Computer discrimination between benign and malignant urothelial cells.
Computer discrimination between benign and malignant cells by means of the TICAS routines and subroutines has been accomplished with a small error of classification, not greater than ten percent. One feature of major diagnostic significance, namely, nuclear texture was singled out for discussion. This study augurs well for the future of computerized cytology of the urinary tract.


Heterotypic antibodies in Liberian sera causing anomalous reactions when using a commercial haemagglutination test for hepatitis-B surface antigen.
Agglutinins reacting with normal and tanned sheep erythrocytes were the probable cause of false positive reactions given by 51 of 214 Liberian sera when using a commercial passive-haemagglutination test for hepatitis-B surface antigen. Absorption showed these agglutinins to be identical to those described earlier in Nigerian sera. Rheumatoid factor and anti-sheep-serum antibodies although present in 12 and five per cent respectively of all sera were not responsible for any false positive reactions. The practical conclusion is that such tests, based on sheep erythrocytes are unsuitable for screening this population.


Psychiatry, German society, and the Nazi "euthanasia" programme.
The paper begins by establishing the position of psychiatry after the First World War, concentrating upon the interplay between economy measures and limited reform during the Weimar Republic. Each therapeutic advance involved the definition of irremediable subgroups within the already socially marginalized psychiatric constituency. Nazi policy towards psychiatric patients during the 1930s involved further economy measures, and the introduction of negative eugenic strategies, were similar in kind if not degree, to those pursued in some other countries at that time. The decision to kill the mentally ill and physically disabled was taken by Hitler in order to clear the decks for war, and was justified with the aid of crude utilitarian arguments, as well as what limited evidence there was regarding popular attitudes on these issues. Many health professionals and psychiatrists accommodated themselves to policies which a few years later became one of the components of the 'Final Solution of the Jewish Question', i.e. Hitler's vengeance against the Jewish people in circumstances of war he had envisaged much earlier.


An examination of the social networks and social isolation in older and younger adults living with HIV/AIDS.
This study examined social networks and social isolation in older (50 years or more) and younger (ages 20 to 39) adults with HIV/AIDS. The author conducted interviews with 88 individuals living with HIV/AIDS in the Pacific Northwest. Both groups' social networks had similar patterns; however, older adults were more likely to live alone. More than 38 percent of older adults and 54 percent of older adults of color were at risk of social isolation compared with 25 percent of those 20 to 39 years of age. Older men and older adults of color had significantly lower scores on the social network scale than others. Having a confidant and receiving instrumental support were significantly correlated with reduced HIV stigma. Implications for social work practitioners are discussed.


Causes and consequences of bacterial adherence to mucosal epithelia during critical illness.
The interaction between host and pathogen during catabolic stress represents a dynamic battlefield, where the microbe's strategy to ensure its survival and multiplication come face to face with the repertoire of the host's immune system. From the microbe's point of view, the ICU offers the least optimal living condition, representing at times an outright holocaust for entire populations of fellow bacteria. This situation is especially true for intestinal bacteria, which can be exposed to all sorts of extreme conditions, such as starvation, turgor pressure, altered temperature, antibiotics, and osmolality changes. These conditions may act as environmental cues and elicit changes in bacterial gene expression that lead to effective coping responses. Starvation countermeasures can be especially strong signals for bacteria to follow chemical trails in search of nutrients. Harming the host is not the microbe's intent; its goal is to prevail. Injury to the host by a microbe struggling to survive is the inadvertent consequence of a threatening environment. This struggle between host and pathogen is particularly apparent at the mucosal surface, especially in the gastrointestinal tract, where microbes have enjoyed the leisurely life of a stable temperature and a constant food supply. The focus of this discussion is on one small aspect of the manner in which microbes ensure their survival during catabolic stress by attaching to host epithelial cells. The conditions and consequences of this process are discussed.


Shift from toll-like receptor 2 (TLR-2) toward TLR-4 dependency in the erosive stage of chronic streptococcal cell wall arthritis coincident with TLR-4-mediated interleukin-17 production.
Toll-like receptors (TLRs) may activate innate and adaptive immune responses in rheumatoid arthritis (RA) through recognition of microbial as well as endogenous ligands that have repeatedly been found in arthritic joints. The objective of this study was to investigate the involvement of TLR-2 and TLR-4 in the development of chronic destructive streptococcal cell wall (SCW)-induced arthritis, in which interleukin-1 (IL-1)/IL-17-dependent T cell-driven pathologic changes replace the macrophage-driven acute phase. Chronic SCW arthritis was induced by 4 repeated intraarticular injections of SCW fragments in wild-type, TLR-2(-/-), and TLR-4(-/-) mice. Clinical, histopathologic, and immunologic parameters of arthritis were evaluated. The TLR-2 dependency of joint swelling during the acute phase was shifted to TLR-4 dependency during the chronic phase. Persistent joint inflammation in the latter phase of the model was significantly suppressed in TLR-4(-/-) mice. In the chronic phase, TLR-4 actively contributed to matrix metalloproteinase (MMP)-mediated cartilage destruction and to osteoclast formation, since the expression of the MMP-specific aggrecan neoepitope VDIPEN and the osteoclast marker cathepsin K was significantly reduced in TLR-4(-/-) mice. Furthermore, TLR-4(-/-) mice expressed less IL-1beta, tumor necrosis factor alpha, IL-6, and IL-23, cytokines that are implicated in IL-17 production. Accordingly, SCW-specific IL-17 production was found to be dependent on TLR-4 activation, since T cells from arthritic TLR-4(-/-) mice produced markedly less IL-17 upon SCW stimulation, whereas interferon-gamma production remained unaffected. These data indicate the involvement of TLR-4 in the chronicity and erosive character of arthritis coincident with the antigen-specific IL-17 response. The high position of TLR-4 in the hierarchy of erosive arthritis provides an interesting therapeutic target for RA.


The rationale of photocoagulation therapy for proliferative diabetic retinopathy: a review and a model.
A model is proposed for initiation and inhibition of growth in retinal vessels including the control of proliferative diabetic retinopathy by photocoagulation. The model assumes that chronic dilatation (constriction) of a retinal blood vessel causes (inhibits) growth. Destruction of rods and cones by photocoagulation allows more choroidal oxygen to reach the inner retina and constrict retinal vessels. The attenuated vessels in late stage retinitis pigmentosa are an analogous and exaggerated effect to that from photocoagulation. The control of proliferative diabetic retinopathy is compared to the cause of retrolental fibroplasma. Following vitrectomy the retina utilizes oxygen from the aqueous which results in dilatation of iris vessels followed by rubeosis iridis. From this model, neovascularization from the disc or angle vessels follows the dilatation resulting from increased flow in their distal vascular beds.


Retinal Mosaicking with Vascular Bifurcations Detected on Vessel Mask by a Convolutional Network.
Mosaicking of retinal images is potentially useful for ophthalmologists and computer-aided diagnostic schemes. Vascular bifurcations can be used as features for matching and stitching of retinal images. A fully convolutional network model is employed to segment vascular structures in retinal images to detect vascular bifurcations. Then, bifurcations are extracted as feature points on the vascular mask by a robust and efficient approach. Transformation parameters for stitching can be estimated from the correspondence of vascular bifurcations. The proposed feature detection and mosaic method is evaluated on retinal images of 14 different eyes, 62 retinal images. The proposed method achieves a considerably higher average recall rate of matching for paired images compared with speeded-up robust features and scale-invariant feature transform. The running time of our method was also lower than other methods. Results produced by the proposed method superior to that of AutoStitch, photomerge function in Photoshop cs6 and ICE, demonstrate that accurate matching of detected vascular bifurcations could lead to high-quality mosaic of retinal images.


Airway management of the severely retrognathic child: use of the laryngeal mask airway.
Successful airway management of an infant or child with moderate to severe retrognathia first requires recognition of a potential problem. If the child cannot be intubated in a standard fashion, the use of a laryngeal mask airway (LMA) should be considered. We describe two cases wherein a toddler and an infant with severe retrognathia failed multiple attempts at traditional intubation. Both had an anterior larynx and hypoplasia of the mandible. In both cases, a subsequent LMA was successfully placed. The severely retrognathic newborn or child presents to the physician a unique challenge in airway management. Techniques to manage this difficult pediatric airway are different from those used in the adult. Otolaryngologists should be aware of this intubation technique and include it in their armamentarium of airway-management strategies. The LMA is not recommended as the technique of choice for securing a difficult airway, but it is an effective alternative when indicated, and it might be life-saving.


Nose-only water-pipe smoking effects on airway resistance, inflammation, and oxidative stress in mice.
Water-pipe smoking (WPS) is a common practice in the Middle East and is now gaining popularity in Europe and the United States. However, there is a limited number of studies on the respiratory effects of WPS. More specifically, the underlying pulmonary pathophysiological mechanisms related to WPS exposure are not understood. Presently, we assessed the respiratory effects of nose-only exposure to mainstream WPS generated by commercially available honey flavored "moasel" tobacco. The duration of the session was 30 min/day and 5 days/wk for 1 mo. Control mice were exposed to air only. Here, we measured in BALB/c mice the airway resistance using forced-oscillation technique. Lung inflammation was assessed histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid, and oxidative stress was evaluated biochemically by measuring lipid peroxidation, reduced glutathione and several antioxidant enzymes. Pulmonary inflammation assessment showed an increase in neutrophil and lymphocyte numbers. Likewise, airway resistance was significantly increased in the WPS group compared with controls. Tumor necrosis factor α and interleukin 6 concentrations were significantly increased in BAL fluid. Lipid peroxidation in lung tissue was significantly increased whereas the level and activity of antioxidants including reduced glutathione, glutathione S transferase, and superoxide dismutase were all significantly decreased following WPS exposure, indicating the occurrence of oxidative stress. Moreover, carboxyhemoglobin levels were significantly increased in the WPS group. We conclude that 1-mo nose-only exposure to WPS significantly increased airway resistance, inflammation, and oxidative stress. Our results provide a mechanistic explanation for the limited clinical studies that reported the detrimental respiratory effects of WPS.


[Alcohol consumption and high blood pressure].
ALCOHOL CONSUMPTION AND HIGH BLOOD PRESSURE. Cardiovascular disease is the second leading cause of alcohol-attributable mortality after cancer. The impact of alcohol consumption on blood pressure and the risk of cardiovascular pathologies are still largely underestimated by the general population and health professionals. However, numerous studies have demonstrated a dose-dependent increase in blood pressure, even at consumption levels close to the consumption guidelines (two drinks i.e. 20g per day). The alleged protective effects of low consumption levels are not confirmed, even in women. The binge drinking pattern has a particularly strong impact on blood pressure. The increase in blood pressure due to alcohol is reversible after reduction of consumption. Several pathophysiological mechanisms have been proposed to explain the hypertensive effects of alcohol. The screening of alcohol consumption by health professionals remains largely insufficient, especially in France, even in hypertensive subjects, although intervention is effective. It seems particularly important to reinforce the training of health professionals and the screening of alcohol consumption for primary prevention and also for secondary prevention when hypertension is already established. Scientific societies and federations should reinforce communication on the risks associated with alcohol consumption.


Acute pneumonia and the cardiovascular system.
Although traditionally regarded as a disease confined to the lungs, acute pneumonia has important effects on the cardiovascular system at all severities of infection. Pneumonia tends to affect individuals who are also at high cardiovascular risk. Results of recent studies show that about a quarter of adults admitted to hospital with pneumonia develop a major acute cardiac complication during their hospital stay, which is associated with a 60% increase in short-term mortality. These findings suggest that outcomes of patients with pneumonia can be improved by prevention of the development and progression of associated cardiac complications. Before this hypothesis can be tested, however, an adequate mechanistic understanding of the cardiovascular changes that occur during pneumonia, and their role in the trigger of various cardiac complications, is needed. In this Review, we summarise knowledge about the burden of cardiac complications in adults with acute pneumonia, the cardiovascular response to this infection, the potential effects of commonly used cardiovascular and anti-infective drugs on these associations, and possible directions for future research.


Twenty-Four-Hour Intraocular Pressure Pattern In Glaucoma Suspects In An African Population.
Twenty-four-hour intraocular pressure measurement (Phasing) among Glaucoma suspects showed higher IOP, greater fluctuation, and more varying peak times occurring mostly outside clinic hours, between 12 midnight and 8 am in 68.9% of them. To characterise twenty-four-hour variation in intraocular pressure (IOP), in glaucoma suspects and normal individuals in an African population. Cross-sectional analytical study was carried out between March and October 2019 at the University of Ilorin Teaching Hospital. A total of 204 study participants, comprising 102 primary open-angle glaucoma suspects and 102 age and sex-matched controls with healthy eyes were recruited. Participants had a comprehensive ophthalmic examination. Measurements of IOP were taken every 2 hours during a 24-hour period using an iCare tonometer. The mean age was 43.64±14.02 SD and 43.02±13.55 SD (P=1.000) for POAG suspects and controls respectively. The mean peak IOP was significantly higher in POAG suspects (21.87± 4.65 mmHg) compared to controls (17.17± 2.32 mmHg) (P<0.001). Whereas, the mean trough IOP reading was not significantly different between the two groups. In both groups of participants, the peak and trough IOP in the majority were recorded outside of clinic hours. The majority (68.9%) of POAG suspects had a peak IOP between midnight and 8 am whereas the control group peaked mostly at 4 pm (16.7%) and 4 am (41.7%). Twenty-four-hour IOP variation was 6 mmHg or less in 73.6% of control eyes while in the POAG suspects, 83.3% of eyes had variation greater than 6 mmHg. Compared to age and sex matched healthy controls, glaucoma suspects of African descent showed significantly higher mean IOP and IOP variation with most peak IOP detected outside of clinic hours.


Heparin-Induced Thrombocytopenia After Mitral Valve Replacement.
Background: Heparin-induced thrombocytopenia (HIT) is a rare autoimmune reaction that involves a decrease in platelet count following heparin exposure and can be associated with life-threatening thrombosis. Because of their prolonged heparin exposure, patients undergoing cardiac surgery are at risk of HIT, with an incidence of 0.1% to 3%. Case Report: A 65-year-old male with severe mitral regurgitation and preoperative ejection fraction of 20% to 25% underwent mitral valve bioprosthetic replacement with coronary artery bypass graft surgery. Heparin anticoagulation was started on postoperative day (POD) 1. Respiratory failure resulted in prolonged mechanical ventilation and heparinization without the ability to initiate warfarin. While the patient was on heparin, his platelet count declined on POD 2 and then steadily increased to above the preoperative level on POD 7. On POD 10, the patient's platelet count dramatically decreased, and on POD 13 he developed acute common femoral artery occlusion necessitating embolectomy. Intraoperative transesophageal echocardiography revealed heavy thrombus burden across the mitral bioprosthesis. HIT was confirmed with a positive heparin-induced platelet antibody and serotonin release assay. Heparin was stopped and argatroban initiated. The patient underwent reoperative bioprosthetic mitral valve replacement on POD 18 using bivalirudin intraoperatively. Despite resolution of HIT, the patient developed sepsis and died on POD 59. Conclusion: The diagnosis of HIT is challenging in patients who undergo cardiopulmonary bypass. Platelet counts often decrease 40% to 60% during the first 72 hours postoperatively, and the frequency of nonspecific anti-platelet factor 4/heparin antibody formation is high. These findings can mask early signs of HIT and delay diagnosis.


Identification of bioactive ingredients with immuno-enhancement and anti-oxidative effects from Fufang-Ejiao-Syrup by LC-MS(n) combined with bioassays.
Fufang Ejiao Syrup (FES) is a widely used immune-boosting Traditional Chinese Medicine (TCM) in Eastern Asian countries. This study attempts to investigate the bioactive compounds in FES. First, FES extract was separated into fractions to facilitate the investigation and 72 compounds were identified using LC-MS(n). Subsequently, Immune-enhancement effects of FES and its components were investigated on bone marrow cells and neuroprotective effects against H2O2 induced oxidative damage were evaluated in SH-SY5Y neuroblastoma cells and bEnd.3. Our results indicated that fraction 3, 5, 6 and 8 showed significant improvements on immune function, while several fractions had cytoprotective effects against H2O2-induced oxidative injury. Jionoside A1 isolated from Radix Rehmanniae Praeparata displayed dose dependent immune-enhancement activity. 20(R)-ginsenoside Rg3 could protect bEnd.3 against oxidative damage. Furthermore, echinacoside, jionoside A1, vitexin-2-O-rhamnoside, acteoside and isoacteoside possessed moderate protective activities on H2O2-treated SH-SY5Y cells. In conclusion, our study provided both chemical and biological evidences to support clinical application of FES.


A core outcome set for localised prostate cancer effectiveness trials.
To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio; which is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 patients with prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs; cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and eight patients. The final COS included 19 outcomes. In all, 12 apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, and sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side-effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions that should be measured in all localised prostate cancer effectiveness trials.


Ion-pair extraction cleanup for liquid chromatographic determination of bentazon in crops and soil.
Bentazon was selectively extracted as an ion pair with tetrabutylammonium ion into dichloromethane. This technique was used to clean up crop and soil samples before determination of bentazon by reverse phase liquid chromatography and UV detection. Recoveries from potatoes, cucumbers, wheat grain, and clay soil were 77-103%, with a detection limit of 0.02 mg/kg.


Synergistically Active NiCo2 S4 Nanoparticles Coupled with Holey Defect Graphene Hydrogel for High-Performance Solid-State Supercapacitors.
Nickel cobalt sulfide nanoparticles embedded in holey defect graphene hydrogel (HGH) that exhibit highly porous structures and uniform nickel cobalt sulfide nanoparticle sizes are successfully prepared by a facile solvothermal-hydrothermal method. As an electrode material for supercapacitors, the as-prepared NiCo2 S4 @HGH shows ultra-high specific capacitances of 1000 F g-1 and 800 F g-1 at 0.5 and 6 A g-1 , respectively, owing to the outstanding electrical conductivity of HGH and high specific capacitance of NiCo2 S4 . After 2100 charge/discharge cycles at a current density of 6 A g-1 , 96.6 % of the specific capacitance was retained, signifying the superb durability of NiCo2 S4 @HGH. Moreover, remarkable specific capacitance (312.6 F g-1 ) and capacity retention (87 % after 5000 cycles) at 6 A g-1 were displayed by the symmetric solid-state supercapacitor fabricated by using NiCo2 S4 @HGH electrodes. These auspicious supercapacitor performances demonstrate that the as-developed solvothermal-hydrothermal approach can be widely used to prepare graphene-coupled binary metal sulfides for high-performance supercapacitor applications.


Optimal partitioning theory revisited: nonstructural carbohydrates dominate root mass responses to nitrogen.
Under optimal partitioning theory (OPT), plants preferentially allocate biomass to acquire the resource that most limits growth. Within this framework, higher root mass under low nutrients is often assumed to reflect an allocation response to build more absorptive surface. However, higher root mass also could result from increased storage of total nonstructural carbohydrates (TNC) without an increase in non-storage mass or root surface area. To test the relative contributions of TNC and non-storage mass as components of root mass responses to resources, we grew seedlings of seven northern hardwood tree species (black, red, and white oak, sugar and red maple, American beech, and black cherry) in a factorial light x nitrogen (N) greenhouse experiment. Because root mass is a coarse metric of absorptive surface, we also examined treatment effects on fine-root surface area (FRSA). Consistent with OPT, total root mass as a proportion of whole-plant mass generally was greater in low vs. high N. However, changes in root mass were influenced by TNC mass in all seven species and were especially strong in the three oak species. In contrast, non-storage mass contributed to increased total root mass under low N in three of the seven species. Root morphology also responded, with higher fine-root surface area (normalized to root mass) under low vs. high N in four species. Although biomass partitioning responses to resources were consistent with OPT, our results challenge the implicit assumption that increases in root mass under low nutrient levels primarily reflect allocation shifts to build more root surface area. Rather, root responses to low N included increases in: TNC, non-storage mass and fine-root surface area, with increases in TNC being the largest and most consistent of these responses. The greatest TNC accumulation occurred when C was abundant relative to N. Total nonstructural carbohydrates storage could provide seedlings a carbon buffer when respiratory or growth demands are not synchronized with photosynthesis, flexibility in responding to uncertain and fluctuating abiotic and biotic conditions, and increased access to soil resources by providing an energy source for mycorrhizae, decomposers in the rhizosphere, or root uptake of nutrients.


Subarachnoid hemorrhage: a preventable disease with a heritable component.
Subarachnoid hemorrhage (SAH) caused by ruptured intracranial aneurysm affects approximately 16 000 Americans annually, and almost 40% of affected patients die within 30 days despite the best current therapy. Prevention of SAH is therefore of paramount importance. We present a preliminary analysis of risk factors for SAH from our population-based, case-control study. Cases were prospectively collected and matched 2:1 by age, race, and gender to controls using random digit dialing. Personal risk factor history, family history, neuroimaging data, and genetic samples were obtained. Univariate and bivariate analyses were performed and population-attributable risks estimated. Multivariable analysis was performed using conditional logistic regression. Between June 1997 and February 2000, 107 cases and 197 controls were enrolled. In bivariate analyses, a large proportion of population-attributable risk for SAH could be explained by modifiable risk factors: smoking, hypertension, and heavy alcohol use. In multivariable analysis, current cigarette smoking, history of hypertension, frequent alcohol use, lower body mass index, and a family history of a relative with SAH or intracranial aneurysm were found to be significant, independent risk factors for SAH. Our data confirm previous reports that SAH clusters within some families independent of environmental risk factors, suggesting that SAH has a significant genetic component. Yet, even among families at increased risk of SAH, smoking cessation, treatment of hypertension, and reduced alcohol intake may substantially decrease SAH risk. The independent associations with heavy alcohol use and low body mass index with SAH may be confounded by smoking and require further study.


[Fabrication of bioactive tissue engineering scaffold for reconstructing calcified cartilage layer based on three-dimension printing technique].
To fabricate organic-inorganic composite tissue engineering scaffolds for reconstructing calcified cartilage layer based on three-dimensional (3D) printing technique. The scaffolds were developed by 3D-printing technique with highly bioactive calcium-magnesium silicate ultrafine particles of 1%, 3% and 5% of mass fraction, in which the organic phases were composed of type I collagen and sodium hyaluronate. The 3D-printed scaffolds were then crosslinked and solidified by alginate and CaCl₂ aerosol. The pore size and distribution of inorganic phase were observed with scanning electron microscope (SEM); the mechanical properties were tested with universal material testing machine, and the porosity of scaffolds was also measured. Pore size was approximately (212.3 ± 34.2) μm with a porosity of (48.3 ± 5.9)%, the compressive modulus of the scaffolds was (7.2 ± 1.2) MPa, which was irrelevant to the percentage changes of calcium-magnesium silicate, the compressive modulus was between that of cartilage and subchondral bone. The porous scaffolds for calcified cartilage layer have been successfully fabricated, which would be used for multi-layered composite scaffolds in osteochondral injury.


A Systematic Review of the Association between Parenting Styles and Narcissism in Young Adults: From Baumrind's Perspective.
The concept 'parenting styles' has been widely examined to understand the etiology of narcissism for decades. This study aimed to systematically review the empirical research literature regarding the association between perceived parenting styles and narcissism. In this study, Ebscohost, Wiley Online Library, Taylor&Francis, Springer Link, PubMed, PsycNet, ScienceDirect, and Google Scholar databases were searched using identified keywords. An extensive database search resulted in 75 identified publications. Of these, 60 were scrutinized, and in the end, ten studies were included in the review for data synthesis. To reach a common conceptualization on the parenting styles, the results were evaluated based on Baumrind's typology. As a result of this systematic review, we can conclude that there is a relationship between narcissism and parenting styles. In particular, perceived permissive parenting was positively correlated with narcissism. However, the relationship between narcissism and other parenting styles is more complex. Therefore, more high-quality empirical studies are needed to investigate the relationship between parenting and narcissism.


Effects of a daily three-meal pattern with different dietary protein contents on pig growth performance, carcass and muscle quality traits.
Recent research related to phase-feeding programmes for pig nutrition do not always account for the variation among individuals, and feeds are usually formulated to optimise the performance of the whole pig population. This study aimed at measuring the effects of a daily three-meal pattern with different dietary protein contents on pig growth performance, carcass and muscle quality traits. The results showed that compared with the 3C treatment, average daily gain (ADG) of pigs in the HCL treatment increased by 14.75% (P < 0.05) during period 1. The carcass weight (P = 0.006) and slaughter weight (P = 0.021) in the HCL group increased when compared with those in the 3C and LCH treatments. Moreover, the LCH feeding sequences contributed to reduce the drip loss in longissimus dorsi (LD) muscle (P < 0.05) when compared with the 3C treatment. The HCL or LCH feeding sequence contributed to increase the meat quality when compared with those receiving the 3C treatment. Collectively, our results indicate that feeding high protein meal in the morning and a gradual reduction of the protein content in meals over the day may improve muscle quality characteristics, maximise performance, and reduce the pig feed cost. © 2017 Society of Chemical Industry.


Feeding and excreta collection techniques in metabolizable energy assays for ducks.
Feeding and excreta collection techniques, lasting 102 h, for the determination of ME in feed ingredients for ducks are described. Eight and 32 h after feed withdrawal, all ducks received 30 g of dextrose in 100 g of water by orogastric administration. By orogastric administration, ducks received 30 g of test ingredients or dextrose (for ducks used in estimation of endogenous losses of energy and nitrogen) in 100 g of water at 48 and 54 h after feed withdrawal. The collection of excreta involved suturing a threaded plastic retainer ring to the vent and screwing a Whirl-Pak plastic bag, mounted on the top portion of a Playtex baby nurser set plastic bottle cut off 3 cm below the threads, to the retainer ring. Excreta were collected by replacing the Whirl-Pak bags at 54, 60, 72, 84, 96, and 102 h after feed withdrawal. In each of two experiments, ducks with an average weight of 3.7 kg were assigned to treatments. In Experiment 1, four ducks were assigned to each of three test ingredients (corn, dehulled oats, and wheat) and four ducks were assigned to be deprived of feed for estimation of endogenous losses of nitrogen and energy. In Experiment 2, six ducks were assigned to each of two test ingredients (corn and sorghum) and six ducks were assigned to be deprived of feed. Ducks lost an average of 537 g (Experiment 1) and 462 g (Experiment 2) during the 102-h experimental period and all the lost weight was regained within 7 d of return to full feed. Losses of nitrogen (milligrams per duck per 54 h) were 292 (Experiment 1) and 461 (Experiment 2) and energy (kilocalories per duck per 54 h) were 12.12 and 22.26 in feed-deprived group. The determined AMEn and TMEn for corn were 3.245 and 3.407, and 3.210 and 3.517 kcal/g for Experiments 1 and 2, respectively. For dehulled oats, wheat, and sorghum, the determined AMEn and TMEn were 3.464 and 3.625, 3.150 and 3.312, and 3.363 and 3.670 kcal/g, respectively.


Cytotoxic T lymphocytes require transcription for infiltration but not target cell lysis.
Effector cytotoxic T lymphocytes (CTLs) are critical for ridding the body of infected or cancerous cells. CTL T cell receptor (TCR) ligation not only drives the delivery and release of cytolytic granules but also initiates a new wave of transcription. In order to address whether TCR-induced transcriptomic changes impact the ability of CTLs to kill, we asked which genes are expressed immediately after CTLs encounter targets and how CTL responses change when inhibiting transcription. Our data demonstrate that while expression of cytokines/chemokines and transcriptional machinery depend on transcription, cytotoxic protein expression and cytolytic activity are relatively robust to transcription blockade, with CTLs lysing nearby target cells for several hours after actinomycin D treatment. Monitoring CTL movement among target cells after inhibiting transcription demonstrates an infiltration defect that is not rectified by provision of exogenous cytokine/chemokine gradients, indicating a cell-intrinsic transcriptional requirement for infiltration. Together, our results reveal differential molecular control of CTL functions, separating recruitment and infiltration from cytolysis.


Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy.
Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy. To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment. Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality. Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.


Information, perspective, and judgments about the self in face and dignity cultures.
People's judgments about their own moral status and well-being were made differently by those from a Dignity culture (Anglo-Americans) and by those from a Face culture (Asian Americans). Face culture participants were more influenced by information processed from a third-person (compared with first-person) perspective, with information about the self having a powerful effect only when seen through another's eyes. Thus, (a) Asian Americans felt the greatest need for moral cleansing when thinking about how others would judge their many (vs. few) transgressions, but this effect did not hold when others were not invoked, and (b) Asian Americans defined themselves as having a rich social network and worthwhile life when thinking about how others would evaluate their many (vs. few) friendships, but again, effects did not hold when others were not invoked. In contrast, Anglo-Americans responded to information about their transgressions or friendships, but effects were pronounced only when other people were not invoked.


Modification of adriamycin pharmacokinetics by direct electric current in rats.
Adriamycin (ADR, doxorubicin), a drug having cardiotoxicity, is electrically charged as a cation in blood. We therefore investigated whether iontophoresis caused by direct electric current (DC; 50 microA, 90 min) would cause systemic modification of ADR pharmacokinetics. Cathode and anode were placed into a right kidney and muscles of the abdominal wall, respectively, in six Donryu rats. Urinary excretion of ADR, as measured by catheterizing into the right kidney, was significantly higher in the DC group than in the controls (p < 0.05). Both plasmic and renal ADR clearances were significantly higher in the DC group (p<0.005 and p<0.001, respectively). Tissue ADR concentrations were significantly lower in the DC group (heart: p<0.003; liver and lung: both p<0.05). These results suggest that electric therapy might potentially induce modification of ADR pharmacokinetics by iontophoresis, and that the therapy might effectively change ADR concentration both locally and systemically.


Effects of temperature, storage and sodium molybdate on the analysis of estrogen and progesterone receptors in rabbit uterine tissue and gynecologic tumor.
The cytoplasmic estrogen receptor (ERc) and progesterone receptor (PRc) in mammary tumors have been recognized as useful biochemical markers for predicting the objective response of patients with advanced breast cancers to endocrine therapy. These proteins are also useful in the prognosis of gynecologic carcinoma. This report presents data showing the effect of sodium molybdate in the stabilization of estrogen and progesterone receptors. In rabbit uterine tissue, molybdate (20 mM) increased the binding of progesterone and estrogen to the receptors in several ways: (a) the apparent loss of detectable receptors during lengthy sucrose gradient analysis and at elevated temperature (30 degrees C) was reduced; (b) the instability of receptors due to storage at -70 degrees C was lessened, and (c) the conversion of the 7S PRc to the 3.5S form was minimized. Similarly, molybdate caused a qualitative and/or a statistically significant quantitative difference in receptor values for some human gynecologic tumors presented herein; the molybdate-associated changes vary with tumor specimen. Of the 8 tumors for which receptor values in the presence of molybdate (M+) and its absence (M-) can be compared, detectable ERc of 6 and PRc of 7 tumors increased with molybdate, and ERc of 2 and PRc of 1 tumor showed no change. In addition to the increase in receptor values, a concomitant shift of the 3-4S molecules to the 7-8S moieties was noted for some tumors (1 of 6 for ERc and 3 of 7 for PRc). In 2 receptor-poor tumor samples, ERc was only detected in M+ cytosols. These results show that molybdate is effective in reducing receptor degradation and stabilizes the 7-8S molecules from converting to 4S moieties. The addition of molybdate may be helpful for better quantitation of steroid receptors in clinical specimens.


Synapsin regulates Basal synaptic strength, synaptic depression, and serotonin-induced facilitation of sensorimotor synapses in Aplysia.
Synapsin is a synaptic vesicle-associated protein implicated in the regulation of vesicle trafficking and transmitter release, but its role in heterosynaptic plasticity remains elusive. Moreover, contradictory results have obscured the contribution of synapsin to homosynaptic plasticity. We previously reported that the neuromodulator serotonin (5-HT) led to the phosphorylation and redistribution of Aplysia synapsin, suggesting that synapsin may be a good candidate for the regulation of vesicle mobilization underlying the short-term synaptic plasticity induced by 5-HT. This study examined the role of synapsin in homosynaptic and heterosynaptic plasticity. Overexpression of synapsin reduced basal transmission and enhanced homosynaptic depression. Although synapsin did not affect spontaneous recovery from depression, it potentiated 5-HT-induced dedepression. Computational analysis showed that the effects of synapsin on plasticity could be adequately simulated by altering the rate of Ca(2+)-dependent vesicle mobilization, supporting the involvement of synapsin not only in homosynaptic but also in heterosynaptic forms of plasticity by regulating vesicle mobilization.


Monitoring the formation of kernel-based topographic maps in a hybrid SOM-kMER model.
A new lattice disentangling monitoring algorithm for a hybrid self-organizing map-kernel-based maximum entropy learning rule (SOM-kMER) model is proposed. It aims to overcome topological defects owing to a rapid decrease of the neighborhood range over the finite running time in topographic map formation. The empirical results demonstrate that the proposed approach is able to accelerate the formation of a topographic map and, at the same time, to simplify the monitoring procedure.


Transplantation of Zebrafish Pediatric Brain Tumors into Immune-competent Hosts for Long-term Study of Tumor Cell Behavior and Drug Response.
Tumor cell transplantation is an important technique to define the mechanisms controlling cancer cell growth, migration, and host response, as well as to assess potential patient response to therapy. Current methods largely depend on using syngeneic or immune-compromised animals to avoid rejection of the tumor graft. Such methods require the use of specific genetic strains that often prevent the analysis of immune-tumor cell interactions and/or are limited to specific genetic backgrounds. An alternative method in zebrafish takes advantage of an incompletely developed immune system in the embryonic brain before 3 days, where tumor cells are transplanted for use in short-term assays (i.e., 3 to 10 days). However, these methods cause host lethality, which prevents the long-term study of tumor cell behavior and drug response. This protocol describes a simple and efficient method for the long-term orthotopic transplantation of zebrafish brain tumor tissue into the fourth ventricle of a 2-day-old immune-competent zebrafish. This method allows: 1) long-term study of tumor cell behaviors, such as invasion and dissemination; 2) durable tumor response to drugs; and 3) re-transplantation of tumors for the study of tumor evolution and/or the impact of different host genetic backgrounds. In summary, this technique allows cancer researchers to assess engraftment, invasion, and growth at distant sites, as well as to perform chemical screens and cell competition assays over many months. This protocol can be extended to studies of other tumor types and can be used to elucidate mechanisms of chemoresistance and metastasis.


A national scale flood hazard mapping methodology: The case of Greece - Protection and adaptation policy approaches.
The present work introduces a national scale flood hazard assessment methodology, using multi-criteria analysis and artificial neural networks (ANNs) techniques in a GIS environment. The proposed methodology was applied in Greece, where flash floods are a relatively frequent phenomenon and it has become more intense over the last decades, causing significant damages in rural and urban sectors. In order the most prone flooding areas to be identified, seven factor-maps (that are directly related to flood generation) were combined in a GIS environment. These factor-maps are: a) the Flow accumulation (F), b) the Land use (L), c) the Altitude (A), b) the Slope (S), e) the soil Erodibility (E), f) the Rainfall intensity (R), and g) the available water Capacity (C). The name to the proposed method is "FLASERC". The flood hazard for each one of these factors is classified into five categories: Very low, low, moderate, high, and very high. The above factors are combined and processed using the appropriate ANN algorithm tool. For the ANN training process spatial distribution of historical flooded points in Greece within the five different flood hazard categories of the aforementioned seven factor-maps were combined. In this way, the overall flood hazard map for Greece was determined. The final results are verified using additional historical flood events that have occurred in Greece over the last 100years. In addition, an overview of flood protection measures and adaptation policy approaches were proposed for agricultural and urban areas located at very high flood hazard areas.


Ultrafast long-distance excitation energy transport in donor-bridge-acceptor systems.
The excited-state dynamics of two energy donor-bridge-acceptor (D-B-A) systems consisting of a zinc tetraphenylporphyrin (ZnP) and a free base tetraphenylporphyrin (FbP) bridged by oligo-p-phenyleneethynylene units with different substituents has been investigated using ultrafast spectroscopy. These systems differ by the location of the lowest singlet excited state of the bridge, just above or below the S(2) porphyrin states. In the first case, Soret band excitation of the porphyrins is followed by internal conversion to the local S(1) state of both molecules and by a S(1) energy transfer from the ZnP to the FbP end on the 10 ns time scale, as expected for a center-to-center distance of about 4.7 nm. On the other hand, if the bridge is excited, the energy is efficiently transferred within 1 ps to both porphyrin ends. Selective bridge excitation is not possible with the second system, because of the overlap of the absorption bands. However, the time-resolved spectroscopic data suggest a reversible conversion between the D*(S(2))-B-A and D-B*(S(1))-A states as well as a transition from the D-B*(S(1))-A to the D-B-A* states on the picosecond time scale. This implies that the local S(2) energy of the ZnP end can be transported stepwise to the FbP end, i.e., over about 4.7 nm, within 1 ps with an efficiency of more than 0.2.


Successful treatment of a lung abscess without surgical intervention in a cat.
An 8-year-old neutered female domestic shorthair cat was referred with complaints of lethargy, anorexia, fever, tachypnoea and a pulmonary mass on thoracic radiography. Whole-body CT revealed the presence of a nodular lesion in the right caudal lobe of the lung. Fine-needle aspiration of the lung mass yielded purulent fluid and cytology showed a large number of mildly to moderately degenerated neutrophils with numerous cocci and bacilli, leading to the diagnosis of a lung abscess. Empirical administration of doxycycline and orbifloxacin was initiated on the day of referral. Bacterial culture and antibiotic susceptibility tests using the collected fluid sample detected two types of bacteria, which were susceptible to both antibiotics. The clinical signs of the cat improved after the initiation of treatment, and the antibiotics were discontinued 28 days later, after the lung lesions disappeared. No recurrence of lung abscess was observed until 588 days after the discontinuation of treatment. Only one case of a lung abscess has been previously reported in cats. Furthermore, while surgical resection is the most common treatment for lung abscesses in the field of veterinary medicine, this is the first report of successful treatment with antibiotic administration alone.


How much should be paid for specialised treatment?
English health policy has moved towards establishing specialist multi-disciplinary teams to care for patients suffering rare or particularly complex conditions. But the healthcare resource groups (HRGs), which form the basis of the prospective payment system for hospitals, do not explicitly account for specialist treatment. There is a risk, then, that hospitals in which specialist teams are based might be financially disadvantaged if patients requiring specialised care are more expensive to treat than others allocated to the same HRG. To assess this we estimate the additional costs associated with receipt of specialised care. We analyse costs for 12,154,599 patients treated in 163 English hospitals in fiscal year 2008/09 according to the type of specialised care received, if any. We account for the distributional features of patient cost data, and estimate ordinary least squares and generalised linear regression models with random effects to isolate what influence the hospital itself has on costs. We find that, for nineteen types of specialised care, patients do not have higher costs than others allocated to the same HRG. However, costs are higher if a patient has cancer, spinal, neurosciences, cystic fibrosis, children's, rheumatology, colorectal or orthopaedic specialised services. Hospitals might be paid a surcharge for providing these forms of specialised care. We also find substantial variation in the average cost of treatment across the hospital sector, due neither to the provision of specialised care nor to other characteristics of each hospital's patients.


Spontaneous Formation of Hydrogen Peroxide in Water Microdroplets.
There is accumulating evidence that many chemical reactions are accelerated by several orders of magnitude in micrometer-sized aqueous or organic liquid droplets compared to their corresponding bulk liquid phase. However, the molecular origin of the enhanced rates remains unclear as in the case of spontaneous appearance of 1 μM hydrogen peroxide in water microdroplets. In this Letter, we consider the range of ionization energies and whether interfacial electric fields of a microdroplet can feasibly overcome the high energy step from hydroxide ions (OH-) to hydroxyl radicals (OH•) in a primary H2O2 mechanism. We find that the vertical ionization energies (VIEs) of partially solvated OH- ions are greatly lowered relative to the average VIE in the bulk liquid, unlike the case of the Cl- anion which shows no reduction in the VIEs regardless of solvation environment. Overall reduced hydrogen-bonding and undercoordination of OH- are structural features that are more readily present at the air-water interface, where the energy scale for ionization can be matched by statistically probable electric field values.


Infectious mononucleosis, mastoiditis, and facial paralysis.
To our knowledge this is the first report of a patient with infectious mononucleosis associated with a mononuclear granulomatous mastoiditis and facial paralysis. Pathologic examination of tissue from this patient, removed at the time of radical mastoidectomy, provides a basis for further speculation about the relationship between facial paralysis and infectious mononucleosis.


Advances in pediatric surgery.
Recent advances in pediatric surgery have been made in several fields. Hydrocephalus is again being treated by draining the cerebrospinal fluid into either the ureter, the mastoid antrum or the peritoneal cavity. Funnel chest should be corrected surgically. Congenital atresia of the esophagus is best treated by a one-stage operative repair. Patent ductus should be closed. Operations are available for cyanotic children. Intussusception is again being treated by barium enema in selected cases. Megacolon can be benefited by surgical procedures, which now are directed at the distal spastic segment rather than the proximal dilated segment.


Altered aldose reductase gene regulation in cultured human retinal pigment epithelial cells.
Aldose reductase (AR2), a putative "hypertonicity stress protein" whose gene is induced by hyperosmolarity, protects renal medullary cells against the interstitial hyperosmolarity of antidiuresis by catalyzing the synthesis of millimolar concentrations of intracellular sorbitol from glucose. Although AR2 gene induction has been noted in a variety of renal and nonrenal cells subjected to hypertonic stress in vitro, the functional significance of AR2 gene expression in cells not normally exposed to a hyperosmolar milieu is not fully understood. The physiological impact of basal AR2 expression in such cells may be limited to hyperglycemic states in which AR2 promotes pathological polyol accumulation, a mechanism invoked in the pathogenesis of diabetic complications. Since AR2 overexpression in the retinal pigment epithelium has been associated with diabetic retinopathy, the regulation of AR2 gene expression and associated changes in sorbitol and myo-inositol were studied in human retinal pigment epithelial cells in culture. The relative abundance of aldehyde reductase (AR1) and AR2 mRNA was quantitated by filter hybridization of RNA from several human retinal pigment epithelial cell lines exposed to hyperglycemic and hyperosmolar conditions in vitro. AR2 but not AR1 mRNA was significantly increased some 11- to 18-fold by hyperosmolarity in several retinal pigment epithelial cell lines. A single cell line with a 15-fold higher basal level of AR2 mRNA than other cell lines tested demonstrated no significant increase in AR2 mRNA in response to hypertonic stress. This cell line demonstrated accelerated and exaggerated production of sorbitol and depletion of myo-inositol upon exposure to 20 mM glucose. Therefore, abnormal AR2 expression may enhance the sensitivity of cells to the biochemical consequences of hyperglycemia potentiating the development of diabetic complications.


Optical properties of Ce-doped ZnO nanowires directionally grown by hydrothermal method.
Well directionally grown Ce-doped ZnO nanowires were successfully synthesized by a simple hydrothermal method. The Ce dopant plays a key role in evolving the morphology, affecting the crystalline size, and forming the uniform nanostructure of the ZnO nanowires. The amount of Ce dopant in the ZnO nanowires also affects the regions of blue-shift in the UV and green emission peaks and the intensities of emission peaks based on the cathodoluminescence spectra of the nanowires. Moreover, the effect of Ce doping amount on the microstructure of the nanowires is also presented.


[Synthesis of lipid A analogs: achievements and perspective].
Data on the synthesis of analogues of lipid A, a biologically active fragment of gram-negative bacteria's lipopolysaccharides, are summarized. Main types of the compounds obtained are systematized, and problems of the synthesis of various parts of the molecule considered. The results of studying biological activity of lipid A analogues are discussed, which led to some conclusions on the structure-function relation. Perspectives of further studies are briefly outlived.


"Four-dimensional" protein structures: examples from metalloproteins.
The fact that an object, for example, a protein, possesses a three-dimensional structure seems an obvious concept. However, when the object is flexible, the concept is less obvious. Growing experimental data over several decades show that proteins are not rigid objects, but they may sample more or less wide ranges of different conformations. To stress this concept, we propose to call the range of sampled conformations the "fourth dimension" of the protein structure. Nuclear magnetic resonance is a precious technique to define this fourth dimension. Examples of conformational heterogeneity taken from the realm of metalloproteins and their functional implications are discussed.


Effect of climate on incidence of respiratory syncytial virus infections in a refugee camp in Kenya: A non-Gaussian time-series analysis.
Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infections (ALRTI) in children. Children younger than 1 year are the most susceptible to RSV infection. RSV infections occur seasonally in temperate climate regions. Based on RSV surveillance and climatic data, we developed statistical models that were assessed and compared to predict the relationship between weather and RSV incidence among refugee children younger than 5 years in Dadaab refugee camp in Kenya. Most time-series analyses rely on the assumption of Gaussian-distributed data. However, surveillance data often do not have a Gaussian distribution. We used a generalized linear model (GLM) with a sinusoidal component over time to account for seasonal variation and extended it to a generalized additive model (GAM) with smoothing cubic splines. Climatic factors were included as covariates in the models before and after timescale decompositions, and the results were compared. Models with decomposed covariates fit RSV incidence data better than those without. The Poisson GAM with decomposed covariates of climatic factors fit the data well and had a higher explanatory and predictive power than GLM. The best model predicted the relationship between atmospheric conditions and RSV infection incidence among children younger than 5 years. This knowledge helps public health officials to prepare for, and respond more effectively to increasing RSV incidence in low-resource regions or communities.


Femur fractures in the pediatric population: abuse or accidental trauma?
Child abuse represents a serious threat to the health and well-being of the pediatric population. Orthopaedic specialists will often become involved when child abuse is suspected as a result of the presence of bony injury. Distinguishing abuse from accidental trauma can be difficult and is often based on clinical suspicion. We sought to determine whether accidental femur fractures in pediatric patients younger than age 4 could be distinguished from child abuse using a combination of presumed risk factors from the history, physical examination findings, radiographic findings, and age. We searched our institution's SCAN (Suspected Child Abuse and Neglect) and trauma databases. We identified 70 patients in whom the etiology of their femur fracture was abuse and compared that group with 139 patients who had a femur fracture in whom accidental trauma was the etiology. A history suspicious for abuse, physical or radiographic evidence of prior injury, and age younger than 18 months were risk factors for abuse. Patients with no risk factors had a 4% chance, patients with one risk factor had a 29% chance, patients with two risk factors had an 87% chance, and patients with all three risk factors had a 92% chance of their femur fracture being a result of abuse. Clinicians can use this predictive model to guide judgment and referral to social services when seeing femur fractures in very young children in the emergency room. Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.


Profile of adult acute cholinesterase inhibitors substances poisoning - a 30 years analysis.
The objective of this study was to assess the pattern and outcome of acute cholinesterase inhibitors substances (CIS) poisoning cases, in a cohort from a regional tertiary care hospital. cases admitted in the Toxicology Clinic of "Sf. Spiridon" Emergency Clinic Hospital Iasi, Romania between 1983 and 2013 were studied. a total number of 606 patients were included. The reason for exposures was intentional in 70% of cases and the commonest route of poisoning was oral in 92.2%. The highest percent of cases was females (56.4), the age group 20-29 (25.4%) and the majority (66.7%) coming from rural areas, 28.2% being agricultural workers. 36.6% of cases were severe clinical forms. Overall mortality rates were 3.8%, more than half of the death patients (65.2%) had concomitant alcohol intake. It was a significant statistical association between decrease level of serum cholinesterase on admittance and severe forms (p 0.000) and between survival and deaths groups (p 0.000). The pattern of poisoning described by our retrospective study suggests that CIS poisoning are mainly preventable. The main effective goals for prevention are restriction in free accessibility to toxic pesticides, together with sustained efforts in education concerning the life-threatening danger of pesticide poisoning.


Bcl-xL modulates apoptosis induced by anticancer drugs and delays DEVDase and DNA fragmentation-promoting activities.
Using an episomal eucaryotic expression vector, we derived three stable transfected human leukemic U-937 variant lines showing differential expression of the Bcl-xL protein. Preventive effect of Bcl-xL on cell death induced by various concentrations of camptothecin (DNA topoisomerase I inhibitor; CPT) was observed in the three lines with most pronounced effect in cells containing the highest level of Bcl-xL expression. These results show that increased cell death protection by Bcl-xL is correlated with its level of expression. The extent of DNA strand break formation and DNA synthesis inhibition following CPT treatments was similar in control and transfected U-937 cells, suggesting that Bcl-xL acts downstream of CPT-DNA topoisomerase I-mediated DNA strand breaks. Modulation of cell death by Bcl-xL was also observed in cells treated with etoposide, vinblastine, paclitaxel, and cisplatinum (II) diammine dichloride. To define whether Bcl-xL functions downstream or upstream of apoptogenic proteolytic cascade activation, we compared kinetics of DNA fragmentation in treated cells with kinetics of caspase 1-like, caspase 3-like, and N-tosyl-L-phenylalanylchloromethyl ketone (TPCK)-sensitive activities. In CPT-treated U-937 cells, caspase 3-like and TPCK-sensitive activities promoting DNA fragmentation in a cell-free system were detected much more rapidly in extracts obtained from CPT-treated U-937 cells compared to those obtained from CPT-treated U-937-Bcl-xL variant cells. These results suggest that Bcl-xL delays their activation that correlates with the occurrence of DNA fragmentation. Addition of recombinant Bcl-xL in extracts containing DEVDase and TPCK-sensitive activities did not inhibit these activities, suggesting that Bcl-xL acts primarily upstream of their activation in the apoptotic process. Taken together, these results suggest that Bcl-xL is a primary checkpoint that can block or delay transmission of cell death signals emerging from DNA damage and prevents activation of an apoptogenic proteolytic cascade.


TPL2 (Therapeutic Targeting Tumor Progression Locus-2)/ATF4 (Activating Transcription Factor-4)/SDF1α (Chemokine Stromal Cell-Derived Factor-α) Axis Suppresses Diabetic Retinopathy.
Diabetic retinopathy is characterized by vasopermeability, vascular leakage, inflammation, blood-retinal barrier breakdown, capillary degeneration, and neovascularization. However, the mechanisms underlying the association between diabetes mellitus and progression retinopathy remain unclear. TPL2 (tumor progression locus 2), a serine-threonine protein kinase, exerts a pathological effect on vascular angiogenesis. This study investigated the role of Nε-(carboxymethyl)lysine, a major advanced glycation end products, and the involved TPL2-related molecular signals in diabetic retinopathy using models of in vitro and in vivo and human samples. Serum Nε-(carboxymethyl)lysine levels and TPL2 kinase activity were significantly increased in clinical patients and experimental animals with diabetic retinopathy. Intravitreal administration of pharmacological blocker or neutralizing antibody inhibited TPL2 and effectively suppressed the pathological characteristics of retinopathy in streptozotocin-induced diabetic animal models. Intravitreal VEGF (vascular endothelial growth factor) neutralization also suppressed the diabetic retinopathy in diabetic animal models. Mechanistic studies in primary human umbilical vein endothelial cells and primary retinal microvascular endothelial cells from streptozotocin-diabetic rats, db/db mice, and samples from patients with diabetic retinopathy revealed a positive parallel correlation between Nε-(carboxymethyl)lysine and the TPL2/chemokine SDF1α (stromal cell-derived factor-α) axis that is dependent on endoplasmic reticulum stress-related molecules, especially ATF4 (activating transcription factor-4). This study demonstrates that inhibiting the Nε-(carboxymethyl)lysine-induced TPL2/ATF4/SDF1α axis can effectively prevent diabetes mellitus-mediated retinal microvascular dysfunction. This signaling axis may include the therapeutic potential for other diseases involving pathological neovascularization or macular edema.


Efficacy of Change to New P2Y12 Receptor Antagonists in Patients High on Treatment Platelet Reactivity Undergoing Percutaneous Coronary Intervention.
Selective intensification of platelet inhibition may improve high on treatment platelet reactivity (HPR). We evaluated the efficacy of dual-antiplatelet therapy, including clopidogrel (CPG), compared to new P2Y12-receptor antagonists in patients with HPR undergoing percutaneous coronary intervention, regarding the outcome of composite major adverse cardiac events (MACEs, including death, acute coronary syndrome [ACS], and stent restenosis). The presence of HPR (71 of 181 patients) almost doubled the risk of MACEs. The new antiplatelet agent reduced MACEs (45.8%, 26%, and 16.7% for CPG, prasugrel, and ticagrelor [TGL]; RR 0.36; 0.13-0.98, P = .03, TGL), specifically in patients with ACS. Failure to reduce HPR after the antiplatelet change and diabetes were independent predictors for MACEs. The HPR was early and effectively reduced after changing the antiplatelet therapy, but the intensity of this reduction did not significantly decrease the risk of MACEs. These findings support the benefit of HPR-guided intensification of platelet inhibition. Whether the intensity of this reduction improves the patient's clinical outcomes deserves further investigation.


[Vac-therapy in the management of tension pneumomediastinum and subcutaneous emphysema].
Pneumomediastinum and subcutaneous emphysema are the main manifestations of gas syndrome in patients with tracheal injury. Traditional mediastinal decompression in case of tension emphysema is carried out through different types of cervical or transpleural mediastinotomy and subsequent passive drainage. Clinical observation of the use of VAC-therapy in the patient with injury of the membranous part of trachea followed by tension pneumomediastinum is presented. Cervicotomy with dissection of anterior mediastinum and installation of vacuum-assisted dressing were performed. Fast regression of subcutaneous emphysema and relief of pneumomediastinum were noted. There were no complications. The patient was discharged in 6 days after admission. Effectiveness of VAC-therapy in patients with tension subcutaneous emphysema and pneumomediastinum was confirmed.


Metformin-associated lactic acidosis.
A 58-year-old female with known type 2 diabetes mellitus continued to take her usual medications, including metformin, an ACE inhibitor and a non-steroidal anti-inflammatory drug, while suffering from diarrhoea and vomiting. On presentation to the emergency department, she was found to have a profound lactic acidosis, cardiovascular instability and acute kidney injury. Despite a pH of 6.6, lactate of 14 mmol/L and a brief asystolic cardiac arrest, supportive treatment and the use of renal replacement therapy resulted in rapid improvement in her acid-base abnormalities and haemodynamic parameters. Metformin-associated lactic acidosis is a rare but life-threatening complication of diabetes management. Patient education and awareness amongst clinicians are paramount in the prevention and treatment of this condition.


Imatinib Dramatically Improved Pulmonary Hypertension Caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) Associated with Metastatic Breast Cancer.
Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, showing rapid progression of respiratory dysfunction and pulmonary hypertension (PH). Accumulating evidence suggests that imatinib, a platelet-derived growth factor (PDGF) receptor-tyrosine kinase inhibitor, might be effective and improve severe PH in patients with PTTM associated with gastric cancer. However, its efficacy in PTTM with breast cancer is generally believed as very limited. We experienced a rare case of PTTM associated with metastatic breast cancer, a rare case who were treated with imatinib, exhibiting significant improvement of respiratory dysfunction and PH.


Plasma lipoprotein subclass variation in middle-aged and older adults: Sex-stratified distributions and associations with health status and cardiometabolic risk factors.
Circulating lipids and lipoproteins mediate cardiovascular risk, however routine plasma lipid biochemistry provides limited information on pro-atherogenic remnant particles. We analysed plasma lipoprotein subclasses including very low-density and intermediate-density lipoprotein (VLDL and IDL); and assessed their associations with health and cardiometabolic risk. From 1,976 community-dwelling adults aged 45-67 years, 114/1071 women (10.6%) and 153/905 men (16.9%) were categorised as very healthy. Fasting plasma lipoprotein profiles comprising 112 parameters were measured using 1H nuclear magnetic resonance (NMR) spectroscopy, and associations with health status and cardiometabolic risk factors examined. HDL cholesterol was higher, and IDL and VLDL cholesterol and triglycerides lower, in very healthy women compared to other women, and women compared to men. IDL and VLDL cholesterol and triglyceride were lower in very healthy men compared to other men. HDL cholesterol and apolipoprotein (apo) A-I were inversely, and IDL and VLDL cholesterol, apoB-100, and apoB-100/apoA-I ratio directly associated with body mass index (BMI) in women and men. In women, LDL, IDL and VLDL cholesterol increased with age. Women with diabetes and cardiovascular disease had higher cholesterol, triglycerides, phospholipids and free cholesterol across IDL and VLDL fractions, with similar trends for men with diabetes. Lipoprotein subclasses and density fractions, and their lipid and apolipoprotein constituents, are differentially distributed by sex, health status and BMI. Very healthy women and men are distinguished by favorable lipoprotein profiles, particularly lower concentrations of VLDL and IDL, providing reference intervals for comparison with general populations and adults with cardiometabolic risk factors.


Some effects of 2537 A on green algae and chloroplast preparations.
1. The kinetics of the inactivation of photosynthesis by 2537 A in Chlorella pyrenoidosa and Scenedesmus D(1) indicate that, while the destruction process is largely a first order effect, higher order effects also occur, which become evident at low exposures. In agreement with previous observations, endogenous respiration is insensitive to exposures which inactivate photosynthesis. 2. In Scenedesmus D(1) a solid dose of ultraviolet has no more effect on the photosynthetic apparatus than a dose of equal total duration interrupted by periods of photosynthesis. Nor is any difference noted if the cells are in a different buffer, e.g. 0.05 M KH(2)PO(4), or carbonate-bicarbonate buffer 9. 3. In C. pyrenoidosa, a solid dose and an interrupted dose cause equal effects on photosynthesis when neutral phosphate buffer is used. If the ultraviolet exposure schedules are identical, equal effects are also noted in cells suspended in buffer 9, and in 0.05 M phosphate (pH 6.2). Solid exposures are, however, much more effective than interrupted exposures, when buffer 9 is used. 4. Oxygen evolution (Hill reaction), photosynthesis, and photoreduction in Scenedesmus D(1) are equally sensitive to a given dose of ultraviolet. The mechanism responsible for adaptation to hydrogen metabolism is not more sensitive to ultraviolet than is the photosynthetic mechanism. The O(2)/H(2)/CO(2) reaction in darkness is less sensitive to ultraviolet than any of the above reactions. 5. Glucose oxidation by C. pyrenoidosa, and colony formation in Scenedesmus D(1) are far more sensitive to a given dose of ultraviolet than photosynthesis in these organisms. 6. The photosynthetic apparatus of C. pyrenoidosa is more sensitive to ultraviolet than that of Scenedesmus D(1). 7. The Hill reaction in chloroplast fragments is also inactivated by 2537 A by a first order process. Exposures which inactivate this reaction completely have no effect on polyphenol oxidase, cytochrome oxidase, or catalase in the same chloroplast preparation. 8. After irradiation, the survival of photosynthesis in Scenedesmus D(1) and of the Hill reaction in chloroplast fragments are independent of the light intensity used to measure these processes. 9. No significant changes occur in the ultraviolet absorption of chloroplasts after an exposure to 2537 A, which completely inactivates the Hill reaction.


Cranial dysraphism mistaken for trephination.
Attention is called to a disputed diagnosis of trephination reported for a perforated skull of a prehistoric New England Indian. The perforation, surrounded by a saucer-like depression, is located exactly in the midline just in front of bregma. The finding of a similar lesion in a prehistoric Indian skull from the North Coast of Peru--where, as in New England, good evidence of the practice of trephination is lacking--provides support for a more reasonable diagnosis for both cases: congenital cranial dysraphism, specifically encephalocele. Information about dysraphic states from modern clinical experience is summarized.


The composition and structure of stones in enlarged prostatic utricles (EPU).
Our objective was to comprehensively test the composition, morphology, and structure of enlarged prostatic utricle (EPU) stones, which, as a kind of biolite in abnormal anatomical structures of the genitourinary system, have not yet been reported. Thirty-one EPU stones coming from 8 patients, who had been treated in our center from 1985 to 2009, were taken out by transurethral fenestration of EPU and were analyzed by scanning electron microscopy, x-ray diffraction (XRD) analysis, and Fourier transformation infrared spectral (FTIS) analysis. Under scanning electron microscope, all these EPU calculi were seen to be constituted of many intensive minicrystals and amorphous matrix. By XRD and FTIS analysis, we determined that the 31 EPU stones in our research were all hydroxyapatite crystal. We consider that EPU calculi should belong to the category of prostatic pseudocalculi and that the formation of EPU calculi is not caused by the abnormal change of urine composition, but should be ascribed to continuously concentrated EPU liquid by absorption of capsule walls and calculous matrix mainly coming from deciduous epithelial cells of EPUs. The role of the amorphous matrix is to link microcrystals, which promotes the growth of EPU stones.


Development of an aggregation-based immunoassay for anti-protein A using gold nanoparticles.
A unique, sensitive, and highly specific immunoassay system for antibodies using gold nanoparticles has been developed. The assay is based on the aggregation of gold nanoparticles that are coated with protein antigens in the presence of their corresponding antibodies. The aggregation of the gold nanoparticles results in an absorption change at 620 nm that is monitored using an absorption plate reader. To demonstrate the analytical capabilities of the new technique, monodispersed protein A-coated gold particles, averaging 10 nm in diameter, were used to determine the level of anti-protein A in serum samples. The effects of the pH, the temperature, and the concentration of protein A-coated gold nanoparticles on the sensitivity of the assay were investigated using transmission electron microscopy (TEM) and UV/vis absorption spectroscopy. A dynamic range of 2 orders of magnitude and a limit of detection of 1 microg/mL of anti-protein A were observed. The new technique could be used for fast, high-throughput screening of antibodies in clinical diagnostic applications.


Fatal Blowhole Obstruction by Eel in Common Bottlenose Dolphins (Tursiops truncatus) in Florida, USA.
Esophageal and pharyngeal obstruction are commonly reported in marine mammals, but asphyxiation from blowhole and nasal cavity obstruction has been reported only rarely: in two long-finned pilot whales (Globicephala melas), several harbor porpoises (Phocoena phocoena), and one common bottlenose dolphin (Tursiops truncatus). We describe two cases of blowhole obstruction and subsequent asphyxiation in bottlenose dolphins caused by eels. A whip eel (Bascanichthys scuticaris) was found obstructing the blowhole of a deceased dolphin from the Indian River Lagoon, Florida, US (2011) and a shrimp eel (Ophichthus gomesii) was found obstructing the blowhole of a deceased dolphin from Tampa Bay, Florida (2020). Normally, the respiratory and digestive tracts of cetaceans do not communicate. Consuming large or oddly shaped prey can result in laryngeal displacement and subsequent interaction between the two systems. It is likely the eels entered the oral cavity while the dolphins were consuming or playing with prey, and laryngeal displacement enabled the eels to slither into and become stuck in the nasal passage, causing asphyxiation. These novel findings underscore the importance of continued investigation into causes of mortality in stranded marine mammals and can contribute to the knowledge of feeding ecology in bottlenose dolphins. As changing environmental conditions contribute to shifts in prey availability and abundance, mortality due to prey-related asphyxiation could become more common in odontocetes.


Improving Silkworm Genome Annotation Using a Proteogenomics Approach.
The silkworm genome has been deeply sequenced and assembled, but accurate genome annotation, which is important for modern biological research, remains far from complete. To improve silkworm genome annotation, we carried out a proteogenomics analysis using 9.8 million mass spectra collected from different tissues and developmental stages of the silkworm. The results confirmed the translational products of 4307 existing gene models and identified 1701 novel genome search-specific peptides (GSSPs). Using these GSSPs, 74 novel gene-coding sequences were identified, and 121 existing gene models were corrected. We also identified 1182 novel junction peptides based on an exon-skipping database that resulted in the identification of 973 alternative splicing sites. Furthermore, we performed RNA-seq analysis to improve silkworm genome annotation at the transcriptional level. A total of 1704 new transcripts and 1136 new exons were identified, 2581 untranslated regions (UTRs) were revised, and 1301 alternative splicing (AS) genes were identified. The transcriptomics results were integrated with the proteomics data to further complement and verify the new annotations. In addition, 14 incorrect genes and 10 skipped exons were verified using the two analysis methods. Altogether, we identified 1838 new transcripts and 1593 AS genes and revised 5074 existing genes using proteogenomics and transcriptome analyses. Data are available via ProteomeXchange with identifier PXD009672. The large-scale proteogenomics and transcriptome analyses in this study will greatly improve silkworm genome annotation and contribute to future studies.


News from health research: toward a better understanding.
News about health research findings, especially regarding controversial topics, can seem confusing and conflicting to students and the general public. Many people eventually develop a "turned-off" attitude toward all health news. Yet medical information is one of the key factors involved in health decision-making, because it influences a person's judgment about the potential health impact of a behavior choice. As part of their health education, youngsters need to learn skills to better understand and evaluate reports of research news, so the information available for health decision-making will be more complete and accurate. Such news is already abundant in television, radio, newspaper and magazine reports and will continue to increase as research advances, knowledge expands and health "facts" are revised. This article outlines concepts and skills to help teachers and students understand the changes and controversies in health news. To most effectively use new information generated by medical research, students need to: 1) understand basic concepts about the nature of research and the research process; 2) apply critical thinking approaches to health news; and 3) locate additional health information resources. Generating ways to address these needs is a high priority of the school health education work at the National Heart, Lung and Blood Institute. Comments are invited on this approach.


Survival analysis of pseudomyxoma peritonei patients treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
To evaluate the survival of patients with pseudomyxoma peritonei (PMP) treated by cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), and to identify factors with prognostic value. PMP is a clinical syndrome characterized by progressive intraperitoneal accumulation of mucous and mucinous implants, usually derived from a ruptured mucinous neoplasm of the appendix. Survival is dominated by pathology. A total of 103 patients (34 men and 69 women) treated at The Netherlands Cancer Institute between 1996 and 2004 were identified. Survival was calculated from date of initial treatment and corrected for a second procedure. PMP was pathologically categorized into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and an intermediate subtype (PMCA-I). Clinical and pathologic factors were analyzed to identify their prognostic value for survival. Median follow-up was 51.5 months (range, 0.1-99.5 months). Recurrence developed in 44%. A second procedure for recurrence was performed in 11 patients. The median disease-free interval was 25.6 months (95% confidence interval [CI], 14.8-43.6 months). The 3-year and 5-year disease-free survival probability was 43.6% (95% CI, 34.4%-55.2%) and 37.4% (95% CI, 28.2%-49.5%), respectively. The disease-specific 3-year and 5-year survival probability was 70.9% (95% CI, 62.0%-81.2%) and 59.5% (95% CI 48.7%-72.5%), respectively. Factors associated with survival were pathological subtype, completeness of cytoreduction, and degree and location of tumor load (P < 0.05). The main prognostic factor, independently associated with survival, was the pathologic subtype (P < 0.01). Cytoreductive surgery in combination with intraoperative HIPEC is a feasible treatment strategy for PMP in terms of survival. The pathologic subtype remains the dominant factor in survival. Patients should be centralized to improve survival by a combination of surgical experience and adequate patient selection.


Chemokine (CC motif) ligand 18 upregulates Slug expression to promote stem-cell like features by activating the mammalian target of rapamycin pathway in oral squamous cell carcinoma.
Chemokine (CC motif) ligand 18 (CCL18) is involved in remodeling of the tumor microenvironment and plays critical roles in oncogenesis, invasiveness, and metastasis. We previously investigated the overexpression of CCL18 in primary oral squamous cell carcinoma (OSCC) tissues and its association with advanced clinical stage in OSCC patients. However, the underlying mechanisms of this CCL18-derived activity remains unidentified. This study showed exogenous CCL18 increased cell migration and invasion and induced cell epithelial-mesenchymal transition (EMT), and that E-cadherin, an epithelial marker, decreased and N-cadherin, a mesenchymal marker, increased, compared to negative control in OSCC cells. Furthermore, we detected that CCL18 induced the acquisition of cancer stem(-like) cell characteristics in oral cancer cells, but also found a significantly positive correlation between the expression of CCL18 and Bmi-1 (P < 0.001) in OSCC surgical specimens by immunohistochemistry analysis. The expression of octamer-binding transcription factor 4 and Bmi-1 were significantly upregulated, and proportions of aldehyde dehydrogenasehigh+ cells and CD133+ cells were markedly increased in CCL18-treated cells compared to untreated cells. Sphere formation ability was observably enhanced when cells were continually exposed to high levels of CCL18. Moreover, CCL18 upregulated Slug expression by stimulating the mammalian target of rapamycin (mTOR) signaling pathway in OSCC cell lines. Inhibition of the mTOR pathway by INK128, or Slug knockdown by RNA interference, reversed CCL18-induced EMT and the stemness response at both molecular and functional levels. In conclusion, our data suggested that CCL18 upregulated Slug expression to promote EMT and stem cell-like features by activating the mTOR pathway in oral cancer. These findings provide new potential targets for the early diagnosis and treatment of OSCC.


Anger, hostility, and cardiac symptoms in women with suspected coronary artery disease: the Women's Ischemia Syndrome Evaluation (WISE) Study.
To determine the relationship of anger and hostility to angiographic coronary artery disease (CAD), symptoms, and functional status among women with suspected CAD. Data were collected from 636 women with suspected CAD referred for diagnostic angiography in the Women's Ischemia Syndrome Evaluation (WISE) Study. CAD was assessed as angiographic presence/absence of disease (> or =50% stenosis in any epicardial coronary artery). Hostility/anger, angina, symptoms, and functional status were assessed by the Cook-Medley Hostility Inventory, Spielberger Anger Expression Scale, cardiovascular symptom history, and the Duke Activity Status Index. Logistic regression revealed that anger-out (i.e., aggressive behavior in response to angry feelings) was independently associated with the presence/absence of angiographic CAD (OR = 1.09, CI 1.01-1.17). Anger and hostility were higher among women reporting increased cardiovascular symptoms. In women without angiographic CAD, those with nonanginal cardiac symptoms had the highest anger-out, anger expression, hostile affect, and aggressive responding scores, and those with typical angina reported the lowest functional status. Among women with CAD, functional status was lowest in women with atypical angina. Among women with suspected CAD, anger-out scores were associated with the presence of angiographic CAD. Anger/hostility traits were associated with increased symptoms, particularly with nonanginal chest pain in women without angiographic CAD. Relationships among psychosocial factors, cardiac symptoms, and angiographic CAD are potentially important in the management of women with suspected CAD.


A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women.
a small number of reports exist on the cognitive effects of soy isoflavones, the findings from which are mixed. Isoflavone efficacy is dependent upon conversion of glycosides contained in soy foods and supplements to the biologically active aglycons. Of particular interest is the production of the metabolite, equol, which is dependent upon intestinal microflora and an integrous digestive system, both being altered by age and age-associated conditions. Unfortunately, few studies enrolled adults over the age of 70, and none included older men. we examined safety, feasibility and cognitive efficacy of soy isoflavone administration in older nondemented men and women (age 62-89 years). in this randomised, placebo-controlled, double-blind pilot study, subjects ingested either 100 mg/day soy isoflavones (glycoside weight) or matching placebo tablets for 6 months. active and placebo-treated subjects exhibited a comparable side-effect profile. Plasma levels of genistein and daidzein (P < 0.001), but not equol, increased with isoflavone administration. While similar at baseline, the two groups differed across 6 months of treatment on 8 of 11 cognitive tests administered. Isoflavone-treated subjects improved on tests of visual-spatial memory (P < 0.01) and construction (P = 0.01), verbal fluency (P < 0.01) and speeded dexterity (P = 0.04). Placebo-treated participants were faster than isoflavone-treated subjects on two tests of executive function (P < 0.05). these data suggest that administration of 100 mg/day of isoflavones was well tolerated. Plasma genistein and daidzein levels, but not equol, increased with isoflavone administration. Finally, data support the potential cognitive effects of soy isoflavones in older adults.


Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening.
Drug development often relies on high-throughput cell-based screening of large compound libraries. However, the lack of miniaturized and parallelized methodologies in chemistry as well as strict separation and incompatibility of the synthesis of bioactive compounds from their biological screenings makes this process expensive and inefficient. Here, we demonstrate an on-chip platform that combines solution-based synthesis of compound libraries with high-throughput biological screenings (chemBIOS). The chemBIOS platform is compatible with both organic solvents required for the synthesis and aqueous solutions necessary for biological screenings. We use the chemBIOS platform to perform 75 parallel, three-component reactions to synthesize a library of lipidoids, followed by characterization via MALDI-MS, on-chip formation of lipoplexes, and on-chip cell screening. The entire process from the library synthesis to cell screening takes only 3 days and about 1 mL of total solutions, demonstrating the potential of the chemBIOS technology to increase efficiency and accelerate screenings and drug development.


Involvement of central alpha-pressor and beta-depressor adrenoceptors in the cardiovascular response to intracerebroventricular catecholamines in the rat.
Microinjections of catecholamines were performed into the lateral ventricle of anesthetized and unanesthetized rats and the blood pressure effects recorded prior to or after the administration of pharmacological antagonists. Injections of 20-100 micrograms normetanephrine (alpha-agonist) produced only pressor responses in both groups of animals. Injections of 10-20 micrograms of norepinephrine (preferentially an alpha-agonist) produced mainly pressor in awake and only depressor responses in anesthetized animals, whereas injections of 10-20 micrograms of epinephrine (preferentially a beta-agonist) produced only depressor responses in both groups of animals. Intracerebroventricular pretreatment with the beta-blocker propranolol (40-100 micrograms) blocked the depressor responses to the catecholamines or even reverted them into clear pressor response. Pretreatment with the alpha-blocker phentolamine (100 micrograms) reduced the pressor effects induced by the intraventricular injection of catecholamines. The existence of central alpha-pressor and beta-depressor mechanisms mediating the blood pressure responses to the intracerebroventricular administration of catecholamines is proposed.


Long-Term Impact of Iatrogenic Bile Duct Injury.
Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including anastomotic strictures, recurrent cholangitis, and secondary biliary cirrhosis. We provide a comprehensive overview of current literature on the long-term outcome of BDI. Considering the availability of only limited data regarding treatment of anastomotic strictures in literature, we also retrospectively analyzed patients with anastomotic strictures following a hepaticojejunostomy (HJ) from a prospectively maintained database of 836 BDI patients. Although clinical outcomes of endoscopic, radiologic, and surgical treatment of BDI are good with success rates of around 90%, quality of life (QoL) may be impaired even after "clinically successful" treatment. Following surgical treatment, the incidence of anastomotic strictures varies from 5 to 69%, with most studies reporting incidences around 10-20%. The median time to stricture formation varies between 11 and 30 months. Long-term BDI-related mortality varies between 1.8 and 4.6%. Of 91 patients treated in our center for anastomotic strictures after HJ, 81 (89%) were treated by percutaneous balloon dilatation, with a long-term success rate of 77%. Twenty-four patients primarily or secondarily underwent surgical revision, with recurrent strictures occurring in 21%. The long-term impact of BDI is considerable, both in terms of clinical outcomes and QoL. Treatment should be performed in tertiary expert centers to optimize outcomes. Patients require a long-term follow-up to detect anastomotic strictures. Strictures should initially be managed by percutaneous dilatation, with surgical revision as a next step in treatment.


Detection of chronic wasting disease prion seeding activity in deer and elk feces by real-time quaking-induced conversion.
Chronic wasting disease (CWD) is an emergent prion disease affecting cervid species in North America, Canada, South Korea, and recently, Norway. Detection of CWD has been advanced by techniques that rely on amplification of low levels of prion amyloid to a detectable level. However, the increased sensitivity of amplification assays is often compromised by inhibitors and/or activators in complex biologic samples including body fluids, excreta, or the environment. Here, we adapt real-time quaking-induced conversion conditions to specifically detect CWD prions in fecal samples from both experimentally infected deer and naturally infected elk and estimate environmental contamination. The results have application to detection, surveillance and management of CWD, and potentially to other protein-misfolding diseases.


Scaling laws for multi-walled carbon nanotube growth by catalyzed chemical vapor deposition.
The synthesis of C nanotubes by catalyzed chemical vapor deposition at 600 degrees C is investigated, using yield and purity degree of C deposits to monitor the reaction outcome. From the reaction, carried out in C4H10-H2-He environment over Al2O3 supported Fe catalysts, multi-walled C nanotubes are attained, which, after purification, are analyzed by routinely-used diagnostics techniques. In order to clarify the role of the growth parameters, various experiments are performed changing flow rates of reactive gases, as well as, amount, metal load and reduction temperature of Fe/Al2O3 catalysts in the ranges 15-90 cc/min, 0.25-2.00 g, 10-40 wt% and 500-700 degrees C, respectively. Correspondingly, carbon yield varies between 47 wt% and 913 wt%, while purity degree between 56 wt% and 93 wt%. Owing to the lack of any correlation between these changes, it is initially quite difficult to envisage the effect, produced by any change of the growth conditions, on the final reaction outcome. The problem is solved by applying a semi-empirical approach, through which the "original" growth variables are combined to give dimensionless arguments (scaling laws for the reaction parameters), able to account for all the variation of yield and purity in the ranges considered. As final result, the growth issue can be easily predicted because carbon yield and purity degree can be approximated through very simple functions of the "new" process variables.


The dynamics of actin-based motility depend on surface parameters.
In cells, actin polymerization at the plasma membrane is induced by the recruitment of proteins such as the Arp2/3 complex, and the zyxin/VASP complex. The physical mechanism of force generation by actin polymerization has been described theoretically using various approaches, but lacks support from experimental data. By the use of reconstituted motility medium, we find that the Wiskott Aldrich syndrome protein (WASP) subdomain, known as VCA, is sufficient to induce actin polymerization and movement when grafted on microspheres. Changes in the surface density of VCA protein or in the microsphere diameter markedly affect the velocity regime, shifting from a continuous to a jerky movement resembling that of the mutated 'hopping' Listeria. These results highlight how simple physical parameters such as surface geometry and protein density directly affect spatially controlled actin polymerization, and play a fundamental role in actin-dependent movement.


Study: poor performers have best improvement.
Greatest improvement seen in three measures for smoking cessation counseling. Increased documentation may have contributed to reports of greater compliance. Room for improvement seen in heart failure discharge instructions, beta-blocker usage.