Intraspecific variability in allelopathy of Heracleum mantegazzianum is linked to the metabolic profile of root exudates.
Allelopathy may drive invasions of some exotic plants, although empirical evidence for this theory remains largely inconclusive. This could be related to the large intraspecific variability of chemically mediated plant-plant interactions, which is poorly studied. This study addressed intraspecific variability in allelopathy of Heracleum mantegazzianum (giant hogweed), an invasive species with a considerable negative impact on native communities and ecosystems. Bioassays were carried out to test the alleopathic effects of H. mantegazzianum root exudates on germination of Arabidopsis thaliana and Plantago lanceolata. Populations of H. mantegazzianum from the Czech Republic were sampled and variation in the phytotoxic effects of the exudates was partitioned between areas, populations within areas, and maternal lines. The composition of the root exudates was determined by metabolic profiling using ultra-high-performance liquid chromatography with time-of-flight mass spectrometry, and the relationships between the metabolic profiles and the effects observed in the bioassays were tested using orthogonal partial least-squares analysis. Variance partitioning indicated that the highest variance in phytotoxic effects was within populations. The inhibition of germination observed in the bioassay for the co-occurring native species P. lanceolata could be predicted by the metabolic profiles of the root exudates of particular maternal lines. Fifteen compounds associated with this inhibition were tentatively identified. The results present strong evidence that intraspecific variability needs to be considered in research on allelopathy, and suggest that metabolic profiling provides an efficient tool for studying chemically mediated plant-plant interactions whenever unknown metabolites are involved.


Sequence of contactin, a 130-kD glycoprotein concentrated in areas of interneuronal contact, defines a new member of the immunoglobulin supergene family in the nervous system.
The primary amino acid sequence of contactin, a neuronal cell surface glycoprotein of 130 kD that is isolated in association with components of the cytoskeleton (Ranscht, B., D. J. Moss, and C. Thomas. 1984. J. Cell Biol. 99:1803-1813), was deduced from the nucleotide sequence of cDNA clones and is reported here. The cDNA sequence contains an open reading frame for a 1,071-amino acid transmembrane protein with 962 extracellular and 89 cytoplasmic amino acids. In its extracellular portion, the polypeptide features six type 1 and two type 2 repeats. The six amino-terminal type 1 repeats (I-VI) each consist of 81-99 amino acids and contain two cysteine residues that are in the right context to form globular domains as described for molecules with immunoglobulin structure. Within the proposed globular region, contactin shares 31% identical amino acids with the neural cell adhesion molecule NCAM. The two type 2 repeats (I-II) are each composed of 100 amino acids and lack cysteine residues. They are 20-31% identical to fibronectin type III repeats. Both the structural similarity of contactin to molecules of the immunoglobulin supergene family, in particular the amino acid sequence resemblance to NCAM, and its relationship to fibronectin indicate that contactin could be involved in some aspect of cellular adhesion. This suggestion is further strengthened by its localization in neuropil containing axon fascicles and synapses.


Laparoscopic management of ureteropelvic junction obstruction in patients with upper urinary tract anomalies.
We report our experience with the laparoscopic management of ureteropelvic junction obstruction in patients with upper urinary tract abnormalities. Between July 1994 and May 2002, 7 men and 4 women with upper urinary tract anatomical abnormalities were referred to our institution for management of symptomatic ureteropelvic junction obstruction. Anomalies included horseshoe kidneys in 5 cases, pelvic kidneys in 3, a pancake kidney in 1, a malrotated kidney in 1 and a duplicated collecting system in 1. Three patients had associated renal stones that were extracted during reconstruction. Mean patient age was 37.4 years (range 25 to 60). One patient had undergone a previously unsuccessful endopyelotomy and 2 had a history of abdominal surgery. Mean operative time was 195 minutes (range 85 to 403) and mean estimated blood loss was 122 cc (range 20 to 300). No patient in this series required transfusion. Average length of hospital stay was 3.2 days (range 2 to 5). Renal function failed to improve after surgery in 1 patient with poor renal function and severe hydronephrosis. The remaining 10 patients (91%) had durable clinical and/or radiographic success during a followup of 32.6 and 21.3 months, respectively. There were no major complications. Laparoscopic pyeloplasty is an effective treatment alternative for ureteropelvic junction obstruction associated with renal or urinary tract anomalies.


Spontaneous Neural Oscillations Bias Perception by Modulating Baseline Excitability.
The brain exhibits organized fluctuations of neural activity, even in the absence of tasks or sensory input. A prominent type of such spontaneous activity is the alpha rhythm, which influences perception and interacts with other ongoing neural activity. It is currently hypothesized that states of decreased prestimulus α oscillations indicate enhanced neural excitability, resulting in improved perceptual acuity. Nevertheless, it remains debated how changes in excitability manifest at the behavioral level in perceptual tasks. We addressed this issue by comparing two alternative models describing the effect of spontaneous α power on signal detection. The first model assumes that decreased α power increases baseline excitability, amplifying the response to both signal and noise, predicting a liberal detection criterion with no effect on sensitivity. The second model predicts that decreased α power increases the trial-by-trial precision of the sensory response, resulting in improved sensitivity. We tested these models in two EEG experiments in humans where we analyzed the effects of prestimulus α power on visual detection and discrimination using a signal detection framework. Both experiments provide strong evidence that decreased α power reflects a more liberal detection criterion, rather than improved sensitivity, consistent with the baseline model. In other words, when the task requires detecting stimulus presence versus absence, reduced α oscillations make observers more likely to report the stimulus regardless of actual stimulus presence. Contrary to previous interpretations, these results suggest that states of decreased α oscillations increase the global baseline excitability of sensory systems without affecting perceptual acuity. Spontaneous fluctuations of brain activity explain why a faint sensory stimulus is sometimes perceived and sometimes not. The prevailing view is that heightened neural excitability, indexed by decreased α oscillations, promotes better perceptual performance. Here, we provide evidence that heightened neural excitability instead reflects a state of biased perception, during which a person is more likely to see a stimulus, whether or not it is actually present. Therefore, we propose that changes in neural excitability leave the precision of sensory processing unaffected. These results establish the link between spontaneous brain activity and the variability in human perception.


The distribution of serotonin in the CNS of an elasmobranch fish: immunocytochemical and biochemical studies in the Atlantic stingray, Dasyatis sabina.
The distribution of serotonin (5HT) in the brain of the Atlantic stingray was studied with peroxidase-antiperoxidase immunocytochemistry and high-pressure liquid chromatography. The regional concentrations of 5HT determined for this stingray fell within the range of values previously reported for fishes. A consistent trend in vertebrates for the hypothalamus and midbrain to have the highest concentrations and the cerebellum the lowest was confirmed in stingrays. Neuronal cell bodies and processes exhibiting 5HT-like immunoreactivity were distributed in variable densities throughout the neuraxis. Ten groups of 5HT cells were described: (I) spinal cord, (II-IV) rhombencephalon, (V, VI) mesencephalon, (VII, VIII) prosencephalon, (IX) pituitary, and (X) retina. There were three noteworthy features of the 5HT system in the Atlantic stingray: (1) 5HT cells were demonstrated in virtually every location in which 5HT-containing cells have been described or alluded to in the previous literature. The demonstration of immunopositive cells in the spinal cord, the retina, and the pars distalis of the pituitary suggests that 5HT may be an intrinsic neurotransmitter (or hormone) in these regions. (2) The distribution of 5HT cells in the brainstem shared many similarities with that in other vertebrates. However, there were many 5HT cells outside of the raphe nuclei, in the lateral tegmentum. It appears that the hypothesis that "lateralization" of the 5HT system is an advanced evolutionary trend cannot be supported. (3) 5HT fibers and terminals were more widely distributed in the Atlantic stingray brain than has been reported for other nonmammalian vertebrates on the basis of histofluorescence. It appears that this feature of the 5HT system arose early in phylogeny, and that the use of immunohistochemistry might reveal a more general occurrence of widespread 5HT fibers and terminals.


Axillary mononeuropathy after herpes zoster infection mimicking subacromial impingement syndrome.
Subacromial impingement syndrome is a frequent cause of shoulder pain and it is readily confused with other shoulder problems. We present a patient with herpes zoster infection associated with axillary mononeuropathy that was initially misdiagnosed as subacromial impingement syndrome. A 75-yr-old female patient was admitted to the internal medicine clinic because of pain and weakness in her right shoulder. As she did not respond to medical treatment and local injection therapy, magnetic resonance imaging of the right shoulder was ordered. As the magnetic resonance imaging revealed subacromial impingement of the supraspinatus tendon, the patient was referred to the physical medicine and rehabilitation department for rehabilitation. In our initial physical examination, her shoulder abductor muscle strength was 2/5 and her shoulder external rotator muscle strength was 3/5. A subacromial injection test with 10 ml of 1% lidocain was negative and the magnetic resonance imaging did not show a complete rotator tendon rupture that could explain such a muscle strength loss. So, an electrodiagnostic evaluation was performed and the patient was diagnosed to have a right axillary neuropathy. A more detailed questioning of the patient disclosed a history of herpes zoster approximately 3 mos ago. Herpes zoster-associated axillary neuropathy can mimic subacromial impingement syndrome, and magnetic resonance imaging examination alone may lead to a misdiagnosis. Therefore, we imply that clinical and electrophysiological evaluations would be of great importance in relevant patients with shoulder problems.


Benefits and drawbacks of the use of oral fluoropyrimidines as single-agent therapy in advanced colorectal cancer.
One of the most widely used cytotoxic agents is 5-fluorouracil. The use of infusional regimens has become commonplace and with this has come a realization of the limitations of this mode of administration. A number of oral fluoropyrimidines have been developed. Of these, capecitabine is the most established, with registrations in most countries for breast and colorectal cancer. The trials with this agent have mainly attempted to show equivalence with a "standard" intravenous comparator. In most cases, this endpoint has been met or exceeded. In addition, the trials have demonstrated reduced toxicity (except for hand-foot syndrome), and aspects of patient acceptability and cost-effectiveness have been integrated into these studies. Patients seem to prefer oral therapy but not at the expense of anticancer activity. However, the absence of intravenous access devices and complications associated with their use is a major bonus for oral therapy. The drawbacks are somewhat less obvious. Some patients are concerned that oral therapy is in some way inferior (ie, soft option) to intravenous chemotherapy. Compliance with oral therapy is always questionable. Although very few trials in which compliance has been formally assessed have been performed, the issue of overcompliance has not been addressed; in other words, there may be a problem of patients continuing to take the medication even in the face of toxicity and advice to stop treatment. Oral chemotherapy requires just as much care as intravenous chemotherapy and probably requires more attention to patient education and involvement in care decisions.


University student well-being in the United Kingdom: a scoping review of its conceptualisation and measurement.
Well-being is a multifaceted construct, and measuring well-being, both within particular groups and at a national level, is a priority for policy and practice. This national agenda on measuring well-being is mirrored in the Higher Education sector. This is the first conceptual review of how well-being is measured among university students in the UK. The aims of the review were to identify (i) the definitions or conceptualisations of well-being guiding the selection of well-being indicators for research within this population and (ii) measures of well-being used in university students in the UK. A scoping review method was used. Twenty-eight validated indicators used to measure well-being in UK students were identified. While many were direct measures of (primarily mental or psychological) well-being, indirect "proxy" indicators, including measures of mental health symptoms, were identified. This review has highlighted that there are inconsistencies in defining and measuring university student well-being, and the measures that have been used in this population are focused on subjective experience. These findings are in line with reviews of well-being measures in the general population. Implications for further research are discussed.


Chronic E-Cigarette Use Increases Neutrophil Elastase and Matrix Metalloprotease Levels in the Lung.
Rationale: Proteolysis is a key aspect of the lung's innate immune system. Proteases, including neutrophil elastase and MMPs (matrix metalloproteases), modulate cell signaling, inflammation, tissue remodeling, and leukocyte recruitment via cleavage of their target proteins. Excessive proteolysis occurs with chronic tobacco use and is causative for bronchiectasis and emphysema. The effect of e-cigarettes (vaping) on proteolysis is unknown. Objectives: We used protease levels as biomarkers of harm to determine the impact of vaping on the lung. Methods: We performed research bronchoscopies on healthy nonsmokers, cigarette smokers, and e-cigarette users (vapers), and determined protease levels in BAL. In parallel, we studied the effects of e-cigarette components on protease secretion in isolated human blood neutrophils and BAL-derived macrophages. We also analyzed the nicotine concentration in induced sputum and BAL. Measurements and Main Results: Neutrophil elastase, MMP-2, and MMP-9 activities and protein levels were equally elevated in both vapers' and smokers' BAL relative to nonsmokers. In contrast, antiprotease levels were unchanged. We also found that exposure of isolated neutrophils and macrophages to nicotine elicited dose-dependent increases in protease release. After vaping, measurable levels of nicotine were detectable in sputum and BAL, which corresponded to the half-maximal effective concentration values for protease release seen in immune cells. Conclusions: We conclude that vaping induces nicotine-dependent protease release from resident pulmonary immune cells. Thus, chronic vaping disrupts the protease-antiprotease balance by increasing proteolysis in lung, which may place vapers at risk of developing chronic lung disease. These data indicate that vaping may not be safer than tobacco smoking.


Nontumorous Portal Vein Thrombosis in Liver Cirrhosis: Possible Role of β-Blockers.
Nonselective β-blockers (NSBB) are used in liver cirrhosis (LC) to prevent variceal bleeding because they decrease portal pressure. A main risk factor for the development of portal vein thrombosis (PVT) in LC is decreased portal vein inflow velocity. The aim of our study was to examine retrospectively the incidence of PVT and its correlation with the use of β-blockers in a cohort of LC patients. Data from 230 LC patients (90% Child-Pugh class A), who had been followed up for at least 5 years, were reviewed. The diagnosis of PVT was made by ultrasound. The presence of PVT was evaluated with multiple logistic regression analysis where the independent variables were those significant in the univariate analysis. The prevalence of PVT at baseline was 4.5%, and the incidence was 4.3% at 5 years; among the subjects taking β blockers, 46.4% were taking NSBB. A total of 19 PVT cases were found. Grade of esophageal varices (p < 0.01), PLT (p < 0.003), INR (p < 0.03), spleen diameter (p < 0.001) and PLT/spleen ratio (p < 0.0005) were significantly associated with PVT. The use of NSBB indicated a higher risk of PVT compared to selective β-blockers (SBB) (p < 0.05). In logistic regression analysis only the grade of esophageal varices was significant (p < 0.02). Univariate analysis of patients taking β-blockers showed an association of PVT with grade of esophageal varices (p < 0.01), CP class (p < 0.02), AST (p < 0.03), ALT and albumin (p < 0.02), PLT count and PLT/LD (p < 0.03), longitudinal diameter of the spleen (p < 0.005), ascites (p < 0.05), portal vein (p < 0.0001) and NSBB (OR 8.1; 95% CI 1.7-38.8). NSBB seem to play a role in PV thrombogenesis. Further studies are needed, especially in decompensated LC patients.


Genomic DNA isolation of Acrocomia aculeata (Arecaceae) from leaf and stipe tissue samples for PCR analysis.
Macaw palm, Acrocomia aculeata is an oleaginous species of the Arecaceae family; it has been identified as one of the most promising plants for sustainable production of renewable energy, especially biodiesel. We developed an efficient protocol of genomic DNA extraction for A. aculeata using leaf and stipe tissues, based on the cationic hexadecyltrimethylammonium bromide method, and we evaluated the quantity, purity, and integrity of the resultant DNA. We also determined whether these procedures interfere with PCR amplification using SSR molecular markers. The lowest concentration of DNA was obtained from stipe tissues (135 ng/μL), while fresh leaf tissues provided the highest concentration of DNA (650 ng/μL). Good quality DNA was obtained from fresh leaf, lyophilized leaf, and stipe tissues (relative purity, 1.79-1.89 nm). Differences in quantity and quality of DNA extracted from different tissues did not interfere with general patterns of PCR amplification based on SSR markers.


Dietary fibre intake and risk of prediabetes in China: results from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) Cohort Study.
High dietary fibre intake has been associated with a lower risk of diabetes, but the association of dietary fibre with prediabetes is only speculative, especially in China, where the supportive data from prospective studies are lacking. This study aimed to examine the association between dietary fibre intake and risk of incident prediabetes among Chinese adults. We performed a prospective analysis in 18 085 participants of the Tianjin Chronic Low-grade Systemic Inflammation and Health cohort study who were free of diabetes, prediabetes, cancer and CVD at baseline. Dietary data were collected using a validated 100-item FFQ. Prediabetes was defined based on the American Diabetes Association diagnostic criteria. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95 % CI. During 63 175 person-years of follow-up, 4139 cases of incident prediabetes occurred. The multivariable HR of prediabetes for the highest v. lowest quartiles were 0·85 (95 % CI 0·75, 0·98) (P for trend = 0·02) for total dietary fibre, 0·84 (95 % CI 0·74, 0·95) (P for trend < 0·01) for soluble fibre and 1·05 (95 % CI 0·93, 1·19) (P for trend = 0·38) for insoluble fibre. Fibre from fruits but not from cereals, beans and vegetables was inversely associated with prediabetes. Our results indicate that intakes of total dietary fibre, soluble fibre and fibre derived from fruit sources were associated with a lower risk of prediabetes.


Nonenzymatic galactosylation of human serum albumin. In vitro preparation.
Incubation of purified human serum albumin with D-[1-14C]galactose (5 mM) or D-[1-14C]glucose (5 mM) in vitro for 7 days under physiological conditions resulted in the time-dependent accumulation of radioactivity into trichloroacetic acid-precipitable material. Comparative studies indicated that the rate of sugar incorporation into albumin increased with increasing pH and temperature of incubation and followed a first order dependence with regard to monosaccharide and albumin concentrations. The extent of nonenzymatic galactosylation of human albumin was approximately 300% greater than the extent of nonenzymatic glucosylation under equivalent experimental conditions. Prolonged dialysis of the modified albumins against a large excess of the unlabeled monosaccharides failed to alter the amount of protein-bound radiolabeled carbohydrate, suggesting that the linkage between sugar and albumin is covalent in nature. The post-translational modification of proteins by nonenzymatic galactosylation may be of physiological significance in individuals with reduced galactokinase or galactose-1-phosphate uridyl transferase activities.


Substrate binding-induced changes in the EPR spectra of the ferrous nitric oxide complexes of neuronal nitric oxide synthase.
A versatile diatomic physiological messenger, nitric oxide (NO), is biosynthesized by a group of flavo-heme enzymes, the nitric oxide synthases. We have examined the active site of the neuronal isoform by EPR spectroscopy of the ferrous nitric oxide complex. The nitric oxide complex of the substrate-free enzyme exhibits a cytochrome P450-type EPR spectrum typical of a hexacoordinate NO-heme complex with a non-nitrogenous proximal axial heme ligand. The NO complex of the substrate-free enzyme is rather unstable and spontaneously converts to a cytochrome P420 type pentacoordinate denatured form. Binding of L-arginine (l-Arg) enhances the stability of the hexacoordinate NO form. The EPR spectrum of the NO adduct of the enzyme-substrate complex has an increased g-anisotropy and well-resolved hyperfine couplings due to the 14N of nitric oxide. Significant perturbations in the NO EPR spectrum were observed upon Nomega-monomethyl-L-Arg and Nomega-hydroxy-L-Arg binding. The perturbations in the EPR spectrum indicate that L-Arg and its derivatives bind on the distal site of the heme in very close proximity to the bound NO to cause alterations in the heme-NO coordination structure. Interactions between the bound NO and the substrate or its analogues appear to affect the Fe-NO geometry, resulting in the observed spectral changes. We infer that analogous interactions with oxygen might be involved in the hydroxylation events during enzyme catalysis of nitric oxide synthase.


Endolimax piscium sp. nov. (Amoebozoa), causative agent of systemic granulomatous disease of cultured sole, Solea senegalensis Kaup.
A new amoeba species pathogenic for Senegalese sole is described based on ultrastructural analysis and SSU rDNA phylogenetic inference. The parasite presents round to ovoid trophozoites (<5 μm) with a high degree of intracellular simplification. No mitochondria were observed, but mitosome-like organelles were present. No cysts could be detected. Phylogenetic analysis confirmed the Senegalese sole parasite as an amitochondriate Archamoeba related to Endolimax nana and Iodamoeba spp., and we tentatively describe it as a new species in the genus Endolimax, Endolimax piscium. However, the genetic distance with E. nana is quite large, with only 60% pairwise identity between both SSU rDNA genotypes. Although the overall topology of the Archamoebae cladograms containing E. piscium was consistent, the support for the branching of Endolimax spp. relative to its closest neighbours was variable, being higher with distance or parsimony-based inference methods than with ML or Bayesian trees. The use of stringent alignment sampling masks also caused instability and reduced support for some branches, including the monophyly of Endolimax spp. in the most conservative data sets. The characterization of other Archamoebae parasitizing fish could help to clarify the status of E. piscium and to interpret the large genetic distance observed between Endolimax species.


High-Intensity, Unilateral Resistance Training of a Non-Paretic Muscle Group Increases Active Range of Motion in a Severely Paretic Upper Extremity Muscle Group after Stroke.
Limited rehabilitation strategies are available for movement restoration when paresis is too severe following stroke. Previous research has shown that high-intensity resistance training of one muscle group enhances strength of the homologous, contralateral muscle group in neurologically intact adults. How this "cross education" phenomenon might be exploited to moderate severe weakness in an upper extremity muscle group after stroke is not well understood. The primary aim of this study was to examine adaptations in force-generating capacity of severely paretic wrist extensors resulting from high intensity, dynamic contractions of the non-paretic wrist extensors. A secondary, exploratory aim was to probe neural adaptations in a subset of participants from each sample using a single-pulse, transcranial magnetic stimulation (TMS) protocol. Separate samples of neurologically intact controls (n = 7) and individuals ≥4 months post stroke (n = 6) underwent 16 sessions of training. Following training, one-repetition maximum of the untrained wrist extensors in the control group and active range of motion of the untrained, paretic wrist extensors in the stroke group were significantly increased. No changes in corticospinal excitability, intracortical inhibition, or interhemispheric inhibition were observed in control participants. Both stroke participants who underwent TMS testing, however, exhibited increased voluntary muscle activation following the intervention. In addition, motor-evoked potentials that were unobtainable prior to the intervention were readily elicited afterwards in a stroke participant. Results of this study demonstrate that high-intensity resistance training of a non-paretic upper extremity muscle group can enhance voluntary muscle activation and force-generating capacity of a severely paretic muscle group after stroke. There is also preliminary evidence that corticospinal adaptations may accompany these gains.


Dynamics of blood flow and oxygenation changes during brain activation: the balloon model.
A biomechanical model is presented for the dynamic changes in deoxyhemoglobin content during brain activation. The model incorporates the conflicting effects of dynamic changes in both blood oxygenation and blood volume. Calculations based on the model show pronounced transients in the deoxyhemoglobin content and the blood oxygenation level dependent (BOLD) signal measured with functional MRI, including initial dips and overshoots and a prolonged poststimulus undershoot of the BOLD signal. Furthermore, these transient effects can occur in the presence of tight coupling of cerebral blood flow and oxygen metabolism throughout the activation period. An initial test of the model against experimental measurements of flow and BOLD changes during a finger-tapping task showed good agreement.


[Ultrastructural characteristics of SARS associated virus in infected cells].
Electron microscopical study of infected cells to identify the pathogenic agent of SARS. Vero E6 cells infected with lung autopsy samples or nasopharyngeal swabs from SARS patients of Beijing and Guangzhou were inoculated. The supernatant and cultured cells exhibiting identifiable cytopathic effect (CPE) were prepared for electron microscopic study. Examination of CPE cells on thin-section revealed characteristic coronavirus particles within the cisternae of endoplasmic reticulum, Golgi apparatus, vesicles and extracellular space. They were mainly spherical or oval in shape, annular or dense, about 80 nm in diameter. Negative-stain electron microscopy identified coronavirus particles in culture supernatant, 80 - 120 nm in diameter, with club-shaped surface projections. Elongated, rod-, kidney- or other irregular shaped virons with the size of 100 - 200 nm by 60 - 90 nm were also found in the cultured cells infected with the lung samples from the Guangdong patients. Infectious virons entered cells by endocytosis or membrane fusion and released through a budding process. These data indicate a novel coronavirus as the causative agent of SARS. Most viral particles showed typical characteristics of coronavirus. The potential role of special shape viruses is expected to be further investigated.


Risk factor changes for sudden infant death syndrome after initiation of Back-to-Sleep campaign.
To test the hypothesis that the profile of sudden infant death syndrome (SIDS) changed after the Back-to-Sleep (BTS) campaign initiation, document prevalence and patterns of multiple risks, and determine the age profile of risk factors. The San Diego SIDS/Sudden Unexplained Death in Childhood Research Project recorded risk factors for 568 SIDS deaths from 1991 to 2008 based upon standardized death scene investigations and autopsies. Risks were divided into intrinsic (eg, male gender) and extrinsic (eg, prone sleep). Between 1991-1993 and 1996-2008, the percentage of SIDS infants found prone decreased from 84.0% to 48.5% (P < .001), bed-sharing increased from 19.2% to 37.9% (P < .001), especially among infants <2 months (29.0% vs 63.8%), prematurity rate increased from 20.0% to 29.0% (P = .05), whereas symptoms of upper respiratory tract infection decreased from 46.6% to 24.8% (P < .001). Ninety-nine percent of SIDS infants had at least 1 risk factor, 57% had at least 2 extrinsic and 1 intrinsic risk factor, and only 5% had no extrinsic risk. The average number of risks per SIDS infant did not change after initiation of the BTS campaign. SIDS infants in the BTS era show more variation in risk factors. There was a consistently high prevalence of both intrinsic and especially extrinsic risks both before and during the Back-to-Sleep era. Risk reduction campaigns emphasizing the importance of avoiding multiple and simultaneous SIDS risks are essential to prevent SIDS, including among infants who may already be vulnerable.


Life cycle and description of a new species of brachylaimid (Trematoda: Digenea) in Spain.
The life cycle of Brachylaima llobregatensis n. sp. (Trematoda: Brachylaimidae) is elucidated. Embryonated, operculated, asymmetric eggs (30.9 x 18.2 microm) are eliminated with feces of natural hosts wood mouse Mus spretus; white-toothed shrew, Crocidura russula; and an experimental host, domestic mouse, Mus musculus var. domesticus. The eggs are ingested by the helicid gastropod Helix (Cornu) aspersa, the only natural and experimental first intermediate host. The miracidium hatches from the egg, infects the snails, and develops into a branched sporocyst in the digestive gland. Microcaudate cercariae emerge from this snail and develop into unencysted metacercariae in the kidney of second intermediate host snails H. (C.) aspersa and Otala punctata (natural hosts) and Theba pisana (experimental host). Ingestion of infected snails leads to the infection of definitive hosts, with the adults inhabiting the middle part of the small intestine. There is a chaetotaxic pattern specific on the acetabular (S(II) 5-6 papillae) and body (papillae absent on P(II)) levels. Three types of cercaria papillae were observed by scanning electron microscopy: argentophilic papillae with fingerlike processes (cephalic, body, and acetabular levels); argentophilic papillae with opening (2 papillae in the M body level); and nonargentophilic dome-shaped papillae (on the cephalic C(II) level, alternating with argentophilic S(II) papillae on the ventral sucker). Suckers are subequal, with the acetabulum located in the posterior part of the anterior third of body. Vitellaria extend from anterior margin of acetabulum to between middle level and anterior margin of anterior testis.


Relationship between changes in pulmonary V̇O₂ kinetics and autonomic regulation of blood flow.
Various regulatory mechanisms of pulmonary oxygen uptake (V̇O2) kinetics have been postulated. The purpose of this study was to investigate the relationship between vagal withdrawal, measured using RMSSDRR, the root mean square of successive differences in cardiac interval (RR) kinetics, a mediator of oxygen delivery, and V̇O2 kinetics. Forty-nine healthy adults (23 ± 3 years; 72 ± 13 kg; 1.80 ± 0.08 m) performed multiple repeat transitions to moderate- and heavy-intensity exercise. Electrocardiography, impedance cardiography, and pulmonary gas exchange parameters were measured throughout; time domain measures of heart rate variability were subsequently derived. The parameters describing the dynamic response of V̇O2, cardiac output (Q) and RMSSDRR were determined using a mono-exponential model. During heavy-intensity exercise, the phase II τ of V̇O2 was significantly correlated with the τ of RR (r = 0.36, P < 0.05), Q (r = 0.67, P < 0.05), and RMSSDRR (r = 0.38, P < 0.05). The τ describing the rise in Q explained 47% of the variation in V̇O2 τ, with 30% of the rate of this rise in Q explained by the τ of RR and RMSSDRR. No relationship was evident between V̇O2 kinetics and those of Q, RR, or RMSSDRR during moderate exercise. Vagal withdrawal kinetics support the concept of a centrally mediated oxygen delivery limitation partly regulating V̇O2 kinetics during heavy-, but not moderate-, intensity exercise.


The association between HIV and fertility in a cohort study in rural Tanzania.
Recent studies in sub-Saharan Africa have shown that fertility is reduced among HIV-infected women compared with uninfected women. The size and pattern of this fertility reduction has important implications for antenatal clinic-based surveillance of the epidemic and also for estimates and projections of the demographic impact of the epidemic. This paper examines the association between HIV and fertility in Kisesa, a rural area in Tanzania, where HIV prevalence among adults is about 6% and gradually increasing. The analysis is based on data obtained through a demographic surveillance system in Kisesa during 1994-98 and two large sero-surveys of all residents in 1994-95 and 1996-97. The HIV-associated fertility reduction among women was investigated by estimating fertility rates by HIV status and prevalence rates by fertility status. A substantial reduction (29%) was observed in fertility among HIV-infected women compared with HIV-uninfected women. The fertility reduction was most pronounced during the terminal stages of infection, but no clear association with duration of infection was observed. Use of modern contraception was higher among HIV-infected women. However, both among contracepting and non-contracepting women, a substantial reduction in fertility was seen among HIV-infected women.


Next-generation RNA Sequencing-based Biomarker Characterization of Chromophobe Renal Cell Carcinoma and Related Oncocytic Neoplasms.
Renal cell carcinomas (RCCs) are a heterogeneous group of neoplasms. Recent sequencing studies revealed various molecular features associated with histologic RCC subtypes, including chromophobe renal cell carcinoma (ChRCC). To characterize the gene expression and biomarker signatures associated with ChRCC. We performed integrative analysis on RNA sequencing data available from 1049 RCC specimens from The Cancer Genome Atlas and in-house studies. Our workflow identified genes relatively enriched in ChRCC, including Forkhead box I1 (FOXI1), Rh family C glycoprotein (RHCG), and LINC01187. We assessed the expression pattern of FOXI1 and RHCG protein by immunohistochemistry (IHC) and LINC01187 mRNA by RNA in situ hybridization (RNA-ISH) in whole tissue sections representing a cohort of 197 RCC cases, including both primary and metastatic tumors. The FOXI1 and RHCG IHC staining, as well as the LINC01187 RNA-ISH staining, was evaluated in each case for intensity, pattern, and localization of expression. All primary and metastatic classic ChRCCs demonstrated homogeneous positive labeling for FOXI1, RHCG proteins, and LINC01187 transcript. Unclassified RCC with oncocytic features, oncocytoma, and hybrid oncocytic tumor, as well as all but two cases of eosinophilic ChRCC also stained positive. Importantly, metastatic and primary RCC of all other subtypes did not demonstrate any unequivocal staining for FOXI1, RHCG, or LINC01187. In normal kidney, FOXI1, RHCG, and LINC01187 were detected in the distal nephron segment, specifically in intercalated cells. Two cases of eosinophilic ChRCC with focal expression of FOXI1 and LINC01187, and Golgi-like RHCG staining were found to contain MTOR gene mutations upon DNA sequencing. We demonstrate a pipeline for the identification and validation of RCC subtype-specific biomarkers that can aid in the confirmation of cell of origin and may facilitate accurate classification and diagnosis of renal tumors. FOXI1, RHCG, and LINC01187 are lineage-specific signature genes for chromophobe renal cell carcinoma.


The effect of a virtual ward program on emergency services utilization and quality of life in frail elderly patients after discharge: a pilot study.
Attendance at emergency departments and unplanned hospital readmissions are common for frail older patients after discharge from hospitals. A virtual ward service was piloted to deliver "hospital-at-home" services by community nurses and geriatricians to frail older patients immediately after their discharge from hospital to reduce emergency services utilization. This study examined the impacts of the virtual ward service on changes in the patients' emergency attendance and medical readmissions, and their quality of life (QOL). A matched-control quasi-experimental study was conducted at four hospitals, with three providing the virtual ward service (intervention) and one providing the usual community nursing care (control). Subjects in the intervention group were those who are at high risk of readmission and who are supported by home carers recruited from the three hospitals providing the virtual ward service. Matched control patients were those recruited from the hospital providing usual care. Outcome measures include emergency attendance and medical readmission in the past 90 days as identified from medical records, and patient-reported QOL as measured by the modified Quality-of-Life Concerns in the End of Life Questionnaire (Chinese version). Wilcoxon signed-rank tests compared the changes in the outcome variables between groups. A total of 39 patients in each of the two groups were recruited. The virtual ward group showed a greater significant reduction in the number of unplanned emergency hospital readmissions (-1.41±1.23 versus -0.77±1.31; P=0.049) and a significant improvement in their overall QOL (n=18; 0.60±0.56 versus 0.07±0.56; P=0.02), but there was no significant difference in the number of emergency attendances (-1.51±1.25 versus -1.08±1.48; P=0.29). The study results support the effectiveness of the virtual ward service in reducing unplanned emergency medical readmissions and in improving the QOL in frail older patients after discharge.


Numerical study of a simple transcranial focused ultrasound system applied to blood-brain barrier opening.
In this paper, we investigate the focalization properties of single-element transducers at low frequencies (300 to 1000 kHz) through primate and human skulls. The study addresses the transcranial targeting involved in ultrasound- induced blood-brain barrier (BBB) opening with clinically relevant targets such as the hippocampus and the basal ganglia, which are typically affected by early Alzheimer's and Parkinson's disease, respectively. A finite-difference, timedomain simulation platform is used to solve the 3-D linear acoustic wave equation with CT-based acoustic maps of the skulls. The targeted brain structures were extracted from 3-D brain atlases registered with the skulls and used to virtually position and orient the transducers. The effect of frequency is first investigated and the targeting of the different structures is then tested. The frequency of 500 kHz provided the best tradeoff between phase aberrations and standing wave effects in the human case, whereas the frequency of 800 kHz was most suitable in the case of the primate skull. A fast periodic linear chirp method was developed and found capable of reducing the standing wave effects. Such a simple, affordable, and convenient system is concluded to be feasible for BBB opening in primates and humans and could thus allow for its broader impact and applications.


[The content of pyridine coenzymes in the liver of the adult and old rats in stress].
The concentration of oxidized and reduced NAD and NADP in the liver was studied in 36 adult (10-12 month old) and old (22-25 month old) male Wistar rats exposed to immobilization stress. It was established that content of piridine coenzymes in rat liver does not change with age. Immobilization stress decreases NADP reduction in adult animals, increases percentage of NADN in the total pool of reduced piridine coenzymes in the liver. In old stressed rats reduction of the NADP pool diminished accompanied by a distinct lowering of concentration of reduced NAD compared to its level in adult animals. It is suggested that shifts in the system of piridine coenzymes in the liver of adult rats support maintenance of effective function of the microsomal oxigenase chain in stress, in old animals promotes stress attenuation.


Short-Term Monitoring of Graft Regeneration in Partial Liver Transplantation Recipients.
BACKGROUND Liver regeneration after partial liver transplantation, including living donor liver transplantation and split liver transplantation, is important for successful transplantation. MATERIAL AND METHODS We retrospectively analyzed 68 patients who underwent partial liver transplantation and calculated their regeneration index (RI)-based difference in postoperative and preoperative liver volume. We collected clinical data of donors and recipients and analyzed the correlation between clinical characteristics and RI. According to the above results, the generalized estimating equation (GEE) model included white blood cell count (WBC), neutrophils, lymphocytes, platelets, prothrombin time (PT), and activated partial thromboplastin time (APTT) on Days 1, 3, and 7 after LT and was used to predict the RI. RESULTS The mean RI was 40%, which was used as the cutoff value to divide all patients to the high-RI group and the low-RI group. The percentage of Child-Pugh C patients was 44% in the high-RI group, which was significantly more than that (21%) in the low-RI group (P=0.038). Among the postoperative monitoring parameters, neutrophil (P=0.044) and platelet (P=0.036) levels declined in the high-RI group on Day 3, while APTT was higher on Day 1 compared to the low-RI group. The predictive model based on GEE analysis achieved a good effect, with the area under the receiver operating characteristic curve on Day 1 (0.681; 95% CI, 0.556-0.807) and Day 3 (0.705; 95% CI, 0.578-0.832) showing significant differences (P=0.010 and 0.004, respectively). CONCLUSIONS The combination of decreased counts of WBC, neutrophils, lymphocytes, and platelets, as well as elevated PT and APTT on Day 3 after LT showed a good capability to predict a higher rate of liver regeneration after partial liver transplantation.


Hearing conservation surgery for acoustic tumors--a clinical-pathologic correlative study.
It has been estimated that hearing conservation is possible in 50% of patients with tumors extending medial to the porus acusticus 1.5 cm or less and who maintain speech discrimination scores of 80% or greater. Others have indicated that a hearing level of 30 dB or less and 80% discrimination are ideal candidates for hearing preservation surgery. Twenty-two cases of solitary schwannoma of the eighth nerve are reviewed in which adequate tissue was available for histologic fiber analysis, using the established preoperative predictive criteria for hearing preservation surgery. We describe the histology found in patients meeting these preoperative criteria. The tumors in ten cases measured less than 1.5 cm; five cases had a discrimination score of 80% or greater; and four cases had a pure-tone average of 30 dB or less. Only three cases satisfied any two criteria and only one case satisfied all three criteria. All cases had significant fiber destruction and tumor infiltration. The one case that met all three criteria demonstrated severe tumor infiltration within the cochlear nerve and the trunk of the eighth nerve; in two of five subserial en block tumor-nerve cross-sections no fibers could be identified crossing the tumor. Histologic data suggests that completely removing the tumor while attempting to preserve hearing may be beyond present surgical capabilities. They further suggest that the present preoperative criteria for selection of patients for hearing preservation are inadequate.


HGF protected against diabetic nephropathy via autophagy-lysosome pathway in podocyte by modulating PI3K/Akt-GSK3β-TFEB axis.
Podocyte loss is a detrimental feature and major cause of proteinuria in diabetic nephropathy (DN). Our previous study revealed that hepatocyte growth factor (HGF) prevented high glucose-induced podocyte injury via enhancing autophagy. In the current study, we aimed to assess the role of HGF on podocyte homeostasis in DN and clarify its mechanisms further. Diabetic mice treated with HGF had markedly reduced ratio of kidney weight to body weight, urinary albumin excretion, podocyte loss and matrix expansion compared with that in the non-treated counterpart. Simultaneously, HGF-treated diabetic mice exhibited increased autophagy activity as indicated by the decreased accumulation of sequestosome 1 (SQSTM1/ p62) and increased microtubule-associated proteins 1 light chains 3 (LC3) II/LC3I ratio. These beneficial effects of HGF were blocked by HGF/c-Met inhibitor Crizotinib or phosphatidylinositide 3-kinases (PI3K) inhibitor LY294002. Moreover, HGF treatment obviously prevented inactivation of the protein kinase B (Akt)-glycogen synthase kinase 3 beta (GSK3β)-transcription factor EB (TFEB) axis in high glucose-stimulated podocytes, which was associated with improved lysosome function and autophagy. Accordingly, adenovirus vector encoding constitutively active GSK3β (Ad-GSK3β-S9A) offset whereas small interfering RNA against GSK3β (GSK3β siRNA) recapitulated salutary effects of HGF on lysosome number and autophagy in podocytes. These results suggested that HGF protected against diabetic nephropathy through restoring podocyte autophagy, which at least partially involved PI3K/Akt-GSK3β-TFEB axis-mediated lysosomal function improvement.


Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.
The superfamily of pentameric ligand-gated ion channels includes neurotransmitter receptors that mediate fast synaptic transmission in vertebrates, and are targets for drugs including alcohols, anesthetics, benzodiazepines, and anticonvulsants. However, the mechanisms of ion channel opening, gating, and modulation in these receptors leave many open questions, despite their pharmacological importance. Subtle conformational changes in both the extracellular and transmembrane domains are likely to influence channel opening, but have been difficult to characterize given the limited structural data available for human membrane proteins. Recent crystal structures of a modified Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in multiple states offer an appealing model system for structure-function studies. However, the pharmacology of the crystallographic GluCl construct is not well established. To establish the functional relevance of this system, we used two-electrode voltage-clamp electrophysiology in Xenopus oocytes to characterize activation of crystallographic and native-like GluCl constructs by L-glutamate and ivermectin. We also tested modulation by ethanol and other anesthetic agents, and used site-directed mutagenesis to explore the role of a region of Loop F which was implicated in ligand gating by molecular dynamics simulations. Our findings indicate that the crystallographic construct functionally models concentration-dependent agonism and allosteric modulation of pharmacologically relevant receptors. Specific substitutions at residue Leu174 in loop F altered direct L-glutamate activation, consistent with computational evidence for this region's role in ligand binding. These insights demonstrate conservation of activation and modulation properties in this receptor family, and establish a framework for GluCl as a model system, including new possibilities for drug discovery. In this study, we elucidate the validity of a modified glutamate-gated chloride channel (GluClcryst ) as a structurally accessible model for GABAA receptors. In contrast to native-like controls, GluClcryst exhibits classical activation by its neurotransmitter ligand L-glutamate. The modified channel is also sensitive to allosteric modulators associated with human GABAA receptors, and to site-directed mutations predicted to alter channel opening.


Patient safety during radiological examinations: a nationwide survey of residency training hospitals in Taiwan.
Variations in radiological examination procedures and patient load lead to variations in standards of care related to patient safety and healthcare quality. To understand the status of safety measures to protect patients undergoing radiological examinations at residency training hospitals in Taiwan, a follow-up survey evaluating the full spectrum of diagnostic radiology procedures was conducted. Questionnaires covering 12 patient safety-related themes throughout the examination procedures were mailed to the departments of diagnostic radiology with residency training programmes in 19 medical centres (with >500 beds) and 17 smaller local institutions in Taiwan. After receiving the responses, all themes in 2014 were compared between medical centres and local institutions by using χ(2) or 2-sample t-tests. Radiology Directors or Technology Chiefs of medical centres and local institutions in Taiwan participated in this survey by completing and returning the questionnaires. The response rates of medical centres and local institutions were 95% and 100%, respectively. As indicated, large medical centres carried out more frequent clinically ordered, radiologist-guided patient education to prepare patients for specific examinations (CT, 28% vs 6%; special procedures, 78% vs 44%) and incident review and analysis (89% vs 47%); however, they required significantly longer access time for MRI examinations (7.00±29.50 vs 3.50±3.50 days), had more yearly incidents of large-volume contrast-medium extravasation (2.75±1.00 vs 1.00±0.75 cases) and blank radiographs (41% vs 8%), lower monthly rates of suboptimal (but interpretable) radiographs (0.00±0.01% vs 0.64±1.84%) and high-risk reminder reporting (0.01±0.16% vs 1.00±1.75%) than local institutions. Our study elucidates the status of patient safety in diagnostic radiology in Taiwan, thereby providing helpful information to improve patient safety guidelines needed for medical imaging in the future.


Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.
Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.


Population-specific influence of SLC2A9 genotype on the acute hyperuricaemic response to a fructose load.
SLC2A9 is a strong genetic risk factor for hyperuricaemia and gout. SLC2A9 (GLUT9) is a high capacity urate transporter and reportedly transports glucose and fructose. Intake of fructose-containing beverages is associated with development of hyperuricaemia and gout. To determine whether genetic variation in SLC2A9 influences the acute serum urate response to a fructose load. Following an overnight fast, 76 healthy volunteers (25 Māori, 26 Pacific, 25 European Caucasian) drank a solution containing 64 g fructose. Serum and urine were obtained immediately before and then 30, 60, 120 and 180 min after ingestion. The SLC2A9 single nucleotide polymorphism (SNP) rs11942223 was genotyped and data were analysed based on the presence or absence of the gout protective minor allele (C). The rs11942223 C allele was present in 17 participants (22%). In the entire group, fructose intake led to an increase in serum urate, which peaked 60 min following fructose ingestion (analysis of variance p=0.006). The presence of the C allele was associated with an attenuated hyperuricaemic response (p(SNP)<0.0001) and increased fractional excretion of uric acid (FEUA) (p(SNP)<0.0001) following the fructose load. The effects of rs11942223 variants on serum urate and FEUA in response to fructose were present only in Caucasian ancestral subgroups but not in the Māori and Pacific ancestral subgroup. Variation in SLC2A9 influences acute serum urate and FEUA responses to a fructose load. SLC2A9 genotype may influence the development of gout on exposure to fructose-containing beverages, particularly in European Caucasian populations.


Somatostatin-receptor positive brain stem glioma visualized by octreoscan.
In diffuse brainstem gliomas often surgical biopsies cannot be obtained. The diagnosis relies upon imaging criteria, first line being MRI. Gliomas generally express somatostatin receptors (SSTR), which might enable receptor imaging. We present the case of a female adolescent with acute onset of hallucinations, dysphagia and diplopia. MRI detected a suggestive large pontine glioma. This lesion presented with marked In-111-pentreotide tracer uptake. SSTR-scan provided information about SSTR-expression, tumour viability and extension. Radiopeptide therapy for selected patients might be discussed.


Plant organellar RNA editing: what 30 years of research has revealed.
The central dogma in biology defines the flow of genetic information from DNA to RNA to protein. Accordingly, RNA molecules generally accurately follow the sequences of the genes from which they are transcribed. This rule is transgressed by RNA editing, which creates RNA products that differ from their DNA templates. Analyses of the RNA landscapes of terrestrial plants have indicated that RNA editing (in the form of C-U base transitions) is highly prevalent within organelles (that is, mitochondria and chloroplasts). Numerous C→U conversions (and in some plants also U→C) alter the coding sequences of many of the organellar transcripts and can also produce translatable mRNAs by creating AUG start sites or eliminating premature stop codons, or affect the RNA structure, influence splicing and alter the stability of RNAs. RNA-binding proteins are at the heart of post-transcriptional RNA expression. The C-to-U RNA editing process in plant mitochondria involves numerous nuclear-encoded factors, many of which have been identified as pentatricopeptide repeat (PPR) proteins that target editing sites in a sequence-specific manner. In this review we report on major discoveries on RNA editing in plant organelles, since it was first documented 30 years ago.


A serpin gene from a parasitoid wasp disrupts host immunity and exhibits adaptive alternative splicing.
Alternative splicing (AS) is a major source of protein diversity in eukaryotes, but less is known about its evolution compared to gene duplication (GD). How AS and GD interact is also largely understudied. By constructing the evolutionary trajectory of the serpin gene PpSerpin-1 (Pteromalus puparum serpin 1) in parasitoids and other insects, we found that both AS and GD jointly contribute to serpin protein diversity. These two processes are negatively correlated and show divergent features in both protein and regulatory sequences. Parasitoid wasps exhibit higher numbers of serpin protein/domains than nonparasitoids, resulting from more GD but less AS in parasitoids. The potential roles of AS and GD in the evolution of parasitoid host-effector genes are discussed. Furthermore, we find that PpSerpin-1 shows an exon expansion of AS compared to other parasitoids, and that several isoforms are involved in the wasp immune response, have been recruited to both wasp venom and larval saliva, and suppress host immunity. Overall, our study provides an example of how a parasitoid serpin gene adapts to parasitism through AS, and sheds light on the differential features of AS and GD in the evolution of insect serpins and their associations with the parasitic life strategy.


Optomotor-blind expression in glial cells is required for correct axonal projection across the Drosophila inner optic chiasm.
In the Drosophila adult visual system, photoreceptor axons and their connecting interneurons are tied into a retinotopic pattern throughout the consecutive neuropil regions: lamina, medulla and lobula complex. Lamina and medulla are joined by the first or outer optic chiasm (OOC). Medulla, lobula and lobula plate are connected by the second or inner optic chiasm (IOC). In the regulatory mutant In(1)omb(H31) of the T-box gene optomotor-blind (omb), fibers were found to cross aberrantly through the IOC into the neuropil of the lobula complex. Here, we show that In(1)omb(H31) causes selective loss of OMB expression from glial cells within the IOC previously identified as IOC giant glia (ICg-glia). In the absence of OMB, ICg-glia retain their glial cell identity and survive until the adult stage but tend to be displaced into the lobula complex neuropil leading to a misprojection of axons through the IOC. In addition, adult mutant glia show an aberrant increase in length and frequency of glial cell processes. We narrowed down the onset of the IOC defect to the interval between 48 h and 72 h of pupal development. Within the 40 kb of regulatory DNA lacking in In(1)omb(H31), we identified an enhancer element (ombC) with activity in the ICg-glia. ombC-driven expression of omb in ICg-glia restored proper axonal projection through the IOC in In(1)omb(H31) mutant flies, as well as proper glial cell positioning and morphology. These results indicate that expression of the transcription factor OMB in ICg-glial cells is autonomously required for glial cell migration and morphology and non-autonomously influences axonal pathfinding.


Potato virus X movement in Nicotiana benthamiana: new details revealed by chimeric coat protein variants.
Potato virus X coat protein is necessary for both cell-to-cell and phloem transfer, but it has not been clarified definitively whether it is needed in both movement phases solely as a component of the assembled particles or also of differently structured ribonucleoprotein complexes. To clarify this issue, we studied the infection progression of a mutant carrying an N-terminal deletion of the coat protein, which was used to construct chimeric virus particles displaying peptides selectively affecting phloem transfer or cell-to-cell movement. Nicotiana benthamiana plants inoculated with expression vectors encoding the wild-type, mutant and chimeric viral genomes were examined by microscopy techniques. These experiments showed that coat protein-peptide fusions promoting cell-to-cell transfer only were not competent for virion assembly, whereas long-distance movement was possible only for coat proteins compatible with virus particle formation. Moreover, the ability of the assembled PVX to enter and persist into developing xylem elements was revealed here for the first time.


Clinical diagnosis of colorectal cancer using electrospun triple-blend fibrous mat-based capture assay of circulating tumor cells.
Conventional in vitro circulating tumor cell (CTC) detection methods are always limited by the blood sample volume because of the extremely low abundance of CTCs among the large number of hematologic cells. The aim of this study was to overcome this limitation by designing and constructing an in vitro CTC capture assay. We blended poly(sulfobetaine methacrylate) (PSBMA) and poly(acrylic acid) (PAA) into nylon-6 through electrospinning to generate a fibrous mat-based capture assay of CTCs. The contents of nylon-6, PSBMA, and PAA in the electrospun triple-blend fibrous mats (ETBFMs) were optimized to avoid degradation and to balance between the non-biofouling behavior and the antibody immobilizing efficiency. In addition, we examined the capture ability of CTCs for clinical diagnoses of colorectal cancer, in comparison with the results identified through pathological analyses of biopsies from colonoscopies. For nine individuals with stage II, III, and IV colorectal cancer, our CTC detection with ETBFMs provided complete positive expression. Two of four individuals were diagnosed to possess stage I colorectal cancer. Two of seven individuals without colorectal tumor, as identified through pathological analyses of biopsies, exhibited positive expression of CTCs. These positive results suggest that such ETBFMs are promising materials for in vitro CTC capture assays.


Diagnostic and therapeutic procedures among Australian hospital patients identified as indigenous.
To determine whether hospital patients identified as Indigenous are less likely than other inpatients to have a principal procedure recorded, and the extent to which any disparity in procedure use can be explained by differences in patient, episode and hospital characteristics. Retrospective analysis of routinely collected administrative data from the National Hospital Morbidity Database (NHMD). Australian public and private hospitals. All patients included in the NHMD whose episode type was recorded as acute and whose separation occurred between 1 July 1997 and 30 June 1998. Patients admitted for routine dialysis treatment were excluded. Whether a principal procedure was recorded. In public hospitals, patients identified as Indigenous were significantly less likely than other patients to have a principal procedure recorded, even after adjusting for patient, episode and hospital characteristics (adjusted odds ratio [OR], 0.67; 95% CI, 0.66-0.68). This disparity was apparent for most diseases and conditions. In private hospitals, no significant difference was observed (adjusted OR, 0.94; 95% CI, 0.83-1.06). The disparity in procedure use after adjustment for relevant factors indicates that in Australian public hospitals there may be systematic differences in the treatment of patients identified as Indigenous.


Benchmarking usability of patient portals in Estonia, Finland, Norway, and Sweden.
Poor usability is a barrier to widespread adoption of electronic health records (EHR). Providing good usability is especially challenging in the health care context, as there is a wide variety of patient users. Usability benchmarking is an approach for improving usability by evaluating and comparing the strength and weaknesses of systems. The main purpose of this study is to benchmark usability of patient portals across countries. A mixed-methods survey approach was applied to benchmark the national patient portals offering patient access to EHR in Estonia, Finland, Norway, and Sweden. These Nordic countries have similar public healthcare systems, and they are pioneers in offering patients access to EHR for several years. In a survey of 29,334 patients, both patients' quantitative ratings of usability and their qualitative descriptions of very positive and very negative peak experiences of portal use were collected. The usability scores ranged from good to fair level of usability. The narratives of very positive and very negative experiences included the benefits of the patient portals and experienced usability issues. The regression analysis of results showed that very positive and negative experiences of patient portal use explain 19-35% of the variation of usability scores in the four countries. The percentage of patients who reported very positive or very negative experiences in each country was unrelated to the usability scores across countries. The survey approach could be used to evaluate usability with a wide variety of users and it supported learning from comparison across the countries. The combination of quantitative and qualitative data provided an approximation of the level of the perceived usability, and identified usability issues to be improved and useful features that patients appreciate. Further work is needed to improve the comparability of the varied samples across countries.


A clinical trial of a knowledge-based medical record.
To meet the needs of primary care physicians caring for patients with HIV infection, we developed a knowledge-based medical record to allow the on-line patient record to play an active role in the care process. These programs integrate the on-line patient record, rule-based decision support, and full-text information retrieval into a clinical workstation for the practicing clinician. To determine whether use of a knowledge-based medical record was associated with more rapid and complete adherence to practice guidelines and improved quality of care, we performed a controlled clinical trial among physicians and nurse practitioners caring for 349 patients infected with the human immuno-deficiency virus (HIV); 191 patients were treated by 65 physicians and nurse practitioners assigned to the intervention group, and 158 patients were treated by 61 physicians and nurse practitioners assigned to the control group. During the 18-month study period, the computer generated 303 alerts in the intervention group and 388 in the control group. The median response time of clinicians to these alerts was 11 days in the intervention group and 52 days in the control group (PJJ0.0001, log-rank test). During the study, the computer generated 432 primary care reminders for the intervention group and 360 reminders for the control group. The median response time of clinicians to these alerts was 114 days in the intervention group and more than 500 days in the control group (PJJ0.0001, log-rank test). Of the 191 patients in the intervention group, 67 (35%) had one or more hospitalizations, compared with 70 (44%) of the 158 patients in the control group (PJ=J0.04, Wilcoxon test stratified for initial CD4 count). There was no difference in survival between the intervention and control groups (P = 0.18, log-rank test). We conclude that our clinical workstation significantly changed physicians' behavior in terms of their response to alerts regarding primary care interventions and that these interventions have led to fewer patients with HIV infection being admitted to the hospital.


Orally administered isoflavones are present as glucuronides in the human prostate.
Better knowledge of the bioavailability and metabolism of isoflavones in prostate tissue is needed to further investigate their mechanisms of action in the context of prostate cancer prevention. A total of 12 men with benign prostatic hyperplasia received soy extract supplementation (3 Evestrel capsules, providing a total of 112.5 mg isoflavones aglycone eq/day) for 3 days before prostate surgery. Blood and prostate tissues were sampled and metabolites were identified using electrospray ionization liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) and chemically synthesized standards of glucuronidated isoflavones. The main metabolites were the same in prostate tissue and in plasma, namely, 2 monoglucuronides of daidzein and 2 monoglucuronides of genistein. Concentrations of total isoflavones measured in prostate reached 1.05 +/- 0.62 nmol/g tissue (range 0.30-2.23) at the time of sampling, 12 h after the last isoflavone supplementation. At that time point, prostate concentrations were lower than plasma concentrations in all volunteers: 0.47 nmol/g vs. 0.66 microM for daidzein and 0.58 nmol/g vs. 0.78 microM for genistein. Isoflavone mechanisms of action should thus be investigated in in vitro cell studies using physiological conditions, intracellular concentrations below 5 nmol/g and no intracellular deconjugation of the monoglucuronide metabolites.


The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neogenesis in chronic Helicobacter pylori-induced inflammation.
Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, and Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to be involved in the formation of such tertiary lymphoid tissue. High expression of CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic lymphoid follicles in chronic infectious diseases. Here, we defined the role of CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient mice failed to develop organized gastric lymphoid follicles despite similar bacterial colonization density as infected wild-type mice. CXCR5 deficiency altered Th17 responses but not Th1-type cellular immune responses to H. pylori infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific serum IgG and IgA levels and an overall decrease in chronic gastric immune responses. In conclusion, the development of mucosal tertiary ectopic follicles during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5 signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic immune responses.


Delta Beta-Thalassaemia in two yugoslavian families.
Members of two Yugoslavian families were found to have delta-beta-thalassaemia. Interaction of beta-thalassaemia with delta-beta-thalassaemia occured in two young children producing a clinical condition which is somewhat less severe than that of homozygous beta-thalassaemia. Results from biosynthetic analyses indicate that the degree of globin chain imbalance in double heterozygotes for beta- and delta-beta-thalassaemia is similar to that in homozygous beta-thalassaemia. Fetal haemoglobin of all heterozygotes contained G-gamma and A-gamma chains in an average ratio of about 2:3 whereas that in the two double heterozygotes had G-gamma and A-gamma chains in a ratio of 3:2.


Pemirolast reduces cisplatin-induced kaolin intake in rats.
Emesis is the most feared side effect in patients who are undergoing cancer chemotherapy. In particular, cisplatin causes severe acute and delayed emesis. Although early vomiting is well controlled by 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonists, delayed-phase vomiting is not sufficiently controlled. Substance P is thought to be involved in the development of emesis, and tachykinin NK(1) receptor antagonists can inhibit delayed vomiting. We previously have reported that substance P is involved in the paclitaxel-induced hypersensitivity reaction in rats, and anti-allergic agent pemirolast reduces these reactions via inhibition of substance P release. In the present study, we investigated the effect of pemirolast on cisplatin-induced kaolin intake, which is an index of nausea/vomiting in the rat. Cisplatin (5 mg/kg, i.p.) induced kaolin intake and reduced normal feed intake from days 1 to 5 after injection. Cisplatin-induced kaolin intake was significantly reduced by co-administration of ondansetron (2 mg/kg, i.p.), a 5-HT(3) receptor antagonist, and dexamethasone (2 mg/kg, i.p.) from days 1 to 5. Similarly, pemirolast (10 mg/kg, p.o.) and the tachykinin NK(1) receptor antagonist aprepitant (10 and 30 mg/kg, p.o.) significantly reduced cisplatin-induced kaolin intake on days 3 and 4. Moreover, pemirolast at the same dose significantly reversed the cisplatin-induced increase in the cerebrospinal fluid level of substance P in rats. These results suggest that substance P is involved in cisplatin-induced kaolin intake in rats, and pemirolast reduces kaolin intake by inhibition of substance P release.


Dipyrrin based metal complexes: reactivity and catalysis.
Sometimes named half-porphyrins, bis-pyrrolic dipyrrin ligands endow their metal complexes with unique properties such as the potential to functionalize the heterocyclic backbone or the meso position and the ability to catalyze interesting chemical transformations. Thus, strategies towards the derivatization of or at the meso group and the use of dipyrrin metal complexes for the formation of a broad range of polypyrrolic derivatives such as 2,2'-bis-dipyrrins, nor-/hetero-corroles and porphynoids have been elaborated. Furthermore, the chelating ability of dipyrrins and the possibility of modifying their steric and electronic characteristics by functionalization can be exploited for the development of numerous complexes featuring appealing properties. Hence, C-H activation/amination, polymerization or oxidation reactions can be catalyzed by dipyrrin metal complexes and classical reagents such as Grignard species, Rh-based or Suzuki-Miyaura catalysts have been revisited by incorporation of dipyrrins in the coordination sphere of the metal cations. This contribution aims to review and illustrate all these aspects, highlighting the potential of these complexes for the design and synthesis of valuable organic compounds and metallo-organic architectures.


Integrating cost information with health management support system: an enhanced methodology to assess health care quality drivers.
Changes in health care delivery, reimbursement schemes, and organizational structure have required health organizations to manage the costs of providing patient care while maintaining high levels of clinical and patient satisfaction outcomes. Today, cost information, clinical outcomes, and patient satisfaction results must become more fully integrated if strategic competitiveness and benefits are to be realized in health management decision making, especially in multi-entity organizational settings. Unfortunately, traditional administrative and financial systems are not well equipped to cater to such information needs. This article presents a framework for the acquisition, generation, analysis, and reporting of cost information with clinical outcomes and patient satisfaction in the context of evolving health management and decision-support system technology. More specifically, the article focuses on an enhanced costing methodology for determining and producing improved, integrated cost-outcomes information. Implementation issues and areas for future research in cost-information management and decision-support domains are also discussed.


Macrophages-derived exo-miR-4449 induced by Cryptococcus affects HUVEC permeability and promotes pyroptosis in BEAS-2B via the HIC1 pathway.
Macrophages have recently been discovered to assume a significant role in the progression of cryptococcosis. However, the potential involvement of macrophage-derived exosomes in the pathogenesis of cryptococcosis remains uncertain. In this study, we investigated the changes of microRNAs in macrophage exosomes (exo-miRNAs) in cryptococcal infections and the role of markedly altered exo-miRNAs in the modulation of Human Umbilical Vein Endothelial Cells (HUVEC) permeability and ROS accumulation and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B). Techniques such as microarray analysis and real-time quantitative PCR were used to detect different exo-miRNAs and to screen for the most highly expressed exo-miRNAs. Then its mimics were transfected into HUVEC to study its effect on the monolayer permeability of HUVEC. Finally, the relationship between this exo-miRNAs and the ROS accumulation and pyroptosis was verified by bioinformatics analysis. The results showed that five exo-miRNAs were overexpressed and two exo-miRNAs were reduced, among which, exo-miR-4449 was expressed at the highest level. Exo-miR-4449 could be internalized by HUVEC and enhanced its monolayer permeability. Moreover, exo-miR-4449 was found to promote ROS accumulation and pyroptosis in BEAS-2B through HIC1 pathway. Thus, exo-miR-4449 plays an important role in the pathogenesis of cryptococcosis and holds promise as a significant biomarker for treatment.


Sprayable copper and copper-zinc nanowires inks for antiviral surface coating.
Copper alloys are known for their high antimicrobial efficacy. Retrofitting high-touch surfaces in public space with solid copper components is expensive and often impractical. Directly coating copper onto these high-touch surfaces can be achieved with hot or cold spray, but the procedure is complicated and requires special equipment. This article reports on the development of sprayable copper and copper-zinc nanowire inks for antiviral surface coating applications. Our results show that copper nanowires inactivate the SARS-CoV-2 virus faster than bulk copper. And a trace amount of zinc addition has a significant effect in enhancing the virucidal effect. More importantly, these nanowire inks are sprayable. They can be easily applied on high-touch surfaces with a spray can. When combined with common chemical disinfectants, the copper-based nanowire ink spray may prolong the disinfecting effect well after application.


Identification of strategies to facilitate organ donation among African Americans using the nominal group technique.
African Americans are disproportionately affected by ESRD, but few receive a living donor kidney transplant. Surveys assessing attitudes toward donation have shown that African Americans are less likely to express a willingness to donate their own organs. Studies aimed at understanding factors that may facilitate the willingness of African Americans to become organ donors are needed. A novel formative research method was used (the nominal group technique) to identify and prioritize strategies for facilitating increases in organ donation among church-attending African Americans. Four nominal group technique panel interviews were convened (three community and one clergy). Each community panel represented a distinct local church; the clergy panel represented five distinct faith-based denominations. Before nominal group technique interviews, participants completed a questionnaire that assessed willingness to become a donor; 28 African-American adults (≥19 years old) participated in the study. In total, 66.7% of participants identified knowledge- or education-related strategies as most important strategies in facilitating willingness to become an organ donor, a view that was even more pronounced among clergy. Three of four nominal group technique panels rated a knowledge-based strategy as the most important and included strategies, such as information on donor involvement and donation-related risks; 29.6% of participants indicated that they disagreed with deceased donation, and 37% of participants disagreed with living donation. Community participants' reservations about becoming an organ donor were similar for living (38.1%) and deceased (33.4%) donation; in contrast, clergy participants were more likely to express reservations about living donation (33.3% versus 16.7%). These data indicate a greater opposition to living donation compared with donation after one's death among African Americans and suggest that improving knowledge about organ donation, particularly with regard to donor involvement and donation-related risks, may facilitate increases in organ donation. Existing educational campaigns may fall short of meeting information needs of African Americans.


Two fatty acid delta9-desaturase genes, ole1 and ole2, from Mortierella alpina complement the yeast ole1 mutation.
Genes encoding two distinct fatty acid delta9-desaturases were isolated from strains of the oleaginous fungus Mortierella alpina. Two genomic sequences, delta9-1 and delta9-2, each containing a single intron, were cloned from strain CBS 528.72 while one cDNA clone, LM9, was isolated from strain CBS 210.32. The delta9-1 gene encoded a protein of 445 aa which shared 99% identity with the LM9 gene product. These proteins also showed 40-60% identity to the delta9-desaturases (Ole1p) of other fungi and contained the three conserved histidine boxes, C-terminal cytochrome b5 fusion and transmembrane domains characteristic of endoplasmic reticulum membrane-bound delta9-desaturases. LM9 and delta9-1 are therefore considered to represent the same gene (ole1). The ole1 gene was transcriptionally active in all M. alpina strains tested and its function was confirmed by complementation of the Saccharomyces cerevisiae ole1 mutation. Fatty acid analysis of yeast transformants expressing the CBS 210.32 ole1 gene showed an elevated level of oleic acid (18:1) compared to palmitoleic acid (16:1), the major fatty acid component of wild-type S. cerevisiae. This indicated that the M. alpina delta9-desaturase had a substrate preference for stearic acid (18:0) rather than palmitic acid (16:0). Genomic clone delta9-2 (ole2) also encoded a protein of 445 aa which had 86% identity to the delta9-1 and LM9 proteins and whose ORF also complemented the yeast ole1 mutation. The transcript from this gene could only be detected in one of the six M. alpina strains tested, suggesting that its expression may be strain-specific or induced under certain physiological conditions.


Intrathecal baclofen treatment an option in X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy (X-ALD) is a genetic peroxisomal disorder associated with tissue accumulation of very long chain fatty acids (VLCFAs). In approximately one third of affected males, this causes progressive and irreversible damage to the brain white matter. Progress is often rapid with upper motor neuron damage leading to severe spasticity and dystonia. The increased muscle tone is frequently difficult to alleviate with oral drugs. Here, we describe two patients with X-ALD who have received treatment with intrathecal baclofen pumps (ITB). Both boys had a rapidly progressive cerebral form of the disorder resulting, among other things, in escalating spasticity and dystonia causing severe pain, dramatically reducing their quality of life. Both were treated with a variety of oral medications without adequate relief. Both patients tolerated ITB surgery without complications and the positive clinical effects of treatment with ITB became clear in the following weeks and months, with significantly reduced muscle tone, less pain and better sleep. Moreover, general caretaking became easier. The treatment of spasticity and dystonia in these patients is difficult partly due to the relentless nature of this progressive disorder. In our two patients, ITB has been effective from both a symptomatic and palliative perspective. We recommend that such treatment be considered as an early option for increased muscle tone in boys with the cerebral form of X-ALD.


Cyclin B1 interacts with the BH3-only protein Bim and mediates its phosphorylation by Cdk1 during mitosis.
Protracted mitotic arrest leads to cell death; however, the molecular signals that link these distinct processes remain poorly understood. Here we report that the pro-apoptotic BH3-only family member Bim undergoes phosphorylation in K562 cells following treatment with the microtubule targeting agents Taxol and Nocodazole. The phosphorylation of two Bim isoforms, BimEL and BimL, at the mitochondria correlates with mitotic arrest and precedes cell death induced by Taxol. It was also found that Bim undergoes transient phosphorylation during normal mitosis in K562 cells. In addition, siRNA silencing of Bim reduces sensitivity to Taxol-induced cell death. The transition of K562 cells from mitosis to G1 results in the loss of BimEL and BimL phosphorylation and correlates with the degradation of cyclin B1. The Cdk1 inhibitors, RO-3306 and Purvalanol A, block Bim phosphorylation in mitotically arrested cells. Importantly, it was found that cyclin B1 co-immunoprecipitates with endogenous Bim in mitotic extracts. Furthermore, active recombinant Cdk1/cyclin B1 phosphorylates BimEL and BimL in vitro and Serine 44 on BimL has been identified as a Cdk1 phosphorylation site. Collectively, these results suggest that Cdk1/cyclin B1-dependent hyper-phosphorylation of Bim during prolonged mitotic arrest is an important cell death signal.


Towards the morphology of medical information systems.
A review of research and development in the field of medical information systems shows that, on the whole, technical hardware and specific software problems have been the central consideration. Only recently has it been acknowledged that it is necessary to include the formerly neglected specific functional and organizational aspects. In this respect, morphological approaches enable new perspectives to be opened up for the analysis, design and classification of medical information systems.


Electroporation of synthetic DNA antigens offers protection in nonhuman primates challenged with highly pathogenic avian influenza virus.
Avian influenza highlights the need for novel vaccination techniques that would allow for the rapid design and production of safe and effective vaccines. An ideal platform would be capable of inducing both protective antibodies and potent cellular immune responses. These potential advantages of DNA vaccines remain unrealized due to a lack of efficacy in large animal studies and in human trials. Questions remain regarding the potential utility of cellular immune responses against influenza virus in primates. In this study, by construct optimization and in vivo electroporation of synthetic DNA-encoded antigens, we observed the induction of cross-reactive cellular and humoral immune responses individually capable of providing protection from influenza virus infection in the rhesus macaque. These studies advance the DNA vaccine field and provide a novel, more tolerable vaccine with broad immunogenicity to avian influenza virus. This approach appears important for further investigation, including studies with humans.


Implementing a prenatal oral health program through interprofessional collaboration.
Interprofessional collaboration has become a critical component of accreditation standards in dentistry and medicine. This article reports on implementation in an academic setting of a prenatal oral health program (pOHP) that addresses coordinated care, accreditation standards, and new clinical practice guidelines. The pOHP is an educational intervention for third-year medical students, residents, and faculty members to deliver preventive oral health information and referral to a dental home for pregnant women. At the same time, senior dental students and faculty members are introduced to prenatal oral health principles and delivery of comprehensive oral health care to pregnant women. A systems-based approach was used to guide the pOHP implementation during the 2012-13 academic year. Participants were 96 third-year medical students (50% of the total in an obstetrics and gynecology clerkship) and all 81 fourth-year dental students. During that academic year, 126 dental referrals were made to the School of Dentistry, and 55 women presented for care, resulting in 50% (n=40) of dental students participating in the clinical experience and delivery of simple to complex oral health procedures. The prenatal period is a frequently missed opportunity to address oral health care. The pOHP is an interprofessional collaboration model designed to educate dental and medical providers and provide a system of referral for comprehensive clinical care of pregnant patients, including educating women about their oral health and that of their children. Such programs can help meet interprofessional accreditation standards and encourage implementation of practice guidelines.


Garlic and allopurinol attenuate hepatic apoptosis induced by fipronil in male albino rats.
Fipronil (FPN) can induce oxidative tissue damage and may be contemplated as an apoptosis inducer. Our aim is to investigate the possible hepatoprotective roles of garlic or allopurinol (ALP) against fipronil subacute toxicity. Thirty-six mature male albino rats were randomly divided into six groups; the first group was saved as control (C), the 2nd (G) was orally intubated with 500 mg/kg aqueous garlic extract, and the 3rd (A) received 150 mg/L allopurinol in their drinking water. The 4th group (F) was administered 13.277 mg/kg fipronil by gavage, while the 5th (G + F) and 6th (A + F) groups received the same doses of garlic and allopurinol, respectively two hours before fipronil intoxication. Our results revealed that FPN significantly increased the hepatic malondialdehyde, protein carbonyl levels, and the enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and xanthine oxidase, but it decreased glutathione-S-transferase compared to the control group. Moreover, FPN exhibited significant up-regulation in the hepatic pro-apoptotic (Bax) and caspase-3 genes expression, down-regulation in the anti-apoptotic (Bcl-2) mRNA gene expression and induced DNA fragmentation. Surprisingly, garlic or allopurinol co-treatment ameliorated the hepatic lipid peroxidation, antioxidants disruption, and apoptosis induced by FPN. In conclusion, garlic and allopurinol relieved the oxidative injury and reduced the fipronil-induced apoptosis probably by improving the tissue antioxidant defense system.


Developing Force Fields from the Microscopic Structure of Solutions.
We have been developing force fields designed for the eventual simulation of peptides and proteins using the Kirkwood-Buff (KB) theory of solutions as a guide. KB theory provides exact information on the relative distributions for each species present in solution. This information can also be obtained from computer simulations. Hence, one can use KB theory to help test and modify the parameters commonly used in biomolecular studies. A series of small molecule force fields representative of the fragments found in peptides and proteins have been developed. Since this approach is guided by the KB theory, our results provide a reasonable balance in the interactions between self-association of solutes and solute solvation. Here, we present our progress to date. In addition, our investigations have provided a wealth of data concerning the properties of solution mixtures, which is also summarized. Specific examples of the properties of aromatic (benzene, phenol, p-cresol) and sulfur compounds (methanethiol, dimethylsulfide, dimethyldisulfide) and their mixtures with methanol or toluene are provided as an illustration of this kind of approach.


[Silence in the daily life of the adolescent with HIV/AIDS].
This study is characterized as a qualitative research with the objective of unveiling the perception and experience regarding the antiretroviral treatment of the adolescent with acquired immunodeficiency syndrome. The research was carried out within reference health care centers in two municipalities from the southern region of Brazil. The data production was developed through the creativity and sensitiveness dynamics of talking map type by a group of five participants. One applied the technique of content thematic analysis. The artistic productions and testimonies evidenced their daily experience with use of medications and the silence on the diagnosis of the disease and its treatment that implies the health care. The conclusion drawn is that the involvement of health professionals is needed since it opens spaces for the family besides promoting the dialogue of its members with the adolescent aiming at the adhesion to the treatment.


Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles.
In obesity, metabolic stress and inflammation in injured tissues could favour enhanced shedding of procoagulant microparticles (MPs). At sites of endothelium injury, the swift recruitment of procoagulant leukocyte-derived MPs enables the initiation of blood coagulation and thrombus growth. In obese females, we sought to evaluate the impact of a very low-calorie diet (VLCD) on procoagulant MP levels, fibrinolytic status, inflammation and endothelium damage. Circulating biomarkers of vascular damage, fibrinolytic status, platelet activation and inflammation were measured before, 30 and 90 days after starting a short-term VLCD. MPs were measured by flow cytometry and capture assays. Their procoagulant potential was quantified using functional prothrombinase assays and their cellular origin were determined using flow cytometry (endothelium, platelet, leukocyte, lymphocyte and erythrocyte-derived MP) or capture assays. A total of 24 obese females (39 ± 10 years) with a mean body mass index of 35 ± 4 kg m(-2) were prospectively enroled. Procoagulant leukocyte-derived MPs were associated with the waist circumference at baseline (r=0.534; P=0.010) and at 90 days follow-up (r=0.487; P=0.021). At 90 days, weight reduction (-9.8%) was associated with a lowering of blood pressure, improvement of metabolic parameters and a significant reduction of plasminogen activator inhibitor-1 (PAI-1) (-38%), procoagulant platelet-derived MPs (-43%), leukocyte-derived MPs (-28%) and leptin (-32%) levels. In obese females, a short-term VLCD results in an overall improvement of the haemostatic balance characterized by the reduction of PAI-levels, diminished release of platelet and leukocyte-derived MPs and a reduction in leptin levels, an adipocyte-derived cytokine.


Venovenous carbon dioxide removal in chronic obstructive pulmonary disease: experience in one patient.
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. Acute exacerbations of COPD account for up to 84% of the total economic cost of this disease. The altered mechanics of the COPD patient represent a unique challenge to the clinician instituting assisted ventilation in this population. We developed an alternative mode of limited extracorporeal support termed Venovenous carbon dioxide removal (VVCO2R). We report our first case using VVCO2R, a 42-year-old white woman with a history of COPD and asthma, who was a heavy smoker at the time of admission. We utilized a compact, low flow pediatric extracorporeal circuit interposed with a low resistance gas exchange device. Venovenous carbon dioxide removal allowed for a reduction in the patient's minute ventilation to 30% of baseline with improved arterial blood gases (ABGs), a reduction in peak airway pressures and improvement in her hyperinflation. Our experience demonstrates that this system can effectively remove CO2 safely in a single cannula venous configuration while maintaining minimal anticoagulation. We believe this system could potentially be utilized in any medical or surgical intensive care unit.