Racial Disparities in Renal Outcomes Over Time Among Hospitalized Children With Systemic Lupus Erythematosus.
Racial and ethnic minority groups have excess morbidity related to renal disease in pediatric-onset systemic lupus erythematosus (SLE). This study was undertaken to evaluate temporal trends in renal outcomes and racial disparities among hospitalized children with SLE over a period of 14 years. We identified patients 21 years old or younger with discharge diagnoses of SLE in the Pediatric Health Information System inpatient database (2006-2019). Adverse renal outcomes included end-stage renal disease (ESRD), dialysis, or transplant, analyzed as a composite and separately. We estimated the odds of adverse renal outcomes at any hospitalization or the first occurrence of an adverse renal outcome, adjusted for calendar period, patient characteristics, and clustering by hospital. We tested whether racial disparities differed by calendar period. There were 20,893 admissions for 7,434 SLE patients, of which 32%, 16%, 12%, and 8% were Black, Hispanic White, Hispanic Other, and Asian, respectively. Proportions of admissions with adverse renal outcomes decreased over time (P < 0.01). Black children remained at the highest risk of adverse renal outcomes at any admission (odds ratio [OR] 2.5 [95% confidence interval (95% CI) 1.8-3.5] versus non-Hispanic White patients). Black and Asian children remained at a higher risk of incident adverse renal outcomes, driven by ESRD among Black children (OR 1.6 [95% CI 1.2-2.1]) and dialysis among Asians (OR 1.7 [95% CI 1.1-2.7]). Relative disparities did not change significantly over time. Significant reductions in ESRD and dialysis occurred over time for children with SLE across all racial and ethnic groups. The lack of corresponding reductions in racial disparities highlights the need for targeted interventions to achieve greater treatment benefit among higher risk groups.


Synthesis and Structural Study of Amidrazone Derived Pyrrole-2,5-Dione Derivatives: Potential Anti-Inflammatory Agents.
1H-pyrrole-2,5-dione derivatives are known for their wide range of pharmacological properties, including anti-inflammatory and antimicrobial activities. This study aimed to synthesize new 3,4-dimethyl-1H-pyrrole-2,5-dione derivatives 2a-2f in the reaction of N3-substituted amidrazones with 2,3-dimethylmaleic anhydride and evaluate their structural and biological properties. Compounds 2a-2f were studied by the 1H-13C NMR two-dimensional techniques (HMQC, HMBC) and single-crystal X-ray diffraction (derivatives 2a and 2d). The anti-inflammatory activity of compounds 2a-2f was examined by both an anti-proliferative study and a production study on the inhibition of pro-inflammatory cytokines (IL-6 and TNF-α) in anti-CD3 antibody- or lipopolysaccharide-stimulated human peripheral blood mononuclear cell (PBMC) cultures. The antibacterial activity of compounds 2a-2f against Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Esherichia coli, Pseudomonas aeruginosa, Yersinia enterocolitica, Mycobacterium smegmatis and Nocardia corralina strains was determined using the broth microdilution method. Structural studies of 2a-2f revealed the presence of distinct Z and E stereoisomers in the solid state and the solution. All compounds significantly inhibited the proliferation of PBMCs in anti-CD3-stimulated cultures. The strongest effect was observed for derivatives 2a-2d. The strongest inhibition of pro-inflammatory cytokine production was observed for the most promising anti-inflammatory compound 2a.


A new topographic approach to the spread of breast cancer: the grid method.
In a series of 181 patients with breast cancer treated by mastectomy with axillary lymph node dissection, the authors developed and used an improved topographic technique, which they call the "Grid Method", which maps out the extent of a given cance of the breast. Three types of tumor spread are defined: Type 1, limited (L)(31%); Type 2, multifocal (M)(13.2%); and Type 3, extensive (E)(55.8%). This topographic information allows a more accurate assessment of prognosis when used in conjunction with the morphologic findings. Moreover, the topographic "Grid" study is simple to perform and easy to assess. Of prime importance is the relationship between the topographic and mammographic findings.


A HPLC method for the analysis of germacrone in rabbit plasma and its application to a pharmacokinetic study of germacrone after administration of zedoary turmeric oil.
A validated new, simple and highly sensitive reversed-phase HPLC method is developed for studying the pharmacokinetics of germacrone after intravenous administration of zedoary turmeric oil (ZTO) oil-in-water microemulsion. The method did not require a complex and expensive equipment. A high extraction recovery (>80%) of germacrone was obtained. Linear calibration curves obtained with the peak-area ratio (y) of germacrone to internal standard (tanshinoneIIA) versus drug concentration (x) were found to be linear between 8.08 and 808 ng/ml. The limit of quantitation was 8.08 ng/ml. The monitored compounds were completely separated from others in ZTO and from endogenous species in plasma by HPLC. Pharmacokinetic investigations were performed on 18 male rabbits after intravenous administration of ZTO microemulsion via the ear vein at germacrone doses of 3.2, 6.4 and 9.6 mg/kg. The plasma concentration-time data fit to a two-compartment intravenous model with a weight of 1/C(2) (C: germacrone concentration in plasma). Germacrone exhibited linear pharmacokinetics after intravenous administration of ZTO microemulsion to rabbits over the germacrone dose range 3.2-9.6 mg/ml.


Evaluating the Immunogenicity of recombinant VP1 protein from the foot-and-mouth disease virus encapsulated in nanoliposome in guinea pig animal model.
Foot-and-mouth disease (FMD) is considered as contagious in livestock, which is caused by the Picornavridae virus family known as FMD virus (FMDV). In the present study, the VP1 gene from FMDV (O strain) was expressed and purified. In addition, nanoliposomes were utilized as an adjuvant. After formulating the nanoliposomes with DMPC, DMPG, and cholesterol, the recombinant VP1 protein was encapsulated in the nanoliposomes. Further, the intended nanoliposomes in the sizes of 400 and 200 nm, nanoliposome-inactivated FMDV, Freund's adjuvant-inactivated FMDV, and Freund's adjuvant-recombinant VP1 mixtures, and PBS buffer (negative control) were injected to six groups of five guinea pigs. Furthermore, the guinea pig serums were analyzed through using ELISA and serum neutralization tests after four boosting vaccinations. Based on the results, the immunogenicity of the 200 nm-nanoliposomes encapsulating recombinant VP1 protein was more than that of 400 nm-ones so that 200 nm-nanoliposomes could trigger the immune response against FMDV in guinea pigs.


Disagreement of Radial Peripapillary Capillary Density Among Four Optical Coherence Tomography Angiography Devices.
This prospective study evaluated the agreement among four optical coherence tomography angiography (OCTA) devices in the assessment of radial peripapillary capillary (RPC) density. The study included 48 eyes of 48 subjects (14 healthy, 19 glaucomatous, and 15 non-glaucomatous optic neuropathy). Each participant was scanned using four OCTA devices in a random sequence: RTVue XR Avanti (RTVue), DRI OCT Triton (Triton), Revo NX 130 (Revo), and PLEX Elite 9000 (PlexE). All 6 × 6-mm grayscale OCTA images from each device were analyzed for RPC density using a customized algorithm. Agreement between each pair of devices was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman plots. There was a poor correlation between devices in all comparisons (RTVue-Triton, ICC = 0.34; RTVue-Revo, ICC = 0.31; RTVue-PlexE, ICC = 0.28; Triton-Revo, ICC = 0.31; Triton-PlexE, ICC = 0.17; Revo-PlexE, ICC = 0.34). Significant proportional biases (P < 0.05) and wide limits of agreement with apparent constant biases were identified in all comparisons. The mean difference was greatest for the RTVue-Revo pair (-49.3%; 95% confidence interval [CI], -52.9 to -45.8) and smallest for the Triton-PlexE pair (-7.7%; 95% CI, -10.1 to -5.3). The RPC densities obtained from each device had poor inter-device agreement and significant biases and cannot be used interchangeably. RPC density obtained from different OCTA devices is not interchangeable; thus, the progression of optic neuropathy should be monitored using the same OCTA device.


Studies of biologic parameters for denture design. Part III: Effects of occlusal adjustment, base retention, and fit on masseter muscle activity and masticatory performance.
EMG recordings of ipsilateral and contralateral masseter muscles and standardized masticatory performance tests were made in 20 denture wearers before and after modifications were made to their clinically unsatisfactory dentures. The improvement of retention and stability by correction of gross occlusal prematurities and by the use of a denture adhesive or base reline with a soft tissue-conditioning material did not significantly alter the chewing performance or muscle activity during mastication in denture wearers. The results support our previous findings that the influence of denture factors on chewing ability of denture wearers is limited. To avoid variations in EMG activity caused by changes in electrode positions, all tests for a given subject were made at the same sitting. Thus the study design did not provide time to denture wearers for their neuromuscular mechanism to adapt to the modifications prior to testing masticatory function. A replication of this study that permits sufficient adaptation time after each modification is suggested to validate the findings.


Emergence of inferior Q-waves during tachycardia.
A case is presented where the emergence of inferior, pathologic Q-waves aids in the differential diagnosis.


Application of headspace solid phase dynamic extraction gas chromatography/mass spectrometry (HS-SPDE-GC/MS) for biomonitoring of n-heptane and its metabolites in blood.
Solid phase dynamic extraction (SPDE) is an innovative sample preparation and enrichment technique in connection with gas chromatography (GC). Using SPDE, we developed a method for simultaneous determination of n-heptane and its mono-oxygenated metabolites heptane-4-one, 3-one, 2-one, 4-ol, 3-ol, 2-ol, and 1-ol in blood. After adjustment of various extraction and desorption parameters, method validation resulted in limits of detection (LOD) between 0.006 (heptane-4-one) and 0.021mg/L (heptane-1-ol). Intra-assay coefficients of variation ranged between 4.8% and 20.8% while relative recovery ranged between 100% and 117% (spiked concentration 0.128mg/L, n=8). The method was applied to blood samples, which have been collected from 20 volunteers after controlled inhalative exposure to 167, 333, and 500ppm n-heptane. After 3h of exposure, n-heptane and heptane-2-one were detectable in all samples in concentrations ranging up to 2.903 and 0.495mg/L, while the concentrations of the remaining analytes were closer to the respective LOD or even below. A significant linear relationship with ambient exposure (R(2)=0.701, p<0.001, n=55) was found for n-heptane in blood, which could be helpful for evaluation of biological exposure limits in future. Due to its high abundance in blood, 2-heptanone could be an interesting candidate as a biomarker also in alternative matrices such as urine or saliva.


[When congenital lung malformations have to be operated?].
Both technical and anatomical features and the need for a long follow-up, usually over several years, explain the specificity of lung surgery in children. Apart from the oncological resections, the main indications for this surgery are congenital lung anomalies (cystic adenomatoid malformation, bronchopulmonary sequestration, lobar emphysema), symptomatic postinfectious lesions (bronchiectasis, atelectasis, abscess) and pneumothorax. Advances in miniaturization of the surgical equipment are used to carry the majority of these interventions by thoracoscopy, except when performed at the neonatal period. In the newborn, for which the indications for lung surgical resections are exceptional, ventilatory conditions and the tightness of the chest lead to still prefer open surgery. Pulmonary malformations can also be managed prenatally when they affect lung development or cause heart failure because of compressive complications. These interventions, performed after the 30th week of gestation, are not intended to remove the lesions, but to release the compression. But these procedures are still under evaluation and, in light of possible fetal and maternal complications, they should only be performed in tertiary centers and in the context of specific protocols.


Characteristics of contrast-enhanced ultrasound for diagnosis of solid clear cell renal cell carcinomas ≤4 cm: A meta-analysis.
Now solid renal tumors ≤4 cm is the most common, especially the subtype of clear cell renal cell carcinoma (ccRCC) of malignant kidney tumors in clinical. However, there is not specific characteristics of contrast-enhanced ultrasound (CEUS) be recommended by the EFSUMB Guidelines in distinguish the essence of the kidney tumor with different sizes. Therefore, this meta-analysis aimed to assess the ability of CEUS to diagnose solid ccRCC (sccRCC) ≤4 cm. We comprehensively searched the Cochrane Library, Embase, PubMed, and Web of Science databases from their inception to 28 July 2020, for studies reporting the CEUS features of sccRCC lesions ≤4 cm. Additional articles were identified through the Chinese National Knowledge Infrastructure database. Studies were selected independently by two investigators and the relevant data were extracted. Discrepancies were resolved via discussion with the senior author. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, and the sensitivity and specificity of each study were determined and plotted as a receiver operating characteristic curve. Ten studies were included in this meta-analysis. Hyperenhancement showed medium sensitivity (67%-89%) and specificity (42%-75%) for diagnosing sccRCC ≤4 cm, fast-in contrast agent and heterogeneous enhancement showed high diagnostic abilities (area under curve (AUC) 0.74-0.84), but the presence of a pseudocapsule and fast-out contrast agent had poor diagnostic ability (AUC <0.70). The combination of hyperenhancement and iso-enhancement showed high sensitivity (98%) for diagnosing sccRCC ≤4 cm. Hyperenhancement, fast-in contrast agent, and heterogeneous enhancement may be specific features that could help to identify sccRCC ≤4 cm, while the presence of a pseudocapsule and fast-out of contrast agent may have low diagnostic values. The combination of multiple indexes may improve the diagnostic value of CEUS for sccRCC ≤4 cm.


Molecular and anatomical characterization of parabrachial neurons and their axonal projections.
The parabrachial nucleus (PBN) is a major hub that receives sensory information from both internal and external environments. Specific populations of PBN neurons are involved in behaviors including food and water intake, nociceptive responses, breathing regulation, as well as learning and responding appropriately to threatening stimuli. However, it is unclear how many PBN neuron populations exist and how different behaviors may be encoded by unique signaling molecules or receptors. Here we provide a repository of data on the molecular identity, spatial location, and projection patterns of dozens of PBN neuron subclusters. Using single-cell RNA sequencing, we identified 21 subclusters of neurons in the PBN and neighboring regions. Multiplexed in situ hybridization showed many of these subclusters are enriched within specific PBN subregions with scattered cells in several other regions. We also provide detailed visualization of the axonal projections from 21 Cre-driver lines of mice. These results are all publicly available for download and provide a foundation for further interrogation of PBN functions and connections.


A pilot study of GC/MS-based serum metabolic profiling of acute rejection in renal transplantation.
Acute allograft rejection is one of the important complications after renal transplantation, and it is a deleterious factor for long-term graft survival. Rejection is a complex pathophysiologic process, which has been explained by transcriptome and proteome in RNA transcripts and proteins level respectively. How are serum metabolite levels in response to acute rejection? Can metabolite levels in serum be used to diagnose and explain acute renal allograft rejection? Gas chromatograph-mass spectrometry (GC-MS) was used to analyze serum metabolome in 22 recipients of acute rejection and 15 stable renal transplant recipients. 46 endogenous metabolites included amino acid, fatty acid, carbohydrate and other intermediate metabolites were identified in 37 recipients. Principal component analysis based on these metabolites discriminated acute rejection group from stable recipients. Among these metabolites, the levels of 17 metabolites were significant higher in rejection group than those in stable group. These included amino acid (phenylalanine, serine, glycine, threonine, valine), carbohydrate (galactose oxime, glycose, fructose), carboxylic acid, lipids and other metabolite such as lactate, urea and myo-inositol. The levels of 5 metabolites of alanine, lysine, leucine, aminomalonic acid and tetradecanoic acid were low in rejection group compared to stable group. The prediction accuracy of acute rejection was 77.3% and stable function was 100% by supervised clustering based on these 22 metabolites. This study demonstrated that metabolic profile was changed in response to rejection process and renal function can be reflected by serum metabolite levels. This study showed potential capability to diagnose acute rejection by metabolome analysis.


Regrouping induces anhedonia-like responses in dairy heifers.
Intensively housed dairy cattle are commonly regrouped (mixed into a new social group) as part of routine farm procedures. This stressful procedure triggers heightened levels of agonistic behaviors and disrupts animals' time budgets. However, little is known regarding the effects of regrouping on cattle's affective states. The aim of this study was to explore whether regrouping (involving a change in both the social and physical environment) triggers anhedonia (i.e., the reduced ability to experience pleasure) in 6-mo-old dairy heifers, a phenomenon associated with negative mood. In this study, we assessed anhedonia using changes in the use of a mechanical brush. Holstein heifers (n = 16) were trained to use a mechanical brush and then given the opportunity to individually brush for 10 min every 2 d. Time spent brushing (during a 10-min brush test) was collected before, during, and after regrouping (2-d interval) with the assumption that heifers would reduce their use of the brush during regrouping. Each heifer was individually regrouped into a new social group composed of 12 older and unfamiliar heifers and allowed access to the brush at 8 and 56 h after the onset of regrouping. Immediately after the last test, each heifer was brought back to her original pen and allowed to mingle with familiar pen-mates before being tested again 2 and 4 d later. When tested 8 h after regrouping, heifers reduced time spent brushing by 44 ± 27% (95% confidence interval: -96.18 to -41.8) compared with before regrouping; however, no differences were detected 56 h after regrouping. There was no relationship between the intensity of the decrease in brush use and any behaviors (number of agonistic interactions received, time heifers spent resting, or synchronization at the feed bunk) recorded for the 8 h immediately before testing (i.e., between 0 and 8 h and between 48 and 56 h after regrouping). These results indicate that regrouping induces anhedonia-like responses in dairy heifers on the day of regrouping. This routine procedure may thus induce negative mood in dairy heifers. This response was not related to behaviors typically collected to assess the negative effects of regrouping. Maintaining dairy cattle in stable social groups should be favored.


A simple, versatile method for GFP-based super-resolution microscopy via nanobodies.
We developed a method to use any GFP-tagged construct in single-molecule super-resolution microscopy. By targeting GFP with small, high-affinity antibodies coupled to organic dyes, we achieved nanometer spatial resolution and minimal linkage error when analyzing microtubules, living neurons and yeast cells. We show that in combination with libraries encoding GFP-tagged proteins, virtually any known protein can immediately be used in super-resolution microscopy and that simplified labeling schemes allow high-throughput super-resolution imaging.


The do's, don'ts and don't knows of redressing differential attainment related to race/ethnicity in medical schools.
Systematic and structural inequities in power and privilege create differential attainment whereby differences in average levels of performance are observed between students from different socio-demographic groups. This paper reviews the international evidence on differential attainment related to ethnicity/race in medical school, drawing together the key messages from research to date to provide guidance for educators to operationalize and enact change and identify areas for further research. Authors first identified areas of conceptual importance within differential attainment (learning, assessment, and systems/institutional factors) which were then the focus of a targeted review of the literature on differential attainment related to ethnicity/race in medical education and, where available and relevant, literature from higher education more generally. Each author then conducted a review of the literature and proposed guidelines based on their experience and research literature. The guidelines were iteratively reviewed and refined between all authors until we reached consensus on the Do's, Don'ts and Don't Knows. We present 13 guidelines with a summary of the research evidence for each. Guidelines address assessment practices (assessment design, assessment formats, use of assessments and post-hoc analysis) and educational systems and cultures (student experience, learning environment, faculty diversity and diversity practices). Differential attainment related to ethnicity/race is a complex, systemic problem reflective of unequal norms and practices within broader society and evident throughout assessment practices, the learning environment and student experiences at medical school. Currently, the strongest empirical evidence is around assessment processes themselves. There is emerging evidence of minoritized students facing discrimination and having different learning experiences in medical school, but more studies are needed. There is a pressing need for research on how to effectively redress systemic issues within our medical schools, particularly related to inequity in teaching and learning.


The management of testicular seminoma: Edinburgh 1970-1981.
One hundred and fifty two patients with seminoma of the testis presenting to a regional centre between 1970 and 1981 have been reviewed. One hundred and forty three of these patients were treated primarily with radiotherapy. The actuarial survival of all 152 patients was 84.4% at 5 years and 83.3% at 10 years. The following factors significantly influenced survival: clinical stage; T-stage of the primary tumour; date of first treatment. Patients treated after 1979 had a better prognosis than patients treated before 1973. A group of patients with an actuarial survival of 100% at 5 years could be identified: they were in clinical stage I after lymphography and had T1 primary tumours. We could find no clear relationship between tumour size, duration of symptoms and clinical stage at presentation. We conclude that radiation therapy still has an important role to play in the management of seminoma of the testis. We recommend prophylactic retroperitoneal irradiation for patients in clinical stage I, primary treatment with radiotherapy for patients in clinical stages IIA and IIB, and primary treatment with chemotherapy for patients in clinical stages IIC, III and IV.


The Action of Discoidin Domain Receptor 2 in Basal Tumor Cells and Stromal Cancer-Associated Fibroblasts Is Critical for Breast Cancer Metastasis.
High levels of collagen deposition in human and mouse breast tumors are associated with poor outcome due to increased local invasion and distant metastases. Using a genetic approach, we show that, in mice, the action of the fibrillar collagen receptor discoidin domain receptor 2 (DDR2) in both tumor and tumor-stromal cells is critical for breast cancer metastasis yet does not affect primary tumor growth. In tumor cells, DDR2 in basal epithelial cells regulates the collective invasion of tumor organoids. In stromal cancer-associated fibroblasts (CAFs), DDR2 is critical for extracellular matrix production and the organization of collagen fibers. The action of DDR2 in CAFs also enhances tumor cell collective invasion through a pathway distinct from the tumor-cell-intrinsic function of DDR2. This work identifies DDR2 as a potential therapeutic target that controls breast cancer metastases through its action in both tumor cells and tumor-stromal cells at the primary tumor site.


[Myelodysplastic syndrome : prognostic factors].
The prognostic evaluation of myelodysplastic syndromes has evolved considerably over time, both due to the evolution of diagnostic classifications and the improvement in the prediction of the outcome. Many prognostic scores that have been developed over time take into account number and depth of blood cytopenias, as well bone marrow blast, cytogenetic, and more recently, molecular mutations. All these variables have been grouped together in IPSS-M score since 2022, which should quickly become a reference for the prognostic evaluation of MDS, as soon as molecular information is available for the patient.


Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings.
Common variable immunodeficiency may be complicated by interstitial lung disease, which leads to worsened morbidity and mortality in some. Although immunomodulatory treatment has efficacy, choice of patient, duration of treatment, and long-term follow-up are not available. Interstitial lung disease appears stable in certain instances, so it is not known whether all patients will develop progressive disease or require immunomodulatory therapy. This study aims to determine if all common variable immunodeficiency patients with interstitial lung disease have physiological worsening, and if clinical and/or laboratory parameters may correlate with disease progression. A retrospective review of medical records at Mount Sinai Medical Center in New York was conducted for referred patients with common variable immunodeficiency, CT scan-confirmed interstitial lung disease, and periodic pulmonary function testing covering 20 or more months before immunomodulatory therapy. Fifteen patients were identified from the retrospective review and included in this study. Of the 15 patients with common variable immunodeficiency, 9 had physiological worsening of interstitial lung disease adapted from consensus guidelines, associated with significant reductions in forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of the lung for carbon monoxide. Those with progressive lung disease also had significantly lower mean immunoglobulin G levels, greater increases and highest levels of serum immunoglobulin M (IgM), and more significant thrombocytopenia. Interstitial lung disease resulted in physiological worsening in many, but not all subjects, and was associated with suboptimal immunoglobulin G replacement. Those with worsening pulmonary function tests, elevated IgM, and severe thrombocytopenic episodes appear to be at highest risk for progressive disease. Such patients may benefit from immunomodulatory treatment.


Growth engineering of Propionibacterium freudenreichii shermanii for organic acids and other value-added products formation.
Propionic acid production from glucose was studied using Propionibacterium freudenreichii shermanii. Conditions were optimized for high yields of propionic acid and total organic acids by sequential optimization of parameters like pH, inoculum age, inoculum volume and substrate concentration. Near-theoretical yield (0.54 ± 0.023 g/g) was achieved for propionic acid with fermentation of 1% glucose using 20% (v/v) of 48 hr old P. shermanii at 30°C, pH maintained at 5.5. Total organic acid yield under these conditions was 0.74 ± 0.06 g/g. The study resulted in achieving 98% and 95% theoretical yields of propionic acid and total organic acids, respectively. Under optimized conditions, along with organic acids, P. shermanii also produced vitamin B12 and trehalose intracellularly, showing its potential to be used as a cell factory.


Rotator Cuff Delamination Is Associated With Increased Tendon Retraction and Higher Fatty Muscle Infiltration: A Comparative Study on Arthroscopy and Magnetic Resonance Imaging.
To investigate (1) tendon delamination according to different rotator cuff tear patterns as well as (2) the association of tendon retraction and fatty muscle infiltration with delamination of the rotator cuff. Furthermore, we aimed to establish the accuracy of magnetic resonance imaging for the detection of rotator cuff delamination. Magnetic resonance imaging scans of patients who underwent arthroscopic rotator cuff repair from 2013 to 2015 were retrospectively compared to intraoperative findings. Prevalences of tendon delamination, tendon retraction, and fatty muscle infiltration were categorized according to different rotator cuff tear patterns. For comparability of the amount of tendon retraction of delaminated and non-delaminated rotator cuff tears, we introduced the global retraction index, a description individually assessing tendon retraction in magnetic resonance imaging scans of all visible layers. Of 349 shoulders, tendon delamination was observed in 231 patients (66.2%). Of these, rotator cuff delamination was most commonly seen in posterosuperior rotator cuff tears (84.6%). Delaminated rotator cuff tears presented with a significantly higher global retraction index (P < .001) as well as higher fatty muscle infiltration of the supraspinatus (P = .001) and infraspinatus (P = .001). Magnetic resonance imaging had only moderate accuracy (57.3%) to detect rotator cuff delamination, with a positive predictive value of 100% (95% confidence interval [CI] 95.6% to 100.0%) and a negative predictive value of 44.2% (95% CI 38.1% to 50.4%). Tendon delamination was most commonly observed in posterosuperior rotator cuff tears. Delaminated rotator cuff tears showed a significantly greater tendon retraction as well as a higher amount of fatty muscle infiltration of the supraspinatus and infraspinatus. Magnetic resonance imaging has only moderate accuracy for detection of rotator cuff delamination. III, retrospective cohort study.


Overall safety profile and effectiveness of tramadol hydrochloride/acetaminophen in patients with chronic noncancer pain in Japanese real-world practice.
To evaluate the overall safety profile and clinical effectiveness of tramadol hydrochloride/acetaminophen (TA) combination tablets in Japanese patients with chronic noncancer pain unrelieved by non-opioid drugs for up to 12 weeks in real-world practice. This survey was a multicenter, prospective, longitudinal registry on the use of TA as a newly initiated pain treatment for chronic noncancer pain incurable by non-opioid analgesics that was conducted under the Good Post Marketing Study Practice regulation controlled by the Japan Ministry of Health, Labor and Welfare. Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician's global impression (PGI) during the 12 week observation period. A total of 1316 patients were registered. ADRs were reported in 259 patients (20.5%); most events were nonserious (99.4%), including nausea (n = 87 [6.9%]), constipation (n = 63 [5.0%]), dizziness and somnolence (n = 29 [2.3%] each), and vomiting (n = 21 [1.7%]). No event related to drug dependence or respiratory depression was reported. In addition, 82.8% of patients showed acceptable effectiveness based on PGI at Week 4. Numerical rating scale for intensity of pain and EQ-5D utility scores were improved by -2.7 (SD 2.3) and 0.16 (SD 0.20) at Week 4, respectively, and the improvement was maintained until Week 12. This is a first report to evaluate the risk-benefit profile of TA in Japanese real-world practice using large size registry data. It is suggested that the favorable risk-benefit balance of TA was confirmed for patients with chronic noncancer pain unrelieved by non-opioid drugs in real-world practice. Limitations of this study were those inherent to open-label and non-interventional study designs. This registry survey is registered at umin.ac.jp (identifier: UMIN000015901).


The Impact of the COVID-19 Pandemic on Foreign Body Ingestion Trends in Children: A Comparison of the Pre-Pandemic Period to 2020.
Foreign body ingestion (FBI) among children is associated with morbidity and mortality. We used the National Electronic Injury Surveillance System to compare FBI trends from 2017-2019 to 2020 during the spread of SARS-CoV-2. The pandemic and associated stay-at-home orders were associated with uptrends in button battery and magnet ingestions but unchanged total FBI trends.


Microwave assisted synthesis of novel pyrazolone derivatives attached to a pyrimidine moiety and evaluation of their anti-inflammatory, analgesic and antipyretic activities.
In the present research work, the motto was to develop new chemical entities as potential anti-inflammatory, analgesic and antipyretic agents. Various 4-(2-amino-6-(substituted)pyrimidin-4-yl)-3-methyl-1-(substituted)-1H-pyrazol-5(4H)-one derivatives (5a-5j) and their Schiff bases (6a-6j) were synthesized. The newly synthesized compounds were characterized by TLC and spectral data. The compounds containing pyrazolone and amino pyrimidine as basic moieties (5a-5j), were screened for their anti-inflammatory, analgesic and antipyretic activities, compounds 5a, 5c-5f, 5h exhibited activities nearly similar to the standard. The pharmacological studies reveal that the presence of 4-hydroxy, 4-methoxy, 4-(N,N-dimethylamino) or 2-hydroxy groups on phenyl ring at C6 of amino pyrimidine exhibits anti-inflammatory, analgesic and antipyretic activities nearly similar to the standard and substitutions like 4-chloro, 2-nitro, 3-nitro or 4-nitro on same phenyl ring lead to a decrease in activities.


New method to estimate the sample size for calculation of a proportion assuming binomial distribution.
Nowadays the formula to calculate the sample size for estimate a proportion (as prevalence) is based on the Normal distribution, however it would be based on a Binomial distribution which confidence interval was possible to be calculated using the Wilson Score method. By comparing the two formulae (Normal and Binomial distributions), the variation of the amplitude of the confidence intervals is relevant in the tails and the center of the curves. In order to calculate the needed sample size we have simulated an iterative sampling procedure, which shows an underestimation of the sample size for values of prevalence closed to 0 or 1, and also an overestimation for values closed to 0.5. Attending to these results we proposed an algorithm based on Wilson Score method that provides similar values for the sample size than empirically obtained by simulation.


Intranasal Sendai virus-based SARS-CoV-2 vaccine using a mouse model.
The coronavirus disease 2019 (COVID-19) epidemic remains worldwide. The usefulness of the intranasal vaccine and boost immunization against severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) has recently received much attention. We developed an intranasal SARS-CoV-2 vaccine by loading the receptor binding domain of the S protein (S-RBD) of SARS-CoV-2 as an antigen into an F-deficient Sendai virus vector. After the S-RBD-Fd antigen with trimer formation ability was intranasally administered to mice, S-RBD-specific IgM, IgG, IgA, and neutralizing antibody titers were increased in serum or bronchoalveolar lavage fluid for 12 weeks. Furthermore, in mice that received a booster dose at week 8, a marked increase in neutralizing antibodies in the serum and bronchoalveolar lavage fluid was observed at the final evaluation at week 12, which neutralized the pseudotyped lentivirus expressing the SARS-CoV-2 spike protein, indicating the usefulness of the Sendai virus-based SARS-CoV-2 intranasal vaccine.


Estimation accuracy of percent total body fat and percent segmental fat measured by single-frequency bioelectrical impedance analysis with 8 electrodes: the effect of difference in adiposity.
This study aimed to compare the accuracy of percent total body fat (%TBF) and percent segmental fat (%SF) measurements of new automatic single-frequency bioelectrical impedance analysis with 8 electrodes (SF-BIA8), referenced to the dual-energy X-ray absorptiometry (DXA), between different fatness level female groups. Subjects were 34 overweight females (OWG) and 24 normal females (NG). This study used the BIA analyzer of Tanita BC-118 which is a commercially available single frequency bioelectrical impedance analysis system with 8 tactile electrodes. Test-retest reliability in each method was high (intra-class correlations > or =0.96). The SF-BIA8 tends to overestimate %TBF and %SF in the lower extremities and trunk compared with DXA, and consistency with DXA was especially low in %SFs in the lower extremities (left leg: r=0.475, SEE=4.673, right leg: r=0.494, SEE=4.772). Systematic errors regarding to the difference in fatness were found in %TBF and %SFs in lower extremities in OWG, and were found in %SF in upper extremities in NG. Furthermore, systematic errors regarding to the difference in body fat distribution were found in %SFs in lower extremities in OWG, and found in %SFs in upper extremities and trunk in NG. SF-BIA can provide highly reproducible measurements of %TBF and %SF, but systematic errors based on the differences in fatness and body fat distribution were found. An improved prediction equation considering a variety in fat and body fat distribution will be needed in further investigations.


Probiotic Properties of Pediococcus pentosaceus JBCC 106 and Its Lactic Acid Fermentation on Broccoli Juice.
To understand the biological roles of Pediococcus pentosaceus strains as probiotics isolated from the traditional Korean fermented food, Jangajji, Pediococcus pentosaceus was selected based on its high cinnamoyl esterase (CE) and antioxidant activities. The acid and bile stability, intestinal adhesion, antagonistic activity against human pathogens, cholesterol-lowering effects, and immune system stimulation without inflammatory effects were evaluated. Nitric oxide (NO) levels were measured in co-culture with various bacterial stimulants. Fermentation ability was measured by using a broccoli matrix and the sulforaphane levels were measured. Resistance to acidic and bilious conditions and 8% adherence to Caco-2 cells were observed. Cholesterol levels were lowered by 51% by assimilation. Moreover, these strains exhibited immunomodulatory properties with induction of macrophage TNF-α and IL-6 and had microstatic effects on various pathogens. Co-culture with various bacterial stimulants resulted in increased NO production. Fermentation activity was increased with the strains, and higher sulforaphane levels were observed. Therefore, in the future, the applicability of the selected strain to broccoli matrix-based fermented functional foods should be confirmed.


p38 mitogen-activated protein kinase regulates canonical Wnt-beta-catenin signaling by inactivation of GSK3beta.
The Wnt-beta-catenin canonical signaling pathway is crucial for normal embryonic development, and aberrant expression of components of this pathway results in oncogenesis. Upon scanning for the mitogen-activated protein kinase (MAPK) pathways that might intersect with the canonical Wnt-beta-catenin signaling pathway in response to Wnt3a, we observed a strong activation of p38 MAPK in mouse F9 teratocarcinoma cells. Wnt3a-induced p38 MAPK activation was sensitive to siRNAs against Galpha(q) or Galpha(s), but not against either Galpha(o) or Galpha(11). Activation of p38 MAPK is critical for canonical Wnt-beta-catenin signaling. Chemical inhibitors of p38 MAPK (SB203580 or SB239063) and expression of a dominant negative-version of p38 MAPK attenuate Wnt3a-induced accumulation of beta-catenin, Lef/Tcf-sensitive gene activation, and primitive endoderm formation. Furthermore, epistasis experiments pinpoint p38 MAPK as operating downstream of Dishevelleds. We also demonstrate that chemical inhibition of p38 MAPK restores Wnt3a-attenuated GSK3beta kinase activity. We demonstrate the involvement of G-proteins and Dishevelleds in Wnt3a-induced p38 MAPK activation, highlighting a critical role for p38 MAPK in canonical Wnt-beta-catenin signaling.


Methylthioadenosine serves as a single carbon source to the folate co-enzyme pool in rat bone marrow cells.
[ribose-U-14C]Methylthioadenosine (MTA) was prepared by incubating methionine with [14C-U]ATP in the presence of methionine adenosyltransferase and the resulting S-adenosylmethionine was heated to release MTA. Labelled [14C]MTA, when incubated with rat bone marrow cells, yielded [14C]formate which was used in the synthesis of adenine and guanine. Unlike 14C from sodium, formate, serine and glycine, there was no decline in 14C utilization from MTA with bone marrow cells from rats in which cobalamin had been inactivated by exposure to nitrous oxide. It was concluded that methionine via MTA is a significant contributor of single-carbon units at the formate level of oxidation and that this pathway is maintained in cobalamin 'deficiency'.


A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C.
Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.


Non-blood contacting biventricular support for severe heart failure.
Direct mechanical ventricular actuation (DMVA) is a non-blood contacting method of biventricular support. DMVA employs a vacuum attached, pneumatically regulated, flexible membrane to transfer both systolic and diastolic forces to the ventricular myocardium. The purpose of this study was to determine if DMVA effectively restores pump performance when applied to the severely failing heart. Bovines (n = 10) underwent thoracotomy and were instrumented for continuous hemodynamic monitoring. Cardiac failure was induced by beta1-blockade to achieve a cardiac index of < 1.5 l/min/m2 for 1 hour. Heart rate was maintained at 100 bpm by atrioventricular sequential pacing. Synchronous DMVA support was then applied for 3 hours. Eight animals achieved significant reductions in cardiac index and mean arterial pressures (35%* and 43%* control, respectively; *p < 0.05). DMVA restored cardiac index to baseline and significantly increased arterial pressures (p < 0.05; DMVA versus cardiac failure). Pulmonary flow and mean pulmonary artery pressures were similar to baseline during DMVA (p = NS). Pathologic exam did not demonstrate evidence of significant device trauma. DMVA support can effectively restore pump performance of the acutely failing heart. Synchronization may be inherent to the stimulus of cardiac compression. These data further substantiate DMVA's potential as an adjunct to the field of circulatory support.


A rare case of recurrent eccrine poroma underlying gluteal abscess.
Eccrine poroma is a benign adnexal neoplasm originating from epidermal sweat ducts mainly affecting the palmoplantar skin, buttock as a location of origin of poroma has rarely been reported, it is the first reported case of recurrent poroma in this site. We report an unusual case of eccrine poroma in the gluteal region of a 62 years old female associated with gluteal abscess, surgically excised with histologically clear margins, then recurred after one and half year with a given history of mild trauma. Given the uncommonness of these neoplasms, there stays a general lack of data on pathogenesis, atypical presentation, atypical sites, recurrence and risk of malignant transformation into porocarcinoma. Gluteal skin is an unusual location for a benign poroma. Early recognition and appropriate treatment at the initial presentation by complete resection with histopathology confirmation and follow-up are crucial to ruling out other diagnoses, such as lesions of malignant transformation.


Defining the sources and the fate of nitrate by using dual isotopes and a Bayesian isotope mixing model: Water-nitrate management in cascade dams of Lancang river.
A multi-isotopes approach involving the use of stable nitrate isotopes (δ15N-NO3- and δ18O-NO3-) combined with stable water isotopes (δD-H2O and δ18O-H2O) and SIAR model as tracers can help identify the nitrogen source and understand the transformation process in a river-cascade reservoirs system. In this study, we identify the potential impact of the N source in the Lancang River basin, clarified the seasonal variations in the isotope values and estimated the probability distribution and proportional contribution of multi-terminal NO3--N sources using Bayesian isotope mixing model. In addition, we investigate the factors that led to the seasonal variations of the stable isotopes and evaluated the relationship between the uncertainty of the contribution ratio of the N sources and isotopic variations in the river-cascade reservoirs system. The NO3--N is the main component of DIN (dissolved inorganic nitrogen), accounting for 68.1 % of DIN. The ratios of δ15N-NO3- and δ18O-NO3- ranged from +4.2 ‰ to +10.3 ‰, and from +5.9 ‰ to +9.3 ‰ in the Lancang River. The δD-H2O and δ18O-H2O of the surface waters ranged from -109.47 ‰ to -76.44 ‰, and from -15.13 ‰ to -11.61 ‰, respectively. The SIAR model analysis results show that nitrification of livestock and poultry manure is the main source of NO3--N in the upstream natural reach, accounting for 40.2 %. There is little difference between the wet season and the dry season. Nitrification of soil organic nitrogen is the main source of NO3--N in the cascade development reach, accounting for 42.3 %. The contribution rate of atmospheric precipitation to nitrate concentration in both sampling periods is low (<5 %). This study provides a useful insight for reservoir water environmental managers to verify cascade development river pollution contributors and to better apply remedial solutions.


A report of a spring-summer outbreak of echovirus II infection.
A spring-summer epidemic of echovirus II in New South Wales, Australia, is reported. The symptomatology was found to be age dependent. Neonates and young infants tended to have a severe 'septicaemic' illness. Older infants had a variety of clinical presentations: aseptic meningitis, febrile convulsions, upper respiratory tract infections, and acute enteritis. Children over the age of two in this study uniformly presented with symptoms suggestive of aseptic meningitis--confirmed by cerebrospinal (CSF) cytology in the majority of cases. The clinical presentation of an acute febrile illness in the young child may not allow for distinction between bacterial and viral infection. The importance of the recognition and confirmation of a viral aetiology relates to the subsequent management: i.e. antibiotics may be withheld, hospitalisation may be shortened, and a more favourable prognosis can be made. Certain epidemiological clues and laboratory studies are helpful in suggesting a viral aetiology, but a definitive diagnosis of enteroviral infection may only be readily achieved by virus isolation in tissue culture.


Commercialization of quality.
Without overriding financial imperatives, the commercial marketplace for products and services enabling quality improvement, quality assurance, and quality control has been limited in health care. Companies serving this industry have had a difficult time finding business justification to bring these products to market. However, government initiatives in the past 6 years attempting to reduce health care costs are placing an emphasis on better, more appropriate, and more effective health care delivery through evidence-based medicine. Incentives,penalties, and reimbursements for providers serving Medicare and Medicaid patients are being implemented or altered to encourage this adoption. Within this new environment,quality systems become vital tools in managing optimal operations, and thus, a new commercial marketplace is rapidly evolving for vendors to develop, promote, and profitably sell quality assurance and quality control products and services.With a viable, growing, and competitive market, radiologists, technologists, and radiology administrators may look forward to having a wide choice of quality tools to help them make their departments an invaluable resource in a changing healthcare delivery system.


Influence of storage environment, maturity stage and pre-storage disinfection treatments on tomato fruit quality during winter in KwaZulu-Natal, South Africa.
The aim of this study was to explore influence of evaporative cooling (EC), pre-storage disinfection treatments and maturity stage at harvest on postharvest quality of tomato fruit. The tomato samples (Lycopersicon esculentum Mill. cv. Nemonetta) were harvested, stored for 28 days and data were collected every seven days. The pH, total titratable acidity (TTA), total soluble solids (TSS), firmness, colour, weight loss (PWL) and marketability percentage were analysed. The temperature difference between ambient storage and EC at the fan varied between 4 and 7 °C, the relative humidity (RH) varied between 31 and 86%, while at different locations inside the EC it varied between 2-3 °C and 5-8%, respectively. Maturity had significant influence on the overall quality of tomatoes. The pH value of green, pink and red tomato was 4.86 and 5.03. The TTA content, the TSS content significantly affected over the 14 days of storage. TSS:TA was found to be in the range of 7.8-33.9. The EC storage shows a higher firmness and hue angle, when compared to the ambient conditions stored tomatoes. Compared to ambient storage, EC storage reduced the PWL by 7-10% over 30 days, while ambient storage took 15 days. EC storage and pre-storage treatments improved the shelf-life and marketability of tomatoes. However, variation in temperature and RH inside EC could affect the storability of the produce.


Characteristics of carboxylesterase genes and their expression-level between acaricide-susceptible and resistant Tetranychus cinnabarinus (Boisduval).
Carboxylesterases (CarEs) play important roles in metabolism and detoxification of dietary and environmental xenobiotics in insects and mites. On the basis of the Tetranychuscinnabarinus transcriptome dataset, 23 CarE genes (6 genes are full sequence and 17 genes are partial sequence) were identified. Synergist bioassay showed that CarEs were involved in acaricide detoxification and resistance in fenpropathrin- (FeR) and cyflumetofen-resistant (CyR) strains. In order to further reveal the relationship between CarE gene's expression and acaricide-resistance in T. cinnabarinus, we profiled their expression in susceptible (SS) and resistant strains (FeR, and CyR). There were 8 and 4 over-expressed carboxylesterase genes in FeR and CyR, respectively, from which the over-expressions were detected at mRNA level, but not DNA level. Pesticide induction experiment elucidated that 4 of 8 and 2 of 4 up-regulated genes were inducible with significance in FeR and CyR strains, respectively, but they could not be induced in SS strain, which indicated that these genes became more enhanced and effective to withstand the pesticides' stress in resistant T. cinnabarinus. Most expression-changed and all inducible genes possess the Abhydrolase_3 motif, which is a catalytic domain for hydrolyzing. As a whole, these findings in current study provide clues for further elucidating the function and regulation mechanism of these carboxylesterase genes in T. cinnabarinus' resistance formation.


Efficacy of a voluntary BVDV control programme: Experiences from the Netherlands.
The outcomes of a voluntary bovine viral diarrhoea virus (BVDV) control programme that has been in place in the Netherlands since 1997 were analysed. This 'BVDV-free' programme was studied in dairy herds in the period 1 August 2007 to 1 August 2013. The programme was based on a test and cull approach at the herd level, after which the BVDV status was monitored by testing young stock for antibodies against BVDV or by antigen testing of newborn calves. One of the challenges of the programme was that, without any legislation or subsidies, farmers had to be motivated to pay all costs involved, with eradication of BVDV from their farm as the only incentive. During the study period, the percentage of dairy farms with a 'BVDV-free' status in the Netherlands increased from 13% to 24%, while the prevalence of active BVDV infections in Dutch dairy herds decreased. This may be related to the increasing number of participants in the 'BVDV-free' programme.


Improvement of soil acidification and ammonium nitrogen content in tea plantations by long-term use of organic fertilizer.
Soil acidification is common in some Chinese tea plantations, which seriously affected growth of tea trees. Hence, it is essential to explore soil remediation in acidified tea plantations for sustainable development of the tea industry. We sought to determine how different fertilizers affect acidified soil and their N transformation in tea plantations. Different fertilizers were used on acidified tea plantation soils for 4 years (2017-2021), and changes in soil pH, indices related to soil N transformation and tea yield were analysed to construct interaction networks of these indices and find which had the largest influence on fertilization. Long-term use of sheep manure reduced soil acidification, increased soil pH, enhanced the number and intensity of N-fixing and ammonifying bacteria, urease, protease, asparaginase and N-acetamide glucose ribosidase activity and nifH gene expression. This treatment reduced the number and intensity of soil nitrifying and denitrifying bacteria, nitrate reductase and nitrite reductase activity, while the expression of amoA-AOA, nirK, nirS, narG and nosZ in turn increased ammonium N content of the soil, reduced nitrate N content, and enhanced tea yield. Topsis index weight analysis showed that ammonium N content in the soil had the largest impact among fertilization effects. Long-term use of sheep manure was beneficial in restoring the balance of the micro-ecosystem in acidified soil. This study provides an important practical basis for soil remediation and fertilizer management in acidified tea plantation soils.


The Effects of Repeated Administration of the Micellar Complex of Methylprednisolone on the Locomotor Activity of a Terrestrial Snails.
We studied the effects of repeated injections of methylprednisolone and its micellar complex with block-copolymer on locomotor activity of a terrestrial snail. It was shown that methylprednisolone solution injected into the hemolymph of the animal produced a direct effect on the muscle system of the animal as soon as 1 h after administration: it slowed down snail locomotion and reduced contractile activity of the foot muscles. The micellar complex of methylprednisolone with block-copolymer prevented this effect during the first 2 days of injection and negatively affected locomotion only in 2 days after injection, the decrease in locomotion in this case was not accompanied by a decrease in contractile activity of the foot muscle.


Determinant selection is a macrophage dependent immune response gene function.
Immune response (Ir) genes are linked to the species histocompatibility complex and define as yet uncharacterised phenotypic products which control the immune response to thymus dependent antigens. Antibody formation and antigen induced T lymphocyte proliferation are two examples of immune phenomena which, in vivo and in vitro, operate under Ir gene influence. To clarify their mechanism of action and cellular location, we have examined the contribution of antigen structure (amino acid sequence and conformation to Ir gene control of antigen recognition by T lymphocytes) as well as to the critical role played by the antigen presenting macrophage in expression of that control. We report that immune response gene control of antigen recognition operates at least in part at the level of the macrophage.


[The difficulty of growing old far from home].
Somatic difficulties, solitude and the loss of independence are challenges facing ageing people, whatever their culture. However, when one is far from one's home, one's country, one's family, in a complex political and social context, this stage of life can be even more of an ordeal.


Quantitative analysis of differential protein expression in cervical carcinoma cells after zeylenone treatment by stable isotope labeling with amino acids in cell culture.
Cervical carcinoma is a malignant tumor that poses a serious threat to women's health and survival. Approximately 10-25% of cervical cancers are adenocarcinomas (ACs). AC has high rates of recurrence and mortality, while there is no effective treatment for now. Zeylenone (Zey), which is isolated from an ethanol extract of the leaves of Uvaria grandiflora Roxb. of the family Annonaceae, has shown potent inhibitory activity against various tumor cells, including cervical carcinoma cells. To gain insight into the molecular mechanism underlying the effect of Zey on AC, we quantified protein expression changes in AC cells treated with Zey. We used stable isotope labeling with amino acids in cell culture (SILAC) in combination with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and bioinformatics analysis to compare protein expression profiles in HeLa cells before and after Zey treatment. Of 1805 differentially expressed proteins identified, 229 were screened as key protein molecules and classified into nine categories. Profiling of differentially-expressed proteins contributed to our understanding of the molecular mechanism by which Zey induces HeLa cell apoptosis. Using this method, candidate targets can be identified for developing new drugs against cervical carcinoma.


The conscious self: ontology, epistemology and the mirror quest.
Here we address the notion of the self as the subject of experience, in contrast with its other popular meanings of a state of self-awareness, a body image, or a narrative center. In this perspective, the main player is not consciousness per se (the famous "hard problem"), but its subject. We start by showing that the self as the subject of immediate self-awareness cannot be conceived as an illusion. Then we formulate axioms of the self-concept based on the framework that Chalmers initially developed for consciousness. Using a thought experiments (the "mirror quest"), we show that this framework may require corrections in order to accommodate the subject. We analyze several possibilities that lead to a novel doctrine of "subjective nonreductive functionalism". As an epistemological model, this position has further important implications for brain sciences.


Sex Differences in Percutaneous Coronary Intervention-Insights From the Coronary Angiography and PCI Registry of the German Society of Cardiology.
Several studies have suggested sex-related differences in diagnostic and invasive therapeutic coronary procedures. Data from consecutive patients who were enrolled in the Coronary Angiography and PCI Registry of the German Society of Cardiology were analyzed. We aimed to compare sex-related differences in in-hospital outcomes of patients undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease, non-ST elevation acute coronary syndromes, ST elevation myocardial infarction, and cardiogenic shock. From 2007 until the end of 2009 data from 185 312 PCIs were prospectively registered: 27.9% of the PCIs were performed in women. Primary PCI success rate was identical between the sexes (94%). There were no sex-related differences in hospital mortality among patients undergoing PCI for stable coronary artery disease, non-ST elevation acute coronary syndromes, or cardiogenic shock except among ST elevation myocardial infarction patients. Compared to men, women undergoing primary PCI for ST elevation myocardial infarction have a higher risk of in-hospital death, age-adjusted odds ratio (1.19, 95% CI 1.06-1.33), and risk of ischemic cardiac and cerebrovascular events (death, myocardial infarction, transient ischemic attack/stroke), (age-adjusted odds ratio 1.19, 95% CI 1.16-1.29). Furthermore, access-related complications were twice as high in women, irrespective of the indication. Despite identical technical success rates of PCI between the 2 sexes, women with PCI for ST elevation myocardial infarction have a 20% higher age-adjusted risk of death and of ischemic cardiac and cerebrovascular events. Further research is needed to determine the reasons for these differences.


Noninvasive assessment of characteristics of novel anti-HER2 antibodies by molecular imaging in a human gastric cancer xenograft-bearing mouse model.
Human epidermal growth factor receptor 2 (HER2) overexpression occurs in various types of cancers. Regarding the anti-HER2 targeted therapies showed superior treatment outcomes in several (pre)clinical studies, we used multimodality image to rapidly select novel HER2-targeting antibodies for further therapeutics development. The four anti-HER2 antibodies (H32 IgG, 75 IgG, 61 IgG, and trastuzumab) labeled with either In-111 or a DyLight680 fluorescent dye were applied to perform cellular uptake, endocytosis, optical/microSPECT/CT imaging and biodistribution studies. In vitro and in vivo relative effectiveness of these antibodies were also compared in an N87 gastric cancer xenograft model. The internalized radioactivity of [111In]61 IgG in N87 cells increased from 33% at 12 hr to 56% at 48 hr after incubation, while the majority of other antibodies stayed on the cell membranes. Among these antibodies, 61 IgG showed the highest accumulation in tumors with the tumor-to-muscle ratio (T/M) of 131 ± 61.4 and 19.13 ± 3.42 conducted by IVIS and microSPECT/CT, respectively. We demonstrated that multimodality imaging is a reliable approach for selecting potential antibodies and found that 61 IgG manifested significant tumor accumulation with elevated internalization rate thus could be a suitable candidate for further development of new HER2-targeted therapies.


Cumulative area of peaks in a multidimensional high performance liquid chromatogram.
An algorithm was developed to recognize peaks in a multidimensional separation and calculate their cumulative peak area. To find the retention times of peaks in a one dimensional chromatogram, the Savitzky-Golay smoothing filter was used to smooth and find the first through third derivatives of the experimental profiles. Close examination of the shape of these curves informs on the number of peaks that are present and provides starting values for fitting theoretical profiles. Due to the nature of comprehensive multidimensional HPLC, adjacent cut fractions may contain compounds common to more than one cut fraction. The algorithm determines which components were common in adjacent cuts and subsequently calculates the area of a two-dimensional peak profile by interpolating the surface of the 2D peaks between adjacent peaks. This algorithm was tested by calculating the cumulative peak area of a series of 2D-HPLC separations of alkylbenzenes, phenol and caffeine with varied concentrations. A good relationship was found between the concentration and the cumulative peak area.


Pharmacophore-driven identification of N-methyl-D-receptor antagonists as potent neuroprotective agents validated using in vivo studies.
Alzheimer's disease (AD), apparently the most widespread reason behind dementia, is delineated by a continuous cognitive weakening in the aged. During its progression, N-methyl-D-aspartate receptor (NMDAR) antagonists are known to play a pivotal part in the mechanisms of learning and memory. Since there is an unmet medical need for the treatment of AD, we aim to identify possible chemical compounds targeted toward N-methyl-D-aspartate receptors. Three-dimensional models are developed to unveil some of the essential characteristics of the N-methyl-D-aspartate receptors by using a collection of already discovered N-methyl-D-aspartate receptor inhibitors. This is followed by virtual screening, which results in novel chemical compounds having the potential to inhibit N-methyl-D-aspartate receptors. Molecular docking studies and analysis promulgated two lead compounds with a high LibDock score. The compounds are shortlisted based on high estimated activity, fit values, LibDock score, no violation of Lipinski's, and availability for procuring. Finally, the shortlisted compounds are tested by employing in vivo studies, which we further propose as potential NMDA inhibitors for treating AD.


The association between geriatric assessment, muscle measures, and treatment-related toxicity in older adults with cancer: An Israeli prospective study.
We investigated the associations among frailty, as determined via the comprehensive geriatric assessment (CGA), muscle measures (i.e., sarcopenia), and treatment-related toxicity in older adults with cancer in Israel. This prospective cohort study enrolled patients ≥65 years with newly-diagnosed stage IV lung, breast, or genitourinary cancer. Patients were enrolled and completed CGA before their first line of systemic therapy (chemotherapy, biologic therapy, immunologic therapy, or a combination thereof). CGA was used to classify patients as robust, pre-frail, or frail, and routine pre-treatment computed tomography (CT) images were used to quantify skeletal muscle index (SMI) and skeletal muscle density (SMD) at L3 cross-section. Two sarcopenia definitions were used: i. for women SMI <41 cm2/m2 regardless of body mass index (BMI), and for men SMI <43 cm2/m2 for those with BMI of <25 and < 53 cm2/m2 for those with BMI ≥25; and ii. SMI <38 cm2/m2 for women and < 41 cm2/m2 for men, regardless of BMI. The associations between frailty and muscle measures with the occurrence of at least one adverse event (AE) grade ≥ 2 were examined using the chi-square test, and logistic regression to determine odds ratio (OR) and 95% confidence interval (CI). In total, 51 patients were included in the analysis. The median (interquartile range) age was 72 (68-76) years, 30 (59%) were male, and 26 (51%) had lung cancer. CGA data were available for 48 patients: fifteen (31%), thirteen (27%), and twenty (42%) were defined as robust, pre-frail, and frail, respectively. Overall, 33 (65%) were sarcopenic by the first aforementioned definition, and sixteen (31%) by the second. No statistically significant associations were identified between frailty and having at least one AE grade ≥ 2, or between frailty and sarcopenia. Statistically significant associations were found between having sarcopenia (the second definition) and having at least one AE grade ≥ 2 (P = 0.0217). The corresponding odds ratio (95% CI) was 4.2 (1.2-15.0), P = 0.026. Our findings suggests that sarcopenia is significantly associated with treatment-related toxicity. Further studies with larger sample sizes are warranted.


Arula-7 powder improves diarrhea and intestinal epithelial tight junction function associated with its regulation of intestinal flora in calves infected with pathogenic Escherichia coli O1.
The effects of Arula-7 powder (ASP) on diarrhea and intestinal barrier function associated with its regulation of intestinal microflora in calves infected with pathogenic Escherichia coli O1 (E. coli O1) were studied. Twenty Holstein calves were randomly divided into four treatment groups: normal control (NC), model control (MC), 0.5 mg/kg ciprofloxacin (CIP) and 2.50 g/kg ASP groups. ASP inhibited the relative abundance of Proteobacteria, Selenomonadales, and Enterobacteriales, and increased the relative abundance of Lactobacillus, Faecalibacterium, and Alloprevotella. Moreover, we demonstrated for the first time that the ASP and CIP promoted weight gain, reduced the diarrhea rate (P < 0.05), and enhanced antioxidant capacity (P < 0.05) due to the increase in average daily gain (ADG), total protein (TP), and albumin (ALB). In addition, ASP and CIP increased the expression of Zunola occludens-1 (ZO-1), Occludin, and Claudin-1 in the ileum (P < 0.05), and improved immunity due to increase levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-γ (IFN-γ), immunoglobulin A (IgA), and immunoglobulin G (IgG) in the serum, strengthened CD4+T levels in the ileal mucosa and reducing CD8+T and CD11c+T (P < 0.05). Hence, The intestinal microbiota environment formed by early intervention of ASP powder has a protective effect on the intestinal mucosal function of calves infected with pathogenic E. coli. Video Abstract.


Effects of asphyxia on cardiac output and organ blood flow in the newborn piglet.
Experiments were performed on newborn piglets 6--96 hr of age. When the respiratory dead space was increased arterial pO2 decreased and pCO2 increased. During this time cardiac output was unchanged (Fig. 1), while heart rate, respiratory rate, and blood pressure increased (Figs. 2 and 3). After 90 min of asphyxia blood flow to the stomach and small and large intestines decreased. Changes in blood flow were associated with dilatation of segments of the small and large intestine with scattered areas of hemorrhage. Pathologic examination revealed scattered areas of mucosal necrosis (Fig. 6).


Healthcare Costs Among Patients with Heart Failure: A Comparison of Costs between Matched Decedent and Survivor Cohorts.
Prior research suggests increased costs during the final months of life, yet little is known about healthcare cost differences between patients with heart failure (HF) who die or survive. A retrospective claims study from a large US health plan [commercial and Medicare Advantage with Part D (MAPD)] was conducted. Patients were ≥18 years old with two non-inpatient or one inpatient claim(s) with HF diagnosis code(s). The earliest HF claim date during 1 January 2010-31 December 2011 was the index date. Cohort assignment was based on evidence of death within 1 year (decedents) or survival for >1 year (survivors) post-index. Per-patient-per-month (PPPM) and 1-year (variable decedent follow-up) costs (all-cause and HF-related) were calculated up to 1 year post-index. Cohorts were matched on demographic and clinical characteristics. Independent samples t tests and Pearson's chi-square tests were used to examine cohort differences. Among patients with HF, 8344 survivors were 1:1 matched to decedents [mean age 75 years, 50% female, 88% MAPD; mean time to decedents' death: 150 (SD 105) days]. Compared to survivors, more decedents had no pharmacy claims for HF-related outpatient pharmacotherapy within 60 days post-index (42.1% vs. 27.1%; p < 0.001). Decedents also incurred higher all-cause medical costs (PPPM: $21,400 vs. $2663; 1 year: $60,048 vs. $32,394; both p < 0.001) and higher HF-related medical costs (PPPM: $16,477 vs. $1358; 1 year: $39,052 vs. $16,519; both p < 0.001). Hospitalizations accounted for more than half of all-cause PPPM medical costs (54.6% for survivors, 84.3% for decedents). Patients with HF who died within 1 year after an index HF encounter incurred markedly higher costs within 1 year (despite the much shorter post-index period) and PPPM costs than those who survived, with the majority of costs attributable to hospitalizations for both patient cohorts. There may be opportunities for improving outcomes in HF, considering higher use of pharmacotherapy and lower costs were seen among survivors.


Removal of Pb(II) from water using keratin colloidal solution obtained from wool.
The aim of this study is to investigate the use of keratin colloidal solution, which was obtained from wool, for the removal of Pb(II) from water. The addition of keratin colloidal solution (15 g L(-1), 0.30 mL) to a Pb(II) solution (1.0 mM, 0.90 mL, pH 5.0) resulted in the formation and precipitation of a Pb-keratin aggregate. Measurement of the Pb(II) and protein concentrations in the supernatant solution revealed that 88 and 99 % of the Pb(II) and keratin protein were removed from the solution, respectively. The maximum Pb(II) uptake capacity of keratin in the colloidal solution was 43.3 mg g(-1). In addition, the Pb-keratin aggregate was easily decomposed via the addition of nitric acid, which enabled the recovery of Pb(II). However, aggregation did not occur in solutions with Pb(II) concentrations below 0.10 mM. Therefore, we used a keratin colloidal solution encapsulated in a dialysis cellulose tube to remove Pb(II) from 0.10 mM solutions, which enabled the removal of 95 % of the Pb(II). From these results, we conclude that keratin colloidal solution is useful for the treatment of water polluted with Pb(II).


Eosinophilic pustular folliculitis (Ofuji's disease) in myelodysplastic syndrome.
We describe a case of eosinophilic pustular folliculitis (EPF, Ofuji's disease) in a 12-year-old male who suffered from myelodysplastic syndrome. Bone marrow study revealed an increase in the eosinophil cell line without peripheral blood eosinophilia in our case. We suggest that the immunologic abberations ascribed to myelodysplastic syndrome and the increase in the eosinophil cell line in the bone marrow might play roles in the development of EPF in our case.


A new interpretation of the insulin test validated and then compared with the Burge test.
A prospective study of 40 patients undergoing proximal gastric vagotomy confirmed the validity of a new interpretation of the insulin test in the early postoperative period (Maybury et al., 1977). Of the 30 patients falling into the group expected to be free from recurrent ulceration (low risk group), none had developed symptoms suggestive of this condition, whilst of the 10 in the contrasting high risk group, 6 have already developed proved recurrences (mean follow-up period 26 months). A further group of 24 patients was studied by performing a peroperative Burge test for completeness of vagotomy and comparing these results with a postoperative insulin test. This study showed that the Burge test, properly performed, is a reliable test of the adequacy of vagotomy. The use of this test has led to a better understanding of the operative technique required to achieve the objective of an adequate vagotomy.


Communication and Respect for Patient Value as Significant Factors in Patient-Centered Infertility Care: A Survey of Patients' Experiences in Two Infertility Centers.
The patient-centered infertility care (PCIC) approach emphasizes the patient's role in choosing the most appropriate clinical approach in infertility care. The concept can improve the patient satisfaction with care performed as well as the efficacy of the treatment. In addition, this concept can also lead to improve collaboration between patient and care provider, ultimately supporting a more cost-effective health-care scheme. This study was developed in order to determine patients' experience in their PCIC. This is a descriptive study. We conducted the study in two fertility care clinics, Clinic A and Clinic B. The Patient-Centeredness Questionnaire-Infertility (PCQ-I) was used, consisting of 7 essential themes. The questionnaire was completed by consenting patients in two infertility clinics. The questionnaire was analyzed using the Statistical Package for the Social Sciences 21 version statistical software. Eighty-eight Clinic A patients who completed the questionnaire responded that the best element of their treatment received was communication (correlation with global score [CGS]: 0.747), whereas the least acceptable aspect was the low accessibility (CGS: 0.211). A total of 20 Clinic B patients responded that the best element of their treatment received was respect for the patient's value (CGS: 0.866), whereas the least acceptable aspect was also the low level of accessibility (CGS: 0.193). The PCQ-I can be used to evaluate patients' experience during treatment and may help the health-care provider to improve their performance.


Intracellular peptides in SARS-CoV-2-infected patients.
Intracellular peptides (InPeps) generated by the orchestrated action of the proteasome and intracellular peptidases have biological and pharmacological significance. Here, human plasma relative concentration of specific InPeps was compared between 175 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and 45 SARS-CoV-2 non-infected patients; 2,466 unique peptides were identified, of which 67% were InPeps. The results revealed differences of a specific group of peptides in human plasma comparing non-infected individuals to patients infected by SARS-CoV-2, following the results of the semi-quantitative analyses by isotope-labeled electrospray mass spectrometry. The protein-protein interactions networks enriched pathways, drawn by genes encoding the proteins from which the peptides originated, revealed the presence of the coronavirus disease/COVID-19 network solely in the group of patients fatally infected by SARS-CoV-2. Thus, modulation of the relative plasma levels of specific InPeps could be employed as a predictive tool for disease outcome.


Single and sequential voluntary cough in children with chronic spinal cord injury.
We investigated the impact of spinal cord injury (SCI) on cough capacity in 10 children (Mean ± SD, age 8 ± 4 years) and compared it to 15 typically developing children (age 8 ± 3 years). Participants underwent spirometry, single and sequential cough assessment with surface-electromyography from respiratory muscles. Inspiratory phase duration, inspiratory phase peak flow, inspiratory phase rise time, compression phase duration, expiratory phase rise time, expiratory phase peak airflow (EPPF) and cough volume acceleration (CVA) parameters of single and sequential cough were measured. Root mean square (RMS) values of right pectoralis-major, intercostal, rectus-abdominus (RA), and oblique (OB) muscles were calculated and mean of three trials were compared. The significance criterion was set at P < 0.05. The SCI group produced significantly lower lung volumes, EPPF, CVA, and RMS values of RA and OB during expiratory phases of single and sequential coughs. The decrease in activation in expiratory muscles in the SCI group accounts for the impaired expiratory flow and may contribute to risk of respiratory complications.


[Expression and significance of cyclin D1 in human adenoid cystic carcinoma].
To observe the expression of cyclin D1 in human adnoid cystic carcinoma and its correlation with clinical characters. The expression of cycline D1 was evaluated with immunohistochemical method in forty-one cases of human adnoid cystic carcinoma, 15 cases of PA and 12 cases of normal salivary gland tissue. The expression of cyclin D1 in normal tissue was negative, significantly different from PA and ACC (P < 0.05). The expression level of PA was significantly lower than ACC (P < 0.05). High expression of cyclin D1 was correlated with clinical stage and histological classification (P < 0.05), but not with sex, age, tumor site, recurrence, metastasis. High expression of cyclin D1 promotes the formation and development of ACC.


Unraveling pathophysiologic mechanisms contributing to symptoms in patients with post-acute sequelae of COVID-19 (PASC): A retrospective study.
Patients with post-acute sequelae of COVID-19 (PASC) present with a decrease in physical fitness. The aim of this paper is to reveal the relations between the remaining symptoms, blood volume distribution, exercise tolerance, static and dynamic lung volumes, and overall functioning. Patients with PASC were retrospectively studied. Pulmonary function tests (PFT), 6-minute walk test (6MWT), and cardiopulmonary exercise test were performed. Chest CT was taken and quantified. Patients were divided into two groups: minor functional limitations (MFL) and severe functional limitations (SFL) based on the completed Post-COVID-19 Functional Status scale (PCFS). Twenty one patients (3 M; 18 FM), mean age 44 (IQR 21) were studied. Eighteen completed the PCFS (8 MFL; 10 SFL). VO2 max was suboptimal in both groups (not significant). 6MWT was significantly higher in MFL-group (p = 0.043). Subjects with SFL, had significant lower TLC (p = 0.029). The MFL-group had more air trapping (p = 0.036). Throughout the sample, air trapping correlated significantly with residual volume (RV) in L (p < 0.001). An increase in air trapping was related to an increase in BV5 (p < 0.001). Mean BV5 was 65% (IQR 5%). BV5% in patients with PASC was higher than in patients with acute COVID-19 infection. This increase in BV5% in patients with PASC is thought to be driven by the air trapping in the lobes. This study reveals that symptoms are more driven by occlusion of the small airways. Patients with more physical complaints have significantly lower TLC. All subjects encounter physical limitations as indicated by suboptimal VO2 max. Treatment should focus on opening or re-opening of small airways by recruiting alveoli.


Treating trauma in psychosis with EMDR: a pilot study.
Initial studies have shown that posttraumatic stress disorder (PTSD) can be effectivelytreated in patients with a psychotic disorder. These studies however used adapted treatment protocols, avoided direct exposure to trauma related stimuli or preceded treatment with stabilizing techniques making treatment considerably longer in duration. An open trial in which adult subjects with a psychotic disorder and a comorbid PTSD (n = 27) received a maximum of six Eye Movement Desensitization and Reprocessing (EMDR) therapy sessions. PTSD symptoms, psychotic symptoms and additional symptoms were assessed at baseline and end-of-treatment. The dropout rate was 18.5 percent (five subjects). Only five of the twenty-two completers (22.7%) still met criteria for PTSD after treatment. PTSD symptoms, auditory verbal hallucinations, delusions, anxiety, depression, and self-esteem all improved significantly. Paranoid ideation and feelings of hopelessness did not improve significantly. Treatment did not lead to symptom exacerbation in subjects. There were no adverse events, such as suicide attempts, self-mutilation, aggressive behavior or admission to a general or psychiatric hospital. This pilot study shows that a short EMDR therapy is effective and safe in the treatment of PTSD in subjects with a psychotic disorder. Treatment of PTSD has a positive effect on auditory verbal hallucinations, delusions, anxiety symptoms, depression symptoms, and self-esteem. EMDR can be applied to this group of patients without adapting the treatment protocol or delaying treatment by preceding it with stabilizing interventions.


Stem cell-specific expression of Dax1 is conferred by STAT3 and Oct3/4 in embryonic stem cells.
Embryonic stem (ES) cells are pluripotent cells derived from inner cell mass of blastocysts. An orphan nuclear receptor, Dax1, is specifically expressed in undifferentiated ES cells and plays an important role in their self-renewal. The regulatory mechanism of Dax1 expression in ES cells, however, remains unknown. In this study, we found that STAT3 and Oct3/4, essential transcription factors for ES cell self-renewal, are involved in the regulation of Dax1 expression. Suppression of either STAT3 or Oct3/4 resulted in down-regulation of Dax1. Reporter assay identified putative binding sites for these factors in the promoter/enhancer region of the Dax1 gene. Chromatin immunoprecipitation analysis suggested the in vivo association of STAT3 and Oct3/4 with the putative sites. Furthermore, gel shift assay indicated that these transcription factors directly bind to their putative binding sites. These results suggest that STAT3 and Oct3/4 control the expression of Dax1 to maintain the self-renewal of ES cells.


Preciseness, rather than simplicity, is required to assess pesticide reduction strategies: Findings from rice production in Japan.
Pesticide reduction is given high priority in the worldwide sustainability agenda. The reduction of pesticide impacts, rather than the reduction of application rates, has become a common criterion for monitoring policy progress. However, simplicity-an essential requirement in improving the applicability of pesticide impact assessment-may distort the accuracy of the evaluation and therefore prevent effective pesticide reduction. Here, we present contrasting results that underscore how the selection of evaluation methods that differ in simplicity affects the assessment results of pesticide reduction strategies. Briefly, we analysed the impact of conversion from conventional to low-input management adopting both a simplified linear-based method and a precise method that includes newly calculated nonlinear approach-based characterization factors for 109 active ingredients (AIs). The two methods were then used to estimate the freshwater ecotoxicity impact of eight rice farms in Japan where both conventional pesticide application and pesticide reduction strategies are practiced. The results show that the simplified method generated anomalies at the farm level through overestimation and underestimation of the individual AI impacts. Patterns that contributed to extreme changes of impact at the farm level were also identified. These findings suggest a strong need for a precise evaluation method for effectively monitoring policy progress at the farm level.


The receptor for the plasminogen activator of urokinase type is up-regulated in transformed rat thyroid cells.
Five rat thyroid cell lines were tested for the expression of the cell surface receptor for urokinase type plasminogen activator (uPA). All tested lines were found to bind uPA, but transformed 1-5G and Ki-Mol cells, which are also high uPA producers, bound at least ten times more uPA, as compared to non-producers, 'normal' TL5 cells. Moreover, it was possible to remove membrane-bound uPA by treating the cells with phosphatidylinositol-specific phospholipase C, suggesting that rat uPAR, like its human counterpart, is linked to the membrane by a glucosyl-phosphatidylinositol anchor. The specificity of the binding was tested by competition with three different synthetic peptides corresponding to amino acids 14-37 of human, rat and mouse uPA. The results indicate also that the receptor binding region of rat uPA is located within the growth factor domain of the molecule and that its expression may be dependent on the transformed state of the cells.


Introducing molasses as an alternative feedstock into itaconate production using Ustilago sp.
In this work, we established an efficient process for the production of itaconate from the regionally sourced industrial side-stream molasses using Ustilago cynodontis and Ustilago maydis. While being relatively cheap and more environmentally friendly than refined sugars, there are some major challenges to overcome when working with molasses. Some of those challenges are a high nitrogen load, unknown impurities in the feedstock, and high amounts of ill-favoured carbon sources, such as sucrose or lactate. We could show that the activity of the sucrose-hydrolysing enzyme invertase plays a crucial role in the efficiency of the process and that the fructose utilisation differs between the two strains used in this work. Thus, with a higher invertase activity, the ability to convert fructose into the desired product itaconate, and an overall higher tolerance towards undesired substances in molasses, U. maydis is better equipped for the process on the alternative feedstock molasses than U. cynodontis. The established process with U. maydis reached competitive yields of up to 0.38 g g-1 and a titre of more than 37 g L-1. This shows that an efficient and cost-effective itaconate production process is generally feasible using U. maydis, which has the potential to greatly increase the sustainability of industrial itaconate production.


[Bipolarity, monopolarity and "dichotomous functional decay" as principles of differential diagnosis and "functional pathology" of endogenous psychoses].
On the basis of Leonhard's Classification of the endogenous psychoses an attempt is made to trace the phenomenology of the monopolar and bipolar affective psychoses as well as Leonhard's "unsystematic schizophrenias" to three different functional anomalies. The differential diagnosis between the "cycloid psychoses" and the "unsystematic schizophrenias" as well as the problem of the so-called schizoaffective psychoses connected with them, is of particular interest. The arrangement to "functional areas" seems to be suitable.


[Diet and physiologic pregnancy: energy and macronutrients requirements].
This article briefly reviews the most important issues of past and present medical literature on maternal nutrition and fetal well-being, with particular attention to energy and macronutrients requirements (proteins, lipids, carbohydrates) in pregnancy. Guidelines for nutrition in pregnancy and a few examples of diets for physiological pregnancy will be presented.


[Ultrasonography in jaundice: signs and results in 199 cases (author's transl)].
Ultrasonic patterns of bile ducts dilatation were studied in 199 cases. In the most recent series of obstructive jaundices (50 cases) examined with a high resolution machine, the diagnosis of dilatation was made in 92% of cases, the diagnostic of level of obstruction in 92% of cases, and the diagnosis of cause of obstruction in 61% of cases (but in 22 out of 23 jaundices due to a pancreatic lesion: 95%). No false positive diagnosis was made in non obstructive jaundice. Improved technology had a definite impact on the quality of results.


Classifying Pituitary Adenoma Invasiveness Based on Radiological, Surgical and Histological Features: A Retrospective Assessment of 903 Cases.
Invasiveness is a major predictor of surgical outcome and long-term prognosis in patients with pituitary adenomas (PAs). We assessed PA invasiveness via radiological, surgical and histological perspectives to establish a classification scheme for predicting invasive behavior and poor prognosis. We retrospectively analyzed 903 patients who underwent transnasal-transsphenoidal surgery between January 2013 and December 2019. Radiological (hazard ratio (HR) 5.11, 95% confidence interval (CI): 3.98−6.57, p < 0.001) and surgical (HR 6.40, 95% CI: 5.09−8.06, p < 0.001) invasiveness better predicted gross-total resection (GTR) and recurrence/progression-free survival (RPFS) rates than did histological invasiveness (HR 1.44, 95% CI: 1.14−1.81, p = 0.003). Knosp grades 2 (HR 4.63, 95% CI: 2.13−10.06, p < 0.001) and 3 (HR 2.23, 95% CI: 1.39−3.59, p = 0.011) with surgical invasiveness were better predictors of prognosis than corresponding Knosp grades without surgical invasiveness. Classifications 1 and 2 were established based on radiological, surgical and histological invasiveness, and Knosp classification and surgical invasiveness, respectively. Classification 2 predicted RPFS better than Knosp classification and Classification 1. Overall, radiological and surgical invasiveness were clinically valuable as prognostic predictors. The convenience and good accuracy of Invasiveness in Classification 2 is useful for identifying invasive PAs and facilitating the development of treatment plans.


Clinicopathologic studies of a case of aortic arch syndrome.
The clinicopathologic features of a 62-year-old woman with the aortic arch syndrome who presented with ischemic ocular inflammation, followed by complete loss of vision, is presented. The pathophysiology and ocular manifestations of chronic ocular ischemia are discussed.


Estimating firing rates from calcium signals in locust projection neurons in vivo.
Combining intracellular electrophysiology and multi-photon calcium imaging in vivo, we studied the relationship between calcium signals (sampled at 500-750 Hz) and spike output in principal neurons in the locust antennal lobe. Our goal was to determine whether the firing rate of individual neurons can be estimated in vivo with calcium imaging and, if so, to measure directly the accuracy and resolution of our estimates. Using the calcium indicator Oregon Green BAPTA-1, we describe a simple method to reconstruct firing rates from dendritic calcium signals with 80-90% accuracy and 50 ms temporal resolution.


Taxonomic study of the leafhopper genus Agnesiella Dworakowska (Hemiptera: Cicadellidae: Typhlocybinae) from China, with descriptions of 13 new species.
Thirteen new species of the leafhopper genus Agnesiella Dworakowska, Agnesiella (Agnesiella) protensa, A. (A.) recurve, A. (A.) polita, A. (Draberiella) gaura, A. (D.) longisagittata, A. (D.) eleganta, A. (D.) glabra, A. (D.) exigua, A. (D.) mitrata, A. (D.) apiculata, A. (D.) tridigitata, A. (D.) lata and A. (D.) stipitata spp. nov., are described and illustrated. A. (A.) marginata and A. (D.) irma are recorded from China for the first time. A checklist and key to the species (males) from China in Agnesiella are provided.


Direct measurement of the viscoelasticity of adsorbed protein layers using atomic force microscopy.
Thick layers of the protein lysozyme have been deposited on mica, and their force-distance hysteresis measured using atomic force microscopy in the presence of different salts. Sodium thiocyanate, which is known to lower the melting temperature of proteins and increase their solubility, increases lysozyme deformability and lowers the viscosity of the protein layer, compared with sodium chloride. Sodium phosphate, known to raise the melting temperature and lower the solubility, decreases deformability and increases the viscosity.


Extended cervical mediastinoscopy in the diagnosis of anterior mediastinal masses.
Although transthoracic needle biopsy (TNB) has been the preferred method for the diagnosis of anterior mediastinal masses, it has inherent limitations in accuracy. In particular, lymphoma and thymoma are diagnosed less reliably using needle biopsy. Videothoracoscopy has been advocated as an alternative method for diagnosis. Our goal was to assess the usefulness of extended cervical mediastinoscopy (ECM) in the diagnosis of anterior mediastinal masses. The ECM technique was performed in 9 patients in whom TNB and Tru-cut biopsies had been inefficient for histologic diagnosis. All lesions were in the anterior mediastinum. Extended cervical mediastinoscopy was carried out using the same incision as in a standard cervical mediastinoscopy and dissection was performed behind the sternum as previously published. Mean operative time was 50 minutes (range 40 to 70 minutes) and mean hospital stay was 8 hours (range 5 to 36 hours). Diagnosis of lymphoma in 4 cases, thymoma in 3 cases, and thymic hyperplasia in 2 cases were obtained by ECM. In 1 of 2 patients with suspected thymoma who underwent resectional surgical procedures, final histologic diagnosis was non-small cell lung carcinoma. There was no surgical mortality or intraoperative complication. One patient had minimal pneumothorax requiring no intervention. We conclude that ECM in the diagnosis of anterior mediastinal masses is technically feasible and provides an alternative to the conventional approaches in patients with paraaortic or aortopulmonary masses.


Cell survival in B16 melanoma after treatment with combinations of cytotoxic agents: lack of potentiation.
The extent of tumour, cell kill, produced by treating B16 melanomas with vincristine, cyclophosphamide, 5-fluorouracil and gamma-rays, alone and in combination, was determined using an in vitro colony assay. Cell kill by vincristine was revealed as a reduction in the yield of cells obtained by trypsinization, and as a decrease in the colony-forming ability of the extracted cells. The reduction in cell yield was interpreted as evidence of rapid cell lysis. Cyclophosphamide and gamma-rays also reduced both cell yield and surviving fraction, but in this case the small decrease in cell yield was due to an increase in cell volume. FU had no effect on cell yield, but surviving fraction was reduced. Tumour weight was also measured, and used in conjunction with cell yield and surviving fraction data to calculate the fraction of surviving cells per tumour following treatment with the agents. In combination studies, single doses of two different cytotoxic agents were given either simultaneously, or up to 24 h apart in either sequence, and assays were performed 24 h after the second drug was given. Combinations of vincristine + cyclophosphamide and 5-fluorouracil + gamma-rays were chosen because they had been shown by other workers to exhibit marked schedule dependency, including considerabl potentiation, against leukaemic cell lines. However, in the B16 melanoma there was no evidence of schedule-dependent cell killing with either of these combinations. For all sequences studied, the fraction of surviving cells per tumour was slightly greater than the predicted additive response calculated from single-drug controls.