Anaplastic thyroid carcinoma following radioactive iodine therapy for graves' disease.
Radioactive iodine (RAI) therapy has been used as a treatment option for Graves' disease, and it has been widely accepted to be safe. On the other hand, some evidence suggests that RAI therapy is possibly associated with a small increased risk of thyroid cancer. Herein, we report a rare case of anaplastic thyroid carcinoma (ATC) associated with Graves' disease, following RAI treatment. A 42-year-old woman had been diagnosed with Graves' disease and although she was treated with an antithyroid drug, she remained in a hyperthyroid state, which led to two RAI treatments. More than 10 years later, the patient revisited our clinic due to hoarseness, dysphagia, and dyspnea, which had lasted for 2 months. Neck computed tomography suggested thyroid carcinoma and a lymph node biopsy showed metastatic papillary carcinoma. The patient underwent total thyroidectomy and was finally diagnosed as having an ATC. It is not clear if the occurrence of ATC reported here was influenced by the RAI therapy or alternatively, it may only represent the delayed recognition of a rare change in the natural history of Graves' disease. Nevertheless, this report is worthwhile since it presents a very rare case of ATC that occurred eleven years after the RAI therapy for Graves' disease.


Malformations in twins and their siblings, Norway, 1967-79.
During 1967-79 the population-based Medical Birth Registry of Norway registered 7,660 twin pairs (1% of births) born to 7,596 mothers, who gave birth to 6,608 additional infants (twin siblings). The total rate of malformations among twins (278.1/10,000) was not significantly different than among singletons (302.1/10,000), nor among twin siblings (314.8/10,000). By specific type of defect, twins had significantly higher rates than singletons of central nervous system (CNS) defects (Rate Ratio = 1.8) and cardiovascular defects (RR = 1.5). The twins also had a significantly low rate of congenital hip dislocation (RR = 0.4), which may explain the relatively low incidence of malformations in twins. Like-sex (LS) twins had a slightly higher rate of malformations than unlike-sex (US) twins (RR = 1.1), as well as a higher rate of CNS defects (RR = 3.0). The siblings also had a significantly increased rate of CNS defects compared to singletons (RR = 1.9), but not of cardiovascular defects (RR = 0.9). The results indicate that twins have elevated rates of at least some congenital malformations. The observations about CNS defects suggest common factors that can lead to either like-sex twinning, CNS defects, or both. The increased frequency of cardiovascular defects in twins appears to be associated with the biologic conditions of twinning.


Association between MYOC.mt1 promoter polymorphism and risk of primary open-angle glaucoma: a systematic review and meta-analysis.
The aim was to review all published studies that investigated the association between MYOC.mt1 polymorphism and the risk of primary open-angle glaucoma (POAG). Electronic databases were searched for relevant articles in English. Inclusion and exclusion criteria were established according to the criteria of the Cochrane Methods Group. Studies were included if participants were patients with POAG (adult- or juvenile-onset), had extractable data on both genotypes of MYOC.mt1, phenotypes of severity, and reasonable controls. Statistical analysis was performed using SPSS 13.0 for Windows and RevMan 4.2. Four case-control studies of 835 cases and 530 controls were included in the meta-analysis. The pooled odds ratio (OR) to develop POAG with and without MYOC.mt1 from a fixed-effects model was 1.06 (95%CI: 0.81-1.38, P=0.67), i.e. MYOC.mt1 carriers did not have significantly higher risk of developing POAG than non-carriers. There was also no significant association between the -1000G allele and increased risk (OR=1.05, 95%CI: 0.83-1.32, P=0.71). Comprehensive summarization was done to determine the influence of MYOC.mt1 on the severity of optic disk changes and visual function loss in POAG cases. There was evidence of publication bias from funnel-plot asymmetry and Egger's test. Evidence for an association between MYOC.mt1 and the risk of POAG is limited. These results suggest that MYOC.mt1 polymorphism does not have significant influence on the risk of POAG development or its severity. However, the evidence of publication bias suggests that more large prospective cohort studies with precise design are required to confirm an association between MYOC.mt1 and POAG.


Oral controlled release formulation for highly water-soluble drugs: drug--sodium alginate--xanthan gum--zinc acetate matrix.
An oral controlled release formulation matrix for highly water-soluble drugs was designed and developed to achieve a 24-hour release profile. Using ranitidine HCl as a model drug, sodium alginate formulation matrices containing xanthan gum or zinc acetate or both were investigated. The caplets for these formulations were prepared by direct compression and the in vitro release tests were carried out in simulated intestinal fluid (SIF, pH 7.5) and simulated gastric fluid (SGF, pH 1.2). The release of the drug in the sodium alginate formulation containing only xanthan gum completed within 12 hours in the SIF, while the drug release in the sodium alginate formulation containing only zinc acetate finished almost within 2 hours in the same medium. Only the sodium alginate formulation containing both xanthan gum and zinc acetate achieved a 24-hour release profile, either in the SIF or in the pH change medium. In the latter case, the caplet released in the SGF for 2 hours was immediately transferred into the SIF to continue the release test. The results showed that the presence of both xanthan gum and zinc acetate in sodium alginate matrix played a key role in controlling the drug release for 24 hours. The helical structure and high viscosity of xanthan gum might prevent zinc ions from diffusing out of the ranitidine HCl--sodium alginate--xanthan gum--zinc acetate matrix so that zinc ions could react with sodium alginate to form zinc alginate precipitate with a cross-linking structure. The cross-linking structure might control a highly water-soluble drug to release for 24 hours. Evaluation of the release data showed the release mechanism for the novel formulation might be attributed to the diffusion of the drug.


[Breast echography].
The ultrasonography of the breast is an essential technique in the diagnosis of mammary disease as mammography and fine needle aspiration. Ultrasound is extremely reliable in differentiating cystic from solid lesions. Three signs are the most significant in the diagnosis between benign tumors and well circumscribed cancer: shape and margins of the mass, depth/width ratio, feature of the connective tissue and adjacent structures. In association with mammography, sonography is most likely significant in breast screening cancer.


Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation.
Protein tyrosine phosphatases (PTPs) catalyze the hydrolysis of phosphotyrosine from specific signal-transducing proteins. Although regulatory mechanisms for protein kinases have been described, no general mechanism for controlling PTPs has been demonstrated. Numerous reports have shown that cellular redox status plays an important role in tyrosine phosphorylation-dependent signal transduction pathways. This study explores the proposal that PTPs may be regulated by reversible reduction/oxidation involving cellular oxidants such as hydrogen peroxide (H2O2). Recent reports indicated that H2O2 is transiently generated during growth factor stimulation and that H2O2 production is concomitant with relevant tyrosine phosphorylation. By use of recombinant enzymes, the effects of H2O2 on three PTPs [PTP1, LAR (leukocyte antigen-related), and VHR (vaccinia H1-related)] and three distinct serine/threonine protein phosphatases (PPs: PP2Calpha, calcineurin, and lambda phosphatase) were determined. Hydrogen peroxide had no apparent effect on PP activity. In contrast, PTPs were rapidly inactivated (kinact = 10-20 M-1 s-1) with low micromolar concentrations of H2O2 but not with large alkyl hydroperoxides. PTP inactivation was fully reversible with glutathione and other thiols. Because of the slower rate of reduction, modification occurred even in the presence of physiological thiol concentrations. By utilization of a variety of biochemical techniques including chemical modification, pH kinetic studies, and mutagenesis, the catalytic cysteine thiolate of PTPs was determined to be the selective target of oxidation by H2O2. By use of the electrophilic reagent 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole (NBD-Cl), it was shown that a cysteine sulfenic acid intermediate (Cys-SOH) is formed after attack of the catalytic thiolate on H2O2. A chemical mechanism for reversible inactivation involving a cysteine sulfenic acid intermediate is proposed.


Abnormal haemoglobins, thalassaemias, and hereditary ovalocytosis in the Papuan Gulf area.
In 50 Kerema or Kairuku individuals of the Papuan Gulf Area, the amount of beta thalassaemia as indicated by the finding of a raised level of Hb A2 was found to be 6%, and of hereditary ovalocytosis 16%. There was one example of both conditions occurring together. No haemoglobin abnormalities apart from raised Hb A2 level were found.


Preparedness and the importance of meeting the needs of healthcare workers: a qualitative study on Ebola.
Healthcare workers (HCWs) face specific challenges in infectious disease outbreaks, which provide unusual, new events with exposure risk. The fear of infection or new, unknown tasks in an unfamiliar setting, for example, may complicate outbreak management. To gain insight into how healthcare organizations can prepare to meet the needs of their HCWs by capturing the experiences of HCWs with patients with suspected Ebola virus disease. We conducted 23 in-depth interviews with HCWs, of whom 20 worked in a Dutch university hospital and three worked in a regional ambulance service. We invited HCWs who cared for patients with suspected Ebola or who were on the team preparing for admission of such patients in the period 2014-2015. The HCWs were stressed and anxious, but most rated their overall experience as positive. We categorized the reported experiences in three main themes, namely, experiences related to: (i) the novelty of the threat, (ii) the risk of infection and fear of transmission, and (iii) the excessive attention. Our results underline the importance of a supportive working environment suitable for crises. The experiences of HCWs dealing with patients with suspected Ebola can direct improvements in generic preparedness for highly transmissible diseases.


The expression and purification of LpxA of Chlamydia trachomatis and preparation of its polyclonal antibody.
The purpose of this study is to purify the LpxA protein of Chlamydia trachomatis (Ct) and prepare the polyclonal antibody against LpxA protein, so as to lay a foundation for studying the function of LpxA protein. The LpxA gene was amplified by PCR. The expression plasmid pET28a-LpxA was constructed by using pET28a as the vector. The fusion protein containing 6 histidine tag was induced by IPTG and purified by Ni2+ chromatography gel. The purified His-LpxA protein was used as an immunogen to immunize New Zealand rabbits subcutaneously through the back to prepare polyclonal antibody. Immunoblotting was used to detect the reaction between the antibody and His-LpxA. The determination of polyclonal antibody titer was detected by ELISA. The relative molecular weight of His-LpxA was 32.8 kDa, and it could be expressed in Escherichia coli. The purity of the purified protein was about 95%. After immunizing New Zealand rabbits, the antiserum was able to recognize the recombinant His-LpxA protein with a titer greater than 1:10240. In this study, LpxA protein was successfully purified and antiserum was prepared, which provided an experimental basis for studying the function of LpxA protein.


2018 international consensus meeting on musculoskeletal infection: Summary from the biofilm workgroup and consensus on biofilm related musculoskeletal infections.
Biofilm-associated implant-related bone and joint infections are clinically important due to the extensive morbidity, cost of care and socioeconomic burden that they cause. Research in the field of biofilms has expanded in the past two decades, however, there is still an immense knowledge gap related to many clinical challenges of these biofilm-associated infections. This subject was assigned to the Biofilm Workgroup during the second International Consensus Meeting on Musculoskeletal Infection held in Philadelphia USA (ICM 2018) (https://icmphilly.com). The main objective of the Biofilm Workgroup was to prepare a consensus document based on a review of the literature, prepared responses, discussion, and vote on thirteen biofilm related questions. The Workgroup commenced discussing and refining responses prepared before the meeting on day one using Delphi methodology, followed by a tally of responses using an anonymized voting system on the second day of ICM 2018. The Working group derived consensus on information about biofilms deemed relevant to clinical practice, pertaining to: (1) surface modifications to prevent/inhibit biofilm formation; (2) therapies to prevent and treat biofilm infections; (3) polymicrobial biofilms; (4) diagnostics to detect active and dormant biofilm in patients; (5) methods to establish minimal biofilm eradication concentration for biofilm bacteria; and (6) novel anti-infectives that are effective against biofilm bacteria. It was also noted that biomedical research funding agencies and the pharmaceutical industry should recognize these areas as priorities. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.


Automated morphometric description of human corneal endothelium from in-vivo specular and confocal microscopy.
Corneal images acquired by in-vivo specular and confocal microscopy provide clinical information on the cornea endothelium health state. Indeed, the normal hexagonal shape of endothelial cells is usually affected by age and pathologies. At present, the analysis is based on manual or semi-automatic methods and the segmentation of a large number of endothelial cells is required for a meaningful estimation of the clinical parameters. We propose an automated method that detects the centers of endothelial cells by convolving the original image with customized two-dimensional kernels, derives a structure made by connected vertices from the recognized centers using the Euclidean distance, and fine-tunes the derived structure through a genetic algorithm, which combines information about the typical regularity of endothelial cells shape with the pixels intensity of the actual image. The final structure of connected vertices forms a set of polygons that fit the underlying cells contours. From these contours the morphometric parameters of clinical interest can be easily computed. The procedure was applied to 15 images acquired with the SP-3000P (Topcon, Japan) specular microscope and 15 images acquired with the Confoscan4 (Nidek Technologies, Italy) confocal microscope, from both healthy and pathological subjects. Ground truth values for the morphometric parameters were obtained from manually carefully drawn cell contours. Results show that the mean percent absolute difference between the automated and the manual estimate of the clinical parameters is between 2 and 6%, and no statistically significant difference was found between them. The proposed totally automatic method appears capable of detecting contour of hundreds of cells covering a large area, and of obtaining a reliable estimation of the relevant morphometric parameters used in clinical practice.


syn-Selective Difunctionalization of Bicyclobutanes Enabled by Photoredox-Mediated C-S σ-Bond Scission.
Given the importance of cyclic frameworks in molecular scaffolds and drug discovery, it is intriguing to precisely forge and manipulate ring systems in synthetic chemistry. In this field, the intermolecular synthesis of densely substituted cyclobutanes with precise diastereocontrol under simple reaction conditions remains a challenge. Herein, a photoredox strategy for the difunctionalization of bicyclo[1.1.0]butanes (BCBs) under high regio- and syn-selectivity is disclosed. C-S σ-bond cleavage of partially unsaturated sulfur-containing bifunctional reagents in an overall strain-release-driven process enables the thio-alkynylation, -alkenylation, and -allylation of BCBs under mild conditions and demonstrates the generality of this protocol. Mechanistic studies suggest that the intermediacy of cyclic distonic radical cations might be key for the efficient scission of C-S σ-bonds and the origin of diastereoselectivity.


Interstitial high-dose-rate brachytherapy as salvage treatment for locally recurrent prostate cancer after definitive radiation therapy: Toxicity and 5-year outcome.
We report our results with interstitial high-dose-rate brachytherapy (HDR-BT) as a salvage therapy option after external beam therapy with or without BT. Emphasis was put on toxicity and 5-year outcome. From 2003 to 2011, 29 patients with local failure after previous radiotherapy for prostate cancer were treated with salvage interstitial HDR-BT. The diagnosis of local recurrence was made on the basis of choline positron emission tomography. Salvage HDR-BT was given in three fractions with a single dose of 10 Gy per fraction and weekly. The target volume covered the peripheral zone of the prostate and the positron emission tomography-positive area. Acute and late toxicities were documented according to common terminology criteria for adverse events (CTCAE v 4.0). Twenty-two patients with minimum followup of 60 months were analyzed. The 5-year overall survival was 95.5% with a disease-specific survival of 100%. The 5-year biochemical control was 45%. Late grade 2 gastrointestinal toxicities were observed in two patients (9%). No grade 3 or higher gastrointestinal late toxicities were observed. Urinary incontinence found in 2 patients (9%) and grade 2 obstruction of urinary tract occurred in one patient (4%). Interstitial HDR-BT was feasible and effective in the treatment of locally recurrent prostate cancer after definitive radiotherapy. The long-term toxicity was low and acceptable.


Phyllanthin inhibits MOLT-4 leukemic cancer cell growth and induces apoptosis through the inhibition of AKT and JNK signaling pathway.
Among cancers, leukemia is a multistep progression that involves genetic modifications of normal hematopoietic progenitor cells to cancerous cells. In recent times, leukemia cases and their mortality rate have increased rapidly. Therefore, the immense need for a therapeutic approach is crucial that can control this type of cancer. Phyllanthin is a lignan compound constituent from the Phyllanthus species and has numerous beneficial effects as a dietary component. The present study aims to determine the impact of phyllanthin on the MOLT-4 cytotoxic effect. MOLT-4 cells and MS-5 cells were cultured at different concentrations of phyllanthin (5, 10, 25, 50, 75, and 100 μM/ml), and the viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The level of reactive oxygen species, the membrane potential of mitochondria, apoptosis by 2',7'-dichlorofluorescin-diacetate (DCF-DA), rhodamine, acridine orange (AO)/ethidium bromide (EB), 4',6-diamidino-2-phenylindole (DAPI)/propidium iodide (PI) staining, gene expression of signaling molecules, and protein levels were assessed by reverse-transcription polymerase chain reaction and western blot analysis. Phyllanthin did not show toxicity toward MS-5 cells and significantly decreased the cell viability of MOLT-4 cells with an IC50 value of 25 µM/ml. Also, phyllanthin induced the production of reactive oxygen species and led to the loss of mitochondrial membrane potential. AO/EB and DAPI/PI staining fluorescent image confirmed the induction of apoptosis by phyllanthin treatment. The messenger RNA (mRNA) expression of cell cycle regulator cyclin D1, antiapoptotic gene Bcl-2, NF-κB, and TNF-α decreased, but the proapoptotic Bax mRNA expression was increased. The phosphorylated protein levels of p-PI3K1/2, p-ERK1/2, and p-AKT were decreased, whereas the levels of p-p38 and p-JNKT1/2 increased. Our results confirmed that phyllanthin inhibits the MOLT-4 cells, increases apoptosis, and inhibits MOLT-4 migration and cell invasion. Therefore, phyllanthin can be used as a potential target for leukemia treatment.


[1-(Phenylseleno)alkyl]stannanes-mixed selenium/tin analogs of acetals: preparation from alpha-hydroxystannanes and use for generating selenium-stabilized carbanions.
Selenium-stabilized carbanions are available by a route that does not involve acid-catalyzed formation of selenoacetals. Aldehydes are converted first into alpha-hydroxystannanes and then into alpha-(phenylseleno)stannanes. Treatment with BuLi affords selenium-stabilized carbanions by preferential Sn/Li exchange.


Experimental endolymphatic hydrops and glycerol. Electrophysiologic study.
The object of the present study was to evaluate electrophysiologically the therapeutic effect of glycerol on the cochlear function of guinea pigs in which experimental hydrops had been surgically induced. Fifteen albino guinea pigs were used. Each animal was chronically implanted to follow the evolution of hearing. The experimental protocol considered 3 groups of guinea pigs (5 animals each). Group 1 received no drug treatment, while groups 2 and 3 were given glycerol orally at 0.75 and 0.50 g/kg of body weight once a day for 4 months. The audiograms of the animals treated with glycerol showed a statistically significant hearing improvement compared with the control group. Clinically, our results seem to support the view of those who favor the use of glycerol for the medical treatment of Meniere's disease at an early stage.


The role played by tumor necrosis factor during localized and systemic infection with Streptococcus pneumoniae.
Tumor necrosis factor (TNF) has been proposed as a major mediator of host resistance in murine models of Streptococcus pneumoniae infection; in humans, anti-TNF therapies have been implicated in increased susceptibility to pneumococcal infection. Here, we use nonlethal (serotype 6B) and lethal (serotype 3) S. pneumoniae, neutralizing monoclonal antibodies to TNF, and TNF gene-deficient mice to reexamine the role played by TNF in antistreptococcal responses. After nonlethal challenge, primary resistance and all examined parameters of the cellular inflammatory response occurred independently of TNF activity. After lethal challenge, TNF deficiency resulted in more-rapid death but did not affect lung inflammation. However, the livers of the TNF gene-deficient mice, but not of the control mice, exhibited extensive signs of systemic disease. TNF, therefore, is dispensable for a complete cellular pulmonary inflammatory response to S. pneumoniae infection but enhances survival from disseminated lethal infection, at least in part by delaying systemic organ damage.


Self inflicted corneal abrasions due to delusional parasitosis.
The authors report a case of self inflicted bilateral corneal abrasions and skin damage due to ophthalmic and cutaneous delusional parasitosis. A male in his 50s presented with a 10 year history of believing that parasites were colonizing his skin and biting into his skin and eyes. The patient had received extensive medical evaluations that found no evidence that symptoms were due to a medical cause. He was persistent in his belief and had induced bilateral corneal abrasions and skin damage by using heat lamps and hair dryers in an attempt to disinfect his body. The patient was treated with olanzapine along with treatment for his skin and eyes. His delusional belief system persisted but no further damage to his eyes and skin was noted on initial follow-up.


Dentoskeletal effects of the maxillary splint headgear in the early correction of Class II malocclusion.
To compare dentoskeletal changes produced by the maxillary splint headgear and cervical headgear appliance during the early phase of Class II treatment, specially the initial overjet and upper incisors position. In this retrospective study, 28 Class II patients treated with the maxillary splint headgear (MSG, mean age 10.1 ± 1.9 years) and 28 Class II patients treated with cervical headgear (CHG, mean age 9.5 ± 1.9 years) were evaluated before and after treatment. Statistical comparisons between the two groups for cephalometric measurements at T1 and for T2-T1 changes were performed by means of independent sample t tests. The MSG showed a significantly greater reduction of the overjet in comparison to the CHG (- 2.4 mm and - 0.7 mm, respectively) and a significantly greater maxillary incisor uprighting (- 1.8 mm and 0.4 mm, respectively). In the MSG, overjet correction was due mainly to mandibular advancement (3.5 mm), while the correction of molar relationship (3.9 mm) was 64% skeletal and 36% dentoalveolar. In the CHG, the overjet correction was also more skeletal, due to mandibular growth (1.8 mm), while correction of molar relationship (3.5 mm) was 63% dentoalveolar and 37% skeletal. Both groups showed favorable skeletal mandibular changes, which was more significant in the MSG. Regarding tooth movement, the maxillary splint headgear was more effective in uprighting upper incisors and reducing the overjet than cervical headgear appliance.


Histologic Chorioamnionitis and Bronchopulmonary Dysplasia in Preterm Infants: The Epidemiologic Study on Low Gestational Ages 2 Cohort.
To investigate the association between histologic chorioamnionitis (HCA) and bronchopulmonary dysplasia (BPD) in very preterm infants, both in a general population and for those born after spontaneous preterm labor and after preterm premature rupture of membranes (pPROM). This study included 2513 live born singletons delivered at 24-31 weeks of gestation from a national prospective population-based cohort of preterm births; 1731 placenta reports were available. HCA was defined as neutrophil infiltrates in the amnion, chorion of the membranes, or chorionic plate, associated or not with funisitis. The main outcome measure was moderate or severe BPD. Analyses involved logistic regressions and multiple imputation for missing data. The incidence of HCA was 28.4% overall: 38% in cases of preterm labor, 64% in cases of pPROM, and less than 5% in cases of vascular disorders. Overall, the risk of BPD after adjustment for gestational age, sex, and antenatal steroids was reduced for infants with HCA (HCA alone: aOR 0.6 [95% CI 0.4-0.9]; associated with funisitis: aOR 0.5 [95% CI 0.3-0.8]). This finding was explained by the high rate of BPD and low rate of chorioamnionitis among children with fetal growth restriction. HCA was not associated with BPD in the preterm labor (13.4% vs 8.5%; aOR 0.9; 95% CI 0.5-1.8) or in the pPROM group (12.9% vs 12.1%; aOR 0.6; 95% CI 0.3-1.3). In homogeneous groups of infants born after preterm labor or pPROM, HCA is not associated with BPD.


[Community practice in units of primary care at the rural level: an experience with medical students].
During the three weeks of vacation from the sixth semester of medical school in May 1982, a group of six students and a professor in the Department of Social Medicine of Valle University, Colombia, conducted a voluntary experimental exercise in some of the rural primary care units of Tuluá Regional Hospital in Valle del Cauca department, using the hospital's Administration as their operational center. The purpose of the exercise, called "Ruralito," was to compile a health census of the general characteristics of the rural communities constituting the primary health care service area. The teaching process employed was designed to encourage the students to act on their own initiative and in their own way and to exchange experiences and plan measures even after completion of the three years of the exercise. The article describes the salient features of the relationship between teaching practice and public health practice in this first exercise, in which a new instructional framework was introduced for the area of medicine; the students' highly favorable reaction to this exercise and the substantial gains made justify the expectation that it will serve as an example for future student exercises in similar processes.


[Serum cholesterol in the dog].
The reference values of cholesterol were examined in two groups of healthy dogs. In a group of 591 dogs a value of 122-389 mg/dl or 3.2-10.1 mmol/l was calculated (95% percentile). Statistically significant variations occurred with age, sex, breed, and feeding; however they were small and do not require consideration in diagnostic procedures. Serum cholesterol is increased in numerous diseases. It is questionable whether the consideration of serum cholesterol helped in the diagnosis of hypothyroidism.


Risk of cancer mortality according to the metabolic health status and degree of obesity.
We investigated the risk of cancer mortality according to obesity status and metabolic health status using sampled cohort data from the National Health Insurance system. Data on body mass index and fasting blood glucose in the sampled cohort database (n=363,881) were used to estimate risk of cancer mortality. Data were analyzed using a Cox proportional hazard model (Model 1 was adjusted for age, sex, systolic blood pressure, diastolic blood pressure, total cholesterol level and urinary protein; Model 2 was adjusted for Model 1 plus smoking status, alcohol intake and physical activity). According to the obesity status, the mean hazard ratios were 0.82 [95% confidence interval (CI), 0.75-0.89] and 0.79 (95% CI, 0.72-0.85) for the overweight and obese groups, respectively, compared with the normal weight group. According to the metabolic health status, the mean hazard ratio was 1.26 (95% CI, 1.14-1.40) for the metabolically unhealthy group compared with the metabolically healthy group. The interaction between obesity status and metabolic health status on the risk of cancer mortality was not statistically significant (p=0.31). We found that the risk of cancer mortality decreased according to the obesity status and increased according to the metabolic health status. Given the rise in the rate of metabolic dysfunction, the mortality from cancer is also likely to rise. Treatment strategies targeting metabolic dysfunction may lead to reductions in the risk of death from cancer.


Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks.
Repair of DNA double-strand breaks (DSBs) requires eviction of the histones around DNA breaks to allow the loading of numerous repair and checkpoint proteins. However, the mechanism and regulation of this process remain poorly understood. Here, we show that histone H2B ubiquitination (uH2B) promotes histone eviction at DSBs independent of resection or ATP-dependent chromatin remodelers. Cells lacking uH2B or its E3 ubiquitin ligase Bre1 exhibit hyper-resection due to the loss of H3K79 methylation that recruits Rad9, a known negative regulator of resection. Unexpectedly, despite excessive single-strand DNA being produced, bre1Δ cells show defective RPA and Rad51 recruitment and impaired repair by homologous recombination and response to DNA damage. The HR defect in bre1Δ cells correlates with impaired histone loss at DSBs and can be largely rescued by depletion of CAF-1, a histone chaperone depositing histones H3-H4. Overexpression of Rad51 stimulates histone eviction and partially suppresses the recombination defects of bre1Δ mutant. Thus, we propose that Bre1 mediated-uH2B promotes DSB repair through facilitating histone eviction and subsequent loading of repair proteins.


Perfluoroheptane-Loaded Hollow Gold Nanoshells Reduce Nanobubble Threshold Flux.
The threshold flux for nanobubble formation and liposome rupture is reduced by 50-60% by adding a liquid mixture of tetradecanol and perfluoroheptane to the interior cavity of 40 nm diameter hollow gold nanoshells (HGN), and allowing the tetradecanol to solidify to hold the perfluoroheptane in place. On absorption of picosecond pulses of near-infrared light, the perfluoroheptane vaporizes to initiate cavitation-like nanobubbles as the HGN temperature increases. The lower spinodal temperature and heat capacity of perfluoroheptane relative to water causes the threshold flux for nanobubble formation to decrease. The perfluoroheptane-containing HGN can be linked via thiol-PEG-lipid tethers to carboxyfluorescein-containing liposomes and shows a similar decreased flux necessary for liposome contents release.


Evaluation of Educational Environment for Medical Students of a Tertiary Pediatric Hospital in Tehran, Using DREEM Questionnaire.
Tertiary pediatric hospitals usually provide excellent clinical services, but such centers have a lot to do for educational perfection. This study was performed to address under-graduate educational deficits and find feasible solutions. This cross-sectional study was done in a target population of 77 sixth year undergraduate medical students (response rate = 78%) who spent their 3-month pediatric rotation in the Children's Medical Center, the Pediatrics Center of Excellence in Tehran, Iran. The Dundee ready educational environment measure (DREEM) instrument was used for assessing educational environment of this subspecialized pediatric hospital. Among 60 students who answered the questionnaires, 24 were male (40%). Participants' age ranged from 23 to 24 years. The mean total score was 95.8 (48%). Comparison of scores based on students' knowledge showed no significant difference. Problematic areas were learning, academic self-perception, and social self-perception. Having an accurate schedule to train general practitioner, using new teaching methods, and providing a non-stressful atmosphere were suggested solutions.


Porcine CD8αdim/-NKp46high NK cells are in a highly activated state.
Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46- and NKp46+ cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46high phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α+NKp46- and NKp46+ NK-cell subsets in spleen and blood. Additionally NKp46high NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46high NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46high NK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46high NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ.


Interactions between developing autonomic neurons and their target tissues.
Neurons critically depend on contact with the correct target tissue in order to survive and mature. The number of neurons surviving in a nerve centre directly depends on the size of the peripheral field in innervates. It has been proposed that target tissues release a neurotrophic substance (retrophin) which is internalized by nerve terminals and retrogradely transported to the perikarya where its action results in the survival of appropriate neurons. In the sympathetic nervous system, nerve growth factor probably acts as a retrophin. Similar retrophins must exist for other neuronal systems. In order to identify a parasympathetic retrophin two approaches have been taken. One was to grow appropriate target tissues with radiolabelled amino acids and to determine whether the proteins synthesized and released by these target tissues were retrogradely transported by parasympathetic neurons in vivo. The other approach was to show that a purified neurotrophic factor for the chick ciliary ganglion could be retrogradely transported by parasympathetic neurons. The results have suggested that at least two retrophins are involved in the normal development of the autonomic nervous system: one, nerve growth factor, for the sympathetic nervous system and the other, as yet unnamed, for the parasympathetic system.


Psychosocial risk factors and treatment of new onset and recurrent depression during the post-partum period.
When developing maternity care services, it is important to know how psychosocial factors affect the course of post-partum depression (PPD), and how depressed mothers are treated. The aim of this study is to assess how adverse childhood experiences, poor present support and violence, and low socioeconomic status (SES) associate with PPD, specifically in new onset and recurrent post-partum depression. The second aim is to assess the treatment received for PPD. This is a cross-sectional study. The study group comprises 104 mothers with a current episode of PPD, and a control group of 104 mothers without an episode. The Structured Clinical Interview for DSM-IV Axis I Disorders was used for data collection. Psychosocial risk factors, treatment issues, and the course of depression were assessed with a structured self-report questionnaire. In age-adjusted multivariate analyses, adverse childhood experiences, a low level of present support in close relationships, and a poor SES were associated significantly with PPD. Childhood adversity was associated with both new onset and recurrent depression. Nevertheless, a low level of support and a poor SES were also associated with recurrent depression. A quarter of mothers with a major depressive episode in the post-partum period attended psychiatric services. In mothers with new onset depression, the proportion was only 5%. There is an urgent need to develop the diagnostics of depression in maternity care services. An awareness of psychosocial risk factors might help in this. More depressed mothers should be referred to psychiatric services.


Simultaneous HPLC determination of four active compounds in fengshiding capsules, a chinese medicine.
A high performance liquid chromatography method was established for simultaneously determining four bioactive components, salicin, liquiritin, paeonolum, and imperatorin in Fengshiding capsule, a widely used traditional Chinese medicine for treating rheumatic disease. The chromatographic separation was performed on a Shimadzu Shim-pack Stable Bond C18 column using gradient elution with methanol and water. The analytical method was validated through precision, repeatability and stability, and the relative standard deviation values were less than 3%, respectively. The recoveries of the four investigated compounds ranged from 95.80 to 101.21% with relative standard deviation values less than 3.2%. Then this proposed method was successfully applied to determine six batches of Fengshiding commercial products of capsule dosage form from two pharmaceutical factories. This study might provide a basis for quality control for this traditional Chinese medicine preparation.


Evaluating ocular blood flow.
Studies have shown that vascular impairment plays an important role in the etiology and pathogenesis of various ocular diseases including glaucoma, age-related macular degeneration, diabetic retinopathy, and retinal venous occlusive disease. Thus, qualitative and quantitative assessment of ocular blood flow (BF) is a topic of interest for early disease detection, diagnosis, and management. Owing to the rapid improvement in technology, there are several invasive and noninvasive techniques available for evaluating ocular BF, with each of these techniques having their own limitations and advantages. This article reviews these important techniques, with a particular focus on Doppler Fourier domain optical coherence tomography (OCT) and OCT-angiography.


Depressive symptom trajectories over a 6-year period following myocardial infarction: predictive function of cognitive appraisal and coping.
The association between distinct patterns of depression and coping variables in myocardial infarction (MI) survivors over the long-term is unclear. The study aims to evaluate depressive trajectories and their covariates, including coping and cognitive appraisal, following MI over a period of 6 years. Depressive symptoms were assessed in 200 patients a few days after the first MI, and 1 month, 6 months and 6 years later. Cognitive appraisal and coping were assessed during the first three time points. Three latent depressive trajectories were identified: chronic (high; increasing then decreasing; n = 49), rising (moderate; decreasing then increasing; n = 121) and low (low; decreasing then stabilizing; n = 30). The chronic trajectory was associated with higher negative appraisal and emotion-focused coping. The findings clarify the long-term longitudinal trajectories of post-MI depressive symptoms and their association with coping variables, revealing the unfavorable impact of negative cognition and palliative coping.


Intricacy of missing data in clinical trials: Deterrence and management.
Missing data is frequently encountered in clinical studies. Unfortunately, they are often neglected or not properly handled during data analysis and this may significantly bias the results of the study, reduce study power and lead to invalid conclusions. Substantial instances of missing data are a serious problem that undermines the scientific trustworthiness of causal conclusions from clinical trials. The assumption that statistical analysis methods can compensate for such missing data is not justified. Hence aspects of clinical trial design that limit the probability of missing data should be an important objective, while planning a clinical trial. In addition to specific aspects of trial design, many components of clinical trial conduct can also limit the extent of missing data. The topic of missing data is often not a major concern until it is time for data collection and data analysis. This article discusses some basic issues about missing data as well as prospective "watch outs" which could reduce the occurrence of missing data. It provides some possible design considerations that should be considered in order to alleviate patients from dropping out of a clinical trial. In addition to these the concept of the missing data mechanism has also been discussed. Three types of missing data mechanisms missing completely at random, missing at random and not missing at random have been discussed in detail.


Use of video-feedback, reflection, and interactive analysis to improve nurse leadership practices.
The chronic shortage of registered nurses (RNs) affects patient safety and health care quality. Many factors affect the RN shortage in the workforce, including negative work environments, exacerbated by ineffective leadership approaches. Improvements in the use of relationship-based leadership approaches lead to healthier work environments that foster RN satisfaction and reduce RN turnover and vacancy rates in acute care settings. In this article, an innovative approach to reduce nurse turnover and decrease vacancy rates in acute care settings is described. Video feedback with reflection and interactive analysis is an untapped resource for nurse leaders and aspiring nurse leaders in their development of effective leadership skills. This unique method may be an effective leadership strategy for addressing recruitment and retention issues in a diverse workforce.


Cyclic chronopotentiometry as a detection tool for flowing solution systems.
Cyclic chronopotentiometry provides a very simple detection method, which may be particularly useful in capillary electrophoresis (CE) and microseparation systems. It has been shown that for disk microelectrodes it is possible to define safe reduction and oxidation currents that would never lead to the formation of H2 or O2 gas bubbles, even if they are applied for an indefinitely long time period. During end-column CE detection, currents passing through the working microelectrode can be completely controlled by the external electronic circuit and they are not affected by the separation current. Consequently, problems created by the offset potential in CE can be completely eliminated. The detection can be accomplished through a variety of different mechanisms; however, generation of the electrode response as a result of analyte adsorption seems to be most common. The method is applicable to many analytes, which do not have to be electroactive. The analytical signal is obtained by monitoring the change in the average electrode potential (calculated for either a cathodic or an anodic half-cycle) caused by an analyte interacting with the electrode. The analytical signal is proportional to the analyte concentration, within a concentration range extending over approximately 2 orders of magnitude.


Investigations of ocular changes, extraocular muscle thickness, and eye movements in Graves' ophthalmopathy.
The aim of this study was to evaluate ocular changes, to measure the thickness of extraocular muscles, and to assess eye movements in patients with active Graves' ophthalmopathy. We examined 27 patients (18 women and 9 men) with Graves' ophthalmopathy. Their age ranged from 17 to 59 years; mean age was 42.7+/-2.9 years. The control group consisted of 30 healthy persons aged 43.6+/-2.6 years. All patients underwent a complete ophthalmic examination including best-corrected Snellen visual acuity testing, measurements of proptosis using Hertel exophthalmometer, echography using A/B mode Mentor Advent ultrasonic diagnostic imaging system, ocular motility, slit-lamp and ophthalmoscopic examination. The examination showed a significant increase of proptosis, periorbital edema in 66.67%, chemosis in 59.26%, injection of conjunctiva in 45.15% of patients. The majority of patients with infiltrative form of Graves' ophthalmopathy had a significant enlargement of medial rectus muscle (from 5.0 to 5.9 mm in 46.3%, from 6.0 to 6.9 mm in 22.22% of eyes) and inferior rectus muscle thickness (from 5.0 to 5.9 mm in 33.33%, from 6.0 to 6.9 mm in 24.07% of eyes), disturbances in upward (less than 30 degrees in 62.96%) and lateral eye movements (from 30 to 50 degrees in 77.78%). The results of ocular examination showed an increase of proptosis, periorbital edema, chemosis and injection of conjunctiva in patients with Graves' ophthalmopathy. Ultrasound investigations showed a marked increase in the volume of medial and inferior eye muscle. In patients with Graves' ophthalmopathy, the changes in ocular motility (upward and lateral gaze) were detected.


Temperature and concentration effects on the solvophobic solvation of methane in aqueous salt solutions.
We perform molecular dynamics (MD) simulations of aqueous salt (NaCl) solutions using the TIP4P-Ew water model (Horn et al., J. Chem. Phys. 2004, 120, 9665) covering broad temperature and concentration ranges extending deeply into the supercooled region. In particular we study the effect of temperature and salt concentration on the solvation of methane at infinite dilution. The salt effect on methane's solvation free energy, solvation enthalpy and entropy, as well as their temperature dependence is found to be semi-quantitatively in accordance with the data of Ben-Naim and Yaacobi (J. Phys. Chem. 1974, 78, 170). To distinguish the influence of local (in close proximity to ions) and global effects, we partition the salt solutions into ion influenced hydration shell regions and bulk water. The chemical potential of methane is systematically affected by the presence of salt in both sub volumes, emphasizing the importance of the global volume contraction due to electrostriction effects. This observation is correlated with systematic structural alterations similar to water under pressure. The observed electrostriction effects are found to become increasingly pronounced under cold (supercooled) conditions. We find that the influence of temperature and salt induced global density changes on the solvation properties of methane is well recovered by simple scaling relation based on predictions of the information theory model of Garde et al. (Phys. Rev. Let. 1999, 77, 4966).


[Religion and spirituality in education and nursing assistance].
Intersectional study between nursing discourse and precepts which embrace religion/religiousness and spirituality, and how these were incorporated and their reflection upon nursing practice, education and the history of the organization of the profession. For bibliographic review LILACS and BDENF databases of the Electronic Health Library were used. A total of 57 full-text articles, published from 1957 to 2007, were analyzed upon the light of the ideas of Maurice Halbwachs, about " collective memory" . The results show that Brazilian nursing has a religious root with profound ramifications on its development. This configuration is so embedded in the collective memory that, even with the expansion of non-religious institutions, the Christian precepts remain present and strong.


Review: The effect of nutrition on timing of pubertal onset and subsequent fertility in the bull.
The advent of genomic selection has led to increased interest within the cattle breeding industry to market semen from young bulls as early as possible. However, both the quantity and quality of such semen is dictated by the age at which these animals reach puberty. Enhancing early life plane of nutrition of the bull stimulates a complex biochemical interplay involving metabolic and neuroendocrine signalling and culminating in enhanced testicular growth and development and earlier onset of sexual maturation. Recent evidence suggests that an enhanced plane of nutrition leads to an advancement of testicular development in bulls at 18 weeks of age. However, as of yet, much of the neuronal mechanisms regulating these developmental processes remain to be elucidated in the bull. While early life nutrition clearly affects the sexual maturation process in bulls, there is little evidence for latent effects on semen traits post-puberty. Equally the influence of prevailing nutritional status on the fertility of mature bulls is unclear though management practices that result in clinical or even subclinical metabolic disease can undoubtedly impact upon normal sexual function. Dietary supplements enriched with various polyunsaturated fatty acids or fortified with trace elements do not consistently affect reproductive function in the bull, certainly where animals are already adequately nourished. Further insight on how nutrition mediates the biochemical interaction between neuroendocrine and testicular processes will facilitate optimisation of nutritional regimens to optimise sexual maturation and subsequent semen production in bulls.


Statins for primary prevention of cardiovascular mortality in women: a systematic review and meta-analysis.
The benefits of statins on prevention of coronary heart disease in women without heart disease have not been clarified. The authors systematically reviewed all the published literature on primary prevention trials and found 6 primary prevention trials to date with sex-specific data on mortality and coronary heart disease events in women. The summary risk ratio for primary prevention of all-cause mortality was 0.90 (95% confidence interval, 0.60-1.35; P=.61) and for any coronary heart disease event was 0.78 (95% confidence interval, 0.64-0.96; P=.02). This review reveals that statin therapy along with diet and exercise in moderately hyperlipidemic women without a previous history of cardiovascular disease is of significant benefit in preventing coronary heart disease events but of no proven benefit in preventing all-cause mortality.


Extreme synergy: spatiotemporal correlations enable rapid image reconstruction from computer-generated spike trains.
Over the brief time intervals available for processing retinal output, the number of spikes generated by individual ganglion cells can be quite variable. Here, two examples of extreme synergy are used to illustrate how realistic long-range spatiotemporal correlations can greatly improve the quality of retinal images reconstructed from computer-generated spike trains that are 25-400 ms in duration, approximately the time between saccadic eye movements. Firing probabilities were specified both explicitly: using time-varying waveforms consistent with stimulus-evoked oscillations measured experimentally, and implicitly: by superimposing realistic fixational eye movements on a biophysical model of primate outer retina. Synergistic encoding was investigated across arrays of model neurons up to 32 x 32 in extent, containing over 1 million pairwise correlations. The difficulty of estimating pairwise, spatiotemporal correlations on single trials from only a few events was overcome by using oscillatory, local multiunit activity to weight contributions from all spike pairs. Stimuli were reconstructed using either an independent rate code or the first principal component of the single-trial, pairwise correlation matrix. Spatiotemporal correlations mediated dramatic improvements in signal/noise without eliminating fine spatial detail, demonstrating how extreme synergy can support rapid image reconstruction using far fewer spikes than required by an independent rate code.


Are there neighborhood effects on young adult neighborhood attainment? Evidence from mixed-logit models.
Studies of racial residential attainment show an intergenerational transmission of racial contexts from youth to adulthood, but it is unclear why this transmission is so robust. It is possible that experiences in racial contexts during youth have lasting effects on neighborhood selection in adulthood, but evidence for this claim has come from research using statistical methods that suffer from problems of ecological dependence and conflation of other neighborhood characteristics. In this study, we address these limitations using mixed-logit models, a form of discrete choice analyses, allowing us to control for differences across metropolitan areas and for multiple characteristics of neighborhoods that may affect the selection of destination neighborhoods. Data for the analyses come from the National Educational Longitudinal Study, the 1990 and 2000 Censuses, and other sources. We find that most of the intergenerational process results from young adults moving to neighborhoods short distances from their origin ones, but the models also suggest a contextual effect of youth experiences in racial compositions on neighborhood selection. The latter finding indicates that policies promoting integration among youth can have long-lasting effects on residential attainment.


A pragmatic approach to assess the exposure of the honey bee (Apis mellifera) when subjected to pesticide spray.
Plant protection spray treatments may expose non-target organisms to pesticides. In the pesticide registration procedure, the honey bee represents one of the non-target model species for which the risk posed by pesticides must be assessed on the basis of the hazard quotient (HQ). The HQ is defined as the ratio between environmental exposure and toxicity. For the honey bee, the HQ calculation is not consistent because it corresponds to the ratio between the pesticide field rate (in mass of pesticide/ha) and LD50 (in mass of pesticide/bee). Thus, in contrast to all other species, the HQ can only be interpreted empirically because it corresponds to a number of bees/ha. This type of HQ calculation is due to the difficulty in transforming pesticide field rates into doses to which bees are exposed. In this study, we used a pragmatic approach to determine the apparent exposure surface area of honey bees submitted to pesticide treatments by spraying with a Potter-type tower. The doses received by the bees were quantified by very efficient chemical analyses, which enabled us to determine an apparent surface area of 1.05 cm(2)/bee. The apparent surface area was used to calculate the exposure levels of bees submitted to pesticide sprays and then to revisit the HQ ratios with a calculation mode similar to that used for all other living species. X-tomography was used to assess the physical surface area of a bee, which was 3.27 cm(2)/bee, and showed that the apparent exposure surface was not overestimated. The control experiments showed that the toxicity induced by doses calculated with the exposure surface area was similar to that induced by treatments according to the European testing procedure. This new approach to measure risk is more accurate and could become a tool to aid the decision-making process in the risk assessment of pesticides.


FINE-GRAINED SPATIAL AND TEMPORAL VARIATION IN SELECTION DOES NOT MAINTAIN GENETIC VARIATION IN ERIGERON ANNUUS.
Because interactions among plants are spatially local, the scale of environmental heterogeneity can have large effects on evolutionary dynamics. However, very little is known about the spatial patterns of variation in fitness and the relative magnitude of spatial and temporal variation in selection. Replicates of 12 genotypes of Erigeron annuus (Asteraceae) were planted in 288 locations within a field, separated by distances of 0.1 to 30.0 m, and replicated in two years. In a given year, most spatial variation in relative fitness (genotype-environment [G × E] interactions for fitness) occurred over distances of only 50 cm. Year effects were as large or larger than the spatial variation in fitness; in particular there was a large, three-way, genotype-year-environment interaction at the smallest spatial scale. The genetic correlation of fitness across years at a given location was near zero, 0.03. Thus, the relative fitness of genotypes is spatially unpredictable and a map of the selective environment has constantly shifting locations of peaks and valleys. Including measurements of soil nutrients as covariates in the analysis removed most of the spatial G × E interaction. Vegetation and microtopography had no effect on the G × E terms, suggesting that differential response to soil nutrients is the cause of spatial variation in fitness. However, the slope of response to NH4 and P04 was negative; therefore the soil nutrients are probably just indicators of other, unknown, environmental factors. We explored via simulation the evolutionary consequences of spatial and temporal variation in fitness and showed that, for this system, the spatial scale of variation was too fine grained (by a factor of 3 to 5) to be a powerful force maintaining genetic variation in the population. The inclusion of both spatial and temporal variation in fitness actually reduced the coexistence of genotypes compared to pure spatial models. Thus the presence of spatial or temporal variation in selection does not guarantee that it is an effective evolutionary force maintaining diversity. Instead the pattern of selection favors generalist genotypes.


Measurement of quality of life in atopic dermatitis: correlation and validation of two different methods.
Atopic dermatitis is a chronic relapsing condition that can have considerable effects on the lives of sufferers. It is apparent that good, valid measures of life quality are necessary for quantifying the patients' perspective of the severity of their disease and the Dermatology Life Quality Index is often employed in clinical research. In a community study of atopic dermatitis we have assessed disability using the Dermatology Life Quality Index and the Patient Generated Index and compared the results from both indices. The results were significantly correlated and reflected the range of disability in patients in the community. Some items of the Dermatology Life Quality Index were not relevant for atopic dermatitis patients in the community and others, including swimming and sleep loss, were often cited in the Patient Generated Index but are not included in the Dermatology Life Quality Index. The Patient Generated Index is a novel, flexible approach to quality of life measurement that may be suitable for reflecting the wide variety of disability that is experienced by dermatological patients.


Contributions of host- and disease-related attributes to the outcome of patients with acute myelogenous leukemia.
Three sequential trials of treatment for acute myelogenous leukemia (AML) involving 173 patients were analyzed to identify clinical and myeloblast-cell progenitor properties in culture related to outcome. The latter, including self-renewal capacity expressed as plating efficiency (PE2) and drug sensitivity, were determined for a representative group of 45 patients. Despite increasingly intensive remission induction therapy, similar response rates were achieved in the three trials and no increase in the duration of survival was observed. Clinical attributes at presentation by multivariate analyses were not consistently predictable of outcome. Of the blast cell attributes, only PE2 was predictive of duration of survival (p less than 10(-6)). For patients in remission the relapse rate during the first year was 0.63 compared with 0.15 in subsequent years. The percentage marrow myeloblasts at presentation, a measure of disease activity, was significantly higher for the patients having remissions lasting less than one year. These studies demonstrate the importance of disease-related attributes on the outcome of patients with AML.


Extensive ureteral stricture after percutaneous nephrolithotomy.
To present a previously unreported long term complication of percutaneous nephrolithotomy for exclusive renal stone. A 30-years-old woman underwent percutaneous nephrolithotomy for a obstructive pelvic stone, through inferior calix access achieving a stone free status. During the procedure occurred an inadvertent pelvis perforation, but the early evolution was otherwise uneventful. Patient was asymptomatic during the follow-up. However, a urinary ultrasound disclosed important pielocalyceal dilation, and further investigation demonstrated extensive proximal ureteral stricture. Ureteral stricture may rarely occur as a late complication of percutaneous nephrolithotomy. A review of the literature of this quite uncommon complication was performed and the authors discuss the possible etiology and preventive measures.


Genome-wide scanning reveals complex etiology of oculo-auriculo-vertebral spectrum.
Oculo-auriculo-vertebral spectrum (OAVS) is a common developmental disorder involving first and second pharyngeal arches. Although some family cases and such patients showing chromosomal aberrations suggest that OAVS have a genetic basis, no consistent genetic defects have been recorded at present time. Thus, we conducted genetic studies of a three-generation family with five OAVS patients to identify a causative variant for OAVS. Cytogenetic studies revealed those family members had a normal karyotype and no causative mutations were founded in SALL1 and TCOF1, which known to be responsible for two other syndromes that have clinical overlapping with OAVS. Genotyping with commercially available BeadChips was performed on 13 individuals in the same family, showing no significant difference between the affected and normal members in terms of copy number variations (CNVs) in either number or size and no definitive causative CNV. A total of 8,224 informative autosomal SNPs that are evenly distributed throughout the genome were selected for both parametric and non-parametric linkage analysis. Significant negative LOD scores were obtained for the reported OAVS locus, providing further evidence for genetic heterogeneity of this complex disorder. The highest LOD score of 1.60 was noted on chromosome 15q26.2-q26.3 showing a potential linkage to this locus. The variable phenotypes of the affected members and the failure to identify a causative variant indicate that a complex etiology may be present even in a consanguineous family, which makes it more challenging to ascertain the cause of OAVS in further analysis.


Autoradiographic study of the effects of estrogen on in vivo incorporation of 3H-uridine into uterine smooth muscle and stromal RNA in the aging ovariectomized mouse.
An autoradiographic study was made of de novo RNA synthesis and nuclear area in endometrial stroma and myometrium in ovariectomized C57B1/6J mice. A comparison of uterine tissue from young adult (4 to 7 month old) mice was made with tissue from animals of the age of decreased fertility (15 months of age). In mice receiving exogenous estradiol-17 beta there was an age related decrease in nuclear grain counts 60 min after injection of 3H-uridine which was more pronounced in endometrial stroma than in myometria when mice were compared with oil injected controls of the same age. The mean nuclear area of both cell types was greater in estrogenized mice than in control mice. The decrease in endometrial stromal response to exogenous estrogen is consistent with, and may contribute to, decreasing fertility with advancing maternal age.


Radiation therapy after radical prostatectomy: A single-centre radiation oncology experience in trends of referral and treatment practices.
Our objective was to assess whether referral and treatment practices have changed since publication of the Southwest Oncology Group (SWOG) 8794 Trial in 2009, the first randomized study to demonstrate an overall survival advantage of adjuvant radiation therapy (RT) after radical prostatectomy (RP). We retrospectively reviewed all medical charts of men who received RT at our institution between 2004 and 2014 following RP. All RT was conducted by a single radiation oncologist (DT). We divided the cohort into 2 groups according to first referral date before or after the SWOG 8794 trial publication (i.e., before 2010 and after 2010). Medical charts were available for 161/165 patients (97.6%). RP was performed at the same institution in 58% of cases. The median time between surgery and first referral for RT decreased significantly from 672 days (interquartile range [IQR] 295-1449) before 2010 to 300 days (IQR 225-1023) after 2010 (p = 0.04). This trend was associated with lower median prostate-specific antigen (PSA) at RT referral (0.26 μg/L [IQR 0.17-0.48] vs. 0.46 μg/L [IQR 0.25-0.90], respectively; p = 0.001). Androgen-deprivation therapy with RT nearly tripled over time from 13% before 2010 to 37% after 2010 (p = 0.003). Throughout the study period, the time interval between surgery and RT initiation was positively correlated with pT-stage (p = 0.001), Gleason score (p = 0.005) and PSA doubling time (p < 0.001). At our tertiary-referral academic institution, post-RP patients are notably referred earlier for RT and at lower PSA values compared to men treated prior to 2010. Further study is necessary to evaluate this impact on biochemical recurrence-free survival.


Human SAA1-derived amyloid deposition in cell culture: a consistent model utilizing human peripheral blood mononuclear cells and serum-free medium.
Amyloid A (AA) amyloidosis is a fatal disease caused by extracellular deposition of fibrils derived from serum AA (SAA). AA amyloid fibril formation has previously been modeled in macrophage cultures using highly amyloidogenic mouse SAA1.1, but attempts to do the same with human SAA invariably failed. Our objective was to define conditions that support human SAA-derived amyloid formation in peripheral blood mononuclear cell (PBMC) cultures. Two conditions were found to be critical - omission of fetal calf serum and use of StemPro34, a lipid-enriched medium formulated for hematopoietic progenitor cells. Cultures maintained in serum-free StemPro34 and provided with recombinant human SAA1 in the complete absence of amyloid-enhancing factor exhibited amyloid deposition within 7 d. Amyloid co-localized with cell clusters that characteristically included cells of fibrocytic/dendritic morphology as well as macrophages. These cells formed networks that appeared to serve as scaffolding within and upon which amyloid accumulated. Cells in amyloid-forming cultures demonstrated increased adherence, survival and expression of extracellular matrix components. Of the three human SAA1 isoforms, SAA1.3 showed the most extensive amyloid deposition, consistent with it being the most prevalent isoform in Japanese patients with AA amyloidosis. Attesting to the reproducibility and general applicability of this model, amyloid formation has been documented in cultures established from eight PBMC donors.


Risk factors for gastric aspirate culture contamination in children evaluated for tuberculosis in Botswana.
Gastric aspirate (GA) sample culture is commonly performed in children evaluated for tuberculosis (TB) who cannot expectorate sputum. Contamination limits culture yield and negatively impacts care. To evaluate the proportion of and factors associated with GA contamination at a central TB reference laboratory in Botswana. This was a 5-year cross-sectional study of untreated children aged 12 years evaluated for TB with the first GA sample registered at the National Tuberculosis Reference Laboratory. We performed descriptive statistics to assess the risk of contamination with patient age, sex, transport time and distance, culture medium, and facility type. We generated multivariable logistic regression models using generalized estimating equation extension. We analyzed 3642 samples. The median age was 2 years (interquartile range [IQR] 1-4), median transport time was 4 days (IQR 2-7), and 64.1% of samples were from clinics or health posts. TB culture positivity was 1.6% (60/3642), and contamination was observed in 35.6% (1298/3642). Hospital collection was associated with lower contamination risk (adjusted OR [aOR] 0.53, 95%CI 0.40-0.69) and Mycobacteria Growth Indicator Tube vs. Löwenstein-Jensen medium with higher risk (aOR 1.88, 95%CI 1.51-2.34). In routine care settings, high sample contamination and low TB culture yield were observed. This raises questions about the collection technique and storage in lower-level facilities and affirms higher risk with a liquid culture medium.


Componentry for lower extremity prostheses.
Prosthetic components for both transtibial and transfemoral amputations are available for patients of every level of ambulation. Most current suspension systems, knees, foot/ankle assemblies, and shock absorbers use endoskeletal construction that emphasizes total contact and weight distribution between bony structures and soft tissues. Different components offer varying benefits to energy expenditure, activity level, balance, and proprioception. Less dynamic ambulators may use fixed-cadence knees and non-dynamic response feet; higher functioning walkers benefit from dynamic response feet and variable-cadence knees. In addition, specific considerations must be kept in mind when fitting a patient with peripheral vascular disease or diabetes.


Integrating functional genomics to accelerate mechanistic personalized medicine.
The advent of deep sequencing technologies has resulted in the deciphering of tremendous amounts of genetic information. These data have led to major discoveries, and many anecdotes now exist of individual patients whose clinical outcomes have benefited from novel, genetically guided therapeutic strategies. However, the majority of genetic events in cancer are currently undrugged, leading to a biological gap between understanding of tumor genetic etiology and translation to improved clinical approaches. Functional screening has made tremendous strides in recent years with the development of new experimental approaches to studying ex vivo and in vivo drug sensitivity. Numerous discoveries and anecdotes also exist for translation of functional screening into novel clinical strategies; however, the current clinical application of functional screening remains largely confined to small clinical trials at specific academic centers. The intersection between genomic and functional approaches represents an ideal modality to accelerate our understanding of drug sensitivities as they relate to specific genetic events and further understand the full mechanisms underlying drug sensitivity patterns.


Silver/gold core-shell nanoprism-based plasmonic nanoprobes for highly sensitive and selective detection of hydrogen sulfide.
A simple and highly sensitive and selective hydrogen sulfide assay utilizing plasmonic nanoprobes is presented in this report. The assay employs the etching of silver in the Ag/Au core-shell nanoprisms, accompanied by surface plasmon resonance (SPR) signal depression and shift. Briefly, thin layers of gold are first coated onto silver nanoprisms. The thin gold layer not only guarantees the high stability of the plasmonic nanoprobes but also ensures the high selectivity toward hydrogen sulfide. Once hydrogen sulfide is introduced, the silver core is converted to Ag2S mainly from its lateral walls. Moreover, the SPR peak is located in the NIR region that makes these plasmonic nanoprobes more appealing for the detection of hydrogen sulfide in real-world samples and in in vivo applications.


Androgen-sensitive changes in regulation of restraint-induced adrenocorticotropin secretion between early and late puberty in male rats.
Regulation of ACTH secretion changes between early (40 d) and late (60 d) puberty in male rats. We tested whether this occurs because of activating effects of testosterone on the brain. We measured testosterone and ACTH responses to repeated restraint in adrenalectomized, corticosterone-replaced rats entering and leaving puberty with or without treatment with flutamide, a nonsteroidal androgen-receptor antagonist. Flutamide increased testosterone. ACTH responses were high and suppressed by flutamide at 40 d. At 60 d, ACTH responses were low and increased by flutamide. On d 4, basal arginine vasopressin (AVP) mRNA was increased by restraint, but not age, in the medial parvicellular paraventricular nucleus (mpPVN) and medial amygdala and increased with age in the bed nucleus of the stria terminalis. We counted numbers of AVP-immunoreactive (AVP-ir) and corticotropin-releasing factor (CRF)-ir neurons. In medial amygdala, there was no change in AVP+ cells. With restraint, CRF+ cells in the central nucleus decreased at 40 d and increased at 60 d. Flutamide did not affect the response at 40 d but blocked restraint-induced increases at 60 d. After restraint, the bed nucleus of the stria terminalis AVP-ir correlated negatively with mpPVN CRF-ir at 40 d and with mpPVN AVP-ir at 60 d. In PVN, there were no effects on CRF+ cells. However, AVP+ cells increased only with restraint plus flutamide at 40 d and tended to increase with restraint and decrease with restraint plus flutamide at 60 d. We conclude that during puberty testosterone induces marked changes in regulation of neuropeptides in pathways known to determine autonomic, neuroendocrine, and behavioral responses to chronic stress.


Imiquimod as an adjuvant treatment measure for desmoplastic trichoepithelioma.
Desmoplastic trichoepithelioma is a rare benign adnexal tumor. Although it is a benign lesion, patients often want to treat it due to cosmetic concerns when it occurs in an easily visible site. For our two cases, topical 5% imiquimod was an attractive treatment option as it is applied by the patients themselves and it has minimal side effects, including leaving no scar. However, the lesions recurred after clinical remission. To the best of our knowledge, this is the only report on utilizing imiquimod to treat a benign adnexal tumor, and especially desmoplastic trichoepithelioma.


Evaluation of the characteristics of various types of finishing coils for the embolization of intracranial aneurysms in an experimental model with radiolucent coils.
In endovascular coil embolization of intracranial aneurysms, very soft coils, often called "finishing coils," are usually selected in the final stage of coil embolization. The authors developed a radiolucent coil made of thin nylon thread to evaluate the performance of coils under a situation simulating the course of embolization. The characteristics of various types of finishing coils were investigated using radiolucent coils. Experimental embolization was performed with a silicone aneurysm filled with radiolucent coils simulating the final stage of embolization. Three indices, i.e. area, perimeter, and circularity of the inserted coils, were investigated on the X-ray images after coil insertion. The coils used were as follows: Target Ultra Helical, MicroPlex Hypersoft, Axium Helix, ED Coil Extrasoft, and DeltaPlush. In the analysis of area and perimeter, there were significant differences in multiple comparisons. There was no significant difference in circularity, although it was generally ranked in order by coil brand. Target Ultra and MicroPlex Hypersoft had higher scores for area and perimeter and lower scores for circularity, in contrast to DeltaPlush, which had lower scores for area and perimeter and a higher score for circularity. Based on these results, the finishing coils were divided into three groups: Target Ultra Helical and MicroPlex Hypersoft; Axium Helix and ED Coil Extrasoft; DeltaPlush. They are better for use in early, midst, and end of finishing, respectively. The characteristics of various finishing coils were evaluated, and the results obtained reflected actual clinical experience and provide useful information to appropriately select finishing coils.


[Clinicopathological evaluation and treatment of bucillamine induced membranous nephropathy].
We discussed clinicopathological evaluation and treatment of bucillamine induced renal destruction. Thirteen cases of rheumatoid arthritis were investigated in whom proteinuria had developed while being treated with bucillamine. The dose of bucillamine ranged from 100 to 300 mg/day, and many of them were treated with a dose of 200-300 mg/day. The total dose was in the range of 9-57 g. Proteinuria had developed within 3 months after perceiving the efficacy of bucillamine in many of the cases. The details of renal histology revealed that membranous nephropathy was noted in all of the 13 cases and that mesangial proliferative gromerulonephritis was noted in eight cases (61.5%), thin basement membrane was noted in four cases (30.8%) and in one case (7.7%) amyloidosis were identified in parallel. After suspending further administration of bucillamine, the proteinuria was gradually reduced without any specific treatment or without increase in the dose of corticosteroid, and was eliminated in all cases within 10 months. There were some cases in whom proteinuria was eliminated within a short period of time by the administration of corticosteroid in a moderate dose (prednisolone 30 mg/day). It is necessary to initiate the administration of bucillamine from a small dose such as 100 mg/day and pay attention to onset of any side effect. It was also seemed necessary to confirm the renal histology by renal biopsy as far as feasible because a large variety of pathological findings are developed in the kidney of these cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Photoinduced energy transfer processes within dyads of metallophthalocyanines compactly fused to a ruthenium(II) polypyridine chromophore.
An unsymmetric, peripherally octasubstituted phthalocyanine (Pc) 1, which contains a combination of dipyrido[3,2-f:2',3'-h] quinoxaline and 3,5-di-tert-butylphenoxy substituents, has been obtained via a statistical condensation reaction of two corresponding phthalonitriles. Synthetic procedures for the selective metalation of the macrocyclic cavity and the periphery of 1 were developed, leading to the preparation of the key precursor metallophthalocyanines 3-5 in good yields. Two different strategies were applied to the synthesis of compact dyads MPc-Ru(II) 6-8 (M = Mg(II), Co(II), Zn(II)). Intramolecular electronic interactions in these dyads were studied by absorption, emission, and transient absorption spectroscopy. Upon photoexcitation, these dyads exhibit efficient intramolecular energy transfer from the Ru(II) chromophore to the MPc moiety.


Second hand smoke exposure in pregnant women in Dehradun, Uttarakhand: A cross sectional study.
The aim of this study was to estimate the percentage and sources of secondhand smoke (SHS) exposure among non-smoking pregnant women. It was a cross-sectional study conducted among the non-smoking pregnant women registered at the primary health center (PHC) under the All India Institute of Medical Science (AIIMS), Rishikesh. All registered pregnant women at sub-center in the field practice area (Raiwala) of the Department of Community and Family Medicine, AIIMS Rishikesh were recruited in the study. In this study, a questionnaire was used for measuring the exposure of SHS. Mean and standard deviation (SD), median, minimum, and maximum were used for continuous variables. A Chi-square test was used to compare the association of categorical variables. Out of the total participants, 62% were exposed to SHS. 33% of participants were exposed to SHS at home only, 24% at public places only, and 5% were the ones exposed both at home and public places. More than half (69%) of the participants were having inadequate knowledge about the harms caused by SHS. More than half of the participants were exposed to SHS. Inadequate knowledge among the participants about adverse effects of SHS exposure and insufficient practices and action were observed.


The effectiveness of relapse prevention with offenders: a meta-analysis.
Although relapse prevention models have been applied within offender treatment, there has been little controlled outcome research evaluating their effectiveness. This meta-analysis of 40 tests of relapse prevention treatment revealed moderate mean reductions in recidivism (0.15), and certain elements of the relapse prevention model (i.e., training significant others in the program model and identifying the offense chain) yielded stronger effects than others (i.e., provision of booster/aftercare sessions and developing coping skills). Further analyses revealed that the clinically relevant and psychologically informed principles of risk, need, and general responsivity yielded the strongest reductions in recidivism. The implications for future research and treatment are discussed.


Blood pressure change and cognition in childhood and early adulthood: a systematic review.
High blood pressure in midlife is an established risk factor for cognitive decline and dementia but less is known about the impact of raised blood pressure on cognition in childhood and early adulthood. We systematically reviewed and quantified the existing evidence base relating to blood pressure in early life and subsequent cognitive performance. Medline, Embase, PsycINFOo, Scopus, and Web of Science were searched from inception to July 2020. We included longitudinal cohort and case-control studies involving participants aged 0-40 years with a baseline and at least one follow-up blood pressure assessment alongside at least one measure of cognition, occurring at the same time as, or subsequent to blood pressure measures. Risk of bias was assessed independently by two reviewers. PROSPERO registration CRD42020214655. Of a total of 5638 records identified, three cohort and two case-control studies were included with ages ranging from 3 to early 30s. Repeated blood pressure measurements averaged over 25 years or cumulative blood pressure in the 25-30 years prior to assessment of cognitive function were associated with poorer cognitive performance in the two largest cohort studies. The smallest cohort study reported no evidence of an association and the results from the two case-control studies were contradictory. All studies were at risk of bias. Overall, the evidence in this area is lacking and study quality is mixed. Our review highlights an urgent need for studies evaluating the potential for a relationship between raised blood pressure and poorer cognition in early life given the potential for possible risk reduction if such a relationship exists.


A phenomenological interpretation of holistic nursing.
Phenomenology contributes to holistic nursing by interpreting the first-person encounter with the lived world. Holistic nursing care integrates biopsychosociological knowledge with the practical care that is the legacy of generations of practicing nurses. A practice, when interpreted phenomenologically, is a historically developed way of fostering human well-being. Nursing is the practice of caring. Because nursing care concerns helping persons to live better in their world, it includes the moral, esthetic, and interpersonal aspects of care. These spiritual aspects are integrally enmeshed in holistic nursing. The spiritual in holistic nursing also designates the value dimension of meaning that gives life its worth and patients and nurses the courage to be. Interpreted phenomenologically, holistic nursing integrally relates scientific meaning with the meanings of nursing practice, the lived world of patients, and the meaning that gives patients and nurses the courage to seek well-being in a world altered by illness and debilitation.


Single-fluxon controlled resistance switching in centimeter-long superconducting gallium-indium eutectic nanowires.
The ability to manipulate a single quantum object, such as a single electron or a single spin, to induce a change in a macroscopic observable lies at the heart of nanodevices of the future. We report an experiment wherein a single superconducting flux quantum, or a fluxon, can be exploited to switch the resistance of a nanowire between two discrete values. The experimental geometry consists of centimeter-long nanowires of superconducting Ga-In eutectic, with spontaneously formed Ga nanodroplets along the length of the nanowire. The nonzero resistance occurs when a Ga nanodroplet traps one or more superconducting fluxons, thereby driving a Josephson weak-link created by a second nearby Ga nanodroplet normal. The fluxons can be inserted or flipped by careful manipulation of the magnetic field or temperature to produce one of many metastable states of the system.


Velocity fluctuations in a steadily sheared model foam.
Numerical simulations are conducted to calculate velocity fluctuations in a simple two-dimensional model of foam under steady shear. The width of the velocity distribution increases sublinearly with the shear rate, indicating that velocity fluctuations are large compared to the average flow at low shear rates (stick-slip flow) and small compared to the average flow at large shear rates. Several quantities reveal a crossover in behavior at a characteristic strain rate gamma(x), given by the yield strain divided by the duration of a bubble rearrangement event. For strain rates above gamma(x), the velocity correlations decay exponentially in space and time, and the velocity distribution is a Gaussian. For strain rates below gamma(x), the velocity correlations decay as stretched exponentials in space and time, and the velocity distribution is broader than a Gaussian.


The distribution and differential risks of human papillomavirus genotypes in cervical preinvasive lesions: A Taiwan Cooperative Oncologic Group Study.
To clarify the distribution and relative risk of different human papillomavirus (HPV) genotypes in cervical preinvasive lesions, 1246 women with abnormal Papanicolaou smear including atypical squamous cell of unknown significance (ASCUS), atypical glandular cell of unknown significance (AGUS), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) were enrolled in a multicenter, cross-sectional study. Colposcopy and HPV tests with hybrid capture 2 and polymerase chain reaction-reverse line blot were performed. The prevalences of HPV in ASCUS/AGUS-negative histology, ASCUS/AGUS, LSIL, HSIL, and invasive cancer were 33.8%, 38.3%, 74.9%, 84.3% and 100%, respectively, with an overall positive rate of 68.8%. The most common HPV types were HPV 16 (18.5%), 52 (16.5%), 58 (13.2%), 33, 51, 53, 18, 39, 59, 66, MM8, and 31. In comparing the relative risk of HPV infection in different disease status, LSIL and HSIL/carcinoma had a 4.64 (95% CI: 2.98-7.24) and 10.53 (95% CI: 6.69-16.58) folds of risk of high-risk HPV infection than the negative group. The same was true in mixed HPV infection, but not in low-risk type infection. Looking into each high-risk HPV type, the relative infection risks for LSIL and HSIL/carcinoma, in comparison with the negative group, were 1.67 (0.63-4.43) and 8.67 (3.46-21.70), 2017 (1.01-4.68) and 3.04 (1.42-6.47), and 1.40 (0.52-3.77) and 5.22 (2.07-13.19) for HPV type 16, 52 and 58, respectively. The study confirmed the high prevalence and risky nature of HPV 52 and 58 in Taiwanese population and conveyed the need to include these HPV types in vaccine development.


Cystic epithelial-stromal tumor of the seminal vesicle.
A cystic tumor composed of atypical glands in a cellular stroma arose in the pelvis of a 49-year-old man. Two years later an identical tumor was again excised from the pelvis. Morphologic, immunohistochemical and ultrastructural studies indicate that this neoplasm arose in the seminal vesicle, possibly from a seminal vesicle cyst. The tumor did not involve the prostate gland, and immunohistochemical stains for prostate-specific antigen and prostatic acid phosphatase were negative. Ultrastructural study showed that both the glandular and mesenchymal components of the tumor recapitulated features of normal seminal vesicle, further establishing origin from this site. This tumor resembles the rare cystadenoma of the seminal vesicle, yet the cytologic atypia suggests low grade malignant potential. Following the second excision, the patient has had a disease-free interval of 18 months. Long term follow-up and recognition of additional cases is necessary to define the biologic potential of this unusual tumor.


Review of past research and current concepts on the etiology of moyamoya disease.
Research on moyamoya disease has progressed remarkably in the past several decades. Indeed, many new facts concerning the epidemiology of the disease have been revealed and surgical treatments have been drastically improved. However, despite extensive research, the mechanism of moyamoya disease is still unknown. Consequently, the cardinal treatment of this disease has not yet been developed. For further clarification of its etiology, innovative studies are therefore indispensable. The aim of this paper is to review research on the pathogenesis of moyamoya disease to identify milestones in the direction of its true solution. Many hypotheses of the pathogenesis of moyamoya disease have been proposed in the past half century, including infection (viral and bacterial), autoimmune disorders, proteins abnormality, and gene abnormality. Some of these are now considered to be historical achievements. Others, however, can be still subjected to contemporary research. Currently, several genetic abnormalities are considered to offer the most probable hypothesis. In addition, interesting papers have been presented on the role of the endothelial progenitor cell on the pathogenesis of moyamoya disease. Intuitively, however, it appears that a single theory cannot always explain the pathogenesis of this disease adequately. In other words, the complex mechanism of several factors may comprehensively explain the formation of moyamoya disease. The "double hit hypothesis" is probably the best explanation for the complicated pathology and epidemiology of this disease.


Quantification of metastatic load in a syngeneic murine model of metastasis.
Bioluminescence imaging (BLI) is an established method for evaluating metastatic load in preclinical cancer models; however, BLI can produce observational error due to differences in substrate concentration and signal depth. In our syngeneic murine model of metastasis (VM-M3), we used a quantitative polymerase chain reaction (qPCR) method of DNA quantification to bypass these limitations. Liver, spleen, and brain from VM/Dk (VM) mice bearing VM-M3 tumor cells were first imaged ex vivo with BLI. qPCR quantification of tumor cell DNA was then performed on DNA extracted from these organs. Linear regression indicated that qPCR data predicted BLI data in solid tissue. Furthermore, the tumor cell detection limit was lower for qPCR analysis than for BLI analysis. In order to validate qPCR for use in detecting blood metastases, qPCR quantification was performed on whole blood collected from mice whose global organ metastatic load (summation of liver, spleen, kidneys, lungs, and brain) was quantified through BLI. Linear regression indicated that qPCR data in blood predicted BLI data in solid tissue. The results demonstrate that qPCR is an accurate and sensitive method of metastatic quantification in syngeneic murine models.


Predictors of British Isles Lupus Assessment Group-based outcomes in patients with systemic lupus erythematosus: Analysis from the Systemic Lupus International Collaborating Clinics Inception Cohort.
We aimed to identify factors associated with a significant reduction in SLE disease activity over 12 months assessed by the BILAG Index. In an international SLE cohort, we studied patients from their 'inception enrolment' visit. We also defined an 'active disease' cohort of patients who had active disease similar to that needed for enrolment into clinical trials. Outcomes at 12 months were; Major Clinical Response (MCR: reduction to classic BILAG C in all domains, steroid dose of ≤7.5 mg and SLEDAI ≤ 4) and 'Improvement' (reduction to ≤1B score in previously active organs; no new BILAG A/B; stable or reduced steroid dose; no increase in SLEDAI). Univariate and multivariate logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) and cross-validation in randomly split samples were used to build prediction models. 'Inception enrolment' (n = 1492) and 'active disease' (n = 924) patients were studied. Models for MCR performed well (ROC AUC = .777 and .732 in the inception enrolment and active disease cohorts, respectively). Models for Improvement performed poorly (ROC AUC = .574 in the active disease cohort). MCR in both cohorts was associated with anti-malarial use and inversely associated with active disease at baseline (BILAG or SLEDAI) scores, BILAG haematological A/B scores, higher steroid dose and immunosuppressive use. Baseline predictors of response in SLE can help identify patients in clinic who are less likely to respond to standard therapy. They are also important as stratification factors when designing clinical trials in order to better standardize overall usual care response rates.


Delay and death-thought accessibility: a meta-analysis.
The dual-process component of Terror Management Theory (TMT) proposes that different types of threats lead to increases in death-thought accessibility (DTA) after different delay intervals. Experimental studies of terror management threats' effect on DTA were collected and coded for their use of explicitly death-related (vs. not explicitly death-related) threats, and for their use of delay and task-switching during the delay. Results reveal that studies using death-related threats achieved larger DTA effect-sizes when they included more task-switching or a longer delay between the threat and the DTA measurement. In contrast, studies using threats that were not explicitly death-related achieved smaller DTA effect-sizes when they included more task-switching between the threat and the DTA measurement. These findings provide partial support for the dual-process component's predictions regarding delay and DTA. Limitations and future directions are discussed.


Two-week Course of Preoperative Radiotherapy for Locally Advanced Rectal Adenocarcinoma: 8 Years' Experience in a Single Institute.
To evaluate local control and survival in locally advanced rectal adenocarcinoma patients who underwent a preoperative 2-week course of radiotherapy (RT) and to identify prognostic factors influencing the survival rate. We analyzed 377 consecutively treated patients with locally advanced (T3/T4 or node positive) rectal adenocarcinoma. All patients underwent a preoperative 2-week course of RT (30 Gy in 10 fractions) followed by curative surgery. Regression model was used to examine prognostic factors for the disease-free survival (DFS) and overall survival (OS) rates. The Statistical Analysis System software package, version 9.3, was used for analysis. The median follow-up for all living patients was 63.8 months (range, 5.1 to 131.7). The 5-year DFS and OS rates were 64.5% (95% CI, 59.0-69.4) and 75.6% (95% CI, 70.5-80.0), respectively. The 5-year cumulative incidences of local recurrence and distant metastases were 5.4% (95% CI, 2.9-7.9) and 29.0% (95% CI, 23.9-30.1), respectively. The pathologic complete response rate was achieved in 17 patients (4.5%). The Multivariate Cox Regression model showed that factors affecting DFS were the surgical technique, pre-RT pathologic grade, ypT, ypN, and comorbidity; and factors improving OS were low anterior resection, low pre-RT grade, low ypT, and low ypN. Patients treated with preoperative RT with 30 Gy in 10 fractions had similar local control, 5-year DFS and OS to reported long course RT regimen. The surgical technique, pre-RT pathologic grade, ypT, and ypN seemed to affect the OS. Further study on combining a 2-week course of preoperative RT with concurrent chemotherapy would be warranted.