Comparison of bronchodilator responsiveness in asthma and chronic obstructive pulmonary disease.
While asthmatics are known to have a greater response to bronchodilators than patients of chronic obstructive pulmonary disease (COPD), whether the pattern of response also differs has not been explored. Forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV1) were measured before and 20 minutes after inhalation of 200 microg salbutamol in patients of bronchial asthma (n=133) and (COPD) (n=116). Three types of responses (defined as > or = 12% and 200 ml increase in FEV1 or FVC) were identified: increase in (i) only FVC (FVC response), (ii) only FEV1 (FEV1 response), and, (iii) both FVC and FEV1 (double response). The mean +/- SEM absolute increase in FEV1 was significantly greater in asthmatics (307+/-17ml) as compared to 120+/-12 ml in COPD patients (p<0.0001). On the other hand, the increase in FVC was not different in the two groups (296+/-22 ml and 230+/-24 ml, respectively, p>0.05). The proportion of subjects showing a > or = 200 ml increase in FEV1 was greater among asthmatics as compared to COPD (p<0.0001) but the proportions showing a > or = 200 ml in FVC were similar (p>0.05). All the three types of responses were observed in asthmatics with a double response being the commonest. In COPD, an FVC response was the predominant response while the FEV1 response was rare. Multinomial logistic regression revealed that younger subjects (below 45 years) were more likely to have a double or exclusive FEV1 response. Greater severity of obstruction was associated with higher odds for each of the three responses, the odds being especially very high for an exclusive FEV1 response. The odds for a double response and an exclusive FEV1 response were significantly increased in asthmatics as compared to COPD. For FVC response, age category and disease were not significant determinants. It was concluded that bronchodilator responsiveness in asthma and COPD differs not only quantitatively but also in the pattern.


Indications and Outcomes of Splenectomy for Hematological Disorders.
Splenectomy is a frequent component of the diagnosis and treatment of hematological disorders. The aim of this study was to define the indications and outcomes of splenectomy for benign and malign hematological disorders. One hundred and two patients with hematological disease who had splenectomy at Hacettepe University Hospital between the years of 2010 and 2018 were evaluated. A total of one hundred and two patients were included in this study. The median age was 52 (20-82) years at the time of splenectomy. Most of the patients were female (57.9%). The median follow up time was 11.0 (0.03-87.9) months after splenectomy. Splenectomy was performed to diagnose thirty patients (29.4%). Seventy-two patients underwent splenectomy for the treatment of hematological disease (70.6%). Twenty-seven patients (90%) were diagnosed with various lymphomas. Two patients (6.7%) were diagnosed with hairy cell leukemia and one patient (3.3%) was diagnosed with large granular lymphocytic leukemia. In conclusion, an improvement in medical therapy, especially with monoclonal antibodies, the indications and outcomes of splenectomy for hematologic disorders have changed extremely in last years. Nevertheless, splenectomy has an important role for diagnosis and treatment of benign and malign hematological disorders.


Sealing ability of dentin adhesives/desensitizer.
This in vitro study evaluated the sealing ability of dentin adhesives and a desensitizer. Standardized Class V cavities were prepared on the buccal and lingual surfaces of 55 freshly extracted human molars. The teeth were cut into two sections in a mesio-distal direction. All specimens were randomly divided into 11 groups (n = 10). In each group, the cavities were treated with one of eight different dentin adhesives, a dentin desensitizer or a special combination of these, except for the control group. After all the cavities had been stained for 24 hours with 0.5% methlyene blue solution, the teeth were longitudinally cut into two sections through the center of the cavities. Dye penetration was recorded according to the stained areas. Epoxy resin replicas of two specimens per group were analyzed by SEM. All dentin adhesives/desensitizer significantly reduced dentinal permeability (p < 0.05). The sealing ability of the different dentin adhesives/desensitizer was significantly different (p < 0.001). The degree of dye penetration corresponded well with the surface morphology of the dentin surfaces after the various treatments. None of the dentin adhesives/desensitizer could completely block fluid percolation through the dentinal tubules, but current dentin adhesives/desensitizers can significantly reduce dentin permeability.


[Clinical features of atopic asthma and their relation to the T-regulatory cells and total immunoglobulin E].
Allergic diseases are among the most popular in the world. Scientific hypothesis formation and multifactorial pathogenesis of atopic asthma (AA) is constantly updated. Our purpose of this study was to investigate the relationship of humoral and cellular immunity with features clinical and anamnestic data in patients AA. Found that AA is genetically determined disorders, mainly transmitted through the maternal line, characterized polisensibilization, most of household allergens. AA is often associated with other allergic nosology (62.2%) and gastrointestinal diseases (44.4%). In the absence of clinical evidence of disease at CD4+/CD25+/Foxp3+, IgE and IL-4 in patients with AA is higher than in healthy individuals. When polyvalent allergy has been a significant increase in IgE (199.3 +/- 22.2) and IL-4 (79.2 +/- 16.5) and reduced expression of molecules CD4+/CD25+/Foxp3+ compared with sensitization to one or two allergens.


[Comparison of efficiency and safety of laparoscopic manual esophagoenterostomy and esophagoenterostomy with mechanical anastomotic devices after laparoscopic gastrectomy for stomach cancer].
To compare laparoscopic manual esophagoenterostomy and esophagoenterostomy with mechanical stapling anastomotic devices after laparoscopic gastrectomy for stomach cancer. There were 34 patients who underwent laparoscopic gastrectomy for stomach in 2015-2018. Roux-en-Y esophagoenterostomy was used to reconstruct the gastrointestinal tract. Manual anastomoses were performed in 18 patients (group 1), stapled anastomoses (endogia 45 mm, covidien, mansfield, ma, usa) - in 16 patients (group 2). There was no randomization. Surgery duration, length of icu-stay, terms of enteral nutrition initiation, postoperative complications, hospital-stay were analyzed. Mean duration of surgery in the first group was 217 (184-302) min, in the second group - 201 (162-311) min. Duration of surgery in the first group was 1.08-fold higher than in the second group (95% CI 1.03-1.13, p=0.05). Mean blood loss was 145 ml in both groups. Mean icu-stay was 20.2 (17-42) hours in the first group and 21.1 (16.2-46) hours in the second group (ratio 0.96, 95% CI 0.92-1.01, p=0.06). Total enteral feeding (sipping) was initiated on the third day in both groups. Mean postoperative hospital-stay was 9.21 (6-13) days in the first group and 9.23 (6-12 days) days in the second group (ratio 0.99, 95% CI 0,95-1.02, p=0.06). Postoperative morbidity was 5.5% in the first group and 6.25% in the second group. Laparoscopic manual esophagoenterostomy proposed by our surgical team does not have disadvantages in comparison with stapling anastomotic devices and these methods may be alternative to each other.


Luteinizing hormone secretion and corticotropin-releasing factor gene expression in the paraventricular nucleus of rhesus monkeys following cortisol synthesis inhibition.
Corticotropin-releasing Factor (CRF) is an important inhibitory neuromodulator of GnRH/LH secretion, and mediates in part the inhibitory effects of stress on the hypothalamic-pituitary-gonadal axis. The purpose of the present study was to further investigate CRF's role in regulating LH secretion in primates. This was accomplished by examining LH secretion in ovariectomized rhesus monkeys (n = 7) following cortisol synthesis inhibition with metyrapone. Infusion of metyrapone (5 mg/kg per h) for 4 h decreased cortisol levels to less than 20% of controls while increasing ACTH approximately 10-fold. LH concentrations were not affected by this acute activation of the hypothalamic-corticotroph axis. In a second experiment, metyrapone was infused for 10 h before collecting serial blood samples every 15 min for 6 h. Although this protocol produced a sustained increase in ACTH, no apparent effect on pulsatile LH secretion compared with saline controls was observed. Mean LH (+/- SEM) levels calculated for consecutive 2-h increments were 87.6 +/- 9.2 (0-2 h) 82.1 +/- 5.5 (2-4 h), and 80.7 +/- 4.8 (4-6 h) ng/ml in saline pretreated animals compared with 83.6 +/- 4.9, 79.8 +/- 5.8, and 72.5 +/- 6.2 ng/ml, respectively, in metyrapone pretreated monkeys. The same regimen of metyrapone infusion increased CRF messenger RNA levels in the paraventricular nucleus by approximately 33% (P < 0.0002). In a final experiment designed to examine the potential synergy between CRF and cortisol, the LH response to insulin-induced hypoglycemia was contrasted in saline and metyrapone pretreated monkeys. LH concentrations were reduced to approximately 40% of basal levels following insulin in both metyrapone and saline pretreated monkeys. Therefore, even though inhibition of cortisol synthesis leads to an increase in CRF messenger RNA in the paraventricular nucleus and a robust increase in ACTH secretion in rhesus monkeys, presumably due in part to increased neuroendocrine CRF secretion, LH secretion was not inhibited during either the acute or more chronic phase of corticotroph activation. Absence of LH inhibition was not due to low cortisol concentrations resulting from metyrapone because metyrapone did not prevent hypoglycemia-induced suppression of LH secretion. We conclude that increased neuroendocrine CRF secretion following metyrapone does not inhibit LH secretion under these conditions. Several explanations for this result are discussed.


Bilateral Ureteral Duplication of Complete Left and Incomplete Right Side with Lower Pole Kidney Stone.
Bilateral ureteral duplication is a very rare anomaly, a result of two separate ureteric buds arising from a mesonephric duct. Most of the patients are asymptomatic and diagnosed incidentally. Recurrent urinary tract infections, incontinence, haematuria, stone formation and flank pain are common clinical symptoms. Intravenous urography, computed tomography urography, and magnetic resonance imaging are the diagnostic modalities. In this report, a case of bilateral ureteral duplication with stone formation in the lower pole of the right kidney is presented along with its management.


Cohort follow-up of couples with primary infertility in an ART programme using frozen donor semen.
This study was designed to determine the crude cumulative live-birth rates in a cohort initiating frozen donor semen treatment until completion. This cohort study included 588 couples with primary infertility in one University Hospital centre. The treatment sequence involved first artificial insemination (AID) followed by IVF if necessary (IVF-D). Live birth, drop-out for personal or medical reasons and recourse to IVF-D were recorded for all patients. Live births and drop-out were expressed both as rates per cycle and crude cumulative rates. At the completion of AID and IVF-D cycles, 406 couples in the cohort (69%) achieved a live-birth and 182 couples (31%) discontinued treatment. In most cases, couples stopped treatment for personal reasons (74%) whereas fewer couples were denied further treatment for medical reasons (26%). This is the first report on the crude cumulative live-birth rate in a cohort after AID and IVF-D cycles. Although calculation based on crude cumulative live-birth rate shows lower results in comparison with life table analysis, this method allows patients to obtain an insight into their actual chances of achieving a successful pregnancy.


Risk exposure factors influencing the frequency of road crashes during the COVID-19 pandemic in Ciudad Juarez, Mexico. A negative binomial spatial regression model.
The article aims to investigate the influence of risk exposure factors on the frequency of road crashes from January to August 2020 in Ciudad Juarez, Mexico. It is a longitudinal study with four data sets: road crashes, population and housing census, location of economic activities, and road network information. Specifically, this study investigates the relationship between exposure factors - demographics, main roads and land use - and road crashes. A mixed method analysis was employed, (1) spatial analysis using GIS techniques; and (2) a negative binomial spatial regression model. The results showed a strong spatial dependence (0.274; p-value 0.00) of road crashes in the census tracts, and this effect was statistically significant (0.007) in the spatial regression model. In the model, a high probability (<0.05) of road crashes in the census tracts was found with the population aged 15 to 65 years, the length of main roads and the level of road coverage (Engel index), land uses with economic activities of an industrial and commercial character. The findings of this study successfully capture the social, economic, and urban conditions during the January-August 2020 period in the context of the COVID-19 pandemic. This new knowledge could help create preventive plans and policies to address the frequency of road crashes.


F-induced changes and its reversal by ITP in membrane turbidity and adenylate cyclase activity of chick brain microsomes.
The activation of adenylate cyclase by NaF was dependent on the previous incubation time and the concentration of F-. The activation by F- was irreversible and Mg2+ was required for the maximum effect. Turbidity of microsome suspension was also greatly increased by F- plus Mg2+. These effects on adenylate cyclase and membrane turbidity were specific for F- and F- saturation curves for both were similar, though Mg2+-saturation curves for both were dissimilar. The increase in turbidity induced by F- plus Mg2+ was rapidly reversed by ATP, GTP, ITP, UTP and CTP. However, ITP only, among all the triphospho-nucleotides tested, reversed the activity of adenylate cyclase previously activated by NaF plus MgC12. The activity of the enzyme reversed by ITP was not, however, re-enhanced by the presence of NaF in the assay medium. These results suggest the possiblity that F- induces a change in the membrane structure itself, and this change can be reversed by incubation with ITP. Consequently, adenylate cyclase may be conformed either to an activated or an unactivated state.


A Survey of Otolaryngology Residency Programs on Adapting to the United States Medical Licensing Examination (USMLE) Step 1 Transitioning to Pass/Fail.
Objectives In February 2020, the National Board of Medical Examiners (NBME) announced that the United States Medical Licensing Examination (USMLE) Step 1 licensing examination would change from a numerical score to Pass/Fail (P/F). After implementation, many believe that USMLE-Step 2-Clinical Knowledge (CK) will become an important metric for students applying to otolaryngology (ENT). The purpose of this study is to determine factors important to resident selection after these changes. Methods A survey containing 15 questions related to resident selection practices and how changing USMLE Step 1 to P/F would impact future resident selection was designed. It was distributed to all ENT residency programs accredited by the Accreditation Council for Graduate Medical Education (ACGME). Results Forty percent of programs responded; 66% (95% confidence interval (CI): 51.1%-78.4%) felt that changing Step 1 scoring would not lead to students being more prepared for clinical rotations; 55% believe class rank will increase in significance (95% CI: 35.7%-64.3%). There was also an increase in the importance of Step 2 CK, which had a mean ranking of 10.67 prior to changes in Step 1 scoring and increased to 7.80 after P/F. Conclusions The changes in Step 1 scoring will likely lead to increasing importance of other objective measures like class rank or Step 2 CK. This may defeat the intended purpose put forth by the NBME. Therefore, further guidance on measures correlated with student performance as a resident will be integral to the selection process.


Managing changes during a clinical investigation, Part I.
During the course of a clinical investigation, changes may need to be made to the device, the manufacturing process, the investigational plan or other aspects of the investigation. Part I of this article discusses the United States requirements for managing these types of changes. Part II will discuss European requirements and the need for developing a standard operating procedure to help ensure consistent compliance.


[Reversible cognitive decline in a patient with relapsing polychondritis].
Patient A, 58 years, is referred by the Rheumatologist to the Geriatrician concerning apathy. History reviews skipping arthritis, reddened and inflamed eyes, apathy and loss of interest. Physical examination revealed red tearing eyes, bradyphrenia and bradykinesia. Laboratory examination showed inflammation markers. The patient develops fever and bilateral reddened and inflamed ears. Diagnosis of relapsing polychondritis is made, the patient is treated with prednisone and the symptoms disappear. Relapsing polychondritis is a chronical disease associated with inflammation and destruction of cartilaginous structures and proteoglycan rich structures. We diagnosed Relapsing Polychondritis with a reversible dementia, probably due to cerebral vasculitis.


Alpha-keratin and corneous beta protein in the parakeratinized epithelium of the tongue in the domestic goose (Anser anser f. domestica).
The parakeratinized epithelium is a common epithelium in the oral cavity in birds and is characterized by the presence of cell nuclei in the cells of the cornified layer. This epithelium covers almost the entire dorsal surface of the tongue in the domestic goose apart of the lingual nail and conical papillae. So far no study has identified the molecular proteins alpha-keratin (IF-keratin) and/or corneous beta protein (CBP), which are responsible for keratinization or cornification processes in the parakeratinized epithelium of domestic geese. The study was performed using immunohistochemical (IHC) methods to identify alpha-keratin. The innovative method of Raman microspectroscopy was used to determine the presence of CBP and specify their percentage in epithelial layers of the parakeratinized epithelium. The results revealed that alpha-keratin is present in the whole parakeratinized epithelium. A strong staining reaction was detected in the basal and intermediate layers and a less strong staining reaction in the cornified layer. Raman microspectroscopy analysis confirmed the presence of alpha-keratin and demonstrated that its percentage decreases from the basal layer to the cornified layer. The Raman microspectroscopy technique revealed the occurrence of CBP in the parakeratinized epithelium and demonstrated that the percentage of this protein increases from the basal layer to the cornified layer. Performed analysis determines that parakeratinized epithelium undergoes cornification. However, the lower percentage of CBP in the cornified layer of parakeratinized epithelium than in orthokeratinized epithelium points to the fact that parakeratinized epithelium has a weaker protective function.


Identification of the dwarf gene GmDW1 in soybean (Glycine max L.) by combining mapping-by-sequencing and linkage analysis.
GmDW1 encodes an ent-kaurene synthase (KS) acting at the early step of the biosynthesis pathway for gibberellins (GAs) and regulates the development of plant height in soybean. Plant height is an important component of plant architecture, and significantly affects crop breeding practices and yield. Here, we report the characterization of an EMS-induced dwarf mutant (dw) of the soybean cultivar Zhongpin 661 (ZDD23893). The dw mutant displayed reduced plant height and shortened internodes, both of which were mainly attributed to the longitudinally decreased cell length. The bioactive GA1 (gibberellin A1) and GA4 (gibberellin A4) were not detectable in the stem of dw, and the dwarf phenotype could be rescued by treatment with exogenous GA3. Genetic analysis showed that the dwarf trait of dw was controlled by a recessive nuclear gene. By combining linkage analysis and mapping-by-sequencing, we mapped the GmDW1 gene to an approximately 460-kb region on chromosome (Chr.) 8, containing 36 annotated genes in the reference Willliams 82 genome. Of these genes, we identified two nonsynonymous single nucleotide polymorphisms (SNPs) that are present in the encoding regions of Gmdw1 and Glyma.08G165100 in dw, respectively. However, only the SNP mutation (T>A) at nucleotide 1224 in Gmdw1 cosegregated with the dwarf phenotype. GmDW1 encodes an ent-kaurene synthase, and was expressed in various tissues including root, stem, and leaf. Further phenotypic analysis of the allelic variations in soybean accessions strongly indicated that GmDW1 is responsible for the dwarf phenotype in dw. Our results provide important information for improving our understanding of the genetics of soybean plant height and crop breeding.


SubTap, a Versatile 3D Printed Platform for Eavesdropping on Extracellular Interactions.
Communication within the microbiome occurs through an immense diversity of small molecules. Capturing these microbial interactions is a significant challenge due to the complexity of the exometabolome and its sensitivity to environmental stimuli. Traditional methods for acquiring exometabolomic data from interacting microorganisms are limited by their low throughput or lack of sampling depth. To address this challenge, we introduce subtapping (short for substrate tapping), a technique for tapping into extracellular metabolites that are being transferred through the growth substrate during coculture. High-throughput subtapping is made possible by a new coculturing platform, named SubTap, that we engineered to resemble a 96-well plate. The three-dimensional (3D) printed SubTap platform captures the exometabolome in an agar compartment that connects physically separated growth chambers, which permits cell growth without competition for space. We show how SubTap facilitates replicable and quick detection of exometabolites via direct infusion mass spectrometry analysis. Using bacterial isolates from the soil, we apply SubTap to characterize the effects of growth medium, growth duration, and mixed versus unmixed coculturing on the exometabolome. Finally, we demonstrate SubTap's versatility by interrogating microbial interactions in multicultures with up to four strains. IMPORTANCE Improvements in experimental techniques and instrumentation have led to the discovery that the microbiome plays an essential role in human and environmental health. Nevertheless, there remain major impediments to conducting large-scale interrogations of the microbiome in a high-throughput manner, particularly in the field of exometabolomics. Existing methods to coculture microorganisms and interrogate their interactions are labor-intensive and low throughput. This inspired us to develop a solution for coculturing that was (i) open source, (ii) inexpensive, (iii) scalable, (iv) customizable, and (v) compatible with existing mass spectrometry instrumentation. Here, we present SubTap-a 3D printed coculturing platform that permits tapping directly into the growth substrate between physically separated, but interconnected, growth compartments. SubTap allows multiculture (with up to four distinct growth compartments) in spatially mixed or unmixed configurations and enables repeatable results with mass spectrometry, as shown by our validation with known compounds and cultures of one to four organisms.


[National guideline 'Cryopreservation of ovarian tissue'].
The treatment of children and young adults with cancer increasingly results in cure, but for a number of female patients this is at the expense of infertility. For women and girls with cancer and the wish to have children in the future, cryopreservation of ovarian tissue may be a solution in the absence of alternatives for the conservation of fertility. Because of the uncertain effectiveness and safety of cryopreservation of ovarian tissue, the Dutch national guideline 'Cryopreservation of ovarian tissue' advises removing and freezing ovarian tissue only if this is done within the framework of scientific research. Reimbursement of this procedure and financing of the relevant and necessary research have not yet been arranged.


Bibliometrics and Co-Citation Network Analysis of Systematic Reviews of Evidence-Based Nursing Guidelines for Preventing Inpatient Falls.
Advances in bibliometrics and co-citation analysis provide the opportunity to analyze quantitatively the large amount of nursing research used in evidence-based nursing. Numerous nursing researchers have attempted to obtain evidence that using evidence-based nursing improves the quality of nursing practices. However, little is known about how these efforts comply with the rigorous methods required for a systematic review in a subject area. This study explored the comprehensiveness of systematic reviews in four guidelines for preventing inpatient falls using bibliometrics and a co-citation network technique. Citations (n = 659) and 9417 unique bibliographic records written by 6537 authors were collected from the guidelines in January 2020. The results showed none of the references spanned all four authoring bodies, whereas only 0.1% and 4.7% of the references spanned three and two of the authoring bodies, respectively. The co-citation analysis revealed differences in the scope and primary concerns among the development groups, even in the same setting, with differences in the highly influential articles and authors. These findings imply that although the systematic reviews of guidelines on fall prevention were of good quality, there remain areas for improvement in terms of harmonizing the selection of bibliographic citations comprehensively.


Surface proteins of the human eosinophil. I. Isolation of eosinophil IgG binding proteins.
Proteins involved in the attachment of eosinophils to immobilized antigen-antibody complexes were isolated. Eosinophils, purified from normal human peripheral blood, were surface labelled with 125I-iodide in the presence of lactoperoxidase and hydrogen peroxide. Immobilized immune complexes were prepared by covalent coupling of tetanus toxoid antigen to cellulose and treatment of the fixed antigen with human anti-tetanus IgG. Intact cells were allowed to interact with the antigen-antibody complex and the cells were then lysed in situ with a salt solution containing the non-ionic detergent NP40. After exhaustive washing to remove unattached proteins, the bound proteins were eluted with a buffer containing mercaptoethanol with or without SDS. A major protein of mol. wt 16K and a minor protein of mol. wt 18K were isolated. These proteins were unaffected by the temperature of attachment of eosinophils to the fixed IgG antigen complexes or by the presence of protease inhibitors and did not therefore appear to be proteolytic cleavage products.


A black hole nova obscured by an inner disk torus.
Stellar-mass black holes (BHs) are mostly found in x-ray transients, a subclass of x-ray binaries that exhibit violent outbursts. None of the 50 galactic BHs known show eclipses, which is surprising for a random distribution of inclinations. Swift J1357.2-093313 is a very faint x-ray transient detected in 2011. On the basis of spectroscopic evidence, we show that it contains a BH in a 2.8-hour orbital period. Further, high-time-resolution optical light curves display profound dips without x-ray counterparts. The observed properties are best explained by the presence of an obscuring toroidal structure moving outward in the inner disk, seen at very high inclination. This observational feature should play a key role in models of inner accretion flows and jet collimation mechanisms in stellar-mass BHs.


Self-Guided Deep Multiview Subspace Clustering via Consensus Affinity Regularization.
Multiview subspace clustering (MVSC) leverages the complementary information among different views of multiview data and seeks a consensus subspace clustering result better than that using any individual view. Though proved effective in some cases, existing MVSC methods often obtain unsatisfactory results since they perform subspace analysis with raw features that are often of high dimensions and contain noises. To remedy this, we propose a self-guided deep multiview subspace clustering (SDMSC) model that performs joint deep feature embedding and subspace analysis. SDMSC comprehensively explores multiview data and strives to obtain a consensus data affinity relationship agreed by features from not only all views but also all intermediate embedding spaces. With more constraints being cast, the desirable data affinity relationship is supposed to be more reliably recovered. Besides, to secure effective deep feature embedding without label supervision, we propose to use the data affinity relationship obtained with raw features as the supervision signals to self-guide the embedding process. With this strategy, the risk that our deep clustering model being trapped in bad local minima is reduced, bringing us satisfactory clustering results in a higher possibility. The experiments on seven widely used datasets show the proposed method significantly outperforms the state-of-the-art clustering methods. Our code is available at https://github.com/kailigo/dmvsc.git.


Equivalent leak definitions for Smart LDAR (leak detection and repair) when using optical imaging technology.
Controlling fugitive emissions from leaks in petrochemical industry process equipment now requires periodic monitoring of valves, flanges, pumps etc., typically on a quarterly basis. Previous studies have shown that over 90% of the reducible emissions come from approximately 0.1% of the components, i.e. the large leakers. A new, and more cost-effective approach for controlling these large leakers would entail more frequent monitoring of process equipment, allowing for the detection and repair of the highly leaking components that contribute the most to emissions. This approach has been called "Smart LDAR." New optical imaging instruments, which significantly reduce monitoring costs, are now available to implement such an alternative work practice. This work describes the determination of the leak detection sensitivity (equivalency threshold) that an optical imaging instrument must achieve to ensure that it will provide at least the equivalent emission control of the current leak detection and repair practice. Equivalency thresholds were developed for various monitoring intervals. The U.S. Environment Protection Agency's Monte Carlo simulation approach was used to perform the analysis and to demonstrate that optical imaging, which is capable of identifying all of the largest leakers, can provide better control of fugitive emissions.


Surface membrane determinants on childhood acute lymphocytic leukemia cells: immunoglobulin, Fc and C3 receptors.
Most reports have now described two populations of childhood ALL patients: those with thymic (T) cell receptors and those lacking receptors on their neoplastic cells. Assays for the surface receptors of the T and thymic-independent (B) system were used to study forty-seven patients with ALL whose bone marrow contained a mean of 85% leukaemic cells. Two patients had T-cell disease and thirty-six were non-T and non-B. nine patients were identified whose leukaemic cells had membrane properties associated with the B-cell system: surface immunoglobulin, Fc receptors and/or complement receptors. Combined T and B receptors were found in one case. The same surface characteristics were found on leukaemic cells from these patients' bone marrow, blood, pleural and cerebrospinal fluid. Studies showed that the leukaemic cells were not of monocytic or granulocytic origin. Although a remission was obtained in each patient, the relapse rate of the B-cell group was worse than a similarly treated group of thirty-six non-T, non-B ALL patients (P less than 0.001). Initial total leucocyte counts of the B-cell group were greater than the non-T, non-B group (P 0.05), but when the patients in both groups with total leucocyte counts greater than 25,000/mm3 were compared, the relapse rate of the B-cell patients was significantly worse (P less than 0.025). The results show that patients with leukaemic cells possessing B-cell properties comprise a significant proportion of ALL cases, and their presence on leukaemic cells has an ominous significance.


Evaluation of family history as a risk factor and screening tool for detecting undiagnosed diabetes in a nationally representative survey population.
We examined the utility of a three-level familial risk stratification system as a screening tool for diabetes in a nationally representative sample of the U.S. adult population. National Health and Nutrition Examination Survey data were used to assess the prevalence and distribution of familial risk for diabetes, the association between three levels of familial risk and undiagnosed diabetes, and the use of familial risk as a screening tool for diabetes, alone and in combination with body mass index and age. The prevalence of undiagnosed diabetes was 3% and increased with increasing familial risk (average = 2%, moderate = 4%, high = 10%). High familial risk was significantly associated with undiagnosed diabetes (adjusted odds ratio = 4.6; 95% confidence interval: 1.9-11.3). The use of a three-tiered familial risk stratification for diabetes screening yielded higher specificity (94%) and positive predictive value (9.9%) for high familial risk than body mass index > or = 25 (specificity = 38%, positive predictive value = 4.2%). High familial risk and body mass index > or = 25 combined had higher specificity (97%) and positive predictive value (13.4%); the addition of age > or = 45 years further improved positive predictive value (21.0%) without reducing specificity. There was a strong and proportional association between familial risk and undiagnosed diabetes, suggesting that a three-tiered assessment of familial diabetes risk may increase the effectiveness of diabetes screening.


Jones' fracture.
The Jones' fracture is defined as a transverse fracture of the proximal fifth metatarsal diaphysis within 1.5 cm of the tuberosity. It is classified radiographically as acute, delayed union and nonunion. Some orthopedists also have added a classification of stress fractures. The best form of treatment is based on the presence or absence of medullary sclerosis adjacent to the fracture site. In addition, the prescribed treatment must be adhered to by the patient to prevent increased morbidity associated with this fracture.


Anemia with LDH-elevation in a patient with aortic valve replacement.
In a 63-year old patient with a history of aortic valve replacement in 1986, a reduced hemoglobin of 91 g/l was found by a family physician. Since serum LDH was also increased, the patient was diagnosed to suffer from mechanically induced, hemolytic anemia and presented at our hospital for further diagnosis and evaluation of the aortic valve prosthesis.


Molecular Tests for the Choice of Cancer Therapy.
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays. For example, administration of PARP inhibitors is tailored to a comprehensive testing of BRCA1 and BRCA2 genes, and is likely to be supplemented in the future by even more systematic assessment of DNA repair pathways. The detection of an androgenindependent splice-variant of androgen-receptor (AR-V7) in castration-resistant prostate cancer is achieved through the isolation of circulating tumor cells (CTCs). The efficacy of immune check-point inhibitors correlates with the overall mutational tumor load, therefore the companion diagnostic assays may involve genome-wide scanning. Integration of next-generation sequencing (NGS) into clinical oncology is expected to boost the use of predictive tests in the forthcoming years.


Regulatory Mechanisms Underlying Arsenic Uptake, Transport, and Detoxification in Rice.
Arsenic (As) is a metalloid environmental pollutant ubiquitous in nature that causes chronic and irreversible poisoning to humans through its bioaccumulation in the trophic chain. Rice, the staple food crop for 350 million people worldwide, accumulates As more easily compared to other cereal crops due to its growth characteristics. Therefore, an in-depth understanding of the molecular regulatory mechanisms underlying As uptake, transport, and detoxification in rice is of great significance to solving the issue of As bioaccumulation in rice, improving its quality and safety and protecting human health. This review summarizes recent studies on the molecular mechanisms of As toxicity, uptake, transport, redistribution, regulation, and detoxification in rice. It aims to provide novel insights and approaches for preventing and controlling As bioaccumulation in rice plants, especially reducing As accumulation in rice grains.


Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine.
We report a case of a patient with mild chronic renal insufficiency who had been taking simvastatin for over a year and developed acute weakness within 3 weeks after the start of treatment with colchicine for acute gouty bursitis. Profound muscle weakness of lower extremities with inability to stand up and/or walk was present. Elevated muscle enzymes and findings on electromyography were consistent with myopathy. Rapid improvement in muscle strength accompanied by prompt resolution of abnormal elevation of muscle enzymes followed cessation of both medications. Both colchicine and statin therapy may be associated with myopathy, which usually occurs after several months of therapy. The concomitant use, however, of colchicine and statin has been associated with the rapid onset of muscle weakness. Four patients with similar clinical and laboratory characteristics to our patient's after the combined use of colchicine and statins have been described in the literature. Patients receiving combination therapy with colchicine and simvastatin, particularly in the presence of renal insufficiency, should be monitored for the development of myopathy, including rhabdomyolysis.


Folding pathway mediated by an intramolecular chaperone.
The N-terminal propeptide of subtilisin, a serine protease, functions as an intramolecular chaperone which is crucial for proper folding of the active enzyme. This nascent N-terminal propeptide is removed after completion of the folding process. Here we present a possible pathway by which intramolecular chaperones mediate protein folding. Using circular dichroism to analyze acid-denatured subtilisin we have identified a folding-competent state which can refold to an active conformation in the absence of the propeptide. Earlier work had shown that guanidine hydrochloride-denatured subtilisin was in a state incapable of folding in absence of its propeptide. Comparison of the folding-incompetent and folding-competent states indicates that refolding is facilitated by the presence of residual structure present only in the folding-competent state. The analysis further indicates that the propeptide is essential for inducing this state. Therefore the folding-competent state may lie on--or be in rapid equilibrium with an intermediate on--the folding pathway of subtilisin. In the absence of the propeptide, formation of such a state--and hence refolding--is extremely slow.


Principles of definitive soft tissue coverage with flaps.
Despite the emergence of negative pressure wound therapy with reticulated open cell foam (NPWT/ROCF) as delivered by V.A.C.(R) Therapy (KCI, San Antonio, TX) for orthopaedic trauma, vascularized tissue transfer whether it be pedicle, free, or tissue transfer using the operating microscope or as an island, remains the mainstay of soft tissue reconstruction for orthopaedic traumatology. The critisism of microvascular procedures has been that they are lengthy, costly, and required technical expertise to perform. While technical skills are required, microsurgical care has evolved into a routine operation with high degrees of success in experienced hand. The problem that still remains is access to surgeons who are interested in soft tissue reconstruction and can perform definitive coverage with flaps. There is a need in the orthopaedic community to solve the problem of lack of flap surgeons and as a result, NPWT/ROCF has been touted as the answer to flap reconstruction. NPWT/ROCF is an important addition to soft tissue reconstruction but it serves as a bridge rather than definitive coverage in many hands. Just as wound technology is evolving with tissue substitutes, growth factors and NPWT/ROCF flaps technology continues to advance with new perforator flaps and local regional flaps, particularly the sural flap, coming on line as mainstays of soft tissue reconstruction.


Implementing and expanding HIV testing in immigrant populations in Europe: Comparing guideline's recommendations and expert's opinions.
Immigrant populations, especially those from endemic countries, living in the European Union (EU) suffer a disproportionate burden of HIV, delayed diagnosis and poorer access to antiretroviral treatment. While International Organisations are developing recommendations aimed at increasing the uptake of HIV testing, the feasibility and real outcomes of these measures remain unexplored. The aim of this review was, firstly to identify the recommendations of the main International Organisations (IO) on HIV testing in immigrants. Secondly, to describe the challenges for implementing and expanding HIV testing and counselling interventions targeting immigrants by interviewing key informants. The importance of HIV testing in immigrants is discussed, along with the appropriateness of universal HIV testing approaches vs most at risk targeted approaches. Also addressed is, pre- and post-HIV test counselling characteristics and community initiatives suitable to reach this population and, finally the legal issues regarding access to treatment for illegal immigrants.


P2X7 Nucleotide and EGF Receptors Exert Dual Modulation of the Dual-Specificity Phosphatase 6 (MKP-3) in Granule Neurons and Astrocytes, Contributing to Negative Feedback on ERK Signaling.
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) play a central role in the intracellular signaling of P2X7 nucleotide receptors in neurons and glial cells. Fine spatio-temporal tuning of mitogen-activated protein (MAP) kinases is essential to regulate their biological activity. MAP kinase phosphatases (MKPs) are dual specificity protein phosphatases (DUSPs) that dephosphorylate phosphothreonine and phosphotyrosine residues in MAP kinases. This study focuses on how DUSP, DUSP6/MKP3, a phosphatase specific for ERK1/2 is regulated by the P2X7 nucleotide receptor in cerebellar granule neurons and astrocytes. Stimulation with the specific P2X7 agonist, BzATP, or epidermal growth factor (EGF) (positive control for ERK activation) regulates the levels of DUSP6 in a time dependent manner. Both agonists promote a decline in DUSP6 protein, reaching minimal levels after 30 min yet recovering to basal levels after 1 h. The initial loss of protein occurs through proteasomal degradation, as confirmed in experiments with the proteasome inhibitor, MG-132. Studies carried out with Actinomycin D demonstrated that the enhanced transcription of the Dusp6 gene is responsible for recovering the DUSP6 protein levels. Interestingly, ERK1/2 proteins are involved in the biphasic regulation of the protein phosphatase, being required for both the degradation and the recovery phase. We show that direct Ser197 phosphorylation of DUSP6 by ERK1/2 proteins could be part of the mechanism regulating their cytosolic levels, at least in glial cells. Thus, the ERK1/2 activated by P2X7 receptors exerts positive feedback on these kinase's own activity, promoting the degradation of one of their major inactivators in the cytosolic compartment, DUSP6, both in granule neurons and astrocytes. This feedback loop seems to function as a common universal mechanism to regulate ERK signaling in neural and non-neural cells.


Tlx3 Function in the Dorsal Root Ganglion is Pivotal to Itch and Pain Sensations.
Itch, a sensation eliciting a desire to scratch, is distinct from but not completely independent of pain. Inspiring achievements have been made in the characterization of itch-related receptors and neurotransmitters, but the molecular mechanisms controlling the development of pruriceptors remain poorly understood. Here, our RNAseq and in situ hybridization data show that the transcription factor Tlx3 is required for the expression of a majority of itch-related molecules in the dorsal root ganglion (DRG). As a result, Tlx3F/F;Nav1.8-cre mice exhibit significantly attenuated acute and dry skin-induced chronic itch. Furthermore, our study indicates that TRPV1 plays a pivotal role in the chronic itch evoked by dry skin and allergic contact dermatitis (ACD). The mutants also display impaired response to cold and inflammatory pain and elevated response to capsaicin, whereas the responses to acute mechanical, thermal stimuli and neuropathic pain remain normal. In Tlx3F/F;Nav1.8-cre mice, TRPV1 is derepressed and expands predominantly into IB4+ non-peptidergic (NP) neurons. Collectively, our data reveal a molecular mechanism in regulating the development of pruriceptors and controlling itch and pain sensations.


Evaluation of Areawide Forecasts of Wind-borne Crop Pests: Sugarcane Aphid (Hemiptera: Aphididae) Infestations of Sorghum in the Great Plains of North America.
Airborne pests pose a major challenge in agriculture. Integrated pest management programs have been considered a viable response to this challenge, and pest forecasting can aid in strategic management decisions. Annually recurrent areawide sugarcane aphid [Melanaphis sacchari (Zehntner) (Hemiptera: Aphididae)] infestations of sorghum [Sorghum bicolor (L.) Moench (Poales: Poaceae)] in the Great Plains of North America is one of such challenges. As part of the response, a spatially-explicit individual-based model was developed that simulates sugarcane aphid infestations over the southern-to-central part of the region. In this work, we evaluated model forecasts using 2015-2018 field data. The ranges of forecasted days of first infestation significantly overlapped with those observed in the field. The average days of first infestation observed in the field were approximated by the model with differences of less than 28 days in Texas and southern Oklahoma (2015-2018), and in northern Oklahoma (2016-2017). In half of these cases the difference was less than 14 days. In general, the modeled average day of first infestation was earlier than the observed one. As conceptual modeling decisions may impact model forecasts and as various socio-environmental factors may impact spatio-temporal patterns of field data collection, agreement between the forecasts and the observed estimates may vary between locations and seasons. Predictive modeling has the potential to occupy a central position within areawide integrated pest management programs. More detailed consideration of local agricultural practices and local environmental conditions could improve forecasting accuracy, as could broader participation of producers in field monitoring efforts.


Organising pneumonia as the first manifestation of rheumatoid arthritis.
Organising pneumonia (OP) is an inflammatory lung disease with distinctive clinicopathological features. OP can be evident during the course of rheumatoid arthritis (RA) with increased disease activity. The authors report an OP associated with RA case in which pulmonary symptoms preceded the onset of joint symptoms. An OP patient with elevated serum anticyclic citrullinated peptide antibody is likely to manifest RA in the near future, reflecting its high disease activity. Thus, an early rheumatologic consultation should be taken into consideration to make an early decision to initiate disease-modifying antirheumatic drugs therapy.


Preparation of AgCl Nanocubes and Their Application as Efficient Photoinitiators in the Polymerization of N-Isopropylacrylamide.
Uniform AgCl nanocubes with an average size of about 360 nm have been synthesized. Under UV illumination, a layer of silver nanoparticles with surface plasmon resonance was produced and covered the surface of AgCl particles in a short time, and the Ag/AgCl particles remained quite stable as shown in XRD patterns. The as-synthesized AgCl particles were tried for the first time as photoinitiator to polymerize N-isopropylacrylamide under UV-irradiation, and a high efficiency and conversion rate were realized. The structure of the polymers was studied by FTIR spectrophotometer. The results of turbidimetric method showed that the polymers were temperature sensitive and their lower critical solution temperature was about 33 °C. The effects of photoinitiators concentration, monomers concentration, and irradiation time on the polymer yield were investigated. The reaction mechanism was discussed by using salicylic acid as scavengers of hydroxyl radicals and conducting the reaction under oxygen atmosphere, respectively. The results proved that hydroxyl radicals were essential to chain initiation.


Three-way and two-way rearrangements involving chromosomes 10, 2, 5 and 5, 2 in two marker chromosomes of a human melanoma cell line.
Two marker chromosomes (mar1 and mar2), provided with two closely spaced heterochromatic bands, were observed in the 14932 cell line established from a human metastatic melanoma. Fluorescence in situ hybridization (FISH) with the alphoid sequence p82H common to all human centromeres showed strong signals over the double C-bands of mar1 and mar2. These were recognized by a chromosome 2-specific alphoid probe, although chromosome in situ suppression (CISS) hybridization with a chromosome 2 library failed to reveal any painting along mar1 and mar2. The centromere of mar1 was identified by a chromosome 10-specific alphoid sequence and the marker chromosome was decorated from pter to a region proximal to the interpolated C-band by a chromosome 10 library. The centromere of mar2 could not be recognized by any chromosome-specific alphoid probe, but the whole mar2 was decorated by a chromosome 5 library. This library also painted the distal q arm of mar1, which was not painted by the chromosome 10 library, as well as a small band proximal to the double C-band. Identification of the two marker chromosomes reveals their common origin and indicates a role for chromosomes 2, 5 and 10 in the genesis and/or progression of the 14932 melanoma. Alteration to the chromosome-specific alphoid sequence in the centromere of mar2 provides evidence for rearrangement of constitutive heterochromatin alphoid sequences in human tumours.


Antibacterial properties of 2-acetylpyridine-1-oxide thiosemicarbazones.
We have investigated the in vitro antibacterial activity of 13 2-acetylpyridine-1-oxide thiosemicarbazones and 5 thiosemicarbazides against 80 clinically significant bacterial cultures, including 13 isolates with known antibiotic resistance. Of the thiosemicarbazones tested, 5 had minimal inhibitory concentrations (MICs) of 0.25 microgram/ml for Neisseria gonorrhoeae isolates; 1 of these had an MIC range of 0.25-0.5 microgram/ml for the Neisseria meningitidis cultures, and 2 had MICs of 2 and 2-4 micrograms/ml for Staphylococcus aureus and Streptococcus faecalis isolates, respectively. Two of the thiosemicarbazides had MICs of 0.25 microgram/ml for N. gonorrhoeae, whereas 2 others had MICs of 2-4 and 4-8 micrograms/ml for S. aureus and S. faecalis isolates, respectively. The test compounds were ineffective against the gram-negative enteric cultures and the Pseudomonas isolates.


Iatrogenic Abdominal Aortic Rupture During Transpedicular Bone Grafting for Thoracolumbar Burst Fractures Successfully Treated by Endovascular Stent Implantation.
Vascular injury resulting from transpedicular bone grafting in the treatment of thoracolumbar burst fractures has not been reported but can be lethal. The management of patients with iatrogenic aortic injury remains a difficult clinical problem. This study describes a case of iatrogenic abdominal aortic rupture at the level of L2 during transpedicular bone grafting for the first time. A 55 year-old male patient suffered from a T12 vertebral body mild compression fracture and an L2 vertebral body burst fracture due to falling. This patient was treated with posterior open reduction and pedicle screw fixation combined with transpedicular bone grafting in the L2 vertebrae using a paravertebral approach. Unfortunately, during transpedicular bone grafting, the abdominal aorta was punctured by the tip of the graft funnel. The use of endovascular stent implantation successfully averted a clinical catastrophe. The patient had a good clinical outcome, and no complications associated with vascular trauma were apparent at a 1-year follow-up examination. For the repair of vascular injury caused by transpedicular bone grafting, endovascular techniques can provide a safe, minimally invasive, and effective treatment option. Surgeons should carefully evaluate the specificity of the patient's anatomical structures preoperatively and be more cautious during transpedicular bone grafting in the treatment of thoracolumbar burst fractures.


Image-guided lens extraction surgery: a systematic review.
A systematic review of the recent literature regarding the current image-guided systems used for cataract surgery or refractive lens exchange was performed based on the PubMed and Google Scholar databases in March 2018. Literature review returned 21 eligible studies. These studies compared image-guided systems with other keratometric devices regarding their accuracy, repeatability and reproducibility in measurement of keratometric values, astigmatism magnitude and axis, as well as in IOL power calculation. Additionally, the image-guided systems were compared with conventional manual ink-marking techniques for the alignment of toric IOLs. In conclusion, image-guided systems seem to be an accurate and reliable technology with measurements of high repeatability and reproducibility regarding the keratometry and IOL power calculation, but not yet interchangeable with the current established and validated keratometric devices. However, they are superior over the conventional manual ink-marking techniques for toric IOL alignment.


Host parent responses to heterospecific parasite nestling alarm calls are independent of past and current experience with experimental brood parasitism.
Communication between parents and dependent offspring is critical not only during provisioning, but also in antipredator contexts. In altricial birds, a top cause of reproductive failure is nest predation, and alarm calls both by parents and chicks can serve to alert others and increase the likelihood of offspring escaping predation. Understanding the factors that determine the strength of parental antipredator responses to different nestling alarm calls can provide insight into parent-offspring recognition. The prothonotary warbler (Protonotaria citrea), a host of the obligate brood parasite, the brown-headed cowbird (Molothrus ater), never rejects cowbird young and raises the parasite together with its own offspring. To determine whether warbler parents learn cowbird nestling alarm calls, we presented experimentally parasitized or non-parasitized parents with playbacks of conspecific warbler, parasitic cowbird, and a harmless heterospecific control, eastern bluebird (Sialis sialis), nestling alarm calls. We recorded the latency to respond and the number of chips given by members of the resident warbler pair. We found that parents were most likely to respond to warbler nestling alarm calls, least likely to respond to bluebird calls, with a statistically intermediate likelihood of responding to cowbird calls. Critically, current and past parasitism status did not affect the likelihood of response to any playback or the number of chips given, however, currently parasitized parents had greater response latencies to playbacks than non-parasitized parents. These results suggest that warbler parents do not learn cowbird alarm calls from breeding experiences and, in turn, that cowbirds may employ a generalized, bet-hedging alarm call.


Skin manifestations of rheumatoid arthritis.
Rheumatoid arthritis is a chronic systemic disease that, in addition to articular involvement, may exhibit a variety of extraarticular manifestations. The skin is frequently involved mainly in the most severe forms of the disease. Rheumatoid nodules, accelerated rheumatoid nodulosis, rheumatoid nodulosis, Felty syndrome, rheumatoid vasculitis, pyoderma gangrenosum, rheumatoid neutrophilic dermatosis, interstitial granulomatous dermatitis, and palisaded neutrophilic granulomatous dermatitis are reviewed both clinically and histologically. Moreover, cutaneous reactions related to treatments of rheumatoid arthritis, in particular to biologic agents, are described. Early recognition of these entities through a clinical and histological correlation permit to optimize the management of patients.


The feasibility of low-dose CT protocols for coronary artery calcium scoring and PET attenuation correction in cardiac PET/CT.
The purpose of this study was to investigate the feasibility of using low-dose computed tomography (CT) in coronary artery calcium scoring and PET attenuation correction for patients in different weight categories undergoing cardiac PET/CT examinations. Calcium scoring computed tomography (CSCT) scans and PET scans of anthropomorphic cardiac phantoms simulating normal-weight, mildly obese, and severely obese patients were acquired with a hybrid PET/CT scanner. CSCT images were acquired at 120 kVp, with tube current ranging from 10 to 550 mA. PET scans were performed in three-dimensional mode, with acquisition time of 3 min/bed position. The image quality of cardiac PET/CT was evaluated by assessing the signal-to-noise ratio. CT-based coronary artery calcium quantification was performed using the Agatston scoring system. On the basis of our results, the CSCT protocols using tube currents of 50 and 150 mA should be able to achieve the lowest possible radiation dose while maintaining the desired image quality for normal-weight and mildly obese patients undergoing cardiac PET/CT examinations, respectively. When the proposed low-dose CSCT protocols were performed, radiation dose could be reduced by 83.34 and 50% compared with those from CSCT scans acquired with standard tube current settings for normal-weight and mildly obese patients, respectively. In the scanning of severely obese patients, an increase in tube voltage or current would help improve the reliability of image information provided by cardiac PET/CT. Our study demonstrated the feasibility of low-dose CT protocols for coronary artery calcium scoring and PET attenuation correction in cardiac PET/CT to examine patients in different weight categories. The calculations performed in this work should be able to provide practical information to achieve necessary diagnostic information while keeping radiation dose as low as reasonably achievable.


Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease.
A variety of Alzheimer's disease (AD) mouse models overexpress mutant forms of human amyloid precursor protein (APP), producing high levels of amyloid β (Aβ) and forming plaques. However, the degree to which these models mimic spatiotemporal patterns of Aβ deposition in brains of AD patients is unknown. Here, we mapped the spatial distribution of Aβ plaques across age in three APP-overexpression mouse lines (APP/PS1, Tg2576, and hAPP-J20) using in vivo labeling with methoxy-X04, high throughput whole brain imaging, and an automated informatics pipeline. Images were acquired with high resolution serial two-photon tomography and labeled plaques were detected using custom-built segmentation algorithms. Image series were registered to the Allen Mouse Brain Common Coordinate Framework, a 3D reference atlas, enabling automated brain-wide quantification of plaque density, number, and location. In both APP/PS1 and Tg2576 mice, plaques were identified first in isocortex, followed by olfactory, hippocampal, and cortical subplate areas. In hAPP-J20 mice, plaque density was highest in hippocampal areas, followed by isocortex, with little to no involvement of olfactory or cortical subplate areas. Within the major brain divisions, distinct regions were identified with high (or low) plaque accumulation; for example, the lateral visual area within the isocortex of APP/PS1 mice had relatively higher plaque density compared with other cortical areas, while in hAPP-J20 mice, plaques were densest in the ventral retrosplenial cortex. In summary, we show how whole brain imaging of amyloid pathology in mice reveals the extent to which a given model recapitulates the regional Aβ deposition patterns described in AD.


Neuroprotection by Therapeutic Hypothermia.
Hypothermia therapy is an old and important method of neuroprotection. Until now, many neurological diseases such as stroke, traumatic brain injury, intracranial pressure elevation, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy have proven to be suppressed by therapeutic hypothermia. Beneficial effects of therapeutic hypothermia have also been discovered, and progress has been made toward improving the benefits of therapeutic hypothermia further through combination with other neuroprotective treatments and by probing the mechanism of hypothermia neuroprotection. In this review, we compare different hypothermia induction methods and provide a summarized account of the synergistic effect of hypothermia therapy with other neuroprotective treatments, along with an overview of hypothermia neuroprotection mechanisms and cold/hypothermia-induced proteins.


Behaviour of Tetrabenazine in Acid Medium: Reassessment and Impact on Formulation.
Thorough studies of previous analytical stress data of tetrabenazine, a dopamine depleting agent, showed a potential susceptibility to acidic conditions. Hence, the behavior of tetrabenazine acidic solutions was studied by LC-MS and NMR spectroscopy. Reverse-phase LC-MS analysis of tetrabenazine acidic aqueous solutions consistently showed a main lipophilic impurity in a proportion of 15 to 20%. NMR spectroscopy studies did not allow to completely ascertain its structure. However, we hypothesize an interconversion of trans-tetrabenazine with its unstable cis isomer via an open isoquinolinium intermediate. Evaluation of tetrabenazine integrity in orodispersible films was reassessed in light of these observations after formulation and during stability study. Even if interconversion of trans-tetrabenazine with its cis isomer was observed in orodispersible films containing tetrabenazine, this phenomenon seems not to have any consequences for the overall tetrabenazine bioavailability.


The effect of unemployment on household composition and doubling up.
"Doubling up" (sharing living arrangements) with family and friends is one way in which individuals and families can cope with job loss, but relatively little research has examined the extent to which people use coresidence to weather a spell of unemployment. This project uses data from the Survey of Income and Program Participation (SIPP) to provide evidence on the relationship between household composition and unemployment across working ages, focusing on differences in behavior by educational attainment. Using the SIPP panels, I find that individuals who become unemployed are three times more likely to move in with other people. Moving into shared living arrangements in response to unemployment is not evenly spread across the distribution of educational attainment: it is most prevalent among individuals with less than a high school diploma and those with at least some college.


Differentiation of pityriasis rubra pilaris from plaque psoriasis by dermoscopy.
Pityriasis rubra pilaris (PRP) and plaque psoriasis (PP) are two distinctive erythemato-squamous skin diseases that often have to be differentiated from each other and from other similar dermatoses. Dermoscopy has been proven to aid the clinical diagnosis of several inflammatory disorders, minimizing the need for skin biopsy. Our aim was to determine the dermoscopic patterns of PRP compared to PP and to assess the significance of certain dermoscopic criteria in the diagnosis of PRP. This case-control study included 11 patients with biopsy proven PRP and 25 patients with biopsy proven plaque psoriasis. The most recently developed lesion of each patient was examined by non-contact dermoscopy. Whitish keratotic plugs and linear vessels in yellowish background are significant dermoscopic features of PRP compared to white diffuse scales and dotted vessels in a light red background in PP. In conclusion, PRP and PP reveal specific distinguishing dermoscopic patterns that may assist in their clinical diagnosis and may also be useful for the differential diagnosis from other resembling dermatoses.


In vitro differentiation and proliferation of purified human thymic and bone marrow CD7+CD2- T-cell precursors.
It is well established that CD7, gp40 antigen is one of the first antigens detected on the surfaces of cells of the human T-cell lineage. Using complement-dependent cytotoxicity and immunoadherence to anti-CD7-coated surfaces, we were able to purify CD7+2-3-4-8-TcR- cells with greater than 90% purity from both human thymus and bone marrow. Limiting dilution analysis showed that these cells displayed high ability to generate mature T-cell clones when they were cultured in the appropriate conditions. These precursors needed phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM) as a differentiation signal before being able to respond to PHA and recombinant interleukin 2 (rIL2). CD7+CD2- precursors differed from more mature CD7+CD2+ thymocytes because they were not sensitive to PHA, IL2, or CD2 triggering. Bone marrow-derived clones were mostly CD4+, whereas thymic cells generated more CD8+ than CD4+ clones. Together, this study indicates that the CD7+CD2- precursor is one of the earliest prothymocytes able to differentiate and proliferate in vitro.


Molecular genetics of papillary thyroid carcinoma: great expectations.
Papillary thyroid carcinoma (PTC) is the most prevalent type of endocrine cancer and, in recent epidemiological surveys, one of the types of human cancer whose incidence is growing. Despite the favourable outcome and long survival rates of most patients, some tumours display an aggressive behaviour and may progress to the highly aggressive and lethal, anaplastic thyroid carcinoma. In recent years, several progresses have been made on the molecular characterization of PTC, in general, and in the genetic alterations underlying the histotype diversity of this type of cancer, in particular. This holds true regarding alterations on nuclear DNA as well as mitochondrial DNA. In this review we have summarized the most recent findings in the genetic characterization of PTC, giving a particular emphasis to the genotype-phenotype associations, the prognosis implications, and the diagnostic and therapeutic value of the newly identified genetic markers.


Fluorine NMR functional screening: from purified enzymes to human intact living cells.
The substrate- or cofactor-based fluorine NMR screening, also known as n-FABS (n fluorine atoms for biochemical screening), represents a powerful method for performing a direct functional assay in the search of inhibitors or enhancers of an enzymatic reaction. Although it suffers from the intrinsic low sensitivity compared to other biophysical techniques usually applied in functional assays, it has some distinctive features that makes it appealing for tackling complex chemical and biological systems. Its strengths are represented by the easy set-up, robustness, flexibility, lack of signal interference and rich information content resulting in the identification of bona fide inhibitors and reliable determination of their inhibitory strength. The versatility of the n-FABS allows its application to either purified enzymes, cell lysates or intact living cells. The principles, along with theoretical, technical and practical aspects, of the methodology are discussed. Furthermore, several applications of the technique to pharmaceutical projects are presented.


Predicting academic self-handicapping in different age groups: the role of personal achievement goals and social goals.
Academic self-handicapping refers to the use of impediments to successful performance on academic tasks. Previous studies have shown that it is related to personal achievement goals. A performance goal orientation is a positive predictor of self-handicapping, whereas a task goal orientation is unrelated to self-handicapping. The aim of this study was to examine the relationship between academic self-handicapping, goal orientations (task, performance-approach, performance-avoidance), social goals, future consequences and achievement in mathematics. An additional aim was to investigate grade-level and gender differences in relation to academic self-handicapping. Participants were 702 upper elementary, junior and senior high school students with approximately equal numbers of girls and boys. There were no grade-level or gender differences as regards the use of self-handicapping. The correlations among the variables revealed that, when the whole sample was considered, self-handicapping was positively related to performance goal orientations and pleasing significant others and negatively to achievement in mathematics. The results of hierarchical regression analysis showed that, in upper elementary and junior high schools, the association between achievement in mathematics and self-handicapping was mediated by performance-avoidance goals. In senior high school, only task goal orientation was a negative predictor of self-handicapping.


Glucuronide conjugation reduces the cytotoxicity but not the mutagenicity of benzo(a)pyrene in the CHO/HGPRT assay.
Benzo(a)pyrene (B[a]P) is biotransformed by the mixed-function oxidase (MFO) system to numerous metabolites some of which are cytotoxic and/or mutagenic to mammalian cells. However, conjugation of B(a)P metabolites with glucuronic acid in vivo is a major pathway of detoxication and elimination. The effects of glucuronide conjugation on B(a)P-induced cytotoxicity and mutagenicity were studied using the CHO/HGPRT assay with a rat liver homogenate preparation containing MFO system cofactors (S9 mix) and uridine diphosphate alpha-D-glucuronic acid (UDPGA). B(a)P metabolites proximate to the biologically active B(a)P quinones (B[a]P 6-OH) and to the B(a)P 7,8-diol-9,10 epoxide isomers (B[a]P 7,8-diol), were also assayed with S9 mix in the absence and presence of UDPGA. The addition of UDPGA to S9 mix reduced B(a)P-induced cytotoxicity but did not affect mutagenicity. B(a)P 6-OH-mediated cytotoxicity was also reduced in the presence of UDPGA. UDPGA had no effect on B(a)P 7,8-diol-induced cytotoxicity or mutagenicity. B(a)P phenols have been shown to be the preferred B(a)P-metabolite substrates for UDP-glucuronyltransferase enzymes. Thus, the reduction of B(a)P and B(a)P 6-OH-induced cytotoxicity by glucuronide conjugation is likely due to the elimination of cytotoxic phenols and quinones. Since B(a)P 7,8-diol is a poor substrate for UDP-glucuronyltransferase enzymes, no effects on B(a)P-induced mutagenicity or B(a)P 7,8-diol-induced cytotoxicity and mutagenicity were observed.


Increasing iron and zinc in pre-menopausal women and its effects on mood and cognition: a systematic review.
Iron and zinc are essential minerals often present in similar food sources. In addition to the adverse effects of frank iron and zinc-deficient states, iron insufficiency has been associated with impairments in mood and cognition. This paper reviews current literature on iron or zinc supplementation and its impact on mood or cognition in pre-menopausal women. Searches included MEDLINE complete, Excerpta Medica Database (EMBASE), psychINFO, psychARTICLES, pubMED, ProQuest Health and Medical Complete Academic Search complete, Scopus and ScienceDirect. Ten randomized controlled trials and one non-randomized controlled trial were found to meet the inclusion criteria. Seven studies found improvements in aspects of mood and cognition after iron supplementation. Iron supplementation appeared to improve memory and intellectual ability in participants aged between 12 and 55 years in seven studies, regardless of whether the participant was initially iron insufficient or iron-deficient with anaemia. The review also found three controlled studies providing evidence to suggest a role for zinc supplementation as a treatment for depressive symptoms, as both an adjunct to traditional antidepressant therapy for individuals with a diagnosis of major depressive disorder and as a therapy in its own right in pre-menopausal women with zinc deficiency. Overall, the current literature indicates a positive effect of improving zinc status on enhanced cognitive and emotional functioning. However, further study involving well-designed randomized controlled trials is needed to identify the impact of improving iron and zinc status on mood and cognition.


A gestational choriocarcinoma of the ovary diagnosed by DNA polymorphic analysis: a case report and systematic review of the literature.
Choriocarcinoma of the ovary is rare. This tumor can arise from gestational tissue or pure germ cells of the ovary, the former results in gestational choriocarcinoma. The clinical characteristics and histology of both tumor types are identical, differentiation of these tumors is necessary for effective treatment. One strategy for the differentiation of these tumors types is to identify the presence of paternal DNA by DNA polymorphic analysis. In the present case, a 27-year-old patient with a history of amenorrhea, lower abdominal pain and vaginal bleeding received a laparoscopic dissection of cystic mass of the right ovary according to an initial diagnosis of ectopic pregnancy. Primary choriocarcinoma of the ovary was diagnosed by pathology, but its origin was uncertain. DNA polymorphic analysis was then performed and a gestational origin was confirmed. The patient subsequently exhibited an excellent response to chemotherapy, achieved complete remission and gave birth to a healthy baby. Differentiation between two etiologies of primary choriocarcinoma can be achieved with DNA polymorphic analysis and it is necessary to distinguish between them to approach to an appropriate treatment of a patient.


[Medicine and law. Legal aspects of the epilepsies].
In this paper we review the relation between epilepsy and the law, more precisely with regard to penal and civil law. Since the new Spanish penal code came into effect in 1996, and especially in view of recent advances in medical knowledge, it is important for doctors and lawyers to make an effort to develop a language which is common to both professions. We particularly refer to the psychiatric comorbidity of epilepsy, especially the association between violence and epilepsy, in the context of psychotic changes in epilepsy. The subject is still under discussion. In the future a consensus must be reached between all the professions involved to ensure correct practice when managing the psychiatric comorbidity of epilepsy.


The management of pain due to amputation.
Current approaches to the management of pain due to amputation are presented by two Spanish pain specialists with additional commentaries on care of such patients by pain specialists from Belgium and the United Kingdom. Contemporary pharmacotherapy and nondrug interventions are described.


Gain-induced trapping of microcavity exciton polariton condensates.
We have performed real and momentum space spectroscopy of exciton polariton condensates in a GaAs-based microcavity under nonresonant excitation with an intensity-stabilized laser. An effective trapping mechanism is revealed, which is due to the stimulated scattering gain inside the finite excitation spot combined with the short lifetime. We observe several quantized modes while the lowest state shows Heisenberg-limited real and momentum space distributions. The experimental findings are qualitatively reproduced by an open dissipative Gross-Pitaevskii equation model.


An extension and test of Sutherland's concept of differential social organization: the geographic clustering of Japanese suicide and homicide rates.
In an effort to explain the spatial patterning of violence, we expanded Sutherland's (1947) concept of differential social organization to include the level of deviance exhibited by neighboring areas. To test the value of this extension, the geographic clustering of Japanese suicide and homicide rates is assessed using 1985 and 1995 data for prefectures. Univariate results show that both types of violence cluster significantly in space. Inconsistent with the proposed expansion of differential social organization, multivariate results show that proximity to homicide does not increase the risk of homicide in Japan. Results for suicide are supportive and suggest that proximity to higher rates of suicide exposes residents to cultural values that support suicide and to role models who have committed suicide.


Fluorine-fluorine spin-spin coupling constants in aromatic compounds: correlations with the delocalization index and with the internuclear separation.
This paper describes a new empirical approach for the evaluation of fluorine-fluorine spin-spin coupling constants (J(FF)) in aromatic compounds. The correlations between J(FF) and the delocalization index calculated within the framework of the theory of atoms in molecules (AIM) and with the fluorine-fluorine internuclear separation are investigated. Both the internuclear separation and the delocalization index are found to be highly correlated with J(FF). A regression model in which the experimental J(FF) coupling constant is fitted exponentially to the internuclear separation and linearly to the delocalization index yields a squared correlation coefficient as high as 0.96 for a data set consisting of 33 coupling constants spread over a range of 85 Hz.


Effects of common interest groups on rural women and youth livelihood: A qualitative study from Central Ethiopia.
The study was conducted to examine the implications of the Common Interest Group (CIG) scheme for rural livelihood change in the selected areas of the Wara-Jarso woreda, Central Ethiopia. The study focuses on the activities of the CIGs, their effectiveness, Strengths, Weaknesses, Opportunities, and Threats, along with the changes in the livelihood status of CIG members. Four CIGs that fits into the aim of the study were purposively selected from the CIGs operating in the woreda. Among a qualitative research approach, a case study was employed. The data were collected from January 1, 2021 to February 28, 2021. Primary data were gathered using Focus Group Discussions and Key Informant Interviews. A thorough desk review of official documents and other secondary sources was made as an auxiliary method to capture sets of relevant information. The data organization was performed by the MAXQDA 2020 qualitative data analysis package program. The data were analyzed using thematic analysis, relational analysis, and content analysis methods. It was found that the CIGs have encouraged strong social capital among members and becomes an important alternative financial source. It was also found that the CIGs operation has encountered problems related to lack of entrepreneurial education and skill training, monitoring and evaluation, workplace, coordination among stakeholders, inadequate and improper financial use, and non-existence of market linkage. Their strengths, weaknesses, and opportunities were also indicated. For successful rural women and youth livelihood change through the CIGs scheme, the study recommends access to entrepreneurial skill training, coordination among relevant stakeholders, strong monitoring and evaluation, access to market linkage and workplace, and adequate funding.


Role of carbonyl sulfide in acute lung injury following limb ischemia/reperfusion in rats.
To investigate the effect of carbonyl sulfide (COS) on limb ischemia/reperfusion (I/R)-induced acute lung injury (ALI) and the associated mechanism in rats. ALI was induced by bilateral hind limb I/R in Sprague-Dawley (SD) rats. Sixty-four SD rats were randomly divided into the control group, I/R group, I/R + COS group, and I/R + AIR group. We observed the survival rate of the rats and the morphological changes of lung tissues, and we measured the change in the lung coefficient, the expression levels of the intercellular adhesion factor-1 (ICAM-1) protein in lung tissue, the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-lβ, and interleukin (IL)-6 in both lung tissue and serum, and cell apoptosis. Limb I/R caused significant lung tissue damage. The number of polymorphonuclear neutrophil in alveolar septa, the expression level of the ICAM-1 protein in lung tissue, the expression levels of TNF-α, IL-1, and IL-6 in lung tissue and serum, the lung coefficient, and cell apoptosis all increased. When a low dose of COS gas was administered prior to limb I/R, the variation of the above indicators was significantly reduced, while an increase in the dose of COS did not reduce the lung injury but rather increased the mortality rate. Carbonyl sulfide is another new gaseous signaling molecule, and a low dose of exogenous COS may play a protective role in I/R-induced ALI by acting as an anti-inflammatory agent by promoting the production of antioxidants and by inhibiting the expression of adhesion molecule proteins.


Rapid Evaluation of Small Molecule Cellular Target Engagement with a Luminescent Thermal Shift Assay.
Determination of target engagement for candidate drug molecules in the native cellular environment is a significant challenge for drug discovery programs. The cellular thermal shift assay (CETSA) has emerged as a powerful tool for determining compound target engagement through measurement of changes to a protein's thermal stability upon ligand binding. Here, we present a HiBiT thermal shift assay (BiTSA) that deploys a quantitative peptide tag for determination of compound target engagement in the native cellular environment using a high throughput, plate-based luminescence readout. We demonstrate that BiTSA can rapidly assess cellular target engagement of small molecule ligands against their cognate targets and highlight two applications of BiTSA for differentiating small molecules targeting mutant KRAS and TP53.


The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC): IUPHAR Review 19.
Acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC) are both members of the ENaC/degenerin family of amiloride-sensitive Na(+) channels. ASICs act as proton sensors in the nervous system where they contribute, besides other roles, to fear behaviour, learning and pain sensation. ENaC mediates Na(+) reabsorption across epithelia of the distal kidney and colon and of the airways. ENaC is a clinically used drug target in the context of hypertension and cystic fibrosis, while ASIC is an interesting potential target. Following a brief introduction, here we will review selected aspects of ASIC and ENaC function. We discuss the origin and nature of pH changes in the brain and the involvement of ASICs in synaptic signalling. We expose how in the peripheral nervous system, ASICs cover together with other ion channels a wide pH range as proton sensors. We introduce the mechanisms of aldosterone-dependent ENaC regulation and the evidence for an aldosterone-independent control of ENaC activity, such as regulation by dietary K(+) . We then provide an overview of the regulation of ENaC by proteases, a topic of increasing interest over the past few years. In spite of the profound differences in the physiological and pathological roles of ASICs and ENaC, these channels share many basic functional and structural properties. It is likely that further research will identify physiological contexts in which ASICs and ENaC have similar or overlapping roles.


The IRI release from insulin gene-transduced hepatic cells responds to ambient glucose concentration.
Insulin gene was induced into differentiated hepatic cell line. These cells released immunoreactive insulin (IRI) of which molecular weight was greater than mature insulin. The secretion of IRI was responsive to glucose concentration and inhibited by glucose metabolism antagonist, 2-deoxy glucose (2-DOG). The mRNA of GLUT2 and glucokinase (GK) were not detected in these cells by Northern blotting. The glucose metabolism process is supposed to play an important role in the glucose responsive IRI release. It is assumed that hepatic cells have metabolic "glucose sensor", and insulin gene transduction to hepatic cells can be a physiological way of gene therapy for IDDM.


Efficient second- and higher-order harmonic generation from LiNbO3 metasurfaces.
Lithium niobate (LiNbO3) is a material that has drawn great interest in nonlinear optics because of its large nonlinear susceptibility and wide transparency window. However, for complex nonlinear processes such as high-harmonic generation (HHG), which involves frequency conversion over a wide frequency range, it can be extremely challenging for a bulk LiNbO3 crystal to fulfill the phase-matching conditions. LiNbO3 metasurfaces with resonantly enhanced nonlinear light-matter interaction at the nanoscale may circumvent such an issue. Here, we experimentally demonstrate efficient second-harmonic generation (SHG) and HHG from a LiNbO3 metasurface enhanced by guided-mode resonance. We observe a high normalized SHG efficiency of 5.1 × 10-5 cm2 GW-1. Moreover, with the alleviated above-gap absorption of the material, we demonstrate HHG up to the 7th order with the shortest generated wavelength of 226 nm. This work may provide a pathway towards compact coherent white-light sources with frequency spanning into the deep ultraviolet region for applications in spectroscopy and imaging.


Absolute configuration determination of chiral molecules in the solution state using vibrational circular dichroism.
Advances in the measurement, calculation, and application of vibrational circular dichroism (VCD) for the determination of absolute configuration are described. The purpose of the review is to provide an up-to-date perspective on the capability of VCD to solve problems of absolute stereochemistry for chiral molecules primarily in the solution state. The scope of the article covers the experimental methods needed for the accurate measurement of VCD spectra and the theoretical steps required to systematically deduce absolute configuration. Determination of absolute configuration of a molecule by VCD requires knowledge of its conformation or conformational distribution, and hence VCD analysis necessarily provides solution-state conformation information, in many cases available by no other method, as an additional benefit. Comparisons of the advantages and limitations of VCD relative to other available chiroptical methods of analysis are also presented.


[The specific features of bacterial isolation and drug resistance of Mycobacteria in extrapulmonary tuberculosis].
The reduced viability and enzymatic activity of the pathogen from the foci of extrapulmonary tuberculosis are twice more frequently than those in pulmonary tuberculosis. The isolation of mycobacterial L-forms and the use of polymerase chain reaction significantly enhance the efficiency of the etiological diagnosis of extrapulmonary tuberculosis. There are extremely poor trends for drug resistance to develop in mycobacteria, in 2005 the rate of which was 92.5% in pulmonary tuberculosis and 83.4% in extrapulmonary tuberculosis. However, multidrug resistance is much less common in extrapulmonary tuberculosis than in pulmonary tuberculosis; the rates were 33.9 and 73.9%, respectively. Levofloxacin resistance was also completely preserved so the reserves for the treatment of extrapulmonary tuberculosis are higher than those in pulmonary tuberculosis.


Tumor necrosis factor-alpha augments pulmonary arterial transendothelial albumin flux in vitro.
Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator of pulmonary vascular endothelial injury. We studied the effect of human recombinant TNF alpha (rTNF alpha) on transfer of 14C-labeled bovine serum albumin (BSA) across cultured bovine pulmonary arterial endothelial cell monolayers. rTNF alpha induced a dose-, time-, and temperature-dependent increment in transendothelial [14C]BSA flux. Only after an incubation time of greater than or equal to 4 h did rTNF alpha significantly (P less than 0.005) increase transendothelial albumin flux. rTNF alpha exposure times as brief as 5 min induced significantly (P less than 0.005) increased albumin transfer at 6 h. Although this initial rTNF alpha-endothelial interaction was not temperature dependent, the subsequent barrier dysfunction could only be generated at 37 degrees C. The rTNF alpha-induced changes could not be ascribed to endothelial cell cytotoxicity and was not blocked by protein synthesis inhibition. The effects of rTNF alpha on endothelial permeability were reversible and not specific for albumin transfer. Therefore, rTNF alpha may influence the movement of macromolecules across the pulmonary vascular endothelial barrier.


Long-term functional outcomes and quality of life in patients with Hirschsprung's disease.
It is unclear whether functional outcomes improve or deteriorate with age following surgery for Hirschsprung's disease. The aim of this cross-sectional study was to determine the long-term functional outcomes and quality of life (QoL) in patients with Hirschsprung's disease. Patients with pathologically proven Hirschsprung's disease older than 7 years were included. Patients with a permanent stoma or intellectual disability were excluded. Functional outcomes were assessed according to the Rome IV criteria using the Defaecation and Faecal Continence questionnaire. QoL was assessed by means of the Child Health Questionnaire Child Form 87 or World Health Organization Quality of Life questionnaire 100. Reference data from healthy controls were available for comparison. Of 619 patients invited, 346 (55·9 per cent) responded, with a median age of 18 (range 8-45) years. The prevalence of constipation was comparable in paediatric and adult patients (both 22·0 per cent), and in patients and controls. Compared with controls, adults with Hirschsprung's disease significantly more often experienced straining (50·3 versus 36·1 per cent; P = 0·011) and incomplete evacuation (47·4 versus 27·2 per cent; P < 0·001). The prevalence of faecal incontinence, most commonly soiling, was lower in adults than children with Hirschsprung's disease (16·8 versus 37·6 per cent; P < 0·001), but remained higher than in controls (16·8 versus 6·1 per cent; P = 0·003). Patients with poor functional outcomes scored significantly lower in several QoL domains. This study has shown that functional outcomes are better in adults than children, but symptoms of constipation and soiling persist in a substantial group of adults with Hirschsprung's disease. The persistence of defaecation problems is an indication that continuous care is necessary in this specific group of patients.


Studies on lymphokines: the production of antibody to guinea pig lymphotoxin and its use to distinguish lymphotoxin from migration inhibitory factor and mitogenic factor.
Guinea pig lymphotoxin, which was produced by stimulating immune lymph node cells with the specific antigen, ovalbumin, was partially purified by the sequential use of Pevikon block electrophoresis, ion exchange chromatography on DEAE-cellulose, and polyacrylamide disc gel electrophoresis. The lymphotoxin recovered from the final step was purified approximately 200- to 300-fold as compared to the starting material, but nevertheless contained at least one major contaminant protein. Rabbits were immunized with the partially purified lymphotoxin, and an antiserum capable of neutralizing the cytotoxic effect of lymphotoxin was obtained. The anti-lymphotoxin activity was shown to be due predominantly to IgM immunoglobulin. The antiserum neutralized concanavalin A-induced lymphotoxin with equal efficiency as antigen-induced lymphotoxin. On the other hand, the anti-lymphotoxin serum did not neutralize preformed mitogenic factor or migration inhibitory factor (MIF) which had been produced by antigen-stimulated immune lymph node cells. Thus these activities appear to be due to substances which are antigenically distinct from lymphotoxin. Likewise, anti-lymphotoxin serum, when present in cultures of antigen-stimulated immune lymphoid cells, caused no diminution in the amount of mitogenic factor or MIF which was produced, indicating that it had no direct deleterious effect on the function of the lymphoid cells responsible for producing these lymphokines.


Effects of deposit-feeding macrofauna on benthic bacteria, viruses, and protozoa in a silty freshwater sediment.
In microcosm experiments, we simultaneously tested the effects of increased numbers of deposit-feeding macrofauna (chironomids, oligochaetes and cladocerans) on the standing stock, activities and interactions of heterotrophic bacteria, viruses, and bacterivorous protozoa (heterotrophic nanoflagellates and ciliates) in the aerobic layer of a silty littoral freshwater sediment. On average, bacterial secondary production was stimulated between 11 and 29% by all macrofaunal groups compared to control experiments without macrofauna addition. Bacterial standing stock increased significantly by 8 and 13% in case of chironomids and cladocerans, respectively. Oligochaetes and chironomids produced significant negative effects on viral abundance while the results with cladocerans were inconsistent. The addition of oligochaetes and chironomids resulted in a significant decrease by on average 68 and 32% of viral decay rates, respectively, used as a measure of viral production. The calculated contribution of virus-induced lysis to benthic bacterial mortality was low, with 2.8 to 11.8% of bacterial secondary production, and decreased by 39 to 81% after the addition of macrofauna compared to the control. The abundances of heterotrophic nanoflagellates were significantly reduced by 20% by all tested macrofauna groups, while ciliates showed inconsistent results. The importance of heterotrophic nanoflagellate grazing on benthic bacteria was very low (<1% of bacterial secondary production) and was further reduced by elevated numbers of macrofauna. Thus, the selected deposit feeding macrofauna groups seem to have several direct and indirect and partly antagonistic effects on the benthic bacterial compartment through the enhancement of bacterial production and the reduction of virus-induced cell lysis and protozoan grazing.


Infection with human immunodeficiency virus (HIV) and cytomegalovirus in a London health district 1980-4.
By testing serum samples taken between 1980 and 1984 from men attending a department of sexually transmitted diseases, it was shown that antibodies to human immunodeficiency virus (HIV) first appeared in 1981. Homosexual men were significantly more likely to have antibodies to HIV and to cytomegalovirus (CMV) than were heterosexual men attending the same clinic. This shows that homosexuals are exposed to both HIV, the cause of the acquired immune deficiency syndrome (AIDS), and to CMV, which can reactivate to cause life threatening disease once immunosuppression has developed. All homosexuals, not just those with antibodies against HIV, had raised levels of CMV antibodies. This suggests that they experience frequent antigenic stimulation after reinfections with CMV or reactivation of endogenous virus.


Pulmonary function in adult survivors of severe acute lung injury treated with inhaled nitric oxide.
Following an episode of acute respiratory distress syndrome (ARDS), some degree of measurable pulmonary impairment may be anticipated. ARDS is thought to be the more severe form of acute lung injury (ALI) and a recently proposed addition to conventional therapy in ALI/ARDS is inhaled nitric oxide (INO). We carried out a non-randomised follow-up study with pulmonary function tests on survivors of severe ALI/ARDS treated with INO. Sixteen previously healthy pulmonary patients, survivors of severe ALI/ARDS, were evaluated with pulmonary function tests >8 months after the acute event. The tests included static and dynamic spirometry, diffusion capacity for carbon monoxide (DLCO), blood gas analysis and evaluation of a chest radiograph. The most common abnormality seen was a low DLCO in 69% of the patients. Abnormally low values were seen in forced vital capacity in 31%, in forced expiratory volume in 1 s in 13%, and in residual volume and total lung capacity in 6%. Blood gas data were within normal limits in 15/16 patients. All chest radiographs showed resolution of the interstitial and alveolar changes present during the acute event. In this non-randomised follow-up study we conclude that a degree of measurable pulmonary impairment after INO treatment in severe ALI/ARDS was common, but did not differ markedly from other published studies on pulmonary function in similar patient material. No late unexpected major abnormalities due to the inhaled nitric oxide treatment could be identified in these survivors.