Expression of bar in the plastid genome confers herbicide resistance.
Phosphinothricin (PPT) is the active component of a family of environmentally safe, nonselective herbicides. Resistance to PPT in transgenic crops has been reported by nuclear expression of a bar transgene encoding phosphinothricin acetyltransferase, a detoxifying enzyme. We report here expression of a bacterial bar gene (b-bar1) in tobacco (Nicotiana tabacum cv Petit Havana) plastids that confers field-level tolerance to Liberty, an herbicide containing PPT. We also describe a second bacterial bar gene (b-bar2) and a codon-optimized synthetic bar (s-bar) gene with significantly elevated levels of expression in plastids (>7% of total soluble cellular protein). Although these genes are expressed at a high level, direct selection thus far did not yield transplastomic clones, indicating that subcellular localization rather than the absolute amount of the enzyme is critical for direct selection of transgenic clones. The codon-modified s-bar gene is poorly expressed in Escherichia coli, a common enteric bacterium, due to differences in codon use. We propose to use codon usage differences as a precautionary measure to prevent expression of marker genes in the unlikely event of horizontal gene transfer from plastids to bacteria. Localization of the bar gene in the plastid genome is an attractive alternative to incorporation in the nuclear genome since there is no transmission of plastid-encoded genes via pollen.


Traditional medicine in China for ischemic stroke: bioactive components, pharmacology, and mechanisms.
Ischemic stroke is an acute cerebrovascular disease and the third most common cause of death after ischemic heart disease. Increasing attention is being paid to finding effective treatments through traditional medicine. Thus, studying the traditional medicine for the treatment of ischemic stroke is of great importance. Traditional medicine in China includes traditional Chinese medicine (TCM) and other ethnic medicines, which is rich in variety and resources. This review first introduces the treatment mechanisms associated with ischemic stroke, such as antioxidant nitrification, antiexcitotoxic, antiapoptotic, anti-inflammatory, antiplatelet and anticoagulation mechanisms. Then, we calculated the frequency of prescription use for ischemic stroke and summarized the treatments for ischemic stroke by investigating 13 drug monographs and standards. We found 192 prescriptions from the traditional medical system for ischemic stroke, including Angong Niuhuang pill, Qishiwei Zhenzhu Pills, Ginkgo biloba leaf, and other traditional Chinese patent medicines and national medicines. There were 398 kinds of traditional medicine, including 301 kinds of plant-based medicines, 54 kinds of animal-based medicines, 28 kinds of mineral-based medicines, and 15 kinds of other medicines. We introduced the names, families, medicinal components, traditional uses, phytochemical information, and pharmacological activities of the commonly used Chinese patent medicines and TCMs. In addition, some chemicals were introduced. These medicines may be potential candidates for the treatment of ischemic stroke. This work provides a reference for the research and clinical use of new drugs for ischemic stroke.


Tumour doubling times and the length bias in breast cancer screening programmes.
Screening for early detection of breast cancer is considered to be an important element of preventive medicine. In this paper, we use numerical simulations to examine the length bias in regular interval screening programmes, by computing the doubling times of breast cancer tumours detected through regular mammographies compared to self-detection. Our analysis shows that doubling times of tumours detected by a regular screening programme are longer than doubling times in the original whole population and considerably longer than those self-detected. Hence regular interval mammographies may be missing a high proportion of fast growing tumours and therefore the benefits of current screening programmes may need to be re-evaluated. We examine the likely size of the length bias for the present UK breast cancer screening programme and perform a sensitivity analysis by varying the screen detection probabilities to reflect future advances in mammographic detection.


Nuclear retention elements of U3 small nucleolar RNA.
The processing and methylation of precursor rRNA is mediated by the box C/D small nucleolar RNAs (snoRNAs). These snoRNAs differ from most cellular RNAs in that they are not exported to the cytoplasm. Instead, these RNAs are actively retained in the nucleus where they assemble with proteins into mature small nucleolar ribonucleoprotein particles and are targeted to their intranuclear site of action, the nucleolus. In this study, we have identified the cis-acting sequences responsible for the nuclear retention of U3 box C/D snoRNA by analyzing the nucleocytoplasmic distributions of an extensive panel of U3 RNA variants after injection of the RNAs into Xenopus oocyte nuclei. Our data indicate the importance of two conserved sequence motifs in retaining U3 RNA in the nucleus. The first motif is comprised of the conserved box C' and box D sequences that characterize the box C/D family. The second motif contains conserved box sequences B and C. Either motif is sufficient for nuclear retention, but disruption of both motifs leads to mislocalization of the RNAs to the cytoplasm. Variant RNAs that are not retained also lack 5' cap hypermethylation and fail to associate with fibrillarin. Furthermore, our results indicate that nuclear retention of U3 RNA does not simply reflect its nucleolar localization. A fragment of U3 containing the box B/C motif is not localized to nucleoli but retained in coiled bodies. Thus, nuclear retention and nucleolar localization are distinct processes with differing sequence requirements.


Basosquamous Carcinoma: Comprehensive Clinical and Histopathological Aspects, Novel Imaging Tools, and Therapeutic Approaches.
Basosquamous carcinoma (BSC), an uncommon and aggressive nonmelanoma skin cancer exhibiting characteristics ranging from basal cell carcinoma (BCC) to squamous cell carcinoma (SCC), is a subject of controversy in terms of its classification, pathogenesis, histologic morphology, biologic behavior, prognosis, and management. This narrative review is based on an electronic search of English-language articles in PubMed that included the terms "basosquamous carcinoma" and/or "metatypical carcinoma of the skin" in their titles. The review aims to succinctly present and assess current data on the epidemiology, clinical presentation, dermoscopic, LC-OCT, and histopathologic characteristics, as well as the genetics and management of BSC, providing insight into this intriguing entity. As a conclusion, dermoscopy, deep incisional biopsies, and immunohistologic techniques should be applied in clinically suspicious lesions to achieve an early diagnosis and better prognosis of this tumor. Surgical treatments, including wide excision and Mohs' micrographic surgery, remain the treatment of choice. Finally, Hedgehog pathway inhibitors and checkpoint inhibitors, must be thoroughly investigated with large controlled trials, since they may offer an alternative solution to irresectable or difficult-to-treat locally advanced cases of basosquamous carcinoma.


Immunohistochemical expression of Mina53 and Ki67 proteins in human primary gingival squamous cell carcinoma.
Studies have reported the presence of relationships between the Myc target gene Mina53 and poor prognostic factors in several cancers including esophageal cancer. In this study, we investigated the relationships between Mina53 expression in gingival squamous cell carcinoma and clinicopathological factors. Seven samples of normal and dysplastic gingival tissues and 15 samples of gingival squamous cell carcinoma were immunostained for Mina53 and Ki67, and examined for the relationships between their expression and differentiation degree, lymph node metastasis, stage, tumor diameter, and prognosis. In normal and dysplastic gingival tissues, the localization of the expression of Mina53 and Ki67 was similar, but that in gingival squamous cell carcinoma tissue varied depending on the degree of differentiation. In well-differentiated GSCC with pearl formation, Mina53 was negative at the center of the clearly keratinized cancer nest, but positive in the nuclei of cells in the periphery and adjacent area of the cancer nest. In diffusely proliferating undifferentiated and moderately-differentiated GSCC showing no pearl formation, both Mina53 tended to be positive in the nuclei of cancer cells in the entire cancer nest. A significant correlation was found between the expression of Mina53 and that of Ki67 in patients with gingival squamous cell carcinoma or dysplastic gingiva. No significant correlation was noted between the expression of Mina53 or Ki67 and prognostic factors such as the degree of differentiation, lymph node metastasis, stage, and tumor diameter. In gingival squamous cell carcinoma, Mina53 expression was correlated with the proliferation of tumor cells, but unlike esophageal and other squamous cell carcinomas, not with the prognosis. The absence of correlations with prognostic factors suggests that may differ gingival squamous cell carcinoma differs biologically from esophageal squamous cell carcinoma which is correlated with Mina53 in terms of the biological expression of Mina53.


Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder.
While there has been considerable concern over possible adverse effects of psychostimulants on brain development, this issue has not been examined in a prospective study. The authors sought to determine prospectively whether psychostimulant treatment for attention deficit hyperactivity disorder (ADHD) was associated with differences in the development of the cerebral cortex during adolescence. Change in cortical thickness was estimated from two neuroanatomic MRI scans in 43 youths with ADHD. The mean age at the first scan was 12.5 years, and at the second scan, 16.4 years. Nineteen patients not treated with psychostimulants between the scans were compared with an age-matched group of 24 patients who were treated with psychostimulants. Further comparison was made against a template derived from 620 scans of 294 typically developing youths without ADHD. Adolescents taking psychostimulants differed from those not taking psychostimulants in the rate of change of the cortical thickness in the right motor strip, the left middle/inferior frontal gyrus, and the right parieto-occipital region. The group difference was due to more rapid cortical thinning in the group not taking psychostimulants (mean cortical thinning of 0.16 mm/year [SD=0.17], compared with 0.03 mm/year [SD=0.11] in the group taking psychostimulants). Comparison against the typically developing cohort without ADHD showed that cortical thinning in the group not taking psychostimulants was in excess of age-appropriate rates. The treatment groups did not differ in clinical outcome, however. These findings show no evidence that psychostimulants were associated with slowing of overall growth of the cortical mantle.


Kohler disease: diagnoses and assessment by bone scintigraphy.
Limping is a frequent occurrence in children and may be caused by various conditions, including trauma, inflammation, infection, and malignancy. Nontraumatic avascular necrosis of the tarsal bones should be included in the differential diagnosis. Accumulated data have supported the superiority of bone scans to radiography in the early diagnosis of avascular necrosis. Bone scintigraphy is a useful tool for investigating pain when symptoms, laboratory examinations, and radiography do not point to a specific diagnosis. In the early phase of disease, bone scans may demonstrate decreased tracer uptake (photopenic region), subsequently a hot area is seen during the reparative process. Although magnetic resonance imaging has important implications in the diagnosis of avascular necrosis, bone scintigraphy with its ready availability has a significant role as a primary tool in the evaluation of a limping child.


Effects of anaerobic digestion enhanced by ultrasound pretreatment on the fuel properties of municipal sludge.
In this study, effects of ultrasound pretreatment on combustion characteristics and elemental composition of municipal sludge were examined for energy-based evaluation of sludge pretreatment. Waste activated sludge (WAS) from a municipal wastewater treatment plant was pretreated with ultrasound at varying durations and was subjected to anaerobic digestion in a biochemical methane potential (BMP) assay. Changes in gas production rates, calorific value (CV), elemental compositions, and ash contents of sludge samples were examined to assess the effects of pretreatment and digestion. Sonication at 0.73 W/mL enhanced gas production by 28%. Moreover, volatile solids (VS) and chemical oxygen demand (COD) removals increased from 41 to 45% and 33 to 37%, respectively. Following anaerobic digestion, CVs of samples decreased by about 18%. Sonicated samples exhibited a higher decrease. In order to quantify the change in overall energy content, total solids (TS) reduction was also taken into account. Loss was magnified as both CV and the amount of TS that would provide the overall energy were reduced. This loss was 38% for the control group and 41% for the 15 min sonicated sludge. Digestion decreased the C content of sludge by about 20% and H content by 50% due to biogas production. Ash content increased relatively as some of the combustible solids were lost due to digestion. Experimental results indicate that if sludge is to be combusted, digestion with or without ultrasound pretreatment may be disadvantageous if the aim is to maximize energy gain from sludge.


Effects of Transcranial Direct Current Stimulation (tDCS) Combined With Wrist Robot-Assisted Rehabilitation on Motor Recovery in Subacute Stroke Patients: A Randomized Controlled Trial.
Both transcranial direct current stimulation (tDCS) and wrist robot-assisted training have demonstrated to be promising approaches for stroke rehabilitation. However, the effects of the combination of the two treatments in subacute stroke patients are not clear yet. To investigate the effectiveness of combining tDCS and wrist robot-assisted rehabilitation in subacute stroke patients in comparison with the wrist robotic training only, a single-blind, randomized, sham-controlled trial was performed with 40 subacute stroke patients (25 ± 7 days from stroke onset time). Patients were randomly assigned to experimental group (EG, n = 20 ) where patients receive real tDCS [2 mA, 20 min, and the anodal electrode on the primary motor cortex-M1-area of the affected hemisphere (C3/C4 in the 10-20 EEG system and the cathodal electrode on the contralateral orbit bone)] or control group (CG, n = 20 ) where patients receive sham tDCS (5 s) during wrist robotic rehabilitation training. The effects of the treatment were evaluated by means of the upper extremity, shoulder-elbow, and wrist subsections of the Fugl-Meyer assessment scale, Modified Ashworth Scale, Motricity Index and Box and Block Test together with kinematic parameters. One out of 20 patients in the CG did not complete the treatment. All the clinical outcome measures except the Modified Ashworth Scale showed a significant increase after the treatment in both groups. However, no significant difference in the average changes after treatment between groups was observed. The movement velocity and smoothness showed significant increases after the training, even though no significant difference between groups was observed. The combination of wrist robot-assisted training and tDCS did not show additional effects in comparison with wrist robot-assisted training only in subacute stroke patients. The negative results found in this paper are specific for the specific intervention. The timing of delivering the tDCS and the robot-assisted therapy has to be deeply investigated to enhance the effectiveness of the training.


Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal.
Recently, two "fixed triple" single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for patients with COPD. This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of "fixed triple" (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form "open triple" combinations. Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium. Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio. Furthermore, triple therapy showed a promising signal in terms of improved survival. The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia. Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma-COPD overlap.


Aqueous flare intensity in relation to different stages of diabetic retinopathy.
To compare laser flare intensity in patients with diabetes mellitus (DM) type I and type II to different stages of diabetic retinopathy (DR) and controls. This study comprised 88 consecutive patients with DM type I and 40 controls in the same age range, divided into two age groups: 20-34 years and 35-50 years; 108 consecutive patients with DM type II and 32 controls were also divided into two age groups: 45-59 years and 60-75 years. Patients with glaucoma, exfoliation syndrome, media opacities, uveitis, within 96 hours after laser photocoagulation, treatment with topical and systemic drugs which can affect aqueous protein concentration, were excluded. One eye was randomly selected from each diabetic patient and control. Flare intensity was measured with a laser flare meter without mydriatic drops, and was then correlated with the stages of DR within each age group. Eyes with advanced DR, such as moderate-severe, severe non-proliferative DR and proliferative DR (PDR), had significantly higher flare intensity than controls and eyes without retinopathy in all age groups (p<0.05). Flare intensity values were similar for controls and eyes with mild-moderate DR in all age groups except the older patients with DM type II, particularly those with clinically significant macular edema (CSME) (p<0.05). Eyes with regressed proliferative DR and no indication for laser photocoagulation had significantly lower flare values than eyes with an indication for therapy (p<0.05). Eyes with iris rubeosis (IR) had significantly higher flare than those without IR (p<0.05). Flare values were significantly correlated with the duration of diabetes in DM types I and II (p<0.05). Flare intensity was increased in eyes with mild-moderate DR with CSME, and in eyes with advanced and severe stages of DR. Aqueous flare was related to the duration of diabetes.


Rational design and characterization of platelet factor 4 antagonists for the study of heparin-induced thrombocytopenia.
Patients with heparin-induced thrombocytopenia (HIT) remain at risk for recurrent thromboembolic complications despite improvements in management. HIT is caused by antibodies that preferentially recognize ultralarge complexes (ULCs) of heparin and platelet factor 4 (PF4) tetramers. We demonstrated previously that a variant PF4(K50E) forms dimers but does not tetramerize or form ULCs. Here, we identified small molecules predicted to bind PF4 near the dimer-dimer interface and that interfere with PF4 tetramerization. Screening a library of small molecules in silico for binding at this site, we identified 4 compounds that inhibited tetramerization at micromolar concentrations, designated PF4 antagonists (PF4As). PF4As also inhibited formation of pathogenic ULCs, and 3 of these PF4As promoted the breakdown of preformed ULCs. To characterize the ability of PF4As to inhibit cellular activation, we developed a robust and reproducible assay that measures cellular activation by HIT antibodies via FcγRIIA using DT40 cells. PF4As inhibit FcγRIIA-dependent activation of DT40 cells by HIT antibodies as well as platelet activation, as measured by serotonin release. PF4As provide new tools to probe the pathophysiology of HIT. They also may provide insight into the development of novel, disease-specific therapeutics for the treatment of thromboembolic complications in HIT.


Abundant ammonia in primitive asteroids and the case for a possible exobiology.
Carbonaceous chondrites are asteroidal meteorites that contain abundant organic materials. Given that meteorites and comets have reached the Earth since it formed, it has been proposed that the exogenous influx from these bodies provided the organic inventories necessary for the emergence of life. The carbonaceous meteorites of the Renazzo-type family (CR) have recently revealed a composition that is particularly enriched in small soluble organic molecules, such as the amino acids glycine and alanine, which could support this possibility. We have now analyzed the insoluble and the largest organic component of the CR2 Grave Nunataks (GRA) 95229 meteorite and found it to be of more primitive composition than in other meteorites and to release abundant free ammonia upon hydrothermal treatment. The findings appear to trace CR2 meteorites' origin to cosmochemical regimes where ammonia was pervasive, and we speculate that their delivery to the early Earth could have fostered prebiotic molecular evolution.


Casualty radiology with lightweight X-ray machine.
A small lightweight X-ray machine is needed for use in military medicine for humanitarian service missions, training exercises, and even tactical situations. In such circumstances, the large size and great weight of conventional X-ray equipment limit its use and make this diagnostic modality unsuitable. I have used a small lightweight X-ray machine and obtained adequate X-ray exams in a high percentage of patients.


The impact of obstructive interval and sperm granuloma on outcome of vasectomy reversal.
We studied the impact of the interval from vasectomy to reversal and presence of sperm granuloma on outcomes of reversal. A total of 213 microsurgical vasectomy reversals performed by a single surgeon were stratified according to obstructive intervals of less than 5 years, 5 to 10 years, 10 to 15 years and greater than 15 years. The effects of obstructive interval on patency and pregnancy rates were assessed using multivariate logistical regression. The impact of sperm granuloma on patency and pregnancy was assessed using the chi-square test. Patency did not change with increasing obstructive intervals as can be seen with 91% patency at less than 5 years, 88% at 5 to 10 years, 91% at 10 to 15 and 89% at greater than 15 years. There was no difference in pregnancy rates (89%, 82% or 86%) at obstructive intervals of 0 to 5, 5 to 10 or 10 to 15 years, respectively. Pregnancy rates were significantly lower (44%, p <0.05) with obstructive intervals greater than 15 years. Men with at least unilateral sperm granuloma had patency of 95% vs 78% without granulomas, a trend which did not quite reach statistical significance (p = 0.07). There was no difference in pregnancy rates with or without granulomas. Vasectomy reversal patency rates are high regardless of time since vasectomy. Pregnancy rates are lower more than 15 years after vasectomy. Sperm granuloma had a favorable impact on patency. Our data indicate that for obstructive intervals less than 15 years vasectomy reversal yields much higher pregnancy rates than in vitro fertilization and intracytoplasmic sperm injection, and that even for intervals greater than 15 years reversal outcomes equal or exceed those of in vitro fertilization and intracytoplasmic sperm injection.


Dissociative electron attachment to the nitroamine HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine).
In the present study, dissociative electron attachment (DEA) measurements with gas phase HMX, octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine, C4H8N8O8, have been performed by means of a crossed electron-molecular beam experiment. The most intense signals are observed at 46 and 176 u and assigned to NO2(-) and C3H6N5O4(-), respectively. Anion efficiency curves for 15 negatively charged fragments have been measured in the electron energy region from about 0-20 eV with an energy resolution of ~0.7 eV. Product anions are observed mainly in the low energy region, near 0 eV, arising from surprisingly complex reactions associated with multiple bond cleavages and structural and electronic rearrangement. The remarkable instability of HMX towards electron attachment with virtually zero kinetic energy reflects the highly explosive nature of this compound. Substantially different intensity ratios of resonances for common fragment anions allow distinguishing the nitroamines HMX and royal demolition explosive molecule (RDX) in negative ion mass spectrometry based on free electron capture.


[Feeding and defecation of Rhodnius (hemiptera: Reduviidae) fed human blood].
Feeding and defecation behavior of Rhodnius prolixus Stal, 1859, R. robustus Larrousse, 1927, R. neivai Lent, 1953 and R. pictipes Stal, 1872, artificially fed on human blood, were studied under laboratory conditions. In all species, first instar nymphs did not defecate in the first 30 minutes after feeding. R. pictipes did not accept artificial feeding but fed directly on humans. Nymph and adult R. prolixus had a higher defecation index (DI) than other species; third instar nymphs had the highest DI = 1.62. In all instars, most individuals accepted the food in 3 Pounds minutes and finished feeding in less than 15 minutes.


Biallelic sequence variants in INTS1 in patients with developmental delays, cataracts, and craniofacial anomalies.
The Integrator complex subunit 1 (INTS1) is a component of the integrator complex that comprises 14 subunits and associates with RPB1 to catalyze endonucleolytic cleavage of nascent snRNAs and assist RNA polymerase II in promoter-proximal pause-release on protein-coding genes. We present five patients, including two sib pairs, with biallelic sequence variants in INTS1. The patients manifested absent or severely limited speech, an abnormal gait, hypotonia and cataracts. Exome sequencing revealed biallelic variants in INTS1 in all patients. One sib pair demonstrated a missense variant, p.(Arg77Cys), and a frameshift variant, p.(Arg1800Profs*20), another sib pair had a homozygous missense variant, p.(Pro1874Leu), and the fifth patient had a frameshift variant, p.(Leu1764Cysfs*16) and a missense variant, p.(Leu2164Pro). We also report additional clinical data on three previously described individuals with a homozygous, loss of function variant, p.(Ser1784*) in INTS1 that shared cognitive delays, cataracts and dysmorphic features with these patients. Several of the variants affected the protein C-terminus and preliminary modeling showed that the p.(Pro1874Leu) and p.(Leu2164Pro) variants may interfere with INTS1 helix folding. In view of the cataracts observed, we performed in-situ hybridization and demonstrated expression of ints1 in the zebrafish eye. We used Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 to make larvae with biallelic insertion/deletion (indel) variants in ints1. The mutant larvae developed typically through gastrulation, but sections of the eye showed abnormal lens development. The distinctive phenotype associated with biallelic variants in INTS1 points to dysfunction of the integrator complex as a mechanism for intellectual disability, eye defects and craniofacial anomalies.


Occupational and patient doses for interventional radiology integrated into a dose management system.
The International Commission on Radiological Protection recommends managing patient and occupational doses as an integrated approach, for the optimisation of interventional procedures. The conventional passive personal dosimeters only allow one to know the accumulated occupational doses during a certain period of time. This information is not enough to identify if there is a lack of occupational radiation protection during some procedures. This paper describes the use of a dose management system (DMS) allowing patient and occupational doses for individual procedures to be audited. The DMS manages patient and occupational doses measured by electronic personal dosimeters. One dosemeter located at the C-arm is used as a reference for scatter radiation. Data have been collected from five interventional rooms. Dosimetry data can be managed for the whole procedure and the different radiation events. Optimisation is done through auditing different sets of parameters for individual procedures: patient dose indicators, occupational dose values, the ratio between occupational doses, and the doses measured by the reference dosemeter at the C-arm, and the ratio between occupational and patient dose values. The managed data correspond to the year 2021, with around 4500 procedures, and 8000 records on occupational exposures. Patient and staff dose data (for 11 cardiologists, 7 radiologists and 8 nurses) were available for 3043 procedures. The DMS allows alerts for patient dose indicators and occupational exposures to be set. The main advantage of this integrated approach is the capacity to improve radiation safety for patients and workers together, auditing alerts for individual procedures. The management of patient and occupational doses together (measured with electronic personal dosimeters) for individual interventional procedures, using dose management systems, allows alerting optimisation on high-dose values for patients and staff.


[Low galectin-3 capacity to discriminate thyroid lesions].
Galectin-3 is considered useful in identifying lesions included in the term follicular tumour. To evaluate galectin-3's power to discriminate among diverse thyroid lesions and to identify a set point of expression at which there is the least possible false positive results. 26 follicular carcinomas and 104 assorted thyroid lesions were analysed (8 Hashimoto's thyroiditis, 18 goiter, 44 adenoma, 27 papillary carcinoma and 7 normal glands). Immunohistochemistry for galectin-3 was performed way (NCL-GAL-3, 1:100, Novocastra, UK). In a blinded manner intensity and percentage of expression were evaluated, as was its capacity to identify the previously mentioned thyroid entities with 2 x 2 tables. Minimum reactivity set point values were identified and the one which presented the least false positive cases was selected. A reaction was considered positive when 25% of the cells were marked, in which case neither the Hashimoto's thyroiditis, goiter, nor the residual tissue were positive for galectin-3. A positive galectin-3 reaction was identified in 4/44 adenomas, 5/26 follicular carcinomas and 18/27 papillary carcinomas. From a total of 53 carcinomas, 23 showed positive and 30 a negative reaction to galectin-3. Thus, galectin-3's sensitivity to discriminate between benign and malignant lesions was 94% while its specificity was 43%. When comparing follicular carcinoma with adenoma, sensibility was 19% while specificity was 91%. The positive predictive value was 56% and the negative predictive value 66%. Galectin-3 was most useful for identifying papillary thyroid carcinoma. Galectin-3 has limited value to distinguish benign from malignant thyroid lesions. The reaction must be considered positive when at least 25% of cells are marked.


[Investigation of peripheral hemodynamics with the use of ultrasonic dopplerography under the conditions of 7-day immersion].
Ultrasonic dopplerograpy of peripheral, including transcranial, blood circulation was performed in 8 normal volunteers for 7-day dry immersion experiment. Linear blood velocity (LBV) was measured in main arteries and veins of the head and lower extremities. Investigations were conducted on days 2 and 5 of immersion and on day 2 of recovery. The data were compared with baseline values determined before the experiment. LBV slowed down in all the vessels under investigation; the effect was most pronounced in the veins. On day 5, behavior of venous cerebral circulation in some of the volunteers indirectly attested to elevation of intracranial pressure. In the period of recovery, arterial LBV was largely equal to baselines values. Slower recovery of venous blood circulation was treated as an aftereffect of support deprivation.


Clinical specialty and organizational features of acute hospital wards.
Ward clinical specialty is a variable which has been largely ignored in studies of nursing organization and effectiveness. Analysis of data collected from a nationally representative sample of 83 acute medical, surgical and orthopaedic hospital wards demonstrates that while wards had similar staffing resources, differences exist in the likelihood of adopting a nursing organizational system with devolved authority, in nurses' views of prevailing hierarchical attitudes, and their perceived influence over a range of organizational features of the ward. Medical wards were more likely to have developed organizational practices associated with increasing nursing autonomy.


Interaction of resin-modified glass-ionomer cements with moist dentine.
The objective of this study was to report on a novel phenomenon that occurs when resin-modified glass-ionomer cements (RMGICs) are bonded to moist human dentine. Dentine surfaces from extracted third molars were abraded with 180-grit SiC paper. Ten teeth were prepared for each of the two RMGICs tested (Fuji II LC, GC Corp. and Photac-Fil Quick, 3M ESPE). RMGIC buildups were made according to the manufacturers' instructions. After storage at 37 degrees C, 100% humidity for 24 h, the bonded specimens were cut occlusogingivally into 0.9 x 0.9 mm beams. Dentine surfaces bonded with the two RMGICs were examined along the fractured RMGIC/dentine interfaces. Additional beams fractured within the RMGICS and at 3 mm away from the interfaces were used as controls. The fractured beams were examined using scanning electron microscopy (SEM), field emission-environmental SEM (FE-ESEM) and transmission electron microscopy (TEM). SEM and FE-ESEM revealed numerous solid spherical bodies along the RMGIC/dentine interfaces. By contrast, no spherical bodies could be identified within the RMGIC fractured 3 mm distant from the bonded interface. TEM and energy dispersive X-ray analyses performed on carbon-coated ultrathin sections showed that these solid spherical bodies consisted of a thin aluminum and silicon-rich periphery and an amorphous hydrocarbon core within the air voids of the original resin matrix. The spherical bodies probably represent a continuation of GI reaction and poly(HEMA) hydrogel formation that results from water diffusion from the underlying moist dentine. Their existence provides evidence for the permeation of water through RMGIC/dentine interfaces.


[<RNA World"--an unlikely scenario of the life origin and early ecolution on Earth].
The most widely accepted modern scenario of prebiotic evolution that led to the emergence of the first cells on our planet is the "RNA World"--a hypothetical period of the early Earth's biosphere, when the information transfer and all the processes necessary for the functioning of the primary systems were provided by replicating RNA molecules. The essence of the "RNA World" hypothesis is based on two postulates: 1) at the initial stages of the origin of life, RNA molecules performed all functions necessary for reproduction and replication of biological molecules: informational, catalytic and structural; 2) at a certain stage of evolution arose separation of RNA and DNA, appeared genetically encoded proteins and occurred a transition to the modern world of living systems functioning. However, the analysis shows that the hypothesis of "RNA World" has a number of unsurmountable problems of chemical and informational nature. The biggest of them are: a) the unreliability of the initial components synthesis; b) a catastrophic rise of polynucleotide chains instability with their elongation; c) catastrophically low probability of formation of sequences possessing meaningful information; d) lack of a mechanism determining the regularities division of the membrane vesicles permeable to nitrogen bases and other RNA components; e) lack of driving forces for the transition from the RNA world to the much more complex world based on DNA and RNA. Therefore, the "RNA World" scenario seems unlikely.


[A man with calcifications in his legs].
A 70-year-old man had ulcers on his right lower leg for a year; he also had pitting oedema. On X-ray of his legs soft tissue calcifications were seen. These were caused by venous insufficiency.


Coronary versus carotid blood flow and coronary perfusion pressure in a pig model of prolonged cardiac arrest treated by different modes of venoarterial ECMO and intraaortic balloon counterpulsation.
Extracorporeal membrane oxygenation (ECMO) is increasingly used in cardiac arrest (CA). Adequacy of carotid and coronary blood flows (CaBF, CoBF) and coronary perfusion pressure (CoPP) in ECMO treated CA is not well established. This study compares femoro-femoral (FF) to femoro-subclavian (FS) ECMO and intraaortic balloon counterpulsation (IABP) contribution based on CaBF, CoBF, CoPP, myocardial and brain oxygenation in experimental CA managed by ECMO. In 11 female pigs (50.3 ± 3.4 kg), CA was randomly treated by FF versus FS ECMO ± IABP. Animals under general anesthesia had undergone 15 minutes of ventricular fibrillation (VF) with ECMO flow of 5 to 10 mL/kg/min simulating low-flow CA followed by continued VF with ECMO flow of 100 mL/kg/min. CaBF and CoBF were measured by a Doppler flow wire, cerebral and peripheral oxygenation by near infrared spectroscopy. CoPP, myocardial oxygen metabolism and resuscitability were determined. CaBF reached values > 80% of baseline in all regimens. CoBF > 80% was reached only by the FF ECMO, 90.0% (66.1, 98.6). Addition of IABP to FF ECMO decreased CoBF to 60.7% (55.1, 86.2) of baseline, P = 0.004. FS ECMO produced 70.0% (49.1, 113.2) of baseline CoBF, significantly lower than FF, P = 0.039. Addition of IABP to FS did not change the CoBF; however, it provided significantly higher flow, 76.7% (71.9, 111.2) of baseline, compared to FF + IABP, P = 0.026. Both brain and peripheral regional oxygen saturations decreased after induction of CA to 23% (15.0, 32.3) and 34% (23.5, 34.0), respectively, and normalized after ECMO institution. For brain saturations, all regimens reached values exceeding 80% of baseline, none of the comparisons between respective treatment approaches differed significantly. After a decline to 15 mmHg (9.5, 20.8) during CA, CoPP gradually rose with time to 68 mmHg (43.3, 84.0), P = 0 .003, with best recovery on FF ECMO. Resuscitability of the animals was high, both 5 and 60 minutes return of spontaneous circulation occured in eight animals (73%). In a pig model of CA, both FF and FS ECMO assure adequate brain perfusion and oxygenation. FF ECMO offers better CoBF than FS ECMO. Addition of IABP to FF ECMO worsens CoBF. FF ECMO, more than FS ECMO, increases CoPP over time.


Full thickness cartilage palisade tympanoplasty with malleus interposition: a study of the long term results.
The aim of this retrospective study is to review long term results of full-thickness cartilage palisade tympanoplasty (FTCPT) with malleus head interposition performed on 51 patients (56 ears); 36 women and 15 men (7-73 years, 44 years average). The pathology of ears which encourages this technique of tympanoplasty is presented. On average 12 years after surgery we have elaborated anatomic and functional results. Anatomic results were categorized based on empiric evaluation of the new tympanic membrane status: 40 (71%) tympanic membranes without anatomic irregularities, 14 (25%) with irregularities and 2 (4%) with secondary perforation. Functional results (tonal audiogram) are based on pure tone average air-bone gap (PTA-ABG) at 4 frequencies. Main functional results of 51 ears (51 audiograms performed): pre- and post-operative average PTA-ABGs were 27.07 +/- 9.98 and 10.77 +/- 7.85 dB (t = 10.36; p < 0.001). In the group of ears with a tympanic membrane with no anatomic irregularities, pre- and post-operative average PTA-ABGs were 27.30 +/- 10.56 and 10.82 +/- 8.33 dB (t = 8.09; p < 0.001). In the group of ears with cartilage resorption, pre- and post-operative PTA-ABGs were 24.92 +/- 8.19 and 9.33 +/- 6.58 dB (t = 6.21; p < 0.001). The differences between the two groups are irrelevant. Postoperative PTA-ABG values of ears after first surgery (N = 34) and revision surgery (N = 17) was significantly different (8.75 +/- 5.75 and 15.16 +/- 9.62 dB) (t = 2.60; p = 0.016). In spite of the thickness of the new tympanal membrane, FTCPT is a successful technique for solving advanced ear pathology.


Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma.
Although the immunophenotype of plasma cells (PCs) from multiple myeloma (MM) patients has been extensively explored, information on the phenotypic characteristics of PCs in monoclonal gammopathy of undetermined significance (MGUS) patients is scanty and frequently controversial. Thus, the question of whether or not PCs are phenotypically different in the two disorders and whether this criteria could be useful for the differential diagnosis between MGUS and MM remains to be explored. In the present study, the immunophenotypic profile of bone marrow PCs (BMPCs) from a group of 76 MGUS patients has been analyzed by flow cytometry and compared with that of BMPCs present in both MM patients (n = 65) and control subjects (n = 10). For that purpose, a large panel of monoclonal antibodies against PC-related antigens was used together with a sensitive methodology in which a minimum of 10(3) PCs were studied. In all MGUS cases studied, two clearly defined and distinct PC subpopulations could be identified. One PC subpopulation, population A (33 +/- 31% of total PCs), constantly displayed a high CD38 expression with low forward light scatter (FSC)/side light scatter (SSC) and was positive for CD19 and negative for CD56 (only a small proportion of these PCs were weakly positive for CD56). The other PC subpopulation, population B (67 +/- 31% of total PCs), showed the opposite pattern; the antigen CD56 was strongly positive and CD19 was constantly negative, and it showed a lower CD38 expression and higher FSC/SSC values than population A. Clonality studies (cytoplasmic light chain restriction, DNA content studies, and polymerase chain reaction assessment) confirmed the clonal nature of PCs from population B and the polyclonal origin of PCs from population A. Moreover, the polyclonal PCs from MGUS displayed a phenotypic profile identical to that found in PCs from healthy individuals. By contrast, clonal PCs from all MGUS patients displayed a similar antigenic profile to myelomatous PCs, with clear phenotypic differences with respect to normal PCs: lower intensity of CD38 expression and a variable reactivity for markers that were not expressed in normal PCs, such as CD28, CD117, and sIg. Although the presence of residual polyclonal PCs was a constant finding in MGUS patients, it was a rare event in MM and, when present (only 22% of MM cases), its frequency was significantly lower than that observed in MGUS (0.25% versus 32.9%, respectively; P < 0.0001). Only 1.5% of patients with MM had more than 3% of normal PCs, whereas 98% of patients with MGUS had more than 3%. Moreover, as shown by multivariate analysis, the number of residual polyclonal PCs was the most powerful single parameter for the discrimination between MGUS and MM patients at diagnosis, even when only stage I MM cases were considered.


Characterization of the expression pattern of adrenergic receptors in rat taste buds.
Taste buds signal the presence of chemical stimuli in the oral cavity to the central nervous system using both early transduction mechanisms, which allow single cells to be depolarized via receptor-mediated signaling pathways, and late transduction mechanisms, which involve extensive cell-to-cell communication among the cells in the bud. The latter mechanisms, which involve a large number of neurotransmitters and neuropeptides, are less well understood. Among neurotransmitters, multiple lines of evidence suggest that norepinephrine plays a yet unknown role in the taste bud. This study investigated the expression pattern of adrenergic receptors in the rat posterior taste bud. Expression of alpha1A, alpha1B, alpha1D, alpha2A, alpha2B, alpha2C, beta1, and the beta2 adrenoceptor subtypes was observed in taste buds using RT-PCR and immunocytochemical techniques. Taste buds also expressed the biosynthetic enzyme for norepinephrine, dopamine beta-hydroxylase (DbetaH), as well as the norepinephrine transporter. Further, expression of the epinephrine synthetic enzyme, phenylethanolamine N-methyltransferase (PNMT), was observed suggesting a possible role for this transmitter in the bud. Phenotyping adrenoceptor expression patterns with double labeling experiments to gustducin, synaptosomal-associated protein 25 (SNAP-25), and neural cell adhesion molecule (NCAM) suggests they are prominently expressed in subsets of cells known to express taste receptor molecules but segregated from cells known to have synapses with the afferent nerve fiber. Alpha and beta adrenoceptors co-express with one another in unique patterns as observed with immunocytochemistry and single cell reverse transcription polymerase chain reaction (RT-PCR). These data suggest that single cells express multiple adrenergic receptors and that adrenergic signaling may be particularly important in bitter, sweet, and umami taste qualities. In summary, adrenergic signaling in the taste bud occurs through complex pathways that include presynaptic and postsynaptic receptors and likely play modulatory roles in processing of gustatory information similar to other peripheral sensory systems such as the retina, cochlea, and olfactory bulb.


[Radiation absorption, water content and contrast medium impregnation of gallstones].
Gallstones extracted by surgery were examined for CT density, which was compared with the x-ray-film, floating performance and chemical analysis of the stones. So far, the water content of the biliary concrements--14% on the average--has not been given much attention. Drying will considerably reduce the density; examination of dried gallstones yields a false picture of direct ray absorption. Pure cholesterol stones do not float in water, and they show positive values on Hounsfield's scale (+30--+60). The article discusses the question whether CT is suitable for effecting a better selection of gallstone patients who can be treated by drug therapy.


Evaluation by monte carlo simulation of the pharmacokinetics of two doses of meropenem administered intermittently or as a continuous infusion in healthy volunteers.
Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The pharmacokinetics of meropenem were studied in two groups, each comprising eight healthy volunteers who received the following doses: 500 mg as an intravenous infusion over 30 min three times a day (t.i.d.) versus a 250-mg loading dose followed by a 1,500 mg continuous infusion over 24 h for group A and 1,000 mg as an intravenous infusion over 30 min t.i.d. versus a 500-mg loading dose followed by a 3,000-mg continuous infusion over 24 h for group B. Meropenem concentrations in plasma and urine were determined by liquid chromatography-mass spectrometry/mass spectrometry and high-performance liquid chromatography with UV detection, respectively. Pharmacokinetic calculations were done by use of a two-compartment open model, and the data were extrapolated by Monte Carlo simulations for 10,000 simulated subjects for pharmacodynamic evaluation. There were no significant differences in total clearance and renal clearance between group A and group B or between the intermittent treatment and the continuous infusion. The analyses of the probability of target attainment by MIC for the high- and low-dose continuous infusions were robust up to MICs of 4 mg/liter and 2 mg/liter, respectively. The corresponding values for intermittent infusions were only 0.5 mg/liter and 0.25 mg/liter. When these observations were correlated with MICs obtained from the MYSTIC database, intermittent infusion results in adequate activity against two of the most common nosocomially acquired pathogens, Klebsiella pneumoniae and Enterobacter cloacae. However, against Pseudomonas aeruginosa, the evaluation shows a clear advantage of high-dose therapy administered as a continuous infusion. We believe that in the empirical therapy situation, the continuous-infusion mode of administration is most worth the extra efforts. We conclude that clinical trials for evaluation of the continuous infusions of meropenem in critically ill patients are warranted.


Clinical experience with the therapeutic hydrophilic contact lens.
Hydrophilic contact lenses were prescribed for 62 patients with a variety of corneal diseases. The lens was must successful for relief of pain in bullous keratropathy and in the healing of recurrent erosions. Its value in improving vision in bullous keratopathy depends on the stage of corneal edema and is not impressive in long-standing edema with scarring. The lens may be of value in patients with sterile indolent ulcers and in alkali-burned corneas with large epithelial defects after conventional therapy has failed. Caution is advised in fitting patients with the dry eye syndromes. Patients with minimal corneal scars due to keratoconus may benefit from a soft lens. Complications related to the use of hydrophilic lenses in this group of 62 patients are also discussed.


Structure and activation mechanism of the rice Salt Overly Sensitive 1 (SOS1) Na+/H+ antiporter.
Salinity is one of the most severe abiotic stresses that adversely affect plant growth and agricultural productivity. The plant Na+/H+ antiporter Salt Overly Sensitive 1 (SOS1) located in the plasma membrane extrudes excess Na+ out of cells in response to salt stress and confers salt tolerance. However, the molecular mechanism underlying SOS1 activation remains largely elusive. Here we elucidate two cryo-electron microscopy structures of rice (Oryza sativa) SOS1, a full-length protein in an auto-inhibited state and a truncated version in an active state. The SOS1 forms a dimeric architecture, with an NhaA-folded transmembrane domain portion in the membrane and an elongated cytosolic portion of multiple regulatory domains in the cytoplasm. The structural comparison shows that SOS1 adopts an elevator transport mechanism accompanied by a conformational transition of the highly conserved Pro148 in the unwound transmembrane helix 5 (TM5), switching from an occluded conformation in the auto-inhibited state to a conducting conformation in the active state. These findings allow us to propose an inhibition-release mechanism for SOS1 activation and elucidate how SOS1 controls Na+ homeostasis in response to salt stress.


[Sonographic findings in celiac trunk stenosis in the real time B image].
Ultrasonography, especially real-time-B-mode, is outstandingly suitable for detecting larger alterations of abdominal blood vessels or stenosis of the truncus coeliacus. This stenosis could be detected in 18 cases by real-time-scanning. 10 of these diagnosis were confirmed by angiography. The clinical value of these findings is discussed.


Helping pregnant smokers quit: a multi-centre randomised controlled trial of electronic cigarettes versus nicotine replacement therapy.
Some pregnant smokers try e-cigarettes, but effectiveness and safety of such use are unknown. To compare effectiveness and safety of nicotine patches and e-cigarettes in pregnancy. A pragmatic multi-centre randomised controlled trial. Twenty-three hospitals across England, and a Stop Smoking Service in Scotland. One thousand one hundred and forty pregnant daily smokers (12-24 weeks' gestation) motivated to stop smoking, with no strong preference for using nicotine patches or e-cigarettes. Participants in the e-cigarette arm were posted a refillable e-cigarette device with two 10 ml bottles of tobacco-flavoured e-liquid (18 mg nicotine). Participants in the nicotine patches arm were posted a 2-week supply of 15 mg/16-hour nicotine patches. Supplies were provided for up to 8 weeks. Participants sourced further supplies themselves as needed. Participants in both arms received support calls prior to their target quit date, on the quit date, and weekly for the next 4 weeks. The primary outcome was validated prolonged abstinence at the end of pregnancy. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers. Secondary outcomes included self-reported abstinence at different time points, treatment adherence and safety outcomes. Only 55% of self-reported abstainers mailed back useable saliva samples. Due to this, validated sustained abstinence rates were low (6.8% vs. 4.4% in the e-cigarettes and nicotine patches arms, respectively, risk ratio = 1.55, 95% confidence interval 0.95 to 2.53; Bayes factor = 2.7). In a pre-specified sensitivity analysis that excluded abstainers using non-allocated products, the difference became significant (6.8% vs. 3.6%, risk ratio = 1.93, 95% confidence interval 1.14 to 3.26; Bayes factor = 10). Almost a third of the sample did not set a target quit date and the uptake of support calls was low, as was the initial product use. At end of pregnancy, 33.8% versus 5.6% of participants were using their allocated product in the e-cigarettes versus nicotine patches arm (risk ratio = 6.01, 95% confidence interval 4.21 to 8.58). Regular use of e-cigarettes in the nicotine patches arm was more common than use of nicotine replacement products in the e-cigarette arm (17.8% vs. 2.8%). Rates of adverse events and adverse birth outcomes were similar in the two study arms, apart from participants in the e-cigarette arm having fewer infants with low birthweight (<2500 g) (9.6% vs. 14.8%, risk ratio = 0.65, 95% confidence interval 0.47 to 0.90; Bayes factor = 10.3). Low rates of validation reduced the study power. A substantial proportion of participants did not use the support on offer sufficiently to test its benefits. Sample size may have been too small to detect differences in less frequent adverse effects. E-cigarettes were not significantly more effective than nicotine patches in the primary analysis, but when e-cigarettes use in the nicotine patches arm was accounted for, e-cigarettes were almost twice as effective as patches in all abstinence outcomes. In pregnant smokers seeking help, compared to nicotine patches, e-cigarettes are probably more effective, do not pose more risks to birth outcomes assessed in this study and may reduce the incidence of low birthweight. Routine monitoring of smoking cessation and birth outcomes in pregnant women using nicotine patches and e-cigarettes and further studies are needed to confirm these results. This trial is registered as ISRCTN62025374 and Eudract 2017-001237-65. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 13. See the NIHR Journals Library website for further project information.


Rapid lamina propria retraction and zipper-like constriction of the epithelium preserves the epithelial lining in human small intestine exposed to ischaemia-reperfusion.
To ensure a sufficient barrier between a host and noxious luminal content, the intestinal epithelium must be equipped with efficient mechanisms to limit damage to the epithelial lining. Using a human model, we were able to investigate these mechanisms in the human gut exposed to ischaemia-reperfusion (IR) over the time course of 150 min. In 10 patients a part of jejunum, to be removed for surgical reasons, was selectively exposed to IR. Control tissue was collected, as well as tissue exposed to 30 min of ischaemia with 0, 30 or 120 min of reperfusion. Haematoxylin/eosin staining demonstrated the appearance of subepithelial spaces following 30 min of ischaemia, while the epithelial lining remained intact at this stage. Western blot for myosin light chain kinase (MLCK) revealed a significant increase in protein levels after ischaemia (p < 0.01), and selective staining of MLCK and phosphorylated MLC (pMLC) in lamina propria muscle fibres indicated that appearance of subepithelial spaces was a consequence of active villus contraction. Early during reperfusion, accumulation of pMLC was observed exclusively at the basal side of enterocytes that had lost contact with the collagen-IV-positive basement membrane. These epithelial sheets were pulled together like a zipper, even before these cells were shed. This constriction, verified by increased F-actin and pMLC double staining, accounted for a 45% reduction in virtual wound surface (p < 0.001) at 30 min of reperfusion. In addition, these mechanisms were involved in resealing remaining small epithelial defects, resulting in a fully restored epithelial lining within 120 min of reperfusion. In conclusion, we show in a human in vivo model that the human jejunum has the ability to preserve the epithelial lining during intestinal IR by rapid lamina propria contraction and zipper-like constriction of epithelial cells that are to be shed into the lumen. These newly described phenomena limit exposure to noxious luminal content.


[Large-scale production of monoclonal antibodies using hollow fiber bioreactor].
Development of large-scale monoclonal antibody production using industrial scale hollow fiber bioreactor is described. Hybridoma cell lines H505AC and A306AA were cultivated in the hollow fiber perfusion bioreactor with a total fiber surface area of 7.2 m2 (6 x 1.2 m2) to produce anti-hepatitis B surface antigen (anti-HBsAg) monoclonal antibody IgM and anti-alpha-fetal protein (anti-AFP) monoclonal antibody IgG. The highest anti-HBsAg IgM productivity obtained during 49 days cultivation of H505AC was 0.135 g/day and the total accumulated IgM was 1.90 g. Results from the cultivation of A306AA in the hollow fiber module for 23 days showed the highest anti-AFP IgG productivity and the total accumulated IgG were 0.672 g/day and 7.21 g, respectively.


Clinical characteristics of non-radiographic versus radiographic axial spondyloarthritis in Asia and non-radiographic axial spondyloarthritis in other regions: results of the cross-sectional ASAS-COMOSPA study.
To delineate characteristics of non-radiographic axial spondyloarthritis (nr-axSpA) in Asia versus non-Asian regions, and compare radiographic axSpA (r-axSpA) with nr-axSpA within Asia. Data were collected from the Assessment of SpondyloArthritis international Society-COMOrbidities in SPondyloArthritis database. Categorising patients by region, we compared clinical characteristics between nr-axSpA from Asia vs elsewhere (Europe, the Americas and Africa). Within Asians, we additionally compared patient characteristics of those with nr-axSpA versus r-axSpA. Among 3984 SpA cases, 1094 were from Asian countries. Of 780 axSpA patients in Asia, 112 (14.4%) had nr-axSpA, less than in non-Asian countries (486/1997, 24.3%). Nr-axSpA patients in Asia were predominantly male (75.9% vs 47.1%), younger at onset (22.8 vs 27.8 years) and diagnosis (27.2 vs 34.5 years), and experienced less diagnostic delay (1.9 vs 2.9 years) compared with nr-axSpA in non-Asian countries. Nr-axSpA in Asia exhibited higher human leucocyte antigens-B27 prevalence (90.6% vs 61.9%), fewer peripheral SpA features (53.6% vs 66.3%) and similar extra-articular and comorbid disease rates compared with those with nr-axSpA in non-Asian countries. Disease activity, functional impairment and MRI sacroiliitis were less in nr-axSpA in Asia, with higher rates of non-steroidal anti-inflammatory drug response and less methotrexate and biological disease-modifying antirheumatic drugs use. Within Asia, r-axSpA showed higher disease activity and structural damage compared with nr-axSpA, with no differences in other features. Among axSpA, lower frequency of nr-axSpA was observed in Asia. Our results offer an opportunity to better understand clinical characteristics and optimise diagnostic strategies, such as ensuring access and availability of MRI resources for accurate diagnosis of nr-axSpA in Asia.


Very low risk of light-induced retinal damage during Boston keratoprosthesis surgery: a rabbit study.
The aim of this study was to assess the possibility of light damage to the retina by a surgical microscope during implantation of a Boston Keratoprosthesis (B-KPro) in rabbits. The retinal irradiance from a Zeiss OPMI Lumera S7 operating microscope was measured at the working distance (16.5 cm). Light transmittance through an isolated B-KPro was measured. A B-KPro was implanted into 1 eye of 12 rabbits with the optic covered during the procedure. The operated eyes were then continuously exposed to a fixed light intensity under the microscope for 1 hour. Fluorescein angiography was carried out on days 2 and 9 postsurgery, after which the animals were euthanized. Further, we compared the potential of these retinal exposures to well-accepted light safety guidelines applicable to humans. Light transmittance of B-KPro revealed a blockage of short wavelengths (<390 nm) and of long wavelengths (1660-1750 nm) of light. In addition, the surgical microscope filtered a part of the blue, ultraviolet, and infrared wavelengths. Neither fluorescein angiography nor a histological examination showed any morphological retinal changes in our rabbits. Moreover, the retinal exposures were well below the safety limits. Modern surgical microscopes have filters incorporated in them that block the most damaging wavelengths of light. The B-KPro is made of 100% poly(methyl methacrylate), which makes it in itself a blocker of short wavelengths of light. No damage could be demonstrated in the animal study, and the retinal exposures were well below the safety limits. Together, these results suggest that light exposures during B-KPro surgery present a low risk of photochemical damage to the retina.


Utilization of hepatitis C virus infected donors in heart transplant recipients with elevated MELD-XI score.
The advent of direct-acting antivirals has helped to increase the safe utilization of organs from hepatitis C virus positive (HCV+) donors. However, the outcomes of heart transplantation (HT) using an HCV+ donor are unclear in recipients with underlying liver disease represented by an elevated model for end-stage liver disease excluding international normalized ratio (MELD-XI). The United Network of Organ Sharing database was queried from Jan 2016 to Dec 2021. Post-transplant outcomes stratified by recipient MELD-XI score (low <10.37, medium, 10.38-13.39, and high >13.4) was compared between patients with HT from HCV+ (N = 792) and patients with HT from HCV-negative donors (N = 15,266). The median MELD-XI score was comparable (HCV+, 12.1, vs. HCV-negative, 11.8, p = .37). In the HCV+ group, donors were older (33 vs. 31 years, p < .001). Ischemic time of donor hearts (3.48 vs. 3.28 h, p < .001) and travel distance (250 vs. 157 miles, p < .001) were longer in HCV+ group. In the Kaplan Meier analysis with a median follow-up of 750 days, survival was comparable between the two groups (2-year survival, MELD-XI Low: HCV+, 92.4 ± 3.6% vs. HCV-negative, 91.1 ±.8%, p = .83, Medium: HCV+ 89.2 ± 4.3% vs. HCV-negative, 88.2 ± 1.0%, p = .68, and High: HCV+, 84.9 ± 4.5% vs. HCV-negative, 84.6 ± 1.1%, p = .75) In multivariate Cox hazard models, HCV donors were not associated with mortality in each MELD-XI subgroup (Low: adjusted hazard ratio (aHR), 1.02, p = .94; Medium: aHR, .95, p = .81; and High: aHR, .93, p = .68). Utilization of HCV+ hearts was not associated with an increased risk of adverse outcomes in recipients with an elevated MELD- XI score.


[Cutaneous and mucosal reactions to dental materials].
The concentration of substances released by dental materials is usually too low to cause systemic-toxic effects, but there is the potential to induce dermatoses in especially dentists as well as mucositis in mainly dental patients. The cytotoxic irritative and allergic diseases are successively described categorized according to their pathogenesis. The identification of the diseases, which often have a similar appearance, depends on history-taking and patch testing. Non-dental sensitization is of diagnostic importance.


Early small bowel perforation due to aflibercept.
In patients with malignancy who receive aflibercept based chemotherapy, gastrointestinal perforation is among the reported adverse events with a prevalence of 1.9%. This complication may lead to mortality up to 10.8%. We here report a case of small bowel perforation that occurred fifteen days after the first cycle of aflibercept in a 58-year old female who had metachronous colorectal liver metastases. Emergency laparotomy was performed and revealed a small bowel perforation without any anastomotic dehiscence. Surgery was followed by uneventful outcome. The use of aflibercept in patients with malignancy may be associated with very early gastrointestinal perforation and this should be known by oncologist and surgeons.


Re-alimentation strategy to manoeuvre body condition and carcass characteristics in cull ewes.
Improvement in body condition and carcass traits through nutritional intervention was studied in cull ewes. Sixty-eight adult non-productive Malpura ewes (average body weight 26.7 ± 0.33 kg) were randomly divided into four equal groups: G0 maintained on free grazing for 8 h on protected natural rangeland with ad libitum guar (Cyamopsis tetragonoloba) straw (GS) after grazing; G1, G2 and G3 fed with supplemental concentrate at the rate of 250 g, 2.5% of live weight (LW) and ad libitum, respectively. The experiment was continued for 90 days and daily feed intake, weekly LW and body condition score (BCS) were recorded. Intake and digestibility of nutrients were assessed by indicator method. Rumen fermentation attributes and blood biochemical profile were studied to assess the dietary effects and animals were slaughtered at the end of experiment for evaluation of carcass characteristics. Higher dry matter (DM) intake and improvement in plane of nutrition was observed in G2 and G3 with a higher LW gain (LWG) and improvement in BCS than in G0. The digestibility of DM, organic matter, CP, ADF and cellulose was higher (P < 0.05) in G2 and G3 than in G0. A lower ruminal pH and ammonia N but higher total N and trichloroacetic acid-precipitable N, an increase in holotrichs, spirotrichs and total protozoa population, increase in haemoglobin but decrease in serum total cholesterol and non-esterified fatty acids were observed in high-concentrate-fed groups. Carcass attributes revealed increase (P < 0.05) in empty LW, dressing yield, eye muscle area, subcutaneous and intramuscular fat, decrease in shear force value and higher (P < 0.05) protein content in Longissimus dorsi muscle in test groups than in the control. Above all, the G2 animals had better rumen environment and blood biochemical attributes and consumed more feed with enhanced digestibility that supported higher LWG at better feed conversion efficiency, improvement in BCS and carcass quality. Thus, re-alimentation of cull ewes with challenged feeding of concentrate at 2.5% of LW on a basal roughage diet for a period of 3 months may have promise for better economic return to the farmers with possibly meeting quality mutton for human consumption.


Outcome of treatment in alcoholic women.
One hundred and seventy-eight females (mean age 40.6 +/- 10.2 years) were retrospectively studied by questionnaires for a mean duration of 46 (17-75) months. Sixty-two percent were married or living maritally. One third were working. The mean alcohol intake was 157 +/- 76 g/day and 57.3% had alcohol dependence for less than 5 years. Twenty-seven patients (15%) were lost to follow-up; out of the 151 remaining patients, 7 (4%) refused to answer and 18 (12%) died. Suicide and alcoholism complications were a frequent cause of death. One hundred and twenty-six questionnaires were obtained. Twenty-eight women (22%) were abstinent. A good outcome determined by the state of alcoholization (abstinence or moderate consumption) and the improvement of quality of life, was found in 44% of patients. Absence of marital life and greater alcohol intake were related to a poor outcome, whereas enrollment in a fellowship of recovering alcoholics was more frequent in abstinent patients. The mortality rate was important in alcoholic females. A number of factors were related to the outcome.


Infection control practices in gastrointestinal endoscopy in the United States: a national survey.
To ascertain current infection control practices, endoscope cleaning procedures, perceived risks of infection, and implementation of universal precautions in gastrointestinal endoscopy units in the United States. National mailed survey of gastroenterology nurses and associates conducted anonymously in March 1988. Completed surveys were received from all 50 states and Puerto Rico and from all practice settings. The most common practice setting was private/community hospitals (66%). Of the 4,952 survey forms mailed to all members and to interested nonmembers of the Society of Gastrointestinal Nurses and Associates, 2, 158 (44%) were returned and 2,030 (41%) were completed and evaluable. Of the respondents, 1,487 (73%) were registered nurses. Sixty-seven percent (n = 1,358) of the respondents routinely used an enzymatic cleaner as a step in the instrument decontamination process; 93% (n = 1,879) chemically disinfected instruments after each case; and 88% (n = 1,779) disinfected endoscopes with an aqueous glutaraldehyde product. Respondents reported that they and a significantly smaller proportion of physicians (p less than .001) employed barrier precautions for all endoscopic cases involving possible contact with blood/body fluids of patients known (66% versus 57%, respectively) and not known (12% versus 8%, respectively) to have a bloodborne infection. Endoscopy-related infections, usually bacterial, were reported to have occurred at their institutions by 6% (n = 116) of respondents. We conclude that cleaning, disinfection, and sterilization procedures for gastrointestinal endoscopic instruments vary, that appropriate protective apparel is not always worn, and that some practices may lead to preventable endoscopy-related infection in patients.


Review of recent non-hyperbaric oxygen interventions for mild traumatic brain injury.
Traumatic brain injury (TBI) affects 3.2 to 5.3 million persons in the United States (U.S.), and the impact in the U.S. military is proportionally higher. Consensus is lacking regarding an accepted outcome to measure the effectiveness of interventions to improve the symptoms associated with TBI, and no standard-of-care treatment exists for mild TBI (mTBI). A recent literature review evaluated hyperbaric oxygen therapy (HBO₂) interventions, and findings were mixed. We conducted a systematic review of non-HBO₂ mTBI interventional trials published in 2005-2015 in military and civilian populations. A total of 154 abstracts, seven randomized controlled trials (RCTs) and five pilot studies were reviewed. RCTs were evaluated using Consolidated Standards of Reporting Trials criteria. Results indicated that studies published within the period of review were small pilot studies for rehabilitation therapy and motion capture or virtual reality gaming interventions. Neuropsychological assessments were commonly specified outcomes, and most studies included a combination of symptom and neuropsychological assessments. Findings indicated a lack of large-scale, well-controlled trials to address the symptoms and sequelae of this condition, but results of small exploratory studies show evidence of potentially promising interventions.


Prognostic value of the ankle-brachial index in patients undergoing drug-eluting stent implantation.
Limited data are available regarding the prognostic value of the brachial-ankle index (ABI) in patients with a history of drug-eluting stent (DES) implantation. This study sought to determine the relationship between the ABI and coronary events in patients with DES. A total of 322 patients who underwent both DES implantation and ABI measurement during initial hospitalization were reviewed. Cardiovascular events, including cardiac death, non-fatal acute myocardial infarction and coronary revascularization, were assessed. During the mean follow-up period of 298 ± 58 days, there were 32 cases of cardiovascular events (9.9%). The patients with a lower ABI had more events (2.8% in the highest tertile versus 10.3% in the middle tertile versus 16.8% in the lowest tertile, p = 0.001). According to the multiple Cox regression analysis, the ABI was independently associated with clinical events (the lowest tertile versus the highest tertile of ABI, hazard ratio: 6.35, 95% confidence interval: 1.37-29.32, p=0.018). In addition, the cumulative event rate according to the ABI tertile differed significantly in the Kaplan-Meier curves (log-rank p=0.009), whereas the receiver-operating characteristic curve analysis showed a sensitivity and specificity for predicting cardiovascular events of 62.5% and 66.2%, respectively, with an ABI of 1.057 as the best cut-off value. A lower ABI is associated with poorer cardiovascular outcomes in patients with DES implantation. As a simple and non-invasive parameter, the ABI has the benefit of predicting future cardiovascular events in this population.


Effect of inferior oblique myectomy on primary position when combined with lateral rectus recession for intermittent exotropia.
To evaluate the surgical success and need for adjustment due to overcorrection in patients who undergo inferior oblique myectomy (IOM) combined with lateral rectus recession (LRc) for intermittent exotropia in the setting of inferior oblique overaction. A retrospective chart review was conducted of patients with intermittent exotropia who underwent LRc using adjustable sutures alone versus LRc combined with IOM between January 2010 and July 2018 at our institution. Binocular alignment was recorded before and within one week of surgery. Evaluation measures noted were surgical success (defined as distance alignment of ⩽10 prism diopters) and need for postoperative adjustment due to overcorrection. Of 48 patients, 24 underwent LRc alone and 24 underwent LRc combined with IOM; all 48 patients had adjustable sutures. Surgical success was significantly higher in the LRc alone group (91.6%) compared with the LRc with IOM group (62.5%) (p = 0.036). The need for postoperative adjustment due to overcorrection was also significantly higher in the LRc with IOM group (20.8%) compared with the LRc alone group (0%) (p = 0.049). In this study, more patients needed adjustment for overcorrection after undergoing LRc combined with IOM versus LRc alone. Since the tertiary action of the inferior oblique is abduction it is possible that, in patients with inferior oblique overaction, surgically weakening the inferior oblique causes more esodeviation and overcorrection. Thus, surgical correction of exotropia and inferior oblique overaction using LRc combined with IOM may lead to overcorrection and increased need for postoperative adjustment.


Idiopathic facial nerve palsy.
Paralysis of the face is the commonest peripheral neuropathy, but in the majority of cases the cause remains obscure. The aetiology and management of idiopathic facial paralysis (Bell's palsy) with special reference to experience at the Facial Nerve Clinic of Groote Schuur Hospital are discussed. With reservations, treatment with prednisolone in the very early stages is justified and recommended. Although it is argued that the management of this disorder does not require the special skills of the otologic surgeon, warning is made of the need for caution, especially as regards those patients whose symptom pattern and neurological behaviour are not typical of Bell's palsy.


Mapping of Micro-Tom BAC-End Sequences to the Reference Tomato Genome Reveals Possible Genome Rearrangements and Polymorphisms.
A total of 93,682 BAC-end sequences (BESs) were generated from a dwarf model tomato, cv. Micro-Tom. After removing repetitive sequences, the BESs were similarity searched against the reference tomato genome of a standard cultivar, "Heinz 1706." By referring to the "Heinz 1706" physical map and by eliminating redundant or nonsignificant hits, 28,804 "unique pair ends" and 8,263 "unique ends" were selected to construct hypothetical BAC contigs. The total physical length of the BAC contigs was 495, 833, 423 bp, covering 65.3% of the entire genome. The average coverage of euchromatin and heterochromatin was 58.9% and 67.3%, respectively. From this analysis, two possible genome rearrangements were identified: one in chromosome 2 (inversion) and the other in chromosome 3 (inversion and translocation). Polymorphisms (SNPs and Indels) between the two cultivars were identified from the BLAST alignments. As a result, 171,792 polymorphisms were mapped on 12 chromosomes. Among these, 30,930 polymorphisms were found in euchromatin (1 per 3,565 bp) and 140,862 were found in heterochromatin (1 per 2,737 bp). The average polymorphism density in the genome was 1 polymorphism per 2,886 bp. To facilitate the use of these data in Micro-Tom research, the BAC contig and polymorphism information are available in the TOMATOMICS database.


Multi-stage phase retrieval algorithm based upon the gyrator transform.
The gyrator transform is a useful tool for optical information processing applications. In this work we propose a multi-stage phase retrieval approach based on this operation as well as on the well-known Gerchberg-Saxton algorithm. It results in an iterative algorithm able to retrieve the phase information using several measurements of the gyrator transform power spectrum. The viability and performance of the proposed algorithm is demonstrated by means of several numerical simulations and experimental results.


Bacterial bioreporter detection of arsenic associated with iron oxides.
Bacterial bioreporters are engineered microorganisms that have found recent application as a low-cost method of detecting arsenic (As) in environmental systems. However, no assessment exists of bioreporter detection of particle-bound As. We applied an Escherichia coli-based bioreporter to assess the bioavailability of As(v) adsorbed by goethite (α-FeOOH), 2-line ferrihydrite and As(v) co-precipitated with Fe(iii). We found that As(v) bound to the surface of crystalline goethite was not detected by the bioreporters, which contrasted sharply the 50% detection of As(v) adsorbed by ferrihydrite. In addition, the presence of Ca2+ caused a systematic decrease in the bioreporter-detected As(v) fraction in the ferrihydrite samples. For co-precipitated As(v)-Fe(iii) samples, we found a similar bioreporter-detected As(v) fraction (<0.2) regardless of crystallite size (0.7-2.5 nm) or As Fe-1 surface loading (10-60 mol%). Our results reveal that the bioreporter response depends largely on aggregated particle size, which is expected to physically isolate As(v) from bioreporters by encapsulating surface-bound As(v) in coagulated flocs. Our results show that while bioreporters do not perform optimally in water that contains Fe particles, this method could be developed for sludge testing and for monitoring As levels in the product water of decentralized Fe-based As treatment systems.


Cryosurgery in chronic nasal obstruction.
This is a paper presented to show the results that have been achieved by the utilization of cryosurgery in chronic rhinitis. In my hands, it has worked out very successfully and I offer this as an encouraging modality of treatment for a troublesome group of cases.


Central serous chorioretinopathy: a review of epidemiology and pathophysiology.
Central serous chorioretinopathy (CSCR) is a common retinal cause of vision loss. This review surveys the epidemiology, risk factors, clinical presentation, natural history and pathophysiology of CSCR. Studies suggest an annual incidence rate of 10 per 100 000 in men, with CSCR occurring six times more commonly in men compared with women. Most acute CSCR cases resolve spontaneously within 2-3 months. Prognosis is highly dependent on presenting visual acuity; patients with initial visual acuities of 6/6 remain at that level, while patients with initial visual acuities of less than 6/9 recover on average two to three Snellen lines over the next few years. The main risk factors for CSCR are systemic corticosteroid use, type A personality, pregnancy and endogenous Cushing's syndrome. The pathophysiology of CSCR remains obscure, although disorders in both the choroidal circulation and retinal pigment epithelium are implicated.


DNA methylation pattern of the SLC25A43 gene in breast cancer.
Solute carrier family 25A member 43 (SLC25A43) gene is a putative tumor suppressor gene that undergoes loss of heterozygosity (LOH) in human epidermal growth factor receptor 2 (HER2) positive breast cancer. Also, knockdown of SLC25A43 in cell lines influences cell turnover and metabolism. Absence of mutations in this gene in breast cancers prompted us to study methylation as an alternate mechanism for gene inactivation of this X encoded gene. Quantification of CpG site methylation using pyrosequencing was performed upstream of the SLC25A43 gene and at its 5' end in a cohort of breast tumor tissues (n = 80, HER2 positive or negative) with different SLC25A43 gene deletion status. Compared with control tissue, cancer tissues had lower levels of methylation at the 5' and 3' shores of the gene. Cancer tissues with no deletion in the SLC25A43 gene (Del (-)) had higher methylation in the CpG island (CGI) of the gene than cancers carrying the deletion (Del (+)). Methylation in the CGI of the SLC25A43 gene was negatively correlated with age at diagnosis. In HER2 positive breast cancer, ER negativity and lymph node positivity was associated with higher methylation in the CGI and in the adjacent shores of this gene. Our results suggest that methylation in the CGI of the SLC25A43 gene could be an alternate mechanism of gene silencing in the absence of LOH. Also, associations between site-specific methylation and clinicopathological parameters suggest that epigenetic changes in SLC25A43 gene could be of importance in breast carcinogenesis.


Alloantigen-activated lymphocytes from mice bearing a spontaneous "nonimmunogenic" adenocarcinoma inhibit its growth in vivo by recruiting host immunoreactivity.
Nylon wool columns eluting lymphocytes from the spleen of mice bearing a clinically evident spontaneous, nonimmunogenic adenocarcinoma of recent origin (TS/A) do not display cytotoxic response, release of lymphokines, and proliferation in vitro against TS/A cells, nor do they inhibit TS/A tumor growth in a Winn-type neutralization assay in vivo. After 5-day co-culture with allogeneic spleen cells from mice differing at multiple minor histocompatibility antigens only, these lymphocytes are still noncytolytic against TS/A cells, whereas they release interferon-gamma, mediate delayed-type hypersensitivity (DTH) reactions, and inhibit TS/A tumor growth in the Winn assay. In the Winn test, alloactivated lymphocytes from TS/A tumor-bearing mice are more effective than those from normal mice on a per cell basis. The induction of this TS/A tumor inhibition ability depends on the presence in the cultures of Thy-1+ lymphocytes. The presence of Lyt-2+ lymphocytes is also important, whereas that of asialo GM1+ is not. The TS/A inhibition in vivo by alloactivated lymphocytes mostly depends on Thy-1+, Lyt-2- and asialo GM- lymphocytes, even though a few Thy- cells are also very efficient tumor inhibitors. The alloactivated lymphocytes inhibit TS/A tumor growth by recruiting the radiosensitive effector mechanisms of the recipient mice required for ultimate tumor rejection. TS/A tumor rejection leaves a specific DTH and an immunologic memory resulting in rejection of a second lethal TS/A challenge in a significant number of mice.


Serum levels of copper but not zinc are associated with head and chest cold in the NHANES.
Common colds are among the top reasons why children miss school and adults miss work. The Centers for Disease Control and prevention estimates that there are millions of cases of the common cold in the United States each year. The essential trace elements zinc and copper have immunomodulatory functions, and zinc has been reported to reduce the general risk of infection, whereas the copper-to-zinc ratio has been associated with an increased risk of incident infections in middle-aged men. Studies involving these two trace elements are generally scarce and were often limited to men. We used data from the National Health and Nutrition Examination Surveys (NHANES) to examine potential associations between head or chest cold events and serum levels of copper and zinc in n = 2795 NHANES participants enrolled between 2011 and 2016. Comparing participants with and without an event of head or chest cold in the last 30 days, no significant differences were found in the serum levels of both trace elements. Notably, copper levels tended to be slightly higher in participants with a recent infection (121.56 (2.69) µg/dl) as compared to participants without infection (117.755 (1.04) µg/dl; p = 0.119). In multivariate logistic regression models adjusting for confounders, copper levels were significantly associated with increased odds for a previous head/chest cold (OR: 1.93 (CI: 1.07-3.47), p = 0.028). Notably, no significant associations were found for zinc and the copper-to-zinc ratio. Elevated copper levels were associated with head and chest cold events in the past 30 days. Whether elevated copper levels reflect a pro-inflammatory infection-predisposing status or whether they were elevated subsequent to the infectious event in some individuals in the sense of a reversed causality remains subject to future research.


Meal-specific dietary patterns and their contribution to overall dietary patterns in the Japanese context: Findings from the 2012 National Health and Nutrition Survey, Japan.
Most studies on dietary patterns have focused on the total daily intake of foods without differentiating intake at specific eating occasions. The aim of this study was to identify meal-specific (breakfast, lunch, and dinner) dietary patterns and examine their contribution to overall dietary patterns, using data from the 2012 National Health and Nutrition Survey, Japan. Dietary intake was assessed with a 1-d weighed dietary record for 15 618 Japanese adults ≥20 y of age. Using principal component analysis based on daily consumption of 22 food groups, four overall dietary patterns were identified: vegetable/fruit/fish/pulse, bread/dairy, meat/fat, and noodle/seasoning patterns. Four meal-specific dietary patterns, which were independently identified in the same manner based on consumption at each eating occasion, were as follows: • Breakfast: rice/vegetable/fish/pulse/seasoning, bread/dairy/fruit/sugar, meat/egg/fat, and tea/coffee patterns; • Lunch: bread/dairy, noodle/seasoning, meat/fat, and vegetable/pulse/potato/sugar patterns; and • Dinner: meat/vegetable/seasoning, noodle/alcoholic beverage, fish/sugar/alcoholic beverage, and other grains/fat patterns. The major contributors to interindividual variation in the vegetable/fruit/fish/pulse overall dietary pattern included the rice/vegetable/fish/pulse/seasoning breakfast (28%), the vegetable/pulse/potato/sugar lunch (15%), and the fish/sugar/alcoholic beverage dinner (19%). For other overall dietary patterns, the major contributors were generally patterns with similar characteristics, namely the bread/dairy/fruit/sugar breakfast (33%) and the bread/dairy lunch (24%) for the bread/dairy overall dietary pattern; the meat/egg/fat breakfast (13%), the meat/fat lunch (33%), the meat/vegetable/seasoning dinner (28%), and the other grains/fat dinner (11%) for the meat/fat overall dietary pattern; and the noodle/seasoning lunch (51%) and the noodle/alcoholic beverage dinner (25%) for the noodle/seasoning overall dietary pattern. Major meal-specific dietary patterns were identified in the Japanese context, which differentially contributed to major overall dietary patterns.


CCRT (computer controlled radiation therapy) for non-small cell lung cancer: sensitivity of clinical gains to organ tolerance restrictions.
A method is described for allowing the entrance angles of beams to vary along the longitudinal axis of the target volume using a computer controlled radiation therapy (CCRT) treatment technique. The increase in tumor dose potentially available with this technique is evaluated for the case of a non-small cell carcinoma of the lung for which treatment is constrained by a clinically relevant tolerance condition. Tolerance is expressed in terms of that volume of unaffected contralateral lung allowed to receive greater than 20 Gy. The evaluation is repeated with small changes made to the constraining condition in order to explore the sensitivity of the dose gain to the definition of tolerance. For the chosen example, at least an additional 10 Gy could be prescribed to the tumor with the CCRT technique when the 20 Gy contralateral lung volume was held to less than 30%. A gain of 7 Gy was found when the 20 Gy volume was held to 27% and 1 Gy when the 20 Gy volume was reduced to 25%. CCRT treatment can result in a significant dose gain under a clinically relevant condition for tolerance. Its measured advantage strongly depends on the dose constraints specified. Sensitivity analysis is necessary to meaningfully evaluate the merits of alternative treatment techniques.


Interplay of Ferritin Accumulation and Ferroportin Loss in Ageing Brain: Implication for Protein Aggregation in Down Syndrome Dementia, Alzheimer's, and Parkinson's Diseases.
Iron accumulates in the ageing brain and in brains with neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Down syndrome (DS) dementia. However, the mechanisms of iron deposition and regional selectivity in the brain are ill-understood. The identification of several proteins that are involved in iron homeostasis, transport, and regulation suggests avenues to explore their function in neurodegenerative diseases. To uncover the molecular mechanisms underlying this association, we investigated the distribution and expression of these key iron proteins in brain tissues of patients with AD, DS, PD, and compared them with age-matched controls. Ferritin is an iron storage protein that is deposited in senile plaques in the AD and DS brain, as well as in neuromelanin-containing neurons in the Lewy bodies in PD brain. The transporter of ferrous iron, Divalent metal protein 1 (DMT1), was observed solely in the capillary endothelium and in astrocytes close to the ventricles with unchanged expression in PD. The principal iron transporter, ferroportin, is strikingly reduced in the AD brain compared to age-matched controls. Extensive blood vessel damage in the basal ganglia and deposition of punctate ferritin heavy chain (FTH) and hepcidin were found in the caudate and putamen within striosomes/matrix in both PD and DS brains. We suggest that downregulation of ferroportin could be a key reason for iron mismanagement through disruption of cellular entry and exit pathways of the endothelium. Membrane damage and subsequent impairment of ferroportin and hepcidin causes oxidative stress that contributes to neurodegeneration seen in DS, AD, and in PD subjects. We further propose that a lack of ferritin contributes to neurodegeneration as a consequence of failure to export toxic metals from the cortex in AD/DS and from the substantia nigra and caudate/putamen in PD brain.


Decoding Polarization in a Single Achiral Gold Nanostructure from Emitted Far-Field Radiation.
The emergence of optical chirality in the light emitted from plasmonic nanostructures is commonly associated with their geometrical chirality. Although it has been demonstrated that even achiral structures can exhibit chiral near-fields, the existence of chiroptical far-field responses of such structures is widely neglected. In this paper, we present a detailed analysis of the polarization state in a single planar achiral plasmonic nanostructure that sustains more than one prominent plasmon mode. In consideration of the relative phase, the superposition of the fields associated with these modes determines the polarization state of the emitted light in the far-field. Supported by simulations of the surface charge distribution of the particle, we show that the polarization state of the emitted light is already determined in the near-field. The chiroptical far-field responses are analyzed by polarized single-particle dark-field scattering spectroscopy. We introduce an analytical model that enables us to obtain the polarization information from the spectra of structures with dipolar resonances taken under unpolarized illumination. The same principle is confirmed in polarimetric spectroscopy measurements on rhomboids with systematically varied angles, therefore, introducing increasing values of geometrical chirality to the structures. The agreement between the calculation and measurement demonstrates the general validity of our model for both chiral and achiral structures.


Neurosurgical rotations or clerkships in US medical schools.
Medical student exposure to neurosurgery is limited. To improve the educational interactions between neurosurgeons and medical students as well as neurosurgical medical student rotations or clerkships (NSCs) we must first understand the current status. Two questionnaires were sent, one to every neurosurgery course coordinator or director at each US neurosurgery residency program (99 questionnaires) and one to the associated parent medical school dean's office (91 questionnaires), to assess the current status of NSCs and the involvement of neurosurgeons at their respective institutions. We received responses from 86 (87%) of 99 neurosurgery course coordinators or directors and 64 (70%) of 91 medical school deans' offices. Most NSCs do not have didactic lectures (53 [62%] of 86 NSCs), provide their medical students with a syllabus or educational handouts (53 [62%] of 86), or have a recommended/required textbook (77 [90%] of 86). The most common method of evaluating students in NSCs is a subjective performance evaluation. Of 64 medical school deans, 38 (59%) felt that neurosurgery should not be a required rotation. Neurosurgical rotations or clerkships are primarily offered to students in their 4th year of medical school, which may be too late for appropriate timing of residency applications. Only 21 (33%) of 64 NSCs offer neurosurgery rotations to 3rd-year students. There is significant room for improvement in the neurosurgeon-to-medical student interactions in both the NSCs and during the didactic years of medical school.


Hepatic epithelioid hemangioendothelioma associated with acute disseminated encephalomyelitis by a possible paraneoplastic process.
Epithelioid hemangioendothelioma (EHE) is a low-grade, malignant vascular neoplasm that frequently involves the liver, lungs, bone, and soft tissue. Although not commonly associated with a paraneoplastic syndrome, paraneoplastic syndromes in the setting of EHE have been reported. Acute disseminated encephalomyelitis (ADEM) is an acute, autoimmune, demyelinating disorder of the central nervous system that most commonly occurs after an infection or vaccination. We present the case of a 23 year old female who developed the acute onset of fevers, tremors, right sided hemiplegia, global aphasia, and incontinence of urine and stool. MRI demonstrated findings consistent with a demyelinating disorder and brain biopsy confirmed the diagnosis of ADEM. The patient's work up revealed multiple liver lesions which were biopsy proven EHE. This case report discusses the diagnosis and treatment of two concurrent rare disease processes and the possible association of the processes via a paraneoplastic syndrome.


Antisocial behavioral syndromes among residential drug abuse treatment clients.
We compared residential addictions treatment clients meeting full criteria for antisocial personality disorder (ASPD+) with those reporting syndromal levels of antisocial behavior only in adulthood (AABS+) on demographics, antisocial symptomatology, drug history, axis I comorbidity and characteristics of index treatment episode. We examined these issues in the sample as a whole, as well as separately in male and female respondents. Among both men and women, ASPD+ initiated their antisocial behavior earlier, met more ASPD criteria and endorsed more violent symptoms, than AABS+. Male ASPD+ also met criteria for more lifetime axis I diagnoses and reported more years of drug involvement than male AABS+. Trends were observed toward poorer retention in treatment among ASPD+ than among AABS+ participants of both genders randomized to a planned duration of 180 days, but retention did not differ between ASPD+ and AABS+ randomized to a planned duration of 90 days. Our findings, which replicate and extend previously published results, carry potential implications for treatment programming and for the nosology of ASPD.