Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials.
Carbon monoxide (CO) therapy has emerged as a hot topic under exploration in the field of gas therapy as it shows the promise of treating various diseases. Due to the gaseous property and the high affinity for human hemoglobin, the main challenges of administrating medicinal CO are the lack of target selectivity as well as the toxic profile at relatively high concentrations. Although abundant CO releasing molecules (CORMs) with the capacity to deliver CO in biological systems have been developed, several disadvantages related to CORMs, including random diffusion, poor solubility, potential toxicity, and lack of on-demand CO release in deep tissue, still confine their practical use. Recently, the advent of versatile nanomedicine has provided a promising chance for improving the properties of naked CORMs and simultaneously realizing the therapeutic applications of CO. This review presents a brief summarization of the emerging delivery strategies of CO based on nanomaterials for therapeutic application. First, an introduction covering the therapeutic roles of CO and several frequently used CORMs is provided. Then, recent advancements in the synthesis and application of versatile CO releasing nanomaterials are elaborated. Finally, the current challenges and future directions of these important delivery strategies are proposed.


DPVisCreator: Incorporating Pattern Constraints to Privacy-preserving Visualizations via Differential Privacy.
Data privacy is an essential issue in publishing data visualizations. However, it is challenging to represent multiple data patterns in privacy-preserving visualizations. The prior approaches target specific chart types or perform an anonymization model uniformly without considering the importance of data patterns in visualizations. In this paper, we propose a visual analytics approach that facilitates data custodians to generate multiple private charts while maintaining user-preferred patterns. To this end, we introduce pattern constraints to model users' preferences over data patterns in the dataset and incorporate them into the proposed Bayesian network-based Differential Privacy (DP) model PriVis. A prototype system, DPVisCreator, is developed to assist data custodians in implementing our approach. The effectiveness of our approach is demonstrated with quantitative evaluation of pattern utility under the different levels of privacy protection, case studies, and semi-structured expert interviews.


ALS Clinical Trials Review: 20 Years of Failure. Are We Any Closer to Registering a New Treatment?
Amyotrophic lateral sclerosis (ALS) is a devastating condition with an estimated mortality of 30,000 patients a year worldwide. The median reported survival time since onset ranges from 24 to 48 months. Riluzole is the only currently approved mildly efficacious treatment. Riluzole received marketing authorization in 1995 in the USA and in 1996 in Europe. In the years that followed, over 60 molecules have been investigated as a possible treatment for ALS. Despite significant research efforts, the overwhelming majority of human clinical trials (CTs) have failed to demonstrate clinical efficacy. In the past year, oral masitinib and intravenous edaravone have emerged as promising new therapeutics with claimed efficacy in CTs in ALS patients. Given their advanced phase of clinical development one may consider these drugs as the most likely near-term additions to the therapeutic arsenal available for patients with ALS. In terms of patient inclusion, CT with masitinib recruited a wider, more representative, less restrictive patient population in comparison to the only successful edaravone CT (edaravone eligibility criteria represents only 18% of masitinib study patients). The present manuscript reviews >50 CTs conducted in the last 20 years since riluzole was first approved. A special emphasis is put on the analysis of existing evidence in support of the clinical efficacy of edaravone and masitinib and the possible implications of an eventual marketing authorisation in the treatment of ALS.


Increased intake of vegetable oil rich in n-6 PUFA enhances allergic symptoms and prevents oral tolerance induction in whey-allergic mice.
Increased intake of vegetable oils rich in n-6 PUFA, including soyabean oil, has been associated with an increase in allergic disease. The present study aimed to determine the effect of an increasing dose of dietary vegetable oil on allergic outcomes in mice. To study this, mice received a 7 v. 10 % soyabean oil diet before and during oral sensitisation with whey or whey hyperimmune serum transfer. Another group of mice received partial whey hydrolysate (pWH) while being fed the diets before oral sensitisation. The acute allergic skin response, serum Ig level, mouse mast cell protease-1 (mMCP-1) concentration and/or splenic T-cell percentages were determined upon whey challenge. When the diets were provided before and during oral sensitisation, the acute allergic skin response was increased in mice fed the 10 % soyabean oil diet compared with the 7 % soyabean oil diet. Whey IgE and IgG1 levels remained unaltered, whereas mMCP-1 levels increased in mice fed the 10 % soyabean oil diet. Furthermore, allergic symptoms were increased in naive mice fed the 10 % soyabean oil diet and sensitised with whey hyperimmune serum. In addition to enhancing the mast cell response, the 10 % soyabean oil diet increased the percentage of activated Th1 and Th2 cells as well as increased the ratios of Th2:regulatory T cells and Th2:Th1 when compared with the 7 % soyabean oil diet. Oral tolerance induction by pWH was abrogated in mice fed the 10 % soyabean oil diet compared with those fed the 7 % soyabean oil diet during pretreatment with pWH. In conclusion, increased intake of soyabean oil rich in n-6 PUFA suppresses tolerance induction by pWH and enhances the severity of the allergic effector response in whey-allergic mice. Dietary vegetable oils rich in n-6 PUFA may enhance the susceptibility to develop or sustain food allergy.


Dose calculation for hypofractionated volumetric-modulated arc therapy: approximating continuous arc delivery and tongue-and-groove modeling.
Hypofractionated treatments generally increase the complexity of a treatment plan due to the more stringent constraints of normal tissues and target coverage. As a result, treatment plans contain more modulated MLC motions that may require extra efforts for accurate dose calculation. This study explores methods to minimize the differences between in-house dose calculation and actual delivery of hypofractionated volumetric-modulated arc therapy (VMAT), by focusing on arc approximation and tongue-and-groove (TG) modeling. For dose calculation, the continuous delivery arc is typically approximated by a series of static beams with an angular spacing of 2°. This causes significant error when there is large MLC movement from one beam to the next. While increasing the number of beams will minimize the dose error, calculation time will increase significantly. We propose a solution by inserting two additional apertures at each of the beam angle for dose calculation. These additional apertures were interpolated at two-thirds' degree before and after each beam. Effectively, there were a total of three MLC apertures at each beam angle, and the weighted average fluence from the three apertures was used for calculation. Because the number of beams was kept the same, calculation time was only increased by about 6%-8%. For a lung plan, areas of high local dose differences (> 4%) between film measurement and calculation with one aperture were significantly reduced in calculation with three apertures. Ion chamber measurement also showed similar results, where improvements were seen with calculations using additional apertures. Dose calculation accuracy was further improved for TG modeling by developing a sampling method for beam fluence matrix. Single element point sampling for fluence transmitted through MLC was used for our fluence matrix with 1 mm resolution. For Varian HDMLC, grid alignment can cause fluence sampling error. To correct this, transmission volume averaging was applied. For three paraspinal HDMLC cases, the average dose difference was greatly reduced in film and calculation comparisons with our new approach. The gamma (3%, 3 mm) pass rates have improved significantly from 74.1%, 90.0%, and 90.4% to 99.2%, 97.9%, and 97.3% for three cases, for calculation without volume averaging and calculation with volume averaging, respectively. Our results indicate that more accurate MLC leaf position and transmission sampling can improve accuracy and agreement between calculation and measurement, and are particularly important for hypofractionated VMAT that consists of large MLC movement.


Computer vision and natural constraints.
Computer vision, the automatic construction of scene descriptions from image input data, has just entered its second decade. Approaches have varied widely, especially in the amounts of symbolic, domain-dependent knowledge and inference that are incorporated into the vision process. Much current research addresses the extraction of physical properties of the scene (depth, surface orientation, reflectance) from images by using only a few general assumptions about the scene domain. Extraction of physical parameters is part of a hierarchy of operations needed to transform image input data to symbolic descriptions. Two other processes that serve as examples are stereo fusion and the partitioning of image phenomena into related groups. Computer vision research is influencing theories of animal perception as well as the design of computing architectures for artificial intelligence.


Practical biophysics: Sensors for rapid detection of biological targets utilizing target-induced oligonucleotide annealing.
Detection and quantitation of biomolecules is one of the most commonly performed measurements in biomedical research and clinical diagnostics. There is high demand for convenient, rapid and sensitive biomolecule detection methodologies. In this review we discuss a family of sensors that have been developed in our laboratory that share a common simple biophysical mechanism of action and that are capable of rapid detection of a diverse range of biological targets. The sensors generate fluorescence signal in the presence of the target molecule through target-induced association of short fluorochrome-labeled complementary oligonucleotides that are attached to target recognition elements of the sensors (antibodies, aptamers, etc.) via nanometer scale flexible linkers. This sensor design can be used for detecting proteins, antibodies, nucleic acids and whole cells. The assays using these sensors require only adding a sample to the sensor mix followed by simple fluorescence intensity readout. The simplicity, the speed of detection and the potential for miniaturization are the main assets of these sensors.


The Relationship between Retained Primitive Reflexes and Hemispheric Connectivity in Autism Spectrum Disorders.
Autism Spectrum Disorder (ASD) can be identified by a general tendency toward a reduction in the expression of low-band, widely dispersed integrative activities, which is made up for by an increase in localized, high-frequency, regionally dispersed activity. The study assessed ASD children and adults all possessing retained primitive reflexes (RPRs) compared with a control group that did not attempt to reduce or remove those RPRs and then examined the effects on qEEG and brain network connectivity. Analysis of qEEG spectral and functional connectivity was performed, to identify associations with the presence or absence of retained primitive reflexes (RPRs), before and after an intervention based on TENS unilateral stimulation. The results point to abnormal lateralization in ASD, including long-range underconnectivity, a greater left-over-right qEEG functional connectivity ratio, and short-range overconnectivity in ASD. Clinical improvement and the absence of RPRs may be linked to variations in qEEG frequency bands and more optimized brain networks, resulting in more developmentally appropriate long-range connectivity links, primarily in the right hemisphere.


Silybin and silymarin--new and emerging applications in medicine.
This review critically surveys the literature published mainly within this millennium on the new and emerging applications of silybin (pure, chemically defined substance) and silymarin (flavonoid complex from Silybum marianum - milk thistle seeds). These compounds used so far mostly as hepatoprotectants were shown to have other interesting activities, e.g. anticancer and canceroprotective and also hypocholesterolemic activity. These effects were demonstrated in a large variety of illnesses of different organs, e.g. prostate, lungs, CNS, kidneys, pancreas and also in the skin protection. Besides the cytoprotective activity of silybin mediated by its antioxidative and radical-scavenging properties also new functions based on the specific receptor interaction were discovered. These were studied on the molecular level and modulation of various cell-signaling pathways with silybin was disclosed--e.g. NF-kappaB, inhibition of EGFR-MAPK/ERK1/2 signaling, activity upon Rb and E2F proteins, IGF-receptor signaling. Proapoptotic activity of silybin in pre- and/or cancerogenic cells and anti-angiogenic activity of silybin are other important findings that bring silymarin preparations closer to respective application in the cancer treatment. Discovery of the inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors by silybin and some of its new derivatives contribute further to the better understanding of silybin activity on the molecular level. Silymarin application in veterinary medicine is reviewed as well. Recent works using optically pure silybin diastereomers clearly indicate extreme importance of the use of optically active silybin namely in the receptor studies. Significance of silymarin and its components in the medicine is clearly indicated by an exponential growth of publications on this topic--over 800 papers in the last 5 years.


The entry of HMOs into the Medicare market: implications for TEFRA's mandate.
The Tax Equity and Fiscal Responsibility Act of 1982, under rules implemented in April 1985, creates incentives for HMOs and other competitive medical plans to significantly expand their participation in Medicare on an at-risk basis. In an attempt to gauge the likely response of HMOs to the new incentives, we examined data on a census of HMOs operating in 1982 to look for differences between HMOs that entered the Medicare program at risk under the earlier National Medicare Competition demonstration and those that did not. The most consistent difference we found was that HMOs in areas with a high adjusted average per capita cost were more likely to enter the Medicare market. HMOs with prior experience serving Medicare beneficiaries were also more likely to join the demonstration, as were HMOs that were federally qualified. No other HMO characteristics appeared to significantly affect the likelihood of entry.


Palliative Radiation Therapy for Recurrent Ovarian Cancer: Efficacy and Predictors of Clinical Response.
This study aimed to report response rates and predictors of response to palliative radiotherapy (RT) for recurrent ovarian cancer. Database review identified 64 patients with symptomatic ovarian cancer recurrence who received a total of 76 courses of RT for 103 indications from March 2003 to August 2014. Radiotherapy indications were pain (44%), bleeding (32%), obstruction (15%), and other (9%). Responses were categorized as complete, partial, or none; all response (AR) was the sum of complete and partial responses. Response rates were compared using a χ test. Multivariate analysis was performed using logistic regression. Patients were followed up for symptom recurrence and death. Response rates were significantly higher for pain (AR, 87%) and bleeding (93%) than for obstruction (62%) and other (60%; P < 0.01). Patients treated for pain at nonbony sites had higher response rates (AR 96%) compared with those treated at bony sites (75%; P = 0.04). Patients with clear cell histology had the lowest response rates (AR, 60%) compared with those with serous (82%), endometrioid (95%), or other Müllerian histology (85%; P = 0.01). Platinum status at diagnosis or the time of RT was not associated with response, nor was tumor size or number of prior chemotherapy regimens. On multivariate analysis, histology, RT indication, and RT dose were independent predictors of response (all P < 0.01). Palliative RT provides relief of pain and bleeding in most patients with ovarian cancer recurrence. Patients with symptomatic obstruction, bony involvement, and clear cell histology may experience lower clinical response rates.


Presence of Human Papillomavirus and Epstein-Barr Virus, but Absence of Merkel Cell Polyomavirus, in Head and Neck Cancer of Non-Smokers and Non-Drinkers.
Determine the presence and prognostic value of human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCPyV), and cell cycle proteins in head and neck squamous cell carcinoma (HNSCC) of non-smokers and non-drinkers (NSND). Clinical characteristics and tumors of 119 NSND with HNSCC were retrospectively collected and analyzed on tissue microarrays. RNAscope in situ hybridization (ISH) was used to screen for the presence of HPV and MCPyV mRNA. Immunohistochemistry was performed for expression of p16 as surrogate marker for HPV, Large T-antigen for MCPyV, and cell cycle proteins p53 and pRb. Positive virus results were confirmed with polymerase chain reaction. For EBV, EBV encoded RNA ISH was performed. Differences in 5-year survival between virus positive and negative tumors were determined by log rank analysis. All oropharyngeal tumors (OPSCC) (n = 10) were HPV-positive, in addition to one oral (OSCC) and one nasopharyngeal tumor (NPSCC). The other three NPSCC were EBV-positive. MCPyV was not detected. Patients with HPV or EBV positive tumors did not have a significantly better 5-year disease free or overall survival. Over 70% of virus negative OSCC showed mutant-type p53 expression. In this cohort, all OPSCC and NPSCC showed HPV or EBV presence. Besides one OSCC, all other oral (n = 94), hypopharyngeal (n = 1), and laryngeal (n = 9) tumors were HPV, EBV, and MCPyV negative. This argues against a central role of these viruses in the ethiopathogenesis of tumors outside the oro- and nasopharynx in NSND. So, for the majority of NSND with virus negative OSCC, more research is needed to understand the carcinogenic mechanisms in order to consider targeted therapeutic options.


Knowledge of Human Papillomavirus and Cervical Cancer among Women Attending Gynecology Clinics in Pretoria, South Africa.
Cervical cancer is mainly caused by human papillomavirus (HPV). Worldwide, knowledge of HPV and cervical cancer among women is reported to be inadequate. The study aimed to assess the knowledge and awareness of HPV and cervical cancer among women attending gynecology clinics at a tertiary hospital in Pretoria, South Africa. The study also intended to identify socio-demographic factors influencing women's knowledge about HPV and cervical cancer risk factors. This was a clinic-based analytic cross-sectional study conducted among women aged 18 years and older. Participants were enrolled in the clinic waiting rooms while waiting to be attended to by the clinician. A self-administered questionnaire to assess knowledge of HPV, cervical cancer, and risk factors for developing cervical cancer was distributed to the participants. A total of 527 women aged ≥18 years and older were randomly enrolled with a 99.8% response rate. Less than half (47.1%) of the participants had been previously screened for cervical cancer using a Papanicolaou (Pap) test. Few (18.8%) women correctly mentioned cervical cancer risk factors. Unemployed women were less likely to have correct knowledge of cervical cancer causes/risk factors (OR: 0.63; 95% CI 0.40-0.97) compared to employed women. Divorced/separated/widowed women were more likely to have good HPV knowledge compared to single participants (OR: 2.74; 95% CI 1.46-5.15). From this study, it is evident that cervical cancer screening is very low, and women lack knowledge of HPV and cervical cancer disease symptoms and its risk factors. There is a need for policies to prioritize providing accurate information to the public to reduce cervical cancer morbidity and mortality.


Inferior gluteal vein varicosities: a rare cause of sciatica.
A 77-year-old woman presented with gradually progressing right sciatica of 2 years duration. She was investigated with a magnetic resonance imaging of the lumbosacral spine which did not reveal any abnormality. Magnetic resonance imaging of the pelvis was then performed and revealed right inferior gluteal vein varicosities causing compression of the adjacent sciatic nerve resulting in sciatica. Pain was relieved by walking likely due to collapse of the vein. This patient declined surgery but benefit has been reported in similar cases.


Mixture toxicity of SN2-reactive soft electrophiles: 1. Evaluation of mixtures containing α-halogenated acetonitriles.
The concept of multiple modes of toxic action denotes that an individual chemical can induce two or more toxic effects within the same series of concentrations, for example, reactive toxicity and narcosis. It appears that such toxicity confounds the ability to develop precise predictions of mixture toxicity and makes it more difficult to clearly link a dose-additive combined effect to agents in the mixture having a single common mechanism of toxic action. This initial study of a three-part series begins to examine this issue in greater detail by testing three α-halogenated acetonitriles: (1) in sham combinations, (2) in true combinations, and (3) with a nonreactive nonpolar narcotic. Iodo-, bromo-, and chloro-derivatives of acetonitrile were selected for testing based on their electro(nucleo)philic reactivity, via the S(N)2 mechanism, and their time-dependent toxicity individually. Reactivity of each agent was assessed in tests with the model nucleophile glutathione (GSH). Each acetonitrile was reactive with GSH, but the nonpolar narcotic 3-methyl-2-butanone was not. In addition, toxicity of the agents alone and in mixtures was assessed using the Microtox(®) acute toxicity test at three time points: 15, 30, and 45 min of exposure. Each of the three agents alone had time-dependent toxicity values of about 100%, making it likely that most of the toxicity of these agents, at these times, was due to reactivity. In contrast, the nonpolar narcotic agent lacked time-dependent toxicity. In mixture testing, sham combinations of each acetonitrile showed a combined effect consistent with predicted effects for dose-addition at each time point, as did the sham combination of the nonpolar narcotic. Mixture toxicity results for true acetonitrile combinations were also consistent with dose-addition, but the acetonitrile-nonpolar narcotic combinations were generally not consistent with either the dose-addition or independence models of combined effect. Based on current understanding of mixture toxicity, these results were expected and provide a foundation for the second and third studies in the series.


The interactive association of dietary diversity scores and breast-feeding status with weight and length in Filipino infants aged 6-24 months.
To assess how breast-feeding and dietary diversity relate to infant length-for-age Z-score (LAZ) and weight-for-age Z-score (WAZ). Breast-feeding, dietary and anthropometric data from the Cebu Longitudinal Health and Nutrition Survey were analysed using sex-stratified fixed-effects longitudinal regression models. A dietary diversity score (DDS) based on seven food groups was classified as low (<4) or high (≥ 4). The complementary feeding patterns were: (i) non-breast-fed with low DDS (referent); (ii) breast-fed with low DDS; (iii) non-breast-fed with high DDS; and (iv) breast-fed with high DDS (optimal). Interactions between age, energy intake and complementary feeding patterns were included. Philippines. Infants (n 2822) measured bimonthly from 6 to 24 months. Breast-feeding (regardless of DDS) was significantly associated with higher LAZ (until 24 months) and WAZ (until 20 months). For example, at 6 months, breast-fed boys with low DDS were 0.246 (95% CI 0.191, 0.302) sd longer and 0.523 (95% CI 0.451, 0.594) sd heavier than the referent group. There was no significant difference in size between breast-fed infants with high v. low DDS. Similarly, high DDS conferred no advantage in LAZ or WAZ among non-breast-fed infants. There were modest correlations between the 7-point DDS and nutrient intakes but these correlations were substantially attenuated after energy adjustment. We elucidated several interactions between sex, age, energy intake and complementary feeding patterns. These results demonstrate the importance of prolonged breast-feeding up to 24 months. The DDS provided qualitative information on infant diets but did not confer a significant advantage in LAZ or WAZ.


The inhibitory effect of halides and carboxylates on hepatic NADH: cytochrome b5 oxidoreductase.
The inhibitory effect of several halides and carboxylates on bovine liver microsomal NADH: cytochrome b5 oxidoreductase (EC 184.108.40.206) was examined. The magnitude of inhibition was altered by various anion species but not by cation species. The order of effectiveness was F- less than acetate less than Cl- less than Br- less than I- less than succinate congruent to citrate. The kinetics of these inhibitions was competitive with cytochrome b5, and non-competitive with NADH, indicating that these anions inhibit the interaction of the enzyme with cytochrome b5.


Calcium, magnesium, phosphorus and vitamin D fortification of complementary foods.
Provision of the bone minerals and vitamin D as fortificants in food or as dietary supplements designed for older infants and toddlers in Latin America is likely to be beneficial and safe. Currently available data are inadequate to establish the precise amounts of these nutrients that would be required for such a supplement. These amounts would vary according to the local base diet. However, reasonable estimates can be made on the basis of current dietary recommendations as well as existing data on bioavailability and customary intake. The strongest case can be made for calcium and vitamin D supplementation. Because excessive dietary calcium can reduce zinc absorption as a result of interactive effects within the intestine, an appropriate ratio of calcium to zinc should be used, even if this means adding zinc as a fortificant or supplement. Magnesium supplementation may be appropriate in some circumstances but it cannot be routinely advocated at present. It is unlikely that phosphorus supplementation is needed for most population groups because of the relatively high usual dietary phosphorus intakes, primarily from phosphate salts added to carbonated beverages and as food preservatives.


Outcomes in patients undergoing periprocedural interruption of warfarin or direct oral anticoagulants.
Differences in clinical outcomes following a temporary interruption of warfarin or a direct oral anticoagulant (DOAC) for a surgical procedure are not well described. Differences in patient characteristics from practice-based cohorts have not typically been accounted for in prior analyses. To describe risk-adjusted differences in postoperative outcomes following an interruption of warfarin vs DOACs. Patients receiving care at six anticoagulation clinics participating in the Michigan Anticoagulation Quality Improvement Initiative were included if they had at least one oral anticoagulant interruption for a procedure. Inverse probability of treatment weighting (IPTW) was used to balance baseline differences between the warfarin cohort and DOAC cohort. Bleeding and thromboembolic events within 30 days following the procedure were compared between the IPTW cohorts using the Poisson distribution test. A total of 525 DOAC patients were matched with 1323 warfarin patients, of which 923 were nonbridged warfarin patients and 400 were bridged warfarin patients. The occurrence of postoperative minor bleeding (10.8% vs. 4.7%, p < .001), major bleeding (2.9% vs. 1.1%, p = .01) and clinically relevant nonmajor bleeding (CRNMB) (6.5% vs. 3.0%, p = .002) was greater in the DOAC cohort compared with the nonbridged warfarin cohort. The rates of postoperative bleeding outcomes were similar between the DOAC and the bridged warfarin cohorts. Perioperative interruption of DOACs, compared with warfarin without bridging, is associated with a higher incidence of 30-day minor bleeds, major bleeds, and CRNMBs. Further research investigating the perioperative outcomes of these two classes of anticoagulants is warranted.


[YAG-laser treatment for traumatic hemophthalmia].
The paper deals with noninvasive YAG-laser surgery that is used in the treatment of hemophthalmia, particularly hemophthalmia of posttraumatic genesis. A Visulas YAG laser unit ("Karl Zeiss") was used for YAG laser radiation. Its energy parameters were 0.8 to 9.2 mJ; 2-10 impulses; 1-30 laser treatment sessions. YAG-laser radiation affected the altered part of vitreous body: from fresh blood to the emergence of hemophthalmia as adhesions and conglomerates. YAG-laser applied to pathological vitreous body changes in hemophthalmia is effective and causes their elimination with subsequent lysis. YAG-laser vitreolysis is the operation of choice in traumatic hemophthalmia and may be used not only as an independent surgical technique, but also an additional one in the surgical and medical treatment of hemophthalmia. YAG-laser application to the vitreous body reduces the time of treatment for traumatic hemophthalmia.


Regulation of sulfate uptake in carrot cells: Properties of a hypercontrolled variant.
Sulfate uptake in haploid carrot cultures can be experimentally controlled by the sulfur source provided for growth. The rate of sulfate uptake is low in cells grown on cystine or sulfate and high in sulfur-starved cells. A selenate-resistant variant cell line has been isolated from a haploid carrot line. The variant shows hypersuppression of sulfate uptake by cystine and essentially normal control by the other treatments. While both lines efflux intracellular sulfate in the presence of external sulfate, the rate of efflux from the variant is 4-6 times higher at comparable levels of initial intracellular sulfate. Further, properties of the efflux and uptake in both lines suggest that they are mediated by the same system. We propose that the variant possesses an altered uptake-efflux system that is more readily reversed and more subject to control by some metabolite derived from cystine.


Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors.
New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic-clonic seizures and 49 focal to bilateral tonic-clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had <1 false alarm every 4 days, with an FAR below their seizure frequency. When increasing the sensitivity to 100% (no missed seizures), the FAR is up to 13 times lower than with the previous detector. Furthermore, all detections occurred before the seizure ended, providing reasonable latency (median = 29.3 s, range = 14.8-151 s). Automatically estimated seizure durations were correlated with true durations, enabling reliable annotations. Finally, EDA measurements confirmed the presence of postictal autonomic dysfunction, exhibiting a significant rise in 73% of the convulsive seizures. The proposed multimodal wrist-worn convulsive seizure detectors provide seizure counts that are more accurate than previous automated detectors and typical patient self-reports, while maintaining a tolerable FAR for ambulatory monitoring. Furthermore, the multimodal system provides an objective description of motor behavior and autonomic dysfunction, aimed at enriching seizure characterization, with potential utility for SUDEP warning.


[Urban stress of a megalopolis resident: stress factors and correctioN].
Residents of a megalopolis are constantly exposed to urban stress - the combined effects of a number of different extreme factors and living conditions of the urban environment. Urban stress of a megalopolis resident has an extreme complex multifactorial effect on his body and psyche. The features of the existing subspecies of urban stress (ecological, psychological, social, informational, professional, related to the pandemic), as well as the main stress factors causing them, are considered. The medical and social features of urban stress are described. The consequences of exposure to urban stress, directly related to human health disorders, include the so-called «urban stress diseases» or «diseases of civilization», primarily psychosomatic diseases. It is determined that urban stress is a multifactorial complex of stress factors affecting the physical and mental health of megalopolis residents. Due to the fact that an increasing number of megalopolis residents are experiencing the negative impact of an aggressive urban environment, it is necessary both to formalize stress factors in order to possibly correct them to improve the quality of life of citizens, and to develop appropriate optimizing medical and social recommendations. Modern organizational and medical and social measures aimed at reducing the negative impact of urban stress on the health of megalopolis residents are considered. It is proposed to minimize the negative impact of extreme urban stress factors on the physical and mental health of megalopolis residents by using therapeutic and preventive strategies to increase their stress resistance. There are a number of different organizations and departments in Moscow that provide psychological and psychotherapeutic support. Also, in order to determine the level of the body's reserves and stress resistance, it is possible to undergo a comprehensive examination both in the nearest polyclinic and in the nearest park within the framework of the Healthy Moscow program.


An Evaluation of Personal Cooling Systems for Reducing Thermal Strain Whilst Working in Chemical/Biological Protective Clothing.
The use of personal cooling systems to mitigate heat strain on first-responders achieves two potential performance benefits relative to the absence of such cooling: (1) the completion of a workload with less effort; and/or (2) the completion of a greater workload for the same effort. Currently, claims made by manufacturers regarding the capability of their products for use in conjunction with chemical/biological protective clothing remain largely unsubstantiated. The purpose of this investigation was to evaluate the means by which heat strain can be alleviated during uncompensable heat stress in chemical/biological clothing, using the ASTM F2300-10 methodology. Eight healthy males completed five trials of continuous walking (4.5 km h-1; 35°C; 49% RH) for up to 120 min while wearing one of four cooling systems and/or a National Fire and Protection Association 1994 Class-3 chemical/biological ensemble. The four cooling methods (ice vest [IV], phase-change vest [PCM], water-perfused suit [WS], and combination ice slurry/ice vest [SLIV]) and no cooling (CON). We observed significant improvements in trial times for IV (18 ± 10 min), PCM (20 ± 10 min) and SLIV (22 ± 10 min), but no differences for WS (4 ± 7 min). Heart rate, rectal, mean skin, and body temperatures were significantly lower in all cooling conditions relative to control at various matched time points in the first 60 min of exercise. Thermal sensation, comfort and perceived exertion all had significant main effects for condition, and time, there were no differences in their respective interactions. The IV, PCM, and SLIV produced lower heart rate, mean skin, rectal and mean body temperatures in addition to improved work times compared to control. The WS did not improve work times possibly as a result of the cooling capacity of the suit abating, and magnifying thermal insulation. Considering the added time and resources required to implement combination cooling in the form of ice slurry and ice vest (SLIV), there was no significant additive effect for perception, cardiovascular strain, rectal temperature and total trial time relative to the phase change vest or ice vest alone. This may be a product of a "ceiling" effect for work limit set to 120 min as part of ASTM F2300-10.


A dissection of the mechanisms generating and stabilizing polarity in mouse 8- and 16-cell blastomeres: the role of cytoskeletal elements.
Pairs of 8-cell or 16-cell blastomeres were cultured for up to 9 h after their formation from isolated 1/4 or 1/8 blastomeres respectively. Blastomeres were examined for the incidence and orientation of their surface polarity, as assessed by binding of FITC-Con A and by distribution of microvilli, and of their cytoplasmic polarity, as assessed by distribution of cytoplasmic actin, clathrin and a 100 kD antigen associated with the lysosomal/acid vesicle fraction of membranous organelles. The effect on polarity of incubating the pairs of cells in taxol, nocodazole, cytochalasin D or in a combination of nocodazole plus cytochalasin D for different parts of the incubation period was examined. Neither the development nor the stability of the surface polarity in 8-cell blastomeres was blocked by any treatment and only the use of CCD in combination with nocodazole affected the incidence of surface polarity appreciably. However, with some treatments, the form and position of the surface poles were modified. In the presence of microtubule inhibitors surface poles extended over a larger area of the cell surface, while exposure to CCD led to poles that were not opposite to the contact point between cells. In contrast to surface polarity, the development of cytoplasmic polarity was suppressed by both microtubule- and microfilament-inhibiting drugs, which also reversed it rapidly. In polar 16-cell blastomeres surface polarity was influenced in a similar manner to that of 8-cell blastomeres, only the combined use of cytochalasin D and nocodazole having any major effect. Polarization of clathrin in polar 16-cell blastomeres was inhibited almost completely by all drug treatments applied including cytochalasin D. The focal concentration of lysosomal antigen that occurs during the 16-cell stage was reduced only in the continuous presence of nocodazole plus cytochalasin D, but once established was not reversed appreciably by any drug. However, the localization of the lysosomal antigen to the basal region of polarized cells did not seem to occur in the presence of any drug. The dissociation of surface and cytoplasmic polarity revealed in these experiments leads us to conclude that either surface polarity is a prerequisite for the organization of cytoplasmic polarity, and mediates the latter via the cytoskeleton, or surface and cytoplasmic polarity develop by parallel but separate mechanisms.


Fish diversification at the pace of geomorphological changes: evolutionary history of western Iberian Leuciscinae (Teleostei: Leuciscidae) inferred from multilocus sequence data.
The evolutionary history of western Iberian Leuciscinae, obligatory freshwater fish, is directly linked to the evolution of the hydrographic network of the Iberian Peninsula after its isolation from the rest of Europe, which involved dramatic rearrangements such as the transition from endorheic lakes to open basins draining to the Atlantic. Previous phylogenetic research on western Iberian leuciscines, using mainly mitochondrial DNA and more recently one or two nuclear genes, has found contradictory results and there remain many unresolved issues regarding species relationships, taxonomy, and evolutionary history. Moreover, there is a lack of integration between phylogenetic and divergence time estimates and information on the timing of geomorphological changes and paleobasin rearrangements in the Iberian Peninsula. This study presents the first comprehensive fossil-calibrated multilocus coalescent species tree of western Iberian Leuciscinae (including 14 species of Achondrostoma, Iberochondrostoma, Pseudochondrostoma and Squalius endemic to the Iberian Peninsula, seven of which endemic to Portugal) based on seven nuclear genes, and from which we infer their biogeographic history by comparing divergence time estimates to known dated geological events. The phylogenetic pattern suggests slow-paced evolution of leuciscines during the Early-Middle Miocene endorheic phase of the main Iberian river basins, with the shift to exorheism in the late Neogene-Quaternary allowing westward dispersals that resulted in many cladogenetic events and a high rate of endemism in western Iberia. The results of this study also: (i) confirm the paraphyly of S. pyrenaicus with respect to S. carolitertii, and thus the possible presence of a new taxon in the Portuguese Tagus currently assigned to S. pyrenaicus; (ii) support the taxonomic separation of the Guadiana and Sado populations of S. pyrenaicus; (iii) show the need for further population sampling and taxonomic research to clarify the phylogenetic status of A. arcasii from the Minho basin and of the I. lusitanicum populations in the Sado and Tagus basins; and (iv) indicate that A. occidentale, I. olisiponensis and P. duriensis are the most ancient lineages within their respective genera.


Development of an adapted Clinical Global Impression scale for use in Angelman syndrome.
The Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) scales are widely accepted tools that measure overall disease severity and change, synthesizing the clinician's impression of the global state of an individual. Frequently employed in clinical trials for neuropsychiatric disorders, the CGI scales are typically used in conjunction with disease-specific rating scales. When no disease-specific rating scale is available, the CGI scales can be adapted to reflect the specific symptom domains that are relevant to the disorder. Angelman syndrome (AS) is a rare, clinically heterogeneous condition for which there is no disease-specific rating scale. This paper describes efforts to develop standardized, adapted CGI scales specific to AS for use in clinical trials. In order to develop adapted CGI scales specific to AS, we (1) reviewed literature and interviewed caregivers and clinicians to determine the most impactful symptoms, (2) engaged expert panels to define and operationalize the symptom domains identified, (3) developed detailed rating anchors for each domain and for global severity and improvement ratings, (4) reviewed the anchors with expert clinicians and established minimally clinically meaningful change for each symptom domain, and (5) generated mock patient vignettes to test the reliability of the resulting scales and to standardize rater training. This systematic approach to developing, validating, and training raters on a standardized, adapted CGI scale specifically for AS is described herein. The resulting CGI-S/I-AS scales capture six critical domains (behavior, gross and fine motor function, expressive and receptive communication, and sleep) defined by caregivers and expert clinicians as the most challenging for patients with AS and their families. Rigorous training and careful calibration for clinicians will allow the CGI-S/-I-AS scales to be reliable in the context of randomized controlled trials. The CGI-S/-I-AS scales are being utilized in a Phase 3 trial of gaboxadol for the treatment of AS.


Incidence of venous thromboembolism in patients undergoing craniotomy and motor mapping for glioma without intraoperative mechanical prophylaxis to the contralateral leg.
Evidence-based reviews support the use of venous thromboembolism (VTE) prophylaxis in the form of compression devices and/or stockings for patients undergoing craniotomy. In patients undergoing craniotomy with motor mapping for glioma, the contralateral lower extremity should remain visible so that motor responses can be accurately identified. As a consequence, these patients could be placed at a higher risk to develop VTE. The authors have quantified the incidence of VTE in patients undergoing craniotomy with motor mapping and have shown that there is no increased risk of developing a VTE in the contralateral lower extremity when compression devices are not used. One hundred eighty consecutive cases (1997-2000) of craniotomy with motor mapping for glioma were retrospectively reviewed to determine the incidence and location of VTEs during the early postoperative course. Intraoperative VTE prophylaxis in all patients consisted of ipsilateral (that is, ipsilateral to the hemisphere being mapped) lower-extremity mechanical prophylaxis (antiembolism stocking plus compression device). Postoperatively, all patients received bilateral mechanical prophylaxis. Patients were observed until discharge and received clinical follow up. Venous thromboembolism, classified as deep venous thrombosis (DVT) or pulmonary embolism (PE) occurring within 6 weeks postoperatively, was confirmed by Doppler ultrasonography, spiral computerized tomography scanning, or both. The average duration of postoperative hospitalization was 5 days (range 2-59 days). Six patients (3.3%) experienced VTE. Of those, in four (2.2%) the DVT was localized to the contralateral (three patients) or ipsilateral (one patient) lower extremity. Two other patients (1.1%) only had PE. There were no deaths from thromboembolic complications and no statistically significant predisposition to VTE in the contralateral lower extremity among patients not receiving intraoperative prophylaxis. The incidence of VTE in patients undergoing craniotomy with motor mapping is comparable to that in patients receiving bilateral lower-extremity mechanical VTE prophylaxis. The practice of leaving the contralateral lower extremity free from intraoperative prophylaxis does not appear to place patients at a higher risk for developing VTE. There appears to be no preferential distribution of VTE in contralateral lower extremities that do not receive immediate preoperative and intraoperative mechanical prophylaxis.


Renal Na+-K+-ATPase in renin release.
The effects of ouabain and furosemide on renin secretion, renal function, and renal Na+-K+-ATPase were investigated in anesthetized dogs. Furosemide (2 mg/kg) induced significant diuresis, natriuresis, an increase in renal blood flow (RBF), and a fivefold increase in renin secretory rate (RSR), but no changes in glomerular filtration rate (GFR). Infusion of ouabain (1 microgram . kg-1 . min-1) into one renal artery during furosemide diuresis increased fractional sodium excretion from 22 +/- 2 to 30 +/- 3% from the ipsilateral kidney but did not change urine flow, RBF, or GFR, whereas RSR fell to control values (698 +/- 203 to 137 +/- 43). When ouabain preceded furosemide, the rise in RBF and RSR induced by furosemide was abolished but sodium excretion increased. Ouabain infused in vivo inhibited Na+-K+-ATPase in microsomal fractions from cortex (34%) and medulla (27%) as compared with control. Neither saline nor furosemide exerted any effect on Na+-K+-ATPase. Moreover, the effect of ouabain alone on Na+-K+-ATPase was not different from that of ouabain plus furosemide. No changes in Mg2+-ATPase were detected in any of the experiments. These results indicate that inhibition of renal Na+-K+-ATPase abolishes furosemide-induced renin secretion despite potentiation of the natriuretic effect of the diuretic. It is apparent that the level of activity of Na+-K+-ATPase is of prime importance for renin secretion. In addition, ouabain may act directly on the juxtaglomerular cells to inhibit renin secretion.


[Biological screening of the level of anthropogenic environmental pollution and its hazard for the health of the population].
A possibility was examined to use a screening cytogenetic method for calculating micronuclei in frog blood cells as an indicator of the degree of environmental pollution and its hazard to human health. Data obtained correlate with an increased rate of reproductive function disorders in women and congenital malformations in children, living in regions where the cytologic studies of biological objects were carried out. The informational value of biogeochemical screening with the use of test objects for the assessment of the region ecological imbalance is stressed.


Vanadium interferes with siderophore-mediated iron uptake in Pseudomonas aeruginosa.
Vanadium is a metal that under physiological conditions can exist in two oxidation states, V(IV) (vanadyl ion) and V(V) (vanadate ion). Here, it was demonstrated that both ions can form complexes with siderophores. Pseudomonas aeruginosa produces two siderophores under iron-limiting conditions, pyoverdine (PVD) and pyochelin (PCH). Vanadyl sulfate, at a concentration of 1-2 mM, strongly inhibited growth of P. aeruginosa PAO1, especially under conditions of severe iron limitation imposed by the presence of non-utilizable Fe(III) chelators. PVD-deficient mutants were more sensitive to vanadium than the wild-type, but addition of PVD did not stimulate their growth. Conversely, PCH-negative mutants were more resistant to vanadium than the wild-type strain. Both siderophores could bind and form complexes with vanadium after incubation with vanadyl sulfate (1:1, in the case of PVD; 2:1, in the case of PCH). Although only one complex with PVD, V(IV)-PVD, was found, both V(IV)- and V(V)-PCH were detected. V-PCH, but not V-PVD, caused strong growth reduction, resulting in a prolonged lag phase. Exposure of PAO1 cells to vanadium induced resistance to the superoxide-generating compound paraquat, and conversely, exposure to paraquat increased resistance to V(IV). Superoxide dismutase (SOD) activity of cells grown in the presence of V(IV) was augmented by a factor of two. Mutants deficient in the production of Fe-SOD (SodB) were particularly sensitive to vanadium, whilst sodA mutants deficient for Mn-SOD were only marginally affected. In conclusion, it is suggested that V-PCH catalyses a Fenton-type reaction whereby the toxic superoxide anion O(2)- is generated, and that vanadium compromises PVD utilization.


The Gudaga Study: establishing an Aboriginal birth cohort in an urban community.
This paper describes the establishment of the Gudaga Study, an Aboriginal birth cohort in south-west Sydney, and our approach to follow-up of participants. The Study describes the health, development, and services use of Aboriginal infants and their mothers. The research team works closely with the local Aboriginal community to implement the research. All mothers in the maternity ward of an urban hospital were surveyed to identify mothers with an Aboriginal infant. These and some additional mothers identified through other networks were recruited to the study. The number of mothers were surveyed was 2,108. Mothers of Aboriginal infants were younger (25.3 years compared to 28.4 years, p<0.001), less likely to be married (16.1% cf. 58.4%, p<0.001) and to have completed school (63.2% cf. 77.8%, p=0.002) than mothers of non-Aboriginal infants. Of 155 identified mothers of Aboriginal infants, 136 were recruited and 23 through other networks. At 12 months, 85.5% of infants were followed up. This study, to our knowledge, is the first cohort study of this kind on the eastern seaboard of Australia. The study has strong community support and follow-up, contrary to views that Aboriginal people are reluctant to participate in research. These data have national and regional significance.


The contribution of dietary factors to dental caries and disparities in caries.
Frequent consumption of simple carbohydrates, primarily in the form of dietary sugars, is significantly associated with increased dental caries risk. Malnutrition (undernutrition or overnutrition) in children is often a consequence of inappropriate infant and childhood feeding practices and dietary behaviors associated with limited access to fresh, nutrient dense foods, substituting instead high-energy, low-cost, nutrient-poor sugary and fatty foods. Lack of availability of quality food stores in rural and poor neighborhoods, food insecurity, and changing dietary beliefs resulting from acculturation, including changes in traditional ethnic eating behaviors, can further deter healthful eating and increase risk for early childhood caries and obesity. America is witnessing substantial increases in children and ethnic minorities living in poverty, widening the gap in oral health disparities noted in Oral Health in America: A Report of the Surgeon General. Dental and other care providers can educate and counsel pregnant women, parents, and families to promote healthy eating behaviors and should advocate for governmental policies and programs that decrease parental financial and educational barriers to achieving healthy diets. For families living in poverty, however, greater efforts are needed to facilitate access to affordable healthy foods, particularly in urban and rural neighborhoods, to effect positive changes in children's diets and advance the oral components of general health.


Anxiety and Emotional Intelligence: Comparisons Between Combat Sports, Gender and Levels Using the Trait Meta-Mood Scale and the Inventory of Situations and Anxiety Response.
The present study compared emotional intelligence and anxiety between six combat sports of lower, intermediate and high-level female and male athletes. The sample was composed by 444 athletes (age: 24.7 ± 8.8 years, body mass: 72.4 ± 12.1 kg, height: 1.82 ± 0.3 m, and practice time: 13.1 ± 7.4 years) separated by sex (male n = 273, female n = 171) from different combat sports (jiu-jitsu n = 142, judo n = 137, karate n = 57, kendo n = 63, taekwondo n = 25, and freestyle wrestling n = 20) of three levels (high-level n = 57, intermediate n = 137 and low-level n = 142). Inventory of situations and anxiety response (ISRA) provided an independent evaluation for the three systems: cognitive, motor and physiological, as well as a total with four factors of analysis (anxiety before the evaluation, interpersonal, phobic and before habitual, and daily situations). Trait Meta-Mood Scale (TMMS-24) verified emotional intelligence scales. Descriptive results are demonstrated by percentage or median (first quartile Q1; third quartile Q3), Kruskal-Wallis and Mann-Whitney tests were conducted to compare groups, p ≤ 0.05. The main results demonstrated 10% more total anxiety for wrestling and judo compared to the other groups (p ≤ 0.05). Female athletes showed 15% more anxiety than men, while emotional attention demonstrated 10% better results for women. Significant differences were observed between high- versus low-level athletes in the total anxiety with 85 (44; 143) versus 122 (69; 186) of ISRA index and emotional repair with 30 (25; 34) versus 27 (22; 32) of TMMS-24 index. Emotional intelligence seems to be higher in female and in higher level, while anxiety appears to be prevalent in judo and wrestling, low-level and in female athletes. These outcomes provide support for the hypothesis that emotional abilities are an important contributor to emotional intelligence, particularly differentiating high level athletes than other levels. Results can be incorporated into strategies for reducing anxiety and improving emotional intelligence, considering particularities of gender and level groups.


Passiflin, a novel dimeric antifungal protein from seeds of the passion fruit.
The intent was to isolate an antifungal protein from seeds of the passion fruit (Passiflora edulis) and to compare its characteristics with other antifungal proteins and bovine beta-lactoglobulin in view of its N-terminal amino acid sequence similarity to beta-lactoglobulin. The isolation procedure entailed ion-exchange chromatography on Q-Sepharose, hydrophobic interaction chromatography on Phenyl-Sepharose, ion-exchange chromatography on DEAE-cellulose, and FPLC-gel filtration on Superdex 75. The isolated 67-kDa protein, designated as passiflin, exhibited an N-terminal amino acid sequence closely resembling that of bovine beta-lactoglobulin. It is the first antifungal protein found to have a beta-lactoglobulin-like N-terminal sequence. Its dimeric nature is rarely found in antifungal proteins. It impeded mycelial growth in Rhizotonia solani with an IC(50) of 16 microM and potently inhibited proliferation of MCF-7 breast cancer cells with an IC(50) of 15 microM. There was no cross-reactivity of passiflin with anti-beta-lactoglobulin antiserum. Intact beta-lactoglobulin lacks antifungal and antiproliferative activities and is much smaller in molecular size than passiflin. However, it has been reported that hydrolyzed beta-lactoglobulin shows antifungal activity. The data suggest that passiflin is distinct from beta-lactoglobulin.


The Human Thalamus Is an Integrative Hub for Functional Brain Networks.
The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks.SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks.


Medical Complications in Anorexia and Bulimia Nervosa.
Anorexia Nervosa (AN), Bulimia Nervosa (BN) and their variants are characterized by persistent alteration of eating behaviour, such as restricted intake or bingeing and purging, as well as excessive concerns about body shape and body weight. Purging behaviour may include self induced vomiting and/or abuse of laxatives, diuretics and physical hyperactivity. Unlike other psychiatric disorders, patients suffering from AN and BN have a high prevalence of many different medical complications, through the sequelae of undernutrition and purging, often with a serious impairment of health status and quality of life. This article describes the main diagnostic and clinical aspects of medical complications in AN and BN. The medical complications of ED are extremely variable and can occur with only modest biological and physical damage up to extremely serious and life-threatening conditions; the mortality rate of young subjects with AN is 4 - 11% with a risk of death about 12 times higher than that of subjects of the same age of the general population. The management of the medical-internship aspects of AN and BN is rightly placed within complex and articulated programs of interdisciplinary treatment with different levels of intensity of care (outpatient, semi-residential/residential, hospital in cases of emergency/medical and/or psychiatric emergency). the results of the investigations carried out, describe the functions of the various organs and apparatuses and the alterations detected, the possible complications and physiological adaptations to malnutrition.


[Study on key techniques and intervention in reducing birth defects].
To investigate key techniques and intervention in reducing birth defects. Down's syndrome (DS), trisomy-18 (Edwards syndrome, ES), neural tube defects (NTD), Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), thalassemia, and glucose-6-phosphate dehydrogenase deficiency (G6PD) were chosen as target disease. From Jan. 2007 to Dec. 2009, the condition of intake folic acid were investigated in 5004 pregnant women in Panlong District and Wuhua District of Kunming City. All of the 27 660 pregnant women undergoing prenatal examination were enrolled into the study from the First People's Hospital of Yunnan Province, the Second People's Hospital of Yunnan Province, the First People's Hospital of Qujing City, the Second People's of Qujing City, Qujing Women and Children's Hospital, People's Hospital of Lincang City, Kunming Maria Women's Hospital, Maternal and Infant's Care Unit of Panlong District of Kunming City, Maternal and Infant's Hospital of Dali City. The screening was performed on serum of those pregnant women at 8 - 20(+6) gestational weeks. Prenatal cytogenetic analysis and fetal ultrasonograpy were performed on the high risk or indicated women after genetic counseling. DNA analysis was administered on those women with family or childbearing history of DMD, SMA, thalassemia, or G6PD. Outcome of pregnancy was followed up to evaluate the effect of intervention. Approximately 30.10% (1506/5004) of pregnant women were administered by oral folic acid during perinatal period. Two thousand three hundred and thirteen women with high risks of DS, ES, or NTD fetuses were observed among 27 660 undergoing maternal serum screening. Two thousand and ninety-six pregnant women including two twins pregnant women were performed cytogenetic analysis. Other 67 pregnant women at high risk of DMD, SMA, thalassemia, and G6PD accepted genetic counseling and prenatal gene analysis. Two thousand one hundred and sixty-three pregnant women (2165 fetuses) underwent prenatal examination. One hundred and two cases chromosome abnormalities, 17 cases NTD, 4 cases DMD, 1 cases α-thalassemia major were found. All of the 91 fetuses with major birth defects were terminated after genetic counseling. Another affected DS fetus in a twin pregnancy dead intrauterine at 24 gestational weeks. Thirty-two women bearing fetuses with balanced translocations or inversions continued their pregnancies. Totally 2071 normal term fetuses were born in the prenatal diagnosis group. Two fetuses with normal chromosome were lost within 1 week after amniocentesis. Four affected DS fetuses were born from their high risk mothers who refused further prenatal diagnosis service. In a random sampling follow-up cohort of 5000 mothers at low risk, none of affected child suffering target diseases was found. The DS detection rate of maternal serum screening was 84% (27/32), with the false positive rate was 6.153% (1702/27 660). Folic acid intake before conception and in the first trimester would reduce the risk of birth defects, only 1/3 reproductive women took folic acid actively. Maternal serum screening could effectively detect high risk of DS, ES and NTD. The genetic counseling is critical in women at high risk or who had family history of inherited disorders. The prenatal screening and diagnosis combined with routine obstetric care could reduce the incidence of major birth defects, which should become prenatal care strategy in our country.


Hourly personal exposures to fine particles and gaseous pollutants--results from Baltimore, Maryland.
A study to characterize 1-hr multi-pollutant exposures was performed in Baltimore, MD, during the summer of 1998 and the winter of 1999, and was conducted over a 15-day period in each of the two seasons. Personal exposures were measured by a trained field technician, who wore a newly developed Roll-Around System (RAS) to measure 1-hr PM2.5 and gaseous (CO, O3, NO2, SO2, volatile organic compounds [VOCs]) exposures. One-hour O3, NO2, and SO2 personal exposures were measured using samplers developed in our laboratory, while short-term PM2.5, CO, and VOCs exposures were measured using currently available monitors. All 1-hr multi-pollutant exposures were measured while the technician performed pre-determined activities, beginning at 7:00 a.m. and ending at 7:00 p.m. of the same day. Activities were scripted to simulate activities performed by older adults (65+ years of age). Corresponding 1-hr ambient pollutant concentrations were obtained from federal or state monitoring networks. In this paper, we discuss the results from our study and present our descriptive analysis of the 1-hr personal particulate and gaseous exposure data. Personal PM2.5, O3, CO, and VOCs exposures showed substantial variability over the 12-hr sampling periods. Multiple pairwise comparison tests showed that 1-hr personal O3 exposures were significantly lower in indoor microenvironments as compared with outdoor microenvironments. One-hour personal CO exposures measured in vehicles were significantly higher than those measured in other microenvironments. The associations between 1-hr personal exposures and corresponding ambient concentrations differed by pollutant and by microenvironment. For example, the correlation between personal PM2.5 exposures and ambient concentrations was lowest (rs = 0.36, p < 0.05) in the winter for indoor non-residential microenvironments, and was highest (rs = 0.90, p < 0.05) in the winter for in-vehicle microenvironments. For O3, the correlation between personal exposures and ambient levels was weakest in the winter for residential microenvironments (rs = 0.05, p > 0.05), and was strongest in the summer for outdoor near-roadway microenvironments (rs = 0.91, p < 0.05).


Breast restoration after mastectomy for cancer.
The clinical problems encountered in the reconstruction of breasts of patients who have undergone mastectomy for cancer are presented. The indications and contraindications for reconstruction of the breast are arbitrarily defined. Various methods are available to reconstruct the breast. We favor implantation of a preformed silicone prosthesis under the skin and subcutaneous tissue overlying either the pectoralis major muscle or the chest wall. The advantages of this procedure outweigh those of other methods. Seven cases are presented to illustrate our experience in this rehabilitative procedure. It is suggested that breast reconstruction should be offered to a much higher proportion of patients undergoing mastectomy for breast cancer.


Body Mass Index (BMI) and Cognitive Functions in Later Life.
The findings from previous studies exploring the association between BMI and cognitive function in the elderly are conflicting. The purpose of the present study is twofold; to verify the association between BMI and cognitive functions and examine whether this association is impacted by height, when adjusted for possible covariates. The data for this study, consisted of 2287 older adults aged 60 years and above, drawn from a nationally representative population-based survey entitled "Determinants of Wellness among Older Malaysians: A Health Promotion Perspective" conducted in 2009. The mean age of the respondents was 68.7 (SD=6.6) years. The average score of cognitive function, measured by MMSE was 24.5 (SD=5.6). About 40% of the respondents were classified as overweight. Results of the multiple linear regression analysis revealed a significant association between BMI and cognitive function (Beta=.10, p<.001). The Factorial ANCOVA revealed significant interaction effect between BMI and height on cognitive function (F= 10.8, p<.001), after adjusting for possible covariates. The findings from the current study indicating the positive association between BMI and cognitive function depends on height, therefore it is suggested that short people might be targeted for dementia prevention.


The human urine virome in association with urinary tract infections.
While once believed to represent a sterile environment, the human urinary tract harbors a unique cellular microbiota. We sought to determine whether the human urinary tract also is home to viral communities whose membership might reflect urinary tract health status. We recruited and sampled urine from 20 subjects, 10 subjects with urinary tract infections (UTIs) and 10 without UTIs, and found viral communities in the urine of each subject group. Most of the identifiable viruses were bacteriophage, but eukaryotic viruses also were identified in all subjects. We found reads from human papillomaviruses (HPVs) in 95% of the subjects studied, but none were found to be high-risk genotypes that are associated with cervical and rectal cancers. We verified the presence of some HPV genotypes by quantitative PCR. Some of the HPV genotypes identified were homologous to relatively novel and uncharacterized viruses that previously have been detected on skin in association with cancerous lesions, while others may be associated with anal and genital warts. On a community level, there was no association between the membership or diversity of viral communities based on urinary tract health status. While more data are still needed, detection of HPVs as members of the human urinary virome using viral metagenomics represents a non-invasive technique that could augment current screening techniques to detect low-risk HPVs in the genitourinary tracts of humans.


Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels.
A retrospective evaluation of asymptomatic subjects with persistent elevation of serum creatine kinase (CK) levels (hyperCKemia) was made in order to verify the presence of subclinical myopathy or idiopathic hyperCKemia and to define the most appropriate diagnostic pathway. Persistently increased serum CK levels are occasionally encountered in healthy individuals. In 1980 Rowland coined for them the term idiopathic hyperCKemia. Despite the increase of scientific knowledge, several healthy subjects with hyperCKemia still represent a problem for the clinician. We made a retrospective evaluation of 114 asymptomatic or minimally symptomatic individuals with incidentally detected persistent hyperCKemia. They underwent neurological examination and laboratory/instrumental evaluation. Skeletal muscle biopsy was performed and thoroughly investigated. Biochemical and genetic investigations were added in selected cases. Logistic regression analysis was applied. We diagnosed a neuromuscular disorder in 21 patients (18.4%), and found, by muscle biopsy and/or EMG, pathological but not conclusive findings in 57 subjects (50%). The statistic correlation between elevated serum CK levels and the probability of making a diagnosis changed according to the age of the patient. Muscle biopsy is the basic tool for screening asymptomatic subjects with hyperCKemia. It allowed us to make a diagnosis of disease in 18.4% of patients, and to detect skeletal muscle abnormalities in 38.6% of the subjects. Interestingly, 31.6% of individuals had completely normal muscle findings. These best fit the "diagnosis" of idiopathic hyperCKemia.


Changes in the Nature and Severity of Invasive Pneumococcal Disease in Children Before and After the Seven-valent and Thirteen-valent Pneumococcal Conjugate Vaccine Programs in Calgary, Canada.
Since the introduction of childhood pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) incidence has decreased in children and the predominant serotypes causing disease have changed. This study describes changes in the clinical features of IPD in children (<18 years) before and after the conjugate vaccine introduction. The Calgary Area Streptococcus pneumoniae Epidemiology Research study collects information on all IPD cases in Calgary, Alberta, Canada. Descriptive and regression analyses were used to compare IPD in the pre-vaccine (January 2000 to August 2002), post-7-valent protein-polysaccharide conjugate vaccine (September 2002 to June 2010) and post-13-valent protein-polysaccharide conjugate vaccine (PCV13) (July 2010 to December 2015) periods; intensive care unit and inpatient admissions were outcome measures. The incidence of IPD in children (<18 years) decreased from an average of 17 cases/100,000/yr in 2000-2001 to 4 cases/100,000/yr in 2015. The median age of children presenting with IPD shifted from 2.0 years (interquartile range: 2.5) in the pre-vaccine period to 3.9 years (interquartile range: 6.2) in the post-PCV13 period. The proportion of children with a comorbidity that is an indication for pneumococcal vaccination did not change. Invasive disease with focus (meningitis, pneumonia, empyema, peritonitis) compared with invasive disease with bacteremia only increased from 44.6% in pre-vaccine to 64.0% and 61.4% in the post-7-valent protein-polysaccharide conjugate vaccine and post-PCV13 periods, respectively (P = 0.017). Having IPD in the post-PCV13 period compared with the pre-vaccine period was associated with an increased odds of hospitalization [Odds ratio (OR): 2.9; 95% Confidence Interval (CI): 1.4-6.2]. Clinical features of IPD have changed since pneumococcal conjugate vaccines were introduced, with a shift toward more focal infections requiring hospitalization. Although overall IPD cases have declined, disease that does occur appears to be more severe.


Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke.
Reactive astrogliosis is an essential feature of astrocytic response to all forms of central nervous system (CNS) injury and disease, which may benefit or harm surrounding neural and non-neural cells. Despite extensive study, its molecular triggers remain largely unknown in term of ischemic stroke. In the current study we investigated the role p38 mitogen-activated protein kinase (MAPK) in astrogliosis both in vitro and in vivo. In a mouse model of middle cerebral artery occlusion (MCAO), p38 MAPK activation was observed in the glia scar area, along with increased glial fibrillary acidic protein (GFAP) expression. In primary astrocyte cultures, hypoxia and scratch injury-induced astrogliosis was attenuated by both p38 inhibition and knockout of p38 MAPK. In addition, both knockout and inhibition of p38 MAPK also reduced astrocyte migration, but did not affect astrocyte proliferation. In a mouse model of permanent MCAO, no significant difference in motor function recovery and lesion volume was observed between conditional GFAP/p38 MAPK knockout mice and littermates. While a significant reduction of astrogliosis was observed in the GFAP/p38 knockout mice compared with the littermates. Our findings suggest that p38 MAPK signaling pathway plays an important role in the ischemic stroke-induced astrogliosis and thus may serve as a novel target to control glial scar formation.


Mammary cell activity and turnover in dairy cows treated with the prolactin-release inhibitor quinagolide and milked once daily.
To assess the regulation of mammary cell activity, survival, and proliferation by prolactin (PRL), 5 Holstein cows in early lactation received daily i.m. injections of 1mg of quinagolide, a suppressor of PRL release, for 9 wk, whereas 4 control cows received the vehicle (water) only. During the last week of treatment, one udder half was milked once a day (1×) and the other twice a day (2×). Mammary biopsies were harvested 1 wk before and 4 and 8 wk after the start of quinagolide treatment. The quinagolide injections reduced milk yield and resulted in lower levels of κ-casein and α-lactalbumin mRNA in the mammary biopsies at wk 4 compared with the control cows. In the mammary tissue of the quinagolide-treated cows at wk 8 of treatment, cell proliferation (as determined by proliferating cell nuclear antigen labeling) was lower and apoptosis (as determined by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) was higher than in the mammary tissue of the control cows. During differential milking, mammary epithelial cells (MEC) were extracted from the milk by centrifugation and purified by immunocytochemical binding to allow variations in the levels of mammary transcripts to be observed. After 9 wk of treatment, levels of α-lactalbumin and κ-casein mRNA were lower in the MEC isolated from milk of the quinagolide-treated cows. This effect was associated with lower PRL receptor mRNA levels and a tendency toward lower viability in the milk-isolated MEC from the 2×-milked glands. The decrease from 2× milking to 1× milking also downregulated α-lactalbumin and κ-casein transcripts in the milk-isolated MEC. Viability was higher for the MEC collected from the 1×-milked udder halves compared with the 2×-milked halves. In conclusion, the reduction in milk yield after chronic administration of the PRL-release inhibitor quinagolide is associated with a reduction in mammary cell activity, survival, and proliferation in lactating dairy cows. Reduced milking frequency was also associated with a decrease in MEC activity.


Optimizing the dose and duration of therapy for chronic hepatitis C.
Recent studies indicate that antiviral treatment with pegylated interferon alfa and ribavirin for hepatitis C can be individualized based on viral and host characteristics and the pattern of virologic response during the initial months of antiviral treatment. Patients with a low initial viral load who demonstrate a rapid virologic response to antiviral therapy may be treated with a shorter duration of therapy and are less sensitive to reduced dosing of ribavirin. Patients with delayed virologic response will require a longer duration of therapy - up to 72 weeks for patients with genotype 1 - in order to optimize chances of a sustained virologic response. Patients who were nonresponders or relapsed after an acceptable course of antiviral therapy may be retreated using a more intensive regimen and/or a longer duration of therapy. Previous nonresponders to pegylated interferon alfa and ribavirin are less likely to respond to retreatment unless they demonstrate a virologic response within the first three months of retreatment, lack advanced fibrosis, and can tolerate a more intensive and/or lengthier treatment. Individualized treatment based on viral genotype, viral load, the presence of advanced fibrosis, and initial virologic response can improve therapy for some patients and save resources in others.


Fournier's gangrene: a review of 1726 cases.
Although there is much consensus, certain controversies exist regarding the management of Fournier's gangrene. Publications in English on Fournier's gangrene from January 1950 to September 1999 were obtained through the Medline database and relevant reference lists in publications. It was possible to identify 1726 cases for study. Data extracted for review included country of reported cases, number of patients in each report and relevant clinical features. Fournier's gangrene occurs worldwide. However, its definition has generated considerable controversy as efforts are made to refine the original description in the light of increasingly understood aetiological factors. Attempts to classify the disease into primary and secondary forms have not been successful. The basic pathological process, necrotizing fasciitis, has been identified in the perineum of women and children, although the disease afflicts the male more often than the female. Most reported cases have occurred in the USA and Canada. The major sources of sepsis are the local skin, colon, anus and rectum, and the lower urinary tract. Colonic, anal and rectal sources carry the worst prognosis. Diabetes mellitus is important in aetiological terms. Rare causes include vasectomy and circumcision. Investigations are essential to define the cause of an episode but not for the diagnosis of the disease. Early aggressive treatment of Fournier's gangrene and underlying conditions is essential. Hyperbaric oxygen and honey are treatment modalities yet to be universally adopted. Risk of death, 16 per cent overall in this series, is related to the patient's condition at presentation. Controversies over the definition of Fournier's gangrene persist but these do not affect the treatment options. The diagnosis is made on clinical grounds. The occurrence of the disease in women is under-reported and may go unrecognized by some clinicians. Some treatment options, such as hyperbaric oxygenation and radical excision, remain controversial.


Decreasing Phosphatidylcholine on the Surface of the Lipid Droplet Correlates with Altered Protein Binding and Steatosis.
Alcoholic fatty liver disease (AFLD) is characterized by an abnormal accumulation of lipid droplets (LDs) in the liver. Here, we explore the composition of hepatic LDs in a rat model of AFLD. Five to seven weeks of alcohol consumption led to significant increases in hepatic triglyceride mass, along with increases in LD number and size. Additionally, hepatic LDs from rats with early alcoholic liver injury show a decreased ratio of surface phosphatidylcholine (PC) to phosphatidylethanolamine (PE). This occurred in parallel with an increase in the LD association of perilipin 2, a prominent LD protein. To determine if changes to the LD phospholipid composition contributed to differences in protein association with LDs, we constructed liposomes that modeled the LD PC:PE ratios in AFLD and control rats. Reducing the ratio of PC to PE increased the binding of perilipin 2 to liposomes in an in vitro experiment. Moreover, we decreased the ratio of LD PC:PE in NIH 3T3 and AML12 cells by culturing these cells in choline-deficient media. We again detected increased association of specific LD proteins, including perilipin 2. Taken together, our experiments suggest an important link between LD phospholipids, protein composition, and lipid accumulation.


A new on-line SPE LC-HRMS method for simultaneous analysis of selected emerging contaminants in surface waters.
In recent years emerging contaminants (ECs) have received significant attention due to their widespread detection in surface waters and concerns that these compounds can cause adverse ecological and/or human health effects. Therefore, accurate methods for determining and quantifying ECs in surface water are essential for estimating their environmental impact. This work describes the development, validation and application of a sensitive multiclass method for simultaneous determination of 22 per and polyfluorinated alkyl substances (PFASs), 3 pharmaceuticals, 15 pesticides, and 2 bisphenols in surface water using on-line solid phase extraction (SPE) coupled with ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). The method allows simultaneous sample clean-up from interfering matrices and lower limits of detection (LODs) by injecting a large sample volume into the LC system without compromising chromatographic efficiency and resolution. Linearity of response over several orders of magnitude was demonstrated for all tested compounds (R2 > 0.99), with the LODs ranging from 0.8 and 33.7 pg mL-1, allowing detection of ECs at trace levels in surface water. The method showed acceptable accuracy and precision (CV, % and RE below 20%) for all tested ECs. It also provided recoveries between 60% and 130% for all tested ECs. The validated method was successfully applied for analysis of surface water samples from three rivers (Cam, Ouse and Thames) in England. Several ECs, including perfluorooctanesulfonic acid (PFOS), perfluorobutanesulfonic acid (PFBS), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), dimethyl-metatoluamide (DEET) and ibuprofen were observed in analysed surface water above the method's limit of quantitation (LOQ), with concentrations ranging between 3.5 and 460 pg mL-1.


Sex-lethal interactions with protein and RNA. Roles of glycine-rich and RNA binding domains.
Sex-lethal (Sxl) is an RNA-binding protein, containing two conserved RNA binding domains (RBDs) and a glycine-rich region, which functions as a regulator of alternative splicing in Drosophila sex determination. Previous work demonstrated that Sxl monomers interact cooperatively upon binding to target RNAs and that the cooperativity depends on the glycine-rich N terminus. Here we use band shift experiments to show that RNA binding patterns are altered when Sxl is combined with other proteins having similar glycine-rich domains, including mammalian heterogeneous nuclear (hn) RNP L and Drosophila Hrb87F (an hnRNP A/B homolog). Direct involvement of the Sxl glycine-rich region in protein interactions was verified by Far-Western analysis. Two interaction domains, the Sxl N terminus and the Sxl first RNA binding domain, were suggested by the yeast two-hybrid assay. In a systematic examination of the RNA binding properties of Sxl domains, it was found that the Sxl termini as well as the RBDs influence RNA binding specificity. Finally, selection of the Sxl optimal binding site (SELEX) confirms the importance of U-runs in the Sxl binding site and suggests a second type of non-U-run target that may be associated with RNA secondary structure.


Aspiration and evaluation of gastric residuals in the neonatal intensive care unit: state of the science.
The routine aspiration of gastric residuals (GR) is considered standard care for critically ill infants in the neonatal intensive care unit (NICU). Unfortunately, scant information exists regarding the risks and benefits associated with this common procedure. This article provides the state of the science regarding what is known about the routine aspiration and evaluation of GRs in the NICU focusing on the following issues: (1) the use of GRs for verification of feeding tube placement, (2) GRs as an indicator of gastric contents, (3) GRs as an indicator of feeding intolerance or necrotizing enterocolitis, (4) the association between GR volume and ventilator-associated pneumonia, (5) whether GRs should be discarded or refed, (6) the definition of an abnormal GR, and (7) the potential risks associated with aspiration and evaluation of GRs. Recommendations for further research and practice guidelines are also provided.


Remediation of heavy metal contaminated soil by asymmetrical alternating current electrochemistry.
Soil contamination by heavy metals constitutes an important environmental problem, whereas field applicability of existing remediation technologies has encountered numerous obstacles, such as long operation time, high chemical cost, large energy consumption, secondary pollution, and soil degradation. Here we report the design and demonstration of a remediation method based on a concept of asymmetrical alternating current electrochemistry that achieves high degrees of contaminant removal for different heavy metals (copper, lead, cadmium) at different initial concentrations (from 100 to 10,000 ppm), all reaching corresponding regulation levels for residential scenario after rational treatment time (from 30 min to 6 h). No excessive nutrient loss in treated soil is observed and no secondary toxic product is produced. Long-term experiment and plant assay show the high sustainability of the method and its feasibility for agricultural use.


Role of free radicals in septic shock.
The available data supporting the role of oxygen radicals (OR0) as fundamental--though not unique--mediators in the pathogenesis of sepsis and septic shock are reviewed. The main questions are 1) Are there any signs of OR0 overgeneration during sepsis and septic shock? 2) Are there any indirect signs of OR0 damage during sepsis and septic shock? 3) Does OR0 inactivation affect the evolution and severity of sepsis and septic shock? 4) May the pathophysiology of sepsis and septic shock be viewed as a consequence of OR0 overgeneration? All these questions might receive affirmative answers; thus the relationships of OR0 with other mediators of sepsis and septic shock are discussed. It emerges that all the molecules which are being considered as mediators of sepsis and septic shock (cytokines, endothelins, platelet activating factor, complement) may act on granulocytes and other phagocytic cells to stimulate OR0 production. There are also very close relationships with nitric oxide, another free radical. The data in favour of an antioxidant therapy of sepsis and septic shock in humans are too few to be conclusive.


Biomimetic self-assembly of recombinant marine snail egg capsule proteins into structural coiled-coil units.
The egg capsules of the marine snails from the Melongenidea family feature unique biomechanical properties, including large reversible elasticity combined with a relatively high stiffness and outstanding strain energy absorption, making it an attractive biomimetic model system for restorative and tissue engineering applications. The capsules' building blocks are proteins called egg capsule proteins (ECPs), which we recently sequenced. ECPs are predicted to contain relatively large coiled-coil domains, which are directly responsible for the high elasticity arising from the extension of α-helical coiled-coil domains into extended β-sheet domains. In this work, de novo synthesized ECPs genes were cloned and expressed in a bacterial expression system. Following purification under denaturing conditions by strong ion-exchange chromatography, individual and paired mixtures of ECPs were self-assembled using a controlled dialysis protocol, resulting in the folding of ECPs into soluble coiled-coil units. Circular Dichroism (CD) spectroscopy of the fibrils suggested that ECPs self-assembled into heteromeric coiled-coil units. The enhancement of the α-helical coiled-coil content during pair assembly was confirmed by Fourier Transform Infrared (FTIR) spectroscopy. Transmission Electron Microscopy (TEM) imaging of covalently-fixed self-assembled units corroborated the formation of elongated intermediate filaments-like structures. Polymer statistical analysis of Atomic Force Microscopy (AFM) images of unfixed self-assembled fibrils suggested that the observed coiled-coils were made of dimeric subunits. This study establishes the key protein engineering and physicochemical parameters needed to assemble ECPs into building blocks that can be processed into biomaterials that mimic the unique biomechanical properties of marine snail egg capsules.


Adult intussusception - 14 case reports and their outcomes.
To analyze diagnostic and therapeutic options depending on the clinical symptoms, location, and lesions associated with intussusception, together with their follow-up and complications. Patients admitted to the Morales Meseguer General University Hospital (Murcia) between January 1995 and January 2009, and diagnosed with intestinal invagination. Data related to demographic and clinical features, complementary explorations, presumptive diagnosis, treatment, follow-up, and complications were collected. There were 14 patients (7 males and 7 females; mean age: 41.9 years-range: 17-77) who presented with abdominal pain. The most reliable diagnostic technique was computed tomography (8 diagnoses from 10 CT scans). A preoperative diagnosis was established in 12 cases. Invaginations were ileocolic in 8 cases (the most common), enteric in 5, and colocolic in 2 (coexistence of 2 lesions in one patient). The etiology of these intussusceptions was idiopathic or secondary to a lesion acting as the lead point for invagination. Depending on the nature of this lead point, the cause of the enteric intussusceptions was benign in 3 cases and malignant in 2. Ileocolic invaginations were divided equally (4 benign and 4 malignant), and colocolic lesions were benign (2 cases). Conservative treatment was implemented for 4 patients and surgery for 10 (7 in emergency). Five right hemicolectomies, 3 small-bowel resections, 2 left hemicolectomies, and 1 ileocecal resection were performed. Surgical complications: 3 minor and 1 major (with malignant etiology and subsequent death). The lesion disappeared after 3 days to 6 weeks in patients with conservative management. Mean follow-up was 28.25 months (range: 5-72 months). A suitable imaging technique, preferably CT, is important for the diagnosis of intussusception. Surgery is usually necessary but we favor conservative treatment in selected cases.


Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging.
The aim of the study was to evaluate the diagnostic value of the prostate-specific membrane antigen (PSMA) ligand (68)Ga-HBED-CC (PSMA PET/CT) in patients with prostate cancer and evaluate the value of early imaging of the pelvis. The files of 28 patients were retrospectively evaluated. All patients had a histopatological confirmation of prostate cancer. PSMA PET/CT images were obtained at 5 and 60 min after injection from all patients. Intense pathologic radiotracer uptake was observed in 23 patients (77%) at the site of primary tumour. Lymph node metastases were detected in 10 patients (36%) and bone metastases were detected in seven patients (25%). Bone scan (n=25) results revealed metastatic bone lesions in four patients, equivocal results in nine patients and normal results in 12 patients. PSMA PET/CT confirmed bone metastases in all four patients. Pathologic radiotracer uptake in PSMA PET/CT scans was observed only in one patient among those who had equivocal bone scans. PSMA PET/CT showed additional bone lesions in two patients who had a normal bone scan. When we compared early and late pelvic images we found no difference in the number of lesions detected. The maximum standardized uptake value (SUV(max)) for primary tumour, lymph nodes and bone metastases was significantly higher in late images. PSMA PET/CT imaging seems to be a valuable imaging modality for evaluation of primary prostate cancer and it seems to have potential for the detection of lymph node and bone metastases. Early images 5 min p.i. can help to better distinguish between urinary bladder (before tracer accumulation occurs) and tumour lesions.


Net interorgan transport of L-glutamate in rats occurs via the plasma, not via erythrocytes.
Glutamate is concentrated within RBC, but this intracellular glutamate is often ignored in studies of glutamate metabolism in vivo. The objective of this work was to determine the size of the plasma and cellular glutamate pools in rat blood and to clarify the role of RBC in the interorgan transport of glutamate. Approximately 20% of whole-blood glutamate was associated with isolated RBC membranes, but this was easily removed by washing with high salt solutions. Arterial plasma glutamate levels were relatively stable and did not show marked differences with starvation, streptozotocin diabetes or feeding 60% casein diets. In rats fed 5% casein, the plasma glutamate level was slightly higher (P < 0.05) than in most other groups. In contrast, RBC glutamate levels showed considerable variation. In rats consuming 5% casein, cellular glutamate levels were approximately 100% higher (P < 0.05) than in control, starved, diabetic or 20 or 60% casein-fed rats. Cellular glutamate levels were also higher (P < 0.05) in rats fed 60% casein than in those consuming 20% casein or the control diet. Rat erythrocytes in vitro did not take up or release free glutamate, confirming that they do not possess a glutamate transporter. Arteriovenous difference measurements across the portal drained viscera indicated a net glutamate release into the portal vein in control, 60% casein-fed and diabetic rats. In all cases, the net change in blood glutamate across the tissue occurred via the plasma, with no change in cellular glutamate levels. Therefore analyses of glutamate metabolism in rats in vivo may be made confidently using measurements of either whole-blood or plasma glutamate concentrations.


Meckel's cave access: anatomic study comparing the endoscopic transantral and endonasal approaches.
Recent advances in endonasal endoscopy have facilitated the surgical access to the lateral skull base including areas such as Meckel's cave. This approach has been well documented, however, few studies have outlined transantral specific access to Meckel's. A transantral approach provides a direct pathway to this region obviating the need for extensive endonasal and transsphenoidal resection. Our aim in this study is to compare the anatomical perspectives obtained in endonasal and transantral approaches. We prepared 14 cadaveric specimens with intravascular injections of colored latex. Eight cadavers underwent endoscopic endonasal transpterygoid approaches to Meckel's cave. Six additional specimens underwent an endoscopic transantral approach to the same region. Photographic evidence was obtained for review. 30 CT scans were analyzed to measure comparative distances to Meckel's cave for both approaches. The endoscopic approaches provided a direct access to the anterior and inferior portions of Meckel's cave. However, the transantral approach required shorter instrumentation, and did not require clearing of the endonasal corridor. This approach gave an anterior view of Meckel's cave making posterior dissection more difficult. A transantral approach to Meckel's cave provides access similar to the endonasal approach with minimal invasiveness. Some of the morbidity associated with extensive endonasal resection could possibly be avoided. Better understanding of the complex skull base anatomy, from different perspectives, helps to improve current endoscopic skull base surgery and to develop new alternatives, consequently, leading to improvements in safety and efficacy.