Simulations: their selection and use in developing nursing competencies.
Efficient and effective use of simulations for teaching or review requires that they be matched carefully to a target nursing competency. Guidelines are provided to assist nursing staff development educators in selecting and using simulations for psychomotor assessment and interpersonal skills as well as problem solving.


Occult fetomaternal hemorrhage in women with pathological placenta with respect to permeability.
Women with pre-eclampsia (PE), placenta previa (PP), placental abruption (PA), and placental mesenchymal dysplasia (PMD) have been described as having placental permeability dysfunction. This study was performed to determine whether occult fetomaternal hemorrhage (FMH) is common in women with such complications and in women with non-reassuring fetal status. Forty-one antenatal and 39 postnatal blood samples were obtained from 46 women, including 11 with placental permeability dysfunction (5, 3, 2, and 1 with PE, PP, PA, and PMD, respectively) and 35 controls without such complications. To estimate the amount of fetal red blood cells, flow cytometry was performed using the fetal cell count system with two antibodies against fetal hemoglobin and carbonic anhydrase and the β-γ system with two monoclonal antibodies against hemoglobin β-chain and hemoglobin γ-chain. A diagnosis of FMH was made when the fraction size of the isolated cell population on scatter plots expressing fetal hemoglobin alone or hemoglobin γ-chain alone accounted for ≥0.02% of the total cell population on scatter plots. FMH was identified in five women, including one each with PE, PA, PP, PMD, and no complications. Thus, the prevalence rate of FMH was significantly higher in women with complications than in controls (36% [4/11] vs 2.9% [1/35], respectively, P = 0.009). The FMH occurrence rate did not differ between women with and without non-reassuring fetal status (7.7% [1/13] vs 12% [4/33], respectively, P = 1.000). The risk of fetal red blood cells trafficking into the maternal circulation may be increased in women complicated with PE, PA, PP, and PMD.


Effects of intracerebroventricular anandamide administration on feed intake and milk yield of dairy cows.
Among the endocannabinoids, N-arachidonylethanolamide (AEA; anandamide) plays a key role in regulating energy homeostasis and energy intake. Recent studies suggest the existence of a peripheral mechanism by which AEA increases feed intake in the short term and modulates whole-body energy metabolism in dairy cows. Here, we aimed to test the hypothesis that AEA has a long-lasting central effect in increasing feed intake that leads to an increase in milk yield of dairy cows. In the present pilot study, 3 nonpregnant Holstein dairy cows were equipped with an intracerebroventricular (i.c.v.) catheter. Cows were deprived from feed for 2 h and received either no injection or an i.c.v. injection of either 12 μg of AEA or DMSO (control), followed by measurement of feed intake for 10 h and milk yield. Administration of AEA increased 10-h dry matter intake (DMI) by between 1.13 and 2.06 kg, whereas 22-h DMI was only marginally altered. However, compared with the control treatment, AEA reduced daily milk yield by 0.3 to 1.4 L/d in all 3 cows. The results demonstrate that i.c.v. administration of 12 µg of AEA increased 10-h DMI but decreased daily milk yield by a central mechanism.


Changes in blood flow and metabolism in a neurovascular island skin flap after a burn.
In 8 male white Yorkshire pigs weighing approximately 42 kg each, 12 buttock neurovascular island skin flaps were dissected. Baseline recordings were made of blood flow and O2 consumption in the flap. Two series of experiments were carried out. In control animals (5), the flap was dissected and the "cold" aluminum plate was applied for 10 seconds. In the burned flaps (7) a contact burn of 2.68 calories/cm2 was created with a heated aluminium plate applied to the skin for 10 seconds. After this the flaps were studied for 4 hours. In the control flaps, blood flow and O2 consumption did not change. The burned flaps showed no change in blood flow, while O2 consumption increased significantly from .07 +/- .01 (SE) ml/100 g/min to .18 +/- .08 (SE) ml/100 g/min (p less than .05).


Anticoagulant thrombins.
Thrombin plays both procoagulant and anticoagulant roles in the blood coagulation cascade. This dual role is influenced allosterically by the binding of Na(+) near the primary specificity pocket of the enzyme. Recent findings demonstrate that it is possible to engineer recombinant thrombins that have practically lost anticoagulant activity but retain their anticoagulant properties. These anticoagulant thrombins bear substitutions in or around the Na(+) binding site, provide important clues on structure-function relations, and offer a promising alternative to current anticoagulant therapies. In addition, they demonstrate the importance of Na(+) as a coagulation factor and broaden our understanding of the function and regulation of all vitamin K-dependent clotting enzymes.


[Plastic surgery coverage in the dorsal trunk area].
Defects of the trunk are major plastic surgical challenges. In the posterior trunk these defects are congenital or acquired. Most of the defects are due to major tumor resections, rarely after trauma or burns. With regional or local flaps most of the defects can be covered adequately. Presently musculocutaneous and perforator flaps are favoured. An interdisciplinary cooperation is mandatory for a successful result.


[Construction of SDF-1P2G54, a specific antagonist of CXCR4].
To obtain a specific antagonist of CXCR4, SDF-1P2G54 by mutating SDF-1 second proline (P) into glycin (G) and removing the α-helix of its C-terminal. SDF-1p2g54 gene amplified by PCR was inserted into the vector pET-30a (+) and transformed into Escherichia coli (E. coli) strain BL21. After IPTG induction of E. coli, the expressed recombinant protein was purified with nickel-affinity chromatography column under denaturing conditions and refolded with gradient dilution and ultra-filtration. The chemotactic effect of SDF-1P2G54 on Jurkat cells and its antagonistic effect against SDF-1 were determined by transwell assay; flow cytometry was used to assay the ability of SDF-1P2G54 to induce calcium influx and CXCR4 internalization in MOLT4 cells. The recombinant protein SDF-1P2G54 completely lost the functions to activate CXCR4 or to induce transmembrane migration of Jurkat cells and calcium influx in MOLT4 cells, but maintained a high affinity to CXCR4. SDF-1P2G54 effectively inhibited the chemotactic effect of wild-type SDF-1 to Jurkat cells, and induced rapid CXCR4 internalization in MOLT4 cells. SDF-1P2G54 is a new antagonist of CXCR4 with a potential value as an effective inhibitor of HIV-1 infection, cancer metastasis or other major diseases.


A Biomechanical Comparison of Different Suture Materials Used for Arthroscopic Shoulder Procedures.
To evaluate the viscoelastic properties of 4 commercially available cord-like sutures and 2 commercially available suture tapes when subjected to physiological loads, as well as to compare them with each other and to identify the clinically most desirable combination of suture material properties. Six suture materials (Ethibond, FiberWire, FiberTape, Orthocord, Ultrabraid, and Ultratape) underwent creep testing (n = 7, 60 N, 10 minutes) to determine specimen stiffness, initial elongation at 60 N of load, static creep (during 10 minutes of loading), and relaxed elongation (material recovery 3 minutes after removal of load). Furthermore, cyclic testing (n = 7, 10-45 N, 0.5 Hz, 500 cycles) was carried out to determine dynamic creep, peak-to-peak displacement, and relaxed elongation. Mechanical testing was conducted on a material testing machine in 37°C phosphate-buffered saline solution. FiberTape showed the greatest stiffness (23.9 ± 3.2 N/mm, P < .001), the smallest amounts of static (0.38 ± 0.10 mm, P < .001) and dynamic (0.16 ± 0.09 mm, P = .003) creep, and the smallest peak-to-peak displacement (0.20 ± 0.02 mm, P < .001). FiberTape and FiberWire showed the smallest initial elongation (1.17 ± 0.17 mm and 1.63 ± 0.25 mm, respectively; P < .001). Ultrabraid showed the greatest relaxed elongation, both statically (4.73 ± 0.73 mm, P < .001) and dynamically (4.18 ± 0.83 mm, P = .002). FiberTape consistently displayed less creep, greater stiffness, and less extensibility than the other suture types. Ultrabraid showed the largest amount of relaxed elongation on both static and dynamic testing. When considering high stiffness in combination with low initial extension and low static creep to be ideal parameters to achieve optimal initial construct stability and considering low dynamic creep in combination with low peak-to-peak displacement to be ideal conditions for the repetitive loading of the construct during the healing process, tapes seem to be superior to cord-like sutures for performing rotator cuff repair.


N-terminal domain of PB1-F2 protein of influenza A virus can fold into amyloid-like oligomers and damage cholesterol and cardiolipid containing membranes.
PB1-F2 protein is a factor of virulence of influenza A viruses which increases the mortality and morbidity associated with infection. Most seasonal H1N1 Influenza A viruses express nowadays a truncated version of PB1-F2. Here we show that truncation of PB1-F2 modified supramolecular organization of the protein in a membrane-mimicking environment. In addition, full-length PB1-F2(1-90) and C-terminal PB1-F2 domain (53-90), efficiently permeabilized various anionic liposomes while N-terminal domain PB1-F2(1-52) only lysed cholesterol and cardiolipin containing lipid bilayers. These findings suggest that the truncation of PB1-F2 may impact the pathogenicity of a given virus strain.


Sonochemical syntheses of a nano-sized copper(II) supramolecule as a precursor for the synthesis of copper(II) oxide nanoparticles.
Nanoparticles of a three-dimensional supramolecular, [Cu(L)(2)(H(2)O)(2)] (1), (L(-)=1H-1,2,4-triazole-3-carboxylate), have been synthesized by a sonochemical process and characterized by scanning electron microscopy, X-ray powder diffraction, IR spectroscopy and elemental analyses. The thermal stability of compound 1 both its bulk and nano-size has been studied by thermal gravimetric (TG) and differential thermal analyses (DTA) and compared each other. Concentration of initial reagents effects on size and morphology of nano-structured compound 1, have been studied. Calcination of the nano-sized compound 1 at 600°C under air atmosphere yields CuO nanoparticles.


Quantitative profiling of polar glycerolipid species from organs of wild-type Arabidopsis and a phospholipase Dalpha1 knockout mutant.
Lipid profiling is a targeted metabolomics platform that provides a comprehensive analysis of lipid species with high sensitivity. Profiling based on electrospray ionization tandem mass spectrometry (ESI-MS/MS) provides quantitative data and is adaptable to high throughput analyses. Here we report the profiling of 140 apparent molecular species of polar glycerolipids in Arabidopsis leaves, flower stalks, flowers, siliques, roots, and seeds. Considerable differences in lipid species occur among these organs, providing insights into the different lipid metabolic activities in a specific organ. In addition, comparative profiling between wild-type and a knockout mutant pldalpha1 (locus ID: AT3G15730) provides insight into the metabolic function of phospholipase D (PLD) in different organs. PLDalpha1 contributes significantly to phosphatidic acid (PA) levels in roots, seeds, flowers, and flower stalks, but little to basal PA levels in siliques and leaves. In seeds of the pldalpha1 mutant plants, levels of PA, lysophosphatidylcholine, and lysophosphatidylethanolamine were significantly lower than those of wild-type seeds, suggesting a role for PLDalpha1 in membrane lipid degradation in seeds.


Decreased coronary vascular reserve in Watanabe heritable hyperlipidemic rabbits.
Watanabe heritable hyperlipidemic (WHHL) rabbits have severe hypercholesterolemia due to a genetic defect in their low density lipoprotein receptors. Therefore, they develop severe premature atherosclerosis of the large arteries including the coronary arteries. In the present study, we measured the coronary vascular reserve of these rabbits to evaluate the total cross-sectional coronary surface area. This method allowed us to quantify the functional consequences of the coronary atherosclerotic lesions. To evaluate coronary vascular reserve, we measured coronary blood flow with the radioactive microsphere technique before and after induction of maximal coronary vasodilation by an intravenous dose of 9 mg/kg of carbocromen. A group of pure-bred WHHL rabbits was compared to a group of normal Burgundy rabbits at ages of 100 and 300 days. At 100 days, there was no difference in coronary vascular reserve between the two groups. However, at 300 days, the coronary vascular reserve in WHHL rabbits was 48% smaller than in the normal Burgundy rabbits (p less than 0.001). In addition, by making corrosion casts and morphological studies, we were able to show that at 300 days nearly all the WHHL rabbits had severe coronary atherosclerotic lesions located mainly at the origin of the large coronary arteries. We conclude that WHHL rabbits at 300 days have a severe impairment of their coronary vascular reserve due to proximal atherosclerotic lesions in the coronary arteries.


In-Solution Hybridization for the Targeted Enrichment of the Whole Mitochondrial Genome.
A detailed protocol is presented for the targeted enrichment of whole mitochondrial genomes based on an in-solution hybridization strategy. Bait is produced in-house by sonication of two long-range PCR amplicons and ligation of biotinylated double-stranded adapters. Indexed target DNA is hybridized with the bait in a multiplex enrichment reaction and pulled down using magnetic streptavidin beads followed by subsequent post-enrichment PCR and sequencing on an Illumina MiSeq. This strategy removes the need for expensive commercial bait probes while allowing enrichment of multiple samples in a single hybridization reaction. The method is particularly suitable for degraded DNA as it is able to enrich short DNA fragments and is not susceptible to polymerase artifacts introduced during PCR-based assays.


Human pharmacokinetic and pharmacodynamic profiles of leuprorelin acetate depot in prostatic cancer patients.
A total of 21 patients with advanced prostatic cancer and one patient with benign prostatic hypertrophy received 3.75, 7.5 or 15 mg leuprorelin acetate depot subcutaneously. Serum leuprorelin concentrations increased immediately after injection, reaching a peak concentration (range 13.1-54.5 ng/ml), which was directly proportional to dose, within 3 h. Mean drug levels subsequently declined to a plateau directly proportional to dose at 5 weeks. There was also a significant (P less than 0.01) dose-dependent increase in the area under the concentration-time curve for 0-35 days. Serum concentrations of luteinizing hormone and follicle stimulating hormone rose initially with all doses, followed by a rise in serum testosterone and dihydrotestosterone concentrations, which then fell sharply, within 3 weeks. A reduced level of follicle stimulating hormone subsequently occurred in all 20 evaluable patients and was maintained in 17 patients over 5 weeks. There was also marked initial suppression of luteinizing hormone levels in 15 patients and in 13 this continued. Castration levels of testosterone and dihydrotestosterone were maintained in all patients for up to 5 weeks. In two patients there was a complete response, in 14 a partial response and in three stable disease, with no significant differences in relation to dose. Clinical improvement and serum hormonal changes suggest that leuprorelin acetate depot is effective at a dose as low as 3.75 mg when given once every 4 weeks.


Temporal alterations in the bovine buttermilk glycome from parturition to milk maturation.
The bovine milk fat globule membrane (MFGM) has many associated biological activities, many of which are linked with specific carbohydrate structures of MFGM glycoconjugates. Bovine buttermilk is a commercially viable source of MFGM and is an under-valued by-product of butter making. However, the changes in buttermilk glycosylation over the course of lactation have not been extensively investigated. In this study, buttermilk was generated from three individual multiparous cows at 13 time points over the first three months of lactation. Buttermilk glycosylation was profiled using lectin microarrays and lectin blotting. Suggested differences in glycosylation, including N-glycosylation, sialylation and fucosylation, were observed between early and late time points and between individual animals. Overall, these data suggest temporal changes in the glycosylation of buttermilk proteins which may have an important impact on commercial isolation of glycosylated ingredients.


Rehabilitation following first-time patellar dislocation: a randomised controlled trial of purported vastus medialis obliquus muscle versus general quadriceps strengthening exercises.
We aimed to define whether distal vastus medialis (VM) muscle strengthening improves functional outcomes compared to general quadriceps muscle strengthening following first-time patellar dislocation (FTPD). Fifty patients post-FTPD were randomised to either a general quadriceps exercise or rehabilitation programme (n=25) or a specific-VM exercise and rehabilitation regime (n=25). The primary outcome was the Lysholm knee score, and secondary outcomes included the Tegner Level of Activity score, the Norwich Patellar Instability (NPI) score, and isometric knee extension strength at various knee flexion ranges of motion. Outcomes were assessed at baseline, six weeks, six months and 12months. There were statistically significant differences in functional outcome and activity levels with the Lysholm knee score and Tegner Level of Activity score at 12months in the general quadriceps exercise group compared to the VM group (p=0.05; 95% confidence interval (CI): -14.0 to 0.0/p=0.04; 95% CI: -3.0 to 0.0). This did not reach a clinically important difference. There was no statistically significant difference between the groups for the NPI score and isometric strength at any follow-up interval. The trial experienced substantial participant attrition (52% at 12months). Whilst there was a statistical difference in the Lysholm knee score and Tegner Level of Activity score between general quadriceps and VM exercise groups at 12months, this may not have necessarily been clinically important. This trial highlights that participant recruitment and retention are challenges which should be considered when designing future trials in this population. Therapeutic study, Level I.


Acute cholecystitis after orthopaedic operations.
When acute cholecystitis follows orthopaedic operations, the disease is frequently obscure and fulminating, with rapid progress to gangrene and perforation of the gallbladder, which may be fatal. Three cases are reported and the literature is reviewed. Various aspects of the disorder are discussed. It is important that orthopaedic surgeons should be aware of the condition in order to be able to make an early diagnosis and so prevent a lethal outcome.


Adsorption and photocatalytic conversion of ethyl mercaptan to diethyl disulfide on Fe2O3-loaded HNbMoO6 nanosheet.
Ethyl mercaptans which commonly exist in natural gas need to be removed due to their toxic, odorous, and corrosive properties. Herein, a novel Fe2O3-modified HNbMoO6 nanosheet catalyst (Fe2O3@e-HNbMoO6) was prepared by an exfoliation-impregnation method for the ethyl mercaptans removal. In the heterojunction catalyst, e-HNbMoO6 can be excited by visible light to generate the photogenic charge and has certain adsorption property for ethyl mercaptan with hydrogen bonding (Nb-OH or Mo-OH as the hydrogen bonding donor); Fe2O3 plays the role of accelerating photogenerated electrons and holes, and enhancing the adsorption of ethyl mercaptan with another hydrogen bonding (Fe-OH as the hydrogen bonding donor and receptor). Results showed that the adsorption capacity of Fe2O3@e-HNbMoO6 is 69.9 μmol/g for ethyl mercaptan. In addition, the photocatalytic conversion efficiency of ethyl mercaptan to diethyl disulfide is nearly 100% and it is higher than that of the other Nb-Mo based photocatalysts, such as LiNbMoO6, Fe1/3NbMoO6, Ce1/3NbMoO6, TiO2-HNbMoO6, e-HNbMoO6, CeO2@e-HNbMoO6, and Ag2O@e-HNbMoO6. Under the experimental conditions, the photocatalytic conversion efficiency is greater than the adsorption efficiency over Fe2O3@e-HNbMoO6, and there is no ethyl mercaptan output in the process of adsorption and photocatalytic conversion. Fe2O3@e-HNbMoO6 heterojunction catalyst has practical value and reference significance for purifying methane gas and enhancing photocatalytic conversion of ethyl mercaptan.


Comparative efficacy of diabetes medications on liver enzymes and fat fraction in patients with nonalcoholic fatty liver disease: A network meta-analysis,.
This network meta-analysis (NMA) aimed to evaluate the relative rank-order of existing diabetes medications in patients with nonalcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM). A systematic literature search was conducted using the Medline, Embase and Cochrane databases. Clinical trials comparing the efficacy of diabetes medications with other interventions, including lifestyle modification and placebo, in patients with NAFLD were included. The results from the NMA are presented as the weighted mean difference (WMD) of the continuous results and the corresponding 95% confidence intervals (95% CIs). The articles presented the results of 49 trials involving 3,836 subjects published between 2013 and 2021. According to our results, thiazolidinedione (TZD) was ranked as the best diabetes medication in the reduction of alanine aminotransferase (ALT) (WMD = -10.10, 95% CI: -15.18, -5.01), followed by dipeptidyl peptidase-4 inhibitor (DPP4i) (WMD = -8.90, 95% CI: -14.41, -3.40). DPP4i also resulted in the greatest reduction in aspartate aminotransferase (AST) (WMD = -6.89, 95% CI: -11.72, -2.07). γ-Glutamyl transferase (γ-GT) reduction was highest in patients treated with glucagon-like peptide 1 receptor agonists (GLP1RAs) (WMD = -15.48, 95% CI: -30.93, -0.02). Ultimately, SGLT2is and GLP1RAs were superior to other diabetes medications or placebo in reducing liver fat fraction (LFF) (WMD = -6.09, 95% CI: -10.50, -1.68; WMD = -5.55, 95% CI: -10.40, -0.69, respectively). Diabetes medications, including TZD, DPP4i and GLP1RAs, were found to be suitable alternatives for liver enzyme reduction in the treatment of NAFLD patients. SGLT2is are considered the most effective therapies for lipid modulation in these patients.


Isolation of a napin-like polypeptide with potent translation-inhibitory activity from Chinese cabbage (Brassica parachinensis cv green-stalked) seeds.
A heterodimeric napin-like polypeptide was isolated from Brassica parachinensis seeds with a procedure involving ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, FPLC-ion exchange chromatography on Mono S and FPLC-gel filtration on Superdex 75. The N-terminal sequence of the 5 kDa subunit of the polypeptide (PAGPFRIPKKRKKEE) showed high homology with other 2S storage proteins like napins and albumins. The polypeptide potently inhibited translation in a cell free system with an IC50 of 6.2 nM. The translation-inhibiting activity of the polypeptide was relatively stable in the pH range 6-11 and in the temperature range 10-50 degrees C.


Brain activity during interval timing depends on sensory structure.
Precise timing is crucial for accurate perception and action in the range of hundreds of milliseconds. One still unresolved question concerns the influence of sensory information content on timing mechanisms. Numerous studies have converged to suggest that the CNV (Contingent Negative Variation), a slow negative wave that develops between two events, notably reflects temporal processing of the interval between these two events. The present study aimed at investigating CNV activity in duration discrimination tasks using either filled (continuous tones) or empty intervals (silent periods bounded by two brief tones). Participants had to compare a test duration with a 600-ms standard. Time perception was markedly better in the 'empty' than in the 'filled' condition. Electrophysiological analyses performed on the longest test duration (794 ms) of the comparison phase revealed an effect of the sensory structure on both the CNV amplitude and CNV time-course. The CNV amplitude was larger for filled than for empty intervals, suggesting a superimposition of timing-dependent activity and sensory sustained activity. Furthermore, the CNV time-course paralleled the temporal structure of the memorized sensory event: for filled intervals, the CNV amplitude stopped increasing at 600 ms, i.e. the expected end of the continuous tone; for empty intervals, in contrast, the CNV amplitude precisely increased at 600 ms, i.e. the expected onset of the second brief tone. These results suggest that the CNV reflects the mental rehearsal of the memorized sensory event, in line with the idea that temporal processing in the sub-second range is based on sensory information.


Potentially avoidable hospitalizations for older patients transferred from long-term care hospitals: a nationwide cross-sectional analysis of potential healthcare consequences.
Multiple chronic disorders and disabilities among older patients in long term care hospitals (LTCH) tends to increase the healthcare burden by causing overcrowding, particularly in emergency departments. Therefore, access to timely and adequate healthcare for LTCH patients is an increasingly important issue, and potentially avoidable hospitalizations (PAHs) and hospitalizations during non-office hours can result as indicators of emergency department overcrowding. The study aimed to evaluate PAHs and hospitalizations during non-office hours in emergency departments for older patients transferred from LTCH compared to patients living at home. We performed a cross-sectional study using the National Emergency Department Information System database from January 2018 to December 2019, in South Korea, with older patients (≥ 65 years) who visited nationwide emergency departments. Adjusted odds ratio (aOR) and 95% confidence interval (CI) for indicators of overcrowding as PAHs and hospitalizations during non-office hours were calculated by logistic regression. Among the 2,177,663 older patients who visited the emergency departments, 98,434 patients were living in LTCH and 2,079,229 patients were living at home. The older patients living in LTCH was associated with PAHs (aOR: 1.90, 95% CI 1.87-1.94) and hospitalizations during non-office hours (aOR: 1.76, 95% CI 1.73-1.78). LTCH patients showed more hospital visits, extended stay in the emergency department, greater prevalence of chronic diseases, greater rates of transfer as well as higher admission rates and mortality as compared to the patients living at home. The LTCH older patients were associated with the indicators of emergency department overcrowding, which impacts health care quality in hospitals. Introduction of policy and training programs for LTCH staff are recommended to manage vulnerable groups in advance.


Fusion or gemination? An unusual mandibular second molar.
Fusion and gemination is not an uncommon finding and affected most primary dentition and the permanent maxillary incisors. These changes can develop a series of complication. A 11-year-old male presented radiography finding: an unusual mandibular second molar. A well-documented case brings a challenge for radiologists classify between fusion and gemination. In conclusion, this alteration although common in other regions, there are no case in the literature involving "second and third" molar.


Rnd3 is necessary for the correct oligodendrocyte differentiation and myelination in the central nervous system.
Rho small GTPases are proteins with key roles in the development of the central nervous system. Rnd proteins are a subfamily of Rho GTPases, characterized by their constitutive activity. Rnd3/RhoE is a member of this subfamily ubiquitously expressed in the CNS, whose specific functions during brain development are still not well defined. Since other Rho proteins have been linked to the myelination process, we study here the expression and function of Rnd3 in oligodendrocyte development. We have found that Rnd3 is expressed in a subset of oligodendrocyte precursor cells and of mature oligodendrocytes both in vivo and in vitro. We have analyzed the role of Rnd3 in myelination using mice lacking Rnd3 expression (Rnd3gt/gt mice), showing that these mice exhibit hypomyelination in the brain and a reduction in the number of mature and total oligodendrocytes in the corpus callosum and striatum. The mutants display a decreased expression of several myelin proteins and a reduction in the number of myelinated axons. In addition, myelinated axons exhibit thinner myelin sheaths. In vitro experiments using Rnd3gt/gt mutant mice showed that the differentiation of the precursor cells is altered in the absence of Rnd3 expression, suggesting that Rnd3 is directly required for the differentiation of oligodendrocytes and, in consequence, for the correct myelination of the CNS. This work shows Rnd3 as a new protein involved in oligodendrocyte maturation, opening new avenues to further study the function of Rnd3 in the development of the central nervous system and its possible involvement in demyelinating diseases.


A fluorescence-switchable luminogen in the solid state: a sensitive and selective sensor for the fast "turn-on" detection of primary amine gas.
The emission of pyrrole-substituted benzoic acid can be repeatedly switched between the dark and bright states in the solid state by chemical fuming and heating processes, enabling it to work as a rapid sensitive fluorescent sensor for primary amine detection.


Effects of centrally acting muscle relaxants on post-rotatory nystagmus in the rabbit.
1. The effects of some centrally acting muscle relaxants on the post-rotatory nystagmus induced by rotatory stimulation were investigated in the rabbit, to examine the action of the drugs on vestibular function. 2. Tolperisone-HCl (5-10 mg/kg, i.v.) and baclofen (1-3 mg/kg, i.v.) decreased the number of post-rotatory nystagmus beats dose-dependently, whereas mephenesin (40-80 mg/kg, i.v.) and diazepam (0.5-1.0 mg/kg, i.v.) prolonged it dose-dependently. 3. The inhibitory effects of tolperisone-HCl and baclofen may provide some suggestions as to the mechanisms and sites of actions of centrally acting muscle relaxants, while the significance of the prolonging action of mephenesin remains unclear. 4. The prolonging action of diazepam is discussed with reference to GABAergic mechanisms.


Does youth participation in the farming program impact farm productivity and household welfare? Evidence from Nigeria.
One significant issue in the Global South, particularly in sub-Saharan Africa, is youth unemployment. This is a result of the aging and shrinking agriculture industry, increased unemployment rates mixed with a sizable unskilled workforce, and rapid population expansion. Studies have shown that farming programs, when supported by increased investment and regulatory frameworks, provide opportunities for meaningful employment for many young people. This study attempts to estimate the impact of youth participation in farming programs on farm productivity and welfare using rice-growing household data from northern Nigeria. We used propensity score matching (PSM) and endogenous switching regression (ESR) to address biases that may arise from both observed and unobserved factors. Our results show that age, education, household size, farm size, extension, access to credit, and membership of a social group are positive and significantly associated with youth participation in farming programs. The outcome demonstrates that participants fare better than non-participants in terms of farm productivity and welfare status. Furthermore, youth participation in farming programs has implications for heterogeneity within the participant group, which depends on socio-economic characteristics such as access to finance, association membership, and education, emphasizing the need for specific interventions and focusing on particular youth groups. Therefore, access to credit through relevant agencies with low interest rates and flexible payment options, strengthening youth organization could encourage participation in farming programs and job opportunities for the prosperity of the rural economy.


Biomarkers: an overview for oncology nurses.
To provide an overview of the basic principles of biomarker use in clinical oncology practice and discuss the range of biomarker forms (from genes to constitutional characteristics), biomarker functions (both disease- and drug-related), modalities (protein expression patterns to patient history), the criteria for biomarker validation, and the integral role of bioinformatics. Published nursing and medical literature. The premise of nursing assessment is the same as that of biomarker use - biological variables that appear at one level of biological organization (eg, molecule, organelle, cell, tissue, organ, and organism) correspond to processes or events occurring at other levels of biologic organization. The advent of genomic technologies has logarithmically increased the volume of biomarkers, which are expected to provide new insights that improve patient care. Nurses and patients will benefit greatly from the incorporation of molecular biomarkers into patient care. Nurses will be able to better assess (and anticipate) patient needs with the new insights that are available in the post-genomic, personalized medicine era of health care. Although the rapid rate of technological changes and new discoveries will require continuing concerted educational efforts, the improved quality of patient care will be rewarded by better outcomes.


Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt.
Forkhead box O (FOXO) transcription factors, the key regulators of cell survival, are negatively controlled through the PI3K-Akt signaling pathway. Phosphorylation of FOXO by Akt leads to cytoplasmic localization and subsequent degradation via the ubiquitin-proteasome system. Here we show a paradigm of FOXO1 regulation by the protein arginine methyltransferase PRMT1. PRMT1 methylated FOXO1 at conserved Arg248 and Arg250 within a consensus motif for Akt phosphorylation; this methylation directly blocked Akt-mediated phosphorylation of FOXO1 at Ser253 in vitro and in vivo. Silencing of PRMT1 by small interfering RNA enhanced nuclear exclusion, polyubiquitination, and proteasomal degradation of FOXO1. PRMT1 knockdown led to a decrease in oxidative-stress-induced apoptosis depending on the PI3K-Akt signaling pathway. Furthermore, stable expression of enzymatic inactive PRMT1 mutant increased resistance to apoptosis, whereas this effect was reversed by expression of phosphorylation-deficient FOXO1. Our findings predict a role for arginine methylation as an inhibitory modification against Akt-mediated phosphorylation.


Productivity of the clinical dietitian: measurement by a regression model.
Productivity of 283 clinical dietitians employed in 40-bed to 1,200-bed medical centers and community and general hospitals nationwide was measured from a survey. Stepwise multiple linear regression statistical analyses were used to analyze data. Five measures of productivity were developed; hours in non-patient care divided by total hours worked and the activity level in activities nonproductive in relation to the job description activities produced the better models for measuring productivity of the clinical dietitian. Activity levels measured in the study showed high-level task activities (consuming a large amount of work time) were conducting individual diet instructions, conducting nutrition assessments, reviewing and recording in medical records, and supervising support personnel. Taking anthropometric measurements, participating in medical rounds, attending professional conferences, and purchasing and dispensing specialized products were found to be low-level task activities (consuming little work time). The average amount of time spent on the job per week was 42.7 hours with a mean of 20.4 hours spent in direct patient care, 13.6 hours in indirect patient care, and 7.3 hours in nonpatient care.


High level of endostatin in epididymal epithelium: protection against primary malignancies in this organ?
Rete testis and epididymis are rare locations for primary tumors or metastasis. Assuming that this may be related to expression level of angiogenic inhibitors, we focused our study on the expression pattern of collagen 18/endostatin. In situ hybridization and immunohistochemistry for collagen 18 and endostatin were carried out on sections of human rete testis and epididymis as well as on epididymal adenoma and human testicular tissue with or without carcinoma in situ (CIS). In situ hybridization revealed strong expression of collagen 18 mRNA in rete testis, efferent ducts and epididymal duct. Immunostaining showed collagen 18 in epithelium and basement membrane as well as in blood vessels of rete testis. Further, in both efferent ducts and epididymal duct, collagen 18 was mainly localized in the basement membrane of these ducts and of the blood vessel wall. Endostatin immunostaining was localized in the epithelium of rete testis, efferent ducts and epididymal duct. This pattern of endostatin staining was absent in epididymal adenoma tissue while tumor associated blood vessels exhibited strong endostatin staining. No endostatin staining was detectable in normal germinal epithelium and CIS cells while Leydig cells exhibited strong endostatin staining. High endostatin expression in epididymis may protect this organ against tumor development. Gene therapeutic strategies providing high expression of endostatin in normal epithelia may be useful to prevent tumor development.


Effects of fat mass reduction by dieting and by lipectomy on carbohydrate metabolism in obese patients.
The interrelation of enlarged body fat mass (BFM) with reduced carbohydrate tolerance and hyperinsulinemia was studied in obese subjects with chemical diabetes. These patients were subjected to lipectomy following weight loss induced by a low-calorie, low-carbohydrate diet. An improvement in glucose tolerance and in insulin sensitivity and a reduction in insulin release during OGTT was observed after a diet-induced BFM loss of 9.9 +/-1.2 kg. Subsequent surgical reduction of BFM by 6.0 +/- 0.5 kg had no further effect upon carbohydrate tolerance, insulin release or insulin sensitivity though a marked decrease in basal plasma FFA values was observed. These findings suggest that fat mass enlargement per se has no effect on blood glucose homeostasis after oral or i.v. loading. The improvement in carbohydrate tolerance and in insulin resistance usually observed following diet-induced loss of BFM seems to be due to the reduction in calorie and carbohydrate intake rather than to decrease of BFM.


Deficient cancellation of the vestibular ocular reflex in schizophrenia.
Schizophrenia has long been associated with difficulties in visual tracking of a moving object. Deficits are most notable in tracking tasks that require inhibition of saccades during active smooth pursuit. In order to assess whether there is a more global problem in inhibition of other eye movement systems while the smooth pursuit system is active, this study examined cancellation of the vestibular ocular reflex (VOR). Cancellation of the VOR occurs in a task in which the subject is rotated while looking at a target that is also being rotated. This requires the subject to use the pursuit system to override the VOR, maintain the eye at a stable location within the orbit, and thus retain visual gaze upon the target. Thirteen individuals with schizophrenia and 15 normals were assessed during clockwise rotation at 60 degrees s-1. Schizophrenic subjects had a significant increase in counterclockwise slow velocity eye movements, suggesting an impaired ability to cancel the VOR. Cancellation of the VOR is thus another example of a breakthrough of an alternative eye movement system while the smooth pursuit system is active. Because of the simplicity of the VOR and its suitability for animal modeling, investigation of this phenomenon may delineate more precisely the mechanisms of visual tracking dysfunction in schizophrenia.


A selective plasmin inhibitor, trans-aminomethylcyclohexanecarbonyl-L-(O-picolyl)tyrosine-octylamide (YO-2), induces thymocyte apoptosis.
The treatment of rat thymocytes with YO-2, a novel inhibitor of plasmin, resulted in an increase in DNA fragmentation. DNA fragmentation was also induced by another YO compounds such as YO-0, -3, -4 and -5. These YO compounds are the inhibitor of plasmin activity. On the other hand, YO-1, -6 and -8 that hardly inhibit plasmin activity had no effect on DNA fragmentation. Analysis of fragmented DNA from thymocytes treated with YO-2 by agarose gel electrophoresis revealed that the compound caused internucleosomal DNA fragmentation. In addition, judging from a laser scanning microscopy, annexin V-positive and propidium iodide-negative cells were increased by the treatment of the cells with the compound. Moreover, chromatin condensation was observed in thymocytes treated with the compound. These results demonstrated that YO-2 induces thymocyte apoptosis. There seemed to be some correlation between the apoptosis induced by YO compounds and their plasmin inhibitory effect. However, because the other protease inhibitors including pepstatin A, leupeptin, AEBSF, DFP and E-64-d did not affect DNA fragmentation, YO compounds are likely to have unique mechanism on plasmin or to show the effect on the other plasmin-like proteases. The plasmin inhibitory activity may have an important role in YO-2-induced apoptosis. Furthermore, the stimulations of caspase-8, -9 and -3-like activities were observed in thymocytes treated with YO-2. These results suggest that YO-2 induces thymocyte apoptosis via activation of caspase cascade.


What Impact Does Participation in a Communication Skills Training Program Have on Health Professionals' Communication Behaviors: Findings from a Qualitative Study.
Communication skills training can enhance health professionals' knowledge and repertoire of effective communication practices. This paper describes the conceptual model underlying a 3-day retreat communication skills training program, methods used for training, and participant perception of outcomes from the training using qualitative interviews. Repeated qualitative telephone interviews (approximately 6 months apart) with participants of a 3-day Clinical Consultation Skills Retreat. Fourteen participants (70% response, 57% doctors) took part at Time 1, with 12 participating at Time 2. Semi-structured interviews were recorded and transcribed, and directional content analysis was conducted to assess themes in areas of key learnings, implementation of skills, and barriers. The training was received very positively with participants valuing the small group learning, role play, and facilitator skills. Key learnings were grouped into two themes: (i) tips and strategies to use in clinical practice and (ii) communication frameworks/methods, with the second theme reflecting an awareness of different communication styles. Most participants had tried to implement their new skills, with implementation reported as a more deliberate activity at T1 than at T2. Those implementing the new skills noted more open conversations with patients. Practical barriers of lack of time and expectations of others were mentioned more often at T2. A 3-day retreat-based communication training program was positively received and had a positive impact on the use of new communication skills. While further work is needed to determine whether effects of training are evidenced in objective clinical behaviors, the positive longer-term benefits found suggest this work would be worthwhile.


Long-term follow-up of patients with persistent/recurrent, isolated haematuria: a Hungarian multicentre study.
A retrospective multicentre study of 341 children with persistent/recurrent, isolated haematuria is described. The haematuria was isolated for at least 6 months at the beginning of observation. The duration of follow-up was 2-5 years in 201, 5-10 years in 119, 10-15 years in 19, and over 15 years in 2 cases. Of these patients 47.8% became symptom-free. In 18.4% the haematuria remained isolated; in 13.8% it was combined with proteinuria over 250 mg/day more than 2 years later. The occurrence of associated proteinuria increased progressively with time. It was 8.6% between the 3rd and 5th years, and 37.0% after the 5th year. Renal biopsy was performed because of the symptoms of glomerular disease in 47 cases at an average time of 12 months following the appearance of proteinuria. Proteinuria appeared after a 2-5, 5-10, 10-15 and more than 15 years follow-up period in 16, 23, 6, and 2 patients respectively; 14 of them had Alport's nephropathy. The percentage of more serious azotaemia was 1.7 (creatinine clearance: 10-50 ml/min per 1.73 m2) and 0.3 (creatinine clearance: less than 10 ml/min per 1.73 m2). Mortality was 0.58%. Most of the patients who developed severe azotaemia had persistent microscopic haematuria at the beginning. The prevalence of hypertension was only 1.2%. The time of its appearance was above 5 years in 2 and below 5 years in 2 cases. All these patients had chronic glomerulonephritis. The haematuria was associated with hypercalciuria in 19.9%. In 14.3% of the overall group of patients urolithiasis developed 2-15 years after onset. All of these had hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)


Thank you for biting: dispersal of beneficial microbiota through 'antagonistic' interactions.
Multicellular organisms harbor populations of microbial symbionts; some of these symbionts can be dispersed through the feeding activities of consumers. Studies of consumer-mediated microbiota dispersal generally focus on pathogenic microorganisms; the dispersal of beneficial microorganisms has received less attention, especially in the context of 'antagonistic' trophic interactions (e.g., herbivory, parasitism, predation). Yet, this 'trophic transmission' of beneficial symbionts has significant implications for microbiota assembly and resource species (e.g., prey) health. For example, trophic transmission of microorganisms could assist with environmental acclimatization and help resource species to suppress other consumers or competitors. Here, we highlight model systems and approaches that have revealed these potential 'silver-linings' of antagonism as well as opportunities and challenges for future research.


Current and emerging therapies for Achondroplasia: The dawn of precision medicine.
Achondroplasia is a rare disease affecting bone growth and is caused by a missense mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. In the past few years, there were multiple experimental drugs entering into clinical trials for treating achondroplasia including vosoritide, the first precision medicine approved for this indication. This perspective presents the mechanism of action, benefit, and potential mechanistic limitation of the drugs currently being evaluated in clinical trials for achondroplasia. This article also discusses the potential impact of those drugs not only in increasing the growth of individuals living with achondroplasia but also in improving their quality of life.


Pharyngocutaneous fistula after total laryngectomy: A systematic review and meta-analysis of risk factors.
The pharyngocutaneous fistula (PCF) is the troublesome complication after total laryngectomy. Despite a large number of investigations having been performed, there is still controversy about which factors are most significant for PCF. The objective of the present meta-analysis was to analyze the potential risk factors for PCF after total laryngectomy. Published English-language literature. PubMed, Ovid, Cochrane, and Web of Science databases were systematically searched using multiple search terms. Twenty-one studies with 3832 patients were identified. The quality of evidence was assessed by The National Institute for Health and Clinical Excellence. Sixteen studies involving 2598 patients were included for the meta-analysis. The results showed that, tumor subsite (RR=0.64, 95% CI 0.47-0.88, P<0.01), T stage (RR=0.70, 95% CI 0.51-0.96, P=0.03), previous radiotherapy (RR=0.62, 95% CI 0.46-0.84, P<0.01), postoperative hemoglobin <12.5g/L (RR=0.46, 95% CI 0.27-0.76, P<0.01), and surgical margin (RR=0.41, 95% CI 0.22-0.74, P<0.01) were the risk factors associated with the development of PCF. From the results of our study, several significant risk factors for PCF are identified. Methodologically high-quality comparative studies are needed for further evaluation.


Medicaid physician fees and the use of primary care services: evidence from before and after the ACA fee bump.
We examine whether fees paid by Medicaid for primary care affects the use of health care services among adults with Medicaid coverage who have a high school or less than high school degree. The analysis spans the large changes in Medicaid fees that occurred before and after the ACA-mandated fee increase for primary care services in 2013-2014. We use data from the Behavioral Risk Factors Surveillance System and a difference-in-differences approach to estimate the association between Medicaid fees and whether a person has a personal doctor; a routine check-up or flu shot in the past year; whether a woman had a pap test or a mammogram in the past year; whether a person has ever been diagnosed with asthma, diabetes, cardiovascular diseases, cancer, COPD, arthritis, depression, or kidney diseases; and, whether a person reports good-to-excellent health. Estimates indicate that Medicaid fee increases were associated with small increases in the likelihood of having a personal doctor, or receiving a flu shot, although only having a personal doctor remained significant when accounting for multiple hypothesis testing. We conclude that Medicaid fees did not have a major impact on the use of primary care or on the consequences of that care.


Overexpression of glucose-regulated protein 78 in colon cancer.
The 78 kDa glucose-regulated protein (GRP78) has been implicated in the development of tumorigenicity, drug resistance, and cytotoxic immunology. We investigated the expression pattern of GRP78 at the protein and mRNA level in human colon carcinoma, colon adenoma and normal colon mucosa. Two-dimensional (2-D) gel electrophoresis, electrospray ionization tandem mass spectrometry, immunoblot analysis, reverse-transcriptase PCR and immunohistochemistry were used on colon normal and cancer tissues. Comparative 2-D gel electrophoresis of individual-matched colon normal and cancer tissues revealed 15 protein spots with concordantly increased and 20 protein spots with concordantly decreased intensity in tumor tissue. Fourteen of these proteins were identified by tandem mass spectrometry. One of the identified proteins, GRP78, exhibited a marked up-regulation in colon cancer tissue. This result was further confirmed by Western blot and immunohistochemical analysis. Immunohistochemistry also revealed increased cytoplasmic GRP78 expression with progression along the normal tissue-adenoma-carcinoma sequence. However, to our surprise, there was essentially no difference in the relative mRNA expression levels of GRP78 between normal and colon tumors. Our findings indicate that overexpression of GRP78 protein may be an important biomarker for malignant transformation, and increased expression might be related with the posttranscriptional regulation of GRP78 in tumor tissues.


Drosophila selected for extended longevity are more sensitive to heat shock.
It has been demonstrated in several animal models that a brief non-lethal application of high temperature is capable of inducing an increased longevity. It is also known that an even briefer exposure to a non-lethal elevated temperature enables some organisms to subsequently survive what would normally be a lethal exposure to high temperature. Our long-lived La strain is significantly resistant to oxidative stress due to an enhanced expression of certain antioxidant defense genes and enzyme activities. We collected survival data on 12, 463 adults of normal-lived and long-lived strains of Drosophila melanogaster in order to determine if animals selected for extended longevity also had an enhanced resistance to heat shock, and whether they exhibited thermotolerance as well. We find that normal-lived animals exhibit a heat-induced longevity extension but that long-lived animals already resistant to oxidative stress exhibit a heat-induced longevity shortening. The effects of temperature stress on longevity are strain dependent and are separable from thermotolerance effects. The trait of extended longevity based on an increased resistance to oxidative stress in the adult may be purchased at the price of a decreased fitness of the adult to other important environmental parameters.


Barriers to spousal contribution to childbirth pain relief in Nigeria.
The aim of this study was to investigate the barriers inhibiting the use of spousal presence for childbirth pain relief in health facilities and recommendations from three perspectives: the midwife, the woman, and the spouse. Spousal presence is a non-invasive, participatory and inexpensive technique used in pain management during childbirth. Although it contributes to a large extent in relieving childbirth pain, it is underutilized in Nigerian hospitals. Overcoming the challenges impeding spousal presence and participation during childbirth will improve maternal outcome, satisfaction and midwifery care practices. A cross-sectional survey conducted in four hospitals in Nigeria involving midwives (n = 100), women (n = 142) and their spouses (n = 142) from June to December 2014 using pretested questionnaires. Five themes were identified: poor infrastructural facility, lack of adequate pain management policy, lack of midwife pain management practices, midwives' attitudes towards spousal presence during childbirth and feelings about spousal presence during childbirth pain relief. Infrastructural defects in the health facilities resulting in the lack of privacy in maternity units for both spouses and partners negatively influence the presence of a spouse during childbirth and pain relief. Adopting effective strategies such as good infrastructural facilities, staff training and spouse-friendly hospital policies will encourage spouses to fully participate in and contribute to childbirth pain relief. This study identified poor staff attitudes towards pain relief and spousal presence during childbirth as barriers. Providing adequate policies on pain management, continuous staff education and orientation on spousal relationship will improve active spousal participation and maternal satisfaction during childbirth.


In vivo evaluation of monopolar intravascular PO2 electrodes.
Ten intravascular electrodes were evaluated on ten rabbits. The mean stabilized time of 118 +/- 52 min was excessively long for clinical use. The in vitro cal factor was not reproducible nor accurate. The differences between the PO2 values measured by the electrode and those obtained from intermittent blood samples were within +/- 10 mm Hg during the first 12 hr using the in vivo calibration after electrode stabilization. After 12 hr, the electrode PO2 values using the in vitro cal factor or based upon the in vivo calibration were increased significantly indicating a possible membrane rupture. This occured more rapidly in the animal experiments than in the in vitro studies using a tonometer, suggesting that continuous flow and pressure changes inside of the aorta contribute greatly to mechanical breakage of the membrane. Histologic evaluation indicated the electrode catheter system was thrombogenic at the level of the electrode tip and this thrombogenicity was primarily related to intimal injury caused by the electrode tip movement as a result of flow and pressure changes inside the aorta.


Minimal impact of ZAP on lentiviral vector production and transduction efficiency.
The antiviral protein ZAP binds CpG dinucleotides in viral RNA to inhibit replication. This has likely led to the CpG suppression observed in many RNA viruses, including retroviruses. Sequences added to retroviral vector genomes, such as internal promoters, transgenes, or regulatory elements, substantially increase CpG abundance. Because these CpGs could allow retroviral vector RNA to be targeted by ZAP, we analyzed whether it restricts vector production, transduction efficiency, and transgene expression. Surprisingly, even though CpG-high HIV-1 was efficiently inhibited by ZAP in HEK293T cells, depleting ZAP did not substantially increase lentiviral vector titer using several packaging and genome plasmids. ZAP overexpression also did not inhibit lentiviral vector titer. In addition, decreasing CpG abundance in a lentiviral vector genome did not increase its titer, and a gammaretroviral vector derived from murine leukemia virus was not substantially restricted by ZAP. Overall, we show that the increased CpG abundance in retroviral vectors relative to the wild-type retroviruses they are derived from does not intrinsically sensitize them to ZAP. Further understanding of how ZAP specifically targets transcripts to inhibit their expression may allow the development of CpG sequence contexts that efficiently recruit or evade this antiviral system.


Inhibition by adenosine triphosphate of heart microsomal neutral lipase activity.
Triacylglycerol lipolysis was inhibited by palmitate in the isolated perfused normal rat heart. Acetate or acetylcarnitine could reproduce the inhibitory effects of palmitate. Since heart neutral lipase plays an important role in the lipolysis of heart triacylglycerols, the effects of acetylcarnitine, acetyl CoA and related metabolites on the microsomal neutral lipase activity were studied. ATP inhibited the enzyme activity in a concentration-dependent manner without a lag phase. AMP and adenylyl imidodiphosphate, two compounds structurally related to ATP but whose phosphate groups cannot be transferred, did not inhibit the microsomal lipase activity. These results suggested that ATP inhibited the lipase activity through the transfer of its phosphate group. It is proposed that cellular ATP concentration is a determinant of tricylglycerol lipolysis in the heart.


Preparation and characterization of sodium alginate modified with collagen peptides.
Collagen peptides grafted sodium alginate (SA-COP) was prepared by reacting alginate with collagen peptide via amide linkage in presence of 1-ethyl-(dimethylaminopropyl) carbodiimide (EDC) and N-hydroxy sulfosuccinimide (NHS). The reaction conditions affected the degree of substitution (DS) were studied including the mass ratio of collagen peptide to sodium alginate, reaction temperature and reaction time. The hydrogen peroxide scavenging activity could be controlled by adjusting the DS, concentration and molecular weight. MTT assay was used to investigate the cell viability of SA-COP. The results indicated that the SA-COP exhibited better cell viability, and with the DS and concentration increasing of SA-COP, cell viability increased. The improved functionalities of the derivative might be explained by peptides characteristics.


Estimation of Toll-like receptor 9 in gingival tissues of patients with chronic periodontitis with or without hyperlipidemia and its association with the presence of Porphyromonas gingivalis.
Recent evidence suggests the interactions between bacterial DNA and nucleic acid receptors to play a role in inflammatory tissue destruction. The current study aims to evaluate the expression of Toll-like receptor 9 (TLR9) in periodontal disease associated with or without hyperlipidemia and to associate it with the presence of Porphyromonas gingivalis. Thirty participants in the age range of 25-50 years were randomly recruited and divided into three groups, i.e., healthy (Group I), chronic periodontitis without hyperlipidemia (Group II), and chronic periodontitis with hyperlipidemia (Group III). The gingival tissue samples were analyzed for TLR9 using immunohistochemistry, and plaque samples were analyzed for P. gingivalis using polymerase chain reaction. The TLR9-positive cell ratio in gingival connective tissue for Group II and Group III was 0.95 ± 0.03 and 0.94 ± 0.03, respectively, which was significantly higher than that of Group I, with P < 0.001 (0.88 ± 0.04). These groups also demonstrated significantly higher presence of P. gingivalis as compared to Group I with P < 0.001. There was a positive association between TLR9 in gingival connective tissue and presence of P. gingivalis. The results of this study reveal a potential role of TLR9 in chronic periodontitis, in association with P. gingivalis. Furthermore, these variables do not show an appreciable change in hyperlipidemics suggesting a weak relation between TLR9 and lipid levels.


t-BuOOH induces ferroptosis in human and murine cell lines.
Reactive oxygen species (ROS)-induced apoptosis has been extensively studied. Increasing evidence suggests that ROS, for instance, induced by hydrogen peroxide (H2O2), might also trigger regulated necrotic cell death pathways. Almost nothing is known about the cell death pathways triggered by tertiary-butyl hydroperoxide (t-BuOOH), a widely used inducer of oxidative stress. The lipid peroxidation products induced by t-BuOOH are involved in the pathophysiology of many diseases, such as cancer, cardiovascular diseases, or diabetes. In this study, we exposed murine fibroblasts (NIH3T3) or human keratinocytes (HaCaT) to t-BuOOH (50 or 200 μM, respectively) which induced a rapid necrotic cell death. Well-established regulators of cell death, i.e., p53, poly(ADP)ribose polymerase-1 (PARP-1), the stress kinases p38 and c-Jun N-terminal-kinases 1/2 (JNK1/2), or receptor-interacting serine/threonine protein kinase 1 (RIPK1) and 3 (RIPK3), were not required for t-BuOOH-mediated cell death. Using the selective inhibitors ferrostatin-1 (1 μM) and liproxstatin-1 (1 μM), we identified ferroptosis, a recently discovered cell death mechanism dependent on iron and lipid peroxidation, as the main cell death pathway. Accordingly, t-BuOOH exposure resulted in a ferrostatin-1- and liproxstatin-1-sensitive increase in lipid peroxidation and cytosolic ROS. Ferroptosis was executed independently from other t-BuOOH-mediated cellular damages, i.e., loss of mitochondrial membrane potential, DNA double-strand breaks, or replication block. H2O2 did not cause ferroptosis at equitoxic concentrations (300 μM) and induced a (1) lower and (2) ferrostatin-1- or liproxstatin-1-insensitive increase in lipid peroxidation. We identify that t-BuOOH and H2O2 produce a different pattern of lipid peroxidation, thereby leading to different cell death pathways and present t-BuOOH as a novel inducer of ferroptosis.


Interactive effects of cocaine and gender on thymocytes: a study of in vivo repeated cocaine exposure.
This study used a mouse model including both sexes to assess the impact of repeat cocaine exposure on the differentiation and function of T cell in thymus. Cocaine hydrochloride in 0.9% saline, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice for 10 days. Thymocytes were obtained 24 h after the 10th injection. Repeat in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A and Con-A plus anti-CD28. The proliferation induced by IL-2 in the Con-A stimulated T blasts was attenuated in cocaine treated mice. These effects were seen at a lower cocaine dose in female mice. The total number of thymocytes was reduced. Although the percentage of mature thymocytes (CD4+ CD8- and CD4- CD8+ cells) was not altered, the absolute cell numbers were attenuated. Both percentage and absolute cell number of immature thymocytes (CD4+ CD8+) decreased and the pre-mature (CD4- CD8-) cells increased. CD28 and CD25 expression were attenuated in Con-A stimulated thymocytes of mice treated with cocaine at 40 mg/kg. Interleukin 2 production was not significantly altered, however, gamma-IFN production was decreased by cocaine exposure at 40 mg/kg. In conclusion, cocaine exerts inhibitory effects on the function of mature thymocytes, and on the differentiation of thymocytes. A gender difference in response to cocaine was noted in that female mice were more sensitive to lower dose of cocaine exposure.


Implications of disease-related mutations at protein-protein interfaces.
Protein-protein interfaces have been attracting great attention owing to their critical roles in protein-protein interactions and the fact that human disease-related mutations are generally enriched in them. Recently, substantial research progress has been made in this field, which has significantly promoted the understanding and treatment of various human diseases. For example, many studies have discovered the properties of disease-related mutations. Besides, as more large-scale experimental data become available, various computational approaches have been proposed to advance our understanding of disease mutations from the data. Here, we overview recent advances in characteristics of disease-related mutations at protein-protein interfaces, mutation effects on protein interactions, and investigation of mutations on specific diseases.


Response of hypertension to conventional antihypertensive treatment and/or steroidogenesis inhibitors in Cushing's syndrome.
To evaluate the effect of conventional antihypertensive drugs and/or inhibitors of steroid production in the management of hypertension in Cushing's syndrome. A retrospective open clinical study with pre- and post-treatment assessment. A university hospital, where patients were initially admitted and then followed-up in an ambulatory clinic over a period of 6 years. Forty consecutive hypertensive patients with Cushing's syndrome. Patients were divided into two groups according to the different management of hypertension. The first group (group 1) of 28 patients included those treated with antihypertensive drugs at full dose (diuretics, calcium antagonists, angiotensin converting enzyme [ACE] inhibitors, as single agents or in combination). The second group (group 2) of 12 patients received ketoconazole alone. Blood pressure variations compared to pre-treatment levels. Blood pressure normalization was obtained in four of the 28 patients of group 1. In 12 of the remaining patients, ketoconazole, an inhibitor of steroid production, was subsequently added and this normalized blood pressure in all but the one in whom cortisol was not decreased. In the 12 patients of group 2, ketoconazole alone lowered blood pressure within normal limits in all but one who had long-standing hypertension. In hypertensive patients with Cushing's syndrome, conventional antihypertensive therapy is mostly ineffective. Blood pressure response is satisfactory only after the restoration of normal cortisol levels, indicating the need for a specific treatment for hypertension in this disorder.


Radical neck dissections for squamous carcinomas: pathological findings and their clinical implications with particular reference to transcapsular spread.
Two hundred fifty radical neck dissections, undertaken for mucosal squamous carcinomas of the head and neck, were reviewed with reference to pathological findings and their clinical implications. No major differences in descriptive surgical pathology were established between irradiated and non-irradiated resections. In general, irradiated dissections had lower total node counts and somewhat fewer nodal metastases involving a smaller number of different nodal groups. The topography of nodal deposits was similar in irradiated and non-irradiated resections. Palpable keratin granulomas (without intact tumor) were almost confined to irradiated patients. Transcapsular spread of tumor from involved lymph nodes was common: it was demonstrated in 160/188 'positive' dissections (85%) and was subclassified as 'macroscopic' in 90 and 'microscopic' in 70. The incidence and extent of transcapsular spread was similar in irradiated and nonirradiated resections. It was more frequently observed in association with large nodal masses but it was also regularly found with small nodal deposits less than 3 cm in diameter. Statistical analyses showed strong associations (p less than 0.0005) between the presence and/or extent of transcapsular spread and subsequent recurrence in the operated neck and overall survival. The predictive value of other clinical and pathological features vis-a-vis local neck recurrence such as numbers of involved nodal groups was weaker. Macroscopic transcapsulr spread emerges as the major prognostic factor for recurrent disease in the neck (p less than 0.0001). Attention is drawn to the advantages of accurate descriptive categories ('macroscopic', 'microscopic') for this critical prognostic feature.


Clinically severe portal hypertension: role of multi-detector row CT features in diagnosis.
To explore the CT signs which permit estimation of clinically severe portal hypertension (PH) [≥ 12 of hepatic vein pressure gradient (HVPG)]. One-hundred and seven consecutive patients who underwent HVPG measurement in the PH group and 52 controls were included. The diameters of main portal vein (øMPV), superior mesenteric vein (øSMV), splenic vein (øSV), and left gastric vein, øMPV/øSV, øSMV/øSV, as well as estimated spleen volumes were evaluated on the CT scan. The grade of varix and ascites were also evaluated semi-quantitatively. We explored the statistically significant CT features related to severe PH and performed a logistic regression analysis for an estimation model for severe PH. øMPV/øSV and øSMV/øSV tended to gradually increase as the PH became severer, and the difference between severe and not severe groups was statistically significant (p = 0.015 and 0.038, respectively). According to the regression analysis, øSMV/øSV and the grade of esophageal varix and ascites were finally included as related variables for predicting severe PH. The odds ratio (OR) of øSMV/øSV was 4.596, and large esophageal varix (OR 4.135) and mild (OR 3.051) and large amount of ascites (OR 21.781) were statistically significantly related to severe PH. Changing diameters of portal system, the grades of esophageal varices and ascites on multi-detector row computed tomography might be indicative features for clinically severe PH.


Chronic Toxoplasma gondii Infection Alleviates Experimental Autoimmune Encephalomyelitis by the Immune Regulation Inducing Reduction in IL-17A/Th17 Via Upregulation of SOCS3.
Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), a demyelinating autoimmune disease caused by the infiltration of a harmful autoreactive Th1 and Th17 cells. To mitigate MS, which is impossible to cure with medication only, immunomodulatory interventions that prevent Th17 cell activation are ideal. The objective of the present study was to analyze the effect of Toxoplasma gondii infection on the onset of EAE. Our results found that Toxoplasma gondii infection in the brain increases SOCS3 expression and decreases the phosphorylation of STAT3, resulting in reducing IL-17A and IL-23, which suppress the differentiation and expansion of pathogenic Th17 cells, an important factor in MS development. These immune responses resulted in a reduction in the clinical scoring of EAE induced by myelin oligodendrocyte glycoprotein 35-55 immunization. In the EAE group with T. gondii infection (Tg + EAE group), Th17-related immune responses that exacerbate the onset of EAE were reduced compared to those in the EAE group. This study suggests that the alleviation of EAE after T. gondii infection is regulated in a SOCS3/STAT3/IL-17A/blood-brain barrier integrity-dependent manner. Although parasite infection would not be permitted for MS treatment, this study using T. gondii infection identified potential targets that contribute to disease attenuation.


Cloning and differential expression of FOXL2 during ovarian development and recrudescence of the catfish, Clarias gariepinus.
FOXL2 is a member of the forkhead/HNF-3-related family of transcription factors which provides tissue-specific gene regulation. It is known to regulate ovarian aromatase, (cyp19a1a) which plays a crucial role in ovarian differentiation. To understand the role of FOXL2 in gonads and brain during ovarian development and recrudescence, we cloned the full-length cDNA of FOXL2 and analyzed its spatio-temporal expression both at transcript and protein levels in the air-breathing catfish, Clarias gariepinus. Based on its deduced amino acid sequence, an antigenic peptide conjugated with a carrier protein was synthesized which was then used for raising antibody that reacted specifically with FOXL2. Tissue distribution pattern of FOXL2 revealed its presence prominently in ovary and female brain with sexual dimorphism. Highest expression of FOXL2 was observed in ovary and brain during prespawning phase indicating an important role for this correlate in ovarian recrudescence. Human chorionic gonadotropin (hCG) treatment, in vitro and in vivo, induced FOXL2 expression in the ovary during preparatory and prespawning phases. Similar type of enhanced expression was evident in brain after hCG-induction during the prespawning phase. The ontogeny of FOXL2 showed sexual dimorphic expression pattern both in gonads and brain. Based on our previous studies, the expression pattern of FOXL2 was found to be synchronous not only with that of ovarian cyp19a1a but also with brain cyp19a1b. Present study substantiates the role of FOXL2 in the regulation of aromatase in teleosts and also designates FOXL2 as a potential ovary and brain marker during female sex development in catfish.


An adult female case of autoimmune pancreatitis with gastric outlet obstruction complicated by annular pancreas.
A 65-year-old woman presented with epigastric pain persisting for more than 3 months. She was diagnosed with autoimmune pancreatitis (AIP), based on high serum IgG4 levels (981 mg/dL) and diffuse pancreatic enlargement with a capsule-like rim on computed tomography (CT). Additionally, the main pancreatic duct was indistinct on magnetic resonance cholangiopancreatography. CT, esophagogastroduodenoscopy, and upper gastrointestinal radiography revealed stenosis with gastric outlet obstruction (GOO) in the second part of the duodenum. Prednisolone administration was initiated as treatment; on day 3 of treatment, the patient's symptoms improved. After 2 weeks, CT and endoscopic ultrasonography of the duodenal bulbs revealed improvement of the enlarged pancreas. The second part of the duodenum ran into the pancreatic head, and no malignant lesions were observed. Based on the above findings, we suspect that she developed AIP in the annular pancreas (AnnP), where duodenal stenosis worsened with diffuse pancreatic enlargement, resulting in GOO. She is currently under careful observation with tapering of prednisolone-without surgical treatment for AnnP. The pathogenesis of GOO caused by AIP without malignancy is rare. One case of GOO caused by AIP, wherein AIP developed in the AnnP (similar to the present case), has been reported, highlighting the novelty of our report.


Short-length Homologous Region exhaustive Search algorithm (SHRS): A primer design algorithm for differentiating bacteria at the species, subspecies, or strain level based on a whole genome sequence.
In fields such as the food industry, it is very important to identify target bacteria at the species level or lower for optimal product quality control. Bacteria identification at the subspecies or lower level requires time-consuming and high-cost analyses such as multi-locus sequence typing and amplified fragment length polymorphism analyses. Herein, we developed a primer design algorithm for precisely identifying bacteria based on a whole genome DNA sequence that is easy to apply. The algorithm designs primer sets that produce fragments from all input sequences and maximizes the differences in the amplicon size or amplicon sequence among input sequences. We demonstrate that the primer sets designed by the algorithm clearly classified six subspecies of Lactobacillus delbrueckii, and we observed that the resolution of the method is equal to that of a multi-locus sequence analysis. The algorithm allows the easy but precise identification of bacteria within a short time. (SHRS is available freely from PyPI under the MIT license.).


A complication in prescan strategy when using surface coils.
The "prescan" process for setting the gain of an MRI scanner can be confounded by an effect arising from the spatial variation of the angle between the vector reception field of a local or surface coil and the excitation field of a whole-body coil. It is most pronounced when the phase-encoding direction is parallel to the plane of the coil but not along the magnetic field. The largest signal is shown to reside in a data row that is shifted from the one that corresponds to zero phase-encoding gradient. The effect depends on the field-of-view and the dimensions of the receiving coil. Strategies are suggested by which manufacturers of scanners can cope with this intrinsic problem. In the meantime, users of surface coils should be aware of the difficulty.


Functional toner for office laser printer and its application for printing of paper-based superwettable patterns and devices.
Laserjet printing is a kind of facile and digital do-it-yourself strategies, which is of importance to fabricate inexpensive paper-based microfluidic devices. However, the printed hydrophobic barrier is not hydrophobic enough due to the weak hydrophobicity and requires subsequent heating, which can lead to the pyrolysis of cellulose in the paper and influence the detection results. Here, for the first time, we report a kind of functional toner including toner and polydopamine (PDA) nanocapsules which contains oleic acid modified ferric tetroxide (OA-Fe3O4) and octadecylamine (ODA), which is suitable for printing with desired shapes and sizes to lead to formation of superhydrophobic barriers. Moreover, patterns printed with functional toner have good stability, including resistance to moisture, ultraviolet (UV) and bending. Finally, a proof-of-concept of metal and nitrite ions testing is demonstrated using colorimetric analysis, and the results show that the printed devices successfully perform instant detection of ions. The developed functional toner offers easy fabrication, cost-effectiveness and mass production of paper-based devices. In general, this strategy provides a new idea and technical support for the rapid prototyping of microfluidic paper-based analytical devices (μPADs) using laserjet printing.


Influence of technical, cognitive and socio-emotional factors on digital literacy in nursing students assessed using structural equation modeling.
Digital literacy is one of the 21st-century skills that nursing students should develop and acquire. Several factors influencing digital literacy have been identified, but the predictive role of technical, cognitive, and socio-emotional factors in digital literacy remains unexplored in nursing students. This study aimed to explore the digital literacy level and determine the predictive role of technical, cognitive, and socio-emotional factors in digital literacy among nursing students in Turkey using a structural equation modeling (SEM)-based approach. A web-based, predictive, cross-sectional study. This study was conducted among first-, second-, third- and fourth-year students in a nursing faculty located in the capital of Turkey in the academic year 2021-2022. Overall, 210 nursing students were recruited for this study. The use of a digital literacy model guided data collection. Data were collected between 8 and 28 June 2022 using online Google Forms. The data were analyzed using descriptive statistics and SEM. Nursing students' digital literacy mean score was 67.29 (13.60). Internet self-efficacy (β = 0.31, p < 0.001), online information search strategies (β = 0.20, p = 0.003), and online privacy concerns (β = 0.14, p = 0.024) were positive predictors, whereas social media use (β = -0.13, p = 0.032) was a negative predictor of digital literacy. Among these variables, Internet self-efficacy had the most significant influence on the digital literacy level. The four variables contributed to 22 % of variance in the digital literacy level. This study shows nursing students' digital literacy level is above average. Our findings suggest that technical, cognitive, and socio-emotional factors influence digital literacy.


What is a "normal" right ventricle?
The aim of this project was to define normal values of right ventricular (RV) volumes and ejection fraction (EF) in healthy population using 2D echocardiography. The "patient" group comprised 91 healthy volunteers aged 17-62 years. RV volumetry was based on ellipsoidal shell model method. Left ventricular (LV) volumes were assessed by Teichholz formula. All volumes were indexed per m(2) of BSA and the rate distribution of measured and calculated values were evaluated. The normal range of individual parameters was expressed as mean value+/-2 standard deviations (delta). A pair test was used to compare corresponding results of the RV and LV measurements. The regression analysis was used to test the relationship between LV and RV volumes and age. Indexed enddiastolic and endsystolic RV volumes were 79.1+/-29.9ml and 32.6+/-19.7ml, respectively, EF being 50+/-9.7% in men and 58+/-13.6% in women. No correlation with patient's age was observed. Enddiastolic and endsystolic volumes of RV were significantly higher than those of LV. EF of RV was lower as compare to LV. Right ventricular EF in men was lower than that in women. There was no correlation between EF and patient's age.


Relocating built-up land for biodiversity conservation in an uncertain future.
Land use changes associated with habitat loss, fragmentation, and degradation exert profoundly detrimental impacts on biodiversity conservation. Urban development is one of the prevailing anthropogenic disturbances to wildlife habitat, because these developments are often considered permanent and irreversible. As a result, the potential benefits of built-up land relocation for biodiversity conservation have remained largely unexplored in environmental management practices. Here, we analyze recent built-up land relocation in Shanghai and explore how such restoration programs can affect future land change trajectories with regards to biodiversity conservation. Results show that 187.78 km2 built-up land in Shanghai was restored to natural habitat between 2017 and 2020. Further simulation analysis highlights that relocating built-up land can substantially promote conserve biodiversity. In particular, there would be less habitat loss, better natural habitat quality and more species habitat-suitable range under the scenarios with built-up land relocation. Species extinction assessment suggest that amphibians, mammals, and reptiles will all have an increasingly high extinction risk without built-up land relocation. However, there will even be a marginal decrease in extinction risk over time for mammals and reptiles if the relocation of built-up land is permitted, but still a moderate increase in extinction risk for amphibians. This study highlights the importance of incorporating rigorous conservation planning prior to development activities, thereby underpinning a sustainable approach to environmental management.


Efficacy and safety of complementary and alternative medicine therapy for gastroparesis: A protocol for systematic review and meta-analysis.
Gastroparesis affects the quality of life of many patients, but there is no effective treatment. Now, complementary and alternative medicine originated from China is gradually accepted by the world because of its unique treatment principles and relatively safe treatment methods. However, at present, there is still a lack of more definitive clinical application evidence for the treatment of gastroparesis with complementary and alternative medicine to confirm the safety and efficacy of complementary and alternative medicine in the treatment of gastroparesis caused by various causes. More comprehensive and stronger evidence-based medicine evidence is needed. We will retrieve literatures using Medline, Embase, the Cochrane Library database, Web of science, CNKI, VIP, CBM, and WanFang. We will look for RCTs or CCTs on the use of complementary and alternative medicine in the treatment of gastroparesis, and extract relevant data into the excel sheet. The whole retrieval and data extraction process were carried out by 2 researchers independently. Then we will use meta-analysis to make statistical analysis of all the results and make a systematic review of all the included literatures. All results and safety data were analyzed for a comprehensive evaluation and/or descriptive analysis of the efficacy and safety of complementary and alternative therapies for gastroparesis. This study will provide more comprehensive clinical evidence for the treatment of gastroparesis with complementary and alternative therapies. The research has been registered and approved on the INPLASY.COM website. The registration number is INPLASY2020100033.


Common and Uncommon CT Findings in CVID-Related GL-ILD: Correlations with Clinical Parameters, Therapeutic Decisions and Potential Implications in the Differential Diagnosis.
To investigate computed tomography (CT) findings of Granulomatous Lymphocytic Interstitial Lung Disease (GL-ILD) in Common Variable Immunodeficiency (CVID), also in comparison with non-GL-ILD abnormalities, correlating GL-ILD features with functional/immunological parameters and looking for GL-ILD therapy predictive elements. CT features of 38 GL-ILD and 38 matched non-GL-ILD subjects were retrospectively described. Correlations of GL-ILD features with functional/immunological features were assessed. A logistic regression was performed to find a predictive model of GL-ILD therapeutic decisions. Most common GL-ILD CT findings were bronchiectasis, non-perilymphatic nodules, consolidations, Ground Glass Opacities (GGO), bands and enlarged lymphnodes. GL-ILD was usually predominant in lower fields. Multiple small nodules (≤10 mm), consolidations, reticulations and fibrotic ILD are more indicative of GL-ILD. Bronchiectasis, GGO, Reticulations and fibrotic ILD correlated with decreased lung performance. Bronchiectasis, GGO and fibrotic ILD were associated with low IgA levels, whereas high CD4+ T cells percentage was related to GGO. Twenty out of 38 patients underwent GL-ILD therapy. A model combining Marginal Zone (MZ) B cells percentage, IgA levels, lower field consolidations and lymphnodes enlargement showed a good discriminatory capacity with regards to GL-ILD treatment. GL-ILD is a lower field predominant disease, commonly characterized by bronchiectasis, non-perilymphatic small nodules, consolidations, GGO and bands. Multiple small nodules, consolidations, reticulations and fibrotic ILD may suggest the presence of GL-ILD in CVID. MZ B cells percentage, IgA levels at diagnosis, lower field consolidations and mediastinal lymphnodes enlargement may predict the need of a specific GL-ILD therapy.


Dopamine and vesicular monoamine transport loss supports incidental Lewy body disease as preclinical idiopathic Parkinson.
Incidental Lewy body disease (ILBD) is a neuropathological diagnosis of brains with Lewy bodies without clinical neuropsychiatric symptoms. Dopaminergic deficits suggest a relationship to preclinical Parkinson's disease (PD). We now report a subregional pattern of striatal dopamine loss in ILBD cases, with dopamine found significantly decreased in the putamen (-52%) and only to a lower extent in the caudate (-38%, not statistically significant); this is similar to the pattern in idiopathic PD in various neurochemical and in vivo imaging studies. We aimed to find out if our recently reported impaired storage of dopamine in striatal synaptic vesicles prepared from striatal tissue of cases with idiopathic PD might be an early or even causative event. We undertook parallel measurements of [3H]dopamine uptake and vesicular monoamine transporter (VMAT)2 binding sites by the specific label [3H]dihydrotetrabenazine on vesicular preparation from caudate and putamen in ILBD. Neither specific uptake of dopamine and binding of [3H]dihydrotetrabenazine, nor mean values of the calculated ratios of dopamine uptake and VMAT2 binding, a measure of uptake rate per transport site, were significantly different between ILBD and controls. ATP-dependence of [3H]dopamine uptake revealed significantly higher rates in putamen than in caudate at saturating concentrations of ATP in controls, a subregional difference lost in ILBD. Our findings support a loss of the normally higher VMAT2 activity in putamen as a contributing factor to the higher susceptibility of the putamen to dopamine depletion in idiopathic PD. Moreover, we suggest ILBD postmortem tissue as a valuable source for testing hypotheses on processes in idiopathic PD.


In vitro hemodynamic investigation of the embryonic aortic arch at late gestation.
This study focuses on the dynamic flow through the fetal aortic arch driven by the concurrent action of right and left ventricles. We created a parametric pulsatile computational fluid dynamics (CFD) model of the fetal aortic junction with physiologic vessel geometries. To gain a better biophysical understanding, an in vitro experimental fetal flow loop for flow visualization was constructed for identical CFD conditions. CFD and in vitro experimental results were comparable. Swirling flow during the acceleration phase of the cardiac cycle and unidirectional flow following mid-deceleration phase were observed in pulmonary arteries (PA), head-neck vessels, and descending aorta. Right-to-left (oxygenated) blood flowed through the ductus arteriosus (DA) posterior relative to the antegrade left ventricular outflow tract (LVOT) stream and resembled jet flow. LVOT and right ventricular outflow tract flow mixing had not completed until approximately 3.5 descending aorta diameters downstream of the DA insertion into the aortic arch. Normal arch model flow patterns were then compared to flow patterns of four common congenital heart malformations that include aortic arch anomalies. Weak oscillatory reversing flow through the DA junction was observed only for the Tetralogy of Fallot configuration. PA and hypoplastic left heart syndrome configurations demonstrated complex, abnormal flow patterns in the PAs and head-neck vessels. Aortic coarctation resulted in large-scale recirculating flow in the aortic arch proximal to the DA. Intravascular flow patterns spatially correlated with abnormal vascular structures consistent with the paradigm that abnormal intravascular flow patterns associated with congenital heart disease influence vascular growth and function.


Different transcriptional responses of heat shock protein 70/90 in the marine diatom Ditylum brightwellii exposed to metal compounds and endocrine-disrupting chemicals.
Environmental hazard assessments using diatoms have been well documented; however, their molecular toxicology has not been sufficiently studied. In this study, we characterized heat shock protein (HSP) 70/90 of the diatom Ditylum brightwellii (Db) and evaluated their transcriptional profiles in response to various environmental stresses (e.g., thermal shocks and metal and non-metal pollutants). Putative DbHSP70 (658aa, 71.7 kDa) and DbHSP90 (707aa, 80.2 kDa) proteins had conserved HSP family motifs but different C-terminus motifs, that is, "EEVD" in DbHSP70 and "MEEVD" in DbHSP90. Phylogenetic analyses of both proteins showed that D. brightwellii was well clustered with other diatoms. Real-time PCR analysis showed that thermal stress considerably upregulated DbHSP70 and DbHSP90. As for chemical pollutants, DbHSP70 greatly responded to CuSO4 and NiSO4 exposure, but not CuCl2 or NiCl2. However, DbHSP90 was significantly upregulated by all the metal compounds tested (CuSO4, NiSO4, CuCl2, and NiCl2). Strikingly, the expression of both genes was not induced by the organic pollutants tested, such as endocrine-disrupting chemicals. These data suggest that DbHSP70 and DbHSP90 are differentially involved in the defense response against various environmental stressors. Moreover, metal toxicity may be specifically affected by the conjugated anion in the metal compounds (e.g., SO4(2-) and Cl(-)).


Distribution of gonococcal lipopolysaccharide biosynthesis genes among strains of Neisseria gonorrhoeae and other neisserial species.
A plasmid, pTME6, containing Neisseria gonorrhoeae lipopolysaccharide biosynthesis genes was used as a probe to analyze DNA from strains of N. gonorrhoeae, N. meningitidis and various commensal Neisseria by Southern blotting. Chromosomal DNA from 26 gonococcal strains probed with 32P-labeled pTME6 produced five different hybridization patterns. No correlation between hybridization pattern and auxotype, serotype, serum sensitivity or SDS-urea-PAGE migration of LPS was observed. DNA from strains of N. meningitidis, N. lactamica and N. cinerea, but not other commensal Neisseria species, hybridized strongly to pTME6.


Author Correction: Assessing the quality of supplementary sensory feedback using the crossmodal congruency task.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.


Immediate and long-term results of mitral balloon valvotomy for restenosis following previous surgical or balloon mitral commissurotomy.
This study compared immediate with long-term results of mitral balloon valvotomy (MBV) in patients who underwent MBV as an initial procedure versus those who underwent repeat MBV. Fifty-six patients who were a mean age of 28 +/- 8.8 years (group A) and had mitral restenosis after surgical or balloon commissurotomy underwent MBV and were compared with 524 patients who were a mean age of 31 +/- 11 years (group B) and underwent MBV as an initial procedure. Prospective data obtained included demographic, hemodynamic, echocardiographic, and clinical follow-up for 0.5 to 15 years after MBV. No deaths or technical failure were encountered after MBV. Mitral regurgitation >2/4 occurred in 1 patient (2%) in group A and in 9 patients (2%) in group B (p = 0.24). Fifty-two of 56 patients (93%) in group A had good immediate results (mitral valve area >or=1.5 cm(2), mitral regurgitation <2/4), as did 504 of 524 patients (96%) in group B (p = 0.4). Actuarial values for freedom from restenosis at 10 years were 58 +/- 7% for group A versus 69 +/- 3% for group B (p = 0.18). Ten-year event-free survival rate was 54 +/- 7% for group A versus 80 +/- 3% for group B (p <0.005). The predictors of event-free survival were age (p = 0.003), echocardiographic score (p <0.0001), and baseline atrial fibrillation (p = 0.01). In conclusion, MBV is safe and provides good immediate results in patients who have restenosis. Long-term results are inferior compared with de novo mitral stenosis but is still satisfactory. More than 50% of patients remained improved at 10 years, thus enabling the operation or reoperation to be deferred.


Galanin and neurokinin-1 receptor immunoreactive [corrected] spinal neurons controlling the prostate and the bulbospongiosus muscle identified by transsynaptic labeling in the rat.
Ejaculation requires the coordination of sympathetic, parasympathetic and somatic neural outputs. Timely occurrence of the emission and expulsion of sperm results from an interplay between spinal nuclei innervating the seminal tract and the sexual accessory glands including the prostate on the one hand, and on the other hand perineal striated muscles, particularly the bulbospongiosus muscle. A group of cells essential for ejaculation, located around the central canal and referred to as lumbar spinothalamic neurons have been recently identified. Lumbar spinothalamic neurons are immunoreactive for galanin and neurokinin-1 receptor. In order to investigate the anatomical relationships between lumbar spinothalamic neurons and both the prostate and the bulbospongiosus muscle, pseudorabies virus retrograde tracing technique was used combined with immunohistochemistry. Three to five days after pseudorabies virus injection in the bulbospongiosus muscle or the prostate in male rats, spinal cord sections were processed for double immunofluorescence against pseudorabies virus and galanin or neurokinin-1 receptor. Immunocytochemical experiments against pseudorabies virus and choline acetyltransferase were also performed to discriminate between motoneurons and preganglionic neurons, or interneurons. Spinal sections were examined with confocal laser scanning microscope. Three days after pseudorabies virus injection within the prostate and the bulbospongiosus muscle, sympathetic preganglionic neurons and motoneurons of the dorsomedial nucleus were retrogradely labeled, respectively. Five days after pseudorabies virus injection, transsynaptically labeled choline acetyltransferase-negative neurons were found mainly located in the medial gray surrounding the central canal from L1 to S1. At the L3-L4 level, most of transsynaptically labeled neurons were immunoreactive for galanin and to a lesser extent for neurokinin-1 receptor, strongly suggesting that they could be the lumbar spinothalamic cells. We have thus evidenced connections between these cells and motoneurons of the dorsomedial nucleus and both sympathetic and parasympathetic preganglionic neurons innervating the bulbospongiosus muscle and the prostate, respectively. These anatomical data reinforce the crucial role for lumbar spinothalamic cells in coordinating the spinal control of ejaculation.