Baseline characteristics and outcomes of end-stage renal disease patients after in-hospital sudden cardiac arrest: a national perspective.
End-stage renal disease (ESRD) is a well-recognized risk factor for the development of sudden cardiac arrest (SCA). There is limited data on baseline characteristics and outcomes after an in-hospital SCA event in ESRD patients. For the purpose of this study, data were obtained from the National Inpatient Sample from January 2007 to December 2017. In-hospital SCA was identified using the International Classification of Disease, 9th Revision, Clinical Modification and International Classification of Disease, 10th Revision, Clinical Modification codes of 99.60, 99.63, and 5A12012. ESRD patients were subsequently identified using codes of 585.6 and N18.6. Baseline characteristics and outcomes were compared among ESRD and non-ESRD patients in crude and propensity score (PS)-matched cohorts. Predictors of mortality in ESRD patients after an in-hospital SCA event were analyzed using a multivariate logistic regression model. A total of 1,412,985 patients sustained in-hospital SCA during our study period. ESRD patients with in-hospital SCA were younger and had a higher burden of key co-morbidities. Mortality was similar in ESRD and non-ESRD patients in PS-matched cohort (70.4% vs. 70.7%, p = 0.45) with an overall downward trend over our study years. Advanced age, Black race, and key co-morbidities independently predicted increased mortality while prior implantable defibrillator was associated with decreased mortality in ESRD patients after an in-hospital SCA event. In the context of in-hospital SCA, mortality is similar in ESRD and non-ESRD patients in adjusted analysis. Adequate risk factor modification could further mitigate the risk of in-hospital SCA among ESRD patients.


Prognostic Value of Growth Differentiation Factor 15 in Kidney Donors and Recipients.
Growth differentiation factor-15 (GDF15) is associated with inflammatory conditions, chronic kidney disease, cardiovascular disease and mortality. There is very limited data on GDF15 after kidney donation and transplantation. We analyzed serum samples of patients who donated a kidney (54 living donors) or who underwent kidney transplantation (104 recipients) at the University Hospital of Münster (Germany) between 2013 and 2015, for GDF15 levels immediately prior and one year after surgery. GDF15 levels were significantly elevated in end-stage renal disease patients compared to healthy individuals (2844 (IQR 2087, 3361) pg/ml vs. 384 (IQR 307, 487) pg/ml, p < 0.001). GDF15 was strongly associated with the dialysis vintage. While kidney transplantation led to a significant decrease of GDF15 (913 (IQR 674, 1453) pg/ml, p < 0.001), kidney donation caused a moderate increase of GDF15 (510 (IQR 420, 626), p < 0.001) one year after surgery. GDF15 levels remained significantly higher in recipients and kidney donors than in healthy controls (735 (IQR 536, 1202) pg/ml vs. 384 (IQR 307, 487) pg/ml, p < 0.001). GDF15 is increased in patients with kidney disease and is associated with dialysis vintage. Given its decrease after transplantation and its increase after uni-nephrectomy, GDF15 might be a marker of kidney function. However, since it correlates only to the eGFR in transplanted patients it may indicate chronic kidney disease.


Lclet 4 enhances pro-apoptotic and anti-invasive effects of mitoxantrone on human prostate cancer cells - in vitro study.
Triterpene saponosides are widely distributed plant secondary metabolites characterized by relatively low systemic cytotoxicity and a range of biological activities. These include anti-inflammatory, antimicrobial, vasoprotective and antitumor properties. In particular, the ability of saponins to enhance the cytotoxicity of chemotherapeutic drugs opened perspectives for their application in combined cancer chemotherapy. Here, we used human prostate cancer DU-145 cells as an in vitro model to elucidate the synergy of the interactions between biological activities of an oleanane type 13β,28-epoxy triterpene saponoside (Lclet 4) and mitoxantrone, which is a cytostatic drug commonly used in prostate cancer therapy. No cytotoxic or pro-apoptotic effect of Lclet 4 and mitoxantrone administered at the concentrations between 0.05 and 0.1 µg/ml could be seen. In contrast, cocktails of these agents exerted synergistic pro-apoptotic effects, accompanied by the activation of the caspase 3/7 system. This effect was paralleled by attenuating effects of Lclet 4/mitoxantrone cocktails on the invasive potential, metalloproteinase expression and motility of DU-145 cells. Multifaceted and additive effects of Lclet 4 and mitoxantrone on basic cellular traits crucial for prostate cancer progression indicate that the combined application of both agents at systemically neutral concentrations may provide the basis for new promising strategies of prostate cancer chemotherapy.


Japanese cedar pollen-specific interleukin-4 production develops immediately after the first exposure to pollens in infants with atopic dermatitis.
Japanese cedar pollens (JCPs) spread over most areas of Japan from February to April and cause pollenosis. While IgE synthesis against JCPs starts after age 1, it remains to be clarified when JCP-specific T helper cells acquire the ability to produce IL-4, a cytokine that induces IgE synthesis. This study aimed to clarify when the sensitization of T cells to JCPs develops. Peripheral blood mononuclear cells from 153 children with atopic dermatitis (AD) aged 0-15 years were stimulated with a standardized JCP allergen. As parameters of T cell responsiveness, lymphocyte proliferation and the production of IL-4 and IFN-gamma were measured. T cell responses against JCPs were negative before March in infants with AD who had never been exposed to JCPs or who were exposed for less than a month (nine, seven and nine subjects for lymphocyte proliferation, cytokine production and IgE synthesis, respectively). Lymphocyte proliferation distinctly increased in 67.6% (23/34) of infants with AD examined between March and June. JCP-specific IL-4 production was observed in 56.0% (14/25) of infants with AD examined between March and June. Correspondingly, a slight increase in the level of serum JCP-specific IgE antibody was seen in 17.2% (five of 29) of infants with AD examined between April and June. These results demonstrate that the sensitization of T cells to JCPs is effectively completed within a few months after the first exposure to JCPs.


Allergic contact dermatitis to multiple sawdust allergens.
A 73-year-old man presented with an 8-year history of a dermatitis affecting his face, dorsum of hands, and forearms. He was a retired cabinet maker but still carried out some timber work at home. He was patch tested and found to be positive to colophony and saw-dust samples from four different timbers: Silky Oak, Queensland Hoop Pine, Radiata Pine and Australian red cedar.


Endarteriectomy of the left coronary artery (LCA) as a supplementary surgical means of myocardial revascularization with aortocoronary vein bypass procedure.
In order to establish a satisfactory vein bypass anastomosis during myocardial revascularization, 2 findings are of special importance: the local wall quality and the actual lumen of the coronary artery, both altered by the arteriosclerotic disease. In certain cases, with diffuse triple vessel disease, the intraoperative decision for an endarteriectomy as a supplementary surgical means appears to be a logical consequence. In our own patient group of 50 restudied patients with an endarteriectomy of the LCA, we had a patency rate of 72%; in a subgroup it was as high as 84%, if performed locally and under full vision. Compared with extended core extraction, the latter technique only showed minor vessel irregularities proximal and distal to the bypass anastomosis and thus, in a long-term view, it opens up additional revascularization possibilities for severe coronary artery sclerosis.


Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera.
Lactobacilli are a diverse group of species that occupy diverse nutrient-rich niches associated with humans, animals, plants and food. They are used widely in biotechnology and food preservation, and are being explored as therapeutics. Exploiting lactobacilli has been complicated by metabolic diversity, unclear species identity and uncertain relationships between them and other commercially important lactic acid bacteria. The capacity for biotransformations catalysed by lactobacilli is an untapped biotechnology resource. Here we report the genome sequences of 213 Lactobacillus strains and associated genera, and their encoded genetic catalogue for modifying carbohydrates and proteins. In addition, we describe broad and diverse presence of novel CRISPR-Cas immune systems in lactobacilli that may be exploited for genome editing. We rationalize the phylogenomic distribution of host interaction factors and bacteriocins that affect their natural and industrial environments, and mechanisms to withstand stress during technological processes. We present a robust phylogenomic framework of existing species and for classifying new species.


Changes of hepatic volume after successful Kasai operation.
The number of long term survivors who have undergone Kasai operation for biliary atresia is increasing, but some have a hepatic dysfunction likely to require liver transplantation in the near future. Hepatic volume possibly reflects whole liver function, and our objective was to assess the changes of hepatic volume after Kasai operation. Ten patients were studied. Ages ranged from 3 to 27 years. They underwent Kasai operation at ages ranging from 50 to 80 days. Liver areas (cm2) on CT images were measured with an image processing and analysis program (NIH Image 1.57). Hepatic volume (cm3) was calculated by summing up the areas of each image and multiplying by slice thickness (cm). After Kasai operation, the size of the liver increased to 1.7-1.9 times the standard volume, and then reduced to normal size around 5 years of age. In the teens, hepatic volume decreased below the standard volume. Segmental hypertrophy accompanying atrophy of other hepatic segments was observed in 9 out of 10 patients; right lobe hypertrophy: 6, medial segment: 2, and lateral segment: 1. Therefore, progressive hepatic atrophy begins in the teens, but is compensated for by segmental hypertrophy.


Chk2-dependent HuR phosphorylation regulates occludin mRNA translation and epithelial barrier function.
Occludin is a transmembrane tight junction (TJ) protein that plays an important role in TJ assembly and regulation of the epithelial barrier function, but the mechanisms underlying its post-transcriptional regulation are unknown. The RNA-binding protein HuR modulates the stability and translation of many target mRNAs. Here, we investigated the role of HuR in the regulation of occludin expression and therefore in the intestinal epithelial barrier function. HuR bound the 3'-untranslated region of the occludin mRNA and enhanced occludin translation. HuR association with the occludin mRNA depended on Chk2-dependent HuR phosphorylation. Reduced HuR phosphorylation by Chk2 silencing or by reduction of Chk2 through polyamine depletion decreased HuR-binding to the occludin mRNA and repressed occludin translation, whereas Chk2 overexpression enhanced (HuR/occludin mRNA) association and stimulated occludin expression. In mice exposed to septic stress induced by cecal ligation and puncture, Chk2 levels in the intestinal mucosa decreased, associated with an inhibition of occludin expression and gut barrier dysfunction. These results indicate that HuR regulates occludin mRNA translation through Chk2-dependent HuR phosphorylation and that this influence is crucial for maintenance of the epithelial barrier integrity in the intestinal tract.


Mbandakamine-Type Naphthylisoquinoline Dimers and Related Alkaloids from the Central African Liana Ancistrocladus ealaensis with Antiparasitic and Antileukemic Activities.
Four new dimeric naphthylisoquinoline alkaloids, michellamine A5 (2) and mbandakamines C-E (4-6), were isolated from the Congolese plant Ancistrocladus ealaensis, along with the known dimer mbandakamine A (3). They represent constitutionally unsymmetric dimers, each consisting of two 5,8'-coupled naphthylisoquinoline monomers. While the molecular halves of michellamine A5 (2) are linked via C-6' of both of the naphthalene moieties, i.e., via the least-hindered positions, so that the central biaryl axis is configurationally unstable and not an additional element of chirality, the mbandakamines 3-6 possess three consecutive stereogenic axes. Their monomeric units are linked through an unprecedented 6',1″-coupling in the binaphthalene core, leading to a high steric load, since the central axis is located in one of the peri-positions, neighboring one of the outer axes. In addition, four new 5,8'-coupled monomeric naphthylisoquinolines, viz., ancistroealaines C-F (7-10), were identified, along with four "naphthalene-devoid" tetra- and dihydroisoquinolines, named ealaines A-D (11-14). The new mbandakamines C (4) and D (5) showed pronounced activities against the malaria parasite Plasmodium falciparum, and they were likewise found to display strong cytotoxic activities against human leukemia (CCRF-CEM) and multi-drug-resistant tumor cells (CEM/ADR5000).


Simultaneous detection of plant growth regulators jasmonic acid and methyl jasmonate in plant samples by a monoclonal antibody-based ELISA.
Methyl jasmonate (MeJA) and its free-acid form, jasmonic acid (JA), collectively referred to as jasmonates (JAs), are natural plant growth regulators that are widely present in higher plants. Simultaneous detection of JA and MeJA in plant samples is of significance and is a great challenging issue. In this study, coupling with two extraction methods, a sensitive monoclonal antibody (mAb) based enzyme-linked immunosorbent assay (ELISA) for simultaneous detection of JA and MeJA in plant samples was developed. The JA-bovine serum albumin (BSA) conjugate was used as an immunogen for the production of mAb. As the produced mAb exhibited higher recognition ability towards MeJA than towards JA, ELISA was established using MeJA as the standard. Under optimal experimental conditions, the IC50 and LOD values of ELISA for MeJA were 2.02 ng mL-1 and 0.20 ng mL-1, respectively. In the first extraction method, MeJA in plant samples was evaporated and only JA was extracted. In the second extraction method, both JA and MeJA were extracted. After methylation, JA in the extracts was converted into MeJA, and the whole MeJA in the extracts was measured by ELISA. Plant samples including the leaves of Salvia splendens, the flowers of Salvia splendens and the fruit of grapes were collected. JA and MeJA in these samples were detected by the proposed ELISA. It was found that the concentrations of JA in these three plant samples were about 3-5 times higher than those of MeJA in those samples. ELISA was also confirmed by HPLC. There was a good correlation between ELISA and HPLC.


Quality and fertility of frozen ovine spermatozoa from epididymides stored at room temperature (18-25 °C) for up to 48 h post mortem.
This study investigates the effect of time of storage of epididymides at room temperature and the addition of 20% of seminal plasma to the cryopreservation extender, on post thaw quality and fertility of ovine spermatozoa collected from the cauda epididymis. Spermatic kinetics, integrity and the stability of plasma membrane, damage to the acrosome and fertility following laparoscopic artificial insemination were evaluated in samples collected in an artificial vagina (AV) and from epididymides stored at room temperature for zero (G0), six (G6), twelve (G12), twenty-four (G24) and forty-eight (G48) hours post mortem. There were no significant differences in spermatic parameters between the methods of sample collection, except for progressive motility and velocity according to the straight path(VSL). G48 samples had significant lower total motility(TM), progressive motility(PM), kinetic parameters, viability and acrosomal integrity. Pregnancy rate after insemination was similar for samples collected using AV, and the G0, G6, G12 and G24 samples. In conclusion, ovine epididymides can be exposed to room temperature, for up to 24 h post mortem, with no effect on viability and fertility of cryopreserved seminal samples. The addition of seminal plasma to the cryopreservation extender had no effect on spermatozoa quality nor fertility.


ConfGen: a conformational search method for efficient generation of bioactive conformers.
We describe the methodology, parametrization, and application of a conformational search method, called ConfGen, designed to efficiently generate bioactive conformers. We define efficiency as the ability to generate a bioactive conformation within a small total number of conformations using a reasonable amount of computer time. The method combines physics-based force field calculations with empirically derived heuristics designed to achieve efficient searching and prioritization of the ligand's conformational space. While many parameter settings are supported, four modes spanning a range of speed and quality trades-offs are defined and characterized. The validation set used to test the method is composed of ligands from 667 crystal structures covering a broad array of target and ligand classes. With the fastest mode, ConfGen uses an average of 0.5 s per ligand and generates only 14.3 conformers per ligand, at least one of which lies within 2.0 A root-mean-squared deviation of the crystal structure for 96% of the ligands. The most computationally intensive mode raises this recovery rate to 99%, while taking 8 s per ligand. Combining multiple search modes to "fill-in" holes in the conformation space or energy minimizing using an all-atom force field each lead to improvements in the recovery rates at higher resolutions. Overall, ConfGen is at least as good as competing programs at high resolution and demonstrates higher efficiency at resolutions sufficient for many downstream applications, such as pharmacophore modeling.


Loosening of Total Knee Arthroplasty after Brucellosis Infection: A Case Report.
In this report we describe a 78-year-old man whose total knee arthroplasty showed the symptoms of infection with brucella with radiographic signs of loosening 5 years after the index surgery. The patient was treated successfully after a 2-stage revision arthroplasty surgery along with using rifampicin and doxycycline for 8 weeks.


Levy-Reid hypothesis.
The inconsistencies in the research findings looking to test for the Levy-Reid hypothesis on the relationship between hand posture and laterality have been accounted for in various ways. Some authors (Cohen, 1991; Weber and Bradshaw, 1981) have suggested that existing methodologies for experimentally establishing laterality of language functioning are unreliable. To overcome this constraint, we have taken Halsey, Blauenstein, Wilson, and Wills' (1980) suggestion of using cerebrovascular accident (CVA) patients in which laterality of expressive speech has been established incontrovertibly. We examined 74 CVA subjects assessing hand posture, handedness, and side of stroke. Our findings lend support for Levy-Reid, nevertheless further examination of the hypothesis using a cross-cultural sample underscores the impact education and culture have on hand posture.


One-component nanomedicine.
One-component nanomedicine (OCN) represents an emerging class of therapeutic nanostructures that contain only one type of chemical substance. This one-component feature allows for fine-tuning and optimization of the drug loading and physicochemical properties of nanomedicine in a precise manner through molecular engineering of the underlying building blocks. Using a precipitation procedure or effective molecular assembly strategies, molecularly crafted therapeutic agents (e.g. polymer-drug conjugates, small molecule prodrugs, or drug amphiphiles) could involuntarily aggregate, or self-assemble into nanoscale objects of well-defined sizes and shapes. Unlike traditional carrier-based nanomedicines that are inherently multicomponent systems, an OCN does not require the use of additional carriers and could itself possess desired physicochemical features for preferential accumulation at target sites. We review here recent progress in the molecular design, conjugation methods, and fabrication strategies of OCN, and analyze the opportunities that this emerging platform could open for the new and improved treatment of devastating diseases such as cancer.


Alterations in regional homogeneity of resting-state brain activity in ketamine addicts.
Ketamine is a non-competitive anatognist of the N-methyl-D-aspartate (NMDA) receptor commonly used as an anesthetic and analgesic. In sub-anesthetic doses, it can induce temporary psychotic symptoms and has served as a pharmacological model for schizophrenia. While its acute effects on brain and behavior have been studied, the effects of long-term exposure to ketamine on brain activity have been largely unexplored. In this study, we aimed to examine such effects on spontaneous brain dynamics measure using resting-state functional magnetic resonance imaging (fMRI). Forty-one patients with ketamine dependence and forty-four healthy control subjects were imaged with BOLD fMRI using a 3.0-Tesla Siemens scanner at the Magnetic Resonance Center of Hunan Provincial People's Hospital, analyzed with the regional homogeneity (ReHo) method. Compared with healthy controls, decreased ReHo was found in ketamine users in the right anterior cingulate cortex and increased ReHo was found in left precentral frontal gyrus (p<0.05, cluster-level corrected). We also observed negative correlations between increased ReHo in precentral frontal gyrus and estimated total lifetime ketamine consumption and ketamine craving levels. To our knowledge, this is the first study the long-term effects of ketamine exposure on brain functional activity. Our findings indicate that ketamine dependence is associated with alterations in the functional connectivity of medial and lateral prefrontal cortices.


Correlation between Different Postoperative Serum Cortisol Cut-off Values Measured in Different Periods and Long-term Outcomes in Patients with Cushing's Disease.
Objective To investigate the correlation between different postoperative serum cortisol cut-off values measured in different periods and the long-term outcomes in patients with Cushing's disease (CD). Methods The clinical data of 102 CD patients undergoing transsphenoidal surgery (TSS) in Peking Union Medical College Hospital from May 1985 to July 2008 were analyzed retrospectively. The differences of long-term outcomes were compared between patients with cortisol levels below 2 μg/dl (2 μg/dl group) and levels between 2 and 5 μg/dl (5 μg/dl group) in the 1st postoperative day and 3 and 6 months after surgery. Results The mean follow-up duration was (10.7±1.7) years (range:5-29.1 years). Among these 102 patients,the disease was cured in 74 patients (72.5%) and recurred in 28 patients (27.5%). On the 1st postoperative day,there were 63 patients in the 2 μg/dl group,in which 48 patients (76.2%) achieved long-term cure;there were 39 patients in the 5 μg/dl group,in which 26 (66.7%) achieved long-term cure. The difference was not statistically significant (χ2=1.097,P=0.295). Three months after TSS,the long-term cure rate was 84.2% (48/57) in the 2 μg/dl group,which was significantly higher than that (65.0%,26/40) in the 5 μg/dl group (χ2=4.795,P=0.029). Six months after TSS,the long-term cure rate was 88.7% (47/53) in the 2 μg/dl group,which was significantly higher than that(69.2%,27/39) in the 5 μg/dl group(χ2=5.400,P=0.020). Conclusion The serum cortisol level of below 2 μg/dl is more useful than 2-5 μg/dl 3 months and 6 months after surgery in predicting the prognosis of CD patients.


Effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy requirements in isolated rabbit heart.
The majority of patients with implanted cardioverter defibrillators (ICD) require antiarrhythmic (AR) drugs. ARs may increase defibrillation energy requirements. This study investigated the effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy needs. In 24 isolated rabbit hearts, the 50 and 80% successful defibrillation energy (ED50, ED80) was calculated in four phases: predrug baseline condition (phase 1), and phases 2, 3, and 4 with increasing concentrations of lidocaine, ajmaline, diltiazem (n = 18). Control experiments (n = 6) with only Tyrode's solution infusion indicated that the preparation was stable over time. Defibrillation energy requirements significantly (p < 0.05) increased with all ARs. Low, medium, and high lidocaine concentrations increased ED50 and ED80 to 146, 223, and 312% and 139, 207, and 285%, respectively. Ajmaline increased ED50 and ED80 to 133, 175, and 251% and 135, 208, and 285%, respectively. Diltiazem increased ED50 and ED80 by 175, 236, and 334% and 158, 212, and 286%, respectively. The results of this study demonstrate a dose-dependent increase in defibrillation energy requirements by using lidocaine, diltiazem, and ajmaline. In patients with ICDs, administration of these drugs might cause a critical increase in defibrillation energy requirements, resulting in device failure.


Moringa induces its beneficial effect via hormesis.
Moringa oleifera, a traditional Indian herb, is widely known for its capacity to induce antioxidant, anti-inflammatory and other chemoprotective effects in a broad range of biomedical models. These perspectives have led to an extensive number of studies using various moringa extracts to evaluate its capacity to protect biological systems from oxidative stress and to explore whether it could be used to slow the onset of numerous age-related conditions and diseases. Moringa extracts have also been applied to prevent damage to plants from oxidative and saline stresses, following hormetic dose–response patterns. The present paper provides the first integrated and mechanistically based assessment showing that moringa extracts commonly induce hormetic dose responses and that many, perhaps most, of the beneficial effects of moringa are due to its capacity to act as an hormetic agent.


Polymeric N-halamine latex emulsions for use in antimicrobial paints.
A new N-halamine monomer, N-chloro-2,2,6,6-tetramethyl-4-piperidinyl methacrylate (Cl-TMPM), was synthesized and used to prepare water-based polymeric N-halamines by emulsion polymerization. The chemical structures of the samples were characterized with Fourier transform IR, (13)C NMR, UV/vis, and differential scanning calorimetry analyses. Upon the addition of a small amount of the polymeric N-halamine latex emulsions into commercial water-based latex paints as antimicrobial additives, the new paints provided potent antimicrobial activities against Staphylococcus aureus (S. aureus; Gram-positive bacteria), methicillin-resistant S. aureus (MRSA; drug-resistant Gram-positive bacteria), vancomycin-resistant enterococcus (VRE; drug-resistant Gram-positive bacteria), Escherichia coli (E. coli; Gram-negative bacteria), Candida tropicalis (C. tropicalis; fungi), MS2 virus (15597-B; virus), and Stachybotrys chartarum spore (S. chartarum; mold), and they successfully prevented biofilm formation and development. The antimicrobial functions of the new paints were long-lasting for more than 1 year under normal in-use conditions, easily monitorable by a simple potassium iodine/starch test, and readily rechargeable if the functions were accidentally lost as a result of challenging conditions such as heavy soil, flooding, etc.


Minimally invasive treatment of white spot enamel lesions.
This article describes a technique used to treat superficial white spot lesions by a minimally invasive approach. The proposed technique is based on reactivation of enamel by elimination of its hypermineralized external layer through microabrasion, followed by daily home application of casein phosphopeptide-amorphous calcium phosphate complexes (CCP-ACP). The technique may allow elimination of white spot lesions without involving restorative procedures. Microabrasion followed by long-term daily home application of CCP-ACP may be considered an interesting alternative to the restorative approach for treatment of white spot lesions.


Prevalence of anti-vif antibodies in HIV-1 infected individuals assessed using recombinant baculovirus expressed vif protein.
A 630 base pair fragment of the HIV-1 genome encompassing the entire vif open reading frame has been produced by the polymerase chain reaction and cloned into the baculovirus transfer vector pAcYM1. Extracts from insect cells infected with a recombinant baculovirus expressing the HIV-1 vif gene product were used in a radioimmunoassay to analyse 238 sera from HIV infected individuals for the presence of anti-vif antibodies. The overall prevalence of anti-vif antibodies in this group of patients was 25.3%. Stratification of the group according to CD4 levels showed that anti-vif antibodies were more prevalent in patients with CD4 counts below the median of the group (155 x 10(6) cells/L; P = 0.005). A significant increase in anti-vif antibodies was observed in patients with CD4 levels less than 280 x 10(6) cells/L (P < 0.01) and in patients with symptomatic HIV infection (P = 0.0003). However, there was no significant difference in the prevalence of anti-vif antibodies in patients stratified according to p24 antigen status. The implications of these findings in the context of HIV replication are discussed.


Microbiological profile of teicoplanin.
The in-vitro antibacterial activity of teicoplanin, a new glycopeptide antibiotic, previously named teichomycin A2, was tested against 258 gram-positive anaerobic bacterial strains, recently clinically isolated, by measuring the minimum inhibitory concentrations. Comparisons were made with other drugs, clindamycin, rifampicin, netilmicin, enoxacin, vancomycin, widely utilized for the treatment of bacterial infections. Teicoplanin was very active against the tested species and showed the highest activity against all the tested strains, with a geometric mean of MICs, a MIC 50 and MIC 90 of 0.125, 0.12 and 0.5 microg/ml, respectively.


Low plasma androgens in women with systemic lupus erythematosus.
The high ratio of women with systemic lupus erythematosus (SLE) has remained unexplained, despite the recent description of metabolic abnormalities of estrogen and androgen metabolism. Alterations of steroid metabolism in patients with SLE could be important in the pathogenesis of this disease, since it has been reported that gonadal steroids modulate the immune system. Moreover, research with inbred lupus mice has shown that estrogens have adverse effects on the disease in both sexes, whereas androgen therapy or oophorectomy is protective in females. Recently, the finding of elevated testosterone oxidation at C-17 in females with SLE suggested that plasma androgen levels in males and females with SLE should be examined more closely. We studied the varying degrees of clinical activity, with regard to plasma levels of 4 significant androgens: testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in a series of 5 male and 42 female SLE patients. Decreased levels of all androgens were observed in women with SLE. The lowest levels of plasma androgens were found in female patients who had active disease, as determined by laboratory and clinical assessment. These data support the fact that specific abnormalities of androgen metabolism in the female are associated with SLE, and may contribute in some way to morbidity and mortality. More importantly, these data may have implications for future therapeutic regimens based on male hormone replacement.


A search for a model tissue for studying effects of thiazide diuretics.
A search was made for a model tissue of NaCl absorption which would be sensitive to inhibition by diuretics of the thiazide type. A lack of such a model through the years has hampered the analysis of the cellular mechanism of action of this important class of drugs. Using the short-circuit current technique, the urinary bladders of the toads Bufo spinosus and Bufo marinus, and the frog Rana temporaria were investigated regarding the effects of various thiazides. These bladders have NaCl absorptive properties similar to those of the distal renal tubules, and are claimed to be sensitive to the inhibitory effect of thiazides on sodium transport. The short-circuit current (SCC), which is representative of the sodium transport across the epithelium, was reduced by cyclopenthiazide and polythiazide, but only at high concentrations (above 0.1 mM). To rule out the possibility that this was an unspecific effect, attempts were made to block the effect by the 'thiazide blocker' Ex 4877, but without success. This finding, together with the fact that dose-response curves were difficult to obtain, would indicate that these epithelia are not suitable for the stated purpose. Preliminary studies were also conducted on the urinary bladder of the plaice, Pleuronectes platessa, which has a different system of NaCl absorption that is claimed to be rapidly and reversibly inhibited by thiazides. Polythiazide, added to both sides of the bladder, had no effect on SCC.


[The farmost unknown disease of postoperative permanent hypoparathyroidism--feasibility and validation of an innovative questionnaire instrument].
Aim of our study has been the systematic evaluation concerning the still farmost unknown disease of postoperative, permanent hypoparathyroidism. For this we designed a specific questionnaire as measuring instrument--it was evaluated by experts and validated by 3 control groups--to examine then a patient group (n = 20) with symptomatic postoperative, permanent hypoparathyroidism. The application of the questionnaire was very feasible, the reliability of measuring scales according to Cronbach's alpha > or = 0.70. The validity of content and construct validity fully existed (Pearson's correlation coefficient r > or = - 0.27; p < 0,05). The farmost frequent clinical complaints were peripheral cold sensations (65 %), pains in joints (55 %), sensation of heaviness and weakness in extremities (55 %) and paresthesias (45 %). Most frequent clinical symptoms were brittle nails (40 %) and diarrhoea (35 %). Sum and distress level scores for classification of illness severity were determined. In conclusion our questionnaire is a valid instrument and from a clinical point of view easy to apply, reasonable and very feasible in practical use. It represents a novel, optimum instrument to determine disease condition and illness severity of hypoparathyroid patients and makes it possible to gain further information of this up to now less systematically analysed disease.


Is food insecurity contributing to malnutrition in older adults in Switzerland? - A cross-sectional study.
Food insecurity has been defined as "limited access to food, at the level of individuals or households, due to lack of money or other resources" and may increase the nutritional risk, which in turn leads to poor health, development of chronic diseases, poor psychological and cognitive functioning, and substandard academic achievements. There is limited data on the importance of food insecurity in a rich country such as Switzerland. This is a cross-sectional analysis of data from a structured survey in an elderly population of Switzerland. The data was assessed between June and August 2021 in the course of a 7-year phone call follow-up from the EFFORT trial, which included medical inpatients at nutritional risk from 2014 to 2018. A validated questionnaire (Six-Item Short Form 2012 of the U.S: Household Food Security Survey Module) was used to assess food security status. Of the 433 included patients, 30 (6.9%) were food insecure. A significant association between food insecurity and age, governmental financial support and self-reported loneliness was found. When compared with the food secure group, there was a significant lower quality of life measured by the EQ-5D VAS. In an older Swiss population of patients at nutritional risk, food insecurity was named as a contributing factor for malnutrition in about 7% of patients, particularly younger individuals with financial support, and self-reported loneliness. In the assessment of malnutrition, physician and dieticians should ask for food insecurity and if detect take appropriate actions.


[Brown bone tumor as the first manifestation of primary hyperparathyroidism].
We report a clinical case of a 26 years old female who had a 2 years evolution chin tumour with hypercalcemia (11.8 mg/dl) and PTH (paratohormone) of 761 pg/ml. She underwent a CT scan and MRI of the mandible, as well as a biopsy followed by excision of the tumour by the maxilofacial surgeons. Our ENT Department asked for a Scintigraphy (Tc99s-mibi) and thoracic-cervical CT, which showed a lesion that turned out to be an adenoma of the lower right parathyroid gland after surgery and pathological examination. The patient suffered a Primary hyperparathyroidism that was the main stimulus for the Brown Tumour made up by macrophagos and multinuclear giant cells, being this the first manifestation of the metabolic disorder. This form of hyperparathyroidism is very rare in the clinic. We do a literature review to establish the differential diagnosis for such pathology.


Time-dependent communication between multiple amino acids during protein folding.
Cooperativity is considered to be a key organizing principle behind biomolecular assembly, recognition and folding. However, it has remained very challenging to quantitatively characterize how cooperative processes occur on a concerted, multiple-interaction basis. Here, we address how and when the folding process is cooperative on a molecular scale. To this end, we analyze multipoint time-correlation functions probing time-dependent communication between multiple amino acids, which were computed from long folding simulation trajectories. We find that the simultaneous multiple amino-acid contact formation, which is absent in the unfolded state, starts to develop only upon entering the folding transition path. Interestingly, the transition state, whose presence is connected to the macrostate cooperative behavior known as the two-state folding, can be identified as the state in which the amino-acid cooperativity is maximal. Thus, our work not only provides a new mechanistic view on how protein folding proceeds on a multiple-interaction basis, but also offers a conceptually novel characterization of the folding transition state and the molecular origin of the phenomenological cooperative folding behavior. Moreover, the multipoint correlation function approach adopted here is general and can be used to expand the understanding of cooperative processes in complex chemical and biomolecular systems.


Bedside coagulation monitoring in heparin-treated patients with active thromboembolic disease: a coronary care unit experience.
Patients with active venous and arterial thromboembolic disorders are known to benefit from systemic anticoagulation with heparin. Clinical studies have shown, however, that therapeutic anticoagulation is rarely achieved rapidly and often is not maintained over time. Prolonged laboratory turnaround time of the activated partial thromboplastin time (aPTT) may contribute directly to these common problems. A total of 272 aPTT determinations were performed on 120 heparin-treated patients admitted to the coronary care unit. The time from sample collection to data availability was 126 +/- 84 minutes with standard laboratory aPTT testing. In contrast, a bedside coagulation device provided an aPTT within 3 minutes (p < 0.001). Subtherapeutic aPTT values (< 65 seconds) were documented in 21% of all patients; in each, the heparin dose was changed and a repeat aPTT was required. In a separate study of 33 heparinized patients randomized to either bedside or central laboratory aPTT testing (264 aPTT determinations), the time to achieve a therapeutic state of systemic anticoagulation was 8.2 hours and 18.1 hours, respectively (p < 0.005). The time from aPTT determination to a decision regarding heparin titration adjustments was 14.5 minutes and 3 hours with bedside and laboratory testing, respectively (p < 0.001). Thus bedside coagulation monitoring provides a convenient, rapid, and accurate assessment of systemic anticoagulation among heparin-treated patients with active thromboembolic disease in the coronary care unit. This technology warrants further clinical investigation.


Loss of Notch1 disrupts the barrier repair in the corneal epithelium.
The corneal epithelium is the outermost layer of the cornea that directly faces the outside environment, hence it plays a critical barrier function. Previously, conditional loss of Notch1 on the ocular surface was found to cause inflammation and keratinization of the corneal epithelium. This was in part attributed to impaired vitamin A metabolism, loss of the meibomian glands and recurrent eyelid trauma. We hypothesized that Notch1 plays an essential role in the corneal epithelial barrier function and is a contributing factor in the pathologic changes in these mice. Notch1 was conditionally deleted in adult Notch1(flox/flox), K14-Cre-ERT(+/-) mice using hydroxy-tamoxifen. The results indicated that conditional deletion of Notch1 on the ocular surface leads to progressive impairment of the epithelial barrier function before the onset of corneal opacification and keratinization. Loss of the barrier was demonstrated both by an increase in in vivo corneal fluorescein staining and by enhanced penetration of a small molecule through the epithelium. Corneal epithelial wounding resulted in significant delay in recovery of the barrier function in conditional Notch1(-/-) mice compared to wild type. Mice with conditional deletion of Notch1 did not demonstrate any evidence of dry eyes based on aqueous tear production and had normal conjunctival goblet cells. In a calcium switch experiment in vitro, Notch1(-/-) cells demonstrated delayed membrane localization of the tight junction protein ZO-1 consistent with a defect in the epithelial tight junction formation. These findings highlight the role of Notch1 in epithelial differentiation and suggest that intrinsic defects in the corneal epithelial barrier recovery after wounding is an important contributing factor to the development of inflammatory keratinization in Notch1(-/-) mice.


Activation of late transition metal catalysts for olefin polymerizations and olefin/CO copolymerizations.
The late transition metal catalysts for homo- and copolymerizations of olefins expand the polymer properties and the usable monomer feedstock of early transition metal catalysts. A critical step for a polymerization is the activation of catalyst precursors and the generation of the actual active site. This perspective discusses possible activation protocols for two well-known catalyst systems, the a-diimine Ni or Pd olefin polymerization catalysts and the Pd catalysts for alkene/CO copolymerization. The general concept of catalyst activation is outlined and similarities as well as differences between single-component catalysts and in situ activated systems are highlighted.


[Surveillance of susceptibility of clinical isolates to panipenem between 2000 and 2003].
For the post-marketing surveillance of panipenem/betamipron (PAPM/BP, Carbenin), MICs of injectable beta-lactam antibacterials including PAPM against clinical isolates from 15 medical institutions all over Japan are measured yearly and the incidence rates of resistance in various species are also evaluated. In the first surveillance from June 2000 to March 2001, 1,356 isolates of 28 species were tested, 1,221 isolates of the same 28 species were tested in the second surveillance from April 2001 to March 2002, and 1,403 isolates of the same 28 species were tested in the third surveillance from April 2002 to March 2003. No remarkable changes in the activity of PAPM were observed in these surveillances spanning three years. The activity of PAPM in this study was comparable to that in the studies conducted before Carbenin was launched. This result suggests that PAPM still maintains potent activity. In these surveillances spanning three years, the incidence rates of resistance in various species were as follows (2000.6-2001.3 --> 2001.4-2002.3 --> 2002.4-2003.3): methicillin-resistant Staphylococcus aureus (39.3% --> 43.9% --> 47.3%), penicillin-intermediate Streptococcus pneumoniae (48.9% --> 44.2% --> 25.7%), penicillin-resistant S. pneumoniae (PRSP, 13.8% --> 26.3% --> 43.2%), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (0.9% --> 0% --> 1.4%), ESBL-producing Klebsiella pneumoniae (3.4% --> 1.3% --> 3.1%), beta-lactamase-producing Haemophilus influenzae (19.2% --> 8.9% --> 42.9%), beta-lactamase-negative ampicillin-resistant H. influenzae (BLNAR, 22.1% --> 30.7% --> 33.0%), and metallo-beta-lactamase-producing Pseudomonas aeruginosa (1.0% --> 4.4% --> 1.0%). PAPM showed the most potent activity among tested drugs against PRSP, whose incidence rate increased notably. BLNAR, whose incidence rates also increased, exhibited low susceptibility to all tested drugs and metallo-beta-lactamase-producing P. aeruginosa also exhibited high resistance. The findings of this surveillance indicate that it is necessary to pay careful attention to the trends of resistant bacteria such as PRSP, BLNAR, and metallo-beta-lactamase producing strains.


Managing dysfunctions and reinterventions in endoscopic ultrasound-guided choledochoduodenostomy with lumen apposing metal stents: Illustrated technical review (with videos).
Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with lumen apposing metal stent is emerging both as a rescue strategy and a primary treatment for distal malignant biliary obstruction. The large-scale diffusion of the procedure and improved overall survival of patients with pancreatobiliary neoplasms is resulting in a growing population of long-term EUS-CDS lumen apposing metal stent carriers. Recent studies have reported a need for reintervention during follow-up as high as 55%, and the Leuven-Amsterdam-Milan Study Group classification has been developed, identifying five mechanisms of stent dysfunction and 11 possible rescue strategies aimed at restoring biliary drainage. This illustrated technical review aims to further dissect the recent classification through a comprehensive analysis of nine illustrative cases, offering insights into the pathophysiology underlying dysfunction and clinical reasoning behind rescue interventions, as well as technical considerations and practical tips and tricks. By exploring mechanisms of dysfunction, this review also assists clinicians in selecting the ideal candidates for EUS-CDS while identifying patients deemed high risk for dysfunction or clinical failure.


Quantification of three-dimensional left ventricular segmental wall motion and volumes from gated tomographic radionuclide ventriculograms.
Tomographic radionuclide ventriculograms may be used for three-dimensional wall motion analysis. We propose that automatic quantification of these images is possible, and here we describe the implementation and validation of a method to perform this task. Automatic computer methods were developed to locate the left ventricular (LV) endocardial surfaces in all time frames of the cardiac cycle. Global, regional, and local motion and volume were computed. Results were displayed using three-dimensional graphics. The methods were validated using phantom, canine, and human studies. Actual phantom values correlated well with experimentally determined volumes, y = 1.01x + 1.29ml, r = 0.99. In the canine model, the LV endocardial surfaces were located to within an average of 1.9 mm and 3.7 mm at end-diastole and end-systole, respectively. Areas of obvious wall motion abnormalities in automatically processed patient studies corresponded well with angiographically documented coronary artery disease. End-diastolic and end-systolic volumes computed automatically from single photon emission computed tomography averaged errors of 9% and 38%, respectively, when compared with contrast ventriculographic volumes. These results indicate that it is possible to automatically identify the left ventricular endocardial surface in gated tomographic radionuclide ventriculograms. The location of these surfaces corresponds well with the location of implanted endocardial markers, and global volume computed from these surfaces corresponds well with known volumes.


Single-Pot Asymmetric Approach toward Enantioenriched Quaternary Stereocenter-Containing Alkylidenecyclobutanes.
Enantioenriched alkylidenecyclobutanes possessing a quaternary stereogenic center, usually difficult to access, have been synthesized by combining a double boron-homologation and an allylboration through a highly efficient and diastereoselective one-pot process. Starting from commercially available substrates, this protocol represents a simple way of accessing chiral unsaturated four-membered ring systems with excellent stereoisomeric ratios.


Monteggia fracture with unreducable anterior dislocation of the radial head and a lesion of the external collateral ligament of the elbow.
Monteggia described a fracture of the proximal third of the ulna with anterior dislocation of the radial head from both the proximal radioulnar and radiocapitellar joints. The key treatment principle in Monteggia fractures is stable anatomic alignment of the ulna. We present an uncommon case of a Monteggia fracture-dislocation with an unreducable anterior dislocation of the radial head and associated with a lesion of the lateral collateral ligament of the elbow. The patient in our report had a successful clinical outcome and functional range of motion after rigid fixation of the ulnar shaft fracture and exploration of the elbow joint, reduction of the radial head and repair of the lateral collateral ligament. This case is unusual because of the association of a complete tear of the external collateral ligament of the elbow.


Clinical trials designed to evaluate therapeutic preferences.
We present an experimental design for the evaluation of therapeutic preferences among well established similar modes of therapy. The measure of the degree of preference is based on clinical decisions to continue or discontinue the current treatment at each patient visit. Such a trial simulates decision-making in ordinary clinical practice, while adhering to the scientific principles of experimental design, and it alleviates some of the ethical problems inherent in randomized allocation of a treatment for a period of fixed length in conventional control trials. We discuss the design and methods of analysis and illustrate their application with data from a trial comparing three alternative drug treatments for chronic asthma. Such clinical trials provide a mechanism for examining concordance between the relative efficacy of treatments predicted from conventional controlled clinical trials and their ultimate performance in ordinary clinical practice, expressed in terms of therapeutic preferences.


An evaluation of infection control in private and public sector intensive care units in South Africa.
Appropriate infection control policies and practices are key to reducing the risk of healthcare-associated infections in patients in intensive care units (ICUs). To evaluate infection control in ICUs using the Infection Control Assessment Tool (ICAT). Six public and five private adult ICUs were included. Seven modules from the ICAT were administered including ICU, hand hygiene, and isolation and standard precautions. Modules were scored on a quantitative scale as per the tool guidelines and trained independent nurses observed practices. All ICUs reported to have a 1:1 nurse-to-patient ratio. One public ICU did not have the required 1:2 hand wash basin-to-bed ratio. We observed 100% adherence to handwashing or alcohol rub at each of the five moments of hand hygiene; however, the correct amount of alcohol rub was used in only 2% (n = 2) of the 117 observations. The median score for isolation and standard precautions was 79%. There was good infection control practice in ICUs. However, ICUs did not have isolation policies for all the infections listed in the ICAT and did not screen visitors to the ICU. We identified shortcomings in the ICAT and a more suitable tool is required for our healthcare setting.


Rhenium-catalyzed insertion of aldehyde into a C-H bond: synthesis of isobenzofuran derivatives.
A rhenium complex, [ReBr(CO)3(thf)]2, catalyzed reactions of aromatic ketimines with aldehydes to give isobenzofuran derivatives in good to excellent yields. In contrast to ruthenium and rhodium catalysts, aldehydes, which are polar unsaturated molecules, inserted into the C-H bond after activation by the rhenium complex.


[Relationship between activation of endometrial CD56+ natural killers and the character of leiomyoma nodules growth in patients with uterine leiomyoma.]
In patients with different clinical variants of uterine leiomyoma (large or small size, presence or absence of intensive proliferation of tumor cells) the comparative analysis of endometrial CD56+ natural killers (NK) activation was carried out. The relative content of CD56+ cells, expressing of CD158a and CD158i molecules from KIR (killer immunoglobuline-like receptors) family, interferon γ (IFNγ) and transforming growth factor β1 (TGFβ1), was estimated by flow cytometry method. It was found that in the endometrium of all patients with uterine leiomyoma independently of tumor size the content of CD56+ cells and the amount of NK, expressing both activating (CD158i) and inhibitory (CD158a) receptors, were increased. In group of women with stably small uterine leiomyoma the amount of CD56+IFNγ+ lymphocytes was increased, and in women with rapidly growing tumor the elevation of NK, expressing TGFβ1, was noted. Differential analysis of data in patients with large leiomyoma in dependence of type of leiomyoma growth was shown that in patients with the high level of tumor cells proliferation the amount of CD56+ NK and the ratio of NK with activating and inhibitory receptors were lower and the content of CD56+TGFβ1+ lymphocytes was higher than that in women with leiomyoma, which grew due to accumulation of the extracellular matrix components. Received results showed on the suppression of cytotoxic activity of endometrial NK in patients with uterine leiomyoma with increased proliferation. These changes can be used as additional diagnostic criteria of type of leiomyoma growth.


Vacuum-assisted mini-percutaneous nephrolithotomy: a new perspective in fragments clearance and intrarenal pressure control.
To describe the vacuum-assisted mini-percutaneous nephrolithotomy (vmPCNL) technique performed via the 16Ch ClearPetra sheath, to evaluate its outcomes and to analyze intrarenal pressure (IRP) fluctuations during surgery. Data from all consecutive vmPCNL procedures from September 2017 to October 2019 were prospectively collected. Data included patients' and stones characteristics, intra and peri-operative items, post-operative complications and stone clearance. Patients undergoing vmPCNL from March to October 2019 were submitted to IRP measurement during surgery. A total of 122 vmPCNL procedures were performed. Median stone volume was 1.92 cm3. Median operative time was 90 min and median lithotripsy and lapaxy time was 28 min. Stone clearance rate was 71.3%. Thirty-one (25.2%) patients experienced post-operative complications, seven of which were Clavien 3. Postoperative fever occurred in nine (7.4%) patients and one (0.8%) needed a transfusion. No sepsis were observed. IRPs were measured in 22 procedures. Mean IRP was 15.3 cmH2O and median accumulative time with IRP > 40.78 cmH2O (pyelovenous backflow threshold) was 28.52 sec. Maximum IRP peaks were reached during the surgical steps when aspiration is closed (mainly pyelograms), whereas during lithotripsy and suction-mediated lapaxy, the threshold of 40.78 cmH2O was overcome in three procedures. vmPCNL is a safe procedure with satisfactory stone clearance rates. Mean IRP was always lower than the threshold of pyelo-venous backflow and the accumulative time with IRP over this limit was short in most of the procedures. During lithotripsy and vacuum-mediated lapaxy, IRP rarely raised over the threshold.


Depressive symptoms and their association with age, chronic conditions and health status among middle-aged and elderly people in peri-urban Tanzania.
Depression is a global mental health challenge. We assessed the prevalence of depressive symptoms and their association with age, chronic conditions, and health status among middle-aged and elderly people in peri-urban Dar es Salaam, Tanzania. Depressive symptoms were measured in 2,220 adults aged over 40 years from two wards of Dar es Salaam using the ten-item version of the Center of Epidemiologic Studies Depression Scale (CES-D-10) and a cut-off score of 10 or higher. The associations of depressive symptoms with age, 13 common chronic conditions, multimorbidity, self-rated health and any limitation in six activities of daily living were examined in univariable and multivariable logistic regressions. The estimated prevalence of depressive symptoms was 30.7% (95% CI 28.5-32.9). In univariable regressions, belonging to age groups 45-49 years (OR 1.35 [95% CI 1.04-1.75]) and over 70 years (OR 2.35 [95% CI 1.66-3.33]), chronic conditions, including ischemic heart disease (OR 3.43 [95% CI 2.64-4.46]), tuberculosis (OR 2.42 [95% CI 1.64-3.57]), signs of cognitive problems (OR 1.90 [95% CI 1.35-2.67]), stroke (OR 1.56 [95% CI 1.05-2.32]) and anemia (OR 1.32 [95% CI 1.01-1.71]) and limitations in activities of daily living (OR 1.35 [95% CI 1.07-1.70]) increased the odds of depressive symptoms. Reporting good or very good health was associated with lower odds of depressive symptoms (OR 0.48 [95% CI 0.35-0.66]). Ischemic heart disease and tuberculosis remained independent predictors of depressive symptoms in multivariable regressions. Depressive symptoms affected almost one in three people aged over 40 years. Their prevalence differed across age groups and was moderated by chronic conditions, health status and socioeconomic factors.


Salivary evaluation of pediatric patients with cancer, before and after antineoplasic treatment.
This study evaluated the salivary biochemical and immunological status of children with cancer undergoing to antineoplasic treatment in an attempt to identify alternatives for a less invasive and less painful monitoring of these patients. Unstimulated whole saliva samples were obtained from 115 children without cancer (control) and 32 children with cancer (CA). Children with cancer were also evaluated after antineoplasic treatment (CAT, n = 17). The salivary concentrations of glucose, triglycerides, total cholesterol, alkaline phosphatase, gamma-glutamyltransferase (GGT), urea, insulin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), levothyroxine (T4), and immunoglobulin A (IgA) were determined. Acute lymphocytic leukemia, acute myeloid leukemia, and Hodgkin's lymphoma were the most frequent cancers, although cases of non-Hodgkin's lymphoma, medulloblastoma, ependymoma, osteosarcoma, nephroblastoma, Ewing's sarcoma, and endodermal sinus tumor were also observed. The salivary concentration of cholesterol, triglycerides, or GGT did not differ between groups. Instead, the concentrations of alkaline phosphatase and T4 were higher in patients with cancer, irrespective of treatment. TSH levels were higher in the CA group and urea concentration was lower in the CAT group. T3 was undetectable in all groups. Antineoplasic treatment increased the glucose level and decreased the insulin concentration. Salivary concentration of total IgA was lower in children with cancer, irrespective of treatment. Cancer and antineoplasic treatment affected biochemical and immunological parameters in the saliva of children, shedding new light on the potential usefulness of saliva for monitoring children with cancer, especially to patients undergoing immunosuppressive therapy.


SERS mapping combined with chemometrics, for accurate quantification of methotrexate from patient samples.
Despite the technological development in Raman instrumentation that has democratized access to 2D sample scanning capabilities, most quantitative surface-enhanced Raman scattering (SERS) analyses are still performed by only acquiring a single or a few spectra per sample and performing univariate data analysis on those. This strategy can however reach its limit when analytes need to be detected and quantified in complex matrices. In that case, surface fouling and competition between the target analyte and interfering compounds can impair univariate SERS data analysis, underlining the need for a more in-depth data analysis strategy based on exploiting of full-spectrum information. In this paper, a multivariate data analysis strategy was developed, for analyzing SERS maps of methotrexate (MTX) from patient samples, including all steps from baseline correction, selection of wavelength, and the relevant pixels in the map (image threshold segmentation), as well as quantitative model construction based on partial-least squares regression. Among the different baseline correction methods evaluated, standard normal variable transformation and Savitzky-Golay smoothing proved to be more suitable, while the genetic algorithm wavelength screening method was able to screen out MTX-related SERS spectral regions more efficiently. Importantly, with the here-developed process, it was sufficient to use MTX-spiked commercial serum when building quantitative models, removing the need to work with MTX-spiked patient samples, and consequently enabling time- and resource-saving quantitative analyses. Besides, the developed multivariate data analysis approach showed superior performances compared with univariate analysis, with 30 % improved sensitivity (detection limit of 5.7 µM), 25 % higher reproducibility (average relative standard variation of 15.6 %), and 110 % better accuracy (average prediction error of -10.5 %).


The history of direct pulp capping.
The first method of capping exposed pulps, using gold foils, was described by Pfaff in 1756. Thereafter, numerous agents for direct pulp capping have been recommended. Until the end of the 19th century, most materials were used empirically with the idea that the pulp tissue must be irritated by etching or cauterization to heal. Later, more attention was drawn to disinfecting agents, because it became obvious that microorganisms were the reason for pulp inflammation - but these agents were cytotoxic. Since insufficient or inappropriate diagnoses were made before treatment, even necrotic pulps were capped. The first scientific clinical study to compare different capping materials was made by Dätwyler in 1921, whereupon zinc oxide-eugenol showed the best results. One year later, Rebel performed the first animal experiments with disastrous results, so he regarded the exposed pulp as a doomed organ. In 1920 Hermann, introduced calcium hydroxide for root canal fillings. Between 1928 and 1930 he studied the reaction of vital pulp tissue to calcium hydroxide to prove that it was a biocompatible material. Since then, calcium hydroxide has been recommended by several authors for direct pulp capping, but it took until the middle of 20th century until it was regarded as the standard of care.


Comparison between the working environment of nurse managers and nursing assistants in the hospital context.
Objective Comparing the working environment of nurse managers and nursing assistants in the hospital context. Method A mixed methods research with concomitant triangulation of data developed in a university hospital in the South of Brazil. Participants in the quantitative study were 94 nursing assistants and 12 nurse managers. The data were collected using the Brazilian Nursing Work Index - Revised (B-NWI-R) and analyzed through descriptive and inferential statistics. Eight (8) nurse managers and 18 nursing assistants were interviewed for the qualitative study. The data were analyzed through thematic analysis. Results The total B-NWI-R mean score for nurse managers was 2.15±0.39, and for nursing assistants it was 2.22±0.39. No statistical significance was identified in the comparison between the groups (p=0.508). The qualitative results show the existence of collaborative relationships between nurse managers and nursing assistants. Conclusion The working environment was similarly evaluated by nurse managers and nursing assistants in the hospital context.


Screen for Footprints of Selection during Domestication/Captive Breeding of Atlantic Salmon.
Domesticated animals provide a unique opportunity to identify genomic targets of artificial selection to the captive environment. Here, we screened three independent domesticated/captive Atlantic salmon (Salmo salar) strains and their wild progenitor populations in an effort to detect potential signals of domestication selection by typing of 261 SNPs and 70 microsatellite loci. By combining information from four different neutrality tests, in total ten genomic regions showed signs of directional selection based on multiple sources of evidence. Most of the identified candidate regions were rather small ranging from zero to a few centimorgans (cM) in the female Atlantic salmon linkage map. We also evaluated how adaptation from standing variation affects adjacent SNP and microsatellite variation along the chromosomes and, by using forward simulations with strong selection, we were able to generate genetic differentiation patterns comparable to the observed data. This study highlights the significance of standing genetic variation during the early stages of adaptation and represents a useful step towards identifying functional variants involved in domestication of Atlantic salmon.


Interaction of the E. coli alkaline phosphatase precursor with model phospholipid membranes.
An interaction of a precursor of the E. coli secreted alkaline phosphatase (prePhoA) containing a signal peptide and model bilayer membranes prepared from the lipids of E. coli has been studied. The interaction was evaluated by monitoring of the state of the lipid phase by fluorescence spectroscopy. The role of the signal peptide in this process was evaluated by a comparative study of the interaction of the mature alkaline phosphatase which does not contain the signal peptide with the model membranes. The precursor was shown to be inserted into the lipid bilayer since the fluorescence anisotropy of a hydrophobic probe, diphenylhexatriene, was enhanced. The intensity of the process is determined by the presence of the signal peptide and depends on the pH of the medium. The data indicate that the mature polypeptide chain of the enzyme also has affinity for the membrane.


Association of usual sleep quality and glycemic control in type 2 diabetes in Japanese: A cross sectional study. Sleep and Food Registry in Kanagawa (SOREKA).
Excessively short and long sleep durations are associated with type 2 diabetes, but there is limited information about the association between sleep quality and diabetes. Accordingly, the present study was performed to investigate this relationship. The subjects were 3249 patients with type 2 diabetes aged 20 years or older. Sleep quality was assessed by using the Pittsburgh Sleep Quality Index (PSQI). A higher global PSQI score indicates worse sleep quality, and a global PSQI score >5 differentiates poor sleepers from good sleepers. The mean global PSQI score was 5.94 ± 3.33, and 47.6% of the patients had a score of 6 or higher. Regarding the components of the PSQI, the score was highest for sleep duration, followed by subjective sleep quality and then sleep latency in decreasing order. When the patients were assigned to HbA1c quartiles (≤ 6.5%, 6.6-7.0%, 7.1-7.8%, and ≥ 7.9%), the top quartile had a significantly higher global PSQI score than the other quartiles. The top HbA1c quartile had a sleep duration of only 6.23 ± 1.42 hours, which was significantly shorter than in the other quartiles. Also, sleep latency was 25.3 ± 31.8 minutes in the top quartile, which was significantly longer (by approximately 20 minutes) than in the other quartiles. When analysis was performed with adjustment for age, gender, BMI, smoking, and other confounders, the global PSQI score was still significantly higher and sleep duration was shorter in the top HbA1c quartile (HbA1c ≥ 7.9%). Japanese patients with type 2 diabetes were found to have poor subjective sleep quality independently of potential confounders, especially those with inadequate glycemic control. Impairment of sleep quality was associated with both increased sleep latency and a shorter duration of sleep.


Effect of changes in litter size at mid-lactation on lactation in rats.
The effect of altering the number of pups per litter from ten to two or two to ten at day 14 of lactation in rats was investigated. Reducing litter size had no effect on the daily live weight gain whereas increasing the litter size resulted in an initial weight loss followed by an impaired weight gain. Maternal food consumption decreased to values appropriate for rats feeding two pups within 2 days after litter reduction, but required at least 5 days after the increase in litter size to increase to values appropriate for rats feeding large litters from parturition. Altering the litter size resulted in maternal serum insulin concentrations that were intermediate between those expected for rats feeding two or ten pups from parturition. Maternal serum prolactin concentrations increased after litter sizes were increased and decreased initially after litter reduction before being restored to normal levels. The activities of the lipogenic enzymes, fatty acid synthase, glucose-6-phosphate dehydrogenase and 'malic' enzyme in the mammary gland all decreased within 72 h of litter reduction to levels appropriate for rats feeding two pups. Although all three enzymes increased in activity after litter size increase, only fatty acid synthase had reached values appropriate for rats feeding ten pups by 72 h.


[Normal connective tissue in penis and its changes in patients with erectile dysfunction and Peyronie's disease].
The aim of this study was to examine the connective tissue of penis in normal individuals and in patients with erectile dysfunction (ED) and Peyronie's disease (PD) using computer methods of image analysis. Penis tissues were obtained from 20 males aged 20-40 years who died in accidents, penis biopsies were taken from 23 patients with ED and 9 patients with PD (average age: 51 +/- 11.5 years). In both groups of patients, the volumetric fraction of collagen fibers in the tunica albuginea and corpora cavernosa was increased, while that one of elastic fibers was decreased. At the same time, the changes of elastic fibers were noted: the fibers become thinner and formed "rods". The reduction of the amplitude and the wavelength in the collagen fibers of the tunica albuginea in patients with ED and the presence of fibrous plaques in corpora cavernosa in in patients with PD were registered. The methods of computer image analysis may improve the morphologic diagnosis of ED and PD.


[Expression of bone morphogenetic proteins in kidneys].
Bone morphogenetic proteins (BMPs) are a large group of growth factors. More than 20 members of BMP family have been identified to date. Based on their structural and functional properties, BMPs can be divided into 4 subgroups: BMP 2/4, BMP 5/6/7/8a/8b, BMP 9/10 and BMP 12/13/14. Each BMP has a unique structural feature that differentiates it from all other family members. BMPs take part in different stages of kidney development. For example, BMP-2 inhibits branching morphogenesis in ureteric buds; BMP-4 is expressed in metanephritic mesenchyme along the Wolff canal before kidney development, its expression is also found in the mesenchyme surrounding the ureteric bud before the invasion of the mesenchymal cells in the ureteric stem and induction completion; BMP-7 is the only bone morphogenetic protein that is crucial in kidney development. BMP family members are also included in maintaining normal kidney structure and function. Experimental models have shown that BMP-7 prevents ischemia/reperfusion damage. Expression of BMP-7 is reduced in the samples of kidney tissue with diabetic nephropathy. Also, BMP-7 mRNA is reduced in clear cell kidney carcinomas, indicating its protective effects in maintaining normal kidney structure and function. Bone morphogenetic proteins are some of the key players in regulating normal kidney development, but their role also extends into maintaining normal kidney structure and function.


Unique Case of Hearing Recovery After Otic Capsule Destruction and Complete Sensorineural Hearing Loss Caused by Langerhans Cell Histiocytosis.
: A 14-year-old woman presented with right-sided otologic and vestibular symptoms after presenting with hormonal disturbances earlier that year. Imaging showed a gross destruction of the temporal bone, mastoid air cells, and external acoustic meatus with invasion into the otic capsule. The patient experienced complete sensorineural hearing loss in the right ear. Biopsy diagnosed Langerhans cell histiocytosis (LCH) and the patient was treated with chemotherapy. After 1 year of treatment, the patient's hearing partially recovered and imaging showed reconstitution of the temporal bone including the otic capsule. Our case is the first report of complete sensorineural hearing loss with partial recovery after LCH treatment.


Investigation of the influence of mode-mismatch errors on active coherent polarization beam combining system.
In this manuscript, we theoretically and experimentally investigate the influence of mode mismatch errors on active coherent polarization beam combining (CPBC) system. Firstly, by incorporating a piezo-mounted mirror (PMM) to generate artificial tilt phase aberrations, we design an experimental system to theoretically and experimentally investigate the influence of mode-mismatch errors induced by tilt phase aberrations on the combining efficiency of CPBC system. Further, by employing a spatial light modulator (SLM) to impose higher-order phase aberrations, the impact of mode-mismatch errors induced by higher-order phase aberrations on the CPBC system is also studied specifically. In the situation of adding each man-made aberration, experimental results correspond well with the theoretical ones. By theoretical and experimental analysis, we also show that the combining efficiency of the CPBC system is susceptible to the phase mismatch errors among different channels while has high tolerance on the intensity mismatch errors, which is compatible with the analysis in other CBC configurations. Besides, experimental results also show that the combining efficiency of the CPBC system is independent on the modulation frequency of dynamical tilt phase aberrations. Our analysis and designs provide useful approaches to diagnose the influence of mode-mismatch errors on CPBC system and optimize the whole CPBC system specifically.


Influence of diet on the development of nephrocalcinosis in the rat.
A histological examination of the effect of a purified diet containing 20% alpha protein (an alkali-treated soyprotein) on the development of nephrocalcinosis induced by intraperitoneal injections of 0.5 neutral (pH 7.4) sodium phosphate was carried out in female weanling rats. Animals that were fed a standard commercial laboratory diet and given daily injections of phosphate for six or ten days developed a form of nephrocalcinosis that consisted mainly of intraluminal (intratubular) calcification at the junction of the outer and inner stripes of the outer medulla and in the inner stripe of the outer medulla. By contrast, rats that were fed the alpha protein diet and given injections of phosphate for six or ten days developed a form of nephrocalcinosis that was characterized primarily by a type of tubular basement membrane calcification at the junction of the inner stripe of the outer medulla and the inner medulla. The differences in nephrocalcinosis between the two dietary groups and the fact that an alpha protein diet by itself can cause renal calcification, leads to the suggestion that some component(s) or factor(s) in the alpha protein diet strongly influence(s) the development of nephrocalcinosis induced by injected neutral sodium phosphate.


Bedside education in the art of medicine (BEAM): A learner's perspective on arts-based teaching.
In today's culture of the medical profession, it is fairly unusual for students to actually witness physicians talking with patients about anything outside scientific explanation. That other side of medicine - the one that goes beyond explanation to understanding - goes unexplored, and the patient's personal narrative is consequently less understood. Meanwhile, though reflective writing is the most frequently used didactic method to promote introspection and deeper consolidation of new ideas for medical learners, there is robust evidence that other art forms - such as storytelling, dance, theatre, literature and the visual arts - can also help deepen reflection and understanding of the human aspect of medical practice. The overall goal of the Bedside Education in the Art of Medicine (BEAM) project is to redress these issues through early interventions within the culture of the medical profession. By creating an arts-based humanities curriculum, we hope to broaden medical learners' understanding and shine a light on what it means - for patients and clinicians - to be human, live well, experience loss, encounter disease, and engage in a therapeutic relationship. BEAM is envisioned as a modular, online resource of "third things" that any clinician anywhere will be able to access via a smartphone application to deliver brief, focused, humanistic clinical teaching in either hospital or ambulatory care settings. This commentary foregrounds a learner's perspective to model BEAM's usage in an in-depth manner; it examines the relation of a painting by Edward Hopper to medical education through the lens of a poem by Victoria Chang, in the context of the BEAM web-based app educational resource. By assessing the poignancy of the painting via the poem, I demonstrate the capacity of the arts and humanities in medical education, with a specific focus on the development of interpretative skills and tolerance for ambiguity that all authentic, engaged physicians need.


Arterial bypass grafting of the coronary circulation.
Surgical coronary bypass has evolved continually, and recent developments favor performing coronary grafts with all-arterial conduits in order to obtain better long-term graft patencies. With bilateral internal mammary artery grafts and both radial arteries, four excellent arterial conduits exist for revascularization of the majority of multivessel disease patients, including those with valve disorders. Using contemporary surgical techniques, it is possible to obtain greater than 95% overall long-term graft patencies that translate into better outcomes, including improved survival, freedom from myocardial infarction, percutaneous coronary intervention , and redo coronary bypass. Two-thirds of patients receive a right internal mammary artery to the left anterior descending , a left internal mammary artery to the circumflex coronary artery system, and a radial artery to the right coronary artery Using newer management techniques, early postoperative complications, including the incidence of sternal infections, are extremely uncommon, and all-arterial grafts currently are used in over 75% of multivessel patients including those with concomitant valve disease. Because patencies and outcomes are so much better than with standard coronary bypass or percutaneous coronary intervention, referring physicians frequently favor all-arterial bypass as the primary therapy for patients with prognostically serious multivessel obstruction. Thus, all-arterial bypass could play an increasingly important role in the future treatment of severe coronary atherosclerosis.


Afferent neural pathways in cough and reflex bronchoconstriction.
Cough and bronchoconstriction are airway reflexes that protect the lung from inspired noxious agents. These two reflexes can be evoked both from the larynx and tracheobronchial tree and also from some extrarespiratory sites. Within the airways, certain sites are particularly sensitive to stimulation of cough (larynx and points of proximal airway branching), whereas bronchoconstriction can be triggered from the whole of the tracheobronchial tree. In the larynx, "irritant" receptors with myelinated afferents mediate cough and bronchoconstriction. Little seems to be known about laryngeal nonmyelinated afferents and their reflexes. In the tracheobronchial tree and lung, slowly adapting stretch receptors (SARs) and rapidly adapting stretch receptors (RARs) have opposing effects on airway tone, the former mediating bronchodilation and the latter bronchoconstriction. In cough, on the other hand, they operate concurrently, a mediatory role for RARs and a facilitatory role for SARs. C-fiber endings (bronchial and pulmonary) mediate bronchoconstriction. Inhalation of so-called "selective" C-fiber stimulants induces cough, but excitation of RARs has not been eliminated, and the possibility also exists that the cough is secondary to other lung actions mediated by these nerve endings. Although cough and bronchoconstriction may be mediated by the same type of receptor, they seem to have separate afferent neural pathways.


Protein kinase C activators and calcium-mobilizing agents synergistically increase GH, LH, and TSH secretion from anterior pituitary cells.
A series of studies was designed to determine the effects of protein kinase C activators on TSH, LH, and GH release from anterior pituitary cells. A 15-min incubation of cultured pituitary cells with synthetic diacylglycerol or phorbol myristate acetate, stimulators of protein kinase C, increased GH, LH, and TSH release. Similarly phospholipase C, which liberates endogenous diacylglycerol, stimulated GH, LH, and TSH secretion. The potentiation of the effects of protein kinase C activators is achieved by calcium mobilization in various cell types. The results of the present studies show that calcium ionophore A23187 or calcium channel activator maitotoxin potentiate diacylglycerol-, phorbol ester-, or phospholipase C-induced GH, LH, or TSH release. These findings suggest that activation of protein kinase C by diacylglycerol and mobilization of calcium may be synergistically involved in the regulation of GH, LH, and TSH release.


Spectral peak resolution and speech recognition in quiet: normal hearing, hearing impaired, and cochlear implant listeners.
Spectral peak resolution was investigated in normal hearing (NH), hearing impaired (HI), and cochlear implant (CI) listeners. The task involved discriminating between two rippled noise stimuli in which the frequency positions of the log-spaced peaks and valleys were interchanged. The ripple spacing was varied adaptively from 0.13 to 11.31 ripples/octave, and the minimum ripple spacing at which a reversal in peak and trough positions could be detected was determined as the spectral peak resolution threshold for each listener. Spectral peak resolution was best, on average, in NH listeners, poorest in CI listeners, and intermediate for HI listeners. There was a significant relationship between spectral peak resolution and both vowel and consonant recognition in quiet across the three listener groups. The results indicate that the degree of spectral peak resolution required for accurate vowel and consonant recognition in quiet backgrounds is around 4 ripples/octave, and that spectral peak resolution poorer than around 1-2 ripples/octave may result in highly degraded speech recognition. These results suggest that efforts to improve spectral peak resolution for HI and CI users may lead to improved speech recognition.


The application of a modified technique of SCP under DHCA during total aortic arch replacement combined with stented elephant trunk implantation.
We reviewed the perfusion experiences of 60 cases with a modified technique of selected cerebral perfusion (SCP) under deep hypothermic circulatory arrest (DHCA) during ascending aorta and total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta for acute and chronic type A aortic dissection. Right auxiliary artery cannulation was routinely used for cardiopulmonary bypass (CPB) and SCP in this procedure. Generally, this technique requires two main pumps for two arterial lines before we applied the modified technique; one for CPB and the other for SCP. In order to simplify the circuit of the extracorporeal circuit (ECC) to operate easily, the arterial line was separated into two branches with a Y-connector on the operating table, one for axillary artery perfusion and the other for graft perfusion connected to the ECC set-up. This method is easy for the perfusionist to install and convenient for the surgeon. This is a safe and simple to use modified technique for SCP under DHCA during ascending aorta and total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta.


Estimating Spatial and Temporal Trends in Environmental Indices Based on Satellite Data: A Two-Step Approach.
This paper presents a method for employing satellite data to evaluate spatial and temporal patterns in environmental indices of interest. In the first step, linear regression coefficients are extracted for each area in the image. These coefficients are then employed as a response variable in a boosted regression tree with geographic coordinates as explanatory variables. Here, a two-step approach is described in the context of a substantive case study comprising 30 years of satellite derived fractional green vegetation cover for a large region in Queensland, Australia. In addition to analysis of the entire image and timeframe, separate analyses are undertaken over decades and over sub-regions of the study region. The results demonstrate both the utility of the approach and insights into spatio-temporal trends in green vegetation for this site. These findings support the feasibility of using the proposed two-step approach and geographic coordinates in the analysis of satellite derived indices over space and time.


Persistent Expression of Dopamine-Synthesizing Enzymes 15 Years After Gene Transfer in a Primate Model of Parkinson's Disease.
Restoring dopamine production in the putamen through gene therapy is a straightforward strategy for ameliorating motor symptoms for Parkinson's disease (PD). In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity-based primate model of PD, we previously showed the safety and efficacy of adeno-associated viral (AAV) vector-mediated gene delivery to the putamen of three dopamine-synthesizing enzymes (tyrosine hydroxylase [TH], aromatic l-amino acid decarboxylase [AADC], and guanosine triphosphate cyclohydrolase I [GCH]) up to 10 months postprocedure. Although three of four monkeys in this study have previously undergone postmortem analysis, one monkey was kept alive for 15 years after gene therapy to evaluate long-term effects. Here, we report that this monkey showed behavioral recovery in the right-side limb that remained unchanged for 15 years, at which time euthanasia was carried out owing to onset of senility. Immunohistochemistry of the postmortem brain from this monkey revealed persistent expression of TH, AADC, and GCH genes in the lesioned putamen. Transduced neurons were broadly distributed, with the estimated transduction region occupying 91% of the left postcommissural putamen. No signs of cytotoxicity or Lewy body pathology were observed in the AAV vector-injected putamen. This study provides evidence of long-term safety and efficacy of the triple-transduction method as a gene therapy for PD.


Genomic and non-genomic regulation of L-type calcium channels in rat ventricle by thyroid hormone.
Hyperthyroidism is associated with low exercise tolerance despite high cardiac output and sometimes with the development of heart failure. L-type calcium channels may play a role in the mechanism, but this has not been fully understood. We examined the effects of thyroid hormone on gene expression and function of L-type calcium channels in rat ventricles by the ribonuclease protection assay and whole-cell patch-clamp technique, respectively. The effects of bisoprolol, beta-blocking agent, on the regulation of calcium channel by thyroid hormone was also studied. In hyperthyroid animals, the mRNA of the calcium channel alpha1c subunit was reduced on day 4, compared with that in euthyroid animals, and remained low on day 8. Bisoprolol did not affect the thyroid hormone mediated decrease in alpha1c subunit mRNA. While L-type calcium current was greater in hyperthyroid than euthyroid myocytes on day 4, it was smaller on day 8. In addition, the isoproterenol-induced increase in calcium current in euthyroid rats was attenuated in hyperthyroid rats. Acetylcholine decreased calcium current in hyperthyroid myocytes, but not in euthyroid myocytes. In conclusion, L-type calcium current was increased by thyroid hormone in rat ventricular myocytes by the activation of the adenylate cyclase cascade, despite a decreased calcium channel gene expression. These genomic and non-genomic modifications may play an important role in the association of high cardiac output with low exercise tolerance, and in the development of heart failure in hyperthyroidism.


[High-polymeric xenogenic RNA as an antitumor immunity stimulator].
To immunize CC57BR mice a suspension of live cells of Krebs-2 ascites tumour was administered intradermally into the tail partially amputated afterwards. The growth of the tumour transplanted intraperitoneally was inhibited by 23% only after twofold immunization. Single immunization with tumour cell incubated with the cattle liver RNA preparation in conjunction with intraperitoneal administration of RNA following tumour transplantation inhibited its growth by 43--53%, while twofold administration by 84--88%. The high polymeric fraction of the preparation enhanced the immunization effect to the same measures the initial overall preparation. The treatment of the preparation with RNAase and partial depolymerization of RNA in the course of isolation resulted in the activity loss. It is concluded that the capacity of the RNA preparation for stimulating antitumour immunity is due to high polymeric fraction of RNA.


In-vitro interaction of cephalosporin and the immune system.
In this study we have evaluated the effects of an antibiotic, such as cefonicid, on some immune reactivities in vitro. The following immune parameters have been analyzed: i) interferon-gamma and interleukin-2 production and ii) lymphocyte proliferation following mitogen stimulation in the presence of cefonicid concentrations ranging from 50 to 500 microg/ml. No. decrease in lymphokine production in the presence of cefonicid concentrations up to 250 microg/ml was observed between untreated or antibiotic-treated lymphocyte cultures. When lymphocyte proliferation upon Con A stimulation, as evaluated by 3H-dHtd incorporation, was measured in the presence of cefonicid, no differences were observed with untreated controls. These results demonstrate that the in vitro interaction of cefonicid with the immune system does not lead to a decrease of the immune response.


Nottingham mothers stop smoking project -- baseline survey of smoking in pregnancy.
In the largest survey of smoking in pregnancy to date in the United Kingdom, 3882 women attending the two antenatal clinics in Nottingham during July and August 1986, were asked about their smoking habits. Thirty-seven per cent of pregnant women were smoking and only one in four of these was successful at stopping at some point during pregnancy. However, 55 per cent of the mothers who smoked at the start of pregnancy claimed to smoke less during pregnancy. No change was reported in the habits of one-quarter of the mothers who smoked during pregnancy and this proportion may represent an 'irreducible minimum'. Mothers were more likely to continue to smoke if younger (14-20 years), single, living with a partner who smoked, who left school at 16 years and were from manual working families. Those who succeeded in giving up smoking during pregnancy were more likely to be from professional and managerial families. Antenatal booklets about the dangers of smoking were the source of information cited most frequently. Half of the smoking mothers claimed not to have received advice from their family practitioners about the hazards of smoking nor information about how to give up the habit. Even fewer received such advice from hospital doctors, or midwives. This represents a major challenge to professional training in health education.


The current state of knowledge on the use of the benchmark dose concept in risk assessment.
This review deals with the current state of knowledge on the use of the benchmark dose (BMD) concept in health risk assessment of chemicals. The BMD method is an alternative to the traditional no-observed-adverse-effect level (NOAEL) and has been presented as a methodological improvement in the field of risk assessment. The BMD method has mostly been employed in the USA but is presently given higher attention also in Europe. The review presents a number of arguments in favor of the BMD, relative to the NOAEL. In addition, it gives a detailed overview of the several procedures that have been suggested and applied for BMD analysis, for quantal as well as continuous data. For quantal data the BMD is generally defined as corresponding to an additional or extra risk of 5% or 10%. For continuous endpoints it is suggested that the BMD is defined as corresponding to a percentage change in response relative to background or relative to the dynamic range of response. Under such definitions, a 5% or 10% change can be considered as default. Besides how to define the BMD and its lower bound, the BMDL, the question of how to select the dose-response model to be used in the BMD and BMDL determination is highlighted. Issues of study design and comparison of dose-response curves and BMDs are also covered.


DEVELOPMENTAL STABILITY IN LEAVES OF CLARKIA TEMBLORIENSIS (ONAGRACEAE) AS RELATED TO POPULATION OUTCROSSING RATES AND HETEROZYGOSITY.
Four natural populations of Clarkia tembloriensis, whose levels of heterozygosity and rates of outcrossing were previously found to be correlated, are examined for developmental instability in their leaves. From the northern end of the species range, we compare a predominantly selfing population (t̂ = 0.26) with a more outcrossed population (t̂ = 0.84), which is genetically similar. From the southern end of the range, we compare a highly selfing population (t̂ = 0.03) with a more outcrossed population (t̂ = 0.58). We measured developmental stability in the populations using two measures of within-plant variation in leaf length as well as calculations of fluctuating asymmetry (FA) for several leaf traits. Growth-chamber experiments show that selfing populations are significantly more variable in leaf length than more outcrossed populations. Developmental instability can contribute to this difference in population-level variance. Plants from more homozygous populations tend to have greater within-plant variance over developmentally comparable nodes than plants from more heterozygous populations, but the difference is not significant. At the upper nodes of the plant, mature leaf length declines steadily with plant age, allowing for a regression of leaf length on node. On average, the plants from more homozygous populations showed higher variance about the regression (MSE) and lower R2 values, suggesting that the decline in leaf length with plant age is less stable in plants from selfing populations than in plants from outcrossing populations. Fluctuating asymmetry (FA) was calculated for four traits within single leaves at up to five nodes per plant. At the early nodes of the plant where leaf arrangement is opposite, FA was also calculated for the same traits between opposite leaves at a node. Fluctuating asymmetry is significantly greater in the southern selfing population than in the neighboring outcrossed population. Northern populations do not differ in FA. Fluctuating asymmetry can vary significantly between nodes. The FA values of different leaf traits were not correlated. We show that developmental stability can be measured in plants using FA and within-plant variance. Our data suggest that large differences in breeding system are associated with differences in stability, with more inbred populations being the least stable.


Safety and Acceptability of Esophageal Cytosponge Cell Collection Device in a Pooled Analysis of Data From Individual Patients.
Diagnosis and surveillance of Barrett's esophagus (BE) and eosinophilic esophagitis (EoE) have become emerging public health issues. Cytosponge is a novel, minimally invasive esophageal cell collection device. We aimed to assess the data on safety and acceptability of this device. We performed a patient-level review of 5 prospective trials assessing Cytosponge performance in patients with reflux disease, BE and EoE in primary and secondary care. Acceptability of Cytosponge and subsequent endoscopy were recorded with visual analogue scale (VAS), wherein 0 and 10 denoted lowest and highest acceptability. Median VAS scores were compared using a Mann-Whitney test. The number of attempts, failures in swallowing the device and occurrence of adverse events were analyzed. Risk factors for failure in swallowing were analyzed using a multivariate regression model. In total, 2672 Cytosponge procedures were performed, in 2418 individuals from 2008 through 2017. There were 2 adverse events related to the device: a minor pharyngeal bleed and a case of detachment (<1:2000). The median acceptability score for the Cytosponge was 6.0 (interquartile range [IQR], 5.0-8.0), which was higher than the score for endoscopy without sedation (median 5.0; IQR, 3.0-7.0; P < .001) and lower than the score for endoscopy with sedation (median 8.0; IQR, 5.0-9.0; P < .001). Nearly all patients (91.1%) successfully swallowed the Cytosponge, most on the first attempt (90.1%). Failure to swallow the device was more likely to occur in secondary care (odds ratio, 5.13; 95% CI, 1.48-17.79; P < .01). The Cytosponge test is a safe procedure with good acceptability ratings in a variety of health care settings.