Enhancing the efficacy of thrombolysis by AMPA receptor blockade with NBQX in a rat embolic stroke model.
Efficacy and safety of combined alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor blockade and thrombolytic therapy with human recombinant tissue plasminogen activator (TPA) was tested in a rat embolic stroke model. Sixty-three rats were embolized in the right internal carotid territory with a 200 microliters suspension of microclots formed by alternate moving of 150 microliters whole blood and 50 microliters of thrombin between two interconnected syringes for 4 min. Sixteen embolized rats served as controls, and 16 rats were treated with NBQX immediately after embolization. Thirty-one rats were treated with TPA 2 h following embolization, and in 16 of these rats additional NBQX treatments were initiated 90 min following embolization. Hemispheric cerebral blood flow (CBF) was measured by an intraarterial 133Xenon injection method before and after embolization. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and infarct volumes were measured. Median CBF was reduced by 70-77% in the affected hemispheres following embolization. Significant recanalization occurred in all groups except those treated with NBQX. TPA-treated rats had significantly better reperfusion compared to controls judged by angiography 3 h following embolization (P = 0.04). NBQX alone and TPA alone caused insignificant reduction in infarct volume but, when combined, total infarct volume was reduced by 77% compared to controls (P = 0.02). Separate measurement of cortical infarct revealed significantly smaller infarcts (P = 0.05) in the combined treatment group compared to the TPA treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)


Radiological findings in cerebral venous thrombosis presenting as subarachnoid hemorrhage: a series of 22 cases.
The main objectives of the present study are to assess the incidence of cerebral venous thrombosis (CVT) presenting as isolated subarachnoid hemorrhage (SAH) and to determine the occurrence of cortical venous thrombosis (CoVT). Among 332 patients with CVT, investigated with the same CT and MR standardized protocol, 33 (10 %) presented with SAH, associated in 11 cases with hemorrhagic infarct or intracerebral hemorrhage. This study is based on 22 cases of CVT presenting as SAH in the absence of hemorrhagic brain lesion. Diagnosis of sinus thrombosis was established on T2* and magnetic resonance venography and that of CoVT on T2* sequence. Diagnostic of SAH was based on fluid-attenuated inversion recovery (FLAIR) sequence. CVT involved lateral sinus in 18 patients, superior sagittal sinus in 16, and straight sinus in 1. Cortical veins were involved in all patients, in continuity with dural sinus thrombosis when present. SAH was circumscribed to few sulci in all cases and mainly localized at the convexity (21 cases). CoVT implied different areas on the same side in four patients and was bilateral in seven. There was no perimesencephalic or basal cisterns hemorrhage. Cortical swelling was present in 12 cases, associated with localized edema. All patients except one had a favorable outcome. This report shows that the incidence of CVT presenting as isolated SAH is evaluated to 6.4 % and that SAH is, in all cases, in the vicinity of CoVT and when dural thrombosis is present in continuity with it.


Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1.
Angiogenesis is essential to match the size of blood vessel networks to the metabolic demands of growing tissues. While many genes and pathways necessary for regulating angiogenesis have been identified, those responsible for endothelial cell (EC) survival during angiogenesis remain largely unknown. We have investigated the in vivo role of myeloid cell leukemia 1 (MCL1), a pro-survival member of the BCL2 family, in EC survival during angiogenesis. EC-specific deletion of Mcl1 resulted in a dose-dependent increase in EC apoptosis in the angiogenic vasculature and a corresponding decline in vessel density. Our results suggest this apoptosis was independent of the BH3-only protein BIM. Despite the known link between apoptosis and blood vessel regression, this was not the cause of reduced vessel density observed in the absence of endothelial MCL1. Rather, the reduction in vessel density was linked to ectopic apoptosis in regions of the angiogenic vasculature where EC proliferation and new vessel growth occurs. We have therefore identified MCL1 as an essential survival factor for ECs that is required for blood vessel production during angiogenesis.


A Propensity-Matched Cohort Study of Tocilizumab in Patients With Coronavirus Disease 2019.
To determine the impact of tocilizumab, a monoclonal antibody against the interleukin 6 receptor, on survival in patients with coronavirus disease 2019. Observational cohort study of patients hospitalized with coronavirus disease 2019 between March 1, 2020, and April 24, 2020. A propensity-matched (1:1) analysis was used to compare patients who received tocilizumab to controls who did not. Competing risk survival analysis was used to determine the primary outcome of time to mortality, and adjusted log-linear and logistic regression for secondary outcomes. Three hospitals within the NYU Langone Health system in New York. Consecutive adult patients hospitalized with coronavirus disease 2019. Tocilizumab 400-mg IV once in addition to standard of care or standard of care alone. Data from 3,580 severe acute respiratory syndrome coronavirus 2 positive qualifying hospitalized patients were included, of whom 497 (13.9%) were treated with tocilizumab. In the analysis of tocilizumab-treated patients and matched controls, fewer tocilizumab-treated patients died (145/497, 29.2%) than did controls (211/497, 42.4%). In the adjusted competing risk regression model, tocilizumab therapy was associated with improved survival relative to controls (hazard ratio = 0.24, 95% CI = 0.18-0.33, p < 0.001). Tocilizumab-treated patients and controls had similar adjusted time to discharge from hospital (hazard ratio = 0.96, 95% CI = 0.78-1.17, p = 0.67). However, they had longer adjusted ICU length of stay (rate ratio = 3.1, 95% CI = 2.5-3.7, p < 0.001) and a higher adjusted infection rate (odds ratio = 4.18, 95% CI = 2.72-6.52, p < 0.001) than controls. Tocilizumab therapy was associated with significantly improved survival in coronavirus disease 2019 patients. This survival benefit was associated with increased ICU length of stay and increased infection rate, even as more patients in the tocilizumab group were rescued from rapid death. A prospective, randomized, placebo-controlled trial is needed to confirm these findings.


Combining remote sensing analysis with machine learning to evaluate short-term coastal evolution trend in the shoreline of Venice.
With increasing storminess and incessant sea-level rise, coastal erosion is becoming a primary issue along many littorals in the world. To cope with present and future climate change scenarios, it is important to map the shoreline position over years and assess the coastal erosion trends to select the best risk management solutions and guarantee a sustainable management of communities, structures, and ecosystems. However, this objective is particularly challenging on gentle-sloping sandy coasts, where also small sea-level changes trigger significant morphological evolutions. This study presents a multidisciplinary study combining satellite images with Machine Learning and GIS-based spatial tools to analyze short-term shoreline evolution trends and detect erosion hot-spots on the Venice coast over the period 2015-2019. Firstly, advanced image preprocessing, which is not frequently adopted in coastal erosion studies, was performed on satellite images downloaded within the same tidal range. Secondly, different Machine Learning classification methods were tested to accurately define shoreline position by recognizing the land-sea interface in each image. Finally, the application of the Digital Shoreline Analysis System tool was performed to evaluate and visualize coastal changes over the years. Overall, the case study littoral reveals to be stable or mainly subjected to accretion. This is probably due to the high presence of coastal protection structures that stabilize the beaches, enhancing deposition processes. In detail, with respect to the total length of the considered shoreline (about 83 km), 5 % of the coast is eroding, 36 % is stable, 52 % is accreting and 7 % is not evaluable. Despite a significant coastal erosion risk was not recognized within this region, well-delimited erosion hot-spots were mapped in correspondence of Caorle, Jesolo and Cavallino-Treporti municipalities. These areas deserve higher attention for territorial planning and prioritization of adaptation measures, facing climate change scenarios and sea-level rise emergencies in the context of Integrated Coastal Zone Management.


Influence of base material particle features on petrophysical properties of synthetic carbonate plugs.
Rocks with representative physical and chemical properties are essential to understanding fluid-solid flow behaviors at the pore scale. In this way, studying the pore space characteristics is a key point for evaluating and providing petrophysical properties for distinct rock types, such as synthetic rocks, with controlled and representative properties like natural ones. This work studies the petrophysical properties of synthetic carbonate plugs with a novel approach by correlating particle size, particle size fraction, and the morphology of particles with porosity and permeability, which could guide the scientific community to further forming of carbonate rocks with a controlled pore network. Results indicated that particle shape influenced the accommodation of particles in the porous space and, therefore, in the petrophysical properties, where an increase in particle size decreases porosity and increases permeability. Also, the obtained plugs showed the following petrophysical features: gas porosity from 10% to 17%, mercury porosity from 11% to 19%, gas permeability from 0.07 mD to 0.70 mD, and mercury permeability from 0.02 mD to 0.35 mD, providing important insight on controlling pore space in synthetic carbonate rocks.


Acaricidal efficacy evaluation of amitraz and diazinon against Amblyomma variegatum tick species in Waghimra zone, northern Ethiopia.
Ticks pose a substantial economic burden associated with production loss and treatment costs globally. Ethiopia has tremendous livestock resources, but its productivity is hindered by various animal health challenges in which ticks are the top priority, with a limited response to acaricidal treatments. Hence, we designed an acaricidal efficacy trial for the top commercially available Chemicals (amitraz and diazinon) to examine their efficacy against the widely distributed tick species (Amblyoma variegatum). Ticks were collected from animals admitted to veterinary clinics with no history of treatment with acaricides. Adult Immersion Technique (AIT) was employed to detect acaricidal resistance, and the mean percent control and antiparasitic efficacy were used to estimate tick susceptibility with a completely randomized laboratory-based trial (CRT). The mean weights of eggs laid by ticks subjected to amitraz and diazinon indicated that amitraz had a better egg-laying-inhibition effect than diazinon. The mean control percentages of amitraz and diazinon were 92.8 ± 5.6% and 69.7 ± 3.1%, respectively, with a highly significant difference (P-value = 0.00). The antiparasitic efficacy of the two drugs was 57.5 ± 0.96 and 37.5% ± 0.96 for amitraz and diazinon, respectively, which revealed that amitraz was statistically better than diazinon in killing adult ticks (P-value =0.026). In general, ticks treated with diazinon showed evidence of resistance development, and amitraz is relatively the most effective acaricide; we recommend its use in the study area and other locations with similar settings.


Assessment of spirituality and implications for service planning.
Assessing the role that religious or spiritual concerns play in the lives of people with severe mental disorders is crucial if clinicians are to determine whether those concerns can be successfully incorporated into service planning.


Effects of continuous administration of paroxetine on ligand binding site and expression of serotonin transporter protein in mouse brain.
Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine, are utilized in the treatment of depression and anxiety disorders. Although SSRIs potently interfere with the activity of brain serotonin transporter (SERT) after acute treatment, clinical improvement of psychiatric diseases is observed only after the repeated administration for several weeks (2-6 weeks). The present study was undertaken to investigate the effects of continuous administration of paroxetine on specific [3H]paroxetine binding sites and expression of SERT protein in mouse brain. Mice continuously and subcutaneously received paroxetine at doses of 2.67 or 13.3 mumol/kg/day for 21 days by using osmotic minipumps, and the steady-state plasma drug levels were within the range of reported concentrations in the clinical therapy. Continuous administration of paroxetine at theses doses produced significant (25-46%) reduction of [3H]paroxetine binding in each brain region (cerebral cortex, striatum, hippocampus, thalamus, midbrain) of mice. In Western blot analysis, expression levels of SERT protein in the thalamus and midbrain of mice were significantly (51% and 61%, respectively) decreased on day 21 after the implantation of minipumps at the higher dose. In conclusion, this study has firstly shown that continuous administration of paroxetine induces significant reduction of not only ligand binding sites of SERT but the protein expression level in mouse brain. Such down-regulation of SERT may partly underlie the therapeutic effect of long-term treatment with SSRIs in human.


A spectrum of coexistent tuberculosis and carcinoma in the breast and axillary lymph nodes: report of five cases.
Tuberculosis (TB) and breast cancer are common diseases in developing countries. Their coexistence in the breast and axillary lymph nodes is, however, rare. It can lead to overstaging of the breast cancer. Treatment compliance may also be difficult when two major illnesses exist. Five cases of coexistent breast cancer and TB are presented with regard to presentation and outcome, with a review of the literature.


Pharmacokinetic considerations in testing hypoxic cell radiosensitizers in mouse tumours.
Bilateral kidney ligation of mice immediately before injection of misonidazole (MIS) prolongs the plasma half-life of this radiosensitizer from about 2 h (in normal mice) to 10-11 h, similar to that in man. Kidney ligation does not, however, change the relative proportions of MIS and its O-demethylated metabolite, Ro-05-9963, for the first 12 h after MIS injection. Kidney ligation was used with the two radiosensitizers, MIS and Ro-05-9963, to investigate the influence of plasma half-life both on peak plasma levels and on the tumour/plasma ratio of sensitizer concentration in the EMT6 mouse tumour. Although the acute LD50 of Ro-05-9963 in normal mice was twice that of MIS, this apparent advantage was offset by peak tumour levels 50% or less of those achieved by equimolar injected doses of MIS. However, by comparing the plasma and tumour levels in mice in which the drug half-lives were prolonged by bilateral kidney ligation, it was concluded that the lower plasma and tumour levels of Ro-05-9963 were a result of its shorter plasma half-life, rather than of an intrinsic barrier to tumour penetration. Because of this rapid clearance, the radiosensitization produced by Ro-05-9963 was less than that produced by equimolar injected doses of MIS. As this difference did not occur in kidney-ligated mice, and hence would not be expected to occur in man, the comparison of MIS and Ro-05-9963 in mice produces an artificially low radiosensitization for Ro-05-9963 and possibly also for other compounds with short plasma half-lives. Although the short plasma half-life of Ro-05-9963 appeared to be responsible for its low peak plasma concentration, it did not produce a low tumour/plasma ratio. Within the limits of plasma nitroimidazole half-lives investigated (0.5-10 h) the tumour/plasma ratio was insensitive to plasma half-life, being 50-70% for both MIS and Ro-05-9963 in both normal and kidney-ligated mice. It is concluded that the common assumption that tumour/plasma ratios of MIS in the mouse are less than those in man is unjustified.


Isolation of new alkylthiosulfides from the essential oil and extracts from the bark of Scorodophloeus zenkeri Harms.
2,3,5-trithiahexane, 2,3,4,6-tetrathiaheptane, 2,4,5,7-tetrathiaoctane, two pentathianonanes, 2,4,5,7,9-pentathiadecane and two hexathiaundecanes were isolated from the essential oil and extracts from the bark of Scorodophloeus zenkeri Harms. Four other thioalkanes were found in small amounts in the essential oil.


Development of in vitro embryo production systems for red deer (Cervus elaphus). Part 1. Effect of epithelial oviductal monolayers and heparin on in vitro sperm motility and penetration of in vitro matured oocytes.
In vitro fertilisation (IVF) protocols for red deer have yielded low fertilisation rates, with no embryo development beyond the eight-cell stage when heparin was used as the in vitro capacitation agent. As this low fertilisation rate may result from reduced motility, the present study investigated the use of red deer oviduct epithelial cell monolayers (COEM) and conditioned medium (Cm) from the monolayers to maintain red deer sperm motility in vitro. A second experiment compared the fertilisability of red deer sperm pre-incubated for 4-12h on COEM or for 4h in TALP medium supplemented with 20 microg of heparin.COEM was superior in maintaining red deer sperm motility compared with either Sp-TALP alone or Cm (P<0.05). COEM sustained sperm motility at levels comparable to the initial motility over the 24h period. The motility of sperm incubated in Sp-TALP and Cm was similar and had declined to less than 10% by 4h and no motile sperm were observed by 8h. Overall, the penetration rates of in vitro red deer oocytes were low (5-28%) regardless of sperm treatment. Sperm pre-incubated on COEM penetrated more oocytes than sperm incubated with heparin (P<0.001). Penetration rates were similar for 4-12h pre-incubation of sperm on COEM (P>0.50). Penetration rates were greater across all treatments when both sperm and oocytes were co-incubated for 24h compared to 12h (P<0.001). There were no differences in penetration rates among the four donor stags used in the study. It was concluded that COEM sustains red deer sperm motility in vitro during the 24h observation period. Pre-incubating sperm on COEM does increase sperm penetration rates compared with heparin alone, but at a rate too low and variable to be used on a routine basis. Overall, the penetration rates were comparable to those previously reported for red deer even though differences in heparin concentration, fertilisation systems and stags were used.


Current progress in the study on biosynthesis and regulation of ganoderic acids.
Ganoderic acids (GAs) isolated from Ganoderma lucidum, which have shown remarkable pharmacological activities and a variety of therapeutic effects on a number of human diseases, have provided an important resource for the development of new medicines. The yield of GAs in field cultivation is still limited, which is mainly due to a scarcity of information regarding its biosynthesis pathway and its regulation. Here, we review the recent publication that has been made in the biosynthesis and regulation of GAs. From these studies, researchers have identified part of the biosynthesis pathway of GAs named mevalonate pathway. They have cloned and characterized the genes involved in the biosynthesis pathway. Additionally, they found that expression of the genes involved in GA biosynthesis is closely related to the impact of environmental factors through transcriptional profiling analysis. Moreover, this review focuses on suggesting new directions for studying GAs and attempts to gain some insights for better understanding of the biosynthesis and regulation of GAs.


Chain length effects on helix-hairpin distribution in short peptides with Aib-DAla and Aib-Aib segments.
The Aib-D Ala dipeptide segment has a tendency to form both type-I'/III' and type-I/III β-turns. The occurrence of prime turns facilitates the formation of β-hairpin conformations, while type-I/III turns can nucleate helix formation. The octapeptide Boc-Leu-Phe-Val-Aib-DAla-Leu-Phe-Val-OMe (1) has been previously shown to form a β-hairpin in the crystalline state and in solution. The effects of sequence truncation have been examined using the model peptides Boc-Phe-Val-Aib-Xxx-Leu-Phe-NHMe (2, 6), Boc-Val-Aib-Xxx-Leu-NHMe (3, 7), and Boc-Aib-Xxx-NHMe (4, 8), where Xxx=DAla, Aib. For peptides with central Aib-Aib segments, Boc-Phe-Val-Aib-Aib-Leu-Phe-NHMe (6), Boc-Val-Aib-Aib-Leu-NHMe (7), and Boc-Aib-Aib-NHMe (8) helical conformations have been established by NMR studies in both hydrogen bonding (CD3OH) and non-hydrogen bonding (CDCl3) solvents. In contrast, the corresponding hexapeptide Boc-Phe-Val-Aib-DAla-Leu-Phe-Val-NHMe (2) favors helical conformations in CDCl3 and β-hairpin conformations in CD3 OH. The β-turn conformations (type-I'/III) stabilized by intramolecular 4→1 hydrogen bonds are observed for the peptide Boc-Aib-D Ala-NHMe (4) and Boc-Aib-Aib-NHMe (8) in crystals. The tetrapeptide Boc-Val-Aib-Aib-Leu-NHMe (7) adopts an incipient 3(10)-helical conformation stabilized by three 4→1 hydrogen bonds. The peptide Boc-Val-Aib-DAla-Leu-NHMe (3) adopts a novel α-turn conformation, stabilized by three intramolecular hydrogen bonds (two 4→1 and one 5→1). The Aib-DAla segment adopts a type-I' β-turn conformation. The observation of an NOE between Val (1) NH↔HNCH3 (5) in CD3OH suggests, that the solid state conformation is maintained in methanol solutions.


Fabrication of silica nanotubes by using self-assembled gels and their applications in environmental and biological fields.
This critical review focuses on the preparation methods of a variety of the silica nanotubes by self-assembled organogels and the recent development of silica-based organic-inorganic hybrid nanomaterials for use as chemosensors in environmental studies as well as adsorbents for inorganic guest molecules and in biological applications for delivery of organic guest molecules (127 references).


Quadriceps Neuromuscular Function During and After Exercise-Induced Fatigue in Patients With Patellofemoral Pain.
Exercise-induced fatigue reduces muscle force production and motoneuron pool excitability. However, it is unclear if patients with patellofemoral pain (PFP) experience further loss in quadriceps neuromuscular function due to fatigue during exercise and postexercise. To observe how quadriceps maximal strength, activation, and force-generating capacity change during and after repetitive bouts of isokinetic knee-extension exercise in patients with PFP. Cross-sectional study. Laboratory. Twenty-two patients with PFP (visual analog scale mean pain severity = 4.2 of 10 cm, mean symptom duration = 38.6 months) and 19 healthy control individuals matched on age and body mass index. Quadriceps peak torque (PT), central activation ratio (CAR), and rate of torque development (RTD) were assessed at baseline and immediately after every 5 sets of knee-extension exercise (times 1-5). Participants continued knee-extension exercises until the baseline quadriceps PT dropped below 50% for 3 consecutive contractions. No group-by-time interaction was observed for quadriceps PT (F5,195 = 1.03, P = .40). However, group-by-time interactions were detected for quadriceps CAR (F5,195 = 2.63, P= .03) and RTD (F5,195 = 3.85, P = .002). Quadriceps CAR (-3.6%, P = .04, Cohen d = 0.53) and RTD (-18.9%, P = .0008, Cohen d = 1.02) decreased between baseline and time 1 in patients with PFP but not in their healthy counterparts (CAR -1.9%, P = .86; RTD -9.8%, P = .22). Quadriceps RTD also decreased between times 4 and 5 in patients with PFP (-24.9%, P = .002, Cohen d = 0.89) but not in the healthy group (-0.9%, P = .99). Patients with PFP appeared to experience an additional reduction in quadriceps activation, force-generating capacity, or both during the early and late stages of exercise compared with healthy individuals. Clinicians should be aware of such possible acute changes during exercise and postexercise and use fatigue-resistant rehabilitation programs for patients with PFP.


Mechanical strain breaks planar symmetry in embryonic epithelia via polarized microtubules.
Mechanical strain can act as a global cue to orient the core planar cell polarity pathway (Fz-PCP) in developing epithelia, but how strain directs a Fz-PCP vector is not known. Here we use live cell imaging of apical microtubules (MTs) and components of the Fz-PCP pathway to analyze epithelial cells in Xenopus embryos as they respond to anisotropic mechanical strain and form a Fz-PCP axis. We find that a Fz-PCP axis can be detected approximately 40 min after the application of strain. By contrast, the density and length of apical MTs increases rapidly (5-10 min) in response to strain, independently of Fz-PCP. These early-forming apical MTs are planar polarized: they align to the strain axis and display a marked bias in plus-end orientation that invariably points towards the cell edge opposite the direction of strain application. We show that these MTs can promote the vectorial transport of Dvl3-GFP containing vesicles along the apical surface in a directed manner, perhaps explaining why PCP signaling fails when MTs are disrupted. Finally, we provide evidence that the Fz-PCP axis feeds back after an hour to stabilize oriented apical MTs. These results provide insights into how mechanical strain acts as a developmental cue within the appropriate time frame and with the appropriate vector to promote planar axis formation.


GCDCA down-regulates gene expression by increasing Sp1 binding to the NOS-3 promoter in an oxidative stress dependent manner.
During the course of cholestatic liver diseases, the toxic effect of bile acids accumulation has been related to the decreased expression of endothelial nitric oxide synthase (NOS-3) and cellular oxidative stress increase. In the present study, we have investigated the relationship between these two biological events. In the human hepatocarcinoma cell line HepG2, cytotoxic response to GCDCA was characterized by the reduced activity of the respiratory complexes II+III, the increased expression and activation of the transcription factor Sp1, and a higher binding capacity of this at positions -1386, -632 and -104 of the NOS-3 promoter (pNOS-3). This was associated with a decreased promoter activity and a consequent reduction of NOS-3 expression. The use of antioxidants in GCDCA-treated cells caused a lower activation of Sp1 and the recovery of the pNOS-3 activity and NOS-3 expression and activity. Similarly, the specific inhibition of Sp1 resulted in the improvement of NOS-3 expression. Both, antioxidant treatment and Sp1 inhibition were associated with the reduction of cell death-related parameters. Bile duct ligation in rats confirmed in vitro results concerning the activation of Sp1 and the reduction of NOS-3 expression. Our results provide direct evidence for the involvement of Sp1 in the regulation of NOS-3 expression during cholestasis. Thus, the identification of Sp1 as a potential negative regulator of NOS-3 expression represents a new mechanism by which the accumulation of bile acids causes a cytotoxic effect through the oxidative stress increase, and provides a new potential target in cholestatic liver diseases.


Dendritic cells in human peripheral blood: effective enrichment from the nonadherent cells.
Dendritic cells (DC) from human peripheral blood were enriched using a method including adherence on plastic, depletion of phagocytic cells, flotation on density gradient column and panning on antibody-coated surfaces. The course of cell separation was evaluated by characterizing the morphological, antigenic and functional features of the different cell fractions. Using the population depleted of strongly adherent cells as the source, we were able to achieve a cell fraction containing 40-65% of DC (the main contaminants being monocytes and natural killer cells). Functionally these cells were highly stimulatory in autologous mixed leukocyte reaction. On the other hand, cells which primarily adhered well and were detached after overnight culture contained less than 5% of DC (the main contaminants being monocytes) after the same purification protocol. The calculated yields of DC were 1-2 X 10(6) and less than 0.5 X 10(6) from the nonadherent and adherent populations, respectively. Thus we concluded that the adhesiveness of DC from human blood is so weak that they can more efficiently and in a more reproducible way be enriched from the primarily nonadherent cell fraction.


Radiographic diagnosis, surgical treatment, and long-term follow-up of cholesterol granulomas of the petrous apex.
Cholesterol granuloma is an unusual lesion of the petrous apex. Accurate preoperative differentiation of the various lesions of the petrous apex by computed tomography scanning only has been difficult. We reviewed the clinical findings, computed tomography and magnetic resonance imaging scans, surgical approaches, and long-term follow-up in 10 patients with cholesterol granuloma of the petrous apex who were seen between 1971 and 1988. Headache and deficits of the 5th, 6th, 7th, and 8th cranial nerves were common presenting symptoms. Magnetic resonance imaging with special imaging techniques was accurate in diagnosing cholesterol granuloma in four patients preoperatively and three patients prior to revision surgery. The optimal surgical approach was chosen on the basis of clinical and radiographic findings and included the transsphenoidal, infralabyrinthine, transcochlear, and suboccipital routes. Our review reveals that magnetic resonance imaging is more specific than computed tomography in establishing a preoperative diagnosis and is also the technique of choice in follow-up. The long-term results are discussed.


Adhatoda vasica and Calotropis procera as a resource of novel chemical compounds, their biological bioluminescence assay, and investigation of morphological features of bacterial growth through advanced technologies.
This article reports the three principal groups of compounds for the first time from Adhatoda vasica and Calotropis procera plants species using nuclear magnetic resonance methods in which aliphatic, oxy heterocyclic, and tannins compounds were detected from these plants. The leaves of both species were subjected to testing tyrosinase inhibition and antioxidant activities. ATP bioluminescence use for indirect measurement of the amount of organic residue on the surface of the leaves that provide support to microbial growth. The distinguishing characteristics and intraoperative findings of bacterial diseases involved in treatments were conducted against the positive and negative microbial strains using a scanning electron microscope (SEM). The methanolic extracts of leaves of both species were applied to bacterial strains through broth microdilution method to determine the minimum inhabitation concentrations (MICs) for both species. It was concluded that both plants are a rich resource of bioactive compounds. Their extract may also be used to treat various bacterial diseases and in drug manufacturing. HIGHLIGHTS: New chemical compounds of oxy-heterocyclic, aliphatic, and tannins derivatives are isolated from herbal plants as a source of various drugs. 1 H NMR spectrum and 13 C NMR spectrum of each new derivate were calculated. NMR-spectral analysis of new compound of chemistry class was studied and further applied in various bacterial strains. Tyrosinase inhibition property of bacteria strains by application of active compounds on these strains. Agar overlay bioassays were used to evaluate intercellular morphological features of strains applied on extracts by electron microscope (SEM). a-Glucosidase inhibition assay determined with antioxidants activity through FRAP assay methods.


Covered metallic stent for ischemic hilar biliary stricture.
Compared with surgery, endoscopic treatment is safe and highly effective for a postoperative hilar benign bile duct stricture (BDS). However, the long-term outcome of conventional placement of a single biliary stent for hilar benign BDS is generally poor. Although the placement of multiple biliary stents is preferred, multiple stenting in a BDS is difficult. Alternatively, single or multiple stent placement above the papilla ('inside stent') or fully-covered self-expandable metallic stents (SEMS) are feasible approaches for benign BDS. Nevertheless, controversy remains regarding whether and how to perform endoscopic biliary drainage for a hilar benign BDS. In patients with hilar benign BDS, endoscopic biliary drainage can be performed by placing conventional plastic stents across the papilla, plastic stents above the papilla or fully-covered SEMS. Individualized treatment should be considered. We report the placement of a fully-covered SEMS for a hilar benign biliary stricture after extended left hepatectomy.


Receipt of Recommended Follow-up Care After a Positive Lung Cancer Screening Examination.
Maximizing benefits of lung cancer screening requires timely follow-up after a positive screening test. The American College of Radiology (ACR) Lung CT Screening Reporting and Data System (Lung-RADS) recommends testing and follow-up timing based on the screening result. To determine rates of and factors associated with recommended follow-up after a positive lung cancer screening examination by Lung-RADS category. This prospective cohort study of lung cancer screening examinations performed from January 1, 2015, through July 31, 2020, with follow-up through July 31, 2021, was conducted at 5 academic and community lung cancer screening sites in North Carolina. Participants included 685 adults with a positive screening examination, Lung-RADS categories 3, 4A, 4B, or 4X. Statistical analysis was performed from December 2020 to March 2022. Individual age, race, sex, smoking exposure, year of lung cancer screening examination, chronic obstructive pulmonary disease, body mass index, referring clinician specialty, rural or urban residence. Adherence, defined as receipt of recommended follow-up test or procedure after the positive screen per ACR Lung-RADS timeframes: 6 months for Lung-RADS 3 and 3 months for Lung-RADS 4A. For Lung-RADS 4B or 4X, adherence was defined as follow-up care within 4 weeks, as ACR Lung-RADS does not specify a timeframe. Among the 685 individuals included in this study who underwent lung cancer screening with low-dose computed tomography, 416 (60.7%) were aged at least 65 years, 123 (18.0%) were Black, 562 (82.0%) were White, and 352 (51.4%) were male. Overall adherence to recommended follow-up was 42.6% (292 of 685) and varied by Lung-RADS category: Lung-RADS 3 = 30.0% (109 of 363), Lung-RADS 4A = 49.5% (96 of 194), Lung-RADS 4B or 4X = 68.0% (87 of 128). Extending the follow-up time increased adherence: Lung-RADS 3 = 68.6% (249 of 363) within 9 months, Lung-RADS 4A = 77.3% (150 of 194) within 5 months, and Lung-RADS 4B or 4X = 80.5% (103 of 128) within 62 days. For Lung-RADS 3, recommended follow-up was less likely among those currently smoking vs those who quit (adjusted odds ratio [aOR], 0.48; 95% CI, 0.29-0.78). In Lung-RADS 4A, recommended follow-up was less likely in Black individuals vs White individuals (aOR, 0.35; 95% CI, 0.15-0.86). For Lung-RADS 4B or 4X, recommended follow-up was more likely in female individuals vs male individuals (aOR, 2.82; 95% CI, 1.09-7.28) and less likely in those currently smoking vs those who quit (aOR, 0.31; 95% CI, 0.12-0.80). In this cohort study, adherence to recommended follow-up after a positive screening examination was low but improved among nodules with a higher suspicion of cancer and after extending the follow-up timeline. However, the association of extending the follow-up time of screen-detected nodules with outcomes at the population level, outside of a clinical trial, is unknown. These findings suggest that studies to understand why recommended follow-up is lower in Black individuals, male individuals, and individuals currently smoking are needed to develop strategies to improve adherence.


Visual impairment and mortality in patients with type 2 diabetes.
To evaluate whether visual acuity impairment was an independent predictor of mortality in patients with type 2 diabetes. This is a 19-year follow-up of a cohort of 1241 patients newly diagnosed with type 2 diabetes and aged 40 years or over. Visual acuity was assessed by practicing ophthalmologists both at diabetes diagnosis and after 6 years. The logarithmic value of the visual acuity (logMAR) was the exposure. Multivariable Cox regression models were adjusted for multiple potential confounders including cardiovascular disease, and censored for potential mediators, that is, fractures/trauma. Primary outcomes were from national registers: all-cause mortality and diabetes-related mortality. Visual impairment at diabetes diagnosis was robustly associated with subsequent 6-year all-cause mortality. Per 1 unit reduced logMAR acuity the incidence rate of all-cause mortality increased with 51% (adjusted HR: 1.51; 95% CI 1.12 to 2.03) and of fractures/trauma with 59% (HR: 1.59; 95% CI 1.18 to 2.15), but visual acuity was not associated with diabetes-related mortality. After censoring for fractures/trauma, visual acuity was still an independent risk factor for all-cause mortality (HR: 1.68; 95% CI 1.23 to 2.30). In contrast, visual acuity 6 years after diabetes diagnosis was not associated with the subsequent 13 years' incidence of any of the outcomes, as an apparent association with all-cause mortality and diabetes-related mortality was explained by confounding from comorbidity. Visual acuity measured by ophthalmologists in patients newly diagnosed with type 2 diabetes was an independent predictor of mortality in the short term.


An x-ray CT polymer gel dosimetry prototype: II. Gel characterization and clinical application.
This article reports on the dosimetric properties of a new N-isopropylacrylamide, high %T, polymer gel formulation (19.5%T, 23%C), optimized for x-ray computed tomography (CT) polymer gel dosimetry (PGD). In addition, a new gel calibration technique is introduced together with an intensity-modulated radiation therapy (IMRT) treatment validation as an example of a clinical application of the new gel dosimeter. The dosimetric properties investigated include the temporal stability, spatial stability, batch reproducibility and dose rate dependence. The polymerization reaction is found to stabilize after 15 h post-irradiation. Spatial stability investigations reveal a small overshoot in response for gels imaged later than 36 h post-irradiation. Based on these findings, it is recommended that the new gel formulation be imaged between 15-36 h after irradiation. Intra- and inter-batch reproducibility are found to be excellent over the entire range of doses studied (0-28 Gy). A significant dose rate dependence is found for gels irradiated between 100-600 MU min⁻¹. Overall, the new gel is shown to have promising characteristics for CT PGD, however the implication of the observed dose rate dependence for some clinical applications remains to be determined. The new gel calibration method, based on pixel-by-pixel matching of dose and measured CT numbers, is found to be robust and to agree with the previously used region of interest technique. Pixel-by-pixel calibration is the new recommended standard for CT PGD. The dose resolution for the system was excellent, ranging from 0.2-0.5 Gy for doses between 0-20 Gy and 0.3-0.6 Gy for doses beyond 20 Gy. Comparison of the IMRT irradiation with planned doses yields excellent results: gamma pass rate (3%, 3 mm) of 99.3% at the isocentre slice and 93.4% over the entire treated volume.


HPLC-NMR of fatty alcohol ethoxylates.
The application of HPLC-NMR for the analysis of a mixture of fatty alcohol ethoxylates (FAEs) is described. The use of the new generation, cryogenically cooled probes is investigated in respect of the sensitivity advantage that they provide. The FAE mixture is separated using liquid chromatography at the critical point of adsorption. The ability of the method to differentiate between the different end groups and the degree of polymerization of the mixture constituents is investigated. Both on-flow and stop-flow HPLC-NMR techniques were used together with two-dimensional NMR spectroscopy. The results are compared with those obtained by using an evaporative light scattering detector for the HPLC.


CDK12 Promotes Breast Cancer Progression and Maintains Stemness by Activating c-myc/β -catenin Signaling.
CDK12 is a promising therapeutic target in breast cancer with an effective ability of maintaining cancer cell stemness. We aim to investigate the mechanism of CDK12 in maintaining breast cancer stemness. CDK12 expression level was accessed by using RT-qPCR and IHC. CDK12-altered breast cancer cell lines MDA-MB-231-shCDK12 and SkBr-3-CDK12 were then established. CCK8, colony formation assays, and xenograft model were used to value the effect of CDK12 on tumorigenicity. Transwell assay, mammosphere formation, FACS, and lung metastasis model in vivo were determined. Western blot further characterized the mechanism of CDK12 in breast cancer stemness through the c-myc/β-catenin pathway. Our results showed a higher level of CDK12 exhibited in breast cancer samples. Tumor formation, cancer cell mobility, spheroid forming, and the epithelial-mesenchymal transition will be enhanced in the CDK12high group. In addition, CDK12 was associated with lung metastasis and maintained breast cancer cell stemness. CDK12high cancer cells presented higher tumorigenicity and a population of CD44+ subset compared with CDK12low cells. Our study demonstrated c-myc positively expressed with CDK12. The c-myc/β-catenin signaling was activated by CDK12, which is a potential mechanism to initiate breast cancer stem cell renewal and may serve as a potential biomarker of breast cancer prognosis. CDK12 overexpression promotes breast cancer tumorigenesis and maintains the stemness of breast cancer by activating c-myc/β-catenin signaling. Inhibiting CDK12 expression may become a potential therapy for breast cancer.


Comparison of the efficacies of peloid therapy and paraffin treatment given as an adjuncts to exercise therapy in patients with hallux rigidus: a randomized, uncontrolled, prospective study.
Although it is thought that peloid and paraffin treatments may have positive effect on pain, functional status, and quality of life in patients with hallux rigidus (HR), there are no comprehensive and comparative studies with a high level of evidence. We aimed to compare peloid and paraffin treatments in symptomatic hallux rigidus patients. A total of 113 patients diagnosed with HR between May 2019 and June 2021 were included in the study. After exclusion criteria, the remaining 90 patients were randomly divided into two groups: the peloid therapy group (peloid therapy + home exercise) and the paraffin therapy group (paraffin therapy + home exercise). Peloid and paraffin treatments were applied for 2 weeks (5 days a week for a total of 10 sessions). Patients were evaluated before treatment, at the end of treatment, and one month after treatment. The groups were compared in terms of pain, functional status, quality of life, and joint range of motion. In the final analysis, 40 patients in each treatment group were compared. Statistically significant improvements were achieved for all parameters at the end of treatment and at follow-up, and the treatments were found to be highly effective. As a result of the comparison, the methods were not found to be superior to each other. The present study is the first randomized study comparing peloid therapy and paraffin therapy given as an adjuncts to exercise therapy. Exercise therapy plus peloid and exercise therapy plus paraffin treatments seem to have similar effects on HR; however, controlled trials are necessary for confirmation of our results.


Skin temperature of the shoulder: circadian rhythms in normal and pathologic shoulders.
Circadian rhythm of the shoulder skin temperature was studied in 21 shoulders of 20 patients with rotator cuff tears (average age, 58 years) and 4 shoulders of 4 patients with rotator cuff tendinitis (average age, 34 years). Fourteen of the 23 uninvolved shoulders with no abnormalities on magnetic resonance imaging were also studied as normal shoulders. With a portable thermometer with the probes attached to the anterior surface of both shoulders, the skin temperature was recorded every 5 minutes from 1:00 PM to 9:00 AM (20 hours). Both the normal and cuff tear shoulders showed a similar circadian rhythm with the temperature at night significantly lower than the temperature during the daytime (P < .0001). On the other hand, the tendinitis shoulders did not show this circadian rhythm; the temperature did not change significantly through the range of measurement. We conclude that the skin temperature shows a circadian rhythm in normal shoulders, and this rhythm may be affected by certain pathologic conditions of the shoulder.


Inter-facet junction effects on particulate photoelectrodes.
Particulate semiconductor photocatalysts are paramount for many solar energy conversion technologies. In anisotropically shaped photocatalyst particles, the different constituent facets may form inter-facet junctions at their adjoining edges, analogous to lateral two-dimensional (2D) heterojunctions or pseudo-2D junctions made of few-layer 2D materials. Using subfacet-level multimodal functional imaging, we uncover inter-facet junction effects on anisotropically shaped bismuth vanadate (BiVO4) particles and identify the characteristics of near-edge transition zones on the particle surface, which underpin the whole-particle photoelectrochemistry. We further show that chemical doping modulates the widths of such near-edge surface transition zones, consequently altering particles' performance. Decoupled facet-size scaling laws further translate inter-facet junction effects into quantitative particle-size engineering principles, revealing surprising multiphasic size dependences of whole-particle photoelectrode performance. The imaging tools, the analytical framework and the inter-facet junction concept pave new avenues towards understanding, predicting and engineering (opto)electronic and photoelectrochemical properties of faceted semiconducting materials, with broad implications in energy science and semiconductor technology.


Prostate specific-antigen distribution in asymptomatic Canadian men with no clinical evidence of prostate cancer.
To examine prostate specific-antigen (PSA) levels and percentage free/total PSA (f/tPSA) distributions as well as digital rectal examination (DRE) profiles in asymptomatic Canadian men with no established prostate cancer diagnosis, as recent data indicate that a man's risk of developing prostate cancer is higher if his baseline PSA level is above the median for his age group. We used data obtained during an early prostate cancer-detection event. An invitation to an onsite DRE, PSA level and f/tPSA assessment was accepted by 313 men. Serum PSA level and f/tPSA were measured before the DRE. A suspicious DRE and/or PSA level of > or = 2.5 ng/mL or f/tPSA of < or = 15% represented indications for a systematic 12-core ultrasonography-guided prostate biopsy. Of all the 313 men, most (235, 75%) had PSA levels of 0.01-1.53 ng/mL and an f/tPSA of >15% (285, 91.1%). The median (range) PSA level was 0.8 (0-34.2) ng/mL and f/tPSA was 27.4 (6.7-100)%. Age-specific median PSA levels and f/tPSA were, respectively, 0.7, 0.9, 1.0, 1.5 ng/mL and 31%, 27%, 26%, 25% for men aged 40-49, 50-59, 60-69 and 70-79 years. A suspicious DRE was recorded in 55 (17.6%) men, with eight (8.8%), 26 (20.0%), 14 (20.6%), and seven (28.9%) having suspicious DRE findings according to above age categories. Overall, seven (2.2%) prostate cancers were detected. The median age-specific baseline PSA levels and f/tPSA represent valuable indicators of prostate cancer risk. The population-specific baseline median PSA level should not be >1.0 ng/mL and the baseline f/tPSA should be >30%. Men with values outside of these ranges should be considered at greater risk of prostate cancer.


Slow softening of Kanzi apples (Malus×domestica L.) is associated with preservation of pectin integrity in middle lamella.
Kanzi is a recently developed apple cultivar that has an extremely low ethylene production, and maintains its crispiness during ripening. To identify key determinants of the slow softening behaviour of Kanzi apples, a comparative analysis of pectin biochemistry and tissue fracture pattern during different ripening stages of Kanzi apples was performed against Golden Delicious, a rapid softening cultivar. While substantial pectin depolymerisation and solubilisation was observed during softening in Golden Delicious apples, no depolymerisation or increased solubilisation was observed in Kanzi apples. Moreover, tissue failure during ripening was mainly by cell breakage in Kanzi apples and, in contrast, by cell separation in Golden Delicious apples. Kanzi apples had lower activity of beta-galactosidase, with no decline in the extent of branching of the pectin chain. A sudden decrease in firmness observed during senescence in Kanzi apples was not due to middle lamella dissolution, as tissue failure still occurred by cell breakage.


Changes in chromosome organization during PHA-activation of resting human lymphocytes measured by cryo-FISH.
During interphase, chromosomes are arranged into territories within a highly organized nuclear space containing several compartments. It is becoming clear that this complex nuclear arrangement is important for gene regulation and therefore expression. The study of chromosome organization in interphase requires high-resolution imaging methods that at the same time allow for flexible labelling strategies and preserve nuclear structure. Tokuyasu cryosections of cells or tissues provide a simple, high-resolution platform for performing immunolabelling and fluorescence in situ hybridization (FISH) on well-preserved samples. Here we show how FISH performed on thin cryosections (cryo-FISH) can be used for the study of chromosome organization at high resolution and in a quantitative manner. We have measured chromosome intermingling, volume and radial position, in resting and activated human lymphocytes, and observed chromosome-specific differences between the two cellular states. These differences are in part related to the nuclear expansion that occurs during activation, but are also likely to be tied to their different transcriptional profiles. Extrapolation of our dataset to the whole genome suggests that activated cells contain a lower amount of chromatin involved in intermingling than resting cells.


Television viewing and abdominal obesity in young adults: is the association mediated by food and beverage consumption during viewing time or reduced leisure-time physical activity?
The behavioral pathways through which television (TV) viewing leads to increased adiposity in adults are unclear. We wanted to determine whether the association between TV viewing and abdominal obesity in young adults is mediated by food and beverage consumption during TV viewing time or by a reduction in overall leisure-time physical activity (LTPA). This study involved a cross-sectional analysis of data from 2001 Australian adults aged 26-36 y. Waist circumference (WC) was measured at study clinics, and TV viewing time, frequency of food and beverage consumption during TV viewing, LTPA, and demographic characteristics were self-reported. Women watching TV > 3 h/d had a higher prevalence of severe abdominal obesity (WC: > or = 88 cm) compared with women watching < or = 1 h/d [prevalence ratio (PR): 1.89; 95% CI: 1.32, 2.71]. Moderate abdominal obesity (WC: 94-101.9 cm) was more prevalent in men watching TV > 3 h/d than in men watching < or = 1 h/d (PR: 2.16; 95% CI: 1.37, 3.41). Adjustment for LTPA made little difference, but adjustment for food and beverage consumption during TV viewing attenuated the associations (PR: 1.48; 95% CI: 1.01, 2.17 for women; PR: 1.73; 95% CI: 1.06, 2.83 for men). The association between TV viewing and WC in young adults may be partially explained by food and beverage consumption during TV viewing but was not explained by a reduction in overall LTPA. Other behaviors likely contribute to the association between TV viewing and obesity.


Right hepatic duct emptying into the cystic duct: report of a case.
Anomalous insertion of the right hepatic duct into the cystic duct is a rare anatomic variation. At this writing, only nine cases have been reported in the literature. In the patients presenting with this anomaly, the surgeon may accidentally transect the right hepatic duct during cholecystectomy. We encountered a case of anomalous insertion of the right hepatic duct into the cystic duct, which was clearly demonstrated in the intraoperative cholangiography during laparoscopic cholecystectomy. As the half-cut point of the cystic duct happened to be on the gallbladder side of the cystic duct, cholecystectomy was accomplished laparoscopically. In anomalous insertion of the right hepatic duct into the cystic duct, hepatic duct transection could happen. Preoperative precise evaluation of the biliary duct, awareness of potential biliary variations, and identification of all anatomic structures before ligation and division were essential to prevent bile duct injury.


A new Stenotrophomonas maltophilia strain producing laccase. Use in decolorization of synthetics dyes.
Laccase activity was detected in a soil bacterium Stenotrophomonas maltophilia AAP56 identified by biochemical and molecular methods. It was produced in cells at the stationary growth phase in Luria Bertani (LB) medium added by 0.4 mM copper sulfate. The addition of CuSO(4) in culture medium improved production of laccase activity. However, one laccase enzyme was detected by native polyacrylamide gel electrophoresis. The enzyme showed syringaldazine (K (m) = 53 microM), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (K (m) = 700 microM), and pyrocatechol (K (m) = 25 microM) oxidase activity and was activated by addition of 0.1% (v/v) Triton-X-100 in the reaction mixture. Moreover, the laccase activity was increased 2.6-fold by the addition of 10 mM copper sulfate; the enzyme was totally inhibited by ethylenediaminetetraacetic acid (5 mM), suggesting that this laccase is a metal-dependant one. Decolorization activity of some synthetic dyes (methylene blue, methyl green, toluidine blue, Congo red, methyl orange, and pink) and the industrial effluent (SITEX Black) was achieved by the bacteria S. maltophilia AAP56 in the LB growth medium under shaking conditions.


A functional prolipoprotein signal peptide with a deletion of four amino acid residues from the hydrophobic region.
The deletion of several codons within the signal sequence coding region of the Escherichia coli lipoprotein gene has been accomplished by oligonucleotide-directed site-specific mutagenesis. The deletion of the Leu-13 residue in a mutant in which two glycine residues had previously been deleted from the hydrophobic region (Inouye, S., Vlasuk, G., Hsiung, H., and Inouye, M. (1984) J. Biol. Chem. 259, 3729-3733) was found to cause the accumulation of the unmodified form of the protein in the cytoplasm and cytoplasmic membrane. This mutation also caused a cessation in cell growth within 15 min after synthesis of the mutant protein was induced. A deletion of the Val-7 residue was capable of suppressing the effect of the Leu-13 deletion when both are present. However, by itself the Val-7 deletion appeared to have little effect on the glycine mutant. The ability of the signal sequence to mediate the secretion of the protein after the deletion of 4 residues from the hydrophobic region demonstrates a surprising degree of flexibility in the length of this region. The deletion mutations were also found to have an unusual effect on the rate of synthesis of lipoprotein.


[Odontogenic keratocyst related to a Gorlin syndrome: a case report].
We are reporting here, the case of a 9 years old boy with Gorlin syndrome diagnosis. Current knowledge on this syndrome is reviewed.


Management of upper ureteral calculi with extracorporeal shock wave lithotripsy.
The results of 471 extracorporeal shock wave lithotripsy treatments in 465 patients with solitary ureteral stones managed by several different techniques are reported. In situ treatment was performed in 123 cases without instrumentation and in 47 after placement of a ureteral catheter. Retrograde stone manipulation was performed in 245 cases immediately before extracorporeal shock wave lithotripsy and an additional 56 were manipulated with ureteral stent placement at least 1 week before extracorporeal shock wave lithotripsy. The success rate was significantly greater if the stone was manipulated into the kidney before extracorporeal shock wave lithotripsy. Significantly less energy (p less than 0.0001) was required for complete disintegration if the stone was free floating in the kidney. The need for subsequent procedures was significantly less (p less than 0.0001) for stones manipulated successfully into the kidney. Complications were infrequent, with the most common being ureteral perforation in 5.1 per cent of the cases, all of which were managed conservatively. Extracorporeal shock wave lithotripsy is the treatment of choice for proximal ureteral calculi because it is less morbid than percutaneous approaches and provides significantly better results than ureteroscopy. An attempt at manipulation of proximal ureteral calculi back into the kidney should be made before extracorporeal shock wave lithotripsy.


Clinical and radiographic findings in multiple epiphyseal dysplasia caused by MATN3 mutations: description of 12 patients.
Multiple epiphyseal dysplasia (MED) is characterized by pain and stiffness in joints and delayed and irregular ossification of epiphyses. Causative mutations have been recognized in six different genes. We have identified disease-causing mutations in the gene encoding matrilin-3, an extracellular matrix protein, in seven families with autosomal dominant MED. Review of the clinical and radiographic features in 12 of the affected family members shows a uniform pattern of skeletal anomalies in all patients with considerable degree of variability in severity, both between and within families. The characteristic clinical findings are onset of symptoms in early childhood with predominance of knee and hip related complaints, normal stature, and early-onset osteoarthritis. Radiographs show small and irregular epiphyses and mild metaphyseal irregularities and striations, especially at the knees and hips and mild spinal changes. Despite overlap, both clinically and radiographically, with other forms of MED, the described features may help to differentiate this particular form from other entities within the MED spectrum.


Experimental analysis of alternative models of charge movement in frog skeletal muscle.
A series of pulse procedures was used to distinguish experimentally between a 'capacitative' (Schneider & Chandler, 1973) and a 'resistive' (Matthias, Levis & Eisenberg, 1980) model of 'charge movements' in skeletal muscle. A general condition describing the conservation of charge in a non-linear capacitor that was used as the basis for the experiments is derived in the Appendix. It was shown that earlier criteria concerning equality of 'on' and 'off' charge in response to large steps are insufficient to exclude resistive models. However, the capacitative, but not the resistive model successfully explained results bearing on charge conservation assessed through pulse procedures involving: (i) small, 10 mV voltage steps from a series of prepulse voltages, (ii) voltage steps to a fixed potential from a series of hyperpolarized voltages, (iii) pulse sequences incorporating a 'staircase' of voltage steps. It is concluded that the earlier use of 'on' and 'off' equality in response to large voltage steps is insufficient to exclude a resistive basis for the non-linear transient. However pulse procedures explicitly designed to distinguish the two models give results consistent with a capacitative model for the non-linear charge and at variance with a resistive one.


Fibrogenic structure-activity study of the bleomycin molecule.
In the present study the fibrogenic potential of intact bleomycins as well as their acetyldipeptide and terminal polyamine constituents have been assessed. Administration of Blenoxane, bleomycin A2, or bleomycin B2 to rats produced histopathologic evidence of pulmonary fibrosis when tissues were examined 28 days following a single intratracheal dose. These compounds also produced a readily detectable increase in pulmonary collagen synthesis as evidenced by an approximate twofold increase over control values in the formation of [3H]hydroxyproline in an in vitro lung mince system. Lung collagen synthetic activity remained significantly elevated over control values for up to 2 weeks. However, neither the acetyldipeptides nor the polyamine constituents of bleomycin A2 and B2 produced detectable increases in lung collagen synthesis or in histopathologic evidence of pulmonary injury. Spermine and spermidine, the terminal amine components associated with bleomycin-A6 and with tallysomycin A, tallysomycin B, and bleomycin-A5, respectively, did produce significant pulmonary fibrotic injury in rats following intratracheal administration. Out of an extensive series of polyamines, bleomycin acetyldipeptides and intact bleomycin and tallysomycin analogs, only spermine and spermidine were found to produce hydrogen peroxide and acrolein upon incubation in vitro with amine oxidase, a common pulmonary enzyme. Conclusions regarding the relative toxicity of different bleomycin analogs based solely on the toxicity produced by administration of their terminal amine constituent must therefore be made with caution.


[Convergence of preganglionic fibers on the vasomotor neurons of the sympathetic ganglia of cats].
By means of intracellular recordings from the neurons of isolated lumbar ganglia III-IV it is shown that B1-, B2- and C-preganglionic fibres widely converge on these neurons. The neurons antidromically activated by stimulation of muscular and cutaneous branches were identified as vasomotor ones. The latter had distinct features of preganglionic fibre convergence. Only B2- and C-preganglionic fibres were able to activate them, but the efficacy of the B2-fibres excitatory action was considerably higher. The vasomotor neurons had a lower conduction velocity in its axons (0.95 +/- 0.05 m/s) as compared to other postganglionic neurons (1.30 +/- 0.15 m/s).


Comparative Assessment of Total Versus Hemi Glossectomy Defects Reconstructed With Anterolateral Thigh Free Flap.
Free tissue transfers for reconstruction following tongue resection has become standard practice. This study sought to evaluate volume shrinkage of the anterolateral thigh free (ALTF) reconstructing tongue defects at 6 months postoperative. The aim was to estimate a shrinkage factor for ALTF reconstructing hemi and total glossectomy. This was an IRB-approved retrospective cohort study conducted at the head and neck service at the University of Florida, College of Medicine, Jacksonville (FL). This study targeted patients with tongue cancer from January 2018 to April 2022. patients with tongue squamous cell carcinoma (SCC) who were surgically treated by either hemi or total glossectomy and reconstructed with ALTF. Patients had to have a postoperative computer tomography scans at 1 and 6 months post-surgery. Patients with constant body mass index during 6 months postreconstruction. Additionally, the patients were to have been treated with adjuvant radiotherapy. patients with recurrent tongue cancer and those who weren't reconstructed or managed with other treatment modalities. Type of tongue resection hemi versus total glossectomy for treatment of tongue SCC. Shrinkage percentage of ALTF reconstructing tongue defects at 6 months postoperatively. Age and gender. Paired t-test and student t-test with level of significance P ≤ .05 were used to statistically analyze ALTF volume changes at 1 and 6 months postoperatively and ALTF shrinkage percentage at 6 months postreconstruction, respectively. We identified 85 patients who were treated for tongue SCC during the time period of study. Out of the 85 patients, 11 patients were reconstructed with an ALTF. Eight males and 3 females with a mean age of 62.3 years old. Six patients had total glossectomy and 5 had hemi glossectomy. Patients with hemi glossectomy had a significant difference in mean average flap shrinkage of 39.6%, while in those with total glossectomy had 17.7% (P = .004). According to our results, we recommend that the flap size should be larger than the defect to adjust for volume shrinkage (1.4 times and 1.2 times for cases of hemi and total glossectomy, respectively).


Registered Nurse to Bachelor of Science in Nursing: nesting a fast-track to traditional generic program, teachings from nursing education in Burkina Faso.
Nursing education has evolved over time to fit societies' increasing care needs. Innovations in nursing education draw thorny debates on potential jeopardy in the quality, safety, and efficacy of nurse graduates. Accelerated nursing education programs have been among landmark strategic changes to address the persistent bedside nurse shortage. Despite the dearth of empirical studies in sub-Saharan Africa (SSA), the National School of Public Health of Burkina Faso has developed a State Diploma Nursing (SDN) fast-track program. With innovative features, the program is nested into the traditional SDN program. This study investigates preliminary outcomes of the implemented policy using the initial cohort that went through the program. Comparison of the traditional generic program and the fast-track one is drawn to inform nursing education policy. The study was conducted in the three campuses delivering the SDN program. Data collected from a representative sample included 255 students from the 2006-2009 cohort, after concluding the program. Surveyed students were assessed according to the program entry status. Outcomes were measured using students' academic performance. Besides descriptive analysis, bivariate t-test, F-test, and multivariate ordinary least square regression (OLSR) were employed to determine the comparative pattern between the traditional generic and the newly nested fast-track program. Students' varied statuses (private pre-registration, state pre-registration, private post-registration, and state post-registration) were kept to better outline the findings trend. A fifth (19.6 %) of surveyed students were enrolled in the fast-track stream from which, one third (33.7 %) consisted of post-registered students. Fast-track students comparatively achieved the best academic performance (mean: 73.68/100, SD: 5.52). Multivariate OLSR confirmed that fast-track students performed better (β: 5.559, p < 0.001), and further informed differences between campuses. Students entry status also displayed significant differences, yet the academic performance of post-registered students from traditional generic versus fast-track was similar (p = 0.409). Findings suggest that fast-track program students performed better than the ones from the traditional generic program. The uniqueness and success of this mixed nursing program experience sheds light for nursing educators engaged in policy making. The study results can serve as a crucial foundation for policymakers to alleviate the nurse shortage in SSA.


The effects of estrus cycle on drug metabolism in the rat.
The effect of the female rat estral cycle on microsomal drug metabolism in-vivo and in-vitro has been studied. Two microsomal enzymes, aminopyrine-N-demethylase and aniline hydroxylase showed a greater specific activity (p less than 0.01) in the diestrus phase of the estral cycle while the oxidative enzyme aryl hydrocarbon hydroxylase and the conjugative enzyme, glucuronyl transferase, were not affected. In vivo studies which included theophylline and antipyrine metabolism, and hexobarbital sleeping times showed no difference between the different phases of the estral cycle. Conflicting evidence about the effect of steroid sex hormones on hepatic drug metabolism is discussed.


Communicating unexpected pharmacogenomic results to biobank contributors: A focus group study.
The goals of this study were to explore 1) the impact of returning unexpected pharmacogenomic (PGx) results to biobank contributors, and 2) participant views about improving communication. We conducted a qualitative focus group study with biobank participants (N = 54) who were notified by mail of an individual research result indicating increased risk for adverse events associated with the common cancer drug 5-fluorouracil (5-FU). We employed a framework approach for analysis. Our results revealed three themes illustrating participants' questions and uncertainty, especially regarding how to share results with health providers and family members, and remember them over time. Participants valued results for themselves and others, and for the future of medicine. Risk perception was framed by health identity. "Toxicity narratives," or familiarity with another's adverse reaction to chemotherapy, increased the sense of importance participants reported. These focus group results highlight research participant remaining questions and high valuation of PGx results, even when unexpected. We identify PGx research participants' needs for clear clinical translation messaging that attends to health identity, pragmatics of sharing information with family members, and patient perceptions of barriers to transferring research results to a clinical context.


Synthesis of prostaglandins by the ductus arteriosus of the bovine fetus.
Previous studies demonstrated that prostaglandins are local or tissue hormones which can be released from blood vessel walls. In the present study, we investigated the capacity of bovine ductus arteriosus to synthetize prostaglandins in vitro. After incubation of slices of ductus arteriosus in Krebs' solution with (1-14C) arachidonic acid for 3 hours, more than 40% of the radiolabeled material recovered from the incubating medium were metabolites of arachidonic acid. The major product was indistinguishable from 6 keto-PGF1alpha as determined by its chromatographic motility and resistance to alkaline conversion to PGB. The PGI2 synthetic capacity of the ductus arteriosus, as revealed by the predominance of its major metabolite 6 keto-PGF1alpha, suggests that this metabolic pathway of arachidonic acid may contribute to the hemodynamic changes occurring during fetal life and at birth.


Informal learning in postgraduate medical education: from cognitivism to 'culturism'.
Work-based learning occupies a central role in the training and ongoing development of the medical workforce. With this arises the need to understand the processes involved, particularly those relating to informal learning. Approaches to informal learning in postgraduate medical education have tended to consider the mind as an independent processor of information. In this paper, such cognitive approaches are critiqued and an alternative socio-cultural view on informal learning described. Recent and imminent changes in postgraduate medical education are identified, namely the reduction in patient experience, the fragmentation of teaching, and the development of competency frameworks and structured curricula. It is argued that although the latter may be useful in the construction of formal learning programmes, they will do little to enhance the progression of the individual from newcomer to old-timer or the cultural assimilation of the learner into a profession. Strategies for enhancing informal learning in the workplace are recommended in which increased attention is paid to the development of the medical apprentice within a community of social practice. These include the establishment of strong goals, the use of improvised learning practices, attention to levels of individual engagement and workplace affordances, immersion in professional discourse and behaviours, support in relation to the development of a professional identity and the provision of opportunities to transform social practice.


Positioning of glucocorticosteroids in asthma and allergic rhinitis guidelines (versus other therapies).
Asthma and allergic rhinitis are both characterized by airway inflammation, and glucocorticosteroids form the cornerstone of their pharmacologic treatment. All patients with asthma should be prescribed rapid-acting inhaled beta2-agonists as needed to use as rescue therapy in case of symptoms. As soon as patients experience symptoms at least once a week, controller medications should be started on a daily basis to achieve and maintain control of their asthma. Intranasal corticosteroids are given as first-line therapy for moderate to severe persistent rhinitis. Depending on the dominant symptom, H1-antihistamines, decongestants, or ipratropium can be added after re-evaluation.


Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function.
The concentrations of quinidine, (3S)-3-hydroxyquinidine (3-OH), and 2'-oxoquinidinone (2'-OXO) in serum samples from 25 patients on long-term quinidine therapy were determined by a high-pressure liquid chromatography assay. Large individual variation in the levels of each of the compounds measured was observed. After correcting for differences in protein binding, the ratio of 3-OH/quinidine in serum water is 0.61 +/- 0.31 (SD) and the ratio of 2'-OXO/quinidine is 0.39 +/- 0.44. Seven of the 25 patients had serum water levels of one of these metabolites similar to or greater than that of quinidine. The quinidine levels, after normalizing for dose, are significantly higher in hemodialysis patients (about twice) than in nonazotemic patients; azotemic patients have mean values intermediate between them. Quinidine, 3-OH, and 2'-OXO are equally potent antiarrhythmic drugs (ED50 = 0.18, 0.17, and 0.21 mmoles/kg, respectively) when tested against chloroform- and hypoxia-induced ventricular fibrillation in mice. O-Desmethylquinidine, a new metabolite detected in urine of quinidine-treated patients, is less active. Quinidine and 2'-OXO are equally potent (ED50 = 0.010 mmoles/kg), while 3-OH seems less potent and more toxic when tested against BaCl2-induced ventricular arrhythmias in rabbits. Thus, these metabolites appear to contribute to the effects of quinidine and may make a significant contribution in some cases.


Expression of a functional barley sucrose-fructan 6-fructosyltransferase in the methylotrophic yeast Pichia pastoris.
The cDNA encoding sucrose-fructan 6-fructosyltransferase (6-SFT) from barley (Hordeum vulgare) has been expressed in the methylotrophic yeast Pichia pastoris, using a translational fusion into vector pPICZ alphaC, containing the N-terminal signal sequence of Saccharomyces cerevisiae alpha-factor to allow entry into the secretory pathway. Transformed Pichia produced and secreted a functional 6-SFT which had characteristics similar to the barley enzyme, but had a pronounced additional 1-SST activity when incubated with sucrose.


Relationship between patient-based outcome score and conventional objective outcome scales in post-operative total knee arthroplasty patients.
Evaluations for knee osteoarthritis (OA) or post-operative total knee arthroplasty (TKA) have mainly been assessed by objective scales. Though the Knee injury and Osteoarthritis Outcome Score (KOOS) is attracting attention as a patient-based outcome score, the relationship with conventional objective scales after TKA remains controversial. The purpose of this study was to investigate the relationship between KOOS and conventional objective scales and evaluate the features of patient-based outcome scores. Subjects were 130 post-operative patients involving 186 knees treated with TKA. Their mean age was 74.0 ± 8.0 years, and the follow-up period was 43 months. Japanese Orthopaedic Association (JOA) score, original Knee Society Score (KSS) and surgeon's satisfaction score were scored as conventional objective scales besides KOOS. Spearman's correlation coefficient was estimated between these scales. Comparisons between OA and rheumatoid arthritis (RA) as well as primary and revision surgery were performed by the Mann-Whitney U test. There were strong correlations between KOOS activities of daily living (ADL) and JOA score (r = 0.806), KSS function score (r = 0.803) and between KOOS pain and KSS knee score (r = 0.689). However, there was a poor correlation between KOOS and surgeon's satisfaction score (r = 0.188-0.321). TKA for RA showed poorer results only in KOOS pain (p = 0.003), and revision surgery showed poorer results in KSS function, KOOS symptoms and KOOS quality of life (QOL). This study suggested that conventional objective scales reflected mainly ADL disturbances in post-operative TKA patients. Furthermore, patient-based outcome scores made it possible to evaluate and detect a minute change of knee pain and QOL in TKA patients. The Japanese KOOS was a useful tool to evaluate conditions after TKA.


Evaluation of a long-acting converting enzyme inhibitor (enalapril) for the treatment of chronic congestive heart failure.
Converting enzyme inhibition of the renin-angiotensin system has proved a valuable therapeutic approach in patients with severe chronic congestive heart failure. In the present study, a new long-acting converting enzyme inhibitor (enalapril) was evaluated with acute single dose testing (10, 20 or 40 mg) in nine patients with severe chronic congestive heart failure. Four hours after administration, there was a significant reduction of systemic vascular resistance (-19%) and pulmonary wedge pressure (-19%); in addition, there were related increases of cardiac index (+16%) and stroke index (+19%) (probability [p] less than or equal to 0.05 for all changes). This was associated with an increase of plasma renin activity (9 +/- 3 to 35 +/- 11 ng/ml per hour) and a decrease of plasma aldosterone (19 +/- 4 to 9 +/- 2 ng/100 ml) (p less than 0.02 for both). With long-term therapy (1 month), there was improvement of exercise tolerance time and lessening of symptoms based on the New York Heart Association classification. Hemodynamic improvement was maintained in most, but not all, patients. There was no orthostatic hypotension during head-up tilt and hemodynamic values in the upright position were associated with normalization of intracardiac pressures. Long-term converting enzyme inhibition was indicated by a persistent increase of plasma renin activity (16 +/- 2 ng/ml per hour) and a decrease of plasma aldosterone (8 +/- 3 ng/100 ml). In addition, relative angiotensin II receptor occupancy was decreased as judged by the pharmacodynamic response to infusion of the angiotensin II analog saralasin. In conclusion, the long-acting converting enzyme inhibitor, enalapril, was effective in patients with chronic congestive heart failure; however, additional studies will be necessary to further delineate the optimal dose range and identify those patients who are most likely to respond to the drug.


Aglycone specificity of Escherichia coli alpha-xylosidase investigated by transxylosylation.
The specificity of the aglycone-binding site of Escherichia coli alpha-xylosidase (YicI), which belongs to glycoside hydrolase family 31, was characterized by examining the enzyme's transxylosylation-catalyzing property. Acceptor specificity and regioselectivity were investigated using various sugars as acceptor substrates and alpha-xylosyl fluoride as the donor substrate. Comparison of the rate of formation of the glycosyl-enzyme intermediate and the transfer product yield using various acceptor substrates showed that glucose is the best complementary acceptor at the aglycone-binding site. YicI preferred aldopyranosyl sugars with an equatorial 4-OH as the acceptor substrate, such as glucose, mannose, and allose, resulting in transfer products. This observation suggests that 4-OH in the acceptor sugar ring made an essential contribution to transxylosylation catalysis. Fructose was also acceptable in the aglycone-binding site, producing two regioisomer transfer products. The percentage yields of transxylosylation products from glucose, mannose, fructose, and allose were 57, 44, 27, and 21%, respectively. The disaccharide transfer products formed by YicI, alpha-D-Xylp-(1-->6)-D-Manp, alpha-D-Xylp-(1-->6)-D-Fruf, and alpha-d-Xylp-(1-->3)-D-Frup, are novel oligosaccharides that have not been reported previously. In the transxylosylation to cello-oligosaccharides, YicI transferred a xylosyl moiety exclusively to a nonreducing terminal glucose residue by alpha-1,6-xylosidic linkages. Of the transxylosylation products, alpha-d-Xylp-(1-->6)-D-Manp and alpha-d-Xylp-(1-->6)-D-Fruf inhibited intestinal alpha-glucosidases.


[Effect, on kidney structure, of the use of antitumor preparations combined with diacarb and furosemide].
It has been shown in experiments on rats with transplanted sarcoma 45 that cyclophosphane (10 mg/kg) and 6-mercaptopurine (25 mg/kg) produced hemodynamic changes in the kidneys, as well as swelling of the endothelium of the glomerular capillaries and of the epithelium of the tubules, and focal interstitial fibrosis. Concurrent administration of antineoplastic drugs with diacarb (200 mg/kg) or furosemide (50 mg/kg) returned the hemodynamics to normal and reduced nephrotoxicity of the antineoplastic drugs used.


Bile acid malabsorption in cystic fibrosis; membrane vesicles, a tool for revealing the role of the ileal brush border membrane.
Increased fecal bile acid loss in cystic fibrosis (CF) may result from ileal dysfunction. A method to quantitate in vitro Na+-dependent taurocholate uptake into brush border membrane vesicles prepared from frozen ileum and ileal biopsy specimen is described. This transport across the ileal brush border membrane can be measured selectively, in contrast to in vivo measurements which represent a complex overall process. Preliminary results obtained with ileal specimen of 2 CF patients, suggest that in vitro bile acid uptake is low but not abnormal.


The human factor H-related gene 2 (FHR2): structure and linkage to the coagulation factor XIIIb gene.
The human factor H-related gene 2 (FHR2) encodes a serum protein structurally and immunologically related to complement factor H. We describe the isolation and genomic organization of the human FHR2 gene from a yeast artificial chromosome library. The FHR2 gene is organized in five exons and spans about 7 kilobases (kb) of human genomic DNA. A comparison with the corresponding cDNA sequence (clone DDESK59) shows that the analyzed FHR2 gene has a deleted region within exon 4. A new splice acceptor site created in the truncated exon indicates that the analyzed gene could be translated to a truncated protein. Further, we demonstrate that the genes for FHR2 and beta subunit of coagulation factor XIII are located in the same 165 kb YAC DNA. Thus, the three structurally related genes FXIIIb, FHR2, and factor H are linked on human chromosome 1 in the regulators of complement activation (RCA) gene cluster. The physical linkage of the FHR2 and the factor H genes provides additional evidence for a close relatedness of complement factor H and the factor H-related proteins. The linkage and the almost exclusive organization in short consensus repeat-containing domains indicates a close evolutionary relationship of the FXIIIb, FHR2, and factor H genes.


Polycaprolactone thin-film drug delivery systems: Empirical and predictive models for device design.
To define empirical models and parameters based on theoretical equations to describe drug release profiles from two polycaprolactone thin-film drug delivery systems. Additionally, to develop a predictive model for empirical parameters based on drugs' physicochemical properties. Release profiles from a selection of drugs representing the standard pharmaceutical space in both polycaprolactone matrix and reservoir systems were determined experimentally. The proposed models were used to calculate empirical parameters describing drug diffusion and release. Observed correlations between empirical parameters and drug properties were used to develop equations to predict parameters based on drug properties. Predictive and empirical models were evaluated in the design of three prototype devices: a levonorgestrel matrix system for on-demand locally administered contraception, a timolol-maleate reservoir system for glaucoma treatment, and a primaquine-bisphosphate reservoir system for malaria prophylaxis. Proposed empirical equations accurately fit experimental data. Experimentally derived empirical parameters show significant correlations with LogP, molecular weight, and solubility. Empirical models based on predicted parameters accurately predict experimental release data for three prototype systems, demonstrating the accuracy and utility of these models. The proposed empirical models can be used to design polycaprolactone thin-film devices for target geometries and release rates. Empirical parameters can be predicted based on drug properties. Together, these models provide tools for preliminary evaluation and design of controlled-release delivery systems.


Placental and plasma early predictive biomarkers for gestational diabetes mellitus.
Gestational diabetes mellitus (GDM) is a common disease that can give rise to adverse obstetric outcomes. For successful early intervention, more studies on novel predictive biomarkers for GDM are required. The protein expression profiles of placental tissue from patients with GDM and normal pregnant women were investigated using data-independent acquisition proteomics with five biological replicates. Early pregnancy maternal plasma samples from the GDM (n = 79) and control (n = 81) groups were used for further validation of candidate biomarkers. We identified 37 differentially expressed proteins between the two groups. CD109 antigen (CD109) and endosialin (CD248) were identified as hub proteins. In the validation experiments, CD109 expression was lower in the early pregnancy maternal plasma of patients with GDM compared with that in normal pregnant women, and CD248 expression was higher in the GDM group. The area under the curve of CD109, CD248, and their combination as indicators in early pregnancy maternal plasma was 0.681, 0.609, and 0.695, respectively. The present study is the first to obtain preliminary evidence that CD109 and CD248 can predict GDM during early pregnancy, as well as providing proteome-level insights into this disease's pathological mechanisms.


Advances in extracorporeal ventilation.
Mechanical ventilation remains the signature tool of critical care; however, within the past decade, a growing body of evidence suggests that positive pressure ventilation in acute respiratory failure is a double-edged sword that is associated with life-threatening complications such as nosocomial pneumonia and low cardiac performance. Essentially, solutions are required to provide adequate gas exchange and stable acid-base status while optimizing and maximizing pulmonary as well as remote organ protection. Recently, the first commercially available extracorporeal membrane ventilator was approved for clinical lung support, the Interventional Lung Assist. This article gives an overview of the potential indications for this device and the current clinical evidence in extracorporeal ventilation.


Evolution of antennules of cytheroidean ostracods (Crustacea).
Phylogenetic analysis and fossil records indicate that antennules with whip-like setae are the most plesiomorphic state in cytheroidean ostracods and that antennulae with claw-like setae are derived from antennulae with whip-like setae. Character distributions on the 18S rDNA molecular phylogenetic tree suggest that two phenotypic features of cytheroidean antennules (W/L ratio and claw-like/whip-like setae) have morphological plasticity. These features have evolved as an ethological adaptation rather than due to phylogenetic constraints such as the evolution of shell outline in cytheroideans. However, the species of the Leptocytheridae-Trachyleberididae clade generally have stout, robust antennules, indicating a phylogenetic constraint. The character state of setae (claw/whip) in cytheroidean ostracods is reflected more through their ethology than the W/L ratio of the antennules. On the basis of the present analysis and the fossil record, diversification in the morphology of the antennules seems to have occurred during the early Mesozoic.


Enteric media: pre-poured or in-house?
(1) To evaluate the performance of in-house and pre-poured commercially available enteric agar by challenge with a large number of positive clinical specimens. (2) To set the standard (critical independent evaluation) which new products should reach. (3) To publish this information, so that others can make informed decisions about enteric media. Thirteen media of anonymous source were challenged with "known" positive stool samples. In-house desoxycholate citrate agar performed best for overall pathogen isolation rates, for shigella isolation rates, and for most pathogens available on primary culture. Desoxycholate citrate agar made by our own laboratory yielded the most pathogens and proved the most effective.


Treatment of Class II, Division 2 in the late growth period.
The "Deckbiss" with skeletal Class II jaw relationship sometimes presents a considerable therapeutic problem, particularly in the late growth period (DP3U), as regards the coordination of dental and skeletal treatment objectives. An effective treatment approach was demonstrated: a modified Herbst appliance used simultaneously with fixed appliances in the maxilla. The sample comprised 12 male (14.0 +/- 0.9 years old) and 10 female (12.3 +/- 0.4 years old) patients. Correction of the distal occlusion was achieved in all patients by means of the Herbst appliance, which was removed after an average time period of 6.4 +/- 0.2 months. In the mandible the multibracket appliances were then immediately inserted, and Class II elastics were used for retention. Maximum anchorage was required in the maxilla as well as in the mandible. Complete diagnostic records were made at the beginning of the treatment as well as 6 and 12 months later, in order to document skeletal and dental changes. A dental and skeletal Class I relationship was achieved in all cases. A significant improvement was recorded in the vertical jaw base relationship; this was still stable after a period of 12 months. In the dental area in particular, a so-called high-pull headgear effect (intrusion and distalization 16, 26) and intrusion of teeth 34, 44 were registered. Only a minor protrusion of the mandibular incisors was observed. Reinforcement of the bands reduced the failure rate significantly. The Herbst appliance does not represent a standard treatment for Class II. Its indication range is limited.


Comparison of oxidative metabolism in vitro in endothelial cells from different species and vessels.
Oxygen consumption was compared in confluent cultures of endothelial cells from human umbilical cord veins, rat pulmonary arteries, and bovine aortas. A microrespirometric method utilizing oxygenated hemoglobin as oxygen supply and indicator of respiration was used. Respiratory rate was equal in human and murine cells (2.0 X 10(-6) and 2.2 X 10(-6) microliters O2/cell/hour respectively), compared on a cell-to-cell basis, while respiratory rate of the bovine endothelium was significantly lower (0.4 X 10(-6) microliters O2/cell/hour) (P less than .001).


Biocontrol efficiency of Meyerozyma guilliermondii Y-1 against apple postharvest decay caused by Botryosphaeria dothidea and the possible mechanisms of action.
Apple ring rot, caused by Botryosphaeria dothidea, is one of the important diseases in China. This pathogen infects branches and fruit and also results in fruit decay during storage. Biocontrol agents have been proposed to reduce apple decays during storage and are considered as a promising alternative strategy to traditional chemical treatment. In this study, Meyerozyma guilliermondii Y-1, isolated from healthy grape fruit, was firstly evaluated for its biocontrol efficiency against B. dothidea in postharvest apple fruit, and the possible mechanisms were investigated. The results revealed that M. guilliermondii Y-1 treatment effectively reduced apple ring rot caused by B. dothidea in vivo. The disease incidence and lesion diameter were reduced by 32.22% and 57.51% compared with those of control fruit. Furthermore, the use of filtrate and autoclaved culture of M. guilliermondii Y-1 also showed a certain degree of control efficiency against fruit ring rot. M. guilliermondii Y-1 significantly inhibited the mycelial growth and spore generation of B. dothidea in vitro and exhibited an obvious ability to colonize in apple fruit wounds and surface at 25 °C or 4 °C. In addition, M. guilliermondii Y-1 treatment significantly enhanced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), phenylalanine ammonialyase (PAL), and polyphenoloxidase (PPO), promoted the total phenolics content, and alleviated lipid peroxidation in apple fruit. As expected, we found that the expression of four pathogenesis-related proteins genes (MdPR1, MdPR5, MdGLU, and MdCHI) was remarkably increased by M. guilliermondii Y-1 treatment. Our data together suggest that M. guilliermondii Y-1 is a potential biocontrol agent against B. dothidea postharvest infection in apple fruit, partially through inhibiting mycelial growth and spore germination of B. dothidea, competing for space and nutrient with pathogen, and inducing resistance in apple fruit by stimulating a series of defense responses.


Magnetic structure and uniaxial negative thermal expansion in antiferromagnetic CrSb.
Negative thermal expansion (NTE) has been found in a growing number of ferromagnetic and ferrimagnetic materials; however, it remains a challenge to discover antiferromagnetic (AFM) NTE materials. Here, we report the uniaxial NTE properties of AFM intermetallic CrSb systematically, and reveal its uniaxial NTE mechanism for the first time. The present AFM intermetallic CrSb shows uniaxial NTE at high temperature and over a broad temperature window (αa = -6.55 × 10-6 K-1, 360-600 K). The direct experimental evidence of neutron powder diffraction reveals that NTE is induced by the AFM ordering of the Cr atom. The present study demonstrates that due to the transition from an AFM ordered structure to a paramagnetic disordered configuration, the negative contribution to the thermal expansion from the magnetovolume effect overwhelms the positive contribution from anharmonic phonon vibration. This study is of interest to find antiferromagnetic NTE materials.


MiR-300 promotes the proliferation, migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis by targeting IL-37.
Fibroblast-like synoviocytes (FLS) are crucial regulators in the pathogenesis of rheumatoid arthritis (RA). Reportedly, microRNA (miR) participates in regulating the pathogenesis of RA. In this study, we explored the regulatory effects of miR-300 on the proliferation, migration and invasion of FLS, which were obtained from RA patients. qPCR was utilized to detect miR-300 expression and interleukin-37 (IL-37) mRNA expression in the synovial tissue of RA patients and healthy controls. Cell counting kit-8 (CCK-8) assay and Transwell assay were performed to investigate the regulatory function of miR-300 on the proliferation, migration and invasion of FLS. ELISA was employed to detect TNF-α, IL-6 and IL-8 levels, to evaluate the inflammatory response. Bioinformatics analysis and luciferase reporter assay were applied to validate the targeting relationship between miR-300 and IL-37. Western blot assay was executed to detect IL-37 protein expression in FLS. MiR-300 was revealed to be markedly down-modulated in the synovial tissue and FLS of RA patients; meanwhile, IL-37 expression was up-modulated. The transfection of miR-300 mimics enhanced RA-FLS growth, migration, invasion and inflammatory response; transfection of miR-300 inhibitors repressed the growth, migration, invasion and inflammatory response of RA-FLS. IL-37 was identified as a downstream target of miR-300, and IL-37 partially counteracted the enhanced growth, migration, invasion and inflammatory response of RA-FLS induced by miR-300. MiR-300 facilitates growth, migration, invasion and inflammatory response of FLS by targeting IL-37, suggesting it was a crucial regulator in the pathogenesis of RA.