2020 ACR Data Science Institute Artificial Intelligence Survey.
The ACR Data Science Institute conducted its first annual survey of ACR members to understand how radiologists are using artificial intelligence (AI) in clinical practice and to provide a baseline for monitoring trends in AI use over time. The ACR Data Science Institute sent a brief electronic survey to all ACR members via email. Invitees were asked for demographic information about their practice and if and how they were currently using AI as part of their clinical work. They were also asked to evaluate the performance of AI models in their practices and to assess future needs. Approximately 30% of radiologists are currently using AI as part of their practice. Large practices were more likely to use AI than smaller ones, and of those using AI in clinical practice, most were using AI to enhance interpretation, most commonly detection of intracranial hemorrhage, pulmonary emboli, and mammographic abnormalities. Of practices not currently using AI, 20% plan to purchase AI tools in the next 1 to 5 years. The survey results indicate a modest penetrance of AI in clinical practice. Information from the survey will help researchers and industry develop AI tools that will enhance radiological practice and improve quality and efficiency in patient care.


The emergence of Nervennahrung: Nerves, mind and metabolism in the long eighteenth century.
Morphological assumptions concerning the form, structure and internal life of the brain and nervous system profoundly influenced contemporary physiological concepts about nerve actions throughout the 'long eighteenth century'. This article investigates some early theories of mind and metabolism. In a bottom-up fashion, it asks how eighteenth-century theories regarding the physiological actions of the body organs shaped the conceptions of the structure of the brain and nervous tissue themselves. These proposed that a healthy Nervennahrung (the German word for 'nerve nutrition', which might be rendered as brain food in modern English), not only guaranteed the integrity and stability of neuronal structures in the body, but also explained the complex texture of the brain and spinal cord in physiological terms. Eighteenth-century nerve theories already embodied a Leitmotiv of neurology and brain psychiatry from the later nineteenth century: 'Without phosphorus there is no thought!'


Norplant-2 rods contraceptive subdermal implants: two-year experience in Singapore.
Norplant-2 contraceptive implants consist of two Silastic rods in which levonorgestrel has been incorporated with the polymer. This on-going study describes our two-year experience with 100 acceptors of Norplant-2 rods in Singapore. No pregnancies occurred during the first two years of use. Desire for planned pregnancy and menstrual irregularities accounted for 86.4% of the removals during this period. The continuation rate at the end of two years was 78%. The post-removal conception rate in women desiring planned pregnancy was 54.5% at the end of one year. Apart from this apparent slow return of fertility requiring future close surveillance, it appears that the Norplant-2 rod system offers a highly effective and convenient means of contraception.


Motorcycle rider error and engagement in distracting activities: A study using the Attention-Related Driving Errors Scale (ARDES-M).
Research on motorcycle rider distraction and inattention is limited, especially when compared to that on car drivers. This study examines motorcycle rider error and its relationship with engagement in distracting activities. Additionally, it provides an adaptation of the Attention-Related Driving Errors Scale for use with motorcycle riders (ARDES-M). A sample of 418 motorcyclists responded to a web questionnaire consisting of the ARDES-M, a self-report measure of Involvement in Distracting Activities (IDA), a measure of everyday inattention (ARCES, Attention Related Cognitive Errors Scale) and socio-demographic and riding-related questions. Riding errors were associated with a higher level of engagement in distracting activities and a greater propensity for inattention in daily life. ARDES-M scores were associated with various types of self-reported traffic crashes and near-crashes, while self-reported distractions (IDA) were only linked with near-crashes. The most widely self-reported distracting activities were using map navigation, listening to the radio or to music and adjusting vehicle devices. The various uses of cell phones were relatively minor. Young riders reported higher levels of engagement in distracting activities and committing more riding errors. The ARDES-M showed good psychometric properties for the sample in Spain.


Primary Pulmonary Involvement in Mucosa-associated Lymphoid Tissue Lymphoma.
Pulmonary nodules have a broad differential diagnosis with primary lung cancer, lung metastases, benign tumors, carcinoid tumors, and infectious granulomas as their common cause. While relatively rare, pulmonary lymphoproliferative disorders such as primary pulmonary lymphomas, primary pulmonary plasmacytomas, secondary lymphomas involving the lung, multiple myeloma involving the lung, leukemias involving the lung should be considered in these patients presenting with lung nodules. Primary pulmonary non-Hodgkin's lymphoma (NHL) is an extremely rare lung tumor accounting for 0.4% of all lymphomas. Mucosa-associated lymphoid tissue (MALT) lymphoma accounts for about 70%-90% of all primary pulmonary lymphomas, constituting less than 0.5% of all the lung neoplasms. Though it usually remains localized, it is a clonal B-cell neoplasm with a potential for systematic spread and transformation to an aggressive B-cell lymphoma. We hereby discuss the case of a 66-year-old woman with primary pulmonary MALT lymphoma.


Extract of Ganoderma sinensis spores induces cell cycle arrest of hepatoma cell via endoplasmic reticulum stress.
Ganoderma sinensis Zhao, Xu et Zhang (Ganodermataceae) has been used for the prevention or treatment of a variety of diseases, including cancer. We investigated the antitumor activity and mechanism of an extract from G. sinensis against hepatocellular carcinoma. A G. sinensis extract (GSE) was obtained from sporoderm-broken G. sinensis spores by supercritical fluid carbon dioxide extraction. Hepatoma cells, HepG2 cells, were treated with emulsified sample of GSE at 12.5, 25, 50, 100 and 150 μg/mL for 24 h. The Alamar Blue assay was used to examine growth inhibitory effects. Changes in cell structure and morphology were assessed via transmission electron microscopy and confocal laser scanning microscope. Cell cycle distribution was analysed by flow cytometry. GSE suppressed the proliferation of HepG2 cells (IC50=70.14 μg/mL). Extensive cytoplasmic vacuolation originating from dilation of the endoplasmic reticulum (ER) was shown in GSE-treated HepG2 cells. GSE treatment also upregulated the expression of ER stress-related proteins in HepG2 cells. Cells tended to be arrested at the G2/M cell cycle stage after GSE treatment (30.8 ± 1.4% and 42.2 ± 2.6% at GSE with 50 μg/mL and 100 μg/mL vs. 21.03 ± 1.10%, control). Pre-treatment with salubrinal, an inhibitor of ER stress, effectively attenuated cell cycle arrest induced by GSE. Our findings provide new evidence that GSE suppresses growth of cancer cells in vitro through activating the ER stress pathway. The GSE may be clinically applied in the prevention and/or treatment of cancer.


Glycosylation of Methoxylated Flavonoids in the Cultures of Isaria fumosorosea KCH J2.
Flavonoids are widely described plant secondary metabolites with high and diverse pro-health properties. In nature, they occur mostly in the form of glycosides. Our research showed that an excellent way to obtain the sugar derivatives of flavonoids is through biotransformations with the use of entomopathogenic filamentous fungi as biocatalysts. In the current paper, we described the biotransformations of five methoxylated flavonoid compounds (2'-methoxyflavanone, 3'-methoxyflavanone, 4'-methoxyflavanone, 6-methoxyflavanone, and 6-methoxyflavone) in cultures of Isaria fumosorosea KCH J2. As a result, we obtained twelve new flavonoid 4-O-methylglucopyranosides. The products were purified with methods that enabled the reduction of the consumption of organic solvents (preparative TLC and flash chromatography). The structures of the products were confirmed with spectroscopic methods (NMR: ¹H, 13C, HSQC, HMBC, COSY). The compounds obtained by us expand the library of available flavonoid derivatives and can be used in biological research.


Evaluation of immune responses of stabilised SAT2 antigens of foot-and-mouth disease in cattle.
Foot-and-mouth disease (FMD) vaccines with improved stability and less reliant on a cold-chain are needed to improve the longevity of immune responses elicited in animals. This is especially so for serotypes O and SAT2 which are unstable in mildly acidic pH conditions or at elevated temperatures leading to dissociation of the capsid (146S particle) and loss of immunogenicity. Previously, stabilised SAT2 viruses were generated by reverse genetic approaches and assessed in vitro and in vivo with a guinea pig trial. Here we investigated the efficacy and comparative immunological responses of two thermostable and wild-type SAT2 vaccines over 5months followed by challenge. We assessed humoral immune responses elicited in cattle in terms of total and neutralizing antibodies and IgG1/2 isotyping; and cell-mediated responses of IFN-γ as in vitro markers of protection. Whilst there were significant differences in total and neutralizing antibodies for the vSAT2-93H group compared to other vaccinated groups after the first vaccination, there were no significant differences after the second immunization. Following intra-dermolingual challenge all vaccinated groups were fully protected as determined by the absence of generalized lesions. These results provide proof that two vaccine doses, consisting of SAT2 antigen combined with ISA206B adjuvant, administered 4-6 weeks apart were able to protect animals up to 5months pv. Additionally, vSAT2-93Y had significantly higher levels of IFN-γ after challenge and had a lower clinical score indicative of better protection compared to other vaccinated groups and the importance of cell mediated responses and antigen stability in protection.


Colorimetric Metal-Free Detection of Carbon Monoxide: Reversible CO Uptake by a BNB Frustrated Lewis Pair.
We report two BNB-type frustrated Lewis pairs which feature an acceptor-donor-acceptor functionalized cavity, and which differ in the nature of the B-bound fluoroaryl group (C6 F5 vs. C6 H3 (CF3 )2 -3,5, Arf ). These receptor systems are capable of capturing gaseous CO, and in the case of the -BArf 2 system this can be shown to occur in reversible fashion at/above room temperature. For both systems, the binding event is accompanied by migration of one of the aryl substituents to the electrophilic carbon of the CO guest. Experiments utilizing an additional equivalent of Pt Bu3 allow the initially formed (non-migrated) CO adduct to be identified and trapped (via demethylation), while also establishing the reversibility of the B-to-C migration process. When partnered with the slightly less Lewis acidic -BArf 2 substituent, this reversibility allows for release of the captured carbon monoxide in the temperature range 40-70 °C, and the possibility for CO sensing, making use of the associated colourless to orange/red colour change.


A review on genotoxicity in connection to infertility and cancer.
Genotoxicity has been identified as the main cause of infertility and a variety of cancers. The mechanisms affect the structure, quality of the information or the segregation of DNA and are not inherently correlated with mutagenicity. The concept of genotoxicity, the chemical classes that cause genetic damage and the associated mechanisms of action are discussed here. Hazardous effects of pharmaceuticals, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials are, in large part, identified by genotoxicity and mutagenicity tests. These are critical and early steps in industrial and regulatory health assessment. Though several in vitro experiments are commonly used and approval by regulatory agencies for commercial licensing of drugs, their accuracy in human predictions for genotoxic and mutagenic effects is frequently questioned. Treatment of real and functional genetic toxicity problems depends in detail on the knowledge of mechanisms of DNA damage in the molecular, subcellular, cellular and tissue or organ system levels. Current strategies for risk assessment of human health need revisions to achieve robust and reliable results for optimizing their effectiveness. Additionally, computerized methods, neo-biomarkers leveraging '-omics' approaches, all of which can provide a convincing genotoxicity evaluation to reduce infertility and cancer risk.


Rapid antibiotic susceptibility testing of bacteria from patients' blood via assaying bacterial metabolic response with surface-enhanced Raman spectroscopy.
Blood stream infection is one of the major public health issues characterized with high cost and high mortality. Timely effective antibiotics usage to control infection is crucial for patients' survival. The standard microbiological diagnosis of infection however can last days. The delay in accurate antibiotic therapy would lead to not only poor clinical outcomes, but also to a rise in antibiotic resistance due to widespread use of empirical broad-spectrum antibiotics. An important measure to tackle this problem is fast determination of bacterial antibiotic susceptibility to optimize antibiotic treatment. We show that a protocol based on surface-enhanced Raman spectroscopy can obtain consistent antibiotic susceptibility test results from clinical blood-culture samples within four hours. The characteristic spectral signatures of the obtained spectra of Staphylococcus aureus and Escherichia coli-prototypic Gram-positive and Gram-negative bacteria-became prominent after an effective pretreatment procedure removed strong interferences from blood constituents. Using them as the biomarkers of bacterial metabolic responses to antibiotics, the protocol reported the susceptibility profiles of tested drugs against these two bacteria acquired from patients' blood with high specificity, sensitivity and speed.


Acquiescent renal infection.
The relationship between bacterial infection of the renal parenchyma with Escherichia coli and the establishment of pathologic lesions has been investigate experimentally. Infection was established in one kidney and the bacteriologic, pathologic and immunologic features of infection were compared in the pyelonephritic and contralateral unmanipulated kidney. Whereas active bacterial infection was associated with pathologic changes in the pyelonephritic kidney, a poor correlation was found between bacterial growth and the gross pathology and histopathologic changes in the contralateral kidney. The conclusion from these studies is that infection of the kidney is not always associated with pathologic changes. The term "acquiescent infection" has been used to describe this host-parasite relationship in which active, persistent, bacterial infection is not associated with pathologic lesions. Evidence is presented that bacteria in the contralateral unmanipulated kidney are present in the renal parenchyma and that bacterial proliferation can be induced following renal trauma. Activation of infection and bacterial proliferation did not always result in histopathologic damage to the kidney and was not associated with an increase in serum antibody.


Absolute angle measurement using the earth-field-referenced hall effect sensors.
A miniaturized absolute angle sensor utilizing Hall generators referenced to the Earth's ambient magnetic field has been developed. The sensor has three-dimensional angular sensitivity which allows the output to be self-normalized resulting in high immunity to both B-field and temperature induced errors. The individual Hall generator elements were operated with a final sensitivity of 4.07 V G-1. The Earth's field, magnitude 0.486 G with a surface declination angle of 58.2 degrees (San Diego, California), was used as the excitation/reference field. Bandwidth limiting, low-noise design, and active/passive thermal compensation techniques were employed resulting in a sensor bandwidth of DC to 100 Hz with a maximum signal-to-noise ratio of 44.5 dB. The maximum angular resolution of the sensor was measured to be +/- 0.27 degrees. Temperature induced error was measured to be less than 2% from 25 degrees C to 40 degrees C. The measurement of shoulder joint rotation was used as the test case application for the sensor with excellent agreement between theoretical and experimental performance.


Physiochemical properties of rice starch for production of vermicelli with premium quality.
Rice vermicelli is a main food consumed in China and Southeast Asia. Quality of rice vermicelli varies with rice cultivars. Parameters including amylose content, amylopectin distribution, thermal and pasting characteristics, gel texture and starch granules of three rice cultivars "Zhongjiazao 17", "Xiangzaoxian 24" and "Thai Jasmine Rice", were studied for their impacts on vermicelli quality. Results showed significant differences for the measurements of the quality traits and indicated that a favorable quality of vermicelli was not determined by any single factor instead of a combination of multi-parameters. A vermicelli with a favorable quality could be produced from a rice variety with a high apparent amylose content (>25%), a protein content of 11%, an intermediate gelatinization temperature and gel consistency, and a gel hardness (~3 N for a Rapid Viscosity Analyzer pasting) and moderate retrogradation capacity (a setback viscosity of 30-100 RVU).


Assessing the impact on nursing practice of CDMS.
Two perspectives for assessing the impact of clinical data management systems on nursing are suggested. The microscopic view is the unit-level, direct patient care perspective. A macroscopic view entails consideration of national nursing issues. Nursing role issues can arise during system selection and implementation and these issues can affect system effectiveness. Professional issues influence the decisions made about CDMS and subsequent system usefulness to nursing. A shift in evaluation emphasis from time savings to assessment of effect is necessary. Suggested nursing areas to be examined are system impact on the development and use of nursing theory in practice, support for the cognitive work of nursing, and changes in the physical work of nursing.


Efficiency limitation of thin film coated planar semiconductor thermal neutron detector.
Semiconductor thermal neutron detectors are increasingly been used in in-core thermal neutron flux measurements in nuclear reactors. One limitation of these detectors is that they suffer from low detection efficiency. In this work, the maximum efficiency of a planar structure thermal neutron detector was determined using two widely used computer codes: Geant4 and MCNP6. Diamond and SiC are used as based materials in this work because of their large electron-hole pair production efficiency which generally translates to high detection efficiency. The electron-hole pair production efficiency is the fraction of energy that goes into electron-hole pair creation and depends on the band-gap energy and the W-values. These two materials are also not susceptible to radiation damage which makes them suitable for high radiation environments such as nuclear reactors. Thermal neutron detection is achieved using 10B and 6LiF conversion layers coated on the surface of the detector. The maximum efficiency for 10B conversion layer was achieved at a thickness of 2 μm. The efficiency at this thickness is 5.57 ± 0.09% and 5.49±0.09% for diamond and silicon carbide, respectively. When 6LiF was used as a thermal neutron conversion layer, the maximum thickness of the conversion layer was determined to occur at 17 μm. The efficiency at this thickness is 5.47 ±0.06% and 5.38±0.06% for diamond and SiC, respectively.


A novel peroxiredoxin activity is located within the C-terminal end of Rhodospirillum rubrum adenylyltransferase.
Adenylyltransferase (GlnE) catalyzes the reversible adenylylation of glutamine synthetase. In this report we present, for the first time, evidence for a peroxiredoxin activity of Rhodospirillum rubrum GlnE, through the carboxyl-terminal AhpC/thiol-specific antioxidant (TSA) domain. The combination of GlnE and AhpC/TSA domains within the same polypeptide constitutes a unique domain architecture that has not previously been identified among proteobacteria.


Semisynthetic beta-lactam antibiotics. II. Synthesis and antibacterial activity of 7beta-[2-(acylamino)-2- (2-aminothiazol-4-yl)acetamido]cephalosporins.
Cephalosporin derivatives (I) substituted with a neutral, acidic or basic amino acid group as the terminal group attached to the 2-amino-2-(2-aminothiazol-4-yl)acetamido side chain at the C-7 position were synthesized, and the effect of each group on antibacterial activity was examined. The derivatives bearing an amidino or guanidino group showed broad spectra of antibacterial activity similar to those of cefotaxime, but they were relatively sensitive to beta-lactamases.


Lectins but not antifungal proteins exhibit anti-nematode activity.
A variety of lectins and antifungal proteins were tested for toxicity against the plant parasitic nematodes Ditylenchus dipsaci and Heterodera glycines. It was found that lectins from the mushrooms Xylaria hypoxylon, Agrocybe cylindracea and Tricholoma mongolicum (TML-1) were the most potent against D. dipsaci, with EC(50) being 4.7, 9, and 20mg/ml, respectively. Lectins from Pseudostellaria heterophylla, samta tomato, and the mushrooms T. mongolicum (TML-2), Ganoderma lucidum, and Boletus edulis, and antifungal proteins from Ginkgo biloba toward D. dipsaci and pumpkin Cucurbita moschata had much lower anti-nematode potencies and could be considered as inactive for practical purposes. All lectins except that from P.heterophylle were potent against H.glycines.


On the efficacy of linear system analysis of renal autoregulation in rats.
In order to assess the linearity of the mechanisms subserving renal blood flow autoregulation, broad-band arterial pressure fluctuations at three different power levels were induced experimentally and the resulting renal blood flow responses were recorded. Linear system analysis methods were applied in both the time and frequency domain. In the frequency domain, spectral estimates employing FFT, autoregressive moving average (ARMA) and moving average (MA) methods were used; only the MA model showed two vascular control mechanisms active at 0.02-0.05 Hz and 0.1-0.18 Hz consistent with previous experimental findings [Holstein-Rathlou et al., Amer. J. Physiol., vol. 258, 1990.]. In the time domain, impulse response functions obtained from the MA model indicated likewise the presence of these two vascular control mechanisms, but the ARMA model failed to show any vascular control mechanism at 0.02-0.05 Hz. The residuals (i.e., model prediction errors) of the MA model were smaller than the ARMA model for all levels of arterial pressure forcings. The observed low coherence values and the significant model residuals in the 0.02-0.05 Hz frequency range suggest that the tubuloglomerular feedback (TGF) active in this frequency range is a nonlinear vascular control mechanism. In addition, experimental results suggest that the operation of the TGF mechanism is more evident at low/moderate pressure fluctuations and becomes overwhelmed when the arterial pressure forcing is too high.


Developing Protein-Based Nanoparticles as Versatile Delivery Systems for Cancer Therapy and Imaging.
In recent years, it has become apparent that cancer nanomedicine's reliance on synthetic nanoparticles as drug delivery systems has resulted in limited clinical outcomes. This is mostly due to a poor understanding of their "bio-nano" interactions. Protein-based nanoparticles (PNPs) are rapidly emerging as versatile vehicles for the delivery of therapeutic and diagnostic agents, offering a potential alternative to synthetic nanoparticles. PNPs are abundant in nature, genetically and chemically modifiable, monodisperse, biocompatible, and biodegradable. To harness their full clinical potential, it is important for PNPs to be accurately designed and engineered. In this review, we outline the recent advancements and applications of PNPs in cancer nanomedicine. We also discuss the future directions for PNP research and what challenges must be overcome to ensure their translation into the clinic.


Serum bactericidal activity against Enterobacteriaceae producing broad-spectrum beta-lactamases in volunteers administered ofloxacin and cefotaxime, alone or combined.
The activity of ofloxacin and cefotaxime, alone or combined, against four strains of Enterobacteriaceae was evaluated both in vitro and in sera from volunteers given a single infusion over 30 min of 200 mg ofloxacin or 1 g cefotaxime. The strains showed resistance or decreased susceptibility to third-generation cephalosporins. The combination was not found to be synergistic in vitro. Analysis of the bactericidal titres and killing kinetics of sera taken at the time of the peak concentration and 6 h after the infusion, respectively, confirmed the absence of synergy between the drugs against these strains.


A 48-week, randomized, open-label comparison of three abacavir-based substitution approaches in the management of dyslipidemia and peripheral lipoatrophy.
The mechanisms by which dyslipidemia and lipoatrophy develop during antiretroviral therapy are not clear. No treatment of lipoatrophy is currently established. This was an open-label randomized study of HIV-positive individuals on a first-line therapy containing stavudine (d4T) with either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) and with hypercholesterolemia (defined as total cholesterol >5.2 mmol/L or >180 mg/dL) and/or lipoatrophy and with a viral load of <50 copies/mL. Patients switched d4T to abacavir (ABC) (group 1), a PI or NNRTI to ABC (group 2), or d4T and PI or NNRTI to ABC plus AZT (group 3). Patients were followed-up with fasting blood levels, dual-energy X-ray absorptiometry (DXA), and computed tomography (CT) scans for 48 weeks. Thirty patients were included, with 27 completing 48 weeks of therapy. One ABC hypersensitivity reaction was the only serious adverse event. All patients' viral loads remained at <50 copies/mL. CD4 cell counts rose in groups 2 and 3 but fell modestly in group 1. Total and low-density lipoprotein cholesterol improved significantly in groups 2 and 3. Triglycerides fell significantly in group 2. In contrast, total, arm, and leg fat mass (by DXA) rose significantly in group 1 but fell modestly in groups 2 and 3. Visceral adiposity (by CT scan) was unaffected in all groups. Abacavir represents a virologically effective replacement for d4T, PI, or NNRTI in persons on successful first-line therapy. Replacement of a PI or NNRTI with ABC leads to modest improvement in both cholesterol and triglycerides. Replacement of d4T with ABC leads to modest improvements in fat mass.


1H NMR studies at 360 MHz of the aromatic amino acid residues in ferrocytochrome c-552 from Euglena gracilis.
The resonances of the aromatic rings in the 1H NMR spectra at 360 MHz of ferrocytochrome c-552 of Euglena gracilis were investigated by double resonance techniques. The spin systems of the two tryptophan and four of the tyrosine residues could be identified. This analysis of the aromatic region of the 1H NMR spectrum provided evidence that His-14 is bound to the heme iron. It gave also some insight into the molecular dynamics of ferrocytochrome c-552 in that it showed that of the six aromatic rings, four tyrosines were rotating rapidly about the Cbeta-Cgamma bond, while one tyrosine and the single phenylalanine were restricted in their rotational mobilities by their environmnent in the protein.


A Large Vascular Leiomyoma Arising from the Superficial Femoral Artery: Case Report and Systematic Review.
Vascular leiomyomas are rare begin tumor comprising mature vascular smooth muscles that originate in the tunica media of the blood vessels. Most of the tumors arise from the veins. Only a dozen cases of artery-arising vascular leiomyoma have been reported, most of which are presented as small nodules in the hand. Here we report an interesting case of a large artery-arising vascular leiomyoma and perform a systematic review. A 55-year-old man complained a 6 × 3 cm firm, mobile, tender and pulseless mass in the medial region of his left thigh. The computed tomography showed a well-demarcated fusiform tumor encircling the superficial femoral artery and was enhanced significantly with contrast. The patency of the superficial femoral artery was intact. The magnetic resonance image exhibited slightly hypointense relative to skeletal muscle on T1-weighted images and a heterogeneous appearance on T2-weighted images. We performed the en bloc resection of the tumor and used a vascular graft to revascularize the artery through end-to-end anastomosis. After histopathological assessments, the tumor was diagnosed as an artery-arising vascular leiomyoma. We also performed a systematic review on artery-arising leiomyomas, discovering 21 cases. Most of the artery-arising vascular leiomyomas were small nodules (mean length: 2.4cm) and most of them were superficial solitary mass located in the hand (13 cases, 62%). Excision of the tumor was an effective treatment. The histological subtype of the artery-arising vascular leiomyoma in all cases was solid type. During the follow-up of each patient, there was no recurrence. Artery-arising vascular leiomyomas are extremely rare. Most of them are painless and locate in the hand. Their pathological subtype is solid type in all patients. Due to their begin nature, excision is a cure with little chance of recurrence.


Pleuropulmonary involvement in patients with systemic lupus erythematosus from a Latin American inception cohort (GLADEL).
Objectives The objectives of this study were to examine the demographic and clinical features associated with the occurrence of pleuropulmonary manifestations, the predictive factors of their occurrence and their impact on mortality in systemic lupus erythematosus (SLE) patients. Materials and methods The association of pleuropulmonary manifestations with demographic and clinical features, the predictive factors of their occurrence and their impact on mortality were examined in GLADEL patients by appropriate univariable and multivariable analyses. Results At least one pleuropulmonary manifestation occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most frequent (24.0%). Age at SLE onset ≥30 years (OR 1.42; 95% CI 1.10-1.83), the presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05-4.96), non-ischemic heart disease (OR 3.17; 95% CI 2.41-4.18), ischemic heart disease (OR 3.39; 95% CI 2.08-5.54), systemic (OR 2.00; 95% CI 1.37-2.91), ocular (OR 1.58; 95% CI 1.16-2.14) and renal manifestations (OR 1.44; 95% CI 1.09-1.83) were associated with pleuropulmonary manifestations, whereas cutaneous manifestations were negatively associated (OR 0.47; 95% CI 0.29-0.76). Non-ischemic heart disease (HR 2.24; 95% CI 1.63-3.09), SDI scores ≥1 (OR 1.54; 95% CI 1.10-2.17) and anti-La antibody positivity (OR 2.51; 95% CI 1.39-4.57) independently predicted their subsequent occurrence. Cutaneous manifestations were protective of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI 0.43-0.90). Pleuropulmonary manifestations independently contributed a decreased survival (HR: 2.79 95% CI 1.80-4.31). Conclusion Pleuropulmonary manifestations are frequent in SLE, particularly pleuritis. Older age, respiratory tract infection, cardiac, systemic and renal involvement were associated with them, whereas cutaneous manifestations were negatively associated. Cardiac compromise, SDI scores ≥1 and anti-La positivity at disease onset were predictive of their subsequent occurrence, whereas cutaneous manifestations were protective. They independently contributed to a decreased survival in these patients.


Supplementary factors required for serum-free culture of rat kidney cells of line NRK-49F.
Factors required as supplements to basal tissue culture medium for the multiplication of cells of the cloned rat fibroblast line called normal rat kidney 49F (NRK-49F) were identified as epidermal growth factor, fibronectin, insulin, and retinoic acid. The requirement for fibronectin was manifested on a clean glass surface but not on the polystyrene plastic surface tested. This set of required factors differs substantially from the factor sets required by the Madin-Darby canine kidney (MDCK) and LLC-PK1 pig kidney lines of epithelial cells and the baby hamster kidney 21 (BHK-21) line of fibroblasts. The serum-free medium supplemented with the four factors supported rapid growth of NRK-49F cells when the initial cell population density was about 8,000 cells/cm2 or greater. At lower initial densities, cell multiplication was markedly increased by adding serum-free medium that had been conditioned by NRK-49F cells. Cell growth rate in the defined serum-free medium stayed high through two serial passages but declined in the third serial passage unless the cell-conditioned medium was added.


Exploring an expedient IMDA reaction approach to construct the guanacastepene core.
Construction of the [5-7-6] tricyclic core of guanacastepenes was attempted by using the intramolecular Diels-Alder (IMDA) reaction and Me(3)Al-mediated ring opening of the oxabridge as key synthetic steps. The illustrated chemistry demonstrated a synthetic feasibility to build up the framework of guanacastepenes by the IMDA reaction. [reaction: see text]


Sodium-ypochlorite injection in antecubital fossa: A case report and literature review.
Caustic cutaneous injections are rare and may result in challenging soft tissue defects necessitating urgent surgical reconstruction to preserve vital structures. We report a unique case of self-inflicted sodium hypochlorite injection to the left antecubital fossa as a suicidal attempt, which resulted in an exposed median nerve and brachial artery. The adventitia of the brachial artery was injured in this case; hence, the risk of an arterial blowout was considerable. After thorough debridement, the defect was reconstructed successfully with a reverse lateral arm flap. Household bleach (sodium hypochlorite) injections are rare and may result in challenging soft tissue defects necessitating urgent surgical reconstruction to preserve vital structures.


The prevalence of anxiety and depression and its association with coping strategies, supportive care needs, and social support among women with breast cancer.
Diagnosis of breast cancer and its treatment dramatically affects women's psychological health. This study investigated the prevalence of depression and anxiety and their related factor in breast cancer women. We conducted a cross-sectional study with a sample of 120 women with breast cancer in Zahedan, Iran, 2020. Data were collected using instruments included: Hospital Anxiety and Depression Scale (HADS), Supportive Care Needs Survey (SCNS-SF34), Multidimensional Scale of Perceived Social Support (MSPSS), The adjustment to illness measurement inventory for Iranian women with breast cancer (AIMI-IBC). We analyzed the data using the ANOVA, independent sample t-test, Kruskal Wallis, Mann-Whitney U test, Pearson's and Spearman's correlation coefficients. The prevalence of depression and anxiety in women with breast cancer was 66.6% and 60%, respectively. A significant positive correlation was found between anxiety and depression and unmet psychological needs, care/support needs, and emotional turmoil coping strategy, while reasonable efforts and avoidance coping strategies and adjusting to disease were negatively correlated with anxiety and depression. Also, linear regression results indicated unmet psychological needs, emotional turmoil coping strategy, and a high level of depression predicted a high anxiety level. A lower level of depression was indicated by reasonable efforts strategy and less level of anxiety. Women with breast cancer reported a high level of depression and anxiety in Zahedan, and clinicians should pay more attention to these patients' psychological distress. Resolving the unmet need of patients, increasing social support, and using the right coping strategy have an essential role in breast cancer women's psychological distress control.


Management of replacement breeding animals.
In conclusion, replacement gilts should be finally selected before 110 kg body weight and should have been stimulated to reach puberty by this time. Currently, the best method for achieving this is ad libitum feeding and the correct use of boar exposure. However, whether ad libitum feeding will always be the best feeding strategy remains to be seen. The impressive success of selection programs and the potential for the use of growth promoters and repartitioning agents in the feeder barn may require that future replacements be identified at an early stage and raised under a separate feeding regimen. To produce a large first litter, gilts should be bred at their second estrus. There is unlikely to be any further increase in litter size by delaying mating to third estrus. A major consideration when choosing when to breed replacements is the length of their productive life. For many farms, this may be maximized by delaying breeding until the sow is 120 to 130 kg body weight with a minimum backfat depth of 18 mm. For the producer who is able to exert control over lactation condition loss, however, breeding replacements at about 110 kg body weight with backfat depths of 14 to 16 mm should not adversely affect long-term performance. Although it is true that, under some conditions, the lean gilt may become a problem, it is equally true that her potential is as great as her fatter contemporaries. Whether this potential is realized is largely under the producer's control. Regarding the boar, nutritional management need not vary from that provided for gilts. However, if replacement boars are raised on-farm, it is of great importance that they be allowed to socially interact with other pigs. Failure to provide this opportunity will result in a boar with reduced libido.


Obesity and infectious diseases: pathophysiology and epidemiology of a double pandemic condition.
The current pandemic due to widespread SARS-CoV-19 infection has again highlighted the role of obesity, whose global prevalence increased up to 13%, as a risk factor for both susceptibility to infections and the occurrence of a more severe disease course. To date, this association has not been sufficiently explored. Obesity-related susceptibility to infectious diseases is mostly thought to be due to an impairment of both innate and adaptive immune responses and vitamin D deficiency. Several cofactors can indirectly favour the onset and/or worsening of infectious diseases, such as impairment of respiratory mechanics, skin and subcutaneous tissue homoeostasis, obesity-related comorbidities and inappropriate antimicrobial therapy. Subjects with obesity have a higher incidence of cutaneous infections, probably due to changes in skin barrier functions and wound healing. Excess weight is also associated with an increased risk of urinary tract infection and its recurrence, as well as with a higher prevalence of both lower and higher respiratory tract infections. Moreover, patients with obesity appear to have an increased risk of surgical site infections when undergoing general, orthopaedic, gynaecological, and bariatric surgery. Data concerning the different infectious diseases related to obesity are rather limited since anthropometric parameters are usually poorly recorded. Furthermore, specific therapeutic protocols in subjects with obesity are lacking, especially regarding antibiotic therapy and further supplements. This review summarizes etiopathogenetic and epidemiological evidence and highlights areas of uncertainty in the field of infectious diseases and obesity, which require further research. It is important to raise public awareness of this additional risk related to obesity and to raise awareness among the scientific community to develop specific clinical protocols for subjects with obesity.


Proteolytic degradation patterns of the receptor for advanced glycation end products peptide fragments correlate with their neuroprotective activity in Alzheimer's disease models.
The receptor for advanced glycation end products (RAGE) plays an essential role in Alzheimer's disease (AD). We previously demonstrated that a fragment (60-76) of RAGE improved the memory of olfactory bulbectomized (OBX) and Tg 5 × FAD mice - animal models of AD. The peptide analog (60-76) with protected N- and C-terminal groups was more active than the free peptide in Tg 5 × FAD mice. This study investigated proteolytic cleavage of the RAGE fragment (60-76) and its C- and N-terminally modified analog by blood serum using HPLC and mass spectrometry. The modified peptide was proteolyzed slower than the free peptide. Degrading the protected analog resulted in shortened fragments with memory-enhancing effects, whereas the free peptide yielded inactive fragments. After administering the different peptides to OBX mice, their performance in a spatial memory task revealed that the effective dose of the modified peptide was five times lower than that of the free peptide. HPLC and mass spectrometry analysis of the proteolytic products allowed us to clarify the differences in the neuroprotective activity conferred by administering these two peptides to AD animal models. The current study suggests that the modified RAGE fragment is more promising for the development of anti-AD therapy than its free analog.


Acute lymphocytic leukemia masquerading as acute osteomyelitis. A report of two cases.
Two children each developed a focal destructive bone lesion accompanied by intermittent fever, swelling, tenderness and elevated ESR. Blood counts were normal; bone marrow aspiration showed acute leukemia. The bone lesions healed in both patients after anti-leukemic therapy. We suggest that the similar roentgenographic appearance of osteomyelitis, bone infarction and focal destructive lesions in leukemia probably reflects a common, basically ischemic process of bone.


Cyclin D3 mediates synthesis of a hyaluronan matrix that is adhesive for monocytes in mesangial cells stimulated to divide in hyperglycemic medium.
Serum-starved, growth-arrested, near confluent rat mesangial cell cultures were stimulated to divide in medium with low (5.6 mM) or high (25.6 mM) glucose. In high glucose cultures Western blots showed large increases in cyclin D3 and CCAAT/enhancer-binding protein alpha (C/EBPalpha) at 48-72 h, concurrent with the production of a monocyte-adhesive hyaluronan matrix, whereas low glucose and mannitol osmotic control cultures did not. Cyclin D3 small interfering RNA inhibited both the synthesis of this matrix and the up-regulation of C/EBPalpha in cultures exposed to high glucose, indicating that cyclin D3 is a key mediator in regulating responses of dividing mesangial cells to hyperglycemia. A complex with cyclin D3, cyclin-dependent kinase 4, and C/EBPalpha was observed at 48-72 h in the hyperglycemic cultures, and cyclin D3 and C/EBPalpha were spatially co-localized in coalesced perinuclear honeycomb-like structures with embedded hyaluronan. Furthermore, microtubule-associated protein 1 light chain 3, a marker for autophagy, colocalizes with these structures. These results suggest that cyclin D3 is a central coordinator that controls the organization of a complex set of proteins that regulate autophagy, formation of the monocyte-adhesive hyaluronan matrix, and C/EBPalpha-mediated lipogenesis. Abnormal deposits of hyaluronan, cyclin D3, and C/EBPalpha were present in glomeruli of kidney sections from hyperglycemic rats 4 weeks after streptozotocin treatment, indicating that similar processes likely occur in vivo. Mesangial cell cultures treated with poly(I:C) or tunicamycin in normal glucose media synthesized monocyte-adhesive hyaluronan matrices but with concurrent down-regulation of cyclin D3. This indicates that the cyclin D3 mechanism is induced by hyperglycemia and is distinct from those involved in these cell stress responses.


The oxygen performance of contemporary hydrogel contact lenses.
The oxygen performance of a hydrogel contact lens is arguably its most important property when considering the possible physiological response of the eye. However, information about this aspect of a contact lens can frequently be difficult to obtain, and there are numerous pitfalls in the interpretation and application of the available data. This paper presents the oxygen permeability and oxygen transmissibility of 17 different lens types as measured by one technician in one laboratory across a short time interval. The clear relationship between water content and oxygen permeability is confirmed, and the transmissibilities of three lens types across a wide power range are reported.


Down-Regulated Calcium-Sensing Receptor in Keratinocytes and Skin from Aged Mice and Humans Impairs Function.
The calcium-sensing receptor (CaSR) is important in the skin, contributing to several epidermal functions, including differentiation, water permeability barrier repair, and wound healing. Celli et al. (2021) show that CaSR levels are reduced in keratinocytes/skin from aged individuals, with resulting impairment of key functions. CaSR agonists can correct these defects, suggesting a possible therapy to combat aging-related delayed skin wound healing.


Speciation of Cr(III) and Cr(VI) in geological and water samples by ytterbium(III) hydroxide coprecipitation system and atomic absorption spectrometry.
A novel coprecipitation method with ytterbium(III) hydroxide has been established for speciation of Cr(III) and Cr(VI) in geological and water samples. At pH 10, while Cr(III) was quantitatively recovered, Cr(VI) was recovered under 10% levels. Total chromium was determined reducing of Cr(VI) to Cr(III) in acidic media with KI reagent. The concentration of Cr(VI) was calculated by the concentration difference between the total chromium and Cr(III). For the quantitative recovery of Cr(III), parameters such as pH, amount of ytterbium, centrifugation time and speed, matrix effect, KI amount, and sample volume were investigated. The preconcentration factor was 30. The limit of detection was obtained as 1.1 μg/L for Cr(III). The accuracy was checked by analyte addition and analyses of standard reference materials (TMDA-54.4 Certified Reference Water, NIST 2710 Montana Soil). Method has been successfully applied to the chromium speciation for industrial waste water of leather factories located in Bor-Nigde, and also for mine and soil samples.


A cross-sectional study examining computer task completion by adolescents with cerebral palsy across the Manual Ability Classification System levels.
The aim of this study was to analyze the cursor trajectories of adolescents with cerebral palsy (CP) when using a mouse for point-and-click computer tasks. By identifying some of the factors limiting cursor movement and gaining a better understanding of human movement, it will be possible to design more accessible computer interfaces. This study evaluated cursor trajectories of 29 individuals with bilateral CP who had different levels of upper limb function as measured by the Manual Ability Classification System, and compared the results with those of 12 adolescents with typical development. Among adolescents with typical development, movement time increases linearly as the index of difficulty increases (Fitts' law); however, this linearity was not apparent in adolescents with bilateral CP. Interfaces for members of the population are designed around Fitts' law, with low precision requirements at indices of difficulty lower than 4. We found that interactive displays for adolescents with CP should be limited to an index of difficulty of 2.


Ewing's sarcoma. Radiotherapy versus surgery for local control.
Significant strides in the treatment of Ewing's sarcoma, the second most common bone tumor of childhood, have resulted in cure for approximately 50% of patients. Successful therapy requires systemic chemotherapy for the eradication of microscopic or overt metastatic disease and surgery or irradiation therapy for control of the primary lesion. The article debates the controversy over the extent to which surgical resection should play a role in the local management of this disease.


Differential effect of PMS777, a new type of acetylcholinesterase inhibitor, and galanthamine on oxidative injury induced in human neuroblastoma SK-N-SH cells.
In the search for highly selective and potent cholinesterase inhibitors (AChEI) being able to improve oxidative injury, PMS777, a tetrahydrofuran derivative, was designed as a novel dual PAF and acetylcholinesterase inhibitor. The aim of this study was to investigate the modulatory effects of PMS777 and galanthamine, another AChEI, on the oxidative injury induced in neuronal cells. The SK-N-SH cells stimulated with LPS+IL-(1beta) were selected to investigate the direct inhibitory effect of PMS777 and galanthamine. LPS+IL-(1beta) induced oxidative injury as assessed by ROS production (29%), GSH depletion (11%) and loss of mitochondrial activity (22%). GSH depletion was never decreased by either drug. In contrast, ROS production and mitochondrial activity were totally prevented by addition of PMS777 but not galanthamine. PMS777 also inhibits butylcholinesterase and it shows selectivity for acetylcholinesterase. Thus, this PAF antagonist inaugurates a new type of AChEI, able to fight oxidative injury. Therefore, PMS777 could be of interest on patients with cognitive impairments and inflammatory damage, as in AD.


Pancreatic lipase inhibition by C-glycosidic flavones Isolated from Eremochloa ophiuroides.
Activity-guided fractionation of a methanolic extract of the leaves of Eremochloa ophiuroides (centipede grass) using a pancreatic lipase inhibitory assay led to the isolation and identification of a new C-glycosidic flavone, luteolin 6-C-ß-D-boivinopyranoside (1), as well as eight known compounds. The structures of these compounds were established on the basis of interpretation of their spectroscopic data. Among these isolates, the C-glycosidic flavones 1-5 showed potent inhibitory effects on pancreatic lipase, with IC₅₀ values ranging from 18.5 ± 2.6 to 50.5 ± 3.9 μM.


Transjugular intrahepatic portosystemic shunt in decompensated cirrhotic patients in a tertiary hospital in southern Brazil.
The aim of the present study was to evaluate the outcomes of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. A retrospective longitudinal observational study was carried out evaluating 38 cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt. The outcomes were evaluated in an outpatient follow-up period of 3 months. The assumed significance level was 5%. The indications for transjugular intrahepatic portosystemic shunt were refractory ascites in 21 (55.3%), variceal hemorrhage in 13 (34.2%), and hydrothorax in 4 (10.5%) patients. There was development of hepatic encephalopathy in 10 (35.7%) patients after transjugular intrahepatic portosystemic shunt. From the 21 patients with refractory ascites, resolution was observed in 1 (3.1%) patient, and in 16 (50.0%) patients, there was ascites control. Regarding transjugular intrahepatic portosystemic shunt after variceal bleeding, 10 (76.9%) patients remained without new bleeding or hospitalizations in the follow-up period. The global survival in the follow-up period in patients with and without hepatic encephalopathy was 60 vs. 82%, respectively (p=0.032). Transjugular intrahepatic portosystemic shunt can be considered in decompensated cirrhotic patients; however, the development of hepatic encephalopathy which can shorten survival should be focused.


Lead concentration in different compartments of the bovine eye.
It is known that lead is a metabolic substitute of calcium and recently, in vitro results showed that glycosaminoglycans and proteins are capable of binding lead. Therefore, in this work, the level of lead in aqueous humor, vitreous humor, lens and sclera of bovine eyes was analyzed in order to establish a relationship between lead concentration and the contents of glycosaminoglycans, proteins, water and calcium in those structures. Lead was determined by means of atomic absorption spectrometry after acid digestion. Our results suggest a direct relationship between the contents of proteins and glycosaminoglycans, and the ability of the different eye structures to retain lead. Nevertheless, an inverse relationship between water content and lead concentration was found. No association between calcium and lead concentrations was observed.


Addressing the insidious health and financial burden of tobacco use in Missouri: the role of medical and public health professionals.
Despite the widespread knowledge that tobacco use causes death and debilitating disease, tobacco control efforts in Missouri remain inadequate. No other health issue combines the prevalence, lethality, and neglect of tobacco addiction. This paper discusses comprehensive tobacco-use prevention and cessation programs that could, if implemented, effectively reduce tobacco-related health problems. Successful tobacco control efforts change society by creating an environment in which nonsmoking is the norm and quitting smoking is supported. This paper concludes that it is time for medicine and public health professionals to communicate, collaborate, and assume leadership in reducing the health burden of tobacco use in Missouri.


Hemangioma of the upper arm associated with massive hemorrhage in a neonate.
A rare case of an ulcerated hemangioma of the upper arm in a neonate is described herein. Resection of the huge hemangioma, which occupied the axilla and extended down the entire length of the upper arm, was necessary due to massive hemorrhage from the ulcer and progressive heart failure caused by the arteriovenous fistula in the hemangioma. After complete resection of the hemangioma, extensive defects of the skin and subcutaneous tissue were replaced by a skin flap closure technique which involved considerable difficulty. However, the arm gradually recovered its size and function with good wound healing. The present case illustrates that rapid surgical intervention may be required to prevent clinical deterioration in such cases.


Reproducibility of arterial stiffness indices in different vascular territories and between different observers.
Increased arterial stiffness (AS) corresponds to an increase in cardiovascular risk. According to recent guidelines AS parameters can be measured on all superficial arteries. Proceeding from the assumption that viscoelastic properties differ along the arterial tree we set ourselves the task to study the reproducibility of AS indices measured at the common carotid, brachial and femoral arteries. The initial study population included 75 patients (40 ± 14.5 years, 45% males) with a variable distribution of cardiovascular risk factors and without clinical evidence of coronary artery disease. AS parameters were measured at the common carotid, brachial and femoral arteries in all patients using echo-tracking (ET) technique. In a subgroup of 36 patients we tested the interobserver variability in the three vascular territories. We found that there was a significant correlation between AS indices measured at the common carotid and femoral artery (with the only exception for augmentation index) and that AS parameters measured at the brachial artery did correlate neither with common carotid nor with femoral artery indices. The interobserver variability of ET derived AS parameters was good when they were measured at the carotid or femoral artery. The values of AS indices at the brachial artery however showed considerably lower interobserver agreement. The reproducibility of ET derived AS parameters was good when AS was measured at the common carotid or femoral arteries. On the basis of our results brachial artery is probably not a reliable site for AS measurement.


Veterinary migration: why do vets move abroad?
Migration of veterinary professionals to and from the UK has important consequences for the profession. Gareth Enticott believes that not enough is known about the motivations for migration and that more time should be spent analysing the reasons.


Application of recombinant Pediococcus acidilactici BD16 (fcs +/ech +) for bioconversion of agrowaste to vanillin.
Biotechnological production of vanillin is gaining momentum as the natural synthesis of vanillin that is very expensive. Ferulic acid (FA), a costly compound, is used as the substrate to produce vanillin biotechnologically and the making process is still expensive. Therefore, this study investigated the practical use of an agrobiomass waste, rice bran, and provides the first evidence of a cost-effective production of vanillin within 24 h of incubation using recombinant Pediococcus acidilactici BD16 (fcs +/ech +). Introduction of two genes encoding feruloyl CoA synthetase and enoyl CoA hydratase into the native strain increased vanillin yield to 4.01 g L-1. Bioconversion was monitored through the transformation of phenolic compounds. A hypothetical metabolic pathway of rice bran during the vanillin bioconversion was proposed with the inserted pathway from ferulic acid to vanillin and compared with that of other metabolic engineered strains. These results could be a gateway of using recombinant lactic acid bacteria for industrial production of vanillin from agricultural waste.


Robotic-assisted Ivor Lewis esophagectomy, a review of the technique.
Esophageal resection is a key component of the multidisciplinary management of esophageal cancer. Robotic-assisted minimally invasive esophagectomy is gaining widespread approval amongst few centers with promising early data. There is significant variability in the operative approach utilized by different centers and this review describes, step-by-step, the operative technique at a high-volume tertiary center. The cornerstone of management is individualized surgical approach, based on patient, tumor and technical factors. Although our approach is based on aforementioned factors, our preferred approach is an Ivor Lewis esophagectomy and this review focuses on that. The procedure is broken down into three key parts, starting with an abdominal exploration and creation of the gastric conduit, placement of jejunostomy tube, moving to thoracic mobilization and creation of the side-side 6 cm stapled esophagogastric anastomosis with a final abdominal portion to assure proper positioning of the conduit and reducing redundancy. This approach is fully robotic and a side to side anastomosis facilitates the creation of a widely patent anastomosis therefore minimizing the risk of anastomotic leaks and strictures. Our experience with minimally invasive esophagectomy, as has been previously published, is associated with a 5.1% of anastomotic leak and 7.6% of anastomotic stricture. The robotic platform further optimizes this technique and helps us safely accomplish a side to side stapled anastomosis. Superior instrument dexterity in a restricted thoracic space is facilitated by intracorporeal suturing and robotic stapling. Thus, it obviates the need for a larger thoracotomy incision, which is typically needed for an EEA anastomosis, and that is traditionally associated with higher stricture rate.


Adaptive regulation of hepatic bile salt transport: role of bile salt hydrophobicity and microtubule-dependent vesicular pathway.
The hepatic transport of bile salts can be regulated by changes in bile salt pool size and/or in the flux of bile salts through the liver. Prolonged bile salt pool depletion is associated with down-regulation of maximum taurocholate transport and decreased canalicular membrane specific bile salt binding sites. This study was undertaken to investigate: a) whether adaptive down-regulation of maximum hepatic bile salt transport occurs to the same extent for bile acids of different hydrophobicity; and b) the role of microtubule-dependent vesicular pathway in the adaptive changes of bile salt transport capacity. Male rats were subjected to 24-h or 48-h external biliary diversion to induce bile salt pool depletion. Basal bile flow, bile salt secretion and lipid secretion, maximum secretory rate of three bile salts of different hydrophobicity (tauroursodeoxycholate, taurocholate and taurochenodeoxycholate) and changes in the biliary excretion of two markers of the microtubule-dependent vesicular pathway (horseradish peroxidase and polyethyleneglycol molecular weight-900) were measured in control and bile salt-depleted rats. Taurocholate-stimulated horseradish peroxidase biliary excretion was also assessed in order to define whether the restoration of bile salt flux across the hepatocytes increased the excretion of this marker in bile salt-depleted rats. The reduction in the maximum secretory rate of the three bile salts under study observed after prolonged biliary diversion was clearly related to their hydrophobicity, with greater reduction for taurochenodeoxycholate and smaller reduction for tauroursodeoxycholate, compared with taurocholate. The biliary excretion of vesicular transport markers was significantly reduced in bile salt-depleted rats. However, when stimulated by taurocholate, biliary excretion of horseradish peroxidase was similar to controls. The magnitude of the decrease of the hepatic bile salt maximum transport capacity seen after bile salt pool depletion is directly related to the hydrophobicity of the bile salt infused. A functionally depressed vesicular transport pathway appears to be also a contributing factor to this phenomenon.


Primary culture of adult mouse lung fibroblasts in serum-free medium: responses to growth factors.
We report a completely serum-free system for primary culture of fibroblasts from explants of adult mouse lung tissue which permits bioassays for cytokine activity to be performed using unselected populations of cells at low passage number, without interference by serum binding proteins or interacting growth factors. Cultures were established on collagen-coated surfaces in medium MCDB 201 containing albumin, transferrin, epidermal growth factor, lipids, prostaglandin E1, vitamin E, and reducing agents. The cells were morphologically and ultrastructurally typical of fibroblasts in culture and demonstrated expression of vimentin and induction of expression of desmin in culture. Proliferation of the cells was reproducible between different primary cultures and was growth factor dependent. Both cycling and growth-arrested cells exhibited increased DNA synthesis when stimulated with epidermal growth factor, platelet-derived growth factor, or basic fibroblast growth factor, which functioned as complete mitogens, but did not respond to insulin, tumor necrosis factor or interleukin-1 beta. Maximal induction of DNA synthesis by epidermal growth factor required the continued presence of the mitogen in the culture medium. These results cannot be satisfactorily explained by the competence-progression model of responses to mitogenic stimuli but support and extend the findings of other studies using diploid fibroblasts.


Membrane potential, contractile activation and relaxation rates in voltage clamped short muscle fibres of the frog.
1. Voltage clamped short (approximately 1.5 mm) muscle fibres of the frog can develop maximum tension of 4.3 kg/cm2. 2. The time course of contractile responses to prolonged depolarization is markedly dependent on the fibre membrane potential. With sufficiently long pulses the responses present a plateau and a spontaneous relaxation phase. 3. At room temperature (20--22 degrees C), and at membrane potentials of -10 mV the plateau duration is about 2 sec and the spontaneous relaxation rate is 0.50 sec-1. At membrane potentials of -35 mV the plateau duration is 4.6 sec and the spontaneous relaxation rate is 0.28 sec-1. 4. When the fibres are depolarized at room temperature with relatively short pulses (less than 2 sec), the contractile responses are cut short at the end of the pulse, and the fibres relax at a rate (11 sec-1) which is independent on the pulse amplitude and duration. 5. The relaxation rate after a short pulse can be affected by membrane potential only in the region near the contractile threshold where further release of contractile activator is expected to occur. 6. The time course of contractile responses to prolonged depolarization may be shortened by conditioning depolarization. 7. The system responsible for the release of contractile activator may be tentatively described by three states, resting, activated, and inactivated, in analogy with the model proposed by Chandler, Rakowski & Schneider (1976) to describe the possible configurations of the potential dependent charge movement in muscle.


Intragenic localization of amber and temperature-sensitive rpoD mutations affecting RNA polymerase sigma factor of Escherichia coli.
A set of multi-copy plasmids carrying part or all of the rpoD gene of Escherichia coli have been used to localize several amber and temperature-sensitive mutations affecting RNA polymerase sigma factor. In contrast to the plasmid carrying a complete rpoD sequence, plasmids carrying part of rpoD could not complement any of the rpoD mutations tested. However, the mutants harboring some of the latter plasmids produced wild-type recombinants at high frequency, provided that they carry the recA+ gene. The results permitted us to localize the rpoD mutations into one of the three intragenic segments. Thus, the rpoD285(ts) mutation (Harris et al. 1978) was located on the 0.8 kilobase segment defined by the Bg/II and BamHI sites in the middle segment, and the amber mutation rpoD40 (Osawa and Yura 1980) in the N-terminal 0.8 kilobase segment. Four additional amber mutations were also identified and classified into one of the segments of rpoD. It was further revealed that plasmids carrying certain amber mutations (rpoD47 or rpoD63) in the C-terminal segment of rpoD render all rpoD mutants tested (including rpoD47 and rpoD63 mutants themselves) able to grow at the restrictive condition. It is suggested that the enhanced synthesis of incomplete sigma polypeptides encoded by rpoD47 or rpoD63 phenotypically suppresses the defects in sigma function at least partially.


Postsynthetic changes of glutathione peroxidase (EC 18.104.22.168) and glutathione reductase (EC 184.108.40.206) in the ageing bovine lens.
Postsynthetic changes in the enzyme and structural proteins play an important role in the mechanisms of ageing of the lens, when development of protein aggregates and -S-S- linking occurs. Protection of the free -SH groups through the glutathione peroxidase and glutathione reductase system is a prerequisite to avoid these phenomena. Investigations on these two enzymes in young and old bovine lens tissues showed that they are themselves subjected to age-dependent modifications. With increasing age, the specific activity decreases while a simultaneous increase in heat lability occurs. This means that in the course of postsynthetic processes the stability of the conformation decreases and that finally the catalytic properties are lost.


Towards structural understanding of feedback control of arginine biosynthesis: cloning and expression of the gene for the arginine-inhibited N-acetyl-L-glutamate kinase from Pseudomonas aeruginosa, purification and crystallization of the recombinant enzyme and preliminary X-ray studies.
N-Acetyl-L-glutamate kinase (NAGK) catalyzes the second step in the pathway of arginine biosynthesis in microorganisms and plants. In many species, it is the pathway-controlling enzyme and is subject to feedback inhibition by arginine. The gene for the best characterized arginine-inhibitable NAGK, that from Pseudomonas aeruginosa, has been cloned in a pET22 plasmid and overexpressed in Escherichia coli. The enzyme was purified in three steps to 95% purity and was shown by cross-linking to form dimers. It was crystallized by the hanging-drop vapour-diffusion method at 277 K in the presence of ADP, Mg and N-acetyl-L-glutamate. The crystallization solution contained 0.1 M sodium cacodylate pH 6.5, 150-170 mM magnesium acetate and 13% polyethylene glycol 8000. Prismatic crystals of maximum dimension approximately 0.5 mm diffract to 2.75 A resolution and belong to space group P1 (unit-cell parameters a = 71.86, b = 98.78, c = 162.9 A, alpha = 91.49, beta = 92.03, gamma = 107.56 degrees ). Packing density considerations agree with 6-18 NAGK monomers in the asymmetric unit, with a corresponding solvent content of 79-36%. Self-rotation function calculations confirm the space group and suggest the presence of 3-7 dimers in the unit cell.


[Mixed neuropathies in rheumatoid arthritis. Motor and sensory nerve conduction velocities].
Nerve conduction studies and analysis of the sensory action potential (110 nerves investigated) demons treated abnormalities in 15 to 20 patients with rheumatoid arthritis. It is concluded that moderate, often subclinical peripheral neuropathy is a common complication in rheumatoid arthritis.


Genetic deletion of Cyp26b1 negatively impacts limb skeletogenesis by inhibiting chondrogenesis.
Cyp26b1, a retinoic acid (RA)-metabolising enzyme, is expressed in the developing limb bud, and Cyp26b1(-/-) mice present with severe limb defects. These malformations might be attributable to an RA-induced patterning defect; however, recent reports suggest that RA is dispensable for limb patterning. In this study, we examined the role of endogenous retinoid signalling in skeletogenesis using Cyp26b1(-/-) mice and transgenic mice in which Cyp26b1 is conditionally deleted under control of the Prrx1 promoter beginning at ~E9.5 (Prrx1Cre(+)/Cyp26b1(fl/fl)). We found that the limb phenotype in Prrx1Cre(+)/Cyp26b1(fl/fl) mice was less severe than that observed in Cyp26b1(-/-) animals and that a change in retinoid signalling contributed to the difference in phenotypes. We systematically examined the role of endogenous RA signalling in chondrogenesis and found that Cyp26b1(-/-) cells and limb mesenchymal cells treated with a CYP inhibitor, are maintained in a pre-chondrogenic state, exhibit reduced chondroblast differentiation and have modestly accelerated chondrocyte hypertrophy. Furthermore, Cyp26b1(-/-) mesenchyme exhibited an increase in expression of genes in a closely related tendogenic lineage, indicating that retinoid signals in the limb interfere with differentiation and maintain progenitor status. Together, these findings support an important function for RA in regulating the behaviour of mesenchymal progenitors, and their subsequent differentiation and maturation.


Association of extracellular vesicle inflammatory proteins and mortality.
Even before the COVID-19 pandemic declines in life expectancy in the United States were attributed to increased mortality rates in midlife adults across racial and ethnic groups, indicating a need for markers to identify individuals at risk for early mortality. Extracellular vesicles (EVs) are small, lipid-bound vesicles capable of shuttling functional proteins, nucleic acids, and lipids. Given their role as intercellular communicators and potential biomarkers of disease, we explored whether circulating EVs may be markers of mortality in a prospective, racially, and socioeconomically diverse middle-aged cohort. We isolated plasma EVs from 76 individuals (mean age = 59.6 years) who died within a 5 year period and 76 surviving individuals matched by age, race, and poverty status. There were no significant differences in EV concentration, size, or EV-associated mitochondrial DNA levels associated with mortality. We found that several EV-associated inflammatory proteins including CCL23, CSF-1, CXCL9, GDNF, MCP-1, STAMBP, and 4E-BP1 were significantly associated with mortality. IL-10RB and CDCP1 were more likely to be present in plasma EVs from deceased individuals than in their alive counterparts. We also report differences in EV-associated inflammatory proteins with poverty status, race, and sex. Our results suggest that plasma EV-associated inflammatory proteins are promising potential clinical biomarkers of mortality.


The association between hospital case-volume and postoperative outcomes after esophageal cancer surgery: A population-based retrospective cohort study.
Recent advances in esophageal cancer treatment require a reevaluation of the relationship between institutional case-volume and patient outcome. The aim of this study was to analyze and update the association between surgical case-volume and both in-hospital and long-term mortality after esophagectomy for esophageal cancer. Data of all adult patients who received esophageal cancer surgery in Korea between 2004 and 2017 were extracted from the database of the National Health Insurance Service. Hospitals were categorized into three groups according to the average annual number of esophageal cancer surgery: low-volume (<12 cases/year), medium-volume (12-48 cases/year), and high-volume centers (>48 cases/year). Postoperative in-hospital and 1-, 3-, and 5-year mortality were analyzed according to the categorized groups using logistic regression. In total, 11, 346 esophageal cancer surgeries in 122 hospitals were analyzed. In-hospital mortality in the high-, medium-, and low-volume centers were 3.4%, 6.4%, and 11.1%, respectively. In-hospital mortality was significantly higher in low- volume (adjusted odds ratio, 3.91; confidence interval, 3.18-4.80; p < 0.001) and medium volume (adjusted odds ratio, 2.21; confidence interval, 1.80-2.74, p < 0.001) centers compared to high-volume centers. Patients who received esophageal cancer surgery in a low-or medium-volume center also had higher 1-, 3-, and 5-year mortality compared to patients who received the surgery in a high-volume center. Conclusions Centers with lower case-volume showed higher in-hospital mortality and long-term mortality after esophageal cancer surgery.


[Study on the mass spectrometry of natural products. XI. The MIKES of fast atom bombardment mass spectra of sodium adduct ions of phenylpropanoid glycosides].
The fast atom bombardment (FAB) mass spectra and mass-selected ion kinetic energy spectra [MIKES] of sodium adduct ions [M + Na]+ of six phenylpropanoid glycosides have been studied. An intense sodium adduct appeared in their FAB mass spectra, which was more abundant than the corresponding protonated molecular ion [M + H]+ and may give more definite information about molecular weight of the sample. The MIKES of these [M + Na]+ ions provided a convenient way for sugar sequence analysis of such glycosides.


Migration of endothelial cells into photo-responsive hydrogels with tunable modulus under the presence of pro-inflammatory macrophages.
Cell migration in three-dimensional environment is extremely important for tissue regeneration and other biological processes. In this work, a model system was developed to study how endothelial cells (ECs) migrate into photo-responsive hydrogels under the presence of pro-inflammatory macrophages. The hydrogel was synthesized from hyaluronic acid grafted with coumarin and methacrylate moieties by both carbon-carbon covalent linking and coumarin dimerization under UV irradiation at 365 nm. The structure of the hydrogel was conveniently modulated by UV irradiation at 254 nm to decompose the coumarin dimers, leading to the significant decrease of modulus and increase of swelling ratio and mesh size. Under the presence of M1 macrophages, ECs were induced to migrate into the hydrogels with a different degree. A significant larger net displacement of ECs was found in the softer hydrogel obtained by irradiation with UV at 254 nm than in the stiffer original one at day 7.


Anti-fibrotic potential of erythropoietin signaling on bone marrow derived fibrotic cell.
The number of patients with end stage kidney disease (ESKD) are increasing world-side. While interstitial fibrosis (IF) is a common step for the progression to ESKD, therapeutic options for IF is still limited in clinical settings. We have reported that bone marrow-derived fibrotic cell, fibrocyte, is involved in the pathogenesis of kidney fibrosis. Also recent studies revealed that erythropoietin has protective effect on kidney diseases. However, it is unknown whether erythropoietin (EPO) inhibits fibrosis in progressive kidney injury. Therefore, we explored the impacts of EPO on kidney fibrosis with focusing on fibrocyte. Fibrocyte was differentiated from peripheral mononuclear cells of healthy donor. Fibrocyte was stimulated with transforming growth factor beta (TGF)-β with/without EPO treatment. Moreover, the therapeutic effect of EPO was evaluated in murine unilateral ureteral obstruction (UUO) model. TGF-β stimulation increased the expression of COL1 mRNA in fibrocyte. EPO signal reduced the expression of COL1 mRNA in dose dependent manner. EPO reduced mitochondrial oxidative stress and ameliorated mitochondrial membrane depolarization induced by TGF-β stimulation. Moreover, EPO reduced the mRNA expression of mitochondria related molecules, TRAF6, in fibrocyte. In addition, the count of CD45+/αSMA + double-positive fibrocyte was decreased in the EPO-administered UUO kidneys. EPO signals function to prevent kidney fibrosis, particularly in fibrocyte. Regulating the renal accumulation of fibrocyte is a part of the anti-fibrotic functions of EPO.


The Effect of Hepatic Impairment on the Pharmacokinetics of Dacomitinib.
Dacomitinib is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations. To evaluate the effect of hepatic impairment on the pharmacokinetics of dacomitinib, two dedicated studies were conducted to inform optimal dosing. Study 1 (NCT01571388) evaluated the effect of mild and moderate hepatic impairment on the plasma pharmacokinetics, safety, and tolerability after a single oral dose of dacomitinib 30 mg, and Study 2 (NCT03865446) evaluated the same endpoints in a severe hepatic impairment population. Both studies were phase I, open-label, parallel-group studies. A one-way analysis of variance (ANOVA) with unequal variance assumption and hepatic impairment group as a fixed effect was used to compare the natural log of area under the plasma concentration-time curve extrapolated to infinite time (AUCinf), AUC from time zero to the last quantifiable concentration (AUClast), and maximum plasma concentration (Cmax) for each hepatic impairment group to the respective normal hepatic function group. Since dacomitinib is a cytochrome P450 (CYP) 2D6 substrate, only participants with extensive or intermediate CYP2D6 phenotypes were included in the primary analysis. The AUCinf for participants with mild, moderate, or severe hepatic impairment decreased by 6%, decreased by 23%, and increased by 4%, respectively, compared with normal hepatic function, while the Cmax for participants with mild, moderate, or severe hepatic impairment increased by 3%, decreased by 20%, and increased by 31%, respectively, compared with normal hepatic function. A single oral dose of dacomitinib 30 mg was well tolerated in all participants. Based on these pharmacokinetic results, dacomitinib pharmacokinetics of participants with mild, moderate, or severe hepatic impairment were not statistically different relative to participants with normal hepatic function based on the ANOVA analysis. No dacomitinib dose adjustments for patients with hepatic impairment are recommended. ClinicalTrials.gov NCT01571388, registered 5 April 2012; ClinicalTrials.gov NCT03865446, registered 6 March 2019.


Correlation between physical and sensorial properties of gummy confections with different formulations during storage.
Gummy confections are popular products formulated with sucrose, glucose syrups, gelling agents, acids, flavourings and colouring agents. They have various commercial types in terms of formulation, texture, taste and colour, however, there is inadequate investigation on storage behavior of these products. The aim of this study is to investigate the effects of glucose syrup:sucrose ratio (1.1 and 1.5), starch (0% and 1.5%) and gelatine concentration (3% and 6%) on texture profile, colour and sensory properties of gummy confections during storage. It was also aimed to correlate sensorial changes with physical properties measured by instrumental techniques during storage at 10 °C, 20 °C and 30 °C. The highest increase in hardness was observed for formulation with 1.1 glucose syrup:sucrose ratio, no starch and 6% gelatine. Storage temperature had no significant effect on cohesiveness. It was seen that rate of colour change increased with storage time and temperature. Formulation with glucose syrup:sucrose ratio of 1.5, no starch and 6% gelatine had the highest sensory scores. This formulation was found to be the most stable formulation in terms of hardness and gumminess, meaning that it would need a stable mastication during storage. Sensorial changes of gummy confections were found to be correlated with instrumental results of texture and colour.


In vivo and In vitro Identification of Endocannabinoid Signaling in Periodontal Tissues and Their Potential Role in Local Pathophysiology.
The endocannabinoid system (ECS) with its binding receptors CB1 and CB2 impacts multiple pathophysiologies not only limited to neuronal psychoactivity. CB1 is assigned to cerebral neuron action, whereas CB2 is mainly expressed in different non-neuronal tissues and associated with immunosuppressive effects. Based on these tissue-selective CB receptor roles, it was the aim of this study to analyze potential expression in periodontal tissues under physiological conditions and inflammatory states. In vivo, CB receptor expression was investigated on human periodontal biopsies with or without bacterial inflammation and on rat maxillae with or without sterile inflammation. In vitro analyses were performed on human periodontal ligament (PDL) cells at rest or under mechanical strain via qRT-PCR, Western blot, and immunocytochemistry. P < 0.05 was set statistical significant. In vivo, CB1 expression was significantly higher in healthy PDL structures compared to CB2 (13.5% ± 1.3 of PDL tissues positively stained; 7.1% ± 0.9). Bacterial inflammation effected decrease in CB1 (9.7% ± 2.4), but increase in CB2 (14.7% ± 2.5). In contrast, sterile inflammation caused extensive CB1 (40% ± 1.9) and CB2 (41.7% ± 2.2) accumulations evenly distributed in the tooth surrounding PDL. In vitro, CB2 was ubiquitously expressed on gene and protein level. CB1 was constitutively expressed on transcriptional level (0.41% ± 0.09), even higher than CB2 (0.29% ± 0.06), but undetectable on protein level. Analyses further revealed expression changes of both receptors in mechanically loaded PDL cells. CB1 and CB2 are varyingly expressed in periodontal tissues, both adjusted by different entities of periodontal inflammation and by mechanical stress. This indicates potential ECS function as regulatory tool in controlling of periodontal pathophysiology.


Side effects of dexedrine in hyperactive children: operationalization and quantification in a short-term trial.
1. Four common side effects of dexedrine use (viz., anorexia, insomnia, stomach pains, and weight loss) were operationalized and quantified for use by parents in monitoring these effects over a 6 week clinical trial. 2. A weighted summary score, reflecting the frequency and intensity of each side effect, was used to determine the magnitude of each effect during treatment. 3. Four hyperactive children taking 2,5 mg twice daily, and six other hyperactive children taking either 5 or 10 mg twice daily, served as subjects. 4. Results indicated that the average weighted summary scores for all effects did not exceed minimal levels as defined in this study, regardless of dosage. 5. The implications, importance, and usefulness of this side effects scale in treating hyperactive children were discussed.


Revisiting serum β-hCG cut-off levels and pregnancy outcomes using single embryo transfer.
The objective of this study is to identify the pregnancy outcomes based on day-16 β-hCG level assessed with modern assays, in fresh single embryo transfers. A retrospective cohort study at a single academic center between 2013 and 2017. A total of 1076 pregnancies were included. Pregnancies were divided into 10% groupings of 107-108 patients each. The 10 groups did not differ for baseline characteristics. There was no difference on outcomes based on cleavage or blastocyst transfer. At a serum β-hCG level of 103 ± 13 (range 74-135), 50% had a biochemical loss. Biochemical pregnancy losses remained 21% at serum β-hCG range (136-197). It was only once serum β-hCG level reached 199-252 that the probability of a biochemical pregnancy loss was 12%. Interestingly, if a clinical pregnancy is present even at low day-16 serum β-hCG levels, the likelihood of live birth is approximately 50%. This maximizes to 75% when the serum β-hCG level was at least 253 IU/L. The relationship between serum day-16 β-hCG levels and clinical pregnancy or live birth is quite strong with correlation coefficients above 0.8 which accounted for more than 75% of the variability in outcomes in both cases. Receiver operator curves determined that the cut-off for a clinical pregnancy was 190 and for live birth, it was 213 IU/L. An increase in the serum β-hCG levels at which to expect a reassuring outcome is required based on modern assays, as compared with the old cut-off levels.


Maternal ego development and mother-infant interaction in drug-abusing women.
The purpose of this study was to expand our knowledge about factors in substance-abusing women, other than chronic drug abuse, that may influence maternal caregiving behaviors. Specifically, the study explored relationships between maternal characteristics and mother-infant interaction in a sample of drug-abusing women to determine whether drug-addicted mothers' level of ego development affected mother-infant interaction at 1 month. Data collection occurred during a prenatal lab visit and 1 month postpartum and included a clinical interview, self-report on participants' addiction severity, clinical personality inventory, ego development test, and videotaped observation of mother-infant feeding interactions. Only ego development, and to a lesser degree psychological symptoms associated with substance abuse, were found to be significant predictors of maternal-child interaction at 1 month. This points to the need to focus on building internal resources in providing substance abuse treatment and other services for substance-abusing mothers.


Dynamic cardiomyoplasty in chronic Chagas' heart disease: clinicopathological data.
We report a 44-year-old man with chronic chagasic cardiomyopathy who underwent latissimus dorsi dynamic cardiomyoplasty and died 4 months later. The clinicopathological findings are discussed, and the literature is reviewed.


A molecular mechanism of enantiorecognition of tertiary alcohols by carboxylesterases.
Carboxylesterases containing the sequence motif GGGX catalyze the hydrolysis of esters of chiral tertiary alcohols, albeit with only low to moderate enantioselectivity, for three model substrates (linalyl acetate, methyl-1-pentin-1-yl acetate, 2-phenyl-3-butin-2-yl acetate). In order to understand the molecular mechanism of enantiorecognition and to improve enantioselectivity for this interesting substrate class, the interaction of both enantiomers with the substrate binding sites of acetylcholinesterases and p-nitrobenzyl esterase from Bacillus subtilis was modeled and correlated to experimental enantioselectivity. For all substrate-enzyme pairs, enantiopreference and ranking by enantioselectivity could be predicted by the model. In p-nitrobenzyl esterase, one of the key residues in determining enantioselectivity was G105: exchange of this amino acid for an alanine residue led to a sixfold increase of enantioselectivity (E = 19) towards 2-phenyl-3-butin-2-yl acetate. However, the effect of this mutation is specific: the same mutant had the opposite enantiopreference towards the substrate linalyl acetate. Thus, depending on the substrate structure, the same mutant has either increased enantioselectivity or opposite enantiopreference compared to the wild-type enzyme.


Changes of rat striatal neuronal membrane morphology and steroid content during the estrous cycle.
It is well documented that sex steroids affect striatal dopamine systems. However, the mechanism(s) of these hormonal effects in the striatum is still not well understood. We now report that gonadal steroid hormones during the estrous cycle affect the morphology and steroid hormone content of the rat striatum. Rats displaying at least two consecutive estrous cycles were included in this study as well as a group of female rats ovariectomized two weeks before being killed. The striatum was dissected from one half of each brain and used for morphological studies. From the other half of each brain, the striatum was dissected and steroid hormone concentrations in striatum and the remainder of the brain were determined. Tissues and serum concentrations of 17 beta-estradiol, progesterone and prolactin were measured by specific radioimmunoassays. Serum 17 beta-estradiol and prolactin concentrations peaked in proestrus, while progesterone was high in diestrus and proestrus. 17 beta-Estradiol levels were higher in the striatum than in the rest of the brain; both were also shown to fluctuate during the estrous cycle and with a pattern similar to that observed in serum. Progesterone serum levels showed a similar pattern of changes during the estrous cycle to progesterone concentrations in the striatum and the rest of the brain. The ultrastructure of the striatal dendritic membranes was studied by freeze-fracture. A significant difference in the content of intramembranous particles in dendritic shafts, which are mainly contacted by dopaminergic synapses, was found during the estrous cycle. The numerical density of large (greater than 10 nm) intramembranous particles was increased in diestrus I and II and in the afternoon of proestrus compared to estrus, the morning of proestrus and ovariectomized rats. In contrast, the numerical density of small (less than 10 nm) intramembranous particles was decreased in cycling animals compared to ovariectomized rats and fell in the afternoon of proestrus and then progressively increased in the following days to peak in the morning of proestrus. A negative correlation between steroid concentrations and small intramembranous particle density was observed, while the correlation was positive for large particles. No changes were observed in the membranes of dendritic spines, the main postsynaptic target for cortical afferents. In summary, this is the first report that concentrations of 17 beta-estradiol and progesterone in the striatum fluctuate during the estrous cycle. This is associated with estrous cycle-dependent changes of intramembranous particle density of striatal dendritic membranes. Our data therefore indicate that the striatum is a brain region hormonally modulated under physiological conditions.


Replacing saturated fatty acids with polyunsaturated fatty acids increases the abundance of Lachnospiraceae and is associated with reduced total cholesterol levels-a randomized controlled trial in healthy individuals.
Improving dietary fat quality strongly affects serum cholesterol levels and hence the risk of cardiovascular diseases (CVDs). Recent studies have identified dietary fat as a potential modulator of the gut microbiota, a central regulator of host metabolism including lipid metabolism. We have previously shown a significant reduction in total cholesterol levels after replacing saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFAs). The aim of the present study was to investigate the effect of dietary fat quality on gut microbiota, short-chain fatty acids (SCFAs), and bile acids in healthy individuals. In addition, to investigate how changes in gut microbiota correlate with blood lipids, bile acids, and fatty acids. Seventeen participants completed a randomized, controlled dietary crossover study. The participants received products with SFAs (control) or PUFAs in random order for three days. Fecal samples for gut microbiota analyses and fasting blood samples (lipids, fatty acids, and bile acids) were measured before and after the three-day intervention. Of a panel of 40 bacteria, Lachnospiraceae and Bifidobacterium spp. were significantly increased after intervention with PUFAs compared with SFAs. Interestingly, changes in Lachnospiraceae, as well as Phascolarlactobacterium sp. and Eubacterium hallii, was also found to be negatively correlated with changes in total cholesterol levels after replacing the intake of SFAs with PUFAs for three days. No significant differences in SCFAs or bile acids were found after the intervention. Replacing SFAs with PUFAs increased the abundance of the gut microbiota family of Lachnospiraceae and Bifidobacterium spp. Furthermore, the reduction in total cholesterol after improving dietary fat quality correlated with changes in the gut microbiota family Lachnospiraceae. Future studies are needed to reveal whether Lachnospiraceae may be targeted to reduce total cholesterol levels. The study was registered at Clinical Trials ( https://clinicaltrials.gov/ , registration identification number: NCT03658681).


Molecular cloning and characterization of rabbit pancreatic triglyceride lipase.
Pancreatic lipase (triacylglycerol acylhydrolase, EC 220.127.116.11) has been cloned from a gt11 cDNA library made from poly A+ RNA of adult rabbit pancreas. Pancreatic lipase (PL) assists the absorption of dietary triglycerides by hydrolyzing them at 1 and 3 positions to free fatty acids and 2-monoacylglycerol in the presence of bile acids and colipase in the intestinal lumen. Since rabbits are classifically used for the study of the diet induced changes in the lipid metabolism, as a prelude to studying the diet and age dependent changes in the expression of this enzyme, a full length PL cDNA clone was obtained from its pancreas. The coding region of rabbit pancreatic lipase cDNA consists of 1407 base pairs contained in an open reading frame encoding 469 amino acids including the 16 that constitute the signal peptide. Northern blot analysis revealed a band around 1.5 kb. When rabbit enzyme is compared to other species, an over all homology of 70-80% was observed at the nucleotide level. High homology in the amino acid sequence and composition is also apparent between rabbit and other species like dog (65%), pig (76%) and rat (63%). Highest homology is found to be around active-site serine. The regions of homology with other species may help to define sites of interaction of lipase with co-lipase.


Pseudomembranous Tracheobronchitis With Severe Tracheal Stenosis and Masked Bronchial Obstruction.
Pseudomembranous tracheobronchitis (PMTB) is a rare condition characterized by the formation of endobronchial pseudomembranes. PMTB overlaps with necrotizing tracheobronchitis or plastic bronchitis. The reported infectious etiology mainly includes invasive aspergillosis. PMTB can cause serious airway obstruction; however, urgent tracheotomy is rarely required. A 46-year-old woman was transferred to the emergency department (ED) with a 1-week history of progressive dyspnea and cough that was preceded by fever and sore throat. She was previously healthy except for a 20-year history of mild palmoplantar pustulosis. Stridor was evident. Nasolaryngoscopy performed in the ED revealed severe tracheal stenosis caused primarily by mucosal edema and secondarily by pseudomembranes. Initially, tracheitis was considered the sole cause of dyspnea. Although she underwent urgent tracheotomy to prevent asphyxia, her respiration deteriorated progressively. Bronchoscopy revealed massive pseudomembranes obstructing the bilateral bronchi, which led to the clinical diagnosis of PMTB. Subsequent toilet bronchoscopy markedly improved her ventilation. The causative pathogen was not identified despite extensive work-up, including molecular biological testing. Histopathologic examination of the pseudomembranes revealed fibrin with abundant neutrophils, which was consistent with PMTB. Associated conditions, including immunodeficiency, were not found. Her condition improved with antibiotics and repeated toilet bronchoscopy. WHY SHOULD AN EMERGENCY PHYSICIANS BE AWARE OF THIS?: PMTB is an important differential diagnosis of airway emergencies. PMTB can present with critical edematous tracheal stenosis and masked bronchial pseudomembranous obstruction. Emergency physicians should include PMTB in the differential diagnosis in adult patients with acute central airway obstruction because it requires prompt multimodal treatment.