RRR-alpha-tocopheryl succinate inhibition of lectin-induced T cell proliferation.
The effect of RRR-alpha-tocopheryl succinate (VES) on lectin-induced chicken T cell proliferation was investigated. The T cell mitogens concanavalin A and phytohemagglutinin induce chicken thymic and splenic T cell proliferation. Addition of VES to the in vitro cultures inhibited T cell proliferation in a dose-dependent manner. Addition of VES to spleen cell cultures at different times after mitogen stimulation also suppressed T cell mitogenesis, suggesting that VES is not mediating its antiproliferative effects by interfering with ligand (mitogen)-receptor binding or early ligand-bound receptor-signaling events. Three lines of evidence suggest that the growth-inhibitory properties of VES are unique and may not involve antioxidant properties. 1) Three other forms of vitamin E, dl-alpha-tocopherol, d-alpha-tocopherol, and d-alpha-tocopherol acetate, do not inhibit the proliferation of mitogen-stimulated chicken spleen cells. 2) Spleen cells were treated with an inhibitor of nonspecific esterases to prevent the conversion of VES, which does not exhibit antioxidant properties to d-alpha-tocopherol, a lipid-soluble antioxidant. Treatment of spleen cells with the inhibitor did not affect VES's growth-inhibitory properties. 3) Trolox, a water-soluble vitamin E analogue with potent antioxidant properties and two lipid-soluble antioxidants, butylated hydroxyanisole and butylated hydroxytoluene, did not inhibit mitogen-induced T cell proliferation. Attempts to reverse VES's antiproliferative effects by addition of exogenous interleukin-2 or addition of sodium selenite, an enhancer of interleukin-2 receptors, failed. Acetylsalicylic acid had no effect on VES's inhibition of mitogen-activated T cell proliferation. These studies support the role of VES as a growth inhibitor of lectin-activated normal T cells in chickens.


Palatal flap modifications allow pedicled reconstruction of the skull base.
Defects after endoscopic expanded endonasal approaches (EEA) to the skull base, have exposed limitations of traditional reconstructive techniques. The ability to adequately reconstruct these defects has lagged behind the ability to approach/resect lesions at the skull base. The posteriorly pedicled nasoseptal flap is our primary reconstructive option; however, prior surgery or tumors can preclude its use. We focused on the branches of the internal maxillary artery, to develop novel pedicled flaps, to facilitate the reconstruction of defects encountered after skull base expanded endonasal approaches. Feasibility. We reviewed radiology images with attention to the pterygopalatine fossa and the descending palatine vessels (DPV), which supply the palate. Using cadaver dissections, we investigated the feasibility of transposing the standard mucoperiosteal palatal flap into the nasal cavity and mobilizing the DPV for pedicled skull base reconstruction. We transposed the palate mucoperiosteum into the nasal cavity through limited enlargement of a single greater palatine foramen. Our method preserves the integrity of the nasal floor mucosa, and mobilizes the DPV from the greater palatine foramen to their origin in the pterygopalatine fossa. Radiological measurements and cadevaric dissections suggest that the transposed, pedicled palatal flap (the Oliver pedicled palatal flap) could be used to reconstruct defects of the planum, sella, and clivus. Our novel modifications to the island palatal flap yield a large (12-18 cm(2)) mucoperiosteal flap based on a approximately 3 cm pedicle. The Oliver pedicled palatal flap shows potential for nasal cavity and skull base reconstruction (see video, available online only).


Fabrication of GaN truncated nanocone array using a pre-deposited metallic nano-hemispheres template for efficient solar water splitting.
The GaN truncated nanocone is an excellent candidate for better photoelectrochemical efficiency than other GaN nanostructures. Here the highly ordered GaN truncated nanocone array was fabricated using a pre-deposited metallic nano-hemispheres template on a wafer scale. The highly ordered profiles of pre-deposited metallic nano-hemispheres template were defined by anodic aluminum oxide (AAO) masks through electron beam evaporation. The formation mechanism for the profiles of nano-hemispheres and GaN truncated nanocones were investigated. The results elucidate that proper selection of AAO parameters enables controllability of desired profiles and depth of Cr nano-hemispheres template, further controllability of desired profiles and depth of the GaN truncated nanocones. The optical and photoelectrochemical characterizations show the substantial improvements in ultraviolet light absorption and photoelectrochemical efficiency with photocurrent density by 300% times with respect to planar counterpart. The presented synthetic strategy will pave the way towards low-cost and mass production of GaN truncated nanocone photoelectrode for efficient photocatalysis.


Temporary Endobronchial Stent as a Bridge to Corrective Surgery For Severe Kyphoscoliosis-associated Central-Airway Extrinsic Compression.
Kyphoscoliosis is known to compromise lung function, with the primary mechanism being reduced chest wall compliance with a resultant restrictive pulmonary physiology. Severe scoliosis can also cause extrinsic compression of the central airways, leading to recurrent respiratory infections, lobar atelectasis, and potentially acute respiratory failure. Definitive therapy is corrective surgery of the spine. However, patients with severe scoliosis are at a potentially high risk of perioperative pulmonary complications. To our knowledge, we report the first successful use of retrievable endobronchial stents as a bridge to corrective surgery for kyphoscoliosis-associated complete central-airway extrinsic compression in a patient who was considered as too high risk for surgical correction due to her respiratory status. After surgery, the stents were removed and our patient experienced sustained improvement in pulmonary function and the clinical respiratory status.


Risk factors for incidence and persistence of disability in chronic major depression and alcohol use disorders: longitudinal analyses of a population-based study.
Major depression and alcohol use disorders are risk factors for incidence of disability. However, it is still unclear whether a chronic course of these health conditions is also prospectively associated with incidence of disability. The aim of the present study was, first, to confirm whether chronic major depression (MD) and alcohol use disorders (AUD) are, respectively, risk factors for persistence and incidence of disability in the general population; and then to analyze the role of help-seeking behavior in the course of disability among respondents with chronic MD and chronic AUD. Data from two assessments in the National Epidemiologic Survey on Alcohol and Related Conditions were analyzed. Disability was measured by eight domains of the Short Form 12 Health Survey version 2 (SF-12). Generalized estimating equations and logistic regression models were run to estimate risk factors for persistence and incidence of disability, respectively. Analyses conducted on data from the US general population showed that chronic MD was the strongest risk factor for incidence and persistence of disability in the social functioning, emotional role and mental health domains. Chronic AUD were risk factors for incidence and persistence of disability in the vitality, social functioning, and emotional role domains. Within the group of chronic MD, physical comorbidity and help-seeking were associated with persistent disability in most of the SF-12 domains. Help-seeking behavior was also associated with incidence of problems in the mental health domain for the depression group. Regarding the AUD group, comorbidity with physical health problems was a strong risk factor for persistence of disability in all SF-12 domains. Help-seeking behavior was not related to either persistence or incidence of disability in the chronic alcohol group. Chronic MD and chronic AUD are independent risk factors for persistence and incidence of disability in the US general population. People with chronic MD seek help for their problems when they experience persistent disability, whereas people with chronic AUD might not seek any help even if they are suffering from persistent disability.


Aminopyrazole-based ligand induces gold nanoparticle formation and remains available for heavy metal ions sensing. A simple "mix and detect" approach.
A novel way to synthesize gold nanoparticles based on the use of N-alkylaminopyrazole is shown. This ligand has a triple functionality: induces AuNPs formation, stabilizes the formed nanoparticles, and even remains available for an external coordination with heavy metal ions. The availability of N-alkylaminopyrazole ligands onto the AuNPs surface is studied using UV-vis and NMR techniques. The mechanism of formation of AuNPs along with the synthesis optimization and characterization are studied using voltammetry and UV-vis, and the results are discussed in detail. The application of N-alkylaminopyrazole-derived gold nanoparticles in the heavy metal ions sensing is also tested showing a high sensitivity for mercury detection at low concentration level. The functionalization of metal nanoparticles with these receptors followed by heavy metal ions detection represents a simple "mix and detect" approach with interest for several other sensing applications.


Endogenous emotion generation ability is associated with the capacity to form multimodal internal representations.
Training the capacity to self-generate emotions can be a potent "vaccine" against negative stressors and be an effective intervention for affective psychopathology. However, due to a lack of knowledge about sources of individual differences in generation abilities, it is unclear how to optimally design such interventions. We investigated one potential source of variation, namely preference for using different information modalities (Visual Imagery, Auditory Imagery, Bodily Interoception, and Semantic Analysis). A representative sample of 293 participants self-induced positive and negative emotional states, freely choosing to use these modalities singly or in combination. No evidence was found for modality usage being associated with differential efficacy at generating of positive or negative emotion. Rather, usage of all modalities (except Auditory Imagery) predicted success at generation of both positive and negative emotional states. Increasing age predicted capacity to generate, especially negative, emotions. While no specific combinations of modalities were superior, the overall degree to which participants adopted multimodal implementations did predict generation efficacy. These findings inform interventions aimed at improving emotional self-generation, suggesting these must be mindful of individual differences in generation abilities and implementation tendencies, and that they should focus on enhancing the capacity to use multiple modalities.


Breath hydrogen concentrations of cats given commercial canned and extruded diets indicate gastrointestinal microbial activity vary with diet type.
Breath hydrogen (H(2)) concentration, an indicator of intestinal microbial abundance, was determined in cats given purified and commercial canned and dry-type diets. Before measurements, the cats were fed diets for more than 2 wk and habituated to a daily feeding interval of 4 hr. Breath H(2) concentrations were determined before a meal (approximately 25% daily MER) and then every 20 min for 8 hr or hourly for 10 hr. A clear rise above baseline breath H(2) concentrations, 1-2 ppm, was not observed in 6 males given a casein-based purified diet. A mean (+/- SEM) peak breath H(2) concentration of 22 +/- 4 ppm was observed in 6 other males, 6.3 hr after ingestion of a canned diet with protein, fat, and carbohydrate proportions similar to those of the purified diet. Area-under-the-curve (AUC) breath H(2) responses to the canned diet were substantially greater (p < 0.05) than responses observed in 5 males given a dry-type diet, but similar to responses observed in 12 males given an uncooked form of the canned diet. Gamma irradiation to inactivate microbes in the uncooked diet did not affect the breath H(2) response. Breath H(2) responses to 2 other canned and 2 other dry-type diets were evaluated in 8 adult females using a 4 x 4 Latin-square design. Peak and AUC responses to the canned diets were similar but approximately 2 times greater (p < 0.05) than responses to the dry diets. Relative to dry-type diets, canned diets induce a substantially greater breath H(2) production, and therefore appear to support a greater intestinal microbial population.


A new family of intrinsically disordered proteins: structural characterization of the major phasin PhaF from Pseudomonas putida KT2440.
Phasins are intracellular polyhydroxyalkanoat4e (PHA)-associated proteins involved in the stabilization of these bacterial carbon storage granules. Despite its importance in PHA metabolism and regulation, only few reports have focused so far on the structure of these proteins. In this work we have investigated the structure and stability of the PhaF phasin from Pseudomonas putida KT2440, a protein that is involved in PHA granule stabilization and distribution to daughter cells upon cell division. A structural, three-dimensional model of the protein was built from homology modeling procedures and consensus secondary structure predictions. The model predicts that PhaF is an elongated protein, with a long, amphipathic N-terminal helix with PHA binding capacity, followed by a short leucine zipper involved in protein oligomerization and a superhelical C-terminal domain wrapped around the chromosomal DNA. Hydrodynamic, spectroscopical and thermodynamic experiments validated the model and confirmed both that free PhaF is a tetramer in solution and that most part of the protein is intrinsically disordered in the absence of its ligands. The results lay a molecular basis for the explanation of the biological role of PhaF and, along with an exhaustive analysis of phasin sequence databases, suggest that intrinsic disorder and oligomerization through coiled-coils may be a widespread mechanism among these proteins.


Ethics and human rights issues experienced by nurses in leadership roles.
The aims of this study were to identify (1) the ethics and human rights issues experienced by nurses in leadership roles (NLs); (2) how frequently these issue occurred in the NLs'practices; and (3) how disturbed the NLs were by the issues. Dillman's Total Design Method (1978) for mailed surveys guided the study design. Data analysis was performed on 470 questionnaires from New England RNs in nursing leadership roles. The most frequently experienced ethics and human rights issues during the previous 12 months were (1) protecting patient right and human dignity; (2) respecting or not respecting informed consent to treatment; (3) use or nonuse of physical or chemical restraints; (4) providing care with possible risks to the RN's health; (5) following or not following advance directives; and (6) staffing patterns that limit patient access to nursing care. The most disturbing ethics and human rights issues experienced by the NLs were staffing patterns that limited patient access to nursing care, prolonging the dying process with inappropriate measures, working with unethical, incompetent, or impaired colleagues, implementing managed care policies that threaten quality of care, not considering quality of the patient's life, and caring for patients and families who are uninformed or misinformed about treatment, prognosis, or medical alternatives. Nearly 39% of the NLs reported experiencing ethics and human rights issues one to four times a week or more, and more than 90% handled their most recent ethics issue by discussing it with nursing peers. Study findings have implications for ethics education and resource support for nurses in leadership roles, and for further research on how NLs handle ethics and human rights issues in the workplace.


The painful nonruptured tendon: clinical aspects.
Tendon conditions cause a great deal of morbidity in both elite and recreational athletes, and outcome of treatment is often unsatisfactory. Evidence that the common clinical conditions (e.g., Achilles, patellar, elbow and rotator cuff tendinopathies) are due to tendinosis has been present for many years, yet the misnomer "tendinitis" is still widely used for these conditions in clinical practice. Clinical practice remains very different from evidence-based recommendations [8], but this is a common challenge in medical practice. Thus, in addition to further research in an area of medicine rife for such endeavor, there must be attention to knowledge translation--ensuring that the patient benefits from what is already known.


The clinical neurophysiology of COVID-19-direct infection, long-term sequelae and para-immunization responses: A literature review.
The COVID-19 pandemic resulting from the SARS-CoV-2 virus is in its third year. There is continuously evolving information regarding its pathophysiology and its effects on the nervous system. Clinical neurophysiology techniques are commonly employed to assess for neuroanatomical localization and/or defining the spectrum of neurological illness. There is an evolving body of literature delineating the effects of the SARS-CoV-2 virus on the nervous system as well as para-immunization responses to vaccination against this virus. This review focuses on the use of neurophysiological diagnostic modalities in the evaluation of potential acute and long-term neurological complications in patients that experience direct infection with SARS-CoV-2 and analyzes those reports of para-immunization responses to vaccination against the SARS-CoV-2 virus. The neurophysiological modalities to be discussed include electroencephalography (EEG), evoked potentials (EPs), nerve conduction studies and electromyography (EMG/NCV), autonomic function tests, transcranial magnetic stimulation (TMS) and Transcranial Doppler ultrasound (TCD).


Implant placement in fresh extraction sockets and simultaneous osteotome sinus floor elevation: a case series.
The purpose of this study was to evaluate the clinical success of implants placed in fresh extraction sockets with simultaneous maxillary sinus floor elevation using the osteotome technique. Twelve patients were included. All the patients required the extraction of a maxillary premolar--close to the maxillary sinus--and were scheduled for immediate implant placement. One experimental implant was placed per patient, with an 18-month follow-up period. The graft materials used in both sinus augmentation and peri-implant bone defects were a mixture of collagen gel and corticocancellous porcine bone particles. All implants were allowed to heal for 6 months prior to prosthetic rehabilitation. One of the 12 experimental implants failed because of an abscess during early healing. No implants failed after definitive prosthetic rehabilitation. No significant bone loss was detected at the final follow-up visit. The mean bone height before sinus elevation and implant placement was 7.8 mm. Eighteen months after surgery, the mean bone height was 12 mm. When adequately performed, the surgical procedure described in the present study--immediate implant placement and simultaneous sinus floor elevation--appears to be unproblematic and predictable in terms of clinical success.


Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct.
We tested whether severe congestive heart failure (CHF), a condition associated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting duct. CHF was induced by left coronary artery ligation. Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pressures (LVEDP): 26.9 +/- 3.4 vs. 4.1 +/- 0.3 mmHg, and reduced plasma sodium concentrations (142.2 +/- 1. 6 vs. 149.1 +/- 1.1 mEq/liter). Quantitative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 +/- 53%, n = 12) relative to sham-operated controls (100 +/- 13%, n = 14). In contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective. Furthermore, postinfarction animals without LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 +/- 28% of sham levels, n = 6). Immunocytochemistry and immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellular vesicles in collecting duct cells from rats with severe CHF, consistent with enhanced trafficking of AQP2 to the apical plasma membrane. The selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retention and hyponatremia in severe CHF.


Occupational health challenges and success in developing countries: a South African perspective.
Implementation of occupational health and safety practices in South Africa is impeded not only by lack of funds, expertise, and technologic sophistication but also by worker apathy and employer ignorance, such that there is no pressure on government even to enforce existing regulations. The author explores the reasons for the problem, describes sporadic successes that have been achieved, and offers practical suggestions for improvement.


New opportunities and emerging themes of research in microwave spectroscopy.
It is easy to set a frisbee spinning but hard to flip a javelin end-over-end. The properties of a rotating body are determined by its moment of inertia. Changes in the energy associated with the rotation of a single molecule are incremental, or quantized, in contrast with the everyday examples of the frisbee and the javelin. Only photons with energies that correspond to specific discrete frequencies of electromagnetic radiation can be absorbed or emitted to cause transitions between different rotational energy levels. Photons that cause rotational transitions generally have microwave or millimetre-wave frequencies. Microwave spectroscopy thus provides a basis for exploring molecular structure through studies of molecular rotation. The first experiments involving microwave spectroscopy exploited technology developed for radio detection and ranging during the Second World War. Microwave spectroscopy is now being applied to study chemical reactions significant in atmospheric chemistry and to probe superfluidity in Hen clusters. This article reviews the research themes that were the focus of the past 50 years and surveys new opportunities.


[Caspase 3 activation and apoptosis inducing factor translocation in noise exposure induced out hair cells apoptosis].
To investigate the pathway and mechanism of noise exposure induced out hair cells (OHC) apoptosis. The cochleae of control and noise exposure group were dissected. The activity of caspase 3, an important mediator of apoptosis, in OHC, was examined with carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors. The apoptosis inducing factor (AIF) translocation from mitochondria in OHC were further examined by immunohistology method. The nuclei were labeled with PI and the mitochondrion was labeled with Mito-tracker. Whole mount organ of Corti was prepared. Morphological and fluorescent change was observed use confocal microscope. In the normal OHC, AIF is distributed where the mitochondria were located and no activated caspase 3 was observed. After the animals exposed to broadband noise at 122 dB in 4 h/day for 2 days, both apoptosis and necrosis were appeared in OHC. AIF translocated from mitochondrion to nuclei in apoptotic and necrotic OHC following noise exposure. The noise exposure triggered activation of caspase 3 in apoptic hair cells. But no caspase 3 activation appeared in necrotic OHC. These findings indicated that the caspase-dependent pathway is an important pathway in noise exposure induced apoptosis. And AIF also involves OHC death pathway following noise exposure.


CT diagnosis of actinomycosis of the neck.
Actinomycosis is an unusual bacterial infection that most often affects the head and neck region. Abscesses occasionally associated with a draining sinus may result secondary to extensive tissue destruction. We report the CT appearance in a case of actinomycosis of the neck. A thick walled enhancing mass with a low attenuation center was identified between the sternocleidomastoid muscle and the strap muscles of the neck. Enhancement of the adjacent muscles was present. Surgery confirmed an abscess with inflammation of the adjacent muscle. Histologic examination of the specimen showed the presence of multiple yellow (sulfur) granules containing Actinomyces. Computed tomography correctly determined the extent of the mass and lack of involvement of the deep structures of the neck.


A rapid method for detection of putative RNAi target genes in genomic data.
RNAi, inhibition of gene expression by double stranded RNA molecules, has rapidly become a powerful laboratory technique to study gene function. The effectiveness of the procedure raised the question of whether this laboratory technique may actually mimic a natural cellular control mechanism that works on similar principles. Indeed recent evidence is accumulating to suggest that RNAi is a natural control mechanism that might even serve as a primitive immune response against RNA viruses and retroposons. Three different interference scenarios seem to be utilized by various RNAi mechanisms. One of the mechanisms involves degradation of mRNA molecules. Here we suggest a method to systematically scan entire genomes simultaneously for RNAi elements and the presence of cellular genes that are degraded by these RNAi elements via exact short base-pair matching. The method is based on scanning the genomes using a suffix tree data structure that was specifically modified to identify sets of combinations of repeated and inverted repeated sequences of 20 bp or more. Initial scan suggest that a large number, about 7% of C.elegans and 3% of C.briggsae genes, have the potential to be subject to natural RNAi control. Two methods are proposed to further analyze these genes to select the cases that are more likely to be actual cases of RNAi control. One method involves looking for ESTs that can provide direct evidence that RNAi control element are indeed expressed. The other method looks for synteny between C.elegans and C.briggsae assuming that genes that might be under RNAi control in both organisms are more likely to be biological significant. Taken together, supportive evidence was found for about 70 genes to be under RNAi control. Among these genes are: transposase, hormone receptors, homeobox proteins, defensin, actins, and several types of collagens. While our method is not capable of detecting all cases of natural RNAi control, it points to a large number of potential cases that can be further verified by experimental work.


Using mathematical models to describe aerial dispersal and silk ball formation of peanut red spider mite, Tetranychus ogmophallos (Acari: Tetranychidae).
Peanut red spider mite, Tetranychus ogmophallos, exhibits a peculiar dispersal behavior using silk balls, which involves clustering of mites and spinning of webs at the top of plants. Such a dispersal mechanism has not been studied for this species yet. Therefore, this study aimed at using mathematical models to describe aerial dispersal and silk ball formation of peanut red spider mite on peanut plants. The influence of wind speed, generated by a wind tunnel, on the dispersal of mites was studied in two experiments, one with 500 mites per plant and one with 1000 mites per plant, and six wind speeds (5, 10, 15, 20, 25, and 30 km h-1) for each mite density. The proportion of displaced mites and the distance they were blown were measured. Another series of experiments considered the formation of silk balls to assess how fast balls were formed as a function of time and the number of mites present on a peanut plant. Data from the wind tunnel experiments were analyzed by logistic regression and multiple regression to assess the proportion of displaced mites and the distance moved, respectively, as functions of wind speed and the initial density of mites on the donor plant. The distribution of dispersal distances from the donor plant was fitted by a mathematical model proposed by Ricker (J Fish Res Board Can 11:559-623, 1954). The number of mites moving upwards on a plant to be involved in silk ball formation was modeled as a function of time based on the initial number of spider mites and their estimated birth, death and movement rates per capita. Logistic regression was used to analyze the presence of balls as a function of time elapsed since a plant was infested with spider mites. Finally, non-linear regression was applied to link ball size to the total number of mites occupying the ball. The data analyses revealed that wind speed had a significant positive effect on take-off probability and distance moved by individual mites, whereas mite density had little influence. Ricker's model adequately described the distribution of dispersal distances. The models describing silk ball formation also described data very well. Ball size was found to increase almost linearly with the number of mites found in the ball. We expect that the knowledge provided by the present study will help to develop efficient management strategies against T. ogmophallos in peanut crops as dispersal seems to be a key factor in the species' capability to become a serious pest.


Post-Flood Rapid Needs Assessment in Srinagar City, Jammu and Kashmir State, India, September, 2014.
Torrential rainfall and flooding from September 2-6, 2014 submerged >350 villages in Jammu and Kashmir state. We conducted rapid needs assessment in capital Srinagar from 27 September to 1 October to assess population health and safety needs. Based on Community Assessment for Public Health Emergency Response (CASPER) methodology, we selected 7 households each from 30 census blocks using 2-stage cluster sampling. We collected information on demographics, needs, and illnesses using structured questionnaire. Of the 210 households surveyed, an estimated 57% (CI: 41%-73%) reported significant damage, 50% (CI: 36%-63%) were evacuated, and 16% (CI: 10%-22%) reported injuries. Households lacked electricity (22%; CI: 8.8%-36%), tap water (13%; CI: 5%-21%), working toilets (11%; CI: 4%-19%), and adequate food supply (14%; CI: 8%-20%). Moreover, 55% (CI: 45%-64%) of households reported cough, cold, fever, rashes, or diarrhea; 68% (CI: 59%-77%) experienced agitation, anxiety, depression, or nightmares since the flooding. Of the households with a member on medicines for non-communicable diseases, 40% did not have a week's supply. Restoring basic essentials (30%; CI: 22%-37%) and repairing houses (30%; CI: 19%-40%) were the most urgent needs expressed. Floods damaged >1/2 of households in Srinagar, disrupting basic essentials, and causing mental trauma. These findings helped authorities prioritize assistance with psychological symptoms and availability of prescription medicines. (Disaster Med Public Health Preparedness. 2019;13:133-137).


Innate immune recognition of lipopolysaccharide by endothelial cells.
The endothelium is an active component of the innate immune response to bacterial invasion. Endothelial cells comprise mechanisms to recognize structural patterns expressed by pathogens and subsequently initiate the transcription of inflammatory genes. The purpose of this article is to summarize the molecular processes that underlie the endothelial innate immune response to microbial components, with a particular focus on responses to Gram-negative bacterial lipopolysaccharide. Personal observations and review of the literature as revealed by the National Library of Medicine. Endothelial cells recognize the presence of microbial components such as lipopolysaccharide via a receptor complex that contains at least three important cell surface components: CD14, Toll-like receptor-4, and MD-2. CD14 and MD-2 exist as soluble receptor components and are thought to bind to both lipopolysaccharide and Toll-like receptor-4, whereas Toll-like receptor-4 itself is the transmembrane signal transducer. Single-point mutations in MD-2 or the cytoplasmic portion of Toll-like receptor-4 abrogate the response to lipopolysaccharide. The composition of this receptor and the recruitment and activation of various cytoplasmic proteins afford at least five levels of ligand specificity and suggest that there are at least as many potential therapeutic targets for Toll-like receptor-mediated inflammatory states, including sepsis.


Caring for frail older people in the last phase of life - the general practitioners' view.
Frail older people are an increasingly important group in primary care due to demographic change. For these patients, a palliative care approach may be useful to sustain the quality of life in the last phase of their lives. While general practitioners (GPs) play a key role in the primary care for older patients, general palliative care is still in its infancy and little is known in Germany about caring for frail older people towards the end of life. This study aims to explore the tasks and challenges regarding the care for frail older patients in the last phase of life from the GPs' point of view, and the latter's perception of their own role and responsibilities. Explorative qualitative study based on semi-structured in-depth interviews with 14 GPs from urban and rural regions in Lower Saxony, Germany. Analysis was carried out according to the principles of Grounded Theory. The GPs' key commitment "caring for frail older patients until the end" as an integral part of primary care was worked out as a key category, flanked by central issues: "causal conditions and challenges," which include patients' preconditions and care needs as well as communication and cooperation aspects on the carers' level. "Barriers and facilitators within the health system" refers to prerequisites of the German healthcare system, such as high caseloads. Regarding "strategies to comply with this commitment", various self-developed strategies for the care of frail older people are presented, depending on the GPs' understanding of their professional role and individual circumstances. The GPs show a strong commitment to caring for the frail older patients until the end of life. However, it is a challenging and complex task that requires significant time, which can take GPs to their limits. There is a great need to improve patient-and family-centered proactive communication, as well as interprofessional cooperation. Strengthening the team approach in primary care could relieve the burden on GPs, especially in rural areas, while simultaneously improving end-of-life care for their patients.


Effects of study methodology on adverse outcome occurrence and mortality.
To assess the impact of variables related to setting, study design and definition on adverse outcome occurrence and mortality in hospitalized patients. Pubmed and Embase. Articles in English from 1980 onwards, in non-selected patients or surgical patients only. Data were extracted independently by two authors using a predefined form. Included study methodology variables were general variables such as setting, patient variables like age, study variables like number of reviewers and definition and the resulting adverse outcome occurrence and mortality. Eleven studies reporting on 76 617 non-selected patients and 18 studies representing 136 292 surgical patients were included. Adverse outcomes were estimated to occur in 16% (12-19%) of non-selected patients and in 18% (14-22%) of surgical patients, taking into account the heterogeneity between studies. The study methodology variables were not statistically significant in explaining variation in adverse outcome occurrence, but the individual studies, when used as a random effect variable, were significant. Conversely, the study variable was not significant to explain variation in mortality rates, whereas the study methodology variables were: having more than one reviewer increased mortality by 30-80%, older study populations resulted in higher mortality and including a cause in the definition halved the mortality rate. Study methodology variables do not explain differences in adverse outcome occurrence between studies. Other inter-study differences are more important. However, study methodology is an important predictor for mortality differences and should be taken into account when interpreting differences between studies.


Identification and isolation of a major cell surface glycoprotein of Pneumocystis carinii.
Radioiodination of rat-derived Pneumocystis carinii obtained from an in vitro culture demonstrated the presence of a major surface glycoprotein (gp120). The glycoprotein was of the high mannose type. It exhibited adherence properties similar to those observed in the intact organism. Under nonreducing conditions, it existed as an aggregate with a molecular weight in excess of 2 x 10(6). Surface aggregating behavior and adherent quality prevented isolation of the glycoprotein by conventional methods. The glycoprotein was purified by chromatography on hydroxyapatite in the presence of sodium dodecyl sulfate under reducing conditions.


An Unexpected Diagnosis of Second Primary Malignancy in a Breast Cancer Survivor: A Case Report.
Breast cancer survival rates are increasing more than ever with the development of better diagnostic and therapeutic techniques. Survivors of breast cancer have an increased risk of developing second primary malignancies, which may be mistaken for breast cancer recurrence and lead to delayed diagnosis and poor prognosis. We report a case of a 62-year-old female who presented with shortness of breath and bone pain. She had a history of left triple-positive invasive ductal carcinoma (T1N0M0) treated with bilateral skin-sparing mastectomy, adjuvant Taxotere, and trastuzumab-based therapy and then continued on trastuzumab and letrozole. She underwent imaging to explore the source of her symptoms at which new pulmonary nodules were discovered. During workup, she was found to have elevated tumor markers. They were initially suspected to be breast cancer recurrence metastases based on elevated tumor markers; however, further investigations confirmed that the nodules were a second primary lung adenocarcinoma with a different molecular profile. The patient had disease progression despite chemotherapy and eventually succumbed to her disease. This case highlights the importance of considering second primary malignancies in breast cancer survivors and utilizing advanced diagnostic modalities to efficiently diagnose such cases.


Prediction of Posterior-to-Anterior Corneal Curvature Radii Ratio in Myopic Patients after LASIK, SMILE, and PRK Using Multivariate Regression Analysis.
The ratio of posterior-to-anterior curvature radii of the cornea (P/A ratio) is an important element in determining corneal refractive power. P/A ratio has been well studied in patients prior to undergoing refractive surgery, but its postoperative value remains less so. We aimed to examine the value of preoperative characteristics of refractive surgery patients in predicting the 1-year postoperative P/A ratio in LASIK, PRK, and SMILE using both linear and multivariate regression analyses. This was a retrospective study that included patients with manifest refraction spherical equivalents (MRSE) from -7.71D to -0.25D. In total, 164 eyes underwent LASIK, 183 underwent PRK, and 46 underwent SMILE. All patients had preoperative and 1-year postoperative front sagittal and back sagittal keratometry measurements at 4, 5, and 6 mm around the corneal vertex. Postoperative P/A after LASIK, PRK, and SMILE was found to be significantly correlated with MRSE and preoperative P/A. Stepwise variable selection in multivariate regression revealed that spherical equivalent was the most significant predictor of postoperative P/A. When coupled with other preoperative characteristics, including P/A, age, asphericity, and keratometry, the multivariate regressions were able to produce models with high predictive value in LASIK (adjusted R2: 0.957), PRK (adjusted R2: 0.934), and SMILE (adjusted R2: 0.894).


Treatment expectations for cognitive-behavioral therapy and light therapy for seasonal affective disorder: Change across treatment and relation to outcome.
To examine the dynamic relationship between treatment expectations and treatment outcome over the course of a clinical trial for winter seasonal affective disorder (SAD). Currently depressed adults with Major Depression, Recurrent with Seasonal Pattern (N = 177) were randomized to 6 weeks of group-delivered cognitive-behavioral therapy for SAD (CBT-SAD) or light therapy (LT). The majority were female (83.6%) and white (92.1%), with a mean age of 45.6 years. Treatment expectations for CBT-SAD and LT were assessed using a modification of the Treatment Expectancy and Credibility Survey (Borkovec & Nau, 1972). Depression severity was assessed using the Beck Depression Inventory-Second Edition (Beck, Steer, & Brown, 1996). All measures were administered at pretreatment, midtreatment, and posttreatment. As treatment progressed, expectations for the treatment received increased across time steeply in CBT-SAD patients and moderately in LT patients. Collapsing across time, patients with higher treatment expectations had lower depression severity than those with lower treatment expectations. In a cross-lagged panel path analysis, there was a significant effect of treatment expectations at midtreatment on depression severity at posttreatment among CBT-SAD patients. Treatment expectations changed across treatment, affected outcome, and should be assessed and monitored repeatedly throughout treatment. Findings suggest that treatment expectations at midtreatment are a mechanism by which CBT-SAD reduces depression, which should be replicated in SAD samples and examined for generalizability to nonseasonal depression. These findings underscore the importance of further research examining treatment expectations in mediating CBT's effects in depression and other types of psychopathology. (PsycINFO Database Record


The tragedy of the commodity and the farce of AquAdvantage Salmon.
The US Food and Drug Administration is expected to approve AquAdvantage Salmon as the first genetically modified animal for human consumption. The genetic modifications allow the proprietary fish to grow at a rate twice as fast as a wild salmon, leading to greater 'efficiency' in terms of reduced costs and reduced time to market. This article provides an analysis of the ways in which AquAdvantage Salmon exemplifies capitalist market forces controlling and guiding the terms of salmon recovery and conservation. The authors trace historical developments within the salmon industry to demonstrate how capitalist commodity production has impacted fishing communities. They reject the oft-cited 'tragedy of the commons' hypothesis offered to explain fisheries crises. In its place, they offer the conceptual framework of the 'tragedy of the commodity' to explore how capitalist market forces and complicit state regulations amplify rather than resolve global environmental problems.


Stressed or stressed out: what is the difference?
The term "allostasis" has been coined to clarify ambiguities associated with the word "stress". Allostasis refers to the adaptive processes that maintain homeostasis through the production of mediators such as adrenalin, cortisol and other chemical messengers. These mediators of the stress response promote adaptation in the aftermath of acute stress, but they also contribute to allostatic overload, the wear and tear on the body and brain that result from being "stressed out". This conceptual framework has created a need to know how to improve the efficiency of the adaptive response to stressors while minimizing overactivity of the same systems, since such overactivity results in many of the common diseases of modern life. This framework has also helped to demystify the biology of stress by emphasizing the protective as well as the damaging effects of the body's attempts to cope with the challenges known as stressors.


N-(7-Eth-oxy-1H-indazol-4-yl)-4-methyl-benzene-sulfonamide.
The mol-ecule of the title heterocyclic compound, C(16)H(17)N(3)O(3)S, is bent at the S atom with an C-SO(2)-NH-C torsion angle of 80.17 (8)°. The phenyl substituent at the S atom is rotated out of the plane of the 1H-indazole ring [inter-planar angle = 46.24 (8)°]. In the crystal, inter-molecular N-H⋯N and N-H⋯O hydrogen bonds build up a ribbon developing parallel to the b-axis direction. C-H⋯O hydrogen bonds link these ribbons, forming a layer parallel to the bc plane.


Comprehending Conceptual Anaphors.
English pronouns must agree with their antecedents in number. But in some situations, pronouns violate this constraint, as in "I think I'll order a frozen margarita. I just love them." Three situations are identified in which such violations occur: (1) Plural (and technically illegal) pronouns are used to refer to frequently or multiply occurring items or events (as opposed to a unique item/event); (2) plural pronouns are used to refer to generic types (as opposed to a specific token); and (3) plural pronouns are used to refer to animate members of a collective set (as opposed to an individual member of a set). When sentences contained illegal, plural pronouns that referred to multiple items/events, generic types or collective sets, they were rated more natural (Experiment 1) and comprehended more rapidly (Experiment 2) than when the same sentences contained legal, singular pronouns. But when the sentences contained legal, singular pronouns and referred to unique items/events, specific tokens or individual members of a set, they were rated more natural and comprehended more rapidly. The results underscore the role that pragmatic information - perhaps in the form of mental models - plays in the on-line interpretation of conceptual anaphors, such as pro-nouns.


Designing an Algorithm for Cancerous Tissue Segmentation Using Adaptive K-means Cluttering and Discrete Wavelet Transform.
Breast cancer is currently one of the leading causes of death among women worldwide. The diagnosis and separation of cancerous tumors in mammographic images require accuracy, experience and time, and it has always posed itself as a major challenge to the radiologists and physicians. This paper proposes a new algorithm which draws on discrete wavelet transform and adaptive K-means techniques to transmute the medical images implement the tumor estimation and detect breast cancer tumors in mammograms in early stages. It also allows the rapid processing of the input data. In the first step, after designing a filter, the discrete wavelet transform is applied to the input images and the approximate coefficients of scaling components are constructed. Then, the different parts of image are classified in continuous spectrum. In the next step, by using adaptive K-means algorithm for initializing and smart choice of clusters' number, the appropriate threshold is selected. Finally, the suspicious cancerous mass is separated by implementing the image processing techniques. We Received 120 mammographic images in LJPEG format, which had been scanned in Gray-Scale with 50 microns size, 3% noise and 20% INU from clinical data taken from two medical databases (mini-MIAS and DDSM). The proposed algorithm detected tumors at an acceptable level with an average accuracy of 92.32% and sensitivity of 90.24%. Also, the Kappa coefficient was approximately 0.85, which proved the suitable reliability of the system performance. The exact positioning of the cancerous tumors allows the radiologist to determine the stage of disease progression and suggest an appropriate treatment in accordance with the tumor growth. The low PPV and high NPV of the system is a warranty of the system and both clinical specialists and patients can trust its output.


[Relation between the clinical course of Vogt-Koyanagi-Harada's disease and human leukocyte antigen (HLA)-DR4 subtypes].
Vogt-Koyanagi-Harada's disease (VKH) is an autoimmune disorder affecting melanocyte-containing tissues. VKH is strongly related to human leukocyte antigen (HLA)-DR4, a heterogeneous HLA specificity consisting of at least 12 different genotypes. The disease has two types: prolonged and non-prolonged, depending upon the clinical course. Fifty-four Japanese patients comprising 27 with the prolonged type, 15 with the non-prolonged type, and 12 new cases of VKH were included in this study. Ninety-three percent of the patients with all types had HLA-DR4. All 27 patients with the prolonged type had either the DRB1*0405 or *0410 genotype, and the non-prolonged type included two DR4-negative and four DRB1*0405 and *0410 negative patients. Our results indicate that the clinical course of VKH is determined partly by the patient's HLA genotype.


Observational evidence that urbanisation and neighbourhood deprivation are associated with escalation in chronic pharmacological pain treatment: a longitudinal population-based study in the Netherlands.
To examine, in the light of the association between urban environment and poor mental health, whether urbanisation and neighbourhood deprivation are associated with analgesic escalation in chronic pharmacological pain treatment and whether escalation is associated with prescriptions of psychotropic medication. Longitudinal analysis of a population-based routine dispensing database in the Netherlands. Representative sample of pharmacies, covering 73% of the Dutch nationwide medication consumption in the primary care and hospital outpatient settings. 449 410 patients aged 15-85 years were included, of whom 166 374 were in the Starter group and 283 036 in the Continuation group of chronic analgesic treatment. Escalation of analgesics (ie, change to a higher level of analgesic potency, classified across five levels) in association with urbanisation (five levels) and dichotomous neighbourhood deprivation was analysed over a 6-month observation period. Ordered logistic multivariate model evaluating analgesic treatment. In both Starter and Continuation groups, escalation was positively associated with urbanisation in a dose-response fashion (Starter group: OR (urbanisation level 1 compared with level 5): 1.24, 95% CI 1.18 to 1.30; Continuation group: OR 1.18, 95% CI 1.14 to 1.23). An additional association was apparent with neighbourhood deprivation (Starter group: OR 1.07, 95% CI 1.02 to 1.11; Continuation group: OR 1.04, 95% CI 1.01 to 1.08). Use of somatic and particularly psychotropic co-medication was associated with escalation in both groups. Escalation of chronic analgesic treatment is associated with urban and deprived environments and occurs in a context of adding psychotropic medication prescriptions. These findings suggest that pain outcomes and mental health outcomes share factors that increase risk and remedy suffering.


[The health and will of the patient--applied to extended surgical procedures].
Austria is also becoming increasingly aware of the problems involved in the giving of information to the patient by the doctor. In individual cases, the patient seeks to enforce claims on the basis of having been inadequately informed. The principle that the extent of the information must, in the first place, take into consideration the patient's wellbeing and only in second place the patient's right to self-determination is generally valid, in particular with respect to ad hoc decisions taken during an operation. Notwithstanding, especially during operations conflict situations arise whenever the duty to give medical aid in the genuine interest of the patient and the patient's right to self-determination have to be weighed up against each other. General medico-legal principles and relevant jurisdiction with provide support for the doctor in these difficult decisions.


Voices of children and adolescents on phase 1 or phase 2 cancer trials: A new trial endpoint?
Pediatric participants on phase 1 or phase 2 clinical trials for incurable cancer are at risk of experiencing toxicities (adverse events [AEs]) related to trial participation. Multiple AEs are subjective; thus, the real impact of trial treatment cannot be known unless patient subjective reports are solicited. The authors assessed the feasibility and acceptability of soliciting symptom, function, and quality of life (QOL) reports from participants aged 8 to 18 years who were enrolled on phase 1/2 clinical trials at 4 cancer centers during the first course of chemotherapy. The authors also assessed the reliability and validity of 6 self-report Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric measures and 4 open-ended interview questions at 2 time points (at the time of trial enrollment [T1] and 3 to 4 weeks later [T2]). The enrollment rate of 75.9% (20 participants) exceeded the feasibility criterion, and missingness of measures by person, measure, and items at T1 and T2 were lower than the acceptability criteria. New QOL themes were limited to the impact of treatment on families and being away from home, family, and friends for treatment. All but one measure at T1 met the reliability criterion and all measures did so at T2. Validity support was limited however because as theorized, mobility decreased and fatigue increased as AEs increased. Soliciting and documenting symptom, function, and QOL reports from patients aged 8 to 18 years who are enrolled on a phase 1/2 clinical trial is feasible and acceptable to participants, particularly when embedded in trials. Reliable and valid findings can result, making patient self-reported outcomes a possible new trial endpoint. Cancer 2017;123:3799-3806. © 2017 American Cancer Society.


The postcranial anatomy of the saurolophine hadrosaurid Laiyangosaurus youngi from the upper cretaceous of Laiyang, Shandong, China.
Laiyangosaurus youngi was erected as a saurolophine hadrosaurid on the basis of several cranial elements from the Jingangkou Formation, Wangshi Group, Upper Cretaceous of Laiyang, Shandong, China. The postcranial elements of this taxon are described in detail here, providing additional postcranial characteristics to L. youngi. The phylogenetic analysis included postcranial elements of L. youngi, indicating that L. youngi still lies in the Edmontosaurini clade and no more supplement of postcranial autapomorphy. However, three new postcranial autapomorphies can help distinguish L. youngi from other members of Edmontosaurini: a poorly expanded deltopectoral crest of the humerus, a brevis shelf at the base of the postacetabular process of the ilium, and a well-defined medioventral ridge on the medial side of the postacetabular process. This study is to increase our knowledge on the anatomy and phylogeny of hadrosaurids of Edmontosaurini and provide new valuable evidence for discussing on the taxonomic position and validity of hadrosauroids in the Laiyang Hadrosauroid Fauna.


Localization of the fast skeletal muscle troponin I gene (TNNI2) to 11p15.5: genes for troponin I and T are organized in pairs.
We have localized the gene encoding the fast skeletal muscle isoform of troponin I (TNNI2) to 11p15.5 by PCR-based analysis of somatic cell hybrid panels: based on the Genebridge4 radiation hybrid panel, TNNI2 is coincident with the marker D11S922. The gene encoding the fast skeletal muscle troponin T gene (TNNT3) has been previously assigned to 11p15.5 suggesting that TNNI2 and TNNT3 may be closely linked. The overall location of genes encoding troponin I and T isoforms now reveals that they are organized at three loci each containing a troponin I/troponin T gene pair. This organization contrasts with all other sarcomeric protein genes and has implications for the evolution of these two gene families, for their regulation and for the analysis of mutations suspected to result in cardiomyopathy.


Active sites of stoichiometric cerium oxide cations (CemO2m+) probed by reactions with carbon monoxide and small hydrocarbon molecules.
Cerium oxide cluster cations (Ce(m)O(n)(+), m = 2-16; n = 2m, 2m +/- 1 and 2m +/- 2) are prepared by laser ablation and reacted with carbon monoxide (CO) and small hydrocarbon molecules (CH(4), C(2)H(4), and C(2)H(6)) in a fast flow reactor. A time of flight mass spectrometer is used to detect the cluster distribution before and after the reactions. The observation of oxygen reduction and hydrogen pickup of Ce(m)O(2m)(+) clusters strongly suggests the following reactions: (1) Ce(m)O(2m)(+) + C(2)H(4) --> Ce(m)O(2m-1)(+) + C(2)H(4)O (m = 2-6); (2) Ce(m)O(2m)(+) + CO --> Ce(m)O(2m-1)(+) + CO(2) (m = 4-6); and (3) Ce(m)O(2m)(+) + CH(4)/C(2)H(6) --> Ce(m)O(2m)H(+) + CH(3)/C(2)H(5) (m = 2-4). Density functional theory (DFT) calculations are performed to study reaction mechanisms of Ce(2)O(4)(+) + X (X = CO, CH(4), C(2)H(4), and C(2)H(6)). The calculated results are in good agreement with the experimental observations. The structural and bonding properties of Ce(m)O(2m)(+) (m = 2-5) clusters are also investigated by the DFT calculations. The unpaired electron in each of the clusters is mainly distributed over one Ce atom (4f and 5p orbitals) and two O atoms (2p orbital) in a CeO(2) moiety, which can be considered as the active site in the cluster. To further understand the nature of the active sites in Ce(m)O(2m)(+) clusters, the fast flow reaction experiments are also carried out on zirconium oxide clusters Zr(m)O(n)(+), because both Zr ([Kr]4d(2)5s(2)) and Ce ([Xe]4f(1)5d(1)6s(2)) have the same number of valence electrons while the latter has one more f and one less d electrons. In addition to the oxygen transfer reactions such as Zr(m)O(2m)(+) + C(2)H(4) --> Zr(m)O(2m-1)(+) + C(2)H(4)O (m = 1-4) reported in the literature, hydrogen abstraction reactions Zr(m)O(2m)(+) + CH(4)/C(2)H(6) --> Zr(m)O(2m)H(+) + CH(3)/C(2)H(5) are also identified. The rate constants of CO oxidation as well as hydrogen abstraction by Ce(m)O(2m)(+) and Zr(m)O(2m)(+) are very different. The reactivity and selectivity of Ce(m)O(2m)(+) versus Zr(m)O(2m)(+) can be well rationalized based on the DFT calculations. The oxygen transfer and hydrogen abstraction reactions studied in this work are of widespread importance. The nature of the active sites of Ce(m)O(2m)(+) clusters is unique and may be considered in the use and design of cerium oxide based catalysts.


Study of self-organized CdS Q-dots.
Self-organized cadmium sulfide quantum dots assembled using wet synthesis route on glass/ITO as well as Si(100) substrates have been investigated, using X-ray diffraction and transmission electron microscopy. The quantum dots have been shown to grow with a strong (111) orientation with narrow size distribution. Self-organized growth of the quantum dots was examined by high resolution imaging with an atomic force microscope. It is shown that increased self-organization is obtained on silicon substrate. The role of surfactant in imparting self-organization has been invoked to explain the observed morphological features. The as grown Q-dots exhibited size dependent blue shift in the absorption edge. The luminescence behavior of the quantum dots self-organized on glass/ITO as well as Si(100) substrate has also been examined. It is shown that substantial enhancement in luminescence yield is obtained for quantum dots grown on silicon substrate. A model to explain the observed luminescence enhancement has also been presented.


Prediction of proteasome cleavage motifs by neural networks.
We present a predictive method that can simulate an essential step in the antigen presentation in higher vertebrates, namely the step involving the proteasomal degradation of polypeptides into fragments which have the potential to bind to MHC Class I molecules. Proteasomal cleavage prediction algorithms published so far were trained on data from in vitro digestion experiments with constitutive proteasomes. As a result, they did not take into account the characteristics of the structurally modified proteasomes--often called immunoproteasomes--found in cells stimulated by gamma-interferon under physiological conditions. Our algorithm has been trained not only on in vitro data, but also on MHC Class I ligand data, which reflect a combination of immunoproteasome and constitutive proteasome specificity. This feature, together with the use of neural networks, a non-linear classification technique, make the prediction of MHC Class I ligand boundaries more accurate: 65% of the cleavage sites and 85% of the non-cleavage sites are correctly determined. Moreover, we show that the neural networks trained on the constitutive proteasome data learns a specificity that differs from that of the networks trained on MHC Class I ligands, i.e. the specificity of the immunoproteasome is different than the constitutive proteasome. The tools developed in this study in combination with a predictor of MHC and TAP binding capacity should give a more complete prediction of the generation and presentation of peptides on MHC Class I molecules. Here we demonstrate that such an approach produces an accurate prediction of the CTL the epitopes in HIV Nef. The method is available at www.cbs.dtu.dk/services/NetChop/.


Effect of Functional Scapular Stabilization Training on Function and Pain in Frozen Shoulder Syndrome: A Randomized Controlled Trial.
The purpose of this study was to determine the effect of functional scapular stabilization training compared with the standard physical therapy on function and pain in people with frozen shoulder syndrome (FSS). In a single-blind randomized controlled trial, 86 people with FSS were randomly allocated into the intervention group (functional stabilization training [n = 43]) and control group (standard physical therapy [n = 43]) using block randomization for 12 weeks. The primary outcome measures were the Shoulder Pain and Disability Index and the numeric pain rating scale. The secondary outcome measures were range of motion (ROM), range of passive abduction, and coracoid pain test. All the outcome measures were carried out by an independent blind outcome assessor at baseline and at the end of 12 weeks. A significant group × time interaction effect was observed for the Shoulder Pain and Disability Index (95% CI, 2.95-16.74; P < .01) and the numeric pain rating scale (95% CI, 0.67-2.07; P < .01) at the end of 12 weeks. The external rotation ROM showed a statistical significance with a mean change of 7.8° and P value of <.01. The present findings show that scapular functional stabilization training resulted in improvement of function, reduction in pain, and greater improvement in external rotation ROM in patients with FSS. Also, our study findings suggest the involvement of rotator interval and inferior soft-tissue structures as indicated by the coracoid pain test and range of passive abduction.


Probiotics from research to market: the possibilities, risks and challenges.
Probiotic foods can affect large parts of the population, while therapeutic applications have a less wide scope. While commercialization routes and regulatory requirements differ for both applications, both will need good scientific support. Today, probiotics are mainly used for gastrointestinal applications, their use can easily be extended to skin, oral and vaginal health. While most probiotics currently belong to food-grade species, the future may offer new functional microorganisms in food and pharma. This review discusses the crosstalk between probiotic producers, regulatory people, medical care and healthcare workers, and the scientific community.


Pharmacokinetics and analgesic effect of slow-release oral morphine sulphate in volunteers.
Sustained-release oral morphine sulphate (MST) 20 mg was administered to 11 healthy volunteers. Mean peak plasma morphine concentration was 14.8 ng ml-1, and occurred at a mean time of 142.5 min after ingestion. Analgesia assessed by an ischaemic forearm pain test increased to a maximum approximately 40 min after the calculated peak plasma concentration of morphine had been achieved, and remained greater than control values as plasma morphine concentration decayed. However, there was not a significant correlation between analgesia and plasma morphine concentration. This may result from delay in brain penetration by morphine. The mean systemic availability of morphine in the first 7 h after administration of MST was 18.3%.


Primary Effusion Lymphoma-like ATL Developing during Hemodialysis.
We herein report a patient with primary effusion lymphoma-like adult T-cell leukemia/lymphoma (PEL-like ATL) that developed during hemodialysis. A 77-year-old man developed a fever and ascites. Elevated levels of lactate dehydrogenase (LDH), calcium and soluble interleukin-2 receptor (sIL-2R) along with antibodies to human T-cell leukemia virus type 1 (HTLV-1) were seen in his blood. Lymphoma cells in ascites were positive for HTLV-1 proviral DNA, but there were no neoplastic cells in peripheral blood or bone marrow and no lymphadenopathy. He was therefore diagnosed with PEL-like ATL, acute-type. After administration of brentuximab vedotin, his serum LDH, sIL-2R and atypical cells in ascites cytology decreased. The development of novel effective molecular-targeted therapies is warranted.


Long-term outcome for large meniscal defects treated with small intestinal submucosa in a dog model.
Large meniscal defects are a common problem for which current treatment options are limited. Treatment of posterior medial meniscal defects in dogs with small intestinal submucosa is superior to partial meniscectomy in terms of clinical limb function, chondroprotection, and amount and type of new tissue in the defect. Controlled laboratory study. A total of 51 mongrel dogs underwent medial arthrotomy with creation of standardized meniscal defects. The dogs were divided into groups based on defect treatment: small intestinal submucosa meniscal implant (n = 29) or meniscectomy (n = 22). The dogs were assessed for lameness by subjective scoring after surgery and sacrificed at 3, 6, or 12 months and assessed for articular cartilage damage, gross and histologic appearance of the operated meniscus, amount of new tissue in the defect, equilibrium compressive modulus of meniscal tissue, and relative compressive stiffness of articular cartilage. Dogs in the meniscectomy groups were significantly (P < .001) more lame than dogs treated with small intestinal submucosa. Joints treated with small intestinal submucosa had significantly (P <.001) less articular cartilage damage, based on india ink staining, than did those treated with meniscectomy. Menisci receiving small intestinal submucosa had more tissue filling in the defects than did menisci receiving no implants, and this new tissue was more mature and meniscus-like and better integrated with remaining meniscus. Small intestinal submucosa scaffolds placed in large meniscal defects resulted in production of meniscus-like replacement tissue, which was consistently superior to meniscectomy in amount, type, and integration of new tissue; chondroprotection; and limb function in the long term. Small intestinal submucosa implants might be useful for treatment of large posterior vascular meniscal defects in humans.


Potential role of platelet-leukocyte aggregation in trauma-induced coagulopathy: Ex vivo findings.
Platelet dysfunction has been identified as an important contributor of trauma-induced coagulopathy, but the underlying mechanism still remains to be elucidated. Trauma-associated proinflammatory stimuli strongly activate leukocytes, which in turn bind activated platelets. Therefore, we investigated the role of platelet-leukocyte aggregation (PLA) as a potential feature of trauma-induced platelet dysfunction. Whole blood from 10 healthy donors was exposed to selective and collective platelet and leukocyte agonists in order to simulate differential states of activation. PLA formation and CD11b expression as a measure of leukocyte activation were determined by flow cytometry. Platelet-mediated hemostatic function was measured by thromboelastometry (ROTEM) and impedance aggregometry (Multiplate). Activation of platelets and leukocytes was associated with diminished platelet-mediated hemostatic potential. Aggregation of platelets with monocytes rather than granulocytes resulted in a reduction of hemostatic function, as indicated by an impaired responsiveness in platelet aggregometry and a reduction of thromboelastometric maximum clot firmness. This finding was irrespective of CD11b expression and was not paralleled by a reduction of measurable platelet counts. PLA formation occurs primarily between monocytes and activated platelets and is associated with impaired platelet-mediated hemostatic function. PLA formation was not paralleled by a reduction in platelet complete blood counts.


Potential of circulatory procalcitonin as a biomarker reflecting inflammation among South Indian diabetic foot ulcers.
Diabetic foot ulcer (DFU), the major complication associated with diabetes mellitus, has been shown to precede amputation in up to 90% of cases. Recent data reveal that procalcitonin (PCT) is a valid marker for the diagnosis of bacterial infections compared with traditional markers like white blood cell count, C-reactive protein levels, and erythrocyte sedimentation rate in DFU patients. Furthermore, cytokines are proposed to act as modulators and mediators for the expression and release of PCT into the circulation. Hence, this preliminary study was conducted to evaluate the diagnostic accuracy of PCT compared with other traditional markers and to predict the association of PCT plasma levels with inflammatory cytokines and clinical parameters of incident diabetes among South Indian DFU subjects. There were 185 subjects with type 2 diabetes mellitus (T2DM) selected in this cross-sectional study, subdivided into three groups: group I, control/T2DM subjects free from DFU (n = 75; male, 43; female, 32); group II, T2DM subjects with noninfected DFU (n = 34; male, 19; female, 15); and group III, T2DM subjects with infected DFU (IDFU; n = 76; male, 46; female, 30). Patients with IDFU were further divided into three subgroups as per the Infectious Diseases Society of America-International Working Group on the Diabetic Foot classification criteria: grade 2 (n = 27), grade 3 (n = 38), and grade 4 (n = 11). Subjects with type 1 diabetes, gestational diabetes, pneumonia, sepsis, inflammatory bowel disease, meningitis, or hematologic diseases and those who underwent surgery in the past 2 to 3 weeks were excluded from this study. For investigation of clinical parameters, blood samples were drawn from all the study subjects; plasma samples were used for estimating PCT by the enzyme-linked immunosorbent assay method. The profiling of plasma cytokines was carried out using a multiplex bead-based assay. Data are presented as mean ± standard deviation for clinical and biochemical variables and as geometric mean with 95% confidence interval (CI) for cytokines. All analysis was done using the Statistical Package for the Social Sciences (version 20.0; IBM Corp, Armonk, NY); P < .05 was considered to be statistically significant. We found PCT to be a valid diagnostic marker for IDFU with higher sensitivity and specificity than other traditional markers. For PCT, the area under the receiver operating characteristic curve was found to be high (0.99; 95% CI, 0.96-1.0), followed by C-reactive protein levels (0.78; 95% CI, 0.65-0.81), white blood cell count (0.76; 95% CI, 0.67-0.86), and erythrocyte sedimentation rate (0.74; 95% CI, 0.68-0.80) in IDFU subjects. We found the cutoff value of ≥0.5 ng/mL to have 54% sensitivity and 100% specificity for PCT with a positive predictive value of 100% and a negative predictive value of 12% for IDFU diagnosis. Moreover, PCT circulatory levels showed a positive correlation with helper T-cell subtype 1 cytokines, such as interferon γ (r = 0.21; P = .03) and interleukin 28A (r = 0.31; P = .003), and subtype 17 cytokines, such as interleukin 29/interferon λ1 (r = 0.20; P = .037). PCT could be a valuable marker for diagnosis of T2DM patients with IDFU.


[Total arthroscopic internal drainage technique for the treatment of popliteal cyst].
To compare the clinical effects of total arthroscopic internal drainage and arthroscopic combined with posterior small incision in the treatment of popliteal cyst. From January 2015 to January 2017, 60 patients with popliteal cyst were treated, including 29 males and 31 females, aged 30 to 65(47.8±2.5) years old, with a course of disease (8.5±4.2) months. Among them, 30 cases received total arthroscopic internal drainage for popliteal fossa cyst(total arthroscopic group), 30 cases received arthroscopic combined with posterior small incision for popliteal fossa cyst(arthroscopic combined with small incision group). The operation time, intraoperative bleeding volume, incision length, Rauschning and Lindgren grade 0 recovery rate and Lysholm score were compared between the two groups. Twenty-nine patients in total arthroscopy group were followed up, and 28 patients in arthroscopy combined with small incision group were followed up for 8 to 20(12.8±2.1) months. Operation time: total arthroscopic group(45.32±5.71) min, arthroscopic combined small incision group (44.56±3.85) min; Rauschning and Lindgren grade 0 recovery: 23 cases in total arthroscopic group, 22 cases in arthroscopic combined small incision group; postoperative Lysholm score: total arthroscopic group 84.5±11.2, arthroscopic combined small incision group 83.2±12.7; there was no significant difference between the two groups(P>0.05). Intraoperative bleeding volume: total arthroscopic group(5.32±1.25) ml, arthroscopic combined small incision group(20.75±8.18) ml; incision length: total arthroscopic group (1.51±0.34) cm, arthroscopic combined small incision group (7.34±0.75) cm; the difference between the two groups was significant(P<0.05). At the last follow-up, the knee joint was examined by magnetic resonance imaging, and no recurrence of cyst was found. Total arthroscopic internal drainage and arthroscopic combined with posterior small incision technique for popliteal fossa cyst with intra-articular lesions have the same clinical effect, but less trauma and faster recovery.


Strain dependent variation of immune responses to A. fumigatus: definition of pathogenic species.
For over a century microbiologists and immunologist have categorized microorganisms as pathogenic or non-pathogenic species or genera. This definition, clearly relevant at the strain and species level for most bacteria, where differences in virulence between strains of a particular species are well known, has never been probed at the strain level in fungal species. Here, we tested the immune reactivity and the pathogenic potential of a collection of strains from Aspergillus spp, a fungus that is generally considered pathogenic in immuno-compromised hosts. Our results show a wide strain-dependent variation of the immune response elicited indicating that different isolates possess diverse virulence and infectivity. Thus, the definition of markers of inflammation or pathogenicity cannot be generalized. The profound understanding of the molecular mechanisms subtending the different immune responses will result solely from the comparative study of strains with extremely diverse properties.


[Renal malacoplakia--a rare diagnosis. Imaging with sonography and computerized tomography].
A 61-year-old man with septic enophthalmitis and cramps in the upper abdominal region, fever and leukocytosis was admitted to hospital. Ultrasound examination revealed an inhomogenous enlargement of the left kidney with normal conturation and swollen, in part almost transonic, renal parenchyma. In the area of the left kidney CT demonstrated an enlarged tumor with inhomogenous and destroyed structures. The left kidney was removed. Histology confirmed the diagnosis of renal parenchymal malakoplakia.


Molecular heterogeneity of Vicia villosa-recognized perineuronal nets surrounding pyramidal and nonpyramidal neurons in the guinea pig cerebral cortex.
Of three monoclonal antibodies (mAbs Cat 301, 1B5 and 473) which recognize epitopes on perineuronal nets (PnNs), only mAb 473 displayed considerably varied degrees of staining intensity on Vicia villosa-labeled pyramidal (P) neurons (5%, intensely; 54%, very weakly; and 41%, unstained). These results indicate the heterogeneity on molecular structure or composition of the terminal N-acetylgalactosamine-containing PnNs within P class as well as between P and nonpyramidal classes.


Energy of a single bead bouncing on a vibrating plate: experiments and numerical simulations.
The energy of a single bead bouncing on a vibrating plate is determined in simulations and experiments by tracking the bead-plate collision times. The plate oscillates sinusoidally along the vertical with the dimensionless peak acceleration Gamma, and the bead-plate collisions are characterized by the velocity restitution coefficient epsilon. Above the threshold dimensionless peak acceleration Gamma(s) approximately 0.85, which does not depend on the restitution coefficient, the bead energy is shown to initially increase linearly with the vibration amplitude A, whereas it is found to scale like v(2)(p)/(1-epsilon), where v(p) is the peak velocity of the plate, only in the limit Gamma>>Gamma(s). The threshold Gamma(s) is shown to decrease when the bead is subjected, in simulations, to additional nondissipative collisions occurring with the typical frequency nu(c). As a consequence, the bead energy scales like v(2)(p)/(1-epsilon) for all vibration strengths in the limit nu(c)>>nu(*)(c). From the experimental and numerical findings, an analytical expression of the bead energy as a function of the experimental parameters is proposed.


Synthesis and immunogenicity of the rotavirus major capsid antigen using a baculovirus expression system.
Rotaviruses are the major pathogens that cause life-threatening diarrhea in young children and animals. We inserted a simian rotavirus SA11 gene 6 cDNA into the genome of the baculovirus Autographa californica nuclear polyhedrosis virus adjacent to the strong polyhedrin promoter. The major capsid antigen (VP6) was expressed in high yields (20 to 150 micrograms/10(6) cells) when Spodoptera frugiperda cells were infected with baculovirus recombinants containing SA11 gene 6 inserts. Reactivity with monospecific polyclonal and monoclonal antibodies suggested that VP6, expressed intracellularly or found in the media, maintained native antigenic determinants. VP6 purified from the media from infected cells also possessed a native oligomeric structure, was immunogenic in guinea pigs, and was able to spontaneously assemble into morphologic subunits. Antisera from immunized guinea pigs failed to neutralize virus in plaque reduction assays, but detected homologous and heterologous rotavirus strains when tested by immunofluorescence, immunoprecipitation, and enzyme-linked immunosorbent assays.


The impact of individual and area characteristics on urban socioeconomic differences in health and smoking.
In general, poor health and lifestyles occur more frequently among individuals of low socioeconomic status (SES) and in deprived areas. An explanation for the latter may simply be the on average lower SES of residents of these areas. It is possible, however, that living in a deprived area contributes to poor health and lifestyles. This study examines whether such an area-contribution exists in urban settings. Data on health, smoking, and individual SES were collected on 5121 residents of Amsterdam, the Netherlands, by face-to-face interviews (response: 61.4%). Area deprivation was measured by indicators used previously, on 22 areas. Odds ratios (OR) for poor health (poor self-rated health, long-term limitations, health complaints and obesity) and smoking were computed comparing tertiles of area deprivation. All analyses employed multilevel techniques, with residents hierarchically nested within areas. The age- and gender-adjusted prevalences of poor health and smoking are higher in deprived urban areas. Most of the differences in poor health can be explained by the on average lower SES of residents of deprived areas. Only for long-term limitations and obesity, some statistically significant area-differences remain. The higher prevalence of smoking in deprived areas can only partially be explained by the SES of residents. Adverse health status in deprived areas is mainly due to a lower individual SES and not to contextual factors. For smoking, living in a deprived area contributes to a higher prevalence. This shows the necessity of community-based preventive interventions in deprived areas.


The prevalence, incidence, and associated factors of pressure injuries among immobile inpatients: A multicentre, cross-sectional, exploratory descriptive study in China.
The aim of this study was to assess the prevalence, incidence, and the associated factors of pressure injuries (PIs) among immobile hospitalised patients in China. Being immobile during hospitalisation put these patients at a higher risk of PIs. There is little literature about pressure injury (PI) prevalence or PI incidence in immobile hospitalised patients in hospitals in China. This was a multicentre, cross-sectional, exploratory descriptive study. A total of 23 985 immobile patients were recruited from 25 general hospitals in six provinces of China from November 1, 2015 to March 18, 2016. Information was collected on demographic characteristics, physical assessment information, and treatment and nursing care measures. The PI period prevalence was 3.38%, and the PI cumulative incidence was 1.23%. Most PIs (84.03%) were Stage 1 or Stage 2. A total of 48.22% of PIs occurred in the sacrum or heel region. In the multivariate analysis, the following factors were associated with higher PI prevalence: age, gender, length of immobility, type of hospital, modified Braden Scale score, urinary incontinence, faecal incontinence, low serum albumin, the usage of fixation or restraint devices, and patient's discharge diagnosis (lower limb fracture, malnutrition, and spinal cord injury). PI prevalence for immobile hospitalised patients in the study was lower than those reported in literature. However, because of the large population in China, the number of patients who suffer with PIs can be very high. The relating factors of higher PI prevalence identified in this study were consistent with current literature. Patients with a higher number of these associated factors should be monitored more closely, and preventative measures should be taken to prevent PI occurrence in high-risk populations.


A case of propylthiouracil-induced antineutrophilic cytoplasmic antibody-positive vasculitis successfully treated with radioactive iodine.
Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis is one of the rare complications of propylthiouracil treatment. Having a variable clinical spectrum, it may be presented with both skin limited vasculitis and life-threatening systemic vasculitis. In this study, we present a case that developed ANCA-positive vasculitis with skin and kidney involvement (hematuria and proteinuria) six months after propylthiouracil treatment was initiated for toxic nodular goiter. Proteinuria recovered dramatically subsequent to radioactive iodine treatment following ceasing the drug.


Observation of laser-assisted electron scattering in superfluid helium.
Laser-assisted electron scattering (LAES), a light-matter interaction process that facilitates energy transfer between strong light fields and free electrons, has so far been observed only in gas phase. Here we report on the observation of LAES at condensed phase particle densities, for which we create nano-structured systems consisting of a single atom or molecule surrounded by a superfluid He shell of variable thickness (32-340 Å). We observe that free electrons, generated by femtosecond strong-field ionization of the core particle, can gain several tens of photon energies due to multiple LAES processes within the liquid He shell. Supported by Monte Carlo 3D LAES and elastic scattering simulations, these results provide the first insight into the interplay of LAES energy gain/loss and dissipative electron movement in a liquid. Condensed-phase LAES creates new possibilities for space-time studies of solids and for real-time tracing of free electrons in liquids.


Long-term Treatment Outcomes Between Surgical Correction and Conservative Management for Penile Fracture: Retrospective Analysis.
Early surgical management is the standard of care for penile fracture. Conservative treatment is an option with recent reports revealing lower success rates. We reviewed the data and long-term outcomes of patients with penile injury submitted to surgical or conservative treatment. Between January 2004 and February 2012, 42 patients with penile blunt trauma on an erect penis were admitted to our center. We analyzed the following variables: age, etiology, symptoms and signs, diagnostic tests, treatment used, complications and erectile function during the follow-up. One patient was excluded due to missing information. Thirty-five patients underwent surgical repair and 6 patients were submitted to conservative management. Mean follow-up was 19.2 months (range, 7 days to 72 months). The mean elapsed time from trauma to surgery was 21.3±12.5 hours. Trauma during sexual relationship was the main cause (80.9%) of penile fracture. Urethral injury was present in five patients submitted to surgery. Dorsal vein injury occurred in three patients with false penile fracture and concomitant spongious corpus lesion was present in three patients. During follow-up, 31 cases (88.6%) of the surgical group and four cases (66.7%) of the conservative group reported sufficient erections for intercourse, with no voiding dysfunction and no penile curvature. However, the remaining two patients (33.3%) from the conservative group developed erectile dysfunction and three patients (50%) developed penile deviation. Surgical approach provides excellent functional outcomes and lower complications. Early surgical management of penile fracture provides superior results and conservative approach should be avoided.


Effect of laparoscopic myomectomy on serum levels of IL-6 and TAC, and ovarian function.
Effect of laparoscopic myomectomy on the serum levels of interleukin-6 (IL-6) and total antioxidant capacity (TAC), and the ovarian function of patients with uterine fibroids was studied. Ninety patients with uterine fibroids admitted to The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, from March 2013 to July 2014, were randomly divided into the experimental group (n=45) and the control group (n=45). The experimental group was treated with laparoscopic myomectomy, and the control group was treated with abdominal myomectomy. ELISA was used for detecting IL-6 and TAC content. Radioimmunoassay (RIA) was used for detecting serum ovarian function indicators, including estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Patients in the experimental group had significantly lower intraoperative blood loss, postoperative exhaust time, number of days to recovery and return to work, number of intraoperative fibroids removed, and length of stay than those in the control group (P<0.05). TAC expression level was significantly higher in the experimental group than that in the control group, on the 1st, 3rd and 5th day after surgery (P<0.05), while IL-6 expression was significantly lower in the experimental group than that in the control group at the same time points (P<0.05). FSH and LH expression levels were significantly lower in the experimental group than those in the control group (P<0.05) at 1, 3 and 6 months after surgery, while E2 expression level was significantly higher in the experimental group than that in the control group at the same time points (P<0.05). The incidence of postoperative complications of patients in the experimental group was significantly lower than that in the control group (P<0.05). Patients in the experimental group had significantly higher successful pregnancy rate than those in the control group (χ2=6.75, P<0.05). Reducing its effect on ovarian function, serum pain index and oxidative damage index of patients with uterine fibroid, laparoscopic myomectomy also reduces the incidence of postoperative complications and increases the pregnancy rate.


Maturation in liver mitochondria of Ruthenium Red-sensitive calcium-ion-transport activity and the influence of glucagon administration in vivo and in utero.
The maturation of Ca(2+) transport in mitochondria isolated from rat liver was examined, from 5 days before birth. The mitochondria used were isolated from liver homogenates by centrifugation at 22000g-min. Ca(2+) transport by mitochondria isolated from foetal liver is energy-dependent and Ruthenium Red-sensitive. The transmembrane pH gradient in these mitochondria is higher by about 7mV and the membrane potential lower by about 20mV than in adult mitochondria. The inclusion of 2mm-P(i) in the incubation medium enhances the protonmotive force by approx. 30mV. The rate of Ca(2+) influx in foetal mitochondria measured in buffered KCl plus succinate is low until about 2-3h after birth, when it increases to about 60% of adult values; approx. 24h later it has reached near-adult values. Higher rates of Ca(2+) influx are observed in the presence of 2mm-P(i); 3-5 days before birth the rates are about one-third of adult values and decline slightly as birth approaches. By 2-3h post partum they have reached adult values. The inclusion of 12.5mum-MgATP with the P(i) stimulates further the initial rate of Ca(2+) influx in foetal mitochondria. The rates observed are constant over the prenatal period examined and are 50-60% of those observed in adult mitochondria. Mitochondria isolated from foetal livers 4-5 days before birth retain the accumulated Ca(2+) for about 50min in the presence of 2mm-P(i). In the period 2 days before birth to birth, this ability is largely lost, but by 2-3h after birth Ca(2+) retention is similar to that of adult mitochondria. The presence of 12.5mum-MgATP progressively enhances the Ca(2+) retention time as development proceeds until 2-3h after birth, when it becomes less sensitive to added MgATP. Glucagon administration to older foetuses in utero enhances both the rate of mitochondrial Ca(2+) influx assayed in the presence of 2mm-P(i) and the time for which mitochondria retain accumulated Ca(2+) in the presence of 12.5mum-MgATP and 2mm-P(i). Its administration to neonatal animals leads to an increase in mitochondrial Ca(2+) retention similar to that seen in adult mitochondria. The data provide evidence that the Ruthenium Red-sensitive Ca(2+) transporter is potentially as active in foetal mitochondria 5 days before birth as it is in adult mitochondria. They also show that foetal mitochondria have an ability to retain accumulated Ca(2+) reminiscent of mitochondria from tumour cells and from hormone-challenged rat liver.


No evidence that amifostine influences the plasma pharmacokinetics of topotecan in ovarian cancer patients.
This aim of this study was to compare the pharmacokinetics of topotecan in the presence and absence of preceding amifostine to reduce the risk of side effects in patients with advanced ovarian cancer. Ten patients with advanced ovarian cancer received topotecan, 1.5 mg/m(2) for 5 days, as second-line therapy in an open phase-II study after previous platinum-containing first-line therapy. Patients were randomised to receive intravenous (IV) amifostine at a daily dose of 300 mg/m(2) prior to topotecan in the first cycle and topotecan alone in the second cycle or vice versa. Thereafter all patients were given amifostine and topotecan for additional four cycles. Topotecan was given as a 30-min IV infusion. On day 1 of the first and second treatment cycles, venous blood samples were collected up to 24 h after the start of topotecan infusion. Plasma concentrations of total topotecan and its active lactone form were determined using high-performance liquid chromatography. There was a rapid decline in total topotecan plasma concentrations after the end of the infusion followed by a slower decay. The initial decline was even faster for the lactone form. The inter-individual variability was pronounced and the area under the plasma concentration-time curve from time zero to infinity (AUC(0-infinity)) of the total topotecan plasma concentration ranged from 182 nmol/l h to 725 nmol/l h for topotecan alone and from 188 nmol/l h to 574 nmol/l h for topotecan and amifostine. The geometric mean of AUC(0-infinity) values were 326 nmol/l h and 297 nmol/l h, respectively ( P=0.41). In the cycles when the patients received topotecan alone, the plasma AUC of the lactone averaged 40% of the AUC of the total concentration compared with 39% in the cycles when topotecan was given after amifostine. The peak plasma concentration (C(max)) of the lactone averaged 72% of the C(max) of the total topotecan concentration in the topotecan-only group. The corresponding figure after topotecan and amifostine was 80% ( P=0.11). A large intra-individual pharmacokinetic of topotecan between cycles 1 and 2 was also observed. Amifostine, 300 mg/m(2), does not significantly affect the pharmacokinetics of topotecan and there are pronounced intra- and inter-individual variabilities in the topotecan pharmacokinetics.


Molluscicidal effect of nicotinanilide and its intermediate compounds against a freshwater snail Lymnaea luteola, the vector of animal schistosomiasis.
The molluscicidal effect of nicotinanilide was evaluated and compared with niclosamide (2',5-dichloro-4'-nitrosalicylanilide, ethanolamide salt) against different stages of the freshwater snail Lymnaea luteola i.e., eggs, immature, young mature, and adults. Calculated values of lethal concentrations (LC50 and LC90) showed that both nicotinanilide and niclosamide as toxic against eggs, immature, and adults. The young mature stage of the snails was comparatively more tolerant to both molluscicides than the other stages. The toxicity of the intermediate compounds of nicotinanilide against the young mature stage of the snails showed them as ineffective. The mortality pattern of the snails exposed to LC90 concentration of these molluscicides showed niclosamide to kill faster (within 8 to 9 h) than nicotinanilide (26 to 28 h). In view of the above studies it may be concluded that both molluscicides are toxic against all the stages of the L. luteola snails.


Does CPAP lead to change in BMI?
Obesity is an important risk factor for obstructive sleep apnea syndrome (OSAS), and weight loss can reduce apnea severity or even lead to resolution in some patients. Effective CPAP therapy may lead to weight loss by any of several proposed mechanisms, including, but not limited to, increased physical activity and increased responsiveness to leptin. This retrospective study sought to determine whether subjects who adhered to prescribed CPAP treatment for OSAS would lose weight, or gain less weight than control subjects who were either untreated or did not adhere to prescribed CPAP treatment. BMI was determined at the time of diagnosis and at followup approximately 1 year (10-14 months) later. Subjects who used CPAP > or = 4 h per night and > or = 70% of nights were considered treatment subjects. Control subjects used no treatment for OSAS or used CPAP < 4 hours per night or < 70% of nights for 1 year. BMI of treatment and control subjects did not significantly differ (p = 0.3157). BMI increased with 1 year of CPAP use in women but not men (p = 0.0228) and in non-obese subjects (p = 0.0443). BMI did not significantly decrease in any group treated with CPAP. CPAP was associated with weight gain in some; none lost weight. CPAP may affect weight in ways not measured here. Physicians should stress an active weight loss plan and not assume CPAP alone will lead to weight loss. A larger, prospective study may help clarify these findings.


[Imaging in rheumatology. Degenerative diseases of the spine].
Degeneration of the spine is a common reason for pain in the musculoskeletal system. Radiography is an important tool for diagnosis and differential diagnosis. Cost efficacy and economy of time are advantages in using conventional x-rays. Although narrowing of intervertebral disc spaces, irregular ossification of the vertebral end-plate as well as osteophytes, facet joint osteoarthritis and spondylolisthesis can be observed, early changes in the discs or the subdiscal bone can not be detected by x-rays. Moreover, 3-dimensional imaging is not possible. Computer tomography (CT) and magnetic resonance imaging (MRI) are reliable for identifying disorders of the spine and soft-tissue. Differentiation between inflammation, trauma and tumor is possible. There is still a problem with the relationship between the information obtained by x-rays or MRI and clinical symptoms. Therefore, interpretation of radiological examinations assumes a knowledge of clinical symptoms and the different kinds of diseases which are possible.