Influence of Respiration on Collateral Flow in the Fontan Population Using Real-time Phase-contrast Cardiovascular Magnetic Resonance: Collateral Flow Does Not Protect the Ventricle From Volume Deficiency and Diastolic Dysfunction.
The clinical significance of collateral flow for the ventricular function of patients with univentricular hearts is often debated. This study evaluates the impact of collateral flow on respiration-dependent preload modification and diastolic function in Fontan patients assessed by systemic and pulmonary vein (PV) flow patterns. Real-time phase-contrast cardiovascular magnetic resonance was performed in the right upper PV, ascending aorta, superior, and inferior vena cava (IVC) in 21 Fontan patients and 11 healthy individuals. The patients' respiratory cycle was divided into 4 periods to generate respiratory-dependent stroke volumes (SV i ). Conventional quantitative blood flow measurements were used to quantify and differentiate between low (group A) and high (group B) collateral flow. Group B showed significantly lower SV i IVC in inspiration, end-inspiration, expiration, and SV i ΔIVC compared with group A (23.6±4.8 mL/m 2 to 33.4±8.0; P =0.005). PV flow resulted in a lower mean SV i PV (11.6±7.6 mL/m 2 , vs. 14.0±11.4 mL/m 2 ) as well as a significantly lower peak systolic S-wave velocity (S max ) ( P =0.005), S/D-ratio (S max /peak diastolic wave velocity) ( P =0.015), and shorter diastolic deceleration time (DT D ; P =0.030; median DT D =134 ms) compared with group A (DT D =202 ms). This study demonstrates the incapability of Fontan patients to properly increase preload by inspiration in the presence of significant collateral flow. The results further show that collateral flow is associated with a volume-deprived ventricle and impaired diastolic function.


The biotin-streptavidin system in a two-site ELISA for the detection of plasmodial sporozoite antigen in mosquitoes.
A two-site ELISA has been designed for the detection of sporozoite antigen in mosquitoes. Biotin-labelled monoclonal antibodies against sporozoites and a streptavidin-biotin-peroxidase complex were used to visualize the antigen. Evaluation of the sensitivity and specificity of the procedure was carried out and background levels of reactivity on the basis of negative mosquitoes were calculated. The test has been deliberately kept as simple as possible for use in the tropics and was designed using Anopheles stephensi infected with in vitro cultivated Plasmodium falciparum gametocytes. A minimum of about 100-350 sporozoites could be detected in mature salivary gland infections; in addition sporozoite antigen was detected in mosquitoes several days before the entry of sporozoites into the salivary glands. No reaction was demonstrable either with bloodstage or ookinete antigens of P. falciparum, or with mosquitoes carrying sporozoites of other plasmodial species. The number of sporozoites in positive mosquitoes and the generating capacity of a single oocyst could be assessed by the use of a calibration curve based on dilution data of a known sporozoite suspension. It was found that a single oocyst can produce about 10,000 sporozoite equivalents.


Teaching Lessons from the Coronavirus Disease 2019 (COVID-19) Pandemic in Telemedicine.
The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY.


Resolving cargo-motor-track interactions with bifocal parallax single-particle tracking.
Resolving coordinated biomolecular interactions in living cellular environments is vital for understanding the mechanisms of molecular nanomachines. The conventional approach relies on localizing and tracking target biomolecules and/or subcellular organelles labeled with imaging probes. However, it is challenging to gain information on rotational dynamics, which can be more indicative of the work done by molecular motors and their dynamic binding status. Herein, a bifocal parallax single-particle tracking method using half-plane point spread functions has been developed to resolve the full-range azimuth angle (0-360°), polar angle, and three-dimensional (3D) displacement in real time under complex living cell conditions. Using this method, quantitative rotational and translational motion of the cargo in a 3D cell cytoskeleton was obtained. Not only were well-known active intracellular transport and free diffusion observed, but new interactions (tight attachment and tethered rotation) were also discovered for better interpretation of the dynamics of cargo-motor-track interactions at various types of microtubule intersections.


Association between Helicobacter pylori infection and metabolic syndrome: a systematic review and meta-analysis.
To systematically review and quantify the effect of Helicobacter pylori (H. pylori) infection on the risk of metabolic syndrome (MS) and metabolic parameters in individuals with H. pylori infection. A systematic search of MEDLINE and EMBASE was performed. Inclusion criteria were observational studies assessing the association between H. pylori infection and MS in adult participants. We calculated the pooled effect estimate of MS with 95% confidence interval (CI) between patients infected with H. pylori and those without by using a random-effects model. The secondary outcomes were the differences between groups in homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), body mass index (BMI) and systolic blood pressure (SBP). Altogether 18 trials with 27 544 participants met the inclusion criteria. Six trials were included in the analysis of MS. There was a statistically significant association between H. pylori and MS with a pooled odds ratio of 1.34 (95% CI 1.17-1.53, I(2) = 39%, Pheterogeneity < 0.01). Between the infected and non-infected groups there were significant differences in FBG, HDL-C, BMI, triglyceride, HOMA-IR and SBP (all P < 0.05). H. pylori infection is positively associated with MS. Infection with H. pylori is also associated with higher triglyceride, FBG, BMI, HOMA-IR, SBP and lower HDL-C.


Resin-tooth interfacial morphology and sealing ability of one-step self-etch adhesives: microleakage and SEM study.
To compare microleakage of three self-etch adhesives and to analyze enamel surface morphology and interfacial morphology of resin-enamel and resin-dentin interface under scanning electron microscope (SEM). Study was conducted in 65 extracted human premolars. Class V cavities were prepared in 45 teeth and assigned to three groups (n = 15) according to three self-etch adhesives (OptiBond All-in-One, iBond, and Adper Prompt L-Pop). After restoration, 10 samples from each group were used to assess microleakage at enamel and dentin margin. Five samples from each group were used for analysis of interfacial morphology at resin-enamel and resin-dentin interface under SEM. Remaining 20 teeth were used to prepare flat enamel buccal surfaces to analyze the difference in surface morphology after treatment with three adhesives (n = 5 each) and 36% phosphoric acid treatment (n = 5). At enamel margin, Prompt L-Pop depicted least leakage of all the three adhesives and also showed best interfacial adaptation under SEM. At dentin margin, OptiBond All-in-One showed significant less leakage than iBond and Prompt L-Pop. On flat enamel surface, phosphoric acid produced the most retentive etching pattern when compared with the three adhesives. Prompt L-Pop showed the best bonding effectiveness in enamel, whereas OptiBond All-in-One performed significantly better in dentin.


Intercellular network in articular cartilage of pigs with experimentally induced arthritis. I. Fact or artifact?
Porcine articular cartilage from cases of experimentally induced Erysipelas arthritis was examined with different histological techniques and by electron microscopy. A small percentage of specimens of osteoarthritic cartilage revealed an interlacunar network in the extracellular matrix. These "matrix-streaks" showed characteristic features of densely packed fibrillar elements and collagenous fibrils, as narrow bands connecting adjacent chondrocytes. In a given cartilage site the network had a constant pattern. It is hypothesized that the network formation is correlated with altered joint metabolism and represents regressive changes in cartilage matrix as a result of external mechanical forces. Using a variety of methods, the possibility of the network being an artifact of histological processing could virtually be ruled out. As there are so far only few and contradictory reports on the interlacunar network of articular cartilage, its precise biological significance remains to be established.


Uniform aligned bioconjugation of biomolecule motifs for integration within microfabricated microfluidic devices.
Full details and a step-by-step guide suitable for printing proteins aligned to micron-sized sensors and subsequent integration and alignment of microfluidic structures are presented. The precise alignment and grafting of micron-sized biomolecule patterns with an underlying substrate at predefined locations is achieved using a novel semi-automated microcontact printer. Through integration of optical alignment methods in the x, y, and z directions, uniform contact of micron-sized stamps is achieved. Feature compression of the stamp is avoided by fine control of the stamp during contact. This printing method has been developed in combination with robust, compatible bioconjugate chemistry for patterning of a dextran-functionalized silicon oxide substrate with a NeutrAvidin-"inked" stamp and subsequent incubation with a biotin-functionalized protein. The bioconjugate chemistry is such that uniform coverage of the protein (without denaturation) over the printed motif is obtained and reproduction of the initial mask shape and dimensions is achieved. Later integration with a microfluidic structure aligned with the printed motif on the substrate is also described.


DNM2 levels normalization improves muscle phenotypes of a novel mouse model for moderate centronuclear myopathy.
Dynamin 2 (DNM2) is a ubiquitously expressed GTPase regulating membrane trafficking and cytoskeleton dynamics. Heterozygous dominant mutations in DNM2 cause centronuclear myopathy (CNM), associated with muscle weakness and atrophy and histopathological hallmarks as fiber hypotrophy and organelles mis-position. Different severities range from the severe neonatal onset form to the moderate form with childhood onset and to the mild adult onset form. No therapy is approved for CNM. Here we aimed to validate and rescue a mouse model for the moderate form of DNM2-CNM harboring the common DNM2 R369W missense mutation. Dnm2R369W/+ mice presented with increased DNM2 protein level in muscle and moderate CNM-like phenotypes with force deficit, muscle and fiber hypotrophy, impaired mTOR signaling, and progressive mitochondria and nuclei mis-position with age. Molecular analyses revealed a fiber type switch toward oxidative metabolism correlating with decreased force and alteration of mitophagy markers paralleling mitochondria structural defects. Normalization of DNM2 levels through intramuscular injection of AAV-shDnm2 targeting Dnm2 mRNA significantly improved histopathology and muscle and myofiber hypotrophy. These results showed that the Dnm2R369W/+ mouse is a faithful model for the moderate form of DNM2-CNM and revealed that DNM2 normalization after a short 4-week treatment is sufficient to improve the CNM phenotypes.


Immune and nonimmune effector functions of IgG3 mouse monoclonal antibody R24 detecting the disialoganglioside GD3 on the surface of melanoma cells.
R24, an IgG3 mouse monoclonal antibody reactive with the disialoganglioside GD3, was found to be a potent mediator of human complement cytotoxicity and human effector cell cytotoxicity. Cytotoxicity correlated with the degree of antibody binding (GD3 cell surface expression) for each of the melanoma cell lines and melanocyte cell cultures tested. Melanoma cell lines binding low amounts of R24 (low GD3 cell surface expressors) were not lysed in R24-directed immune reactions, suggesting that a threshold number of R24 molecules bound per cell is necessary to initiate these cytotoxic mechanisms. Since both complement- and cell-mediated reactions lysed the same subpopulations of cells in each cell line, both mechanisms appeared to depend on similar threshold quantities of bound R24 molecules. However, due to the heterogeneity of R24 binding in each cell line, the numerical value for this threshold could not be determined. Only in cell lines binding greater than 10(7) R24 molecules per cell were greater than 90% of the cells lysed. Normal melanocytes in culture were not lysed by R24-directed immune mechanisms, due to their low GD3 expression, indicating that monoclonal antibodies such as R24 may show tumor specificity with regard to effector functions even though normal cells express the relevant antigen. In contrast to the potent in vitro activity of R24, treatment of nu/nu mice bearing human melanoma grafts resulted in tumor inhibition only when started within 3 days of tumor cell inoculation. No effect was seen on established tumors. Thus, this in vivo mouse model failed to predict the clinical and pathological findings observed in treatment trials of R24 in human melanoma patients--urticaria involving skin metastases, cellular infiltration of tumor tissue, and tumor regression. In addition to activating immunologic effector functions, R24 had direct effects on melanoma cells, blocking their ability to attach to surfaces and causing tumor cell aggregation. These effects were again related to the number of R24 molecules bound to the cell surface; no aggregation was seen with cell lines binding less than 4 X 10(5) molecules per cell. Both immune and nonimmune effector functions may be involved in the tumor inhibitory activity of R24 in humans.


The effectiveness of school-based physical activity interventions for adolescent girls: A systematic review and meta-analysis.
Physical activity (PA) decreases during the transition from childhood to adolescence, with larger declines observed in girls. School-based interventions are considered the most promising approach for increasing adolescents' PA levels although, it is unclear which types of school-based interventions have the greatest impact. The objective of this systematic review is to assess the impact and design of school-based PA interventions targeting adolescent girls. A systematic search was conducted using four electronic databases (PubMed, Web of Science, SPORTDiscus and PsychInfo). This systematic review was registered with PROSPERO (Registration number: CRD42016037428) and PRISMA guidelines (2009) were followed throughout. Twenty studies were identified as meeting the inclusion criteria and were included in a narrative synthesis. Seventeen studies were eligible for inclusion in a meta-analysis. There was a significant small positive treatment effect for school-based PA interventions for adolescent girls (k=17, g=0.37, p<0.05). After an outlier was removed (residual z=7.61) the average treatment effect was significantly reduced, indicating a very small positive effect (k=16, g=0.07, p=0.05). Subgroup analysis revealed very small significant effects for multi-component interventions (k=7, g=0.09, p<0.05), interventions underpinned by theory (k=12, g=0.07, p<0.05), and studies with a higher risk of bias (k=13, g=0.09, p<0.05). Intervention effects were very small which indicates that changing PA behaviors in adolescent girls through school-based interventions is challenging. Multi-component interventions and interventions underpinned by theory may be the most effective approaches to positively change adolescent girls' PA.


PYY-mediated fatty acid induced intestinal differentiation.
An essential process for fatty acid digestion, absorption and assimilation is the constant replacement of mature intestinal epithelial cells by differentiating stem cells. Free fatty acids (FFA) and PYY may act in concert to alter mucosal cell differentiation through the cytoskeletal-extracellular matrix interactions. PYY induced expression of tetraspanins and intestinal fatty acid binding protein (I-FABP) may be part of a mechanism whereby FFA modulate expression of differentiation dependent proteins in the mucosa. This modulation provides a means for FFA to act as signal molecules in the feedback regulation of their own assimilation.


Global and regional differences in cerebral blood flow after asphyxial versus ventricular fibrillation cardiac arrest in rats using ASL-MRI.
Both ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest (ACA) are frequent causes of CA. However, only isolated reports compared cerebral blood flow (CBF) reperfusion patterns after different types of CA, and even fewer reports used methods that allow serial and regional assessment of CBF. We hypothesized that the reperfusion patterns of CBF will differ between individual types of experimental CA. In a prospective block-randomized study, fentanyl-anesthetized adult rats were subjected to 8min VFCA or ACA. Rats were then resuscitated with epinephrine, bicarbonate, manual chest compressions and mechanical ventilation. After the return of spontaneous circulation, CBF was then serially assessed via arterial spin-labeling magnetic resonance imaging (ASL-MRI) in cortex, thalamus, hippocampus and amygdala/piriform complex over 1h resuscitation time (RT). Both ACA and VFCA produced significant temporal and regional differences in CBF. All regions in both models showed significant changes over time (p<0.01), with early hyperperfusion and delayed hypoperfusion. ACA resulted in early hyperperfusion in cortex and thalamus (both p<0.05 vs. amygdala/piriform complex). In contrast, VFCA induced early hyperperfusion only in cortex (p<0.05 vs. other regions). Hyperperfusion was prolonged after ACA, peaking at 7min RT (RT7; 199% vs. BL, Baseline, in cortex and 201% in thalamus, p<0.05), then returning close to BL at ∼RT15. In contrast, VFCA model induced mild hyperemia, peaking at RT7 (141% vs. BL in cortex). Both ACA and VFCA showed delayed hypoperfusion (ACA, ∼30% below BL in hippocampus and amygdala/piriform complex, p<0.05; VFCA, 34-41% below BL in hippocampus and amygdala/piriform complex, p<0.05). In conclusion, both ACA and VFCA in adult rats produced significant regional and temporal differences in CBF. In ACA, hyperperfusion was most pronounced in cortex and thalamus. In VFCA, the changes were more modest, with hyperperfusion seen only in cortex. Both insults resulted in delayed hypoperfusion in all regions. Both early hyperperfusion and delayed hypoperfusion may be important therapeutic targets. This study was approved by the University of Pittsburgh IACUC 1008816-1.


Consequences of teleworking using the internet among married working women: Educational careers investigation.
Nowadays, women constitute a considerable part of employees in the society that according to the multiple roles that they play (mother, wife, employee), more flexibility is needed in their career affairs. This study aimed to investigate the effects of teleworking using the Internet on married working women working in educational settings (advantages and disadvantages of teleworking). For this purpose, this study includes qualitative and quantitative parts with samples including 16 and 404 married women working in educational settings (i.e. school and university). In the qualitative part that interviews were conducted with 16 married women who were selected as experts in educational occupations, the findings showed that teleworking brings six major advantages for women. These six advantages are economic, psychological, health, family, organizational, and educational. Moreover, when the qualitative part was ended, the researchers prepared a questionnaire according to the findings and selected 404 married and working women in educational settings to rate advantages and disadvantages of teleworking during Covid-19 pandemic and according to qualitative results, teleworking has disadvantages such as role conflict, lack of face-to-face position, and reworking. The quantitative results showed that participants' feedback was positive in six advantages and two variables of family and psychological were the most important variables among teleworking advantages (p < .05). According to the findings of this study, it can be concluded that teleworking has a considerable effect on family cohesion and psychological security of women. Therefore, according to the current status of the society (covid-19), facilities should be considered for married women.


Rhythmic firing of neurons in the medulla of conscious freely behaving rats: rhythmic coupling with baroreceptor input.
Recent investigations emphasized the importance of neural control of cardiovascular adjustments in complex behaviors, including stress, exercise, arousal, sleep-wake states, and different tasks. Baroreceptor feedback is an essential component of this system acting on different time scales from maintaining stable levels of cardiovascular parameters on the long-term to rapid alterations according to behavior. The baroreceptor input is essentially rhythmic, reflecting periodic fluctuations in arterial blood pressure. Cardiac rhythm is a prominent feature of the autonomic control system, present on different levels, including neuron activity in central circuits. The mechanism of rhythmic entrainment of neuron firing by the baroreceptor input was studied in great detail under anesthesia, but recordings of sympathetic-related neuron firing in freely moving animals remain extremely scarce. In this study, we recorded multiple single neuron activity in the reticular formation of the medulla in freely moving rats during natural behavior. Neurons firing in synchrony with the cardiac rhythm were detected in each experiment (n = 4). In agreement with prior observations in anesthetized cats, we found that neurons in this area exhibited high neuron-to-neuron variability and temporal flexibility in their coupling to cardiac rhythm in freely moving rats, as well. This included firing in bursts at multiples of cardiac cycles, but not directly coupled to the heartbeat, supporting the concept of baroreceptor input entraining intrinsic neural oscillations rather than imposing a rhythm of solely external origin on these networks. It may also point to a mechanism of maintaining the basic characteristics of sympathetic neuron activity, i.e., burst discharge and cardiac-related rhythmicity, on the background of behavior-related adjustments in their firing rate.


Gliomatosis cerebri: a review of 296 cases from the ANOCEF database and the literature.
Gliomatosis cerebri (GC) is a rare disease, defined as a diffuse neoplastic glial cell infiltration of the brain. Diagnosis and management of GC are difficult. This study analyzed 296 individual cases (90 patients followed through the ANOCEF network, and 206 cases from the literature), aged 1 month to 85 years (median 42), sex ratio=1.31. Median survival was 14.5 months. It was higher for patients younger than 42 years (17 months vs. 13 months), with performance status>or=80 (27 months vs. 9 months), low grade gliomatosis (grade 2=20 months, grade 3=11.5 months, grade 4=8.5 months), oligodendroglial subtype (36 months compared to 14 months for mixed GC and 11 months for astrocytic GC). Male population was younger (median 39 years vs. 45), had a higher incidence of oligodendroglial GC (22% vs. 13%), which may explain their better prognosis (median survival 17 months vs. 11.5 months) than female population. Despite a high rate of stabilization, the impact on survival of whole brain radiotherapy, which carries the risk of severe toxicity, is still unclear. Up-front chemotherapy benefit to some patients and may be preferred to whole brain radiotherapy. However, the many bias of such retrospective heterogeneous data claim for multicentric clinical trials in this rare disease.


Glutamine requirements in the generation of lymphokine-activated killer cells.
The role of glutamine (GLN) in the generation of lymphokine-activated killer (LAK) cell activity was investigated. LAK cells were derived from healthy donors and peripheral blood mononuclear cells (PBMC) were obtained using either unseparated PMBC or DR(-) CD3(-) CD16(+) CD56(+) enriched cells. PBMC were cultured for 6 or 10 days in medium supplemented with recombinant interleukin-2 (rlL-2; 100 U/ml) in the presence of different concentrations of GLN. K562 (natural killer-NK-sensitive targets), 1301 and U-937 (NK-resistant targets) cells were used as targets in the cytotoxic assays. Furthermore, the limiting dilution (LD) culture system was applied as an alternative to the bulk cell culture system. It was found that GLN affects the lytic potential of cultured cells while the frequency of responding cells did not significantly differ between the compared cell cultures performed in the presence of different amounts of GLN. Data on cell proliferation with IL-2 stimulation showed significant differences in cultures performed in the presence or absence of GLN. The results of present investigation suggest a supportive role of GLN in the generation of LAK cells. GLN deficit affects LAK cell killing activity by limiting the number of generated effector cells while acquisition of broad-range killing capacity was not affected.


Impacts of percutaneous nephrolithotomy on the estimated glomerular filtration rate during the first few days after surgery.
Long-term effects of percutaneous nephrolithotomy (PCNL) on renal function have been evaluated in many studies but there are little data on the renal effects of PCNL immediately after surgery in human patients. The aim of this study was to evaluate estimated glomerular filtration rate (GFR) during the first few days after PCNL. From July to September 2008, we gathered preoperative and postoperative serum creatinine data of all the patients who underwent PCNL at our center. Children and patients who received transfusion during surgery were excluded. Creatinine clearance was estimated by Cockcroft-Gault equation and was used to estimate GFR. 94 patients met the inclusion criteria. The mean ± SD of creatinine clearance by Cockcroft-Gault equation was 87.5 ± 32.2 cc/min before operation. It decreased to 85.5 ± 29.4 cc/min, 77.0 ± 26.8 cc/min and 75.9 ± 25.0 cc/min at 6, 24 and 48 h after operation and then increased slightly to 81.9 ± 26.4 cc/min 72 h after operation. Renal GFR decreases immediately after PCNL reaches a nadir 48 h after operation, and then, increases slowly. It seems advisable to avoid factors that can bear a negative influence on renal function during the early postoperative period such as nephrotoxic drugs, contrast agents, shock wave lithotripsy and Re-PCNL.


Primitive neuroectodermal tumor: CT, MRI, and angiographic findings.
Primitive neuroectodermal tumors (PNETs) are uncommon CNS neoplasms found usually in the first decade of life. This article presents a proven case of this lesion in a 14-month-old boy located deep in the left frontal lobe. This lesion was studied by CT, MRI, and cerebral angiography. The radiologic findings of this tumor were assessed and compared with those cases reported in the medical literature.


Multifocal Ewing's sarcoma of the brain, calvarium, leptomeninges, spine and other bones in a child.
Ewing's sarcoma (ES) is a malignant osseous neoplasm that mostly affects children and young male adults, and usually presents as a solitary bony lesion. Multifocal ES of the central nervous system is extremely rare, with an incidence ranging from 1.1% to 4.3%. Clinically, ES may mimic osteomyelitis. In this report, we describe the case of an 11-year-old boy who had multiple calvarial, leptomeningeal, spinal and various other bony lesions of ES, which were diagnosed radiologically and histopathologically. To the best of our knowledge, this is the first time that multiple brain, calvarial and spinal lesions of ES in a single patient have been reported in the English-language literature. We discuss possible mechanisms and differential diagnoses for this rare pathology.


The sensitizers nickel sulfate and 2,4-dinitrofluorobenzene increase CD40 and IL-12 receptor expression in a fetal skin dendritic cell line.
Dendritic cells (DCs) are antigen-presenting cells (APCs) capable of capturing haptens and to process and present them to T lymphocytes. In order to sensitize T cells for contact hypersensitivity (CHS), skin DCs suffer a maturation process with modifications on their surface molecules. The aim of this work was to evaluate changes induced by two contact sensitizers, 2,4-dinitrofluorobenzene (DNFB) and nickel sulfate (NiSO4), and a non-sensitizer 2,4-dichloronitrobenzene (DCNB), on the protein levels of two activation markers, CD40 and IL-12 receptor (IL-12R), in a mouse skin dendritic cell line (FSDC). The expression of CD40 and IL-12R proteins was evaluated by western blot assay and direct immunofluorescence microscopy. The results showed that CD40 and IL-12R expression increased significantly after cell exposure to NiSO4 and DNFB, although DNFB exhibited a stronger activity. There was no effect with DCNB. The epidermal cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), also used in the experiments, slightly increased the expression of both CD40 and IL-12R and when tested together with the sensitizers the effect was partially additive. The results suggest that the sensitizers DNFB and NiSO4 are directly involved on the changes of the surface markers CD40 and IL-12R in skin DCs, during the sensitization phase of CHS, and this effect may be enhanced by GM-CSF. In contrast, no effect was observed with DCNB.


A visual monitor for piped oxygen supply systems to anaesthetic machines.
A pressure sensitive recording device for monitoring piped oxygen systems supplying anaesthetic machines is described. The monitor displays a colour change and is powered by pressure of oxygen from the piped oxygen supply line.


Metabolism of adriamycin in hepatocytes isolated from the rat and the rabbit.
Metabolism of adriamycin, an anthracycline antibiotic, was characterized in both rat and rabbit hepatocytes under aerobic conditions. Adriamycin was the predominant fluorescent species within the cell in hepatocytes from both the rat and the rabbit. In the rat hepatocyte, the primary intracellular metabolite was deoxyadriamycin aglycone, while significant levels of deoxyadriamycinol aglycone were also synthesized; little adriamycinol was observed in the cells or the incubation medium. In contrast, in the rabbit hepatocyte, significant levels of adriamycinol as well as deoxyadriamycinol aglycone were formed; deoxyadriamycinol aglycone was the primary intracellular metabolite while low levels of deoxyadriamycin aglycone were observed. The relative formation of deoxyadriamycinol aglycone and deoxyadriamycin aglycone suggests that adriamycinol may be metabolized more effectively to the deoxyaglycone derivative than the parent drug. Conjugates of adriamycin were not observed in hepatocytes from either the rat or the rabbit or in the incubation medium.


Genetic variation of Fusarium oxysporum isolates forming fumonisin B(1) and moniliformin.
Thirty single-spore isolates of a toxigenic fungus, Fusarium oxysporum, were isolated from asparagus spears and identified by species-specific polymerase chain reaction (PCR) and translation elongation factor 1-α (TEF) sequence analysis. In the examined sets of F. oxysporum isolates, the DNA sequences of mating type genes (MAT) were identified. The distribution of MAT idiomorph may suggest that MAT1-2 is a predominant mating type in the F. oxysporum population. F. oxysporum is mainly recognised as a producer of moniliformin-the highly toxic secondary metabolite. Moniliformin content was determined by high-performance liquid chromatography (HPLC) analysis in the range 0.05-1,007.47 μg g(-1) (mean 115.93 μg g(-1)) but, also, fumonisin B(1) was detected, in the concentration range 0.01-0.91 μg g(-1) (mean 0.19 μg g(-1)). There was no association between mating types and the mycotoxins biosynthesis level. Additionally, a significant intra-species genetic diversity was revealed and molecular markers associated with toxins biosynthesis were identified.


Absence of radiographic progression of hip arthritis during infliximab treatment for ankylosing spondylitis.
This study aims to examine the impact of long-term treatment with the anti-TNF antibody infliximab on radiographic progression of hip arthritis in ankylosing spondylitis. Anteroposterior X-rays of the pelvis obtained at baseline from consecutive patients with ankylosing spondylitis and bilateral hip arthritis were compared with X-rays obtained after 6 ± 2.5 years (mean ± SD) of continuous infliximab treatment. Analysis was performed by the Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-h) scoring system (min 0, max 4). Hip joint space width was also assessed by the average of measurements at three distinct sites between the acetabulum and femoral head. In 23 patients with active disease (21 men, mean age and disease duration of 45 and 16 years, respectively), the BASRI-h score at baseline was 1 in 7, 2 in 16, 3 in 16, and 4 in 7 hips (including two arthroplasties). Individual BASRI-h scores at baseline (2.50 ± 0.86, mean ± SD) remained unchanged in all patients at end of follow-up. At baseline, the average width of the whole joint space (3.56 ± 0.70 mm, n = 44) was not associated with disease activity measurements but negatively correlated with BAS functional index (Spearman r = -0.5, P = 0.007). After 2-10 years of infliximab treatment, the average width of the whole joint space in these patients (3.59 ± 0.79 mm) was not reduced. These results suggest that radiographic progression of hip arthritis in ankylosing spondylitis may be arrested during infliximab treatment.


Food contact of paper and plastic products containing SiO2, Cu-Phthalocyanine, Fe2O3, CaCO3: Ranking factors that control the similarity of form and rate of release.
The paper industry is an important sector annually consuming kilotons of nanoforms and non-nanoforms of fillers and pigments. Fillers accelerate the rate of drying (less energy needed) and product cost (increasing the load of low-cost fillers). The plastic industry is another use sector, where coloristic pigments can be in nanoform, and many food containers are made of plastic. Use of paper to wrap both wet and dry food is consumer practice, but not always intended by producers. Here we compare the release behavior of different nano-enabled products (NEPs) by changing a) nanoform (NF) characteristics, b) NF load, c) the nano-enabled product (NEP) matrix, and d) food simulants. The ranking of these factors enables an assessment of food contact by concepts of analogy, specifically via the similarities of the rate and form of release in food during contact. Three types of matrices were used: Paper, plastic ((Polylactic Acid (PLA), Polyamide (PA6), and Polyurethane (PU)), and a paint formulation. Two nanoforms each of SiO2, Fe2O3, Cu-Phthalocyanine were incorporated, additionally to the conventional form of CaCO3 that is always contained in paper to reduce cellulose consumption. Tests were guided by the European Regulation EC 1935/2004 and EU 10/2011. No evidence of particle release was observed: the qualitative similarity (the form of release) was high regarding the food contact of all NEPs with embedded NFs. Quantitative similarity of releases depended primarily on the NEP matrix, as this controls the penetration of the simulant fluid into the NEP. The solubility of the NF and impurities in the simulant fluid was the second decisive factor, as dissolution of the NF inside the NEP is the main mechanism of release. This led to complete removal of CaCO3 in acidic medium, whereas Fe and Si signals remained in the paper, consistent with the low release rates in an ionic form. In our set of 16 NEPs, only one NEP showed a dependence on the REACH NF descriptors (substance, size, shape, surface treatment, crystallinity, impurities), specifically attributed to differences in soluble impurities, whereas for all others the substance of the nanoform was sufficient to predict a similarity of food contact release, without influences of size, shape, surface treatment and crystallinity.


Novel protocol for optimal utilization of HPSD approach for pulmonary vein isolation.
The efficiency of pulmonary vein isolation (PVI) depends on the durability of RF lesions. Recent studies documented sustained continuity of ablation lines, improvements in durability, and expected clinical outcomes through altered settings in duration and power. However, the ablation strategy has not been adapted to this new approach and different biophysics of lesion formation. The aim of this study was to demonstrate that by adjusting the ablation approach to the broader geometry of lesions by increasing the minimal spacing between adjacent RF, a further significant reduction of procedural time while maintaining sufficient long-term outcomes is achievable. The presented study was a prospective, observational multi-center trial. The periprocedural data were compared with data from a consecutively collected historical cohort. In total, 196 patients were included (mean age 62 ± 11 years, male 64.3%). Procedural duration, RF time, and LA dwelling time were significantly shorter in the HPSD group compared with the standard group (73 ± 26 min vs. 98 ± 36 min, p < .001; 14 ± 7 min vs. 33 ± 12 min, p < .001; and 59 ± 21 min vs. 77 ± 32 min, p < .001, respectively). Mean AF-free survival in the first year of follow-up was 304 ± 14 days in the HPSD group versus 340 ± 10 days in the standard group (log-rank p = .403). There were no statistically significant differences in the complication rates between the groups. Increasing the minimal distance between individual application points simplifies AF ablation and further reduces procedure time without negative effects on efficacy and safety. Larger studies are needed to optimally utilize this approach.


Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of the SUV3 gene results in mouse embryonic lethality.
The SUV3 gene is present in all eukaryotes and encodes an RNA/DNA helicase which operates both in mitochondria and cell nuclei. To assess its function in mammals we generated a mouse mutant strain in which the 3' part of the SUV3 gene is disrupted. The mutated allele is a hypomorph transmitted from one generation to another at a frequency about 35% lower than expected while mice homozygous for the mutation die in utero before midgestation. Using ELISA binding assays we show that human SUV3 protein interacts with human WRN and BLM helicases. The binding to BLM protein was 10-fold stronger (with a K(d) of 0.5nM) than to WRN protein (K(d) of 5nM). Silencing of the SUV3 gene in the human cell line HeLa resulted in elevation of homologous recombination as measured by the frequency of sister chromatid exchange during mitotic cell division. These results indicate that the SUV3 protein is required in mammalian development and in somatic cells participates in genome maintenance through interaction with other genome fidelity housekeepers.


Light-Induced Formation of Thymine-Containing Mercury(II)-Mediated Base Pairs.
By applying caged thymidine residues, DNA duplexes were created in which HgII -mediated base pair formation can be triggered by irradiation with light. When a bidentate ligand was used as the complementary nucleobase, an unprecedented stepwise formation of different metal-mediated base pairs was achieved.


[Resorbable interference screws. Histologic study 4.5 years postoperative].
The use of degradable implants in recent years has brought not only good results. Foreign body reactions to implantation of degradable polymers clearly curtailed the initial expectations. Bioabsorbable polymers have been used for sutures, vascular clips, and fixation implants for both intra-articular fractures and malleolar fractures. In the literature these implants are controversial. Potential benefits remain for the use of this material for interference screws if the problems of inflammation are minimal and the fixation properties are sufficient. There is no need for a second operation for removal. In one patient, 4,5 years after to implantation of an degradable interference screw (Copolymer 85/15 D,L lactide glycolide; Biologically Quiet, Instrument Makar, Inc. Mount Hope, MI 48864, USA) we took an biopsy and made histological examinations. No foreign body reaction or inflammation signs could be detected.


Ultrasonography for Skin and Soft Tissue Infections, Noninfectious Cysts, Foreign Bodies, and Burns in the Critical Care Setting.
There are multiple opportunities for the use of ultrasonography in the diagnosis of skin and soft tissue differentials. Ultrasonography is inexpensive, easily reproducible, and able to provide real-time data in situations where condition changes and progression are common. Not only does bedside ultrasonography provide the clinician an in-depth look beyond epidermal structures into body cavities, it remains a safe, nonionizing radiating, effective, cost-efficient, reliable, and accessible tool for the emergency management of life- and limb-threatening integumentary infections. Unnecessary invasive procedures are minimized, providing improved patient outcomes. Integumentary abnormalities secondary to trauma, surgery, and hospitalization are common among critical care patients. This article provides a brief overview and evidence-based recommendations for the use of ultrasonography in the critical care setting for integumentary system conditions, including common skin and soft tissue differentials, foreign bodies, and burn depth assessment.


Immunogenicity Rates After SARS-CoV-2 Vaccination in People With End-stage Kidney Disease: A Systematic Review and Meta-analysis.
Adults receiving dialysis treatment have a higher likelihood of death when infected with SARS-CoV-2 than adults not receiving dialysis treatment. To date, the immune response of people receiving dialysis after SARS-CoV-2 vaccination has not been systematically discussed. To assess immunogenicity rates in people with end-stage kidney disease (ESKD) receiving SARS-CoV-2 vaccines, explore postvaccination potential risk factors for nonresponse, and assess whether receiving dialysis is associated with different antibody response rates compared with the nondialysis population. This systematic review and meta-analysis used articles from PubMed, Medline, and Embase published before July 30, 2021, as well as articles in the medRxiv preprint server. Studies that evaluated the immunogenicity rate according to the postvaccine antibody response rate in patients with ESKD receiving dialysis were selected. The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A random-effects model was used. Two independent reviewers conducted the literature search and extracted the data. The primary outcome was the pooled antibody postvaccine response rates in individuals with ESKD. The secondary outcomes were pooled response rates in individuals receiving and not receiving dialysis. Subgroup analysis and meta-regression were conducted to identify the sources of heterogeneity. A total of 32 studies were included. The overall immunogenicity rate of the dialysis group was 86% (95% CI, 81%-89%). Meta-regression showed a significant difference was detected in the postvaccine response rate on the basis of prevalence of diabetes (regression coefficient, -0.06; 95% CI, -0.10 to -0.02; P = .004). Compared with nondialysis controls, patients in the dialysis group had a lower response rate after the first (relative risk [RR], 0.61; 95% CI, 0.47-0.79; I2 = 70.2%) and second (RR, 0.88; 95% CI, 0.82-0.93; I2 = 72.2%) doses, with statistically significantly increased RR between first and second doses (P = .007). These findings suggest that the immunogenicity rate among patients receiving dialysis was 41% after the first dose and 89% after the second dose. Diabetes might be a risk factor for nonresponse in the dialysis population. Patients receiving dialysis had a poorer antibody response rate than did individuals not receiving dialysis, particularly after the first dose.


Achieving Healthy NC 2030 Goals: Life Expectancy.
The following is a review of policies related to life expectancy indicators in North Carolina as highlighted by authors in this issue. It is not an endorsement of any policy or bill; it is meant to serve as a resource for policy-makers, health care stakeholders, and other readers of the NCMJ.


Use of the C-terminal octapeptide of cholecystokinin in clinical radiology: II. The small bowel.
The octapeptide of cholecystokinin (C8-CCK) administered by bolus (20 ng/kg) and by infusion (4 ng/kg/min for 30 minutes) doses produced significant shortening of small bowel transit time. Significantly, fewer side effects occurred with the infusion method. The problems encountered in studies of small bowel motility are discussed.


The effect of oxidized cholesterol on barrier functions and IL-10 mRNA expression in human intestinal epithelium co-cultured with dendritic cells in the transwell system.
The intestinal epithelium is exposed to oxygenated cholesterol products present in foodstuffs. In vitro studies demonstrate the effect of oxysterols on cytokine release by intestinal cells cultured alone. However, physiologically, the response of the intestinal epithelium to external agents occurs in the presence of dendritic cells (DCs). The aim of the study was to analyze the effect of 7-ketocholesterol on the barrier functions and IL-10 mRNA expression of Caco-2 cells in the presence of DCs, and secondly, on IL-10 mRNA expression in DCs. Caco-2 cells were co-cultured with monocyte-derived dendritic cells and induced with 7-ketocholesterol in a transwell system. DCs did not affect the transepithelial electrical resistance (TER) of the Caco-2 cell monolayer, but increased IL-10 mRNA expression in Caco-2 cells. 7-ketocholesterol decreased the TER of Caco-2 cells co-cultured with DCs and diminished IL-10 mRNA expression in Caco-2 cells induced by the presence of DCs. IL-10 mRNA expression fell in DCs co-cultured with Caco-2 cells after treatment with 7-ketocholesterol. Oxidized cholesterols present in gut mucosa may contribute to the decrease of epithelial barrier functions and the inappropriate development of an inflammatory response to food compounds.


Comparative sensitivities of avian neural esterases to in vitro inhibition by organophosphorus compounds.
The inhibitory power of organophosphorus compounds in vitro was compared against neurotoxic esterase (also known as neuropathy target esterase, NTE), acetylcholinesterase and carboxylesterase activities in brains from chickens, turkeys, quail and rats. Brains from the species most susceptible to clinical signs of organophosphorus-induced delayed neuropathy (chicken, turkey) contained more NTE than did rat and quail. Higher concentrations of organophosphorus compounds were required to inhibit rat NTE and quail acetylcholinesterase than were necessary for inhibition of these enzymes in chicken and turkey brains. Total carboxylesterase and acetylcholinesterase activities were less in rats than in the avian species.


Utilization of a modified Clavien Classification System in reporting complications after ultrasound-guided percutaneous nephrostomy tube placement: comparison to standard Society of Interventional Radiology practice guidelines.
To report our results on percutaneous nephrostomy (PCN) and classify our complications with the Standard of Practice Committee of the Society of Interventional Radiology guidelines and the modified Clavien Classification System (CCS). Three hundred eighty-nine PCN insertions were performed in 322 patients (224 men and 98 women) at our institution. PCN insertion was performed under ultrasound for dilated pelvicalyceal system and ultrasound/fluoroscopy for nondilated system. PCN was considered successful if the catheter was drained urine spontaneously. Number of complications was registered. Primary successful PCN insertion was achieved in 368 of the 389 procedures (94.6%). The success rates for nondilated and dilated systems were 82.7% and 96.4%, respectively. Major complications occurred in 9.6% and minor complications in 9.9% according to the Society of Interventional Radiology. According to the modified CCS grades I, II, III, IV, and V was 9.9%, 1.2%, 6.8%, 1.2%, and 0.3%, respectively. Age, grade of the hydronephrosis, serum creatinine levels, and mean hemoglobin levels were statistically significant parameters for the occurrence of complications on univariate analysis. The nondilated system has statistically significant parameters affecting the complication rates on multivariate analysis (P = .001, odds ratio [OR] = 6.1, 95% confidence interval [CI] = 2-18.4). Percutaneous nephrostomy is a well-known procedure in the treatment of temporary or permanent drainage of an obstructed system. It is very important to define the complications related to interventions for interpretation of clinical comparisons more accurately. Modified CCS is a reproducible system to evaluate the complications.


Supramolecular assembly of poly(β-cyclodextrin) block copolymer and benzimidazole-poly(ε-caprolactone) based on host-guest recognition for drug delivery.
A well-defined double hydrophilic poly(β-cyclodextrin)-containing diblock copolymer PEG-b-PCD was synthesized by atom transfer radical polymerization (ATRP). Complex micelles with defined core-shell structure were formed based on the host-guest interactions between poly(β-cyclodextrin) block copolymer and benzimidazole modified poly(ε-caprolactone) (BM-PCL). The hydrophobic PCD/BM-PCL resided in the core of micelles, while the hydrophilic poly(ethylene glycol) (PEG) chains acted as the micelles shell. The micelles exhibited regular spheres with diameter of about 255nm. The drug loading efficiency of micelles for doxorubicin (DOX) was high due to the hydrophobic core containing poly(β-CD) and PCL. The in vitro release demonstrated that DOX-loaded polymer micelles exhibited an enhanced sustained manner after an initial burst release. The release of drugs was accelerated as the pH reduced from 7.0 to 2.0 and the temperature increased from 25 to 37°C. These results indicate that the complex micelles have potential applications in controlled drug delivery.


Role of mitochondria in serum withdrawal-induced apoptosis of immortalized neuronal precursors.
The intracellular mechanisms controlling apoptosis in immature neurons are still largely unknown. Taking immortalized hippocampal neuronal precursors (mouse cell line HN9.10e) as a model, we have analyzed the cellular events associated to apoptosis induced by serum deprivation. We observed translocation of Bax from cytosol to mitochondria after 1 h of serum withdrawal followed, 2 h later, by cytochrome c release from mitochondria. These events occurred without mitochondrial membrane potential loss nor mitochondrial calcium raise. As calcium is implicated in several cell death pathways, we analyzed intracellular calcium levels after longer periods of serum deprivation. After 6 h, an increase of cytosolic Ca2+ was detected in HN9.10e cells loaded with the Ca2+ indicator Fluo3-AM. This increase of calcium preceded morphological signs of apoptosis such as cell shrinkage and nuclear fragmentation, and was followed by a more pronounced raise that persisted until the terminal phases of the apoptotic process. Cells serum-deprived for 4 h and then grown in complete medium for 20 h fully recovered viability. Summarizing, in HN9.10e cells, calcium deregulation occurs in the late phases of apoptosis; earlier events involve translocation of Bax, release of cytochrome c, and maintenance of mitochondrial functionality. This allows an enlargement of the temporal window in which commitment to death is reversible.


Polymeric Nitrogen A7 Layers Stabilized in the Confinement of a Multilayer BN Matrix at Ambient Conditions.
Polymeric nitrogen, as a potential high-energy-density material (HEDM), has attracted many theoretical calculations and predictions for its potential applications, such as energy storage, propellants and explosives. Searching for an effective method to stabilize polymeric nitrogen in ambient conditions of temperature and pressure has become a hot topic. Herein, we propose a new hybrid material where polymeric nitrogen layers are intercalated in a multilayer BN matrix forming a three-dimensional structure, by means of ab initio density functional theory. It is demonstrated polymeric nitrogen layers can be stable at ambient conditions and can release tremendous energy just above 500 K, more gentle and controllable. Further calculations reveal the new hybrid material exhibits a much smaller charge transfer than that of previous reports, which not only stabilizes polymeric nitrogen layer at ambient conditions, but also favours energy releasing at milder conditions. It is also very exciting that, the weight ratio of polymeric nitrogen in new material is up to 53.84%, approximately three times higher than previous one-dimensional hybrid materials. The energy density (5.4 KJ/g) also indicates it is a promising HEDMs candidate. Our findings provide a new insight into nitrogen-based HEDMs capture and storage.


Size-specific mortality patterns in two species of forest floor Collembola.
Forest floor populations of Orchesella cincta (L) and Tomocerus minor (Lubbock) (Collembola; Entomobryidae) have been sampled over two generations and from length frequency distributions survivorship curves were constructed for each generation. Size-specific mortality rates were computed from size-specific survivorship data. The results reveal an asymmetrically U-shaped mortality pattern, with disproportionally high juvenile mortality. The pattern changes from one generation to the next, in particular the post-hatching mortality. Evidence from behavioural ecological research on a Collembola-specialized ground beetle is cited in favour of the hypothesis that size-specific mortality patterns are moulded by size-specific predation.


Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women.
Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and spontaneous preterm labor and delivery. We conducted a secondary analysis of inflammatory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women. Women with concentrations of the inflammatory markers sTNFR2, CHI3L1, and IL18BP in the highest quartile before 24 weeks gestation and women with anti-angiogenic factors sEndoglin and sFlt-1/PlGF ratio in the highest quartile at 28-33 weeks gestation had an increased relative risk of preterm birth. Mediation analysis further supported a potential causal link between early inflammation, subsequent angiogenic dysregulation detrimental to placental vascular development, and earlier gestational age at delivery. Interventions designed to reduce the burden of preterm birth may need to be implemented before 24 weeks of gestation.


Appropriate scenarios for mercury emission control from coal-fired power plant in Thailand: emissions and ambient concentrations analysis.
Optimum control of mercury released from the coal-fired power plant is evaluated by determining its efficiency and appropriateness in reducing emissions and ambient air concentrations. The 2400 MW power plant fueled by lignite located in Thailand is demonstrated in this study. Emissions of mercury from the coal-fired power plant are calculated under 3 major scenarios. The first scenario is the amount of mercury released under the existing operation of the power plant. Emission rate of mercury is calculated as 41 g/h which indicates a co-benefit of mercury removal from the installation of existing conventional air pollution treatment systems (electrostatic precipitator and wet flue gas desulfurization) as compare with the 2nd scenario of without equipping of air pollution control devices at the power plant (374 g/h of mercury emission). Adding controlling measures to existing operation of the power plant can lead to decreasing of mercury emissions at different levels. The relationship between changing of emissions affected to ambient air concentrations of mercury is evaluated using the CALPUFF air dispersion model. Results indicate small decreasing of predicted ambient concentrations after applying additional mercury control measures to the BAU of the power plant. This study reveals the co-benefit of existing air pollution treatment devices in controlling mercury emission. It also illustrates that the efficiency and appropriateness of current air pollution control system is in an optimal and acceptable levels in mercury control. Finding and methodology in this study can be used as a case study in quantitative evaluation of the effectiveness and appropriateness of environmental control mitigation measures added to the existing operations. It clearly illustrates the need to analyze the co-benefit of current air pollution control system towards the accomplishment on controlling emissions of other emerging air pollutants which will provide the best optimum air pollution control to the emission source.


Utility of Magnetic Resonance Imaging in the Evaluation of Intraoperatively Confirmed Pelvic Adhesions.
The aim of this study was to evaluate the ability of magnetic resonance imaging (MRI) to identify pelvic adhesions. This was an institutional review board-approved retrospective analysis. Ninety-nine patients met inclusion criteria and constituted our study population. patients who underwent MRI and subsequent gynecologic abdominal surgery within 6 months after MRI. All imaging and operative reports were reviewed for the presence of pelvic adhesions by independent and blinded specialists. The findings were compared to calculate MRI sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the evaluation of pelvic adhesions. The specificity of MRI in the detection of pelvic adhesions was greater than 90% in all locations with the exception of the posterior cul-de-sac. Accuracy was highest in the anterior cul-de-sac at 88%. The positive predictive value was greater than 85% for prediction of non-location-specific adhesions. Magnetic resonance imaging is very specific in the evaluation of pelvic adhesions.


Targeting ferroptosis in renal cell carcinoma: Potential mechanisms and novel therapeutics.
Renal cell carcinoma (RCC) is an increasingly prevalent urologic malignancy that impacts human health worldwide. Surgery is an effective strategy for early RCC treatment, but advanced RCC is resistant to chemotherapy, thus development of other potential therapeutic strategies is urgent. Ferroptosis is a newly defined form of programmed cell death characterized by accumulation of iron-dependent lipid peroxides and plays a crucial role in the tumor progression and drug resistance. Recent studies have shown that ferroptosis participates in RCC progression and chemoresistance. Therefore, identifying the potential role of ferroptosis in RCC could develop novel therapeutic targets and clinical markers for this disease. This review concisely summarizes the regulatory role of iron, amino acid, and lipid metabolism in ferroptosis, as well as discusses the relationship between ferroptosis and RCC, and details the role of ferroptosis in tumor progression, which indicates that various ferroptosis regulators are dysregulated in RCC and exert paradoxical effects, either tumor-suppressive or oncogenic. These ferroptosis-related regulators are expected to be used as clinical markers for RCC prognosis. Thus, targeting these regulators to trigger ferroptosis may be the key to the development of potential therapeutic strategies for this disease.


Cryptotanshinone (Dsh-003) from Salvia miltiorrhiza Bunge inhibits prostaglandin E2-induced survival and invasion effects in HA22T hepatocellular carcinoma cells.
Human hepatocellular carcinoma (HCC) is currently the second most common cancer and one of the leading causes of cancer-related mortality in Taiwan. Previous reports show that the expression of (E-type prostaglandin 2) EP2 and (E-type prostaglandin 4) EP4 are elevated in HCC and further demonstrate that Prostaglandin E2 (PGE2) induces HA22T cell proliferation and metastasis through EP2 and EP4 receptor. Danshen (root of Salvia miltiorrhiza Bunge) is a very important and popular traditional Chinese herbal medicine which is widely and successfully used against breast cancer, leukemia, pancreatic cancer, and head and neck squamous carcinoma cells. In this study, we used Cryptotansinone (Dsh-003) (MW 269.14) from Danshen to investigate their effect and corresponding mechanism of action in PGE2-treated HA22T cells. Dsh-003 inhibited HA22T cell viability and further induced cell apoptosis in PGE2-treated HA22T cells. Furthermore, Dsh-003 inhibited EP2, EP4, and their downstream effector such as p-PI3K and p-Akt expression in HA22T hepatocellular carcinoma cells. We also observed that Dsh-003 blocked PGE2-induced cell migration by down-regulating PGE2-induced β-catenin expression and by up-regulating E-cadherin and GSK3-β expression. All these findings suggest that Dsh-003 inhibit human HCC cell lines and could potentially be used as a novel drug for HCC treatment.


Profiles of the acute-phase reactants C-reactive protein and ferritin related to the disease course of patients with systemic lupus erythematosus.
To obtain insight in the acute-phase response in SLE. The clinical history, SLEDAI, CRP and ferritin concentrations were analysed throughout the disease course of 10 SLE patients. During a mean follow-up of 4.8 years, 10 exacerbations (SLEDAI > or = 11) occurred. Throughout the disease course, CRP and SLEDAI correlated positively in 5 patients, whereas the correlation between SLEDAI and ferritin was positive in 7 patients. However, elevated CRP concentrations together with elevated ferritin levels were only observed during 4 exacerbations. Ferritin concentrations were exceptionately high (> 1500 microg/L) during 4 flare-ups. CRP and ferritin levels remained normal during 5 exacerbations. SLE is characterised by highly variable and unusual CRP and ferritin responses that do not always reflect the extent of inflammation in individual patients. Despite severe disease activity, ferritin levels can remain well within the normal range, limiting its clinical usefulness as a marker for disease activity.


JAKs and STATs from a Clinical Perspective: Loss-of-Function Mutations, Gain-of-Function Mutations, and Their Multidimensional Consequences.
The JAK/STAT signaling pathway plays a key role in cytokine signaling and is involved in development, immunity, and tumorigenesis for nearly any cell. At first glance, the JAK/STAT signaling pathway appears to be straightforward. However, on closer examination, the factors influencing the JAK/STAT signaling activity, such as cytokine diversity, receptor profile, overlapping JAK and STAT specificity among non-redundant functions of the JAK/STAT complexes, positive regulators (e.g., cooperating transcription factors), and negative regulators (e.g., SOCS, PIAS, PTP), demonstrate the complexity of the pathway's architecture, which can be quickly disturbed by mutations. The JAK/STAT signaling pathway has been, and still is, subject of basic research and offers an enormous potential for the development of new methods of personalized medicine and thus the translation of basic molecular research into clinical practice beyond the use of JAK inhibitors. Gain-of-function and loss-of-function mutations in the three immunologically particularly relevant signal transducers STAT1, STAT3, and STAT6 as well as JAK1 and JAK3 present themselves through individual phenotypic clinical pictures. The established, traditional paradigm of loss-of-function mutations leading to immunodeficiency and gain-of-function mutation leading to autoimmunity breaks down and a more differentiated picture of disease patterns evolve. This review is intended to provide an overview of these specific syndromes from a clinical perspective and to summarize current findings on pathomechanism, symptoms, immunological features, and therapeutic options of STAT1, STAT3, STAT6, JAK1, and JAK3 loss-of-function and gain-of-function diseases.


Magnetite Nanoparticles for Medical MR Imaging.
Nanotechnology has given scientists new tools for the development of advanced materials for the detection and diagnosis of disease. Iron oxide nanoparticles (SPIONs) in particular have been extensively investigated as novel magnetic resonance imaging (MRI) contrast agents due to a combination of favorable superparamagnetic properties, biodegradability, and surface properties of easy modification for improved in vivo kinetics and multifunctionality. This review discusses the basics of MR imaging, the origin of SPION's unique magnetic properties, recent developments in MRI acquisition methods for detection of SPIONs, synthesis and post-synthesis processes that improve SPION's imaging characteristics, and an outlook on the translational potential of SPIONs.


Oncologists' Reluctance to Use the Terms Hope and Cure: A Bibliometric Analysis of Articles From Two High-Impact Oncology Journals.
The words cure and hope are important terms in oncology, reflecting a balance of aspirations and realism for physicians and patients. Yet, some have suggested that oncologists are reluctant to use these terms. We tested this hypothesis by performing a bibliometric analysis of the frequency of use of these words in JAMA Oncology (JAMA Oncol) and the Journal of Clinical Oncology (JCO). The text of all articles in 3 categories-primary research, editorials, and narrative essays-appearing in JCO from 2000 to 2018 and in JAMA Oncol from 2015 to 2019 was analyzed. These analyses compared, across these categories, the proportion of articles containing the words cure and hope, as well as the proportion of total sentences containing these words. There were statistically significant differences in frequency of the use of the terms cure and hope as a function of the type of article published in the JCO and JAMA Oncol (2-sided P values ranging from .005 to <.001). Results were similar for both journals, with minor exceptions. Both hope and cure were used in a greater number of articles and sentences in the narrative and editorial categories than in primary research. Moreover, hope was used more often in narrative essays than in editorials. The relative reluctance to use these terms in more scientifically oriented original reports, despite concomitant improvements in oncologic outcomes, may reflect a bias worthy of future exploration.


Dopamine-beta-hydroxylase-, neurotensin-, substance P-, vasoactive intestinal polypeptide- and enkephalin-immunohistochemistry of paravertebral and prevertebral ganglia in the cat.
Para- and prevertebral ganglia of the cat were investigated for immunoreactivity (IR) against neurotensin (NT), vasoactive intestinal polypeptide (VIP), substance P (SP) and enkephalin (ENK). Dopamine-beta-hydroxylase-(DBH)-IR was studied in consecutive sections to correlate the distribution of noradrenergic/adrenergic neurons with that of peptidergic nerve fibres and cells. In paravertebral (cervical and thoracic) ganglia, NT-IR or ENK-IR nerve fibres were seen in areas in which DBH-IR fibre networks also occurred. NT-IR varicosities were often in close contact with perikarya of principal ganglionic cells on which DBH-IR varicosities also terminated. Such an association was rarely seen between ENK-IR and DBH-IR fibre baskets. NT-IR and ENK-IR fibre baskets were not found to occur around the same principal ganglionic cell. The distribution of VIP-IR and SP-IR nerve fibres did not coincide with that of DBH-IR fibres. In prevertebral ganglia (celiac-superior mesenteric and inferior mesenteric) DBH-IR or VIP-IR varicosities surrounded the majority of principal ganglionic neurons. ENK-IR or SP-IR fibres were closely associated with only a minority of the neurons; NT-IR networks were rather sparse. Some principal neurons were approached by DBH-IR fibres and by different peptide-IR fibres. In paravertebral ganglia some principal ganglionic cells contained VIP-IR, a few of which were also surrounded by NT-IR varicosities. VIP-IR perikarya in prevertebral ganglia were extremely rare. No NT-IR, SP-IR or ENK-IR principal ganglionic cells were found. Glomus-like paraganglionic cell clusters in paravertebral and prevertebral ganglia exhibited DBH-IR cell bodies.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevalence and clinical, electrocardiographic, and electrophysiologic characteristics of ventricular arrhythmias originating from the noncoronary sinus of Valsalva.
Idiopathic ventricular arrhythmias (VAs) can be rarely ablated from the noncoronary cusp (NCC) of the aorta. The purpose of this study was to investigate the prevalence and the clinical, electrocardiographic, and electrophysiologic characteristics of idiopathic NCC VAs. We studied 90 consecutive patients who underwent successful catheter ablation of idiopathic aortic root VAs (left coronary cusp [LCC] 33, right coronary cusp [RCC] 32, junction between LCC and RCC 19, NCC = 6). NCC VAs occurred in significantly younger patients (all <40 years old) and exhibited a shorter QRS duration (all but one <150 ms), smaller R-wave amplitude ratio in leads II and III (III/II), earlier ventricular activation in the His bundle (HB) region (all but one preceded QRS onset by >25 ms), and larger atrial to ventricular electrogram amplitude ratio (A/V) at the successful ablation site (all but one >1) than the other VAs. QRS morphology of the NCC VAs was similar to that of RCC VAs, but NCC VAs always exhibited a left bundle branch block and left superior (n = 1) or inferior axis (n = 5). All NCC VAs exhibited ventricular tachycardias, although premature ventricular contractions were dominant in the other VAs. NCC VAs were very rare (7%) and occurred in significantly younger patients than those among the other aortic root VAs. In a limited set of six patients, the ECG and electrophysiologic characteristics of NCC VAs were similar to those of RCC VAs but were characterized by narrower QRS duration, smaller III/II ratio, earlier ventricular activation in the HB region, and A/V ratio >1 at the successful ablation site.


Treatment of chronic viral hepatitis.
Interferon-alpha therapy has proved effective for up to 40% of patients with adult-acquired chronic hepatitis B virus (HBV) infection and for 20-25% of those with chronic hepatitis C virus (HCV) infection. Nucleoside analogues, such as lamivudine and famciclovir, are showing promise as antiviral agents for chronic HBV and the combination of interferon-alpha and ribavirin is proving to be successful therapy for 40-50% of patients with chronic HCV. In this article we review current therapy and discuss future strategies of the therapy of chronic viral hepatitis.


Salmonella infections modelling in Mississippi using neural network and geographical information system (GIS).
Mississippi (MS) is one of the southern states with high rates of foodborne infections. The objectives of this paper are to determine the extent of Salmonella and Escherichia coli infections in MS, and determine the Salmonella infections correlation with socioeconomic status using geographical information system (GIS) and neural network models. In this study, the relevant updated data of foodborne illness for southern states, from 2002 to 2011, were collected and used in the GIS and neural networks models. Data were collected from the Centers for Disease Control and Prevention (CDC), MS state Department of Health and the other states department of health. The correlation between low socioeconomic status and Salmonella infections were determined using models created by several software packages, including SAS, ArcGIS @RISK and NeuroShell. Results of this study showed a significant increase in Salmonella outbreaks in MS during the study period, with highest rates in 2011 (47.84 ± 24.41 cases/100,000; p<0.001). MS had the highest rates of Salmonella outbreaks compared with other states (36 ± 6.29 cases/100,000; p<0.001). Regional and district variations in the rates were also observed. GIS maps of Salmonella outbreaks in MS in 2010 and 2011 showed the districts with higher rates of Salmonella. Regression analysis and neural network models showed a moderate correlation between cases of Salmonella infections and low socioeconomic factors. Poverty was shown to have a negative correlation with Salmonella outbreaks (R(2)=0.152, p<0.05). Geographic location besides socioeconomic status may contribute to the high rates of Salmonella outbreaks in MS. Understanding the geographical and economic relationship with infectious diseases will help to determine effective methods to reduce outbreaks within low socioeconomic status communities.


[Critical evaluation of growth hormone treatment in children with chronic renal insufficiency].
Growth failure remains a major complication of chronic renal insufficiency in children, which greatly affects their quality of life. Based upon the data published in the literature it appears that growth hormone therapy improves growth in these children, with little secondary effects. However, some uncertainties persist concerning the safety and efficacy of this therapy, so that careful evaluations must continue.


Sc(OTf)3-catalyzed three-component cyclization of arylamines, β,γ-unsaturated α-ketoesters, and 1,3-dicarbonyl compounds for the synthesis of highly substituted 1,4-dihydropyridines and tetrahydropyridines.
A Sc(OTf)3-catalyzed three-component cyclization reaction of arylamines, β,γ-unsaturated α-ketoesters and 1,3-dicarbonyl compounds was developed to synthesize highly substituted 1,4-dihydropyridines and fused bicyclic tetrahydropyridines carrying a quaternary all-carbon center.


Selective binding of sucralfate to gastric ulcer in man.
Sucralfate is a basic aluminum salt of a sulfated disaccharide. In this study, patients with gastric ulcer were given oral multiple doses of sucralfate prior to partial gastrectomy, and binding of the drug to the ulcer lesion and to nonulcerated mucosa was estimated by chemical determination of aluminum and sulfated disaccharide. The ulcerated mucosa was found to contain, on the average, 6-7 times more sucralfate per square centimeter than the control mucosa (P less than 0.01 and less than 0.05 for aluminum and sulfated disaccharide, respectively). The high affinity of sucralfate for ulcerated mucosa, particularly the sucrose sulfate moiety, supports previous data that the beneficial effect of sucralfate in ulcer disease is due in part to complex formation between sucrose sulfate and proteins at the ulcer site.


On the promise of personalized learning for educational equity.
Students enter school with a vast range of individual differences, resulting from the complex interplay between genetic dispositions and unequal environmental conditions. Schools thus face the challenge of organizing instruction and providing equal opportunities for students with diverse needs. Schools have traditionally managed student heterogeneity by sorting students both within and between schools according to their academic ability. However, empirical evidence suggests that such tracking approaches increase inequalities. In more recent years, driven largely by technological advances, there have been calls to embrace students' individual differences in the classroom and to personalize students' learning experiences. A central justification for personalized learning is its potential to improve educational equity. In this paper, we discuss whether and under which conditions personalized learning can indeed increase equity in K-12 education by bringing together empirical and theoretical insights from different fields, including the learning sciences, philosophy, psychology, and sociology. We distinguish between different conceptions of equity and argue that personalized learning is unlikely to result in "equality of outcomes" and, by definition, does not provide "equality of inputs". However, if implemented in a high-quality way, personalized learning is in line with "adequacy" notions of equity, which aim to equip all students with the basic competencies to participate in society as active members and to live meaningful lives.


MicroRNA-30b is a multifunctional regulator of aortic valve interstitial cells.
Calcific aortic valve disease is an active process involving a wide range of pathologic changes. Valve interstitial cells are the most prevalent cells in the heart valve and maintain normal valve structure and function. MicroRNAs (miRNAs) are essential posttranscriptional modulators of gene expression, and miRNA-30b is a known repressor of bone morphogenetic protein 2-mediated osteogenesis. We hypothesized that miRNA-30b is a multifunctional regulator of aortic valve interstitial cells during calcification. To determine the role of miRNA-30b in calcific aortic valve disease, we evaluated miRNA expression in human calcific aortic valve leaflets obtained intraoperatively. Furthermore, human valve interstitial cells were evaluated with regard to miRNA-30b expression and osteogenesis by quantitative real-time polymerase chain reaction, Western blotting, flow cytometry, and alkaline phosphatase assays. In this study, we demonstrated that miRNA-30b attenuates bone morphogenetic protein 2-induced osteoblast differentiation by targeting Runx2, Smad1, and caspase-3. Transfection of a mimic of miRNA-30b led to decreases in alkaline phosphatase activity and expressions of Runx2, Smad1, and caspase-3. Furthermore, dual luciferase reporter assays confirmed that Runx2, Smad1, and caspase-3 are direct targets of miRNA-30b. We demonstrated a remarkable role of miRNA-30b in calcific aortic valve disease as a regulator of human aortic valvular calcification and apoptosis through direct targeting of Runx2, Smad1, and caspase-3. Targeting of miRNA-30b could serve as a novel therapeutic strategy to limit progressive calcification in aortic stenosis.


[Administration of cytostatic drugs by intra-arterial route. Theoretical basis].
The Authors discuss the theoretical principles of the intra-arterial administration route of antineoplastic drug in the treatment of primaries or metastatic diseases.


Differences in ocular biometry between urban and rural children matched by refractive error: the Shandong Children Eye Study.
To determine the differences in mean ocular dimensions between urban and rural children and identify possible influencing factors. This work uses previously published data from the Shandong Children Eye Study, which was based on a random cluster sampling applied to a cross-sectional school-based study design in the rural Guanxian County and Weihai city. All children underwent auto-refractometry and biometry under cycloplegia. The study included 3290 children (aged 9.35 ± 2.93 years), consisting of 888 pairs of boys and 757 pairs of girls matched by sex, age and refractive error (each pair matching one child from urban cohort with one from the rural cohort). Overall urban children were significantly taller and heavier than rural children (t-test; p < 0.001), which was confirmed for all age groups for weight. Urban ocular axial lengths were significantly longer by 0.23 mm compared to the rural population (t-test; p < 0.001), mostly in younger children and boys. Meanwhile, corneal curvatures were flatter in the urban cohort by 0.08 mm (p < 0.001). This association of axial length with urban vs rural region was reduced in magnitude by 69.7% after accounting for height. For the same, matched refractive error, children from urban regions had significantly longer eyes and flatter corneal curvature than rural children. Since corneal curvature is defined during the first 2 years of life, early environmental factors may be the source of these differences in ocular dimensions.


The presence-absence situation and its impact on the assemblage structure and interspecific relations of Pronophilina butterflies in the Venezuelan Andes (Lepidoptera: Nymphalidae).
Assemblage structure and altitudinal patterns of Pronophilina, a species-rich group of Andean butterflies, are compared in El Baho and Monte Zerpa, two closely situated and ecologically similar Andean localities. Their faunas differ only by the absence of Pedaliodes ornata Grose-Smith in El Baho. There are, however, important structural differences between the two Pronophilina assemblages. Whereas there are five co-dominant species in Monte Zerpa, including P. ornata, Pedaliodes minabilis Pyrcz is the only dominant with more than half of all the individuals in the sample in El Baho. The absence of P. ornata in El Baho is investigated from historical, geographic, and ecological perspectives exploring the factors responsible for its possible extinction including climate change, mass dying out of host plants, and competitive exclusion. Although competitive exclusion between P. ornata and P. minabilis is a plausible mechanism, considered that their ecological niches overlap, which suggests a limiting influence on each other's populations, the object of competition was not identified, and the reason of the absence of P. ornata in El Baho could not be established. The role of spatial interference related to imperfect sexual behavioral isolation is evaluated in maintaining the parapatric altitudinal distributions of three pairs of phenotypically similar and related species of Pedaliodes, Corades, and Lymanopoda.


The involvement of DNA-damage and -repair defects in neurological dysfunction.
A genetic link between defects in DNA repair and neurological abnormalities has been well established through studies of inherited disorders such as ataxia telangiectasia and xeroderma pigmentosum. In this review, we present a comprehensive summary of the major types of DNA damage, the molecular pathways that function in their repair, and the connection between defective DNA-repair responses and specific neurological disease. Particular attention is given to describing the nature of the repair defect and its relationship to the manifestation of the associated neurological dysfunction. Finally, the review touches upon the role of oxidative stress, a leading precursor to DNA damage, in the development of certain neurodegenerative pathologies, such as Alzheimer's and Parkinson's.


Overexpression of MSK1 is associated with tumor aggressiveness and poor prognosis in colorectal cancer.
Mitogen- and stress-activated protein kinase 1 (MSK1) has recently been implicated in cell proliferation and neoplastic transformation. However, the involvement of MSK1 in colorectal cancer (CRC) has not been addressed. This study aimed to evaluate the expression and potential functions of MSK1 in CRC. The MSK1 expression was investigated by immunohistochemistry, western blot and reverse transcription-polymerase chain reaction. The associations between clinicopathological characteristics and MSK1 expression were assessed. Kaplan-Meier analysis and Cox regression models were carried out. CRC cells with MSK1 knockdown or overexpression were generated. A range of experiments were performed to demonstrate MSK1's role in CRC. MSK1 was overexpressed in 148 out of 329 CRC patients. CRC patients with high MSK1 expression had shorter overall survival than those with low MSK1 (P=0.033), especially among patients with stage III tumors (P=0.005). Knockdown of MSK1 in CRC cells suppressed cell proliferation, anchorage-independent growth, migration and invasion, and promoted 5-fluorouracil chemosensitivity and intracellular NADP+/NADPH ratio. However, overexpression of MSK1 had the opposite effects. Overexpression of MSK1 is associated with poor prognosis in CRC and is connected to tumor aggressiveness. MSK1 is a potential target for new therapies and a candidate of biomarker for prognosis.


Success of Same-Day Discharge Total Hip and Knee Arthroplasty: Does Location Matter?
Same calendar day discharge (SCDD) following total joint arthroplasty is desirable for patients and surgeons alike. The aim of this study was to compare the success rate of SCDD in an ambulatory surgical center (ASC) versus hospital setting. A retrospective analysis was performed on 510 patients who underwent primary hip and knee total joint arthroplasty over a 2-year period. The final cohort was divided into 2 groups based on location of surgery: ASC (N = 255) or hospital (N = 255). Groups were matched for age, sex, body mass index, American Society of Anesthesiologists score, and Charleston Comorbidity Index. Successes of SCDD, reasons for failure of SCDD, length of stay (LOS), and 90-day readmission and complication rates were recorded. All SCDD failures were from the hospital setting (36 [65.6%] total knee arthroplasty [TKA] and 19 [34.5%] total hip arthroplasty [THA]). There were no failures from the ASC. The main causes of failed SCDD in both THA and TKA included failed physical therapy and urinary retention. Regarding THA, the ASC group had a significantly shorter total LOS (6.8 [4.4 to 11.6] versus 12.8 [4.7 to 58.0] hours, P < .001). Similarly, TKA patients had a shorter LOS in the ASC (6.9 [4.6 to 12.9] versus 16.9 [6.1 to 57.0], P < .001). Total 90-day readmission rates were higher in the ASC group (2.75% versus 0%), where all but 1 patient underwent TKA. Similarly, complication rates were higher in the ASC group (8.2% versus 2.75%), where all but 1 patient underwent TKA. TJA performed in the ASC, compared to the hospital setting, allowed for reduced LOS and improved success of SCDD.


[Molecular subtypes of urothelial carcinoma of the bladder-background and clinical relevance].
Advanced and metastatic stages of bladder cancer are associated with a poor prognosis. Therapy options are currently limited to systemic therapy with chemo- and immunotherapeutics. In order to improve individual therapy and especially to achieve a more favorable prognosis for these patients, intrinsic molecular subtypes have recently been identified in urothelial carcinoma of the bladder. This review article presents the latest developments, background, and clinical relevance of molecular subtypes in urothelial carcinoma of the bladder. The existing literature and current study data were analyzed to present and evaluate the different molecular classification systems. A focus was placed on the possible therapeutic implications of these molecular subtypes. Although promising progress has been made in the molecular subtyping of urothelial carcinoma, this classification has not yet found its way into clinical application. Multicenter prospective studies with standardized study protocols are still lacking. Previous studies differ in molecular markers, sample collection and preparation procedures, and analytical protocols. Standardization is urgently needed before guidelines can be established and targeted treatment regimens implemented. In principle, the aim should be to develop a stable and as simple as possible methodology, enabling personalized treatment based on molecular subtypes to be broadly applied, and not just in specialized expert centers.


PLG A91 and PLG M6: two new plasminogen allotypes in Japan.
In the Japanese two new inherited plasminogen allotypes were observed, PLG A91 and PLG M6, which migrated closely to PLG A and showed normal antigenic levels and functional activities.


[Graf's ultrasound examination method in assessment of dysplasia and congenital dislocation of infant hip].
To discuss the application of Graf's sonographic method in assessment of developmental dysplasia and dislocation of infant hip. 2258 infants (4516 hips) were examined and evaluated by Graf's method. The analysis of data showed that type I hip accounted too 78.99%, type II 20.56%, and type III and type IV 0.45%. Graf's method can provide qualitative and quantitative evaluation for hips of infants in 3 months after birth. It is an effective in developmental dysplasia of the hip (DDH) and is also useful for early treatment and follow-up of DDH.


Extension of a state-of-the-art optimization criterion to predict co-contraction.
Most studies concerned with the prediction of muscle forces have tried to predict a physiologically reasonable, synergistic muscle behavior. In addition to the load sharing of synergistic muscles, co-contraction of antagonistic muscles also occurs. An extension to a standard quadratic criterion for the calculation of muscle forces is presented in this study. This extension however is not limited to quadratic optimization. The extension is applied to a planar, one degree of freedom model of the human knee. For this model an analytical solution is presented. With the extended criterion it was possible to predict and control the amount of co-contraction for the knee model. The enforced antagonistic muscle activity led to higher agonistic muscle activity. In the absence of an external load flexor and extensor muscles were activated. As a consequence the knee joint was preloaded. This might indicate that antagonistic muscle activity is generated to maintain or improve joint stability. In conclusion, this study presents a novel approach to predict co-contraction when using optimization techniques to determine muscle forces by introducing a shift parameter for the optimization criterion.


Polymorphisms in apoptosis genes predict response to infliximab therapy in luminal and fistulizing Crohn's disease.
Infliximab treatment is effective in 70-80% of patients with refractory luminal and fistulizing Crohn's disease. The effect of infliximab is ascribed to induction of apoptosis. To study whether polymorphisms in apoptosis genes predict the response to infliximab and whether they interact with clinical predictors. Cohort of 287 consecutive patients treated with infliximab for refractory luminal (n = 204) or fistulizing (n = 83) Crohn's disease was genotyped for 21 polymorphisms in apoptosis genes. Short-term clinical response was assessed at week 4 (luminal Crohn's disease) or 10 (fistulizing Crohn's disease) after the first infliximab infusion. The response rate was 69% in luminal and 80% in fistulizing Crohn's disease. In luminal Crohn's disease, two genetic predictors were identified: (i) patients with the Fas ligand -843 CC/CT genotype (n = 135) responded in 75%, with the TT genotype (n = 21) in 38% only (P = 0.002; OR = 0.11; 95% CI: 0.08-0.56). (ii) Patients with the caspase-9 93 TT (n = 9) genotype all responded, in contrast with 67% (n = 147) with the CC and CT genotype (P = 0.04; OR = 1.50; 95% CI: 1.34-1.68). Concomitant azathioprine/mercaptopurine therapy overcame the effect of unfavourable genotypes. In the fistulizing Crohn's disease cohort, the same Fas ligand -843 CC/CT genotype was the only predictor of response (P = 0.002; OR = 1.66; 95% CI: 1.21-2.29), interacting with caspase-9 93 polymorphism but not with azathioprine/mercaptopurine. We observed that polymorphisms in FasL/Fas system and caspase-9 influence the response to infliximab in luminal and fistulizing Crohn's disease. The strongest association was seen between the Fas ligand -843 TT genotype and non-response. Concomitant mercaptopurine/azathioprine therapy, however, was able to overcome the effect of unfavourable genotypes in luminal disease.


Reduction by lead of hydrocortisone-induced glycerol phosphate dehydrogenase activity in cultured rat oligodendroglia.
Time- and dose-dependent toxic effects of lead (Pb) acetate on astroglia, oligodendroglia, and meningeal fibroblasts cultured from immature rat brain were measured. Cultures were exposed for 3 d to Pb (1, 10, and 100 microM) and then examined immediately (Day 0) or 3 or 10 d after Pb treatment was discontinued. The percentages of astroglia and fibroblasts excluding dye were unaffected by Pb, whereas the percentage of oligodendroglia excluding dye decreased significantly (P less than 0.01) at all time points after exposure to 100 microM Pb. Lead (100 microM) also reduced the total cell numbers of astroglia, oligodendroglia, and meningeal fibroblasts. Amino acid incorporation into protein by oligodendroglia was stimulated after exposure to 100 microM Pb at all time points and also by 1 and 10 microM on Day 3. Incorporation was stimulated in astroglia only on Day 0 by 10 and 100 microM. Hydrocortisone-stimulated glycerolphosphate dehydrogenase (GPDH) activity was assayed in oligodendroglia cultures. A significant decrease in specific activity was seen after a 4-d exposure to lead. Because oligodendroglia are responsible for myelin synthesis in the central nervous system, and GPDH may synthesize a precursor for myelin lipid synthesis, it was proposed that the hypomyelination observed in lead-intoxicated neonatal rats may result partially from a primary toxic effect on oligodendroglia. GPDH activity was not inhibited by Pb in mixed glial cultures containing both astroglia and oligodendroglia. This result suggests that astroglia in culture have the ability to delay the lead-induced inhibition of oligodendroglial GPDH activity and supports the hypothesis that astroglia in culture serve a protective function.


Decision Support System for Breast Cancer Detection Using Biomarker Indicators.
Breast cancer is the second most common type of cancer among women in the USA, and it is very common to appear in its invasive form. Detecting its presence in the early stages can potentially aid in the mortality rate depletion since at that point large tumours are highly unlikely to have developed. Technological advances of the last decades have provided advanced tools that employ machine learning for early detection. Common techniques include tumour imaging using special equipment that in most cases is not widely accessible. In order to overcome this limitation, new techniques that employ blood-based biomarkers are being explored. In the current work machine learning algorithms are exploited for the development of a decision support system for breast cancer using easily obtainable user information, age, body mass index, glucose and resistin. The explored algorithms include Logistic Regression, Naive Bayes, Support Vector Machine and Gradient Boosting Classification, all of which are used for the classification of new patients based on a dataset that includes information from previous breast cancer incidents. The results depict that the optimal algorithm based on the current methodology and implementation is the Gradient Boosting Classification which exhibits the highest prediction scores. In order to ensure wide accessibility, a mobile application is developed. The user can easily provide the required information for the prediction to the application and obtain the results rapidly.


Heavy metal contamination in tailings and rocksamples from an abandoned goldminein Southwestern Nigeria.
Active and abandoned primary and secondary goldmines have been observed to be major sources of metals into the environment. This study assessed the level of metal concentrations in rock and tailing samples collected from the abandoned primary goldmine site at Iperindo. A total of five rock and ten tailing samples were collected for this study. The tailing samples were subjected to physicochemical analysis using standard methods. The samples were analyzed for metals using inductively coupled plasma/optical emission spectrometry technique. The results obtained indicated that tailings were acidic (pH 5.02), with electrical conductivity 133.4 μS/cm, cation exchange capacity 8.95 meq/100 g, available phosphorus was 4.74 mg/L, organic carbon 5.58 %, and organic matter 9.63 %. The trends for metal concentrations within the samples were in the order: Zn > Cu > Co > Pb > Cr > As > Cd for rock samples, Cu > Zn > Cr > Pb > As > Co > Cd in tailing samples. Cd, Pb, and Zn in the rock were above the Abundance of Elements in Average Crustal Rocks standards. Principal component analysis showed higher variations among samples in Iperindo. Cd, Pb, Cr, Co, Cu, As, and Zn were strongly loaded to principal component 1, with these metals significantly contributing to variations in 65.76 % of rock and 53.24 % of tailing. This study suggests that the metal concentration in tailings is a reflection of the metal composition of the rocks.


Fatigue failure of reverse shoulder humeral tray components of a single design.
Modularity in shoulder arthroplasty provides surgical flexibility and facilitates less-complex revision surgery. Modular designs must fit in the glenohumeral joint space, necessitating minimal thickness and careful material selection. The potential for fatigue fracture is higher, and fatigue fracture has been experienced by patients. The purpose of this study was to determine the impact of geometry and materials used for modular humeral trays from a single manufacturer. We consecutively retrieved 8 humeral trays of nearly identical designs: 4 Ti-6Al-4V (Ti) and 4 CoCrMo (CoCr). Optical microscopy and scanning electron microscopy were used, along with metallurgical techniques. Finite element and fatigue analyses of the stresses at the humeral tray taper informed observation interpretation. Two Ti devices were revised for in vivo fracture. Scanning electron microscopy showed cracking in the other 2 Ti trays and no evidence of cracking in the CoCr components. A geometric difference in the CoCr devices resulted in a 25% decreased stress under simulated activities of daily living. Accounting for the tray material properties, the fatigue failure envelope ranged from 1000 to 1 million cycles for Ti and from 30,000 to >10 million cycles for CoCr. All Ti humeral tray retrievals fractured in vivo or were cracked at the taper fillet. No CoCr retrievals showed signs of cracking. Finite element and fatigue analyses predict a 10-fold lifetime increase for the CoCr devices compared with the Ti devices. This study shows that fatigue failure is possible for some reverse shoulder components and is likely exacerbated by fillet radius, tray thickness, and material choice.