Glucose and cholesterol elevations during thiazide therapy: intention-to-treat versus actual on-therapy experience.
This nonrandomized, parallel-group, prospective clinical series in consecutive patients was conducted to determine if the method of analysis of biochemical data collected in long-term treatment trials can explain the controversy regarding the effects of thiazides on plasma glucose or cholesterol. Fasting serum glucose, potassium, and cholesterol levels were determined before therapy, and yearly thereafter (4.0 +/- 0.1 years) in 634 consecutive patients treated for more than 1 year with antihypertensive monotherapy. When the data were analyzed by the intention-to-treat paradigm (ignoring changes in therapy), glucose and cholesterol levels in the thiazide group were significantly higher (compared to baseline or to the other therapy group) only at year 1. When the data were analyzed by actual on-therapy experience (censoring patients when therapy is altered)--a more traditional way to examine side effects--these differences were significant for all 5 years studied. Even if as few as 8% of patients who changed therapies were included in an intention-to-treat analysis, these differences became nonsignificant. These comparisons not only indicate why a dichotomy might exist between clinical practice (analyzed by actual on-therapy experience) and randomized trials (analyzed by intention-to-treat methods), regarding biochemical changes in glucose and cholesterol during thiazide therapy, but also that, for secondary hypotheses, analyzing data by both methods of assignment is important.


Validation of non-fluorescent methods to reliably detect acrosomal and plasma membrane integrity of common marmoset (Callithrix jacchus) sperm.
Simple, rapid and stable sperm evaluation methods which have been optimized for common marmoset (Callithrix jacchus) are critical for studies involving collection and evaluation of sperm in the field. This is particularly important for new species groups such as Callitrichidae where the sperm have been little studied. Of this family, C. jacchus is the best known, and has been chosen as a model species for other members of the genus Callithrix. The fundamental evaluation parameters for sperm of any species are viability and acrosomal status. Semen samples were collected by penile vibratory stimulation. To evaluate sperm plasma membrane integrity, Eosin-Nigrosin was tested here for the common marmoset sperm to be used under field conditions. Further, a non-fluorescent stain for acrosome, the "Simple" stain, developed for domestic and wild cats, was tested on common marmoset sperm. This was compared with a fluorescent staining, Fluorescein isothiocyanate-Pisum sativum agglutinin (FITC-PSA), routinely used and validated for common marmoset at the German Primate Centre to evaluate acrosomal integrity. Results obtained with the "Simple" stain showed a marked differentiation between sperm with intact and non-intact acrosome both with and without ionophore treatment and closely correlated with results obtained with FITC-PSA. Temperature had no effect on the results with the "Simple" stain and the complete processing is simple enough to be carried out under field conditions. These findings indicated that the "Simple" stain and Eosin-Nigrosin provide rapid and accurate results for C. jacchus sperm and that those methods can be reliably used as field tools for sperm evaluation for this species.


Experimental Investigation of Damage Formation in Planar Fibrous Networks During Stretching.
This paper presents the results of unidirectional strain-controlled experiments on fibrous electrospun networks used to study damage formation during elongation. The experimental loading curve shows a symmetrical parabolic type dependence at large scale and saw tooth-like force-extension behaviour at small scale. The damage formation was quantified by determining the number and the magnitude of abrupt force drops. The experiments evidenced that damage evolution is a consequence of strain induced random events. The frequency distribution of the number of damages as well as the magnitude of rupture force were represented by histograms. The results of the present study provide a better insight into damage tolerance and complex nonlinear tensile properties of electrospun networks. In addition, it could suggest a possible probabilistic approach to the fiber bundle model which has mainly motivated this study.


Asking the right questions: the relationship between incident ventilator-associated pneumonia and mortality.
Whether ventilator-associated pneumonia is a manifestation of severity of illness or an independent cause of mortality in ventilator-dependent patients is not known. In this complex area, which cannot be readily subjected to randomized controlled trials, studies should focus on the underlying questions of relevance, how to improve care of ventilated patients.


Tunable Synthetic Hydrogels to Study Angiogenic Sprouting.
Angiogenic sprouting, the formation of new blood vessels from pre-existing vasculature, is tightly regulated by the properties of the surrounding tissue microenvironment. Although the extracellular matrix has been shown to be a major regulator of this process, it is not clear how individual biochemical and mechanical properties influence endothelial cell sprouting. This information gap is largely due to the lack of suitable in vitro models that recapitulate angiogenic sprouting in a 3D environment with independent control over matrix properties. Here, we present protocols for the preparation of endothelial cell spheroid-laden synthetic, dextran-based hydrogels, which serve as a highly tunable 3D scaffold. The adjustment of the hydrogels' adhesiveness, stiffness, and degradability is demonstrated in detail. Finally, we describe assays to elucidate how individual matrix properties regulate angiogenic sprouting, including their analysis by immunofluorescence staining and imaging. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Synthesis of methacrylated dextran (DexMA) Basic Protocol 2: Generation of endothelial cell spheroids in microwells Basic Protocol 3: Endothelial cell sprouting in hydrogels of tunable stiffness Basic Protocol 4: Endothelial cell sprouting in hydrogels of tunable adhesiveness Basic Protocol 5: Endothelial cell sprouting in hydrogels of tunable degradability Basic Protocol 6: Imaging of endothelial cell spheroid-laden hydrogels Support Protocol 1: Preparation of pro-angiogenic cocktail for endothelial cell sprouting.


[Dystonia, tremor and repetitive instrumental use].
Three characteristic observations are presented along with three tables presenting 24 patients with the following elements in common: excessively repeated use of an instrument such as a pen, a musical instrument or a tool. The appearance after that use of a central pathological phenomenon that includes a local dystonia of a hand or the mouth, a tremor, or the association of a tremor and a dystonia, all within the muscular domain corresponding to that of the use. The discussion, which is based exclusively on the clinical findings, deals with the following elements: the role of the use of the instrument rather than task itself, the predominant pathogenic factor which is the repetitive action, to which is added a genetic component in one incompletely penetrant case of DYT 1, and a probable genetic susceptibility in the others. The absence of improvement with rest distinguishes this central pathology from rheumatologic or orthopaedic problems involving repetitive activities. The evolution is slowly declining when the responsible action is continued. This occurs in three stages: a specific disorder involving only the use of the particular instrument, a more enlarged involvement affecting other activities and eventually a dystonia associated with a tremor or a postural tremor always located to the initial area. The therapeutic interventions suggested by the pathologic role of the repetitive movement is: (1) to advise a new training for the instrument that excludes the habitual movement; (2) to advise the patient to vary any newly acquired repetitive movements.


Silica-based, hyper-crosslinked acid stable stationary phases for high performance liquid chromatography.
A new family of hyper-crosslinked (HC) phases for use under very aggressive acid conditions including those encountered in ultra-fast, high temperature two-dimensional liquid chromatography (2DLC) has been recently introduced. This type of stationary phase shows significantly enhanced acid and thermal stability compared to the most acid stable, commercial RPLC phases. In addition, the use of "orthogonal" chemistry to make surface-confined polymer networks ensures good reproducibility and high efficiency. One of the most interesting features of the HC phases is the ability to derivatize the surface aromatic groups with various functional groups. This has led to the development of a family of hyper-crosslinked phases possessing a wide variety of chromatographic selectivities by attaching hydrophobic (e.g. -C₈), ionizable (e.g. -COOH, -SO₃H), aromatic (e.g. -toluene) or polar (e.g. -OH) species to the aromatic polymer network. HC reversed phases with various degrees of hydrophobicity and mixed-mode HC phases with added strong and weak cation exchange sites have been synthesized, characterized and applied. These silica-based acid-stable HC phases, with their attractive chromatographic properties, should be very useful in the separation of bases or biological analytes in acidic media, especially at elevated temperatures. This work reviews prior research on HC phases and introduces a novel HC phase made by alternative chemistry.


Efficacy of doramectin against experimental infections by some nematode parasites in cattle in New Zealand.
A study was undertaken to determine the efficacy of the novel avermectin, doramectin, against experimental larval and adult infections of three species of nematode parasite important to cattle production in New Zealand. Eighteen worm-free dairy bull beef calves were randomly allocated on live weight to three similar treatment groups. Each calf was given 30,000 Ostertagia ostertagi, 20,000 Cooperia spp. and 10,000 Trichostrongylus axei infective larvae as a single dose. One group was treated with doramectin 6 days after infection while the remaining groups received saline or doramectin 27 days after infection. Given as a single subcutaneous injection behind the ear, doramectin at 200 microg/kg removed 99.9-100% of adult and larval stages of O. ostertagi, Cooperia spp. and T. axei when compared to infections established in untreated controls (p<0.001). No adverse reactions were observed following treatment in the doramectin-treated animals. No injection site lesions were found by palpation following treatment or by injection site examination at necropsy.


The American Board of Surgery Certifying Examination: a retrospective study of the decreasing pass rates and performance for first-time examinees.
There has been a noticeable decrease in the pass rate for the American Board of Surgery Certifying Examination during the last 5 years. We hypothesize that this decline is statistically significant, and we wish to determine whether the pass rates had any geographic patterns of distribution. In this retrospective cohort trial, publically available electronic data sets of pass rates on the American Board of Surgery Certifying Examination were evaluated from the American Board of Surgery website. χ(2) tests were used to determine whether there was any association between the pass rates and the academic year. A descriptive geographic evaluation of program-specific pass rates for first-time examinees was also performed. From 2006 to 2010, there has been a 7% decrease in the pass rate for the American Board of Surgery Certifying Examination. A χ(2) test shows that there is a statistically significant association with the pass percentage on the American Board of Surgery Certifying Examination and the year (p < 0.0001). Subgroup analysis demonstrated a difference in pass rate between 2006 and 2007 (p = 0.02). Geographic analysis showed the pass rates for first-time examinees were the highest in Rhode Island (100%) and the lowest in Puerto Rico (63%) from 2005 to 2010. Three of the 5 highest-performing states are on the Pacific Coast, and 4 of the 9 lowest-performing states are in the southern United States. There are differences between these 2 groups of states (p < 0.001). There was a significant decrease in the pass rate for the American Board of Surgery Certifying Examination from 2006 to 2010. There also were some geographic patterns relating to first-time examinee performance from 2005 to 2010.


All fiber magnetic field sensor with Ferrofluid-filled tapered microstructured optical fiber interferometer.
An ultra-compact optical fiber magnetic field sensor based on a microstructured optical fiber (MOF) modal interference and ferrofluid (FF) has been proposed and experimentally demonstrated. The magnetic field sensor was fabricated by splicing a tapered germanium-doped index guided MOF with six big holes injected with FF to two conventional single-mode fibers. The transmission spectra of the proposed sensor under different magnetic field intensities have been measured and theoretically analyzed. Due to an efficient interaction between the magnetic nanoparticles in FF and the excited cladding mode, the magnetic field sensitivity reaches up to117.9pm/mT with a linear range from 0mT to 30mT. Moreover, the fabrication process of the proposed sensor is simple, easy and cost-effective. Therefore, it will be a promising candidate for military, aviation industry, and biomedical applications, especially, for the applications where the space is limited.


A modified device to place abomasal infusion lines for rumen-cannulated cattle.
A previously developed abomasal infusion device was modified for easy and successful placement of infusion lines into the abomasum of dairy cows. Similar to the original device, the modified device consists of 2 pieces: an insertion tool and a delivery tool. Updates include streamlining both the insertion and delivery tools by slightly altering dimensions and design, then smoothing all rough edges. The primary changes include a parallel cut along the entire length of the insertion and delivery tools and encasement of the infusion line inside both tools, allowing for smoother insertion through the reticulum-omasum orifice and into the omasum and abomasum. Additionally, increasing the outside diameter of the delivery tool to reduce the gap between the delivery tool and insertion tool, increasing the length of the tools, and making a loop of cord attached to the insertion tool facilitate insertion and easy ejection of the flange into the abomasum. By using this modified device, placement of abomasal infusion lines (including flange) was more successful.


Unspecific and specific stimulating effects of 3',5'-cyclic nucleotides (cGMP, cAMP, cIMP, cCMP) on the in vitro biosynthesis of proteochondroitin-4,-6-sulfate and on other anabolic processes from calf rib cartilage.
With cartilage slices from calf ribs, cGMP as well as cAMP accelerate dose-dependently and specifically label rates of Ch-4-,-6-S protein; they slightly elevate rates of anaerobic glycolysis dose-independently and unspecifically, similar to their 5-monophosphate compounds. cAMP, but not cGMP, slightly stimulates labeling of total protein dose-dependently. Guanosine and adenosine (as well as adenine) accelerate more significantly all three anabolic processes in the order Ch-4-,-6-S protein formation greater than or equal to total protein labeling greater than anaerobic glycolysis. Acceleration of some of the processes rises further after adding theophylline or SQ 20.009, depending on the nucleoside used. diBu-cAMP (but not 8-Br-cAMP) stimulates the three processes more than cAMP; diBu-cGMP and 8-Br-cGMP alone increase the labeling rates of protein more than cGMP, cCMP and cIMP slightly accelerate at least one of the three processes dose-independently and unspecifically, similar to their 5-monophosphate compounds. cUMP was almost inactive. The results point to specific and unspecific effects of cGMP similar or different to those of cAMP.


A qualitative investigation of the decision-making process of couples considering prenatal screening for Down syndrome.
The aim of this study was to investigate how couples regard screening information and how they make subsequent decisions about undergoing prenatal screening for Down syndrome. Twenty semi-structured interviews were conducted to explore aspects of the decision-making process. Interviews were digitally recorded and transcribed verbatim, and data were analysed using the framework approach. Couples reported a strong desire for a joint but ultimately private decision-making process and saw the main role of their midwife as an information provider. Considerable confusion existed over which screening tests were available via the National Health Service and which were offered privately. Provision of experiential information regarding both subsequent diagnostic tests and the experience of living with Down syndrome would have been beneficial. This study shows that couples would benefit from receiving experiential information when they are deciding about Down syndrome screening. Future research should be conducted to establish what form such information should take, the most helpful means to provide such information, and whether such information would also be useful in other contexts where people need to make decisions whether to undergo screening.


Intracardiac thrombus in a patient with autoimmune hemolytic anemia leading to a diagnosis of antiphospholipid syndrome.
We report a case of antiphospholipid syndrome (APS) which presented with clinical and laboratory signs of an autoimmune hemolytic anemia (AHA), in the absence of manifestations typically related to APS. The diagnosis of APS was made only after the occurrence of a sudden severe heart failure due to an intraventricular thrombus requiring a surgical approach. An accurate thrombophilic screening is warranted also in patients with apparently idiopathic AHA.


Pulmonary immune profiling of SIDS: impaired immune maturation and age-related cytokine imbalance.
For sudden infant death syndrome (SIDS), an impaired immunocompetence has been discussed for a long time. Cytokines and chemokines are soluble immune mediators (SIM) whose balance is essential for the immune status. We hypothesized that an imbalanced immune response might contribute to the etiology of SIDS. We investigated 27 cytokines, chemokines, and growth factors in protein lysates of lungs derived from 29 SIDS cases and 15 control children deceased for other reasons. Except for the CCL5, no significant differences were detected in the lungs between SIDS cases with and without mild upper respiratory tract infections. In contrast, IL-1RA, IL-7, IL-13, and G-CSF were decreased in the merged SIDS cases compared to control cases without evidence of infection. Plotting SIM concentrations against infant age resulted in increasing concentrations in control but not in SIDS lungs, indicating a disturbed immune maturation. Moreover, an age-dependent shift towards a Th2-related pattern was observed in SIDS. Our findings suggest that an impaired maturation of the immune system, an insufficient response to respiratory pathogens, and an immune response modulated by Th1/Th2 imbalance might play a possible role in triggering SIDS. These findings might in part be explained by chronic stress. Maturation of the cytokine and chemokine network may be impaired in SIDS. An imbalance between Th1- and Th2-related cytokines, which may reflect a state of chronic stress causing a more Th2 shift. An impaired immune maturation, an insufficient response to respiratory pathogens, and an immune response modulated by Th1/Th2 imbalance might play a possible role in SIDS.


Vascular integrity of the distal ureter following combined tapering and cross trigonal reimplantation.
Massive unilateral hydroureteronephrosis was created in 20 female dogs by ligating the urographically normal prevesical ureter. Over a 14-day period the obstructed ureter dilated to an average of 15.3 mm. A ureteral tapering procedure was performed by lateral darting and posterior folding of the resultant flap, followed by a cross-trigonal reimplantation. One anastomotic stricture resulted; in the remaining 19 animals, ureteral peristalsis was restored, the ureteral diameter was reduced 61.9 per cent and hydronephrosis was resolved. Histological studies on the tapered segments of these 19 animals showed that the subadventitial blood supply was preserved with fibrotic occlusion of the folded flaps. These results demonstrate that no significant vascular compromise after ureteral tapering and cross-trigonal reimplantation occurs. Success rates comparable to those of conventional ureteral tailoring can be achieved by this technically simplified form of reconstructive surgery.


Mandibular Osteonecrosis Associated with Antacid Therapy (Esomeprazole).
Osteonecrosis of the jaw has been consistently reported in the literature associated to the high-dose intravenous bisphosphonate therapy. However, osteonecrosis can also occur in patients who have other risk factors. An unusual case of ONJ in a patient being treated with esomeprazole is reported. The probable association between proton pump inhibitor intake and osteonecrosis of the jaw should alert clinicians. Collaborations between medical and dental doctor and an early diagnosis might prevent or reduce the morbidity resulting from advanced destructive lesions of the jaw bone. Osteonecrosis of the jaw (ONJ) can occur in patients treated with bisphosphonates and corticosteroids and is associated with oral surgical procedures involving bone.Antacid drugs commonly used to treat gastro-oesophageal reflux could affect bone metabolism although no cases of ONJ in patients using proton pump inhibitors have been reported.Medical and dental practitioners should collaborate to prevent ONJ, identify previously unreported drug interactions, and treat patients in a more comprehensive manner.


Competition between glycoprotein hormones and horseradish peroxidase for mannose-specific binding sites in cells of endocrine organs.
Mannose-specific binding sites for horseradish peroxidase (HRP) were studied in paraformaldehyde-fixed, frozen sections of endocrine organs by a cytochemical method reported previously. In the testis, HRP was bound to interstitial cells, probably macrophages, and to sites extending along the surface of spermatozoa in the seminiferous tubules. In the epididymis, cells in the connective tissue, probably fibroblasts or macrophages, showed the specific reaction. In the ovaries, the reaction for lectin-bound HRP was observed in connective tissue cells of the theca externa, and in the mucosa of the uterus, binding of HRP occurred to many fibroblasts. The glycoprotein was also bound to cells in the connective tissue of the thyroid, probably mast cells, as well as to endothelial cells in the adrenal medulla and cortex. In all cases, the binding reaction required Ca2+ and was suppressed by mannose or mannan. Partially purified and highly purified preparations of glycoprotein hormones [ovine follicle-stimulating hormone, ovine luteinizing hormone, bovine thyroid-stimulating hormone, and human chorionic gonadotropin] as well as bovine thyroglobulin and yeast invertase competed with the binding of HRP to all the cells mentioned thus showing that the hormones were bound to the same sites as HRP. When 1 microM HRP was present in the incubation medium, the addition of 15-25 microM of highly purified hormones almost suppressed the reaction for lectin-bound HRP and competitive effects could be observed at even lower concentrations of the hormones.


Severity of SARS-CoV-2 Omicron XBB subvariants in Singapore.
Several XBB subvariants such as XBB.1.5, XBB.1.9, XBB.1.16 and XBB.2.3 co-circulate in Singapore. Despite the different viral properties of XBB.1.16 as compared to other XBB subvariants, comparison on their severity is limited. In this study, we investigate the outcomes of hospitalisation and severe COVID-19 infection in individuals infected with different XBB subvariants, adjusted for potential confounders such as age and vaccination history. Overall, our preliminary analysis showed that the risk of severe outcomes when infected with XBB.1.16 is higher than that of XBB.1.5 or XBB.1.9 but there is no difference in the risk of hospitalisation across different XBB subvariants.


Multiparametric Analysis of Focal Adhesions in Bidimensional Substrates.
Focal adhesions in planar substrates constitute an excellent cellular resource to evaluate different parameters related to cell morphology, cytoskeletal organization, and adhesive strength. However, their intrinsic heterogeneity in terms of size, molecular composition, orientation, and so on complicates their analysis. Here, we describe a simple and straightforward ImageJ/Fiji-based method to quantify several parameters that describe the morphology and relative composition of focal adhesions. This type of analysis can be implemented in various ways and become useful for drug and shRNA screenings.


Single-Electron Transmetalation: Photoredox/Nickel Dual Catalytic Cross-Coupling of Secondary Alkyl β-Trifluoroboratoketones and -esters with Aryl Bromides.
The first cross-coupling of secondary alkyl β-trifluoroboratoketones and -esters has been achieved through application of photoredox/nickel dual catalysis. Although the related β-trifluoroboratoamides have been effectively cross-coupled via Pd-catalysis, the corresponding ketones and esters had proven recalcitrant prior to this report. Reactions occur under mild conditions, and a variety of functional groups and sterically and electronically diverse reaction partners are tolerated.


Long-term histopathologic and morphologic changes after thermal endometrial ablation.
To outline long-term histologic features of endometrial ablation. Prospective longitudinal study (Canadian Task Force classification II-3). Tertiary-care teaching hospital. Twenty-six patients. Thermal ablation followed by second-look office hysteroscopy with endometrial biopsy. Mean follow-up time to second-look hysteroscopy after ablation was 33.4 +/- 2,1 months. Complete atrophy, partial adhesions or obliteration of the cavity, and fibrosis were observed at second-look hysteroscopy. Whereas all random biopsies were normal before ablation, biopsies after ablation revealed diminished endometrial glands with necrosis and scarring. The number of endometrial glands was not correlated with amount of bleeding or menstrual pattern. No premalignant or malignant lesions were found after ablation. Although efficacy of endometrial ablation is related to initial thermal destruction and correlated with postablation hysteroscopic and histologic findings, endometrial regrowth is an expected development, not a failure of ablation.


The Development and Content Validation of the Care Partner Hospital Assessment Tool.
When aging adults are hospitalized due to a major health event, they often turn to care partners ('family members or friends') for support. Assessment of care partners' needs during hospital care may be important to inform and target information and skills training that will equip them to fulfill caregiving tasks for the aging adults. The objectives of this study were to develop and complete content validation of the Care Partner Hospital Assessment Tool (CHAT). Based on standard instrumentation methodology and an assessment framework recommended by the National Center on Caregiving at the Family Caregiving Alliance, three steps were followed to develop and validate CHAT: (1) generation of a 24-item tool grouped into three content domains (background, plans and preferences, skills and supports), and a survey by a multidisciplinary team, (2) administration of an online survey of care partners and experts, and (3) assessment of item and scale-content validity indices (I-CVI and S-CVI). A total of four care partners that provide unpaid care to a family member or friend age 65 years or older with a chronic illness or disability either before or after a hospitalization, and 19 leading experts in gerontology, caregiving, and health services completed an online survey in English. Twenty-two items were accepted by having an I-CVI at or above the acceptable 78% cut point; the S-CVI for the tool was 85%. Most revisions to the tool were associated with modifying or clarifying language within each item. For example, participants shared the following open-ended suggestions for revising CHAT: (1) change the "do you prefer" sentence stem to "do you want" (n = 12), define "training" (n = 6), and (2) allow care partners to provide an unsure response (n = 5). CHAT may be a promising way to increase health care practitioner's understanding of care partners' backgrounds, preferences and plans, and potential information or training needs during a patient's hospital stay. Initial evaluation of CHAT reveals strong conceptual development and content validity.


[Interdisciplinary multimodal pain therapy under the protective measures of the COVID-19 pandemic : Analysis and progress report].
Due to the COVID-19 pandemic, elective medical services have had to be reduced to a minimum, which has also affected care in pain medicine. Following these drastic cutbacks, a cautious resumption of elective care is planned. This also applies to the delivery of inpatient and day-care interdisciplinary multimodal pain therapy (IMPT). Since the majority of pain medicine centers have been closed to date, the question has arisen as to whether a resumption of regular care can be easily provided under the required protective measures. To answer this question, the authors conducted a survey among patients that were in a position to make a direct comparison between IMPT under normal conditions as well as under the currently required protective measures. The survey recorded the level of disruption caused by the different protective measures in the various treatment modules. An evaluation of the questionnaires, which were completed by two patient groups and all therapists involved, revealed that interdisciplinary multimodal pain therapy is possible without significant impairments even under the required protective measures. In particular, wearing protective masks proved to be the protective measure with the greatest negative impact. However, options like the use of protective visors or relocating treatment modules to the outdoors offer practicable alternative solutions for protection. Both patient and therapist satisfaction was high despite these constraints, and personal concern regarding possible infection low.


Changes in oral corticosteroid use in asthma treatment-A 20-year Danish nationwide drug utilisation study.
Oral corticosteroids (OCS) are used in asthma management but can cause serious adverse effects. We aimed to investigate the usage trends in a nationwide asthma cohort in Denmark from 1999 to 2018. Using national registers, we identified young adults (18-45 years) with two or more asthma drug collections within 12 months since the age of 15 years as indicative of active asthma. OCS exposure level was stratified as high use (≥5 mg prednisolone/day/year) and low use (<5 mg/day/year). Lorenz curves were computed to illustrate potential skewness of consumption among the OCS users. We identified 318 950 individuals with a median age of 29 years (IQR 20-38 years) whereof 57% were women. The 1-year prevalence of OCS users was stable at 4.8% (median, IQR 4.7%-4.8%), but with nearly 40% decrease in high-users from 0.54% in 1999 to 0.33% in 2018. The median annual exposure decreased from 500 mg/year (1999) to 250 mg/year (2018). We found a substantial skewness in the distribution of OCS usage with 10% of users accounting for almost 50% of all OCS use. The prevalence of OCS users among young adults with active asthma has been relatively stable from 1999 to 2018, but with a decreasing prevalence of high-users and annual consumption.


Silver-Decorated TiO2 Inverse Opal Structure for Visible Light-Induced Photocatalytic Degradation of Organic Pollutants and Hydrogen Evolution.
TiO2 inverse opal (TIO) structures were prepared by the conventional wet chemical method, resulting in well-formed structures for photocatalytic activity. The obtained structures were functionalized with liquid flame spray-deposited silver nanoparticles (AgNPs). The nanocomposites of TIO and AgNPs were extensively characterized by various spectroscopies such as UV, Raman, X-ray diffraction, energy-dispersive spectroscopy, and X-ray photoelectron spectroscopy combined with microscopic methods such as scanning electron microscopy, transmission electron microscopy (TEM), and high-resolution TEM. The characterization confirmed that high-quality heterostructures had been fabricated with evenly and uniformly distributed AgNPs. Fabrication of anatase TiO2 was confirmed, and formation of AgNPs was verified with surface plasmon resonant properties. The photocatalytic activity results measured in the gas phase showed that deposition of AgNPs increases photocatalytic activity both under UVA and visible light excitation; moreover, enhanced hydrogen evolution was demonstrated under visible light.


What advice do patients with infectious mononucleosis report being given by their general practitioner?
The aim of this study was to describe the advice that patients with acute infectious mononucleosis recall having been given by their general practitioner (GP; family or primary care doctor). Individuals with a recent diagnosis of infectious mononucleosis were recruited for a randomised controlled trial assessing the effectiveness of a brief educational intervention on recovery. All participants were asked at their initial assessment what advice that they had been given by their GP. They were not given any prompts and were free to give several responses. Responses were grouped into various themes. Seventy-one patients took part. Of these, 11 (15%) recalled being given no specific advice. Of the remaining 60 participants, 70% recalled being given advice to rest, or to "take it easy", usually without any qualification; 10% recalled being given dietary advice, and 17% advice on simple symptom management. The majority of individuals with recent onset infectious mononucleosis recall being given advice to rest by their GPs. This finding is discussed in relation to evidence suggesting that rest may be unhelpful.


Use of micro-CT-based finite element analysis to accurately quantify peri-implant bone strains: a validation in rat tibiae.
Although research has been addressed at investigating the effect of specific loading regimes on bone response around the implant, a precise quantitative understanding of the local mechanical response close to the implant site is still lacking. This study was aimed at validating micro-CT-based finite element (μFE) models to assess tissue strains after implant placement in a rat tibia. Small implants were inserted at the medio-proximal site of 8 rat tibiae. The limbs were subjected to axial compression loading; strain close to the implant was measured by means of strain gauges. Specimen-specific μFE models were created and analyzed. For each specimen, 4 different models were created corresponding to different representations of the bone-implant interface: bone and implant were assumed fully osseointegrated (A); a low stiffness interface zone was assumed with thickness of 40 μm (B), 80 μm (C), and 160 μm (D). In all cases, measured and computational strains correlated highly (R (2) = 0.95, 0.92, 0.93, and 0.95 in A, B, C, and D, respectively). The averaged calculated strains were 1.69, 1.34, and 1.15 times higher than the measured strains for A, B, and C, respectively, and lower than the experimental strains for D (factor = 0.91). In conclusion, we demonstrated that specimen-specific FE analyses provide accurate estimates of peri-implant bone strains in the rat tibia loading model. Further investigations of the bone-implant interface are needed to quantify implant osseointegration.


Arrestin2 and arrestin3 are differentially expressed in the rat brain during postnatal development.
Arrestins are adaptor proteins involved in homologous desensitization and trafficking of G protein-coupled receptors. Arrestins bind to activated phosphorylated receptors thus precluding further signal transduction. Two subtypes of non-visual arrestins, arrestin2 and arrestin3, have been cloned. Recently, specificity of various receptors to arrestins and differences in kinetics of receptor desensitization mediated by arrestins have been demonstrated. Both arrestins are expressed in the rat brain. However, quantitative assessment of their expression and detailed distribution are lacking. Here, we used quantitative ribonuclease protection assay and western blot to measure arrestin2 and arrestin3 mRNA and protein in the rat brain during postnatal development. In situ hybridization histochemistry was employed to study the detailed distribution of arrestin mRNAs in the adult and developing brain. Both arrestins were expressed from birth in all regions studied. Arrestin2 mRNA levels increased with development until the 14th postnatal day and then decreased, whereas arrestin2 protein levels continued to rise. Arrestin3 mRNA was maximal in neonates and then decreased, while arrestin3 protein changed little. In newborns and adults, the concentration of arrestin2 mRNA was two- to three-fold higher than that of arrestin3. In neonates, the excess of the arrestin2 protein over arrestin3 was commensurate with the excess of the arrestin2 mRNA (three-fold) but in the adult, the ratio was much higher (10-20-fold). Each arrestin demonstrated a unique distribution, although in many areas there was overlap suggesting co-localization. Both arrestins were highly expressed in the cortex and hippocampus. Arrestin2 was abundant in the thalamus, particularly in the anterior, intralaminar, and midline nuclei, while arrestin3 was abundant in the medial habenular. Arrestin3 was relatively abundant in most hypothalamic nuclei and extended amygdala. In the developing brain, arrestin3 was highly expressed in the subventricular zone, whereas arrestin2 was more abundant in differentiated areas. Our data demonstrate that arrestin2 is the major arrestin subtype in the rat brain, although arrestin3 is expressed in specific cell populations including postnatal proliferative zones. Because each arrestin appears to mediate receptor desensitization in a specific way, different kinetics of trafficking of the same receptor should be expected in different cells due to varying arrestin2/arrestin3 ratios. Thus, the response of receptors to specific drugs stimulating or blocking these receptors may depend on complement of arrestins in their target cells.


Multiple, large aneurysms of pulmonary arteries in Behçet's disease. Clinical remission and radiologic resolution after corticosteroid therapy.
We describe the case of a young European woman with Behçet's disease, hemoptysis, and multiple, large aneurysms of pulmonary arteries as confirmed by computed tomographic scan and angiography. Complete resolution of hemoptysis and radiologic signs of pulmonary artery aneurysms was observed three months after prednisone treatment, and a persisting remission was noted after ten months. We reviewed the literature on this rare complication and described the therapeutic approaches.


The characteristic phenotype of distal 9q3 trisomy is due to duplication of band 9q32.
In this report we describe a 6-month-old female child with inverted duplication of bands 9q32-9q33. The phenotypic findings are identical to the clinical syndrome previously reported to be associated with 9q31-9q32 duplication. The findings in the present child indicate that the minimal segment of overlap in this partial trisomy syndrome is 9q32.


Distal muscle weakness is a common and early feature in long-term enzyme-treated classic infantile Pompe patients.
Enzyme replacement therapy (ERT; alglucosidase alfa) has improved the prospects for patients with classic infantile Pompe disease considerably. However, over time we noticed that many of these children exhibit distal muscle weakness at an early age, which is in contrast to the primarily proximal and axial muscle weakness in patients with late-onset Pompe disease. This was reason to study the prevalence and severity of distal muscle weakness, and the sequence of muscle involvement over time in patients that had learned to walk under ERT. In this prospective, single-center cohort study, we studied 16 classic infantile patients. We used video recordings that were made during regular standardized assessments to investigate distal muscle function (active dorsiflexion of the feet during walking; ability to use a pincer grasp/actively extend the fingers) and proximal muscle function (standing up from a supine position; raising the arms above the head). Median age at start of ERT was 3.2 months (0.1-5.8 months), median age at study end was 5.6 years (2.9-18.2 years). Six patients (6/16, 38%) initially had no evident signs of distal muscle weakness and developed a gait with active dorsiflexion of the feet. The other 10 patients never exhibited active dorsiflexion of the feet during walking. At study-end two patients showed no loss of distal muscle function. A subset of five patients (5/16, 31%) developed also weakness of the hands, particularly of the extensors of the 3rd and 4th digit. We found that the majority (14/16, 88%) of patients who had learned to walk exhibited distal muscle weakness of the lower extremities, while a subset (5/16, 31%) also developed weakness of the hands. The distal muscle weakness was often more serious than, and preceded the development of, the proximal muscle weakness.


Sparing of the familiarity component of recognition memory in a patient with hippocampal pathology.
Subject KN has a persistent anterograde amnesia as a result of brain injury following meningitis in 1993. MRI scans reveal a bilateral decrease in the volume of his hippocampal region (dentate gyrus, CA1-4, subicular cortices) of approximately 45% in both the right and left hemispheres, although the volume of his perirhinal cortex appears normal. Aside from some changes to his occipital lobe and bilateral shrinkage of the amygdala, the rest of his brain appears normal on recent quantitative MRI scans. A striking feature of his memory loss is his ability to perform at normal levels on some tests of recognition, despite his consistent deficit on tests of recall. Two tests designed specifically to distinguish performance of two putative divisions of recognition memory (the Remember/Know procedure and the use of receiver operating characteristics to distinguish familiarity and recollection), provide evidence for a selective sparing of the familiarity component of recognition. The dissociation within recognition memory supports dual-process models of recognition, and also supports proposals that anatomically linked regions within the medial temporal lobe make qualitatively different contributions to recognition.


A spatio-temporal analysis of fire occurrence patterns in the Brazilian Amazon.
Wildfires in the Amazon significantly impact the forest structure and carbon cycle. Understanding the patterns of fire occurrence is crucial for effective management. A novel spatio-temporal point process framework was used to analyze changes in fire occurrence patterns in the Brazilian Amazon. A dynamic representation of a Log Gaussian Cox process was used to model the intensity function, which was decomposed into trend, seasonality, cycles, covariates, and spatial effects. The results show a marked decrease in long-term fire occurrence movements between the start of the sample and 2012, followed by an increase until the end of the sample, attributed to governance measures and market mechanisms. Spatial variability of fire occurrence rates in the Brazilian Amazon was successfully captured, with regions having more dry seasons experiencing higher fire occurrence rates. This analysis provides valuable insights into fire occurrence patterns in the Amazon region and the factors driving them.


Frequent occurrence of familial aggregations of high lipoprotein(a) levels associated with small apolipoprotein(a) isoforms.
School-age children with high lipoprotein(a) [Lp(a)] levels were screened and family studies were conducted to examine the relationship between high Lp(a) levels and apolipoprotein(a) [apo(a)] isoforms in families. All the probands from 17 families had one of the A2 to A12 apo(a) isoforms, which are the smaller apo(a) isoforms of the 25 different isoforms thus far detected. The ratio of subjects with high plasma Lp(a) levels was 0.47 among the first-degree relatives. All 15 relatives with high plasma Lp(a) levels shared one of the small apo(a) isoforms with the proband in each family, while 16 of 17 relatives with normal Lp(a) levels did not. These data indicate the frequent occurrence of familial aggregations of high Lp(a) levels associated with one of the small apo(a) isoforms.


Effect of temperature on stability of marker constituents in Echinacea purpurea root formulations.
Stability of an alkamide and a phenolic phytochemical marker in a hydro-alcoholic extract of Echinacea purpurea root and a dried powder prepared by evaporation of the extract was assessed in storage for 7 months at three temperature regimes: -20, 25 and 40 degrees Celsius. In the extract, the major alkamide, dodeca-2E, 4E, 8Z, 10E/Z-tetraenoic acid isobutyl amide, was not significantly affected by storage at any of the temperatures, but cichoric acid content declined as significantly (P = 0.05) at both 25 degrees C and 40 degrees C as compared to low-temperature storage. In the powder, the major alkamide showed a significantly reduced level at 25 degrees C and 40 degrees C while cichoric acid did not decline significantly. These results suggest that more attention should be given to the effect of formulation and temperature on storage of Echinacea products.


GABA A receptors are associated with retinal ganglion cell death induced by oxidative stress.
A previously proteomic study from our laboratory showed that the expression of the protein of the GABA A receptor beta1 subunit was significantly increased in the retina of EAAC1-deficient (EAAC1-/-) mice, a mouse model of glaucoma. The purpose of this study was to investigate the role played by GABA A receptor beta1 subunit in the death of retinal ganglion cells (RGCs) caused by oxidative stress. The retinal sites and expression pattern of GABA A receptor beta1 subunit were determined by immunohistochemistry in the retina of ICR mice. A RGC line, RGC-5, was exposed to GABA A receptor agonist and antagonist, and the cell viability was determined by the MTS assay. The effect of GABA A receptor antagonist on the death of RGCs, and the activation of oxidative stress signaling induced by hydrogen peroxide was investigated. Our results showed that the GABA A receptor beta1 subunit was expressed on the RGCs of ICR mice. GABA A receptor agonist induced RGCs death, and this death was inhibited by bicuculline, a GABA A receptor antagonist. The hydrogen peroxide-induced death of RGCs was reduced by GABA A receptor antagonist, and the oxidative stress signaling activated by hydrogen peroxide was also inhibited. These results indicate that GABA A receptors are expressed on RGCs and may play a role in the death of RGCs induced by oxidative stress.


Palbociclib and letrozole in hormone-receptor positive advanced breast cancer: Predictive response and prognostic factors.
CDK 4/6 inhibitors have been yielding propitious results when with hormone therapy in the management of Her2-negative and hormone-receptor (HR)-positive metastatic breast cancer, palbociclib being one of the first molecules investigated in this setting. However, the response to CDK4/6 inhibitors is variable. To identify predictive and prognostic factors of response to this therapeutic regimen. Eligible patients were females with HR+ and Her2- advanced breast cancer, receiving Palbociclib in combination with Letrozole. PFS was the primary endpoint in the evaluation of response to treatment. This survival was then further segregated according to various characteristics: histological (type, grade, hormone receptors), metastatic site, line of treatment, response type at initial assessment, and best response achieved. The data was then processed by two statistical analysis models: Kaplan-Meier and univariate preceding multivariate Cox proportional risks. Sixty patients were included and followed for a median follow-up duration of 15.98 months. PFS recorded a median of 19.07 months (95% CI=15.43-22.71). PFS had a median of 12.99 months in the absence of progesterone receptors (vs 20.05 months in the case of positive estrogen and progesterone receptors; P = 0.046), a median of 13.02 months in the presence of liver metastases (vs 22.98 months in the absence of liver metastases; P = 0.007), and 15.94 months in the case of second-line and beyond (vs 22.98 months in the case of first-line; P = 0.033). Regarding the Hazard Ratio of progression, we note age (HR 0.941; P = 0.019), liver metastases (HR 2.751; P = 0.051), response at initial evaluation (HR<1; P < 0.001) and best response (HR<1; P = 0.003). PFS reached similar figures to those of international studies. The absence of progesterone receptors, presence of liver metastases, and use as second-line or beyond are associated with a reduced median PFS. One year age increase (protective factor), liver metastases (risk factor), response at initial evaluation, and best response achieved are identified as the most predictive factors of the response to this treatment regimen and of the progression risk.


Assessment of RET/PTC oncogene activation in thyroid nodules utilizing laser microdissection followed by nested RT-PCR.
Single palpable nodules of the thyroid gland are common in clinical practice; the majority of such lesions are benign. However, noninvasive thyroid nodules that exhibit borderline morphological signs of papillary cancer represent a diagnostic challenge. Rearrangements of the RET oncogene have been proposed as a marker for papillary thyroid cancer. In this chapter, methods for the analysis of the RET oncogene in laser microdissected papillary thyroid cancer tissue are described.


Effect of omeprazole on gastric acid secretion in rat: evaluation of dose, duration of effect, and route of administration.
The effect of omeprazole on gastric acid output was studied in rats before and during stimulation by continuous administration of tetragastrin at 50 micrograms/kg-hour. From 5 to 20 mg/kg of omeprazole was given to animals intraperitoneally, perorally and intravenously from 2 to 24 hours before the gastric secretory study was started, and the respective effects on acid secretion were compared. In each administration group, 20 mg/kg of omeprazole was the most potent among the groups receiving 5, 10 or 20 mg/kg, when the drug was given 2 hours before the study. There were statistically significant differences between the control group given tetragastrin only and each of the groups given 20 mg/kg of omeprazole perorally, intraperitoneally and intravenously. There was no significant difference among the groups given 20 mg/kg of omeprazole intraperitoneally, intravenously and perorally. The effect of 20 mg/kg of omeprazole continued at least 24 hours after the agent was administered perorally.


More than cool: promiscuous relationships of menthol and other sensory compounds.
Several temperature-activated transient receptor potential (thermoTRP) ion channels are the molecular receptors of natural compounds that evoke thermal and pain sensations. Menthol, popularly known for its cooling effect, activates TRPM8--a cold-activated thermoTRP ion channel. However, human physiological studies demonstrate a paradoxical role of menthol in modulation of warm sensation, and here, we show that menthol also activates heat-activated TRPV3. We further show that menthol inhibits TRPA1, potentially explaining the use of menthol as an analgesic. Similar to menthol, both camphor and cinnamaldehyde (initially reported to be specific activators of TRPV3 and TRPA1, respectively) also modulate other thermoTRPs. Therefore, we find that many "sensory compounds" presumed to be specific have a promiscuous relationship with thermoTRPs.


Effect of isolated inferior oblique muscle myectomy in the management of superior oblique muscle palsy.
Thirty-three patients with superior oblique palsy were treated with an inferior oblique myectomy temporal to the inferior rectus muscle. The mean effect of surgery was 11.91 +/- 1.38 in all positions of gaze and for all age groups. The operative result in both children and adults was the same. The mean effect of surgery correlated with the size of the preoperative hyperdeviation in the fields of action of both inferior and superior oblique muscles. Inferior oblique muscle myectomy was followed by return of normal function to the superior oblique muscle in 63% of cases. Ocular torticollis was eliminated in 90% of the patients. Persistent overaction of inferior oblique muscle was encountered in three patients. Postoperative underaction of the myectomized muscle was not observed in any of our patients. A myectomy is recommended as a primary procedure in patients with superior oblique muscle palsy when the direct antagonist is overacting and the hyperdeviation is 10 to 15 prism diopters or more in primary position or the fields of action of the paretic superior oblique muscle or the overacting inferior oblique muscle.


[The adherence in the treatment of chronic hepatitis C].
The most effective therapy for patients with chronic hepatitis C is combined therapy with pegylated interferon plus ribavirin. Adherence has been shown to enhance the sustained viral response (SVR) in patients receiving standard or pegylated interferon plus ribavirin. Treatment - related side effects affects on treatment quality of life and impact upon the ability of a patient to adhere to treatment. It is essential that they are managed quickly and effectively. In the work authors presented side effect of the therapy of chronic hepatitis C and management of this side effects providing to reduction them.


The Synthesis of 1,3,5-triazine Derivatives and JNJ7777120 Analogues with Histamine H4 Receptor Affinity and Their Interaction with PTEN Promoter.
The involvement of histamine and H4 receptor (H4 R) in cancer has been investigated recently using the H4 R agonists and antagonists. The scope of the research project was synthesis and exploration of the consequences of a group of compounds with histamine H4 receptor (H4 R) affinity on the promoter of PTEN gene encoding the antitumor PTEN protein. The series of novel compounds based either on H4 R antagonists JNJ7777120 structure or 1,3,5-triazine scaffold were synthesized, evaluated for histamine H4 R affinity and used in this study. Compounds 5 and 7 belonging to the group of JNJ7777120 analogues showed the highest interaction with the promoter of PTEN gene and weak affinity against H4 R with Ki value >100 μm. These compounds showed no significant effect on neuroblastoma IMR-32 cells viability indicating no correlation between PTEN gene promoter affinity and antitumor activity. Compound 6, another JNJ7777120 analogue, showed the highest effect on IMR-32 viability with calculated IC50 = 23.27 μm. The 1,3,5-triazine derivatives exhibited generally low or medium interaction with PTEN gene promoter. However, the 1,3,5-triazine derivative 11 with the para-bromo substituent showed the highest affinity against H4 R with Ki value of 520 nm and may be considered as a new lead structure.


[Birth analgesia: late effects on newborn infants? (author's transl)].
Based upon scanty literature we discuss, whether unexpected fatal apneic spells of two full-term, apparently vigorous newborn infants at an age of 3 and 37 hours, respectively, may be related to Pethidine (+ Levallorphane) given to their mothers shortly before birth.


Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases.
We have studied the effect of an inhibitor of matrix metalloproleinases, BB-1101, on a delayed-type hypersensitivity (DTH) response in the CNS. We used a recently described model in which heat-killed bacillus Calmette-Guérin (BCG) sequestered behind the blood-brain barrier (BBB) is targeted by a T-cell mediated response after subcutaneous injection of BCG (Matyszak and Perry, 1995). The DTH lesions are characterised by breakdown of the BBB, macrophage and lymphocyte infiltration and tissue damage including myelin loss. Treatment with BB-1101, which is not only a potent inhibitor of matrix metalloproteinases but also strongly inhibits TNF-alpha release, dramatically attenuated the CNS lesions. Breakdown of the BBB and the recruitment of T-cells into the site of the lesion were significantly reduced. There were many fewer inflammatory macrophages in DTH lesions than in comparable lesions from untreated animals. There was also significantly less myelin damage (assessed by staining with anti-MBP antibody). The DTH response in animals treated with dexamethasone was also reduced, but to a lesser degree. No significant effect was seen after administration of pentoxifylline, a phosphodiesterase inhibitor with effects including the inhibition of TNF-alpha production. Our results suggest that inhibitors of matrix metalloproteinases may be of considerable therapeutic benefit in neuroinflammatory diseases.


Childhood monosomy 7 revisited.
Monosomy 7 is found in acute myeloid leukaemia (AML) and myelodysplasia and is characteristic of a rare chronic myeloproliferative disease (MPD) of young children. We have seen 16 children with monosomy 7. Their clinical features and response to treatment are discussed. Monosomy 7 diseases appear to have a particularly poor prognosis. The AML is often resistant to treatment and relapse is common. Children with chronic MPD die of bone marrow failure or evolve to AML or myelofibrosis. We have treated these children intensively with combination chemotherapy and allogeneic bone marrow transplantation. Four children with MPD received supportive care and low dose chemotherapy alone. They all died, surviving between 4 months and 4 years. Six children with MPD received intensive chemotherapy: three remitted, one relapsing after 9 months, the others remaining in remission at 18 months and 3 years. One child with MPD has undergone successful BMT and survives 7 1/2 years after presentation. Remission was achieved in three of four cases of AML. They all relapsed within 9 months. Bone marrow transplantation was successful in one child with myelofibrosis. Intensive chemotherapy and early bone marrow transplantation is likely to offer these children their best chance of survival.


Block of some non-adrenergic inhibitory responses of smooth muscle by a substance from haemolysed erythrocytes.
1. A preparation of haemolysed rat erythrocytes (the haemolysate) blocked the relaxations of both the bovine retractor penis and the rat anococcygeus muscles in response to field stimulation of their non-adrenergic inhibitory nerves. The effective concentration range was 5-20 mul./ml. of haemolysate, equivalent to 0.25-1.0 mul./ml. of blood. The active principle in the haemolysate was a non-dialysable, heat-labile material of molecular weight between 50,000 and 100,000 daltons. If, as appeared probable, the active component of the haemolysate was oxyhaemoglobin, its effective blocking concentration was 0.5-2 muM.2. Haemolysate (5-20 mul./ml.) also blocked the relaxation of both the bovine retractor penis and the rat anococcygeus to the inhibitory factor extracted from the bovine retractor penis, an observation supporting the possibility that this inhibitory factor may be the transmitter released by the inhibitory nerves in these tissues. In the bovine retractor penis, haemolysate was also effective in blocking relaxations in response to sodium nitroprusside, but relaxations produced by prostaglandin E(1) or isobutylmethylxanthine were unchanged or only slightly reduced.3. In contrast, in the taenia of the guinea-pig caecum, haemolysate did not block the non-adrenergic inhibitory response to field stimulation, nor the relaxation produced by ATP, although it did block the relaxation produced by the inhibitory factor.4. In spiral strips of isolated rabbit aorta, haemolysate (10 mul./ml.) increased the contraction produced by noradrenaline and blocked the relaxation produced by the inhibitory factor. These were shown to be independent effects.5. Apamin, which blocked the relaxation of the taenia of the guinea-pig caecum elicited by either ATP or field stimulation of its non-adrenergic nerves, was without effect on relaxations of the bovine retractor penis or rat anococcygeus muscles in response to field stimulation of inhibitory nerves or to inhibitory factor.6. These differences in the blocking effects of apamin and haemolysate suggest either that the transmitter in the bovine retractor penis and rat anococcygeus differs from that in the guinea-pig taenia, or, if the transmitter is the same, then its mechanism of action differs.


Exploring the Unmet Needs of Postpartum Mothers: A Qualitative Study.
This study aimed to identify unmet needs of mothers in the postpartum period. Semi-structured telephone interviews were conducted two weeks postpartum with a convenience sample of 26 mothers who gave birth at an academic medical center. Topics included mothers' concerns, levels of preparedness, educational needs and preferences during antepartum, labor and birth, and postpartum periods. Data were qualitatively analyzed using NVivo and a combination of open coding and theoretical coding, based on the Perinatal Maternal Health Promotion Model. Three major themes emerged: concerns, expectations, and positive coping strategies, with variations by previous maternal experience. Findings suggest the need for different models of care with more anticipatory, mother-centered care to better meet mothers' needs and enhance postpartum outcomes and breastfeeding success.


Editorial Commentary: The Nonoperative Instability Severity Index Score Can, in Part, Help to Predict Failure After Nonoperative Management of Anterior Shoulder Instability: Fix Them All Versus Wait and See?
The optimal management of anterior shoulder instability remains a heated topic of debate, particularly after first-time shoulder dislocation. From expedited rehabilitation to arthroscopic Bankart repair and Latarjet coracoid transfer, the shoulder community has staunchly defended its approach with carefully tailored data describing patient satisfaction, instability recurrence, revision surgery, and timeline to return to play or preinjury activity. However, not all patients require surgical stabilization, and a "wait-and-see" approach can often result in favorable outcome. The Nonoperative Instability Severity Index Score has been proposed as a unique tool to stratify risk for failure among athletes after an anterior shoulder instability event. While not a standalone tool for predicting further shoulder dislocation in a broader athletic population, the Nonoperative Instability Severity Index Score reflects a movement toward personalized medicine, where clinical decision making is executed on the individual level based on unique risk factors and circumstances.


ATP dependence of NHE-1, the ubiquitous isoform of the Na+/H+ antiporter. Analysis of phosphorylation and subcellular localization.
ATP is not hydrolyzed during the transport cycle of the Na+/H+ exchanger (NHE), yet depletion of the nucleotide drastically reduces the rate of cation exchange. The mechanism underlying this inhibition was investigated in fibroblasts transfected with NHE-1, the growth factor-sensitive isoform of the antiport. NHE-1 was found to be phosphorylated in serum-starved, unstimulated cells. Acute ATP depletion induced a profound inhibition of transport without detectable changes in NHE-1 phosphorylation. Analysis of cells transfected with truncated mutants of NHE-1 indicated that the carboxyl-terminal cytosolic domain of the antiport is required for expression of its ATP dependence. To define whether inhibition of Na+/H+ exchange resulted from internalization of NHE-1, extracellularly exposed proteins were labeled with impermeant biotin derivatives. The proportion of NHE-1 exposed to the surface was comparable before and after ATP depletion. Immunofluorescence determinations revealed focal accumulations of NHE-1 on the membrane of untreated cells. NHE-1 redistributed following ATP depletion, showing a more homogeneous localization. F-actin, which co-localizes with the antiport in untreated cells, also redistributed when cells were ATP depleted. These findings suggest an interaction of NHE-1 with the cytoskeleton. Accordingly, disassembly of actin filaments with cytochalasin D induced redistribution of the antiport. However, Na+/H+ exchange activity was unaltered by cytochalasin D. We propose that ancillary proteins confer ATP sensitivity to the antiporter and may also mediate its association with the cytoskeleton. Depletion of the nucleotide would alter the interaction between NHE-1 and the putative regulator, inhibiting Na+/H+ exchange and inducing subcellular redistribution. However, disruption of the cytoskeleton at distal sites, such as induced by cytochalasins, is insufficient to inactivate the antiport.


Fibrinogen-templated gold nanoclusters for fluorometric determination of cysteine and mercury(II).
Gold nanoclusters (Au NCs) using fibrinogen (FBG) protein as template are fabricated via one-pot reduction strategy, and applied for fluorometric detections of cysteine (Cys) and mercury(II). The modified FBG-Au NCs exhibit red fluorescence, with excitation/emission maxima at 360/620 nm, a 7% quantum yield, and a 2.2 μs decay time. The fluorescence of the nanoprobe is quenched by Cys and Hg(II). Cys can be determined by fluorometry in the 0.01 to 150 μmol L-1 concentration range and with a detection limit of 0.79 μmol L-1. Due to the oxidation of Hg(II), it can be detected in the 0.01 to 10 μmol L-1 concentration range. The properties of the FBG-Au NCs and the analytical performance are comparable with previously reported peptide/protein-templated Au NCs, supplying a promising candidate for Au NCs nanoprobes synthesis and applications. Graphical abstractSchematic representation of the preparation of gold nanoclusters (Au NCs) using fibrinogen (FBG) as the template. The modified Au NCs were applied to the fluorometric detection of cysteine (Cys) and mercury ion (Hg(II)).


Comparison of phosphorylation and assembly of photosystem complexes and redox homeostasis in two wheat cultivars with different drought resistance.
Reversible phosphorylation of proteins and the assembly of thylakoid complexes are the important protective mechanism against environmental stresses in plants. This research was aimed to investigate the different responses of the antioxidant defense system and photosystem II (PSII) to osmotic stress between drought-resistant and drought-susceptible wheat cultivars. Results showed that the decrease in PSII photochemistry and six enzyme activities was observed in drought-susceptible wheat compared with drought-resistant wheat under osmotic stress. In addition, a lower accumulation of reactive oxygen species (ROS) and cell death were found in the resistant wheat compared with the susceptible wheat under osmotic stress. Western blot analysis revealed that osmotic stress led to a remarkable decline in the steady state level of D1 protein in drought-susceptible wheat. However, the CP29 protein was strongly phosphorylated in drought-resistant wheat compared with the susceptible wheat under osmotic stress. Our results also showed that drought-resistant wheat presented higher phosphorylated levels of the light-harvesting complex II (LHCII), D1, and D2 proteins and a more rapid dephosphorylated rate than drought-susceptible wheat under osmotic stress. Furthermore, the PSII-LHCII supercomplexes and LHCII trimers were more rapidly disassembled in drought-susceptible wheat than the drought-resistant wheat under osmotic stress. These findings provide that reversible phosphorylation of thylakoid membrane proteins and assembly of thylakoid membrane complexes play important roles in plant adaptation to environmental stresses.


First report on facultative parthenogenetic activation of eggs in sterlet sturgeon, Acipenser ruthenus.
This study reported facultative parthenogenetic cleavage development of sterlet sturgeon Acipenser ruthenus eggs and quantified the percentage of parthenogenetically developed eggs in relation to the fertilization ability of different females. When eggs were activated in freshwater, 5.1-13.7% of eggs developed parthenogenetically, while among those activated eggs 3.6-9.4% developed to 2 cells, 0.4-4.5% developed to 4 cells, and 0-0.8% developed to 8 cells. The mean percentage of fertilized and parthenogenetically activated eggs among the females was negatively correlated (R(2)=0.71, p=0.036), which indicates that parthenogenetic activation rate of sterlet eggs depends on the quality of eggs in terms of fertilization rate.


Factors to consider in performing survival studies with insect cells.
Insect cell lines are not well-suited to colony formation in liquid medium following low-density cell plating. The present studies demonstrate that the time of addition of fetal bovine serum to the culture medium and the number of gamma-irradiated feeder cells added to each plate are important factors in developing a useful colony formation assay. TN-368 lepidopteran and WR69-DM-1 dipteran cell lines were used for these experiments. Both cell types display increased plating efficiencies if serum is added to the medium one or more days prior to plating as compared to adding serum immediately before plating. Growth curves obtained by seeding cells at higher densities also indicate that cell growth is slightly better if serum is added one or more days before seeding. These findings are especially important for survival and toxicity studies because the results demonstrate that even seemingly minor factors involved in cell survival assays may benefit treated cells to a greater degree than untreated control cells, thus providing an erroneous assessment of cell survival.


Quantification of diffusion distance within the spongy myocardium of hearts from antarctic fishes.
We developed a stereological method for quantifying diffusion distance within spongy myocardium. Using this method we compared the hearts of three species of Antarctic fishes that vary in expression of oxygen-binding proteins. We examined hearts from Gobionotothen gibberifrons, a red-blooded species whose ventricle has myoglobin (Mb), and hearts of two species of icefish that lack hemoglobin (Hb) and vary in expression of cardiac Mb; Chionodraco rastrospinosus expresses Mb, Chaenocephalus aceratus does not. Average diffusion distance within ventricular tissue is greater in red-blooded Antarctic teleosts (9.82 + or - 1.37 microm) compared with icefish (C. rastrospinosus, 6.20 microm + or - 0.86; C. aceratus, 6.23 + or - 0.41 microm). Average diffusion distance to a mitochondrion parallels this trend because mitochondria are uniformly distributed within cardiac muscle. Results show that loss of Hb is correlated with increased trabeculation of heart ventricle. Loss of Mb however, is not correlated with an increase in trabeculation of ventricular tissue, despite significant differences in cellular ultrastructure compared with species that express the protein.


Reliability and validity of the quality of life-Alzheimer disease Chinese version.
To evaluate the psychometric properties of the quality of life-Alzheimer disease (QOL-AD) Chinese version in patients with dementia in mainland, China and to compare patient and caregiver reports of patient QOL. The QOL-AD Chinese version was established following standard guidelines for cross-cultural adaptation of measures. The reliability was assessed by internal consistency and test-retest reliability. The validity included construct and convergent validity. A paired Student t test was performed to determine differences between patient reports and caregiver reports. The reliability for both patient and caregiver reports on the QOL-AD was good (Cronbach α values of 0.66 and 0.87; intraclass correlation coefficients of 0.84 and 0.90 for patient and caregiver reports, respectively). The validity of patient and caregiver reports was supported by correlation with domain measures. All of the multitrait-multimethod correlations demonstrated a high relationship between patient reports and caregiver reports, ranging from 0.26 to 0.55. The caregivers rated patient QOL significantly higher than did the patients. The findings support the use of the Chinese version of the QOL-AD as a generic instrument to measure QOL of AD in mainland China. Further research is needed to clarify the relationship between patient and caregiver reports of patient QOL.


Amiloride-induced stimulation of HCO-3 reabsorption in turtle bladder.
Amiloride in the mucosal fluid (at concentrations of 5 . 10(-6) M to 10(-4) M) reversibly stimulates the HCO-3-dependent moiety of the short-circuiting current (Isc) in ouabain-treated turtle bladders bathed by Na-free Ringer solutions with or without Cl-. This effect is uniquely different from the known inhibitory effect of this agent on Na+ transport. Thus, any comprehensive hypothesis on the action of amiloride over a wide dosage-response range should take into account its effect on HCO-3 transport.


A metabolite of endophytic fungus Cadophora orchidicola from Kalimeris indica serves as a potential fungicide and TLR4 agonist.
To investigate the bioactive metabolite of endophytic fungus from Kalimeris indica. A strain ZJLQ336 was separated from the leaves of K. indica. It was identified as Cadophora orchidicola based on the phylogenetic analysis of ITS-rDNA sequences. From the fermentation broth a metabolite cercosporamide (compound 1) was isolated, and its structure was determined by spectroscopic analysis. Additionally, this compound was subjected to bioactivity assays, including antifungal activity against seven plant pathogenic fungi, as well as its potential immunoregulatory effects on HEK-BLUE™-hTLR4 cells, splenocytes and macrophages. The results showed that cercosporamide had strong growth inhibition against five common plant pathogenic fungi, including Pestalotia diospyri, Botrytis cinerea, Fusarium oxysporum, Sclerotium rolfsii and Penicillum digitatum with EC50 values of 5·29 × 10-3 , 0·61, 0·93, 2·89 and 6·7 μg ml-1 respectively. Among which S. rolfsii was one of the main pathogens in K. indica. Moreover, cercosporamide not only significantly stimulated TLR4 activation, splenocyte proliferation and production of cytokines, IFN-γ and TNF-α, but also up-regulated the production of TNF-α and NO in RAW264.7 macrophages clearly. This is the first report of endophytic C. orchidicola from K. indica and its metabolite cercosporamide. The results of pharmacological tests highlight the potential fungicide and TLR4 agonist of cercosporamide. This study indicates endophytic fungi are good resources for natural bioactive metabolites. It also suggests that cercosporamide is a potential fungicide and TLR4 agonist.


Serum models accurately predict liver-related clinical outcomes in chronic hepatitis C.
This study developed liver outcome scores in chronic hepatitis C (CHC) that directly predict liver-related death, hepatocellular carcinoma (HCC), and liver decompensation. Six hundred seventeen CHC patients were followed up for a mean of 6 years and randomized into a training set (n = 411) and a validation set (n = 206). Clinical outcomes were determined using a population-based data linkage system. In the training set, albumin, gamma-glutamyl transpeptidase, hyaluronic acid, age, and sex were in the final model to predict 5-year liver-related death (area under receiver operating characteristic curve [AUROC] 0.95). Two cut points (4.0 and 5.5) defined three risk groups with an incidence rate for liver-related death of 0.1%, 2%, and 13.2%, respectively (P < 0.001). Albumin, gamma-glutamyl transpeptidase, hyaluronic acid, age, and sex were used to predict 5-year liver decompensation (AUROC 0.90). A cut point of 4.5 gave a sensitivity of 94% and a specificity of 84% to predict 5-year decompensation and defined two groups with an incidence rate for decompensation of 0.2% and 5.8%, respectively (P < 0.001). Alkaline phosphatase, α2-macroglobulin, age, and sex were used to predict 5-year HCC occurrence (AUROC 0.95). A cut-point of eight had a sensitivity of 90% and specificity of 88% to predict 5-year HCC occurrence and defined two groups with an incidence rate for HCC of 0.2% and 5.6%, respectively (P < 0.001). Similar results were obtained using the validation set. All three liver outcome scores had excellent predictive accuracy and were able to stratify risk into clinical meaningful categories for CHC patients.


Fetal and uteroplacental haemodynamics during short-term atenolol treatment of hypertension in pregnancy.
Fetal circulation was studied by means of combined real-time and pulsed Doppler ultrasound in 14 women with pregnancy-associated hypertension before and during the first and third days of treatment with the beta 1-selective blocker, atenolol; in seven of the women the maternal uterine arcuate blood velocity waveform was also studied. Blood flow characteristics were normal both in the fetus and in the maternal arcuate artery, compared with those in uncomplicated pregnancies of corresponding gestational ages. Volume blood flow remained unchanged in the fetal descending aorta, and in the umbilical vein during atenolol treatment, whereas the pulsatility index increased in the fetal descending aorta and in the arcuate artery. This suggests that the peripheral vascular resistance, both on the maternal and fetal side of the placenta, increased during short-term antihypertensive treatment with atenolol.


[RELATIONS BETWEEN STANISŁAW ESTREICHER AND THE ACADEMY OF ARTS AND SCIENCES AND THE POLISH ACADEMY OF ARTS AND SCIENCES (IN THE LIGHT OF ITS FILES)].
Stanisław Estreicher, member of the Estreicher family, which rendered great service to Polish science and culture, was one of the most prominent Polish researchers in the history of law and vice-chancellor of the Jagiellonian University. This future professor for the first time appeared in the files of the Academy already in 1888. In 1914 he was elected associate member and in 1930--full member of the Academy. Because of his diverse interests, Estreicher's activity in the Academy included, i.a., his involvement with the Academy's authorities and the Department of History and Philosophy, his work dealing with general publications of the Academy, publishing his own writings and source editions, activity on the forums of six commissions, representing the Academy and giving opinions on scientific works to be published by the Academy. His involvement in the Academy was growing but these ties did not dominate his diverse activities. From the point of view of the Academy, the most of important was Professor Estreicher's participation in general publications' issues and his increasing influence on the institution's authorities, on the Department of History and Philosophy and the Legal Committee. On the other hand, from the point of view of Professor Estreicher himself, the most significant was "Polish Bibliography".


Endoscopic management of duodenal diverticular bleeding.
Although the presence of a duodenal diverticulum is usually asymptomatic, bleeding in this tissue is sometimes difficult to diagnose and treat. To investigate the strategy for treatment, we reviewed the clinical data of patients diagnosed and treated for duodenal diverticular bleeding. Retrospective case series. Single tertiary-referral center. Seven consecutive patients with bleeding from a duodenal diverticulum (mean age, 73.7 +/- 3.4 years old). The clinical characteristics, endoscopic findings, and treatment strategy for duodenal diverticular bleeding. All 7 patients achieved hemostasis. Six of 7 patients were treated endoscopically. There were no complications with endoscopic treatment. Three patients bled from diverticula located at the second portion of the duodenum, and 4 patients bled from that located at the third portion. In 6 of 7 patients, lesions were identified and treated endoscopically with hemoclips, hypertonic saline solution and epinephrine (HSE), and/or 1% polidocanol injection. In 1 case, the lesion could not be detected during the first endoscopic examination, and the patient, therefore, was treated with transarterial embolization followed by surgical resection. This preliminary case series described the feasibility of the endoscopic treatment. However, optimal management, including angiography and/or surgery, should be individualized to the patients, location, and type of hemorrhage. Bleeding from a duodenal diverticulum should be considered in the case of upper-GI bleeding of unknown origin. An endoscopy may be an effective alternative to surgery in the management of a bleeding duodenal diverticulum.


EBV noncoding RNA EBER2 interacts with host RNA-binding proteins to regulate viral gene expression.
Epstein-Barr virus (EBV) produces a highly abundant noncoding RNA called EBV-encoded RNA 2 (EBER2) that interacts indirectly with the host transcription factor paired box protein 5 (PAX5) to regulate viral latent membrane protein 1/2 (LMP1/2) gene expression as well as EBV lytic replication. To identify intermediary proteins, we isolated EBER2-PAX5-containing complexes and analyzed the protein components by mass spectrometry. The top candidates include three host proteins splicing factor proline and glutamine rich (SFPQ), non-POU domain-containing octamer-binding protein (NONO), and RNA binding motif protein 14 (RBM14), all reported to be components of nuclear bodies called paraspeckles. In vivo RNA-protein crosslinking indicates that SFPQ and RBM14 contact EBER2 directly. Binding studies using recombinant proteins demonstrate that SFPQ and NONO associate with PAX5, potentially bridging its interaction with EBER2. Similar to EBER2 or PAX5 depletion, knockdown of any of the three host RNA-binding proteins results in the up-regulation of viral LMP2A mRNA levels, supporting a physiologically relevant interaction of these newly identified factors with EBER2 and PAX5. Identification of these EBER2-interacting proteins enables the search for cellular noncoding RNAs that regulate host gene expression in a manner similar to EBER2.


Lipoprotein patterns in follicular fluid.
Samples of follicular fluid have been obtained from 23 women in order to evaluate the concentration of the different classes of lipoproteins. In the Authors' preliminary experience the determination of these biochemical parameters could help the diagnosis of LUF syndrome.


Occurrence in vivo of sister chromatid exchanges at the same locus in successive cell divisions caused by nonrepairable lesions induced by gamma rays.
The capacity of lesions induced by gamma radiation to produce sister chromatid exchanges (SCE) in successive divisions in mouse bone marrow cells in vivo was evaluated using a protocol for the three-way differentiation of sister chromatids. Evidence was obtained that exposure to gamma radiation induces DNA lesions that result in the formation of SCE at the same locus in two successive cell divisions. The relevance of this observation with respect to DNA repair and mutagenesis is discussed.


DNA-based assessment of root lesion nematode infections in cereal roots.
Root lesion nematodes (RLN) of the genus Pratylenchus are causing significant damage in cereal production worldwide. Due to climate change and without efficient and environment-friendly treatments, the damages through RLNs are predicted to increase. Microscopic assessments of RLNs in the field and the greenhouses are time-consuming and laborious. As a result, cereal breeders have mostly ignored this pest. We present a method measuring RLN in infected cereal roots using a standardized PCR approach. Publicly available Pratylenchus neglectus primer combinations were evaluated. An optimal primer combination for RT-qPCR assay was identified to detect and quantify P. neglectus within infected cereal roots. Using the RT-qPCR detection assay, P. neglectus could be clearly distinguished from other plant parasitic nematodes. We could identify P. neglectus DNA in barley and wheat roots as low as 0.863 and 0.916 ng/µl of total DNA, respectively. A single P. neglectus individual was detected in water suspension and within barley and wheat roots. The RT-qPCR detection assay provides a robust and accurate alternative to microscopic nematode identification and quantification. It could be of interest for resistance breeding, where large populations must be screened to detect and quantify P. neglectus in farmer's fields.


Regulated shuttling of the histone deacetylase HDAC5 to the nucleus may put a brake on cocaine addiction.
The histone deacetylase HDAC5 has been shown to regulate behavioral adaptations to cocaine. In this issue of Neuron, Taniguchi et al. (2012) describe a cAMP-dependent signaling pathway that regulates nuclear accumulation of HDAC5, suggesting a mechanism to couple cocaine with changes in HDAC5 function.


Undesired meeting of lymphocytes: organ-specific infiltration and the organization of ectopic lymphoid tissue in a murine experimental autoimmune gastritis.
Autoimmune diseases are caused by the misdirected attack of the immune system against the body's own components. Delicate balance between the activities of several CD4+ T cell subsets is crucial for determining the initiation of autoimmunity and disease state. In addition, complicated interactions between immune effector cells and tissue resident cells take place in the target organ and construct the inflammatory microenvironment. During the acute/deterioration phase, autoreactive and cytotoxic effector cells leave blood vessels to infiltrate the target site through a multi-step mechanism involving various molecular processes, and disease pathology progresses though a vicious cycle of accumulation and activation of effector cells. In the chronic phase, long-lasting infiltration of activated lymphocytes in the focal site occasionally results in the formation of ectopic lymphoid tissue that possibly plays important roles in sustaining self-reactivity. The murine experimental model of autoimmune gastritis is one of the most useful systems for studying the complicated cellular events associated with chronic inflammatory disease.


Acceptability of voluntary HIV testing by pregnant women in developing countries: an international survey. Ghent International Working Group on Mother-to-Child Transmission of HIV.
To evaluate acceptability of voluntary HIV counselling and testing (VCT) by pregnant women in the context of clinical trials assessing interventions to reduce mother-to-child transmission (MCT) of HIV in developing countries. During September-October 1997, 13 studies located in West (Abidjan, Bobo Dioulasso), East (Nairobi, Mombasa, Dar Es Salaam, Blantyre, Lusaka, Harare) and South Africa (Soweto, Durban), and Thailand (Bangkok) were included in a cross-sectional mailing survey about the acceptability of VCT in antenatal clinics. Acceptance rate, return rate, overall acceptability of VCT (acceptance of both pre- and post-VCT sessions) were obtained using a standardized questionnaire. The median overall acceptability of VCT was 69% (range, 33-95%). Overall acceptability of VCT most frequently depended on return rates because acceptance rates were generally high. Where several studies were conducted in parallel in the same city or the same country, overall acceptability rates of HIV testing were generally comparable even if the intervention programmes differed. Overall acceptability rates of VCT were high in antenatal clinics where a particular effort in implementing VCT programmes had been made. This international survey shows that despite many obstacles, VCT is feasible and acceptable for pregnant women aiming to reduce their risk of transmitting HIV to their children.


Human mobile robot interaction in the retail environment.
As technology advances, Human-Robot Interaction (HRI) is boosting overall system efficiency and productivity. However, allowing robots to be present closely with humans will inevitably put higher demands on precise human motion tracking and prediction. Datasets that contain both humans and robots operating in the shared space are receiving growing attention as they may facilitate a variety of robotics and human-systems research. Datasets that track HRI with rich information other than video images during daily activities are rarely seen. In this paper, we introduce a novel dataset that focuses on social navigation between humans and robots in a future-oriented Wholesale and Retail Trade (WRT) environment ( https://uf-retail-cobot-dataset.github.io/ ). Eight participants performed the tasks that are commonly undertaken by consumers and retail workers. More than 260 minutes of data were collected, including robot and human trajectories, human full-body motion capture, eye gaze directions, and other contextual information. Comprehensive descriptions of each category of data stream, as well as potential use cases are included. Furthermore, analysis with multiple data sources and future directions are discussed.


ORF3 of duck circovirus: a novel protein with apoptotic activity.
Duck circovirus (DuCV) is classified in the genus Circovirus of the Circoviridae family. Two major open reading frames (ORFs), encoding the replicase (ORF1/rep) and the capsid protein (ORF2/cap), have been recognized for DuCV. Sequence analysis show that another major conserved ORF (named ORF3) is located in the complementary strand of ORF1/rep of DuCV, and its function remains to be investigated. In this study, the ORF3 of DuCV was expressed in recombinant baculovirus-infected Sf9 cells. By IFA and Western blot analysis, the ORF3 protein was positive for the sera from ducks infected with DuCV. The percentages of apoptotic cells of the Sf9 cells infected with the recombinant baculovirus encoding ORF3 of DuCV were significantly higher than (P<0.05) that of the Sf9 cells infected with wild-type baculovirus at 24, 48 and 72 h postinfection. Based on our knowledge, we deduced that the ORF3 protein of DuCV might play an important role in viral pathogenesis via its apoptotic activity.


[Suicidal behavior in dermatology].
Even in dermatology one can potentially encounter suicidal patients. A risk of suicide can be preexisting, appear as complication of skin disorders or be triggered by medications such as interferons. Patients at risk must be specifically asked about suicidal ideations and tendencies. Acute suicide risk requires immediate crisis intervention. In dermatology suicide risk has been described in severe acne conglobata (especially men) and metastatic melanoma. Patients with chronic or potentially fatal disease or severe pain may be suicidal. In addition patients with depression, alcohol dependency, substance abuse, schizophrenia or borderline personality disorder are at special risk. We review psychodermatological diseases with risk of suicide and point out treatment strategies. More attention should be focused on the early recognition of a possible risk of suicide in dermatology patients.


Gelatinous lanthanide coordination polymer with aggregation-enhanced antenna effect for ratiometric detection of endogenous alkaline phosphatase.
Aggregation-induced emission (AIE) and antenna effect (AE) are two significant behaviors that have attracted increasing attention. However, it is challenging to achieve the synergistic effect of AIE and AE in luminescent materials for more extensive applications. Here, four gelatinous Ln3+ coordination polymers (Ln-CPs) are synthesized by self-assembly of ciprofloxacin (CIP), adenosine monophosphate (AMP), and Ln3+ ions in aqueous medium. Encouragingly, a remarkable increase in the characteristic fluorescence of Ln3+ and a significant decrease in CIP are observed along with increasing concentration of Ln-CPs, which is attributed to the large aggregates formed by self-assembly that strictly constrain the intramolecular motions of antenna ligands, thereby achieving the aggregation-enhanced AE. More meaningfully, Eu-CP not only shows a rice-like morphology at high aggregation state, but also provides an opportunity for the selective detection of alkaline phosphatase (ALP). A new flower-like polymer is formed upon incubating Eu-CP with ALP, accompanied by the fluorescence quenching of Eu3+ and recovery of CIP, a ratiometric determination of ALP in the range of 0.1-6.0 U·L-1 is thus achieved. Additionally, ALP assay in human serum and bioimaging in living cells have been successfully performed. This research opens a new horizon for the fabrication of Ln3+-based luminescent materials with promising applications.


Using claims data to measure and improve the MMR immunization rate in an HMO.
Health maintenance organizations (HMOs) are increasingly being expected to show evidence of the quality of care provided. One such quality measure is the measles, mumps, and rubella (MMR) immunization rate. This article describes how Blue Choice, an individual practice association (IPA)-model HMO, located in Rochester, New York, with more than 350,000 members, set up a three-phase study to improve immunization compliance rates. The first phase of the study amounted to calculating baseline compliance figures consistent with the American Academy of Pediatrics Immunization protocol using paid claims and membership databases. The second phase was to recalculate the MMR immunization rate based on survey information gathered from primary care physicians and to analyze and address reasons for any observed discrepancies. The third phase was to use Blue Choice Quality Assurance nursing staff to follow up with the remaining noncompliant members and determine the impact of intervention on the MMR immunization rate. Our baseline MMR immunization compliance study yielded a rate of 91.7%, which, as a first check of quality, is quite good in comparison to the nationally reported MMR compliance figures of 79.3%. Phase II analysis demonstrated that by seeking chart information, the overall MMR compliance rate was actually 96.7% Reasons for noncompliance are described, as well as the process used and improvements made, in phase III.


The effectiveness of a relaxation training program for women with preterm labour on pregnancy outcomes: a controlled clinical trial.
Prenatal maternal stress is associated with adverse birth outcomes. Few studies have been published on the effectiveness of relaxation techniques focusing on women with preterm labour. The object of this study was to examine the effectiveness of a relaxation training program on pregnancy outcomes in women experiencing preterm labour. A single-blinded, controlled clinical trial was used. The study was conducted in two hospitals. Both of the study hospitals located in northern Taiwan are also large teaching hospitals and share the same treatment protocols of preterm labour. Inclusion criteria were being pregnant and diagnosed with preterm labour, singleton, hospitalized at time of entry into the study, at gestation between 20 and 34 weeks, and having a cervical dilatation of less than 3 cm. Exclusion criteria were if they had one or any combination of the following: antepartum hemorrhage, infection, hypertension, gestational diabetes mellitus, or immunologic disease. The experimental group (n=68) participants received a mini mp3 player containing a 13-min relaxation audio program, which they were instructed to follow daily, while the control group (n=59) received only routine prenatal care. Pregnancy outcomes were obtained from medical charts after each woman gave birth. Survival analysis demonstrated that the experimental group had a significant pregnancy prolongation compared to the control group (p=0.048). Participants receiving the relaxation training program had a significant lower proportion of extreme preterm birth, a higher rate of not being admitted to a NICU, and a lower rate of stay days within 30 days when compared with the control group. No significant differences were found on pregnancy outcomes in terms of the rate of preterm birth, low birth weight, Apgar score at 1 and 5 min, mode of birth, and perinatal mortality between the two groups. Relaxation training for women with preterm labour is effective in delaying of delivery and enhancing positive pregnancy outcomes. This relaxation intervention is cost-effective, noninvasive, and easily applicable in women with preterm labour.


Differentiation of alcoholics by family history.
Alcoholics having a family history of alcoholism tended to drink at an earlier age and to have more social and personal problems than do alcoholics not having a family history of alcoholism.