Fundamentals of Diagnostic Error in Imaging.
Imaging plays a pivotal role in the diagnostic process for many patients. With estimates of average diagnostic error rates ranging from 3% to 5%, there are approximately 40 million diagnostic errors involving imaging annually worldwide. The potential to improve diagnostic performance and reduce patient harm by identifying and learning from these errors is substantial. Yet these relatively high diagnostic error rates have persisted in our field despite decades of research and interventions. It may often seem as if diagnostic errors in radiology occur in a haphazard fashion. However, diagnostic problem solving in radiology is not a mysterious black box, and diagnostic errors are not random occurrences. Rather, diagnostic errors are predictable events with readily identifiable contributing factors, many of which are driven by how we think or related to the external environment. These contributing factors lead to both perceptual and interpretive errors. Identifying contributing factors is one of the keys to developing interventions that reduce or mitigate diagnostic errors. Developing a comprehensive process to identify diagnostic errors, analyze them to discover contributing factors and biases, and develop interventions based on the contributing factors is fundamental to learning from diagnostic error. Coupled with effective peer learning practices, supportive leadership, and a culture of quality, this process can unquestionably result in fewer diagnostic errors, improved patient outcomes, and increased satisfaction for all stakeholders. This article provides the foundational elements for implementing this type of process at a radiology practice, with examples to help radiologists and practice leaders achieve meaningful practice improvement. ©RSNA, 2018.


Symptoms of depression and anxiety before and after myocardial infarction: The HUNT 2 and HUNT 3 study.
The long-term effect of having a myocardial infarction (MI) and to what extent post-MI anxiety and depression can be attributed to pre-MI anxiety and depression are not known. Anxiety as an independent risk factor for the onset of MI is not clear and studies treating anxiety and depression as continuous variables are lacking. Baseline data in this prospective study were obtained from the Health Study of Nord-Trøndelag County (HUNT 2). Anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS) at HUNT 2. Age, gender, waist circumference, hypertension, total cholesterol, diabetes, and years of daily smoking were included as control variables. In the sample of 28,859 participants, 770 MI were reported in the follow-up study 5-8 years later (HUNT 3). The level of depressive symptoms at HUNT 2 was a significant and independent predictor of MI at HUNT 3, while symptoms of anxiety were not. Level of anxiety and depression at HUNT 3 was best predicted by baseline anxiety and depression. Having an MI had only a marginal effect on the levels of anxiety and depressive symptoms at HUNT 3. In the MI group, time since MI was not a significant predictor of anxiety and depression.


Apoptotic activity in Libyan breast cancer.
We evaluated the relationship of the apoptotic activity index (AI) and the standardized mitotic-apoptotic ratio (SMI/AI) with clinicopathological features and prognosis in Libyan female breast cancer (BC) patients. We then compared our results with corresponding results in Finnish and Nigerian female BC patients. Histological samples of breast carcinoma from 130 patients were retrospectively studied: an estimation of the apoptotic activity per square millimeter (expressed as apoptotic activity index (AI)), and standardized mitotic-apoptotic ratio (SMI/AI) was made, and the results compared with the clinicopathological features and the patient's survival. There was a statistically significant correlation between the AI and most of the clinicopathological features; the strongest association was observed for clinical stage lymph node (LN) status (P = 0.005). There were also correlations between AI and histological grade (P = 0.035), large tumor size (P = 0.011) and the clinical stage (P = 0.009). There were, however, prominent AI differences between Libyan, Nigerian and Finnish populations. The mean values of AI and SMI/AI in Libyan BC patients were 12.8 apoptotic figures per square millimeter and 2.8, respectively. The Libyan AI is slightly higher than in Nigeria, but much higher than in Finland. The differences between countries are seen throughout the samples as well as being present in certain subgroups. The survival analysis indicated that short survival time was associated with high apoptotic indices values and so can identify aggressive tumors and provide significant prognostic support. The cutoff (4 and 18 apoptosis/mm2) of AI might be applied as a quantitative criterion for Libyan BC to separate the patients into good, moderate and bad prognosis groups. The results indicated that the differences in AI among the three countries may be due to the known variation in the distribution of genetic markers in these populations. Improvement in health care and introduction of screening programs, however, could be very helpful in the Libyan population.


Provision of care to the underserved populations by National Health Service Corps alumni dentists.
This study examined factors associated with dentists continuing to provide care to the underserved populations beyond their National Health Service Corps (NHSC) obligation period. Self-administered questionnaires were mailed in 1998 to 404 dentists who had completed their service obligation between 1980 and 1997. The outcome variable was dentist self-report of continuing to work with the underserved population past NHSC obligation. Among 249 respondents (62% response rate), 46 percent of alumni dentists continued to work with an underserved population. Multivariate analyses found that being an African American (odds ratio [OR] = 3.2), higher final salary during the NHSC assignment (OR = 1.2), and higher altruistic motivation to work with the underserved populations prior to entering NHSC (OR = 1.1) were significantly associated with continued service to the underserved populations. A small number of factors were associated with alumni NHSC dentists' decisions to continue to provide care for the underserved populations. Targeting African-American students and students interested in caring for the underserved may improve the long-term commitment of dentists to provide care for the underserved populations. Attention will also need to be given to increased salary as a potential intervention to increase the numbers of dentists who continue to serve the underserved populations.


HSP27 Inhibitory Activity against Caspase-3 Cleavage and Activation by Caspase-9 Is Enhanced by Chaperone O-GlcNAc Modification in Vitro.
One of the O-GlcNAc modifications is the protection of cells against a variety of stressors that result in cell death. Previous experiments have focused on the overall ability of O-GlcNAc to prevent protein aggregation under stress as well as its ability to affect stress-response signaling pathways. Less attention has been paid to the potential role for O-GlcNAc in the direct inhibition of a major cell-death pathway, apoptosis. Apoptosis involves the sequential activation of caspase proteases, including the transfer of cell-stress information from initiator caspase-9 to effector caspase-3. Cells have multiple mechanisms to slow the apoptotic cascade, including heat shock protein HSP27, which can directly inhibit the activation of caspase-3 by caspase-9. We have previously shown that O-GlcNAc modification increases the chaperone activity of HSP27 against amyloid aggregation, raising the question as to whether this modification may play important roles in other facets of HSP27 biology. Here, we use protein chemistry to generate different versions of O-GlcNAc modified HSP27 and demonstrate that the modification enhances this antiapoptotic function of the chaperone, at least in an in vitro context. These results provide additional molecular insight into how O-GlcNAc functions as a mediator of cellular stress with important implications for human diseases like cancer and neurodegeneration.


A challenging case of an ectopic cushing syndrome.
Bronchopulmonary carcinoids are rare pulmonary neoplasms although they account for most cases of ectopic ACTH syndromes. When feasible, the mainstay treatment is surgical resection of the tumor. We report the case of a 52-year-old woman with signs and symptoms suggestive of hypercortisolism for 12 months, admitted to our department because of community acquired pneumonia. Blood hormone analysis showed increased levels of ACTH and urinary free cortisol and nonsuppressibility to high- and low-dose dexamethasone tests. Pituitary MRI showed no lesion and no central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. CRH stimulation test suggested an ectopic ACTH source. Thoracic CT scan revealed a nodular region measuring 12 mm located in the inferior lingular lobule of the left superior lung with negative uptake by (18)-FDG-PET scan and negative SRS. The patient was successfully treated with an atypical lung resection and histology revealed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. This was an interesting case because the patient was admitted due to pneumonia that may have been associated with her untreated and chronic hypercortisolism and a challenging case of ectopic ACTH syndrome due to conflicting results on the diagnostic exams.


The cost of in-patient care in Western Australia in the last years of life: a population-based data linkage study.
This study aimed to explore patterns of health expenditure for in-patient care in the last 3 years of life so as to understand how age and time to death contribute to health-care expenditure. Records of all deaths occurring in Western Australia from 1997 to 2000 inclusive were extracted from the WA mortality register and linked to records from the hospital morbidity data system (HMDS) via the WA Data Linkage System. Inflation adjusted hospital costs were assigned to all in-patient events occurring within 3 years of death from five major causes of death using DRG costing information. Prior to the last 5 months of life the mean cost of hospitalisation was positively associated with age; however, the magnitude of the cost increase in the last 5 months of life was inversely related to age such that the cost in the last month of life was similar across age groups. The finding that increased costs are associated with proximity to death, but that the magnitude of the increase is inversely associated with age, has implications for the ongoing debate about whether proximity to death or age is the dominant driver of health-care costs. The results of this study suggest that models forecasting future health-care expenditure should take into account the interaction of age, time to death and cause of death. In addition, we propose that due to the differences observed across causes of death it may be that a single general population model may not be capable of fully capturing the relationship and that this may be why the debate regarding age and time to death has yet to be resolved in the literature.


Influence of C-terminal protein domains and protein-lipid interactions on tetramerization and stability of the potassium channel KcsA.
KcsA is a prokaryotic potassium channel formed by the assembly of four identical subunits around a central aqueous pore. Although the high-resolution X-ray structure of the transmembrane portion of KcsA is known [Doyle, D. A., Morais, C. J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T., and MacKinnon, R. (1998) Science 280, 69-77], the identification of the molecular determinant(s) involved in promoting subunit tetramerization remains to be determined. Here, C-terminal deletion channel mutants, KcsA Delta125-160 and Delta120-160, as well as 1-125 KcsA obtained from chymotrypsin cleavage of full-length 1-160 KcsA, have been used to evaluate the role of the C-terminal segment on the stability and tetrameric assembly of the channel protein. We found that the lack of the cytoplasmic C-terminal domain of KcsA, and most critically the 120-124 sequence stretch, impairs tetrameric assembly of channel subunits in a heterologous E. coli expression system. Molecular modeling of KcsA predicts that, indeed, such sequence stretch provides intersubunit interaction sites by hydrogen bonding to amino acid residues in N- and C-terminal segments of adjacent subunits. However, once the KcsA tetramer is assembled, its remarkable in vitro stability to detergent or to heat-induced dissociation into subunits is not greatly influenced by whether the entire C-terminal domain continues being part of the protein. Finally and most interestingly, it is observed that, even in the absence of the C-terminal domain involved in tetramerization, reconstitution into membrane lipids promotes in vitro KcsA tetramerization very efficiently, an event which is likely mediated by allowing proper hydrophobic interactions involving intramembrane protein domains.


Efficacy of Budesonide Nasal Spray on Neutrophilic Chronic Rhinosinusitis with Nasal Polyps: A Combined Clinical and Experimental Study.
Neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNP) occur predominantly in Asian subjects. Appropriate treatments for this endotype have not been elucidated. This study aimed to evaluate the efficacy of budesonide nasal spray on neutrophilic CRSwNP. Fifteen neutrophilic CRSwNP patients were included, and then they received budesonide nasal spray treatment for 3 months. Biopsies of nasal polyps (NPs) were obtained from these subjects. Their clinical indexes were scored using Visual Analog Scale (VAS), Sino-Nasal Outcome Test (SNOT)-22, and Endoscopic Appearances (EAs). Histological analyses were used to assess numbers of neutrophils, goblet cells, and submucosal gland cells in NPs. Percentages of CD8+ T cells and CD4+CD25+Foxp3+ regulatory T cells (Tregs) were evaluated using flow cytometry. Mucin 5AC (MUC5AC), MUC5B, myeloperoxidase (MPO), interferon (IFN)-γ, and interleukin (IL)-1β and their mRNAs were also examined. After that, we cultured NP tissues in vitro and evaluated the abovementioned inflammatory parameters before and after the administration of budesonide. Budesonide nasal spray did not improve clinical evaluations including VAS, SNOT-22, and EA scores. Numbers of neutrophils and goblet cells, the score of submucosal gland cells, percentages of CD8+ T cells and Tregs, MUC5AC, MUC5B, MPO, IFN-γ, and IL-1β and their mRNAs were not decreased in NPs after the budesonide treatment. Furthermore, the administration of budesonide into NP cultures also did not reduce their levels in comparison with those before the treatment. These findings demonstrate that budesonide treatment may not alleviate the inflammatory condition in neutrophilic CRSwNP.


FL118 induces p53-dependent senescence in colorectal cancer cells by promoting degradation of MdmX.
Anticancer agent FL118 was recently identified in screening of small-molecule inhibitors of human survivin expression. Although FL118 is a camptothecin analogue, its antitumor potency is much superior to other FDA-approved camptothecin analogues (irinotecan and topotecan). The mechanism of action (MOA) underlying the antitumor effects of FL118 remains to be fully elucidated. Here, we report that FL118 activates tumor suppressor p53 as a novel MOA in p53 wild-type cancer cells. Our studies show that this MOA involves an induction of proteasomal degradation of MdmX, a critical negative regulator of p53, in a manner largely independent of ATM-dependent DNA damage signaling pathway but dependent on E3-competent Mdm2. FL118 inhibits p53 polyubiquitination and monoubiquitination by Mdm2-MdmX E3 complex in cells and in cell-free systems. In contrast, FL118 stimulates Mdm2-mediated MdmX ubiquitination. Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation. As a result, p53 ubiquitination by Mdm2-MdmX E3 complex is reduced, which in turn activates p53 signaling. Activation of the p53 pathway by FL118 induces p53-dependent senescence in colorectal cancer cells. However, in the absence of p53 or in the presence of MdmX overexpression, FL118 promotes p53-independent apoptosis. These two distinct cellular consequences collectively contribute to the potent effects of FL118 to inhibit clonogenic potential of colon cancer cells. This study identifies a potential application of FL118 as an MdmX inhibitor for targeted therapies.


Overview of overactive bladder, prostatitis, and lower urinary tract symptoms for the primary care physician.
As an increasing number of treatment options for urologic disorders become available, patients with these conditions are more often able to be managed in the primary care setting. Primary care physicians, therefore, must become more knowledgeable of the proper urologic terminology and the screening tools that have traditionally been used by urologists. To that end, this article reviews the terminology associated with lower urinary tract symptoms and describes the evaluation and treatment of patients presenting with these symptoms. The diagnoses of overactive bladder and prostatitis are discussed, as well as the therapeutic options available for these patients.


About spatial intelligence: I.
Spatial intelligence is characterized in terms of a continuum of research perspectives which range from a physiological or sensory awareness to a complex thought and cultural emphasis.


Molecular-Scale Investigation on the Formation of Brown Carbon Aerosol via Iron-Phenolic Compound Reactions in the Dark.
Brown carbon (BrC) is one of the most mysterious aerosol components responsible for global warming and air pollution. Iron (Fe)-induced catalytic oxidation of ubiquitous phenolic compounds has been considered as a potential pathway for BrC formation in the dark. However, the reaction mechanism and product composition are still poorly understood. Herein, 13 phenolic precursors were employed to react with Fe under environmentally relevant conditions. Using Fourier transform ion cyclotron resonance mass spectrometry, a total of 764 unique molecular formulas were identified, and over 85% of them can be found in atmospheric aerosols. In particular, products derived from precursors with catechol-, guaiacol-, and syringol-like-based structures can be distinguished by their optical and molecular characteristics, indicating the structure-dependent formation of BrC from phenolic precursors. Multiple pieces of evidence indicate that under acidic conditions, the contribution of either autoxidation or oxygen-induced free radical oxidation to BrC formation is extremely limited. Ligand-to-Fe charge transfer and subsequent phenoxy radical coupling reactions were the main mechanism for the formation of polymerization products with high molecular diversity, and the efficiency of BrC generation was linearly correlated with the ionization potential of phenolic precursors. The present study uncovered how chemically diverse BrC products were formed by the Fe-phenolic compound reactions at the molecular level and also provide a new paradigm for the study of the atmospheric aerosol formation mechanism.


Serum screening for Down's syndrome: experiences of obstetricians in England and Wales.
To assess the experiences of obstetricians in England and Wales of serum screening for Down's syndrome. Postal questionnaire survey. Questionnaires were sent to all practising obstetricians in England and Wales with nonacademic appointments who had not participated in an earlier (randomly sampled) survey of obstetricians' attitudes (n = 555). Responses were received from 393 (71%), of which 351 were analysed. The data represent about one third of obstetric consultants in England and Wales. The extent of use of serum screening for Down's syndrome, and the problems encountered. Serum screening for Down's syndrome was being offered on some basis by virtually all obstetricians in the survey. Nearly half the sample said that they did not have adequate resources for counselling all the women to whom screening was offered. Many problems were reported, which in all cases were more common than equivalent problems encountered with serum screening for neural tube defects. Over 80% (289) said that women not understanding the test was a problem. There is considerable confusion associated with serum screening for Down's syndrome. The precedent of serum screening for neural tube defects does not seem to have lessened the problems experienced, rather the contrary. Many obstetricians report inadequate resources for counselling, which is consistent with the high prevalence of problems associated with women not understanding the test. There is an urgent need to consider what counselling should consist of and who should undertake it and to ensure that necessary resources are available.


PCR detection of type I polyketide synthase genes in myxobacteria.
The diversity of type I modular polyketide synthase (PKS) was explored by PCR amplification of DNA encoding ketosynthase and acyltransferase domains in myxobacteria. The sequencing of the amplicons revealed that many PKS genes were distantly related to the published sequences. Thus, myxobacteria may be excellent resources for novel and diverse polyketides.


Cyclosporin A inhibits the delayed-type hypersensitivity reaction: impaired production of early pro-inflammatory mediator(s).
The effect of cyclosporin A (CsA) on the delayed-type hypersensitivity (DTH) elicited in mice by sheep red blood cells was investigated. Evidence is presented that a single injection of CsA adversely affects the inflammatory reaction. Sensitized T lymphocytes initiate the DTH reaction by their recruiting activity on phagocytic cells which infiltrate the cutaneous site of antigen deposition. CsA administration has no adverse effect on the recruitment of phagocytic cells at the site of the inflammatory reaction. The present studies show that CsA acts on specific T cells: (a) in adoptive transfer, T-DTH-mediating cells cannot elicit a response in mice treated with CsA 8 h before; (b) when collected 8 h after a single injection of CsA, T-DTH-mediating lymphocytes are no longer able to adoptively transfer the reaction. This conclusion is strengthened by in vitro studies: (a) the frequency of T-DTH-mediating lymphocytes is 50-fold decreased after a short in vitro incubation with CsA; (b) in vitro production by concanavalin A-activated lymphocytes of chemotactic pro-inflammatory mediator(s) is abolished in presence of CsA.


Studies in neotropical polypores 15: new and interesting species from Guyana.
During fieldwork in Guyana several unusual and distinctive taxa of polypores were collected, three of which are described here as new. The first of these, Amauroderma coltricioides is the first species known in the Ganodermataceae with smooth basidiospores. Coltricia verrucata and Coltriciella navispora also are described as new, and a key to the neotropical species of Coltricia is provided. Finally, a checklist of 73 poroid fungi from Guyana is given, of which 29 are new records for the country.


Carbon-based leaving group in substitution reactions: functionalization of sp3-hybridized quaternary and tertiary benzylic carbon centers.
Lewis acid promoted substitution reactions employing Meldrum's acid and 5-methyl Meldrum's acid as carbon-based leaving groups are described which transform unstrained quaternary and tertiary benzylic C(sp(3))-C(sp(3)) bonds into C(sp(3))-X bonds (X = C, H, N). Importantly, this reaction has a broad scope in terms of both suitable substrates and nucleophiles with good to excellent yields obtained (typically >90%).


Mesothelial cells of peritoneal fluid.
Cells in the peritoneal fluid from 159 horses were examined in Giemsa stained preparations using light microscopy. Normal mesothelial cells showed an oval nucleus with finely reticular chromatin and pale blue cytoplasm. Activated mesothelial cells occurred in fluids derived from mesothelium under acute or subacute, non-septic stimulus and were remarkable for their pleomorphism and intense basophilia which may mimic neoplasia. Transformed mesothelial cells seen in chronic inflammatory fluids were sometimes phagocytic and showed conspicuous cytoplasmic vacuolation.


Measurement of scattered radiation in a volumetric 64-slice CT scanner using three experimental techniques.
Compton scatter poses a significant threat to volumetric x-ray computed tomography, bringing cupping and streak artefacts thus impacting qualitative and quantitative imaging procedures. To perform appropriate scatter compensation, it is necessary to estimate the magnitude and spatial distribution of x-ray scatter. The aim of this study is to compare three experimental methods for measurement of the scattered radiation profile in a 64-slice CT scanner. The explored techniques involve the use of collimator shadow, a single blocker (a lead bar that suppresses the primary radiation) and an array blocker. The latter was recently proposed and validated by our group. The collimator shadow technique was used as reference for comparison since it established itself as the most accurate experimental procedure available today. The mean relative error of measurements in all tube voltages was 3.9 +/- 5.5% (with a maximum value of 20%) for the single blocker method whereas it was 1.4 +/- 1.1% (with a maximum value of 5%) for the proposed blocker array method. The calculated scatter-to-primary ratio (SPR) using the blocker array method for the tube voltages of 140 kVp and 80 kVp was 0.148 and 1.034, respectively. For a larger polypropylene phantom, the maximum SPR achieved was 0.803 and 6.458 at 140 kVp and 80 kVp, respectively. Although the three compared methods present a reasonable accuracy for calculation of the scattered profile in the region corresponding to the object, the collimator shadow method is by far the most accurate empirical technique. Nevertheless, the blocker array method is relatively straightforward for scatter estimation providing minor additional radiation exposure to the patient.


Impact of cyclodextrins on postprandial glycemia: evaluation in experimental animal model using the real-time continuous glucose monitoring system.
The impact of cyclodextrins (CDs) on postprandial glycemic response employing the real-time continuous glucose monitoring system (RT-CGMS) was investigated. For this purpose, α-CD, β-CD, γ-CD, HP-β-CD, curdlan, and dextrin at doses of 10 and 100 mg/kg were orally administered in rats. The RT-CGMS was efficient to evaluate the impact of CDs on postprandial glycemia. The results showed that α-CD, β-CD, dextrin, and curdlan did not reduce the glycemic response after the administration of starch. In contrast, the HP-β-CD (100 mg/kg) attenuated the rise in glycemia. Moreover, the γ-CD blunts the postprandial glycemic excursion at doses of 10 and 100 mg/kg. Therefore, γ-CD could attenuate the rise in glycemia promoted by oral administration of starch. Considering that the treatment of postprandial hyperglycemia is necessary to prevent type 2 diabetes, this study opens the perspective of better control of postprandial glycemia by the addition of γ-CD in food.


Influence of cryopreservation on human leukaemic clonogenic cells (CFU-L).
The biological and clinical significance of growth characteristics of leukaemic clonogenic cells (CFU-L) cultured from patients has been the subject of many studies. While some investigators collect leukaemic cells in large numbers from blood of untreated patients and store them in a frozen state before use in experiment, others study fresh cells. Since cryopreservation may alter the proliferation and differentiation of CFU-L, we have followed its influence and that of DMSO, used as protective agent and known to be an inducer of differentiation in leukaemic blasts, on the clonogenicity of peripheral blast cells from patients with AML and CML in blast crisis. Our data show that a short incubation with 7.5% DMSO (with or without cryopreservation) induced increase in the clonogenicity and proliferation rate of CFU-L (without morphological changes). The possible causes of these effects as well as the question of aggressivity of leukaemic blasts after the short incubation with 7.5% DMSO are discussed.


Post-Katrina juvenile competency determinations: a tale of two systems.
Natural disasters such as Hurricane Katrina have resulted in the displacement of families to locations throughout the nation. Juvenile courts have been affected by this mass migration of youths. Post-disaster recovery has been slow. Consequently, a cohort of youths has aged out of the juvenile justice system before their juvenile competency hearings could be held. Some of these young adults now face charges as adults in criminal courts. The author explores what happens when youths awaiting juvenile competency determinations age out of the system and face charges as adults. The evolution of the problem, the current situation, case examples, and possible solutions are reviewed.


Flow cytometric analysis of pituitary tumors. Correlation of nuclear antigen p105 and DNA content with clinical behavior.
Flow cytometric quantitation of the proliferation-associated nuclear antigen p105 and DNA content was performed on nuclear suspensions from 12 paraffin-embedded pituitary macroadenomas and one pituitary carcinoma and correlated with clinical outcome. Median follow-up was 41 months (range, 33 to 48 months). Three of the 13 tumors (23%) had an identifiable aneuploid peak. Of the four tumors that recurred or metastasized, only one was aneuploid. Nuclear antigen analysis of all diploid tumors showed enhanced p105 expression in G2M phase cells compared to G0G1 cells. The G2M/G0G1 fluorescence ratio for p105 was consistently higher (P less than 0.05) for the three diploid tumors that recurred (median, 1.32 arbitrary fluorescence units; range, 1.27 to 1.80) than for the seven nonrecurrent diploid tumors (median, 1.20 arbitrary fluorescent units; range 1.14 to 1.22). These findings indicate a low incidence of DNA aneuploidy among pituitary tumors and suggest that for diploid adenomas, measurement of p105 may provide information useful in predicting prognosis and directing postoperative adjuvant therapy.


Are synchronous chats a silver lining of emergency remote instruction? Text-based chatting is disproportionately favored by women in a non-majors introductory biology course.
The coronavirus disease 2019 (COVID-19) pandemic has led to a reimagining of many aspects of higher education, including how instructors interact with their students and how they encourage student participation. Text-based chatting during synchronous remote instruction is a simple form of student-student and student-instructor interaction. The importance of student participation has been documented, as have clear disparities in participation between those well-represented and those under-represented in science disciplines. Thus, we conducted an investigation into who is texting, what students are texting, and how these texts align with course content. We focused on two sections of a large-enrollment, introductory biology class offered remotely during Fall 2020. Using an analysis of in-class chatting, in combination with student survey responses, we find that text-based chatting suggests not only a high level of student engagement, but a type of participation that is disproportionately favored by women. Given the multiple lines of evidence indicating that women typically under-participate in their science courses, any vehicle that counters this trend merits further exploration. We conclude with suggestions for further research, and ideas for carrying forward text-based chatting in the post-COVID-19, in-person classroom.


Examining the impacts of disaster resettlement from a livelihood perspective: a case study of Qinling Mountains, China.
Disaster resettlement, as a mitigation and preparedness measure, entails significant economic, physical, and social impacts, which continue to challenge understanding of recovery from major events, especially regarding the extent of the context and environmental efforts to rebuild livelihoods. Based on a case study of Qinling Mountains, China, this research investigates the effects of disaster resettlement from a livelihoods perspective. Methodologically, it proposes a framework that combines the pressure-state-response framework and the sustainable livelihoods approach, and it employs a structural equation model to examine how specific factors affect disaster resettlement. The results indicate that conflicts may occur during and after resettlement owing to the difference or disparity between the concerns of resettled peasants and those of the government. Consequently, the risks related to livelihoods need to be taken seriously. Effective risk communication is critical to bridge the gap between different stakeholders. The paper concludes with some practical and policy recommendations.


Button Battery Powered Fidget Spinners: A Potentially Deadly New Ingestion Hazard for Children.
Toys entering the marketplace may have unrecognized hazard risks until data on injury become known. The fidget spinner is a new popular toy mass marketed to children and is primarily sold without warning labels. The US Consumer Product Safety Commission has recently issued a formal statement on potential safety concerns related to ingestion of the toy parts and other hazards. Button batteries within this toy pose the greatest danger to children as ingestion can lead to lethal injury. We report 2 cases of children who swallowed a button battery from a fidget spinner, causing severe esophageal injury. Various aspects of this type of ingestion important for clinicians to be aware of are reviewed.


Primary Care Pharmacist Services Align With Payment Reform and Provider "Joy of Practice".
The implementation and expansion of primary care (PC) pharmacist medication optimization and management services has been hindered mainly by the lack of a payment mechanism for PC providers to engage pharmacist services. If pharmacists expect to be included in new PC team-based payment models, we need to actively engage in ongoing PC practice transformation discussions with PC organizational leaders. In this commentary, examples of integrated PC pharmacist services and payment models are provided to (1) reinforce the feasibility of pharmacist integration into expanded PC teams and (2) share with PC leaders, payers, and policy makers.


In situ characterization of the cellular infiltrate in labial and palatine glands in Sjögren's syndrome.
The inflammatory cells in the minor salivary glands in situ in 11 patients with Sjögren's syndrome were characterized by using intracellular markers for T lymphocytes, plasma cells, mononuclear phagocytes and granulocytes. The methods used to demonstrate the markers were optimized histochemical and immunoperoxidase techniques which did not disturb the simultaneous morphological study of the marker-positive cells. Acid alpha-naphthyl acetate esterase (ANAE)-positive T lymphocytes accounted for 33 +/- 22%, mononuclear phagocytes for 8 +/- 4% and ANEA-negative (B) lymphocytes for 59 +/- 23% of all cells in the periductal lymphocyte-rich infiltrates, indicating great variations between individual patients. However, variations between labial and palatine glands in individual patients were usually less than 10%, indicating that the disease was at the same stage. Plasma cells were located peripherally to the lymphocytic foci and situated between the glandular acini. Equal proportions of plasma cells containing kappa-light chains (34 +/- 8%) and lambda-light chains (31 +/- 10%) were seen in individual patients, indicating polyclonal B lymphocyte activation. The results indicate differences in the local pathogenetic mechanisms or stage of disease in individual patients with Sjögren's syndrome.


Optimization of cyanide elimination from an industrial wastewater on a pilot plant scale.
A pilot plant scale reactor was modelled and assembled to experimentally study the cyanide elimination process. The process was performed by using Ca(OCl)2, Cl2 and H2O2. The elimination was optimized at 25 degrees C for time of reaction, pH and amount of oxidant in a pilot plant scale reactor with synthetic solutions. Moreover some tests were carried out by using a real effluent deriving from a gold production industry.


Artificial neural networks: theoretical background and pharmaceutical applications: a review.
In recent times, there has been a growing interest in artificial neural networks, which are a rough simulation of the information processing ability of the human brain, as modern and vastly sophisticated computational techniques. This interest has also been reflected in the pharmaceutical sciences. This paper presents a review of articles on the subject of the application of neural networks as effective tools assisting the solution of various problems in science and the pharmaceutical industry, especially those characterized by multivariate and nonlinear dependencies. After a short description of theoretical background and practical basics concerning the computations performed by means of neural networks, the most important pharmaceutical applications of neural networks, with suitable references, are demonstrated. The huge role played by neural networks in pharmaceutical analysis, pharmaceutical technology, and searching for the relationships between the chemical structure and the properties of newly synthesized compounds as candidates for drugs is discussed.


Effect of the Location of Endplate Cement Extravasation on Adjacent Level Fracture in Osteoporotic Patients Undergoing Vertebroplasty and Kyphoplasty.
The most widely researched risk/complication following vertebroplasty (VP) or kyphoplasty (KP) is that of adjacent level fracture (ALF). Current literature results regarding the effect of intradiscal extravasation of cement on the risk of ALF is conflicting with about half of the studies concluding there is no added risk with endplate extravasation and half of the studies reporting opposite conclusions. The purpose of the study is to further stratify the data to determine whether specifically the location and extent of endplate cement extravasation more strongly affect ALF risk in osteoporotic patients following either VP or balloon KP. Retrospective cohort study. University teaching hospital. One hundred and fifty-six cemented levels in 80 patients, treated at a single center between 2008 and 2012 were reviewed. Age, gender, T-score, body mass index, and osteoporosis type (primary or secondary) were recorded. An ALF was defined as a fracture: 1) in a non-cemented vertebra; 2) adjacent to a cemented level; and 3) not due to trauma or malignancy. Location of the cement extravasation (anterior, middle, or posterior third of the vertebral body) and extravasation extent (percentage of the intervertebral disc height occupied by the bolus) were measured. A logistic modeling strategy permitted examining the association between the location and extent of extravasation and the odds of ALF. ALF occurred in 14 of the 52 patients (27%) and 20 of the 98 levels (20.4%) remaining after exclusions. Odds of ALF were 5.9 times higher (95% CI: 1.6 to 21.2, P = 0.008) with extravasation when compared to no leakage. Odds of ALF in a given patient were 22.6 times higher (95% CI: 3.0 to 170.9, P = 0.003) with anterior extravasation when compared to no leakage. Leakage in the middle or posterior thirds and extent of extravasation were not associated with ALF. Limitations of the study include the retrospective study design and small sample size as well as the retrospective implementation of follow-up criteria posing risk of selection bias. Cement endplate extravasation isolated to the anterior third of the vertebral body is associated with is significantly higher odds of ALF after VP or KP in patients with osteoporosis.


New insights into the mechanism of neurally mediated syncope.
To determine the role of the cerebral cortex in neurally mediated syncope, the electroencephalograms (EEG) of patients recorded during head up tilt table test were analysed. Retrospective study. University hospital. 18 patients with syncope or near syncope underwent head up tilt table test with simultaneous ECG and EEG monitoring. Standard 70 degrees tilt table test was done with simultaneous ECG and EEG monitoring. EEG waveforms were analysed by both visual inspection and spectral analysis. 6 of 18 patients (33%) had a positive tilt table test. Before syncope slow waves increased in patients with a positive test. In addition, five of six tilt positive patients (83%) had slow wave activity that lateralised to the left side of the brain (mean (SD) 822 (724) v 172 (215) micro V(2), p < 0.05), while none of the tilt negative patients exhibited lateralisation (24 (15) v 26 (19) micro V(2), NS). Spectral analysis showed that the lateralisation occurred in the delta frequency. The lateralisation preceded the event by 5-56 seconds (18 (21) seconds). EEG activity lateralises to the left hemisphere of the brain before syncope. The lateralisation precedes syncope and is associated with the onset of bradycardia, hypotension, and clinical symptoms. These findings suggest that the central nervous system may have a role in neurally mediated syncope.


DNA chain flexibility and the structure of chromatin nu-bodies.
The persistence length of high-molecular-weight, monodisperse-bihelical DNA has been evaluated from low-shear flow birefingence and viscosity data at several temperatures in 2.0 M Nacl neutral pH buffer. At these solvent conditions, both the DNA and histone components of chromatin nu-bodies have structural features similar to those in the intact nucleohistone complex at low ionic strength. The theory of Landau and Lifshitz is used to relate the experimental result to the thermodynamic functions for bending 140 nucleotide pairs of DNA into a plausible model structure: per nu-body, delta Gb=43.8 +/- 5.3 kcal/mole, delta Hb= 45.7 +/- 3.7 kcal/mole, and delta Sb = 6.2 +/- 12.4 entropy units. This bending free energy is comparable to or less than that estimated to be required for a kinked DNA configuration and appears to be well within the range of estimated electrostatic free energies available from DNA-histone interactions in a nu-body assembly.


Antibiotic induced restructuring of the gut microbiota does not affect oral uptake and accumulation of perfluorooctane sulfonic acid (PFOS) in rats.
Perfluorooctane sulfonic acid (PFOS) is a manmade legacy compound belonging to the group of persistent per- and polyfluorinated substances (PFAS). While many adverse health effects of PFOS have been identified, knowledge about its effect on the intestinal microbiota is scarce. The microbial community inhabiting the gut of mammals plays an important role in health, for instance by affecting the uptake, excretion, and bioavailability of some xenobiotic toxicants. Here, we investigated (i) the effect of vancomycin-mediated microbiota modulation on the uptake of PFOS in adult Sprague-Dawley rats, and (ii) the effects of PFOS exposure on the rat microbiota composition. Four groups of twelve rats were exposed daily for 7 days with either 3 mg/kg PFOS plus 8 mg/kg vancomycin, only PFOS, only vancomycin, or a corn oil control. Vancomycin-induced modulation of the gut microbiota composition did not affect uptake of branched and linear PFOS over a period of 7 days, measured in serum samples. 16S rRNA amplicon sequencing of faecal and intestinal samples revealed that vancomycin treatment lowered microbial alpha-diversity, while PFOS increased the microbial diversity in vancomycin-treated as well as in non-antibiotic treated animals, possibly because an observed decrease in the Enterobacteriaceae abundance allows other microbial species to propagate. Colonic short-chain fatty acids were significantly lower in vancomycin-treated animals but remained unaffected by PFOS. Our results suggest that PFOS exposure may disturb the intestinal microbiota, but that antibiotic-induced modulation of the intestinal ecosystem does not affect systemic uptake of PFOS in rats.


Comparison of polymerase chain reaction and culture methods for detection of Mycoplasma pulmonis from nasal, tracheal and oral swab samples of rats.
The polymerase chain reaction (PCR) and culture methods were used to detect Mycoplasma pulmonis in nasal, tracheal and oral swab samples of rats derived from 5 mycoplasma-contaminated and 2 mycoplasma-free facilities, and the results of both methods were compared. Thirty-four/54 and 30/54 in nasal samples, 31/54 and 28/54 in tracheal samples, and 12/39 and 30/39 in oral samples were positive in PCR and cultures, respectively. Agreements in the results of both tests were 48/54 (88.9%) in nasal samples and 49/54 (90.7%) in tracheal samples. This indicates that nasal and tracheal samples are useful for detecting M. pulmonis by PCR. The detection number for M. pulmonis from the oral cavity by PCR was remarkably lower than those of nasal and tracheal sites. These results show that the PCR method has significant potential as a rapid and sensitive method for detecting M. pulmonis in clinical samples collected from the nasal cavity and trachea.


Coal-Bed Methane Water: Effects on Soil Properties and Camelina Productivity.
Every year, the production of coal-bed natural gas in the Powder River Basin results in the discharge of large amounts of coal-bed methane water (CBMW) in Wyoming; however, no sustainable disposal methods for CBMW are currently available. A greenhouse study was conducted to evaluate the potential to use CBMW as a source of irrigation water for camelina [ (L.) Crantz]. We assessed the effects of three CBMW concentrations (0% [1:0], 50% [1:1], and 100% [0:1] tap water to CBMW) on selected soil properties, growth, seed oil, and fatty acid composition of three camelina cultivars: Blaine Creek, Ligena, and Pronghorn. The 100% CBMW reduced seed and estimated biofuel yields by 24 and 23%, respectively, but increased the oil content by 3%, relative to the control. Additionally, the 100% CBMW visibly affected soil through formation of surface crust due to elevated levels of sodium (653 mg Na kg). The 50% CBMW had no significant effects on the seed yield, estimated biofuel yield, and oil content, but the soil Na levels were still high (464 mg kg), which could pose a long-term impact on soil structure. The CBMW tended to reduce the total saturated fatty acid, but it had no significant effects on the total monounsaturated or polyunsaturated fatty acids of camelina seeds. Overall, CBMW diluted with an equal amount of good-quality water could be used to irrigate camelina in the short term. Afterward, only good-quality water would have to be used until the accumulated dissolved solids are flushed out.


A flexible 70 MHz phase-controlled double waveguide system for hyperthermia treatment of superficial tumours with deep infiltration.
Superficial tumours with deep infiltration in the upper 15 cm of the trunk cannot be treated adequately with existing hyperthermia systems. The aim of this study was to develop, characterise and evaluate a new flexible two-channel hyperthermia system (AMC-2) for tumours in this region. The two-channel AMC-2 system has two horizontally revolving and height adjustable 70 MHz waveguides. Three different interchangeable antennas with sizes 20 × 34, 15 × 34 and 8.5 × 34 cm were developed and their electrical properties were determined. The performance of the AMC-2 system was tested by measurements of the electric field distribution in a saline water filled elliptical phantom, using an electric field vector probe. Clinical feasibility was demonstrated by treatment of a melanoma in the axillary region. Phantom measurements showed a good performance for all waveguides. The large reflection of the smallest antenna has to be compensated by increased forward power. Field patterns become asymmetrical when using smaller top antennas, necessitating phase corrections. The clinical application showed that tumours deeper than 4 cm can be heated adequately. A median tumour temperature of 42 °C can be reached up to 12 cm depth with adequate antenna positioning and phase-amplitude steering. This 70 MHz AMC-2 waveguide system is a useful addition to existing loco-regional hyperthermia equipment as it is capable of heating axillary tumours and other tumours deeper than 4 cm.


Controlled DNA Patterning by Chemical Lift-Off Lithography: Matrix Matters.
Nucleotide arrays require controlled surface densities and minimal nucleotide-substrate interactions to enable highly specific and efficient recognition by corresponding targets. We investigated chemical lift-off lithography with hydroxyl- and oligo(ethylene glycol)-terminated alkanethiol self-assembled monolayers as a means to produce substrates optimized for tethered DNA insertion into post-lift-off regions. Residual alkanethiols in the patterned regions after lift-off lithography enabled the formation of patterned DNA monolayers that favored hybridization with target DNA. Nucleotide densities were tunable by altering surface chemistries and alkanethiol ratios prior to lift-off. Lithography-induced conformational changes in oligo(ethylene glycol)-terminated monolayers hindered nucleotide insertion but could be used to advantage via mixed monolayers or double-lift-off lithography. Compared to thiolated DNA self-assembly alone or with alkanethiol backfilling, preparation of functional nucleotide arrays by chemical lift-off lithography enables superior hybridization efficiency and tunability.


Evaluation of rifaximin, placebo and lactulose in reducing the levels of benzodiazepine-like compounds in patients with liver cirrhosis: a pilot study.
Benzodiazepine-like compounds (BZDs), either taken with the diet or synthesized by intestinal bacterial flora, may represent a precipitating factor for hepatic encephalopathy (HE) in cirrhotic patients. We evaluated whether a diet and/or treatment with rifaximin or lactulose can reduce serum concentrations of BZDs in 18 cirrhotic patients without HE. Patients were given a standard diet for 7 days to keep the dietary intake of BZDs constant and were then randomized to a 7-day treatment with rifaximin 1,200 mg/day, lactulose 10-20 g three times daily, or placebo. Blood samples were collected at enrollment, at the end of the diet and drug treatment periods, and 7 days after the drug was stopped (follow-up). Serum concentrations of BZDs were measured by a radioligand binding technique after high-performance liquid chromatography extraction and purification and were expressed as diazepam equivalents (DE). No change in serum BZD concentrations was observed during the diet, while a statistically significant decrease from 105.6 +/- 66.5 to 63.5 +/- 49.5 pmol DE/ml was achieved in rifaximin-treated patients (p < 0.05) but not in patients treated with lactulose or placebo. During the followup, serum BZD concentrations returned to 104.5 +/- 74.0 pmol DE/ml in rifaximin-treated patients (p < 0.05 vs. end-treatment values), while no significant change was observed in the lactulose- and placebo-treated patients. These data indicate that control of bacterial flora with cyclic administration of rifaximin plays a pivotal role in avoiding increased plasma concentrations of BZDs, which represent a precipitating factor for HE inpatients with severe liver disease.


Vaginal microflora in postmenopausal women on hormone replacement therapy.
To study the spectrum of vaginal microflora in postmenopausal women on hormone replacement therapy (HRT) and to compare the efficacy of Papanicolaou (Pap) smears with other methods for their detection. Eighty postmenopausal women were recruited for the study. These included 40 women who had attained spontaneous and were on HRT (User 1); 20 hysterectomised women on only estrogen therapy (User 2) and 20 controls (Non users). Their clinical data was recorded and specimens were collected for vaginal cultures (for aerobic bacteria and fungi), vaginal pH, Gram stain and Pap stain on cervical-vaginal smears and toluidine blue on wet smears. Vaginal pH was significantly lower in Users as compared to Non users. Lactobacilli and Gardnerella were more frequently isolated from Users while Bacteroides and E. coli were more common in Non users. Cultures were significantly more sensitive than Gram stained direct vaginal smears in detection of aerobic bacteria; however, Candida could be detected on Gram stain alone in all the cases. Frequency of detection of organisms significantly improved by application of Gram stain to the cervico-vaginal smears. However, clinically relevant organisms like Candida, Gardnerella and Mobiluncus could be identified on Pap smears alone in >50% cases. Lactobacilli could be readily identified in Pap smears in 98% cases. Wet mounts could detect cocci more easily as compared to Pap smears. Altered vaginal microbial profile in post menopausal women receiving HRT may cause bacterial and fungal vaginitis. Although culture studies remain the gold standard to detect these microorganisms, Pap and Gram stains and wet smears provide useful supplements and may be used as alternative procedures especially in resource limited settings lacking adequate culture facilities.


Isolation and structure of a cDNA expressing a mammalian 3-methyladenine-DNA glycosylase.
A cDNA plasmid expression library was constructed from the poly(A)+ mRNA of H4 cells, a rat hepatoma cell line. The library was introduced into Escherichia coli strain BH290 deficient in the repair of 3-methyladenine (3-meAde) residues in DNA. This DNA repair deficiency renders the stain phenotypically sensitive to treatment with alkylating agents. The cDNA library was screened for survivors to methylmethane sulfonate. BH290 cells hosting one of the plasmids, pAPDG10 (Alkylated N-Purine-DNA Glycosylase), from surviving cells had a sensitivity to MMS equivalent to that of the wild type strain. Crude extracts of BH290 cells harboring the pAPDG10 plasmid released 3-meAde and 7-methylguanine residues from DNA methylated with [methyl-3H]dimethylsulfate. The cDNA sequence of 993 bp inserted in pAPDG10 has a single open reading frame greater than 85 amino acids in length. The derived APDG protein sequence of 253 amino acids and the 3-meAde-DNA glycosylase II of E. coli coded for by the alkA gene have regions of conserved sequences. Analysis of the genomic DNA using Southern hybridization suggests that the APDG gene has a minimal size of 6.5-12 kb. Northern blot analysis shows that the transcript produced in H4 cells is also present in normal rat liver cells.


Isolation and structural elucidation of cyclic tetrapeptides from Onychocola sclerotica.
Three new cyclic tetrapeptides (1-3) have been isolated from the crude fermentation extract of Onychocola sclerotica. The planar structures of 1-3 were elucidated by detailed spectroscopic analyses using one- and two-dimensional NMR experiments and high-resolution mass spectrometry. The absolute configuration of the amino acid residues in each cyclotetrapeptide was established by Marfey's method. Compounds 1-3 displayed activity as cardiac calcium channel blockers (Cav1.2) but did not inhibit the hERG potassium channel and were not cytotoxic. These peptides are the first secondary metabolites ever reported from fungi of the order Arachnomycetales.


Copy number variations in the genome of the Qatari population.
The populations of the Arabian Peninsula remain the least represented in public genetic databases, both in terms of single nucleotide variants and of larger genomic mutations. We present the first high-resolution copy number variation (CNV) map for a Gulf Arab population, using a hybrid approach that integrates array genotyping intensity data and next-generation sequencing reads to call CNVs in the Qatari population. CNVs were detected in 97 unrelated Qatari individuals by running two calling algorithms on each of two primary datasets: high-resolution genotyping (Illumina Omni 2.5M) and high depth whole-genome sequencing (Illumina PE 100bp). The four call-sets were integrated to identify high confidence CNV regions, which were subsequently annotated for putative functional effect and compared to public databases of CNVs in other populations. The availability of genome sequence was leveraged to identify tagging SNPs in high LD with common deletions in this population, enabling their imputation from genotyping experiments in the future. Genotyping intensities and genome sequencing data from 97 Qataris were analyzed with four different algorithms and integrated to discover 16,660 high confidence CNV regions (CNVRs) in the total population, affecting ~28 Mb in the median Qatari genome. Up to 40% of all CNVs affected genes, including novel CNVs affecting Mendelian disease genes, segregating at different frequencies in the 3 major Qatari subpopulations, including those with Bedouin, Persian/South Asian, and African ancestry. Consistent with high consanguinity levels in the Bedouin subpopulation, we found an increased burden for homozygous deletions in this group. In comparison to known CNVs in the comprehensive Database of Genomic Variants, we found that 5% of all CNVRs in Qataris were completely novel, with an enrichment of CNVs affecting several known chromosomal disorder loci and genes known to regulate sugar metabolism and type 2 diabetes in the Qatari cohort. Finally, we leveraged the availability of genome sequence to find suitable tagging SNPs for common deletions in this population. We combine four independently generated datasets from 97 individuals to study CNVs for the first time at high-resolution in a Gulf Arab population.


Technical review of endovenous laser therapy for varicose veins.
In the last decade, several new treatments of truncal varicose veins have been introduced. Of these new therapies, endovenous laser therapy (EVLT) is one of the most widely accepted and used treatment options for incompetent greater and lesser saphenous veins. The objective of this report is to inform clinicians about the EVLT procedure and to review its efficacy and safety in treatment of truncal varicose veins. Also, we discuss some of the underlying theoretical principles and laser parameters that affect EVLT. We carried out a literature review of EVLT;s efficacy and safety. We included reports that included 100 or more limbs with a follow-up of at least 3 months. The principals and procedure of EVLT are described. Of the laser parameters, mode of administration, wavelength, fluence, wattage and pullback speed are discussed. EVLT appears to be a very effective and safe option in the treatment of varicose veins but large randomized comparative studies are needed.


Association of hypothyroidism with acute COVID-19: a systematic review.
There is an increasing body of literature on the impact of COVID-19 on the pituitary-thyroid axis. Therefore, we conducted a systematic review to assess the prevalence of hypothyroidism in patients with COVID-19. A literature review was conducted using LitCOVID for study selection in PubMed and MEDLINE till May 2021. All relevant original articles evaluating thyroid dysfunction were included and information regarding the prevalence of hypothyroid disease in COVID-19 was retrieved from the eligible articles. Out of 32 articles, six articles qualified for the final analysis which included 1160 patients. There was significant heterogeneity among the included articles. Most of the patients had lower mean triiodothyronine (T3) and normal or low thyroid-stimulating hormone (TSH). Increased TSH ranged from 5.1% to 8% while low T3 was present in up to 28% of the patients. In these studies, the prevalence of altered thyroid hormones was significantly more in COVID-19 patients as compared to control groups. A positive correlation between low mean T3 and clinical severity of COVID-19 was reported. This systematic review reveals a significant proportion of hypothyroidism associated with COVID-19. Therefore, routine assessment of thyroid function is warranted in hospitalized COVID-19 patients.


Dose compensation based on biological effectiveness due to interruption time for photon radiation therapy.
To evaluate the biological effectiveness of dose associated with interruption time; and propose the dose compensation method based on biological effectiveness when an interruption occurs during photon radiation therapy. The lineal energy distribution for human salivary gland tumor was calculated by Monte Carlo simulation using a photon beam. The biological dose (Dbio) was estimated using the microdosimetric kinetic model. The dose compensating factor with the physical dose for the difference of the Dbio with and without interruption (Δ) was derived. The interruption time (τ) was varied to 0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, and 120 min. The dose per fraction and dose rate varied from 2 to 8 Gy and 0.1 to 24 Gy/min, respectively. The maximum Δ with 1 Gy/min occurred when the interruption occurred at half the dose. The Δ with 1 Gy/min at half of the dose was over 3% for τ >= 20 min for 2 Gy, τ = 10 min for 5 Gy, and τ = 10 min for 8 Gy. The maximum difference of the Δ due to the dose rate was within 3% for 2 and 5 Gy, and achieving values of 4.0% for 8 Gy. The dose compensating factor was larger with a high dose per fraction and high-dose rate beams. A loss of biological effectiveness occurs due to interruption. Our proposal method could correct for the unexpected decrease of the biological effectiveness caused by interruption time. For photon radiotherapy, the interruption causes the sublethal damage repair. The current study proposed the dose compensation method for the decrease of the biological effect by the interruption.


Effect of nonthermal treatments on selected natural food pigments and color changes in plant material.
In recent years, traditional high-temperature food processing is continuously being replaced by nonthermal processes. Nonthermal processes have a positive effect on food quality, including color and maintaining natural food pigments. Thus, this article describes the influence of nonthermal, new, and traditional treatments on natural food pigments and color changes in plant materials. Characteristics of natural pigments, such as anthocyanins, betalains, carotenoids, chlorophylls, and so forth available in the plant tissue, are shortly presented. Also, the characteristics and mechanism of nonthermal processes such as pulsed electric field, ultrasound, high hydrostatic pressure, pulsed light, cold plasma, supercritical fluid extraction, and lactic acid fermentation are described. Furthermore, the disadvantages of these processes are mentioned. Each treatment is evaluated in terms of its effects on all types of natural food pigments, and the possible applications are discussed. Analysis of the latest literature showed that the use of nonthermal technologies resulted in better preservation of pigments contained in the plant tissue and improved yield of extraction. However, it is important to select the appropriate processing parameters and to optimize this process in relation to a specific type of raw material.


Herpes hepatitis as a complication of total abdominal hysterectomy; an unusual complication of abdominal instrumentation.
Herpes simplex virus hepatitis is a rare but potentially fatal disease without early intervention. Impaired immunity is a major predisposing risk factor but infection in immunocompetent individuals is not unheard of. Diagnosis is complicated by its rarity and nonspecific signs and symptoms on presentation. Identification by liver biopsy is often limited due to concurrent coagulopathy. Early and aggressive treatment is centered on antiviral therapy with acyclovir. We present a case of herpes hepatitis in an immunocompetent woman following abdominal instrumentation.


School engagement mediates long-term prevention effects for Mexican American adolescents.
This 5-year follow-up of a randomized clinical trial evaluated the efficacy of a family-focused intervention delivered in middle school to increase school engagement following transition to high school (2 years post-test), and also evaluated mediated effects through school engagement on multiple problem outcomes in late adolescence (5 years post-test). The study sample included 516 Mexican American adolescents who participated in a randomized trial of the Bridges to High School Program (Bridges/Puentes). Path models representing the direct and indirect effects of the program on four outcome variables were evaluated using school engagement measured in the 9th grade as a mediator. The program significantly increased school engagement, with school engagement mediating intervention effects on internalizing symptoms, adolescent substance use, and school dropout in late adolescence when most adolescents were in the 12th grade. Effects on substance use were stronger for youth at higher risk based on pretest report of substance use initiation. There were no direct or indirect intervention effects on externalizing symptoms. Findings support that school engagement is an important prevention target for Mexican American adolescents.


Seabed acoustics of a sand ridge on the New Jersey continental shelf.
Acoustic measurements were made on a sand ridge on the New Jersey continental shelf. Data collected on two L arrays separated by 20 km from a single multi-frequency tow suggest small horizontal environmental variability. Values for the sound speed structure of the seabed are extracted by first applying a geo-acoustic inversion method to broadband and narrowband acoustic data from short-range sources. Then, a parabolic equation algorithm is used to properly include the bathymetry and sub-bottom layering. Finally, the frequency dependence of the seabed attenuation is inferred by optimizing the model fit to long-range transmission loss data in the 50-3000 Hz band.


Intersegmental coordination of limb movements during locomotion: mathematical models predict circuits that drive swimmeret beating.
Normal locomotion in arthropods and vertebrates is a complex behavior, and the neural mechanisms that coordinate their limbs during locomotion at different speeds are unknown. The neural modules that drive cyclic movements of swimmerets respond to changes in excitation by changing the period of the motor pattern. As period changes, however, both intersegmental phase differences and the relative durations of bursts of impulses in different sets of motor neurons are preserved. To investigate these phenomena, we constructed a cellular model of the local pattern-generating circuit that drives each swimmeret. We then constructed alternative intersegmental circuits that might coordinate these local circuits. The structures of both the model of the local circuit and the alternative models of the coordinating circuit were based on and constrained by previous experimental results on pattern-generating neurons and coordinating interneurons. To evaluate the relative merits of these alternatives, we compared their dynamics with the performance of the real circuit when the level of excitation was changed. Many of the alternative coordinating circuits failed. One coordinating circuit, however, did effectively match the performance of the real system as period changed from 1 to 3.2 Hz. With this coordinating circuit, both the intersegmental phase differences and the relative durations of activity within each of the local modules fell within the ranges characteristic of the normal motor pattern and did not change significantly as period changed. These results predict a mechanism of coordination and a pattern of intersegmental connections in the CNS that is amenable to experimental test.


Efficiency and Specificity of Gene Deletion in Lung Epithelial Doxycycline-Inducible Cre Mice.
The transgenic mouse strains surfactant protein C-reverse tetracycline transactivator (SP-C-rtTA), club cell secretory protein (CCSP)-rtTA, and tetracycline operator (TetO)-Cre have been invaluable for spatiotemporally regulating gene deletion in the pulmonary epithelium. In this study, we measured the efficiency and specificity of gene deletion that can be achieved in these mice using the Rosa26-eYFP reporter. Triple-transgenic mice (tTg or rtTA/TetO-Cre/Rosa-eYFP) were bred and treated with various doxycycline (dox) regimens to induce gene deletion, which was then quantified in various cell populations by flow cytometry. In these crosses, we found that the TetO-Cre transgene must be transmitted through the female parent to avoid germline gene deletion. With dox exposure during lung development, SP-C-tTg mice deleted in ∼65-75% of alveolar epithelial type II (ATII) cells, but in only ∼45-50% of the integrin β4+ population, which consisted of club cells and distal lung progenitor cells. In contrast, CCSP-tTg mice deleted in ∼50% of ATII cells and ∼80% of integrin β4+ cells. Upon dox treatment of adults, deletion in ATII cells and integrin β4+ cells in SP-C-tTg mice dropped significantly to ∼20% and ∼6%, respectively, whereas CCSP-tTg mice deleted in ∼57% of ATII and ∼40% of integrin β4+ cells. Interestingly, untreated CCSP-tTg mice also deleted in ∼40% of integrin β4+ cells, indicating significant leakiness of CCSP-tTg in β4+ cells. In all mouse groups, minimal deletion occurred in mouse tracheal epithelial cells or in mesenchymal or hematopoietic cells. These data provide the first quantitative, side-by-side comparison of the deletion efficiency for these widely used transgenic mouse strains.


Collection of dietary data from children with cystic fibrosis: some problems and practicalities.
The literature on the collection of dietary data is both extensive and confusing. Few practical details are given, particularly for the clinical situation, which are useful to the novice. In response to this, and calls from various authors, the basis for deciding on methods for collecting dietary data from a group of patients in the clinical setting is illustrated here. Practical aspects of data collection and analysis are detailed.


Expected Lifetime in Different Employment Statuses: Evidence From the Economic Boom-and-Bust Cycle in Spain.
This article analyses the impact of the recent economic crisis on the expected time spent in different employment statuses in Spain. Using data from the Economically Active Population Survey and life tables, we estimate the expected time in work, unemployment, retirement, and other types of economic inactivity during the economic boom-and-bust cycle. Differences in expected years of life spent in different employment statuses are decomposed into effects of mortality and employment behavior. Our results show that men's working life expectancy is much more exposed to economic fluctuations. The impact of the ebbs and flows of the business cycle among women is mitigated by the long-term female trend of growing participation in the labor market associated with the increasing educational attainment of women. In addition, the improvement in mortality only partially contributes to gains in time spent in each status, while the main effects correspond to changes in labor market participation.


[A case of initially unresectable gallbladder cancer with surgical resection after chemotherapy with gemcitabine].
A 75-year-old woman was admitted to our hospital with elevated serum hepatic enzyme levels. After evaluation with imaging studies, she was diagnosed as having gallbladder cancer, which had invaded the liver and hepatic artery, with lymph node metastases. The tumor was considered unresectable, and the patient received chemotherapy with gemcitabine (GEM)alone. Six months later, computed tomography(CT)indicated shrinkage of the gallbladder tumor and disappearance of lymph node metastases. Surgical resection was planned. However, liver metastasis was suspected on the basis of macroscopic findings, and the patient underwent gallbladder bed resection. Pathological examination indicated that almost all of the tumor cells in the gallbladder were viable; however, there were no tumor cells in the liver nodule and lymph node. The postoperative course was uneventful. The patient received adjuvant chemotherapy with GEM and was alive without recurrence 17 months after tumor resection. Immunohistochemical analysis showed that 80.9% of the tumor cells were positive for CD133, a cancer stem cell marker. This case illustrates a possible relationship between cancer stem cells and chemoresistance.


Recombination between the postulated CCD/MHE/MHS locus and RYR1 gene markers.
Malignant hyperthermia (MH) susceptibility is considered a subclinical myopathy or a pharmacogenetic trait, and is believed to be closely associated with central core disease (CCD). Data support the notion that MH susceptibility is heterogeneous, with the ryanodine receptor I (RYR1) locus on chromosome 19 being one locus harboring a gene that can cause MH susceptibility. The gene for CCD is believed to reside in the locus on chromosome 19. In the family presented here, a girl has CCD, and several close relatives are MH susceptible (MHS). DNA studies conducted on available family members uncovered recombination between the MH susceptibility locus and RYR1 markers. Consequently, if one postulates that the CCD gene in this family resides in the same locus as the MH susceptibility gene, an additional CCD locus different from the RYR1 locus must also be postulated.


Minimal erythema dose after multiple UV exposures depends on pre-exposure skin pigmentation.
Phototherapy consists of multiple ultraviolet (UV) exposures. Most previous studies have focused on erythema following a single UV exposure in fair-skinned persons. Although it is well known that phototherapy lowers the daily UV-threshold dose for erythema in clinical practice, this is insufficiently documented under controlled experimental conditions. The purpose of this study was to quantify the change in the daily threshold for a dose specific erythema grade after 1-4 consecutive daily UV exposures. Forty-nine healthy volunteers (skin type II-V) with varying pigmentation quantified by skin reflectance. Two UV sources were used: a narrowband UVB (Philips TL01) and a Solar Simulator (Solar Light Co.). Just perceptible erythema after 24 h was chosen as the minimal erythema dose (+); besides + and ++ were assessed. We found a positive and significant exponential relationship between skin pigmentation and UV dose to elicit a specific erythema grade on the back after 1-4 UV exposures. After repetitive UV exposures the UV dose had to be lowered more in dark-skinned persons compared with fair-skinned persons to elicit a certain erythema grade. This applied to both UV sources and all erythema grades. In the dark-skinned persons the daily UV dose after the 4 days UV exposure should be lowered by 40-50% to avoid burns compared with the single UV exposure. For the most fair-skinned persons essentially no reduction in the daily UV dose was needed. Our results indicate that the pre-exposure pigmentation level can guide the UV dosage in phototherapy.


Live your life out loud.
Susan Love, MD, MBA, has dedicated her professional life to the eradication of breast cancer. Author of the bestselling Dr. Susan Love's Breast Book, Dr. Susan Love's Menopause and Hormone Book, and Live a Little, Susan is Chief Visionary Officer of the Dr. Susan Love Research Foundation where she oversees an active research program centered on breast cancer cause and prevention. Susan co-founded the National Breast Cancer Coalition in the early 1990s, and she served on President Clinton's National Cancer Advisory Board from 1998-2004. Her recent projects include recruiting 377,000 women for the Love Army of Women, an Internet program that partners women and scientists to accelerate breast cancer research; and the online Health of Women Study designed to identify the cause of breast cancer. A recipient of six honorary doctorate degrees, Susan is Clinical Professor of Surgery at the David Geffen School of Medicine at the University of California, Los Angeles. In June of 2012, Susan was diagnosed with acute myelogenous leukemia and was treated with an allogenic stem cell transplant.


Open-label Study of Injectable Extended-release Naltrexone (XR-NTX) in Healthcare Professionals With Opioid Dependence.
Healthcare professionals (HCPs) with opioid dependence are at risk for relapse and death, particularly in the first year of recovery; however, maintenance treatment with opioid agonists is controversial in this safety-sensitive group. We evaluated long-term safety, tolerability, and treatment outcomes of injectable, intramuscular, extended-release naltrexone (XR-NTX) in opioid-dependent HCPs. This single-arm, multisite, open-label study was conducted in opioid-dependent HCPs who had been detoxified from opioids for at least 2 weeks. Subjects received monthly XR-NTX injections for up to 24 months, combined with counseling via intensive outpatient substance abuse treatment programs. Assessments included monthly urine opioid drug tests and routine safety assessments, along with a trimonthly short form (36) Health Survey, opioid craving questionnaire, and Treatment Satisfaction Questionnaire for Medication. Of 49 opioid-dependent HCPs screened, 38 enrolled and received at least 1 XR-NTX injection. Most were female (n = 31) and nurses or nursing assistants (n = 30). More than half (n = 21; 55.3%) received at least 12 injections. Seven discontinued due to adverse events (3 anxiety, 2 headache, 1 injection-site mass, 1 derealization). None experienced relapses to opioid dependence necessitating detoxification, overdose, or death during treatment. At 24 months, mean opioid craving fell by 45.2%, and short form (36) mental component scores improved by 31.1% from baseline and approached normal levels. Of 22 unemployed subjects at baseline, 45.5% improved employment status at 24 months. Long-term (2 years) XR-NTX was associated with no new safety concerns, and, compared with shorter-term studies in the general population, similar or better rates of retention, opioid-negative urines, opioid craving reduction, mental health functional quality of life improvement, and re-employment.


Intraspinal grafting procedures: spinal cord effects induced in the adult rat: a clinical, histopathological, and immunohistochemical study.
Intraspinal grafting procedures using peripheral nerve grafts (PNG) or collagen guidance channels (CGC) have been recently used to treat brachial plexus injuries in humans and spinal cord injuries in animals. This study examined the effects of these procedures in the adult rat. In adult rats, we performed an avulsion of left C5, C6, and C7 nerve roots, followed by a myelotomy of the left ventrolateral aspect of the spinal cord between C5 and C6. The rats were subsequently assigned to one of three groups: group A (n = 10), no additional procedure; group B (n = 10), implantation of a PNG following myelotomy; group C (n = 10), implantation of a CGC. Clinical evaluation was postoperatively assessed. Rats were euthanized at day 6 or 21. Spinal cord lesions induced by surgery were assessed by measuring depth and rostrocaudal extent. Reactive astrogliosis, as a reaction to neuroglial damage, was assessed by revealing the glial fibrillary acidic protein with immunochemistry method. No animal showed persistent neurological deficit at day 21. The depth and rostrocaudal extent of tissue damage was comparable in all groups at days 6 and 21. At day 6, the astrocytic reaction observed at the myelotomy/implantation site was statistically stronger in group C (CGC). At day 21, the astrocytic reaction became identical in all groups. This study shows that grafting a PNG or a CGC into the spinal cord does not create significant additional iatrogenic effects and can be used in repair strategies to treat nerve root avulsions or spinal cord injuries.


Changes in psychological symptoms during ambulant detoxification.
Reports suggest a high prevalence of psychological symptoms in alcohol-dependent patients, but there are difficulties in evaluating their significance. To elucidate these relationships, the effect of withdrawal from alcohol on psychological symptoms in men and women detoxifying on an ambulant basis was examined. A prospective study of 65 patients was carried out using a standardized interview which included sociodemographic indices, measures of alcohol dependence and problems. Psychological symptoms were measured using the General Health Questionnaire at three different time points. The majority of alcohol-dependent patients presented for treatment with co-existing psychological symptoms, but, for both men and women, these decreased rapidly after a 10-day detoxification period. For patients who remained abstinent over the next 6 weeks there was a further decline in psychological symptoms to almost asymptomatic levels. For those who resumed drinking, no such improvement was apparent. The clinical implication is that treatment for what may at first appear to be an independent co-morbid disorder may not be necessary once the patient has been withdrawn from alcohol and has achieved a period of abstinence.


Dynamic two-photon imaging of the immune response to Toxoplasma gondii infection.
Toxoplasma gondii is a highly successful parasite that can manipulate host immune responses to optimize its persistence and spread. As a result, a highly complex relationship exists between T. gondii and the immune system of the host. Advances in imaging techniques, and in particular, the application of two-photon microscopy to mouse infection models, have made it possible to directly visualize interactions between parasites and the host immune system as they occur in living tissues. Here, we will discuss how dynamic imaging techniques have provided unexpected new insight into (i) how immune responses are dynamically regulated by cells and structures in the local tissue environment, (ii) how protective responses to T. gondii are generated and (iii) how the parasite exploits the immune system for its own benefit.


[Assessment of dietary intake of overweight and obese adolescents before and after the introduction of dietetic recommendations].
Prevalence of overweight and obesity among children and adolescents continues to increase. Treatment of obesity includes reducing caloric intake through limitation of fat and simple carbohydrate intake supply in meals. The aim of this study was to assess dietary intakes of overweight and obese adolescents before and after the introduction of dietetic recommendations. Participants included 26 overweight and obese 13-19 year old adolescents. They used the reducing diet for 3 months. Dietary intakes were assessed using 3-day dietary recalls administered before and after the introduction of dietetic recommendations. The energy value and content of nutritive components in meals of adolescents were calculated by the Nutritionist IV computer program with Polish data base. After introduction of dietetic recommendations in obese adolescents statistically significant reduction of total fat intake (22.4%), saturated fatty acids intake (23.9%) and cholesterol intake (25.9%) was observed. However, it was accompanied by a significant reduction of mono- (23.6%) and polyunsaturated fatty acids (18.9%) intake. Introduction of the dietetic recommendations in overweight and obese adolescents is able to change their dietary habits in generally favourable manner. However, reducing diet in adolescents needs to be supervised due to the risk of deficiency of some nutrients in their food and possible negative effect on health.


Psychosynthesis: A Foundational Bridge Between Psychology and Spirituality.
Pastoral psychologists have long tried to establish a working model that encompasses the seemingly conflicting disciplines of science and religion. Psychosynthesis, a transpersonal psychology and therapeutic approach, offers such a model of the human personality, in which the psychological and spiritual perspectives can converge. This article explores psychosynthesis psychology and therapy as a theoretical framework for pastoral psychology. Although psychosynthesis psychotherapy relies on an array of techniques, it fundamentally works with the clients' will while emphasizing, exploring, and cultivating their relationships on all levels-intrapersonal, interpersonal, and with the Higher Self. In addition to the subconscious, psychosynthesis includes a higher psychological plane, called the superconscious, from which our higher ethical, aesthetic, scientific, and spiritual values are derived. This article begins by introducing psychosynthesis concepts and techniques. It then provides qualitative findings showing that psychosynthesis counseling helped to awaken spirituality in three out of eleven clients who had formerly identified themselves as atheists. In addition, testimonies are included that show that psychosynthesis counseling also helped all eleven clients to attain personal growth. Finally, the counselor describes her experience of psychosynthesis as a Christian in the therapeutic setting. The framework of psychosynthesis psychology and its techniques are viable methodologies for anyone searching to incorporate spiritual growth into a psychological working model.


Quality of life and objective outcome assessment in women with tape division after surgery for stress urinary incontinence.
Midurethral tapes may cause long-term complications such as voiding dysfunction, groin pain, de novo urgency or mesh erosion, which necessitate a reoperation. There is a paucity of data regarding health related quality of life in patients undergoing tape removal. The aim of the study was to evaluate quality of life (QoL) and objective outcome after midurethral tape division or excision. All patients who underwent a midurethral tape division for voiding difficulties, pain or therapy resistant de novo overactive bladder between 1999 and 2014 were invited for follow-up. A control group with a suburethral tape without division was established in a 1:2 ratio and matched for age, tape used and year of tape insertion. Patients completed the Kings´ Health Questionnaire (KHQ), Incontinence Outcome Questionnaire, Female Sexual Function Index Questionnaire and the Patient Global Impression of Improvement score. Tape division or excision was performed in 32 women. Overall, 15 (60%) of 25 women who were alive were available for clinical examination and completed the questionnaires. Tape division was performed for voiding dysfunction (n = 7), overactive bladder (n = 2), mesh extrusion (n = 3) and ongoing pain (n = 3). Median time to tape division/excision was 10 months. Three women in the tape division group had undergone reoperation for stress urinary incontinence (SUI). At a median follow-up of 11 years (IQR 9-13) subjective SUI rate was 53% (8/15 women) in the tape division group and 17% (5/30) in the control group (p = 0.016), with no significant differences in objective SUI rates between groups. With regard to quality of life, the study group had significantly worse scores in the SUI related domains role limitation, physical limitation, severity measures and social limitations (KHQ) compared to the control group. Women needing tape division or excision have lower SUI related QoL scores compared to controls mostly because of higher subjective SUI rates.


Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population.
The polymorphisms of two genes have recently been associated with complex forms of type 2 diabetes mellitus (T2DM): calpain 10 and peroxisome proliferator-activated receptor-gamma (PPARgamma). Calpain 10 is a member of a large family of intracellular proteases. It was shown in Mexican-Americans and other populations that variants of three single nucleotide polymorphisms (SNPs), -43, -19, and -63, of this ubiquitously expressed protein influence susceptibility to T2DM. However, substantial differences were shown between ethnic groups in at risk alleles and haplotypes as well as in their attributable risk. Thus, it is important to determine the role of calpain 10 in various populations. To examine the role of calpain 10 SNPs -43, -19, and -63 in genetic susceptibility to T2DM in a Polish population. Overall, 377 individuals were examined: 229 T2DM patients and 148 control individuals. The groups were genotyped for calpain 10 SNP-43, SNP-19, and SNP-63. SNP-19 was examined by electrophoresis of the PCR product on agarose gel by size, while the restriction fragment length polymorphism (RFLP) method was used for the two other markers. Differences in allele, genotype, haplotype, and haplotype combination distribution between the groups were examined by chi(2) test. Distributions of alleles, genotypes, and haplotypes at three loci defined by examined SNPs were not significantly different between the groups. However, the homozygote combination of 121 haplotype was more prevalent in the T2DM group than in the controls (17.9% vs 10.1%, P=0.039). No difference was observed in the 112/121 haplotype distribution. This heterozygous haplotype combination was associated with increased risk of T2DM in several populations. The results of our study suggest the association of calpain 10 121/121 haplotype combination created by SNPs -43, -19, and -63 with T2DM in a Polish population. However, we were not able to confirm the previously described role of the heterozygous 112/121 haplotype combination in susceptibility to T2DM.


Extraction of the midsagittal plane from morphological neuroimages using the Kullback-Leibler's measure.
A theoretically simple and computationally efficient method to extract the midsagittal plane (MSP) from volumetric neuroimages is presented. The method works in two stages (coarse and fine) and is based on calculation of the Kullback and Leibler's (KL) measure, which characterizes the difference between two distributions. Slices along the sagittal direction are analyzed with respect to a reference slice to determine the coarse MSP. To calculate the final MSP, a local search algorithm is applied. The proposed method does not need any preprocessing, like reformatting, skull stripping, etc. The algorithm was validated quantitatively on 75 MRI datasets of different pulse sequences (T1WI, T2WI, FLAIR and SPGR) and MRA. The angular and distance errors between the calculated MSP and the ground truth lines marked by the expert were calculated. The average distance and angular deviation were 1.25 pixels and 0.63 degrees , respectively. In addition, the algorithm was tested qualitatively on PD, FLAIR, MRA, and CT datasets. To analyze the robustness of the method against rotation, inhomogeneity and noise, the phantom data were used.


Ventilation heterogeneity measured by multiple breath inert gas testing is not affected by inspired oxygen concentration in healthy humans.
Multiple breath washout (MBW) and oxygen-enhanced MRI techniques use acute exposure to 100% oxygen to measure ventilation heterogeneity. Implicit is the assumption that breathing 100% oxygen does not induce changes in ventilation heterogeneity; however, this is untested. We hypothesized that ventilation heterogeneity decreases with increasing inspired oxygen concentration in healthy subjects. We performed MBW in 8 healthy subjects (4 women, 4 men; age = 43 ± 15 yr) with normal pulmonary function (FEV1 = 98 ± 6% predicted) using 10% argon as a tracer gas and oxygen concentrations of 12.5%, 21%, or 90%. MBW was performed in accordance with ERS-ATS guidelines. Subjects initially inspired air followed by a wash-in of test gas. Tests were performed in balanced order in triplicate. Gas concentrations were measured at the mouth, and argon signals rescaled to mimic a N2 washout, and analyzed to determine the distribution of specific ventilation (SV). Heterogeneity was characterized by the width of a log-Gaussian fit of the SV distribution and from Sacin and Scond indexes derived from the phase III slope. There were no significant differences in the ventilation heterogeneity due to altered inspired oxygen: histogram width (hypoxia 0.57 ± 0.11, normoxia 0.60 ± 0.08, hyperoxia 0.59 ± 0.09, P = 0.51), Scond (hypoxia 0.014 ± 0.011, normoxia 0.012 ± 0.015, hyperoxia 0.010 ± 0.011, P = 0.34), or Sacin (hypoxia 0.11 ± 0.04, normoxia 0.10 ± 0.03, hyperoxia 0.12 ± 0.03, P = 0.23). Functional residual capacity was increased in hypoxia (P = 0.04) and dead space increased in hyperoxia (P = 0.0001) compared with the other conditions. The acute use of 100% oxygen in MBW or MRI is unlikely to affect ventilation heterogeneity.NEW & NOTEWORTHY Hyperoxia is used to measure the distribution of ventilation in imaging and MBW but may alter the underlying ventilation distribution. We used MBW to evaluate the effect of inspired oxygen concentration on the ventilation distribution using 10% argon as a tracer. Short-duration exposure to hypoxia (12.5% oxygen) and hyperoxia (90% oxygen) during MBW had no significant effect on ventilation heterogeneity, suggesting that hyperoxia can be used to assess the ventilation distribution.


A gene from Aspergillus nidulans with similarity to URE2 of Saccharomyces cerevisiae encodes a glutathione S-transferase which contributes to heavy metal and xenobiotic resistance.
Aspergillus nidulans is a saprophytic ascomycete that utilizes a wide variety of nitrogen sources. We identified a sequence from A. nidulans similar to the glutathione S-transferase-like nitrogen regulatory domain of Saccharomyces cerevisiae Ure2. Cloning and sequencing of the gene, designated gstA, revealed it to be more similar to URE2 than the S. cerevisiae glutathione S-transferases. However, creation and analysis of a gstA deletion mutant revealed that the gene does not participate in nitrogen metabolite repression. Instead, it encodes a functional theta class glutathione S-transferase that is involved in resistance to a variety of xenobiotics and metals and confers susceptibility to the systemic fungicide carboxin. Northern analysis showed that gstA transcription is strongly activated upon exposure to 1-chloro-2,4-dinitrobenzene and weakly activated by oxidative stress or growth on galactose as a carbon source. These results suggest that nitrogen metabolite repression in A. nidulans does not involve a homolog of the S. cerevisiae URE2 gene and that the global nitrogen regulatory system differs significantly in these two fungi.


The reductions in monetary cost and gains in productivity with methadone maintenance treatment: one year follow-up.
While methadone maintenance treatment (MMT) is beneficial for heroin dependence, there is little information regarding the reductions in monetary cost and gains in productivity following MMT. The aim of this study was to evaluate the changes in the monetary cost of heroin addiction and productivity after one year of MMT. Twenty-nine participants from an MMT clinic were included. The monetary cost, productivity, quality of life (QOL) and mental health status were assessed at both baseline and one year follow-up. The average annual total cost was approximately US$26,485 (1.43 GDP per capita in 2010) at baseline, and decreased by 59.3% to US$10,784 (0.58 GDP) at follow-up. The mean number of months of unemployment dropped from 6.03 to 2.79, the mean income increased to exceed the basic salary, but only reached 45.3% of the national average monthly earnings. The participants׳ mental health improved, but their QOL scores did not increase significantly. After one year of MMT, the monetary cost of heroin addiction fell, both the productivity and mental health of the participants׳ improved, but limited gains were seen with regard to their QOL.


Understanding uncertainty in the effect of low-head dams on fishes of Great Lakes tributaries.
Small dams represent one of the most widespread human influences on riverscapes. Greater understanding of how these structures affect aquatic organisms is needed to ensure that decisions regarding their construction and removal strike an appropriate balance between components of human and ecosystem services. Within the basin of the Laurentian Great Lakes, the effects that in-stream barriers (dams) used to control the non-native, parasitic sea lamprey (Petromyzon marinus) on the diversity of non-target fishes is a significant concern for fishery managers. A previous study indicated that upstream changes in the species richness of non-target fishes observed in 24 streams with a sea lamprey barrier relative to paired reference streams (a measure of effect size) was variable across the basin. We examined the degree to which the variance in effect size could be attributed to imprecision in the field sampling protocol used to estimate effect sizes, differences in catchment-scale landscape attributes between barrier and reference streams within pairs, and differences in landscape attributes at different spatial scales among barrier streams. Simulation modeling and analyses of repeated field measurements made for a subset of streams demonstrated that a large variance in effect size is expected for the field sampling design and that estimates of effect size measured for individual barrier streams are imprecise. Regression models and multimodel inference methods based on Akaike's Information Criterion provided less support for hypotheses linking effect size to landscape attributes. Mean effect size, adjusted for the influences of landscape characteristics within and across stream pairs, provides the most reliable and least biased estimate of the effect of sea lamprey barriers on the richness of nontarget fish species. With the information currently available, landscape characteristics of catchments cannot be used to help decision makers anticipate effects sizes for candidate streams being considered for future barrier construction. Our findings will help fishery managers in the Laurentian Great Lakes make more informed decisions regarding the use and placement of sea lamprey barriers and achieve their objective of delivering an integrated pest management plan for sea lamprey control that is environmentally and economically sound and socially acceptable.