The Lung Image Database Consortium (LIDC): an evaluation of radiologist variability in the identification of lung nodules on CT scans.
The purpose of this study was to analyze the variability of experienced thoracic radiologists in the identification of lung nodules on computed tomography (CT) scans and thereby to investigate variability in the establishment of the "truth" against which nodule-based studies are measured. Thirty CT scans were reviewed twice by four thoracic radiologists through a two-phase image annotation process. During the initial "blinded read" phase, radiologists independently marked lesions they identified as "nodule >or=3 mm (diameter)," "nodule <3 mm," or "non-nodule >or=3 mm." During the subsequent "unblinded read" phase, the blinded read results of all four radiologists were revealed to each radiologist, who then independently reviewed their marks along with the anonymous marks of their colleagues; a radiologist's own marks then could be deleted, added, or left unchanged. This approach was developed to identify, as completely as possible, all nodules in a scan without requiring forced consensus. After the initial blinded read phase, 71 lesions received "nodule >or=3 mm" marks from at least one radiologist; however, all four radiologists assigned such marks to only 24 (33.8%) of these lesions. After the unblinded reads, a total of 59 lesions were marked as "nodule >or=3 mm" by at least one radiologist. Twenty-seven (45.8%) of these lesions received such marks from all four radiologists, three (5.1%) were identified as such by three radiologists, 12 (20.3%) were identified by two radiologists, and 17 (28.8%) were identified by only a single radiologist. The two-phase image annotation process yields improved agreement among radiologists in the interpretation of nodules >or=3 mm. Nevertheless, substantial variability remains across radiologists in the task of lung nodule identification.


10-year trends in English primary care glaucoma prescribing.
In 2018 NHS prescriptions in England cost £8.83 billion. Within ophthalmic prescribing, glaucoma is the most costly indication. The 2017 glaucoma NICE guideline shows there is little evidence for clinical preference of particular molecules within a therapeutic class, yet the cost of these products varies greatly. We aim to describe trends in glaucoma prescribing and its relation to recent NICE Guidance. Prescription cost analyses for England from 2009 to 2018 were reviewed and data concerning items for the treatment of glaucoma were extracted. Costs and prescription frequencies were normalised for inflation and population. The 2018 cost of glaucoma prescribing was £114.2 million. This cost is 18.1% lower than in 2009 but the annual number of items prescribed per 10,000 people has increased from 1382 to 1668 (20.7%). This is despite an increased prescription of combination drops from 265 to 478 per 10,000 (80.4%). Preservative free item prescriptions rose from 1.7% of total spend in 2009, at £3.4 million in 2009, to 13.9%, in 2018, at £22.5 million. Generic items represented 11.7% of prescriptions in 2009 and 55.2% in 2018. Around half of glaucoma spending is accounted for by the use of preservative free or branded items in the place of the cheapest item in each therapeutic class. Glaucoma prescribing costs the NHS a great deal. There is a broad trend to generic prescribing as per recent NICE guidance, but significant further costs could be saved with no robustly evidenced clinical consequence.


Occupational asthma from reactivity to an alkaline hydrolysis derivative of gluten.
A 29-year-old female subject had been working for 13 years in a company producing biscuits. She was exposed intermittently to an alkaline hydrolysis wheat gluten derivative (AHGD) that was incorporated into marshmallows. Five years before being referred, she started reporting rhinoconjunctivitis and asthmatic symptoms immediately after handling AHGD. When she was first assessed, she had avoided contact with AHGD for 1 year, and she was asymptomatic. Normal spirometry and bronchial responsiveness to histamine (provocative concentration causing a 20% fall in FEV1, 22 mg/ml) were obtained. There was a positive allergy skin test to ragweed pollen and to AHGD at 0.01 mg/ml. Skin tests with individual extracts of cereals, including wheat, were negative. Inhalation challenge with AHGD for 15 seconds caused immediate rhinoconjunctivitis and bronchoconstriction (maximum fall of 40% in FEV1 30 minutes after the exposure) with complete recovery 2 hours later. There was no reaction thereafter, and the provocative concentration of histamine causing a 20% fall in FEV1 was not significantly changed (13.1 mg/ml) 9 hours after the challenge. Inhalation challenge with wheat flour containing native gluten for 30 minutes did not cause any symptoms or significant change in FEV1. IgE RAST counts were greater with the AHGD than with gluten and the whole wheat extract; the opposite was generally found with sera from individuals with baker's asthma and wheat food allergy. With the serum of the affected worker, AHGD completely inhibited the corresponding RAST, but gluten did not. With wheat food allergy, AHGD was relatively inactive inhibition of the wheat and gluten RAST, but gluten was effective.(ABSTRACT TRUNCATED AT 250 WORDS)


Stressful events, pessimism, natural killer cell cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black women at risk for cervical cancer.
This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer. Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women. Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events. A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV.


RPA nucleic acid-binding properties of IFI16-HIN200.
InterFeron-gamma Inducible protein 16 (IFI16) belongs to the interferon inducible HIN200 protein family that contains transcriptional regulators linked to cell cycle regulation and differentiation. All family members contain at most two domains of 200 amino acids, called HIN200, each containing two Oligonucleotide/Oligosaccharide Binding (OB) folds. IFI16 is involved in transcriptional repression and is a component of the DNA repair multi-protein complex known as BASC, which forms after UV-induced DNA damage. In this study, we used fold recognition and biophysical approaches as a tool to infer and validate functions to the HIN200 domain. Since the best template to model IFI16-HIN200 is Replication Protein A (RPA) in complex with single-stranded nucleic acids, we tested six RPA nucleic acid-binding characteristics for IFI16-HIN200. Our results indicate that IFI16-HIN200 is an RPA-like, OB-fold, nucleic acid-binding protein that binds to ssDNA with higher affinity than to dsDNA, recognizes ssDNA in the same orientation as RPA, oligomerizes upon ssDNA binding, wraps and stretches ssDNA, but does not destabilize dsDNA. We finally propose a framework model explaining how the HIN200 domain could prevent ssDNA from re-annealing.


Effects of Bisphenol A on ion channels: Experimental evidence and molecular mechanisms.
Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) produced in huge quantities in the manufacture of polycarbonate plastics and epoxy resins. It is present in most humans in developed countries, acting as a xenoestrogen and it is considered an environmental risk factor associated to several diseases. Among the whole array of identified mechanisms by which BPA can interfere with physiological processes in living organisms, changes on ion channel activity is one of the most poorly understood. There is still little evidence about BPA regulation of ion channel expression and function. However, this information is key to understand how BPA disrupts excitable and non-excitable cells, including neurons, endocrine cells and muscle cells. This report is the result of a comprehensive literature review on the effects of BPA on ion channels. We conclude that there is evidence to say that these important molecules may be key end-points for EDCs acting as xenoestrogens. However, more research on channel-mediated BPA effects is needed. Particularly, mechanistic studies to unravel the pathophysiological actions of BPA on ion channels at environmentally relevant doses.


[Coma with bilateral mydriasis after use of transdermal scopolamine in ICU].
We report the case of an ICU patient with previous medical history of head trauma with hydrocephalus requiring ventricular derivation, presenting a coma (Glasgow Coma Score=8) with bilateral mydriasis after the use of transdermal scopolamine (1 mg) for profuse bronchial secretions. Neurological explorations (CT-scan and electroencephalogram) confirmed the absence of organic cause to the neurological deterioration. Neurological status rapidly and completely improved after removal of transdermal scopolamine suggesting a central anticholinergic syndrome.


Effects of nitrogen and potassium combinations on yields and infestations of maize by Busseola fusca (Lepidoptera: Noctuidae) in the humid forest of Cameroon.
Field trials were set up in the humid forest zone of Cameroon to investigate the effects of combinations of different rates of nitrogen (N) (0, 60, and 120 kg N ha(-1)) and potassium (K) (0, 80, and 160 kg K ha(-1)) applied to the soil on the incidence and damage of the noctuid stemborer Busseola fusca (Fuller), and on maize, Zea mays L., yield. Each N/K combination had an insecticide control to assess yield losses due to borers. In contrast to N, K had no effect on plant growth and borer incidence and damage. Across seasons and days after planting, total plant dry matter (DM) production increased with N level and it was 1.2-1.9 and 1.7-2.2 times, respectively, higher at 60 and 120 kg N ha(-1) compared with 0 kg N ha(-1). Total DM at harvest was strongly related to the N content of the plant at 63 d after planting. At the early growth stage, borer abundance and stem tunneling tended to increase with N level, but percentages of dead hearts did not vary with treatment. Maize grain yields increased linearly with N level, but grain yield losses decreased depending on season. Grain yield losses were 11-18.2 times higher with 0 kg N ha(-1) compared with 120 kg N ha(-1). The findings so far indicated that, soil application of N improves the nutritional status of maize, which consequently enhanced its tolerance to stemborer attacks. Improving soil fertility can thus be a very effective means of complementing integrated stemborer control in the humid forest zone of Cameroon.


Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels.
Interleukin-18 (IL-18) is a pleiotropic cytokine centrally involved in the cytokine cascade with complex immunomodulatory functions in innate and acquired immunity. Circulating IL-18 concentrations are associated with type 2 diabetes mellitus, cardiovascular events, and diverse inflammatory and autoimmune disorders. To identify causal variants affecting circulating IL-18 concentrations, we applied various omics and molecular biology approaches. By genome-wide association study, we confirmed association of IL-18 levels with a single nucleotide polymorphism in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, caspase recruitment domain-containing 4) gene on chromosome 2 (rs385076; P=2.4 × 10(-45)). Subsequent molecular analyses by gene expression analysis and reporter gene assays indicated an effect of rs385076 on NLRC4 expression and differential isoform usage by modulating binding of the transcription factor PU.1. Our study provides evidence for the functional causality of single nucleotide polymorphism rs385076 within the NLRC4 gene in relation to IL-18 activation.


The inhibition of the mitochondrial F1FO-ATPase activity when activated by Ca2+ opens new regulatory roles for NAD.
The mitochondrial F1FO-ATPase is uncompetitively inhibited by NAD+ only when the natural cofactor Mg2+ is replaced by Ca2+, a mode putatively involved in cell death. The Ca2+-dependent F1FO-ATPase is also inhibited when NAD+ concentration in mitochondria is raised by acetoacetate. The enzyme inhibition by NAD+ cannot be ascribed to any de-ac(et)ylation or ADP-ribosylation by sirtuines, as it is not reversed by nicotinamide. Moreover, the addition of acetyl-CoA or palmitate, which would favor the enzyme ac(et)ylation, does not affect the F1FO-ATPase activity. Consistently, NAD+ may play a new role, not associated with redox and non-redox enzymatic reactions, in the Ca2+-dependent regulation of the F1FO-ATPase activity.


Primary anastomosis after intraoperative colonic lavage vs. Hartmann's procedure in generalized peritonitis complicating diverticular disease of the colon.
For complicated diverticulitis Hartmann's procedure remains the favored option in patients with acute complicated sigmoid disease, but there has been increasing interest in primary resection and anastomosis with intraoperative colonic lavage. This study compared primary resection with intraoperative colonic lavage and Hartmann's procedure. Between January 1994 and November 2001, 60 patients underwent emergency laparotomy for diverticular peritonitis (Hinchey stages III and IV). Primary resection and anastomosis with intraoperative colonic lavage was performed in 27 patients and Hartmann's procedure in 33. All data were collected prospectively on a standardized form. Mortality with intraoperative colonic lavage was 11% and with Hartmann's procedure 12%. The incidence of postoperative complication was significantly higher after Hartmann's procedure. The mean hospital stay was significantly longer after Hartmann's procedure than after primary resection with intraoperative colic lavage. Primary resection with intraoperative colonic lavage compares favorably with Hartmann's procedure for diffuse purulent peritonitis in complicated diverticulitis. It should be an alternative to Hartmann's procedure in stercoral peritonitis.


[The research of the heroin and its metabolites analysis in clinical samples].
Heroin can be metabolized easily in body and the mail metabolites are 6-MAM, morphine and so on. At present, there are urine, blood, hair and so on as specimens for detection, while the analytical technology conclude TLC, GC, HPLC, GC/MS, LC/MS, IA, CE etc. In this paper, these technologies used for heroin's metabolites were viewed in order to provide some reference to the study in relative field.


In situ casting of rice husk ash in metal organic frameworks induces enhanced CO2 capture performance.
Incorporation of rice-husk-ash (RHA), an agricultural waste, in situ during the synthesis of MIL-101(Cr) resulted in a significant improvement in the CO2 adsorption properties over the synthesized RHA-MIL-101(Cr). The newly synthesized RHA-MIL-101(Cr) composite exhibited an enhancement of 14-27% in CO2 adsorption capacity as compared to MIL-101(Cr) at 25 °C and 1 bar. The content of RHA incorporated in RHA-MIL-101(Cr) fine tuned the CO2 capture performance to achieve high working capacity (0.54 mmol g-1), high purity (78%), superior CO2/N2 selectivity (18) and low isosteric heat of adsorption (20-30 kJ mol-1). The observed superior CO2 adsorption performance of RHA-MIL-101(Cr) is attributed to the fine tuning of textural characteristics-enhancement of 12-27% in BET surface area, 12-33% in total pore volume and 18-30% in micropore volume-upon incorporation of RHA in MIL-101(Cr).


Role of Saharan dust in the relationship between particulate matter and short-term daily mortality among the elderly in Madrid (Spain).
Saharan dust outbreaks are a common phenomenon in the Madrid atmosphere. The current Directive 2008/50 CE governing air quality in European cities, draws no distinction between which particulate matter (PM(10), PM(2.5) or PM(10-2.5)) would be the best indicator on days with/without Saharan dust intrusions. This study sought to identify the role played by Saharan dust in the relationship between particulate matter (PM(10), PM(2.5) and PM(10-2.5)) concentrations and daily mortality among the elderly in the city of Madrid. We conducted an ecological longitudinal time-series study on daily mortality among the over-75 age group, from 2003 to 2005. Poisson regression models were constructed for days with and without Saharan dust intrusions. The following causes of daily mortality were analysed: total organic causes except accidents (International Classification of Diseases-10th revision (ICD-10): A00-R99); circulatory causes (ICD-10: I00-I99); and respiratory causes (ICD-10: J00-J99). Daily mean PM(10), PM(2.5) and PM(10-2.5) levels were used as independent variables. Control variables were: other ambient pollutants (chemical, biotic and acoustic); trend; seasonalities; influenza epidemics; and autocorrelations between mortality series. While daily mean PM(2.5) concentrations in Madrid displayed a significant statistical association with daily mortality for all the above causes on days without Saharan dust intrusions, this association was not in evidence for PM(10) or PM(10-2.5) in the multivariate models. The relative risks (RRs) obtained for an increase of 10 μg/m(3) in PM(2.5) concentrations were: 1.023 (1.010-1.036) for total organic causes; 1.033 (1.031-1.035) for circulatory causes; and 1.032 (1.004-1.059) for respiratory causes. On Saharan dust days, a significant statistical association was detected between PM(10) (though not PM(2.5) or PM(10-2.5)) and mortality for all 3 causes analysed, with RRs statistically similar to those reported for PM(2.5). The best air quality indicators for evaluating the short-term health effects of particulate matter in Madrid are therefore PM(10) concentrations on days with, and PM(2.5) concentrations on days without Saharan dust outbreaks. This fact should be taken into account in a European Directive regulating ambient air quality in almost all countries in the Mediterranean area.


Sample Collection, DNA Extraction, and Library Construction Protocols of the Human Microbiome Studies in the International Human Phenome Project.
The human microbiome plays a crucial role in human health. In the past decade, advances in high-throughput sequencing technologies and analytical software have significantly improved our knowledge of the human microbiome. However, most studies concerning the human microbiome did not provide repeatable protocols to guide the sample collection, handling, and processing procedures, which impedes obtaining valid and timely microbial taxonomic and functional results. This protocol provides detailed operation methods of human microbial sample collection, DNA extraction, and library construction for both the amplicon sequencing-based measurements of the microbial samples from the human nasal cavity, oral cavity, and skin, as well as the shotgun metagenomic sequencing-based measurements of the human stool samples among adult participants. This study intends to develop practical procedure standards to improve the reproducibility of microbiota profiling of human samples. The online version contains supplementary material available at 10.1007/s43657-023-00097-y.


Experiences of Food Pantry Stakeholders and Emergency Food Providers in Rural Minnesota Communities.
This study aimed to describe the experiences influencing food pantry stakeholders' and emergency food providers' ability to meet their shoppers' needs. We conducted 5 focus groups. Food pantries in Minnesota in late 2019 and early 2020. The sample included 37 participants with various roles in the emergency food system. Barriers and challenges facing emergency food providers/stakeholders and practices and resources providers employ. We identified major themes using a thematic analysis approach. Participants reported multiple barriers to accessing food pantries, that shopper demographics were changing, and shoppers needed nonfood support, such as personal hygiene items and mental health services. Food pantries required appropriate and sustainable food supplies, additional financial, labor, technical support, and physical infrastructure improvements. Participants described the benefits of their relationship with the University of Minnesota Cooperative Extension, explained how pantries offered healthier foods, highlighted innovative service delivery models, and stressed that their organization connected to many facets of their community. Food pantries serving rural areas reported meeting community needs by distributing food to their shoppers in an inclusive and health-promoting way but require additional support. These data support nutrition practitioners working to understand the local, place-based context and needs of emergency food providers while building wider and deeper connections between nutrition professionals and the emergency food system.


Field evaluation and calibration of a small axial passive air sampler for gaseous and particle bound polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs.
Polycyclic aromatic hydrocarbons (PAHs) and their oxygenated analogues (OPAHs) are ubiquitous air pollutants known to cause adverse health effects. PAH air levels are commonly monitored by active sampling but passive sampling has become popular because of its lower cost and simplicity, which facilitate long-term sampling and increased spatial coverage. However, passive samplers are less suitable for short-term sampling and are in general less accurate than active samplers because they require reliable sampling rate (Rs) measurements for individual analytes under diverse environmental conditions. In this study a small passive sampler designed to sample both particle-bound and gaseous compounds was evaluated and calibrated for PAHs and OPAHs in a traffic environment by co-deployment with active samplers for two weeks. Despite the relatively low average air concentrations of PM10 (20 μg/m(3)), PM2.5 (5 μg/m(3)), total PAHs (4.2 ng/m(3)), and OPAHs (2.3 ng/m(3)) at the site, detectable quantities (on average 24 times above blank values) of the full range of PAHs and OPAHs were captured, with low variability (average RSD of 16%). This was accomplished by using a Tenax(®) TA-modified glass fiber substrate that is compatible with highly sensitive thermal desorption GC-MS analysis, which made it possible to achieve detection limits per sample in the pg range. Experiments with inverted samplers revealed that the relative contribution of gravitational settling to the sampling of particles carrying PAHs and OPAHs was around 3.5 times larger than other deposition mechanisms. Average Rs values for individual OPAHs and PAHs were 0.046 ± 0.03 m(3)/day and 0.12 ± 0.07 m(3)/day, respectively, with no appreciable difference between the values for particle-associated and gaseous compounds. Furthermore, the Rs values were competitive with other currently used passive samplers if normalized for substrate area. Overall, the new sampler's performance, simplicity and ability to generate relatively time-resolved data make it a promising candidate for diverse SVOC monitoring studies.


A dual-snake model of high penetrability for ultrasound image boundary extraction.
Most deformable models require the initial contour to be placed close to the boundary of the object of interest for boundary extraction of ultrasound (US) images, which is impractical in many clinical applications. To allow a distant initial contour, a new dual-snake model promising high penetrability through the interference of the noises is proposed in this paper. The proposed dual-snake model features a new far-reaching external force, called the discrete gradient flow, a connected component-weighted image force, and an effective stability evaluation of two underlying snakes. The experimental results show that, with a distant initial contour, the mean distance from the derived boundary to the desired boundary is less than 1.4 pixels, and most snake elements are within 2.7 pixels of the desired boundaries for the synthetic images with CNR > or =1. For the clinical US images, the mean distance is less than 1.9 pixels, and most snake elements are within 3 pixels of the desired boundaries.


Characterization of suramin binding sites on the human group IIA secreted phospholipase A2 by site-directed mutagenesis and molecular dynamics simulation.
Suramin is a polysulphonated naphthylurea with inhibitory activity against the human secreted group IIA phospholipase A(2) (hsPLA2GIIA), and we have investigated suramin binding to recombinant hsPLA2GIIA using site-directed mutagenesis and molecular dynamics (MD) simulations. The changes in suramin binding affinity of 13 cationic residue mutants of the hsPLA2GIIA was strongly correlated with alterations in the inhibition of membrane damaging activity of the protein. Suramin binding to hsPLA2GIIA was also studied by MD simulations, which demonstrated that altered intermolecular potential energy of the suramin/mutant complexes was a reliable indicator of affinity change. Although residues in the C-terminal region play a major role in the stabilization of the hsPLA2GIIA/suramin complex, attractive and repulsive hydrophobic and electrostatic interactions with residues throughout the protein together with the adoption of a bent suramin conformation, all contribute to the stability of the complex. Analysis of the hsPLA2GIIA/suramin interactions allows the prediction of the properties of suramin analogues with improved binding and higher affinities which may be candidates for novel phospholipase A(2) inhibitors.


Flow cytometric analysis of lymphocyte subpopulations in the spleen and thymus of mice exposed to an acute immunosuppressive dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
The objective of the present studies was to determine if acute exposure to an immunotoxic dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces alterations in the expression of lymphocyte surface markers as measured by multiparameter flow cytometry. The immunotoxicity of a single oral dose of TCDD was assessed by the anti-SRBC PFC response; an ED50 of 0.74 micrograms/kg was determined. Subpopulations in the spleen and thymus of C57B1/6 mice were analyzed 2 days following exposure to 2 micrograms/kg TCDD. In addition, splenic lymphocyte subsets were examined on Days 1-4 following SRBC challenge of mice treated with 0, 2, or 5 micrograms/kg TCDD. T and B cells were identified by single parameter analysis of Thy 1.2 and Ig expression. T cell subsets were defined by dual parameter analysis of CD4 and CD8 expression. In TCDD-treated mice, the percentage and the total number of double-positive CD4+ CD8+ thymocytes were significantly decreased while the percentage but not the total number of double-negative CD4- CD8- thymocytes was significantly increased. No changes in the percentage or total number of single positive (CD4+ CD8- or CD4- CD8+) thymocyte subsets were observed. In contrast to the thymus, lymphocyte subsets in the spleen were not significantly altered in percentage or total number 2 days following acute TCDD exposure. When splenic lymphocytes were analyzed daily following SRBC challenge, Ig+, Thy 1.2+, and CD4+ CD8- subpopulations remained relatively unchanged in both control and TCDD-treated animals. A small but significant decrease in the percentage of CD4- CD8+ T cells was observed on Day 3 in mice treated with 2 or 5 micrograms/kg TCDD when compared to that of vehicle-treated mice. The total number of CD4- CD8+ splenocytes was also significantly lower in the 5-micrograms/kg group on Day 3. However, this effect appeared to result from an elevation of the CD4- CD8+ subset in the controls rather than from a reduction in the TCDD-treated groups. Double-positive (CD4+ CD8+) lymphocytes were not detected in either control or TCDD-treated spleens. These results indicate that an acute dose of TCDD which reduced the splenic anti-SRBC response by 65-80% did not cause detectable changes in major splenic lymphocyte subpopulations. This is an important finding from the standpoint of utilizing lymphocyte subset analysis to screen for potential immunotoxic effects of TCDD. Specifically, the absence of subset changes does not preclude the presence of functional immunosuppression.


Surgical Fenestration for Lower Limb Ischemia Developing from Chronic Type B Aortic Dissection: A Report of 2 Cases.
Lower limb ischemia caused by type B aortic dissection typically presents with a leg-threatening condition in the acute phase. However, in some cases, lower limb ischemia symptom develops as intermittent claudication in the chronic phase. Although surgical fenestration has been used for treating ischemic complications of aortic dissection, it has recently become an alternative option for such cases because of the significant advance of endovascular treatments. We report 2 cases of chronic type B aortic dissection complicated by lower limb ischemia. Two male patients aged 57 and 43 years presented with intermittent claudication more than 2 weeks after the onset of the disease. On the basis of anatomic condition of the dissected aorta, we successfully performed surgical fenestration through a median laparotomy. In the current endovascular era, surgical fenestration remains an effective and durable option for treating lower limb ischemia caused by chronic type B aortic dissection.


Three weekly injections (TWI) of low-dose growth hormone (GH) restore low normal circulating IGF-I concentrations and reverse cardiac abnormalities associated with adult onset GH deficiency (GHD).
GH replacement therapy given 3 times weekly (TWI) and adjusted to allow serum IGF-I concentrations in the mid-normal range for sex and age has been shown to be as effective as the daily regimen in improving lipid profile, body composition, bone mass and turnover in adult GH deficient (GHD) patients. Only one study has investigated so far the short-term (6 months) effect of a fixed weight-based TWI dosing schedule on heart structure and function in childhood onset (CO) GHD patients, whereas such a schedule in adult onset (AO) GHD patients has not been studied as yet. Aim of this study was to investigate whether a 1-yr low-dose titrated TWI GH-replacement regimen aimed at achieving and maintaining IGF-I levels within the low normal limits for age and sex is able to affect cardiovascular and heart parameters in a group of AO GHD patients. Eight adult patients (4 women and 4 men, age 35.8 +/- 3.37 yr, body mass index, BMI, 28.7 +/- 2.62 kg/m2) with AO GHD were included in the study, along with 10 healthy subjects, matched for age, sex, BMI and physical activity (6 women and 4 men, age 35.2 +/- 4.05 yr, BMI 28.4 +/- 2.34 kg/m2). M- and B- mode ecocardiography and pulsed doppler examination of transmitral flow were performed in GHD patients at baseline and after 3 and 12 months of GH therapy (mean GH dose 6.7 +/- 0.8 microg/kg/day given thrice a week), while normal subjects were studied once. Treatment with GH for 1 yr induced a significant increase in left ventricular (LV) diastolic and systolic volumes (+11.1 and +16.5%, respectively). Systolic LV posterior wall thickness and LV mass were increased (+10.2 and +7.7%, respectively) by GH administration. Systemic vascular resistance was significantly decreased by 1-yr GH therapy (-13.8% after 1 yr), while stroke volume, cardiac output and cardiac index were increased (+9.4, +11.6 and + 11.9%, respectively). LV end-systolic stress was decreased at the end of GH therapy (-11.2%). E and A wave, significantly reduced at baseline, were increased by 1 yr of GH therapy (+23.3% and +28.1%, respectively); likewise, the abnormally high E peak deceleration time was partially reversed by GH administration (-10.7%). Our study, though conducted in a small sample size, demonstrates that a TWI GH treatment schedule is able to reverse the cardiovascular abnormalities in AO GHD patients and to improve body composition and lipid profile. The maintenance of circulating IGF-I concentrations within the low normal range allows to avoid most of the side-effects reported with higher GH doses while being cost-effective and improving the patient's compliance.


Growth-related lipid peroxidation in tumour microsomal membranes and mitochondria.
Microsomes and mitochondria isolated from Morris hepatomas 3924A (fast-growing) and 44 (slow-growing) and Ehrlich ascites tumour cells exhibit a NADPH-dependent peroxidation of endogenous lipids lower than that of the corresponding fractions from rat liver. Moreover, the O2- and ascorbate-dependent lipid peroxidations are decreased in microsomes from the two Morris hepatomas. The peroxidative activity appears to be inversely related to the growth rate of the tumours. It is suggested that the low susceptibility of tumour membranes to peroxidative agents may be a factor responsible for the high mitotic activity of this tissue.


Sex-related differences in upper limb motor function in healthy subjects and multiple sclerosis patients: a multiparametric MRI study.
We investigated sex-related differences in upper limb motor performance tested with the 9-Hole Peg Test (9HPT) in healthy controls (HC) and multiple sclerosis (MS) patients and their MRI substrates. We enrolled 94 HC and 133 MS patients, who underwent neurological examination, 9HPT and brain 3T MRI, with sequences for regional grey matter volume (GMV), white matter (WM) fractional anisotropy (FA) and resting state (RS) functional connectivity (FC) analysis. Associations between MRI variables and 9HPT performance were analyzed with general linear models. 9HPT performance was better in HC vs MS patients, and in female vs male HC. Regional GMV analysis showed: associations between better 9HPT performance and higher GMV in motor and cognitive cortical areas in HC, with stronger positive correlations in females vs males. In MS, worse 9HPT performance correlated with lower volume in motor and cognitive areas. Sex-related differences were minimal and mostly found in cerebellar areas. WM FA analysis disclosed neither associations with 9HPT performance in HC, nor sex-related differences in MS. RS FC analysis showed: in the sensorimotor network, stronger associations of RS FC with 9HPT performance in female vs male HC and no sex-related differences in MS; in the cerebellar network, no sex-related differences in HC but stronger negative correlation in left cerebellum in male vs female MS patients. Sex influences 9HPT performance in HC, mainly through differences in volume and RS FC of motor and cognitive areas. Sex-related effects on motor performance become secondary but still present in MS.


Evidence that angiotensin-converting enzyme inhibitor use diminishes the need for coronary revascularization after stenting.
Restenosis after stenting, in contrast to balloon angioplasty, is predominantly due to neointima formation. Angiotensin-converting enzyme (ACE) inhibitors diminish neointima formation in animal models of arterial injury. In an observational study, 1,598 patients who were treated from 1994 to 1997 with coronary stents and prospectively followed for clinical events were divided into 2 groups: those receiving ACE inhibitors at the time of stenting (n = 345) and those who did not (n = 1,253). Multivariate logistic regression was used to adjust for imbalances between populations with regard to elements relevant to risk of 12-month coronary revascularization, which was the primary study end point. After adjustment, ACE inhibitor usage remained significantly protective against revascularization (odds ratio [OR] 0.46, 95% confidence interval 0.29 to 0.73, p = 0.001). Protection was not observed in patients treated with balloon angioplasty alone during the same period (OR 1.06, p = 0.33), which is consistent with the results of prior randomized trials. ACE inhibitors appear to decrease late revascularization, possibly due to a reduction in restenosis after coronary stenting.


The effect of t-butylated hydroxytoluene on glutathione linked detoxification mechanisms in rat.
When rats were fed a diet containing 0.4% (w/w) butylated hydroxytoluene (BHT), a three-fold increase in total glutathione (GSH) S-transferase activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was observed in liver but not in lung or kidney. Hepatic GSH S-transferase activities towards styrene oxide (SO) and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were also increased, but to a lesser extent. Isoelectric focusing studies indicated that the activities of most of the rat liver GSH S-transferase isoenzymes were induced. Immunoprecipitation studies of the native and induced enzymes suggested that de novo synthesis of these proteins caused the increase in GSH S-transferase activity in liver. A two-fold increase in glutathione reductase activity in liver upon dietary administration of BHT was observed. Kinetic and physical properties of the native and induced enzymes were similar which may indicate that the induction is due to the synthesis of this enzyme. A significant increase in reduced glutathione (GSH) content in liver and lung was also seen in rats treated with BHT.


Pathogenesis and potential relative risk factors of diabetic neuropathic osteoarthropathy.
Diabetic neuropathic osteoarthropathy (DNOAP) is an uncommon, but with considerable morbidity and mortality rates, complication of diabetes. The real pathogenesis is still unclear. The two popular theories are the neuro-vascular theory and neuro-traumatic theory. Most theories and pathways focused on the uncontrolled inflammations that resulted in the final common pathway, receptor activator of nuclear factor κβ ligand (RANKL)/osteoprotegerin (OPG) axis, for the decreased bone density in DNOAP with an osteoclast and osteoblast imbalance. However, the RANKL/OPG pathway does not explain all the changes, other pathways and factors also play roles. A lot of DNOAP potential relative risk factors were evaluated and reported in the literature, including age, gender, weight, duration and type of diabetes, bone mineral density, peripheral neuropathy and arterial disease, trauma history, and some others. However, most of them are still in debates. Future studies focus on the pathogenesis of DNOAP are still needed, especially for the genetic factors. And, the relationship between DNOAP and those potential relative risk factors are still need to further clarify.


Bossy and nice requests: varying language register in speakers with autism spectrum disorder (ASD).
The ability to vary language style or register is important for successfully navigating social situations. For example, we speak differently to our boss than we do to our children. This project examined whether high-functioning speakers with ASD were able to vary the language used for requests along continua of "politeness/bossiness", whether any such adjustments were similar to those made by appropriately matched controls, and whether speakers with ASD were able to accurately interpret politeness/bossiness registers. High-functioning children and adolescents (aged 6-16) with ASD were compared to matched typically developing children and adolescents on ability to (1) produce both "nice" and "bossy" requests to puppet listeners and, (2) to judge which of two requests was more polite. Contrary to expectations, participants with ASD were as adept as controls in both producing and judging polite and bossy requests. These results suggest that, at least for high-functioning children and adolescents with ASD, some skill at adjusting language register exists in their repertoire. Future research should examine whether this skill is also present in younger children and in unstructured interactions. If these results hold, clinicians may be able to focus their intervention on teaching strategies for successful use of behaviours that already exist rather than training the responses themselves. The reader will become familiar with the functional importance of varying language registers or style according to situational demands. In addition, teaching a strategy for how to determine when a particular language behaviour should be used may sometimes be more effective than training the specific language response.


Stimulation of insulin secretion by acetylenic fatty acids in insulinoma MIN6 cells through FFAR1.
We examined whether the acetylenic fatty acids 6-octadecynoic acid (6-ODA) and 9-octadecynoic acid (9-ODA) perform as ligands for free fatty acid receptors of medium- and long-chain fatty acids FFAR1 and FFAR4, previously called GPR40 and GPR120, respectively. Phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 was increased through FFAR1 but not through FFAR4 expressed in HEK 293 cells, suggesting that 6-ODA and 9-ODA function as an FFAR1 ligand, but not as an FFAR4 ligand. Activation of ERK in FFAR1-expressing HEK293 cells by 6-ODA and 9-ODA peaked at 10 min after stimulation followed by a slow decrease, similar to ERK activation by rosiglitazone, which peaked at 10 min after stimulation and lasted longer. Glucose-dependent production of insulin from MIN6 insulinoma cells was induced by 6-ODA and 9-ODA in an FFAR1-dependent manner. In this process, 6-ODA and 9-ODA stimulated the production of insulin not in the first phase that occurred within 10 min after stimulation but in the second phase. F-actin-remodeling that reflects insulin granule recruiting to the plasma membrane in the second phase of insulin secretion by 6-ODA and 9-ODA suggested that they have an FFAR1-dependent function in insulin secretion from MIN6 cells.


Analysing post-alarm data in a monitoring system in order to accept or reject the alarm.
In a disease monitoring system embracing several diseases and communities, alarms indicating a significant increase in disease incidence will frequently occur even though the false alarm rate has been set quite low. An approach is presented by which an alarm is determined as either confirmed or rejected according to data observed subsequent to the alarm. The suggested procedure is expected to weed out a substantial proportion (say about 75 per cent) of the false alarms at the expense of some delay in detecting a true alarm.


TATA box-binding protein (TBP) is a constituent of the polymerase I-specific transcription initiation factor TIF-IB (SL1) bound to the rRNA promoter and shows differential sensitivity to TBP-directed reagents in polymerase I, II, and III transcription factors.
The role of the Acanthamoeba castellanii TATA-binding protein (TBP) in transcription was examined. Specific antibodies against the nonconserved N-terminal domain of TBP were used to verify the presence of TBP in the fundamental transcription initiation factor for RNA polymerase I, TIF-IB, and to demonstrate that TBP is part of the committed initiation complex on the rRNA promoter. The same antibodies inhibit transcription in all three polymerase systems, but they do so differentially. Oligonucleotide competitors were used to evaluate the accessibility of the TATA-binding site in TIF-IB, TFIID, and TFIIIB. The results suggest that insertion of TBP into the polymerase II and III factors is more similar than insertion into the polymerase I factor.


Antibiotic synergy against biofilm-forming Pseudomonas aeruginosa.
Eight antibiotics (aztreonam, ceftazidim, cefoperazon, cefepim, netilmicin, amikacin, ofloxacin and ciprofloxacin) exhibited antimicrobial activity individually and/or in combinations against 20 wild-type biofilm-forming strains of Pseudomonas aeruginosa. The strains were less susceptible in biofilm; in 10 strains antibiotic synergy was observed for the combination of aztreonam and ciprofloxacin. Synergy was also demonstrated in the case of beta-lactams and aminoglycosides, beta-lactams and fluoroquinolones, aminoglycosides and fluoroquinolones, and for monobactams and beta-lactams although the strains were resistant to the individual antibiotics. Synergism or partial synergism was found with one or more antibiotic combinations against 32.4% of isolates.


Update on new trend and progress of the mechanism of polycyclic aromatic hydrocarbon biodegradation by Rhodococcus, based on the new understanding of relevant theories: a review.
Rapid industrial and societal developments have led to substantial increases in the use and exploitation of petroleum, and petroleum hydrocarbon pollution has become a serious threat to human health and the environment. Polycyclic aromatic hydrocarbons (PAHs) are primary components of petroleum hydrocarbons. In recent years, microbial remediation of PAHs pollution has been regarded as the most promising and cost-effective treatment measure because of its low cost, robust efficacy, and lack of secondary pollution. Rhodococcus bacteria are regarded as one of main microorganisms that can effectively degrade PAHs because of their wide distribution, broad degradation spectrum, and network-like evolution of degradation gene clusters. In this review, we focus on the biological characteristics of Rhodococcus; current trends in PAHs degradation based on knowledge maps; and the cellular structural, biochemical, and enzymatic basis of degradation mechanisms, along with whole genome and transcriptional regulation. These research advances provide clues for the prospects of Rhodococcus-based applications in environmental protection.


Effects of enterally- and parenterally-administered bombesin on intestinal luminal tryptic activity and protein in the suckling rat.
Because of the presence of bombesin-like immunoreactivity in milk, we investigated if enteral administration of bombesin affects the intestinal luminal content of trypsin and protein in 12-14-day-old rats. Bombesin (40 micrograms/kg), given either orogastrically or subcutaneously, produced a significant elevation in the intestinal content of trypsin activity. Thus, enterally-administered bombesin can produce acute biologic effects in suckling rats.


Activation of dihydropyridine sensitive Ca2+ channels in rat hippocampal neurons in culture by parathyroid hormone.
We examined the effects of parathyroid hormone (PTH) on rat hippocampal neurons in culture to determine whether it caused a similar intracellular calcium concentration ([Ca2+]i) increase in these cells to that seen with renal epithelial cells and found that PTH induced the effect in about 30% of the neurons. The effects appeared gradually during continuous administration of full-length PTH(1-84) or its active fragment, PTH(1-34), but not of an inactive fragment, PTH(39-84). However, the active fragment of the PTH-related peptide (PTHrP(1-34)) had little effect on [Ca2+]i during 60 min of administration. The PTH effect was inhibited by nifedipine, an L-type Ca2+ channel antagonist, and facilitated by S-(-)-BAY K 8644, an L-type Ca2+ channel agonist. Our findings suggest that PTH is one of the causal factors for the age-related increase in the density of voltage gated Ca2+ channels in hippocampal neurons.


Changes in three subtypes of tetrodotoxin sensitive sodium channel expression in the axotomized dorsal root ganglion in the rat.
The upregulated expression of tetrodotoxin sensitive (TTXs) Na+ channels is thought to play an important role in the development of ectopic discharges (EDs) in axotomized sensory neurons. The present study examined the levels of mRNAs of three subtypes of TTXs Na(+) channels, Na(v)1.7, Na(v)1.6, and Na(x), in the dorsal root ganglion (DRG) after segmental spinal nerve ligation. Following nerve ligation, the level of mRNAs of Na(v)1.7 and Na(v)1.6 was decreased, while the Nax mRNA level was increased at 5 days, but not at 1 day, postoperatively compared with the normal levels. Thus, if upregulated expression of TTXs Na+ channels contributes to the generation of EDs in axotomized DRG neurons, Na(x) is the most likely contributor among the three tested subtypes.