A guideline for the prevention and management of Fetal Alcohol Spectrum Disorder in South Africa.
Fetal Alcohol Spectrum Disorder (FASD) is a public health problem globally, with South Africa having the highest recorded prevalence of all countries. Government programmes to prevent and manage FASD remain limited because of the lack of a specific policy. Herein, we developed a guideline to inform policy on the prevention and management of FASD in South Africa. We applied a modified version of the World Health Organization's approach to guideline development in three phases. In the first phase, we designed the initial guideline prototype. To do this, we conducted an in-depth interview with policymakers and a focus group with relevant service providers on policy requirements for FASD, a document review of policies on FASD and a scoping review of various interventions for FASD. In phase 2, we refined the initially formulated guideline prototype through a discursive approach with seven local and international experts on FASD. Phase 3 involved refining the prototype using a modified Delphi approach. Forty-three and forty-one experts participated in rounds 1 and 2 of the Delphi approach, respectively. The acceptable consensus for each included policy statement was 85%. We identified three aspects of the proposed guideline, which are the approaches and guiding principles, the prevention measures and the management measures. The guideline proposes that a FASD policy should consider lifespan needs, be culturally diverse, collaborative, evidence-based, multi-sectoral and address social determinants of health contributing to FASD. The essential components of FASD prevention policy consist of awareness and education of the dangers of drinking alcohol, access to treatment for alcohol problems and training of service providers. The management components include capacity building related to diagnosis, educating parents regarding the needs and management, appropriate referral pathways, training of teachers regarding classroom management and support for parents and individuals with FASD. FASD in South Africa deserves urgent attention. Developing a specific policy to guide programmes could enhance and coordinate the efforts towards preventing and managing FASD. The guideline has the potential to assist policymakers in the development of a comprehensive and multi-sectoral policy for prevention and management of FASD, considering the consensus obtained from the experts.


A substrate descriptor based approach for the prediction and understanding of the regioselectivity in caged catalyzed hydroformylation.
The use of data driven tools to predict the selectivity of homogeneous catalysts has received considerable attention in the past years. In these studies often the catalyst structure is varied, but the use of substrate descriptors to rationalize the catalytic outcome is relatively unexplored. To study whether this may be an effective tool, we investigated both an encapsulated and a non-encapsulated rhodium based catalyst in the hydroformylation reaction of 41 terminal alkenes. For the non-encapsulated catalyst, CAT2, the regioselectivity of the acquired substrate scope could be predicted with high accuracy using the Δ13C NMR shift of the alkene carbon atoms as a descriptor (R2 = 0.74) and when combined with a computed intensity of the CC stretch vibration (ICC stretch) the accuracy increased further (R2 = 0.86). In contrast, a substrate descriptor approach with an encapsulated catalyst, CAT1, appeared more challenging indicating a confined space effect. We investigated Sterimol parameters of the substrates as well as computer-aided drug design descriptors of the substrates, but these parameters did not result in a predictive formula. The most accurate substrate descriptor based prediction was made with the Δ13C NMR shift and ICC stretch (R2 = 0.52), suggestive of the involvement of CH-π interactions. To further understand the confined space effect of CAT1, we focused on the subset of 21 allylbenzene derivatives to investigate predictive parameters unique for this subset. These results showed the inclusion of a charge parameter of the aryl ring improved the regioselectivity predictions, which is in agreement with our assessment that noncovalent interactions between the phenyl ring of the cage and the aryl ring of the substrate are relevant for the regioselectivity outcome. However, the correlation is still weak (R2 = 0.36) and as such we are investigating novel parameters that should improve the overall regioselectivity outcome.


Evaluation of the Effectiveness of Systemic Therapy of Spinal Cord Injury of Moderate Severity with Human Umbilical Cord Placental Blood Mononuclear Cells Using Indicators of Dispersion of Articular Angles in the Swimming Test.
Female Sprague-Dawley rats were used as models of moderate contusion spinal cord injury to evaluate the efficiency of single systemic (intravenous) infusion of human mononuclear cord blood cells for restoration of the motor function of hind limbs. The dynamics of recovery of hind limb motor function was assessed using a specially designed method based on calculation of selective dispersion and amplitude-dependent dispersion of hind limbs joint angles measured in the swimming test. The obtained data suggest that systemic application of human mononuclear cord blood cells significantly (p<0.05) promoted recovery of hind limb motor function in the animal models of contusion spinal cord injury of moderate severity in comparison with control animals (without cell therapy).


Electrochemical corrosion in the failure of apical amalgam. Report of two cases.
Apicoectomy with retrograde amalgam is an accepted procedure for treating teeth that cannot be treated by nonsurgical methods. Some of these fail to heal for no apparent reason. Evidence is presented that indicates that some of these failures are caused by corrosion of the apical amalgam. Two cases are described in which the sinus tract that was associated with the failing retrograde amalgam was resolved without further surgery. To bring about the resolution, a zinc-enriched amalgam was placed in the crown that through an intervening conductor, reduced the rate of corrosion at the apex.


Rep68 protein of adeno-associated virus type 2 interacts with 14-3-3 proteins depending on phosphorylation at serine 535.
Rep78/68 proteins of adeno-associated virus type 2 (AAV-2) are involved in many aspects of the viral life cycle, including replication, gene expression, and site-specific integration. To understand the molecular mechanisms of the actions of Rep proteins, we searched for Rep68-interacting cellular proteins by utilizing a one-step affinity purification technique and identified two members of 14-3-3 proteins (14-3-3 epsilon and gamma). We found that phosphorylation of 535Ser at the carboxy terminus of Rep68 was critical for its association with 14-3-3. The association of 14-3-3 proteins to Rep68 resulted in reduction of the affinity of Rep68 for DNA. Furthermore, genome DNA replication of a recombinant mutant virus carrying a phosphorylation-deficient Rep68 (Ser535Ala) was more efficient than that of the wild-type virus. These results suggest that phosphorylation of Rep68 and subsequent association with 14-3-3 proteins regulates Rep-mediated functions during the AAV life cycle.


Cell-mediated immunity: correlation of mixed-leucocyte-macrophage migration inhibition with delayed-type hypersensitivity after immunization and donor-specific transfer of cell migration inhibition by dialyzable leucocyte extract.
Active and adoptive sensitization of rhesus monkeys (Macacca mulatta) as well as the development of a novel sensitive in vitro cell migration inhibition assay for cell-mediated immunity (CMI) in this species are described. First, the correlation of mixed leucocyte-macrophage migration tests (LMMI) with the whole blood lymphocyte transformation (LT) and the delayed hypersensitivity skin test (DH) in immunized animals are shown. Second, these tests are used to demonstrate adoptive transfer of specific/nonspecific cellular immunity (CMI) with dialyzable leucocyte extract (DLE) from immunized donor to unimmunized recipient monkeys. Seventeen animals were immunized with keyhole limpet haemocyanin (KLH) or hepatitis B surface antigen (HBsAg) in Freund's complete adjuvant (FCA) or with FCA alone. Acquisition of antigen-specific cell-mediated immunity was detected by all three tests within 5 weeks of immunization. Positive LMMI responses were associated with positive DH and LT. However, there was no correlation between the magnitude or time of development of the three responses. Therefore, the LMMI test, like the LT test, is an in vitro parameter of DH, but reflects the activity of different subpopulations of lymphocytes and is regulated by different mechanisms. In addition, 12 naive animals received DLE. Within 3 weeks, transfer of sensitivity was detected towards antigens to which the recipients had previously not been reactive but the donors had been. An enhancement of transformation response to phytohaemagglutinin was also seen. Thus, rhesus DLE contains both donor-specific transfer factor-like and nonspecific adjuvant-like activities. In DLE recipients, unlike immunized animals, LMMI responses were dissociated from DH or LT responses in that positive LMMI was mostly seen with negative DH or LT to antigens. Therefore, LMMI emerged as the most sensitive assay for detecting adoptive transfer of CMI by DLE in vivo, supporting the view that different mechanisms regulate LMMI, LT, and DH.


Study of the risk factors associated with Neospora caninum seroprevalence in Algerian cattle populations.
Bovine abortions due to Neospora caninum infection were reported worldwide. The situation in Algeria was unknown. For the evaluation of the prevalence of N. caninum and its associated risk factors, 799 cattle belonging to 87 farms of the north and northeast of Algeria were analyzed. The cattle were divided into imported cattle, local cattle and improved cattle corresponding to breeding between imported and local cattle. Sera were examined for the presence of N. caninum antibodies by indirect fluorescence antibody test. The overall seroprevalence for the 87 farms was 52.87% (41.28-62.71%). The overall animal seroprevalence was 19.64% (16.82-22.45%). The seroprevalence of N. caninum in local cattle (34.28%) was significantly higher (p<0.05) than in modern (16.04%) and improved (18.64%) cattle. The risk factors analysis indicated that cattle population, geographical location, dog presence, season, global farm hygiene or the presence of abortion were significantly associated with seroprevalence.


The relationship between secondhand smoking exposure and mental health among never-smoking adolescents in school: Data from the Global School-based Student Health Survey.
There is no safe level of exposure to secondhand smoking. Adolescence is a stage of rapid psychological development and is highly susceptible to various factors that can cause some mental health problems. This study aims to estimate the prevalence of secondhand smoking exposure in never-smoking school adolescents and evaluate whether there is an association between secondhand smoking exposure and mental health. 70 nationally representative data sets from the Global School-based Student Health Survey, conducted between 2003 and 2017, were used to estimate the prevalence of secondhand smoking exposure and evaluate whether there is an association between secondhand smoking exposure and loneliness, sleeplessness, and suicidal ideation. Total 191, 613 no-smoking school adolescents (43.0% boys) were included in this analysis. The prevalence of secondhand smoking exposure ranged from 15.1% in Tajikistan to 79.6% in Timor-Leste. There was no difference in the prevalence of secondhand smoking exposure between boys and girls in most countries. After adjusted, secondhand smoking exposure was positively associated with loneliness (odds ratio 1.39, 95% CI 1.30-1.49), sleeplessness (odds ratio 1.37, 95% CI 1.28-1.47), and suicidal ideation (odds ratio 1.22, 95% CI 1.15-1.30) in never-smoking school adolescents in overall samples. Use of self-report measures and potentially limited generalizability. Secondhand smoking exposure remains a serious public health issue among never-smoking school adolescents and its impact on adolescent mental health cannot be ignored. Stricter and more comprehensive policies and bans on secondhand smoking should be implemented, and adolescents' mental health should receive more attention.


The effects of the intraocular dye brilliant blue G (BBG) mixed with varying concentrations of glucose on retinal function in an isolated perfused vertebrate retina.
During vitreoretinal surgery, vital dyes such as brilliant blue G (BBG) are used to visualize anatomical structures. By adding glucose to a concentration of 5%, many surgeons try to achieve a dye mixture heavier than water to facilitate staining of the ILM without preceding fluid-air exchange. However, the intraocular use of high glucose concentrations is critical. This study investigated the effect of 0.4 ml BBG (Brilliant Peel™ 0.25 mg/ml, Fluoron, Ulm, Germany) mixed with various glucose concentrations on the retina in an pseudo in vivo model Bovine retinas were isolated and superfused with an oxygen saturated nutrient solution, and the electroretinogram (ERG) was recorded. BBG mixed with 0.05 ml/0.1 ml/0.15 ml glucose 40% was applied epiretinally. ERG recovery was monitored for 75 minutes. 1 mM aspartate was added to the nutrient solution to obtain a-waves. After application of BBG/0.05 ml 40% glucose, a non-significant decrease of the b-wave amplitude was recorded (11.2%). In contrast, higher glucose concentrations showed a significant decrease of the b-wave (23.40% at 0.1 ml glucose, 26% at 0.15 ml glucose). The a-wave amplitudes showed no significant change at the end of the washout for all concentrations. The clinically used mixture of BBG and glucose seems to be safe up to a concentration of 5%. However, higher concentrations of glucose starting from 10% showed strong evidence of a toxic effect on the retinal function and should be avoided.


Association of anti-TPM4 autoantibodies with vasculopathic cutaneous manifestations in juvenile dermatomyositis.
AECAs are detected in multiple forms of vasculitis or vasculopathy, including JDM. High levels of tropomyosin alpha-4 chain (TPM4) gene expression in cutaneous lesions and TPM4 protein expression in some endothelial cells (ECs) have been proven. Furthermore, the presence of autoantibodies to tropomyosin proteins have been discovered in DM. We therefore investigated whether anti-TPM4 autoantibodies are an AECA in JDM and are correlated with clinical features of JDM. The expression of TPM4 protein in cultured normal human dermal microvascular ECs was investigated by Western blotting. Plasma samples from 63 children with JDM, 50 children with polyarticular JIA (pJIA) and 40 healthy children (HC) were tested for the presence of anti-TPM4 autoantibodies using an ELISA. Clinical features were compared between JDM patients with and without anti-TPM4 autoantibodies. Autoantibodies to TPM4 were detected in the plasma of 30% of JDM, 2% of pJIA (P < 0.0001) and 0% of HC (P < 0.0001). In JDM, anti-TPM4 autoantibodies were associated with the presence of cutaneous ulcers (53%; P = 0.02), shawl sign rash (47%; P = 0.03), mucous membrane lesions (84%; P = 0.04) and subcutaneous edema (42%; P < 0.05). Anti-TPM4 autoantibodies significantly correlated with the use of intravenous steroids and IVIG therapy in JDM (both P = 0.01). The total number of medications received was higher in patients with anti-TPM4 autoantibodies (P = 0.02). Anti-TPM4 autoantibodies are detected frequently in children with JDM and are novel myositis-associated autoantibodies. Their presence correlates with vasculopathic and other cutaneous manifestations of JDM that may be indicative of more refractory disease.


High c-di-GMP promotes expression of fpr-1 and katE involved in oxidative stress resistance in Pseudomonas putida KT2440.
Oxidative stress is an unavoidable consequence of interactions with various reactive oxygen species (ROS)-inducing agents that would damage cells or even cause cell death. Bacteria have developed defensive systems, including induction of stress-sensing proteins and detoxification enzymes, to handle oxidative stress. Cyclic diguanylate (c-di-GMP) is a ubiquitous intracellular bacterial second messenger that coordinates diverse aspects of bacterial growth and behavior. In this study, we revealed a mechanism by which c-di-GMP regulated bacterial oxidative stress resistance in Pseudomonas putida KT2440. High c-di-GMP level was found to enhance bacterial resistance towards hydrogen peroxide. Transcription assay showed that expression of two oxidative stress resistance genes, fpr-1 and katE, was promoted under high c-di-GMP level. Deletion of fpr-1 and katE both decreased bacterial tolerance to hydrogen peroxide and weakened the effect of c-di-GMP on oxidative stress resistance. The promoted expression of fpr-1 under high c-di-GMP level was caused by increased cellular ROS via a transcriptional regulator FinR. We further demonstrated that the influence of high c-di-GMP on cellular ROS depend on the existence of FleQ, a transcriptional regulatory c-di-GMP effector. Besides, the regulation of katE by c-di-GMP was also FleQ dependent in an indirect way. Our results proved a connection between c-di-GMP and oxidative stress resistance and revealed a mechanism by which c-di-GMP regulated expression of fpr-1 and katE in P. putida KT2440.


Controlling silica coating thickness on TiO2 nanoparticles for effective photodynamic therapy.
Photosensitive nanoparticles are useful in developing phototherapeutic agents for targeted cancer therapy. In this paper, core-shell structured titanium dioxide-silica (TiO2-SiO2) nanoparticles, with varying shell thickness, were synthesized. The influence of the silica shell thickness on the photoreactivity, cytotoxicity and photo-killing ability of the TiO2 nanoparticles was investigated. Silica coating reduced the photocatalytic reactivity but improved the cytocompatibility of the TiO2 nanoparticles. This effect was amplified with increasing silica shell thickness. When the silica thickness was about 5.5 nm, the coated TiO2 not only retained a high level photodynamic reactivity, comparable to the non-coated TiO2 nanoparticles, but also demonstrated an improved cell compatibility and effective photo-killing ability upon the mouse fibroblast cells (L929).


Spectrum of CLCN1 mutations in patients with myotonia congenita in Northern Scandinavia.
Myotonia congenita is a non-dystrophic muscle disorder affecting the excitability of the skeletal muscle membrane. It can be inherited either as an autosomal dominant (Thomsen's myotonia) or an autosomal recessive (Becker's myotonia) trait. Both types are characterised by myotonia (muscle stiffness) and muscular hypertrophy, and are caused by mutations in the muscle chloride channel gene, CLCN1. At least 50 different CLCN1 mutations have been described worldwide, but in many studies only about half of the patients showed mutations in CLCN1. Limitations in the mutation detection methods and genetic heterogeneity might be explanations. In the current study, we sequenced the entire CLCN1 gene in 15 Northern Norwegian and three Northern Swedish MC families. Our data show a high prevalence of myotonia congenita in Northern Norway similar to Northern Finland, but with a much higher degree of mutation heterogeneity. In total, eight different mutations and three polymorphisms (T87T, D718D, and P727L) were detected. Three mutations (F287S, A331T, and 2284+5C>T) were novel while the others (IVS1+3A>T, 979G>A, F413C, A531V, and R894X) have been reported previously. The mutations F413C, A531V, and R894X predominated in our patient material. Compound heterozygosity for A531V/R894X was the predominant genotype. In two probands, three mutations cosegregated with myotonia. No CLCN1 mutations were identified in two families. Our data support the presence of genetic heterogeneity and additional modifying factors in myotonia congenita.


Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations.
Sunitinib, an oral tyrosine kinase inhibitor approved to treat advanced renal cell carcinoma and gastrointestinal stroma tumor, is associated with clinical cardiac toxicity. Although the precise mechanism of sunitinib cardiotoxicity is not known, both the key metabolic energy regulator, AMP-activated protein kinase (AMPK), and ribosomal S 6 kinase (RSK) have been hypothesized as causative, albeit based on rodent models. To study the mechanism of sunitinib-mediated cardiotoxicity in a human model, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) having electrophysiological and contractile properties of native cardiac tissue were investigated. Sunitinib was cardiotoxic in a dose-dependent manner with an IC₅₀ in the low micromolar range, observed by a loss of cellular ATP, an increase in oxidized glutathione, and induction of apoptosis in iPSC-CMs. Pretreatment of iPSC-CMs with AMPK activators AICAR or metformin, increased the phosphorylation of pAMPK-T172 and pACC-S79, but only marginally attenuated sunitinib mediated cell death. Furthermore, additional inhibitors of AMPK were not directly cytotoxic to iPSC-CMs up to 250 μM concentrations. Inhibition of RSK with a highly specific, irreversible, small molecule inhibitor (RSK-FMK-MEA) did not induce cytotoxicity in iPSC-CMs below 250 μM. Extensive electrophysiological analysis of sunitinib and RSK-FMK-MEA mediated conduction effects were performed. Taken together, these findings suggest that inhibition of AMPK and RSK are not a major component of sunitinib-induced cardiotoxicity. Although the exact mechanism of cardiotoxicity of sunitinib is not known, it is likely due to inhibition of multiple kinases simultaneously. These data highlight the utility of human iPSC-CMs in investigating the potential molecular mechanisms underlying drug-induced cardiotoxicity.


Interactive effects of soil acidity and fluoride on soil solution aluminium chemistry and barley (Hordeum vulgare L.) root growth.
A greenhouse study was conducted to determine if concentrations of fluoride (F), which would be added to acid soils via P fertilisers, were detrimental to barley root growth. Increasing rates of F additions to soil significantly increased the soil solution concentrations of aluminium (Al) and F irrespective of the initial adjusted soil pH, which ranged from 4.25 to 5.48. High rates of F addition severely restricted root growth; the effect was more pronounced in the strongly acidic soil. Speciation calculations demonstrated that increasing rates of F additions substantially increased the concentrations of Al-F complexes in the soil. Stepwise regression analysis showed that it was the combination of the activities of AlF2(1+) and AlF(2+) complexes that primarily controlled barley root growth. The results suggested that continuous input of F to soils, and increased soil acidification, may become an F risk issue in the future.


Engineering Radiosensitizer-Based Metal-Phenolic Networks Potentiate STING Pathway Activation for Advanced Radiotherapy.
Radiotherapy, a mainstay of first-line cancer treatment, suffers from its high-dose radiation-induced systemic toxicity and radioresistance caused by the immunosuppressive tumor microenvironment. The synergy between radiosensitization and immunomodulation may overcome these obstacles for advanced radiotherapy. Here, the authors propose a radiosensitization cooperated with stimulator of interferon genes (STING) pathway activation strategy by fabricating a novel lanthanide-doped radiosensitizer-based metal-phenolic network, NaGdF4 :Nd@NaLuF4 @PEG-polyphenol/Mn (DSPM). The amphiphilic PEG-polyphenol successfully coordinates with NaGdF4 :Nd@NaLuF4 (radiosensitizer) and Mn2+ via robust metal-phenolic coordination. After cell internalization, the pH-responsive disassembly of DSPM triggers the release of their payloads, wherein radiosensitizer sensitizes cancer cells to X-ray and Mn2+ promote STING pathway activation. This radiosensitizer-based DSPM remarkably benefits dendritic cell maturation, anticancer therapeutics in primary tumors, accompanied by robust systemic immune therapeutic performance against metastatic tumors. Therefore, a powerful radiosensitization with STING pathway activation mediated immunostimulation strategy is highlighted here to optimize cancer radiotherapy.


Exploring the molecular mechanisms of the inhibition of acrolein-induced BEAS-2B cytotoxicity by luteolin using network pharmacology and cell biology technology.
Acrolein is a highly reactive unsaturated hazardous air pollutant, which is extremely irritating to the respiratory tract. Luteolin, an active flavonoid compound, possesses multiple biological activities. The purpose of this study was to evaluate the mechanism of the inhibition of acrolein-induced human bronchial epithelial (BEAS-2B) cells cytotoxicity by luteolin using network pharmacology and cell biology technology. Firstly, network pharmacology results indicated that oxidative stress processes might play an important role in luteolin inhibiting lung injury. Next, it was verified at the cellular level. Reactive oxygen species (ROS) generation increased, glutathione (GSH) level decreased after exposure to acrolein. MAPK signaling pathways were activated, which activated downstream IκBα/NF-κB signaling pathways. Meanwhile, acrolein caused oxidative DNA damage and double-strand breaks, induced DNA damage response (DDR) and apoptosis. These adverse effects were significantly reversed by luteolin, which inhibited the activation of MAPK/IκBα/NF-κB and DDR pathways, and reduced the ratio of Bax/Bcl-2. Moreover, luteolin also had a similar effect to antioxidant N-acetyl cysteine (NAC) in the regulation of signaling transduction mechanisms, which indicated that the regulation of oxidative stress played an important role in the process. These results provide an experimental basis for elucidating the molecular mechanisms of the inhibition of acrolein-induced BEAS-2B cytotoxicity with luteolin.


Experimental Models of l-DOPA-Induced Dyskinesia.
Strategies to avoid or minimize dyskinesia and other motor complications of chronic dopamine replacement therapy in Parkinson's disease (PD) remain a significant unmet clinical need. As such, the refinement and development of animal models with which to delineate the underlying molecular mechanisms of dyskinesia and to find effective treatment paradigms remain as necessary as ever. Toxin-based models including the MPTP-lesioned primate and the 6-hydroxydopamine (6-OHDA) lesioned rodent continue to form the bedrock of current l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia modeling approaches. This chapter reviews these models, illustrating their origins, application and strengths as well as problems that accompany their use. We also describe new methodologies that, although still in their infancy, may offer powerful future alternatives by which to better model this debilitating complication of current PD treatment.


Reflected Vision in Surgical Practice-A Novel Method to Circumvent Posture-Related Musculoskeletal Disorders.
Abnormal neck posture while working is a crucial factor that predisposes to incidence of musculoskeletal disorders amongst oral and maxillofacial surgeons. The related spectrum of clinical symptoms may range from severe pain in the lower and upper back, neck and TMJ to neurological deficits of the hand and wrist. These posture-related problems may be prevented by use of reflected vision that ensures a balanced neck posture during surgical procedures.


Fertility preservation in women with malignant tumors and gonadotoxic treatments.
Because of improved survival rates and recent advances in reproductive medicine, fertility preservation methods in women of reproductive age with malignant or autoimmune diseases have risen in importance. Selective literature review based on the authors' clinical and scientific experience. Fertility-preserving techniques are recommended for all girls and women up to age 40 who are at high risk of ovarian failure. As these techniques are complex, special expertise in counseling and treatment is needed; in the German-speaking countries, such expertise is available in centers belonging to the FertiPROTEKT network (www.fertiprotekt.eu). Most of these techniques carry a very low risk and can be performed in two weeks or less. Success rates depend on the patient's age, the experience of the center, and the particular technique used. The highest attainable likelihood of pregnancy after the use of a combination of cryopreservation techniques is estimated at 40% to 50%. Fertility preservation is generally not covered by health insurance; its cost ranges from several hundred to several thousand euros. Girls and women up to age 40 who are about to undergo gonadotoxic treatment should be counseled about the availability of fertility-preserving techniques and, if appropriate, should be treated with such techniques in a specialized center.


Hippocampal mossy fiber-CA3 synapses after chronic alcohol consumption and withdrawal.
A quantitative study of the CA3 pyramidal cells and of the mossy fiber-CA3 synapses (MF-CA3) of the rat hippocampal formation was performed in rats alcohol-fed for 6, 12 and 18 months and respective age-matched controls. Additional groups alcohol-fed for 6 and 12 months and withdrawn for 6 months were also studied. The numerical densities of the CA3 pyramids and of the synapses were calculated applying the disector method to adjacent sections of the CA3 pyramidal cell layer and the stratum lucidum respectively. The results showed a progressive loss of pyramidal cells in alcohol-treated and withdrawal groups and a significant decrease of MF-CA3 synapses after 18 months of alcohol feeding. Taking into account that both hippocampal granule and CA3 pyramidal cells are reduced, the maintenance of the relative number of MF-CA3 synapses in 6- and 12-month alcohol-fed rats suggests the formation of new contacts. The increased proportion of the MF plasmalemma occupied by synapses can also be interpreted as an additional compensation process. These data show that MF-CA3 synapses display plastic and degenerative changes after chronic alcohol consumption and withdrawal which presumably will lead to functional modifications of the hippocampal circuitry.


Evidence for lung epithelial stem cell niches.
Recent studies have identified epithelial stem and progenitor cell populations of the lung. We are just beginning to understand the mechanisms that regulate their homeostatic, regenerative and maladaptive behaviors. Here, we discuss evidence of regulatory niches for epithelial stem cells of the lung.


Foxl1-expressing mesenchymal cells constitute the intestinal stem cell niche.
Intestinal epithelial stem cells that express Lgr5 and/or Bmi1 continuously replicate and generate differentiated cells throughout life1. Previously, Paneth cells were suggested to constitute an epithelium-intrinsic niche that regulates the behavior of these stem cells2. However, ablating Paneth cells has no effect on maintenance of functional stem cells3-5. Here, we demonstrate definitively that a small subset of mesenchymal, subepithelial cells expressing the winged-helix transcription factor Foxl1 are a critical component of the intestinal stem cell niche. We genetically ablated Foxl1+ mesenchymal cells in adult mice using two separate models by expressing either the human or simian diphtheria toxin receptor (DTR) under Foxl1 promoter control. Killing Foxl1+ cells by diphtheria toxin administration led to an abrupt cessation of proliferation of both epithelial stem- and transit-amplifying progenitor-cell populations that was associated with a loss of active Wnt signaling to the intestinal epithelium. Therefore, Foxl1-expressing mesenchymal cells constitute the fundamental niche for intestinal stem cells.


Do Textiles Impact DXA Bone Density or Body Composition Results?
External artifacts can confound dual-energy X-ray absorptiometry (DXA) measurements. It is often accepted that garments free of metal do not affect DXA results; however, little data exist in this regard. It is plausible that some textiles absorb radiation and thereby alter DXA results. We hypothesized that some dense or synthetic textiles, for example, reflective materials, might alter DXA-measured bone and soft tissue mass. Hologic and GE Lunar spine phantoms and a Bioclinica prototype total body phantom were imaged on a GE Lunar iDXA and Prodigy densitometer. Each phantom was scanned 10 times to establish mean values. Subsequently, 2 layers of various fabrics were placed over the entire top surface of the phantom, and 10 scans were performed without repositioning. Samples of natural, synthetic, or embellished fabric (including those with reflective material) and of varying thickness were used. Wilcoxon signed rank tests were used to compare the means between bare phantom and textile-covered phantom. Significant differences were demonstrated often, depending on the scanner, phantom, and textile used. A polyester fabric with reflective strip consistently altered measurements. For example, this fabric increased measured mean lumbar spine bone mineral density and total body bone mineral content by 0.008 g/cm2 and 3.6 g, respectively (p < 0.01). Similarly, mean total body fat decreased (-173 g) and lean mass increased (+213 g; p < 0.01). Fat and lean mass were also affected by metallic thread, wool, blend denim, and shiny polyester (p < 0.05), and lean mass was affected by cotton denim and sweatshirt material (p < 0.0003). In conclusion, textiles can affect DXA-measured bone mineral density and body composition results. Even small amounts of reflective material could alter mass measurements by ~25% of the least significant change. Clothing made of dense textiles (e.g., wool and denim) or those with reflective material and metallic thread should be avoided during DXA scanning.


A Novel QTL Conferring Fusarium Crown Rot Resistance Located on Chromosome Arm 6HL in Barley.
Fusarium crown rot (FCR), caused primarily by Fusarium pseudograminearum, is a devastating disease for cereal production in semi-arid regions worldwide. To identify and characterize loci conferring FCR resistance, we assessed a landrace AWCS799 which is among the best lines identified from a systematic screening of more than 1,000 genotypes. Genetic control of its resistance was investigated by generating and analyzing two populations of recombinant inbred lines with AWCS799 as the common parent. One of the populations was used for QTL detection and the other for validation. A novel QTL, located on the long arm of chromosome 6H (designated as Qcrs.caf-6H), was consistently detected in each of the four FCR severity tests conducted against the mapping population. The QTL explained up to 28.3% of the phenotypic variance, and its effect was confirmed in the validation population. Significant interaction between this resistance locus and either plant height or heading date was not detected, further facilitating its manipulation in breeding programs.


An unusual intrapartum fetal heart rate pattern. A case report.
An unusual fetal heart rate pattern was detected intrapartum in a patient with an otherwise uncomplicated pregnancy. An approach to the evaluation of the unusual fetal heart rate pattern was developed.


Can adjuvant pelvic radiation therapy after local excision or polypectomy for T1 and T2 rectal cancer offer an alternative option to radical surgery?
To determine outcomes after adjuvant pelvic local radiation therapy (RT) +/- concurrent chemotherapy for T1 and T2 rectal carcinomas treated with local excision or polypectomy. We retrospectively identified adult patients with histologically proven T1 and T2 rectal adenocarcinoma, diagnosed incidentally at time of local excision or polypectomy between 01 January 2007 and 31 December 2019, and appropriately staged to confirm N0 M0 status. Patients were excluded if they had recurrent cancer or had received total mesorectal excision (TME): anterior resection (AR) or abdominoperineal resection (APR). Patient, tumour and treatment factors, together with disease and toxicity outcomes were collected from institutional medical records, correspondence and investigation reports. Descriptive statistical analyses were employed. The primary endpoint was loco-regional control and secondary endpoints were treatment-related toxicity, disease free survival, overall survival and rate of surgical salvage for pelvic recurrence. The median age of the 15 eligible patients was 73 (range 49-82 years). There were 9 men (60%) and 6 women (40%). The majority had T1 disease (80%) and most had received endomucosal resection (80%). All patients received 43-52Gy (EQD2) to the primary and 43-48Gy (EQD2) to the pelvis with 46.6% receiving concurrent chemotherapy (infusional 5-FU or oral capecitabine). At median follow up of 51 months, there were no local or regional recurrences. One patient experienced an isolated distant relapse at 48 months without any locoregional recurrence. Our findings demonstrate good locoregional disease control with the use of adjuvant pelvic RT for T1 and T2 rectal adenocarcinoma initially treated with polypectomy or local (non-oncological) excision. These findings indicate that adjuvant pelvic RT may provide an alternative to TME surgery in patients with incidentally detected early rectal cancers.


Immunoprotective potential of in silico predicted Acinetobacter baumannii outer membrane nuclease, NucAb.
Acinetobacter baumannii is an emerging multi-drug resistant pathogen causing significant mortality in hospitalized ICU patients which demands developing new methods for prevention and treatment. A. baumannii 19606 proteome was analysed in silico through the online tool Vaxign for finding potential vaccine candidates. The selected nuclease (NucAb) was predicted to possess all the attributes of a promising vaccine candidate like outer membrane localization, high adhesin probability (0.53), one transmembrane helix only, non-homology to human proteins and presence of B-cell and T-cell epitopes binding with high affinity (percentile rank≤1) to HLA alleles prevalent at high frequency in North Indian populations. nucAb gene was highly prevalent (100%) among the clinical isolates (40/40) and conserved (>98%) among NCBI sequenced Acinetobacter strains. It was cloned in pET28a, purified and its immunoprotective potential was validated in murine pneumonia model. Immunization of BALB/c mice with recombinant NucAb (25μg) elicited high antibody titre (1-5×10(5)) which reduced bacterial load by 5 log cycles in lungs of mice challenged with optimized lethal dose (10(8)CFU). Lung histopathology revealed marked suppression of inflammation. Pro-inflammatory cytokines (TNF-α and IL-6) levels were reduced significantly and anti-inflammatory (IL-10) cytokine increased in lungs and serum leading to decreased severity and slow progression of disease. Though active immunization showed low survival rate (20%), passive immunization improved the survival (40%). This is the first study reporting an outer membrane nuclease as a vaccine candidate in Gram negative bacterium, A. baumannii through reverse vaccinology approach.


Discovery of a novel benzyloxyisoquinoline derivative with potent anti-Helicobacter pylori activity.
The synthesis and in vitro optimization of the anti-Helicobacter pylori activity of a novel series of benzyloxyisoquinoline derivatives discovered by a random screening process, are described. FR180102 (7f), having a 3-acetamido-2,6-dichlorobenzyl moiety, was found to have extremely potent activity against H. pylori and no effect against a series of common Gram-positive and Gram-negative bacteria.


Distinct epitopes on the T8 molecule are differentially involved in cytotoxic T cell function.
The present report attempts to determine if there are distinct epitopes on the T8 molecule that are involved in class I-restricted cytotoxic T lymphocyte (CTL) function. A panel of 9 monoclonal antibodies (OKT8A,B,C,E,F,G,H,I, and OKT5) was produced and all antibodies were shown to bind to the T8 molecule. This panel of antibodies was employed to characterize the distribution of distinct epitopes on the T8 molecule and to block the activity of class I-specific influenza virus-immune and allo-immune CTL effector function. Significant differences in the ability of the anti-T8 antibodies to block CTL function were observed: OKT8C and T8F blocked best (49 and 55% respectively); OKT8A,E,G,H,I, and OKT5 blocked less well (24-31%); and OKT8B blocked marginally (11%). There was no correlation between the capacity of the antibodies to block CTL function and their heavy chain isotype. Competitive binding of the different OKT8 antibodies to the cell surface and differential trypsin sensitivity of the epitopes recognized by the antibodies indicated that OKT8C and T8F were located on topographically distinct regions of the T8 molecule. These results indicate that specific epitopes on the T8 molecule are involved in CTL function, and that there could be more than one functional site on the molecule.


Acquisition and biosynthesis of saturated and unsaturated fatty acids by trypanosomatids.
As components of phospholipids and glycosylphosphatidylinositol anchors, fatty acids are responsible for forming the core of biological membranes and the correct localization of proteins within membranes. They also contribute to anchoring proteins by direct acylation of specific amino acids. Fatty acids can be used as energy sources and serve as signaling molecules or precursors for their synthesis. All these processes highlight the important role of fatty acids in cell physiology, justifying the diverse strategies for their acquisition evolved by different organisms. This review describes several recent findings in the salvage and biosynthesis of fatty acids by parasitic protists belonging to the class Kinetoplastea. They include two biosynthetic routes, the mitochondrial one and a peculiar membrane-associated pathway, the synthesis of polyunsaturated fatty acids, and the scavenging of lysophospholipids and lipoproteins from host plasma. These different processes are also explored as putative targets for chemotherapy.


Differential sensitivity to dexamethasone suppression in an animal model of the DST.
The present study reports the feedback suppression of basal and stimulated corticosterone secretion in rats by low doses of dexamethasone (DEX). DEX suppression of basal secretion 6 hr after administration was observed with doses as low as 0.005 mg/kg. The lowest dose capable of suppressing basal corticosterone levels for 24 hr with a return to normal values by 36 hr was established to be 0.025 mg/kg. The ability of DEX to decrease corticosterone responses to physostigmine, morphine, immobilization, and ether stress was determined. Although the magnitude of the rise in corticosterone did not differ significantly among these evocative stimuli, the degree to which DEX attenuated these responses varied. The response to morphine was completely prevented by 0.025 mg/kg and the rises following ether or immobilization were decreased significantly. In contrast, the response to physostigmine was not affected by DEX. With a higher dose of DEX (0.25 mg/kg), responses to morphine, ether, and immobilization were completely eliminated, but the response to physostigmine was only attenuated partway. The time course of the suppression in basal levels, the attenuation of several stimuli for corticosterone secretion, and the "escape" of physostigmine-induced corticosterone secretion resemble the clinical Dexamethasone Suppression Test of endogenous depression and suggest that this test might be useful in the study of animal models of depression.


Variations in the tangential distribution of postsynaptic glutamate receptors in Purkinje cell parallel and climbing fiber synapses during development.
Major factors affecting the responses of a neuron to release of glutamate include the kinds and distribution of glutamate receptors in the neuron and their distribution along the surface of the postsynaptic membrane (tangential distribution). The latter distribution pattern is established during the development of the synapse and could be modified during maturation of synapse structure/function and through adult synapse plasticity. Parallel and climbing fiber synapses of cerebellar Purkinje cells are good models for studying this pattern because they contain two major kinds of ionotropic glutamate receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and delta, that are involved in adult plasticity and show differences in distribution, and because these two synapse types show complex changes in architecture and glutamate receptor distributions during development. In the present study, both AMPA and delta receptors showed variations in tangential distributions during many stages of development from postnatal day 2 to adult; i.e. qualitative assessment showed that receptors are concentrated either near the center or in outer portions of the synapse, while they are rare or absent from the perisynaptic region. Quantitative analysis showed statistically significant nonuniformities at some ages; the most common nonuniformity in these cases appears to be a drop-off in receptor density in the outer 20% of the synapse. Statistical analyses also indicated that distribution patterns did not change significantly with age. In contrast to the ionotropic receptors, the metabotropic glutamate receptor, mGluR1alpha, was found mainly in the perisynaptic region both during development and in adults. Differences in the distribution of glutamate receptors may be necessary to assure an effective response to glutamate release and may be modified through synaptic plasticity. Our findings show that the basic patterns of distribution of ionotropic and metabotropic glutamate receptors in synapses are established early in development, indicating that the postsynaptic density/membrane region is highly organized even in the immature synapse.


Gender balance and its impact on male and female smoking rates in Chinese cities.
Although gender differences in smoking have received much attention, few studies have explored the importance of contextual effects on male and female smoking rates. The aim of this study is to examine the association between variations in city-level sex ratios and gender differences in smoking in China. Participants included 16,866 urban residents, who were identified through multi-stage sampling conducted in 21 Chinese cities. The study found that, independent of personal characteristics, cities with more males had higher male smoking rates and lower female rates. Our research underscores the importance of city-level contextual effects in understanding gender differences in smoking in China.


The role of caveolin-1 in human breast cancer.
Caveolin-1 is the essential constituent protein of specialised plasma membrane invaginations called caveolae. The unique topology of caveolin-1 facilitates the role of caveolae as molecular hubs, integrating the activity of a multitude of signalling molecules. Despite improvements in our understanding of caveolin-1 interactions and the function of caveolae, the relationship between dysfunctional caveolin-1 and tumourigenesis remains contentious. Perhaps most intriguing has been the demonstration of both oncogenic and tumour suppressor function within particular tumour types, including breast cancer. In this review, the biological and clinical relevance of caveolin-1 in human breast cancer are considered. Evidence is systematically presented for the potential tumour suppressor and oncogenic functions of caveolin-1. Specific reference is made to interactions between caveolin-1 and signalling pathways in the clinical and biological subtypes of breast cancer. Areas of controversy are discussed and technical considerations are highlighted. Translational implications and potential for specific therapeutic manipulation of caveolin-1 are evaluated in the context of evidence from in vitro and in vivo studies.


Retinoblastoma protein modulates gankyrin-MDM2 in regulation of p53 stability and chemosensitivity in cancer cells.
MDM2 is a key ubiquitin E3 ligase for p53 and its activity is critically regulated by a set of modulators, including ARF, p300, YY1 and recently by gankyrin, an oncoprotein frequently overexpressed in human heptocellular carcinomas. We have previously shown that MDM2 binds to and promotes retinoblastoma protein (Rb) degradation. Here we show that Rb inhibits MDM2 E3 ligase activity resulting in stabilization of p53. In addition, we demonstrated that Rb inhibits MDM2-mediated p53 ubiquitination in a gankyrin-dependent manner and the Rb-gankyrin interaction is critical for Rb-induced p53 stabilization. Furthermore, acute ablation of Rb facilitates gankyrin-mediated p53 destabilization, and desensitizes cancer cells for chemotherapy-induced apoptosis. These results indicate that Rb antagonizes gankyrin to inhibit MDM2-mediate p53 ubiquitination in cancer cells and suggest that the status of both p53 and Rb is important for efficacy of cancer chemotherapy.


Adsorption of Cr(VI) from aqueous solutions using novel activated carbon spheres derived from glucose and sodium dodecylbenzene sulfonate.
Cr(VI) is a common wastewater pollutant. Various adsorbents including carbon-based materials are used for the removal of Cr(VI) owing to their high adsorption capacity. Chemical activation is an effective method to increase the specific surface area of adsorbents and, thus, further improve their adsorption capacity. However, research on the adsorption and removal of Cr(VI) from aqueous solutions by chemically activated carbon spheres is limited. Here, glucose and sodium dodecylbenzene sulfonate were used to produce carbon spheres (CSs) via hydrothermal synthesis. Activated carbon spheres (ACSs) were then derived using KOH. The adsorption of Cr(VI) in solution by CS and ACS was investigated through batch experiments. The results indicate that the specific surface area of the ACS was 1491.21 m2 g-1, which was much higher than that of the CS. The adsorption kinetics of the sorbent was consistent with the pseudo-second-order kinetic model and the adsorption isotherm followed the Langmuir model. This indicated that the adsorption process of the ACS with respect to Cr(VI) was mainly via single molecular layer adsorption and chemisorption. In a 200 mg L-1 Cr(VI) solution, the maximum amount of Cr(VI) adsorbed by the ACS was 230.15 mg g-1, and some of these adsorbed Cr(VI) were reduced to Cr(III). These results show that ACSs have strong potential for application in the removal of Cr(VI) from aqueous solutions.


Hydrocarbons in surface sediments from the Changjiang (Yangtze River) Estuary, East China Sea.
Sedimentary aliphatic (AH) and polycyclic aromatic hydrocarbons (PAHs) were studied in the Changjiang Estuary and the adjacent East China Sea. Total AH ranged from 2.20 to 11.82 microg g(-1) and consisted of n-alkanes and a dominant petroleum-related unresolved complex mixture (UCM). Within the n-alkanes, terrestrial plant wax compounds prevailed at nearly all stations. Of the PAHs, biogenic perylene dominated at stations receiving riverine inputs. Anthropogenic PAHs originating from combustion/pyrolysis processes varied from 17 to 157 ng g(-1), while fossil PAH concentrations ranged from 42 to 187 ng g(-1). Both biogenic and anthropogenic hydrocarbons are primarily derived from riverine discharges and accumulate at shallow-water stations. Distinct phase associations lead, nevertheless, to different sedimentation patterns. Fossil PAHs are enhanced at offshore stations where they are introduced directly by shipping activities. Biomarker fingerprints ascribe their source to Chinese crude oils. The overall levels of anthropogenic hydrocarbons are low compared to relevant areas worldwide and reveal a low/moderate level of hydrocarbon pollution.


[Contamination by the patient's affect: a source of trauma for the caregiver].
In complex aid relationships, the caregiver's confrontation with the patient's suffering can lead to trauma, like compassion fatigue and vicarious trauma. During prolonged and repeated exposure to a care situation, the caregiver may be contaminated by the violence of the patient's affects. This requires developing strategies to recognize, counter, and cope with the phenomenon.


Retinoic acid induces PGI synthase expression in human endothelial cells.
Retinoic acid (RA) exhibits anti-inflammatory, anti-tumor, and immuno-modulatory actions, and affects angiogenesis and thrombosis. Arachidonic acid (AA) metabolites are involved in all these processes. We explored the effect of RA on AA metabolism in human umbilical vein endothelial cells (HUVECs). 13-cis-RA increased the release of prostaglandin I(2) (PGI(2)), both spontaneous and thrombin-induced, in terms of 6-oxo-PGF(1alpha) analyzed by enzyme-immunoassay. Coincubation with 13-cis-RA and interleukin-1beta resulted in a synergic increase in the release of PGI(2). Consistently, 13-cis-RA increased the ability of HUVECs to inhibit AA-induced platelet aggregation. 13-cis-RA did not induce cyclooxygenase-isoenzyme expression, determined by immunoblotting, or activity, evaluated by analyzing eicosanoids formed from exogenous labeled AA by HPLC. In contrast, RA induced PGI synthase (PGIS) activity and expression in terms of mRNA and protein determined by real-time PCR and Western blotting, respectively. Results from experiments with several species of RA and with retinoic acid receptor (RAR) and retinoid X receptor (RXR) antagonists showed that the effect of RA on PGIS expression was mediated by RAR. Actinomycin D and cycloheximide both inhibited RA-induced PGIS expression. Furthermore, RA increased PGIS transcriptional activity in transient transfection assays, an effect that was prevented by an RAR antagonist. These results reinforce the concept that RA could be beneficial for patients with cardiovascular risk.


Plant ribosome-inactivating proteins type II induce the unfolded protein response in human cancer cells.
Cytotoxic ribosome-inactivating proteins (RIPs) of type II such as ricin were investigated as anti-cancer agents, but also pose a threat as biological weapons. The molecular mechanism leading to their toxic effects is, however, not yet clear. The current paradigm, which states that the irreversible depurination of 28S rRNA results in a general translational arrest eventually leading to cell death, has been questioned. Using micro-array, qRT-PCR and Western blot, we identified the unfolded protein response (UPR), a cellular mechanism activated in response to endoplasmic reticulum stress, that is induced in HCT116 and MDA-MB-231 cells exposed to the plant type II RIPs ricin, riproximin and volkensin. Apoptosis was induced by concentrations at which translation of UPR-related genes still occurred, despite concomitant ribosomal depurination. We conclude that UPR induction represents a model that better describes the cellular effects of RIP exposure at concentrations at which selected proteins are translated despite ribosomal depurination.


Structural characterization of neutral glycosphingolipids using high-performance liquid chromatography-electrospray ionization mass spectrometry with a repeated high-speed polarity and MSn switching system.
Four types of neutral glycosphingolipids (LacCer, Gb3Cer, Gb4Cer, and IV3αGalNAc-Gb4Cer; 10 pmol each) were analyzed using high-performance liquid chromatography (HPLC)-electrospray ionization quadrupole ion trap time-of-flight (ESI-QIT-TOF) mass spectrometry (MS) with a repeated high-speed polarity and MSn switching system. This system can provide six types of mass spectra, including positive and negative ion MS, MS2, and MS3 spectra, within 1 s per cycle. Using HPLC with a normal-phase column, information on the molecular weights of major molecular species of four neutral glycosphingolipids was obtained by detecting [M+Na]+ in the positive ion mode mass spectra and [M−H]− in the negative ion mode mass spectra. Sequences of glycosphingolipid oligosaccharide were obtained in the negative ion MS2 spectra. In addition, information on the ceramide structures was clearly obtained in the negative ion MS3 mass spectra. GlcCer molecular species were analyzed by HPLC-ESI-QIT-TOF MS with a reversed-phase column using 1 pmole of GlcCer. The structures of the seven molecular species of GlcCer, namely, d18:1-C16:0, d18:1-C18:0, d18:1-C20:0, d18:1-C22:0, d18:1-C23:0, d18:1-C24:1, and d18:1-C24:0, were characterized using positive ion MS and negative ion MS, MS2, and MS3. The established HPLC-ESI-QIT-TOF MS with MSn switching and a normal phase column has been successfully applied to the structural characterization of LacCer and Gb4Cer in a crude mixture prepared from human erythrocytes.


Functional properties of the uptake of amines in immortalised peptidergic neurones (transport-P).
1. Most neurotransmitters are inactivated by uptake into presynaptic nerve terminals and into glial cells. We recently provided evidence for uptake of amines in postsynaptic neurones. Uptake was evident at nanomolar concentrations of prazosin, but at concentrations of unlabelled prazosin greater than 10(-7) M, there was a further activation of uptake, manifested by a paradoxical increase in accumulation of the radioligand. We have now studied further characteristics of amine uptake in immortalised gonadotrophin-releasing hormone (GnRH) neurones. Control cells included SK-N-SH neuroblastoma cells (which possess presynaptic type amine transporters) and non-neuronal (COS-7) cells. 2. [3H]-prazosin bound to intact GnRH cells and was displaced by unlabelled prazosin in concentrations of 10(-9) to 10(-7) M. However, at higher concentrations of unlabelled prazosin, there was an increase in apparent [3H]-prazosin binding, as we had previously described. This paradoxical increase in accumulation of the radioligand was abolished by desipramine. 3. Desipramine had no effect on the association of prazosin with COS-7 cells. There was no paradoxical increase in accumulation of [3H]-prazosin in COS-7 cells, indicating that this effect requires the presence of a desipramine-blockable uptake process. 4. The increase in binding of the radioligand that was observed in the GnRH cells is not a general property of neuronal transporters; in SK-N-SH cells, there was no increase in accumulation of (-)-[3H]-noradrenaline in the presence of concentrations of unlabelled (-)-noradrenaline greater than 10(-7) M. 5. The uptake of prazosin and the increase in accumulation of [3H]-prazosin were abolished in the cold, indicating that this is an active, energy-requiring process. 6. Desipramine-sensitive uptake of prazosin was demonstrable in the GnRH cells in the absence of sodium. Further, the Na+/K(+)-ATPase inhibitor, vanadate, abolished noradrenaline uptake in SK-N-SH cells but had no effect on prazosin uptake in GnRH cells. Thus, the uptake of prazosin does not derive its energy from the sodium pump. 7. Prazosin uptake was inhibited by the V-ATPase inhibitor bafilomycin A1, the H+/Na+ ionophore, monensin and the organic base, chloroquine, indicating that uptake derives its energy from a proton pump. In contrast to other proton-dependent amine transporters, the uptake of prazosin was unaffected by reserpine. 8. Increasing extracellular pH did not increase the uptake of prazosin into GnRH cells, indicating that it is unlikely to be due to non-specific diffusion and concentration of a lysosomotropic drug into intracellular acidic particles. 9. The uptake of prazosin was unaffected by steroid hormones. 10. In COS-7 cells transfected with alpha 1-adrenoceptor cDNA, [3H]-prazosin was displaced by unlabelled prazosin without causing an increase in binding of the radioligand. This indicated that the increase in accumulation of the radioligand is unlikely to be due simply to some function of alpha 1-adrenoceptors. 11. Thus, peptidergic neurones possess an uptake process with properties that are distinguishable from known amine transporters.


Past, present, and future perspectives of biodegradable films for soil: A 30-year systematic review.
Based on the Web of Science Core Collection (WOSCC) database, the academic works published in the past 30 years on biodegradable films for soil were analyzed. In order to ensure the rigor of this experiment, this paper is based on the mathematical double matrix model VOS Viewer software and CiteSpace software. This work shows that publications of biodegradable films for soil are increasing year by year; polymer science is the hottest subject in the field of biodegradable films for soil; China and the United States are the countries with the most significant number of publications in this field, has an important position; Washington State University is the most published institution. This study further identifies and reveals the essential characteristics, research strength, knowledge structure, main research fields, and research hotspots in the late stage of the field of biodegradable films for soil and introduces the Activity Index (AI) and the Attractive Index (AAI), thereby assessing trends and performance in different countries. The paper also further illustrates the importance of biodegradable films by presenting field trials using biodegradable films on different plants. The research in the field of biodegradable films for soil is divided into four categories: "The research field of degradation," "The effect of biodegradable film on soil," "Performance and mechanism of the biodegradable film," and "Effects of biodegradable film on crop growth and development.". The study can be seen as a microcosm of the development of biodegradable films for soils, which will help researchers quickly identify their general patterns. Readers can better understand the changes and development trends in this field in the past 30 years and provide references for future research.


Air pollution and congenital heart defects.
Environmental factors such as ambient air pollution have been associated with congenital heart defects. The aim of this study was to investigate the association between gestational exposure to air pollution and the risk of congenital heart defects. We conducted a registry-based cohort study with a total of 135,527 live- and still-births in the Tel-Aviv region during 2000-2006. We used a Geographic Information System-based spatiotemporal approach with weekly inverse distance weighting modeling to evaluate associations between gestational exposure to ambient air pollution during weeks 3-8 of pregnancy and the risk for congenital heart defects. The following pollutants were studied: carbon monoxide, nitrogen-dioxide, ozone, sulfur-dioxide and particulate matter with aerodynamic diameter smaller than 10 μm and 2.5 μm (PM10, PM2.5 respectively). Logistic models, adjusted for socio-demographic covariates were used to evaluate the associations. We found that maternal exposure to increased concentrations of PM10 was associated with multiple congenital heart defects (adjusted OR 1.05, 95% CI: 1.01 to 1.10 for 10 μg/m(3) increment). An inverse association was observed between concentrations of PM2.5 and isolated patent ductus arteriosus (adjusted OR 0.78, 95% CI: 0.68 to 0.91 for 5 µg/m(3) increment). Sensitivity analyses showed that results were consistent. Generally there were no evidence for an association between gaseous air pollutants and congenital heart defects.Our results for PM10 and congenital heart defects confirm results from previous studies. The results for PM2.5 need further investigations.


Yttrium-aluminum-garnet laser therapy of esophageal granular cell tumor.
Granular cell tumor (GCT) is a rare lesion. Approximately 4% to 6% of these tumors occur in the gastrointestinal tract, one-third of them affecting the esophagus. Almost all GCTs are benign lesions. Approximately 1% to 3% are malignant. Endoscopic ultrasonography (EUS) is a diagnostic support. The best treatment for esophageal GCT is not yet clear, whether surgical excision, periodic observation, endoscopic excision, or yttrium-aluminum-garnet (YAG) laser therapy. From November 1992 to December 2000, four patients with GCTs of the esophagus were observed. All the patients underwent EUS evaluation and endoscopic YAG laser therapy of the esophageal neoplasm. At each session, a biopsy at the tumor site was obtained. The treatment was continued until endoscopic and histologic evidence of the tumor disappeared. After the YAG laser therapy, no evidence of the tumor was found in any of the four patients with esophageal GCT. At this writing, the patients remain disease free after a mean follow-up period of 66 months. No complication has been observed. Only four sessions for each patient were necessary to eliminate the tumor. Therapy with YAG laser was effective in all four patients with esophageal GCT, and complete necrosis of the submucosal neoplastic cells was achieved. Endoscopic YAG laser therapy appears to be a good compromise between esophageal dissection and long-term observation without tumor excision. Esophageal laser therapy is safe if correctly used, and previous EUS evaluation increases treatment safety.


Cytotoxic drugs and the human adrenal cortex: a cell culture study.
Primary monolayer cultures of nonproliferating adult human adrenocortical cells have been used to screen 18 cytotoxic drugs used in cancer chemotherapy for direct effects on corticosteroidogenesis. None of the drugs tested, with the exception of 5-fluorouracil (5-FU) and its metabolite 5-fluorodeoxyuridine, showed significant activity at levels compatible with cortical cell viability and/or likely to be encountered during therapy. These two antimetabolites, however, resulted in a slow but long-lived reversible suppression of corticosteroidogenesis in both ACTH- and monobutyryl cyclic AMP-stimulated, as well as unstimulated cultures of human cells. Thus 10 micrograms/ml resulted in less than 80% inhibition after seven days treatment without any evidence of overt cytotoxicity. High-pressure liquid chromatography showed a suppression of all UV-absorbing steroids secreted. Examination of the ultrastructure of the treated cells showed significant changes in mitochondrial morphology, suggesting a possible site of action for the antisteroidogenic effects of 5-fluorouracil. These in vitro results suggest the possibility of adrenal suppression in vivo during long-term or high dose infusion 5-FU chemotherapy.


Postprandial exocrine pancreatic function during long-term treatment with the somatostatin analogue SMS 201-995 in acromegalic patients.
Long-term treatment with the somatostatin analogue SMS 201-995 (SMS) might impair exocrine pancreatic function, secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP), and pancreatic size. In five acromegalics on chronic treatment with SMS, we investigated postprandial 6-h urinary excretion of p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS) after s.c. injection of 100 micrograms SMS or placebo and after ingestion of 2 mmol nBT-PABA and 2 mmol PAS. In the acromegalics, urinary PABA/PAS ratio (reflecting exocrine pancreatic function) after SMS was similar to that after placebo (P greater than 0.10) and higher than in healthy volunteers (n = 8, P = 0.05). The initial inhibition of plasma CCK secretion by SMS was cancelled during the 3rd h after the meal, whereas PP release remained completely abolished. Pancreatic size as measured by ultrasonography, was not reduced in seven acromegalics compared with 14 healthy volunteers. It is concluded that despite a blunted release of the trophic hormone CCK, long-term treatment with SMS 201-995 neither induces an abnormally small pancreas nor deterioration of postprandial exocrine pancreatic function in patients with acromegaly.


Autoradiographic analysis of Schistosoma mansoni migration from skin to lungs in naive mice. Evidence that most attrition occurs after the skin phase.
A study was performed to determine the extent of attrition of Schistosoma mansoni in naive mice (innate resistance) during the 1st week of infection. Each mouse was exposed to exactly 50 cercariae radiolabeled with [75Se] selenomethionine. On 1, 4, and 7 days postexposure, skin, lungs and liver were analyzed by compressed organ autoradiography for the presence of labeled larvae. Using this technique it was determined that no more than one-third of the 59% attrition that occurred between the cercarial and adult worm stages could be attributed to losses during the skin phase; most of the attrition in naive mice occurred after the migration of larvae to the lungs.


Interleukin-1β mediates high glucose induced phenotypic transition in human aortic endothelial cells.
Previous studies have shown that high glucose (HG) induced endothelial cell (EC) damage via a phenotypic transition of EC. There is increasing evidence suggesting the role of inflammatory cytokines in mediated HG-induced EC damage. However, little is known about the potential role of interleukin-1β (IL-1β) in the process. The aim of present study was to investigate whether IL-1β mediated HG-induced phenotypic transition in human aortic endothelial cells (HAECs) and to determine the possible underlying mechanism. Primary HAECs were exposed to normal glucose (NG, 5.5 nM), high glucose (HG,30 nM), IL-1β (10 ng/ml), HG + IL-1β (10 ng/ml) and HG + anti-IL-1β antibodies (1000 ng/ml) or HG + IL-1β small interfering RNA (siRNA). Pathological changes were investigated using confocal microscopy and electron microscopy. Confocal microscopy was performed to detect the co-expression of CD31 and fibroblast specific protein 1 (FSP1). To study the effect of protein kinase C-β (PKCβ) activation on IL-1β in HAECs, HAECs were stimulated with 30 nM PMA (PKCβ activator) and 0.3 μM PKCβ inhibition (LY317615) for 48 h in the NG or HG group. The expressions of PKCβ and IL-1β were detected by RT-PCR and Western blot. And the concentration of IL-1β in the supernatant of HAECs was measured by ELISA. The expressions of FSP1, a-SMA and CD31 were detected by Western blot. It was shown that the HG resulted in significant increase in the expressions of PKCβ and IL-1β in dose-and time-dependent manners. The HG or exogenous IL-1β alone inhibited the expression of CD31 and markly increased the expressions of FSP1 and α-SMA. Furthermore, we observed that the HG and IL-1β synergistically increased FSP1 and a-SMA expressions compared with the HG or IL-1β alone group (P < 0.05). Confocal microscopy revealed a colocalization of CD31 and FSP1 and that some cells acquired spindle-shaped morphologies and a loss of CD31 staining. Electron microscopy showed that the HG resulted in the increased microfilamentation and a roughened endoplasmic reticulum structure in the cytoplasm. However, the changes above were attenuated by the intervention of anti-IL-1β antibodies or IL-1β siRNA (P < 0.05). In addition, the PMA induced the expressions of PKCβ and IL-1β in HAECs. The PKCβ activation may mediate the effect of the HG on IL-1β production, which could be attenuated by the PKCβ selective inhibitor (LY317615) (P < 0.05). Our findings suggested that HG-induced phenotypic transition of HAECs might require IL-β activation via the PKCβ pathway.


Synthetic glycosylation of peptides using unprotected saccharide beta-glycosylamines.
Glycopeptides can be valuable tools in determining the influence of carbohydrate moieties on the intrinsic properties of glycoproteins. However, glycopeptides of sufficient quantity and purity are as yet not readily available from biological sources. The chemical coupling of a beta-glycosylamino group of an unprotected carbohydrate with an activated aspartic acid residue of an unprotected peptide is a simple method for synthesizing asparagine-linked glycopeptides. In this report we demonstrate that the use of this method is not restricted to beta-glycosylamines of simple monosaccharides or short aspartic acid-containing pentapeptides. This is illustrated by the syntheses of several glycopentapeptides containing N,N'-diacetylchitobiose, a glutamine-linked glycopentapeptide containing a biantennary complex oligosaccharide, and glycosylated variants of two analogs of a polypeptide hormone, atriopeptin, containing N,N'-diacetylchitobiose.


Spatio-temporal clustering of the incidence of schizophrenia in Quebec, Canada from 2004 to 2007.
Exploring spatio-temporal patterns of disease incidence can help to identify areas of significantly elevated or decreased risk, providing potential etiologic clues. In this study, we present a spatio-temporal analysis of the incidence of schizophrenia in Quebec from 2004 to 2007 using administrative databases from the Régie de l'Assurance Maladie du Quebec and the hospital discharge database. We conducted purely spatial analyses for each age group adjusted by sex for the whole period using SatScan (version 9.1.1). Findings from the study indicated variations in the spatial clustering of schizophrenia according to sex and age. In term of incidence rate, there are high differences between urban and rural-remote areas, as well as between the two main metropolitan areas of the province of Quebec (Island of Montreal and Quebec-City).


Development and validation of a carp growth hormone radioimmunoassay.
Purified growth hormone (GH), isolated from pituitary glands of the common carp (Cyprinus carpio), was shown to have biochemical and immunological properties in common with other teleost GH preparations. Intraperitoneal injections of the carp GH, at a dose of 1 microgram/g body wt, resulted in significant increases in body weight in goldfish. In addition, the carp GH was used to prepare an antiserum for the development of a radioimmunoassay (RIA). The displacement curves for serum from goldfish with an intact pituitary gland were parallel to that of the purified cGH in this RIA. In contrast, serial dilutions of serum from hypophysectomized goldfish, and purified goldfish prolactin and carp gonadotropin did not have significant cross reaction. The present study strongly suggests that this RIA is suitable for the measurement of circulating GH levels in the goldfish.


Improvements in the treatment and prognosis of colorectal carcinoma.
In a survey of the surgical results in 709 patients with colorectal carcinoma (CRC) treated between 1976 and 1985 a favourable shift of stage distribution was observed. The tumour was localized (Dukes' classification A or B) in 61 per cent of patients, as compared with 47 per cent in the previous 10-year period. This change was, in part, due to different interpretation of stage definitions. Clear improvements of the results were, however, also noted. Radical surgery was possible in 76 per cent of patients and the primary tumour was removed in 93 per cent. Surgical mortality was 4.4 per cent and complication rate 15 per cent, significantly less than earlier (6.5 and 38 per cent, respectively). Increasing numbers of sphincter-saving operations were performed in rectal cancers (47 per cent as compared with 24 per cent in the previous 10-year period). The overall 5-year survival rate improved from 40.5 to 52.5 per cent. Premalignant conditions were identified in 12.6 per cent of patients: previous CRC 4.8 per cent, cancer family syndrome 4.1 per cent, ulcerative colitis 1.7 per cent and familial adenomatosis 0.6 per cent. In order to sustain the favourable trend of improving survival prospects, more emphasis must be directed to the detection of early stage cancers.


Adaptive noise correction of dual-energy computed tomography images.
Noise reduction in material density images is a necessary preprocessing step for the correct interpretation of dual-energy computed tomography (DECT) images. In this paper we describe a new method based on a local adaptive processing to reduce noise in DECT images An adaptive neighborhood Wiener (ANW) filter was implemented and customized to use local characteristics of material density images. The ANW filter employs a three-level wavelet approach, combined with the application of an anisotropic diffusion filter. Material density images and virtual monochromatic images are noise corrected with two resulting noise maps. The algorithm was applied and quantitatively evaluated in a set of 36 images. From that set of images, three are shown here, and nine more are shown in the online supplementary material. Processed images had higher signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) than the raw material density images. The average improvements in SNR and CNR for the material density images were 56.5 and 54.75%, respectively. We developed a new DECT noise reduction algorithm. We demonstrate throughout a series of quantitative analyses that the algorithm improves the quality of material density images and virtual monochromatic images.


In vivo helper activity of enriched populations of antigen-specific T lymphocytes.
Enrichment of murine antigen-specific T cells was achieved by stimulation of primed lymph node cells with macrophages containing the immunizing antigen. After a week in culture, the in vitro-sensitized lymphocytes had an increased helper activity. Inoculation of 10(7) egg albumin (OVA)-enriched T cells together with hapten coupled to OVA, elevated the number of splenic antihapten-producing cells of primed or unprimed mice. Augmentation of the hapten specific B-cell response could be observed as early as 4 days following the injection of the enriched population and peaked at Day 7. The enhancing effect of the enriched population of antigen-specific T cells was carrier specific since it occurred only in the presence of hapten coupled to the T-cell sensitizer [2,4-dinitrophenol (DNP)-OVA]. When given with the hapten conjugated to an irrelevant carrier [DNP-human gamma globulin (HGG)], the enriched lymphocytes caused a depression in the anti-DNP response. The capacity of in vitro enriched lymphocytes to promote a substantial antigen-specific helper activity (up to 1 anti-DNP producing cell per 10(3) spleen cells) upon adoptive transfer to nonirradiated mice, provides an experimental system for studying B-T collaboration in vivo under the normal physiological conditions.


Impact of pension income on healthcare utilization of older adults in rural China.
In China, rural residents experience poorer health conditions and a higher disease burden compared to urban residents but have lower healthcare services utilization. Rather than an insurance focus on enhanced healthcare services utilization, we aim to examine that whether an income shock, in the form of China's New Rural Pension Scheme (NRPS), will affect outpatient, inpatient and discretionary over-the-counter drug utilization by over 60-year-old rural NRPS residents. Providing a monthly pension of around RMB88 (USD12.97), NRPS covered all rural residents over 60 years old. Fuzzy regression discontinuity design (FRDD) was employed to explore the NRPS causal effect on healthcare services utilization, measured by outpatient and inpatient visits and discretionary over-the-counter drug purchases. The nationwide China Health and Retirement Longitudinal Study (CHARLS) 2018 provided the data. Without significant changes in health status and medication needs, 60-plus-year-old NRPS recipients significantly increased the probability of discretionary OTC drug purchases by 33 percentage points. NRPS had no significant effect on the utilization of outpatient and inpatient utilization. The increase in the probability of discretionary OTC drug purchases from the NRPS income shock was concentrated in healthier and low-income rural residents. Robustness tests confirmed that FRDD was a robust estimation method and our results are robust. NRPS was an exogenous income shock that significantly increased the probability of discretionary over-the-counter drug purchases among over 60-year-old rural residents, but not the utilization of inpatient or outpatient healthcare services. Income remains an important constraint for rural residents to improve their health. We recommend policymakers consider including commonly used over-the-counter drugs in basic health insurance reimbursements for rural residents; provide health advice for rural residents to make discretionary over-the-counter drug purchases; and to mount an information campaign on over-the-counter drug purchasing in order to increase the health awareness of rural residents.


In Situ Assays of Chemotropism During Yeast Mating.
Virtually all eukaryotic cells can grow in a polarized fashion in response to external signals. Cells can respond to gradients of chemoattractants or chemorepellents by directional growth, a process referred to as chemotropism. The budding yeast Saccharomyces cerevisiae undergoes chemotropic growth during mating, in which two haploid cells of opposite mating type grow towards one another. Mating pheromone gradients are essential for efficient mating in yeast and different yeast mutants are defective in chemotropism. Two methods of assessing the ability of yeast strains to respond to pheromone gradients are presented here.


Late-onset right ventricular failure after continuous-flow left ventricular assist device implantation: case presentation and review of the literature.
With the widespread use of implantable left ventricular assist device (LVAD), right ventricular failure (RVF) has become a serious problem that becomes apparent several weeks or later after LVAD implantation. However, there are no marked preoperative signs of RVF. This is called late-onset RVF and is currently a major problem leading to long-term complications following implantable LVAD use. Pathogenically, this could be the result of left ventricular suction by LVAD that causes the septum shift to the left ventricular side. This causes a change in morphology of the right ventricle, resulting in impaired right ventricular function. Aortic insufficiency and ventricular arrhythmia, which are also important as long-term complications after LVAD implantation, are considered to be closely involved in the onset and progression of RVF. Once late-onset RVF develops, exercise capacity declines and inotrope administration may be required. Late-onset RVF was also reported to be significantly associated with increased mortality. Several predictors of RVF have been proposed such as preoperative left ventricular diastolic dimension <64 mm, tricuspid valve annulus diameter ≥41 mm, and so on. However, some reports identified no predictors. The basic treatment strategy for late-onset RVF is to optimize volume status by administering diuretics and ensuring inotrope as needed. β-blockers and antiarrhythmic agents often need to be reduced in terms of dosage or even discontinued because these might reduce right ventricular function. Although their efficacy is unclear, pulmonary vasodilators may be used to reduce right ventricular afterload. It is better to decrease the rotation speed of LVAD to minimize the displacement of the septum; however, this is often difficult because the required flow rate cannot be secured. Progress in the prevention and management of late-onset RVF is required because the number of patients who require longer-term LVAD support will increase with the spread of LVAD use as destination therapy.


Obstetric and gynecologic malpractice claims in Saudi Arabia: Incidence and cause.
The occurrence of a bad outcome, injury or death of a patient during treatment increases the chance of malpractice litigation, increases legal responsibility and leads to increased fees for malpractice insurance. Physicians practicing obstetrics and gynecology face among the highest risks of malpractice litigation, and such litigation has led to an increase in the practice of defensive medicine and has made this specialty less appealing. Previous clinical data from Saudi Arabia have shown that more malpractice litigation concerns claims in obstetrics and gynecology than claims in any other field of medicine. To identify the main causes of obstetrics and gynecology (OBGYN) professional liability claims in Saudi Arabia to have a better understanding and management of risks. All OBGYN claims opened in Saudi Arabia between 2008 and 2013 were analyzed to identify the most common causes of claims. The results of these claims and the times until a final judgment made were also analyzed. Out of a total of 463 malpractice claims that were closed during the study period, 114 (24.6%) claims were in obstetrics and gynecology, and 92 (80.7%) of these claims concerned complications related to delivery room events. The most common causes of obstetric malpractice litigation were shoulder dystocia (brachial plexus injury) and fetal distress (hypoxic ischemic encephalopathy). Urinary system injury was the most common cause of gynecology cases. Most cases were decided in favor of the defendants with the exception of cases for which maternal and/or fetal death was the cause of litigation; nearly all of those cases were decided against the defendants. Obstetricians face a high risk of malpractice claims in Saudi Arabia, although most claims do not end in payments to plaintiffs. However, the effects of such claims on obstetric care should not be underestimated. Adherence to standards of care and careful documentation may decrease litigation and the number of indefensible malpractice claims.


Computed tomography findings in tuberculous mediastinitis.
Tuberculous mediastinitis can be an elusive diagnosis. Computed tomography may be performed in patients before establishing this diagnosis, and one should consider this disease when mediastinal mass with infiltration of adjacent fat planes is noted. Five such cases are described.


Elevated levels of leukocyte tissue factor mRNA in patients with venous thromboembolism.
Tissue factor (TF) mRNA levels in leukocyte and TF antigen in plasma were examined in patients with deep vein thrombosis (DVT). Although TF mRNA levels in leukocytes were higher in patients with DVT than in healthy volunteers, they were lower in patients with DVT than in those with solid cancer and those with disseminated intravascular coagulation (DIC). On the other hand, the plasma levels of TF antigens were markedly high in patients with DVT/pulmonary embolism (PE). Analysis of the role of underlying disease of DVT showed no significant difference in TF mRNA levels and TF antigens among patients with solid cancer, post-surgical, other diseases and those free of underlying diseases. In patients with VTE, plasma levels of D-dimer, soluble fibrin, GE-XDP and plasminogen activator inhibitor-1 did not correlate with TF mRNA or TF antigen. In analysis of 18 patients with PE with and without DVT, TF mRNA levels in leukocytes correlated with the plasma levels of D-dimer. These findings suggest that TF in leukocytes is more likely to be involved in the development of thrombosis in PE than DVT.


Chymase inhibitor suppresses adhesion formation in a hamster experimental model.
To clarify the role of chymase produced by mast cells in adhesion formation, we investigated the preventive effect of a specific chymase inhibitor, Suc-Val-Pro-Phe(p) (OPh)2, on adhesion formation in a hamster experimental model. Hamsters underwent resection of the right uterine body and then 10 microM Suc-Val-Pro-Phe(p) (OPh)2 or placebo was injected into the abdomen. Two weeks after the operation, the scores for adhesion formation in the chymase inhibitor-treated group were significantly lower than that in the placebo-treated group (placebo-treated group, 3.60+/-0.22; chymase inhibitor-treated group, 2.10+/-0.22; P<0.01). This specific chymase inhibitor, Suc-Val-Pro-Phe(p) (OPh)2, significantly suppressed the scores for adhesion formation in a hamster experimental model. Thus, chymase may play an important role in the adhesion formation.


CD4+/CD8+ ratio, age, and risk of serious noncommunicable diseases in HIV-infected adults on antiretroviral therapy.
In virologically suppressed HIV-infected adults, noncommunicable diseases (NCDs) have been associated with immune senescence and low CD4/CD8 lymphocyte ratio. Age differences in the relationship between CD4/CD8 ratio and NCDs have not been described. Observational cohort study. We assessed CD4/CD8 ratio and incident NCDs (cardiovascular, cancer, liver, and renal diseases) in HIV-infected adults started on antiretroviral therapy between 1998 and 2012. Study inclusion began once patients maintained virologic suppression for 12 months (defined as baseline). We examined age and baseline CD4/CD8 ratio and used Cox proportional hazard models to assess baseline CD4/CD8 ratio and NCDs. This study included 2006 patients. Low baseline CD4/CD8 ratio was associated with older age, male sex, and low CD4 lymphocyte counts. In models adjusting for CD4 lymphocyte count, CD4/CD8 ratio was inversely associated with age (P < 0.01). Among all patients, 182 had incident NCDs, including 46 with coronary artery disease (CAD) events. CD4/CD8 ratio was inversely associated with risk of CAD events [adjusted HR per 0.1 increase in CD4/CD8 ratio = 0.87, 95% confidence interval (CI): 0.76-0.99, P = 0.03]. This association was driven by those under age 50 years (adjusted HR 0.83 [0.70-0.97], P = 0.02) vs. those over age 50 years (adjusted HR = 0.96 [0.79-1.18], P = 0.71). CD4/CD8 ratio was not significantly associated with incident noncardiac NCDs. Higher CD4/CD8 ratio after 1 year of HIV virologic suppression was independently predictive of decreased CAD risk, particularly among younger adults. Advanced immune senescence may contribute to CAD events in younger HIV patients on antiretroviral therapy.


Fighting fish parasites with photodynamically active chlorophyllin.
Water-soluble chlorophyll (chlorophyllin) was used in a phototoxic reaction against a number of fish ectoparasites such as Ichtyobodo, Dactylogyrus, Trichodina, and Argulus. Chlorophyllin is applied to the water at concentrations of several micrograms per milliliter for a predefined incubation time, and afterwards, the parasites are exposed to simulated solar radiation. Application in the dark caused only little damage to the parasites; likewise, light exposure without the addition of the photosensitizer was ineffective. In Ichthyobodo, 2 μg/mL proved sufficient with subsequent simulated solar radiation to almost quantitatively kill the parasites, while in Dactylogyrus, a concentration of about 6 μg/mL was necessary. The LD50 value for this parasite was 1.02 μg/mL. Trichodina could be almost completely eliminated at 2 μg/mL. Only in the parasitic crustacean Argulus, no killing could be achieved by a photodynamic reaction using chlorophyllin. Chlorophyllin is non-toxic, biodegradable, and can be produced at low cost. Therefore, we propose that chlorophyllin (or other photodynamic substances) are a possible effective countermeasure against several ectoparasites in ponds and aquaculture since chemical remedies are either forbidden and/or ineffective.


Validity of the Compassionate Engagement and Action Scales with family carers of older adults: confirmatory factor analyses.
To confirm the factor validity of the Compassionate Engagement and Action Scales (CEAS), as set out in the original development study, when used with a sample of family carers of older adults. A series of confirmatory factor analyses were undertaken to test the previously proposed factor solutions of each scale. As part of a larger cross-sectional survey, the scales were completed online or via hard copy between July and December 2019. An international sample of 171 family carers of adults aged 65 years or older. The CEAS are three measures that individually assess Compassion for Self, Compassion to Others, and Compassion from Others. All scales measure two aspects, "engagement" and "actions" (two-factor solution), and Compassion for Self also measures two further dimensions within engagement: "sensitivity to suffering" and "engagement with suffering" (three-factor solution). Results were largely consistent with the two-factor solutions proposed for the three orientations of compassion, with acceptable fit and good internal reliability. There was some support for the three-factor solution of Compassion for Self; however, despite model fit comparable to the two-factor solution, internal reliability of the delineated "engagement" dimensions was low, and there was a weak factor loading for item 5 that measured distress tolerance. Use of the CEAS with family carers of older adults is promising. Further research is recommended with larger samples and to explore distress tolerance as a competency within conceptualization and measurement of compassion.


Safety and efficacy of carboxymethylcellulose in the treatment of glottic insufficiency.
No studies to date have examined the clinical safety and efficacy of carboxymethylcellulose (CMC) for vocal fold injection. The current study investigates the voice outcomes and complications of CMC injection. Retrospective review. All patients who underwent CMC injection from three independent sites in a 1-year period were reviewed. Voice outcomes in the form of voice handicap index-10 (VHI-10) and complications from injection were recorded. Seventy-eight patients with VHI-10 results from 1 to 8 weeks after CMC injection were evaluated. Thirty-eight patients were treated for vocal fold immobility, and 15 patients underwent treatment for hypomobility, 15 for vocal fold atrophy, seven for scar/sulcus, one for previous laryngeal fracture, one for functional dysphonia, and one for persistent granuloma. In 60 patients with available VHI-10 data, overall improvement in voice was seen. There was a mean decrease in VHI-10 of 7.48 (26.4 to 18.9, P < .05), correlating to a 19.9% decrease. Forty-five patients (75%) showed a decrease in VHI-10, nine (15%) showed an increase, and six (10%) showed no change. Statistically significant differences were seen for patients with immobility (decrease of 8.6, or 31%) and hypomobility (decrease of 10.7, or 37.8%). There were no complications of vocal fold stiffness, inflammatory reaction, or scar in the 78 patients during the total follow-up period. CMC is a viable, safe, and efficacious material for the temporary treatment of glottic insufficiency in vocal fold immobility and hypomobility, with minimal risk of permanent adverse voice outcomes.


Cell therapy plus transmyocardial laser revascularization for refractory angina.
We describe the use of autologous bone marrow cells combined with transmyocardial laser revascularization in a 74-year-old man with refractory angina. Baseline cardiac magnetic resonance imaging revealed a markedly depressed left ventricle systolic function and an extensive area of myocardial ischemia. During surgery, 11 laser shots using a CO2 Heart Laser System (PLC Medical Systems, Milford, MA) were fired and a 5-mL cell suspension containing 21.5 x 10(6) bone marrow cells/mL was delivered by multiple injections into the myocardium. At 6 months after the procedure, another cardiac magnetic resonance imaging showed an almost complete resolution of the perfusion defect and an improvement in left ventricular contractility.


Nontuberculous mycobacterial infections: comparison of the fluorescent auramine-O and Ziehl-Neelsen techniques in tissue diagnosis.
Nontuberculous (i.e., atypical) mycobacterial infections are increasing among pediatric and immunosuppressed patients, who commonly present with subcutaneous inflammatory masses or adenitis, which is often surgically excised. Since the most frequently isolated species also grow slowly in culture, early diagnosis may depend on histologic detection of a mycobacterial organism in the biopsy specimen. However, the histologic methods used for this purpose are of uncertain value in the diagnosis of these infections. Biopsy specimens from 22 patients with clinical histories highly consistent with nontuberculous mycobacteriosis in which part of the tissue was cultured were selected for study. Coded tissue blocks and control specimens were stained by the Ziehl-Neelsen (ZN) or auramine-O (A0) fluorescent technique and examined blindly for the presence of characteristic organisms. Results of these studies were compared with the culture results, and predictive values were calculated. This experience showed that the AO technique is technically simpler, allowing faster screening at lower power and showing greater sensitivity and predictive value of a negative result although less specificity than the ZN technique. The lower specificity of AO may be factitious and due to the detection in the tissue of organisms that did not grow in culture. Previous observations that nontuberculous mycobacterial infections may elicit tissue reactions that simulate cat-scratch disease, sarcoidosis, and nonspecific chronic inflammation were also confirmed.


Parent caregiving choices of middle-generation Blacks and Whites in the United States.
This study compares how middle-generation caregivers and non-caregivers differ by race and explores racial differences in activities of daily living (ADL), instrumental activities of daily living (IADL), and financial assistance that middle-generation caregivers provide for their parents. Using 2000 Health and Retirement Study data, racially stratified descriptive analyses and logistic regression models for ADL, IADL, and financial assistance are presented. Parental need and race influence support, with similar patterns of Black and White ADL support, but racial differences in IADL and financial support. Having more children motivates Whites to increase IADL support and reduce financial support; more children decreases Blacks' IADL support. Sibling caregiver networks influence IADL and financial support in ways that vary by race. The number employed is a key determinant for Blacks for all support, but only influences White ADL support. The findings of this article indicate the importance of sample stratification by race and that employment or other subsidies may aid the expansion of caregiving by middle-generation adults.