Pregnancies in renal transplant recipients--with a focus on babies.
We studied 113 pregnancies in 72 renal transplant recipients. The mean duration between the transplant operation and the first pregnancies was 19.9 months (1-72). This paper focuses on the findings in babies and their outcome. The male babies were 34% of the total. 28% of the babies were delivered vaginally and 72% by Caesarian section. It was noted that there was high incidence of preterm delivery in 64% of the pregnancies. The birth weights were also less than that observed in the general population. 84% was under 50th percentile for weight with 19% being under the 10th percentile. (Saudi growth chart, KACST) The mean hospital stay was 18 days (2-44). The Apgar score was less than 7 in only 10% of the cases and 10 in 50.9%. The incidence of congenital defects was low and no different than the general population (we encountered only 4 cases with minor defects). Despite exposure to cyclosporine throughout the pregnancy and having reduced Nephron mass by virtue of their low birth weight we could not find any glomerular or tubular defects, hypertension or prorienuria in 41 children with a mean age of 52 months. We advised against breast feeding in view of the presence of cyclosporine in the mothers' milk.


Diversity and distribution of Aphanomyces astaci in a European hotspot of ornamental crayfish introductions.
Ornamental trade has become an important introduction pathway of non-native aquatic species worldwide. Correspondingly, there has been an alarming increase in the number of established crayfish of aquarium origin in Europe over the previous decade. The oomycete Aphanomyces astaci, the pathogen causing crayfish plague responsible for serious declines of European crayfish populations, is dispersed with introduced North American crayfish. The role of ornamental taxa in introducing and spreading different genotypes of this pathogen in open waters remains unclear. We investigated the distribution, prevalence, and diversity of A. astaci in Budapest, Hungary, which became the hotspot of aquarium crayfish establishment, also due to local thermal waters. We screened for A. astaci in six host taxa from 18 sites sampled between 2018 and 2021: five cambarids (Cambarellus patzcuarensis, Faxonius limosus, Procambarus alleni, P. clarkii, P. virginalis) and one native astacid (Pontastacus leptodactylus). The pathogen was confirmed at five sampled sites in four host taxa: P. virginalis, P. clarkii, F. limosus, and for the first time in European open waters also in P. alleni. Genotyping was successful only in individuals from two different brooks where multiple host species coexisted but revealed unexpected patterns. Mitochondrial B-haplogroup of A. astaci, previously usually reported from Pacifastacus leniusculus or infected European species, was detected in P. virginalis at both sites, and in both F. limosus and P. virginalis sampled from a thermally stable tributary of Barát brook in 2018. In contrast, A-haplogroup of A. astaci was detected in coexisting F. limosus, P. virginalis and P. clarkii sampled in the same watercourse just a few hundred meters downstream in 2020. Additional genotyping methods indicated that a previously unknown A. astaci strain was associated with the latter haplogroup. One P. virginalis individual from 2020 was apparently co-infected by strains representing both mitochondrial haplogroups. The results indicated multiple sources of A. astaci in Budapest, likely directly associated with the introduction of ornamental species, interspecific transmission of this pathogen among ornamental hosts, and potential for a quick spatial or temporal turnover of dominant A. astaci strains at a certain locality. This highlights that in regions with high richness of potential A. astaci hosts, host taxon/pathogen genotype combinations become unpredictable, which might prevent reliable genotyping of pathogen sources in local crayfish mass mortalities.


Dynamic balancing of dual-rotor system with very little rotating speed difference.
Unbalanced vibration in dual-rotor rotating machinery was studied with numerical simulations and experiments. A new method is proposed to separate vibration signals of inner and outer rotors for a system with very little difference in rotating speeds. Magnitudes and phase values of unbalance defects can be obtained directly by sampling the vibration signal synchronized with reference signal. The balancing process is completed by the reciprocity influence coefficients of inner and outer rotors method. Results showed the advantage of such method for a dual-rotor system as compared with conventional balancing.


Stable expression recognition abnormalities in unipolar depression.
Although abnormalities in emotion recognition during a depressed episode have frequently been reported in patients with depression, less is known about the stability of these abnormalities. To examine the stability of emotion recognition abnormalities, this longitudinal study assessed patients with unipolar depression on three separate occasions at 3-monthly intervals. Recognition of sad, angry, fearful, disgusted, happy and neutral facial expressions was assessed in a matching task and a labelling task. Patients performed as well as matched healthy controls on the matching task. On the labelling task, patients showed higher accuracy and higher response bias than controls for sad expressions only, which remained stable over a 6-month interval. Over the same period, symptom severity, as measured with the Beck Depression Inventory and the Hamilton Depression Rating Scale, decreased significantly in the patient group. Furthermore, labelling performance for sad expressions was not associated with symptom severity or with changes in severity over time. This stable bias for sad expressions might signal a vulnerability factor for depression, as proposed by cognitive theories of depression.


Gene Regulatory Network Analysis of Perivascular Adipose Tissue of Abdominal Aortic Aneurysm Identifies Master Regulators of Key Pathogenetic Pathways.
The lack of medical therapy to treat abdominal aortic aneurysm (AAA) stems from our inadequate understanding of the mechanisms underlying AAA pathogenesis. To date, the only available treatment option relies on surgical intervention, which aims to prevent AAA rupture. Identifying specific regulators of pivotal pathogenetic mechanisms would allow the development of novel treatments. With this work, we sought to identify regulatory factors associated with co-expressed genes characterizing the diseased perivascular adipose tissue (PVAT) of AAA patients, which is crucially involved in AAA pathogenesis. We applied a reverse engineering approach to identify cis-regulatory elements of diseased PVAT genes, the associated transcription factors, and upstream regulators. Finally, by analyzing the topological properties of the reconstructed regulatory disease network, we prioritized putative targets for AAA interference treatment options. Overall, we identified NFKB1, SPIB, and TBP as the most relevant transcription factors, as well as MAPK1 and GSKB3 protein kinases and RXRA nuclear receptor as key upstream regulators. We showed that these factors could regulate different co-expressed gene subsets in AAA PVAT, specifically associated with both innate and antigen-driven immune response pathways. Inhibition of these factors may represent a novel option for the development of efficient immunomodulatory strategies to treat AAA.


Adjoint simulation of stream depletion due to aquifer pumping.
If an aquifer is hydraulically connected to an adjacent stream, a pumping well operating in the aquifer will draw some water from aquifer storage and some water from the stream, causing stream depletion. Several analytical, semi-analytical, and numerical approaches have been developed to estimate stream depletion due to pumping. These approaches are effective if the well location is known. If a new well is to be installed, it may be desirable to install the well at a location where stream depletion is minimal. If several possible locations are considered for the location of a new well, stream depletion would have to be estimated for all possible well locations, which can be computationally inefficient. The adjoint approach for estimating stream depletion is a more efficient alternative because with one simulation of the adjoint model, stream depletion can be estimated for pumping at a well at any location. We derive the adjoint equations for a coupled system with a confined aquifer, an overlying unconfined aquifer, and a river that is hydraulically connected to the unconfined aquifer. We assume that the stage in the river is known, and is independent of the stream depletion, consistent with the assumptions of the MODFLOW river package. We describe how the adjoint equations can be solved using MODFLOW. In an illustrative example, we show that for this scenario, the adjoint approach is as accurate as standard forward numerical simulation methods, and requires substantially less computational effort.


Elevated Fra-1 expression causes severe lipodystrophy.
A shift from osteoblastogenesis to adipogenesis is one of the underlying mechanisms of decreased bone mass and increased fat during aging. We now uncover a new role for the transcription factor Fra-1 in suppressing adipogenesis. Indeed, Fra1 (Fosl1) transgenic (Fra1tg) mice, which developed progressive osteosclerosis as a result of accelerated osteoblast differentiation, also developed a severe general lipodystrophy. The residual fat of these mice appeared immature and expressed lower levels of adipogenic markers, including the fatty acid transporter Cd36 and the CCAAT/enhancer binding protein Cebpa. Consequently accumulation of triglycerides and free fatty acids were detected in the serum of fasting Fra1tg mice. Fra-1 acts cell autonomously because the adipogenic differentiation of Fra1 transgenic primary osteoblasts was drastically reduced, and overexpression of Fra-1 in an adipogenic cell line blocked their differentiation into adipocytes. Strikingly, Cebpa was downregulated in the Fra-1-overexpressing cells and Fra-1 could bind to the Cebpa promoter and directly suppress its activity. Thus, our data add to the known common systemic control of fat and bone mass, a new cell-autonomous level of control of cell fate decision by which the osteogenic transcription factor Fra-1 opposes adipocyte differentiation by inhibiting C/EBPα.


Three-Dimensional Printing: A Novel Approach to the Creation of Obturator Prostheses Following Palatal Resection for Malignant Palate Tumors.
A subgroup of patients who have an oronasal fistula live in areas that have limited access to oral prosthetics. For these individuals, a temporary prosthesis, such as a palatal obturator, may be necessary in order to speak, eat, and breath properly. The creation of an obturator, which requires a highly trained prosthodontist, can take time and can be expensive. Through the current proof-of-concept study, there is an attempt to create a patient-specific palatal obturator through use of free and publicly available software, and a low-cost desktop 3-dimensional printer. The ascribed study may provide a means to increase global access to oral prosthetics if suitable biomaterials are developed. Computerized tomography data were acquired from a patient who had an oronasal fistula. Through use of free software, these data were converted into a 3-dimensional image. The image was manipulated in order to isolate the patient's maxilla and was subsequently printed. The palatal obturator models were designed, and reformed, in correspondence with the maxilla model design. A final suitable obturator was determined and printed with 2 differing materials in order to better simulate a patient obturator. Creating a suitable palatal obturator for the specified patient model was possible with a low-cost printer and free software. With further development in biomaterials, it may be possible to design and create an oral prosthesis through use of low-cost 3-dimensional printing technology and freeware. This can empower individuals to attain good healthcare, even if they live in rural, developing, or underserviced areas.


A Two-interval Forced-choice Task for Multisensory Comparisons.
We provide a procedure for a psychophysics experiment in humans based on a previously described paradigm aimed to characterize the perceptual duration of intervals within the range of milliseconds of visual, acoustic, and audiovisual aperiodic trains of six pulses. In this task, each of the trials consists of two consecutive intramodal intervals where the participants press the upward arrow key to report that the second stimulus lasted longer than the reference, or the downward arrow key to indicate otherwise. The analysis of the behavior results in psychometric functions of the probability of estimating the comparison stimulus to be longer than the reference, as a function of the comparison intervals. In conclusion, we advance a way of implementing standard programming software to create visual, acoustic, and audiovisual stimuli, and to generate a two-interval forced-choice (2IFC) task by delivering stimuli through noise-blocking headphones and a computer's monitor.


Unintentional injuries. Patterns within families.
The occurrence of unintentional injuries is known to be influenced by physical and socioeconomic environmental factors as well as human behavior. Questions remain about how personal characteristics interact with the social, psychological, and physical environment to increase the risk of injury. The present study investigated the role of families in the injury experience of individual family members. Health encounter data from 693 families over a six-year period were analyzed. A small number of families accounted for a disproportionately large number of visits for injuries. Individual members of families tended to have similar rates of injury, and these rates were stable over time. Individual accident experience is influenced by the family to which one belongs. Injury prevention programs may find increased success by directing intervention strategies toward families.


Subverting the Narrative: Alternate Technology Approaches for Active Ageing.
This chapter presents two case studies where the dominant narrative was subverted, one by citizen participants and one by researchers. Subversion, as a questioning and challenging stance, in the context of co-creation supports the discovery of new pathways for healthy behaviours even in modest projects. We also illustrate how emotion-led and interest-based design is used to increase adoption by end-users. Here we explore the development of an active ageing portal for a local council and the use of 'Kira' the robot to promote social interaction between older adults living with dementia.


Electroviscous effects in nanofluidic channels.
This paper presents a systematical study of electroviscous effects in nanofluidic channels using a triple layer model and a numerical framework. A chemical dissociation layer is introduced at solid-liquid interfaces to bridge the surface charge condition with the local properties of both solid surfaces and the ionic liquid. The electrokinetic transport in the electrical double layers is modeled by a lattice Poisson-Boltzmann method. The results indicate that there is an ionic concentration leading to the maximum electroviscosity for a given channel height, pH value, and environmental temperature. For a very high ionic concentration, a smaller channel height leads to a higher electroviscosity. When the bulk concentration reduces from 10(-3)M to 10(-6)M, there is a critical channel height that maximizes the electroviscosity for a given ionic concentration, and the critical height increases with the decreasing ionic concentration. The electroviscosity increases with the pH of electrolyte solutions and is nearly proportional to the environmental temperature. The present study may help to improve the understanding of electrokinetic transport in nanofluidic channels.


Strategies for genetic inactivation of long noncoding RNAs in zebrafish.
The number of annotated long noncoding RNAs (lncRNAs) continues to grow; however, their functional characterization in model organisms has been hampered by the lack of reliable genetic inactivation strategies. While partial or full deletions of lncRNA loci disrupt lncRNA expression, they do not permit the formal association of a phenotype with the encoded transcript. Here, we examined several alternative strategies for generating lncRNA null alleles in zebrafish and found that they often resulted in unpredicted changes to lncRNA expression. Removal of the transcription start sites (TSSs) of lncRNA genes resulted in hypomorphic mutants, due to the usage of either constitutive or tissue-specific alternative TSSs. Deletions of short, highly conserved lncRNA regions can also lead to overexpression of truncated transcripts. In contrast, knock-in of a polyadenylation signal enabled complete inactivation of malat1, the most abundant vertebrate lncRNA. In summary, lncRNA null alleles require extensive in vivo validation, and we propose insertion of transcription termination sequences as the most reliable approach to generate lncRNA-deficient zebrafish.


Coherent communication of classical messages.
We define coherent communication in terms of a simple primitive, show it is equivalent to the ability to send a classical message with a unitary or isometric operation, and use it to relate other resources in quantum information theory. Using coherent communication, we are able to generalize superdense coding to prepare arbitrary quantum states instead of only classical messages. We also derive single-letter formulas for the classical and quantum capacities of a bipartite unitary gate assisted by an arbitrary fixed amount of entanglement per use.


[Histological evaluation of the condition of the trepanation cavity coating after radical surgery on the middle ear].
Tissue samples obtained intraoperatively from different parts of the middle ear in the course of the radical operation (35 cases) or reconstructive operations in patients with the history of surgical intervention on the ear (67 cases) were examined histologically. Fibrous-atrophic changes in the trepanation cavity coating correlated with the duration of the disease and the time since the radical operation. Pathomorphological and topographic profile of the changes in the operated ear coating copies relevant picture of otitis media purulenta chronica. The tympanomastoid cavity coating was characterized by increasing fibrous-atrophic changes reflecting regeneratory-plastic insufficiency of the epithelium and persistent tympanofibrosis in conditions of open trepanation cavity with disturbed anatomic relations in the middle ear.


[Plastic surgery in radiation necrosis in the region of projection/of large vessels].
The author reports his experience with treatment of 112 patients having various forms of hypospadias, operated upon after the Landerer technic in the V. I. Rusakov modification. In all patients good immediate results were obtained: the urethra was reconstructed along its whole length and the penis was straightened. The study of late issues in 93 patients revealed good results in 82 of them, satisfactory-in 7, and poor (distortion of the penis remained)-in 4 patients. Penial distortion in these cases was liquidated by means of the tunica albuginea plasty on the posterior aspect of the penis. The method employed would provide good immediate and late results in treatment of various forms of hypospadias.


Surgical management of unusual gastrointestinal bleeding and a left ventricular assist device.
There is growing evidence that patients treated with continuous flow ventricular assist devices are at increased risk for bleeding complications beyond what would be expected for those requiring anti-coagulation therapy. However, the management of these patients is typically medical. We present a case of unusual gastrointestinal bleeding successfully managed with surgical intervention in a patient with a Heartmate II ventricular assist device.


Single-voxel proton MR spectroscopy and positron emission tomography for lateralization of refractory temporal lobe epilepsy.
We compared the metabolic information obtained from single-voxel proton MR spectroscopy and positron emission tomography (PET) in patients with temporal lobe epilepsy. Twenty-nine patients with temporal lobe epilepsy were screened for metabolic abnormalities with both proton MR spectroscopy and PET. Lateralization with MR spectroscopy was possible by using NAA/(Cho+Cr) and an asymmetry index. Hypometabolism as determined by PET was classified as typical or complex. Twenty-four (96%) of 25 patients whose seizure onset could be lateralized to one temporal lobe showed ipsilateral lateralization with either MR spectroscopy or PET, whereas concordant lateralization with both techniques was possible only in 14 (56%) of the 25 patients. MR spectroscopy showed 42 abnormal temporal lobes whereas PET showed only 25 lobes with decreased metabolism. All temporal lobes with hypometabolism at PET also had a low NAA/(Cho+Cr). Five patients (20%) with negative PET studies had seizures lateralized correctly with MR spectroscopy. Proton MR spectroscopy is more sensitive in depicting metabolic abnormalities than is PET in patients with temporal lobe epilepsy. Patients with negative PET studies will benefit from MR spectroscopy for the purpose of lateralization.


Assessment of forearm vasodilator responses to acetylcholine and albuterol by strain gauge plethysmography: reproducibility and influence of strain gauge placement.
To determine the within-subject reproducibility of the forearm blood flow response to acetylcholine and the beta2-adrenoceptor agonist albuterol as measured by strain gauge plethysmography. To examine the influence of strain gauge placement on these responses. Vasodilator response to brachial artery infusion of drugs was assessed by strain gauge plethysmography in six healthy men on each of three occasions separated by 1 week. Strain gauges were placed on both arms at the point of maximum diameter. On the infused arm two further gauges were positioned approximately 4 cm proximal and distal to the middle gauge. Within-subject coefficients of variation (WCV) of absolute blood flow responses for each dose of acetylcholine (7.5, 15, 30 micrograms min(-1)) ranged from 24% to 27%, as compared with WCV values of 41% to 62% for the percentage changes in blood flow ratio (infused : noninfused arm). For albuterol (0.3, 1, 3 micrograms min(-1)) the corresponding WCV values were 16% to 19% and 30% to 55% for absolute blood flow and percentage change in blood flow ratio, respectively. WCV for the area under dose-response curve (AUC) for absolute blood flow was 18% and 13% for acetylcholine and albuterol, respectively. Vasodilator responses were similar whether recorded proximal to or at the point of maximal forearm circumference. Distal strain gauge misplacement underestimated responses and the difference was greater for acetylcholine than for albuterol. In healthy men, the WCV for responses expressed as absolute blood flow, to acetylcholine and albuterol ranges from 16% to 27%.


Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI).
We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.


Measurement of desarginine fibrinopeptide B in human blood.
Thrombin converts fibrinogen to fibrin in two steps. First fibrinopeptide A and fibrin I are formed and then fibrinopeptide B (B beta 1-14) and fibrin II. Since it is postulated that fibrin II is important in the genesis of thrombosis, it is of interest to measure fibrinopeptide B in peripheral blood samples. Previous difficulties in interpreting fibrinopeptide B immunoreactivity in plasma resulted from crossreaction of fibrinogen and of plasmin digest peptides B beta 1-42 and B beta 1-21 and from rapid loss of fibrinopeptide B immunoreactivity resulting from cleavage of arginine 14 by blood carboxypeptidase B. We have obviated these difficulties by removing fibrinogen from plasma by precipitation with ethanol and peptides B beta 1-21 and B beta 1-42 by adsorption on bentonite. Fibrinopeptide B is then converted to a desarginine fibrinopeptide B, which is measured in a new specific assay. Studies of the kinetics of fibrinopeptide cleavage showed that when whole blood was allowed to clot in vitro, fibrinopeptide A was cleaved more rapidly than fibrinopeptide B. In 18 patients on an acute care medical ward, desarginine fibrinopeptide B levels were lower than fibrinopeptide A levels and did not correlate with the levels of fibrinopeptide A or B beta 1-42. Desarginine fibrinopeptide B levels were less than 1 pmol/ml in all but two patients. In six patients receiving intraamniotic infusions of hypertonic saline to induce abortion, desarginine fibrinopeptide B levels increased 10-fold from the preinfusion mean level of 0.4 pmol/ml and then decreased. The pattern of changes resembled that of the fibrinopeptide A levels rather than of the B beta 1-42 levels. On the basis of these data it is suggested that plasma desarginine fibrinopeptide B levels reflect fibrin II formation in vivo.


Use of electronic medical records by ambulatory care providers: United States, 2006.
This report presents 2006 information on adoption of electronic medical records (EMRs) in five ambulatory care settings. Use of EMR systems within these settings is presented by selected provider characteristics. Nationally representative estimates are from 2006 provider-based surveys, including the National Ambulatory Medical Care Survey (NAMCS), the National Hospital Ambulatory Medical Care Survey (NHAMCS), and the National Survey of Ambulatory Surgery (NSAS). In 2006, 62.4 percent of hospital-based ambulatory surgery centers (ASCs) reported using EMR systems, almost triple the percentage reported by freestanding ASCs (22.3 percent). EMR use by hospital emergency departments (EDs) was 46.2 percent, followed by hospital outpatient departments (OPDs) (29.4 percent) and office-based physicians (29.2 percent). Based on items collected in the 2006 NAMCS, NHAMCS, and NSAS, 18.6 percent of hospital-based ASCs, 14.0 percent of hospital EDs, and 10.5 percent of office-based physicians had systems with similar features of a basic system, but only 1.7 percent of hospital EDs and 3.1 percent of office-based physicians had systems with similar features of a fully functional system. Fully functional systems are a subset of basic systems. Physicians in practices with 11 or more physicians were most likely to use EMRs (46.5 percent), whereas physicians in solo practices were least likely to use EMRs (24.0 percent). Use of EMR systems was higher among physicians located in the West (42.3 percent) than in other regions of the country (23.5 percent to 29.3 percent). EMR use did not vary by neighborhood poverty level for any of the ambulatory providers studied. From 2001 through 2005, EMR systems in hospital EDs increased by 47.2 percent. Use of EMRs among office-based physicians increased by 60.4 percent from 2001 through 2006. If those without EMR systems in 2006 with definite plans to install a system actually do so, 85.4 percent of hospital-based ASCs, 72.2 percent of EDs, 62.6 percent of OPDs, 47.3 percent of freestanding ASCs, and 47.0 percent of physicians will be using EMR systems in 2009.


[Physical exercise and bone development in chronically ill children].
Children with chronic diseases are at increased risk of sub-optimal bone mineral acquisition and osteoporosis, especially those who have a growth and pubertal delay, reduced physical activity, inadequate nutrition, malabsorption or take medications which may influence bone development. Weight-bearing physical activity has a beneficial effect on bone development of healthy children but little is known in children with chronic diseases. Preliminary results of our cross-sectional study in children with juvenile idiopathic arthritis (JIA) suggest that hip bone mineral density is positively related with physical fitness and muscle strength and is reduced at the more affected side. We have initiated two randomized controlled trials to determine the effects of a moderate impact exercise training program on bone mineral density of children with JIA and type 1 diabetes mellitus.


Evidence for a general-purpose genotype in Candida albicans, highly prevalent in multiple geographical regions, patient types and types of infection.
Epidemiological studies, using the probe Ca3, have shown that in a given patient population a single cluster of genetically related Candida albicans isolates usually predominates. The authors have investigated whether these local clusters are part of a single group, geographically widespread and highly prevalent as an aetiological agent of various types of candidiasis. An unrooted neighbour-joining tree of 266 infection-causing C. albicans isolates (each from a different individual) from 12 geographical regions in 6 countries was created, based on genetic distances generated by Ca3 fingerprinting. Thirty-seven per cent of all isolates formed a single genetically homogeneous cluster (cluster A). The remainder of isolates were genetically diverse. Using the maximum branch length within cluster A as a cut-off, they could be divided into 37 groups, whose prevalence ranged between 0.3% and 9%. Strains from cluster A were highly prevalent in all but one geographical region, with a mean prevalence across all regions of 41%. When isolates were separated into groups based on patient characteristics or type of infection, strains from cluster A had a prevalence exceeding 27% in each group, and their mean prevalence was 43% across all patient characteristics. These data provide evidence that cluster A constitutes a general-purpose genotype, which is geographically widespread and acts as a predominant aetiological agent of all forms of candidiasis in all categories of patients surveyed.


Impaired episodic memory in PTSD patients - A meta-analysis of 47 studies.
Episodic memory impairments beyond the traumatic event might be a characteristic hallmark of post-traumatic stress disorder (PTSD). Although several studies support such a claim, empirical findings are inconsistent. Therefore, we performed a random-effects meta-analysis including data from a total of 47 studies and 3,062 subjects. As main finding, we can show that PTSD patients show episodic memory deficits compared to all controls. This effect was significantly stronger for PTSD vs. non-traumatized healthy controls as compared to PTSD vs. traumatized controls without PTSD. Finally, episodic memory impairments in PTSD were most pronounced in verbal memory tests as compared to non-verbal memory tests. Our results provide new evidence that PTSD is characterized by impaired episodic long-term memory beyond the traumatic event, and these deficits are particularly pronounced in verbal memory. We will discuss our findings in the context of physiological, psychological and trauma related memory models. From a broader perspective, our findings may have implications for the treatment of PTSD by suggesting that the assessment and, if necessary, training of memory deficits could be included as part of diagnostics and psychotherapeutic treatment.


Exodus-1 (CCL20): evidence for the participation of this chemokine in spontaneous labor at term, preterm labor, and intrauterine infection.
CCL20, also known as MIP-3 alpha, is a chemokine that participates in chemotaxis of immature dendritic cells, effector/memory T-cells, and B-lymphocytes. The objectives of this study were to determine whether CCL20 can be detected in amniotic fluid (AF) and if AF concentration of this chemokine changes with advancing gestational age, parturition (term and preterm), and intra-amniotic infection/inflammation (IAI). A cross-sectional study was conducted including the following groups: (1) mid-trimester of pregnancy (n=65); (2) term not in labor (TNL; n=22); (3) term in labor (TIL; n=47); (4) spontaneous preterm labor (PTL) who delivered at term (n=57); (5) spontaneous PTL without IAI who delivered preterm (n=71); and (6) spontaneous PTL with IAI (n=38). AF CCL20 concentrations were determined using ELISA. (1) The median AF CCL20 concentration in TNL was higher than that of mid-trimester patients; (2) Women in spontaneous labor at term had a higher median AF concentration of CCL20 than patients at term not in labor; (3) Patients with spontaneous PTL and IAI had a significantly higher median AF concentration of CCL20 than those without IAI who delivered preterm and those who delivered at term. Moreover, women with spontaneous PTL without IAI who delivered preterm had a significantly higher median AF concentration than those with PTL who subsequently delivered at term. (1) CCL20 is a physiologic constituent of AF and its concentration increases as term approaches; (2) spontaneous labor (term and preterm) in the absence of IAI is associated with increased bioavailability of AF CCL20 suggesting that an increase in CCL20 is part of the common pathway of human parturition; (3) patients with IAI had dramatic elevations in the AF CCL20 concentrations suggesting that this chemokine participates in the host response to infection or other stimuli associated with intra-amniotic infection.


[Evaluation of a new real-time PCR assay kit for quantification of human immunodeficiency virus RNA in plasma].
We evaluated the use of COBAS TaqMan HIV-1 for highly pure system (COBAS TaqMan) recently developed as a second-generation quantification of human immunodeficiency virus type 1 (HIV-1) RNA. The linearity, sensitivity, reproducibility, and effects of possibly interfering materials were examined and results compared to those of AMPLICOR HIV-1 MONITOR Test version 1.5 (AMPLICOR) using 6 virus isolates that were all different subtypes. Excellent linearity was obtained at 1.67 x 10(2)-1.73 x 10(6) copies/mL (r2 = 0.991). Sensitivity was 40 copies/mL at a 100% hit rate. Intraexperimental CVs were 27.4-50.8%, and interexperimental CVs were 29.3-81.5%. Although COBAS TaqMan showed an excellent titer correlation with AMPLICOR (r2 = 0.960), mean titer obtained with COBAS TaqMan was 3.1 times higher than that with AMPLICOR (p = 0.002), and 7.1 times higher in a sample of subtype C, suggesting discrepancies in HIV-1 RNA quantification between the two kits. This point should be noted when AMPLICOR is replaced by COBAS TaqMan.


The New Face of Berries: A Review of Their Antiviral Proprieties.
Due to rising consumer preference for natural remedies, the search for natural antiviral agents has accelerated considerably in recent years. Among the natural sources of compounds with potential antiviral proprieties, berries are interesting candidates, due to their association with health-promoting properties, including antioxidant, antimutagenic, anticancer, antimicrobial, anti-inflammatory, and neuroprotective properties. The past two decades have witnessed a flurry of new findings. Studies suggest promising antiviral proprieties against enveloped and non-enveloped viruses, particularly of cranberries, blueberries, blackcurrants, black raspberries, and pomegranates. The aim of this review is to assemble these findings, to list the implied mechanisms of action, and thereby point out promising subjects for research in this field, in the hope that compounds obtainable from natural sources such as berries may be used someday to treat, or even prevent, viral infections.


Diagnostic performance of prospectively assigned clear cell Likelihood scores (ccLS) in small renal masses at multiparametric magnetic resonance imaging.
Detection of small renal masses (SRM) is increasing with the use of cross-sectional imaging, although many incidental lesions have negligible metastatic potential. A method to identify this subtype would aid in risk stratification. A previously reported clear cell likelihood score (ccLS; 1-very unlikely, 2-unlikely, 3-equivocal, 4-likely, and 5-very likely), based on retrospective review of multiparametric magnetic resonance imaging (mpMRI), predicted the likelihood of encountering clear cell renal cell carcinoma (ccRCC) at surgery. Here, we assess the performance of ccLS prospectively assigned for prediction of ccRCC. Patients with a known renal mass who underwent mpMRI at a single institution between June 2016 and April 2018 were prospectively assigned a ccLS as part of the clinical MRI report. These patients were retrospectively reviewed, and those with a cT1a lesion and available pathological tissue diagnosis (diagnostic biopsy or extirpative surgery) were selected for analysis. In total, 57 patients (mean age 61.7 ± 14.9 years) with 63 cT1a renal masses were identified. Mean tumor size was 2.7 ± 0.7 cm. Defining ccLS 4-5 lesions as positive demonstrated an overall accuracy of 84%, sensitivity of 89%, specificity of 79%, positive predictive value of 84%, and negative predictive value of 86%. A ccLS of 1-2 demonstrates an 86% accuracy and 100% sensitivity/positive predictive value of identifying non-ccRCC histology. Utilizing prospectively assigned ccLS, we confirm that mpMRI can reasonably identify ccRCC histology in cT1a renal masses. Standardization of imaging protocols and reporting criteria such as the ccLS can be used to aid in the diagnosis and management of small renal masses.


How do we assess musicians' musculoskeletal symptoms?: a review of outcomes and tools used.
Recent reviews of musicians' musculoskeletal symptoms (MSS) have reported heterogeneity in the outcomes reported and data collection tools used, making it difficult to compare and synthesise findings. The purpose of this present review was to improve the consistency of future research, by documenting the outcomes reported in recent studies of musicians' MSS and the data collection tools used. All English language, peer-reviewed studies, published 2007-2016 that reported musicians' self-reported MSS outcomes were identified. Details of the types of outcomes reported and the tools used were extracted, and synthesised descriptively. A range of MSS outcomes were reported, including MSS with a temporal relationship to activities performed, and the consequences of symptoms. Only 24% of studies used standardised questionnaires, with the Nordic Musculoskeletal Questionnaire (NMQ) being the most commonly used. To improve the homogeneity of outcomes and data collection tools when investigating musicians' MSS, we recommend using the NMQ, where appropriate. Recall periods of 12-months and 7-d are the most appropriate for prevalence, and 7-d recall periods for ratings. Importantly, outcomes and the tools used to collect data should be reported in sufficient detail to ensure that the study can be replicated, critiqued, and accurately interpreted.


Successful treatment of patients with von Willebrand disease using a high-purity double-virus inactivated factor VIII/von Willebrand factor concentrate (Immunate).
Fourteen patients with different types of von Willebrand disease (vWD) having acute bleeds or elective surgery were treated with Immunate(sound recording copyright sign), a double-virus inactivated factor VIII/von Willebrand factor (FVIII/vWF) concentrate. The concentrate was applied as a bolus or via continuous infusion. FVIII activity (FVIIIc), vWF antigen (vWF:Ag), ristocetin cofactor activity (vWF:RCo), collagen binding activity (vWF:CB), activated partial thromboplastin time (aPTT), and von Willebrand multimers (vW-multimers) were monitored for 48 hours. Pharmacokinetic analyses were performed. The clinical efficacy was rated excellent or good. Bleeding complications occurred in 3 patients due to an additional FXIII deficiency in one patient, to a surgically induced bleed in another patient, and a rather short substitution period in the third patient. There were no serious adverse experiences. One patient showed a phlebitic reaction at the site of venous access after more than 100 hours of continuous infusion, requiring a change to application via bolus.


Colorectal cancer: chemotherapy as surgical adjuvant treatment.
As we view our past accomplishments in chemotherapy of colorectal cancer, it would seem clear that none of our approaches for any stage of this disease can be regarded as optimal for clinical practice or even as having any established benefit. The use of chemotherapy in the routine clinical practice setting for this disease provides little or no value to the patient today and is a distinct disservice to the patient of tomorrow. Nevertheless, the failure of past accomplishment should not lead to therapeutic nihilism. The major human problem which this disease presents demands intensive and sophisticated clinical research efforts. It would also seem obvious that these efforts require coordination of all concerned disciplines. Such a team effort should include not only the surgeon, medical oncologist, and the radiation therapist but also the laboratory scientist. With integrated and concentrated effort, a foundation can be laid for realistic optimism regarding improvement in therapy for colorectal cancer in the years immediately ahead.


Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for inhibition of myelin repair is incompletely understood. To identify novel regulators of OLP differentiation, potentially dysregulated during repair, we performed a genome-wide screen of 1040 transcription factor-encoding genes expressed in remyelinating rodent lesions. We report that approximately 50 transcription factor-encoding genes show dynamic expression during repair and that expression of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesioned-but not normal-adult white matter. We report that beta-catenin signaling is active during oligodendrocyte development and remyelination in vivo. Moreover, we observed similar regulation of Tcf4 in the developing human CNS and lesions of MS. Data mining revealed elevated levels of Wnt pathway mRNA transcripts and proteins within MS lesions, indicating activation of the pathway in this pathological context. We show that dysregulation of Wnt-beta-catenin signaling in OLPs results in profound delay of both developmental myelination and remyelination, based on (1) conditional activation of beta-catenin in the oligodendrocyte lineage in vivo and (2) findings from APC(Min) mice, which lack one functional copy of the endogenous Wnt pathway inhibitor APC. Together, our findings indicate that dysregulated Wnt-beta-catenin signaling inhibits myelination/remyelination in the mammalian CNS. Evidence of Wnt pathway activity in human MS lesions suggests that its dysregulation might contribute to inefficient myelin repair in human neurological disorders.


Targeting c-MET in gastrointestinal tumours: rationale, opportunities and challenges.
Data from many preclinical studies, including those using cellular models of colorectal, gastric, gastro-oesophageal and gastro-oesophageal junction cancers, indicate that the hepatocyte growth factor (HGF)-hepatocyte growth factor receptor (c-MET) pathway is vital for the growth, survival and invasive potential of gastrointestinal cancers. Following the availability of data from these various studies, and data on c-MET expression as a biomarker that indicates a poor prognosis in patients with gastrointestinal cancer and increased c-MET expression, inhibitors targeting this pathway have entered the clinic in the past decade. However, the design of clinical trials that incorporate the use of HGF/c-MET inhibitors in their most appropriate genetic and molecular context remains crucial. Recognizing and responding to this challenge, the European Commission funded Framework 7 MErCuRIC programme is running a biomarker-enriched clinical trial investigating the efficacy of combined c-MET/MEK inhibition in patients with RAS-mutant or RAS-wild-type metastatic colorectal cancer with aberrant c-MET expression. The design of this trial enables the continued refinement of the predictive biomarker and co-development of companion diagnostics. In this Review, we focus on advances in our understanding of inhibition of the HGF/c-MET pathway in patients with gastro-intestinal cancers, the prominent challenges facing the clinical translation and implementation of agents targeting HGF/c-MET, and discuss the various efforts, and associated obstacles to the discovery and validation of biomarkers that will enable patient stratification in this context.


Graft-versus-leukemia effects of Wilms' tumor 1 protein-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation.
The role of Wilms' tumor 1 protein (WT1)-specific cytotoxic T cells (CTL) in eradicating chronic myeloid leukemia (CML) cells is to be established. The aim of this study was to determine whether WT1 contributed to the graft-versus-leukemia effects (GVLE) for CML following allogeneic hematopoietic stem cell transplantation (HSCT). High-resolution human leukocyte antigen (HLA) class I genotyping was performed by sequence-specific polymerase chain reaction (PCR). Fifteen HLA-A*2402 patients with CML who underwent allogeneic HSCT were enrolled in this study. We monitored the frequency of WT1-specific CTL by pentamer assay and the molecular minimal residual disease by real-time quantitative PCR. A CD8(+) T-cell response to WT1 was observed in 14 of 15 patients after HSCT. The median frequencies of WT1-CTL were 0.54%, 0.62%, 0.81% and 1.28% (%CD8) on days 30, 60, 90 and 180, respectively. The median frequency of WT1-CTL (1.38%) in patients with molecular remission (MoR) was significantly higher than that in those without MoR (0.38%) on day 30, while no significant differences between them were detected on days 60, 90 and 180. The increase of WT1-CTL was associated with a decrease in bcr-abl expression and MoR; and the decrease of WT1-CTL was associated with an increase in bcr-abl expression, suggesting a WT1-driven GVL effect. WT1-CTL had a predominant effector-memory phenotype (CD45RO(+)CD27(-)CD57(+)). The emergence of WT1-CTL with an effector-memory phenotype is associated with GVLE in CML patients after HSCT. This will pave the way for the WT1 vaccines to enhance GVLE after HSCT in CML.


Inhibition of STAT3 signaling pathway by ursolic acid suppresses growth of hepatocellular carcinoma.
The signal transducer and activator of transcription 3 (STAT3) has been found to be constitutively active in liver cancer. There is no STAT3 inhibitors approved to be used clinically for the treatment or prevention of liver cancer. Some dietary compounds including ursolic acid (UA) have been reported to inhibit the growth of cancer cells. However, whether UA could inhibit STAT3 phosphorylation in hepatocellular carcinoma has not been reported. The inhibitory effects of UA on STAT3 phosphorylation, along with cell viability, migration, colony formation in vitro, as well as tumor growth in vivo were examined in human liver cancer cell lines. Our data showed that UA inhibited the P-STAT3 induced by interleukin-6 (IL-6) in Hep3B liver cancer cells which express very low basal level of P-STAT3. The constitutive STAT3 phosphorylation was also inhibited by UA in HEPG2, 7721 and Huh7 human liver cancer cell lines. UA decreased the expression of downstream target genes of STAT3, such as Bcl-2, Bcl-xl and survivin in general, with difference in these cell lines. UA also suppressed cell viability, cell migration and colony formation in liver cancer cells. Furthermore, UA suppressed STAT3 phosphorylation and HEPG2 tumor growth by oral daily treatment in vivo. UA, which exists widely in fruits and herbs, could inhibit STAT3 activation and the growth of human liver cancer cells in vitro and in vivo. It might be a potential health care product that could be used daily for prevention, as well as a promising candidate for chemotherapy of liver cancer.


[Current problems of the technical equipment of clinico-diagnostic laboratories].
A list of the required minimum of devices and apparatus used at present at clinico-diagnostic laboratories of medical establishments of diverse profile and capacity is presented. Future prospects for providing clinico-diagnostic laboratories with processing equipment are discussed.


Seizures at stroke onset: A case-control study.
Seizures occurring at the immediate onset of a stroke, abbreviated "seizures at onset" (SaO), pose a diagnostic and therapeutic challenge for physicians. In this study, we report on the current clinical practice in managing stroke patients with SaO from a large tertiary stroke center in Germany. We selected all patients with SaO and acute ischemic or hemorrhagic stroke admitted to the Department of Neurology at the University Hospital of Cologne between 2019 and 01-01 and 2020-12-31. SaO patients were then compared to patients with acute ischemic or hemorrhagic stroke without SaO from the local stroke registry. Further, we compared SaO patients who received intravenous recombinant tissue-type plasminogen activator (rt-PA) and/or mechanical thrombectomy with matched controls. Overall, 54 out of 2312 stroke patients (2.3 %) in the examined period presented with SaO. The most prevalent SaO semiology was focal to bilateral tonic-clonic (42.6 %). SaO was associated with hemorrhagic strokes and higher in-hospital mortality in all stroke patients. The rate of acute stroke therapy was not influenced by the occurrence of SaO. In patients that received acute stroke therapy, patients with SaO had higher scores on the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) at admission, and longer door-to-needle times for the administration of rt-PA, while none of the examined outcome parameters revealed a difference between patients with and without SaO after adjusting for potential confounders. Data show that SaO is rare in stroke patients but associated with more extensive strokes.


Patients' knowledge of and participation in preventing pressure ulcers- an intervention study.
The aim of this study was to evaluate a patient information pamphlet on pressure ulcer (PU) prevention using a descriptive, comparative pre- and post-test study design. The patient information pamphlet 'How can you help to stop pressure ulcers?' developed by the European PU Advisory Panel in 2012 was implemented in two surgical wards in a university hospital. A total of 61 patients answered pre- and post-test questionnaires. Patients assessed their knowledge of the risks, causes and ways to prevent PUs significantly higher after the intervention than before. Twenty-eight patients (46%) reported that they had participated in PU prevention during the last 24 hours. The patients assessed the content of the PU pamphlet as useful, its language as quite easy to understand and its layout as good. Patients with a PU pamphlet during their hospital stay were more knowledgeable about and more active in their own care. It is important that nurses invite patients to be active partners in preventing PUs but also that they identify patients who need to have a more passive role. The PU pamphlet could be updated to increase its comprehensibility, meaningfulness and manageability for patients.


Pumps, aqueducts, and drought management: vascular physiology in vascular cognitive impairment.
Vascular cognitive impairment has been traditionally defined by structural pathology, an accumulation of infarcts, leading to progressive cognitive decline. Recent evidence, however, suggests that cognitive impairment may be independently mediated by hemodynamic dysfunction, including global and hemispheral hypoperfusion and altered cerebral blood flow regulation. In this review, we examine evidence for the contribution of hemodynamic impairment to cognitive dysfunction in the setting of large vessel disease, cardiac failure, and microvascular disease. If there is a hemodynamic component of vascular cognitive impairment, then treatments proposed to correct impaired vascular physiology may reasonably be expected to treat the cognitive dysfunction as well.


Photoelectrocatalytic H2 evolution in water with molecular catalysts immobilised on p-Si via a stabilising mesoporous TiO2 interlayer.
The development of photoelectrodes capable of light-driven hydrogen evolution from water is an important approach for the storage of solar energy in the form of a chemical energy carrier. However, molecular catalyst-based photocathodes remain scarcely reported and typically suffer from low efficiencies and/or stabilities due to inadequate strategies for interfacing the molecular component with the light-harvesting material. In this study, we report the straightforward preparation of a p-silicon|mesoporous titania|molecular catalyst photocathode assembly that is active towards proton reduction in aqueous media with an onset potential of +0.4 V vs. RHE. The mesoporous TiO2 scaffold acts as an electron shuttle between the silicon and the catalyst, while also stabilising the silicon from passivation and enabling a high loading of molecular catalysts (>30 nmol (geometrical cm)-2). When a Ni bis(diphosphine)-based catalyst is anchored on the surface of the electrode, a high turnover number of ∼1 × 103 was obtained from photoelectrolysis under UV-filtered simulated solar irradiation at 1 Sun after 24 h at pH 4.5. Notwithstanding its aptitude for molecular catalyst immobilisation, the p-Si|TiO2 photoelectrode showed great versatility towards different catalysts and pH conditions, with photoelectrocatalytic H2 generation also being achieved with platinum and a hydrogenase as catalyst, highlighting the flexible platform it represents for many potential reductive catalysis transformations.


Adrenomedullin signaling pathway polymorphisms and adverse pregnancy outcomes.
Reduced maternal plasma levels of the peptide vasodilator adrenomedullin have been associated with adverse pregnancy outcomes. We measured the extent to which genetic polymorphisms in the adrenomedullin signaling pathway are associated with birth weight, glycemic regulation, and preeclampsia risk. We genotyped 1,353 women in the Pregnancy, Infection, and Nutrition Postpartum Study for 37 ancestry-informative markers and for single-nucleotide polymorphisms in adrenomedullin (ADM), complement factor H variant (CFH), and calcitonin receptor-like receptor (CALCRL). We used linear and logistic regression to model the association between genotype and birth weight, glucose loading test (GLT) results, preeclampsia, and gestational diabetes (GDM). All models were adjusted for pregravid body mass index, maternal age, and probability of Yoruban ancestry. p values of < 0.05 were considered statistically significant. Among Caucasian women, ADM rs57153895, a proxy for rs11042725, was associated with reduced birth weight z-score. Among African-American women, ADM rs57153895 was associated with increased birth weight z-score. Two CALCRL variants were associated with GDM risk. CFH rs1061170 was associated with higher GLT results and increased preeclampsia risk. Consistent with studies of plasma adrenomedullin and adverse pregnancy outcomes, we found associations between variants in the adrenomedullin signaling pathway and birth weight, glycemic regulation, and preeclampsia.


Pharmacologic considerations for oseltamivir disposition: focus on the neonate and young infant.
Across much of the world, pandemic H1N1 infection has produced a significant healthcare crisis, reflected in significant morbidity and mortality. Statistics reveal that infection-associated deaths among individuals without pre-existing conditions (e.g. immunosuppression) are clustered in pregnant women and young infants. In developing countries where the availability of influenzae vaccine is limited, the only currently available pharmacologic counter-measure for H1N1 disease is oseltamivir, a neuraminidase inhibitor with excellent in vitro activity against the virus. This drug is available in oral solid and liquid formulations, has excellent peroral bioavailability in adults, and generally has a very favorable safety profile. Many observational studies indicate that oseltamivir treatment is associated with symptomatic improvement in pediatric patients with H1N1 infection and, therefore, is considered to represent a viable therapeutic option for use in children. However, the disposition of the ethyl ester prodrug and its active metabolite has not been well characterized in infants and children. Presently, data are available from only two published investigations and preliminary summary information from a recent presentation of an ongoing study. Given that recent in vitro data support the importance of a target exposure-response profile for the active metabolite of oseltamivir and that many processes known to modulate drug disposition have a developmental basis, understanding the potential impact of age on oseltamivir disposition becomes crucial in the development of age-appropriate dosing regimens for the drug. In this review, the impact of ontogeny on processes that are important in regulating the absorption, distribution, metabolism, and excretion of oseltamivir and its active metabolite are considered. Data from both animal and human investigations are presented in the context of defining how development might influence the dose-exposure relationship and, most importantly, the significant variability associated with it. In addition, the available pediatric pharmacokinetic data for oseltamivir and its active metabolite are summarized and current 'information gaps' deserving of future study are presented.


Can Neutrophil to Lymphocyte Ratio Predict Early Outcome in Patients with Spinal Cord Injury?
Spinal cord injury is a frequent debilitating neurologic condition with increasing prevalence and related morbidity over the last decades. The neutrophil-to-lymphocyte ratio is a promising biomarker for determining different medical conditions' disease course and outcome such as traumatic brain injury (TBI). This study aimed to investigate the predictive value of neutrophil to lymphocyte ratio (NLR) in the outcome of SCI. In a retrospective cross-sectional study from April 2019 to April 2022, all patients 18 to 65 years old, following spinal cord injury who were referred to Imam Khomeini Hospital and met inclusion and exclusion criteria enrolled in the study. A checklist including demographic data, lab, and clinical findings at admission, 24h, 48 h, and discharge were recorded. IBM SPSS Statistics software was used to analyze the data. A P-value of less than 0.05 was considered significant. Six hundred patients met our inclusion criteria and enrolled in the study. The mean age of the patients was 40.93 ± 12.77, with 75% male and 25% female. There was a significant correlation between the N/L ratio at different time points (p.value=0.001), injury type, and ASIA score at admission and discharge (0.001). Furthermore, the NLR had approached significant value alone to predict outcomes in patients enrolled in the study (0.06). A high NLR is unequivocally linked with poor outcomes in patients suffering from acute SCI and should be considered a negative prognostic factor; however, the NLR had approached significant predicting value in patients enrolled in the study.


Common polymorphisms in checkpoint kinase 2 are not associated with breast cancer risk.
A substantial proportion of the familial risk of breast cancer may be attributable to genetic variants each contributing a small effect. Polymorphisms in DNA repair genes are good candidates for such low penetrance breast cancer susceptibility alleles. Checkpoint kinase 2 (CHEK2) is a kinase in which the yeast counterpart regulates a cell cycle checkpoint and causes cells to arrest proliferation after DNA damage. A rare, protein truncating mutation in the CHEK2 gene has recently been shown to confer a modest risk of breast cancer. The aim of this study was to determine whether common polymorphic variants in CHEK2 are associated with an increase in breast cancer risk. We assessed two variants in CHEK2 using a case control study design (n = 1786 cases and 1828 controls). No differences in genotype frequencies were found between cases and control for either the IVS1 + 38insa or the a1013g polymorphisms (P = 0.3 and 0.2 respectively), and no genotype-specific risk was significantly different from unity. The haplotype frequency distribution in cases and controls were also similar (P = 0.3). We conclude that the CHEK2 polymorphisms IVS + 1a and a1013g do not confer an increased risk of breast cancer. It is also unlikely that other, as yet unidentified, common polymorphisms that affect risk are present in the gene in the British population.


Draft genome sequence of multi-resistant Salmonella enterica subsp. enterica serovar Rissen strain 19CS0416 isolated from Vietnam reveals mcr-1 plasmid mediated resistance to colistin already in 2013.
We report the first draft genome sequence of a Salmonella strain with plasmid-mediated resistance to colistin encoded by mcr-1 gene in Vietnam. Salmonella enterica subsp. enterica serovar Rissen was isolated from a Vietnamese pig slaughterhouse in 2013. We can confirm that mcr-1 gene is identical to the first reported mcr-1 gene of the Escherichia coli strain SHP45, isolated in 2015 from a Chinese pig. The plasmid containing this gene in the strain 19CS0416 was highly related (96.86% identity) to the plasmid (pHNSHP45) contained in this Chinese strain. Moreover, this plasmid was determined to be 100% identical to a plasmid (p13P477T-7) belonging to an Escherichia coli (13P477T) found in Hong Kong during the same year in pigs. Our results will aid in understanding the dissemination of mcr-1 gene in East Asia, dating back to as early as 2013.


Depletion of G9a gene induces cell apoptosis in human gastric carcinoma.
G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Evidence suggests that G9a is required to maintain the malignant phenotype, but little documentation show the role of G9a function in mediating tumor growth. We retrospectively analyzed the protein of G9a and monomethylated histone H3 lysine 9 (H3K9 me1), and dimethylated histone H3 lysine 9 (H3K9 me2) in 175 cases of gastric carcinoma by immunohistochemistry. RNAi-based inhibition of G9a in MGC803 cancer cell line was studied. G9a depletion was done by transient transfection using Lipofectamine 2000. Depletion efficiency of G9a was tested using real-time PCR and western blot analysis. Cell apoptosis and proliferation were detected by TUNEL assay and MTT, respectively. The proteins of H3K9 me1, me2, trimethylation of H3K9 (H3K9 me3), monomethylated histone H3 lysine 27 (H3K27 me1), dimethylated histone H3 lysine 27 (H3K27 me2) and histone acetylated H3, apoptotic proteins were studied by western blot analysis. G9a and H3K9 me2 expression was higher in gastric cancer cells compared to the control (p<0.05). Both G9a and H3K9 me2 were positively correlated with the degree of differentiation, depth of infiltration, lymphatic invasions and tumor-node-metastasis stage in gastric carcinoma, (p<0.05). RNAi-mediated knockdown of G9a induced cell apoptosis and inhibited cell proliferation. Depletion of G9a reduced the levels of H3K9 me1 and me2, H3K27 me1 and me2. Nonetheless, it did not activate acetylation of H3 and H3K9 me3. These data suggest that G9a is required in tumorigenesis, and correlated with prognosis. Furthermore, G9a plays a critical role in regulating epigenetics. Depletion of G9a inhibits cell growth and induces cells apoptosis in gastric cancer. It might be of therapeutic benefit in gastric cancers.


Green Tobacco Sickness among Thai Traditional Tobacco Farmers, Thailand.
Traditional Thai tobacco (Nicotiana abacus L.) is known as a non-Virginia type whose mature leaf contains three to four times more nicotine than that of a Virginia type. As such, the process of Thai traditional tobacco production may lead to adverse health effects such as green tobacco sickness (GTS). To investigate the prevalence of GTS and risk factors related to GTS among Thai traditional tobacco farmers in Nan province, northern Thailand. 473 Thai traditional tobacco farmers from rural areas in Nan province were randomly selected and interviewed in person by means of questionnaires and environmental survey. Statistical analyses were used to identify potential risk factors for GTS. The prevalence of GTS was 22.6% (95% CI 19.1% to 26.6%). Multivariate analysis showed various risk factors associated with GTS including gender of the farmer (ORadj 0.44, 95% CI 0.26 to 0.73), smoking (ORadj 4.36, 95% CI 1.41 to 13.47), skin rash (ORadj 0.36, 95% CI 0.19 to 0.68), wearing a wet suit (ORadj 1.91, 95% CI 1.12 to 3.23), process of curing tobacco leaves (ORadj 0.06, 95% CI 0.02 to 0.16), and watering tobacco plants (ORadj 0.42, 95% CI 0.25 to 0.72). The process of traditional Thai tobacco production can result in increased dermal exposure and can be considered a major risk factor for GTS. Body soaking during watering may further increase adverse health effects related to GTS.


[Fetal cardiopathy diagnostic approach at Instituto Nacional de Perinatologia].
Congenital prenatal heart disease diagnosis is made by high definition ultrasound within 16 to 20 weeks of pregnancy, and each day more and more early. To describe fetal heart disease cases, to evaluate its confirmation thorough post-natal diagnosis and perinatal result, and to establish a diagnose management algorithm. Cases series of maternal-fetal medicine department at Instituto Nacional de Perinatología, from January 1996 to June 2006. With the presumptive diagnosis, patients were evaluated thorough echocardiography by pediatrician cardiologist without knowing findings of fetal physician. Descriptive statistics was used: frequencies, percents, and central and dispersion trend mean. Seventy-three cases of diagnosis of fetal heart disease were registered. Mean age was 28 +/- 8 years old. Diabetes was present in 16.4%, and 5.47% had a child with a heart disease. Most frequent defects were Ebstein anomaly (19%), septal defects (20.5%), ventricular-auricular channel (17.8%), and hypoplastic left ventricle (17.8%). Sixty-eight percent of the cases diagnosis was confirmed by post-natal evaluation. It is important to establish right prenatal diagnosis of fetal heart disease, to give accurately advice to parents, perform necessary interventions, and improve fetal and neonatal prognosis.


Observational Research Using Propensity Scores.
In most observational studies, treatments or other "exposures" (in an epidemiologic sense) do not occur at random. Instead, treatments or other such interventions depend on several patient-related and patient-independent characteristics. Such factors, associated with the receipt vs nonreceipt of treatment, may also be-independently-associated with outcomes. Thus, confounding exists making it difficult to ascertain the true association between treatments and outcomes. Propensity scores (PS) represent an intuitive set of approaches to reduce the influence of such "confounding" factors. PS is a computed probability of treatment, a value that is estimated for each patient in an observational study and then applied (in a variety of ways such as matching, stratification, weighting, etc.) to reduce distortion in the true nature of the association between treatment (or any similar exposure) and outcomes. Despite several advantages, PS-based methods cannot account for unmeasured confounding, ie, for factors that are not being included in the computation of PS.


Inhibition of Fibrinolysis by Coagulation Factor XIII.
The inhibitory effect of coagulation factor XIII (FXIII) on fibrinolysis has been studied for at least 50 years. Our insight into the underlying mechanisms has improved considerably, aided in particular by the discovery that activated FXIII cross-links α2-antiplasmin (α2AP) to fibrin. In this review, the most important effects of different cross-linking reactions on fibrinolysis are summarized. A distinction is made between fibrin-fibrin cross-links studied in purified systems and fibrin-α2AP cross-links studied in plasma or whole blood systems. While the formation of γ chain dimers in fibrin does not affect clot lysis, the formation of α chain polymers has a weak inhibitory effect. Only strong cross-linking of fibrin, associated with high molecular weight α chain polymers and/or γ chain multimers, results in a moderate inhibition fibrinolysis. The formation of fibrin-α2AP cross-links has only a weak effect on clot lysis, but this effect becomes strong when clot retraction occurs. Under these conditions, FXIII prevents α2AP being expelled from the clot and makes the clot relatively resistant to degradation by plasmin.


CELL BIOLOGY SYMPOSIUM: Impacts of maternal obesity on placental and gut inflammation and health.
Obesity in pregnant women is a growing public health concern that negatively affects fetal development and has long-term impacts on offspring health. The placenta plays an essential role in nutrient transport to the fetus and supports fetal growth and development. Maternal obesity (MO) induces an exacerbated proinflammatory milieu in the placenta providing an inflammatory environment for fetuses. The gut is one of the largest immune organs and mainly develops during the fetal stage. Maternal obesity and the corresponding inflammatory uteroplacental environment affect gut development, incurring inflammatory responses in the fetal intestine that further prime or program the offspring gut to enhance inflammation and impair intestinal barrier integrity. This review summarizes the impact of MO on inflammatory responses in placenta and fetal intestine and the long-term effects on offspring intestinal health. Because "leaky gut" is one of the main etiological factors for a number of common diseases, including inflammatory bowel diseases, type I diabetes, and related autoimmune diseases, the adverse effect of MO on the overall health of progeny is further discussed.


Blood plasma clinical-chemical parameters as biomarker endpoints for organohalogen contaminant exposure in Norwegian raptor nestlings.
Raptors are exposed to biomagnifying and toxic organohalogenated compounds (OHCs) such as organochlorines, brominated flame retardants and perfluorinated compounds. To investigate how OHC exposure may affect biochemical pathways we collected blood plasma from Norwegian northern goshawk (n=56), golden eagle (n=12) and white-tailed eagle (n=36) nestlings during three consecutive breeding seasons. We found that blood plasma concentrations of calcium, sodium, creatinine, cholesterol, albumin, total protein, urea, inorganic phosphate, protein:creatinine, urea:creatinine and uric acid:creatinine ratios and liver enzymes ALKP and ALAT were positively correlated to PCBs, chlordanes, p,p'-DDE, HCB, PFCs and/or PBDEs. Total bilirubin and glucose were negatively correlated to PCBs while magnesium and potassium were negatively correlated to HCB and p,p'-DDE. In addition, protein:creatinine and ALAT were also negatively correlated to PCBs and PFCs, respectively. The most significant relationships were found for the highly contaminated northern goshawks and white-tailed eagles. The statistical relationships between OHCs and BCCPs indicate that biochemical pathways could be influenced while it is uncertain if such changes have any health effects. The OHC concentrations were below concentrations causing reproductive toxicity in adults of other raptor species but similar to those of concern for endocrine disruption of thyroid hormones in e.g., bald eagles.


A superposable silicon synapse with programmable reversal potential.
We present a novel log-domain silicon synapse designed for subthreshold analog operation that emulates common synaptic interactions found in biology. Our circuit models the dynamic gating of ion-channel conductances by emulating the processes of neurotransmitter release-reuptake and receptor binding-unbinding in a superposable fashion: Only a single circuit is required to model the entire population of synapses (of a given type) that a biological neuron receives. Unlike previous designs, which are strictly excitatory or inhibitory, our silicon synapse implements-for the first time in the log-domain-a programmable reversal potential (i.e., driving force). To demonstrate our design's scalability, we fabricated in 180nm CMOS an array of 64K silicon neurons, each with four independent superposable synapse circuits occupying 11.0×21.5 µm(2) apiece. After verifying that these synapses have the predicted effect on the neurons' spike rate, we explored a recurrent network where the synapses' reversal potentials are set near the neurons' threshold, acting as shunts. These shunting synapses synchronized neuronal spiking more robustly than nonshunting synapses, confirming that reversal potentials can have important network-level implications.


"Get Me Off This Medication!": A Comparison Between Gastroenterology and Primary Care Regarding Patient's Perceptions of Proton Pump Inhibitor Therapy.
Background Not much is known about patient perceptions regarding proton pump inhibitor (PPI) de-escalation. We sought to determine the knowledge of adverse effects (AEs) and willingness to de-escalate therapy among patients presenting to primary care and subspecialty clinics. Methods We conducted an anonymous survey of patients presenting to family medicine, internal medicine, and gastroenterology clinics who use PPIs. Survey topics included awareness of and concern for AEs of PPIs, and willingness to de-escalate PPI therapy. Results The sample comprised 206 participants presenting to the gastroenterology (29.8%), internal medicine (32.2%), and family medicine clinics (38%). Of the participants, 16% were "extremely concerned" about AEs and 28.2% reported attempting to stop PPIs by themselves in the past. Many patients (54.9%) reported that providers had not discussed AEs before initiation. Patients visiting digestive disease clinics were no more likely to report discussions on AEs and de-escalation or discontinuation attempts compared to primary care patients (p-values > 0.05). On logistic regression analysis, concern for AEs and counseling regarding PPI discontinuation were found to be significantly associated with attempts to discontinue PPI. Conclusions Although many patients on PPIs are concerned about AEs, a low number of patients reported provider-initiated discussions on AEs of PPI at initiation.


The care of critically ill children after hematopoietic SCT: a North American survey.
Although potentially curative, hematopoietic SCT (HSCT) is associated with significant morbidity. To improve outcomes, multicenter studies of critical illness in this patient population appear needed. To assist in the design of such studies, a survey was conducted to identify variations in care provided to critically ill pediatric HSCT patients. A survey was conducted of the highest volume pediatric HSCT centers in the United States (n=30) and Canada (n=4). One pediatric critical care medicine (PCCM) physician and one pediatric HSCT physician were surveyed at each institution. Analysis consisted of descriptive statistics. Thirty-three (29 United States/4 Canada) of 34 institutions responded. Although most HSCT units permit fluid boluses and nearly half permit some dose of dopamine, high-dose dopamine and other vasoactive infusions are rarely allowed there. Six institutions (21%) permit non-invasive ventilation on the HSCT unit. Criterion for PCCM consultation and therapies implemented before intubation vary significantly. High-frequency oscillatory ventilation and renal replacement therapy are commonly used for lung injury in patients failing conventional therapy. Variability exists in the location and type of therapy critically ill pediatric HSCT patients receive. Understanding this variability will help facilitate the design of clinical trials.


Anxiety of children and adolescents who stutter: a review.
Adults who stutter have heightened rates of anxiety disorders, particularly social anxiety disorder, compared with non-stuttering controls. However, the timing of anxiety onset and its development in relation to stuttering is poorly understood. Identifying the typical age of anxiety onset in stuttering has significant clinical implications and is crucial for the management of both disorders across the lifespan. The present review aims to determine the scope of the research pertaining to this topic, identify trends in findings, and delineate timing of anxiety onset in stuttering. We examine putative risk factors of anxiety present for children and adolescents who stutter, and provide a review of the research evidence relating to anxiety for this population. Young people who stutter can experience negative social consequences and negative attitudes towards communication, which is hypothesised to place them at increased risk of developing anxiety. The prevalence of anxiety of young people who stutter, and the timing of anxiety onset in stuttering could not be determined. This was due to methodological limitations in the reviewed research such as small participant numbers, and the use of measures that lack sensitivity to identify anxiety in the targeted population. In sum, the evidence suggests that anxiety in stuttering might increase over time until it exceeds normal limits in adolescence and adulthood. The clinical implications of these findings, and recommendations for future research, are discussed. The reader will be able to: (a) discuss contemporary thinking on the role of anxiety in stuttering and reasons for this view; (b) describe risk factors for the development of anxiety in stuttering, experienced by children and adolescents who stutter (c) outline trends in current research on anxiety and children and adolescents with stuttering; and (d) summarise rationales behind recommendations for future research in this area.


DiNAR: health monitoring of IT systems in emergency response.
Disaster management and emergency response mechanisms have come of age post 9/11. Undoubtedly the introduction of Information Technology (IT) in emergency response management has been revolutionary from the perspective of better management of the emergency response. However, the various components which make up the IT infrastructure, such as sensors, computers, PDAs, network devices, etc, are inherently volatile in nature. To overcome this volatility and increasing the robustness of the emergency system we designed and developed a health monitoring tool, denoted DiNAR, for disaster systems. This tool will help the incident commander to actively monitor the state of the IT infrastructure which has been deployed in the field as well as the applications running at remote sites. DiNAR uses Manager-Agent based architecture and a novel agent initiated message exchange.


Expression profile and molecular genetic regulation of cyclin D1 expression in epithelioid sarcoma.
Epithelioid sarcoma is a distinctive, aggressive soft tissue tumor typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Molecular genetic data of well-characterized cases of epithelioid sarcoma are sparse. A recent cytogenetic study of epithelioid sarcoma by conventional metaphase comparative genomic hybridization reported recurrent gains at chromosome 11q13, a region containing many genes, including the cyclin D1 gene. Cyclin D1 is a positive cell cycle regulator that is overexpressed in a variety of neoplasms, including mantle cell lymphoma and breast carcinoma. The objective of this study was to examine cyclin D1 expression in epithelioid sarcoma. Of 24 cases evaluated, 23 (96%) displayed cyclin D1 nuclear expression using immunohistochemical evaluation. Eight cases, which expressed cyclin D1 by immunohistochemistry, were evaluated by fluorescence in situ hybridization (FISH) and RNA in situ hybridization (RISH) for amplification of the cyclin D1 gene and messenger RNA (mRNA) expression, respectively. Seven of eight cases showed a typical eusomic state. One case showed pseudoamplification due to aneusomy/polysomy. There was no evidence of cyclin D1 gene amplification or messenger RNA overexpression detected by FISH or RNA in situ hybridization analyses, respectively. Our data clearly demonstrate that cyclin D1 protein is upregulated in epithelioid sarcoma, suggesting a role for this cell cycle regulator in the pathogenesis of epithelioid sarcoma. The high level of cyclin D1 protein expression in epithelioid sarcoma appears to be regulated by translational and/or post-translational mechanisms.


Gene expression profiles by microarray analysis during matrigel-induced tube formation in a human extravillous trophoblast cell line: comparison with endothelial cells.
Endovascular differentiation of extravillous cytotrophoblasts (EVT) during placentogenesis induces remodeling of spiral arteries that increases blood flow toward the intravillous space and is required for maintaining pregnancy. To address the molecular mechanisms involved in this differentiation, we investigated the gene expression profile during matrigel-induced tube formation in TCL1 cells, a human immortalized EVT cell line, and HUV-EC-C, human umbilical vessel endothelial cells, and compared their profiles. The numbers of genes that showed significant up-regulation (>3-fold expression at both 3 and 6h, and/or >5-fold expression at either 3 or 6h) during tube formation and significant down-regulation (0.33-fold expression at both 3 and 6h, and/or less than 0.2-fold expression at either 3 or 6h), were 969 and 659 in TCL1, respectively. In HUV-EC-C, the numbers of genes that showed significant up-regulation and down-regulation were 86 and 65, respectively. Only 73 of 1628 genes that showed significant expression changes in TCL1 were common with HUV-EC-C. The genes showing significant expression change specifically in TCL1 were associated with cellular, metabolisms, proliferation, anti-apoptosis, proteolysis adhesion, and some known to be involved in EVT differentiation or related to angiogenesis. The gene expression profile in EVT during tube formation is very different from that of endothelial cells. Further investigations based on the current data may help to elucidate mechanisms of normal and abnormal placentogenesis.


Hepatitis B surface antigen-antibody interactions studied by optical tweezers.
The protein-protein interactions between hepatitis B surface antigen (HBsAg) and its antibodies (anti-HBs) were studied by measuring the binding force between microspheres coated with such proteins using optical tweezers. The interaction force between the protein-coated microspheres was found to be strongly influenced by the acidity of the surrounding liquid medium, as well as the experimental temperature, and it reaches a maximum value at around pH 7.5 and temperature around 37°C. By measuring the protein distribution on the surfaces of the microspheres and their contact areas using scanning electron microscopy, the specific binding force between an HBsAg and anti-HBs protein pair is estimated to be around 4.8 pN at the optimum pH value and temperature at an applied loading rate of around 1 pN/s.


Regulation of RNA synthesis by the genomic termini of vesicular stomatitis virus: identification of distinct sequences essential for transcription but not replication.
The RNA-dependent RNA polymerase of vesicular stomatitis virus (VSV), a nonsegmented negative-strand RNA virus, directs two discrete RNA synthetic processes, transcription and replication. Available evidence suggests that the two short extragenic regions at the genomic termini, the 3' leader (Le) and the complement of the 5' trailer (TrC), contain essential signals for these processes. We examined the roles in transcription and replication of sequences in Le and TrC by monitoring the effects of alterations to the termini of subgenomic replicons, or infectious viruses, on these RNA synthetic processes. Distinct elements in Le were found to be required for transcription that were not required for replication. The promoter for mRNA transcription was shown to include specific sequence elements within Le at positions 19 to 29 and 34 to 46, a separate element at nucleotides 47 to 50, the nontranscribed leader-N gene junction. The sequence requirements for transcription within the Le region could not be supplied by sequences found at the equivalent positions in TrC. In contrast, sequences from either Le or TrC functioned well to signal replication, indicating that within the confines of the VSV termini, the sequence requirements for replication were less stringent. Deletions engineered at the termini showed that the terminal 15 nucleotides of either Le or TrC allowed a minimal level of replication. Within these confines, levels of replication were affected by both the extent of complementarity between the genomic termini and the involvement of the template in transcription. In agreement with our previous observations, increasing the extent of complementarity between the natural termini increased levels of replication, and this effect was most operative at the extreme genome ends. In addition, abolishing the use of Le as a promoter for transcription enhanced replication. These analyses (i) identified signals at the termini required for transcription and replication and (ii) showed that Le functions as a less efficient promoter for replication than TrC at least in part because of its essential role in transcription. Consequently, these observations help explain the asymmetry of VSV replication which results in the synthesis of more negative- than positive-sense replication products in infected cells.


Reversible Severe Pulmonary Hypertension after Adenotonsillectomy: A Case Report of a Child Treated at Bugando Medical Centre, Northwestern Tanzania.
Upper airway obstruction (UAO) due to adenotonsillar hypertrophy represents one of the rare causes of pulmonary hypertension in children. We report a case of adenotonsillar hypertrophy, managed at pediatric and otorhinolaryngology departments in Bugando Medical Centre (BMC), northwestern Tanzania, with complete remission of symptoms of pulmonary hypertension following adenotonsillectomy. A 17-month-old boy presented with difficulty breathing, dry cough, and noisy breathing since 1 year. He had facial and lower limb oedema with a pan systolic murmur at the tricuspid area, fine crepitations, and tender hepatomegaly. A grade II tonsillar hypertrophy and hypertrophied adenoids were seen on nasal and throat evaluation. A 2D-echocardiography showed grossly distended right atrium and ventricle, dilated pulmonary artery, and grade III tricuspid regurgitation. His final diagnosis was severe pulmonary hypertension with right-sided heart failure due to adenotonsillar hypertrophy. He had complete remission of cardiopulmonary symptoms after adenotonsillectomy and had normal control echocardiography six and twelve months after surgery. Children with symptoms of upper airway obstruction and cardiopulmonary involvement could benefit from routine screening for pulmonary hypertension. Adenotonsillectomy should be considered for possible complete remission of both UAO and cardiopulmonary symptoms.


Intracellular water homeostasis and the mammalian cellular osmotic stress response.
The cellular response to osmotic stress ensures that the concentration of water inside the cell is maintained within a range that is compatible with biologic function. Single cell organisms are particularly dependent on mechanisms that permit adaptation to osmotic stress because each individual cell is directly exposed to the external environment. Mammals, however, limit osmotic stress by establishing an internal aqueous environment in which intravascular water and electrolytes are subject to sensitive and dynamic, organism-based homeostatic regulation. Recent studies of NFAT5/TonEBP, an essential mammalian osmoregulatory transcription factor, demonstrate the unexpected yet critical significance of cell-based osmotic regulation in vivo. These results highlight the fundamental importance of maintaining intracellular water homeostasis in the face of varying cellular metabolic activity and distinct tissue microenvironments.


Treatment of experimental frostbite with intra-arterial sympathetic blocking drugs.
A number of experimental and clinical studies have shown that early regional surgical sympathectomy decreases tissue loss following frostbite, presumably by relieving vasospasm and increasing blood flow. This study was performed to determine if a decrease in tissue loss following a standard cold injury could be obtained following a regional "medical sympathectomy" achieved by the intra-arterial administration of sympathetic blocking drugs. A standard cold injury was produced in rabbits and the animals were divided into nine treatment groups. Various treatment modalities were evaluated, including rapid rewarming, intra-arterial reserpine and tolazoline, and intravenous low molecular weight dextran. In the slowly rewarmed animals, the usual clinic situation, the regional intra-arterial administration of reserpine and tolazoline significantly reduced tissue loss, equalling the results obtained in the rapidly rewarmed group. These results indicate that the early achievement of a regional "medical sympathectomy" may be of benefit in reducing tissue loss following frostbite in patients, especially in those in whom rapid rewarming cannot be performed.


Seasonal sexual segregation in two Thalassarche albatross species: competitive exclusion, reproductive role specialization or foraging niche divergence?
Sexual segregation by micro- or macrohabitat is common in birds, and usually attributed to size-mediated dominance and exclusion of females by larger males, trophic niche divergence or reproductive role specialization. Our study of black-browed albatrosses, Thalassarche melanophrys, and grey-headed albatrosses, T. chrysostoma, revealed an exceptional degree of sexual segregation during incubation, with largely mutually exclusive core foraging ranges for each sex in both species. Spatial segregation was not apparent during brood-guard or post-guard chick rearing, when adults are constrained to feed close to colonies, providing no evidence for dominance-related competitive exclusion at the macrohabitat level. A comprehensive morphometric comparison indicated considerable species and sexual dimorphism in wing area and wing loading that corresponded, both within and between species, to broad-scale habitat preferences relating to wind strength. We suggest that seasonal sexual segregation in these two species is attributable to niche divergence mediated by differences in flight performance. Such sexual segregation may also have implications for conservation in relation to sex-specific overlap with commercial fisheries.


Expression and function of organic cation and anion transporters (SLC22 family) in the CNS.
A major function of the blood brain barrier (BBB) and blood cerebrospinal fluid barrier (BCSFB) is to exert selective control over the flux of organic cations and anions into and out of the CNS compartment. These barriers are dynamic tissues that accomplish this task by expressing dozens of transporter proteins representing numerous transporter families. One such family, belonging to the Solute Carrier (SLC) superfamily, is the organic cation/anion/zwitterion (SLC22) family of transporters, which includes the organic cation transporters (OCTs/OCTNs) and organic anion transporters (OATs). SLC22 transporters interact with a broad range of compounds that include drugs of abuse, environmental toxins/toxicants, opioid analgesics, antidepressant and anxiolytic agents and neurotransmitters and their metabolites. Defining the transport mechanisms controlling the CNS penetration, disposition and clearance of such compounds is fundamental to advancing our understanding of the underlying mechanisms that regulate CNS homeostasis and impact neuronal health. Such information might help direct efforts to improve the efficacy and clinical outcomes of current and future therapeutic agents used in the treatment of CNS disorders. This review focuses on highlighting the identification of the SLC22 transporter family, current knowledge of OCT and OAT expression within the CNS (including brain capillaries, choroid plexus and brain regions relevant to monoaminergic neuronal signaling), and recent data regarding behavioral changes related to mood and anxiety disorders and altered responses to stimulants and antidepressants in SLC22 loss of functions models (knockout/knockdown). In vitro and in vivo evidence of SLC22 localization and transport characteristics within the CNS compartment are summarized.


Adaptive Sparsity Orthogonal Least Square with Neighbor Strategy for Fluorescence Molecular Tomography.
Fluorescence molecular tomography (FMT) is a highly sensitive and noninvasive optical imaging technique which has been widely applied to disease diagnosis and drug discovery. However, FMT reconstruction is a highly ill-posed problem. In this work, L0-norm regularization is employed to construct the mathematical model of the inverse problem of FMT. And an adaptive sparsity orthogonal least square with a neighbor strategy (ASOLS-NS) is proposed to solve this model. This algorithm can provide an adaptive sparsity and can establish the candidate sets by a novel neighbor expansion strategy for the orthogonal least square (OLS) algorithm. Numerical simulation experiments have shown that the ASOLS-NS improves the reconstruction of images, especially for the double targets reconstruction.Clinical relevance- The purpose of this work is to improve the reconstruction results of FMT. Current experiments are focused on simulation experiments, and the proposed algorithm will be applied to the clinical tumor detection in the future.


Myasthenia gravis: immunological mechanisms and immunotherapy.
This review of the immunological aspects of myasthenia gravis and the immunotherapy of the disease emphasizes the current state of knowledge of the immunological events at the neuromuscular junction, and the immunoregulatory abnormalities noted in myasthenic patients. The treatment modalities available to the clinician are discussed in an attempt to provide information that will allow for a rational approach to therapy.


Syntheses, characterization, crystal structures and applications as sensitizers in solar cells of novel heteroleptic Cu(I) complexes containing nitrile-substituted 2,2'-bipyridyl ligands.
Two novel Cu(I) tetradentate heteroleptic complexes, including nitrile-substituted bipyridines that can be anchored to semiconductor surfaces to be assembled in DSSCs, were synthesized and characterized by spectroscopic and electrochemical techniques. The crystal structures of both species were determined by X-ray diffraction. Results from DFT and TD-DFT calculations were found to be consistent with the experimental data. Emission at room temperature was observed for both complexes in the solid state, making them promising alternatives for the development of light-emitting diodes. We report for the first time the experimental evidence of photovoltaic conversion devices formed by Cu(I) complexes anchored to a TiO2 surface by means of nitrile groups present in substituted bipyridines, and subsequently tested as sensitizers for DSSCs, obtaining efficiency values for light to electrical energy conversion similar to those previously reported for analogous complexes with anchoring carboxylic groups.


Changing expectations in the control of Mycoplasma gallisepticum.
Mycoplasma gallisepticum (MG) is traditionally controlled by maintaining MG-free flocks on single-age production sites and maintaining them MG-free utilizing good biosecurity and a consistent serological monitoring program. In recent years, several changes have taken place which have changed our ways about thinking about MG control. There have been significant improvements in detection methods. For example, polymerase chain reaction now represents a rapid and sensitive method for detecting the organism. ELISA kits are now much improved. DNA technology now allows rapid identification of specific strains (DNA finger-printing) for epidemiological studies. On the other hand, the industry world-wide is growing rapidly, and there are huge populations of poultry in small geographic areas, making control utilizing biosecurity more and more difficult. Also, multi-age production sites are becoming more common, especially in commercial egg production. This has led to increased usage of live MG vaccines, which are effective in controlling economic losses and may be used as tools in eradication programs.