the blastocyst implantation phase and outcomes in the pregnancy index, placenta, and fetus development. Neutrophils were pharmacologically depleted by i.p. injection of anti-Gr1 (anti-neutrophils; 200 µg) 24 hours after plug visualization in allogeneic-mated C57BL/6/BALB/c mice. Depletion of peripheral neutrophils lasted until 48 hours after anti-Gr1 injection (gestational day 1.5-3.5). On gestational day 5.5, neutrophil depletion impaired the blastocyst implantation, as 50% of pregnant mice presented reduced implantation sites. On gestational day 18.5, neutrophil depletion reduced the pregnancy rate and index, altered the placenta disposition in the uterine horns, and modified the structure of the placenta, detected by reduced junctional zone, associated with decreased numbers of giant trophoblast cells, spongiotrophoblast. Reduced number of placenta cells labeled for vascular endothelial growth factor (VEGF), platelet-endothelial cell adhesion molecule (PECAM-1), and intercellular cell adhesion molecule (ICAM-1), important markers of angiogenesis and adhesiveness, were detected in neutrophil depleted mice. Furthermore, neutrophil depletion promoted a higher frequency of monocytes, natural killers, and T regulatory cells, and lower frequency of cytotoxic T cells in the blood, and abnormal development of offspring. Associated data obtained herein highlight the pivotal role of neutrophils actions in the early stages of pregnancy, and address further investigations on the imbricating signaling evoked by neutrophils in the trophoblastic interaction with uterine epithelium.


The relative advantages of criminal versus administrative environmental enforcement actions in Israel.
Most environmental enforcement programs have separate criminal and administrative procedures for addressing violations. Pitting "criminal"versus"administrative" enforcement as mutually exclusive alternatives constitutes a "false dilemma". Clearly, the government response should be influenced by the severity of pollution and the specific circumstances of the polluter. Yet, policy makers seeking to improve environmental compliance need to have a clearer picture about the merits of each approach and their relative effectiveness. This research empirically assesses the effectiveness of criminal versus administrative enforcement activities in Israel. After considering the philosophical implications associated with each regulatory approach, the results of a year-long study are presented. A series of performance indicators are utilized, with particular weight on compliance status in the field, to assess the condition of environmental violations several years subsequent to completion of enforcement activities. The state of 100 violations of air, water and hazardous materials laws that had been addressed through the criminal process were matched with results of comparable violations, against which administrative actions were taken. Results suggest that while criminal enforcement is a longer process, compliance following these actions was significantly greater than in administrative enforcement cases. The findings also underline the significance of a systematic follow-up system for tracking violations after enforcement actions are complete. Finally, the study confirms the benefits of targeted assistance to improve compliance among violators of environmental standards.


Ethanol withdrawal acts as an age-specific stressor to activate cerebellar p38 kinase.
We investigated whether protein kinase p38 plays a role in the brain-aging changes associated with repeated ethanol withdrawal (EW). Ovariectomized young, middle-age and older rats, with or without 17β-estradiol (E2) implantation, received a 90-day ethanol with repeated withdrawal. They were tested for active pP38 expression in cerebellar Purkinje neurons and whole-cerebellar lysates using immunohistochemistry and enzyme-linked immunosorbent assay, respectively. They were also tested for the Rotarod task to determine the behavioral manifestation of cerebellar neuronal stress and for reactive oxygen species (ROS) and mitochondrial protein carbonyls to determine oxidative mechanisms. Middle-age EW rats showed higher levels of pP38-positive Purkinje neurons/cerebellar lysates, which coincided with increased mitochondrial protein oxidation than other diet/age groups. Exacerbated motor deficit due to age-EW combination also began at the middle-age. In comparison, ROS contents peaked in older EW rats. E2 treatment mitigated each of the EW effects to a different extent. Collectively, pP38 may mediate the brain-aging changes associated with pro-oxidant EW at vulnerable ages and in vulnerable neurons in a manner protected by estrogen.


Accuracy of remote diagnoses using intraoral scans captured in approximate true color: a pilot and validation study in teledentistry.
Intraoral scans (IOS) provide three-dimensional images with approximate true colors representing a possible tool in teledentistry for remote examination. The aim of the present cross-sectional validation study was, therefore, to evaluate the levels of agreement between remote diagnoses derived from IOS and diagnoses based on clinical examinations for assessing dental and periodontal conditions. The test sample comprised 10 patients representing different clinical conditions. Following the acquisition of IOS (Trios, 3Shape), a full-mouth dental and periodontal examination was done and periapical radiographs were taken. Ten dentists were asked to perform dental and periodontal scorings for each of the ten patients on a tablet computer presenting the IOS. Scores included diagnosis of gingivitis/periodontitis, and evaluated presence as well as amount of plaque and calculus, and presence of teeth exhibiting gingival recession, furcation involvement, erosion, tooth wear, stain, and non-carious cervical lesion, as well as presence of decayed, filled, and crowned teeth and implants. In a second round of assessments, the periapical radiographs were provided and the dentists were able to change the scores. The time for the remote assessment was recorded. The agreement between remote and clinical scorings (reference) was then analyzed descriptively. The mean time for the tele assessment was 3.17 min and the additional consultation of the radiographs accounted for another 1.48 min. The sensitivity and specificity values were 0.61 and 0.39 for gingivitis and 0.67 and 0.33 for periodontitis, with no relevant changes when radiographs were provided for the diagnosis of periodontitis (0.72 and 0.28). The agreement for dichotomized dental and periodontal indices ranged between 78 and 95%. With the provision of radiographs, the remote examiners were able to detect existing filled teeth, crowned teeth, and implants, whereas the detection of decayed teeth (70%) was not improved. The remote examination using IOS was effective in detecting dental findings, whereas periodontal conditions could not be assessed with the same accuracy. Still, remote assessment of IOS would allow a time-efficient screening and triage of patients. Improvement of the image quality of IOS may further allow to increase the accuracy of remote assessments in dentistry. According to the Swiss Regulation this investigation is not a clinical trial and therefore no registration in a WHO-registry is needed.


Self-disclosure and Channel Difference in Online Health Support Groups.
Online health support groups are places for people to compare themselves with others and obtain informational and emotional support about their disease. To do so, they generally need to reveal private information about themselves and in many support sites, they can do this in public or private channels. However, we know little about how the publicness of the channels in health support groups influence the amount of self-disclosure people provide. Our work examines the extent members self-disclose in the private and public channels of an online cancer support group. We first built machine learning models to automatically identify the amount of positive and negative self-disclosure in messages exchanged in this community, with adequate validity (r>0.70). In contrast to findings from non-health-related sites, our results show that people generally self-disclose more in the public channel than the private one and are especially likely to reveal their negative thoughts and feelings publicly. We discuss theoretical and practical implications of our work.


Topics associated with conflict in print news coverage of the HPV vaccine during 2005 to 2009.
HPV vaccines represent a significant advancement for cancer prevention, but vaccination against a sexually transmitted infection and possible vaccine mandates have created considerable negative publicity. We sought to understand media portrayal of vaccine-related controversy, and potential influences on attitudes and vaccine acceptance. We analyzed characteristics of media coverage of the HPV vaccine in 13 US newspapers between June 2005-May 2009, as well as relationships between conflict and pro-vaccine tone and specific story characteristics. The four-year timeframe was selected to capture coverage during the development of the vaccine, the period immediately pre- and post-approval, and the time of widespread recommendation and initial uptake. This allowed the exploration of a range of issues and provided an understanding of how coverage changed over time. Analysis included 447 news stories and opinion pieces, the majority of which were published in 2007. Most articles were positive (pro-vaccine) in tone, prompted by research/scientific advancement or legislative activities. We deemed 66% of all stories conflict-containing. Fewer articles from 2005-2006 and 2008-2009 contained conflict than those from 2007, suggesting a peak period of concern, followed by gradual acceptance of the HPV vaccine. Legislative activities and content related to sexual activity were sources of conflict in HPV vaccine media messages. Health communication strategies can be improved by understanding and addressing potential sources of conflict in news coverage of public health initiatives.


Biotransformation of 13-cis- and 9-cis-retinoic acid to all-trans-retinoic acid in rat conceptal homogenates. Evidence for catalysis by a conceptal isomerase.
The purpose of this study was to investigate whether and to what extent the steric isomerization of retinoic acids in conceptal tissues can be attributed to enzymatic catalysis in addition to thiol-dependent, nonenzymatic catalysis. Conversions of 13-cis-retinoic acid and 9-cis-retinoic acid to all-trans-retinoic acid catalyzed by cell-free preparations of conceptal rat tissues (gestational day 12.5) were investigated. Substrates and rat conceptal homogenates (RCH) were incubated in sodium phosphate buffer (0.1 M, pH 7.5) at 37 degrees C in the dark. Incubation mixtures were quantitatively analyzed by HPLC. In RCH-catalyzed reactions, conversions of 13-cis-retinoic acid or 9-cis-retinoic acid to all-trans-retinoic acid were very rapid, in comparison with uncatalyzed isomerization reactions (incubations without RCH). Comparisons of the rates of reactions catalyzed by freshly prepared vs. freshly prepared/dialyzed RCH showed no significant differences, indicating that small, suflhydryl-containing molecules such as reduced glutathione did not significantly contribute to the RCH-catalyzed reactions. Furthermore, at physiological concentrations (2.5-10 mM), reduced glutathione exhibited very low specific catalytic activities, indicating that nonenzymatic, sulfhydryl-dependent catalysis was not a major mechanism in catalyzing interconversions of retinoic acids in vivo. Enzymatic catalysis by RCH of the conversion of 13-cis-retinoic acid to all-trans-retinoic acid was further characterized by showing 1) substrate saturation kinetics, 2) reaction rates that increased proportionally with protein concentrations, and (3) much greater sensitivity of the reactions to heat inactivation and denaturation by urea, compared with nonenzymatic, glutathione-catalyzed reactions. Thus, isomerization of retinoids in conceptal tissues appeared to be under enzymatic control.


Brain regions associated with psychological pain: implications for a neural network and its relationship to physical pain.
Research on brain areas involved in experiencing emotion and physical pain is abundant; however, psychological pain has received little attention in studies of the brain. The purpose of this systematic review was to provide an overview of studies on brain function related to psychological pain. The review was limited to studies in which participants experienced actual psychological pain or recalled a significant autobiographical event that may be assumed to have involved psychological pain. Based on results of the studies (N = 18), a tentative neural network for psychological pain is proposed that includes the thalamus, anterior and posterior cingulate cortex, the prefrontal cortex, cerebellum, and parahippocampal gyrus. Results indicated that grief may be a more accurate exemplar of psychological pain than recalled sadness, with indications of greater arousal during psychological pain. The proposed neural network for psychological pain overlaps to some extent with brain regions involved in physical pain, but results suggest a markedly reduced role for the insula, caudate, and putamen during psychological pain. Psychological pain is well known for its association with depression and as a precursor of suicidal behavior. Thus, identification of brain areas involved in psychological pain may help guide development of interventions to decrease mortality and morbidity.


Spousal Caregiving in Community Settings in Canada: Implications for Nursing Professionals.
Objective: Spousal caregivers report significantly more health effects and psychological consequences than caregivers of aging parents. Traditional approaches to assist these caregivers often include lifestyle approaches with a lack of health promotion initiatives. Consequently, alternative approaches to facilitate the adaptation to the social context of spousal caregivers' experiences are needed. Method: This article systematically reviewed literature on spousal caregiving in Canada using a health promotion approach. Nine peer reviewed articles were identified from the health and social care literature and critically analyzed for relevant themes. Results: Gender, social support, health care, and income emerged as themes in the literature published to date. Discussion: The article concludes with directions for future research in Canada and suggested solutions for family nursing practice.


The salivary gland salivation stimulating peptide from Locusta migratoria (Lom-SG-SASP) is not a typical neuropeptide.
The salivary gland salivation stimulating peptide was identified from the salivary glands of the migratory locust by its ability to stimulate cAMP production in the same tissue. The gene coding for this peptide has recently been identified and been shown to code for a precursor consisting of a signal peptide, several copies of the peptide separated by Lys-Arg doublets and a few other peptides. These data are consistent with it being a neuropeptide. However, antiserum raised to this peptide labels the acini of the salivary glands while RT-PCR only gives positive results in the salivary gland, but not in any ganglion of the central nervous system. Thus, this peptide is not a typical neuropeptide as previously assumed.


Reduced prefrontal gyrification in obsessive-compulsive disorder.
Structural magnetic resonance imaging (MRI) studies reveal evidence for brain abnormalities in obsessive-compulsive disorder (OCD), for instance, reduction of gray matter volume in the prefrontal cortex. Disturbances of gyrification in the prefrontal cortex have been described several times in schizophrenia pointing to a neurodevelopmental etiology, while gyrification has not been studied so far in OCD patients. In 26 OCD patients and 38 healthy control subjects MR-imaging was performed. Prefrontal cortical folding (gyrification) was measured bilaterally by an automated version of the automated-gyrification index (A-GI), a ratio reflecting the extent of folding, from the slice containing the inner genu of the corpus callosum up to the frontal pole. Analysis of covariance (ANCOVA, independent factor diagnosis, covariates age, duration of education) demonstrated that compared with control subjects, patients with OCD displayed a significantly reduced A-GI in the left hemisphere (p = 0.021) and a trend for a decreased A-GI in the right hemisphere (p = 0.076). Significant correlations between prefrontal lobe volume and A-GI were only observed in controls, but not in OCD patients. In conclusion, prefrontal hypogyrification in OCD patients may be a structural correlate of the impairment in executive function of this patient group and may point to a neurodevelopmental origin of this disease.


Determination of low-molecular-mass anions in coating samples by capillary electrophoresis with conductometric detection.
A method for the rapid analysis of low-molecular-mass anions in electrodeposition coatings has been developed, employing capillary electrophoresis with a nonsuppressed end-capillary conductivity detector. After optimization of the carrier electrolyte, quantitative determination of all analytes of interest (including inorganic anions and organic acids) was possible in less than 11 min. The results obtained by capillary electrophoresis did not show any significant differences with the manufacturer's data originating from the more time-consuming ion-chromatographic analysis.


Lidocaine given intravenously improves conditions for laryngeal mask airway insertion during propofol target-controlled infusion.
Patient response to laryngeal mask airway insertion during propofol induction depends on many factors. Lidocaine has been used to reduce cardiovascular responses, coughing, and bucking induced by tracheal intubation. The aim of this study was to determine the effects of intravenous lidocaine on laryngeal mask airway insertion conditions during the induction of anaesthesia with propofol target-controlled infusion. Eighty patients, 16-54 years of age, weighing between 45 and 100 kg, who underwent minor surgery, were randomly divided into two groups (the lidocaine and control groups). Anaesthesia was induced with propofol target-controlled infusion at a target plasma concentration of 6 microg ml. The lidocaine group received 1.5 mg kg of lidocaine 50 s after starting target-controlled infusion and the control group received an equivalent volume of saline. Laryngeal mask airways were inserted when propofol effect-site concentrations reached 2.5 microg ml. Laryngeal mask airway insertion conditions (mouth opening, gagging, coughing, movements, laryngospasm, overall ease of insertion, and hiccups) were assessed, and haemodynamic responses were monitored for 3 min after laryngeal mask airway insertion. No significant differences were observed between the two groups in terms of haemodynamic responses. However, the lidocaine group showed lower incidences of coughing (5 vs. 22.5%), gagging (25 vs. 55%), and laryngospasm (2.5 vs. 17.5%) (P < 0.05). Pretreatment with intravenous lidocaine 1.5 mg kg during induction with propofol target-controlled infusion improves laryngeal mask airway insertion conditions.


Mechanical properties of solvent-dehydrated bovine pericardium xeno graft for dura mater repair.
Collagen implants of dehydrated bovine pericardium have been developed as biodegradable materials for the surgical repair of cranial dura mater defects. However, the knowledge of the mechanical properties of the allograft is necessary to assess the reliability of the tissue reconstruction, since it is expected to withstand the functional loading in situ while the natural tissue heals. Tensile and stress-relaxation tests were performed on six rectangular samples of dehydrated bovine pericardium (DBP) graft (Tutogen Medical GmbH, Germany). In order to account for the anisotropic fiber architecture, the tests were run along two perpendicular directions of each graft, aligned to the sample edges. The stress-strain curves were non-linear, with fast stiffening at increasing strains. The stiffness in the transverse direction of the graft was only 1.5 times the one in the longitudinal direction, and for clinical purposes the xenograft can be considered as isotropic. The amount of stress relaxation was affected neither by the magnitude of the applied strain nor by the direction of stretching. The properties of the DBP were compared to the ones of native dura mater. Both the strength and the stiffness of cranial dura mater were well matched by the xenograft, but the graft material exhibited about twice the extensibility: the linear region of the stress-strain curve is attained at larger extension, although the slope of the curve in this region is similar to the native dura one. Pre-tensioning the graft in situ at surgery would reduce this slack strain; and therefore, improve compliance matching with the native tissue.


Regulation of matrix metalloproteinase 2 by oligomeric amyloid β protein.
Matrix metalloproteinases (MMPs) are a group of proteinases that degrade components of the extracellular matrix (ECM). There is increasing evidence for a link between the activation of MMPs and Alzheimer's disease (AD) pathogenesis, in which both beneficial and detrimental actions of MMPs have been suggested. It has been demonstrated that MMPs could degrade amyloid β (Aβ) and play important roles in the extracellular Aβ catabolism and clearance. On the other hand, MMPs could contribute to AD pathogenesis by compromising the blood brain barrier and promoting neurodegeneration. In the present study, we observed that oligomeric Aβ regulates MMP2 expression in a paradoxical manner. In rat primary astrocyte cultures, oligomeric Aβ down-regulated MMP2 transcription and reduced its extracellular activity. However, in a widely used mouse model for AD, immunohistochemistry demonstrated an increase of MMP2 expression in astrocytes surrounding senile plaques in APP/PS1 transgenic mice brains. Using real-time PCR, we found that the MMP2 mRNA level was elevated in APP/PS1 transgenic mice brains. In addition, elevated mRNA levels of MMP stimulating cytokines such as IL-1β and TGFβ were found in the brains of APP/PS1 mice. Our study suggests a complex regulation of MMP2 expression by oligomeric Aβ in astrocytes. While oligomeric Aβ directly down-regulates MMP2 expression and activation in astrocytes, it induces production of proinflammatory cytokines which could serve as strong stimulators for MMP2. Therefore, the ultimate outcome of the oligomeric Aβ on MMP2 activation in astrocytes might be the combination of its direct inhibitory action on astrocyte MMP2 expression and the secondary action of inducing inflammatory cytokines.


Interleukin-33 Contributes to the Induction of Th9 Cells and Antitumor Efficacy by Dectin-1-Activated Dendritic Cells.
We recently discovered that dectin-1-activated dendritic cells (DCs) drive potent T helper (Th) 9 cell responses and antitumor immunity. However, the underlying mechanisms need to be further defined. The cytokine microenvironment is critical for Th cell differentiation. Here, we show that dectin-1 activation enhances interleukin (IL)-33 expression in DCs. We found that blocking IL-33/ST2 inhibits dectin-1-activated DC-induced Th9 cell differentiation. More importantly, the addition of IL-33 further promotes Th9 cell priming and antitumor efficacy induced by dectin-1-activated DCs. Mechanistically, in addition to the promotion of Th9 and Th1 cells, dectin-1-activated DCs combined with IL-33 abolish the activity of IL-33 in the induction of regulatory T cells. Furthermore, the combined treatment of dectin-1-activated DCs and IL-33 increases the frequencies of CD4+ T cells by fostering their proliferation and inhibiting their exhaustive differentiation. Thus, our results demonstrate the important role of IL-33 in dectin-1-activated DC-induced Th9 cell differentiation and antitumor efficacy, and suggest that the combination of dectin-1-activated DCs and IL-33 may present a new effective modality of DC-based vaccines in tumor immunotherapy.


Hospitalizations and Emergency Room Admissions by Mexican American Older Adults with and without Dementia and Caregiver Mental Health.
Evidence from predominately non-Hispanic White populations indicates that emergency room (ER) admissions and hospitalizations by older adults with and without dementia are associated with caregiver stress and depressive symptoms. These results may not generalize to Hispanic populations because of cultural differences in caregiving roles, responsibilities, and perspectives about care burden. Investigate the association between ER admissions and hospitalizations by Mexican American older adults with and without dementia and symptoms of depression and stress among family caregivers. Data came from the 2010/11 wave of the Hispanic Established Populations for the Epidemiologic Study of the Elderly and Medicare claims files. The final sample included 326 older adults and their caregivers. Negative binomial regression was used to model the association between hospitalizations and ER admissions by older adults in the previous two years and caregivers' depressive symptoms and stress in 2010/11. The number of older adult ER admissions and hospitalizations was not associated with caregiver depressive symptoms. Two or more ER admissions (incident rate ratio [IRR] = 1.26, 95% CI = 1.05-1.51) and two or more hospitalizations (IRR = 1.32, 95% CI = 1.07-1.61) were associated with significantly higher caregiver stress. Additionally, ER admissions and hospitalizations for a circulatory disease or injury and poisoning were associated with significantly higher caregiver stress. These associations were not modified by the care recipient's dementia status. Hospitalizations and ER admissions by older Mexican Americans were associated with greater caregiver stress but not depressive symptoms. These associations were similar for caregivers to older adults with and without dementia.


Centile-based early warning scores derived from statistical distributions of vital signs.
To develop an early warning score (EWS) system based on the statistical properties of the vital signs in at-risk hospitalised patients. A large dataset comprising 64,622 h of vital-sign data, acquired from 863 acutely ill in-hospital patients using bedside monitors, was used to investigate the statistical properties of the four main vital signs. Normalised histograms and cumulative distribution functions were plotted for each of the four variables. A centile-based alerting system was modelled using the aggregated database. The means and standard deviations of our population's vital signs are very similar to those published in previous studies. When compared with EWS systems based on a future outcome, the cut-off values in our system are most different for respiratory rate and systolic blood pressure. With four-hourly observations in a 12-h shift, about 1 in 8 at-risk patients would trigger our alerting system during the shift. A centile-based EWS system will identify patients with abnormal vital signs regardless of their eventual outcome and might therefore be more likely to generate an alert when presented with patients with redeemable morbidity or avoidable mortality. We are about to start a stepped-wedge clinical trial gradually introducing an electronic version of our EWS system on the trauma wards in a teaching hospital.


Changes in sobriety in the Swedish population over three decades: age, period or cohort effects?
This study aimed to examine age, cohort and period trends in alcohol abstinence. Two surveys, the Level of Living Survey collected in 1968, 1974, 1981, 1990 and 2000, and the Swedish Panel Study of the Oldest Old (SWEOLD) collected in 1992 and 2002, were studied with graphical depictions of cross-sectional and longitudinal data presented over time and over age. Cross-sectional 10-year age group differences, time-lag differences between waves and within-cohort differences between waves for 10-year birth cohorts were examined. Logistic regression models were applied to confirm the observed patterns. The samples were representative of the Swedish population. Participants ranged in age from 18 to 75 (n = 5000 per wave), and 77+ at later waves (n = 500). Alcohol abstinence was determined by asking 'Do you ever drink wine, beer, or spirits?', where a 'no' response indicated abstinence. Decreases in abstinence rates were observed from 1968 to 2000/02. While cross-sectional analysis indicated increased abstinence with advancing age, the longitudinal analysis suggested otherwise. Inspection of cohort differences revealed little change within cohorts and large differences between cohorts; abstinence rates declined in later-born cohorts up to the 1940s birth cohorts; stability was observed in cohorts born since the 1940s. Logistic regression models indicated that neither age nor period were significant (P > 0.05) predictors of abstinence when cohort (P < 0.001) was included. Decreasing proportions of total alcohol abstainers in Sweden from 1968 to 2000 appear to be attributable primarily to decreases in successive cohorts rather than drinkers becoming abstainers.


Role of clinical pharmacist in the palliative care of adults and elderly patients with cancer: A scoping review.
We conducted this scoping review to map and summarize scientific evidence on the role of clinical pharmacists in the palliative care of adults and elderly patients with cancer. A literature search was performed in MEDLINE, PubMed Central, Embase, Web of Science, Scopus, and BVS/BIREME for studies published until November 22nd, 2020. Studies that reported work experiences adopted by clinical pharmacists in the palliative care of adults and elderly patients with cancer were included. Two independent authors performed study selection and data extraction. Any disagreements were resolved by discussion with the third and fourth authors. The pharmacist interventions identified in the included studies were described based on key domains in the DEPICT v.2. A total of 586 records were identified, of which 14 studies fully met the eligibility criteria. Most of them were conducted in the United States of America (n = 5) and Canada (n = 5) and described the workplace of the pharmacist in clinic/ambulatory (n = 10). Clinical pharmacists performed several activities and provided services, highlighting medication review (n = 12), patient and caregivers education (n = 12), medication histories and-or medication reconciliation (n = 6). The pharmacist interventions were mostly conducted for patients/caregivers (n = 13), by one-on-one contact (n = 14), and by face-to-face (n = 13). Pharmacists were responsible mainly for change or suggestion for change in therapy (n = 12) and patient counselling (n = 12). Pharmacist interventions were well accepted by the clinical team. Overall, studies showed that pharmacists, within an interdisciplinary team, had significant impacts on measured outcomes. In recent years, there have been advances in the role of the pharmacist in palliative care of patients with cancer and there are great opportunities in this field. They play an important role in managing cancer pain and other symptoms, as well as resolving drug related problems. We encourage more research to be carried out to strengthen this field and to benefit patients with advanced cancer with higher quality of life.


What is the current state of care for older people with dementia in general hospitals? A literature review.
This paper summarises a literature review focusing on the literature directly pertaining to the acute care of older people with dementia in general hospitals from 2007 onwards. Following thematic analysis, one overarching theme emerged: the consequences of being in hospital with seven related subthemes. Significantly, this review highlights that overall there remains mostly negative consequences and outcomes for people with dementia when they go into general hospitals. Although not admitted to hospital directly due to dementia, there are usually negative effects on the dementia condition from hospitalisation. The review suggests this is primarily because there is a tension between prioritisation of acute care for existing co-morbidities and person-centred dementia care. This is complicated by insufficient understanding of what constitutes person-centred care in an acute care context and a lack of the requisite knowledge and skills set in health care practitioners. The review also reveals a worrying lack of evidence for the effectiveness of mental health liaison posts and dementia care specialist posts in nursing. Finally, although specialist posts such as liaison and clinical nurse specialists and specialist units/shared care wards can enhance quality of care and reduce adverse consequences of hospitalisation (they do not significantly) impact on reducing length of stay or the cost of care.


Outsiders Within: The Lived Experience of Being Black and Female When Becoming a Nurse Executive.
Few Black nurses occupy positions of leadership, and even fewer Black female nurses advance to careers as nurse executives. The purpose of this 2018 study was to explore the lived experience of being Black and female when becoming a nurse executive, specifically the nuances of being both a racial and gender minority. Using a hermeneutic phenomenological method, this study explored the experiences of a purposive sample of 10 Black female nurse executives through semistructured telephone interviews. van Manen's approach and Collins' Black feminist thought as the theoretical framework guided data analysis. Three themes emerged: (a) living in a constant state of readiness; (b) embracing the responsibility beyond the job description; and (c) overcoming. Participants testified of the psychological dynamics of Black womanness, and the burdens of the intersectionality of race, gender, and class discrimination, while managing the complexities and rigors of a thriving career. Discussing the results of this research will help leaders in nursing, health care, and related professions to understand further the experiences of Black female nurse executives, which will inform efforts to (a) increase minority representation in positions of nursing leadership and (b) improve health equity.


Physical gels made of liquid crystalline B4 phase.
The achiral liquid crystalline materials showing two B4 (HN) phases have been found to exhibit strong gelation ability for various organic solvents with reversible sol-gel phase transition. The gel is formed by helical tubules, which build entangled 3D network, encapsulating the solvent. The equilibrium of left- and right-handed tubules is preserved in the gel, even if the chiral solvent is used.


Examining the treatment gap and risk of subsequent fractures among females with a fragility fracture in the US Medicare population.
Our aim was to evaluate the gap in osteoporosis treatment and the impact of osteoporosis treatment on subsequent fragility fractures. We found osteoporosis medication use lowered risk of subsequent fractures by 21% and that black race, higher CCI scores, dementia, and kidney diseases reduced the likelihood of osteoporosis medication use. The goal of this study was to evaluate the predictors of osteoporosis medication use and compare the risk of fragility fractures within 1 year of a fragility fracture between osteoporosis treated and untreated women. We conducted a retrospective, observational cohort study using the national Medicare database. Elderly women (≥65 years) who were hospitalized or had an outpatient/ER service for fragility fracture between January 1, 2011 and December 31, 2011 were included. The outcomes of interest were the correlates of and time-to-osteoporosis medication use and risk of a subsequent fracture within 12 months for treated and untreated women. Cox regression was used to evaluate the predictors of treatment use and the risk of fracture based on treatment status. Women (28,722) (27.7%) were treated with osteoporosis medication within 12 months of index fracture, and 74,979 (72.2%) were untreated. A number of patient characteristics were associated with a reduced likelihood of osteoporosis medication use, including black race, higher Charlson comorbidity index scores, presence of dementia, and kidney diseases in the baseline. The predictor most strongly and positively associated with osteoporosis medication use after fracture was osteoporosis medication use before fragility fracture (HR = 7.87; 95% CI 7.67-8.07). After adjusting for baseline characteristics, osteoporosis medication use lowered the risk of subsequent fractures by 21% (HR = 0.79, 95% CI 0.75-0.83) over 12 months compared to women without treatment. Demographics and clinical characteristics were strong predictors of osteoporosis medication use. In the US Medicare population, osteoporosis treatment significantly reduced the risk of fragility fractures.


[Effect of cavinton on systemic and cerebral hemodynamics of patients with chronic cerebral circulatory insufficiency].
The effect of cavinton on the systemic (by the method of diluting Evans blue according to Stewart-Hamilton) and cerebral (by the method of rheoencephalography) hemodynamics was examined in 38 patients with chronic insufficiency of the cerebral circulation (CICC) in the presence of either atherosclerosis alone (n = 22) and its combination with arterial hypertension (n = 16). Cavinton decreased the peripheral vascular resistance and the tone of the small and median vessels of the brain, increased the cardiac output and improved the rheological properties of the blood (it lowered the globular volume, viscosity and hematocrit). The best results were attained with the parenteral administration of the drug. Indications for and contraindications to cavinton in patients with CICC are discussed.


Opportunities, challenges and concerns for the implementation and uptake of pelvic floor muscle assessment and exercises during the childbearing years: protocol for a critical interpretive synthesis.
Pregnancy and childbirth are important risk factors for urinary incontinence (UI) in women. Pelvic floor muscle exercises (PFME) are effective for prevention of UI. Guidelines for the management of UI recommend offering pelvic floor muscle training (PFMT) to women during their first pregnancy as a preventive strategy. The objective of this review is to understand the relationships between individual, professional, inter-professional and organisational opportunities, challenges and concerns that could be essential to maximise the impact of PFMT during childbearing years and to effect the required behaviour change. Following systematic searches to identify sources for inclusion, we shall use a critical interpretive synthesis (CIS) approach to produce a conceptual model, mapping the relationships between individual, professional, inter-professional and organisational factors and the implementation, acceptability and uptake of PFME education, assessment and training during the childbearing years. Purposive sampling will be used to identify potentially relevant material relating to topics or areas of interest which emerge as the review progresses. A wide range of empirical and non-empirical sources will be eligible for inclusion to encompass the breadth of relevant individual, professional, inter-professional and organisational issues relating to PFME during childbearing years. Data analysis and synthesis will identify key themes, concepts, connections and relationships between these themes. Findings will be interpreted in relation to existing frameworks of implementation, attitudes and beliefs of individuals and behaviour change. We will collate examples to illustrate relationships expressed in the conceptual model and identify potential links between the model and drivers for change. The CIS review findings and resulting conceptual model will illustrate relationships between factors that might affect the implementation, acceptability and uptake of PFME education, assessment and training during the childbearing years. The model will inform the development and evaluation of a training package to support midwives with implementation and delivery of effective PFME during the antenatal period. The review forms part of the first phase of the United Kingdom National Institute for Health Research funded 'Antenatal Preventative Pelvic floor Exercises And Localisation (APPEAL)' programme (grant number: RP-PG-0514-20002) to prevent poor health linked to pregnancy and childbirth-related UI. PROSPERO: CRD42016042792.


Career flexibility and family-friendly policies: an NIH-funded study to enhance women's careers in biomedical sciences.
Although women receive nearly half of all doctoral degrees and show a high interest in academic careers, the pipeline is leaky. The challenge of balancing life course events with career trajectory is an important determinant leading to premature dropout or slower career advancement. This report describes the findings of the first phase of a National Institute of Health Office of Research on Women's Health (NIH ORWH)-funded study using survey and academic data for exploring satisfaction and awareness of/intent to use specific career flexibility options at the University of California, Davis (UCD). All men and women faculty in the UCD's Schools of Medicine (SOM) and Veterinary Medicine (SVM) and College of Biological Science (CBS) were surveyed. Data also were obtained from deans' offices on use of family-friendly benefits by faculty. Three hundred twenty-five total survey responses were received from the SOM, 83 from SVM, and 64 from CBS, representing 42%, 46%, and 52% of their total faculty, respectively. In each school, large percentages of men (32%-60%) and women (46%-53%) faculty have children under 18 and a moderately high level of demand of family care responsibilities. Women were significantly more likely to be childless, particularly in the SOM (35% vs. 14%, p<0.001). For all schools, documented use of any family-friendly policy was low (0%-11.5%), as was awareness of policies, although both were significantly higher for women than for men. Significantly more women than men wanted to use policies or chose not to, particularly in the SOM (51% vs. 28%, p<0.001, and 37% vs. 23%, p=0.016, respectively), because of multiple barriers. Faculty in all schools agreed/highly agreed that policies were important to recruitment, retention, and career advancement. Family-friendly policies are pertinent to men and women, as both demonstrate interest and need, linked to increased career satisfaction. A family-friendly policy is important, particularly for women in the biomedical sciences.


Electron microscopic analysis of an angiosarcoma of the thyroid from a non-Alpine endemic goiter region: A case report and brief review of the literature.
Angiomatoid tumors of the thyroid gland are rare endocrine neoplasms, which exhibit an aggressive behavior. Angiosarcomas of the thyroid are generally reported from the European Alpine region and have a histogenesis that has been under debate for a number of years. The current study presents a rare case of angiosarcoma of the thyroid in a 62-year-old Turkish female. The patient had a 10-year history of goiter and was from the Black Sea region, an endemic goiter region of Turkey. The patient was not taking any medication at the time of admission and swelling had been observed on the right side of the neck throughout the previous few months. Thyroid function tests, which analyzed the levels of thyroid-stimulating hormone, thyroxine and triiodothyronine, were within the normal limits, however, the histopathological findings were consistent with an angiosarcoma of the thyroid. The patient rejected the complementary surgery and chemotherapy options, and is currently disease-free (as per the 15-month follow-up). The current study describes a case of angiosarcoma that was characterized by Weibel-Palade bodies, and light microscopy and immunohistochemical findings, as well as an endothelial origin, which was demonstrated via electron microscopy. To the best of our knowledge, this is the first reported case of angiosarcoma of the thyroid in a patient from Turkey to be validated by electron microscopy. Furthermore, this case is one of the few reported thyroid angiosarcoma cases in a non-Alpine region.


Contrasting physiological traits of shade tolerance in Pinus and Podocarpaceae native to a tropical Vietnamese forest: insight from an aberrant flat-leaved pine.
The absence of pines from tropical forests is a puzzling biogeographical oddity potentially explained by traits of shade intolerance. Pinus krempfii (Lecomte), a flat-leaved pine endemic to the Central Highlands of Vietnam, provides a notable exception as it seems to compete successfully with shade-tolerant tropical species. Here, we test the hypothesis that successful conifer performance at the juvenile stage depends on physiological traits of shade tolerance by comparing the physiological characteristics of P. krempfii to coexisting species from two taxa: the genus Pinus, and a relatively abundant and shade-tolerant conifer family found in pantropical forests, the Podocarpaceae. We examined leaf photosynthetic, respiratory and biochemical traits. Additionally, we compiled attainable maximum photosynthesis, maximum RuBP carboxylation (Vcmax) and maximum electron transport (Jmax) values for Pinus and Podocarpaceae species from the literature. In our literature compilation, P. krempfii was intermediate between Pinus and Podocarpaceae in its maximum photosynthesis and its Vcmax. Pinus exhibited a higher Vcmax than Podocarpaceae, resulting in a less steep slope in the linear relationship between Jmax and Vcmax. These results suggest that Pinus may be more shade intolerant than Podocarpaceae, with P. krempfii falling between the two taxa. However, in contrast, Vietnamese conifers' leaf mass per areas and biochemical traits did not highlight the same intermediate nature of P. krempfii. Furthermore, regardless of leaf morphology or family assignation, all species demonstrated a common and extremely high carbon gain efficiency. Overall, our findings highlight the importance of shade-tolerant photosynthetic traits for conifer survival in tropical forests. However, they also demonstrate a diversity of shade tolerance strategies, all of which lead to the persistence of Vietnamese juvenile conifers in low-light tropical understories.


A high-throughput system for boron microsublimation and isotope analysis by total evaporation thermal ionization mass spectrometry.
Research on the ocean carbon cycle is vitally important due to the projected impacts of atmospheric CO2 on global temperatures and climate change, but also on ocean chemistry. The direct influence of this CO2 rise on the seawater pH can be evaluated from the boron isotopic composition in biogenic carbonates; however, conscientious laboratory techniques and data treatment are vital in obtaining accurate and precise results. A rapid-throughput boron purification and Total Evaporation Thermal Ionization Mass Spectrometry method was developed for high accuracy and precision boron isotopic analysis for small (ng) sample sizes. An improved microsublimation method, in which up to 20 samples can be processed simultaneously under identical temperature conditions, was developed. Several tests have confirmed the viability of this technique. First, seawater and Porites coral samples were processed with H2 O2 and the results compared with those obtained using microsublimation; second, the impact of various sublimation times was evaluated; and third, quantitative recovery was assessed using standard addition. Microsublimation provides a valid method for the quantitative recovery and separation of boron from both major elements and organic matter under low-blank conditions. The close agreement of our results with published values validates the accuracy of the measurements. The isotopic ratio for SRM 951a boric acid isotopic standard was 4.0328 ± 0.0054 (2 STD, n = 25). The reproducibility of boron isotopic composition for standards including AE121, IAEA B-1 and an in-house coral standard UM-CP1 was ±0.68‰ (2 STD, n = 15), ±1.12‰ (2 STD, n = 24), and ±1.17‰ (2 STD, n = 14), respectively. The sample sizes were <1 ng for each measurement. The developed method for preparing and measuring boron isotopic values in a variety of carbonate materials should facilitate the reconstruction of past ocean pH conditions with decadal-scale resolution.


A surgical technique using the ovarian vein in non-human primate models of potential living-donor surgery of uterus transplantation.
Living donor surgery in organ transplantation should be performed in a minimally invasive manner under conditions that are as safe as possible. The objective of this study is to examine whether the procedure for using the ovarian vein makes donor surgery less invasive in a cynomolgus monkey model of potential living-donor surgery of uterus transplantation. Twenty-two female cynomolgus monkeys aged 6-9 years and with body weights of 3.55 ± 1.28 kg were used in the study. Vessels and tissues surrounding the uterus were dissected while preserving the uterine artery/vein. The deep uterine vein was used as a venous pedicle in four monkeys (Group 1), and the ovarian vein was used instead of the deep uterine vein in 18 monkeys (Group 2). With the uterine artery/vein and deep uterine vein (Group 1) or ovarian vein (Group 2) connected to the uterus, the vaginal canal was cut. The vessels were then clamped to produce a donor surgery model. Surgical time, intraoperative organ and vascular injury were examined in each animal. The average surgical time from laparotomy to clamping of vessels was 230 ± 112 min in all 22 cynomolgus monkeys, and significantly longer in Group 1 (n = 4) than in Group 2 (n = 18) (393 ± 71 vs. 194 ± 84 min, p < 0.05). Surgical time in Group 2 showed a tendency to decrease in animals treated later in the study, with a significantly longer time in the first 10 monkeys compared with the last 8 (253 ± 65 vs. 120 ± 26 min, p < 0.05). All monkeys had no complications, including no injuries to other organs and no unanticipated vascular injury. The procedure using the ovarian vein was less invasive than that using the deep uterine vein in mimicking living-donor surgery in a cynomolgus monkey model of uterus transplantation.


Detection of genes involved in fatty acid elongation and desaturation in thraustochytrid marine eukaryotes.
Heterotrophic marine protists known as thraustochytrids can synthesize polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA). The biosynthetic pathways of PUFAs in thraustochytrids are poorly understood, however. In this study, we attempted to reveal the enzymes involved in DHA synthesis in thraustochytrids. Nine thraustochytrid strains representing 3 genera (Aurantiochytrium, Schizochytrium, and Thraustochytrium) were used for PCR-based detection of the genes encoding Δ5-elongase and Δ4-desaturase and for fatty acid analysis. The degenerate primers were designed to amplify the Δ5-elongase and Δ4-desaturase genes, and the partial sequences of the enzymes were obtained from the genera Thraustochytrium and Schizochytrium. These fragments were identical to those of known Δ5-elongase and Δ4-desaturase. Neither Δ5-elongase nor Δ4-desaturase was detected in the strains belonging to the genus Aurantiochytrium, however, suggesting that this group likely synthesizes DHA not via the elongation/desaturation pathway but via an alternate pathway such as the polyketide synthase pathway. The fatty acid profiles of thraustochytrids were consistent with the presence of genes involved in PUFA biosynthesis in thraustochytrid genera. Thus, our findings suggest that two biosynthetic pathways for PUFAs exist in these organisms.


Evolution of defence cocktails: Antimicrobial peptide combinations reduce mortality and persistent infection.
The simultaneous expression of costly immune effectors such as multiple antimicrobial peptides is a hallmark of innate immunity of multicellular organisms, yet the adaptive advantage remains unresolved. Here, we test current hypotheses on the evolution of such defence cocktails. We use RNAi gene knock-down to explore, the effects of three highly expressed antimicrobial peptides, displaying different degrees of activity in vitro against Staphylococcus aureus, during an infection in the beetle Tenebrio molitor. We find that a defensin confers no survival benefit but reduces bacterial loads. A coleoptericin contributes to host survival without affecting bacterial loads. An attacin has no individual effect. Simultaneous knock-down of the defensin with the other AMPs results in increased mortality and elevated bacterial loads. Contrary to common expectations, the effects on host survival and bacterial load can be independent. The expression of multiple AMPs increases host survival and contributes to the control of persisting infections and tolerance. This is an emerging property that explains the adaptive benefit of defence cocktails.


Feeding behavior and nutrient intake in spiny forest-dwelling ring-tailed lemurs (Lemur catta) during early gestation and early to mid-lactation periods: compensating in a harsh environment.
Strong resource seasonality in Madagascar has led to the evolution of female feeding priority and weaning synchrony in most lemur species. For these taxa, pregnancy/early lactation periods coincide with low food availability, and weaning of infants is timed with increased resources at the onset of the rainy season. Reproductive females experience high metabolic requirements, which they must accommodate, particularly when food resources are scarce. Female ring-tailed lemurs (Lemur catta) residing in spiny forest habitat must deal with resource scarcity, high temperatures (∼36-40°C) and little shade in early to mid-lactation periods. Considered "income breeders," these females must use resources obtained from the environment instead of relying on fat stores; thus, we expected they would differ from same-sized males in time spent on feeding and in the intake of food and nutrients. We investigated these variables in two groups (N = 11 and 12) of Lemur catta residing in spiny forest habitat during early gestation and early to mid-lactation periods. Focal animal data and food plant samples were collected, and plants were analyzed for protein, kcal, and fiber. We found no sex differences for any feeding or nutrient intake variable for the top five food species consumed. Females in early gestation spent more time feeding compared with early/mid-lactation. Physiological compensation for spiny forest-dwelling females may be tied to greater time spent resting compared with gallery forest conspecifics, consuming foods high in protein, calories, and water, reduced home range defense in a sparsely populated habitat, and for Lemur catta females in general, production of relatively dilute milk compared with many strepsirrhines.


[A case of neurologic muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome with a novel mitochondrial mutation m.8729 G>A].
We report a patient having classical clinical feature of neurologic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and a novel mutation, m.8729 G>A in mitochondria DNA. The patient was referred to our hospital because of progressive ataxia in her limbs and trunk. She had a history of incapability of running long distances from childhood. Neurological examination revealed cerebellar ataxia, distal dominant muscle weakness in the limbs, hyporeflexia, hypoesthesia, myoclonus, sensorineural deafness, and retinitis pigmentosa. Magnetic resonance imaging (MRI) showed atrophy of brain stem and cerebellum as well as calcification of basal ganglia. In both serum and cerebrospinal fluid, lactate and pyruvate levels were elevated. Histological examination of biopsied muscle revealed chronic neurogenic changes without ragged red fibers. Genetic analysis of mitochondrial DNA (mtDNA) of the muscle revealed a heteroplasmic mutation, m.8729 G>A. Chemical analysis of the respiratory chain complexes in her muscle specimen demonstrated lower activities of complexes I and V. In our case, novel mutation of m.8729 G>A in mtDNA was indicated as the cause of NARP syndrome.


Four new species of Cladorhizidae (Porifera, Demospongiae, Poecilosclerida) from the Northeast Pacific.
Interest in cladorhizid sponges has grown rapidly in the past 19 years since a unique feeding strategy, carnivory, was described by Vacelet and Boury-Esnault in 1995. Since that time, 31% of the 133 extant cladorhizids have been described. Previously, seven species of cladorhizid sponges were known from the Northeast Pacific. Here we describe four additional species, including two species of Asbestopluma and two species of Cladorhiza. We report on species ranges, habitat, and ecology, including one from a chemosynthetic environment that appears to be using methane-oxidizing bacteria as a nutrient source. In fact, three of the four species described here were found in chemosynthetic habitats. The presence of small crustacean prey was also documented for three of these species.


Shell-cross-linked vesicles synthesized from block copolymers of Poly(D,L-lactide) and Poly(N-isopropyl acrylamide) as thermoresponsive nanocontainers.
A polylactide (D,L-PLA) macroRAFT agent was prepared by utilizing a hydroxyl-functional trithiocarbonate as a coinitiator for the ring-opening polymerization. The length of the resultant polymer was controlled by the concentration of the coinitiator leading to the formation of two PLA polymers with M(n) = 12500 g mol(-)(1) (PDI = 1.46) and M(n) = 20500 g mol(-)(1) (PDI = 1.38) each with omega-trithiocarbonate functionality. Chain extension of PLA via the RAFT (free radical) polymerization of N-isopropyl acrylamide (NIPAAm) resulted in the formation of amphiphilic block copolymers with the PNIPAAm block increasing in size with conversion. TEM measurements of the aggregates obtained by self-organization of the block copolymers in aqueous solutions indicated the formation of vesicles. The sizes of these aggregates were influenced by the ratio of both blocks and the molecular weight of each block. The lower critical solution temperature (LCST) of the block copolymer was largely unaffected by the size of each block. UV turbidity measurements indicated a higher LCST for the block copolymers than for the corresponding PNIPAAm homopolymers. Stabilization of the vesicles was attained by a cross-linking chain extension of the PNIPAAm block using hexamethylene diacrylate. As the trithiocarbonate group was located between the PLA and PNIPAAm blocks, the chain extension resulted in a cross-linked layer between the core and corona of the vesicles.


Effects of polymer-coated urea on nitrate leaching and nitrogen uptake by potato.
Increasing groundwater nitrate concentrations in potato (Solanum tuberosum L.) production regions have prompted the need to identify alternative nitrogen management practices. A new type of polymer-coated urea (PCU) called Environmentally Smart Nitrogen (Agrium, Inc., Calgary, AB) is significantly lower in cost than comparable PCUs, but its potential to reduce nitrate leaching and improve fertilizer recovery has not been extensively studied in potato. In 2006 and 2007, four rates of PCU applied at emergence were compared with equivalent rates of soluble N split-applied at emergence and post-hilling. Additional treatments included a 0 N control, two PCU timing treatments (applied at preplant or planting), and a soluble N fertigation simulation. Nitrate leaching, fertilizer N recovery, N use efficiency (NUE), and residual soil inorganic N were measured. Both 2006 and 2007 were low leaching years. Nitrate leaching with PCU (21.3 kg NO(3)-N ha(-1) averaged over N rates) was significantly lower than with split-applied soluble N (26.9 kg NO(3)-N ha(-1)). The soluble N fertigation treatment resulted in similar leaching as PCU at equivalent N rates. Apparent fertilizer N recovery with PCU (65% averaged over four rates) tended to be higher than split-applied soluble N (55%) at equivalent rates (p = 0.059). Residual soil N and NUE were not significantly affected by N source. Under the conditions of this study, PCU significantly reduced leaching and tended to improved N recovery over soluble N applied in two applications and resulted in similar N recovery and nitrate leaching as soluble N applied in six applications.


In vitro analysis of polychlorinated biphenyls (PCBs) and 2,3,4,7,8-pentachlorodibenzofuran (PCDF) cellular toxicity in PLC/PRF/5 cell proliferation--the effect of ursodeoxycholic acid, inchin-gorei-san and shou-saiko-to on cell toxicity.
We investigated the cell toxicity of polychlorinated biphenyls (PCBs) and 2,3,4,7,8-pentachlorodibenzofuran (PCDF) as an indicator of the quantity of m-RNA, which synthesizes the HBV core antigen region, and secreting protein, which is an HBV surface antigen in PLC/PRF/5 cells. The determination of m-RNA was conducted according to the methods of reverse transcriptase and polymerase chain reaction. Furthermore, the reductive action of ursodeoxycholic acid, shou-saiko-to and inchin-gorei-san on the PCBs and PCDF toxicity was investigated. The cell number of 1 x 10(5)/ml and concentrations of 200 micrograms/ml for PCBs and 500 microM for PCDF were used in these experiments. The titer of HBsAg was gradually increased from 1 in 1 x 10(3)/ml of cell numbers to 100 in 1 x 10(6)/ml of cell numbers. The curve became a plateau in 1 x 10(6)/ml of cell numbers. The cell number of 1 x 10(5)/ml was used in the experiments. The titer of HBsAg decreased following in the increase of concentration of PCBs. The HBsAg, even in the PCBs concentration of 1000 micrograms/ml showed a titer of 22.5%. However, the highest concentration of PCDF in this study, that is, 500 microM of PCDF, did not show any decrease of HBsAg activity. The concentrations of 200 micrograms/ml for PCBs and 500 microM for PCDF were used in the investigation of drug effects. A high titer HBsAg was observed in high concentrations of shou-saiko-to in comparison with a control group. Ursodeoxycholic acid and inchin-gorei-san exhibited a similar tendency.(ABSTRACT TRUNCATED AT 250 WORDS)


Ginsenosides: A Potential Neuroprotective Agent.
Ginseng is a traditional Chinese medicine with a wide range of pharmacological activities. Ginsenosides are the major constituents of ginseng. Ginsenosides have the unique biological activity and medicinal value, such as antitumor, anti-inflammatory, antioxidation, and inhibition of cell apoptosis. With the increase of stress in life, the incidence of nervous system diseases is also increasing. Neurological diseases pose a huge burden on people's life and health. In recent years, some studies have shown that ginsenosides have a certain role in the prevention and treatment of neurological diseases. However, the research is still in its infancy, and the relevant mechanisms are complex. In the paper, we review the effects and mechanisms of ginsenosides on epilepsy, depression, cerebral ischemia reperfusion injury, Alzheimer's disease, and Parkinson's disease. We hope to provide a theoretical basis for the treatment of nervous system diseases by ginsenosides.


Microstructural evolution in a CeO2-Gd2O3 system.
Microstructural evolution in a CeO2-Gd2O3 system at atomic and nanoscale levels with increasing Gd concentration has been comprehensively investigated by transmission electron microscopy. When the Gd concentration was increased from 10 to 80 at.%, the phase transformation from ceria with fluorite structure to solid solution with C-type structure was not a sudden change but an evolution in the sequence of clusters, domains, and precipitates with C-type structure in the fluorite-structured matrix. Moreover, the ordering of aggregated Gd cations and oxygen vacancies in these microstructural inhomogeneities developed continuously with increasing Gd concentration. This microstructural evolution can be further described based on the development of defect clusters containing Gd cations and oxygen vacancies.


Vitamin C: a new auxiliary treatment of epilepsy?
Although many approaches to the therapy of epilepsy exist, most of antiepileptic drugs, beside certain and unquestioned benefits, have convinced disadvantages. That is the reason for looking for new methods of treatment. Ascorbic acid, as an antioxidant and electron donor accumulated in central nervous system, seems to take part in diminishing reactions of oxidative stress in brain and cooperate with other antioxidants like alpha-tocoferol. Vitamin C, easily transported through the blood-brain barrier, is proved to reduce injury in the hippocampus during seizures. Depending on type of seizures, it has mostly inhibitory activity and even decreases mortality. Moreover, vitamin C acts as a neuroprotective factor by consolidating cell membranes and decreasing lipid peroxidation. A possible adjunctive role of vitamin C in epileptic patients needs to be considered.


[Incidence of bronchopulmonary dysplasia].
The incidence of bronchopulmonary dysplasia (BPD) was retrospectively studied in all ventilated newborns at a neonatal intensive care unit of a university based hospital at Santiago, Chile along a 5 years period (1983-1987). BPD incidence among the whole sample of newborn infants requiring artificial ventilation was analysed according to birth weight (BW) and compared with that of newborns surviving after 28 days of life. The possible association of BPD with hyaline membrane disease (HMD), ductus arteriosus (DA) and pulmonary air leak (PAL) was studied. The total number of ventilated newborns was 200, incidence of BPD was 9.5% (19/200) and lethality for BPD was 5.2% (1/19). The incidence of BPD increased progressively with decreasing BW, reaching 37.5% in infants less than 1,000 g (p less than 0.001 chi 2). Among 28 day survivors incidence of BPD in the same BW group increased to 75% (p less than 0.05). These findings support the idea that the incidence of BPD increases with improved survival of low birth weight infants. A positive association of BPD with DA and PAL was seen with 10/19 versus 33/181 incidence for DA (p less than 0.01) and 6/19 versus 16/181 for PAL (p less than 0.01) among patients with and those without BPD respectively, but not with HMD.


Mortality Rates and Cause of Death Among Former Prison Inmates in North Carolina.
BACKGROUND Inmates face challenges upon release from prison, including increased risk of death. We examine mortality among former inmates in North Carolina, including both violent and nonviolent deaths.METHODS A retrospective cohort study among former North Carolina inmates released between 2008 and 2010 were linked with North Carolina mortality data to determine cause of death. Inmates were followed through December 31, 2012. Mortality rates among former inmates were compared with deaths among North Carolina residents using standardized mortality ratios (SMRs).RESULTS Among former inmates (N = 41,495), there were 926 deaths during the study period. Compared to the North Carolina general population, SMRs were higher for all-cause mortality for total deaths (SMR = 2.10, 95% CI: 1.97-2.24), heart disease (SMR = 4.45, 95% CI: 3.64-5.34), cancer (SMR = 3.92, 95% CI: 3.34-4.62), suicide (SMR = 14.46, 95% CI: 10.28-19.76), and homicide (SMR = 7.98, 95% CI: 6.34-10.03).DISCUSSION The death rate among former North Carolina inmates is significantly higher than that of other North Carolina residents. Although more research is needed, identifying areas for interventions is essential for reducing the risk of death among this population.


Converging and emerging threats to health security.
Advances in biological sciences have outpaced regulatory and legal frameworks for biosecurity. Simultaneously, there has been a convergence of scientific disciplines such as synthetic biology, data science, advanced computing and many other technologies, which all have applications in health. For example, advances in cybercrime methods have created ransomware attacks on hospitals, which can cripple health systems and threaten human life. New kinds of biological weapons which fall outside of traditional Cold War era thinking can be created synthetically using genetic code. These convergent trajectories are dramatically expanding the repertoire of methods which can be used for benefit or harm. We describe a new risk landscape for which there are few precedents, and where regulation and mitigation are a challenge. Rapidly evolving patterns of technology convergence and proliferation of dual-use risks expose inadequate societal preparedness. We outline examples in the areas of biological weapons, antimicrobial resistance, laboratory security and cybersecurity in health care. New challenges in health security such as precision harm in medicine can no longer be addressed within the isolated vertical silo of health, but require cross-disciplinary solutions from other fields. Nor can they cannot be managed effectively by individual countries. We outline the case for new cross-disciplinary approaches in risk analysis to an altered risk landscape.


A Functional Signature in the Developing Cerebellum: Evidence From a Preclinical Model of Autism.
Autism spectrum disorders (ASD) are pervasive neurodevelopmental conditions detected during childhood when delayed language onset and social deficits are observed. Children diagnosed with ASD frequently display sensorimotor deficits associated with the cerebellum, suggesting a dysfunction of synaptic circuits. Astroglia are part of the tripartite synapses and postmortem studies reported an increased expression of the glial fibrillary acidic protein (GFAP) in the cerebellum of ASD patients. Astroglia respond to neuronal activity with calcium transients that propagate to neighboring cells, resulting in a functional response known as a calcium wave. This form of intercellular signaling is implicated in proliferation, migration, and differentiation of neural precursors. Prenatal exposure to valproate (VPA) is a preclinical model of ASD in which premature migration and excess of apoptosis occur in the internal granular layer (IGL) of the cerebellum during the early postnatal period. In this study we tested calcium wave propagation in the IGL of mice prenatally exposed to VPA. Sensorimotor deficits were observed and IGL depolarization evoked a calcium wave with astrocyte recruitment. The calcium wave propagation, initial cell recruitment, and mean amplitude of the calcium transients increased significantly in VPA-exposed mice compared to the control group. Astrocyte recruitment was significantly increased in the VPA model, but the mean amplitude of the calcium transients was unchanged. Western blot and histological studies revealed an increased expression of GFAP, higher astroglial density and augmented morphological complexity. We conclude that the functional signature of the IGL is remarkably augmented in the preclinical model of autism.


Variability in the reported energy, total fat and saturated fat contents in fast-food products across ten countries.
Fast foods are often energy dense and offered in large serving sizes. Observational data have linked the consumption of fast foods to an increased risk of obesity and related diseases. We surveyed the reported energy, total fat and saturated fat contents, and serving sizes, of fast-food items from five major chains across ten countries, comparing product categories as well as specific food items available in most countries. MRC Human Nutrition Research, Cambridge, UK. Data for 2961 food and drink products were collected, with most from Canada (n 550) and fewest from the United Arab Emirates (n 106). There was considerable variability in energy and fat contents of fast foods across countries, reflecting both the portfolio of products and serving size variability. Differences in total energy between countries were particularly noted for chicken dishes (649-1197 kJ/100 g) and sandwiches (552-1050 kJ/100g). When comparing the same product between countries variations were consistently observed in total energy and fat contents (g/100 g); for example, extreme variation in McDonald's Chicken McNuggets with 12 g total fat/100 g in Germany compared with 21·1 g/100 g in New Zealand. These cross-country variations highlight the possibility for further product reformulation in many countries to reduce nutrients of concern and improve the nutritional profiles of fast-food products around the world. Standardisation of serving sizes towards the lower end of the range would also help to reduce the risk of overconsumption.


[Comparative analysis of total cell protein electrophoregram of pathogenic Burkholderia].
Whole-cell proteins of 22 strain of Burkhoderia pseudomallei, including 13 B. mallei, 5 B. cepacia strains and 14 strains of opportunistically pathogenic Pseudomonas defined by 1D SDC-PAAG electrophoresis. Electrophoregrams contained 35 to 45 protein fractions sized 19 to 130 kDa, which were highly reproductive. On the basis of computer-aided comparative analysis of protein patterns the interspecies and intraspecies grouping of studied microorganisms was made. The cluster analysis of the similarity matrix of protein spectra made it possible to allocate two groups of strains at the level of similarity of 78%. Group I was formed by Burkholderia species that previously belonged to the II RNA-DNA homology group of Pseudomonas: B. pseudomallei, B. mallei, B. cepacia. All Pseudomonas species were added to the 2nd Group: P. aeruginosa, P. stutzeri, P. testosterone, P. fluorescens, P. putida, P. mendocina. Four phenons were isolated among the strains of B. pseudomallei and 2 phenons--among the strains of B. mallei at the threshold similarity level (89%). The authors conclude that the comparative analysis of electrophoregrams of whole-cell proteins can be useful in the identification and typing of pathogenic Burkholderia.


Predictors of mortality in acute lung injury during the era of lung protective ventilation.
Lung protective ventilation has been widely adopted for the management of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Consequently, ventilator associated lung injury and mortality have decreased. It is not known if this ventilation strategy changes the prognostic value of previously identified demographic and pulmonary predictors of mortality, such as respiratory compliance and the arterial oxygen tension to inspired oxygen fraction ratio (Pao(2)/Fio(2)). Demographic, clinical, laboratory and pulmonary variables were recorded in 149 patients with ALI/ARDS. Significant predictors of mortality were identified in bivariate analysis and these were entered into multivariate analysis to identify independent predictors of mortality. Hospital mortality was 41%. In the bivariate analysis, 17 variables were significantly correlated with mortality, including age, APACHE II score and the presence of cirrhosis. Pulmonary parameters associated with death included Pao(2)/Fio(2) and oxygenation index ((mean airway pressurexFio(2)x100)/Pao(2)). In unadjusted analysis, the odds ratio (OR) of death for Pao(2)/Fio(2) was 1.57 (CI 1.12 to 3.04) per standard deviation decrease. However, in adjusted analysis, Pao(2)/Fio(2) was not a statistically significant predictor of death, with an OR of 1.29 (CI 0.82 to 2.02). In contrast, oxygenation index (OI) was a statistically significant predictor of death in both unadjusted analysis (OR 1.89 (CI 1.28 to 2.78)) and in adjusted analysis (OR 1.84 (CI 1.13 to 2.99)). In this cohort of patients with ALI/ARDS, OI was an independent predictor of mortality, whereas Pao(2)/Fio(2) was not. OI may be a superior predictor because it integrates both airway pressure and oxygenation into a single variable.


Effects of Short-Term Cognitive Remediation on Cognitive Dysfunction in Partially or Fully Remitted Individuals with Bipolar Disorder: Results of a Randomised Controlled Trial.
Cognitive dysfunction is common in bipolar disorder (BD) but is not sufficiently addressed by current treatments. Cognitive remediation (CR) may improve cognitive function in schizophrenia but no randomised controlled trial has investigated this intervention in BD. The present study aimed to investigate the effects of CR on persistent cognitive dysfunction in BD. Patients with BD in partial remission with cognitive complaints were randomised to 12 weeks group-based CR (n=23) or standard treatment (ST) (n=23). Outcomes were improved verbal memory (primary), sustained attention, executive and psychosocial function (secondary) and additional measures of cognitive and psychosocial function (tertiary). Participants were assessed at baseline and weeks 12 and 26. Of the 46 randomised participants five dropped out and one was excluded after baseline. CR (n=18) had no effect on primary or secondary measures of cognitive or psychosocial function compared with ST (n=22). However, CR improved subjective sharpness at week 12, and quality of life and verbal fluency at week 26 follow-up (tertiary outcomes). Although the trial turned out to have suboptimal statistical power for the primary outcome analysis, calculation of the 95% confidence interval showed that it was highly unlikely that an increase in sample size would have rendered any beneficial effects of CR vs. ST on the verbal memory. Short-term group-based CR did not seem to improve overall cognitive or psychosocial function in individuals with BD in full or partial remission. The present findings suggest that that longer-term, more intensive and individualised CR may be necessary to improve cognition in BD. ClinicalTrials.gov NCT01457235.


Modeling auditory processing of amplitude modulation. I. Detection and masking with narrow-band carriers.
This paper presents a quantitative model for describing data from modulation-detection and modulation-masking experiments, which extends the model of the "effective" signal processing of the auditory system described in Dau et al. [J. Acoust. Soc. Am. 99, 3615-3622 (1996)]. The new element in the present model is a modulation filterbank, which exhibits two domains with different scaling. In the range 0-10 Hz, the modulation filters have a constant bandwidth of 5 Hz. Between 10 Hz and 1000 Hz a logarithmic scaling with a constant Q value of 2 was assumed. To preclude spectral effects in temporal processing, measurements and corresponding simulations were performed with stochastic narrow-band noise carriers at a high center frequency (5 kHz). For conditions in which the modulation rate (fmod) was smaller than half the bandwidth of the carrier (delta f), the model accounts for the low-pass characteristic in the threshold functions [e.g., Viemeister, J. Acoust. Soc. Am. 66, 1364-1380 (1979)]. In conditions with fmod > delta f/2, the model can account for the high-pass characteristic in the threshold function. In a further experiment, a classical masking paradigm for investigating frequency selectivity was adopted and translated to the modulation-frequency domain. Masked thresholds for sinusoidal test modulation in the presence of a competing modulation masker were measured and simulated as a function of the test modulation rate. In all cases, the model describes the experimental data to within a few dB. It is proposed that the typical low-pass characteristic of the temporal modulation transfer function observed with wide-band noise carriers is not due to "sluggishness" in the auditory system, but can instead be understood in terms of the interaction between modulation filters and the inherent fluctuations in the carrier.


Characterization of children infected with HIV due to mother-to-child transmission in hospitals in Lima, Peru.
Despite strategies to prevent mother-to-child transmission of the human immunodeficiency virus (HIV), infected children continue to be born. The aim of this study was to describe the status of children infected with HIV due to mother-to-child transmission. Between 2012 and 2018, 84 children were born with HIV in hospitals in Lima and Callao. Of the 68 cases included in this study, 82% of the mothers did not receive antiretroviral treatment and 25% had a negative HIV test during pregnancy. As for the children, 59% were diagnosed with HIV after one year of age, 82% had a viral load below 1,000 copies and 87% were considered healthy. Early diagnosis and treatment of the child with HIV is associated with better quality of life. It is necessary to carry out studies to identify the critical aspects of prenatal care in order to eliminate vertical HIV transmission.


X-linked α-thalassemia with mental retardation is downstream of protein kinase A in the meiotic cell cycle signaling cascade in Xenopus oocytes and is dynamically regulated in response to DNA damage†.
X-linked α-thalassemia with mental retardation (ATRX) is a chromatin remodeling protein that belongs to the SWItch/sucrose non-fermentable (SWI2/SNF2) family of helicase/ATPases. During meiosis, ATRX is necessary for heterochromatin formation and maintenance of chromosome stability in order to ensure proper assembly of the metaphase II spindle. Previously, we established ATRX as a novel progesterone regulated protein during bovine meiotic maturation, in addition to being dynamically regulated in response to DNA damage in oocytes. In the present study, we utilize the Xenopus laevis model system to further elucidate the signaling pathways regulating ATRX expression within the oocyte. Here, we present an analysis of endogenous ATRX protein expression during oogenesis, oocyte meiotic maturation, and early embryonic development. ATRX expression is dynamically regulated as evidenced by loss of the protein in metaphase II of meiosis. The downstream activation of meiosis via protein kinase A inhibition resulted in a similar decrease in ATRX protein expression. We demonstrate that the ATRX protein is detected in ubiquitin immuno-precipitates from germinal vesicle oocyte extracts and experimentally demonstrate that proteosomal degradation is responsible for the decreased expression of ATRX during meiosis. ATRX expression is significantly increased in response to gamma-irradiation induced DNA damage in oocytes and embryos. This increased expression is independent of p53 protein expression in apoptotic embryos, as determined by the expression of active caspase-3. Thus, regulation of ATRX protein expression impacts on G2-M progression and ultimately has consequences for cell survival.


The myositides: the role of imaging in diagnosis and treatment.
The entities encompassing the syndromes collectively known as myopathies and myositis are composed of numerous separate and distinct disorders with a vast spectrum of clinical signs, symptoms, immunopathology, genetic and environmental influences, as well as overall clinical outcome. Classification of the myositides (diseases of skeletal muscle) remains a rather controversial subject due to our lack of complete understanding of this divergent group of disorders. The mainstay of achieving diagnosis of a myopathy has until relatively recently been with a combination of clinical acumen, laboratory assessment, electromyography, and muscle biopsy. The use of modern high-resolution cross-sectional imaging studies is of particular value in confirming the physical findings and identifying suitable sites for biopsy. Imaging is fast becoming an established part of the overall evaluation of myopathies and myositis, helping to delineate the location and extent of the disease process, and it is being recognized as central to a prompt and accurate diagnosis in some cases. Although radiology has mainly been seen to have a subsidiary role in the diagnosis of myositides, newer imaging techniques following recent determined research interests have began to spark a renewed interest in the complex field of skeletal muscle imaging.