5-HT7 receptor deletion enhances REM sleep suppression induced by selective serotonin reuptake inhibitors, but not by direct stimulation of 5-HT1A receptor.
5-HT(7) receptors are involved in REM sleep and possibly in mood disorders. REM sleep suppression and antidepressant-like behavior is observed in 5-HT(7)(-/-) mice and in rats treated with 5-HT(7) receptor antagonists. We recently demonstrated that pharmacological blockade of 5-HT(7) receptors enhances REM sleep suppression and antidepressant-like behavior induced by citalopram in rodents. It has been hypothesized that the effect of citalopram on sleep is essentially mediated by the activation of 5-HT(1A) receptors. The present study investigates the impact of 5-HT(7) receptor gene deletion on the effect of various reuptake inhibitors on REM sleep and probes the role of 5-HT(1A) receptors in this response. Three SSRIs (citalopram, fluoxetine and paroxetine) but not the tricyclic antidepressant desipramine had a significantly stronger REM sleep suppressive effect in 5-HT(7)(-/-) mice compared to 5-HT(7)(+/+) mice. In contrast, REM sleep was similarly reduced in 5-HT(7)(+/+) mice and 5-HT(7)(-/-) mice after treatment with the 5-HT(1A) receptor agonist ipsapirone. Furthermore, both 5-HT(7)(+/+) and 5-HT(7)(-/-) mice displayed the same increase in REM sleep duration produced by the 5-HT(1A) receptor antagonist WAY-100635. These findings indicate that 5-HT(7) receptor deletion augments the effect of various SSRIs on REM sleep suppression and that this effect is distinct from those mediated via 5-HT(1A) receptors.


Study of the in Vivo Functional Role of Mutations in the BTB Domain of the CP190 Protein of Drosophila melanogaster.
The Drosophila transcription factor СР190 is one of the key proteins that determine the activity of housekeeping gene promoters and insulators. CP190 has an N-terminal BTB domain that allows for dimerization. Many of known Drosophila architectural proteins interact with the hydrophobic peptide-binding groove in the BTB domain, which is presumably a mechanisms for recruiting CP190 to regulatory elements. To study the role of the BTB domain in the interaction with architectural proteins, we obtained transgenic flies expressing CP190 variants with mutations in the peptide-binding groove, which disrupts their interaction with architectural proteins. As a result of the studies, it was found that mutations in the BTB domain do not affect binding of the CP190 protein to polytene chromosomes. Thus, our studies confirm the previously obtained data that CP190 is recruited to regulatory elements by several transcription factors interacting, in addition to BTB, with other CP190 domains.


High-resolution NMR spectra in inhomogeneous fields utilizing the CRAZED sequence without coherence selection gradients.
Coherence selection gradients have been considered as indispensable for high-resolution NMR spectroscopy in inhomogeneous fields utilizing the CRAZED-type sequences. However, our experimental results demonstrate that these gradients can be omitted if an appropriate phase cycling is applied. The measured linewidth of reconstructing 1D high-resolution spectral peaks does not depend on the dipolar correlation distance determined by the coherence selection gradients, but is only affected by diffusion and T(2) relaxation. This finding suggests the need to reconsider the mechanism for the iMQC-based high-resolution spectroscopy.


Analog Gated Recurrent Unit Neural Network for Detecting Chewing Events.
We present a novel gated recurrent neural network to detect when a person is chewing on food. We implemented the neural network as a custom analog integrated circuit in a 0.18 μm CMOS technology. The neural network was trained on 6.4 hours of data collected from a contact microphone that was mounted on volunteers' mastoid bones. When tested on 1.6 hours of previously-unseen data, the analog neural network identified chewing events at a 24-second time resolution. It achieved a recall of 91% and an F1-score of 94% while consuming 1.1 μW of power. A system for detecting whole eating episodes-like meals and snacks-that is based on the novel analog neural network consumes an estimated 18.8 μW of power.


Clinical characteristics of 132 healthcare worker cases with COVID-19: A retrospective study from a single center in Wuhan, China.
Many healthcare workers (HCWs) have been confirmed to be infected with SARS-CoV-2 in China. A retrospective, single-center study was conducted. The median age of the 132 HCWs with COVID-19 was 32 years, with 92 (69.7%) being females. There were 47 (35.6%) doctors, 72 (54.6%) nurses, and 13 (9.9%) other HCWs. Ten of the 132 patients (7.6%) had underlying diseases. The most common symptoms of illness onset were fever (70, 53.0%), cough (66, 50.0%), and fatigue (58, 43.9%). All patients were categorized into mild or moderate COVID-19 type on admission to hospital, and five (3.8%) progressed to the severe COVID-19 type. Sixty-six HCWs patients were included in both the early and later discharged group. In the logistic analysis, the later discharged patients had a longer time for illness onset to hospital admission (per 1 day; OR, 1.10; 95% CI, 1.03-1.18; p = .006), a higher proportion of >3 onset symptoms clustering (OR, 3.11; 95% CI, 1.27-7.62; p = .01), and a higher percentage of other HCWs (OR, 6.20; 95% CI, 1.49-25.80; p = .01). HCW patients were young female nurses with fewer comorbidities, and most were mild or moderate COVID-19 type. The later discharged patients exhibited characteristics of longer time for illness onset to hospitalization and clustering of onset symptoms.


Nonlinear desipramine kinetics: prevalence and importance.
Tricyclic antidepressant plasma levels have been used to guide dose adjustment in nonresponding patients, and recently 24-hour drug levels have been advocated for predicting therapeutic doses. Both methods of dose adjustment assume linear drug kinetics. Recent reports have suggested that desipramine kinetics are nonlinear, but the samples described were small, six subjects or fewer. In the current study, plasma desipramine concentrations were examined in 42 inpatients who were depressed who had achieved steady-state conditions with a low initial dose and subsequently with a higher dose. Desipramine concentrations increased significantly more than that predicted by the dose increase; however, only one third of the sample had substantial nonlinear changes (an increase in the concentration 50% greater than expected). In the remainder of the sample, disproportionate increases in plasma concentrations were not likely to be of clinical consequence.


MR urography: technique and results for the evaluation of urinary obstruction in the pediatric population.
MR urography has the potential to revolutionize imaging of the urinary tract in both adults and children, because of its ability to provide an unprecedented level of anatomic information and quantitative functional evaluation of each kidney. MR urography can now provide useful assessment of obstructive uropathy and may provide predictive information about which children will benefit from surgery. It has the potential to identify parameters that indicate a significant obstruction as opposed to self-limited hydronephrosis. Further technical developments in the field will produce greater insights into the pathophysiology of not only urologic disorders but also disorders of the kidney itself.


Outcomes of emergency in situ laser fenestration-assisted thoracic endovascular aortic repair in patients with acute Stanford type A aortic dissection unfit for open surgery.
This study investigated the outcomes of emergency in situ laser fenestration (ISLF)-assisted thoracic endovascular aortic repair (TEVAR) for patients with acute Stanford type A aortic dissection unfit for open surgery. Twenty patients with acute Stanford type A aortic dissection who were found to be unfit for open surgery, underwent emergency ISLF-assisted TEVAR in our center between March 2016 and December 2018. Anatomic criteria for endovascular repair: coronary artery and aortic valve was not involved, proximal landing zone diameter of 45 mm or less, and proximal landing zone length of 20 mm or greater. Their clinical outcomes were reviewed retrospectively. Twenty patients achieved a procedural success of 100.0%. The 30-day mortality was 10%; two patients died, one of severe pneumonia and the other from cerebral hemorrhage after the operation. Rate of stroke at 30 days was 5%. The average follow-up time was 16 months (range, 3-26 months). One death owing to heart failure occurred at 23 months postoperatively. Kaplan-Meier curve analysis revealed that the 24-month survival rate was 77.1%. Two patients had type Ia endoleaks and one had a type II endoleak. There was no stent graft migration or fenestration-related endoleak and all patients had a thrombosed false lumen in the covered section of the stent grafts. No reintervention, myocardial infarction, transient ischemic attacks, cerebral infarction, or other complications occurred during the follow-up period. Emergency ISLF-assisted TEVAR is a safe and effective alternative method for treating acute Stanford type A aortic dissection unfit for open surgery.


Cembranoids from the Red Sea soft coral Sarcophyton glaucum protect against indomethacin-induced gastric injury.
Soft corals and their secondary metabolites represent an exceptional source of potential drugs. In this regard, Sarcophyton glaucum-derived secondary metabolites were examined for their preventive activities against indomethacin-induced gastric ulcer. Extraction and chromatographic processing of a specimen of S. glaucum collected from the Red Sea waters of Jeddah city resulted in the isolation of eight metabolites including two furanone-based cembranoids (1 and 2), two known pyran-based cembranoids (3 and 4), a known aromadendrene derivative (5), a δ-lactone fatty acid derivative (6), and two known gorgostane-type sterols (7 and 8). Compounds 1 and 6 are new chemical structures, named Δ12(20)-sarcophine and sarcoglaucanoate, respectively. In an initial pilot experiment, compounds 1 and 2 showed significant protective activities against indomethacin-induced peptic ulcer in rats. These data were evidenced by their ability to ameliorate the elevated ulcer indices and prevent histopathological alterations observed in the untreated animals. Their effects were mediated by enhanced mucin as shown by Alcian blue and periodic acid-Schiff (PAS) staining of stomach sections. Compounds 1 and 2 exerted significant antioxidant properties as they prevent reduced glutathione (GSH) depletion, malondialdehyde (MDA) accumulation, and superoxide dismutase (SOD) exhaustion. Furthermore, immunohistochemical analyses indicated that both compounds inhibited the expression of interleukin-6 (IL-6) and tumor necrosis-α (TNF-α) as compared to indomethacin alone-treated animals. These actions were accompanied by significant enhancement of tumor growth factor-β (TGF-β) expression. In conclusion, two cembranoids exhibited protective activities against indomethacin-induced peptic ulcer. This is, at least partly, mediated by their pro-mucin, antioxidant, anti-inflammatory, and TGF-β stimulating properties.


Lipocalin 2 and Blood-Brain Barrier Disruption in White Matter after Experimental Subarachnoid Hemorrhage.
We reported previously that subarachnoid hemorrhage (SAH) causes acute white matter injury in mice. In this study, we investigated lipocalin 2 (LCN2) mediated blood-brain barrier (BBB) disruption in white matter, which may lead to subsequent injury. SAH was induced by endovascular perforation in wild-type (WT) and LCN2-knockout (LCN2(-/-)) mice. Sham mice underwent the same procedure without perforation. Mice underwent magnetic resonance imaging (MRI) 24 h after SAH to confirm the development of T2-hyperintensity in white matter. Western blotting and immunohistochemistry were performed to elucidate the mechanisms of LCN2-mediated white matter injury and BBB disruption. It was confirmed that LCN2 expression was significantly increased in white matter of WT mice after SAH by Western blotting (versus sham; p < 0.05). Immunohistochemistry showed that LCN2 receptor 24p3R was expressed in oligodendrocytes, astrocytes, endothelial cells, and pericytes in the white matter. In WT mice with SAH, albumin leakage along the white matter was prominently observed and was consistent with T2-hyperintensity on MRI. As with our previous report, LCN2(-/-) mice scarcely developed T2-hyperintensity on MRI or albumin leakage in white matter. Our results suggest that BBB leakage occurs in white matter after SAH and that LCN2 contributes to SAH-induced BBB disruption.


Depressed jejunal secretion of water and ions in response to prostaglandin E1 in adult celiac disease.
In order to test in man the concept that intestinal fluid secretion originates from the crypts of Lieberkühn, we assessed the jejunal secretory effect of intraluminal prostaglandin E1 (PGE1) (0.9 microgram/kg/min) in untreated adult celiac disease (ACD, N = 7), treated ACD (N = 4) and normal subjects using the intestinal perfusion technique. In untreated ACD (1) water and solutes were malabsorbed (or secreted) in the basal period; (2) fluid and ion secretion seen during PGE1 infusion and net secretory effect of PGE1 (difference in transport between basal and PGE1 periods) were reduced (P less than 0.01); (3) the effects of PGE1 inhibition of sodium insorption, and stimulation of sodium exsorption, were decreased and abolished, respectively. In treated patients PGE1-induced secretion returned towards normal values. Our finding of a depressed secretory response to PGE1 in the face of marked crypt hypertrophy do not support the concept that crypt cells are the major site of intestinal fluid secretion.


The influence of the ratio of protein energy to total energy in the feed on the activity of protein synthesis in vitro, the level of ribosomal RNA and the RNA-DNA ratio in white trunk muscle of Atlantic cod (Gadus morhua).
Cod (Gadus morhua) were fed diets containing protein energy to total energy levels (PE/TE) of 10.0, 20.6, 29.6, 38.4, 56.2 and 74.1% for 21 days. Ribosomes were isolated from the white trunk muscle tissue, the capacity for protein synthesis in vitro determined and related to muscle tissue wet weight rRNA and DNA. Protein concentrations of less than 47.4% PE/TE in the diets reduce the ribosomal capacity for protein synthesis per g wet weight and per mg DNA, and the tissue contents of rRNA and ratio of rRNA/DNA. The capacity for muscle protein synthesis in vitro is a significant and sensitive parameter of protein inadequacy in fish diets.


Anesthesia, the brain, and cardiopulmonary bypass.
The etiology and incidence of neurologic injury occurring after cardiac operations employing cardiopulmonary bypass is reviewed. Results of studies demonstrating the role of microemboli generated by pump oxygenators, and evidence for the efficacy of arterial line filtration to decrease delivery of emboli into the cerebral circulation and to decrease postoperative neuropsychological dysfunction, are similarly reviewed. The impact of different strategies for management of pH during moderate hypothermic cardiopulmonary bypass on cerebral blood flow and coupling of cerebral flow and metabolism, as well as their impact on the incidence of postoperative cognitive dysfunction, are also discussed, along with the results of studies examining the efficacy of various agents including thiopental, nimodipine, and nafamostat to decrease cognitive dysfunction subsequent to bypass.


A putative physiological role of hypothalamic CNTF in the control of energy homeostasis.
Administration of CNTF durably reduces food intake and body weight in obese humans and rodent models. However, the involvement of endogenous CNTF in the central regulation of energy homeostasis needs to be elucidated. Here, we demonstrate that CNTF and its receptor are expressed in the arcuate nucleus, a key hypothalamic region controlling food intake, and that CNTF levels are inversely correlated to body weight in rats fed a high-sucrose diet. Thus endogenous CNTF may act, in some individuals, as a protective factor against weight gain during hypercaloric diet and could account for individual differences in the susceptibility to obesity.


Susceptibility of Giardia lamblia to Hovenia dulcis extracts.
Giardia lamblia is the causative agent of giardiasis, a common parasitic infection of the human and animal digestive tract. Although several drugs have been available to treat this infection, they present unpleasant side effects or cytotoxicity. In order to find a more natural treatment for the disease, we analyzed the effects of the methanolic extract and three fractions obtained from Hovenia dulcis Thunb. (Rhamnaceae) leaves on G. lamblia. Comparing all fractions, dichloromethane was more efficient in reducing Giardia growth. The exposition of G. lamblia to this fraction lead to degenerations in the surface, modifications in the cell shape and alterations in the localization of nuclei. Besides that, the adhesion of G. lamblia was also altered. Experiments revealed that the obtained fraction did not present cytotoxic effects in mammalian cells. In summary, dichloromethane fraction has strong antigiardial effects and could become an important new substance for the treatment of giardiasis.


Evaluation of iron and zinc levels in recurrent tonsillitis and tonsillar hypertrophy.
The aim of this study is to look into the roles of iron and zinc metals in etiopathogenesis of recurrent tonsillitis and tonsillar hypertrophy by evaluating the levels of iron and zinc elements in the palatine tonsillar tissue. In total, 40 patients who underwent a tonsillectomy to treat recurrent tonsillitis and tonsillar hypertrophy were included in the study. Patients were classified into two groups, recurrent tonsillitis and tonsillar hypertrophy, determined by the results of clinical and histopathological examination. The levels of iron and zinc elements were determined for each tonsillar tissue sample. There was a significant difference in the iron and zinc concentrations (p<0.001) between the tonsillar hypertrophy and recurrent tonsillitis groups. The levels of iron and zinc were significantly lower in the recurrent tonsillitis group. This study suggests that low tissue concentrations of iron and zinc may lead to recurrent tonsillitis.


Association between Hepatic Oxidative Stress Related Factors and Activation of Wnt/β-Catenin Signaling in NAFLD-Induced Hepatocellular Carcinoma.
We investigated the association between iron overload, oxidative stress (8-oxo-7,8-dihydroguanine: 8-oxo-dG scores), Wnt/β-catenin pathway activation (expression of glutamine synthetase: GS), and tumor hyperintensity in the Gd-EOB-DTPA-enhanced MRI hepatobiliary phase (relative enhancement ratio: RER). This was a retrospective analysis of 94 hepatocellular carcinoma (HCC) patients who underwent surgical resection. In HBV-, HCV-, and alcohol-associated HCC, serum ferritin levels in the high and low RER groups were equivalent. In contrast, ferritin levels were elevated in the 'high RER' group of patients with nonalcoholic fatty liver disease (NAFLD)-HCC. As predictors of GS positivity, high RER had a sensitivity of 57.2% and a specificity of 100%. High serum ferritin had a sensitivity of 85.7% and a specificity of 85.7%. All cases with serum ferritin ≥275.5 ng/mL and high RER were 8-oxo-dG- and iron staining-positive. Additionally, GS positivity was seen in all cases with "serum ferritin levels above the upper limits or iron staining-positive" and '8-oxo-dG high' cases. Therefore, combining serum ferritin levels with RER may increase the accuracy with which activated Wnt/β-catenin signaling is predicted in NAFLD-HCC. We suggest that 8-oxo-dG accumulates following increased oxidative stress due to hepatic tissue iron deposition; this may activate Wnt/β-catenin signaling and trigger carcinogenesis.


Comparison of response to radiation, hyperthermia and cisplatin in parental and polymerase beta knockout cells.
The role of polymerase beta in response to radiation, cisplatin and hyperthermia was examined in a pair of mouse cell lines, comprising a normal parental line and a derivative with polymerase beta knockout. Cell survival was assessed using the colony survival assay. For irradiation, there was no difference in response between the two cell lines. Treatment with cisplatin for 1 h showed a large increase in resistance in the mutant cell line. The results with hyperthermia were more complex. The mutant was more resistant to 45 degrees C heating, but was slightly more heat sensitive than the wild type at 41 degrees C. Thus, in summary, while the knockout of polymerase beta did not alter radiation sensitivity, it did increase resistance to cisplatin and induced resistance to hyperthermia at higher temperatures (45 degrees C).


A comparative study of unpasteurized and pasteurized frozen whole hen eggs using size-exclusion chromatography and small-angle X-ray scattering.
Hen eggs are rich in proteins and are an important source of protein for humans. Pasteurized frozen whole hen eggs are widely used in cooking and confectionery and can be stored for long periods. However, processed eggs differ from raw eggs in properties such as viscosity, foaming ability, and thermal aggregation. To develop pasteurized frozen whole egg products with properties similar to those of unpasteurized whole eggs, it is necessary to establish a method that can differentiate between the two egg types with respect to the structures of their proteins. In this study, size-exclusion chromatography (SEC) and SEC coupled with small-angle X-ray scattering (SEC-SAXS) were successfully used to differentiate between the proteins in unpasteurized and pasteurized frozen whole eggs. We found that proteins in the plasma fraction of egg yolk, especially apovitellenins I and II, formed large aggregates in the pasteurized eggs, indicating that their structures are sensitive to temperature changes during pasteurization, freezing, and thawing. The results suggest that SEC and SEC-SAXS can be used to differentiate between unpasteurized and pasteurized frozen whole eggs. Additionally, they may be useful in determining molecular sizes and shapes of multiple components in various complex biological systems such as whole eggs.


Suppressors of superoxide production from mitochondrial complex III.
Mitochondrial electron transport drives ATP synthesis but also generates reactive oxygen species, which are both cellular signals and damaging oxidants. Superoxide production by respiratory complex III is implicated in diverse signaling events and pathologies, but its role remains controversial. Using high-throughput screening, we identified compounds that selectively eliminate superoxide production by complex III without altering oxidative phosphorylation; they modulate retrograde signaling including cellular responses to hypoxic and oxidative stress.


Nephrogenic adenoma of the bladder: report of 10 cases.
Nephrogenic adenoma is an uncommon metaplastic lesion of the lower urinary tract that usually is associated with antecedent inflammation or surgical procedures. We report 10 new cases, 8 of which followed renal transplantation and 1 of which followed partial cystectomy for squamous cell carcinoma of the bladder. No predisposing factors could be identified in 1 patient. The nephrogenic adenomas, all of which were located in the bladder, were treated by either biopsy with fulguration or transurethral resection. The lesion recurred locally in 1 patient.


Comparison between EMG to force processing and kinetic analysis for the calf muscle moment in walking and stepping.
In EMG to force processing the force of a muscle or the corresponding muscle moment with respect to the joint is determined from EMG and muscle length by means of a model of the muscle's contractile and elastic properties. In kinetic analysis the joint moment is calculated from the ground reaction force and the positions and accelerations of the body segments by means of Newtonian equations, based on a rigid body segment model. These two fundamentally different methods have been compared by determining simultaneously the calf muscle moment and the total ankle moment in walking at slow, moderate and fast speed and in stepping up and down a low bench. As long as there is no activity of other muscles, the moments obtained by either method should be identical. The analysis was restricted to such periods, as assessed from the EMG of tibialis anterior. In each experimental condition three steps were analyzed in five subjects of 21-22 yr. In comparison with the results of kinetic analysis, EMG processing shows differences between 7 and 54 Nm r.m.s., with an average of 22 Nm r.m.s. Normalized with respect to the r.m.s. value of the moment itself, the differences amount to 0.13-0.51, with an average of 0.22. In the majority of cases there was no systematic deviation between EMG processing and kinetic analysis and the r.m.s. difference was of the same order of magnitude as determined previously in ergometer experiments.


Identifying sources of tick blood meals using unidentified tandem mass spectral libraries.
Rapid and reliable identification of the vertebrate species on which a disease vector previously parasitized is imperative to study ecological factors that affect pathogen distribution and can aid the development of public health programs. Here we describe a proteome profiling technique designed to identify the source of blood meals of haematophagous arthropods. This method employs direct spectral matching and thus does not require a priori knowledge of any genetic or protein sequence information. Using this technology, we detect remnants of blood in blacklegged ticks (Ixodes scapularis) and correctly determine the vertebrate species from which the blood was derived, even 6 months after the tick had fed. This biological fingerprinting methodology is sensitive, fast, cost-effective and can potentially be adapted for other biological and medical applications when existing genome-based methods are impractical or ineffective.


Titania nanowires functionalized polyester fabrics with enhanced photocatalytic and antibacterial performances.
Flexible organic fabrics coated with titania find wide applications in pollutant degradations and antibiosis. Because of the enhanced charge separations, TiO2 with one-dimensional nanostructures exhibits photocatalytic activity superior to that of nanoparticulate films; however, only the later has been achieved on organic substrates through commonly sol-gel techniques till now. In this study, radially aligned TiO2 nanowires were precipitated on polyester fabrics through multi-steps of surface roughening, sol-gel TiO2 seeding, hydrogen titanate nanobelts precipitation, and finally sulfuric acid treatment. Both mesoporous anatase TiO2 nanowires and single-crystalline rutile TiO2 nanorods have been achieved, which, together with some unchanged titanate nanobelts, exhibited an overall narrowed band gap of ca. 2.50eV. The TiO2 nanowires on flexible PET fabrics showed higher photocatalytic activity towards degradations of not only rhodamine B in water but also toluene gas in air under UV light illumination, when compared with either TiO2 nanotube array or commercial Degussa P25 nanoparticulate films on metallic Ti substrates. Remarkable sterilization of E. coli and S. epidermidis under visible light irradiation was also achieved. The excellent photocatalytic and antibacterial performances were attributed to the unique mixed 1D nanostructures, phase junctions, abundant surface hydroxyl groups, and the narrowed band gap.


Enhanced growth of artificial tumor metastases following blood transfusion: the effect of erythrocytes, leukocytes and plasma transfusion.
Clinical and experimental investigations have shown that allogeneic blood transfusions may modulate the growth of tumors. Dependent on the tumor model used in animal studies, the effects observed ranged from inhibition to stimulation of tumor growth. We have demonstrated previously that allogeneic blood transfusions gave rise to enhanced growth of a transplantable sarcoma (LS 175) in BN rats. In the experiments reported here the effect of transfusion of different allogeneic blood constituents on the growth of artificial LS 175 lung metastases was investigated. Erythrocytes and leukocytes were found to promote tumor growth to a similar degree as whole blood transfusions, plasma transfusions had no effect.


Bluetongue antibody in Botswana's domestic and game animals.
Bluetongue precipitating antibody was demonstrated in sera of cattle, camels, sheep, goats and seven game species. Of the domestic species the percentage of sera positive were; cattle 92%, camels 81%, goats 83% and sheep 36%. Sheep sera, unlike those of other domestic species, varied greatly from area to area in the percentage positive. Seroconversions were recorded in adult sheep between September and April. In adult cattle there was a gradual decline in the percentage positive with increasing age. Positive reactions were recorded in the following game species: impala (Aepyceros melampus), lechwe (Kobus leche), kudu (Tragelaphus strepsiceros), blue wildebeest (Connochaetes taurinus), gemsbok (Oryx gazella), springbok (Antidorcas marsupialis) and tsessebe (Damaliscus lunatus).


Genomic comparison between pathogenic Streptococcus agalactiae isolated from Nile tilapia in Thailand and fish-derived ST7 strains.
Streptococcus agalactiae, or Group B streptococcus (GBS), is a highly virulent pathogen in aquatic animals, causing huge mortalities worldwide. In Thailand, the serotype Ia, β-hemolytic GBS, belonging to sequence type (ST) 7 of clonal complex (CC) 7, was found to be the major cause of streptococcosis outbreaks in fish farms. In this study, we performed an in silico genomic comparison, aiming to investigate the phylogenetic relationship between the pathogenic fish strains of Thai ST7 and other ST7 from different hosts and geographical origins. In general, the genomes of Thai ST7 strains are closely related to other fish ST7s, as the core genome is shared by 92-95% of any individual fish ST7 genome. Among the fish ST7 genomes, we observed only small dissimilarities, based on the analysis of clustered regularly interspaced short palindromic repeats (CRISPRs), surface protein markers, insertions sequence (IS) elements and putative virulence genes. The phylogenetic tree based on single nucleotide polymorphisms (SNPs) of the core genome sequences clearly categorized the ST7 strains according to their geographical and host origins, with the human ST7 being genetically distant from other fish ST7 strains. A pan-genome analysis of ST7 strains detected a 48-kb gene island specifically in the Thai ST7 isolates. The orientations and predicted amino acid sequences of the genes in the island closely matched those of Tn5252, a streptococcal conjugative transposon, in GBS 2603V/R serotype V, Streptococcus pneumoniae and Streptococcus suis. Thus, it was presumed that Thai ST7 acquired this Tn5252 homologue from related streptococci. The close phylogenetic relationship between the fish ST7 strains suggests that these strains were derived from a common ancestor and have diverged in different geographical regions and in different hosts.


Experimental and theoretical study of the spread of fluid from a point source on an inclined incontinence bed-pad.
The spread of fluid from a localized source on to a flat fibrous sheet is studied. The sheet is inclined at an angle, alpha, to the horizontal, and the areal flux of the fluid released is Qa. A new experimental study is described where the dimensions of the wetted region are measured as a function of time t, Qa and alpha (>0). The down-slope length, Y, grows according to Y approximately (Qa t)(2/3) (sin alpha)(1/3); for high discharge rates and low angles of inclination, the cross-slope width, X, grows as approximately (Qa t)(1/2), while for low discharge rates or high angles of inclination, the cross-slope transport is dominated by infiltration and X approximately 2(2Ks psi* t)(1/2), where Ks is the saturated permeability and psi* is the characteristic value of capillary pressure. A scaling analysis of the underlying non-linear advection diffusion equation describing the infiltration process confirms many of the salient features of the flow observed. Good agreement is observed between the collapse of the numerical solutions and experimental results. The broader implications of these results for incontinence bed-pad research are briefly discussed.


Retrospective analysis of the impact of pre-transplant implantable cardioverter-defibrillator status on long-term prognosis in heart transplant patients.
Sudden cardiac death (SCD) post-heart transplantation affects 8%-35% of patients; however, the risk profile remains to be completely elucidated. While pre-transplant ICDs are typically removed during transplantation, no information exists to suggest if this pre-transplant risk stratification is also associated with post-transplant outcomes. The objective of this study was to assess the impact of pre-transplant ICD status on long-term prognosis post-heart transplant. The United Network for Organ Sharing registry was queried for all adult heart transplant recipients from 2010 to 2018. Patients were categorized as with versus without ICD prior to heart transplantation. Survival was compared using Kaplan-Meier analysis. Proportional hazards regression analysis assessed the impact of ICDs adjusting for clinical and demographic covariates. Of 19 026 patients included, 78.6% (n = 14 960) had received an ICD at time of registration. Patients with an ICD were older [54.9 (±11.6) years vs. 48.6 (±15.3) years, p < .001], less likely to be female [25.7% (n = 3842) vs. 31.2% (n = 1269), p < .001], and more commonly diabetic [29.3% (n = 4376) vs 23.5% (n = 954), p < .001]. Kaplan-Meier analysis showed no difference in unadjusted survival trajectory by ICD status (chi-square = .48, p = .49). Survival was unrelated to ICD status in the multivariable model (HR = .98; 95% CI .90-1.07). Patients receiving an ICD pre-transplant had a higher prevalence of risk factors for SCD than non-ICD patients, yet ICD status prior to heart transplantation was not associated with a change in long-term prognosis post-heart transplantation.


Influence of age on enzyme activities of pyrimidine metabolism in the chicken heart.
The effect of the aging on the activities of enzymes involved in UMP-CMP metabolism were evaluated in the heart of newborn (1-day-old), young (20-day-old), adult (12-month-old), and aged (30-month-old) chickens. In newborn animals, UMP metabolism proceeds preferentially towards cytidine compounds rather than to breakdown. In addition, two pathways different from those involved in de novo synthesis may contribute to the synthesis of UMP: one, through cytosine deaminase that shows its maximal activity; the other, by uridine kinase, the main "salvage" enzyme of pyrimidine nucleotides. In young chickens, pyrimidine metabolism regards especially UMP. In fact, the lower activities of cytidylate phosphatase and cytosine deaminase, together with the remarkable increase of uridine kinase indicate that the metabolic flux converges on the main salvage pathway. In adult chickens, pyrimidine catabolism is enhanced, as supported by the maximal activity of the enzymes involved in UMP-CMP breakdown. On the contrary, the remarkable reduction of the anabolic enzymes suggests a limited resort to the salvage pathways. Finally, in aged chickens a reduced pyrimidine catabolism and a greater utilization of the salvage pathways appear to take place, thus contributing to the maintenance of pyrimidine nucleotide pool.


Global pattern and associated drivers of grassland productivity sensitivity to precipitation change.
Precipitation is a primary climatic determinant of grassland productivity, with many global change experiments manipulating precipitation. Here we examine the impacts of precipitation addition and reduction treatment intensity and duration on grassland above- (ANPP) and below- (BNPP) ground net primary productivity in a large-scale meta-analysis. We tested, 1) the double asymmetry model of sensitivity, specifically whether the sensitivity of productivity decreases with treatment intensity under increased precipitation and increases with treatment intensity under decreased precipitation, 2) whether the sensitivity of productivity to precipitation change decreases with treatment length, and 3) how the sensitivity of productivity changes with climate conditions. ANPP showed higher sensitivity than BNPP under increased precipitation but similar sensitivity to BNPP under decreased precipitation. The sensitivity of ANPP and BNPP decreased with increasing treatment intensity (e.g., percentage change in precipitation, ΔPPT) and leveled off in the long-term. With increased precipitation, the sensitivity of productivity decreased with increasing treatment length (e.g., experimental duration) and leveled off in the long-term, whereas the sensitivity increased with increasing treatment length under reduced precipitation. Furthermore, the sensitivity of productivity to precipitation change decreased with increasing mean annual precipitation and temperature. Finally, our meta-analysis shows that above- and belowground net primary productivity have asymmetric responses to precipitation change. Together these results highlight the complex mechanisms underlying the impacts of precipitation change, particularly the intensity and duration of such changes, on grassland productivity.


Issues in protocol design for cochlear implant clinical trials in children: the Clarion Pediatric Study.
Clinical trials of the Clarion multichannel cochlear implant in postlingually deaf adults have been ongoing since 1991, and clinical investigation of the device in children is projected to begin in the first quarter of 1995. The purpose of this paper is to present some of the issues encountered in developing research protocols for clinical trials of cochlear implants in the pediatric population, with special reference to the protocol that will be employed in the Clarion pediatric investigation.


The role of centrifugation in the measurement of surfactant in amniotic fluid.
Analysis of amniotic fluid fractions obtained by differential centrifugation has revealed the presence of intact globular-like structures of approximately 1 mu dimensions. These particles, which appear to be representative of fetal lung surfactant, begin precipitating at very low g forces and the extent of their removal by centrifugation was found to significantly alter L/S ratio measurements. This effect is particularly significant when moderate levels of these structures are present, which is usually between 34 and 37 weeks' gestation. False-negative L/S ratios could be attributed to this effect. Centrifugation can be employed to harvest these structures in reasonably pure form and measurement of their concentration, by phospholipid analysis, showed good correlation with fetal lung function in a trial study with 91 patients. These findings suggest that measurement of these surfactant particles harvested from amniotic fluid may provide a simple yet specific index of fetal pulmonary maturity.


Timing of Anticonvulsant Administration in Status Epilepticus.
Investigators from the Pediatric Status Epilepticus Research Group studied the time elapsed from onset of pediatric convulsive status epilepticus (SE) to administration of antiepileptic drugs (AED).


Chromium Exposure Causes Structural Aberrations of Erythrocytes, Gills, Liver, Kidney, and Genetic Damage in Striped Catfish Pangasianodon hypophthalmus.
Heavy metal pollution due to anthropogenic activities poses a great threat to aquatic organisms. The present study was conducted to evaluate the cytotoxic and genotoxic effects of hexavalent chromium (potassium dichromate) on hemato-biochemical, histo-pathological, and genetical changes in striped catfish Pangasianodon hypophthalmus. Three sub-lethal doses (0.8, 1.6, and 3.2 mg/L) of chromium (Cr) were selected and fish were exposed in vivo contrasting with a control (0 mg/L) for 30 days. The study revealed that various hemato-biochemical parameters showed a significant decrease in hemoglobin (Hb), red blood cells (RBCs), and blood glucose content, whereas white blood cells (WBCs) significantly increased in Cr exposed fish. Frequencies of all forms of structural abnormalities of erythrocytes (erythrocytic cellular abnormalities; ECA, erythrocytic nuclear abnormalities; ENA and erythroblasts; Ebs) were significantly increased in higher two test concentrations (1.6 and 3.2 mg/L) when compared to control. Differential leucocyte count exhibited significant increase in neutrophil and decrease in lymphocytes in the highest Cr treated group. The severity of various histo-pathological changes in the gills, liver, and kidney were increased considerably with the increase of Cr concentrations. Similarly, the amount of DNA (ng/μl) decreased significantly in blood and tissues of different vital organs where the liver showed the highest decline compared to control in a concentration-dependent manner. Taken altogether, P. hypophthalmus is susceptible to Cr and can be used as a bio-indicator to assess aquatic metal pollution.


Computer-assisted assessment of colonic polyp histopathology using probe-based confocal laser endomicroscopy.
Probe-based confocal laser endomicroscopy (pCLE) is a promising modality for classifying polyp histology in vivo, but decision making in real-time is hampered by high-magnification targeting and by the learning curve for image interpretation. The aim of this study is to test the feasibility of a system combining the use of a low-magnification, wider field-of-view pCLE probe and a computer-assisted diagnosis (CAD) algorithm that automatically classifies colonic polyps. This feasibility study utilized images of polyps from 26 patients who underwent colonoscopy with pCLE. The pCLE images were reviewed offline by two expert and five junior endoscopists blinded to index histopathology. A subset of images was used to train classification software based on the consensus of two GI histopathologists. Images were processed to extract image features as inputs to a linear support vector machine classifier. We compared the CAD algorithm's prediction accuracy against the classification accuracy of the endoscopists. We utilized 96 neoplastic and 93 non-neoplastic confocal images from 27 neoplastic and 20 non-neoplastic polyps. The CAD algorithm had sensitivity of 95%, specificity of 94%, and accuracy of 94%. The expert endoscopists had sensitivities of 98% and 95%, specificities of 98% and 96%, and accuracies of 98% and 96%, while the junior endoscopists had, on average, a sensitivity of 60%, specificity of 85%, and accuracy of 73%. The CAD algorithm showed comparable performance to offline review by expert endoscopists and improved performance when compared to junior endoscopists and may be useful for assisting clinical decision making in real time.


Detection and identification of Toxocara canis DNA in bronchoalveolar lavage of infected mice using a novel real-time PCR.
Toxocarosis is a zoonosis with worldwide distribution caused by Toxocara spp. of dogs and cats. In humans, diagnosis relies mainly on detection of parasite-specific antibodies. Although serological assays in current use have defined sensitivity and specificity, the problem of cross-reactivity still remains, particularly in areas of endemic polyparasitism. Microscopic detection of the parasite in tissue biopsies is not recommended for diagnosis because larvae can be difficult to locate, and finding the parasite eggs in faeces is not applicable since the larvae do not develop to the adult stage in the human host. In this study we describe a novel real-time PCR ('Nemo-PCR') that, in combination with DNA sequencing, allows the detection and identification of Toxocara canis and other nematodes in the Superfamily Ascaridoidea. Results indicate that this approach can detect Toxocara spp. DNA in bronchoalveolar lavage (BAL) of experimentally-infected mice. For diagnostic purposes further studies are necessary to evaluate this assay including testing human BAL fluid. The availability of such a direct assay would improve diagnosis of toxocarosis particularly for patients with pulmonary signs and symptoms.


Marine bromophenol bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, represses angiogenesis in HUVEC cells and in zebrafish embryos via inhibiting the VEGF signal systems.
Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) is a bromophenol compound derived from marine algae. Our previous reports have shown that BDDE possessed anticancer activity in vitro. However, its antiangiogenesis activity and possible mechanisms remain unclear. The present study demonstrated that BDDE displayed in vitro antiangiogenesis capabilities by significantly inhibiting HUVEC cells proliferation, migration, and tube formation, without any effect on the preformed vascular tube. Western blot analysis revealed that BDDE decreased the protein level of VEGF and VEGFR but not that of EGFR, FGFR, and IGFR. In addition, BDDE inactivated the VEGF downstream signaling molecules including mTOR and Src, whereas activated Akt and ERK. Moreover, BDDE blocked subintestinal vessel formation in zebrafish embryos in vivo and showed toxicity under high concentrations of BDDE. The results of this present study indicated that BDDE, which has unique chemical structure different from current antiangiogenesis agents, could be used as a potential drug candidate for cancer prevention and therapy.


Hydration of counterions in cation exchange resins studied by X-ray absorption fine structure.
X-Ray absorption fine structure has revealed that K(+) is partially desolvated when transferred into the interior of cation-exchange resin, while Rb(+) and Sr(2+) keep their first hydration structures.


Cricopharyngeal dysfunction: A systematic review comparing outcomes of dilatation, botulinum toxin injection, and myotomy.
Cricopharyngeal dysfunction may lead to severe dysphagia and aspiration. The objective of this systematic review was to evaluate the existing studies on the effectiveness of myotomy, dilatation, and botulinum toxin (BoT) injection in the management of cricopharyngeal dysphagia. PubMed and Web of Science databases were searched to identify eligible studies by using the terms "cricopharyngeal dysfunction," "cricopharyngeal myotomy," "cricopharyngeal botox," "cricopharyngeal dilation," and their combinations from 1990 to 2013. This was supplemented by hand-searching relevant articles. Eligible articles were independently assessed for quality by two authors. Statistical analysis was performed. The database search revealed 567 articles. Thirty-two articles met eligibility criteria and were further evaluated. The reported success rates of BoT injections was between 43% and 100% (mean = 76%), dilation 58% and 100% (mean = 81%), and myotomy 25% and 100% (mean = 75%). In logistic regression analysis of the patient-weighted averages, the 78% success rate with myotomy was significantly higher than the 69% success rate with BoT injections (P = .042), whereas the intermediate success rate of 73% with dilation was not significantly different from that of either myotomy (P = .37) or BoT (P = .42). There was a statistically significant difference between endoscopic and open myotomy success rates (P = .0025). Endoscopic myotomy had a higher success rate, with a 2.2 odds ratio. The success rate of myotomy is significantly higher than the success rate of BoT injections in cricopharyngeal dysfunction. Moreover, endoscopic myotomy was found to have a higher success rate compared to open myotomy.


Characterization of beta-amyloid precursor proteins with or without the protease-inhibitor domain using anti-peptide antibodies.
Alternative splicing of the transcript encoding the beta-amyloid precursor protein (BAPP) of Alzheimer's disease produces multiple mRNA species. Translation of these mRNAs predicts protein products of 770, 751, and 695 amino acids. The difference arises from the inclusion in BAPP-770/751 of a 56-residue insert region which is homologous to Kunitz-type protease inhibitors. We have prepared and affinity-purified anti-peptide antibodies that react specifically with either BAPP-770/751 (insert-specific) or BAPP-695 (junction-specific). A detectable level of the mRNA corresponding to the BAPP-770/751 protein was found in all cell lines tested. Immunoprecipitation of 35S-labeled proteins from these cell lines showed them to contain one or two Mr 105,000 bands reactive with the insert-specific serum, i-291. In contrast, only cos-7 cells and the human neuroblastoma cell line, IMR-32, contained mRNA species that encode the BAPP-695 protein, as shown by Northern analysis with a junction-spanning oligonucleotide probe. A band of Mr 95,000 was immunoprecipitated specifically from these two cell lines using the junction-specific serum, J-284. Indirect immunofluorescence labeling of cells corroborated these findings. All cells reacted with the insert-specific antibodies, i-291 and i-324. Only cos-7 and IMR-32 cells reacted with the junction-specific antibody, J-284. These results demonstrate the usefulness of anti-peptide antibodies for the differential detection of the BAPP-695 and BAPP-770/751 proteins.


Cost-minimisation analysis of endometrial thermal ablation in a day case or outpatient setting under different anaesthesia regimens.
To evaluate the cost difference between a daycase endometrial thermal ablation performed under general anaesthesia and an outpatient endometrial ablation using local anaesthetic. Calculations using real reported resource use in 20 daycase procedures and 16 outpatient procedures. The costs were 1865 euros for daycase procedure versus 1065 euros for outpatient procedure. The cost of endometrial thermal ablation can be considerably minimised by taking the procedure out of the theatre and performing it under local anaesthetic instead of general anaesthesia. This setting makes endometrial thermal ablation cost-effective.


Novel genes associated with a placental phenotype in knockout mice also respond to cellular stressors in primary human trophoblasts.
Placental insufficiency is a leading cause of intrauterine growth restriction, contributing to perinatal morbidity and mortality. The molecular regulation of placental development and what causes placental insufficiency is poorly understood. Recently, a panel of genes were found to cause significant placental dysmorphologies in mice with severely growth restricted off-spring. We aimed to assess whether these genes were also implicated in human intrauterine growth restriction. We explored the expression of nine genes in primary cytotrophoblast cells in hypoxic (n = 6) and glucose starvation (n = 5) conditions in vitro. We also explored whether the genes were dysregulated in intrauterine growth restricted human placental samples (n = 11), with (n = 20) or without preeclampsia compared to gestationally matched controls (<34 weeks gestation) (n = 17). Hypoxic stress significantly upregulated the expressions of BRD2 (p = 0.0313), SMG9 (p = 0.0313) genes. In contrast, glucose starvation significantly suppressed Kif1bp (p = 0.0089) in primary cytotrophoblasts. The FRYL, NEK9, CHTOP, PSPH, ATP11A, HM13 genes did not change under hypoxia or glucose starvation conditions. The expression of these genes was not altered in placenta from patients with intrauterine growth restriction, compared to gestationally matched controls. We demonstrate that some of the genes that cause a placental phenotype in mice, respond to hypoxic and glucose mediated stress in human cytotrophoblast isolations. Despite this, they are unchanged in placenta from patients with intrauterine growth restriction. Therefore, dysregulation of these genes is less likely to contribute to preterm intrauterine growth restriction in humans.


Patellar tendon avulsion after total knee arthroplasty. A new technique.
Patellar tendon avulsion is a rare complication of total knee arthroplasty. An easy surgical technique that involves suturing the tendon into a groove carved in the tibial tubercle and tension band wiring is described. Two cases are presented, with an average follow-up period of 21 months. Good clinical results were obtained in each case. No postoperative complications occurred.


Accidental cross-connexion of oxygen and nitrous oxide in an anaesthetic machine.
Oxygen and nitrous oxide pipes were cross-connected during the servicing of an anaesthetic machine. This resulted in the delivery of 100% nitrous oxide instead of 100% oxygen at the end of the operation. The patient fully recovered and was discharged on the 13th day.


A modified, personalized system of education for junior internal medicine clerkship at a multi-campused school.
A personalized system of education is outlined for the junior clerkship in internal medicine at a multi-campus institution. Data are included of student response to the program in general and upon specifics, short-term retention of the cognitive knowledge, and National Board scores. Contrasts are drawn between this program and the former program of instruction.


The Corneal Epithelial Barrier and Its Developmental Role in Isolating Corneal Epithelial and Conjunctival Cells From One Another.
During development, the corneal epithelium (CE) and the conjunctiva are derived from the surface ectoderm. Here we have examined how, during development, the cells of these two issues become isolated from each other. Epithelia from the anterior eyes of chicken embryos were labeled with the fluorescent, lipophilic dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). DiI was placed on the epithelial surface of the developing anterior eye and its diffusion was monitored by fluorescence microscopy. Concomitant morphologic changes in the surface cells of these epithelial were examined by scanning electron microscopy. Immunofluorescence was used to analyze the expression of cytokeratin K3, ZO-1, N-cadherin and Connexin-43 and the function of gap junctions was analyzed using a cut-loading with the fluorescent dye rhodamine-dextran. Prior to embryonic day 8 (E8), DiI placed on the surface of the CE spreads throughout all the epithelial cells of the anterior eye. When older eyes were similarly labeled, dye diffusion was restricted to the CE. Similarly, diffusion of DiI placed on the conjunctival surface after E8 was restricted to the conjunctiva. Scanning electron microscopy showed that developmentally (1) physical separations progressively form between the cells of the CE and those of the conjunctiva, and (2) by E8 these separations form a ring that completely encompasses the cornea. The functional restriction of gap junctions between these tissues did not occur until E14. During ocular development, a barrier to the diffusion of DiI forms between the contiguous CE and conjunctiva prior to the differential expression of gap junctions within these tissues.


Serotonergic modulation of neurotransmission in the rat subicular cortex in vitro: a role for 5-HT1B receptors.
We have studied the effect of serotonin on synaptic transmission in rat hippocampal subiculum slices. Electrical stimulation of the alveus induced a field potential in the subiculum. The non-NMDA glutamate receptor antagonist, NBQX (3 x 10(-6) mol/l) suppressed the response by 78%, indicating that the signal involves glutamatergic neurons. Application of serotonin suppressed (EC50 = 3.6 x 10(-6) mol/l) the amplitude of the evoked potentials in a reversible, concentration-dependent manner. The responses to 5-HT were not altered after pretreatment with the 5-HT uptake blocker, fluvoxamine (10(-5) mol/l) or a combination of the MAO inhibitor pargyline (10(-5) mol/l) and ascorbic acid (10(-4) mol/l). The responses to 5-HT were also unaffected by pretreatment with the 5-HT1A selective antagonist NAN-190 (10(-6) mol/l), the 5-HT2A antagonist ketanserin (10(-6) mol/l) or the 5-HT3/5-HT4 antagonist ICS 205-930 (10(-6) mol/l). The 5-HT1B selective agonist CP 93,129 mimicked the effects of serotonin, but was more potent (EC50 4.1 x 10(-7) mol/l). The 5-HT1B receptor antagonist, (+/-)21-009 (3 x 10(-7) mol/l), antagonized the response to 5-HT and CP 93,129 with a pKB value of 7.1 and 7.2, respectively. These results suggest that the effect of 5-HT in the rat subiculum is mediated by 5-HT1B receptors.


Vitelline vascular remnant causing intestinal obstruction in a patient with TARP syndrome.
TARP syndrome, characterized by talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava, is an X-linked recessive condition caused by deleterious variants in RBM10. Vitelline vascular remnants (VVR) are a rare vitelline duct anomaly with approximately 26 cases previously reported. There are no previously reported cases of VVRs in patients with TARP syndrome. We present a male neonate diagnosed with TARP syndrome via trio whole exome sequencing who had classic features of this syndrome, although his course was additionally complicated by feeding intolerance with multiple episodes of abdominal distension. Serial imaging and contrast studies of the upper GI tract and small bowel demonstrated small bowel obstruction of unclear etiology. Given the poor prognosis associated with this condition, life-sustaining measures were withdrawn, and he passed away at 38 days of age. On autopsy, a VVR was unexpectedly identified with proximal bowel dilation, explaining his feeding intolerance. We highlight the importance of full post-mortem examination in understanding the complete spectrum of manifestations of genetic syndromes and provide a review of the literature.


Immune evasion by Mycobacterium tuberculosis: living with the enemy.
Mycobacterium tuberculosis is successful as a pathogen because of its ability to persist in an immunocompetent host. This bacterium lives within the macrophage, a cell whose function is the elimination of microbes. Recent advances have improved our understanding of how M. tuberculosis evades two major antimicrobial mechanisms of macrophages: phagolysosome fusion and the production of toxic reactive nitrogen intermediates. M. tuberculosis also modulates antigen presentation to prevent the detection of infected macrophages by CD4(+) T cells.


CO2-assisted 'Weathering' of Steel Slag-Derived Calcium Silicate Hydrate: A Generalized Strategy for Recycling Noble Metals and Constructing SiO2-Based Nanocomposites.
The spent adsorbent loaded by toxic metals is a solid hazardous waste which could cause significant secondary pollution due to potential possible additional release of metal ions. Therefore, the main subject is direct reutilization of spent adsorbents which can further economically and realistically offer new features, like recycling metal adsorbed, or formation of functional SiO2-based nanocomposites. The nanoporous structure and negative surface charges enable steel slag-derived amorphous calcium silicate hydrate (CSH) to retain effectively the incoming metal ions (e. g. Au3+, Ag+, Pd2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ce3+, Y3+, and Gd3+) by chemisorption. Sparked by natural carbonation 'weathering', which ultimately sequestrates atmospheric CO2 by alkaline silicate minerals to leach calcium from mineral matrix, the decalcification reactions of metal-bearing CSH results in successful recovery of noble metals (Ag, Au, Pd) upon NaOH etching the resultant SiO2 support. Further, SiO2-based heterostructures, containing nanocrystalline metals (e. g. Au0, Ag0, Pd0, Fe0, Co0, Ni0, Cu0, and Zn0) or rare-earth oxides (e. g. CeO2, Y2O3, and Gd2O3), are formed after reduction in H2/Ar (5 vol% H2) flow, which is also very important for the multipurpose immobilization of diverse hybrid materials on SiO2 surface (e. g. Cu0-Ag0@SiO2, Cu0-CeO2@SiO2, and Cu0-Ag0-CeO2@SiO2).


C99 selectively accumulates in vulnerable neurons in Alzheimer's disease.
The levels and distribution of amyloid deposits in the brain does not correlate well with Alzheimer's disease (AD) progression. Therefore, it is likely that amyloid precursor protein and its proteolytic fragments other than amyloid b (Ab) contribute to the onset of AD. We developed a sensitive assay adapted to the detection of C99, the direct precursor of b-amyloid. Three postmortem groups were studied: control with normal and stable cognition; patients with moderate AD, and individuals with severe AD. The amount of C99 and Aβ was quantified and correlated with the severity of AD. C99 accumulates in vulnerable neurons, and its levels correlate with the degree of cognitive impairment in patients suffering from AD. In contrast, Aβ levels are increased in both vulnerable and resistant brain areas. These results raise the possibility that C99, rather than Aβ plaques, is responsible for the death of nerve cells in AD.


Clinically significant gastropathy associated with nonsteroidal antiinflammatory drug use in children with juvenile rheumatoid arthritis.
To estimate the frequency of documented clinically significant gastrointestinal (GI) side effects secondary to nonsteroidal antiinflammatory drugs (NSAID) therapy and to describe the adverse events. Computerized medical records of 702 patients with juvenile rheumatoid arthritis (JRA) administered NSAID were searched for the occurrence of clinically significant gastropathy (esophagitis, gastritis, peptic ulcer disease). Five children were identified who had a total of 10 events of gastropathy documented by either barium swallow or endoscopy, and thought to be attributable to NSAID therapy. Each child had at least 2 separate events of clinically significant gastropathy. Although mild GI disturbances are frequent side effects associated with NSAID therapy, the number of children with JRA who experience clinically significant gastropathy appears to be low.


The regulation of heat shock proteins and their role in systemic lupus erythematosus.
After a serendipitous suggestion, it was established that a significant subset of patients with systemic lupus erythematosus (SLE) overexpress the 90-kD heat shock protein (Hsp90). In this review, we have analyzed our own data and that of others, to explore the link between Hsp90 and SLE. We performed a detailed literature review focusing on the potential role of Hsp in the etiopathogenesis of SLE. Data are discussed showing surface expression of this Hsp in patients with lupus, a similar overexpression in the splenocytes of MRL/Ipr mice before the onset of disease, the detection of antibodies to Hsp90 in a proportion of both lupus patients and lupus-prone mice, and most recently, an analysis of the transcription factors that regulate the production of this protein and the influence of key cytokines on these factors. These observations provide a model to show how a protein with key physiological roles in healthy individuals may, on occasion, become the target of an autoimmune attack with clinical consequences recognized in both mouse and human. Given that up to now, other heat shock proteins are not targeted in a similar fashion, the specificity of these responses is remarkable.


Integrating network pharmacology and non-targeted metabolomics to explore the common mechanism of Coptis Categorized Formula improving T2DM zebrafish.
Coptis Categorized Formula (CCF) is one of the core prescriptions in Treatise on Febrile Diseases. Its efficacy can be available not only in exogenous diseases but widely in various internal injuries and miscellaneous diseases. CCF (i.e., Huanglian Jiedu Decoction, Huanglian Ejiao Decoction, Dahuang Huanglian Xiexin Decoction, Gegen Qinlian Decoction) is different in composition, but they all play a favorable role in curative effect on type 2 diabetes mellitus (T2DM). Therefore, it is of great significance to reveal the common mechanism of CCF in treating T2DM. Based on network pharmacology and non-targeted metabolomics research strategy, the common mechanism of the CCF treating T2DM was discussed. Firstly, Ultra-high performance liquid chromatography-quadrupole-time of flight/mass spectrometry was used to identify the chemical constituents of the CCF. Then, the targets of these chemical components were used for network pharmacology analysis associated with therapeutic effect. Finally, the diabetic zebrafish model was constructed to further verify the common mechanism of the CCF in treating T2DM. A total of 160 chemical compositions were identified and 16 of them were common chemical compositions of the four CCF, including berberine, baicalin, coptisine and so forth. Network pharmacology results showed that Dipeptidyl peptidase (DPP)-4, cysteinyl aspartate specific proteinase (CASP)3, nitric oxide synthase (NOS)2, NOS3, and other 37 targets were common targets of CCF, and advanced glycation end products (AGE)-receptor of advanced glycation end products (RAGE) signaling pathway in diabetic complications, mitogen-activated protein kinase (MAPK) signaling pathway and hypoxia inducible factor (HIF)-1 signaling pathway were critical pathways of four CCF in the treatment of T2DM. CCF can lessen the blood glucose of diabetic zebrafish. The contents of 25 differential metabolites in diabetic zebrafish were altered. These metabolites were mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, sphingolipid metabolism, and tyrosine metabolism. Our research shows that the common mechanism of CCF in improving T2DM is as follows: berberine, baicalin, coptisine and other chemical components can directionally regulate DPP-4, CASP3, NOS2, NOS3 and other targets, which are mediated by AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and HIF-1 signaling pathway. The content of endogenous metabolites such as L-valine and L-sorbitose changes, and further regulates the metabolism of amino acid metabolism, lipid metabolism, purine metabolism, sphingosine metabolism and arachidonic acid metabolism, so as to play a significant role in regulating glycolipid metabolism, improving insulin resistance, inhibiting cell apoptosis, anti-oxidation and anti-inflammation, and finally ameliorating T2DM.


A Mixed Methods Study to Explore Relevant Metrics for a Results Framework Measuring the Public Health Impact of Reliance-Based Pathways.
Reliance-based pathways for the marketing authorization of medical products have been identified as valuable regulatory tools for the timely provision of effective, safe, quality medicines for people worldwide; however, little research has been conducted on the best way to measure the public health impact of using reliance-based pathways. The current mixed methods study was designed to explore which characteristics or "metrics" could be used to measure the impact of reliance-based pathways. A quantitative survey (n = 70) and in-depth interviews (IDIs) (n = 10) were employed to query various stakeholders (e.g., industry, regulatory authorities, NGOs) about the metrics they believed would be important to include in a framework designed to measure the impact of reliance-based regulatory pathways on advancing public health. Based on survey results, (1) ability to meet targeted product assessment timeline, (2) increased access to expertise, which is limited or not available in the agency, (3) shortened median number of days (annually) to market for medical products, (4) lower morbidity and mortality rates due to greater access to medical products, and (5) movement toward technical standards harmonization were the Top Five most important metrics to be included in a framework. IDI results suggest that, while important, the relevance of the Top Five metrics may vary by region or regulatory authority. Interviewed stakeholders intuitively believe reliance-based regulatory pathways are a worthwhile endeavor; however, there must be "harmonization" within the reliance ecosystem that creates a strong understanding of the factors necessary for reliance-based pathways to be utilized in a successful manner.


Characterization of Prototheca zopfii Genotypes Isolated from Cases of Bovine Mastitis and Cow Barns in China.
Protothecal mastitis, caused mostly by Prototheca zopfii (P. zopfii), is increasing in dairy herds and is being reported globally. The present study was aimed at studying the epidemiology of mastitis and at molecular characterization of P. zopfii isolates from dairy herds and their surroundings in three provinces of China using microbiological, biochemical and molecular methods, and antibiotic susceptibility tests. Samples from milk (n = 620) of mastitic cows and their barns sources (n = 410) including feces, feed, bedding materials and drinking water were analyzed. Among other pathogens recovered from mastitic milk, 84 (13.5%) of the isolates were identified as P. zopfii. All of the P. zopfii isolates recovered from milk were recognized as genotype 2, whereas 58 (73.4%) and 21 (26.6%) isolates from environmental sources were found to be P. zopfii genotypes 1 and 2, respectively. The isolates were susceptible to some antibiotics and antifungal agents, including amikacin (78.1%), streptomycin (58.5%), gentamicin (17.8%), amphotericin B (68.6%) and nystatin (64.4%). Additionally, the two genotypes displayed versatile patterns of susceptibility to different antimicrobials agents. Phylogeny of the genotypes on the basis of 18S SSU rDNA and 28S SSU rDNA was also investigated. The isolates of the two genotypes separated into different clades, and no interrelationship was observed among these as shown by phylogenetic analysis. The genotype 1 isolates from cow barn sources were non-pathogenic and may not present any risk of mastitis. We conclude that P. zopfii genotype 2 might play an important role in bovine mastitis in China.


The Telephone Interview for Cognitive Status (Modified): relation with a comprehensive neuropsychological assessment.
The modified Telephone Interview for Cognitive Status (TICS-m) is a widely used screening instrument for (Alzheimer's) dementia. Psychometric evaluation of the TICS-m is limited. This study examined the relation between the TICS-m and a comprehensive neuropsychological assessment in older persons (n = 243) without cognitive deficits. The TICS-m total score correlated with multiple cognitive domains (range r = .22-.49). Factor analysis of the TICS-m items yielded four interpretable factors: "verbal memory," "orientation/mental tracking," "language/reasoning," and "attention/working memory," which also showed (modest) correlations with the neuropsychological assessment (r = .02-.48). The TICS-m appears to reflect a "general cognitive ability" rather than, for example, memory functioning alone.


Combined micro-endoscopic trans-sphenoid excisions of pituitary macroadenomas.
Refined microsurgical techniques with the operating microscope have greatly facilitated removal of pituitary tumors by the trans-sphenoid approach. However, extensions of macroadenomas in presellar and parasellar regions and in the lateral recesses of the sphenoid sinuses can be partially hidden, resulting in their removal by relatively blind curettage. In 37 patients with pituitary macroadenomas, the rigid 30 degrees angled fiberoptic nasoscope fitted to a suction-irrigation sheath was found to be highly beneficial. Hidden areas could be visualized in 84% of the patients and tumor residues detected in 40.5%. In the majority of the patients with detected tumor residues, adenomatous remnants were safely removed by meticulous endoscopic dissection under optimum visual control after the main part of the tumor had been removed with the operating microscope.


Insidious posterior circulation stroke with rapid deterioration due to vertebral giant cell arteritis.
We report a patient with a posterior circulation stroke that presented insidiously, progressed rapidly and had an unusual aetiology of vertebral giant cell arteritis that was not recognised in a timely fashion. General awareness of this cause might alert clinicians to consider the diagnosis in similar cases, as prompt intervention may improve outcomes.


A method for quick-freezing live muscles at known instants during contraction with simultaneous recording of mechanical tension.
We have developed a quick-freezing method, using a copper block cooled with liquid helium or nitrogen, which permits us to freeze muscles without any cryoprotectant at predetermined, precisely measured points in the recorded tension time-course of a single twitch or tetanus. Our aim is to arrest structural intermediates of the cross-bridge cycle for observation in the electron microscope. Chemically stimulated, demembranated muscles as well as electrically stimulated, live muscles can be frozen on the same apparatus. Good freezing of relaxed and contracting muscles has been obtained to a depth of 10-20 microns, with excellent structural preservation after freeze-substitution.


Induction of long-term depression and potentiation by low- and high-frequency stimulation in the dentate area of the anesthetized rat: magnitude, time course and EEG.
We investigated the possible importance of stimulus train frequency for the induction and magnitude of long-term synaptic plasticity in the perforant path-granule cell pathway. Under the same experimental conditions, low- (15 Hz) or high-frequency (400 Hz) stimulation could elicit a profound long-term depression (LTD), or typical long-term potentiation (LTP), of the population spike amplitude, excitatory postsynaptic potential (EPSP) amplitude and spike onset latency. In addition, changes in the relationship between the EPSP and population spike amplitude indicated that granule cell excitability was enhanced during LTP and reduced during LTD. LTD occurred primarily after low-frequency stimulation (5 of 6 cases), and was always accompanied by striking changes in the EEG, most notably a biphasic slow potential. While the EEG changes were confined to the first 5 min after the tetanus, LTD lasted from 1 to 4 h. The nature of the EEG events is still unclear, it is suggested that they may represent a spreading depression-like episode. Finally, we found that LTP evoked by high-frequency stimulation was larger and generally reached peak magnitude faster than when it followed low-frequency stimulation. A possible mechanism and role for hippocampal LTD is proposed.


Computer analysis, using a digitizer, of ataxic mouse gait due to drugs.
A simple objective method using the irregularity of the spacing of rats' footprints to determine drug-induced locomotor ataxia has been adapted for mice and for computer analysis, by means of a digitizer-based program. Results obtained by the usual manual method of measuring and analyzing the records are compared with results of the computerized method. The computer method improves speed, and perhaps accuracy, of measurement and analysis, especially with large numbers of records, although manual scoring gives satisfactory results and remains essential for unusual records. Inter-observer agreement of the computerized method was high, and there was good agreement between measurements and subjective ratings of ataxia. The use of footprints to measure ataxia, with or without computer aid, is recommended as a routine test in laboratory evaluation of psychoactive drugs. Other uses discussed include determining changes in different characteristics of gait such as step width and step length in animal and human subjects affected not only by drugs, but also by movement disorders such as Parkinsonism.


Inducible degradation of lncRNA Sros1 promotes IFN-γ-mediated activation of innate immune responses by stabilizing Stat1 mRNA.
Interferon-γ (IFN-γ) is essential for the innate immune response to intracellular bacteria. Noncoding RNAs and RNA-binding proteins (RBPs) need to be further considered in studies of regulation of the IFN-γ-activated signaling pathway in macrophages. In the present study, we found that the microRNA miR-1 promoted IFN-γ-mediated clearance of Listeria monocytogenes in macrophages by indirectly stabilizing the Stat1 messenger RNA through the degradation of the cytoplasmic long noncoding RNA Sros1. Inducible degradation or genetic loss of Sros1 led to enhanced IFN-γ-dependent activation of the innate immune response. Mechanistically, Sros1 blocked the binding of Stat1 mRNA to the RBP CAPRIN1, which stabilized the Stat1 mRNA and, consequently, promoted IFN-γ-STAT1-mediated innate immunity. These observations shed light on the complex RNA-RNA regulatory networks involved in cytokine-initiated innate responses in host-pathogen interactions.


Therapeutics for COVID-19.
Vaccines and monoclonal antibody treatments to prevent severe coronavirus disease 2019 (COVID-19) illness were available within a year of the pandemic being declared but there remained an urgent need for therapeutics to treat patients who were not vaccinated, were immunocompromised or whose vaccine immunity had waned. Initial results for investigational therapies were mixed. AT-527, a repurposed nucleoside inhibitor for hepatitis C virus, enabled viral load reduction in a hospitalized cohort but did not reduce viral load in outpatients. The nucleoside inhibitor molnupiravir prevented death but failed to prevent hospitalization. Nirmatrelvir, an inhibitor of the main protease (Mpro), co-dosed with the pharmacokinetic booster ritonavir, reduced hospitalization and death. Nirmatrelvir-ritonavir and molnupiravir received an Emergency Use Authorization in the United States at the end of 2021. Immunomodulatory drugs such as baricitinib, tocilizumab and corticosteroid, which target host-driven COVID-19 symptoms, are also in use. We highlight the development of COVID-19 therapies and the challenges that remain for anticoronavirals.


Quercus infectoria: a candidate for the control of methicillin-resistant Staphylococcus aureus infections.
Acetone, ethyl acetate, 95% ethanol and aqueous extracts of Quercus infectoria (Q. infectoria) demonstrated significant antibacterial activities against all strains of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). Inhibition zones were in the range 11.75-16.82 mm. Both MRSA and MSSA strains exhibited minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values at 0.13 and 0.13-1.00 mg/mL, respectively. At 2 MIC, the growth of two representative MRSA strains was continually inhibited for at least 20 h. Surviving MRSA cells were not detected within 12-14 h after treatment with the extract at 4 MIC concentration. Staphylococcus aureus ATCC 25923 demonstrated similar results.


The C. elegans nuclear receptor gene fax-1 and homeobox gene unc-42 coordinate interneuron identity by regulating the expression of glutamate receptor subunits and other neuron-specific genes.
The fax-1 gene of the nematode C. elegans encodes a conserved nuclear receptor that is the ortholog of the human PNR gene and functions in the specification of neuron identities. Mutations in fax-1 result in locomotion defects. FAX-1 protein accumulates in the nuclei of 18 neurons, among them the AVA, AVB, and AVE interneuron pairs that coordinate body movements. The identities of AVA and AVE interneurons are defective in fax-1 mutants; neither neuron expresses the NMDA receptor subunits nmr-1 and nmr-2. Other ionotropic glutamate receptor subunits are expressed normally in the AVA and AVE neurons. The unc-42 homeobox gene also regulates AVA and AVE identity; however, unc-42 mutants display the complementary phenotype: NMDA receptor subunit expression is normal, but some non-NMDA glutamate receptor subunits are not expressed. These observations support a combinatorial role for fax-1 and unc-42 in specifying AVA and AVE identity. However, in four other neuron types, fax-1 is regulated by unc-42, and both transcriptional regulators function in the regulation of the opt-3 gene in the AVE neurons and the flp-1 and ncs-1 genes in the AVK neurons. Therefore, while fax-1 and unc-42 act in complementary parallel pathways in some cells, they function in overlapping or linear pathways in other cellular contexts, suggesting that combinatorial relationships among transcriptional regulators are complex and cannot be generalized from one neuron type to another.


Endogenous signalling system involved in parotid gland adenosine A(1) receptor-amylase release.
In this study, we have determined signalling pathways involved in adenosine A(1) receptor (A(1) receptor)-dependent stimulation of amylase release in rat parotid gland. Amylase release, binding and cyclic adenosine monophosphate (cAMP) assays, inositol phosphates (IPs) production and nitric oxide synthase (NOS) activity in the presence of cyclopentyl-1,3-dipropylxanthine (CPA) alone or in the presence of different inhibitory drugs were performed. The binding parameters of specific A(1) antagonist [(3)H]-cyclopentyl 1,3-dipropilxanthine ([(3)H]-DPCPX) in parotid gland membranes show a population of high affinity sites with K(d) (nm) 0.53 +/- 0.06 and B(max) (fmol mg(-1) protein) 122.6 +/- 10.2. CPA stimulation of A(1) receptor exerts an increase in amylase release, IPs accumulation, cAMP production and NOS activity. All these A(1) agonist effects were blocked by the A(1) receptor antagonist DPCPX. Inhibitors of phospholipase C (PLC), calcium/calmodulin (CaM), protein kinase C (PKC), and adenylate cyclase, but not NOS, activities attenuated the CPA stimulatory effect on amylase release. The effect of CPA on amylase release significantly correlated with its action either on cAMP or on IPs accumulation. These results suggest that CPA activation of parotid gland A(1) receptor induces a stimulatory effect on amylase release associated with increased production of cAMP and IPs accumulation. The mechanism appears to occur secondarily to stimulation of phosphoinositide turnover via PLC activation. This, in turn, triggers cascade reactions involving CaM and PKC. The CPA stimulation of NOS does not appear to participate in amylase release.


Improvement of the energy conversion efficiency of Chlorella pyrenoidosa biomass by a three-stage process comprising dark fermentation, photofermentation, and methanogenesis.
The effects of pre-treatment methods on saccharification and hydrogen fermentation of Chlorella pyrenoidosa biomass were investigated. When raw biomass and biomass pre-treated by steam heating, by microwave heating, and by ultrasonication were used as feedstock, the hydrogen yields were only 8.8-12.7 ml/g total volatile solids (TVS) during dark fermentation. When biomass was pre-treated by steam heating with diluted acid and by microwave heating with diluted acid, the dark hydrogen yields significantly increased to 75.6 ml/g TVS and 83.3 ml/g TVS, respectively. Steam heating with diluted acid is the preferred pre-treatment method of C. pyrenoidosa biomass to improve hydrogen yield during dark fermentation and photofermentation, which is followed by methanogenesis to increase energy conversion efficiency (ECE). A total hydrogen yield of 198.3 ml/g TVS and a methane yield of 186.2 ml/g TVS corresponding to an overall ECE of 34.0% were obtained through the three-stage process (dark fermentation, photofermentation, and methanogenesis).


Association of Urine Biomarkers With Acute Kidney Injury and Fluid Overload in Infants After Cardiac Surgery: A Single Center Ancillary Cohort of the Steroids to Reduce Systemic Inflammation After Infant Heart Surgery Trial.
To examine the association between three perioperative urine biomarker concentrations (urine cystatin C [uCysC], urine neutrophil gelatinase-associated lipocalin [uNGAL], and urine kidney injury molecule 1 [uKIM-1]), and cardiac surgery-associated acute kidney injury (CS-AKI) and fluid overload (FO) in infants with congenital heart disease undergoing surgery on cardiopulmonary bypass. To explore how urine biomarkers are associated with distinct CS-AKI phenotypes based on FO status. Ancillary prospective cohort study. Single U.S. pediatric cardiac ICU. Infants less than 1 year old enrolled in the Steroids to Reduce Systemic Inflammation after Infant Heart Surgery trial (NCT03229538) who underwent heart surgery from June 2019 to May 2020 and opted into biomarker collection at a single center. Infants with preoperative CS-AKI were excluded. None. Forty infants met inclusion criteria. Median (interquartile) age at surgery was 103 days (5.5-161 d). Modified Kidney Disease Improving Global Outcomes-defined CS-AKI was diagnosed in 22 (55%) infants and 21 (53%) developed FO. UCysC and uNGAL peaked in the early postoperative period and uKIM-1 peaked later. In unadjusted analysis, bypass time was longer, and Vasoactive-Inotropic Score at 24 hours was higher in infants with CS-AKI. On multivariable analysis, higher uCysC (odds ratio [OR], 1.023; 95% CI, 1.004-1.042) and uNGAL (OR, 1.019; 95% CI, 1.004-1.035) at 0-8 hours post-bypass were associated with FO. UCysC, uNGAL, and uKIM-1 did not significantly correlate with CS-AKI. In exploratory analyses of CS-AKI phenotypes, uCysC and uNGAL were highest in CS-AKI+/FO+ infants. In this study, uCysC and uNGAL in the early postoperative period were associated with FO at 48 hours. UCysC, uNGAL, and uKIM-1 were not associated with CS-AKI. Further studies should focus on defining expected concentrations of these biomarkers, exploring CS-AKI phenotypes and outcomes, and establishing clinically meaningful endpoints for infants post-cardiac surgery.


Triglyceride levels and apolipoprotein E polymorphism in patients with acute pancreatitis.
Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon. This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia. We undertook a one-year, prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides. The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption, the presence of co-morbidities and any medications being taken. The patients' progression, etiological diagnosis, hospital stay and clinical and radiological severity were all recorded. Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%); the remaining cases were of biliary (53%), idiopathic (26%), alcoholic (11%) or other (5%) origin. Compared with these remaining cases, the patients with hypertriglyceridemia were significantly younger, had more relapses, and more often had diabetes mellitus. They usually consumed alcohol or consumed it excessively on the days before admission. Also, the ε4 allele of the APOE gene was more common in this group (P<0.05). One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and, especially, alcohol consumption.


Investigations of the roles of arginine 115 and lysine 120 in the active site of 5,10-methenyltetrahydrofolate synthetase from Mycoplasma pneumoniae.
5,10-Methenyltetrahydrofolate synthetase (MTHFS) catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate coupled to the hydrolysis of ATP. A co-crystal structure of MTHFS bound to its substrates has been published (Chen et al., Proteins 56:839-843, 2005) that provides insights into the mechanism of this reaction. To further investigate this mechanism, we have replaced the arginine at position 115 and the lysine at position 120 with alanine (R115A and K120A, respectively). Circular dichroism spectra for both mutants are consistent with folded proteins. R115A shows no activity, suggesting that R115 plays a critical role in the activity of the enzyme. The K120A mutation increases the Michaelis constant (K(m)) for ATP from 76 to 1,200 microM and the K(m) for 5-formylTHF from 2.5 to 7.1 microM. The weaker binding of substrates by K120A may be due to movement of a loop consisting of residues 117 though 120, which makes several hydrogen bonds to ATP and may be held in position by K120.


Evaluation of Training Gaps Among Public Health Practitioners in Washington State.
Identifying training gaps in public health competencies and skills is a first step in developing priorities for advancing the workforce. Our purpose was to identify training gaps in competencies and skills among local, state, and nonjurisdictional public health employees in Washington State. Our secondary aim was to determine whether training gaps differed by employees' work-related and demographic characteristics. We used data from our training needs assessment of the public health workforce, conducted as an online cross-sectional survey in Spring/Summer of 2016. Employees from governmental local, state, and nonjurisdictional public health departments in Washington State. Training gaps were calculated for 8 public health competencies and 8 skills, using a composite score of respondents' ratings of their "training confidence" and "training need." For each domain and skill area, we calculated the percentage of associated items, where respondents rated their training needs as high and their confidence as low to create scores ranging from 0% to 100%. The largest training gaps in public health competencies were in the Financial Planning and Policy Development domains. For skills, Quality Improvement and Developing Effective Communication Campaigns had the largest training gaps. In adjusted models, female employees or employees working in local health departments in select Washington State regions had higher training gaps in Financial Planning, Policy Development, and Quality Improvement, relative to male or state health department employees. Employees who worked in specialized programs, such as Communicable Disease Control, and Maternal, Child, and Family Health, had higher training gaps in Financial Planning and Developing Effective Communication Campaigns than those who worked in Administrative and Support Services. We identified important training gaps in several competency domains and skills. Findings are informing decisions about tailoring training opportunities for public health practitioners in Washington and other states.


Effect of the level of dietary protein intake on fat absorption in children.
The quantity and quality of protein in the diet affect both nitrogen balance and energy utilization in man. One possible mechanism is by a direct effect on the process of fat digestion and absorption. The effect on fat absorption of feeding diets providing 0%, 6.4%, or 12.5% of energy as protein was assessed in nine children. Liquid diets were prepared by high speed blending of calcium caseinate, a soy-cottonsed oil blend (80:20), sucrose, water, vitamins, and a mineral mixture and fed by bottle five times per day. Diets varied in the amount of protein and were fed to maintain constant the intakes of fat and carbohydrate. All children began by consuming the diet providing 6.4% of energy as protein for a period of 6 days: 3 days of adaptation, 3-day dietary periods and metabolic collections followed in one of two sequences: 12.5%, 0%, 6.4% energy as protein in five children; 0%, 12.5%, 6.4% energy as protein in four. Mean fat excretion during the two 6.4% periods did not differ significantly (initial 14.5 +/- 6% of intake; final, 11.7 +/- 5.0% of intake). Fat excretion was significantly greater during the period when no protein was consumed (23.9 +/- 7.7% of intake) than during either the period in which protein provided 6.4% of energy (P less than 0.01) or during that in which protein provided 12.5% of energy (10.0 +/- 2.6% of intake, P less than 0.001). The difference between the 6.4% and 12.5% periods did not attain significance (P = 0.10). Fecal fat expressed as a percentage of fecal dry weight was significantly greater during periods when the diet contained no protein than during periods in which protein provided either 6.4% (P less than 0.05) or 12.5% (P less than 0.01) of energy. Additional studies were carried out in a similar fashion in six children consuming diets in which protein provided 5%, 9.6%, and 15% of energy. All six possible dietary sequences were used. At these intakes fat excretion did not vary significantly with protein intake.


GABAergic ganglion cells in the rabbit retina.
The ganglion cells are the output neurons of the retina. There is, however, relatively little known about the neurotransmitters used by these cells. In the present study, ganglion cells identified with a ganglion cell-specific monoclonal antibody (AB5) are shown in separate double-label experiments to be gamma-aminobutyric acid (GABA)-like immunoreactive and to possess a high-affinity uptake mechanism for [3H]GABA accumulation. The localization of these markers of GABA activity to AB5-labelled ganglion cells provides the first definitive evidence for the presence of a classical transmitter in retinal ganglion cells and suggests that GABA may perform a role as a neurotransmitter in these cells.


The cardiovascular consequences of fatiguing expiratory muscle work in otherwise resting healthy humans.
In 11 healthy adults (25 ± 4 yr; 2 female, 9 male subjects), we investigated the effect of expiratory resistive loaded breathing [65% maximal expiratory mouth pressure (MEP), 15 breaths·min-1, duty cycle 0.5; ERLPm] on mean arterial pressure (MAP), leg vascular resistance (LVR), and leg blood flow ([Formula: see text]). On a separate day, a subset of five male subjects performed ERL targeting 65% of maximal expiratory gastric pressure (ERLPga). ERL-induced expiratory muscle fatigue was confirmed by a 17 ± 5% reduction in MEP (P < 0.05) and a 16 ± 12% reduction in the gastric twitch pressure response to magnetic nerve stimulation (P = 0.09) from before to after ERLPm and ERLPga, respectively. From rest to task failure in ERLPm and ERLPga, MAP increased (ERLPm = 31 ± 10 mmHg, ERLPga = 18 ± 9 mmHg, both P < 0.05), but group mean LVR and [Formula: see text] were unchanged (ERLPm: LVR = 0.78 ± 0.21 vs. 0.97 ± 0.36 mmHg·mL-1·min, [Formula: see text] = 133 ± 34 vs. 152 ± 74 mL·min-1; ERLPga: LVR = 0.70 ± 0.21 vs. 0.84 ± 0.33 mmHg·mL-1·min, [Formula: see text] = 160 ± 48 vs. 179 ± 110 mL·min-1) (all P ≥ 0.05). Interestingly, [Formula: see text] during ERLPga oscillated within each breath, increasing (∼66%) and decreasing (∼50%) relative to resting values during resisted expirations and unresisted inspirations, respectively. In conclusion, fatiguing expiratory muscle work did not affect group mean LVR or [Formula: see text] in otherwise resting humans. We speculate that any sympathetically mediated peripheral vasoconstriction was counteracted by transient mechanical effects of high intra-abdominal pressures during ERL.NEW & NOTEWORTHY Fatiguing expiratory muscle work in otherwise resting humans elicits an increase in sympathetic motor outflow; whether limb blood flow ([Formula: see text]) and leg vascular resistance (LVR) are affected remains unknown. We found that fatiguing expiratory resistive loaded breathing (ERL) did not affect group mean [Formula: see text] or LVR. However, within-breath oscillations in [Formula: see text] may reflect a sympathetically mediated vasoconstriction that was counteracted by transient increases in [Formula: see text] due to the mechanical effects of high intra-abdominal pressure during ERL.


Rigorous formulation for electromagnetic plane-wave scattering from a general-shaped groove in a perfectly conducting plane: comment.
We show that the problem of scattering of an obliquely incident plane wave by a general-shaped groove engraved on a perfectly conducting plane, which was recently studied by Basha et al. [J. Opt. Soc. Am. A24, 1647 (2007)], was solved 11 years ago using the same formulation. This method was further extended to deal with a finite number of grooves and also with complex apertures including several nonlossy and lossy dielectrics, as well as real metals.


Regional blood flows by the microsphere method: reproducibility in portal hypertensive rats and influence of a portal vein catheter.
To determine the reproducibility of splanchnic blood flow measurements by the microsphere method in rats with portal hypertension and the effects of laparotomy with portal vein cannulation, eight groups of 10 rats were studied. Cardiac output and regional blood flows were measured twice, 10 min apart, in pentobarbital anesthetized or awake, sham-operated or portal vein-ligated rats, with or without portal cannulation. Variability between the two successive measurements was not affected by portal hypertension or portal cannulation, and was not different in the splanchnic territory and in other organs. Laparotomy with portal cannulation had no significant effect in sham-operated rats. In awake portal hypertensive rats, cardiac output (53.9 +/- 3.0 vs 45.8 +/- 2.9 ml.min-1.100 g body wt-1, P less than 0.01) and splanchnic blood flow (12.31 +/- 0.72 vs 9.34 +/- 0.85 ml.min-1.100 g body wt-1, P less than 0.01) were lower in portal vein cannulated rats compared with those of non-cannulated animals. In anesthetized portal hypertensive rats blood flows were unaffected by portal cannulation, but arterial pressure (100.2 +/- 4.3 vs 119.9 +/- 3.4 mm Hg, P less than 0.01) and heart rate (366.5 +/- 10.0 vs 405.5 +/- 7.4 beats.min-1, P less than 0.01) were elevated. Anesthesia also decreased portal pressure (14.8 +/- 0.5 vs 12.0 +/- 0.4 mm Hg, P less than 0.05) in portal hypertensive rats. We conclude that the microsphere method remains reproducible in portal hypertensive rat models. Laparotomy with portal cannulation can alter systemic and splanchnic hemodynamics in portal hypertensive rats; these effects can also be changed during pentobarbital anesthesia. Regional blood flow measurements in portal hypertensive rats should be performed in animals without portal cannulation and preferably in the awake state.