Time-dependent changes in neurokinin(3) receptors and tachykinins during adjuvant-induced peripheral inflammation in the rat.
Although considerable evidence exists that spinal neurokinin(1) receptors are involved in central sensitization of nociception, recent evidence from knockout studies indicates that other neurokinin receptors in the spinal cord may mediate a portion of the hyperalgesia caused by substance P and neurokinin A. The present study determined whether the second most abundant class of neurokinin receptors, neurokinin(3) receptors, are regulated during persistent peripheral inflammation. Inflammation in the hind paw of the rat was induced by intraplantar injection of complete Freund's adjuvant. Receptor autoradiography revealed specific binding of [125I]-MePhe(7)-NKB, a selective ligand for neurokinin(3) receptors, in the superficial dorsal horn of the spinal cord. Specific binding of [125I]-MePhe(7)-NKB in the medial dorsal horn was reduced bilaterally two days after unilateral injection of complete Freund's adjuvant. Binding returned to basal levels four days after injection of complete Freund's adjuvant. Neurokinin(3) receptor messenger RNA levels doubled in the dorsal spinal cord at 12h and remained elevated for at least four days. The change in neurokinin(3) receptor binding and messenger RNA during adjuvant-induced inflammation may be a consequence of activation of the receptor. Spinal levels of potential endogenous ligands for spinal neurokinin(3) receptors were measured by radioimmunohistochemistry. Immunoreactive substance P but not neurokinin B peptide 2, a marker for neurokinin B, was reduced bilaterally during adjuvant-induced inflammation.Collectively, these data indicate that spinal neurokinin(3) receptors may play a role in spinal neurotransmission of injured rats and require consideration of other tachykinins as physiologically relevant ligands to spinal neurokinin(3) receptors.


Orthopedic advancement of the cleft maxillary segment: a preliminary report.
An intra-oral appliance has been developed that appears to exploit the anteroposterior adjustment potential of the maxillary sutures in the unilateral cleft lip and palate infant. In the treatment of the depressed alar base and dental arch malalignment in six infants, activation of the appliance produced a forward repositioning of the entire cleft maxilla, levelling of the alar bases, and improvement of arch form in a period of from 9 to 20 days. The new positions were retained for at least 10 days, and the appliance was removed one week before surgery. Continued evaluation of the method appears to be warranted.


The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice.
Depression is two-to-three times more frequent among women. The hypothalamus, a sexually dimorphic area, has been implicated in the pathophysiology of depression. Neuroinflammation-induced hypothalamic dysfunction underlies behaviors associated with depression. The lipopolysaccharide (LPS)-induced mouse model of depression has been well-validated in numerous laboratories, including our own, and is widely used to investigate the relationship between neuroinflammation and depression. However, the sex-specific differences in metabolic alterations underlying depression-associated hypothalamic neuroinflammation remain unknown. Here, we employed the LPS-induced mouse model of depression to investigate hypothalamic metabolic changes in both male and female mice using a metabolomics approach. Through bioinformatics analysis, we confirmed the molecular pathways and biological processes associated with the identified metabolites. Furthermore, we employed quantitative real-time PCR, enzyme-linked immunosorbent assay, western blotting, and pharmacological interventions to further elucidate the underlying mechanisms. A total of 124 and 61 differential metabolites (DMs) were detected in male and female mice with depressive-like behavior, respectively, compared to their respective sex-matched control groups. Moreover, a comparison between female and male model mice identified 37 DMs. We capitalized on biochemical clustering and functional enrichment analyses to define the major metabolic changes in these DMs. More than 55% of the DMs clustered into lipids and lipid-like molecules, and an imbalance in lipids metabolism was presented in the hypothalamus. Furthermore, steroidogenic pathway was confirmed as a potential sex-specific pathway in the hypothalamus of female mice with depression. Pregnenolone, an upstream component of the steroid hormone biosynthesis pathway, was downregulated in female mice with depressive-like phenotypes but not in males and had considerable relevance to depressive-like behaviors in females. Moreover, exogenous pregnenolone infusion reversed depressive-like behaviors in female mice with depression. The 5α-reductase type I (SRD5A1), a steroidogenic hub enzyme involved in pregnenolone metabolism, was increased in the hypothalamus of female mice with depression. Its inhibition increased hypothalamic pregnenolone levels and ameliorated depressive-like behaviors in female mice with depression. Our study findings demonstrate a marked sexual dimorphism at the metabolic level in depression, particularly in hypothalamic steroidogenic metabolism, identifying a potential sex-specific pathway in female mice with depressive-like behaviors.


Expression and self-assembly of virus-like particles from porcine parvovirus and its application in antibody detection.
Porcine parvovirus (PPV) is a major causative agent in reproductive pig disease. The swine industry faces a significant economic and epizootic threat; thus, finding a reliable, quick, and practical way to detect it is essential. In this investigation, recombinant PPV VP2 protein was expressed in the Escherichia coli ( E. coli) expression systems. As shown by electron microscopy (TEM), Western blot, and hemagglutination (HA) assays, the recombinant VP2 protein was successfully assembled into virus-like particles (VLPs) after being expressed and purified. These VLPs had a structure that was similar to that of real PPV viruses and also exhibited HA activity. These VLPs induced high levels of PPV-specific antibody titers in mice after immunization, indicating that the VLPs may be beneficial as potential candidate antigens. VLPs were used as the coating antigens for the VLP ELISA, and the PPV VLPs-based ELISA displayed a high sensitivity (99%), specificity (93.0%) and agreement rate (98.3%) compared to HI assay, and the agreement rate of this ELISA was 97.5% compared to a commercial ELISA kit. Within a plate, the coefficient of variation (CV) was 10%, and between ELISA plates, the CV was 15%. According to a cross-reactivity assay, the technique was PPV-specific in contrast to other viral illness sera. The PPV VLP indirect-ELISA test for PPV detection in pigs with an inactivated vaccine showed that the PPV-positive rate varied among different sample sources from 88.2 to 89.6%. Our results indicate that this ELISA technique was quick, accurate, and repeatable and may be used for extensive serological research on PPV antibodies in pigs.


Provider perspectives on treatment decision-making in nephrotic syndrome.
Managing patients with nephrotic syndrome (NS) remains difficult for the practicing nephrologist. This often young patient population is faced with a debilitating, relapsing and remitting disease with non-specific treatment options that are often poorly tolerated. Clinicians managing these complex patients must attempt to apply disease-specific evidence while considering the individual patient's clinical and personal situation. We conducted qualitative interviews to ascertain the provider perspectives of NS, treatment options and factors that influence recommendations for disease management, and administered a survey to assess both facilitators and barriers to the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. When making treatment recommendations, providers considered characteristics of various treatments such as efficacy, side effects and evaluation of risk versus benefit, taking into account how the specific treatment fit with the individual patient. Time constraints and the complexity of explaining the intricacies of NS were noted as significant barriers to care. Although the availability of guidelines was deemed a facilitator to care, the value of the KDIGO guidelines was limited by the perception of poor quality of evidence. The complexity of NS and the scarcity of robust evidence to support treatment recommendations are common challenges reported by nephrologists. Future development and use of shared learning platforms may support the integration of best available evidence, patient/family preferences and exchange of information at a pace that is unconstrained by the outpatient clinic schedule.


Flow chamber and microfluidic approaches for measuring thrombus formation in genetic bleeding disorders.
Platelet adhesion and aggregation, coagulation, fibrin formation, and fibrinolysis are regulated by the forces and flows imposed by blood at the site of a vascular injury. Flow chambers designed to observe these events are an indispensable part of doing hemostasis and thrombosis research, especially with human blood. Microfluidic methods have provided the flexibility to design flow chambers with complex geometries and features that more closely mimic the anatomy and physiology of blood vessels. Additionally, microfluidic systems with integrated optics and/or pressure sensors and on-board signal processing could transform what have been primarily research tools into clinical assays. Here, we describe a historical review of how flow-based approaches have informed biophysical mechanisms in genetic bleeding disorders, challenges and potential solutions for developing models of bleeding in vitro, and outstanding issues that need to be addressed prior to their use in clinical settings.


Gaucher disease ascertained through a Parkinson's center: imaging and clinical characterization.
Among the genes implicated for parkinsonism is glucocerebrosidase (GBA), which causes Gaucher disease (GD). Despite a growing literature that GD may present as parkinsonism, neuroimaging, olfaction, and neuropsychological testing have not been extensively reported. We describe transcranial sonography (TCS), 18F-fluorodopa (F-dopa) and fluorodeoxyglucose (FDG) Positron emission tomography, olfaction testing, neuropsychological testing, and clinical features in homozygous and compound heterozygous GBA mutation carriers identified through screening of 250 Ashkenazi Jewish parkinsonian individuals treated at a tertiary care center. We identified two individuals with N370S/R496H compound heterozygous mutations and two with N370S homozygous mutations; one individual died before completing detailed evaluation. TCS (n = 3) demonstrated nigral hyperechogenicity that was greater than controls [median area maximal substantia nigra echogenicity (aSNmax) = 0.28 cm(2) vs. 0.14 cm(2), P = 0.005], but similar to idiopathic PD (aSNmax = 0.31 cm(2)). FDG PET (n = 2) demonstrated hypermetabolism of the lentiform nuclei, and F-fluorodopa PET (n = 2), bilateral reduction in striatal F-dopa uptake. Olfaction was markedly impaired in the two tested cases, including onset of smell disturbance in adolescence in one. Neuropsychological features (n = 3) were consistent with Parkinson's disease (PD) or diffuse Lewy body disease (DLB). The imaging, neuropsychological and olfactory markers suggest the GD phenotype includes PD with and without features of DLB, marked olfactory loss, nigral hyperechogenicity on TCS, and F-dopa and FDG PET abnormalities.


Sustainable Development Goals and livestock systems.
Within the framework of the Sustainable Development Goals (SDGs) of the United Nations, particularly those that livestock impact most significantly (SDGs 1, 2, 3, 5, 8, 12, 13, 15 and 17), this paper provides an overview of the livestock sector's impact on food system sustainability and opportunities for building solutions through sustainable livestock options that are supported by robust animal health services. The discourse is shaped by the experiences of the Global Agenda for Sustainable Livestock, a multi-stakeholder partnership which facilitates policy dialogue and action among diverse stakeholders to make livestock systems more sustainable. The Global Agenda for Sustainable Livestock adopted the aforementioned SDGs as the reference framework for its actions, which are organised under four domains (food and nutrition security, animal health and welfare, livelihoods and economic growth, and climate and natural resources). These domains are used to highlight the complexity and diversity of the livestock sector, its positive and negative relationships to development, the integral roles of animal health systems and the opportunities for livestock sector contributions towards a sustainable future.


Supporting adoption of the palliative approach toolkit in residential aged care: an exemplar of organisational facilitation for sustainable quality improvement.
Background: National guidelines and resources to support a palliative approach in residential aged care were designed to improve the provision of palliative and end-of-life care; however, implementation has been sporadic.Objective: To support implementation of a palliative approach in aged care using a facilitation training model and existing palliative approach toolkit resources.Methods: Organisation-wide educational intervention delivered by a specialised Palliative Approach Facilitator for 6 months. Training included palliative approach principles, advance care planning, clinical management, equipment use, case conferencing, care planning and self-care.Results: The intervention included 197 internal and external staff and reviewed advanced care plans for 484 clients. Increased staff knowledge and confidence with discussions involving advance care planning, end-of-life care and supporting bereaving families resulted.Conclusion: This targeted intervention addressed barriers to adoption of a palliative approach, representing a flexible training model for building workforce capacity, promoting quality improvement and sustaining best practice in aged care settings.


Chitosan Films for Microfluidic Studies of Single Bacteria and Perspectives for Antibiotic Susceptibility Testing.
Single-cell microfluidics is a powerful method to study bacteria and determine their susceptibility to antibiotic treatment. Glass treatment by adhesive molecules is a potential solution to immobilize bacterial cells and perform microscopy, but traditional cationic polymers such as polylysine deeply affect bacterial physiology. In this work, we chemically characterized a class of chitosan polymers for their biocompatibility when adsorbed to glass. Chitosan chains of known length and composition allowed growth of Escherichia coli cells without any deleterious effects on cell physiology. Combined with a machine learning approach, this method could measure the antibiotic susceptibility of a diversity of clinical strains in less than 1 h and with higher accuracy than current methods. Finally, chitosan polymers also supported growth of Klebsiella pneumoniae, another bacterial pathogen of clinical significance.IMPORTANCE Current microfluidic techniques are powerful to study bacteria and determine their response to antibiotic treatment, but they are currently limited by their complex manipulation. Chitosan films are fully biocompatible and could thus be a viable replacement for existing commercial devices that currently use polylysine. Thus, the low cost of chitosan slides and their simple implementation make them highly versatile for research as well as clinical use.


Optofluidic marine phosphate detection with enhanced absorption using a Fabry-Pérot resonator.
Real-time detection of phosphate has significant meaning in marine environmental monitoring and forecasting the occurrence of harmful algal blooms. Conventional monitoring instruments are dependent on artificial sampling and laboratory analysis. They have various shortcomings for real-time applications because of the large equipment size and high production cost, with low target selectivity and the requirement of time-consuming procedures to obtain the detection results. We propose an optofluidic miniaturized analysis chip combined with micro-resonators to achieve real-time phosphate detection. The quantitative water-soluble components are controlled by the flow rate of the phosphate solution, chromogenic agent A (ascorbic acid solution) and chromogenic agent B (12% ammonium molybdate solution, 80% concentrated sulfuric acid and 8% antimony potassium tartrate solution with a volume ratio of 80 : 18 : 2). Subsequently, an on-chip Fabry-Pérot microcavity is formed with a pair of aligned coated fiber facets. With the help of optical feedback, the absorption of phosphate can be enhanced, which can avoid the disadvantages of the macroscale absorption cells in traditional instruments. It can also overcome the difficulties of traditional instruments in terms of size, parallel processing of numerous samples and real-time monitoring, etc. The absorption cell length is shortened to 300 μm with a detection limit of 0.1 μmol L-1. The time required for detection is shortened from 20 min to 6 seconds. Predictably, microsensors based on optofluidic technology will have potential in the field of marine environmental monitoring.


Doppler ultrasonographic evaluation of splanchnic blood flow in coeliac disease.
Current knowledge on splanchnic haemodynamics in coeliac disease is limited and incomplete. To evaluate splanchnic arterial and venous blood flow in coeliac disease. In 22 coeliac (13 untreated, nine treated) patients and in nine healthy subjects the following variables were assessed: vessel diameter and mean flow velocity in portal vein, splenic vein, superior mesenteric vein, and superior mesenteric artery. Peak systolic velocity, end diastolic velocity and pulsatility index were also determined in the superior mesenteric artery. Five patients of the untreated group were re-evaluated after nine months on a gluten free diet. Significant differences in haemodynamic variables between the three groups were shown only in the superior mesenteric artery. An increase in both mean flow velocity and end diastolic velocity and a reduction in pulsatility index occurred in untreated patients compared with treated patients (p < 0.002; p < 0.04; p < 0.035) and with healthy controls (p < 0.001; p < 0.025; p < 0.0003). Similar results were obtained for the five patients evaluated before and after treatment (p < 0.03; p < 0.02; p < 0.03), in whom the mean flow velocity in the superior mesenteric vein also decreased after treatment (p < 0.05). No significant differences were noted between treated coeliac patients and healthy controls. In untreated coeliac disease there is a hyperdynamic mesenteric circulation that decreases after treatment.


Carbamazepine in the dyscontrol syndrome associated with limbic system dysfunction.
The literature has long demonstrated an association between certain behavioral problems and EEG abnormalities, particularly the association of aggressive and sometimes violent behavior with foci in the temporal lobes. The concept of "dyscontrol syndromes" has also been established and it is possible that some instances of the dyscontrol syndrome arise from an abnormal sensitization of the limbic system, due to disturbance in or near the temporal lobes. Carbamazepine is an interesting new drug, with both anticonvulsant and psychotropic properties, for which both the behavioral effects and pharmacological actions have been defined. The properties of carbamazepine for blocking polysynaptic reflexes and suppressing post-tetanic potentiation are discussed with respect to this limbic system dysfunction in the dyscontrol syndrome. It is also proposed that this drug might be considered for its psychotropic effect in certain instances of dyscontrol, with or without clinical diagnosis of epilepsy. An illustrative case is cited.


Evaluation of a deformable registration algorithm for subsequent lung computed tomography imaging during radiochemotherapy.
Rating both a lung segmentation algorithm and a deformable image registration (DIR) algorithm for subsequent lung computed tomography (CT) images by different evaluation techniques. Furthermore, investigating the relative performance and the correlation of the different evaluation techniques to address their potential value in a clinical setting. Two to seven subsequent CT images (69 in total) of 15 lung cancer patients were acquired prior, during, and after radiochemotherapy. Automated lung segmentations were compared to manually adapted contours. DIR between the first and all following CT images was performed with a fast algorithm specialized for lung tissue registration, requiring the lung segmentation as input. DIR results were evaluated based on landmark distances, lung contour metrics, and vector field inconsistencies in different subvolumes defined by eroding the lung contour. Correlations between the results from the three methods were evaluated. Automated lung contour segmentation was satisfactory in 18 cases (26%), failed in 6 cases (9%), and required manual correction in 45 cases (66%). Initial and corrected contours had large overlap but showed strong local deviations. Landmark-based DIR evaluation revealed high accuracy compared to CT resolution with an average error of 2.9 mm. Contour metrics of deformed contours were largely satisfactory. The median vector length of inconsistency vector fields was 0.9 mm in the lung volume and slightly smaller for the eroded volumes. There was no clear correlation between the three evaluation approaches. Automatic lung segmentation remains challenging but can assist the manual delineation process. Proven by three techniques, the inspected DIR algorithm delivers reliable results for the lung CT data sets acquired at different time points. Clinical application of DIR demands a fast DIR evaluation to identify unacceptable results, for instance, by combining different automated DIR evaluation methods.


Myricetin Inhibits Islet Amyloid Polypeptide (IAPP) Aggregation and Rescues Living Mammalian Cells from IAPP Toxicity.
The aggregation of the amyloidogenic polypeptide IAPP (Islet Amyloid Polypeptide, amylin) is believed to play a direct role in the death of pancreatic β-islet cells in type II diabetes. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the progression of this disease. Here, we investigate myricetin's potential as an inhibitor of IAPP aggregation. We show that myricetin prevented thioflavin T binding in a concentration dependent manner. Atomic force microscopy revealed that myricetin prevented fiber formation under rigorous conditions conducive to forming IAPP aggregates. Using an IAPP-EGFP (Enhanced Green Fluorescent Protein) protein construct, we find that high concentrations of myricetin slowed the in vivo aggregation of IAPP-EGFP. Myricetin was also found to rescue living mammalian cells from the toxic effects of IAPP. These results indicate that myricetin is a strong inhibitor of IAPP amyloid aggregation and a potential lead molecule for the development of an amyloid inhibiting therapeutic.


Chlorpheniramine maleate containing chitosan-based nanoparticle-loaded thermosensitive in situ gel for management in allergic rhinitis.
The aim of the present study was to fabricate a thermosensitive gel containing chlorpheniramine maleate (CPM)-loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan-based nanoparticles were prepared by a precipitation method followed by the addition of developed NPs within the poloxamer 407- and carbopol 934P-based mucoadhesive thermoreversible gel. Developed formulations were evaluated for particle size, PDI, % entrapment efficiency, and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10 ± 0.414%), and highest drug permeation (90.92 ± 0.531%). The optimized formulation NP3 was then formulated into thermoreversible in situ gel. This intensifies the contact between the nasal mucosa and the drug and increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimized formulation on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the management of allergic rhinitis.


Interaction of motion and color in the visual pathways.
In recent years the idea of parallel and independent processing streams for different visual attributes has become a guiding principle for linking the organization, architecture and function of the visual system. Findings concerning the segregation of motion and color information have been at the forefront of the evidence in favor of the parallel processing scheme. A number of studies have shown that motion perception is impaired for isoluminant stimuli, which are thought to isolate the color system. However, there are now many studies, the results of which are incompatible with the simple idea of segregated pathways. We propose two processing streams for motion that differ mostly in their temporal characteristics. Although neither of the two motion streams is color-blind, as was originally suggested, they differ radically in the way they process color information. The view that we propose provides a framework that reconciles a number of seemingly contradictory results. Evidence to support the new framework comes from psychophysical, physiological and lesion studies.


Microfluidic preparation of flexible micro-grippers with precise delivery function.
We used microfluidic technology for preparing gas-liquid Janus emulsions; we firstly proposed a one-step preparation method of micro-grippers and then characterized the function of oriented and precise delivery behavior. Because of the enrichment of Fe3O4 nanoparticles, the micro-gripper can reach a speed of 1.5 mm s-1 driven by a magnetic field. The micro-gripper's body is made of a poly(N-isopropylacrylamide) hydrogel, a reversible temperature-responsive polymer. The thermo-sensitivity of hydrogels offers the function of grasping, to closely integrate with the target carried, ensuring the stability of the carrying process. The reversible variation of the hydrogel allows the micro-gripper to be reusable and have a long shelf life.


Harnessing donor unrestricted T-cells for new vaccines against tuberculosis.
Mycobacterium bovis bacille Calmette-Guérin (BCG) prevents extrapulmonary tuberculosis (TB) and death among infants but fails to consistently and sufficiently prevent pulmonary TB in adults. Thus, TB remains the leading infectious cause of death worldwide, and new vaccine approaches are urgently needed. T-cells are important for protective immunity to Mycobacterium tuberculosis (Mtb), but the optimal T-cell antigens to be included in new vaccines are not established. T-cells are often thought of as responding mainly to peptide antigens presented by polymorphic major histocompatibility complex (MHC) I and II molecules. Over the past two decades, the number of non-peptidic Mtb derived antigens for αβ and γδ T-cells has expanded rapidly, creating broader perspectives about the types of molecules that could be targeted by T-cell-based vaccines against TB. Many of these non-peptide responsive T-cell subsets in humans are activated in a manner that is unrestricted by classical MHC-dependent antigen-presenting systems, but instead require essentially nonpolymorphic presentation systems. These systems are Cluster of differentiation 1 (CD1), MHC related protein 1 (MR1), butyrophilin 3A1, as well as the nonclassical MHC class Ib family member HLA-E. Thus, the resulting T-cell responses can be shared among a genetically diverse population, creating the concept of donor-unrestricted T-cells (DURTs). Here, we review evidence that DURTs are an abundant component of the human immune system and recognize many antigens expressed by Mtb, including antigens that are expressed in BCG and other candidate whole cell vaccines. Further, DURTs exhibit functional diversity and demonstrate the ability to control microbial infection in small animal models. Finally, we outline specific knowledge gaps and research priorities that must be addressed to realize the full potential of DURTs as part of new TB vaccines approaches.


Comparing Arterial- and Venous-Phase Acquisition for Optimization of Virtual Noncontrast Images From Dual-Energy Computed Tomography Angiography.
Follow-up with computed tomographic angiography is recommended after endovascular aneurysm repair, exposing patients to significant levels of radiation and iodine contrast medium. Dual-energy computed tomography allows virtual noncontrast (VNC) images to be reconstructed from contrast-enhanced images using a software algorithm. If the VNC images are a good-enough approximation of true noncontrast (TNC) images, a reduction in radiation dose can be ensured through omitting a TNC scan. To compare image quality of VNC images reconstructed from arterial phase and venous phase dual-energy computed tomographic angiography to TNC images and to assess which one is more suitable to replace TNC images. Sixty-three consecutive patients were examined using a dual-energy computed tomography as elective follow-up after endovascular aneurysm repair. The examination protocol included 1 unenhanced and 2 contrast-enhanced scans (80 kV/Sn140 kV) of the aorta. Virtual noncontrast data sets were reconstructed from the arterial (A-VNC) and venous (V-VNC) phase scans, respectively. Mean attenuation and image noise were measured for TNC, A-VNC, and V-VNC images within regions of interest at 2 levels in the aorta, the liver, retroperitoneal fat, and psoas muscle. Subjective image quality was assessed on a 4-point scale by 2 blinded readers. The differences between A-VNC and TNC, and between A-VNC and V-VNC, were substantial aorta at the level of diaphragm and aorta at the level of renal arteries. The difference between V-VNC and TNC was, on the other hand, very small and not statistically significant for the renal artery aorta. For liver, fat, and muscle tissue, there were significant differences between both A-VNC and V-VNC compared with TNC, but findings were similar between A-VNC and V-VNC. Virtual noncontrast images based on venous-phase scans appear to be a more accurate representation of TNC scans than VNC images based on arterial-phase scans.


Monitoring Physical Activity Levels Using Twitter Data: Infodemiology Study.
Social media technology such as Twitter allows users to share their thoughts, feelings, and opinions online. The growing body of social media data is becoming a central part of infodemiology research as these data can be combined with other public health datasets (eg, physical activity levels) to provide real-time monitoring of psychological and behavior outcomes that inform health behaviors. Currently, it is unclear whether Twitter data can be used to monitor physical activity levels. The aim of this study was to establish the feasibility of using Twitter data to monitor physical activity levels by assessing whether the frequency and sentiment of physical activity-related tweets were associated with physical activity levels across the United States. Tweets were collected from Twitter's application programming interface (API) between January 10, 2017 and January 2, 2018. We used Twitter's garden hose method of collecting tweets, which provided a random sample of approximately 1% of all tweets with location metadata falling within the United States. Geotagged tweets were filtered. A list of physical activity-related hashtags was collected and used to further classify these geolocated tweets. Twitter data were merged with physical activity data collected as part of the Behavioral Risk Factor Surveillance System. Multiple linear regression models were fit to assess the relationship between physical activity-related tweets and physical activity levels by county while controlling for population and socioeconomic status measures. During the study period, 442,959,789 unique tweets were collected, of which 64,005,336 (14.44%) were geotagged with latitude and longitude coordinates. Aggregated data were obtained for a total of 3138 counties in the United States. The mean county-level percentage of physically active individuals was 74.05% (SD 5.2) and 75.30% (SD 4.96) after adjusting for age. The model showed that the percentage of physical activity-related tweets was significantly associated with physical activity levels (beta=.11; SE 0.2; P<.001) and age-adjusted physical activity (beta=.10; SE 0.20; P<.001) on a county level while adjusting for both Gini index and education level. However, the overall explained variance of the model was low (R2=.11). The sentiment of the physical activity-related tweets was not a significant predictor of physical activity level and age-adjusted physical activity on a county level after including the Gini index and education level in the model (P>.05). Social media data may be a valuable tool for public health organizations to monitor physical activity levels, as it can overcome the time lag in the reporting of physical activity epidemiology data faced by traditional research methods (eg, surveys and observational studies). Consequently, this tool may have the potential to help public health organizations better mobilize and target physical activity interventions.


Putting a price on education: hours and dollars for a general surgery curriculum.
In 2005, a new curricular model was implemented for general surgery residents and a Division of Education created for administrative support. These changes forced an evaluation of available resources to maintain a new curricular model. A retrospective review of resources expended during curricular sessions (June 2007-June 2008) provided to 42 surgical residents was conducted. Resources were evaluated in terms of the number, division, department, and rank of faculty involved. Contact hours and monetary costs were calculated. Total numbers of faculty involved in the postgraduate year (PGY)1, PGY2, and PGY3-5 curriculums were 79, 39, and 22, respectively. Faculty teaching time was 321 hours (PGY1), 187 hours (PGY2) and 36 hours (PGY3-5) for a combined 544 hours. Average teaching time commitment for faculty in the Division of Education was 26.5 hours, compared with 6.7 hours for departmental faculty in other divisions (P = .0002). Total monetary cost was $219,254. The cost to maintain an educational general surgery curriculum is substantial and administrative support must be considered. Faculty with an explicit teaching commitment and responsibility are needed.


[Intracranial pressure measurement in large skull defects].
We measured the intracranial pressure continuously for a period of four days before and after cranioplasty in 12 patients with skull defects larger than 100 cm2. The results were obtained by epidural monitoring. The device used was the "Hellige" pressure measuring device (modified according to Gobiet). We found an increased cranial pressure in more than half of the patients (7). In addition the same patients showed the most marked neurologic and psychic changes. A significant return to normal of the intracranial pressure was noticed in all these patients after the closure of the skull defect. Progressive improvement in the clinical symptoms was also seen. The pathogenesis of this phenomenon has not been completely explained. Several authors consider that an important factor is the difference between the intracranial and the atmospheric pressure, However, we suggest that another important factor is the cicatricial changes ("scar plate") occurring between the cortex, dura and the skin, which exerts pressure on the skull contents. Previously, the neurological symptoms which appeared after a period of time in patients with large skull defects were attributed to other causes. It is only during the past decades--thanks to progress in neuroradiologic diagnostics--that a pathoanatomical correlate been found for these changes.


Diabetes Risk Reduction Diet and Endometrial Cancer Risk.
Diabetes increases endometrial cancer risk. We investigated the role of a diabetes risk reduction diet (DRRD) on the risk of endometrial cancer using data from a multicentric, Italian hospital-based case-control study (1992-2006) enrolling 454 histologically confirmed cases of endometrial cancer and 908 controls matched by age and center. We derived a DRRD score assigning higher scores for higher intakes of cereal fiber, fruit, coffee, polyunsaturated:saturated fatty acid ratio, and nuts and for lower glycemic load and lower intakes of red/processed meat and sugar-sweetened beverages/fruit juices. The odds ratios (OR) of endometrial cancer according to the DRRD score were derived by multiple conditional logistic regression models. The OR for high (DRRD score >24, i.e., third tertile) versus medium-low adherence to the DRRD was 0.73 (95% confidence interval, CI, 0.55-0.97). Similar results were observed after the exclusion of diabetic women (OR 0.75; 95% CI, 0.56-1.00) and allowance for total vegetable consumption (OR 0.80; 95% CI, 0.60-1.07). Inverse associations were observed in most of the analyzed subgroups. The OR for high DRRD combined with high vegetable consumption was 0.45 (95% CI, 0.28-0.73). Our results suggest that diets able to reduce diabetes risk may also reduce endometrial cancer risk. High vegetable consumption combined with high adherence to the DRRD may provide additional benefit in endometrial cancer prevention.


Molecular characterization of replication-competent variants of adenovirus vectors and genome modifications to prevent their occurrence.
Adenovirus (Ad) vectors for gene therapy are made replication defective by deletion of E1 region genes. For isolation, propagation, and large-scale production of such vectors, E1 functions are supplied in trans from a stable cell line. Virtually all Ad vectors used for clinical studies are produced in the 293 cell, a human embryonic kidney cell line expressing E1 functions from an integrated segment of the left end of the Ad type 5 (Ad5) genome. Replication-competent vector variants that have regained E1 sequences have been observed within populations of Ad vectors grown on 293 cells. These replication-competent variants presumably result from recombination between vector and 293 cell Ad5 sequences. We have developed Ad2-based vectors and have characterized at the molecular level examples of replication-competent variants. All such variants analyzed are Ad2-Ad5 chimeras in which the 293 cell Ad5 E1 sequences have become incorporated into the viral genome by legitimate recombination events. A map of Ad5 sequences within the 293 cell genome developed in parallel is consistent with the proposed recombination events. To provide a convenient vector production system that circumvents the generation of replication-competent variants, we have modified the Ad2 vector backbone by deleting or rearranging the protein IX coding region normally present downstream from the E1 region such that the frequency of recombination between vector and 293 cell Ad5 sequences is greatly reduced. Twelve serial passages of an Ad2 vector lacking the protein IX gene were carried out without generating replication-competent variants. In the course of producing and testing more than 30 large-scale preparations of vectors lacking the protein IX gene or having a rearranged protein IX gene, only three examples of replication-competent variants were observed. Use of these genome modifications allows use of conventional 293 cells for production of large-scale preparations of Ad-based vectors lacking replication-competent variants.


The single Marchantia polymorpha FERONIA homolog reveals an ancestral role in regulating cellular expansion and integrity.
Plant cells are surrounded by a cell wall, a rigid structure that is not only important for cell and organ shape, but is also crucial for intercellular communication and interactions with the environment. In the flowering plant Arabidopsis thaliana, the 17 members of the Catharanthus roseus RLK1-like (CrRLK1L) receptor kinase family are involved in a multitude of physiological and developmental processes, making it difficult to assess their primary or ancestral function. To reduce genetic complexity, we characterized the single CrRLK1L gene of Marchantia polymorpha, MpFERONIA (MpFER). Plants with reduced MpFER levels show defects in vegetative development, i.e. rhizoid formation and cell expansion, and have reduced male fertility. In contrast, cell integrity and morphogenesis of the gametophyte are severely affected in Mpfer null mutants and MpFER overexpression lines. Thus, we conclude that the CrRLK1L gene family originated from a single gene with an ancestral function in cell expansion and the maintenance of cellular integrity. During land plant evolution, this ancestral gene diversified to fulfill a multitude of specialized physiological and developmental roles in the formation of both gametophytic and sporophytic structures essential to the life cycle of flowering plants.


Spin torque control of antiferromagnetic moments in NiO.
For a long time, there were no efficient ways of controlling antiferromagnets. Quite a strong magnetic field was required to manipulate the magnetic moments because of a high molecular field and a small magnetic susceptibility. It was also difficult to detect the orientation of the magnetic moments since the net magnetic moment is effectively zero. For these reasons, research on antiferromagnets has not been progressed as drastically as that on ferromagnets which are the main materials in modern spintronic devices. Here we show that the magnetic moments in NiO, a typical natural antiferromagnet, can indeed be controlled by the spin torque with a relatively small electric current density (~4 × 107 A/cm2) and their orientation is detected by the transverse resistance resulting from the spin Hall magnetoresistance. The demonstrated techniques of controlling and detecting antiferromagnets would outstandingly promote the methodologies in the recently emerged "antiferromagnetic spintronics". Furthermore, our results essentially lead to a spin torque antiferromagnetic memory.


The mRNA and RNA-copy pseudogenes encoding TM30nm, a human cytoskeletal tropomyosin.
We have determined the sequence of a 2.5 kb mRNA in human fibroblasts encoding a 248 amino acid cytoskeletal tropomyosin. The protein product of this mRNA is TM30nm, one of five tropomyosin-like proteins in human fibroblasts. The structural gene encoding this mRNA can also produce a 1.3 kb mRNA encoding a 285 amino acid skeletal muscle alpha-tropomyosin by tissue-specific alternative mRNA splicing. However, the multiple RNA-copy pseudogenes of this gene family are derived largely if not exclusively from transcripts processed according to the pattern observed in non-muscle cells.


The effects of accelerated growth rates and estrogen implants in prepubertal Holstein heifers on growth, feed efficiency, and blood parameters.
Sixty-eight Holstein heifers were used to determine the effects of accelerated growth rates by increased nutrient intake and estrogen implants on feed efficiency, structural growth, and blood parameters in heifers between 19 and 39 wk of age. At the beginning of the treatment period, the heifers were assigned to one of four treatment groups by using a randomized complete block design in a 2 x 2 factorial arrangement. The treatments were standard growth rate (700 g/d), accelerated growth rate (1000 g/d), standard growth rate with an estradiol implant, and accelerated growth rate with an estradiol implant. All heifers received the same diet, but dry matter intake was adjusted weekly to achieve the target rate of gain. Accelerating heifer growth rates from 705 to 1007 g/d improved feed efficiency 5.1%, increased the rate of withers height, heart girth, and hip width growth 12, 27, and 27%, respectively, and body condition scores 0.25 points. Estradiol implants improved feed efficiency 2.4% and decreased the rate of withers height 6% and heart girth growth 3.5%. Increased nutrient intake and average daily gain depressed mean plasma growth hormone and urea nitrogen content 17 and 7%, respectively, while elevating insulin-like growth factor-1 levels by 10%. Estradiol implants increased mean plasma growth hormone content by 29% and insulin-like growth factor-1 levels by 17%, but decreased urea nitrogen content by 11%. Feeding prepubertal heifers for accelerated growth rates increased structural growth with a small increase in body condition, whereas estradiol implants improved feed efficiency and decreased the growth rate of withers height and heart girth without affecting the rate of hip width growth.


Respiratory syncytial virüs infections in neonates and infants.
Respiratory syncytial virus is one of the major causes of respiratory tract infections during infancy with high rates of hospitalization and mortality during the first years of life. It is the most common cause of acute bronchiolitis and viral pneumonia in children below two years of age and second the most common cause of postneonatal infant mortality all around the world following malaria. In addition, the virus has been causally linked to recurrent wheezing and associated with pediatric asthma. The respiratory syncytial virus infections tend to be severe in high risk patients such as patients below six months of age, with prematurity, congenital heart diseases, neuromuscular diseases and immune deficiencies. No specific treatment is available for respiratory syncytial virus infections to date. Severe cases require supportive therapy, mainly oxygen supplementation and hydration, and less frequently, ventilatory support. Because there is no vaccine to prevent respiratory syncytial virus infections or clinically effective treatment to administer to children with respiratory syncytial virus infection, immunoprophylaxis with palivizumab is currently the only method for reducing morbidity associated with severe respiratory syncytial virus in high-risk infants.


Interchangeability of stress and amphetamine in sensitization.
In view of similarities between the behavioral, biochemical, and electrophysiological effects of amphetamine and stress, we tested the hypothesis that presentation of a stressor, mild tail pressure, can sensitize an animal to the later effects of amphetamine, and vice versa. Our findings supported this hypothesis and suggest that amphetamine and at least some stressors may be interchangeable in their ability to induce a sensitization. The data raise the possibility that stress might be a common variable contributing to both amphetamine psychosis and some forms of schizophrenia.


Improving mixed-integer temporal modeling by generating synthetic data using conditional generative adversarial networks: A case study of fluid overload prediction in the intensive care unit.
The challenge of mixed-integer temporal data, which is particularly prominent for medication use in the critically ill, limits the performance of predictive models. The purpose of this evaluation was to pilot test integrating synthetic data within an existing dataset of complex medication data to improve machine learning model prediction of fluid overload. This retrospective cohort study evaluated patients admitted to an ICU ≥ 72 h. Four machine learning algorithms to predict fluid overload after 48-72 h of ICU admission were developed using the original dataset. Then, two distinct synthetic data generation methodologies (synthetic minority over-sampling technique (SMOTE) and conditional tabular generative adversarial network (CTGAN)) were used to create synthetic data. Finally, a stacking ensemble technique designed to train a meta-learner was established. Models underwent training in three scenarios of varying qualities and quantities of datasets. Training machine learning algorithms on the combined synthetic and original dataset overall increased the performance of the predictive models compared to training on the original dataset. The highest performing model was the meta-model trained on the combined dataset with 0.83 AUROC while it managed to significantly enhance the sensitivity across different training scenarios. The integration of synthetically generated data is the first time such methods have been applied to ICU medication data and offers a promising solution to enhance the performance of machine learning models for fluid overload, which may be translated to other ICU outcomes. A meta-learner was able to make a trade-off between different performance metrics and improve the ability to identify the minority class.


Diagnostic tests based on human basophils: more potentials and perspectives than pitfalls. II. Technical issues.
Cellular basophil activation tests (BAT) such as histamine or sulfidoleukotriene-release tests for allergy diagnosis have been available for some time, but expression of basophil-activation markers such as CD63 and CD203c detected by flow cytometry has attracted particular attention in recent years. Not only the potential but also the possible pitfalls of flow-cytometric BAT have been stressed recently. Some authors have suggested that the technical problems are still such that BAT should only be performed in specialist laboratories. In an earlier review based on our clinical experience obtained over several years, we showed that, even using different protocols, reproducible and meaningful clinical results can be obtained. In this paper, we review the current knowledge in relation to several technical issues and show that flow-cytometric BAT already represents a major advance in the field of in vitro allergy diagnosis. We conclude that there are no serious technical justifications for depriving allergic patients of clinically indicated BAT tests, which can be performed reliably by any laboratory with the appropriate experience in allergy diagnosis and flow cytometry.


Epigenetic regulation of WNT signaling pathway genes in inflammatory bowel disease (IBD) associated neoplasia.
WNT signaling pathway dysregulation is an important event in the pathogenesis of colorectal cancer (CRC) with APC mutations seen in more than 80% of sporadic CRC. However, such mutations in the WNT signaling pathway genes are rare in inflammatory bowel disease (IBD) associated neoplasia (dysplasia and cancer). This study examined the role of epigenetic silencing of WNT signaling pathway genes in the pathogenesis of IBD-associated neoplasia. Paraffin-embedded tissue samples were obtained and methylation of ten WNT signaling pathway genes, including APC1A, APC2, SFRP1, SFRP2, SFRP4, SFRP5, DKK1, DKK3, WIF1 and LKB1, was analyzed. Methylation analysis was performed on 41 IBD samples, 27 normal colon samples (NCs), and 24 sporadic CRC samples. Methylation of WNT signaling pathway genes is a frequent and early event in IBD and IBD-associated neoplasia. A progressive increase in the percentage of methylated genes in the WNT signaling pathway from NCs (4.2%) to IBD colitis (39.7%) to IBD-associated neoplasia (63.4%) was seen (NCs vs. IBD colitis, p < 0.01; IBD colitis vs. IBD-associated neoplasia, p = 0.01). In the univariate logistic regression model, methylation of APC2 (OR 4.7, 95% CI: 1.1-20.63, p = 0.04), SFRP1 (OR 5.1, 95% CI: 1.1-31.9, p = 0.04), and SFRP2 (OR 5.1, 95% CI: 1.1-32.3, p = 0.04) was associated with progression from IBD colitis to IBD-associated neoplasia, while APC1A methylation was borderline significant (OR 4.1, 95% CI: 0.95-17.5, p = 0.06). In the multivariate logistic regression model, methylation of APC1A and APC2 was more likely to be associated with IBD-associated neoplasia than IBD colitis. (OR APC1A: 6.4, 95% CI: 1.1-37.7 p = 0.04; OR APC2 9.1, 95% CI: 1.3-61.7, p = 0.02). Methylation of the WNT signaling genes is an early event seen in patients with IBD colitis and there is a progressive increase in methylation of the WNT signaling genes during development of IBD-associated neoplasia. Moreover, methylation of APC1A, APC2, SFRP1, and SFRP2 appears to mark progression from IBD colitis to IBD-associated neoplasia, and these genes may serve as biomarkers for IBD-associated neoplasia.


Use of floating seals to exclude oxygen penetration in non-aerated selectors.
It is widely assumed that non-aerated selectors are very efficient in nutrient removal, and especially anaerobic basins may largely contribute to good sludge settleability as well. However, based on results measured in full-scale, this paper draws attention to the fact that with decreasing availability of readily biodegradable carbon source (rbCOD) being experienced worldwide, oxygen penetration into non-aerated basins through the uncovered surface may no longer be considered negligible. When the oxygen mass transfer is significant compared to the available influent rbCOD, non-aerated selectors should be regarded as basins with low dissolved oxygen (low DO) concentrations that may underperform with respect to nutrient removal and favor the growth of filaments, especially during low-loaded conditions. In order to fully exclude oxygen penetration, floating seals have been developed and applied at the North-Budapest Wastewater Treatment Plant in Hungary. Comparative full-scale studies showed prevention of significant amounts of influent rbCOD loss (up to 60 mg/L) through the application of this new technology. This amount of saved, non-oxidised but fermented carbon source could be accordingly used for enhancing biological P-removal. Due to the elimination of microaerophilic conditions, the undesirable growth of filamentous bacteria could also be avoided, leading to significantly better activated sludge settling.


Multi-Atlas Segmentation for Abdominal Organs with Gaussian Mixture Models.
Abdominal organ segmentation with clinically acquired computed tomography (CT) is drawing increasing interest in the medical imaging community. Gaussian mixture models (GMM) have been extensively used through medical segmentation, most notably in the brain for cerebrospinal fluid/gray matter/white matter differentiation. Because abdominal CT exhibit strong localized intensity characteristics, GMM have recently been incorporated in multi-stage abdominal segmentation algorithms. In the context of variable abdominal anatomy and rich algorithms, it is difficult to assess the marginal contribution of GMM. Herein, we characterize the efficacy of an a posteriori framework that integrates GMM of organ-wise intensity likelihood with spatial priors from multiple target-specific registered labels. In our study, we first manually labeled 100 CT images. Then, we assigned 40 images to use as training data for constructing target-specific spatial priors and intensity likelihoods. The remaining 60 images were evaluated as test targets for segmenting 12 abdominal organs. The overlap between the true and the automatic segmentations was measured by Dice similarity coefficient (DSC). A median improvement of 145% was achieved by integrating the GMM intensity likelihood against the specific spatial prior. The proposed framework opens the opportunities for abdominal organ segmentation by efficiently using both the spatial and appearance information from the atlases, and creates a benchmark for large-scale automatic abdominal segmentation.


Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte trafficking.
The effective onset of adaptive immune responses requires that naïve antigen-specific lymphocytes, being inherently rare throughout the body, rapidly encounter foreign antigens. This problem has been elegantly solved in evolution by inventing secondary lymphoid tissues as intersections in the migratory pathway of antigen-presenting dendritic cells and antigen-specific lymphocytes. Chemokines play a central role in guiding cell movements in the course of immune responses and in lymphoid system homeostasis. In particular, the chemokine receptors CCR7 and CXCR5 are key molecules for the entry of lymphocytes and dendritic cells into secondary lymphoid organs and their homing to T-cell and B-cell zones therein. CCR7 and CXCR5 are differentially expressed on the cell surface of lymphocytes and dendritic cells depending on the stage of cellular differentiation and activation, thus allowing these cells to change their homing capacity and prospective traffic routes.


Therapeutic Effects of 6-Gingerol, 8-Gingerol, and 10-Gingerol on Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in Rats.
Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-gingerol, 8-gingerol, and 10-gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-gingerol, and 10-gingerol were then given intraperitoneally at doses of 30 mg kg-1 d-1 for another 7 days, respectively. Body weight change, disease activity index, inflammatory cytokines, and oxidative stress indices were measured, and the colonic tissue injuries were assessed macroscopically and histopathologically. Results showed that all three gingerols attenuated colitic symptoms evoked by dextran sulfate sodium, significantly elevated superoxide dismutase activity, decreased malondialdehyde levels and myeloperoxidase activity in the colon tissue, and markedly reduced the content of tumor necrosis factor alpha and Interleukin 1 beta in the serum. Histological observations showed that all three gingerols obviously accelerated mucosal damage healing. It is concluded that 6-gingerol, 8-gingerol, and 10-gingerol, the three analogues, have a strong and relatively equal efficacy in the treatment of colitis. Copyright © 2017 John Wiley & Sons, Ltd.


Monitoring glucose control.
Type 2 diabetes is increasing in prevalence and is predominantly managed in general practice. This series contains case histories raising some of the metabolic problems which may be encountered in the management of these patients and indicates some of the many issues, other than glycaemic control, that need to be considered.


Classical and quantum ordering of protons in cold solid hydrogen under megabar pressures.
A combination of state-of-the-art theoretical methods has been used to obtain an atomic-level picture of classical and quantum ordering of protons in cold high-pressure solid hydrogen. We focus mostly on phases II and III of hydrogen, exploring the effects of quantum nuclear motion on certain features of these phases (through a number of ab initio path integral molecular dynamics (PIMD) simulations at particular points on the phase diagram). We also examine the importance of van der Waals forces in this system by performing calculations using the optB88-vdW density functional, which accounts for non-local correlations. Our calculations reveal that the transition between phases I and II is strongly quantum in nature, resulting from a competition between anisotropic inter-molecular interactions that restrict molecular rotation and thermal plus quantum fluctuations of the nuclear positions that facilitate it. The transition from phase II to III is more classical because quantum nuclear motion plays only a secondary role and the transition is determined primarily by the underlying potential energy surface. A structure of P2(1)/c symmetry with 24 atoms in the primitive unit cell is found to be stable when anharmonic quantum nuclear vibrational motion is included at finite temperatures using the PIMD method. This structure gives a good account of the infra-red and Raman vibron frequencies of phase II. We find additional support for a C2/c structure as a strong candidate for phase III, since it remains transparent up to 300 GPa, even when quantum nuclear effects are included. Finally, we find that accounting for van der Waals forces improves the agreement between experiment and theory for the parts of the phase diagram considered, when compared to previous work which employed the widely-used Perdew-Burke-Ernzerhof exchange-correlation functional.


Staying Active While Staying Home: The Use of Physical Activity Technologies During Life Disruptions.
One impact of the Covid-19 lockdowns was a restriction on people's ability to engage in physical activity in previously routine ways. This paper presents a two-stage mixed-method study exploring how people used technology to stay physically active during this period. We found that activity trackers reminded people to be active, while virtual coaching (i.e., video tutorials and online classes) helped them stay connected. The lockdown increased people's awareness of their activity levels and removed barriers to exercise, for example by giving them greater control over their time. However, it also created new challenges, with lack of time and space, injuries due to sudden changes in activity, and anxiety around lockdown, putting limits on physical activity. We highlight future directions that must be addressed to maximise the benefits of physical activity technologies for people trying to stay active during major life disruptions.


Intradermal immunization triggers epidermal Langerhans cell mobilization required for CD8 T-cell immune responses.
The potential of the skin immune system for the generation of both powerful humoral and cellular immune responses is now well established. However, the mechanisms responsible for the efficacy of skin antigen-presenting cells (APCs) during intradermal (ID) vaccination still remain to be elucidated. We have previously demonstrated in clinical trials that preferential targeting of Langerhans cells (LCs) by transcutaneous immunization shapes the immune response toward vaccine-specific CD8 T cells. Others have shown that ID inoculation of a vaccine, which targets dermal APCs, mobilizes both the cellular and humoral arms of immunity. Here, we investigated the participation of epidermal LCs in response to ID immunization. When human or mouse skin was injected ID with a particle-based vaccine, we observed significant modifications in the morphology of epidermal LCs and their mobilization to the dermis. We further established that this LC recruitment after ID administration was essential for the induction of antigen-specific CD8 T cells, but was, however, dispensable for the generation of specific CD4 T cells and neutralizing antibodies. Thus, epidermal and dermal APCs shape the outcome of the immune responses to ID vaccination. Their combined potential provides new avenues for the development of vaccination strategies against infectious diseases.


Biologic significance of polyunsaturated fatty acids in the skin.
Deficiency of essential fatty acid (EFA) containing linoleic acid (18:2n-6) in humans or animals induces morphologic changes characterized by severe scaly dermatosis, extensive percutaneous water loss, and hyperproliferation of the epidermis. Microscopically, the epidermis is characterized by hyperkeratosis and acanthosis. The refeeding of safflower oil containing linoleic acid or primrose oil (containing linoleic acid [18:2n-6] and gamma-linolenic acid [18:3n-6]) acids to EFA-deficient guinea pigs reverses the EFA-deficiency symptoms. In contrast, replacement of safflower oil with menhaden fish oil, (containing eicosapentaenoic acid [20:5n-3] and docosahexaenoic acid [22:6n-3]) did not reverse the symptoms of EFA deficiency. These results indicate: (1) that an understanding of the roles of vegetable or fish oil in skin must evolve from an understanding of the roles of each constituent n-6 or n-3 fatty acid, and (2) that the n-3 fatty acids may function to modulate the metabolism and function of the n-6 fatty acids in vivo.


Linking occupational conditions to physical health through marital, social, and intrapersonal processes.
In the present longitudinal study of 330 married men and 300 married women, we use a comprehensive structural equation model to investigate how occupation is linked to physical health. Results show that occupational quality influences health-risk behavior (measured by composite indices) for both men and women through a series of mediating variables: social integration, marital integration, and psychological control. Health-risk behavior is related to adverse change in physical health status over a two-year period. Occupational quality influences social and marital integration and psychological control for both husbands and wives. Social integration and marital integration also enhance husbands' psychological control, but marital integration is the only factor contributing to wives' psychological control. In turn, psychological control is associated with health-risk behaviors for both husbands and wives. In addition, both social and marital integration directly deter husbands' health-risk behaviors, while social integration is the only variable to directly influence wives' health-risk behaviors.


A conserved mechanism of GABA binding and antagonism is revealed by structure-function analysis of the periplasmic binding protein Atu2422 in Agrobacterium tumefaciens.
Bacterial periplasmic binding proteins (PBPs) and eukaryotic PBP-like domains (also called as Venus flytrap modules) of G-protein-coupled receptors are involved in extracellular GABA perception. We investigated the structural and functional basis of ligand specificity of the PBP Atu2422, which is implicated in virulence and transport of GABA in the plant pathogen Agrobacterium tumefaciens. Five high-resolution x-ray structures of Atu2422 liganded to GABA, Pro, Ala, and Val and of point mutant Atu2422-F77A liganded to Leu were determined. Structural analysis of the ligand-binding site revealed two essential residues, Phe(77) and Tyr(275), the implication of which in GABA signaling and virulence was confirmed using A. tumefaciens cells expressing corresponding Atu2422 mutants. Phe(77) restricts ligand specificity to α-amino acids with a short lateral chain, which act as antagonists of GABA signaling in A. tumefaciens. Tyr(275) specifically interacts with the GABA γ-amino group. Conservation of these two key residues in proteins phylogenetically related to Atu2422 brought to light a subfamily of PBPs in which all members could bind GABA and short α-amino acids. This work led to the identification of a fingerprint sequence and structural features for defining PBPs that bind GABA and its competitors and revealed their occurrence among host-interacting proteobacteria.


Terminal cognitive decline: accelerated loss of cognition in the last years of life.
To test the hypothesis that rate of cognitive decline accelerates in the last years of life. Participants are 853 older persons without dementia at study onset. For up to 8 years, they underwent annual clinical evaluations that included a battery of 19 cognitive tests from which previously established composite measures of global cognition and specific cognitive domains were derived. In analyses, we used linear mixed-effects models that allowed rate of cognitive decline to change at a given point before death to estimate the onset of a terminal decline period and rate of cognitive decline before and after that point. In subsequent analyses, we tested potential modifiers of terminal decline. There were 115 deaths. Those who died did not differ from survivors in their level of global cognitive function at study onset, but beginning a mean of 42 months before death, their rate of global cognitive decline sharply increased. The duration and rapidity of terminal decline in global cognition differed from person to person. Terminal cognitive decline was not modified by age, sex, education, or the presence of mild cognitive impairment, but it was not present in those with vascular disease (e.g., stroke and heart attack) or in those without at least one copy of the apolipoprotein E epsilon4 allele, suggesting that Alzheimer's disease pathology may contribute to the phenomenon. In old age, cognitive decline markedly accelerates during the last 3 to 4 years of life, consistent with the terminal decline hypothesis.


[Results of inferior oblique muscle surgery in superior oblique paralysis].
The aim of this study was to evaluate the results of inferior oblique muscle recession in certain cases of superior oblique paralysis. Twenty-three patients with moderate hyperaction of the inferior oblique muscle, secondary to paralysis of the superior oblique muscle, in whom a recession of the ipsilateral inferior oblique was applied were enrolled in this study. These cases were selected among those with congenital superior oblique paralysis and infantile nontraumatic paralysis and those of unknown origin. Isolated recession of the inferior oblique muscle achieved a mean decrease in 8.69 +/- 2.05 D in hypertropia in the primary position. In 19 cases out of 23 (82.6%) who received isolated recession of the inferior oblique muscle, a vertical deviation equal to or less than 4 PD was obtained, showing the efficacy of this method in the surgical treatment of the cases with superior oblique paralysis and a moderate inferior oblique hyperaction.


Acute volume loading and exercise capacity in postural tachycardia syndrome.
Postural tachycardia syndrome (POTS) is associated with exercise intolerance, hypovolemia, and cardiac atrophy, which may contribute to reduced stroke volume and compensatory exaggerated heart rate (HR) increases. Acute volume loading with intravenous (iv) saline reduces HR and improves orthostatic tolerance and symptoms in POTS, but its effect on exercise capacity is unknown. In this study, we determined the effect of iv saline infusion on peak exercise capacity (VO2peak) in POTS. Nineteen patients with POTS participated in a sequential study. VO2peak was measured on two separate study days, following administration of placebo or 1 liter of i.v. saline (NaCl 0.9%). Patients exercised on a semirecumbent bicycle with resistance increased by 25 W every 2 min until maximal effort was achieved. Patients exhibited blood volume deficits (-13.4 ± 1.4% ideal volume), consistent with mild to moderate hypovolemia. At baseline, saline significantly increased stroke volume (saline 80 ± 8 ml vs. placebo 64 ± 4 ml; P = 0.010), increased cardiac output (saline 6.9 ± 0.5 liter/min vs. placebo 5.7 ± 0.2 liter/min; P = 0.021), and reduced systemic vascular resistance (saline 992.6 ± 70.0 dyn-s/cm(5) vs. placebo 1,184.0 ± 50.8 dyn-s/cm(5); P = 0.011), with no effect on HR or blood pressure. During exercise, saline did not produce differences in VO2peak (saline 26.3 ± 1.2 mg·kg(-1)·min(-1) vs. placebo 27.7 ± 1.8 mg·kg(-1)·min(-1); P = 0.615), peak HR [saline 174 ± 4 beats per minute (bpm) vs. placebo 175 ± 3 bpm; P = 0.672] or other cardiovascular parameters. These findings suggest that acute volume loading with saline does not improve VO2peak or cardiovascular responses to exercise in POTS, despite improvements in resting hemodynamic function.


Assessing the current status of tobacco dependence education curricula in U.S. physician assistant programs.
Tobacco use continues to be the single most preventable cause of death and disease in the United States. A paradigm shift is needed in physician assistant (PA) education to address tobacco dependence as a chronic, relapsing disease requiring patient education, counseling, treatment, and follow-up. A national study was conducted to assess the existing tobacco dependence education currently offered in U.S. PA programs. An established tobacco dependence curriculum survey was revised and mailed to the 141 accredited PA programs in the United States during the 2008-2009 academic year. The survey asked respondents to report the following with regard to tobacco dependence education content in their PA program; (1) Perceived self-efficacy and barriers; (2) Medical topics covered and minutes spent; (3) Evaluation of students' competency level; (4) Tobacco courses, topics, and resources used; and (5) Level of tobacco-cessation competency expected upon graduation. A total of 79 surveys were returned (56% response rate). Though, on average, over 827 minutes (14 hours) were devoted to tobacco dependence education curriculum, most minutes (223 minutes) were spent on the health effects of tobacco use, with only 42 minutes spent on cessation counseling, 55 minutes on medications, and 13 minutes on integrating tobacco-cessation into clinical practice. PA educators have the unique opportunity to affect tobacco-related morbidity and mortality. The present study demonstrates that PA instructors are more than adequately teaching students about tobacco use. However, it is not clear if students are being adequately taught how to assist patients to quit using tobacco.


Proteinase activity and stability of natural bromelain preparations.
Bromelain is a complex mixture of proteinases typically derived from pineapple stem. Similar proteinases are also present in pineapple fruit. Beneficial therapeutic effects of bromelain have been suggested or proven in several human inflammatory diseases and animal models of inflammation, including arthritis and inflammatory bowel disease. However, it is not clear how each of the proteinases within bromelain contributes to its anti-inflammatory effects in vivo. Previous in vivo studies using bromelain have been limited by the lack of assays to control for potential differences in the composition and proteolytic activity of this naturally derived proteinase mixture. In this study, we present model substrate assays and assays for cleavage of bromelain-sensitive cell surface molecules can be used to assess the activity of constituent proteinases within bromelain without the need for biochemical separation of individual components. Commercially available chemical and nutraceutical preparations of bromelain contain predominately stem bromelain. In contrast, the proteinase activity of pineapple fruit reflects its composition of fruit bromelain>ananain approximately stem bromelain. Concentrated bromelain solutions (>50 mg/ml) are more resistant to spontaneous inactivation of their proteolytic activity than are dilute solutions, with the proteinase stability in the order of stem bromelain>fruit bromelain approximately ananain. The proteolytic activity of concentrated bromelain solutions remains relatively stable for at least 1 week at room temperature, with minimal inactivation by multiple freeze-thaw cycles or exposure to the digestive enzyme trypsin. The relative stability of concentrated versus dilute bromelain solutions to inactivation under physiologically relevant conditions suggests that delivery of bromelain as a concentrated bolus would be the preferred method to maximize its proteolytic activity in vivo.


Optical properties of mice skull bone in the 455- to 705-nm range.
Rodent brain is studied to understand the basics of brain function. The activity of cell populations and networks is commonly recorded in vivo with wide-field optical imaging techniques such as intrinsic optical imaging, fluorescence imaging, or laser speckle imaging. These techniques were recently adapted to unrestrained mice carrying transcranial windows. Furthermore, optogenetics studies would benefit from optical stimulation through the skull without implanting an optical fiber, especially for longitudinal studies. In this context, the knowledge of bone optical properties is requested to improve the quantitation of the depth and volume of imaged or stimulated tissues. Here, we provide experimental measurements of absorption and reduced scattering coefficients of freshly excised mice skull for wavelengths between 455 and 705 nm. Absorption coefficients from 6 to 8 months mice skull samples range between 1.67 ± 0.28 ?? mm ? 1 at 455 nm and 0.47 ± 0.07 ?? mm ? 1 at 705 nm, whereas reduced scattering coefficients were in the range of 2.79 ± 0.26 ?? mm ? 1 at 455 nm up to 2.29 ± 0.12 ?? mm ? 1 at 705 nm. In comparison, measurements carried out on 4 to 5 weeks mice showed similar spectral profiles but smaller absorption and reduced scattering coefficients by a factor of about 2 and 1.5, respectively.


Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: a receptor for human placental infection.
Malaria during the first pregnancy causes a high rate of fetal and neonatal death. The decreasing susceptibility during subsequent pregnancies correlates with acquisition of antibodies that block binding of infected red cells to chondroitin sulfate A (CSA), a receptor for parasites in the placenta. Here we identify a domain within a particular Plasmodium falciparum erythrocyte membrane protein 1 that binds CSA. We cloned a var gene expressed in CSA-binding parasitized red blood cells (PRBCs). The gene had eight receptor-like domains, each of which was expressed on the surface of Chinese hamster ovary cells and was tested for CSA binding. CSA linked to biotin used as a probe demonstrated that two Duffy-binding-like (DBL) domains (DBL3 and DBL7) bound CSA. DBL7, but not DBL3, also bound chondroitin sulfate C (CSC) linked to biotin, a negatively charged sugar that does not support PRBC adhesion. Furthermore, CSA, but not CSC, blocked the interaction with DBL3; both CSA and CSC blocked binding to DBL7. Thus, only the DBL3 domain displays the same binding specificity as PRBCs. Because protective antibodies present after pregnancy block binding to CSA of parasites from different parts of the world, DBL-3, although variant, may induce cross-reactive immunity that will protect pregnant women and their fetuses.


Defect-mediated selective hydrogenation of nitroarenes on nanostructured WS2.
Transition metal dichalcogenides (TMDs) are well known catalysts as both bulk and nanoscale materials. Two-dimensional (2-D) TMDs, which contain single- and few-layer nanosheets, are increasingly studied as catalytic materials because of their unique thickness-dependent properties and high surface areas. Here, colloidal 2H-WS2 nanostructures are used as a model 2-D TMD system to understand how high catalytic activity and selectivity can be achieved for useful organic transformations. Free-standing, colloidal 2H-WS2 nanostructures containing few-layer nanosheets are shown to catalyze the selective hydrogenation of a broad scope of substituted nitroarenes to their corresponding aniline derivatives in the presence of other reducible functional groups. Microscopic and computational studies reveal the important roles of sulfur vacancy-rich basal planes and tungsten-terminated edges, which are more abundant in nanostructured 2-D materials than in their bulk counterparts, in enabling the functional group selectivity. At tungsten-terminated edges and on regions of the basal planes having high concentrations of sulfur vacancies, vertical adsorption of the nitroarene is favored, thus facilitating hydrogen transfer exclusively to the nitro group due to geometric effects. At lower sulfur vacancy concentrations on the basal planes, parallel adsorption of the nitroarene is favored, and the nitro group is selectively hydrogenated due to a lower kinetic barrier. These mechanistic insights reveal how the various defect structures and configurations on 2-D TMD nanostructures facilitate functional group selectivity through distinct mechanisms that depend upon the adsorption geometry, which may have important implications for the design of new and enhanced 2-D catalytic materials across a potentially broad scope of reactions.


Diversity in general surgery: a period of progress.
Although 1996 to 2002 was a period of declining interest in general surgery (GS) among U.S. medical students (USS), most categorical general surgery (C-GS) training positions offered in the National Residency Matching Program (NRMP) continued to fill. We measured the impact of the decreasing U.S. student applicant volume on C-GS match outcomes and GS resident workforce composition over this time period. Match outcomes were analyzed for 7 applicant categories. Subsequent GS resident workforce compositions were analyzed for proportions of U.S. allopathic medical school graduates (USG), osteopathic medical graduates (OMG), Canadian MG (CMG), foreign MG (FMG), female physicians, and African-American physicians. Mantel-Haenzel chi-square tests measured trends in match percentages, C-GS positions filled, and GS workforce composition. All p-values are 2-sided. Increasing match percentages for USS applicants (p < 0.0001) and USG (p = 0.001), with a decreasing percentage of C-GS positions filled by these applicants (p < 0.0001), were from declining applicant volumes. Increasing match percentage for non-U.S. allopathic medical applicants reflected increases in both applicant volumes and matched applicants, with an increasing percentage of C-GS positions filled by these applicants (p < 0.0001). The subsequent resident workforce included increasing proportions of FMGs and OMGs (each p < 0.001); proportions of USG MDs and CMGs decreased (p < 0.0001 and p < 0.02, respectively). Concurrently, there were increasing numbers and proportions of female physicians (p < 0.0001) and African-American physicians (p < 0.0001) in the general surgery resident workforce. Declining interest among U.S. students in GS has resulted in a workforce comprised of residents from a broad range of educational backgrounds, but also it has provided an opportunity for progress toward achievement of a GS resident physician workforce more equitably representative of the racial and gender composition of our society at large.


A combination of the Arabidopsis DREB1A gene and stress-inducible rd29A promoter improved drought- and low-temperature stress tolerance in tobacco by gene transfer.
The transcription factor DREB1A/CBF3 specifically interacts with the dehydration responsive element (DRE/CRT) and induces expression of genes involved in environmental stress tolerance in Arabidopsis: Overexpression of DREB1A improved drought- and low-temperature stress tolerance in tobacco. The stress-inducible rd29A promoter minimized the negative effects on the plant growth in tobacco. Furthermore, we detected overexpression of stress-inducible target genes of DREB1A in tobacco. These results indicate that a combination of the rd29A promoter and DREB1A is useful for improvement of various kinds of transgenic plants that are tolerant to environmental stress.


Multiple diagnostic measures elicited during the stress ballistocardiogram.
Acceleration Bcgs were recorded on 22 subjects at rest and during acute elevation of blood pressure produced by isometric grip. Measurements on computer averaged graphic waveforms of H/I slope, I/J slope and I-J amplitude were made. The ratios of values during stress, to resting state, helped to select patients with 1,2 or 3 declines of 10% or more from the resting values. The method has the advantage of using each subject as his own control, and may help to elicit varying grades of myocardial pumping dysfunction not evident at rest.


Modelling forest carbon stock changes as affected by harvest and natural disturbances. II. EU-level analysis.
Forests and the forest sector may play an important role in mitigating climate change. The Paris Agreement and the recent legislative proposal to include the land use sector in the EU 2030 climate targets reflect this expectation. However, greater confidence on estimates from national greenhouse gas inventories (GHGI) and more comprehensive analyses of mitigation options are needed to seize this mitigation potential. The aim of this paper is to provide a tool at EU level for verifying the EU GHGI and for simulating specific policy and forest management scenarios. Therefore, the Carbon Budget Model (CBM) was applied for an integrated assessment of the EU forest carbon (C) balance from 2000 to 2012, including: (i) estimates of the C stock and net CO2 emissions for forest management (FM), afforestation/reforestation (AR) and deforestation (D), covering carbon in both the forest and the harvest wood product (HWP) pools; (ii) an overall analysis of the C dynamics associated with harvest and natural disturbances (mainly storms and fires); (iii) a comparison of our estimates with the data reported in the EU GHGI. Overall, the average annual FM sink (-365 Mt CO2 year-1) estimated by the CBM in the period 2000-2012 corresponds to about 7 % of total GHG emissions at the EU level for the same period (excluding land use, land-use change and forestry). The HWP pool sink (-44 Mt CO2 year-1) contributes an additional 1 %. Emissions from D (about 33 Mt CO2 year-1) are more than compensated by the sink in AR (about 43 Mt CO2 year-1 over the period). For FM, the estimates from the CBM were about 8 % lower than the EU GHGI, a value well within the typical uncertainty range of the EU forest sink estimates. For AR and D the match with the EU GHGI was nearly perfect (difference <±2 % in the period 2008-2012). Our analysis on harvest and natural disturbances shows that: (i) the impact of harvest is much greater than natural disturbances but, because of salvage logging (often very relevant), the impact of natural disturbances is often not easily distinguishable from the impact of harvest, and (ii) the impact of storms on the biomass C stock is 5-10 times greater than fires, but while storms cause only indirect emissions (i.e., a transfer of C from living biomass to dead organic matter), fires cause both direct and indirect emissions. This study presents the application of a consistent methodological approach, based on an inventory-based model, adapted to the forest management conditions of EU countries. The approach captures, with satisfactory detail, the C sink reported in the EU GHGI and the country-specific variability due to harvest, natural disturbances and land-use changes. To our knowledge, this is the most comprehensive study of its kind at EU level, i.e., including all the forest pools, HWP and natural disturbances, and a comparison with the EU GHGI. The results provide the basis for possible future policy-relevant applications of this model, e.g., as a tool to support GHGIs (e.g., on accounting for natural disturbances) and to verify the EU GHGI, and for the simulation of specific scenarios at EU level.


Infection after primary anatomic versus primary reverse total shoulder arthroplasty.
Deep periprosthetic infection is a serious complication after total shoulder arthroplasty (TSA) and is associated with suboptimal clinical results. This retrospective study aimed to determine whether a difference in infection rate existed after primary anatomic TSA (aTSA) and primary reverse TSA (rTSA). A TSA database was retrospectively reviewed to identify primary TSAs performed from 2004 to 2012 and isolate cases of confirmed deep periprosthetic infection. Data collected included age, sex, preoperative diagnosis, previous nonarthroplasty operative history, implant type, and infecting organism. From 814 primary TSAs performed, deep periprosthetic infections were confirmed in 16 shoulders. Infections occurred in 6 aTSAs and 10 rTSAs, with no significant difference among the prosthesis types. Pathogens included Staphylococcus spp, Propionibacterium acnes, and Escherichia coli. In the subgroup of shoulders with no previous operations, no significant difference in infection rate was found among the prosthesis types. Shoulders with previous nonarthroplasty operations undergoing primary TSA exhibited a significantly higher (P = .016) infection rate compared with shoulders with no operative history. Both aTSA and rTSA performed in previously operated-on shoulders demonstrated higher infection rates compared with shoulders with no prior operative intervention. The infection rate was significantly higher (P = .016) in the rTSA group. There is no difference in infection rate after primary aTSA and primary rTSA in shoulders that have not undergone previous operative interventions. Infection is more likely to develop in shoulders undergoing primary rTSA that have had one or more nonarthroplasty operative procedures.


Integration and segregation of inputs to higher-order neuropils of the crayfish brain.
Information about the input and output pathways of higher-order brain neuropils is essential for gaining an understanding of their functions. The present study examines the connectivity of two higher-order neuropils in the central olfactory pathway of the crayfish: the accessory lobe and its target neuropil, the hemiellipsoid body. It is known that the two subregions of the accessory lobe, the cortex and medulla, receive different inputs; the medulla receives visual and tactile inputs, whereas the cortex receives neither (Sandeman et al. [1995] J Comp Neurol 352:263-279). By using dye injections into the olfactory lobe, we demonstrate that the accessory lobe cortex and medulla also have differing connections with the olfactory lobe. These injections show that local interneurons joining the olfactory and accessory lobes branch primarily within the cortex with only limited branching within the medulla. Injections of different dyes into the two subregions of the hemiellipsoid body, HBI and HBII, show that the accessory lobe cortex and medulla also have separate output pathways. HBI is innervated by the output pathway from the cortex while HBII is innervated by the output pathway from the medulla. These injections also show that HBI and HBII are innervated by separate populations of local interneurons with differing connections to higher-order neuropils in the olfactory and visual pathways. These results suggest a segregation of olfactory and multimodal (including olfactory) inputs within both the accessory lobe and the hemiellipsoid body and provide evidence of important functional subdivisions within both neuropils.


The Enterococcus hirae R40 penicillin-binding protein 5 and the methicillin-resistant Staphylococcus aureus penicillin-binding protein 2' are similar.
The penicillin-resistant Enterococcus hirae R40 has a typical profile of membrane-bound penicillin-binding proteins (PBPs) except that the 71 kDa PBP5 of low penicillin affinity represents about 50% of all the PBPs present. Water-soluble tryptic-digest peptides were selectively produced from PBP5, their N-terminal regions were sequenced and synthetic oligonucleotides were used as primers to generate a 476 bp DNA fragment by polymerase chain reaction. On the basis of these data, the PBP5-encoding gene was cloned in Escherichia coli by using pBR322 as vector. The gene, included in a 7.1 kb insert, had the information for a 678-amino acid-residue protein. PBP5 shows similarity, in the primary structure, with the high-molecular-mass PBPs of class B. In particular, amino acid alignment of the enterococcal PBP5 and the methicillin-resistant staphylococcal PBP2' generates scores that are 30, for the N-terminal domains, and 53, for the C-terminal domains, standard deviations above that expected for a run of 20 randomized pairs of proteins having the same amino acid compositions as the two proteins under consideration.


'No one prepared me to go home': Cerebrovascular accident survivors' experiences of community reintegration in a peri-urban context.
The South African health system has policies and strategies to ensure effective rehabilitation and reintegration of individuals who have survived a cerebrovascular accident into their respective communities. However, implementation of such guidelines remains an issue. This study sought to explore cerebrovascular accident (CVA) survivors' experiences of community integration. The study was located in a peri-urban community within the KwaZulu-Natal Province, South Africa. An explorative qualitative study with eight purposively selected CVA survivors was conducted via semi-structured individual interviews. Data were audio-recorded and manually transcribed prior to thematic analysis. Trustworthiness of the study was maintained by strategies such as analyst triangulation, an audit trail and use of thick descriptions. Ethical principles of autonomy, informed consent, confidentiality and privacy were also maintained in the study. Six themes emerged that highlighted (1) loss of autonomy and roles, (2) barriers to community reintegration, (3) social isolation of participants, (4) finding internal strength, (5) enablers of community reintegration including the positive influence of support and the benefits derived from rehabilitation and (6) recommendations for rehabilitation. The study revealed both positive and negative influences that impact CVA survivors' ability to effectively reintegrate into their respective communities following a CVA. Recommendations include the need for education and awareness around access to rehabilitation services for CVA survivors, advice on how to improve CVA survivors' ability to mobilise in the community and make environmental adaption to facilitate universal access, provision of home programmes and caregiver training for continuity of care and for inclusion of home-based rehabilitation into current models of care.


Maximizing venous outflow after right hepatic living donor liver transplantation with a venous graft patch.
Between March 2002 and September 2004, 36 patients at Mie University Hospital underwent living donor liver transplantation (LDLT) of a right lobe graft without the middle hepatic vein. The patients were divided into two groups: group I (n = 25) received ordinary hepatic vein anastomoses, and group II (n = 11) received a venous graft patch in the subsequent procedure. Between groups, we compared hepatic vein blood flow (ultrasound), liver volume (CT scan), laboratory data, and ascitic fluid volume. Outflow block developed as a complication in 1 patient in group I. Hepatic vein blood flow on postoperative day (POD) 3 was significantly better in group II, and hepatic vein waveforms of most group II patients showed the triphasic pattern, especially on PODs 3 and 5. The total bilirubin and aspartate aminotransferase values on POD 1 were significantly better in group II, and daily ascitic fluid volume on PODs 3 and 5 was significantly lower in group II. Thus, modified venoplasty with a graft patch in the right hepatic LDLT not only improved hepatic vein hemodynamics (based on the ultrasound findings), but also improved liver function and decreased daily ascitic fluid volume.


[Clinical features of female genital tuberculosis in the period of 1980 to 2005].
Comparative analysis of two groups of patients with female genital tuberculosis treated at the Saint Petersburg Research Institute of Phthiosiopulmonology in 1980 to 2005 has shown that patients of younger age have recently fallen ill with this disease. The genital tuberculous process is commonly preceded or attended by other forms of tuberculosis of various organs and systems, such as the lung, lymph nodes, and kidney. The pain syndrome and impaired menstrual cycle are observed in half the patients; infertility is present in 60%; profound anatomic changes are less frequently seen in the fallopian tubes. Improvement of bacteriological methods promoted the timely diagnosis of the disease.


All-trans Arachidonic acid generates reactive oxygen species via xanthine dehydrogenase/xanthine oxidase interconversion in the rat liver cytosol in vitro.
We previously reported that the all-cis isomer of arachidonic acid, the most naturally occurring isoform of this fatty acid, reduced cuprous copper ion-induced conversion of xanthine dehydrogenase into its reactive oxygen species generating form, xanthine oxidase. In the present study, the effects of all-trans isomer of arachidonic acid, in comparison with cis isomer of arachidonic acid, on the xanthine dehydrogenase/xanthine oxidase interconversion were explored. cis isomer of arachidonic acid alone did not have any significant effect on the activities of xanthine dehydrogenase and xanthine oxidase, but it inhibited the cuprous copper ion-induced conversion of xanthine dehydrogenase to xanthine oxidase in rat liver cytosol in vitro. In contrast, trans isomer of arachidonic acid elicited an increase in xanthine oxidase activity concomitant with a decrease in xanthine dehydrogenase activity, and further potentiated the cuprous copper ion-induced xanthine dehydrogenase/xanthine oxidase interconversion. In primary rat hepatocyte cultures, trans isomer of arachidonic acid increased 2',7'-dichlorofluorescein-fluorescence intensity in the cytosolic fraction from 2',7'-dichlorodihydrofluorescein, an indicator of reactive oxygen species generation. The pretreatment of allopurinol, an xanthine oxidase inhibitor, diminished the trans isomer of arachidonic acid-induced increase in the 2',7'-dichlorofluorescein-fluorescence intensity, indicating the role of xanthine dehydrogenase/xanthine oxidase in mediating trans isomer of arachidonic acid-induced reactive oxygen species generation. These observations suggest that, in contrast to all-cis arachidonic acid, all-trans arachidonic acid has the potential to enhance reactive oxygen species generation via xanthine dehydrogenase/xanthine oxidase interconversion in the liver cytosol in vitro.