Tram-track appearance of the posterior cruciate ligament (PCL): correlations with mucoid degeneration, ligamentous stability, and differentiation from PCL tears.
The purpose of our study was to describe the MRI findings in the posterior cruciate ligament (PCL) analogous to mucoid degeneration in the anterior cruciate ligament (ACL); to correlate MRI findings in the PCL with ligamentous stability; to differentiate the PCL tram-track appearance from the appearance of PCL tears; and to emphasize the coexistence of PCL and ACL mucoid degeneration, cruciate ganglia, and meniscal cysts. The tram-track PCL appearance commonly coexists with ACL mucoid degeneration; ganglia; and, less frequently, meniscal cysts. Both PCL tears and MRI findings suggestive of PCL mucoid degeneration show ligament thickening and increased PCL signal intensity. Tram-track PCLs are usually asymptomatic and typically have no ligamentous instability.


Functional and Structural Assessment of the Effect of Human Umbilical Cord Blood Mesenchymal Stem Cells in Doxorubicin-Induced Cardiotoxicity.
Cardiomyopathy induced by doxorubicin (DOX) was recognized at an early stage and also several years after drug administration. Mesenchymal stem cells (MSCs) have many properties that make them suitable for preventive and/or regenerative therapies. In this study, we evaluated the effect of MSCs in the functional and the structural improvement of DOX-induced cardiomyopathy in rats. Ninety adult male albino rats were randomly divided into three equal groups of thirty rats each: Group I (control): rats received normal saline. Group II (DOX- group): rats received DOX. Group III (DOX-MSCs group): rats received DOX for 2 weeks then human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). Rats in all groups were evaluated for: physical condition, electrocardiography (ECG), and hemodynamic parameters. Serum cardiac troponin I (cTnI), malondialdehyde (MDA), total antioxidant capacity (TAC), and DNA fragmentation on heart tissue isolated DNA were estimated for evaluation of the mechanism and the extent of the damage. Hearts were examined histopathologically for detection of MSCs homing, structural evaluation, with counting of the collagen fibers for evaluation of fibrosis. DOX-administered rats showed significant functional and structural deterioration. DOX-MSCs treated rats (group III) showed improved functional and structural criteria with restoration of all biochemical indicators of cardiac damage and reactive oxygen species (ROS) to normal, as well. In Conclusion, hUCB-MSCs significantly ameliorated the cardiotoxic manifestations as shown by biochemical, functional, and structural cardiac improvement. J. Cell. Biochem. 118: 3119-3129, 2017. © 2017 Wiley Periodicals, Inc.


Absolute alcohol in esophageal vein sclerosis.
Absolute alcohol is a potentially optimal agent for sclerotherapy of esophageal varices. It is cheap and readily available. We compared the efficacy and safety of alcohol with those of a commonly used sclerosing agent, polidocanol. The study was planned to include patients with previous bleeding from esophageal varices randomly assigned to one of the two treatments. After the inclusion of the first 11 patients (6 in the polidocanol group and 5 in the alcohol group), however, the trial was interrupted because of serious complications in patients treated with alcohol (four major bleeding episodes and one esophageal stenosis). The two agents were of comparable efficacy in the small sample of patients studied. The complications were related to the presence of iatrogenic esophageal ulcers which were more frequent (100% vs. 30%) and significantly larger (mean, 1.4 cm vs. 0.7 cm, p less than 0.05) in patients treated with alcohol.


A modified method of microvascular autogenous interposition vein grafting for vascular reconstruction.
A modified technique of vein grafting for vascular reconstruction that facilitates surgical procedures by preventing size, diameter, and length discrepancies as well as twisting, is presented. The distal end of the harvested vein graft is ligated, and the graft is inflated with heparinzed saline. The determination of the small side branches makes ligation easier. Gentle hydrostatic dilation relieves spasm, straightens the vein, and ligation of the proximal end is then performed under tension. As the vein inflated with heparinzed saline achieves maximum size, diameter, and length without torsion, the sausage-like graft can easily be interposed in tunnels, passages, or soft tissues between recipient vessel gaps. As the graft is under adequate tension, it is easy to determine its appropriate length, size, and diameter. Suturing is carried out using double approximating clamps. The graft will not twist or kink, as it is anastomosed under tension. The clamps are left in place until completion of the distal and proximal anastomoses. The distal clamp is released first. With this simple modification, most of the technical difficulties, such as length, size, and diameter discrepancies, and twisting and torsion of the graft, can be eliminated. The risk of failure due to vascular thrombosis at the anastomotic sites is lowered, as the vein graft is filled with heparinzed saline, and no blood flow is permitted during the reconstruction. The surgeon also saves time with this easy, simple, and feasible method.


Safety of Methotrexate in Chronic Urticaria Unresponsive to Omalizumab.
Omalizumab (humanized anti-immunoglobulin IgE) is currently the first choice of treatment for chronic urticaria refractory to high-dose second-generation antihistamines (sgAH). Despite its high safety profile, response to omalizumab is insufficient in one-third of patients. Some studies have suggested that methotrexate is effective in antihistamine-refractory chronic urticaria, but there are no studies on its efficacy and safety in patients unresponsive to omalizumab. This retrospective study aimed to investigate the clinical effectiveness and adverse effects of methotrexate in patients with chronic urticaria unresponsive to omalizumab + high-dose sgAH. The patients were evaluated in terms of age at disease onset, duration of the urticaria episode before methotrexate therapy, treatment before methotrexate therapy, final treatment, treatment responses, 7-day urticaria activity score (UAS7) before and after treatment, and total IgE levels. Methotrexate was administered subcutaneously at a dose of 15 mg once weekly as monotherapy or in combination with other drugs to 10 chronic urticaria patients with a history of nonresponse to omalizumab + high-dose sgAH. The mean age of the patients was 44.6±11.5 (31-65) years, and 9 (90%) of the patients were female. The mean duration of methotrexate therapy was 5.1±2.4 months (1.5-9 months). Complete response or well-controlled response was observed in 70% of the patients and partial response was observed in 1 patient (10%). Methotrexate was well tolerated by 80% of the patients. Methotrexate seems to be a useful treatment option both as monotherapy or combined therapy in patients resistant to omalizumab + sgAH.


Duration and level of transgene expression after gene electrotransfer to skin in mice.
In development of novel vaccines, attention is drawn to DNA vaccinations. They are heat stable and can be easily produced. Gene electrotransfer is a simple and nonviral means of transferring DNA to cells and tissues and is attracting increasing interest. One very interesting perspective with gene electrotransfer is that choice of tissue can determine the duration of transgene expression. With gene electrotransfer to muscle, long-term expression, that is beyond 1 year, can be obtained, whereas gene electrotransfer to skin gives short-term expression, which is desirable in, for example, DNA vaccinations. Level and duration of transgene expression after gene electrotransfer to skin is essential and here we present data from two independent quantitative studies. Using in vivo bioimaging of a far-red fluorescent molecule, Katushka, allowing for continuous monitoring of local gene expression, compared with measurements of a systemic transgene, that is, serum erythropoietin (EPO) after gene electrotransfer with EPO to skin, we found a significant increase in transgene expression (P< 0.01) with a peak 9 days (Katushka) and 14 days (EPO) after transfection. Duration of expression could be 3-4 weeks, which is a suitable time frame for vaccinations and is applicable, for example, in gene therapy for wound healing or treatment of cancer.


Manual aspiration versus chest tube drainage in first episodes of primary spontaneous pneumothorax: a multicenter, prospective, randomized pilot study.
Although there is no agreement on the optimal treatment of patients presenting with a first episode of primary spontaneous pneumothorax, the majority of physicians prefer chest tube drainage for air evacuation. Manual aspiration of air has been proposed by some, but lack of sound comparative data and safety data has limited its use. In this first randomized, prospective, multicenter pilot study, 60 patients with a first episode of primary spontaneous pneumothorax were randomly allocated to manual aspiration (n = 27) or chest tube drainage (n = 33). Immediate success was obtained in 16 out of 27 (59.3%) in the manual aspiration group, and in 21 out of 33 (63.6%) in the chest tube drainage group (p = 0.9). One-week success rates were 25 out of 27 (93%) in the intention-to-treat manual aspiration group and 28 out of 33 (85%) in the chest tube drainage group (p = 0.4). Fourteen of 27 manual aspiration patients (52%) were hospitalized, versus 100% of the chest tube drainage patients (p < 0.0001). Recurrence rates with at least 1-year follow-up were 7 out of 26 (26%) in the manual aspiration group, and 9 out of 33 (27.3%) in the chest tube drainage group (p = 0.9). There were no complications associated with manual aspiration. Although statistical power is insufficient to formally confirm therapeutic equality, this pilot study suggests that in first episodes of primary spontaneous pneumothorax, manual aspiration seems equally effective as chest tube drainage and is safe, well tolerated, and feasible as an outpatient procedure in the majority of patients.


The binding of T4 gene 32 protein to MS2 virus RNA and transfer RNA.
Fluorescence titrations, absorption spectroscopy and stopped-flow techniques were used to study the interaction of T4 coded 32-protein (P 32) with MS2 RNA and total tRNA from E. coli under different ionic conditions. It is shown that the amount of MS2 RNA and tRNA secondary structure melted by P 32 varies markedly and reversibly within a range of ionic conditions under which the binding constant of P 32 to single-stranded nucleic acids unable to form stable hairpins remains higher than 10(8) M-1. Kinetic experiments suggest that P 32 dissociates from the MS2 RNA rewinding strand with a similar rate constant as calculated for the dissociation from single-stranded regions. Possible in vivo consequences of these findings are discussed.


Ethical implications of HIV self-testing: the game is far from being over.
The use of combined Anti-Retroviral Therapy (cART) has been revolutionary in the history of the fight against HIV-AIDS, with remarkable reductions in HIV associated morbidity and mortality. Knowing one's HIV status early, not only increases chances of early initiation of effective, affordable and available treatment, but has lately been associated with an important potential to reduce disease transmission. A public health priority lately has been to lay emphasis on early and wide spread HIV screening. With many countries having already in the market over the counter self-testing kits, the ethical question whether self-testing in HIV with such kits is acceptable remains unanswered. Many Western authors have been firm on the fact that this approach enhances patient autonomy and is ethically grounded. We argue that the notion of patient autonomy as proposed by most ethicists assumes perfect understanding of information around HIV, neglects HIV associated stigma as well as proper identification of risky situations that warrant an HIV test. Putting traditional clinic based HIV screening practice into the shadows might be too early, especially for developing countries and potentially very dangerous. Encouraging self-testing as a measure to accompany clinic based testing in our opinion stands as main precondition for public health to invest in HIV self-testing. We agree with most authors that hard to reach risky groups like men and Men Who Have Sex with Men (MSM) are easily reached with the self-testing approach. However, linking self-testers to the medical services they need remains a key challenge, and an understudied indispensable obstacle in making this approach to obtain its desired goals.


Gastroenterology-Urology Devices; Manual Gastroenterology-Urology Surgical Instruments and Accessories. Final rule; technical amendment.
The Food and Drug Administration (FDA) is amending the identification of manual gastroenterology-urology surgical instruments and accessories to reflect that the device does not include specialized surgical instrumentation for use with urogyencologic surgical mesh specifically intended for use as an aid in the insertion, placement, fixation, or anchoring of surgical mesh during urogynecologic procedures ("specialized surgical instrumentation for use with urogynecologic surgical mesh"). These amendments are being made to reflect changes made in the recently issued final reclassification order for specialized surgical instrumentation for use with urogynecologic surgical mesh.


PROCESS OF INFECTION WITH PHI-X174: EFFECT OF EXONUCLEASES ON THE REPLICATIVE FORM.
When a preparation containing the DNA of the bacteriophage øX174 in its replicative form together with DNA from Escherichia coli is treated with exonucleases, the replicative form retains its characteristic physical properties, while the bacterial DNA is degraded. The evidence suggests that the mature replicative form exists as a closed ring.


Better physician-patient communication; an important milestone in control of hypertension, a multicenter study from Karachi, Pakistan.
Control of hypertension is an important cornerstone in prevention of cardiovascular morbidity and mortality. This study was designed to compare physician encounter score in patients with controlled and uncontrolled hypertension. It was conducted at three tertiary care hospitals in Karachi. Patients were categorized into controlled and uncontrolled hypertension based on their initial blood pressure readings on presentation. Primary outcome variable was control of hypertension and physician encounter score (a composite score of 12 item question) was the main candidate variable. Higher scores reflected favorable encounter with physician. Mean age of participants was 57.7 ± 12 years; 224 (50.1%) were men. Controlled hypertension was present in 72.3% (323) and uncontrolled hypertension was present in 27.4% (124). Mean physician encounter score in uncontrolled hypertensive was 7.25 ± 2.64 versus 7.83 ± 2.22 (p=0.02) in controlled hypertensive. Patient-physician encounter is an important milestone in control of hypertension in hypertensive patients and directly translates into better adherence to antihypertensives in these patients.


Nematic liquid crystal director structures in rectangular regions.
We consider a shallow rectangular well of nematic liquid crystal subject to weak anchoring on the sides of the well. By considering weak anchoring instead of infinitely strong anchoring, we are able to analyze nematic equilibria in the well without the need to exclude point defects at the corners, as done in previous work in the area. For relatively weak anchoring, we are able to derive analytic expressions for the director alignment angle in terms of an infinite series of modes, involving roots of a transcendental equation. The analytic forms of the director configuration are then used to calculate critical anchoring strengths at which uniform and distorted director structures exchange stability. We also consider the asymptotic behavior of the director structure and energy for very strong anchoring. We show that in both cases-for the transitions from uniform to distorted states and the limit of infinitely strong anchoring-the approximate analytic expansions agree very well with corresponding numerical calculations of the full model.


Mandibular Advancement Device-Emergent Central Sleep Apnea Can Resolve Spontaneously: A Case Report.
The development of treatment emergent central sleep apnea (CSA) has been described after almost all obstructive sleep apnea (OSA) therapies. While the course of positive airway pressure (PAP) emergent CSA, is better established; little is known about the natural course of mandibular advancement device (MAD) emergent CSA. Previous reports failed to comment on its natural course or report treatment with advanced ventilator modes such as adaptive servoventilation. We describe spontaneous resolution of MAD emergent CSA in a patient with moderate OSA who refused PAP. We also highlight the need for follow up polysomnography (PSG) after maximal advancement with a MAD and the possible association between MAD emergent CSA and atrial fibrillation. The exact pathophysiology of this phenomenon remains unclear but may relate to high loop gain of the respiratory system resulting in ventilatory overshoot after treatment and atrial fibrillation associated increased susceptibility to periodic ventilation.


Pancreatitis following parathyroid surgery.
While pancreatitis may provide the clue to the diagnosis of hyperparathyroidism preoperatively, the occurrence of pancreatitis following parathyroidectomy is not generally recognized. In this study preoperative and postoperative serum amylase estimations, together with a clinical assessment, were performed on 86 patients undergoing neck exploration for hyperparathyroidism. It was found that postoperative hyperamylasaemia occurred in 35% of the total group, while clinically significant pancreatitis was found in 9% of cases. Pancreatitis was significantly more common when thyroidectomy was performed at the time of parathyroidectomy, occurring in 23% of this group of patients, and may be due to the blunted C-cell response of calcitonin secretion to the induced hypercalcaemia associated with operative manipulation. Careful attention should be paid to postoperative abdominal symptoms, for they may indicate pancreatitis.


Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors.
There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer. This retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0-IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. Membrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated (p < 0.001) and associated with intestinal-type histology (p = 0.001 and p < 0.001, respectively) and advanced age (p = 0.011 and p = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence. According to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2-HER3 heterodimerization inhibitors.


Typology of gay consumers' interaction styles on complaining propensity.
The purpose of this study is to develop a typology of gay male consumers based on self-concept variables related to social interactions. Openness about sexual orientation, collective self-esteem, stigma-consciousness, and negative evaluation were used to identify clusters of gay male consumers. An initial test sample (n = 125) suggested a three-cluster solution, and a validation sample (n = 247) established reproducibility of the proposed typology. Three clusters with distinct interaction styles emerged: "confident gay," "diffident gay," and "guarded gay." Additionally, the usefulness of the typology is demonstrated by comparing the clusters on the basis of complaining propensity. Typologies of each cluster and implications for research and practice are discussed.


Comparative Readability Analysis of Online Patient Education Resources on Inflammatory Bowel Diseases.
The National Institutes of Health recommend a readability grade level of less than 7th grade for patient directed information. In this study, we use validated readability metrics to analyze patient information from prominent websites pertaining to ulcerative colitis and Crohn's disease. The terms "Crohn's Disease," "Ulcerative Colitis," and "Inflammatory Bowel Disease" were queried on Google and Bing. Websites containing patient education material were saved as a text file and then modified through expungement of medical terminology that was described within the text. Modified text was then divided into subsections that were analyzed using six validated readability scales. None of the websites analyzed in this study achieved an estimated reading grade level below the recommended 7th grade. The median readability grade level (after modification) was 11.5 grade levels for both Crohn's disease and ulcerative colitis. The treatment subsection required the highest level of education with a median readability grade of 12th grade (range of 6.9 to 17). Readability of online patient education material from the analyzed popular websites far exceeds the recommended level of being less than 7th grade. Patient education resources should be revised to achieve wider health literacy.


Synthesis, Biological Evaluation and Molecular Docking of Avicequinone C Analogues as Potential Steroid 5α-Reductase Inhibitors.
Avicequinone C (5a), a furanonaphthoquinone isolated from the Thai mangrove Avicennia marina has been shown previously to have interesting steroid 5α-reductase type 1 inhibitory activity. In this study, a series of avicequinone C analogues containing furanonaphthoquinone with different degrees of saturation and substituents at the furan ring were synthesized. The resulting synthetic avicequinone C and analogues (5a-f) along with some related compounds including 2,5-dihydroxy-1,4-benzoquinone (6) and natural naphthoquinones such as lawsone (7a) and lapachol (7b) were evaluated for their in vitro cell viability and steroid 5α-reductase type 1 inhibitory activities using the cultured cell line of human keratinocytes (HaCaT). This cell-based bioassay was performed based on a direct detection of the enzymatic product dihydrotestosterone (2) by using a non-radioactive high performance thin layer chromatography (HPTLC) method. Among the furanonaphthoquinones in this series, 5e having a propionic substituent at furan ring possessed approximately 22-fold more potent than the original isolated compound 5a. However, the compounds without furan motif such as 6, 7a and b could not inhibit the activity of steroid 5α-reductase. Molecular docking results of the in silico three-dimensional steroid 5α-reductase type 1-reduced nicotinamide adenine dinucleotide phosphate (NADPH) binary complex was performed via AutoDock Vina and it illustrated that the furanonaphthoquinone moiety and the substituent at furan ring might play a key role as pharmacophores for the steroid 5α-reductase inhibitory activity.


Recent advances in nuclear cardiology.
Nuclear cardiology is an essential part of functional, non-invasive, cardiac imaging. Significant advances have been made in nuclear cardiology since planar (201)thallium ((201)TI) scintigraphy was introduced for the evaluation of left ventricular (LV) perfusion nearly 40 years ago. The use of nuclear cardiology has been steadily increasing over the last 20 years with important steps being the introduction of (99m)technetium- ((99m)Tc)-labelled perfusion radiotracers, the change from only planar to now much more single photon emission computed tomography (SPECT) and positron emission tomography (PET), electrocardiogram gating of nuclear perfusion imaging, and finally introducing nuclear hybrid imaging using either SPECT or PET together with either computed tomography or magnetic resonance imaging. The indications have extended from nearly only coronary artery diseases to several non-coronary cardiac diseases. The advances in nuclear cardiology are discussed under the four headlines of: 1) myocardial perfusion, 2) cardiac performance including LV and right ventricular (RV) function, 3) myocardial metabolism, and 4) experimental nuclear cardiology.


Oxytocin and its receptor in pregnancy and parturition: current concepts and clinical implications.
To present our current understanding of oxytocin and its receptors during pregnancy and parturition and their potential clinical applications. A MEDLINE search was conducted for pertinent articles from 1966 to October 1996 related to oxytocin and its receptor and their clinical implications during pregnancy and parturition. Review articles, book chapters, and published trials were also searched. Only references in English that were deemed relevant were used. When possible, human data and sometimes animal data pertinent to understanding the interaction of oxytocin and its receptors were selected. Oxytocin is synthesized in the hypothalamus and in many reproductive tissues during pregnancy, whereas the receptors are synthesized in reproductive tissues. The genes for oxytocin and its receptors are on chromosomes 20 and 3, respectively. Oxytocin and its receptors are regulated by sex steroids and by oxytocin itself. The paracrine and autocrine mechanisms regulating oxytocin and its receptor within the fetoplacental-uterine unit are central to the control of uterine contractions and parturition. Such current understanding provides the basis for appropriate oxytocin regimens to induce or augment labor, to inhibit preterm labor by blockade of oxytocin receptors, and to achieve cervical ripening. Advances in our knowledge of oxytocin and its receptor have provided rational and sound principles for current concepts about their role in parturition, the appropriate use of oxytocin to stimulate the pregnant uterus or ripen the cervix, and the use of oxytocin antagonist to inhibit uterine contractions and preterm labor.


The Health Informatics Center of Acadiana--informing health policymaking in post-Katrina/Rita Louisiana.
A "healthy communities" initiative in Louisiana led to creation of the Health Informatics Center of Acadiana(HICA) at The University of Louisiana at Lafayette, in the south central United States. Since hurricanes Katrina and Rita devastated the Louisiana coast in 2005, HICA's role has taken on heightened significance. HICA identifies vulnerable populations, documents their risk factors, and evaluates interventions intended to improve community health. HICA collaborates with the Louisiana Department of Health and Hospitals and the Lafayette Community Health Consortium (LCHC), the latter formed for coordination among local healthcare providers and agencies. Both HICA and LCHC were created when "Bonne Santé à Lafayette!"--a locally developed community health improvement plan--was implemented. This paper reports on methods and experiences of HICA and LCHC, offering these as models for addressing community concerns elsewhere. Of special interest is the discussion of Louisiana HABITS, a consumer survey methodology that HICA has developed to measure healthcare access barriers, to provide information that healthcare organizations and governments need to implement workable business strategy and public policy.


Labouring Together: collaborative alliances in maternity care in Victoria, Australia-protocol of a mixed-methods study.
For over a decade, enquiries into adverse perinatal outcomes have led to reports that poor collaboration has been detrimental to the safety and experience of maternity care. Despite efforts to improve collaboration, investigations into maternity care at Morecambe Bay (UK) and Djerriwarrh Health Services (Australia) have revealed that poor collaboration and decision-making remain a threat to perinatal safety. The Labouring Together study will investigate how elements hypothesised to influence the effectiveness of collaboration are reflected in perceptions and experiences of clinicians and childbearing women in Victoria, Australia. The study will explore conditions that assist clinicians and women to work collaboratively to support positive maternity outcomes. Results of the study will provide a platform for consumers, clinician groups, organisations and policymakers to work together to improve the quality, safety and experience of maternity care. 4 case study sites have been selected to represent a range of models of maternity care in metropolitan and regional Victoria, Australia. A mixed-methods approach including cross-sectional surveys and interviews will be used in each case study site, involving both clinicians and consumers. Quantitative data analysis will include descriptive statistics, 2-way multivariate analysis of variance for the dependent and independent variables, and χ2 analysis to identify the degree of congruence between consumer preferences and experiences. Interview data will be analysed for emerging themes and concepts. Data will then be analysed for convergent lines of enquiry supported by triangulation of data to draw conclusions. Organisational ethics approval has been received from the case study sites and Deakin University Human Research Ethics Committee (2014-238). Dissemination of the results of the Labouring Together study will be via peer-reviewed publications and conference presentations, and in written reports for each case study site to support organisational change.


On pharyngealized vowels in Northern Horpa: An acoustic and ultrasound study.
In the Northern Horpa (NH) language of Sichuan, vowels are divided between plain and pharyngealized sets, with the latter pronounced with auxiliary articulatory gestures involving more constriction in the vocal tract. The current study examines how the NH vocalic contrast is manifested in line with the process of pharyngealization both acoustically and articulatorily, based on freshly gathered data from two varieties of the language (i.e., Rtsangkhog and Yunasche). Along with formant analyses, ultrasound imaging was employed to capture the tongue postures and positions during vowel production. The results show that in contrast with plain vowels, pharyngealized vowels generally feature lower F2 values and higher F1 and F3 values. Mixed results for F2 and F3 suggest that the quality contrasts are vowel-dependent. Ultrasound images, on the other hand, reveal that the vocalic distinction is affected by different types of tongue movements, including retraction, backing, and double bunching, depending on the inherent tongue positions for each vowel. The two NH varieties investigated are found to display differential formant changes and different types of tongue displacements. The formant profiles along with ultrasound images support the view that the production of the NH phonologically marked vowels is characteristic of pharyngealization.


Tackling Pain Associated with Rheumatoid Arthritis: Proton-Sensing Receptors.
Rheumatoid arthritis (RA), characterized by chronic inflammation of synovial joints, is often associated with ongoing pain and increased pain sensitivity. Chronic pain that comes with RA turns independent, essentially becoming its own disease. It could partly explain that a significant number (50%) of RA patients fail to respond to current RA therapies that focus mainly on suppression of joint inflammation. The acute phase of pain seems to associate with joint inflammation in early RA. In established RA, the chronic phase of pain could be linked to inflammatory components of neuron-immune interactions and noninflammatory components. Accumulating evidence suggests that the initial inflammation and autoimmunity in RA (preclinical RA) begin outside of the joint and may originate at mucosal sites and alterations in the composition of microbiota located at mucosal sites could be essential for mucosal inflammation, triggering joint inflammation. Fibroblast-like synoviocytes in the inflamed joint respond to cytokines to release acidic components, lowering pH in synovial fluid. Extracellular proton binds to proton-sensing ion channels, and G-protein-coupled receptors in joint nociceptive fibers may contribute to sensory transduction and release of neurotransmitters, leading to pain and hyperalgesia. Activation of peripheral sensory neurons or nociceptors further modulates inflammation, resulting in neuroinflammation or neurogenic inflammation. Peripheral and central nerves work with non-neuronal cells (such as immune cells, glial cells) in concert to contribute to the chronic phase of RA-associated pain. This review will discuss actions of proton-sensing receptors on neurons or non-neuronal cells that modulate RA pathology and associated chronic pain, and it will be beneficial for the development of future therapeutic treatments.


Molecular and electrophysiological evaluation of human cardiomyocyte subtypes to facilitate generation of composite cardiac models.
Paucity of physiologically relevant cardiac models has limited the widespread application of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes in drug development. Here, we performed comprehensive characterization of hiPSC-derived cardiomyocyte subtypes from 2D and 3D cultures and established a novel 3D model to study impulse initiation and propagation. Directed differentiation approaches were used to generate sinoatrial nodal (SANCM), atrial (ACM) and ventricular cardiomyocytes (VCM). Single cell RNA sequencing established that the protocols yield distinct cell populations in line with expected identities, which was also confirmed by electrophysiological characterization. In 3D EHT cultures of all subtypes, we observed prominent expression of stretch-responsive genes such as NPPA. Response to rate modulating drugs noradrenaline, carbachol and ivabradine were comparable in single cells and EHTs. Differences in the speed of impulse propagation between the subtypes were more pronounced in EHTs compared with 2D monolayers owing to a progressive increase in conduction velocities in atrial and ventricular cardiomyocytes, in line with a more mature phenotype. In a novel binary EHT model of pacemaker-atrial interface, the SANCM end of the tissue consistently paced the EHTs under baseline conditions, which was inhibited by ivabradine. Taken together, our data provide comprehensive insights into molecular and electrophysiological properties of hiPSC-derived cardiomyocyte subtypes, facilitating the creation of next generation composite cardiac models for drug discovery, disease modeling and cell-based regenerative therapies.


Transcriptome analysis of a taxol-producing endophytic fungus Cladosporium cladosporioides MD2.
The shortage of molecular information for taxol-producing fungi has greatly impeded the understanding of fungal taxol biosynthesis mechanism. In this study, the transcriptome of one taxol-producing endophytic fungus Cladosporium cladosporioides MD2 was sequenced for the first time. About 1.77 Gbp clean reads were generated and further assembled into 16,603 unigenes with an average length of 1110 bp. All of the unigenes were annotated against seven public databases to present the transcriptome characteristics of C. cladosporioides MD2. A total of 12,479 unigenes could be annotated with at least one database, and 1593 unigenes could be annotated in all queried databases. In total, 8425 and 3350 unigenes were categorized into 57 GO functional groups and 262 KEGG pathways, respectively, exhibiting the dominant GO terms and metabolic pathways in the C. cladosporioides MD2 transcriptome. One potential and partial taxol biosynthetic pathway was speculated including 9 unigenes related to terpenoid backbone biosynthesis and 40 unigenes involved in the biosynthetic steps from geranylgeranyl diphosphate to 10-deacetylbaccatin III. These results provided valuable information for the molecular mechanism research of taxol biosynthesis in C. cladosporioides MD2.


Fissure micromorphology and sealant adaptation after occlusal enameloplasty.
This study evaluated fissure micromorphology after enameloplasty, and the effect of thermocycling on the adaptation of enamel surfaces of filled and unfilled sealants after different occlusal surface treatments. A total of 150 human noncarious extracted molars were cleaned with a water slurry of fine flour of pumice using Crescent Snap-On pointed brushes in a slow-speed handpiece. The teeth were divided at random into six groups of 20 teeth each: Group 1: Pumice prophylaxis and PrismaShield filled sealant; Group 2: Pumice prophylaxis and Delton opaque unfilled sealant; Group 3: Treatment with a diamond fissure bur (Sorensen Ponta K.G. 2137 F) and PrismaShield sealant; Group 4: Treatment with a diamond fissure bur (Sorensen Ponta K.G. 2137 F) and Delton opaque sealant; Group 5: Treatment with a 1/4 round carbide bur and PrismaShield sealant; Group 6: Treatment with a 1/4 round carbide bur and Delton opaque sealant. Before sealant placement, the enamel occlusal surfaces were acid-etched for 30 seconds using disposable brushes, rinsed and dried. The sealants were light-cured for 40 seconds. Immediately after curing the sealant, all teeth were placed in distilled water for 48 hours. Sixty teeth were thermocycled (x 500, 5 degrees C-55 degrees C, 30-second dwell time) and 60 teeth were not thermocycled. For each treatment modality, five additional teeth served as controls and did not receive the sealant. The results revealed a superior sealant adaptation to enamel when the enameloplasty technique was used. There was no difference in penetration capabilities and adaptation between the filled and the unfilled sealants or between the thermocycled or not thermocycled groups.


[Label-free quantitative peptidomics-based analysis on glycopeptides in deerhorn gelatin and deer-hide gelatin].
Nano-LC-MS/MS was used to analyze trypsin digested deer-horn gelatin( DCG) and deer-hide gelatin( DHG) samples.The glycopeptides in DCG and DHG were quantified by Label-free quantitative( LFQ) peptidomics,on the basis of which the glycopeptides with significant difference in DCG and DHG were determined. As a result,5 736 peptides were identified from DCG samples,including 213 galactosyl-hydroxylysine containing peptides( Gal-Hyl-peptides) and 102 glucosyl-galactosyl-hydroxylysine containing peptides( Glc-Gal-Hyl-peptides),while 6 836 peptides were identified from DHG samples,among which there were 250 Gal-Hyl-peptides and 98 Glc-Gal-Hyl-peptides. With over 3-fold peak area difference and highly significant intergroup difference( P < 0. 01) as the screening criteria,444 differential peptides were determined in DCG and DHG,including 16 Gal-Hyl-peptides and 5 Glc-Gal-Hyl-peptides. Then XIC peak shapes,standard deviation of peak area,and fold change were applied for further screening and 5 glycopeptides with significant differences in DCG and DHG were confirmed,which could serve as potential biomarkers for distinguishing DCG and DHG. The present study provided ideas and strategies for the in-depth investigation on the discrimination of DCG and DHG and is of good theoretical significance and application value for the further research on chemical constituents and quality control of gelatin derived Chinese medicinals.


Diagnostic Challenge of Diffusion Tensor Imaging in a Patient With Hemiplegia After Traumatic Brain Injury.
A 51-year-old man showed hemiplegia on his right side after a traumatic brain injury (TBI). On initial brain computed tomography (CT) scan, an acute subdural hemorrhage in the right cerebral convexity and severe degrees of midline shifting and subfalcine herniation to the left side were evident. On follow-up brain magnetic resonance imaging (MRI), there were multiple microhemorrhages in the left parietal and occipital subcortical regions. To explain the occurrence of right hemiplegia after brain damage which dominantly on the right side of brain, we used diffusion tensor imaging (DTI) to reconstruct the corticospinal tract (CST), which showed nearly complete injury on the left CST. We also performed motor-evoked potentials, and stimulation of left motor cortex evoked no response on both sides of upper extremity. We report a case of patient with hemiplegia after TBI and elucidation of the case by DTI rather than CT and MRI.


Efficacy and safety of teicoplanin in gram-positive pulmonary infections.
Teicoplanin is a new antibiotic obtained from a culture filtrate of Actinoplanes teichomyceticus with potent activity against aerobic and anaerobic gram-positive bacteria and having a high affinity for healthy or inflamed bronchial mucosa and pulmonary parenchyma. To investigate the efficacy and safety of this drug, we selected 13 patients suffering from lower respiratory tract infections caused by gram-positive organisms. Pathogens isolated from sputum or bronchial aspirate were: 8 Staphylococcus aureus, 1 Staphylococcus epidermidis, 3 Streptococcus pneumoniae and 1 Streptococcus species. We began treatment as monotherapy at the dosage of 400 mg daily (200 mg x 2) I.M. only after microbiological evaluation. 11 patients (84.6%) were clinically and bacteriologically cured, 1 (7.7%) showed definite clinical improvement but persistence of causative agent and 1 (7.7%) failed to respond. The mean treatment period was 8.3 days. No major adverse effect was observed. We conclude that teicoplanin is a very efficacious and well-tolerated antibiotic for therapy of gram-positive pulmonary infections.


A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.
The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.


Cancers in Australia in 2010 attributable to tobacco smoke.
To estimate the population attributable fraction (PAF) and numbers of cancers occurring in Australia in 2010 attributable to tobacco smoking, both personal and by a partner. We used a modified Peto-Lopez approach to calculate the difference between the number of lung cancer cases observed and the number expected assuming the entire population developed lung cancer at the same rate as never smokers. For cancers other than lung, we applied the standard PAF formula using relative risks from a large cohort and derived notional smoking prevalence. To estimate the PAF for partners' smoking, we used the standard formula incorporating the proportion of non-smoking Australians living with an ever-smoking partner and relative risks associated with partner smoking. An estimated 15,525 (13%) cancers in Australia in 2010 were attributable to tobacco smoke, including 8,324 (81%) lung, 1,973 (59%) oral cavity and pharynx, 855 (60%) oesophagus and 951 (6%) colorectal cancers. Of these, 136 lung cancers in non-smokers were attributable to partner tobacco smoke. More than one in eight cancers in Australia is attributable to tobacco smoking and would be avoided if nobody smoked. Strategies to reduce the prevalence of smoking remain a high priority for cancer control.


Specific surface area of overlapping spheres in the presence of obstructions.
This study considers the random placement of uniform sized spheres, which may overlap, in the presence of another set of randomly placed (hard) spheres, which do not overlap. The overlapping spheres do not intersect the hard spheres. It is shown that the specific surface area of the collection of overlapping spheres is affected by the hard spheres, such that there is a minimum in the specific surface area as a function of the relative size of the two sets of spheres. The occurrence of the minimum is explained in terms of the break-up of pore connectivity. The configuration can be considered to be a simple model of the structure of a porous composite material. In particular, the overlapping particles represent voids while the hard particles represent fillers. Example materials are pervious concrete, metallurgical coke, ice cream, and polymer composites. We also show how the material properties of such composites are affected by the void structure.


A comparison of N2 cleavage in Schrock's Mo[N3N] and Laplaza-Cummins' Mo[N(R)Ar]3 systems.
The four-coordinate Mo[N(3)N] complex, [N(3)N] = [{RNCH(2)CH(2)}(3)N], R = 3,5-(2,4,6-iPr(3)C(6)H(2))(2)C(6)H(3) (HIPT), which is capable of converting N(2) to ammonia catalytically, reacts with N(2) in a similar manner to Mo[N(R)Ar](3) (R = tBu, Ar = 3,5-C(6)H(3)Me(2)) to form a dinitrogen-bridged dimer intermediate, but unlike its three-coordinate counterpart, N(2) cleavage is not observed. To rationalise these differences, the reaction of N(2) with the model Mo[NH(2)](3)[NH(3)] and full ligand Mo[N(3)N] systems was explored using density functional theory and compared with the results of an earlier study involving the model three-coordinate Mo[NH(2)](3) system. Although the overall reaction is exothermic, the final N-N cleavage step is calculated to be endothermic by 75 kJ mol(-1) for the model system when the Mo-amine cap bond length is fixed to mimic the constraints of the ligand straps, but exothermic by 14 kJ mol(-1) for the full ligand system. In the latter case, the slightly exothermic cleavage step can be attributed to the destabilization of the N(2) bridged dimer relative to the nitride product owing to the steric effects of the bulky R groups. The activation barrier for N-N cleavage is estimated at 151 kJ mol(-1) for the model system, more than twice the calculated value for Mo[NH(2)](3), and even greater, 213 kJ mol(-1), for the full ligand [N(3)N]Mo system. A bonding analysis shows that although the binding of the amine cap helps to stabilize the intermediate dimer, at the same time it destabilizes the metal d-orbitals involved in backbonding to the pi* orbitals on N(2). As a result, backdonation is less efficient and N-N activation reduced compared to the three-coordinate system. Thus, the increased stability of the intermediate dimer on binding of the amine cap combined with the reduced level of N-N activation and higher kinetic barrier, explain why N-N cleavage has not been observed experimentally for the four-coordinate Mo[N(3)N] system.


Differential pulmonary residual volume determinations with radioactive xenon.
A radioactive xenon inhalation procedure was used to determine differential residual volumes (right lung vs. left lung) in 28 normal subjects (6 of whom smoked approximately 1 package of cigarettes per day). The average right lung residual volume represented 54% of the total residual volume, whereas the average left lung residual volumerepresented 46% of the total. In addition, all of the subjects were studied by a standard helium dilution technique and found to have total lung residual comparable to the total lung residual volume as determined by the xenon technique. There was no statistical difference between the data obtained from cigarette smokers vs. nonsmokers. The noninvasive nature of the xenon technique makes this a useful procedure in determining differential residual volumes.


Long Non-Coding RNA LINC01569 Promotes Proliferation and Metastasis in Colorectal Cancer by miR-381-3p/RAP2A Axis.
Long non-coding RNAs (lncRNAs) display regulatory function flexibly in tumor onset and developments. Our study aimed to delve into the roles of lncRNA LINC01569 (LINC01569) in colorectal cancer (CRC) progression to study the potential mechanisms. The genetic expression profiles of miR-381-3p and LINC01569 were measured by RT-PCR. The subcellular localization of LINC01569 in CRC cells was identified using subcellular fractionation location. Loss-of-function assays were performed to explore the potential effects of LINC01569 on CRC progression. Dual-luciferase reporter analysis was employed to verify the binding connections among LINC01569, miR-381-3p, and RAP2A. LINC01569 expression was distinctly increased in CRC. Curiously, if LINC01569 is removed, CRC cells will not migrate, proliferate, and invade remarkably. Molecular mechanism exploration uncovered that LINC01569 acted as a ceRNA competing with RAP2A to bind with miR-381-3p. Furthermore, rescue experiments corroborated the fact that miR-381-3p suppression reversed the inhibitory actions of LINC01569 knockdown on the expression of RAP2A and CRC progression. Overall, our findings indicate that LINC01569 plays a key role in CRC development by means of aiming at the miR-381-3p/RAP2A axis and can be equivalent to an underlying medicinal target to save CRC patients.


GAMETOGENESIS AND REPRODUCTIVE PERIODICITY OF THE SUBTIDAL SEA ANEMONE URTICINA LOFOTENSIS (COELENTERATA: ACTINIARIA) IN CALIFORNIA.
Sexual reproduction of the actiniid sea anemone Urticina (= Tealia) lofotensis was studied for one year (1976-1977) in 105 specimens collected by hand monthly at 7-16 m in Carmel Bay, California. Gametogenesis, evaluated by light microscopy, is typical for an actinian. Oocyte maturation is asynchronous, even within a mesentery, whereas spermiogenesis of each male is synchronous. Each oocyte is associated with a trophonema, and eggs may exceed 1200 µm in diameter. The study population is dioecious, with a significant excess of females. Gonad indices and histological data indicate that the period of maximum female ripeness ends in December as the male maximum begins. The spawning peak appears to occur then, just as water temperature begins to fall from its annual high. Some females contain large oocytes and seem to release eggs throughout the year. Greatest reproductive quiescence is in April and May, when water temperature is at its minimum.


Confinement of Organic Dyes in UiO-66-Type Metal-Organic Frameworks for the Enhanced Synthesis of [1,2,5]Thiadiazole[3,4-g]benzoimidazoles.
Organic dyes as non-noble metal photosensitizers have attracted increasing attention due to their environmental friendliness and sustainability but suffer from fast deactivation and low stability. Here, we reported a fruitful strategy by the confinement and stabilization of visible light-active signal unit organic dyes within the metal-organic frameworks (MOFs) and developed a series of heterogeneous photocatalysts dye@UiO-66s [dye = fluorescein (FL)/rhodamine B (RhB)/eosin Y (EY), UiO-66s = UiO-66, and Bim-UiO-66]. It has been demonstrated that the encapsulated dyes can effectively sensitize MOF hosts and dominate the band structures and photocatalytic activities of dye@UiO-66s regardless of the ligand functionalization of MOFs. Photocatalytic experiments showed that these dye@UiO-66s exhibit enhanced activities relative to free dyes and among them, FL@Bim-UiO-66 displays excellent efficiencies toward the green synthesis of new carbon-bridged annulations, [1,2,5]thiadiazole[3,4-g]benzoimidazoles in the yield of up to 98% at room temperature with outstanding stability and reusability. Furthermore, the intramolecular cyclization intermediate was captured and characterized by the single-crystal X-ray diffraction analysis.


Opioids and Sleep-Disordered Breathing.
Opioid use for chronic pain analgesia, particularly chronic noncancer pain, has increased greatly since the late 1990s, resulting in an increase in opioid-associated morbidity and mortality. A clear link between opioid use and sleep-disordered breathing (SDB) has been established, with the majority of chronic opioid users being affected by the condition, and dose-dependent severity apparent for some opioids. More evidence is currently needed on how to effectively manage opioid-induced SDB. This review summarizes the current state of knowledge relating to management of patients undergoing chronic opioid therapy who have SDB. Initial management of these patients requires a thorough biopsychosocial assessment of their need for opioid therapy, consideration of reduction or cessation of the opioid if possible, and analysis of alternative therapies for treatment of their pain. If opioid therapy must be continued, then management of the associated SDB may be important. Several small- to medium-scale studies have examined the efficacy of noninvasive ventilation, particularly adaptive servo-ventilation (ASV) for the treatment of opioid-associated SDB. This research is particularly important because opioids predispose predominantly to central sleep apnea and also, to a lesser extent, OSA. Generally, these studies have found positive results in treating opioid-associated SDB with ASV in terms of improving outcome measures such as central apnea index and the apnea-hypopnea index. Larger studies that measure longer term health outcomes, patient sleepiness, and compliance are needed, however. Registries of health outcomes of ASV-treated patients may assist with future treatment planning.


Reflectivity enhanced refractive index sensor based on a fiber-integrated Fabry-Perot microresonator.
We discuss a fiber-integrated refractive index sensor with strongly improved detection performance. The resonator has been implemented by means of focused-ion beam milling of a step index fiber and shows a sensitivity of about 1.15µm/RIU. Coating the resonator walls led to a strongly improved mirror reflectivity by a factor of about 26. Design rules for device optimization and a detailed mathematical analysis are discussed, revealing that the sensor operates as an optimized Fabry-Perot resonator. We also show that the performance of such kind of Fabry-Perot sensors is, in general, limited by the detection limit function - a quantity depending on the cavitiy's finesse and on the measurement capabilities used.


[Chronotherapy approaches in the treatment of gastroduodenal ulcer].
Each patient with ulcer has his/her own 24-h biorhythm of acid production, features of food alkalization, duration of duodenogastric and gastroesophageal reflux. Pharmacological test conducted in prolonged 24-h pH-metry helps to select the most effective antisecretory drug, while analysis of 24-h biorhythm of acid production--optimal time for drug intake and number of its daily doses.


External Validation of the Breast Cancer Surgery Risk Calculator (BCSRc): A Predictive Model for Postoperative Complications.
The breast cancer surgical risk calculator (BCSRc) is a prognostic tool that determines a breast cancer patient's unique risk of acute complications following each possible surgical intervention. When used in the preoperative setting, it can help to stratify patients with an increased complication risk and enhance the patient-physician informed decision-making process. The objective of this study was to externally validate the four models used in the BCSRc on a large cohort of patients who underwent breast cancer surgery. The BCSRc was developed by using a retrospective cohort from the National Surgical Quality Improvement Program database from 2005 to 2018. Four models were built by using logistic regression methods to predict the following composite outcomes: overall, infectious, hematologic, and internal organ complications. This study obtained a new cohort of patients from the National Surgical Quality Improvement Program by utilizing participant user files from 2019 to 2020. The area under the curve, brier score, and Hosmer-Lemeshow goodness of fit test measured model performance, accuracy, and calibration, respectively. A total of 192,095 patients met inclusion criteria in the development of the BCSRc, and the validation cohort included 60,144 women. The area under the curve during external validation for each model was approximately 0.70. Accuracy, or Brier scores, were all between 0.04 and 0.003. Model calibration using the Hosmer-Lemeshow statistic found all p-values > 0.05. All of these model coefficients will be updated on the web-based BCSRc platform: www.breastcalc.org . The BCSRc continues to show excellent external-validation measures. Collectively, this prognostic tool can enhance the decision-making process, help stratify patients with an increased complication risk, and improve expectant management.


Effects of white cell reduction on the resistance of blood components to bacterial multiplication.
While prestorage white cell (WBC) reduction by filtration may improve platelet and red cell quality, it also may remove an important anti-bacterial defense mechanism, especially if blood is WBC-reduced shortly after collection. The question of whether WBC reduction of platelet concentrates and red cells altered bacterial proliferation kinetics in components prepared from deliberately contaminated, freshly collected blood was investigated. Two-unit pools of whole blood were inoculated, at a concentration of approximately one colony-forming unit per mL, with one of 17 bacterial species reported to have caused septicemia in transfusion recipients. Each pool was divided after inoculation, and components were prepared from the 2 units after a 7-hour room-temperature holding period. One unit of each AS-1 red cell or platelet pair was WBC-reduced, and the pairs were then stored for 42 days at 4 degrees C (red cells) or for 10 days at 22 degrees C (platelets). Quantitative bacterial cultures were performed at periodic intervals. In red cells, clinically significant bacterial proliferation occurred in only one instance (Serratia marcescens), and growth was less rapid in the WBC-reduced unit than in the control. Three patterns of growth were seen in platelet concentrates. In four cases, there was rapid proliferation in both test and control units, while on 13 occasions there was minimal replication in either pair. On six occasions, substantial growth was noted in control units, while few or no bacteria could be found in the WBC-reduced units. There was no evidence in either red cells or platelets that bacteria proliferated more rapidly in units that had been WBC-reduced before storage than they did in units in which WBCs were retained. Rather than increasing the risk of bacterial proliferation through removal of active phagocytic cells, WBC reduction by filtration before blood storage may act to reduce the likelihood of significant bacterial proliferation, possibly by removal of microorganisms along with WBCs.


Characterization of Different Cable Ferrite Materials to Reduce the Electromagnetic Noise in the 2-150 kHz Frequency Range.
The gap of standardization for conducted and field coupled electromagnetic interferences (EMI) in the 2-150 kHz frequency range can lead to Electromagnetic Compatibility (EMC) problems. This is caused by power systems such as Pulse Width Modulation (PWM) controlled rectifiers, photovoltaic inverters or charging battery units in electric vehicles. This is a very important frequency spectral due to interferences generated in a wide range of devices and, specifically, communication problems in the new technologies and devices incorporated to the traditional grid to convert it into a Smart Grid. Consequently, it is necessary to provide new solutions to attenuate this kind of interference, which involves finding new materials that are able to filter the electromagnetic noise. This contribution is focused on characterizing the performance of a novel material based on nanocrystalline and comparing it to most common material compositions such as MnZn and NiZn. This research is carried out from the point of view of the manufacturing process, magnetic properties and EMI suppression ability. This last item is carried out through two analysis procedures: a theoretical method by determining the attenuation ratio by measuring impedance parameter and proposing a new empirical technique based on measuring directly the insertion loss parameter. Therefore, the main aim of this characterization process is to determine the performance of nanocrystalline compared to traditional cable ferrite compositions to reduce the interferences in this controversial frequency range. From the results obtained, it is possible to deduce that nanocrystalline cable ferrite provides the best performance to filter the electromagnetic noise in the 2-150 kHz frequency range.


Growing intracranial aneurysms.
Cerebral angiography is the best means by which an intracranial aneurysm can be demonstrated and studied in vivo. In 16 cases clinical deterioration paralleled a variable degree of enlargement of the aneurysms. In all patients the aneurysms were irregular and/or bior multilocular. Possible factors causing aneurysmal enlargement are discussed.


VoroMQA: Assessment of protein structure quality using interatomic contact areas.
In the absence of experimentally determined protein structure many biological questions can be addressed using computational structural models. However, the utility of protein structural models depends on their quality. Therefore, the estimation of the quality of predicted structures is an important problem. One of the approaches to this problem is the use of knowledge-based statistical potentials. Such methods typically rely on the statistics of distances and angles of residue-residue or atom-atom interactions collected from experimentally determined structures. Here, we present VoroMQA (Voronoi tessellation-based Model Quality Assessment), a new method for the estimation of protein structure quality. Our method combines the idea of statistical potentials with the use of interatomic contact areas instead of distances. Contact areas, derived using Voronoi tessellation of protein structure, are used to describe and seamlessly integrate both explicit interactions between protein atoms and implicit interactions of protein atoms with solvent. VoroMQA produces scores at atomic, residue, and global levels, all in the fixed range from 0 to 1. The method was tested on the CASP data and compared to several other single-model quality assessment methods. VoroMQA showed strong performance in the recognition of the native structure and in the structural model selection tests, thus demonstrating the efficacy of interatomic contact areas in estimating protein structure quality. The software implementation of VoroMQA is freely available as a standalone application and as a web server at http://bioinformatics.lt/software/voromqa. Proteins 2017; 85:1131-1145. © 2017 Wiley Periodicals, Inc.


Reliability and accuracy of Sequential Organ Failure Assessment (SOFA) scoring.
The Sequential Organ Failure Assessment (SOFA) score was developed to quantify the severity of patients' illness, based on the degree of organ dysfunction. This study aimed to evaluate the accuracy and the reliability of SOFA scoring. Prospective study. Adult intensive care unit (ICU) in a tertiary academic center. Thirty randomly selected patient cases and 20 ICU physicians. Each physician scored 15 patient cases. The intraclass correlation coefficient was .889 for the total SOFA score. The weighted kappa values were moderate (0.552) for the central nervous system, good (0.634) for the respiratory system, and almost perfect (>0.8) for the other organ systems. To assess accuracy, the physicians' scores were compared with a gold standard based on consensus of two experts. The total SOFA score was correct in 53% (n = 158) of the cases. The mean of the absolute deviations of the recorded total SOFA scores from the gold standard total SOFA scores was 0.82. Common causes of errors were inattention, calculation errors, and misinterpretation of scoring rules. The results of this study indicate that the reliability and the accuracy of SOFA scoring among physicians are good. We advise implementation of additional measures to further improve reliability and accuracy of SOFA scoring.


Coulter volume cell sorting to improve the precision of radiation survival assays.
A new method for measuring cell survival at low doses of ionizing radiation has been developed through the use of flow cytometric cell sorting on the basis of Coulter volume signals. The cell sorter is capable of deflecting a precisely known number of cells directly into culture dishes, thus eliminating any errors associated with cell dilution and volume sampling. The use of Coulter volume signals as the sorting parameter is shown to be noncytotoxic for a variety of cell lines. Comparison of radiation survival curves measured above the 10% survival level by either the cell sorter or standard dilution assay demonstrates the increased precision of the cell sorter technique . Because of these advantages of cell sorting over conventional methods of plating cells, this technique has many applications in the field of radiation biology and other studies of cell survival.


Chemical effects in biological systems--data dictionary (CEBS-DD): a compendium of terms for the capture and integration of biological study design description, conventional phenotypes, and 'omics data.
A critical component in the design of the Chemical Effects in Biological Systems (CEBS) Knowledgebase is a strategy to capture toxicogenomics study protocols and the toxicity endpoint data (clinical pathology and histopathology). A Study is generally an experiment carried out during a period of time for the purpose of obtaining data, and the Study Design Description captures the methods, timing, and organization of the Study. The CEBS Data Dictionary (CEBS-DD) has been designed to define and organize terms in an attempt to standardize nomenclature needed to describe a toxicogenomics Study in a structured yet intuitive format and provide a flexible means to describe a Study as conceptualized by the investigator. The CEBS-DD will organize and annotate information from a variety of sources, thereby facilitating the capture and display of toxicogenomics data in biological context in CEBS, i.e., associating molecular events detected in highly-parallel data with the toxicology/pathology phenotype as observed in the individual Study Subjects and linked to the experimental treatments. The CEBS-DD has been developed with a focus on acute toxicity studies, but with a design that will permit it to be extended to other areas of toxicology and biology with the addition of domain-specific terms. To illustrate the utility of the CEBS-DD, we present an example of integrating data from two proteomics and transcriptomics studies of the response to acute acetaminophen toxicity (A. N. Heinloth et al., 2004, Toxicol. Sci. 80, 193-202).


Responses of inferior colliculus neurons to double harmonic tones.
The auditory system can segregate sounds that overlap in time and frequency, if the sounds differ in acoustic properties such as fundamental frequency (f0). However, the neural mechanisms that underlie this ability are poorly understood. Responses of neurons in the inferior colliculus (IC) of the anesthetized chinchilla were measured. The stimuli were harmonic tones, presented alone (single harmonic tones) and in the presence of a second harmonic tone with a different f0 (double harmonic tones). Responses to single harmonic tones exhibited no stimulus-related temporal pattern, or in some cases, a simple envelope modulated at f0. Responses to double harmonic tones exhibited complex slowly modulated discharge patterns. The discharge pattern varied with the difference in f0 and with characteristic frequency. The discharge pattern also varied with the relative levels of the two tones; complex temporal patterns were observed when levels were equal, but as the level difference increased, the discharge pattern reverted to that associated with single harmonic tones. The results indicated that IC neurons convey information about simultaneous sounds in their temporal discharge patterns and that the patterns are produced by interactions between adjacent components in the spectrum. The representation is "low-resolution," in that it does not convey information about single resolved components from either individual sound.


Efficacy of Resistance to Francisella Imparted by ITY/NRAMP/SLC11A1 Depends on Route of Infection.
Natural resistance-associated macrophage protein (NRAMP) encoded by the Slc11a1 gene is a membrane-associated transporter of divalent metal ions. Murine Slc11a1 has two known alleles, a functional Slc11a1Gly169, which is found in DBA2/J, NOD/LtJ, and 129p3/J and related mouse strains, and a non-functional Slc11a1Asp169, that is found in C56Bl/6J (B6) and BALB/cJ mice. B6 mice congenic for Slc11a1Gly169 (B6-Slc11a1G169 ) are markedly resistant to the intracellular pathogens Salmonella, Leishmania, and Mycobacterium tuberculosis. We examined the host cell response and replication of Francisella in B6-Slc11a1G169 mice. Bone marrow-derived macrophages from either B6-Slc11a1G169 or B6 mice were both effectively invaded by Francisella live vaccine strain (LVS). However, at 16 hours post-infection (hpi), the number of LVS bacteria recovered from B6 macrophages had increased roughly 100-fold, while in B6-Slc11a1G169 mice the number decreased 10-fold. When the mice were challenged intranasally (i.n.) B6 mice lost significant amounts (~15%) of weight, where as B6-Slc11a1G169 mice lost no weight. Three days after infection in B6-Slc11a1G169 mice, we failed to recover viable Francisella from the lungs, livers, or spleens. By contrast, B6 mice had bacterial burdens approaching 1 × 106 CFU/organ in all three organs. To further examine the degree of resistance imparted by Slc11a1Gly169 expression, we challenged mice deficient in TLR2, TLR4, and TLR9, but expressing the functional Slc11a1 (B6-Slc11a1G169Tlr2/4/9-/- ). Surprisingly, B6-Slc11a1G169Tlr2/4/9-/- mice had no notable weight loss. Eighty percent of B6-Slc11a1G169Tlr2/4/9-/- mice yielded no detectable Francisella in any organ tested. Additionally, Slc11a1G169 produced little detectable cytokine either in the lung or serum compared to B6 mice. Mice expressing Slc11a1Gly169 survived even high doses (~80 LD50) of LVS inoculation. These data taken together serve to highlight that functional Slc11a1Gly169 can compensate the lack of TLR2/4/9. Thus Slc11a1 is a critical player in murine resistance to pulmonary Francisella infection, but not footpad infection.


Synthesis of functionalized 3D porous graphene using both ionic liquid and SiO2 spheres as "spacers" for high-performance application in supercapacitors.
In this work, a high-capacity supercapacitor material based on functionalized three-dimensional (3D) porous graphene was fabricated by low temperature hydrothermal treatment of graphene oxide (GO) using both ionic liquid (IL) and SiO2 spheres as "spacers". In the synthesis, the introduction of dual "spacers" effectively enlarged the interspace between graphene sheets and suppressed their re-stacking. In addition, the IL also acted as a structure-directing agent playing a crucial role in inducing the formation of unique 3D architectures. Consequently, fast electron/ion transport channels were successfully constructed and numerous oxygen-containing groups on graphene sheets were effectively reserved, which had unique advantages in decreasing ion diffusion resistance and providing additional pseudocapacitance. As expected, the obtained material exhibited superior specific capacitance and rate capability compared to single "spacer" designed electrodes and simultaneously maintained excellent cycling stability. In particular, there was nearly no loss of its initial capacitance after 3000 cycles. In addition, we further assembled a symmetric two-electrode device using the material, which showed outstanding flexibility and low equivalent series resistance (ESR). More importantly, it was capable of yielding a maximum power density of about 13.3 kW kg(-1) with an energy density of about 7.0 W h kg(-1) at a voltage of 1.0 V in 1 M H2SO4 electrolyte. All these impressive results demonstrate that the material obtained by this approach is greatly promising for application in high-performance supercapacitors.


Brown algae fucoxanthin is hydrolyzed to fucoxanthinol during absorption by Caco-2 human intestinal cells and mice.
The metabolic fate in mammals of dietary fucoxanthin, a major carotenoid in brown algae, is not known. We investigated the absorption and metabolism of fucoxanthin in differentiated Caco-2 human intestinal cells, a useful model for studying the absorption of dietary compounds by intestinal cells. Fucoxanthin was taken up by Caco-2 cells incubated with micellar fucoxanthin composed of 1 micromol/L fucoxanthin, 2 mmol/L sodium taurocholate, 100 micromol/L monoacylglycerol, 33.3 micromol/L fatty acids and 50 micromol/L lysophosphatidylcholine. Fucoxanthinol, the deacetylated product of fucoxanthin, was also found in both medium and cells, with its level increasing significantly in a time-dependent manner. No conjugated forms of fucoxanthin and fucoxanthinol were found in either medium or cells. In the animal study, fucoxanthinol (10.4 +/- 5.3 nmol/L plasma, n = 4) was detected in plasma of mice 1 h after intubation of 40 nmol fucoxanthin. These results indicate that dietary fucoxanthin is incorporated as fucoxanthinol, the deacetylated form, from the digestive tract into the blood circulation system in mammals.


Central interleukin-1 beta enhances splenic sympathetic nerve activity in rats.
The central administration of immune cytokines such as interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) results in the suppression of peripheral cellular immunity, which depends, at least partly, on the sympathetic nervous activity. An intrathird cerebroventricular (I3V) infusion of recombinant human IL-1 beta (rhIL-1 beta) (1-5 ng/rat) elicited a dose-dependent increase in the electrical activity of the splenic sympathetic nerve in urethane and alpha-chloralose anesthetized rats. The effect of rhIL-1 beta (1 ng/rat) was completely blocked by pretreatment with an IL-1 receptor antagonist (1 microgram/rat, I3V 10 min before rhIL-1 beta), sodium salicylate (1 microgram/rat), or alpha-melanocyte stimulating hormone (alpha-MSH) (400 ng/rat). Furthermore, an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF9-41 (2 micrograms/rat), completely abolished the rhIL-1 beta-induced increase in the splenic nerve activity, although an I3V infusion of CRF (1 microgram/rat) excited it. These results suggest that IL-1 beta in the brain activates splenic sympathetic activity by its receptor-mediated and prostaglandin-dependent action that is sensitive to alpha-MSH, depending on CRF system. Our findings, together with the previous results, suggest that the splenic sympathetic nerve represents one of the communication channels from the brain to the immune system.


Vitamin D, aging, and the 2005 Dietary Guidelines for Americans.
The 2005 Dietary Guidelines for Americans recommend that older adults, people with dark skin, and those exposed to insufficient ultraviolet radiation (i.e., sunlight) consume extra vitamin D from vitamin D-fortified foods and/or supplements. Individuals in these high-risk groups should consume 25 microg (1000 IU) of vitamin D daily to maintain adequate blood concentrations of 25-hydroxyvitamin D, the biomarker for vitamin D status. This review considers recommendations for vitamin D-rich foods and dietary supplements, as well as specific problems with self-prescribing sun exposure or artificial sources of ultraviolet radiation to meet the vitamin D recommendations for older people.


Proposing "the burns suite" as a novel simulation tool for advancing the delivery of burns education.
Educational theory highlights the importance of contextualized simulation for effective learning. We explored this concept in a burns scenario in a novel, low-cost, high-fidelity, portable, immersive simulation environment (referred to as distributed simulation). This contextualized simulation/distributed simulation combination was named "The Burns Suite" (TBS). A pediatric burn resuscitation scenario was selected after high trainee demand. It was designed on Advanced Trauma and Life Support and Emergency Management of Severe Burns principles and refined using expert opinion through cognitive task analysis. TBS contained "realism" props, briefed nurses, and a simulated patient. Novices and experts were recruited. Five-point Likert-type questionnaires were developed for face and content validity. Cronbach's α was calculated for scale reliability. Semistructured interviews captured responses for qualitative thematic analysis allowing for data triangulation. Twelve participants completed TBS scenario. Mean face and content validity ratings were high (4.6 and 4.5, respectively; range, 4-5). The internal consistency of questions was high. Qualitative data analysis revealed that participants felt 1) the experience was "real" and they were "able to behave as if in a real resuscitation environment," and 2) TBS "addressed what Advanced Trauma and Life Support and Emergency Management of Severe Burns didn't" (including the efficacy of incorporating nontechnical skills). TBS provides a novel, effective simulation tool to significantly advance the delivery of burns education. Recreating clinical challenge is crucial to optimize simulation training. This low-cost approach also has major implications for surgical education, particularly during increasing financial austerity. Alternative scenarios and/or procedures can be recreated within TBS, providing a diverse educational immersive simulation experience.


Morphohistochemical alterations of neurons of the supraoptic nucleus of the rat hypothalamus at different durations of the photoperiod and melatonin administration.
We studied the morphologic and histochemical organization of neurons of the hypothalamic supraoptic nucleus in rats exposed to different durations of photoperiod and injection of melatonin. Morphometric and histochemical analyses of neurons were performed after staining brain histological sections for RNA. Prolonged illumination leads to more pronounced changes in the parameters of hypothalamic structures at 2 a.m. than at 2 p.m., particularly decreasing the concentration of RNA in the cell nuclei. The use of exogenous melatonin does not normalize the revealed changes in the parameters of the studied structures of the neurons of the supraoptic nucleus of the hypothalamus caused by the prolonged stay of rats under conditions of constant illumination.


Unusual Repair of Aortic Coarctation: Transcatheter Intervention Implications.
A 56-year old male was evaluated for exertional dyspnea. He had previously undergone mechanical aortic valve replacement and aortic coarctation repair. Following uncomplicated coronary angiography using Judkins left and right catheters, aortography revealed that the loud murmur was related to an unusual, extra-anatomic surgical repair: transverse aorta to descending aorta bypass. Recognition of an extra-anatomic surgical bypass of coarctation is important, as this repair would leave a continuous murmur on exam.


Investigation of Plantago ovata Husk as Pharmaceutical Excipient for Solid Dosage Form (Orodispersible Tablets).
The objective of the study was to investigate the suitability of the Plantago ovata (PO) husk as a pharmaceutical excipient. Various phytoconstituents of the husk were determined according to the standard test procedures. The Plantago ovata husk was evaluated for various pharmaceutical parameters related to flow, swelling index, and compressibility index. Orodispersible tablets (ODTs) were prepared, containing different concentrations (2.5, 3, 5, 7.5, 10, and 15% w/w) of the Plantago ovata husk. Before compression, all the formulations were evaluated for their flow. Compressed ODTs were evaluated for physical characteristics (physical appearance, weight and weight variation, thickness, and moisture content), mechanical strength (crushing strength, specific crushing strength, tensile strength, and friability), disintegration behavior (disintegration time and oral disintegration time), drug content, and in vitro drug release. Phytochemical evaluation of the Plantago ovata husk confirmed the presence of various phytoconstituents like alkaloids, tannins, glycosides, saponins, flavonoids, and phenols. SEM photograph of the Plantago ovata husk showed that it has a fibrous structure, with a porous and rough surface. The Plantago ovata husk had a high swelling index (380%) which decreased by pulverization (310%). Precompression evaluation of the powder blend for all the formulations of ODTs showed good flow properties, indicating that the Plantago ovata husk improved the rheological characteristics of the powder blend. Compressed ODTs had good mechanical strength, and their friability was within the official limits (<1%). Best disintegration was observed with formulation F-6 containing 10% w/w of the Plantago ovata husk. It is concluded that the Plantago ovata husk can be used as a disintegrant in the formulation of ODTs.


Transposon sequencing: methods and expanding applications.
A comprehensive understanding of genotype-phenotype links in bacteria is the primary theme of bacterial functional genomics. Transposon sequencing (Tn-seq) or its equivalent methods that combine random transposon mutagenesis and next-generation sequencing (NGS) represent a powerful approach to understand gene functions in bacteria on a genome-wide scale. This approach has been utilized in a variety of bacterial species to provide comprehensive information on gene functions related to various phenotypes or biological processes of significance. With further improvements in the molecular protocol for specific amplification of transposon junction sequences and increasing capacity of next generation sequencing technologies, the applications of Tn-seq have been expanding to tackle questions that are important yet difficult to address in the past. In this review, we will discuss the technical aspects of different Tn-seq methods along with their pros and cons to provide a helpful guidance for those who want to implement or improve Tn-seq for their own research projects. In addition, we also provide a comprehensive summary of recent published studies based on Tn-seq methods to give an updated perspective on the current and emerging applications of Tn-seq.


[Hypophosphatasia: Clinical manifestations, diagnostic recommendations and therapeutic options].
Hypophosphatasia is a very rare bone metabolism disorder caused by a deficiency in alkaline phosphatase activity, due to mutations in the ALPL gene. Its clinical hallmark is the impairment of skeletal and teeth mineralisation, although extra-skeletal manifestations are frequent. Its phenotypic spectrum is widely variable from a subtype with exclusive odontological impairment (odontohypophosphatasia) to five subtypes with systemic involvement, classified according to the age at the onset of the first symptoms (four of them in the paediatric age range: perinatal lethal, perinatal benign, infant and childhood hypophosphatasia). Those subtypes of hypophosphatasia with an earliest onset usually involve a worse prognosis, due to the risk of developing potentially lethal complications, such as seizures or severe respiratory insufficiency, secondary to rib cage malformations. Due to the extremely low prevalence of the severe forms of hypophosphatasia, its clinical variability and overlapping phenotypic features with several more prevalent conditions, the diagnosis of hypophosphatasia in the clinical setting is challenging. However, its potential lethality and impact on the patient's quality of life, along with the recent availability of an enzyme replacement therapy, increases the relevance of the early and accurate identification of patients affected with hypophosphatasia. On the basis of published evidence and clinical experience, this article suggests an algorithm with practical recommendations for the differential diagnosis of childhood hypophosphatasia, as well as an updated review of current therapeutic options.


[Early and late mortality of patients with community acquired pneumonia].
Community acquired pneumonia is the most frequent infective cause of severe sepsis and death. The risk of mortality in community acquired pneumonia is predictable by the "pneumonia severity index" and various biomarkers (e.g., procalcitonin, troponin-I). Quantitative testing of pneumococcal load (DNA) in blood has also become possible recently. Early death due to acute myocardial infarction is more frequent among patients with previous community acquired pneumonia. The 1-year and the 5-6 year survival is shorter among these patients. Pro-inflammatory cytokines synthesized during community acquired pneumonia accelerate chronic inflammation ongoing in atherosclerotic plaques. The pro-thrombotic condition present in atherosclerosis is also potentiated by community acquired pneumonia. These pathophysiological mechanisms may explain the epidemiologic fact that community acquired pneumonia is an independent risk factor of cardiovascular mortality.


Automatic Adjustment of Keyboard Settings Can Enhance Typing.
We developed and evaluated a software tool for the automatic configuration of Windows keyboard settings. The software is intended to accommodate the needs of people with physical impairments, with a goal of improved productivity and comfort during typing. The prototype software, called AutoIDA, monitors user activity during performance of regular computer tasks and recommends the Sticky Keys and key repeat settings to meet the user's specific needs. The evaluation study included fourteen individuals with upper extremity impairments. AutoIDA recommended changes to the default keyboard settings for 10 of the 14 participants. For these individuals, average typing speed was essentially the same whether users typed with the default keyboard settings (5.5 wpm) or the AutoIDA-recommended settings (5.3 wpm). Average typing errors decreased with use of the recommended settings, from 17.6% to 13.3%, but this was not quite statistically significant (p = .10). On an individual basis, four participants appeared to improve their overall typing performance with AutoIDA-recommended settings. For more specific metrics, AutoIDA prevented about 90% of inadvertent key repeats (with a revised algorithm) and increased the efficiency and accuracy of entering modified (shifted) characters. Participants agreed that software like AutoIDA would be useful to them (average rating 4.1, where 5 = strongly agree).


Intravascular volume and fluid therapy for severe sepsis.
Hypovolemia is one of the principal defects contributing to cardiovascular instability and circulatory failure during septic shock. Fluid infusion is the mainstay of initial resuscitation. Large amounts of fluids may be required and should be titrated to optimal hemodynamic effects while attempting to minimize the development of pulmonary and systemic edema. Hemoglobin and hematocrit should be carefully monitored, with transfusions being used as necessary to maintain adequate levels of systemic oxygen delivery. Crystalloids and colloids are equally effective, although the volume of fluids required with crystalloids is two to four times that of colloids. In older patients, where high filling pressures may be required for optimal hemodynamic effect, colloids may be associated with a lower frequency of pulmonary edema.


Bi-Phenotypic Trait May Be Conferred by Multiple Alleles in a Germplasm Population.
The Chinese soybean germplasm pool (CSGP) comprises annual wild (WA), farmers' landrace (LR) and released cultivar (RC) populations, and ecoregion subpopulations in WA/LR/RC (ecoregion IV/III/II/I). A representative sample consisted of 1,024 accessions was studied for pubescence color (PC) and flower color (FC). In the evolution from WA (brown PC and mainly purple FC) to LR then to RC, with above wild characteristic changed, while gray PC, and white FC emerged and their frequency increased. Using 36,952 genomic SNPLDB markers with 100,092 haplotypes, the association between markers and bi-phenotypic traits was detected using χ2 association analysis under single locus model and RTM-GWAS procedure under multi-locus model, respectively. Multiple markers co-associated with individual bi-phenotypic trait with the most significant markers containing multiple rather than two haplotypes even for a bi-phenotypic trait. On a marker/locus, each haplotype corresponds to two colors, except one (FC-1-5) out of 11 haplotypes for single color. The major candidate gene was annotated with its alleles identified from the population sequencing data. Similarly, multiple alleles identified and each corresponds to two colors except three (a8/a9/b3) out of 12 alleles for single color. The major haplotypes/alleles in LR and RC were traced to WA ecoregion subpopulations, the WA IV and WA III genotypes showed genetically more close to the cultivated subpopulations, therefore, WA from Ecoregion IV and III were inferred as the common ancestor for cultivated soybeans. The marker-haplotypes/gene-alleles not exactly coincided with the bi-phenotypic trait has challenged to the traditional Mendelian genetics, which was discussed and to be further studied.


Development of echolocation calls in the mustached bat, Pteronotus parnellii.
Adult mustached bats employ Doppler-sensitive sonar to hunt fluttering prey insects in acoustically cluttered habitats. The echolocation call consists of 4-5 harmonics, each composed of a long constant frequency (CF) component flanked by brief frequency modulations (FM). The 2nd harmonic CF component (CF2) at 61 kHz is the most intense, and analyzed by an exceptionally sharply tuned auditory system. The maturation of echolocation calls and the development of Doppler-shift compensation was studied in Cuba where large maternity colonies are found in hot caves. In the 1st postnatal week, infant bats did not echolocate spontaneously but could be induced to vocalize CF-FM signals by passive body motion. The CF2 frequency emitted by the smallest specimens was at 48 kHz (i.e., 0.4 octaves lower than the adult signal). CF-FM signals were spontaneously produced in the 2nd postnatal week at a CF2 frequency of 52 kHz. The CF2 frequencies of induced and spontaneous calls shifted upward to reach a value of 60.5 kHz in the 5th postnatal week. Standard deviations of CF2 frequency were large (up to +/-1.5 kHz) in the youngest bats and dropped to values of +/-250 Hz at the end of the 3rd postnatal week. Some individuals in the 4th and 5th postnatal weeks emitted with adultlike frequency precision of about +/-100 Hz. In the youngest bats, the 1st harmonic CF component (CF1) was up to 22 dB stronger than CF2. Adultlike relative levels of CF1 (-28 dB relative to CF2) were reached in the 5th postnatal week. In spontaneously emitted CF-FM calls, the duration of the CF2 component gradually increased with age from 5 ms to maximum values of 18 ms. Durations of the CF2 component in induced calls averaged 7 +/- 2.6 ms in the 1st postnatal week and 8.2 +/- 1.5 ms in the 5th postnatal week. There were no age-related changes in duration of the terminal FM sweep (3 +/- 0.4 ms) in both induced and spontaneous calls. The magnitude of the terminal FM sweep in spontaneous calls was not correlated with age (mean 13.5 +/- 2 kHz). Values for induced calls slightly increased with age from 11 +/- 2 to 13 +/- 2 kHz. The emission rate of induced CF-FM signals increased with age from values of 2.5 +/- 2 to 17 +/- 5 pulses/s. Values for spontaneously emitted calls were 4.4 +/- 3 and 9 +/- 4.5 pulses/s, respectively. Doppler-shift compensation, as tested in the pendulum task, emerged during the 4th postnatal week in young bats that were capable of very brief active flights, but before the time of active foraging outside the cave.


Successful culture of adult human melanocytes obtained from normal and vitiligo donors.
The development of growth conditions for human melanocytes from uninvolved skin from vitiligo patients and age-matched normal adults is a prerequisite to understanding the etiology of this pigmentary disorder. By using new growth conditions, pure melanocyte cultures were prepared from normal adults and the pigmented skin of vitiligo donors. Both cell types grew without a lag period and were maintained for more than six months (4-8 passages). The cultures could be expanded from several thousand melanocytes in the original cell suspension to several million cells (2-7 x 10(6] in pure culture. To obtain these results, the current standard conditions for the culture of fetal melanocytes were substantially modified. MEM-S medium was less satisfactory than MCDB-153. Adult normal and vitiligo cells also required the presence of exogenous catalase (20 micrograms/ml) during isolation and primary seeding. Thereafter, this enzyme was not necessary. Melanocytes grew best and gave the highest yields if the concentrations of both calcium (200 microM) and the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) were low (4-8 nM). Other growth factors included in the MCDB-153 media were bFGF, crude bovine pituitary extract, insulin, transferrin, hydrocortisone, 5% FCS, and the antioxidant alpha-tocopherol. Cholera toxin and isobutylmethylxanthine (IBMX) were omitted from the MCDB-153 growth medium because they slowed down growth even at very low concentrations. The results indicate adult and vitiligo melanocytes can be cultured. Preliminary studies of the normal and vitiligo cells indicate that vitiligo melanocytes retain some of the ultrastructural abnormalities observed in skin even when grown in culture.


Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients.
The cortical-striatal-thalamic circuit modulates cognitive processing and thus may be involved in the cognitive dysfunction in schizophrenia. The imaging of metabolic rate in the structures making up this circuit could reveal the correlates of schizophrenia and its main symptoms. Seventy male schizophrenic patients underwent [18F]-fluorodeoxyglucose positron emission tomography after a period of at least 4 weeks during which they had not received neuroleptic medication and were compared to 30 age-matched male normal comparison subjects. Analyses revealed decreased metabolism in medial frontal cortex, cingulate gyrus, medial temporal lobe, corpus callosum, and ventral caudate and increased metabolism in the left lateral temporal and occipital cortices in the schizophrenic cohort. Consistent with previous studies, the schizophrenic group had lower hypofrontality scores (ratios of lateral frontal to occipital metabolism) than did comparison subjects. The lateral frontal cortical metabolism of schizophrenic patients did not differ from that of comparison subjects, while occipital cortical metabolism was high, suggesting that lateral hypofrontality is due to abnormalities in occipital rather than lateral frontal activity. Hypofrontality was more prominent in medial than lateral frontal cortex. Brief Psychiatric Rating Scale (BPRS) scores, obtained for each schizophrenic patient on the scan day, were correlated with regional brain glucose metabolic rate. Medial frontal cortical and thalamic activity correlated negatively with total BPRS score and with positive and negative symptom scores. Lateral frontal cortical metabolism and hypofrontality scores did not significantly correlate with negative symptoms. Analyses of variance demonstrated a reduced right greater than left asymmetry in the schizophrenic patients for the lateral cortex as a whole, with simple interactions showing this effect specifically in temporal and frontal cortical regions. Low metabolic rates were confirmed in medial frontal cortical regions as well as in the basal ganglia, consistent with the importance of the cortical-striatal-thalamic pathways in schizophrenia. Loss of normal lateralization patterns was also observed on an exploratory basis. Correlations with negative symptoms and group differences were more prominent in medial than lateral frontal cortex, suggesting that medial regions may be more important in schizophrenic pathology.