The differentiation of chronic obstructive pulmonary disease from asthma: a review of current diagnostic and treatment recommendations.
Global and regional data have shown that chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma are increasing in incidence and prevalence, with detrimental consequences to healthcare resources and the quality of life of patients. A firm diagnosis of COPD or asthma is important because the natural history, treatment, and outcomes differ between the two respiratory diseases. The aim of this review is to provide nurse practitioners (NPs) with the requisite facts to understand and improve the diagnosis and treatment of affected individuals. Articles on the differential diagnosis, treatment, and management of COPD and asthma published in peer-reviewed journals were retrieved from PubMed. Evidence-based respiratory guidelines, World Health Organization disease-related data, and US prescribing information for different respiratory medications served as additional data sources. NPs, along with other primary care professionals, form the frontline in diagnosing, treating, and managing COPD and asthma. Differentiating COPD from asthma has prognostic as well as significant therapeutic implications. Since NPs play a key role in diagnosing and managing patients with COPD and asthma, those with a comprehensive understanding of the diagnostic and therapeutic differences between the two diseases can help to lower the risks of exacerbations and hospitalizations, and improve the quality of life of these patients.


[Irreversible coma and the physician's treatment responsibility].
Whether and how patients with clinically revealed persistant vegetative state (PVS) should be treated is a difficult question. In this paper the different approaches from maximum therapy to forego even nutrition and hydration are analysed and their underlying concepts examined. Within this context the official guidelines of the Swiss, the German as well as the British Medical Association are discussed.


The potential for understanding the synaptic organization of human motor commands via the firing patterns of motoneurons.
Motoneurons are unique in being the only neurons in the CNS whose firing patterns can be easily recorded in human subjects. This is because of the one-to-one relationship between the motoneuron and muscle cell behavior. It has long been appreciated that the connection of motoneurons to their muscle fibers allows their action potentials to be amplified and recorded, but only recently has it become possible to simultaneously record the firing pattern of many motoneurons via array electrodes placed on the skin. These firing patterns contain detailed information about the synaptic organization of motor commands to the motoneurons. This review focuses on parameters in these firing patterns that are directly linked to specific features of this organization. It is now well established that motor commands consist of three components, excitation, inhibition, and neuromodulation; the importance of the third component has become increasingly evident. Firing parameters linked to each of the three components are discussed, along with consideration of potential limitations in their utility for understanding the underlying organization of motor commands. Future work based on realistic computer simulations of motoneurons may allow quantitative "reverse engineering" of human motoneuron firing patterns to provide good estimates of the relative amplitudes and temporal patterns of all three components of motor commands.


The effectiveness of an enhanced invitation letter on uptake of National Health Service Health Checks in primary care: a pragmatic quasi-randomised controlled trial.
The National Health Service Health Check (NHS HC) is a population level public health programme. It is a primary prevention initiative offering cardiovascular risk assessment and management for adults aged 40-74 years (every five years). It was designed to reduce the incidence of major vascular disease events by preventing or delaying the onset of diabetes, heart and kidney disease, stroke and vascular dementia . Effectiveness of the programme has been modelled on a national uptake of 75% however in 2012/13 uptake, nationally, was 49%. Ensuring a high percentage of those offered an NHS HC actually receive one is key to optimising the clinical and cost effectiveness of the programme. A pragmatic quasi-randomised controlled trial was conducted in four general practitioner practices in Medway, England with randomisation of 3511 patients. The aim was to compare attendance at the NHS HC using the standard national invitation template letter (control) compared to an enhanced invitation letter using insights from behavioural science (intervention). The intervention letter includes i) simplification - reducing letter content for less effortful processing ii) behavioural instruction - action focused language iii) personal salience - appointment due rather than invited and iv) addressing implementation intentions with a tear off slip to record the date, time and location of the appointment. Logistic Regression explored the association between control and intervention group and attendance at a health check. 29.3% of patients who received the control letter and 33.5% of those who received the intervention letter attended their NHS HC (adjusted odds ratio 1.26, 95% confidence interval 1.09-1.47, p < 0.01). This was an absolute difference in uptake of 4.2 percentage points for those receiving the intervention letter. An invitation letter applying behavioural insights was more effective than the existing national template letter at encouraging attendance at an NHS HC. Making small, no cost behaviourally informed changes to letter invitations can improve uptake of the NHS HC. Further research is required to replicate the effect with more robust methodology and powered for sub-group analysis including socio-economic status. Current Controlled Trials ISRCTN66757664 , date of registration 28/3/2014.


Eco-Benign Orange-Hued Pigment Derived from Aluminum-Enriched Biogenous Iron Oxide Sheaths.
Inorganic pigments have been widely used due to their low cost of production, strong hiding power, and chemical resistance; nevertheless, they have limited hue width and chromaticity. To eliminate these disadvantages, we herein propose the use of an ingenious biotemplate technique to produce Al-enriched biogenic iron oxide (BIOX) materials. Spectrophotometric color analysis showed that high levels of Al inclusion on heat-treated BIOX samples produced heightened yellowish hues and lightness. The Al-enriched BIOX sheaths exhibited a stable tubular structure and excellent thermal stability of color tones after heating at high temperatures and repetitive heat treatments. Ultrastructural analysis and mechanical destruction experiments revealed that the highly chromatic orange-hue of these pigments are ascribed probably to an ingenious cylindrical nanocomposite architecture composed of putative Fe-included low crystalline Al oxide regions and hematite particles embedded therein. The present work therefore demonstrates that the bioengineered material can serve as an epochal orange-hued inorganic pigment with low toxicity and marked thermostability that should meet large industrial demand.


Critical Appraisal of Mental Health Applications.
Using mobile applications in health is progressing rapidly; hence, assessing them is essential to ensure their quality and standards. The present study was designed to critically evaluate the quality of existing applications in the field of mental health. In this is review the related keywords "Health and Mental health" were used in Persian and English to search in 4 application platforms: App Store, Google Play, Bazar (Persian version of Google Play), Sib app (Persian version of App Store). Inclusion criteria for the applications were either in Persian or English language and compatible with Android or IOS. The exclusion criteria were any application downloaded less than 100 times and those that were one dimensional such as only focusing on sleep disorder. A team of researchers reviewed each app in terms of two sets of criteria: 1) Mobile App Rating Scale (MARS) subdomain scores for reviewing engagement, functionality, esthetics, and information; and 2) personalization level. The search resulted in 958 apps, of which 61 had the inclusion criteria. Most of them (n=59, 97%) were rated as appropriate for all age groups and only two were designed for children. In MARS score, thirty-three percent (n=5) of the Persian apps received the rating of 2.5 or higher, while this score was 53 percent (n=27) for English applications. Eight application (13%) used dialogue boxes for personalization and 11 (18%) had feedback capability. None of the Persian apps could be personalized. Although numerous apps are available, there are only few apps with personalization features, which should be considered as one of the key features when developing this type of apps.


A tale of two global health programs. Smallpox eradication's lessons for the antipolio campaign in India.
India provided one of the most challenging chapters of the worldwide smallpox eradication program. The campaign was converted from a project in which a handful of officials tried to impose their ideas on a complex health bureaucracy to one in which its components were constantly adapted to the requirements of a variety of social, political, and economic contexts. This change, achieved mainly through the active participation of workers drawn from local communities in the 1970s, proved to be a momentous policy adaptation that contributed to certification of smallpox eradication in 1980. However, this lesson appears to have been largely forgotten by those currently managing the Global Polio Eradication Initiative. We hope to show ways in which contemporary efforts to eliminate polio worldwide might profitably draw on historical information, which can indicate meaningful ways in which institutional adaptability is likely to help counter the political and social challenges being encountered in India.


Application of a novel fluorescence probe in the determination of nucleic acids.
A novel fluorimetric method has been developed for rapid determination of DNA and RNA with hypocrellin A (HA) as a fluorescence probe, based on the fluorescence enhancement of HA in the presence of DNA or RNA. Maximum fluorescence is produced in the pH range 3.4-4.0, with maximum excitation and emission wavelengths at 470 and 600 nm, respectively. Under optimal conditions, the calibration graphs are linear over the range 0-200.0 ng cm-3 for calf thymus DNA and 13.0-200.0 ng cm-3 for yeast RNA, respectively. The corresponding detection limits are 5.0 ng cm-3 for calf thymus DNA and 13.0 ng cm-3 for yeast RNA. The relative standard deviation of six replicate measurements is 4.5% for 100 ng cm-3 calf thymus DNA. DNA could be determined in the presence of 20% m/m yeast RNA. The mechanism for the binding of HA to DNA is also studied.


Transforming growth factor-beta is activated by plasmin and inhibits smooth muscle cell death in human saphenous vein.
The effect of activation of endogenous transforming growth factor-beta (TGF-beta) on smooth muscle cell apoptosis was assessed in human saphenous vein. Segments of human saphenous vein, obtained at the time of bypass graft surgery, were cultured for 14 days. During this time, smooth muscle cells accumulated in the intima as a result of proliferation and migration, partly counterbalanced by apoptotic cell death. Addition of exogenous TGF-beta(1) had no effect on smooth muscle cell proliferation or apoptosis. However, antibody neutralization of endogenous TGF-beta(1) caused significant increases in smooth muscle cell death in the media and intima without any change in proliferation. A plasmin inhibitor (alpha-N-acetyl-L-lysine methyl ester), a specific urokinase-type plasminogen activator (uPA) inhibitor (amiloride) and an anti-catalytic anti-uPA antibody all caused decreases in the tissue content of active TGF-beta and increases in smooth muscle cell death in the media and intima. These data suggest that the amount of TGF-beta in human saphenous vein is sufficient, when in the active form, to protect smooth muscle cells against apoptosis. Adding exogenous TGF-beta(1) has no beneficial effect, but decreasing the amount of active TGF-beta causes smooth muscle cells to undergo apoptosis. Plasmin, generated by uPA, appears to be an important activator of endogenous latent TGF-beta.


Sumoylation controls retinal progenitor proliferation by repressing cell cycle exit in Xenopus laevis.
Precisely controlled progenitor proliferation is essential for normal development. However, molecular mechanisms, which control the correct timing of cell cycle withdrawal during development, have been poorly understood. We show here that ubc9, a sumo-conjugating enzyme, controls the cell cycle exit of retinal progenitors. We found that ubc9 is highly expressed in retinal progenitors and stem cells in Xenopus embryos. Ubc9 physically and functionally associates with Xenopus hmgb3, which is required for retinal cell proliferation, and prolonged expression of ubc9 and hmgb3 results in suppression of the cell cycle exit of retinal progenitors in a sumoylation-dependent manner. Overexpression of ubc9 and hmgb3 decreased expression of the cell-cycle inhibitor p27(Xic1). Furthermore, progenitor proliferation is regulated, at least in part, by sumoylation of transcription factor Sp1. These results suggest a significant role of sumoylation for cell cycle regulation in retinal progenitors.


Photo-induced imino functionalizations of alkenes via intermolecular charge transfer.
A catalyst-free photosensitized strategy has been developed for regioselective imino functionalizations of alkenes via the formation of an EDA complex. This photo-induced protocol facilitates the construction of structurally diverse β-imino sulfones and vinyl sulfones in moderate to high yields. Mechanistic studies reveal that the reaction is initiated with an intermolecular charge transfer between oximes and sulfinates, followed by fragmentation to generate a persistent iminyl radical and transient sulfonyl radical. This catalyst-free protocol also features excellent regioselectivity, broad functional group tolerance and mild reaction conditions. The late stage functionalization of natural product derived compounds and total synthesis of some bioactive molecules have been demonstrated to highlight the utility of this protocol. Meanwhile, the compatibility of different donors has proved the generality of this strategy.


Single-PPLN-based simultaneous half-adder, half-subtracter, and OR logic gate: proposal and simulation.
We propose and simulate all-optical simultaneous half-adder, half-subtracter, and OR logic gate at 40 Gbit/s based on the cascaded sum-and difference-frequency generation (SFG+DFG) using only one periodically poled lithium niobate (PPLN) waveguide. The SFG and DFG processes generate the Borrow and Carry outputs, respectively. The Sum/Difference and OR are obtained by properly combining the outputs from PPLN after SFG+DFG. The eye diagrams, pulse width, quality-factor (Q-factor), extinction ratio (ER), and tunability are calculated and discussed, showing impressive operation performance.


MDR1 genotype-dependent regulation of the aldosterone system in humans.
Aldosterone plays a major role in the development of both hypertension and heart failure. As aldosterone is a substrate of the ABCB1 (P-glycoprotein) efflux transporter, whose expression and activity has been shown to be linked to the ABCB1 3435C-->T polymorphism, we tested the impact of the ABCB1 3435C-->T polymorphism on aldosterone disposition, blood pressure, cardiac structure, and kidney function. A homogenous group of 116 young, white male Caucasian individuals with normal or mildlyto moderately elevated, but never treated blood pressure was included. Blood pressure was compared between individuals with ABCB1 3435 CC, CT, and TT genotypes. Moreover, genotype-dependent differences in basal and angiotensin II-stimulated serum aldosterone, cardiac structure, and kidney function were evaluated. Of the 116 volunteers, 35 had the CC, 51 the CT and 30 the TT genotype. At baseline, no significant genotype-dependent differences in serum aldosterone were observed. After infusion of angiotensin II, the increase in aldosterone serum concentration was significantly higher in the TT group than that in the CT and CC groups (CC +11+/-35, CT +18+/-48, TT +45+/-50 pg/ml, P=0.012). Systolic and diastolic blood pressure, left ventricular structure, and function and baseline renal function were not significantly different. After additional oral sodium load (5 g/day over 1 week) urinary sodium excretion was found to be increased in individuals with the CC or CT genotype only but not in those with the TT genotype (CC +71+/-83, CT +52+/-114, TT -11+/-98 mmol/day, P=0.005). The present study demonstrates that the ABCB1 3435 genotype affects angiotensin II-stimulated serum aldosterone levels and salt-stimulated urinary sodium excretion. Although blood pressure and cardiac structure were unchanged in this young study population, our findings indicate a new link between MDR1 genotype and the aldosterone system in humans.


Clinico-Pathological Profile of Deep Neck Space Infection: A Prospective Study.
Deep neck space infections (DNI) has been a common and serious disease, involving several spaces created by planes of greater and lesser resistance between the fascial layers of the neck. Infection of deep neck space has been dangerous due to its potential ease of spread from one space to other space, associated sepsis and upper airway obstruction. This prospective study was done in 45 patients of DNI over a period of 1 year. Patients with age of 1 month to 80 years of both the sexes were included. Patient's particular, clinical presentation and associated co-morbid conditions, physical examination, routine laboratory investigations and radiological investigations were analyzed. Patients were treated, response to the treatment was assessed and follow-up was done. In present study, DNI was more commonly seen in rural population (67%) with a male predominance (69%). Mean age of presentation was 34.4 years. Odontogenic infection (64.11%) was the commonest etiological factor and diabetes mellitus (26.66%) was the commonest co-morbid condition. Most common presenting symptom was neck pain and neck swelling (91.1%) and submandibular space (66.6%) was the most commonly involved space followed by sublingual space (44.6%). Both medical and surgical treatment was needed in most of the cases (77.77%). 77.7% cases showed complete regression, 15.5% showed partial regression and they lost to follow-up, 4.4% expired and 2.2% showed progressive deterioration. DNI is a common and life-threatening disease. Early diagnosis and management is necessary for complete cure and to prevent complications associated with DNIs.


SMAD4 Gene Mutation Renders Pancreatic Cancer Resistance to Radiotherapy through Promotion of Autophagy.
Purpose: Understanding the mechanism of radioresistance could help develop strategies to improve therapeutic response of patients with PDAC. The SMAD4 gene is frequently mutated in pancreatic cancer. In this study, we investigated the role of SMAD4 deficiency in pancreatic cancer cells' response to radiotherapy.Experimental Design: We downregulated SMAD4 expression with SMAD4 siRNA or SMAD4 shRNA and overexpressed SMAD4 in SMAD4 mutant pancreatic cancer cells followed by clonogenic survival assay to evaluate their effects on cell radioresistance. To study the mechanism of radioresistance, the effects of SMAD4 loss on reactive oxygen species (ROS) and autophagy were determined by flow cytometry and immunoblot analysis, respectively. Furthermore, we measured radioresistance by clonogenic survival assay after treatment with autophagy inhibitor (Chloroquine) and ROS inhibitor (N-acetyl-l-cysteine) in SMAD4-depleted pancreatic cancer cells. Finally, the effects of SMAD4 on radioresistance were also confirmed in an orthotopic tumor model derived from SMAD4-depleted Panc-1 cells.Results:SMAD4-depleted pancreatic cancer cells were more resistant to radiotherapy based on clonogenic survival assay. Overexpression of wild-type SMAD4 in SMAD4-mutant cells rescued their radiosensitivity. Radioresistance mediated by SMAD4 depletion was associated with persistently higher levels of ROS and radiation-induced autophagy. Finally, SMAD4 depletion induced in vivo radioresistance in Panc-1-derived orthotopic tumor model (P = 0.038). More interestingly, we observed that the protein level of SMAD4 is inversely correlated with autophagy in orthotopic tumor tissue samples.Conclusions: Our results demonstrate that defective SMAD4 is responsible for radioresistance in pancreatic cancer through induction of ROS and increased level of radiation-induced autophagy. Clin Cancer Res; 24(13); 3176-85. ©2018 AACR.


Amnestic MCI Patients' Perspectives toward Disclosure of Amyloid PET Results in a Research Context.
Researchers currently are not obligated to share individual research results (IRR) with participants. This non-disclosure policy has been challenged on the basis of participants' rights to be aware and in control of their personal medical information. Here, we determined how patients view disclosure of research PET results of brain amyloid and why they believe it is advantageous or disadvantageous to disclose. As a part of a larger diagnostic trial, we conducted semi-structured interviews with patients with amnestic Mild Cognitive Impairment (aMCI). Participants had the option to receive their brain amyloid PET scan result (i.e., their IRR). Interviews were conducted before they received their IRR. A total of 38 aMCI patients (100% of study participants) wanted to know their IRR. The two most frequently mentioned reasons for choosing IRR disclosure were to better understand their brain health status and to be better able to make informed decisions about future personal arrangements (e.g., inheritance tax, moving into a smaller house, end-of-life decisions, etc.). Emotional risk was mentioned as the primary disadvantage of knowing one's IRR. On the other hand, non-disclosure was considered to be emotionally difficult also, as patients would be uncertain about their future health condition. Many patients diagnosed clinically with aMCI want to know their brain amyloid test results, even though this knowledge may be disadvantageous to them. Knowing what is going on with their health and the ability to make informed decisions about their future were the two principal advantages mentioned for obtaining their amyloid PET results. Because of the overwhelming consensus of aMCI patients was to disclose their brain amyloid PET scan results, researchers should strongly consider releasing this information to research subjects.


[Primary structure of tRNA2Leu of bovine mammary gland. Oligonucleotides of T1-RNAse hydrolysate. Reconstruction of a total nucleotide sequence].
The oligonucleotides obtained by digestion of tRNA2Leu from cow mammary gland with T1 RNase were separated by micro-column chromatography on DEAE-cellulose in 7 M urea at pH 7,5 and 3,7, and in addition on Dowex 1 x 2. The digest consisted of 18 individual components, the larger being a tridecanucleotide. Micro-column chromatography of nucleotides on anion-exchanger AG 1 x 8 and nucleosides on Aminex A-6 was used to determine the base composition of the oligonucleotides. The oligonucleotide structure was established using terminal analysis, hydrolysis by pancreatic and U2-RNases and incomplete hydrolysis by snake venom phosphodiesterases. The total primary structure of tRNA2Leu was derived from overlapping fragments isolated after its complete hydrolysis with pancreatic and T1 RNase and using data obtained on S1-nuclease digestion of tRNA. The methods of rapid gel-sequencing were also employed for checking the nucleotide sequence of tRNA2Leu from cow mammary gland.


Structure, catalysis, and inhibition mechanism of prenyltransferase.
Isoprenoids, also known as terpenes or terpenoids, represent a large family of natural products composed of five-carbon isopentenyl diphosphate or its isomer dimethylallyl diphosphate as the building blocks. Isoprenoids are structurally and functionally diverse and include dolichols, steroid hormones, carotenoids, retinoids, aromatic metabolites, the isoprenoid side-chain of ubiquinone, and isoprenoid attached signaling proteins. Productions of isoprenoids are catalyzed by a group of enzymes known as prenyltransferases, such as farnesyltransferases, geranylgeranyltransferases, terpenoid cyclase, squalene synthase, aromatic prenyltransferase, and cis- and trans-prenyltransferases. Because these enzymes are key in cellular processes and metabolic pathways, they are expected to be potential targets in new drug discovery. In this review, six distinct subsets of characterized prenyltransferases are structurally and mechanistically classified, including (1) head-to-tail prenyl synthase, (2) head-to-head prenyl synthase, (3) head-to-middle prenyl synthase, (4) terpenoid cyclase, (5) aromatic prenyltransferase, and (6) protein prenylation. Inhibitors of those enzymes for potential therapies against several diseases are discussed. Lastly, recent results on the structures of integral membrane enzyme, undecaprenyl pyrophosphate phosphatase, are also discussed.


Variation in Recombination Rate: Adaptive or Not?
Rates of meiotic recombination are widely variable both within and among species. However, the functional significance of this variation remains largely unknown. Is the observed within-species variation in recombination rate adaptive? Recent work has revealed new insight into the scale and scope of population-level variation in recombination rate. These data indicate that the magnitude of within-population variation in recombination is similar among taxa. The apparent similarity of the variance in recombination rate among individuals between distantly related species suggests that the relative costs and benefits of recombination that establish the upper and lower bounds may be similar across species. Here we review the current data on intraspecific variation in recombination rate and discuss the molecular and evolutionary costs and benefits of recombination frequency. We place this variation in the context of adaptation and highlight the need for more empirical studies focused on the adaptive value of variation in recombination rate.


Potential cost-effective use of spine radiographs to detect vertebral deformity and select osteopenic post-menopausal women for amino-bisphosphonate therapy.
Prevalent vertebral deformities are predictive of future clinical fractures independent of bone density. We used a Markov model with eight health states to estimate from the societal perspective the cost-effectiveness of using spine radiographs to identify postmenopausal women age 60 or older with one or more vertebral deformities and then treat them with anti-resorptive drug therapy to prevent fractures. We compared three strategies: 5 years of amino-bisphosphonate (alendronate) therapy for all, 5 years of alendronate therapy for only those with prevalent a radiographic vertebral deformity or no initial alendronate treatment. Lifetime direct medical and indirect costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were tracked. For women with one or more prevalent vertebral deformities, the costs per QALY gained ranged from 5,084 dollars (for an 80 year old with a T-score of -2.4) to 61,192 dollars (for a 60 year old with a T-score of -1.0). For women without prevalent vertebral deformity, the costs per QALY gained ranged from 41,897 dollars (for a 60 year old with a T-score of -2.4) to 166,219 dollars (for an 80 year old with a T-score of -1.0). These results were modestly sensitive to reasonable changes in fracture rates, disutility, discount rates and assumptions about the accuracy of spinal radiographs for detecting vertebral deformity. Assuming a societal willingness to pay per QALY gained of 50,000 dollars, the strategy of performing spine radiographs in post-menopausal osteopenic women with T-scores at or below -1.5 and treating those with 1 or more prevalent vertebral deformities is likely to be cost-effective. However, further research on the accuracy of vertebral deformity ascertainment from routine clinical radiographs and on the efficacy of amino-bisphosphonate drugs for reducing the risk of non-vertebral fractures in osteopenic women is needed to define more precisely the subset of osteopenic post-menopausal women in whom use of spinal radiographs is most cost-effective.


Using evolutionary and structural information to predict DNA-binding sites on DNA-binding proteins.
Proteins that interact with DNA are involved in a number of fundamental biological activities such as DNA replication, transcription, and repair. A reliable identification of DNA-binding sites in DNA-binding proteins is important for functional annotation, site-directed mutagenesis, and modeling protein-DNA interactions. We apply Support Vector Machine (SVM), a supervised pattern recognition method, to predict DNA-binding sites in DNA-binding proteins using the following features: amino acid sequence, profile of evolutionary conservation of sequence positions, and low-resolution structural information. We use a rigorous statistical approach to study the performance of predictors that utilize different combinations of features and how this performance is affected by structural and sequence properties of proteins. Our results indicate that an SVM predictor based on a properly scaled profile of evolutionary conservation in the form of a position specific scoring matrix (PSSM) significantly outperforms a PSSM-based neural network predictor. The highest accuracy is achieved by SVM predictor that combines the profile of evolutionary conservation with low-resolution structural information. Our results also show that knowledge-based predictors of DNA-binding sites perform significantly better on proteins from mainly-alpha structural class and that the performance of these predictors is significantly correlated with certain structural and sequence properties of proteins. These observations suggest that it may be possible to assign a reliability index to the overall accuracy of the prediction of DNA-binding sites in any given protein using its sequence and structural properties. A web-server implementation of the predictors is freely available online at http://lcg.rit.albany.edu/dp-bind/.


Norms Affect Prospective Causal Judgments.
People more frequently select norm-violating factors, relative to norm-conforming ones, as the cause of some outcome. Until recently, this abnormal-selection effect has been studied using retrospective vignette-based paradigms. We use a novel set of video stimuli to investigate this effect for prospective causal judgments-that is, judgments about the cause of some future outcome. Four experiments show that people more frequently select norm-violating factors, relative to norm-conforming ones, as the cause of some future outcome. We show that the abnormal-selection effects are not primarily explained by the perception of agency (Experiment 4). We discuss these results in relation to recent efforts to model causal judgment.


Imaging after head trauma. Who needs what?
Decisions about the optimal imaging strategy in patients after acute head trauma can be based on clinical observations. Low-risk patients do not require radiographic imaging. CT is the procedure of choice for imaging moderate- and high-risk patients after head trauma. Because of its limited ability to guide therapy, plain skull radiography should be used sparingly; it may be useful in equivocal cases of bony injury not detected by CT or in selected moderate-risk patients (especially children under the age of 2 years). MR imaging rivals CT in the detection of intracranial injuries but is more expensive and cumbersome in seriously ill subjects and does not image bony structures. MR imaging is recommended after initial CT if subtle acute nonhemorrhagic and subacute hemorrhagic lesions are suspected, especially in the evaluation of child abuse. Otherwise, MR imaging is rarely needed in the emergency department management of acute head injury patients.


The Role of IL-17 in Papulopustular Rosacea and Future Directions.
Rosacea is a chronic, progressive, inflammatory condition phenotypically subtyped into diagnostic features, major features, and minor/secondary features. There is currently no cure for rosacea, and it carries a significant negative psychosocial burden for afflicted patients. While there are a number of treatment modalities at the disposal of the clinician, clinical experience has suggested a need for updated treatments. The pathogenesis of rosacea is multifactorial; however, this paper will focus on the pivotal role of interleukin 17 (IL-17) in the development and progression of the disease. Furthermore, this paper will explore the mechanism of action of standard rosacea treatments and their effect on different stages of the IL-17 pathway. The standard treatments for rosacea are usually effective in controlling the symptoms of the disease in its mild-to-moderate form; however, their efficacy is diminished in the setting of severe and treatment-resistant rosacea. We hypothesize that IL-17 inhibitors, currently used successfully in psoriasis and psoriatic arthritis, could perhaps be used to treat severe and treatment-resistant papulopustular rosacea in the future; however, clinical trials and case reports will be needed to dictate expanded indications of IL-17 inhibitors. Furthermore, the high cost of IL-17 inhibitors presently prevents their use in disease states other than psoriasis or psoriatic arthritis.


Man and his spaceships: Vehicles for extraterrestrial colonization?
The resiliency and adaptive ability of microbial life in real time on Earth relies heavily upon horizontal gene transfer. Based on that knowledge, how likely is earth based microbial life to colonize extraterrestrial targets such as Mars? To address this question, we consider manned and unmanned space exploration, the resident microbiota that is likely to inhabit those vehicles, the adaptive potential of that microbiota in an extraterrestrial setting especially with regards to mobile genetic elements, and the likelihood that Mars like environments could initiate and sustain colonization.


[Associated factors to abnormal glucosylated hemoglobin in the postpartum period].
To demonstrate the association between risk factors and abnormal glucosylated hemoglobin detected in women during the postpartum period. A case and control study was carried out at the Hospital Civil de Guadalajara Dr. Juan I. Menchaca during six months. Glucosylated hemoglobin and glucose concentration from 160 fasting women with a pregnancy > or =28 weeks was obtained during the postpartum period. With an odds ratio and confidence interval (95%) the epidemiological meaning of risk factors was identified. The abnormal glucosylated hemoglobin was significantly associated to: single, separated and divorced women (p < 0.05); major frequency of previous caesarean (OR: 2.78, IC 95%:1.25-6.22), p = 0.006, and higher proportion of children with congenital malformations (OR: 12, IC 95%: 1.38-104), p = 0.01. In the group cases 48% of caesareans was associated to probable gestational diabetes: moderate preeclampsia, eclampsia, fetal macrosomy, and preterm deliveries. It is necessary to make an early detection of risk factors associated to abnormal glucosylated hemoglobin and to prevent adverse effects as congenital malformations and clinical complications that increase the incidence of caesarean.


Reversal of diabetes-evoked changes in mitochondrial protein expression of cardiac left ventricle by treatment with a copper(II)-selective chelator.
Cardiac disease is the commonest cause of death amongst diabetic patients. Diabetic cardiomyopathy, which has a poor prognosis, is characterized by left ventricular hypertrophy and impaired cardiac function and mitochondrial damage is said to contribute to its development. We recently showed that treatment with the Cu(II) -selective chelator, triethylenetetramine (TETA), improved cardiac structure, and function in diabetic subjects without modifying hyperglycemia. Thus, TETA has potential utility for the treatment of heart disease. To further understand the molecular mechanism by which it causes these effects, we have conducted the first study of the effect of oral TETA on protein abundance in the cardiac left ventricle of rats with severe streptozotocin-induced diabetes. Proteomic methods showed that of 211 proteins changed in diabetes, 33 recovered after treatment. Through MS, 16 proteins were identified which may constitute major targets of drug action. Remarkably, most of these were mitochondrial proteins with roles in energy metabolism. In addition to components of the mitochondrial respiratory chain and enzymes involved in fatty acid oxidation, TETA treatment normalized both myocardial expression and enzymatic activity of carnitine palmitoyltransferase 2. These findings indicate that mitochondria constitute major targets in the mechanism by which TETA restores cardiac structure and function in diabetes.


Trojan Horse Siderophore Conjugates Induce Pseudomonas aeruginosa Suicide and Qualify the TonB Protein as a Novel Antibiotic Target.
Rising infection rates with multidrug-resistant pathogens calls for antibiotics with novel modes of action. Herein, we identify the inner membrane protein TonB, a motor of active uptake in Gram-negative bacteria, as a novel target in antimicrobial therapy. The interaction of the TonB box of outer membrane transporters with TonB is crucial for the internalization of essential metabolites. We designed TonB box peptides and coupled them with synthetic siderophores in order to facilitate their uptake into bacteria in up to 32 synthetic steps. Three conjugates repressed the growth of Pseudomonas aeruginosa cells unable to produce their own siderophores, with minimal inhibitory concentrations between 0.1 and 0.5 μM. The transporters mediating uptake of these compounds were identified as PfeA and PirA. The study illustrates a variant of cellular suicide where a transporter imports its own inhibitor and demonstrates that artificial siderophores can import cargo with molecular weights up to 4 kDa.


Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study.
Background: Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. Methods: From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). Results: We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1-10 BMs). The median SRS treatment volume was 0.79 cm3 (range: 0.003-38.18 cm3), and the median SRS prescription dose was 20 Gy (range: 8-24 Gy). The median survival after SRS for BMs was 14 months (range: 3-58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452, p = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143-11.904; p = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689-0.945; p = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. Conclusion: The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.


Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease.
Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia. PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout. After 14 days, a 2-hour intravenous levodopa-infusion was administered. Patient examinations were videotaped before infusion ("off" state) and every 30 minutes during and afterwards until patients returned to "off." The primary endpoint was dyskinesia-severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area-under-curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical-change, and adverse-events. A total of 13 patients were randomized and completed the study (efficacy-evaluable population). Dyskinesia-severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area-under-curve 966.5 vs 1048.8; P = .191 [efficacy-evaluable patients]), and significantly lower in a post-hoc sensitivity analysis of the per-protocol-population (efficacy-evaluable patients with ≥ 80% study-drug-compliance, n = 12) when measured from infusion start to 4-hours post-infusion completion (area-under-curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion-start to return to "off" (13.3 vs 14.9; P = .018 [efficacy-evaluable patients]). A total of 9 patients rated dyskinesia "much/very much improved" on dextromethorphan/quinidine versus 1-patient on placebo. Dextromethorphan/quinidine did not worsen PD-motor scores, was generally well tolerated, and was associated with more frequent adverse events. This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa-induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society.


Bounding the outcome of a two-photon interference measurement using weak coherent states.
The interference of two photons at a beam splitter is at the core of many quantum photonic technologies, such as quantum key distribution or linear-optics quantum computing. Observing high-visibility interference is challenging because of the difficulty of realizing indistinguishable single-photon sources. Here, we perform a two-photon interference experiment using phase-randomized weak coherent states with different mean photon numbers. We place a tight upper bound on the expected coincidences for the case when the incident wavepackets contain single photons, allowing us to observe the Hong-Ou-Mandel effect. We find that the interference visibility is at least as large as 0.995-0.013+0.005.


IFITM3 directly engages and shuttles incoming virus particles to lysosomes.
Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live-cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, IFITM2 and IFITM3 act cooperatively and function in a dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live-cell imaging studies, we show that IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live-cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation.


Obstetric and non-obstetric risk factors for cesarean section in oman.
This study aims to explore the risk factors, profiles and neonatal outcomes of Cesarean sections among selected women in Oman. In this hospital-based case-control study, a total of 500 participants (250 cases who had cesarean section and 250 controls who had spontaneous vaginal delivery), were randomly selected from four hospitals. Cases and controls were matched according to timing and place of delivery. THE FOLLOWING PREDICTORS WERE FOUND TO BE SIGNIFICANTLY ASSOCIATED WITH INCREASED RISK OF CESAREAN SECTION: a) advancing age (above the age of 25 years, OR=1.42; p=0.03), b) prior cesarean section (previous cesarean section=1, OR=22.71; p=0.001), c) increased body mass index (obesity, OR=2.11; p=0.07), d) extremes of neonatal birth weight (neonates birth weight <2.5 kg, OR=5.2; neonates birth weight >4.0 kg, OR=7.3; p<0.001), and e) pre-pregnancy diabetes (OR=9.3; p=0.04). On the contrary, increased parity and history of the use of birth spacing methods (OR=0.38; p=0.03) were associated with decreased risk of cesarean section. The study calls for increasing awareness about clinical and public health majors that would lead to prevention of risk factors associated with increased risk of cesarean section such as maintaining normal BMI and prevention of gestational and type 2 diabetes mellitus.


Chronic pelvic pain in women: an embedded qualitative study to evaluate the perceived benefits of the meridian balance method electro-acupuncture treatment, health consultation and National Health Service standard care.
Chronic pelvic pain (CPP) - defined as intermittent or constant pain in the lower abdomen or pelvis of at least 6 months' duration, not occurring exclusively with menstruation or intercourse and not associated with pregnancy - is estimated to affect 6-27% of women worldwide. In the United Kingdom, over 1 million women suffer from CPP, which has been highlighted as a key area of unmet need. Current medical treatments for CPP are often associated with unacceptable side effects. A specific style of acupuncture, the meridian balance method electro-acupuncture (BMEA) and traditional Chinese medicine health consultation (TCM HC (BMEA + TCM HC = BMEA treatment)), may be effective for CPP in women. Three focus group discussions and semi-structured telephone interviews were embedded in a randomised controlled feasibility trial to gain in-depth description of the perceived benefits of the participants' respective interventions. Women with CPP were randomised into the BMEA treatment, TCM HC or National Health Service standard care (NHS SC). Focus group discussions were recorded, transcribed and analysed thematically. Semi-structured telephone interviews were conducted post focus group discussions. A total of 30 women were randomised into BMEA treatment, TCM HC or NHS SC. A total of 11 participants attended the three focus group discussions. Thematic analysis of focus group discussions showed: a perceived pain reduction, enhanced sleep, energy level and sense of well-being in the BMEA treatment and TCM HC groups; a dislike for the adverse effects of medications, frustration at the lack of effective treatment, heavy reliance on medications and services that are helpful, in the NHS SC group. Semi-structured telephone interviews showed that the methodology was acceptable to the participants. The embedded focus group discussions captured the rich and complex narratives of the participants and provided insights into the perceived benefits of the BMEA treatment, TCM HC and NHS SC interventions.


The identification of endothelial cell autoantigens.
The identity of many endothelial cell autoantigens remains unclear. This study has used human monoclonal anti-endothelial cell autoantibodies isolated from patients with SLE to identify endothelial autoantigens. Thirteen antibodies reactive with endothelial cell membrane preparations were isolated and cloned, one of which has previously been demonstrated to be pro-inflammatory. Western blotting demonstrates that these antibodies recognize a variety of proteins in endothelial cell membrane preparations. Further characterization of five antibodies by cDNA library screening, immunofluorescence and Western blotting proves that two of these antibodies recognized the cytoskeletal proteins tubulin and vimentin. A further antibody identified a clone derived from human collagenase, an identification supported by Western blotting. The multiple clones selected by other antibodies are not compatible with the molecular weight of the antigen recognized in Western blotting studies. This study has clearly identified two endothelial cell autoantigens present in membrane preparations and provides strong evidence as to the identity of a third.


Clinical features of late-onset Pompe disease: a prospective cohort study.
The objective of this 12-month study was to describe the clinical features of late-onset Pompe disease and identify appropriate outcome measures for use in clinical trials. Assessments included quantitative muscle testing (QMT), functional activities (FAA), 6-min walk test (6MWT), and pulmonary function testing (PFT). Percent predicted values indicated quantifiable upper and lower extremity weakness, impaired walking ability, and respiratory muscle weakness. Significant declines in arm and leg strength and pulmonary function were observed during the study period. The outcome measures were demonstrated to be safe and reliable. Symptom duration was identified as the best predictor of the extent of skeletal and respiratory muscle weakness.


Promoting Adoption of Medication for Opioid and Alcohol Use Disorders Through System Change.
The Medication Research Partnership (MRP), a collaboration between a national commercial health plan and nine addiction treatment centers, implemented organizational and system changes to promote use of federally approved medications for treatment of alcohol and opioid use disorders. A difference-in-differences analysis examined change over time in the percentage of patients receiving a prescription medication for alcohol or opioid use disorders treated in MRP (n = 9) and comparison (n = 15) sites. MRP clinics experienced a 2.4-fold increase in patients receiving an alcohol or opioid prescription (13.2% at baseline to 31.7% at 3 years after MRP initiation); comparison clinics experienced significantly less change (17.6% to 23.5%) with an adjusted difference-in-differences of 12.5% (95% CI [5.4, 19.6], p = .001). MRP sites increased the patients with prescriptions to treat opioid use disorder from 17.0% (baseline) to 36.8% (3 years after initiation), with smaller changes observed in comparison sites (23.2% to 24.0%) and a 3-year post-initiation adjusted difference-in-differences of 19% (95% CI [8.5, 29.5], p = .000). Medications for alcohol use disorders increased in both MRP (9.0% to 26.5%) and comparison sites (11.4% to 23.1%). Promoting the use of medications to support recovery required complex interventions. The Advancing Recovery System Change Model, initially developed in publicly funded systems of care, was successfully adapted for commercial sector use. The model provides a framework for providers and commercial health plans to collaborate and increase patient access to medications.


Transperitoneal migration of the ovum. A case report.
Transperitoneal migration of ova resulting in intrauterine pregnancy is probably a common event yet rarely observed. Occasionally a woman lacks an ovary and contralateral fallopian tube; one such patient successfully carried an intrauterine pregnancy to term.


Metabolomics of the Protective Effect of Ampelopsis grossedentata and Its Major Active Compound Dihydromyricetin on the Liver of High-Fat Diet Hamster.
The flavonoid dihydromyricetin (DMY) is the main component of Ampelopsis grossedentata (Hand-Mazz) W. T. Wang (AG), a daily beverage and folk medicine used in Southern China to treat jaundice hepatitis, cold fever, and sore throat. Recently, DMY and AG were shown to have a beneficial effect on lipid metabolism disorder. However, the mechanisms of how DMY and AG protect the liver during lipid metabolism disorder remain unclear. In this study, we first analyzed the chemical compounds of AG by HPLC-DAD-ESI-IT-TOF-MS n . Of the 31 compounds detected, 29 were identified based on previous results. Then, the effects of DMY and AG on high-fat diet hamster livers were studied and the metabolite levels and metabolic pathway activity of the liver were explored by 1H NMR metabolomics. Compared to the high-fat diet group, supplementation of AG and DMY attenuated the high-fat-induced increase in body weight, liver lipid deposition, serum triglycerides and total cholesterol levels, and normalized endogenous metabolite concentrations. PCA and PLS-DA score plots demonstrated that while the metabolic profiles of hamsters fed a high-fat diet supplemented with DMY or AG were both far from those of hamsters fed a normal diet or a high-fat diet alone, they were similar to each other. Our data suggest that the underlying mechanism of the protective effect of DMY and AG might be related to an attenuation of the deleterious effect of high-fat diet-induced hyperlipidemia on multiple metabolic pathways including amino acid metabolism, ketone body metabolism, energy metabolism, tricarboxylic acid cycle, and enhanced fatty acid oxidation.


Multilayer CVD graphene electrodes using a transfer-free process for the next generation of optically transparent and MRI-compatible neural interfaces.
Multimodal platforms combining electrical neural recording and stimulation, optogenetics, optical imaging, and magnetic resonance (MRI) imaging are emerging as a promising platform to enhance the depth of characterization in neuroscientific research. Electrically conductive, optically transparent, and MRI-compatible electrodes can optimally combine all modalities. Graphene as a suitable electrode candidate material can be grown via chemical vapor deposition (CVD) processes and sandwiched between transparent biocompatible polymers. However, due to the high graphene growth temperature (≥ 900 °C) and the presence of polymers, fabrication is commonly based on a manual transfer process of pre-grown graphene sheets, which causes reliability issues. In this paper, we present CVD-based multilayer graphene electrodes fabricated using a wafer-scale transfer-free process for use in optically transparent and MRI-compatible neural interfaces. Our fabricated electrodes feature very low impedances which are comparable to those of noble metal electrodes of the same size and geometry. They also exhibit the highest charge storage capacity (CSC) reported to date among all previously fabricated CVD graphene electrodes. Our graphene electrodes did not reveal any photo-induced artifact during 10-Hz light pulse illumination. Additionally, we show here, for the first time, that CVD graphene electrodes do not cause any image artifact in a 3T MRI scanner. These results demonstrate that multilayer graphene electrodes are excellent candidates for the next generation of neural interfaces and can substitute the standard conventional metal electrodes. Our fabricated graphene electrodes enable multimodal neural recording, electrical and optogenetic stimulation, while allowing for optical imaging, as well as, artifact-free MRI studies.


Utilization of indole compounds by Cryptococcus neoformans to produce a melanin-like pigment.
Several indoles served as substrates for the phenoloxidase of Cryptococcus neoformans and resulted in the production of a melanin-like pigment. In general, a higher percentage of C. neoformans var. neoformans (A and D serotypes) isolates could produce pigment from indoles than could those of var. gattii (B and C serotypes). Only compounds with a hydroxyl or an amino group on the phenyl ring produced pigment; methoxy, nitro, methyl, and fluorine substituents on the phenyl ring were inactive, as was a hydroxyl group at the 2 position on the indole ring. The phenoloxidase of C. neoformans thus appears to differ from that found in Mycobacterium leprae, which cannot use a hydroxyindole, desoxyfructo-5-hydroxytryptamine, as a substrate. In addition, C. neoformans differs from M. leprae in that desoxyfructo-5-hydroxytryptamine does not inhibit the uptake of dihydroxyphenylalanine into the cell.


Tissue-resident macrophages promote extracellular matrix homeostasis in the mammary gland stroma of nulliparous mice.
Tissue-resident macrophages in the mammary gland are found in close association with epithelial structures and within the adipose stroma, and are important for mammary gland development and tissue homeostasis. Macrophages have been linked to ductal development in the virgin mammary gland, but less is known regarding the effects of macrophages on the adipose stroma. Using transcriptional profiling and single-cell RNA sequencing approaches, we identify a distinct resident stromal macrophage subpopulation within the mouse nulliparous mammary gland that is characterized by the expression of Lyve-1, a receptor for the extracellular matrix (ECM) component hyaluronan. This subpopulation is enriched in genes associated with ECM remodeling and is specifically associated with hyaluronan-rich regions within the adipose stroma and fibrous capsule of the virgin mammary gland. Furthermore, macrophage depletion leads to enhanced accumulation of hyaluronan-associated ECM in the adipose-associated stroma, indicating that resident macrophages are important for maintaining homeostasis within the nulliparous mammary gland stroma.


Development of a Novel Prognostic Risk Score for Predicting Complications of Penectomy in the Surgical Management of Penile Cancer.
Penectomy for PC is useful in staging, disease prognosis, and treatment. Limited studies have evaluated its surgical complications. We sought to assess these complications and determine predictive models to create a novel risk score for penectomy complications. A retrospective review of patients undergoing PC surgical management from the 2005-2016 American College of Surgeons National Surgical Quality Improvement Program was performed. Data were queried for partial and total penectomy among those with PC. To develop predictive models of complications, we fit LASSO logistic, random forest, and stepwise logistic models to training data using cross-validation, demographic, comorbidity, laboratory, and wound characteristics as candidate predictors. Each model was evaluated on the test data using receiver operating characteristic curves. A novel risk score was created by rounding coefficients from the LASSO logistic model. A total of 304 cases met the inclusion criteria. Overall incidence of penectomy complications was 19.7%, where urinary tract infection (3.0%), superficial surgical site infection (3.0%), and bleeding requiring transfusion (3.9%) were most common. LASSO logistic, random forest, and stepwise logistic models for predicting complications had area under the curve (AUC) [95% confidence interval] values of 0.66 [0.52-0.81], 0.73 [0.63-0.83], and 0.59 [0.45-0.74], respectively. Eleven variables were included in the risk score. The LASSO model-derived risk score had moderately good performance (area under the curve [95% confidence interval] 0.74 [0.66-0.82]). Using a cutoff point of 6, the score attains sensitivity 0.58, specificity 0.74, and kappa 0.26. PC management through penectomy is associated with appreciable complications rates. Predictive models of penectomy complications performed moderately well. Our novel prognostic risk score may allow for improved preoperative counseling and risk stratification of men undergoing surgical management of PC.


BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language.
The rapid accumulation of knowledge in the field of systems and networks biology during recent years requires complex, but user-friendly and accessible web applications that allow from visualization to complex algorithmic analysis. While several web applications exist with various focuses on creation, revision, curation, storage, integration, collaboration, exploration, visualization and analysis, many of these services remain disjoint and have yet to be packaged into a cohesive environment.Here, we present BEL Commons: an integrative knowledge discovery environment for networks encoded in the Biological Expression Language (BEL). Users can upload files in BEL to be parsed, validated, compiled and stored with fine granular permissions. After, users can summarize, explore and optionally shared their networks with the scientific community. We have implemented a query builder wizard to help users find the relevant portions of increasingly large and complex networks and a visualization interface that allows them to explore their resulting networks. Finally, we have included a dedicated analytical service for performing data-driven analysis of knowledge networks to support hypothesis generation.


Sequential compression device with thigh-high sleeves supports mean arterial pressure during Caesarean section under spinal anaesthesia.
This study investigated the use of a Sequential Compression Device (SCD) with thigh-high sleeves and a preset pressure of 50 mm Hg that recruits blood from the lower limbs intermittently, as a method to prevent spinal hypotension during elective Caesarean section. Possible association of arterial pressure changes with maternal, fetal, haemodynamic, and anaesthetic factors were studied. Fifty healthy parturients undergoing elective Caesarean section under spinal anaesthesia were randomly assigned to either SCD (n=25) or control (n=25) groups. A standardized protocol for pre-hydration and anaesthetic technique was followed. Hypotension was defined as a decrease in any mean arterial pressure (MAP) measurement by more than 20% of the baseline MAP. Systolic (SAP), MAP and diastolic (DAP) arterial pressure, pulse pressure (PP), and heart rate (HR) were noted at baseline and every minute after the spinal block until delivery. A greater than 20% decrease in MAP occurred in 52% of patients in the SCD group vs 92% in the control group (P=0.004, odds ratio 0.094, 95% CI 0.018-0.488). There were no significant differences in SAP, DAP, HR, and PP between the groups. SCD use in conjunction with vasopressor significantly reduced the incidence of a 20% reduction of MAP.


COLIFORMS ASSOCIATED WITH SUGARCANE PLANTS AND JUICES.
A study of the coliforms found on sugarcane plants throughout the growing season indicated that members of the genus Aerobacter comprise a part of the epiphytic microflora. When quantitative determinations were made of the coliforms by means of the most probable number technique, no completed tests were obtained on young sugarcane plants during the test period of February through May; however, Paracolobactrum aerogenoides was isolated frequently. Nine different IMViC types of coliforms were identified among the 198 isolates chosen for study. The predominating coliform found at the top, middle, and bottom portions of the sugarcane plants was A. cloacae, but the type predominating in leaf-sheath water was A. aerogenes. Only once was Escherichia coli found associated with the plants at the high dilutions necessary for determining most probable numbers. The numbers of different coliforms occurring in sugarcane juice were generally divided equally among A. aerogenes, A. cloacae, and E. coli. More variety among the IMViC types seemed to occur on the cane plants than in the leaf-sheath water or the cane juice in the mill.


Maturation-specific polyadenylation: in vitro activation by p34cdc2 and phosphorylation of a 58-kD CPE-binding protein.
During Xenopus oocyte maturation, poly(A) elongation controls the translational recruitment of specific mRNAs that possess a CPE (cytoplasmic polyadenylation element). To investigate the activation of polyadenylation, we have employed oocyte extracts that are not normally competent for polyadenylation. Addition of cell lysates containing baculovirus-expressed cyclin to these extracts induces the polyadenylation of exogenous B4 RNA. The involvement of p34cdc2 kinase in cyclin-mediated polyadenylation was demonstrated by p13-Sepharose depletion; removal of the kinase from oocyte extracts with this affinity matrix abolishes polyadenylation activation. Reintroduction of cell lysates containing baculovirus-expressed p34cdc2, however, completely restores this activity. To identify factors of the polyadenylation apparatus that might be responsible for the activation, we employed UV cross-linking and identified a 58-kD protein that binds the B4 CPE in oocyte extracts. In polyadenylation-proficient egg extracts, this protein has a slower electrophoretic mobility, which suggests a post-translational modification. A similar size shift of the protein is evident in oocyte extracts supplemented with lysates containing baculovirus-expressed cyclin and p34cdc2. This size shift, which is reversed by treatment with acid phosphatase, coincides temporally with cyclin-induced polyadenylation activation. We propose that p34cdc2 kinase activity leads to the phosphorylation of the 58-kD CPE-binding protein and that this event is crucial for the cytoplasmic polyadenylation that occurs during oocyte maturation.


Tissue-advanced glycation end product concentration in dialysis patients.
Tissue-advanced glycation end products (AGE) are a measure of cumulative metabolic stress. Assessment of tissue AGE by skin autofluoresence (AF) correlates well with cardiovascular outcomes in hemodialysis (HD) patients. This study aimed to measure and compare tissue AGE levels in HD and peritoneal dialysis (PD) patients and to evaluate the impact of systemic PD glucose exposure. Tissue AGE were measured in 115 established dialysis patients (62 HD and 53 PD) using a cutaneous AF device (AGE Reader; DiagnOptics). Values were compared with an age-matched non-chronic kidney disease database. Review of all previous PD solution delivery/prescription data determined PD glucose exposure. PD patients were similar in age to HD patients but had a shorter dialysis vintage. There were no differences in ischemic heart disease or smoking history, statin or angiotensin-converting enzyme inhibitor (ACEi) use, lipids, biochemistry, or prevalence of diabetes. More than 90% of both groups had met current dialysis adequacy targets. Skin AF values in PD and HD patients were similar and strongly correlated with historical PD glucose exposure. Skin AF correlated with age in both groups but with dialysis vintage only in PD patients Cumulative metabolic stress and transient hyperglycemia results in grossly elevated levels of tissue AGE in dialysis patients. In PD patients, this high level of AGE deposition is associated with historical glucose exposure. This observation provides a previously unappreciated potential link between PD exposure to glucose and systemic cardiovascular disease.


Effects of alfalfa maturity on energy utilization by cattle and nutrient digestibility by cattle and sheep.
Two comparative slaughter experiments conducted with growing beef steers (300 kg to 480 kg BW) fed alfalfa cubes demonstrated that animal performance diminished as alfalfa matured. In each trial, ADG (empty BW basis) was 10 to 20% greater from pre-bloom than from early-bloom alfalfa. Net energy for maintenance (Mcal/kg) followed a pattern similar to that of ADG, but NEg (Mcal/kg) did not decrease (P greater than .05) as alfalfa maturity increased. Digestion trials with steers and wethers clearly indicated significant reductions in apparent digestibilities of DM, energy, and cell wall fractions as alfalfa matured. Steers fed at 110% of maintenance in digestion Trails 1, 2, and 3 consistently digested cubed alfalfa to a greater extent than wethers fed the same alfalfa ground and pelleted. Digestion coefficients (percentages) for ADF, cellulose, NDF, and crude fiber were 5 to 14% greater for steers fed cubes than for wethers fed pellets. Regression equations calculated from results of three digestion trials indicate that digestible DM % and DE (Mcal/kg) could be predicted from ADF %, but they were 4 to 5% lower for wethers fed pelleted alfalfa than for steers fed cubes.


Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study.
Oral estrogen therapy increases the risk of venous thromboembolism (VTE) in postmenopausal women. Transdermal estrogen may be safer. However, currently available data have limited the ability to investigate the wide variety of types of progestogen. We performed a multicenter case-control study of VTE among postmenopausal women 45 to 70 years of age between 1999 and 2005 in France. We recruited 271 consecutive cases with a first documented episode of idiopathic VTE (208 hospital cases, 63 outpatient cases) and 610 controls (426 hospital controls, 184 community controls) matched for center, age, and admission date. After adjustment for potential confounding factors, odds ratios (ORs) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 (95% CI, 1.5 to 11.6) and 0.9 (95% CI, 0.4 to 2.1), respectively. There was no significant association of VTE with micronized progesterone and pregnane derivatives (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; 95% CI, 0.4 to 2.3, respectively). In contrast, norpregnane derivatives were associated with a 4-fold-increased VTE risk (OR, 3.9; 95% CI, 1.5 to 10.0). Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. If confirmed, these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens.


The leisure-noise dilemma: hearing loss or hearsay? What does the literature tell us?
The authors undertook a review of the literature, focussing on publications describing the following: (1) Pure tone threshold data for adolescents/young adults; (2) Measurements/estimates of noise exposure from leisure activities; and (3) The relationship between hearing threshold levels (HTLs) and leisure-noise exposure. There is a large volume of published materials relevant to these topics, and opinion among authors regarding the relationship between leisure-noise exposure and HTLs varies significantly. At one extreme is the view that the effects of leisure-noise are minimal. The opposing belief is that as a direct result of leisure-noise exposure, significant HTL shifts and possibly significant hearing disability are occurring in a large (and increasing) proportion of young people. It has been claimed that behaviors relating to leisure-noise are "as threatening to young people's health as more traditional risk behaviors" (, p. 55). This view has been reiterated by the popular media. This review revealed that while sufficient data confirm that some leisure pursuits provide potentially hazardous noise levels, the nature of the exposure-injury relationship for leisure-noise is yet to be determined. Specific information about the quality-of-life effects of threshold shift related to leisure-noise exposure is also lacking. The scope and limitations of a large sample of relevant publications and an overview of the methodological issues in this area of research are briefly presented. Considerations for future research are raised.


HYPERTENSION: Mutation Points to Salt Recycling Pathway.
A team of researchers at Yale Medical School has uncovered a gene mutation that leads to early-onset hypertension that may point the way to causes for more common forms of high blood pressure. On page 119, the Yale group reports finding a new mutation in the so-called mineralocorticoid receptor, a protein in kidney cells that is involved in the body's handling of salt. This is the first work to demonstrate how alterations in the receptor could give rise to hypertension; in particular, the findings may explain why some women experience a sharp rise in blood pressure during pregnancy.


Perceptions of Dental Dyschromia by Patients and Dentist.
To assess patient self-perception of overall dental appearance and of potentially localized dyschromic teeth and to compare them to the perception of the treating dentist. A sample of 160 patients from Cluj-Napoca, Romania, answered a questionnaire regarding the self-perception of their dental appearance and of potential localized dental discolorations. The same questions were answered by their dentist, without knowing their answers, after clinical examination of each patient. Each patient and the dentist were asked to indicate a tooth with a pleasant color to be considered as reference. Color measurements of teeth indicated as dyschromic and of the reference teeth were performed using a spectrophotometer. Color differences were calculated using the ΔE00 formula. Tooth color was considered the most disturbing factor of their dental appearance by 41.25% of patients. Most patients (58.12%) acknowledged localized dyschromic teeth in their dental arches. Agreement between patients and dentist regarding the identification of dyschromic teeth was found in 61.87% of cases. The DE00 between the reference teeth and the teeth considered dyschromic by both patients and dentist ranged between 0.8 and 23.1. Disagreement between patients and dentist was found in 38.12% of situations. For teeth considered dyschromic only by patients, the ΔE00 ranged between 0.8 and 23.1. For teeth considered dyschromic only by the dentist, the ΔE00 ranged between 0.8 and 25. Most patients expressed concerns regarding their overall dental color and perceived themselves as having teeth with localized dyschromia. More than a third of the investigated patients had different perceptions regarding dyschromic teeth compared to their dentist. The majority of ΔE00 values calculated between dyschromic and reference teeth exceeded the perceptibility and acceptability thresholds.


Recombinant Fasciola hepatica Fatty Acid Binding Protein as a Novel Anti-Inflammatory Biotherapeutic Drug in an Acute Gram-Negative Nonhuman Primate Sepsis Model.
Due to their phylogenetic proximity to humans, nonhuman primates (NHPs) are considered an adequate choice for a basic and preclinical model of sepsis. Gram-negative bacteria are the primary causative of sepsis. During infection, bacteria continuously release the potent toxin lipopolysaccharide (LPS) into the bloodstream, which triggers an uncontrolled systemic inflammatory response leading to death. Our previous research has demonstrated in vitro and in vivo using a mouse model of septic shock that Fh15, a recombinant variant of the Fasciola hepatica fatty acid binding protein, acts as an antagonist of Toll-like receptor 4 (TLR4) suppressing the LPS-induced proinflammatory cytokine storm. The present communication is a proof-of concept study aimed to demonstrate that a low-dose of Fh15 suppresses the cytokine storm and other inflammatory markers during the early phase of sepsis induced in rhesus macaques by intravenous (i.v.) infusion with lethal doses of live Escherichia coli. Fh15 was administered as an isotonic infusion 30 min prior to the bacterial infusion. Among the novel findings reported in this communication, Fh15 (i) significantly prevented bacteremia, suppressed LPS levels in plasma, and the production of C-reactive protein and procalcitonin, which are key signatures of inflammation and bacterial infection, respectively; (ii) reduced the production of proinflammatory cytokines; and (iii) increased innate immune cell populations in blood, which suggests a role in promoting a prolonged steady state in rhesus macaques even in the presence of inflammatory stimuli. This report is the first to demonstrate that a F. hepatica-derived molecule possesses potential as an anti-inflammatory drug against sepsis in an NHP model. IMPORTANCE Sepsis caused by Gram-negative bacteria affects 1.7 million adults annually in the United States and is one of the most important causes of death at intensive care units. Although the effective use of antibiotics has resulted in improved prognosis of sepsis, the pathological and deathly effects have been attributed to the persistent inflammatory cascade. There is a present need to develop anti-inflammatory agents that can suppress or neutralize the inflammatory responses and prevent the lethal consequences of sepsis. We demonstrated here that a small molecule of 14.5 kDa can suppress the bacteremia, endotoxemia, and many other inflammatory markers in an acute Gram-negative sepsis rhesus macaque model. These results reinforce the notion that Fh15 constitutes an excellent candidate for drug development against sepsis.


Phase II study of interferon-enhanced 131I-labeled high affinity CC49 monoclonal antibody therapy in patients with metastatic prostate cancer.
Adjuvant Interferon (IFN) was given to increase tumor antigen expression and enhance localization with 131I-labeled CC49 radioimmunotherapy in a Phase II trial for hormone resistant metastatic prostate cancer. Patients received four doses of alpha-IFN (3 x 10(6) IU) s.c. on alternate days, from day -5 to day +1 of 75 mCi/m2 131I-CC49 treatment. Toxicity was well tolerated, with the majority of patients experiencing transient grade 3 or 4 neutropenia and/or thrombocytopenia (maximal at 4-6 weeks). The absorbed dose was >25 Gy in four of eight tumors visualized, which represents an increase of >20 fold over whole body radiation dose. Two patients had radiographic minor responses by 6 weeks post-therapy, whereas five of six patients experiencing pain had symptom relief without radiographic changes. The protocol provided modest antitumor effects (pain relief in five of six patients and two minor radiographic responses). This study suggests that the addition of IFN enhanced tumor uptake and antitumor effects as compared to a prior Phase II trial of 131I-CC49 alone.


All that glitters is not gold: prevalence and relevance of psychotic-like experiences in clinical sample of children and adolescents aged 8-17 years old.
Recent studies have examined the prevalence of psychotic-like experiences (PLEs) and their relationship with functioning, psychopathology and distress in adult and mixed young adult and adolescent samples. There is, however, a lack of knowledge about the prevalence and clinical weight of PLEs in clinical child and adolescent (CAD) populations. Available research has primarily been conducted on community populations, and even clinical samples mostly used self-reported questionnaires. These studies also recruited participants 12 years old and older, with a consequent lack of information on children from 8 to 11 years old. We examined the prevalence of PLEs and their relationship with psychiatric diagnosis, functioning, intelligence quotient (IQ), anxiety and depressive symptoms in a clinical sample aged 8-17 years old. The study was conducted on a clinical sample of 46 CAD with PLEs compared to a clinical sample of 60 CAD without PLEs. The two groups were compared on global, social and role functioning, IQ, anxiety and depressive symptoms, and number of psychiatric diagnoses. Global, role and social functioning were significantly lower in the CAD clinical sample with PLEs. These significant differences were maintained when the covariate IQ, number of psychiatric diagnoses or level of anxiety or depression was added. No significant age-related differences in the presence of PLEs were found. The findings of this study show that PLEs are common in a clinical sample of CAD, even those under 12 years old. The presence of PLEs should therefore be investigated and considered in planning treatment of non-psychotic psychiatric disorders in CAD.


Splenic Volume Index Determined Using Computed Tomography upon Admission Is Associated with Readmission for Heart Failure Among Patients with Acute Decompensated Heart Failure.
The spleen is associated with inflammation, and the size of the spleen is affected by hemodynamic congestion and sympathetic stimulation. However, the association between splenic size and prognosis in patients with heart failure remains unknown. Between January 2015 and March 2017, we analyzed 125 patients with acute decompensated heart failure who were assessed by computed tomography (CT) on the day of admission. The spleen was measured by 3-dimensional CT and then the patients were assigned to groups according to their median splenic volume indexes (SpVi; splenic volume/body surface area). We then compared their baseline characteristics and rates of readmission for heart failure after one year. The median SpVi was 63.7 (interquartile range: 44.7-95.3) cm3/m2. Age did not significantly differ between the groups. Patients with a high SpVi had more significantly enlarged left atria and left ventricles. Multiple regression analysis identified significant positive correlations between SpVi and posterior wall thickness as well as left ventricular mass index. Kaplan-Meier analysis revealed lower event-free rates in the patients with a high, than a low SpVi (P = 0.041, log-rank test). After adjustment for potential cofounding factors, SpVi was independently associated with readmission for heart failure (Hazard ratio, 2.25; 95% confidence interval, 1.01-5.02; P = 0.047). In conclusion, increased splenic volume is independently associated with readmission for heart failure among patients with acute decompensated heart failure.


High-oil, high-protein diets and milk secretion by cows.
Intakes of grass silage and yield and composition of milk were examined in cows given high-protein diets to which two quantities of soybean oil had been added either as intracellular or extracellular inclusions. Adding extra protein to the diet did not prevent reduction of dry matter intakes of forage when soybean oil was added to the diet of cows. There is a fundamental difference in the mechanism by which high-starch diets reduce intake of forage dry matter from that of high-oil diets. In diets containing extracellular unsaturated oils, concentration of oil in the total ration, not the amount of oil per se, is the primary determinant reducing milk fat percentage.


Characterization and epitope mapping of a human monoclonal antibody reactive with the envelope glycoprotein of human immunodeficiency virus.
A human monoclonal antibody (IgG2, lambda), 1B8.env, was produced, reactive with the envelope glycoprotein of human immunodeficiency virus (HIV). The antibody specifically stains cells infected with HIV, as assessed by indirect immunofluorescence analysis and reacts with determinants displayed on the surface of infected cells. In Western blot analysis, the antibody reacts with bands of 160 and 41 kD, consistent with the precursor and transmembrane forms of the HIV envelope glycoprotein. The antibody also reacts specifically in immunofluorescence and Western blot analysis with cells infected with the recombinant vaccinia virus VSC-25, which contains the envelope gene of HIV. With the lambda gt11 expression vector, the epitope recognized by 1B8.env was mapped to a region of 11 amino acids in the coding region of gp41. This domain is highly conserved between several otherwise highly variable HIV isolates. In addition, this epitope appears to be recognized by the vast majority of HIV seropositive individuals. Although antibody IB8.env does not neutralize HIV virion infectivity or virally mediated cell fusion, the results presented here demonstrate the feasibility of generating and characterizing human monoclonal antibodies to HIV with these techniques. Additional antibodies produced in this manner will help to further characterize the humoral response to HIV infection, define biologically significant determinants on HIV proteins, and may be useful in clinical applications.


Structural Variability in the RLR-MAVS Pathway and Sensitive Detection of Viral RNAs.
Cells need high-sensitivity detection of non-self molecules in order to fight against pathogens. These cellular sensors are thus of significant importance to medicinal purposes, especially for treating novel emerging pathogens. RIG-I-like receptors (RLRs) are intracellular sensors for viral RNAs (vRNAs). Their active forms activate mitochondrial antiviral signaling protein (MAVS) and trigger downstream immune responses against viral infection. Functional and structural studies of the RLR-MAVS signaling pathway have revealed significant supramolecular variability in the past few years, which revealed different aspects of the functional signaling pathway. Here I will discuss the molecular events of RLR-MAVS pathway from the angle of detecting single copy or a very low copy number of vRNAs in the presence of non-specific competition from cytosolic RNAs, and review key structural variability in the RLR / vRNA complexes, the MAVS helical polymers, and the adapter-mediated interactions between the active RLR / vRNA complex and the inactive MAVS in triggering the initiation of the MAVS filaments. These structural variations may not be exclusive to each other, but instead may reflect the adaptation of the signaling pathways to different conditions or reach different levels of sensitivity in its response to exogenous vRNAs.


Adenosine exerts a glycogen-sparing action in contracting rat skeletal muscle.
The role of adenosine in regulating glycogen breakdown during electrically induced muscle contractions was investigated in isolated rat hindquarters perfused with a standard medium either lacking or containing 100 microU/ml insulin and/or 1.67 nM isoprenaline. Nonselective A1/A2-adenosine receptor antagonism via caffeine enhanced (P < 0.05) glycogen breakdown in contracting fast-oxidative (FO) fibers by 40%, provided they were exposed to both insulin and isoprenaline. Combined A1/A2-receptor antagonism by 8-cyclopentyl-1,3-dipropylxanthine (CPDPX) plus 3,7-dimethyl-1-proparglyxanthine (DMPX) fully reproduced (P < 0.05) this stimulatory effect. Furthermore, CPDPX plus DMPX also enhanced (P < 0.05) glycogenolysis during contractions in soleus but not in white gastrocnemius muscle. In contrast, CPDPX or DMPX alone did not affect glycogenolysis in either fiber type. Muscle adenosine 3',5'-cyclic monophosphate concentration during contractions was increased (P < 0.05) by CPDPX plus DMPX in both fiber types, whereas glycogen synthase fractional activity was depressed (P < 0.05). Phosphorylase activity was not changed by CPDPX plus DMPX. It is concluded that adenosine exerts a glycogen-sparing action in oxidative skeletal muscle exposed to both insulin and beta-adrenergic stimulation during contraction, presumably via stimulation of glycogen synthase activity.


History of home haemodialysis in Australia.
Australia has had an active and slowly expanding home haemodialysis programme; however, this has failed to expand as rapidly as some other methods of treatment of end-stage kidney disease. The technique in Australia has always been a derivative from overseas experience, rather than innovative. It received some minor initial support from the report issued in 1968 by an ad-hoc Committee of the National Health and Medical Research Council on Rationalization of Facilities for Organ Transplantation and Renal Dialysis, but was ultimately disadvantaged because the report promoted transplantation over dialysis to an extent that proved markedly disproportionate to the number of patients who, in succeeding decades, would need maintenance dialysis treatment rather than transplantation. Nevertheless, each state in Australia established home haemodialysis facilities, but major interstate variations occurred in the uptake of the modality. The subsequent development of continuous ambulatory peritoneal dialysis and limited care dialysis centres appeared to have an important negative impact on home haemodialysis, although the recent introduction of daily dialysis is likely to have a positive influence in the future.


GmFT2a, a soybean homolog of FLOWERING LOCUS T, is involved in flowering transition and maintenance.
Flowering reversion can be induced in soybean (Glycine max L. Merr.), a typical short-day (SD) dicot, by switching from SD to long-day (LD) photoperiods. This process may involve florigen, putatively encoded by FLOWERING LOCUS T (FT) in Arabidopsis thaliana. However, little is known about the potential function of soybean FT homologs in flowering reversion. A photoperiod-responsive FT homologue GmFT (renamed as GmFT2a hereafter) was cloned from the photoperiod-sensitive cultivar Zigongdongdou. GmFT2a gene expression under different photoperiods was analyzed by real-time quantitative PCR. In situ hybridization showed direct evidence for its expression during flowering-related processes. GmFT2a was shown to promote flowering using transgenic studies in Arabidopsis and soybean. The effects of photoperiod and temperature on GmFT2a expression were also analyzed in two cultivars with different photoperiod-sensitivities. GmFT2a expression is regulated by photoperiod. Analyses of GmFT2a transcripts revealed a strong correlation between GmFT2a expression and flowering maintenance. GmFT2a transcripts were observed continuously within the vascular tissue up to the shoot apex during flowering. By contrast, transcripts decreased to undetectable levels during flowering reversion. In grafting experiments, the early-flowering, photoperiod-insensitive stock Heihe27 promotes the appearance of GmFT2a transcripts in the shoot apex of scion Zigongdongdou under noninductive LD conditions. The photothermal effects of GmFT2a expression diversity in cultivars with different photoperiod-sensitivities and a hypothesis is proposed. GmFT2a expression is associated with flowering induction and maintenance. Therefore, GmFT2a is a potential target gene for soybean breeding, with the aim of increasing geographic adaptation of this crop.


Interspecies interaction and effect of co-contaminants in an anaerobic dichloromethane-degrading culture.
An anaerobic stable mixed culture dominated by bacteria belonging to the genera Dehalobacterium, Acetobacterium, Desulfovibrio, and Wolinella was used as a model to study the microbial interactions during DCM degradation. Physiological studies indicated that DCM was degraded in this mixed culture at least in a three-step process: i) fermentation of DCM to acetate and formate, ii) formate oxidation to CO2 and H2, and iii) H2/CO2 reductive acetogenesis. The 16S rRNA gene sequencing of cultures enriched with formate or H2 showed that Desulfovibrio was the dominant population followed by Acetobacterium, but sequences representing Dehalobacterium were only present in cultures amended with DCM. Nuclear magnetic resonance analyses confirmed that acetate produced from 13C-labelled DCM was marked at the methyl ([2-13C]acetate), carboxyl ([1-13C]acetate), and both ([1,2-13C]acetate) positions, which is in accordance to acetate formed by both direct DCM fermentation and H2/CO2 acetogenesis. The inhibitory effect of ten different co-contaminants frequently detected in groundwaters on DCM degradation was also investigated. Complete inhibition of DCM degradation was observed when chloroform, perfluorooctanesulfonic acid, and diuron were added at 838, 400, and 107 μM, respectively. However, the inhibited cultures recovered the DCM degradation capability when transferred to fresh medium without co-contaminants. Findings derived from this work are of significant relevance to provide a better understanding of the synergistic interactions among bacteria to accomplish DCM degradation as well as to predict the effect of co-contaminants during anaerobic DCM bioremediation in groundwater.


Differences between young and elderly subjects in seasonal and circadian variations of total plasma proteins and blood volume as reflected by hemoglobin, hematocrit, and erythrocyte counts.
Circadian and seasonal rhythms in total plasma proteins were documented in healthy young men (around 24 years old), and in elderly subjects (both sexes), including senile-dementia patients in their eighties. The concentration of plasma proteins within a given group changed predictably (7-13%), depending on the hour of sampling and the season. Concentrations decreased noticeably around 04:00 h, then peaked around 08:00 h (shortly after waking). The 24-h mean concentrations of total plasma proteins were lower in the elderly groups than in the young men. But the seasonal variations of the 24-h mean values were strikingly larger in the elderly groups (7-8 g/L) than in the young men (2-5 g/L). Moreover, the circadian profiles of plasma proteins differed from the profiles of hematocrit, hemoglobin, and erythrocyte counts. Evidently, circadian variations of blood volume may not be the only element accounting for the variations of plasma protein concentrations. We suggest that the rhythms in plasma protein concentrations be taken into account when reference values are set. Circadian and seasonal variations in plasma proteins may also significantly affect the transport and binding of drugs, especially in the aged.


Oral and Written Naming in Alzheimer's Disease: A Longitudinal Study.
The expressive difficulties in patients with Alzheimer's dementia have been extensively studied, mainly in oral language. However, the deterioration of their writing processes has received much less attention. The present study aims to examine the decline of the performance of patients with Alzheimer's disease in both oral and written picture-naming tasks. Sixty-four participants (half with Alzheimer's disease and half healthy elderly) were compared in the oral and written versions of a picture-naming task. Follow-up lasted two and a half years and patients were evaluated every six months. Cross-sectional data indicate that the controls performed better than the patients, and both groups showed a different pattern of errors. In terms of longitudinal data, the results show a similar pattern of deterioration in both tasks. In terms of errors, lexical-semantics were the most numerous at the beginning and their number remained constant throughout all evaluations. In the case of non-responses, there was a significant increase in the last session, both in oral and written naming. These results replicate those found in previous studies and highlight the utility of the naming task to detect minimal changes in the evolution of patients with Alzheimer's disease.


Toward a universalistic behavioural model of perceived managerial and leadership effectiveness for the health services sector.
Much management and leadership development provision for healthcare professionals has been the subject of considerable criticism, and there have been numerous calls for training programmes explicitly focused on the specific managerial (manager/leader) behaviours healthcare managers, physician leaders and nurse managers need to exhibit to be perceived effective. The aim of our multiple cross-case/cross-nation comparative study has been to: i) identify similarities and differences between the findings of published qualitative critical incident studies of effective and ineffective managerial behaviour observed within British, Egyptian, Mexican and Romanian public hospitals, respectively, and ii) if possible, deduce from the identified commonalities a healthcare-related behavioural model of perceived managerial and leadership effectiveness. Adopting a philosophical stance informed by pragmatism, epistemological instrumentalism and abduction, we used realist qualitative analytic methods to code and classify into a maximum number of discrete behavioural categories empirical source data obtained from five previous studies. We found high degrees of empirical generalization which resulted in the identification of five positive (effective) and four negative (ineffective) behavioural dimensions (BDs) derived, respectively, from 14 positive and 9 negative deduced behavioural categories (BCs). These BDs and underpinning BCs are expressed in the form of an emergent two-factor universalistic behavioural model of perceived managerial and leadership effectiveness. We suggest the model could be used to critically evaluate the relevance and appropriateness of existing training provision for physician leaders, nurse managers and other healthcare managers/leaders in public hospitals or to design new explicit training programmes informed and shaped by healthcare-specific management research, as called for in the literature.