Urinary excretion of antinuclear antibodies.
The frequency of antinuclear antibodies (ANA), the immunoglobulin class of ANA and their specificity for known nuclear antigens were determined in 24-h urine collections from patients with systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Sixteen % of SLE patients had detectable urine ANA by indirect immunofluorescence using mouse kidney substrate. A higher incidence, 32% of SLE and 28% of PSS patients, had detectable ANA in a titer greater than or equal to 1:16 using HEp-2 cell substrate. IgG ANA was the most frequent immunoglobulin class of antibodies present in the urine; 56% of SLE and 29% of PSS patients with urine ANA had more than one immunoglobulin class of antibodies. Antibodies to Sm, nRNP, SS-A and dsDNA were detected in SLE urine; antibodies to SS-A and centromere were detected in PSS urine. Urine ANA detected on mouse kidney substrate and urine dsDNA antibodies correlated with diffuse proliferative glomerulonephritis in patients with SLE. Sixty-two% of SLE patients with urine ANA had proteinuria. In the remaining SLE patients and in all the PSS patients with urine ANA however, protein excretion was normal. SDS-PAGE revealed heavy and light immunoglobulin molecules in both SLE and PSS patients with urine ANA. The intact immunoglobulin was shown to have ANA activity. ANA present in the urine of SLE and PSS patients with apparently normal renal function may be an early sign of altered glomerular capillary membrane permeability.


A process for producing lignin and volatile compounds from hydrolysis liquor.
Hot water hydrolysis process is commercially applied for treating wood chips prior to pulping or wood pellet production, while it produces hydrolysis liquor as a by-product. Since the hydrolysis liquor is dilute, the production of value-added materials from it would be challenging. In this study, acidification was proposed as a viable method to extract (1) furfural and acetic acid from hot water hydrolysis liquor and (2) lignin compounds from the liquor. The thermal properties of the precipitates made from the acidification of hydrolysis liquor confirmed the volatile characteristics of precipitates. Membrane dialysis was effective in removing inorganic salts associated with lignin compounds. The purified lignin compounds had a glass transition temperature (Tg) of 180-190 °C, and were thermally stable. The results confirmed that lignin compounds present in hot water hydrolysis liquor had different characteristics. The acidification of hydrolysis liquor primarily removed the volatile compounds from hydrolysis liquor. Based on these results, a process for producing purified lignin and precipitates of volatile compounds was proposed.


Mapping mesoscale axonal projections in the mouse brain using a 3D convolutional network.
The projection targets of a neuronal population are a key feature of its anatomical characteristics. Historically, tissue sectioning, confocal microscopy, and manual scoring of specific regions of interest have been used to generate coarse summaries of mesoscale projectomes. We present here TrailMap, a three-dimensional (3D) convolutional network for extracting axonal projections from intact cleared mouse brains imaged by light-sheet microscopy. TrailMap allows region-based quantification of total axon content in large and complex 3D structures after registration to a standard reference atlas. The identification of axonal structures as thin as one voxel benefits from data augmentation but also requires a loss function that tolerates errors in annotation. A network trained with volumes of serotonergic axons in all major brain regions can be generalized to map and quantify axons from thalamocortical, deep cerebellar, and cortical projection neurons, validating transfer learning as a tool to adapt the model to novel categories of axonal morphology. Speed of training, ease of use, and accuracy improve over existing tools without a need for specialized computing hardware. Given the recent emphasis on genetically and functionally defining cell types in neural circuit analysis, TrailMap will facilitate automated extraction and quantification of axons from these specific cell types at the scale of the entire mouse brain, an essential component of deciphering their connectivity.


To screen or not to screen? The development of a prediction model for aorto-iliac stenosis in kidney transplant candidates.
Screening for aorto-iliac stenosis is important in kidney transplant candidates as its presence affects pre-transplantation decisions regarding side of implantation and the need for an additional vascular procedure. Reliable imaging techniques to identify this condition require contrast fluid, which can be harmful in these patients. To guide patient selection for these imaging techniques, we aimed to develop a prediction model for the presence of aorto-iliac stenosis. Patients with contrast-enhanced imaging available in the pre-transplant screening between January 1st, 2000 and December 31st, 2018 were included. A prediction model was developed using multivariable logistic regression analysis and internally validated using bootstrap resampling. Model performance was assessed with the concordance index and calibration slope. Three hundred and seventy-three patients were included, 90 patients (24.1%) had imaging-proven aorto-iliac stenosis. Our final model included age, smoking, peripheral arterial disease, coronary artery disease, a previous transplant, intermittent claudication and the presence of a femoral artery murmur. The model yielded excellent discrimination (optimism-corrected concordance index: 0.83) and calibration (optimism-corrected calibration slope: 0.91). In conclusion, this prediction model can guide the development of standardized protocols to decide which patients should receive vascular screening to identify aorto-iliac stenosis. External validation is needed before this model can be implemented in patient care.


Thirty-year experience in preventing haemoglobinopathies in Greece: achievements and potentials for optimisation.
Beta thalassaemia major (β-TM) and sickle-cell disease (SCD) are severe haemogobinopathies requiring life-lasting, advanced medical management. In the Mediterranean region, both conditions occur with high frequency. We assessed the efficacy of the National Program for the Prevention of Haemoglobinopathies in Greece during the last 30 yrs. Data of affected births between 01/01/1980 and 31/12/2009 were collected in a nationwide scale, and expected vs. observed rates of new births were calculated and compared. In a subpopulation of affected births of Greek origin, the causes for occurrence of the new affected birth were also collected and analysed. Overall, the reduction in new cases was 81.1% and 84.6% for β-TM and SCD, respectively. For β-TM, a constant declining trend was recorded over the 30-yr period, whereas for SCD, a transient reversal was observed in the mid-1990s probably due to the significant influx of immigrants of African origin. Programme failure was 2.2 times more common among new β-TM births of Greek origin compared to new SCD cases (P < 0.001). Unawareness and parental choice were more frequent in SCD compared to β-TM (unawareness: OR = 1.4, P = 0.05, parental choice: OR = 1.9, P = 0.01). The main cause for programme failure was carrier misidentification and incorrect genetic advice for β-TM and SCD, respectively. The β-TM and SCD prevention programme in Greece has significantly reduced the numbers of new affected births. The outcomes could be optimised in groups of non-Greek origin, in carrier identification and by offering specialised genetic counselling.


Combination of the chorionic gonadotropin free beta-subunit with alpha.
The rate-limiting event for combination of hCG alpha- and beta-subunits in JAR choriocarcinoma cells is the rate of disulfide bond formation in the beta-subunit. This is accompanied by a conformational change that produces a combination-competent form of the beta-subunit. The combination reaction, however, is incomplete, and 50% of the synthesized beta molecules remain uncombined (free). In addition, 70% of biosynthetically labeled free beta is degraded in the cell. Possible explanations for incomplete dimer formation include 1) biochemical differences between the free and combined beta-subunits that limit combination of free beta, and 2) an inefficient combination reaction due to low intersubunit affinities or limiting concentrations of combination-competent subunits within the cell. To examine whether the biochemical differences between free and combined beta-subunits that we have previously observed affect the combined beta-subunits that we have previously observed affect the combination competence of free beta, free and dimer beta-subunits were purified from the culture medium and lysates of JAR cells and examined for their ability to combine with alpha purified from pregnancy urine in an in vitro combination assay. Secreted free and dimer beta obtained from culture medium combined to the same extent with urinary alpha. Although the combination efficiencies were lower for the intracellular forms, the free and dimer beta-subunits purified from cell lysates also combined to the same extent with urinary alpha. Thus, biochemical differences that exist between the beta forms do not prevent combination of free beta with alpha in an in vitro combination assay. To examine the second possibility, we speculated that if high concentrations of hCG subunits remained in the rough endoplasmic reticulum (ER) for extended periods of time, the extent of dimer formation would increase in the cell. To increase the residence time of hCG subunits in the ER, JAR cells were treated with carbonyl cyanide trifluoromethoxyphenylhydrazone, an agent that inhibits the translocation of hCG subunits from the ER to the Golgi. Treatment of cells with trifluoromethoxyphenylhydrazone in long and short term pulse-chase labeling studies did not result in an increase in the extent of dimer formation. Thus, the subunit combination reaction in JAR cells may be incomplete due to subtle conformational differences in the free beta-subunit; however, these differences do not inhibit the combination of the free beta-subunit in vitro.


Neighborhood design and rates of walking and biking to elementary school in 34 California communities.
This study evaluates the relationship between neighborhood design and rates of students walking and biking to elementary school. Pairwise correlations and multiple regression models were estimated based on a cross-sectional study of elementary schools and their surrounding neighborhoods. Setting and Subjects. Thirty-four (23%) of 150 California public elementary schools holding October 1999 Walk to School Day events participated in the study. Teachers asked fifth-grade students how they arrived to school 1 week before Walk to School Day. 1990 U.S. Census data measured population density and number of intersections per street mile, whereas 1998-1999 California Department of Education data measured school size, the percentage of students receiving public welfare, and the percentage of students of various ethnicities. Population density (p = .000) and school size (p = .053) were significantly associated with walking and biking rates in regression models controlling for number of intersections per street mile, the percentage of students receiving public welfare, and the percentage of students of various ethnicities. The number of intersections per street mile was associated with walking and biking rates in pairwise correlations (p = .003) but not in regression models. The results support the hypothesis that the walking and biking rates are higher in denser neighborhoods and to smaller schools but do not support the hypothesis that rates are higher in neighborhoods with a high number of intersections per street mile. We suggest that detailed data for a larger sample of students would allow statistical models to isolate the effect of specific design characteristics.


Rapid separation of inorganic anions by capillary ion chromatography using monolithic silica columns modified with dilauryldimethylammonium ion.
The rapid separation of inorganic anions was determined by capillary ion chromatography using monolithic silica capillary columns modified with dilauryldimethylammonium bromide. The stability of the modified stationary phase was satisfactory owing to a strong hydrophobic interaction between the lauryl groups of the reagent, even if the eluent did not contain dilauryldimethylammonium ion. Bromide in seawater samples could be determined by the present system. The repeatability of a retention time of bromide for six successive measurements was around 1.8% when a 500 mM sodium chloride aqueous solution was used as the eluent. Seawater samples were directly injected onto the prepared column without any interference of matrix ions, because an aqueous solution of high-concentration sodium chloride could be used as the eluent. Bromide in seawater samples could be determined within 2 min.


A case of tuberculous epididymitis associated with Addison's disease.
A 68-year-old man was admitted to the hospital because of loss of appetite, easy fatigability, and skin pigmentation. Physical examination revealed that the bilateral epididymides were enlarged and hard without tenderness. At 7 a.m., the basal cortisol level in the plasma was 22.4 ng/ml and ACTH 318 pg/ml. The clinical diagnosis was Addison's disease. Biopsy of the right epididymis revealed evidence of active tuberculosis. Hydrocortisone (18 mg/day) and anti-tuberculous drugs were administered, and the patient became well and regained his appetite in a week. In this case, laparotomy was not performed, but all clinical findings and the course indicated that adrenal tuberculosis was the most likely cause of Addison's disease. CT scanning of the adrenal region demonstrated large, bilateral, homogeneous, low density, and non-enhancing mass. This is the first report dealing with CT findings of Addison's disease with tuberculous epididymitis.


Venous thromboembolism prophylaxis among medical patients at US hospitals.
Chemoprophylaxis is recommended for medical patients at moderate to high risk of venous thromboembolism (VTE) and is now a requirement of the Joint Commission on Accreditation of Healthcare Organizations. To see who receives prophylaxis and how far hospitals will need to go to meet this requirement, we examined VTE prophylaxis patterns at US hospitals. We conducted a retrospective cohort study of adult patients with seven medical diagnoses considered to carry moderate to high risk of VTE at 376 acute care facilities in 2004-2005. We excluded patients on warfarin or with hospital stays of <2 days. VTE prophylaxis was assessed by billing codes for any heparin or compression device. We classified patient risk using a VTE risk prediction model. Of 351,535 patients included, 36% received prophylaxis by hospital day 2. Prophylaxis rates were highest among patients with certain VTE risk factors, including mechanical ventilation (67%), restraints (57%), central lines (55%), obesity (46%), and prior VTE (44%). The median hospital rate was 31% (IQR 19% to 42%); only 3% of hospitals had rates >70%. Compared to patients at low risk of VTE (<0.05%), patients at high risk (>1.0%) were more likely to receive prophylaxis (52% vs. 34%, p < 0.001). Hospitals with high rates of prescribing for high-risk patients also had high rates for low-risk patients. VTE prophylaxis rates at US hospitals are substantially below Joint Commission targets, even for patients at highest risk of VTE.


Partners in Recovery program evaluation: changes in unmet needs and recovery.
Objective Partners in Recovery (PIR) is an Australian government initiative designed to provide support and service linkage for individuals with complex needs living with severe and persistent mental illness. The aim of the present study was to examine whether consumers engaged in PIR programs in two large regions of Sydney experienced: (1) a reduction in unmet needs (either via self- or staff report); and (2) progress in their self-reported mental health recovery. Methods Unmet needs were measured using the Camberwell Assessment of Need Short Appraisal Scale and recovery was measured using the Recovery Assessment Scale - Domains and Stages. For individuals with initial and follow-up data, paired t-tests were used to examine change over time. Results At follow-up, individuals reported an average of two to three fewer unmet needs, and recovery scores increased by approximately 5% across each domain and the total score. At follow-up, the most common unmet needs were in the areas of 'company' and 'daytime activities'. Conclusions The results of the present study suggest that PIR services in these two geographical regions have achieved positive results. Individuals with severe and persistent mental illness engaged with PIR appear to have reduced their unmet needs and enhanced their mental health recovery. What is known about the topic? PIR services were established to support individuals with severe and persistent mental illness by creating service linkages to address unmet needs in order to facilitate recovery. Services were delivered through the new role of 'support facilitator'. What does this paper add? By examining routinely collected outcome measures, this paper shows the success of the PIR program. Individuals engaged with PIR reported fewer unmet needs and enhanced recovery over the time they were involved with the program. However, they still faced serious challenges in building successful social interactions, such as developing friendships, and participating in meaningful activities. What are the implications for practitioners? The support facilitator role developed as part of PIR appears to be a useful method of supporting individuals to reduce unmet needs and enhance recovery. However, further work is required to address the challenges associated with overcoming social isolation and participation in meaningful activities.


Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies.
To study cytokine expression in muscle tissues of patients with inflammatory myopathies and to compare the profiles of patients with polymyositis (PM), inclusion body myositis (IBM), and dermatomyositis (DM). We performed indirect immunohistochemistry studies of muscle tissue sections with a panel of 16 different cytokine-specific monoclonal antibodies, directed against interleukin-1alpha, (IL-1alpha), IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth factor beta1 (TGF beta1), TGF beta2, and TGF beta3 in 5 untreated patients each with PM, DM, and IBM and in 4 normal controls. Fresh frozen muscle tissue sections were fixed in formaldehyde before the procedure. The use of saponin as a detergent to permeabilize the cell membranes enabled identification of intracellular cytokine production. The most prominent finding was the expression of IL-1alpha observed in all patients but in none of the normal controls. In all patients with PM, DM, and IBM, IL-1alpha was expressed in endothelial cells of capillaries, arterioles, and venules in areas surrounded by inflammatory cells, and also in areas with no or scarce inflammatory cells in both endomysium and perimysium. Furthermore, IL-1alpha was also expressed in mononuclear inflammatory cells in all 15 cases. IL-1beta was observed in inflammatory cells in 10 of the 15 patients but, in contrast to IL-1alpha, it was not expressed in blood vessel walls. TGF beta1, TGF beta2, and TGF beta3 were strongly positive in all 15 patients, but only scattered cells were positive in the normal controls. The remaining cytokines were observed only in relatively few cells and only in occasional patients (although the patients were selected for the presence of large infiltrates), and in none of the controls. The patterns were similar in PM, DM, and IBM. Cytokine expression in muscle tissue of patients with inflammatory myopathy is dominated by IL-1alpha, IL-1beta, and TGF beta1-3. The predominant IL-1alpha expression in the blood vessels indicates an importance of the endothelial cells in the inflammatory process in PM, IBM, and DM. A sustained, local release of T cell-derived cytokines may not be a requirement for tissue injury in the inflammatory myopathies. There does not appear to be a qualitative difference in cytokine expression patterns in PM, IBM, and DM.


Multi drug resistant Salmonella typhi in Ludhiana (Punjab).
280 Salmonella typhi strains isolated from suspected cases of enteric fever during the year 1990 were studied for susceptibility to the antimicrobial agents chloramphenicol, ampicillin, cotrimoxazole, gentamycin, kanamycin, amikacin, ciprofloxacin by Kirby Baur disc diffusion method. All were blood culture positive cases. 63 strains (21.9%) were found resistant to chloramphenicol, ampicillin, cotrimoxazole, but sensitive to the amino glycosides and ciprofloxacin. Present study shows the prevalence of multi drug resistant Salmonella typhi in this region of Punjab.


Endogenous opioids released by suspending mice by the tail selectively enhance spinal mu opioid analgesia.
In studying the interactions between handling mice and their subsequent analgesic response to an intrathecally (i.t.) administered mu-opioid agonist, DAMGO, it was found that suspending ICR mice by the tail for 1, 5, or 20 sec, 10 min before the tail-flick test, enhanced DAMGO by 5.3-, 7.4- and 23.6-fold, respectively, compared with mice maintained in a level posture. This enhancement was not accompanied by a change in the rostral flow of [3H]-DAMGO (25 ng, i.t.) to the brain (3.7% in 10 min), in its distribution along the neuraxis or in its systemic absorption. However, i.c.v. administration of beta-endorphin (1-27), an antagonist of epsilon opioid receptors, abolished the enhancement of i.t. DAMGO without affecting its basal analgesic potency. Pretreatment with the delta-opioid antagonist naltrindole (5.6 nmol, i.t.,-30 min) also blocked the enhancement of DAMGO without significantly affecting its basal analgesic potency. Alternatively, this same dose of naltrindole injected i.c.v. failed to block the enhancement of DAMGO in suspended mice. A 20-sec suspension failed to enhance i.t. kappa and delta-agonists, but it did enhance i.t. morphine. In mouse strain comparisons, i.t. DAMGO was more potent in C57BL/6J and DBA/2J mice than in C3H/HeJ and ICR mice, but DAMGO was enhanced by a 20-sec suspension in all strains tested. Thus suspending mice by the tail evoked a reflex enhancement of spinal mu agonist-induced analgesia that probably involved both the supraspinal release of beta-endorphin (an endogenous epsilon agonist) and the subsequent spinal release of an endogenous delta-receptor agonist in the reflex pathway.


Effect of gadolinium incorporation on the structure and luminescence properties of niobium-based materials.
In this work, we have investigated how the concentration of Gd3+ ions affects the structural and luminescent properties of niobium oxide-based matrices doped with Eu3+ ions obtained by the adapted non-hydrolytic sol-gel route. X-ray diffractograms revealed that increasing the concentration of Gd3+ ions favored the onset of the Gd2O3 structure decreasing the GdNbO4 phase. The excitation spectra (λ em = 613 nm) presented bands corresponding to the 7F0 → 5LJ transitions (L = D, G, and L, where J = 0-7), attributed to the Eu3+ ions, and a broad band at 270 nm, assigned to the charge transfer of the [Formula: see text] group. The emission spectra contained bands refer to the 5D0 → 7FJ internal configuration transitions (J = 0, 1, 2, 3, and 4). Finally, the CIE chromaticity coordinates met the standard for the color red established by the National Television Standard Committee (NTSC).


[Effect of p38 mitogen-activated protein kinase signaling pathway during stretch-induced differentiation process of C2C12 myoblasts].
To investigate the effect of cyclic stretch on p38 mitogen-activated protein kinase (p38MAPK) signaling pathway during stretch-induced differentiation process of C2C12 myoblasts. C2C12 cells were seeded on Bio Flex 6-well plates, and cells were subsequently subjected to cyclic stretch at an optimal magnitude (10%) and frequency (0.5 Hz). The effects of cyclic stretch were examined at 2, 6, 12, 24 h. Antibodies specific to p38MAPK phosphorylated forms and the total protein levels of the p38MAPK were examined using Western blot analysis. These results indicated that p38MAPK was activated during stretch-induced C2C12 cell differentiation. The level of phosphorylated protein was higher in the p38MAPK signaling pathway. The expression of total protein was maintained at baseline level. There were no significant differences between groups. Treatment of cells with specific p38MAPK inhibitor SB203580 could decrease the expression of myogenin, but not completely abolish the myogenin expression after stretch. p38MAPK signaling pathway plays an important role during stretch-induced differentiation process of C2C12 myoblasts, but is not activated exclusively in this process.


Clofazimine broadly inhibits coronaviruses including SARS-CoV-2.
The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.


Composition-Defined Optical Properties and the Direct-to-Indirect Transition in Core-Shell In1-xGaxP/ZnS Colloidal Quantum Dots.
Semiconductors are commonly divided into materials with direct or indirect band gaps based on the relative positions of the top of the valence band and the bottom of the conduction band in crystal momentum (k) space. It has, however, been debated if k is a useful quantum number to describe the band structure in quantum-confined nanocrystalline systems, which blur the distinction between direct and indirect gap semiconductors. In bulk III-V semiconductor alloys like In1-xGaxP, the band structure can be tuned continuously from the direct- to indirect-gap by changing the value of x. The effect of strong quantum confinement on the direct-to-indirect transition in this system has yet to be established because high-quality colloidal nanocrystal samples have remained inaccessible. Herein, we report one of the first systematic studies of ternary III-V nanocrystals by utilizing an optimized molten-salt In-to-Ga cation exchange protocol to yield bright In1-xGaxP/ZnS core-shell particles with photoluminescence quantum yields exceeding 80%. We performed two-dimensional solid-state NMR studies to assess the alloy homogeneity and the extent of surface oxidation in In1-xGaxP cores. The radiative decay lifetime for In1-xGaxP/ZnS monotonically increases with higher gallium content. Transient absorption studies on In1-xGaxP/ZnS nanocrystals demonstrate signatures of direct- and indirect-like behavior based on the presence or absence, respectively, of excitonic bleach features. Atomistic electronic structure calculations based on the semi-empirical pseudopotential model are used to calculate absorption spectra and radiative lifetimes and evaluate band-edge degeneracy; the resulting calculated electronic properties are consistent with experimental observations. By studying photoluminescence characteristics at elevated temperatures, we demonstrate that a reduced lattice mismatch at the III-V/II-VI core-shell interface can enhance the thermal stability of emission. These insights establish cation exchange in molten inorganic salts as a viable synthetic route to nontoxic, high-quality In1-xGaxP/ZnS QD emitters with desirable optoelectronic properties.


Macrophage function.
Macrophages and their secretory products play a central role in host defense against pathogenic microbes in the development of protective immunity, in pathogenesis of septic shock and of acute and chronic infections, and in the pathophysiology of wound healing, tissue remodeling, and fibrosis. This review provides a bird's-eye view of the vast literature of the macrophage.


Representational Complexity and Memory Retrieval in Language Comprehension.
Mental representations formed from words or phrases may vary considerably in their feature-based complexity. Modern theories of retrieval in sentence comprehension do not indicate how this variation and the role of encoding processes should influence memory performance. Here, memory retrieval in language comprehension is shown to be influenced by a target's representational complexity in terms of syntactic and semantic features. Three self-paced reading experiments provide evidence that reading times at retrieval sites (but not earlier) decrease when more complex phrases occur as filler-phrases in filler-gap dependencies. The data also show that complexity-based effects are not dependent on string length, syntactic differences, or the amount of processing the stimuli elicit. Activation boosting and reduced similarity-based interference are implicated as likely sources of these complexity-based effects.


Foxp1/2/4 regulate endochondral ossification as a suppresser complex.
Osteoblast induction and differentiation in developing long bones is dynamically controlled by the opposing action of transcriptional activators and repressors. In contrast to the long list of activators that have been discovered over past decades, the network of repressors is not well-defined. Here we identify the expression of Foxp1/2/4 proteins, comprised of Forkhead-box (Fox) transcription factors of the Foxp subfamily, in both perichondrial skeletal progenitors and proliferating chondrocytes during endochondral ossification. Mice carrying loss-of-function and gain-of-function Foxp mutations had gross defects in appendicular skeleton formation. At the cellular level, over-expression of Foxp1/2/4 in chondroctyes abrogated osteoblast formation and chondrocyte hypertrophy. Conversely, single or compound deficiency of Foxp1/2/4 in skeletal progenitors or chondrocytes resulted in premature osteoblast differentiation in the perichondrium, coupled with impaired proliferation, survival, and hypertrophy of chondrocytes in the growth plate. Foxp1/2/4 and Runx2 proteins interacted in vitro and in vivo, and Foxp1/2/4 repressed Runx2 transactivation function in heterologous cells. This study establishes Foxp1/2/4 proteins as coordinators of osteogenesis and chondrocyte hypertrophy in developing long bones and suggests that a novel transcriptional repressor network involving Foxp1/2/4 may regulate Runx2 during endochondral ossification.


Patient and provider perspectives on the design and implementation of an electronic consultation system for kidney care delivery in Canada: a focus group study.
We assessed stakeholder perceptions on the use of an electronic consultation system (e-Consult) to improve the delivery of kidney care in Alberta. We aim to identify acceptability, barriers and facilitators to the use of an e-Consult system for ambulatory kidney care delivery. This was a qualitative focus group study using a thematic analysis design. Eight focus groups were held in four locations in the province of Alberta, Canada. In total, there were 72 participants in two broad stakeholder categories: patients (including patients' relatives) and providers (including primary care physicians, nephrologists, other care providers and policymakers). The e-Consult system was generally acceptable across all stakeholder groups. The key barriers identified were length of time required for referring physicians to complete the e-Consult due to lack of integration with current electronic medical records, and concerns that increased numbers of requests might overwhelm nephrologists and lead to a delayed response or an unsustainable system. The key facilitators identified were potential improvement of care coordination, dissemination of best practice through an educational platform, comprehensive data to make decisions without the need for face-to-face consultation, timely feedback to primary care providers, timeliness/reduced delays for patients' rapid triage and identification of cases needing urgent care and improved access to information to facilitate decision-making in patient care. Stakeholder perceptions regarding the e-Consult system were favourable, and the key barriers and facilitators identified will be considered in design and implementation of an acceptable and sustainable electronic consultation system for kidney care delivery.


Metabolism of imidacloprid and DDT by P450 CYP6G1 expressed in cell cultures of Nicotiana tabacum suggests detoxification of these insecticides in Cyp6g1-overexpressing strains of Drosophila melanogaster, leading to resistance.
With the worldwide use of insecticides, an increasing number of pest insect species have evolved target-site or metabolism-based resistance towards some of these compounds. The resulting decreased efficacy of pesticides threatens human welfare by its impact on crop safety and further disease transmission. Environmental concentrations of some insecticides are so high that even natural populations of non-target, non-pest organisms such as the fruit fly Drosophila melanogaster Meig. have been selected for resistance. Cyp6g1-overexpressing strains of D. melanogaster are resistant to a wide range of chemically diverse insecticides, including DDT and imidacloprid. However, up to now there has been no evidence that the CYP6G1 enzyme metabolises any of these compounds. Here it is shown, by heterologous expression in cell suspension cultures of Nicotiana tabacum L. (tobacco), that CYP6G1 is capable of converting DDT (20 microg per cell culture assay) by dechlorination to DDD (18% of applied amount in 48 h), and imidacloprid (400 microg) mainly by hydroxylation to 4-hydroxyimidacloprid and 5-hydroxyimidacloprid (58 and 19% respectively in 48 h). Thus, the gap between the supposed resistance gene Cyp6g1 and the observed resistance phenomenon was closed by the evidence that CYP6G1 is capable of metabolising at least two insecticides.


Fertility and early pregnancy outcomes after conservative treatment for cervical intraepithelial neoplasia.
Cervical intra-epithelial neoplasia (CIN) typically occurs in young women of reproductive age. Although several studies have reported the impact that cervical conservative treatment may have on obstetric outcomes, there is much less evidence for fertility and early pregnancy outcomes. To assess the effect of cervical treatment for CIN (excisional or ablative) on fertility and early pregnancy outcomes. We searched in January 2015 the following databases: the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 12, 2014), MEDLINE (up to November week 3, 2014) and EMBASE (up to week 52, 2014). We included all studies reporting on fertility and early pregnancy outcomes (less than 24 weeks of gestation) in women with a history of CIN treatment (excisional or ablative) as compared to women that had not received treatment. Studies were classified according to the treatment method used and the fertility or early pregnancy endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model and inter-study heterogeneity was assessed with I(2). Two review authors (MK, AM) independently assessed the eligibility of retrieved papers and risk of bias. The two review authors then compared their results and any disagreements were resolved by discussion. If still unresolved, a third review author (MA) was involved until consensus was reached. Fifteen studies (2,223,592 participants - 25,008 treated and 2,198,584 untreated) that fulfilled the inclusion criteria for this review were identified from the literature search. The meta-analysis demonstrated that treatment for CIN did not adversely affect the chances of conception. The overall pregnancy rate was higher for treated (43%) versus untreated women (38%; RR 1.29, 95% CI 1.02 to 1.64; 4 studies, 38,050 participants, very low quality), although the inter-study heterogeneity was considerable (P < 0.01). The pregnancy rates in treated and untreated women with an intention to conceive (88% versus 95%, RR 0.93, 95% CI 0.80 to 1.08; 2 studies, 70 participants, very low quality) and the number of women requiring more than 12 months to conceive (14% versus 9%, RR 1.45, 95% CI 0.89 to 2.37; 3 studies, 1348 participants, very low quality) were no different. Although the total miscarriage rate (4.6% versus 2.8%, RR 1.04, 95% CI 0.90 to 1.21; 10 studies, 39,504 participants, low quality) and first trimester miscarriage rate (9.8% versus 8.4%, RR 1.16, 95% CI 0.80 to 1.69, 4 studies, 1103 participants, low quality) was similar for treated and untreated women, CIN treatment was associated with an increased risk of second trimester miscarriage, (1.6% versus 0.4%, RR 2.60, 95% CI 1.45 to 4.67; 8 studies, 2,182,268 participants, low quality). The number of ectopic pregnancies (1.6% versus 0.8%, RR 1.89, 95% CI 1.50 to 2.39; 6 studies, 38,193 participants, low quality) and terminations (12.2% versus 7.4%, RR 1.71, 95% CI 1.31 to 2.22; 7 studies, 38,208 participants, low quality) were also higher in treated women.The results should be interpreted with caution. The included studies were often small with heterogenous design. Most of these studies were retrospective and of low or very low quality (GRADE assessment) and were therefore prone to bias. Subgroup analyses for the individual treatment methods and comparison groups and analysis to stratify for the cone length was not possible. This meta-analysis suggests that treatment for CIN does not adversely affect fertility, although treatment was associated with an increased risk of miscarriage in the second trimester. These results should be interpreted with caution as the included studies were non-randomised and many were of low or very low quality and therefore at high risk of bias. Research should explore mechanisms that may explain the increase in mid-trimester miscarriage risk and stratify this impact of treatment by the length of the cone and the treatment method used.


Assessment of cardiac time intervals by wavelet transform of the impedance cardiogram.
Impedance cardiography (ICG) is an inexpensive, noninvasive technique for estimating hemodynamic parameters. ICG can be used to obtain the ejection fraction of the left atrium and to monitor systolic time intervals. Traditional ICG technique does not enable unambiguous detection of the left ventricle ejection time (LVET) and the time relationships between specific marker points. This work aims to approbate a new approach for ICG signal processing using wavelet transform (WT) and to investigate the possibilities of this approach for determination of the parameters which are related to the stroke volume (SV), in particular LVET. Thoracic tetrapolar polyrheocardiography method for simultaneous registration of ECG, ICG and phonocardiograms has been used. A control group consisted of eight healthy men aged 20-25 years. In addition, four patients with essential hypertension participated in the study. Wavelet representation of the ICG data produced local maxima in a two dimensional distribution of the wavelet coefficient. Each extremum point was characterized by the amplitude, scale and time, which determine SV. LVET was defined as the scale corresponding to the E-wave maximum related to the systolic phase of the cardiac cycle. Also, we defined the initial systolic time interval (ISTI) as the time interval between R peak in the ECG and E-wave maximum on the wavelet plane. During functional test LVET and ISTI values defined by WT demonstrated a proper hemodynamic response to loading for the control group and patients with essential hypertension. The proposed approach demonstrates the ability of ICG-WT technique for adequate assessment of SV parameters, including cardiac time intervals.


Medically significant concentrations of prostate-specific antigen in serum assessed.
We used the method of Rudolph et al. (Clin Chem 1988; 34:2031-8) to find information in the data from correlated determinations of acid phosphatase (PAP, EC 188.8.131.52; DuPont aca) and prostate-specific antigen (PSA, Hybritech). We described there how we assign medical decision limits for two or more correlated variables and convert the database to a binary coded message, allowing separation of a selected disease class with minimum error. The decision point, analogous to a percentile upper limit on the ordered values of each variable in the reference group, satisfies the maximum entropy constraints of reference, producing a minimum entropy for the binary coded patient database. We found maximum entropy decision points at PAP = 0.75 U/L and PSA = 22.8 micrograms/L. Patients with PSA values exceeding 22.8 micrograms/L had no benign prostatic disease except for five patients with benign prostate hyperplasia (BPH) with adjacent colon carcinoma (95.3), BPH with infarction (27.6), BPH (23.4) 28.1), or acute prostatitis (34.6). We consider PSA exceeding 22.8 micrograms/L as indicative of carcinoma of the prostate, stage C or D, in the absence of disconfirming evidence. Another decision value for PSA is 11.3 micrograms/L. This bounds the region between 11.3 and 22.8 micrograms/L, where the frequency of BPH is 1.5 times that for adenocarcinoma. At PSA less than 11.3 micrograms/L there is a high frequency of BPH. PSA concentration is not correlated with prostatic size (mass) or with prostatitis. A metastatic carcinoma is as likely to be nonprostatic as prostatic when the PSA concentration is less than 11.3 micrograms/L.


Readiness of emergency departments for pediatric patients and pediatric mortality: a systematic review.
Most children who need emergency care visit general emergency departments and urgent care centres; the weighted pediatric readiness score (WPRS) is currently used to evaluate emergency departments' readiness for pediatric patients. The aim of this study was to determine whether a higher WPRS was associated with decreased mortality and improved health care outcomes and utilization. We conducted a systematic review of cohort and cross-sectional studies on emergency departments that care for children (age ≤ 21 yr). We searched MEDLINE (Ovid), Embase (Ovid), the Cochrane Library (Wiley), CINAHL (EBSCO), Global Health (Ovid) and Scopus from inception until July 29, 2022. Articles identified were screened for inclusion by 2 independent reviewers. The primary outcome was mortality, and the secondary outcomes were health care outcomes and utilization. We used the Newcastle-Ottawa Scale to assess for quality and bias of the included studies. The I 2 statistic was calculated to quantify study heterogeneity. We identified 1789 articles. Eight articles were included in the final analysis. Three studies showed an inverse association between highest WPRS quartile and pediatric mortality (pooled odds ratio [OR] 0.45, 95% confidence interval [CI] 0.26 to 0.78; I 2 = 89%, low certainty of evidence) in random-effects meta-analysis. Likewise, 1 study not included in the meta-analysis also reported an inverse association with a 1-point increase in WPRS (OR 0.93, 95% CI 0.88 to 0.98). One study reported that the highest WPRS quartile was associated with shorter length of stay in hospital (β -0.36 days, 95% CI -0.61 to -0.10). Three studies concluded that the highest WPRS quartile was associated with fewer interfacility transfers. The certainty of evidence is low for mortality and moderate for the studied health care outcomes and utilization. The data suggest a potential inverse association between the WPRS of emergency departments and mortality risk in children. More studies are needed to refute or confirm these findings. PROSPERO-CRD42020191149.


Cytologic Investigations for the Diagnosis of Malignant Pleural Effusion in Non-small Cell Lung Cancer: State-of-the-art Review for Pulmonologists.
Lung cancer is the current leading cause of cancer-related deaths worldwide, and malignant pleural effusion, an indicator of the advanced stage of this disease, portends a poor prognosis. Thus, making an accurate diagnosis of malignant pleural effusion is of paramount importance. During the past decade, the prognosis of patients with advanced non-small cell lung cancer has improved substantially, especially in those treated with targeted therapy and immunotherapy. The use of pleural fluid cytology should not only provide diagnoses but also aid in the selection of targeted therapies, especially when obtaining a histologic specimen is too difficult. In this evidence-based review, we address the importance of pleural fluid cytology in non-small cell lung cancer patients, from making the diagnosis to making treatment-related decisions when only pleural fluid is available.


Effect of Gelatin Coating Enriched with Antioxidant Tomato By-Products on the Quality of Pork Meat.
The use of edible biopolymers and natural additives obtained from food processing by-products is a sustainable strategy for food packaging applications. Gelatin is a biopolymer with great potential as a coating due to its low cost, high availability, and technological and functional properties. Among them, gelatin can be used as a carrier of bioactive compounds such as antioxidants, which can retard oxidation processes and thus extend the shelf-life of highly-perishable products. This study evaluated the effect of gelatin coating enriched with antioxidant tomato by-products hydrolysate (TBPH) on the quality of pork meat during cold storage. Results showed that TBPH obtained from Alcalase hydrolysis presented antioxidant activity with good stability against cooking. Additionally, chromatographic and mass spectrometry techniques, as well as in silico analysis, were used for the peptidomic characterisation of TBPH. The application of enriched gelatin coating on meat led to some physicochemical changes including increased weight loss and colour differences; however, the pH and water activity, which control meat spoilage, were maintained during storage. Moreover, coating prevented lipid oxidation of meat, and enriched-coated meat presented high antioxidant activity after cooking. These results suggest the positive role of gelatin coating enriched with TBPH in extending the shelf-life of meat during storage.


Description of the prototype diagnostic residual gas analyzer for ITER.
The diagnostic residual gas analyzer (DRGA) system to be used during ITER tokamak operation is being designed at Oak Ridge National Laboratory to measure fuel ratios (deuterium and tritium), fusion ash (helium), and impurities in the plasma. The eventual purpose of this instrument is for machine protection, basic control, and physics on ITER. Prototyping is ongoing to optimize the hardware setup and measurement capabilities. The DRGA prototype is comprised of a vacuum system and measurement technologies that will overlap to meet ITER measurement requirements. Three technologies included in this diagnostic are a quadrupole mass spectrometer, an ion trap mass spectrometer, and an optical penning gauge that are designed to document relative and absolute gas concentrations.


Aggregation-Induced Emission (AIE) in Super-resolution Imaging: Cationic AIE Luminogens (AIEgens) for Tunable Organelle-Specific Imaging and Dynamic Tracking in Nanometer Scale.
Organelle-specific imaging and dynamic tracking in ultrahigh resolution is essential for understanding their functions in biological research, but this remains a challenge. Therefore, a facile strategy by utilizing anion-π+ interactions is proposed here to construct an aggregation-induced emission luminogen (AIEgen) of DTPAP-P, not only restricting the intramolecular motions but also blocking their strong π-π interactions. DTPAP-P exhibits a high photoluminescence quantum yield (PLQY) of 35.04% in solids, favorable photostability and biocompatibility, indicating its potential application in super-resolution imaging (SRI) via stimulated emission depletion (STED) nanoscopy. It is also observed that this cationic DTPAP-P can specifically target to mitochondria or nucleus dependent on the cell status, resulting in tunable organelle-specific imaging in nanometer scale. In live cells, mitochondria-specific imaging and their dynamic monitoring (fission and fusion) can be obtained in ultrahigh resolution with a full-width-at-half-maximum (fwhm) value of only 165 nm by STED nanoscopy. This is about one-sixth of the fwhm value in confocal microscopy (1028 nm). However, a migration process occurs for fixed cells from mitochondria to nucleus under light activation (405 nm), leading to nucleus-targeted super-resolution imaging (fwhm= 184 nm). These findings indicate that tunable organelle-specific imaging and dynamic tracking by a single AIEgen at a superior resolution can be achieved in our case here via STED nanoscopy, thus providing an efficient method to further understand organelle's functions and roles in biological research.


The impact of calories and fat content of meals on oral ziprasidone absorption: a randomized, open-label, crossover trial.
Food is known to increase the bioavailability of ziprasidone. Therefore, we evaluated the effects of meals of differing caloric and fat content on steady-state ziprasidone exposure in a stable, treated group of subjects with DSM-IV diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, or psychotic disorder (not otherwise specified) who were already receiving oral ziprasidone as their standard therapy. Patients took ziprasidone under 6 meal conditions in randomized sequences (fasted, low calorie/low fat, low calorie/high fat, medium calorie/high fat, high calorie/low fat, and high calorie/high fat); each crossover period was separated by at least 3 days for washout of the previous meal condition. Serial blood samples were obtained over the 12 hours postdose. The study was conducted from July 27 to September 28 of 2006. Maximum ziprasidone exposures in this study were observed with high-calorie meals (1000 kcal), which were nearly twice those observed under fasting conditions. The medium-calorie meal (500 kcal) was associated with exposures similar to the high-calorie meals. Low-calorie meals (250 kcal) were associated with exposures that were approximately 60% to 90% lower than those of medium- and high-calorie meals, and approached exposures seen under fasting conditions. Fat content of the meal had no significant effect on ziprasidone absorption. The ziprasidone exposures observed with medium- and high-calorie meals had less variability than those with low-calorie meals and under fasting conditions. These results confirm that ziprasidone should be taken with food and that a meal equal to or greater than 500 kcal, irrespective of fat content, is required for optimal and reproducible bioavailability of the administered dose.


Contemporary results of transcatheter mitral valve procedures: bi-centric retrospective analysis.
Transcatheter mitral valve-in-valve (TMVIV) or valve-in-ring (TMVIR) replacement offer an alternative therapy for high risk patients. We aimed to highlight the operative and postoperative results of TMVIV and TMVIR procedures. We included all patients underwent TMVIV and TMVIR procedures between 2017 and 2020 at two heart centers in Germany. We included a total of 36 high risk patients in our study where 12 received TMVIV and 24 received TMVIR. All patients underwent TMVIV or TMVIR with Edwards Sapien XT or S3 transcatheter valves (Edwards Lifesciences). The mean age was 79 (75-83 years old). The median (IQR) preoperative STS score was 9 (7-13)% and EuroSCORE II was 14.5% (12-16). The majority of our patients were operated via transapical approach (n = 26) and the minority via transseptal approach (n = 10). Out of our records, none of our patients required reopening for bleeding or any other surgical complications. None of our patients required reintervention during the 6 months follow-up period. One mortality was recorded on fifth postoperative day due to low cardiac output syndrome (obviously because of LVOT obstruction by the anterior mitral leaflet). The average blood loss was 200 ml in the first 24 h in patients underwent transapical approach. Average operative time was 93 min and all patients were immediately extubated after the procedure in the operating room (even the patient with echocardiographically documented LVOT obstruction who died on the fifth postoperative day). Length of Intensive Care Unit stay was 2 ± 1.2 days and length of hospital stay was 4.1 ± 1.2 days. In the follow up period, echocardiograms showed normal prosthetic valve function with low transvalvular gradients, no LVOT obstruction in TMVIR cases and no evidence of valve migration or thrombosis (except in one patient). Concerning 6 months readmission, it was recorded in 2 patients due to right sided heart failure symptoms due to preexisting high degree of tricuspid valve regurge which did not disappear or even decrease after the operation and the other patient due to gastrointestinal bleeding. TMVIV and TMVIR offer an efficient, safe and less invasive alternative in high surgical risk patients.


Relationship of milk intake and physical activity to abdominal obesity among adolescents.
What is already known about this subject Diet and physical activity (PA) are recognized as important factors to prevent abdominal obesity (AO). Studies have found an inverse relationship between milk intake or milk products and body weight and/or body fat in children and adolescents. Evidence suggests that low levels of PA are associated with AO in youth. What this study adds Our study explored the combined association of milk intake and PA on AO in adolescents, which are most often studied in isolation. Our findings suggested that adolescents with high milk intakes, regardless of whether they were active or low active, were less likely to have AO. Our findings could have a great epidemiological interest and bring important evidence in the field of AO management among adolescents. Diet and physical activity (PA) are recognized as important factors to prevent abdominal obesity (AO), which is strongly associated with chronic diseases. Some studies have reported an inverse association between milk consumption and AO. This study examined the association between milk intake, PA and AO in adolescents. A cross-sectional study was conducted with 1209 adolescents, aged 15-18 from the Azorean Archipelago, Portugal in 2008. AO was defined by a waist circumference at or above the 90th percentile. Adolescent food intake was measured using a semi-quantitative food frequency questionnaire, and milk intake was categorized as 'low milk intake' (<2 servings per day) or 'high milk intake' (≥2 servings per day). PA was assessed via a self-report questionnaire, and participants were divided into active (>10 points) and low-active groups (≤10 points) on the basis of their reported PA. They were then divided into four smaller groups, according to milk intake and PA: (i) low milk intake/low active; (ii) low milk intake/active; (iii) high milk intake/low active and (iv) high milk intake/active. The association between milk intake, PA and AO was evaluated using logistic regression analysis, and the results were adjusted for demographic, body mass index, pubertal stage and dietary confounders. In this study, the majority of adolescents consumed semi-skimmed or skimmed milk (92.3%). The group of adolescents with high level of milk intake and active had a lower proportion of AO than did other groups (low milk intake/low active: 34.2%; low milk intake/active: 26.9%; high milk intake/low active: 25.7%; high milk intake/active: 21.9%, P = 0.008). After adjusting for confounders, low-active and active adolescents with high levels of milk intake were less likely to have AO, compared with low-active adolescents with low milk intake (high milk intake/low active, odds ratio [OR] = 0.412, 95% confidence intervals [CI]: 0.201-0.845; high milk intake/active adolescents, OR = 0.445, 95% CI: 0.235-0.845). High milk intake seems to have a protective effect on AO, regardless of PA level.


Endodontic update 2006.
The past 10 years have witnessed more significant changes in the art and science of endodontics than the previous 100 years. This observation is no surprise, given that change is our only constant. The rate of change, however, has been anything but constant. The rate has accelerated so fast that all clinicians in the field of dentistry need a reliable source to guide us in what works. What works today in endodontics is the theme of this update. The discoveries and advancements in endodontic technology, instruments, and materials enable practitioners to achieve treatment outcomes that were previously considered unattainable. For example, in nonsurgical endodontic treatment, nickel titanium technology consistently can produce predictable radicular preparations that can be easily obturated. In nonsurgical re-treatment, the previous endodontic obturation attempt frequently can be removed and successfully re-treated largely because of enhanced vision and coaxial lighting from the operating microscope. Importantly, careful nonsurgical re-treatment usually can be accomplished without disruption to the existing restorations and without risk to ferrule integrity. In endodontic surgery underfilled foramina, and the isthmi between them, predictably can be connected and obturated with state-of-the-art miniature instruments. CLINICAL SIGNIFICANCE This article reviews the clinical endodontic breakthroughs encountered during the last decade and focuses on three primary topics: (1) finding canals; (2) following canals; and (3) finishing canals. Every day, dentists are faced with the interdisciplinary treatment planning question of to "save or not to save a tooth?" Dentists must routinely make the decision of whether to remove or restore the tooth based on biology, structure, function, esthetics, and value.(1) Occasionally, the endodontically treated tooth can be the weakest link in the restorative and esthetic sequence. This article examines the current state of endodontic technology, as well as the fundamentals of endodontic mechanics needed to achieve the most predictable endodontic outcome with the highest degree of success.


Isolated ACTH deficiency.
Isolated ACTH is a rare cause of secondary adrenocortical insufficiency. The diagnosis is made by the demonstration of low cortisol production with low plasma ACTH, absent adrenal responses to stimulation for pituitary or hypothalamus with intact adrenal response to exogenous ACTH, and normal secretory indices of other pituitary hormones. We conclude that the diagnosis of this condition may be difficult due to the varied clinical presentation and etiologies.


Clinician perceptions of using a smartphone app with prolonged exposure therapy.
Clinician perceptions of clinical innovations affect their adoption and spread. This study investigated mental health clinicians' (n = 163) perceptions of a patient-facing smartphone application (app) for prolonged exposure (PE) therapy for posttraumatic stress disorder, before its public release. After reading a description of the app, participants rated perceptions of it based on diffusion of innovations theory constructs. Perceptions were generally favorable regarding the app's relative advantage over existing PE practices, compatibility with their values and needs, and complexity. Age (<40 years), smartphone ownership, and having used apps in care related to more favorable perceptions. Smartphone ownership, relative advantage, and complexity significantly predicted intention to use the app if it were available. These findings suggest that clinicians are receptive to using a PE app and that dissemination efforts should target sub-groups of PE clinicians to maximize adoption.


Radical productions and pi-spin density by UHF/PM3 method on benz[c]acridines and benzo[a]phenothiazines.
On the calculated pi-spin density (rho pi) of benz[c]acridines [1-12], benz[c]acridines [2,8-12] with alternately value of pi-spin density (rho pi) on angular ring, large negative pi-spin density at C-1 and C-3 positions and large positive pi-spin density at C-2 and C-4 positions indicates their carcinogenicity, except for 7-methylbenz[c]acridine [7]. Benz[c]acridines [1,3-6] which do not follow were not carcinogenic. Radical producing benzo[a]phenothiazines [13-16] and non-radical producing benzo[a]phenothiazines [17-19] gave calculated pi-spin density (rho pi) which was positive in radical producing benzo[a]phenothiazines [13-16] at N-12 position, and had the opposite pi-spin density in non-radical producing benzo[a]phenothiazines [17-19].


Growth and sex effects on the expression of syndecan-4 and glypican-1 in turkey myogenic satellite cell populations.
The adult skeletal muscle stem cells, satellite cells, are responsible for skeletal muscle growth and regeneration. Satellite cells represent a heterogeneous cell population that differentially express cell surface markers. The membrane-associated heparan sulfate proteoglycans, syndecan-4, and glypican-1, are differentially expressed by satellite cells during the proliferation and differentiation stages of satellite cells. However, how the population of syndecan-4- or glypican-1-positive satellite cells changes during proliferation and differentiation, and how sex and muscle growth potential affect the expression of these genes is unknown. Differences in the amount of satellite cells positive for syndecan-4 or glypican-1 would affect the process of proliferation and differentiation which would impact both muscle mass accretion and the regeneration of muscle. In the current study, the percentage of satellite cells positive for syndecan-4 or glypican-1 from male and female turkeys from a Randombred Control Line 2 and a line (F) selected for increased 16-week body weight were measured during proliferation and differentiation. Growth selection altered the population of syndecan-4- and glypican-1-positive satellite cells and there were sex differences in the percentage of syndecan-4- and glypican-1-positive satellite cells. This study provides new information on dynamic changes in syndecan-4- and glypican-1-positive satellite cells showing that they are differentially expressed during myogenesis and growth selection and sex affects their expression.


Design and Optimization of Composite Cathodes for Solid-State Batteries Using Hybrid Carbon Networks with Facile Electronic and Ionic Percolation Pathways.
Solid-state batteries (SSBs) have emerged as a promising alternative to conventional liquid electrolyte batteries due to their potential for higher energy density and improved safety. However, achieving high performance in SSBs is difficult because of inadequate contact and interfacial reactions that generate high interfacial resistance, as well as inadequate solid-solid contact between electrodes. These chronic issues are associated with inhomogeneous ion and electron transport networks owing to imperfect solid-solid interfacial contact. This study developed an optimal interfacial engineering strategy to facilitate an ion-electron transport network by designing an active material (NCM622) uniformly filled with a thin layer of a solid electrolyte (garnet-type Li6.25Ga0.25La3Zr2O12) and conductive additives. The optimal composite electrode architecture enhanced the high capacity, high rate capability, and long-term cycle stability, even at room temperature, owing to the percolating network for facile ionic conduction that assured a homogeneous reaction. In addition to mitigating the mechanical degradation of the cathode electrode, it also reduced the crosstalk effects on the anode-solid electrolyte interface. Effectively optimizing the selection and use of conductive additives in composite electrodes offers a promising approach to addressing key performance-limiting factors in SSBs, including interfacial resistance and solid-solid contact issues. This study underscores the critical importance of cathode architecture design for achieving high-performance SSBs by ensuring that the interfaces are intact with solid electrolytes at both the cathode and anode interfaces while promoting uniform reactions. This study provides valuable insights into the development of SSBs with improved performance, which could have significant implications for a wide range of applications.


Women's health and human rights in Afghanistan: continuing challenges.
Physicians for Human Rights has released a ground-breaking survey of more than 1,000 Afghan women and men on their attitudes and experiences regarding health and human rights for Afghan women. Health care for women in Afghanistan still poses daunting challenges.


A comparative immunohistochemical study of splenic arterial hyalinosis in health and disease.
Hyaline deposits in arterioles and arteries of spleen were studied immunohistochemically. Hyaline lesions in arteriosclerotic heart disease were characterized by significant deposits of IgG, IgM, beta1C-beta 1A-globulins and beta-lipoproteins. These corresponded to histochemically stained deposits of acid mucopolysaccharides and microscopic areas of musculoelastic tissue damage in the hyaline masses. While, in young adults and a few other cases of other diseases, an occasional granular to linear deposit of IgG, IgM, beta1C-beta 1A-globulin and beta-lipoprotein was noted, no localization of IgA, rabbit antihuman fibrin and rabbit antihuman fibrinogen was seen. A variety of other histochemical staining reactions were found to be negative. These findings suggest that: a) hyaline deposits in splenic arterioles and arteries occur with greater severity in patients with hypertensive and arteriosclerotic heart disease; b) a possible abnormality related to filtration defects in arteries and arterioles, resulting in the trapping of plasma proteins, appears likely; c) increased localization of acid mucopolysaccharides and destruction of musculoelastic tissue is not an uncommon feature in hyaline masses; d) fibrin is not a component of these deposits and e) further study of other organs is necesary to observe the composition of hyaline in arterioles and arteries.


A Comprehensive and Rapid Quality Evaluation Method of Traditional Chinese Medicine Decoction by Integrating UPLC-QTOF-MS and UFLC-QQQ-MS and its Application.
Decoction is one of the oldest forms of traditional Chinese medicine and it is widely used in clinical practice. However, the quality evaluation and control of traditional decoction is a challenge due to the characteristics of complicated constituents, water as solvent, and temporary preparation. ShenFu Prescription Decoction (SFPD) is a classical prescription for preventing and treating many types of cardiovascular disease. In this article, a comprehensive and rapid method for quality evaluation and control of SFPD was developed, via qualitative and quantitative analysis of the major components by integrating ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry and ultra-fast-performance liquid chromatography equipped with triple quadrupole mass spectrometry. Consequently, a total of 39 constituents were tentatively identified in qualitative analysis, of which 21 compounds were unambiguously confirmed by comparing with reference substances. We determined 13 important constituents within 7 min by multiple reaction monitoring. The validated method was applied for determining five different proportion SFPDs. It was found that different proportions generated great influence on the dissolution of constituents. This may be one of the mechanisms for which different proportions play different synergistic effects. Therefore, the developed method is a fast and useful approach for quality evaluation of SFPD.


Treatment of calcaneonavicular coalition accompanied by an accessory anterolateral talar facet.
The association of accessory anterolateral talar facet (AALTF) and tarsal coalition has been reported recently. However, there is no report in the literature examining the clinical outcomes of operative treatment simultaneously addressing both AALTF and tarsal coalition. In this case series, we report the functional outcomes of operative treatment for both AALTF and calcaneonavicular coalition (CNC). Four male patients were admitted to our institution with foot pain. Radiographic examination revealed CNC and accompanying AALTF in all patients. Five feet of these four patients were operated simultaneously for AALTF and CNC. At the final follow-up, the mean Visual Analog Scale score was 1.7±2.4 (range, 0 to 5.5), the mean American Orthopedic Foot and Ankle Society score was 89.6±11.5 (range, 69 to 97), and the mean Foot Function Index was 15.4±19.1 (range, 0 to 43). In conclusion, simultaneous resection of CNC with AALTF seems to have good postoperative clinical outcomes. As AALTF can emerge along with CNC, every patient scheduled for CNC resection should be evaluated for AALTF.


A FRET-based ratiometric sensor for mercury ions in water with multi-layered silica nanoparticles as the scaffold.
A FRET system was built for ratiometric sensing of Hg(2+) in water with multilayered silica nanoparticles as the scaffold. This architecture ensures the control over the location of both donor and acceptor and their separation distance within nanoparticles, affording higher energy transfer efficiency and higher signal-to-background ratio for particle-based sensing.


Design and benchtop validation of a handheld integrated dynamic breast imaging system for noninvasive characterization of suspicious breast lesions.
We have developed a portable, handheld, integrated, dynamic breast imaging system that integrates a near infrared tissue oximeter, clinical ultrasound, and two pressure sensors for noninvasive detection of pressure-induced structural and functional dynamics of suspicious breast lesions. A series of benchtop tests were conducted to validate multiple performance characteristics of the integrated dynamic near infrared/ultrasound breast imaging system (idNIRUS), including the reconstruction of the absorptive heterogeneities and the generation of the dynamic compression stimuli. In absorptive heterogeneity testing, we reconstructed the absorption coefficients of transparent polypropylene tubing circulated with a skim milk-India ink mixture and embedded in a gel wax tissue simulating phantom. High linear correlations (R(2) greater than 0.989) were observed between the reconstructed and the measured absorption coefficients of the embedded tubing. In dynamic compression testing, five volunteer operators generated ten successive compression sessions by compressing the idNIRUS imager on a breast self examination wearable model following the computer simulated pressure profile. The manually generated pressure profiles demonstrated an accuracy of 95.7% and operator-dependent variation of less than 5%. The results of the current benchtop tests will help to optimize the most appropriate testing conditions for our future planned clinical trial.


A new time-domain frequency-selective quantification algorithm.
In this paper a new time-domain frequency-selective quantification algorithm is presented. Frequency-selective quantification refers to a method that analyzes spectral components in a selected frequency region, ignoring all the other components outside. The algorithm, referred to as MeFreS (Metropolis Frequency-Selective), is based on rank minimization of an opportune Hankel matrix. The minimization procedure is satisfied by the down-hill simplex method, implemented with the simulated annealing method. MeFreS does not use any preprocessing step or filter to suppress nuisance peaks, but the signal model function is directly fitted. In this manner, neither inherent signal distortions nor estimation biases to be corrected occur. The algorithm was tested with Monte Carlo simulations. A comparison with VARPRO and AMARESw algorithms was carried out. Finally, two samples of known content from NMR data were quantified.


Engineered resistance against proteinases.
Exogenous proteinase inhibitors are valuable and economically interesting protective biotechnological tools. We examined whether small proteinase inhibitors when fused to a selected target protein can protect the target from proteolytic degradation without simultaneously affecting the function and activity of the target domain. Two proteinase inhibitors were studied: a Kazal-type silk proteinase inhibitor (SPI2) from Galleria mellonella, and the Cucurbita maxima trypsin inhibitor I (CMTI I). Both inhibitors target serine proteinases, are small proteins with a compact structure stabilized by a network of disulfide bridges, and are expressed as free polypeptides in their natural surroundings. Four constructs were prepared: the gene for either of the inhibitors was ligated to the 5' end of the DNA encoding one or the other of two selected target proteins, the coat protein (CP) of Potato potyvirus Y or the Escherichia coli beta-glucuronidase (GUS). CMTI I fused to the target proteins strongly hampered their functions. Moreover, the inhibitory activity of CMTI I was retained only when it was fused to the CP. In contrast, when fused to SPI2, specific features and functions of both target proteins were retained and the inhibitory activity of SPI2 was fully preserved. Measuring proteolysis in the presence or absence of either inhibitor, we demonstrated that proteinase inhibitors can protect target proteins used either free or as a fusion domain. Interestingly, their inhibitory efficiency was superior to that of a commercial inhibitor of serine proteinases, AEBSF.


Evidence for the priming role of the central retinula cell in ommatidium differentiation of Ephestia kuehniella.
In the developing compound eye of Ephestia kuehniella, within the advancing front of differentiation, regular cell clusters arise which consist of a central cell and two flanking cells. The central cell is destined to become the basal retinula cell later in development. Its crucial role in ommatidium formation is confirmed by 3H-thymidine labelling. Eye anlagen labelled early in the pupal stage incorporate thymidine within two distinct zones along the front of differentiation. After the ommatidia are completely differentiated, both zones contain labelled nuclei of all cell types which participate in ommatidia formation. Within the posterior zone, however, the basal retinula cells are always unlabelled, whereas in the anterior they show labelled nuclei. From this observation it must be concluded that the basal retinula cell first terminates proliferation (either alone or together with a few other cells) to become differentiated as the central retinula cell. These results agree with those found in Drosophila and indicate that the ordered stepwise addition of cells to a central founder cell is a widespread principle of ommatidia formation in insects.


Chronic lymphocytic leukemia with del(17p13.1): a distinct clinical subtype requiring novel treatment approaches.
Chronic lymphocytic leukemia (CLL) is a very heterogeneous disease with significant variation in clinical presentation, time to disease progression, survival, and aggressiveness of clinical course. A subgroup of patients who have been repeatedly identified as having a poor response to therapy are those with del(17p13.1)--identified by either interphase cytogenetics or other comparable strategies. Although there has been much progress over the past few years in the development of new therapeutic targets for CLL patients, this subgroup has continued to lag behind others. Because of the poor response or significant therapy-related toxicity experienced by patients with del(17p13.1)--and the small number of these patients included in clinical trials--current guidelines are unable to provide suggestions for the care of newly diagnosed, symptomatic but untreated patients (as well as relapsed patients) in this subgroup on account of the modest amount of evidence. However, novel agents are on the horizon that appear to be significantly more effective in this patient population, and these will likely shape the standard of care for these patients in the future.


[ROLE OF BIOLOGICAL PROPERTIES OF CORYNEBACTERIA IN ASSOCIATIVE SYMBIOSIS].
Microorganisms of the Corynebacterium genus are examined in the review as a component of a single microecological system of humans in the context of their interaction with the macroorganism, dominant and associative microorganisms under the conditions of both normo- and pathocenosis. Adhesive ability, antagonistic activity, pathogenicity and persistence factors, antibiotics resistance are described. The role of non-pathogenic corynebacteria in the formation of microbiocenoses of human body and realization of colonization resistance is shown on an example of vaginal biotope.


Lactobacillus rhamnosus Endocarditis After Upper Endoscopy.
Lactobacillus rhamnosus is commonly found in gastrointestinal flora and used in probiotics but is a rare human pathogen. We report a case of L. rhamnosus endocarditis following upper endoscopy in a frequent consumer of yogurt containing the organism, who required aortic and mitral valve replacement for cure.


Investigating the role of "Immature Myeloid Cells" as Drivers of Inflammation and Disease Persistence in Psoriatic Arthritis.
Despite the development of treatments targeting T cell co-stimulation and cytokines TNF, IL-12/23, and IL-17, less than half of patients within clinical trials achieve high levels of clinical response. This fact, as well as the absence of prognostic biomarkers represents major unmet clinical needs that necessitate further investigation of the disease pathophysiology. Myeloid cells are critical components of PsA inflammatory mechanisms, being a highly prevalent immune population in biopsies of PsA target tissues, such as the skin and the synovium. Through their antigen-presenting capacity and their pro-angiogenic and pro-inflammatory properties myeloid cells could contribute to persistent inflammation in PsA leading to treatment-resistant disease. To this end, we have recently shown the expansion of monocytes in the blood of PsA patients compared to healthy subjects. Importantly, we have also identified an immature myeloid cell population in patients with highly active, refractory disease, indicating the presence of an "emergency myelopoiesis" process in PsA. In this research protocol, we aim to decipher the pro-inflammatory "myeloid signature" in patients with active PsA and explore the role of immature myeloid cells in disease pathophysiology and their potential as prognostic biomarkers. To address this, we will isolate and analyse monocytes and immature myeloid cells from PsA patients -before and after a 6-month treatment course- focusing on differences between responders and non-responders. In this context, we will perform a thorough phenotypic and functional analysis of these cells, identify their expression signature in an already established whole blood RNA-seq dataset and investigate their presence in target tissues, such as the skin and synovial fluid. This study will elucidate the role of myeloid cells in disease propagation by further defining the involvement of immature myeloid cells in PsA.


Toward a machine learning model for a primary diagnosis of Guillain-Barré syndrome subtypes.
Guillain-Barré Syndrome (GBS) is a neurological disorder affecting people of any age and sex, mainly damaging the peripheral nervous system. GBS is divided into several subtypes, in which only four are the most common, demanding different treatments. Identifying the subtype is an expensive and time-consuming task. Early GBS detection is crucial to save the patient's life and not aggravate the disease. This work aims to provide a primary screening tool for GBS subtypes fast and efficiently without complementary invasive methods, based only on clinical variables prospected in consultation, taken from clinical history, and based on risk factors. We conducted experiments with four classifiers with different approaches, five different filters for feature selection, six wrappers, and One versus All (OvA) classification. For the experiments, we used a data set that includes 129 records of Mexican patients and 26 clinical representative variables. Random Forest filter obtained the best results in each classifier for the diagnosis of the four subtypes, in the same way, this filter with the SVM classifier achieved the best result (0.6840). OvA with SVM classifier reached a balanced accuracy of 0.8884 for the Miller-Fisher (MF) subtype.


Laryngoscopy and pharyngeal pH are complementary in the diagnosis of gastroesophageal-laryngeal reflux.
Pharyngeal pH monitoring and laryngoscopy are routinely used to diagnose gastroesophageal-laryngeal reflux as a cause of respiratory symptoms. Although their use seems intuitive, their ultimate diagnostic value is yet to be defined. We studied 10 asymptomatic (control) subjects and 76 patients with respiratory symptoms. Both patients and control subjects were given a symptom questionnaire. Each underwent direct laryngoscopy using the reflux finding score (RFS) to grade laryngeal injury, esophageal manometry, and 24-hour esophagopharyngeal pH monitoring. The patients were then classified as RFS+, if the score was greater than 7, and pharyngeal reflux (PR)+, if they had more than one episode of PR detected during pH monitoring. The most common symptoms reported by patients were hoarseness (87%), cough (53%), and heartburn (50%). Control subjects had a significantly lower RFS (2.1 vs. 9.6, P < 0.01) and fewer episodes of PR (0.2 vs. 3.4, P < 0.01), than patients. None of the control subjects had more than one episode of PR during a 24-hour period. Fifty patients (66%) were RFS+ and 26 (34%) were RFS-. Thirty-two patients (42%) were PR+ and 44 (58%) were PR-. Fifteen patients had a normal RFS and no PR (group I = RFS-/PR-). Forty patients had discordance between the laryngoscopic findings and the pH monitoring (group II = RFS-/PR+ or RFS+/PR-). Twenty-one patients had both an abnormal RFS and PR (group III = RFS+/PR+). Patients in group III had significantly higher heartburn scores and distal esophageal acid exposure. Eighty-three percent of patients in group III but only 44% in group I improved their respiratory symptoms as a result of antireflux therapy. An abnormal PR or RFS differentiates patients with laryngeal symptoms from control subjects. Agreement between PR and RFS helps establish or refute the diagnosis of gastroesophageal reflux as a cause of laryngeal symptoms. Patients who are RFS+ and PR- may have laryngeal injury from another source, whereas patients who are RFS- and PR+ may not have acid entering the larynx, despite the presence of PR. Patients who are RFS+ and PR+ have more severe gastroesophageal reflux disease and their reflux causes laryngeal damage. Laryngoscopy and pharyngeal pH monitoring should be considered complementary studies in establishing the diagnosis of laryngeal injury induced by gastroesophageal reflux. ( J GASTROINTEST SURG 2002;6:189-194.)


The Age-Specific Association of Waist Circumference and Risk of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus in Shandong, China.
Objective. To examine the association of three most common obesity measures including body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with chronic kidney disease (CKD) risk in patients with type 2 diabetes mellitus (T2D). Design. Cross-sectional evaluation of the effect of anthropometric measures on CKD risk. Setting. Outpatient Department. Subjects. T2D patients who were treated between October 2012 and May 2013. Intervention. None. Main Outcome Measure. CKD risk. Results. On average, the patients had a mean age of 60.2 years, and 40% were males. CKD was present in 46% of all the patients. In multivariate logistic regression using the imputed data, higher WC was associated with greater odds of CKD (OR = 1.019, 95% CI = 1.002-1.006, P = 0.030), but not BMI and WHR. Interestingly, we found that patients with very small WC seemed to have greater odds of CKD. We observed age-specific effect of WC such that the effect of WC on CKD risk is significant only in middle-aged T2D patients. Conclusion. Our study provides evidence for the association of WC with CKD in Chinese patients with T2D. T2D patients, especially middle-aged T2D patients, should reduce their WC to decrease CKD risk.


Role of mathematical models in assessment of risk and in attempts to define management strategy.
Risk assessment of food-borne carcinogens is becoming a common practice at FDA. Actual risk is not being estimated, only the upper limit of risk. The risk assessment process involves a large number of steps and assumptions, many of which affect the numerical value estimated. The mathematical model which is to be applied is only one of the factors which affect these numerical values. To fulfill the policy objective of using the "worst plausible case" in estimating the upper limit of risk, recognition needs to be given to a proper balancing of assumptions and decisions. Interaction between risk assessors and risk managers should avoid making or giving the appearance of making specific technical decisions such as the choice of the mathematical model. The importance of this emerging field is too great to jeopardize it by inappropriately mixing scientific judgments with policy judgments. The risk manager should understand fully the points and range of uncertainty involved in arriving at the estimates of risk which must necessarily affect the choice of the policy or regulatory options available.


Q-Switched 1064 nm Nd:YAG Laser Rejuvenates Photoaging Skin of Rats by Downregulating miR-196b-5p.
Background: Q-switched 1064 nm Nd:YAG laser (1064-QSNYL) is efficient in rejuvenating photoaging skin, and microRNAs (miRNAs) participate in this process. Objective: In this study, we aimed to explore the effects of 1064-QSNYL on miR-196b-5p, TGF-beta receptor II (TGFBR2), and SMAD7 in the photoaging skin of rats. Methods: The relationship between miR-196b-5p and TGFBR2 in HaCaT cells was detected by real-time PCR and western blotting. A skin photoaging model was established in Wistar rats using ultraviolet (UV) radiation (UVR). Dermoscopy, hematoxylin-eosin (HE) staining, Sirius red staining, and hydroxyproline content were used to observe the effect of UVR on rat skin. The 1064-QSNYL was used for skin rejuvenation. The expression of COL3A1, TGFB1, TGFBR2, SMAD2, SMAD3, and SMAD7 was detected by real-time PCR and/or western blotting. Results: TGFBR2 was a specific target of miR-196b-5p in the skin. In HaCaT cells and the photoaging skin of rats, 1064-QSNYL treatment upregulated COL3A1 and TGFBR2 and downregulated SMAD7 and miR-196b-5p. Conclusions: We showed for the first time that 1064-QSNYL treatment rejuvenates photoaging rat skin by regulating TGFBR2 and SMAD7. Downregulation of miR-196b-5p assists in this process by targeting and upregulating TGFBR2.


Mean-field avalanches in jammed spheres.
Disordered systems are characterized by the existence of many sample-dependent local-energy minima that cause a step-wise response when the system is perturbed. In this article we use an approach based on elementary probabilistic methods to compute the complete probability distribution of the jumps (static avalanches) in the response of mean-field systems described by replica symmetry breaking; we find a precise condition for having a power-law behavior in the distribution of avalanches caused by small perturbations, and we show that our predictions are in remarkable agreement both with previous results and with what is found in simulations of three-dimensional systems of soft spheres, either at jamming or at slightly higher densities.


Repeated courses of high dose melphalan and unpurged autologous bone marrow transplantation in children with acute non-lymphoblastic leukemia in first complete remission.
Eleven children between the ages of 1 and 16 years with acute non-lymphoblastic leukemia (ANLL) in first remission were included in a study of double unpurged autologous bone marrow transplantation (ABMT). Prior to each ABMT patients received massive chemotherapy with melphalan at a dosage of 140 mg/m2. The first ABMT was done within a median of 4 months after the achievement of complete remission. As soon as the children had adequate hematologic recovery, a second marrow collection was done, followed by a second course of melphalan and a second ABMT. The duration of aplasia was significantly longer after the second ABMT than after the first, but the non-hematologic toxicity was relatively mild in each case and no patient died from the procedure. Four patients relapsed and seven are alive in unmaintained complete remission with a median duration of leukemia-free survival of 29 months (range 15-56 months) after the first ABMT. These data demonstrate the feasibility of repeating ABMT after melphalan in children with ANLL. The eventual impact of such therapy needs to be demonstrated in prospective randomized studies.


Transformation by the fos or jun oncogene does not increase AP-1 DNA-binding activity.
The c-fos and c-jun proto-oncogenes encode components of the transcription factor AP-1. To determine whether transformation by the v-fos or v-jun oncogene results in alterations in the level or regulation of this factor, we have characterized AP-1 DNA-binding activity in nuclear extracts prepared from v-fos- and c-fos-transformed rat fibroblast cell lines and v-jun-transformed chicken embryo fibroblasts under various growth conditions. During proliferation, the level of AP-1 DNA-binding activity does not differ among the v-fos, c-fos, or v-jun-transformed cells and their normal progenitors, despite constitutive overexpression of the corresponding oncoproteins. Therefore, although necessary, it is not likely that an increase in DNA binding is sufficient for fos or jun transformation. Normal rat and chicken fibroblasts demonstrate very low levels of AP-1 DNA-binding activity when quiescent, and upon serum stimulation a biphasic increase is observed. A similar cyclical pattern is seen in v-fos-transformed cells, but in v-jun-transformed cells AP-1 DNA-binding activity does not fluctuate in response to serum stimulation, which suggests that this level of control may be exerted through the Jun component of the AP-1 complex.


Interaction of RNA with phage display selected peptides analyzed by capillary electrophoresis mobility shift assay.
A sensitive capillary electrophoresis mobility shift assay (CEMSA) to analyze RNA/peptide interactions has been developed. Capillary electrophoresis (CE) has been adapted for investigating the interaction between variously methylated 17-nt analogs of the yeast tRNAPhe anticodon stem and loop domain (ASL(Phe)) and 15-amino-acid peptides selected from a random phage display library (RPL). A peptide-concentration-dependent formation of RNA/peptide complex was clearly visible during CEMSA. In the presence of peptide, the UV-monitored CE peak for ASLPhe with three of the five naturally occurring modifications (2'-O-methylcytidine (Cm32), 2'-O-methylguanine (Gm34) and 5-methylcytidine (m5C40) shifted from 18.16 to 20.90 min. The mobility shift was observed only for methylated RNA. The negative effects of diffusion, electroosmotic flow and adhesion of molecules to the capillary internal wall were suppressed by using a buffer containing a sieving polymer and a polyacrylamide-coated capillary. Under these conditions, well-shaped peaks and resolution of RNA free and bound to peptide were achieved. Peptide tF2, the most populated ligand in the RPL, specifically bound triply methylated ASLPhe in a methylated nucleoside-dependent manner. CE was found to be an efficient and sensitive method for the qualitative analysis of RNA-peptide interaction and should be generally applicable to the study of RNA-peptide (protein) interactions.


National Practitioner Data Bank for Adverse Information on Physicians and Other Health Care Practitioners: reporting on adverse and negative actions. Final rule.
This final rule revises existing regulations under sections 401 through 432 of the Health Care Quality Improvement Act of 1986, governing the National Practitioner Data Bank for Adverse Information on Physicians and Other Health Care Practitioners, to incorporate statutory requirements under section 1921 of the Social Security Act, as amended by section 5(b) of the Medicare and Medicaid Patient and Program Protection Act of 1987 (MMPPPA), and as amended by the Omnibus Budget Reconciliation Act of 1990 (OBRA). The MMPPPA, along with certain additional provisions in the OBRA, was designed to protect program beneficiaries from unfit health care practitioners, and otherwise improve the anti-fraud provisions of Medicare and State health care programs. Section 1921, the statutory authority upon which this regulatory action is based, requires each State to adopt a system of reporting to the Secretary of Health and Human Services (the Secretary) certain adverse licensure actions taken against health care practitioners and health care entities licensed or otherwise authorized by a State (or a political subdivision thereof) to provide health care services. It also requires each State to report any negative actions or findings that a State licensing authority, peer review organization, or private accreditation entity has concluded against a health care practitioner or health care entity.


Comparison of the effects of stability exercise and balance exercise on muscle activity in female patients with chronic low back pain.
Stability exercise (SE) and balance exercise (BE) are generally-applied clinical interventions for back pain. For a proper clinical application, it is necessary to characterize and compare the effects of SE and BE on low back pain (LBP). The purpose of this study was to compare the effects of SE and BE on the activity of trunk muscles in women with chronic LBP. Women with chronic LBP (n=30) who volunteered for this study were randomly divided into two exercise groups of 15 participants. We obtained pre- and postintervention data through application of the visual analogue scale (VAS), Oswestry Disability Index (ODI), and electromyography (EMG). While post-intervention EMG showed decreased activity of the external oblique (EO) in the SE group, the EMG results in the BE group showed increased EO activity (P<0.05). Both groups had increased muscle activity of the erector spinae (P<0.05). Both groups showed significant reductions on the VAS and ODI (P<0.05). Both SE and BE were effective in reducing pain in the study participants. The decrease in EO muscle activity in the SE group seems to be due to the SE inducing cocontraction and distributing the role of the EO to other muscles. In contrast, EO muscle activity was increased in the BE group. It appears that the EO is important in maintaining the center of gravity and base of support during BE. The role of EO seems to maintain trunk stability as it increases muscle activity of EO.


Glycogen in leukocytes from bovine blood and milk.
Glycogen content was determined quantitatively by the Anthrone reagent method in leukocytes obtained from blood and milk of five cows. Distribution of glycogen in leukocytes was studied by microscopic examination of slides stained by Periodic acid-Schiff (PAS) reaction. Blood glucose concentrations were investigated in these animals by standard procedures. In two of five cows both blood glucose levels and blood leukocyte glycogen levels on the same day were determined for six consecutive days. One hundred and two blood leukocyte samples from five cows had a mean glycogen content of 1.32 +/- 0.04 (S.E.) mg/10(9) WBC, and 6.11 +/- 0.17 (S.E.) mg/10(9) PMNs. Leukocyte preparations from 80 samples of milk comprising 97 to 98% PMNs contained 3.81 +/- 0.18 (S.E.) mg glycogen/10(9) milk leukocytes. In PAS preparations of blood and milk leukocytes glycogen was found almost exclusively in PMNs. Glycogen granules, present frequently in PMNs and occasionally in monocytes and large lymphocytes from blood, were not observed in those from milk. The glycogen level in milk leukocytes was significantly lower (P = <0.01) than that of the blood PMNs in every cow, and the overall mean difference between levels for milk leukocytes and blood PMNs was highly significant (P = <0.001). Mean blood glucose concentration in the five cows was 44.46 +/- 0.66 (S.E.) mg%. There was no significant relationship between blood glucose and blood leukocyte glycogen levels in the five corresponding cows; nor between blood glucose and blood PMN glycogen levels on the same day in either of two cows investigated. Leukocyte preparations from milk samples obtained on the second day following intramammary infusion of endotoxin consistently contained markedly less glycogen than the leukocyte preparations from first day post-infusion samples. These tended to level off and became intermediate between first and second day levels. It is postulated that the poor phagocytic competence of leukocytes from bovine mammary glands compared to their counterparts in blood observed by various workers may be due partially to low energy reserves in these cells.