Obesity, Diabetes and Cancer: A Mechanistic Perspective.
Nearly 35% of adults and 20% of children in the United States are obese, defined as having a body mass index (BMI) ≥ 30 kg/m2. Obesity is an established risk factor for many cancers, and obesity-associated metabolic perturbations often manifest in Type 2 diabetes mellitus and/or the metabolic syndrome. As part of the growth-promoting, proinflammatory microenvironment of the obese and/or diabetic state, crosstalk between macrophages, adipocytes, and epithelial cells occurs via metabolically-regulated hormones, cytokines, and other mediators to enhance cancer risk and/or progression. This review synthesizes the evidence on key biological mechanisms underlying the associations between obesity, diabetes and cancer, with particular emphasis on enhancements in growth factor signaling, inflammation, and vascular integrity processes. These interrelated pathways represent mechanistic targets for disrupting the obesity-diabetes-cancer link, and several diabetes drugs, such as metformin and rosiglitazone, are being intensely studied for repurposing as cancer chemopreventive agents.


Supramolecular fullerene polymers and networks directed by molecular recognition between calix[5]arene and C60.
A biscalix[5]arene-C60 supramolecular structure was utilized for the development of supramolecular fullerene polymers. Di- and tritopic hosts were developed to generate the linear and network supramolecular polymers through the complexation of a dumbbell-shaped fullerene. The molecular association between the hosts and the fullerene were carefully studied by using (1) H NMR, UV/Vis absorption, and fluorescence spectroscopy. The formation of the supramolecular fullerene polymers and networks was confirmed by diffusion-ordered (1) H NMR spectroscopy (DOSY) and solution viscometry. Upon concentrating the mixtures of di- or tritopic hosts and dumbbell-shaped fullerene in the range of 1.0-10 mmol L(-1) , the diffusion coefficients of the complexes decreased, and the solution viscosities increased, suggesting that large polymeric assemblies were formed in solution. Scanning electron microscopy (SEM) was used to image the supramolecular fullerene polymers and networks. Atomic force microscopy (AFM) provided insight into the morphology of the supramolecular polymers. A mixture of the homoditopic host and the fullerene resulted in fibers with a height of (1.4±0.1) nm and a width of (5.0±0.8) nm. Interdigitation of the alkyl side chains provided secondary interchain interactions that facilitated supramolecular organization. The homotritopic host generated the supramolecular networks with the dumbbell-shaped fullerene. Honeycomb sheet-like structures with many voids were found. The growth of the supramolecular polymers is evidently governed by the shape, dimension, and directionality of the monomers.


Can treatment response to SGLT2-inhibitors in syndrome of inappropriate antidiuresis be predicted by copeptin, natriuretic peptides and inflammatory markers?
The syndrome of inappropriate antidiuresis (SIAD) is the main cause of hyponatremia and the SGLT2-inhibitor empagliflozin is a promising new treatment option. A biomarker predicting treatment response could optimize treatment success. Secondary analysis of a trial including 84 hospitalized patients with SIAD-induced hyponatremia. Patients were randomized to four days of treatment with empagliflozin 25 mg/d (n = 43) or placebo (n = 41) with both groups receiving fluid restriction <1000 ml/d. Baseline levels of copeptin, the natriuretic peptides MR-proANP and NT-proBNP and C-reactive protein (CRP) were evaluated as predictors for treatment response defined as absolute sodium change, using linear regression models. Additionally, urinary sodium was assessed as predictor for non-response to fluid restriction alone by constructing the receiver-operating characteristic (ROC) curve. No clinically relevant predictive value for treatment response to empagliflozin could be found for copeptin, MR-proANP, NT-proBNP or CRP. A urinary sodium cut-off of >76 mmol/l led to a specificity of 91.7% [95% confidence interval (CI): 75%, 100%] and sensitivity of 51.9% [33.3%, 70.4%] to predict non-response to fluid restriction alone. Based on our data, no biomarker could be identified as predictor for treatment response to empagliflozin. Urinary sodium was confirmed as a good marker for non-response to fluid restriction in SIAD patients. Clinical trial registration: ClinicalTrials.gov (Number: NCT02874807).


Investigation of Alzheimer's disease-related pathology in community dwelling older subjects who committed suicide.
Older people have a higher risk of completed suicide than any other age group worldwide. The contribution of neurodegenerative disease to this risk remains controversial. To investigate prevalence of Alzheimer's disease-related (AD) pathology in older suicide victims. Ratings of AD pathology using Braak and CERAD protocols were compared in 143 community-dwelling suicide victims aged 65 years or more and 59 motor vehicle accident victims autopsied at the request of an Australian Coroner's Court. There were no significant differences in plaque score or neurofibrillary tangle staging between suicide and control groups. None of the subjects with a history of dementia had neuropathologically confirmed AD. Our study is the second and largest investigation of the prevalence of AD neuropathology in the elderly suicide population. Unlike the previous study, we did not find an increased prevalence of AD neuropathology despite a history of dementia in 6.3%, implicating other pathologies such as Lewy Body or Vascular dementia in the aetiology of dementia in elderly suicide victims.


Quantitative evaluation of computed tomography findings in patients with pulmonary embolism: the link between D-Dimer level and thrombus volume.
To investigate the correlation of D-dimer levels and computed tomography properties of pulmonary embolism. A total of 58 treated patients with diagnosis of properties of pulmonary embolism were retrospectively studied. All patients underwent a D-dimer blood test. In computed tomography images, septal angle, interventricular septal thickness, and the diameters of all cardiac chambers and pulmonary arteries were measured. The thrombus volume (load) and density at all pulmonary arteries (main, right, left pulmonary arteries, and segmental arteries) were calculated. A significant correlation was found between D-dimer and total thrombus volume (p=0.009, r=0.342). Total thrombus volume and total thrombus density were calculated with mean value of 23.40±60.63 ml and 66.16±38.48 hounsfield unit (HU), respectively. Right ventricle/left ventricle ratio showed positive correlation with the D-dimer level (p=0.02). Increased D-dimer levels with RV/LV ratio and their correlation with total thrombus volume suggest that it may be a prognostic factor.


Five cases of transient left ventricular apical ballooning--the experience of a Portuguese center.
Transient left ventricular apical dyskinesia (apical ballooning syndrome, ABS) is characterized by transient alterations in regional wall motion, involving the mid and apical segments of the left ventricle, as well as electrocardiographic alterations, mimicking ST-elevation acute myocardial infarction, in the absence of obstructive disease of the epicardial coronary arteries. In this article, we present a series of five cases of ABS and a theoretical review of the syndrome.


Nonclinical toxicological evaluation of occidiofungin, a unique glycolipopeptide antifungal.
Occidiofungin, a glycolipopeptide obtained from the liquid culture of Burkholderia contaminans MS14, has been identified as a novel fungicide. The present study was designed to initially assess the in vitro toxicity in a rat hepatoma (H4IIE) cell line and acute toxicological effects of occidiofungin using a mouse model. In vitro toxicity was observed in all variables at 5 μmol/L. B6C3F1 mice were given single and repeat doses of occidiofungin up to 20 mg/kg. Key effects were a reduction in body and organ weights. However, no significant decrease in body weight was noted at a dose of 1 mg/kg, which is comparable to the dose level of other cyclic glycopeptide antifungal agents currently approved for human use. Microscopic examination of treated mice did not identify any signs of organ-specific toxicity at the dose levels tested.


New closed skin bone-anchored implant: preliminary results in 6 children with ear atresia.
To report preliminary results of a new closed-skin, transcutaneous bone conduction device (BCD) in 6 children with high-grade ear atresia. Tertiary care center; prospective study; we evaluated the gain with masking of the contralateral ear and the benefit of hearing rehabilitation with the transcutaneous BCD in noise: speech-in-noise tests, conducted in real life condition (with contralateral ear unmasked and fitted with a hearing device if done before implantation), with and without BCD, with determination of the speech reception threshold (SRT). Children and parent's satisfaction was assessed. Patients' ages ranged from 6 to 9 years. All had high-grade ear atresia with a preoperative mean pure-tone average (PTA) loss of 71.46 +/- 6.59 dB on air conduction and 14 +/- 4.98 dB on bone conduction. At M6, all children used the implant 5 to 12 hours daily (mean, 10) without pain or cutaneous complications. At M6, the mean air conduction PTA with transcutaneous BCD was 28.45 +/- 1.68 dB, the mean gain 43 +/- 6.96 dB, and the mean SRT gain 33.33 +/- 10.75 dB. Using speech-in-noise tests in real-life conditions, the mean SRT was statistically improved with the transcutaneous BCD (-8 +/- 2.83 dB, p = 0.0313). Both children and parents reported being satisfied or very satisfied. These preliminary results show satisfactory functional gain, cutaneous tolerance, and patients' satisfaction with the new transcutaneous BCD.


New dating of the Matalascañas footprints provides new evidence of the Middle Pleistocene (MIS 9-8) hominin paleoecology in southern Europe.
Hominin footprints were recently discovered at Matalascañas (Huelva; South of Iberian Peninsula). They were dated thanks to a previous study in deposits of the Asperillo cliff to 106 ± 19 ka, Upper Pleistocene, making Neandertals the most likely track-makers. In this paper, we report new Optically Stimulated Luminescence dating that places the hominin footprints surface in the range of 295.8 ± 17 ka (MIS 9-MIS 8 transition, Middle Pleistocene). This new age implies that the possible track-makers are individuals more likely from the Neandertal evolutionary lineage. Regardless of the taxon attributed to the Matalascañas footprints, they supplement the existing partial fossil record for the European Middle Pleistocene Hominins being notably the first palaeoanthropological evidence (hominin skeleton or footprints) from the MIS 9 and MIS 8 transition discovered in the Iberian Peninsula, a moment of climatic evolution from warm to cool. Thus, the Matalascañas footprints represent a crucial record for understanding human occupations in Europe in the Pleistocene.


Extrapyramidal syndrome.
Organophosphate (OP) poisoning is a common occurrence in the rural areas of developing countries like India. Acute cholinergic crisis is one of the important causes of mortality related to OP poisoning. Delayed peripheral neuropathy, extrapyramidal syndromes and neuropsychiatric manifestations are the major consequences of secondary neuronal damage. This case illustrates a 14-year-old girl who ingested 50 mL of OP pesticide and developed extrapyramidal symptoms in the form of parkinsonism and hand dystonia in spite of immediate medical attention. MRI of the brain with T2, fluid attenuated inversion recovery and diffusion-weighted sequences revealed bilateral symmetrical basal ganglia hyperintensities. Further follow-up revealed a significant clinical improvement with marked resolutions of the brain lesions. The reversible extrapyramidal symptoms with disappearance of neuroimaging findings without neuropathy or neuropsychiatric manifestations are unusual in OP poisoning.


Percutaneous nephroscopy using fiberoptic bronchoscope: removal of renal calculus.
A method for percutaneous removal of renal calculus within the collecting system is presented. Thus utilized, a flexible fiberoptic bronchoscope with fluoroscopic guidance provides a safe and quick alternative treatment to reoperative surgery for retained renal calculi.


Teaching psychiatric mental health nursing in the People's Republic of China.
According to the World Health Organization's Health Policy Resource Book, mental disorders account for a high proportion of disability worldwide and are predicted to grow significantly in the coming years. This is especially true in developing countries such as the People's Republic of China (PRC) where, for historical social, political, and economic reasons, psychiatric mental health (PMH) nursing has not been an integral part of nursing curricula. As the number of persons in the PRC increases, so is the demand for mental health nurses, yet the PRC lacks experienced PMH nursing instructors. This article describes the challenges and opportunities that await Western PMH nursing specialists and faculty in the PRC.


[Lens implantation in patients treated with anticoagulants].
The number of patients undergoing anticoagulation therapy is increasing. Interruption of the treatment can potentially result in complications endangering the patient's life. A new surgical technique with corneal incision, phacoemulsification and sutureless wound closure under maintained anticoagulation therapy is presented. Preliminary results after 36 cases seem to show that this technique is superior to those usually employed in cataract surgery, with corneal incision and suture.


Evaluation of obesity in healthcare workers.
Obesity is an international social problem. This study was aimed at evaluating the relationship of overweight and obesity with social dynamics and correlated biological indicators. The study was carried out on a group of healthcare workers employed in a large hospital in the province of Messina (Sicily, Italy). A total of 1010 subjects (377 men and 633 women) aged between 16 and 64 years, living in the province of Messina since birth. The educational level, BMI (Body mass index), arterial blood pressure and ECG of each subject was examined. The results showed that 52% of the men and 66.5% of the women were of normal weight, while the men showed greater susceptibility to overweight (M 33.2% > F 16%). Obesity was found in both sexes (M 13.3%, F 13.6%). Moreover, it was observed that arterial blood pressure tends to increase with age and body weight, and that the incidence of overweight falls as educational level rises. The study supports the hypothesis that there is a growing incidence of overweight and obesity in subjects of working age employed in the healthcare sector.


A comparison of the antiproliferative and antiviral activities of alpha-, beta- and gamma-interferons: description of a unified assay for comparing both effects simultaneously.
An assay system is described which allows simultaneous measurement of antiviral (AV) and antiproliferative (AP) activities of various interferons (IFNs) with the same indicator cells and tests one biological function, i.e. the reduction of DNA synthesis. Human IFN-alpha, -beta, and -gamma preparations were investigated for their respective AV and AP activities. In repeated independent experiments the AP:AV ratio was found to be constant for each IFN preparation. However, striking difference in the AP:AV ratios was found between the preparations, being highest in IFN-gamma and lowest in IFN-alpha. The validity of this assay was substantiated by the observation that the AP activity of the IFNs is not influenced by virus once the cells are protected by sufficient amounts of IFN and that the score of the microscopically assessed cytopathic effect (CPE) strongly correlates with the reduction of [3H]TdR uptake in the cultures. The AP:AV ratio of a Corynebacterium parvum induced IFN resembled that of the IFN-alpha-reference, suggesting that contrary to previous reports, the C. parvum induced is of alpha type. It is suggested that the assay system presented here provides a simple means not only of comparing AP and AV ratios of various IFNs but also of characterizing IFNs of unknown type.


Loss of tyrosine phosphorylation at Y406 abrogates the tumor suppressor functions of the thyroid hormone receptor β.
We have recently identified that phosphorylation at tyrosine (Y)406 is critical for the tumor suppressor functions of the thyroid hormone receptor β1 (TRβ) in a breast cancer line. However, still unclear is whether the critical tumor suppressor role of phosphorylated Y406 of TRβ is limited to only breast cancer cells or could be extended to other cell types. In the present studies, we addressed this question by stably expressing TRβ, a mutated TRβ oncogene (PV), or a TRβ mutated at Y406 (TRβY406F) in rat PCCL3 thyroid follicular cells and evaluated their tumor characteristics in athymic mice with elevated thyroid stimulating hormone. PCCL3 cells stably expressing PV (PCCL3-PV), TRβY406F (PCCL3-TRβY406F), or vector only (PCCL3-Neo) developed tumors with sizes in the rank order of TRβY406F>PV = Neo, whereas PCCL3 cells expressing TRβ (PCCL3-TRβ) barely developed tumors. As evidenced by markedly elevated Ki67, cyclin D1, and p-Rb protein abundance, proliferative activity was high in PV and TRβY406F tumors, but low in TRβ tumors. These results indicate that TRβ acted as a tumor suppressor in PCCL3 cells, whereas TRβY406F and PV had lost tumor suppressor activity. Interestingly, TRβY406F tumors had very low necrotic areas with decreased TNFα-NFκB signaling to lower apoptotic activity. In contrast, PV tumors had prominent large necrotic areas, with no apparent changes in TNFα-NFκB signaling, indicating distinct oncogenic activities of mutant PV and TRβY406F. Thus, the present studies uncovered a novel mechanism by which TRβ could function as a tumor suppressor through modulation of the TNFα-NFκB signaling. © 2016 Wiley Periodicals, Inc.


Process development for cell aggregate arrays encapsulated in a synthetic hydrogel using negative dielectrophoresis.
Spatial patterning of cells is of great importance in tissue engineering and biotechnology, enabling, for example the creation of bottom-up histoarchitectures of heterogeneous cells, or cell aggregates for in vitro high-throughput toxicological and therapeutic studies within 3D microenvironments. In this paper, a single-step process for creating peelable and resilient hydrogels, encapsulating arrays of biological cell aggregates formed by negative DEP has been devised. The dielectrophoretic trapping within low-energy regions of the DEP-dot array reduces cell exposure to high field stresses while creating distinguishable, evenly spaced arrays of aggregates. In addition to using an optimal combination of PEG diacrylate pre-polymer solution concentration and a novel UV exposure mechanism, total processing time was reduced. With a continuous phase medium of PEG diacrylate at 15% v/v concentration, effective dielectrophoretic cell patterned arrays and photo-polymerisation of the mixture was achieved within a 4 min period. This unique single-step process was achieved using a 30 s UV exposure time frame within a dedicated, wide exposure area DEP light box system. To demonstrate the developed process, aggregates of yeast, human leukemic (K562) and HeLa cells were immobilised in an array format within the hydrogel. Relative cell viability for both cells within the hydrogels, after maintaining them in appropriate iso-osmotic media, over a week period was greater than 90%.


[Longitudinal analysis of age at onset and initial symptoms in patients with amyotrophic lateral sclerosis].
To investigate the longitudinal changes in age at onset and the initial symptom of patients with sporadic amyotrophic lateral sclerosis (ALS), we performed a single hospital-based retrospective study over the past 38 years. A total of 280 sporadic ALS patients (169 men and 111 women) hospitalized in our department between 1965 and 2003 were investigated in this study. The clinical features including age at onset and the initial symptom of these patients were obtained from medical records. All the patients underwent an intensive diagnostic evaluation including electrophysiological examination, laboratory examinations of blood and cerebrospinal fluid, and neuroimagings of the brain and spinal cord to exclude other conditions similar to ALS. The mean age at onset was 58.3 +/- 11.3 years and age at onset significantly increased at the rate of 0.459 years per year (r = 0.406, p< 0.001). The percentage of patients whose age at onset was > or = 70 years has increased from 3.0% (1980-1984) to 31.1% (2000-2003). To investigate the initial symptom of senile-onset ALS, patients whose age at onset was > or = 70 years were analyzed. The percentages of bulbar palsy-onset patients with onset in terms of age were 62.5% (30/48 patients; > or = 70 years) and 23.3% (54/232 patients; <70 years). The odd ratio for bulbar palsy was 5.40 (95% confidence interval, 2.79-10.44). Taken together, our study demonstrates that the ratio of senile-onset ALS has significantly increased, and that there were more bulbar palsy-onset patients among the patients.


Subunit molecular weight and genetic variability of proteins in natural populations.
The relationship between subunit molecular weight and heterozygosity was studied in six different groups of organisms, i.e., 9 species of primates, 32 species of rodents, 56 species of reptiles, 12 species of salamanders, 64 species of teleost fishes, and 29 species of Drosophila. The correlation coefficient between them was positive in all groups, and the magnitude of correlation was roughly in agreement with the theoretical expectation under the mutation-drift hypothesis when the incomplete correlation between molecular weight and mutation rate was taken into account. Furthermore, the correlation was higher when the average heterozygosity was high than when this was low, as theoretically expected.


Regional myocardial function: advances in MR imaging and analysis.
Cardiovascular magnetic resonance (MR) imaging can provide three-dimensional analysis of global and regional cardiac function with great accuracy and reproducibility. Quantitative assessment of regional function with cardiac MR imaging previously was limited by long acquisition times and time-consuming analysis. The use of steady-state free precession cine MR imaging substantially improves assessment of myocardial wall motion. Advances in gradient technology and reconstruction techniques have increased MR image acquisition speed and made real-time cine MR imaging possible. Myocardial deformation may be measured with cine MR tagging, and interpretation of the resultant tagged MR images by means of harmonic phase analysis enables prompt and precise strain measurements. Velocity-encoded and stimulated-echo techniques such as phase-contrast MR imaging and displacement encoding with stimulated echoes, or DENSE, provide high-resolution strain maps. Clinical validation of these strain imaging techniques will depend on future assessments of their effect on the management of cardiac disease.


[A meta-analysis of the effectiveness of gestalt therapy].
This metaanalytical assessment of evaluation research in the field of Gestalt therapy has been conducted on the basis of 38 studies which took place between 1970 and 1986. Its scope is substantially broader than the metaanalysis of Smith, Glass and Miller (1980) or the secondary analysis of Grawe's Berner Workgroup documented in Forschungsgutachten zu Fragen eines Psychotherapeutengesetzes (1991). The results indicate Gestalt therapy to be an effective psychotherapeutic treatment which is not inferior to other comparable methods of treatment. No definitive statement can be made concerning differential indication, individual therapy setting or long-term measures.


Somatic aging pathways regulate reproductive plasticity in Caenorhabditis elegans.
In animals, early-life stress can result in programmed changes in gene expression that can affect their adult phenotype. In C. elegans nematodes, starvation during the first larval stage promotes entry into a stress-resistant dauer stage until environmental conditions improve. Adults that have experienced dauer (postdauers) retain a memory of early-life starvation that results in gene expression changes and reduced fecundity. Here, we show that the endocrine pathways attributed to the regulation of somatic aging in C. elegans adults lacking a functional germline also regulate the reproductive phenotypes of postdauer adults that experienced early-life starvation. We demonstrate that postdauer adults reallocate fat to benefit progeny at the expense of the parental somatic fat reservoir and exhibit increased longevity compared to controls. Our results also show that the modification of somatic fat stores due to parental starvation memory is inherited in the F1 generation and may be the result of crosstalk between somatic and reproductive tissues mediated by the germline nuclear RNAi pathway.


The alleged association between artificial fluoridation of water supplies and cancer: a review.
Since 1945, artificial fluoridation of water supplies has been used with success to reduce the incidence of dental caries in many areas where the natural fluoride content of the water is low. However, since 1975, it has been maintained that such artificial fluoridation is followed by an increased risk of cancer. These allegations originate from a single source. The present review, which covers re-examinations of the same data as well as evidence from scientific and governmental bodies in many countries, shows these assertions to be erroneous.


Expression of a nitric oxide degrading enzyme induces a senescence programme in Arabidopsis.
Nitric oxide (NO) has been proposed to act as a factor delaying leaf senescence and fruit maturation in plants. Here we show that expression of a NO degrading dioxygenase (NOD) in Arabidopsis thaliana initiates a senescence-like phenotype, an effect that proved to be more pronounced in older than in younger leaves. This senescence phenotype was preceded by a massive switch in gene expression in which photosynthetic genes were down-regulated, whereas many senescence-associated genes (SAGs) and the 1-aminocyclopropane-1-carboxylic acid (ACC) synthase gene ACS6 involved in ethylene synthesis were up-regulated. External fumigation of NOD plants with NO as well as environmental conditions known to stimulate endogenous NO production attenuated the induced senescence programme. For instance, both high light conditions and nitrate feeding reduced the senescence phenotype and attenuated the down-regulation of photosynthetic genes as well as the up-regulation of SAGs. Treatment of plants with the cytokinin 6-benzylaminopurin (BAP) reduced the down-regulation of photosynthesis, although it had no consistent effect on SAG expression. Metabolic changes during NOD-induced senescence comprehended increases in salicylic acid (SA) levels, accumulation of the phytoalexin camalexin and elevation of leaf gamma-tocopherol contents, all of which occurred during natural senescence in Arabidopsis leaves as well. Moreover, NO fumigation delayed the senescence process induced by darkening individual Arabidopsis Columbia-0 (Col-0) leaves. Our data thus support the notion that NO acts as a negative regulator of leaf senescence.


Toxicity of low and moderate multiplicities of Chlamydia psittaci for mouse fibroblasts (L cells).
When mouse fibroblasts (L cells) were infected in suspension or in monolayer with 10 to 100 50% infectious doses (ID(50)) of Chlamydia psittaci (6BC) per host cell, they showed signs of damage 24 to 48 h later. Host-cell injuries were termed multiplication dependent when both the ingestion and subsequent reproduction of C. psittaci were required; when only ingestion but not replication was needed, the injuries were considered to be multiplication independent. The time that the injury was first apparent, as well as its final magnitude, was proportional to the multiplicity of infection. When L cells ingested infectious or ultraviolet-inactivated C. psittaci, damage was manifested by failure to exclude trypan blue, by leakage of lactic dehydrogenase, by inhibition of reproduction as measured by ability to form colonies, by inhibition of protein and deoxyribonucleic acid synthesis, and eventually by cell disintegration. Infectious, but not ultraviolet-killed, chlamydiae stimulated host-cell glycolysis. Heat-killed chlamydiae were without measurable toxicity. The time of appearance of host-cell injury was always earlier, and its terminal magnitude always greater, with infectious inocula than with ultraviolet-inactivated ones. The multiplication-independent toxicity of ultraviolet-killed C. psittaci disappeared with inocula of less than 10 ID(50) per L cell, but an inoculum of only a single ID(50) of infectious chlamydiae per host cell injured most of the cells it infected, as evidenced by increased trypan blue staining and decreased efficiency of colony formation. The toxicity of multiplicities of infection between 10 and 100 ID(50) of infectious C. psittaci per host cell was the sum of both multiplication-dependent and -independent components. The effects of chloramphenicol and isoleucine deficiency on the ability of C. psittaci to injure L cells suggested that some synthesis of protein by both parasite and host may be essential for expression of multiplication-independent chlamydial toxicity. The failure of infectious chlamydiae to stimulate host-cell glycolysis in the presence of cycloheximide suggested that this multiplication-dependent consequence of chlamydial infection was also dependent on protein synthesis by the host.


CD40 ligand (CD154) stimulation of macrophages to produce HIV-1-suppressive beta-chemokines.
beta-chemokines play an important role in the development of immunologic reactions. Macrophages are major beta-chemokine-producing cells during T-cell directed, delayed-type hypersensitivity reactions in tissues, and have been reported to be important producers of beta-chemokines in the lymph nodes of HIV-1-infected individuals. However, the physiological signals responsible for inducing macrophages to produce beta-chemokines have not been established. Two soluble T cell products, interferon-gamma and granulocyte-macrophage colony stimulating factor, were added to cultured macrophages, but failed to stimulate the production of macrophage inflammatory protein-1alpha and -1beta; regulated upon activation, normal T cell expressed and secreted (RANTES); or monocyte chemoattractant protein-1. Instead, direct cell-cell contact between macrophages and cells engineered to express CD40L (also known as CD154) resulted in the production of large amounts of macrophage inflammatory protein-1alpha and -1beta, and RANTES (all ligands for CCR5), and monocyte chemoattractant protein-1 (a ligand for CCR2). Supernatants from CD40L-stimulated macrophages protected CD4(+) T cells from infection by a nonsyncytium-inducing strain of HIV-1 (which uses CCR5 as a coreceptor). These results have implications for granulomatous diseases, and conditions such as atherosclerosis and multiple sclerosis, where CD40L-bearing cells have been found in the macrophage-rich lesions where beta-chemokines are being produced. Overall, these findings define a pathway linking the specific recognition of antigen by T cells to the production of beta-chemokines by macrophages. This pathway may play a role in anti-HIV-1 immunity and the development of immunologic reactions or lesions.


[The effect of different dose of verapamil and propranolol in kalium cardioplegia on the function of immature rat heart].
To explore the appropriate dose of the verapamil and propranolol in kalium cardiaplegia (KVP) by observation of the effect on the function of ischemic immature rat heart and compared with ST. Thomas II cardiaplegia. 48 isolated hearts from Sprague-Dawley rats of 60 to approximately 80 g body weight, 22 +/- 2 days, male or female are perfused by Langendorff method for 20 min, and assigned to 1 of the following 6 groups (n = 8): control (CON), continuously perfused for 150 min. Ischemia/reperfusion (I/R), perfused with Locke's solution without glucose and oxygen equilibration for 3 min then no perfusion 27 min, repeated 3 cycles (ischemia for 90 min), followed by reperfusion for 60 min. Ischemia protected with ST. Thomas II cardioplegia (ST), each 3 min perfusion with ST. Thomas II cardioplegia during ischemia. Ischemia protected with three dose KVP cardioplegia (L, M, and H), perfused with ST. Thomas II cardioplegia containing verapamil and propranolol (x 10(-7) mol L(-1)) respectively 2.0, 0.34 (L), 6.8, 1.1 (M), 20,3.4 (H) during each 3 min perfusion of ischemia. Heart rate (min (-1), tens on(g), contraction force(g), peak systolic velocity (g.s-1), peak diastole velocity (g.s-), coronary flow (ml x min(-1 ), re-beat time (s) were monitored during the ischemia/ reperfusion. Compared to CON group, heart tension was rose when ischemia for 40 min and kept higher and could not rebeat after reperfusion in I/R group, In ST group, heart tension was rose after ischemia for 60 min and could re-beat but the pulse was weaker. Compared with ST group, KVP decreased the ischemic cardiac tension in dose dependently and the re-beat was stronger in L, M, and H groups. While compared with CON group, in L group, heart tension was rose when ischemia for 60 min and the re-beat was weaker. In H group, the heart tension was maintained lower when ischemia for 40 min and the re-beat was delay and weaker. Only in M group, heart tension was maintained stable during ischemia for 90 min and re-beat was stronger after reperfusion. Kalium cardiaplegia containing verapamil 6.8 x 10(-7) mol x L(-1) and propranolol 1.1 x 10(-7) mol x L(-1) has the best effect to protect the immature heart from ischemic injury.


Meat and dairy products intake is associated with gastric cancer: Case-control study findings.
Countries experiencing a significant shift toward Western lifestyle are facing an increased risk of gastric cancer (GC). While many studies have explored the link between diet and GC, the role of meat and dairy consumption remains uncertain. To delve deeper into this association, we conducted a case-control study in Jordan involving 173 GC cases and 314 controls, matched by age and marital status. Using a validated food frequency questionnaire, we assessed the intake of different dairy and meat products. The adjusted odds ratios and corresponding 95% confidence intervals indicated a strong correlation between high intake of red meat, milk, and buttermilk and GC. Our multinomial logistic regression analysis revealed that daily consumption of red meat (≥1 serving/day; OR, 3.34 [95% CI 1.85-6.03, p value of trend <.001], ≥1 serving/day) and weekly intake of milk (2-3 servings/week; OR, 2.04 [95% CI 1.14-3.64, p value of trend = .041]) and buttermilk (2-3 servings/week; OR, 2.07 [95% CI 1.12-3.83, p value of trend = .018], per 2-3 servings/week) were significantly associated with an increased risk of GC. Furthermore, consuming cooked eggs daily (OR = 2.44, 95% CI 1.24-4.79, p trend <.001) or weekly (OR, 3.34, 95% CI 1.58-7.10, p value of trend <.001) was also associated with an increased risk of GC. These findings highlight the potential health risks associated with excessive meat and some dairy products consumption and suggest that a balanced intake of these products, along with eggs, may help prevent GC.


Evaluation of exposure treatment of burns.
For purposes of comparison with the occlusive dressing method of treating burns, the exposure method was used in 30 cases-16 of first and second degree and 14 of third degree. Attempt was made to simulate the conditions which might be expected to prevail in mass treatment of burned patients-inadequate personnel and materials. Elaborate measures to immobilize burned areas were not employed. Healing of first and second degree burns was natural and the results satisfactory without further treatment. In third degree burns, skin grafting was necessary after the eschar was removed. Cracking of the eschar several days before time to remove it in some cases of third degree burns necessitated use of occlusive dressings in the last few days before skin grafting was done.The exposure method is considered valuable in circumstances in which saving of time, material and personnel is indicated. Generally it is not suitable for treatment of encircling burns of the trunk or extremities, since maintaining the integrity of the eschar is extremely difficult in such situations.


Dimethylfumarate impairs melanoma growth and metastasis.
Dimethylfumarate (DMF) inhibits signals transmitted by Rel proteins and is used for the treatment of inflammatory skin diseases such as psoriasis, but potential effects of DMF on tumor progression have yet not been analyzed. We show that DMF reduced melanoma growth and metastasis in severe combined immunodeficient mouse models. To identify targets of DMF action, we analyzed mRNA expression in DMF-treated melanomas by gene chip arrays. Using BiblioSphere software for data analysis, significantly regulated genes were mapped to Gene Ontology terms cell death, cell growth, and cell cycle. Indeed, we found that DMF inhibited proliferation of human melanoma cells A375 and M24met in vitro. The cell cycle was arrested at the G(2)-M boundary. Moreover, DMF was proapoptotic, as shown by cell cycle analysis and by Annexin V and Apo2.7 staining. These results were confirmed in vivo. DMF reduced proliferation rates of tumor cells as assessed by Ki-67 immunostaining and increased apoptosis as assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining. In conclusion, DMF is antiproliferative and proapoptotic and reduces melanoma growth and metastasis in animal models.


Adolescents' impressions of antismoking media literacy education: qualitative results from a randomized controlled trial.
Although media literacy represents an innovative venue for school-based antismoking programming, studies have not systematically compared student impressions of these and traditional programs. This study utilized data from a randomized trial comparing these two types of programs. After each program, students responded to three open-ended questions related to their assigned curriculum. Two coders, blinded to student assignments, independently coded these data. Coders had strong inter-rater agreement (kappa = 0.77). Our primary measures were spontaneously noted overall assessment, enjoyment/interest and the likelihood of changing smoking behavior. Of the 531 participants, 255 (48.0%) were randomized to the intervention (media literacy) group. Intervention participants had more net positive responses [rate ratio (RR) = 1.27, 95% confidence interval (CI) = 1.05, 1.54], more responses rating the program as compelling (RR = 1.63, 95% CI = 1.16, 2.29) and fewer responses rating the program as non-compelling (RR = 0.62, 95% CI = 0.39, 0.97). However, the intervention group was not more likely to suggest that the curriculum was likely to change behavior positively (RR = 0.57, 95% CI = 0.30, 1.06). Findings suggest that although media literacy provides a compelling format for the delivery of anti-tobacco programming, integration of components of traditional programming may help media literacy programs achieve maximal efficacy.


[BDNF secretion in human mesenchymal stem cells isolated from bone marrow, endometrium and adipose tissue].
The ability of mesenchymal stem cells (MSCs) to differentiate into neuronal lineage determines the potential of these cells as a substrate for a cell replacement therapy. In this paper we compare the neurogenic potential of MSCs isolated from bone marrow (BMSC), subcutaneous adipose tissue (AD MSC) and menstrual blood (eMSC). It was found that the native eMCSs, BMSCs and AD MSCs express neuronal marker β-III-tubulin with a frequency of 90, 50 and 14%, respectively. We also showned that eMSCs have a high endogenous level of brain-derived neurotrophic factor (BDNF), whereas the BMSCs and the AD MSCs are characterized by low basal BDNF levels. As induction of neuronal differentiation in the studied MSCs using differentiation medium containing B27 and N2 supplements, 5-azacytidine, retinoic acid, IBMX and dbcAMF caused changes in the cells morphology, the increased expression of β-III-tubulin, and the appearance of neuronal markers GFAP, NF-H, NeuN and MAP2. BDNF secretion during differentiation was significantly enhanced in the BMSCs and decreased in the eMSCs cultures. However, no correlation between the basal and induced levels of the neuronal markers expression and BDNF secretion in the studied MSCs has been established.


Neuronal dynamics and axonal flow: axonal peristalsis.
By time-lapse, phase-contrast cinemicrography of sensory nerve fibers of young mice, isolated with their originating spinal ganglia in nutrient solution, the postulated peristaltic surface drive of the cellulifugal propulsion of the semisolid axonal column at a rate of the order of 1 mm/day (1 mum/min) could be verified and quantitatively analyzed. The pulse waves follow each other at about 30-min intervals, regardless of whether the continuity of the axon is preserved or disrupted by degenerative fragmentation. Even when the axonal flow is obstructed, surface peristalsis continues.


Taking the strain: social identity, social support, and the experience of stress.
The social identity/self-categorization model of stress suggests that social identity can play a role in protecting group members from adverse reactions to strain because it provides a basis for group members to receive and benefit from social support. To examine this model, two studies were conducted with groups exposed to extreme levels of strain: patients recovering from heart surgery (Study 1), bomb disposal officers and bar staff (Study 2). Consistent with predictions, in both studies there was a strong positive correlation between social identification and both social support and life/job satisfaction and a strong negative correlation between social identification and stress. In both studies path analysis also indicated that social support was a significant mediator of the relationship between (a) social identification and stress and (b) social identification and life/job satisfaction. In addition, Study 2 revealed that group membership plays a significant role in perceptions of how stressful different types of work are. Implications for the conceptualization of stress and social support are discussed.


Novel method for placement of a ureteral stent during laparoscopic ureteroureterostomy.
Lumbar ureteral benign stenosis can be managed by laparoscopy. Prevention of repeat strictures after ureteral anastomosis includes the placement of a ureteral catheter. When laparoscopy is used to perform the anastomosis, a second position is needed to insert the Double J stent. We provide a way to place the double pigtail ureteral catheter only using laparoscopy.


A review of the concepts, terminologies and dilemmas in the assessment of decisional capacity: a focus on alcoholism.
The formal assessment of a person's capacity for making reasoned decisions is an infrequent and usually unappealing clinical task. The purpose of this paper is to dissect the task, consider the component parts, clarify those aspects that can be problematic and highlight those that remain so. The paper reviews the concepts, terminologies and dilemmas around alcoholism, insight, lack of insight, denial, judgement, will, decisional capacity and competence. Assessments of patients suffering from alcoholism (or any other dyscontrol problem such as deliberate self-harm, problem gambling or eating disorders) are likely to evoke unease because of the interweaving of potentially disputable phenomenological, clinical, ethical, semantic and legal aspects. Familiarity with the concepts and terms around decisional capacity helps to orientate clinicians in their work. There remain some particular conceptual issues that are in need of further scholarly attention.


The clinico-oncologic outcomes of elderly patients with glioblastoma after surgical resection followed by concomitant chemo-radiotherapy.
There have been controversies in the treatment of elderly patients with glioblastoma. We introduce the outcome of the treatment of elderly patients with glioblastoma comparing with younger patients. The author's hospital database was used to identify patients with histologically confirmed glioblastoma after surgery between January 2006 and December 2013. Forty-eight patients (control group) were under age 65 and 16 patients (elderly group) were aged 65 years or over at the time of surgery. The median age of the elderly group was 71 years and control group was 50 years. Mean number of medical comorbidities was 1.8 in the elderly group vs. 0.5 in the control group. The median progression free survival (PFS) was 5.6 months and the median overall survival (OS) was 19.9 months in all patients. The elderly group had a median PFS of 4.2 months vs. 8 months for the control group (log-rank test, p=0.762). Median OS was 8.2 months in the elderly group vs. 20.9 months in the control group (log-rank test, p=0.457). Major complications occurred in 5 cases (7.8%) for all patients. The ratio of completion of concomitant chemo-radiotherapy (CCRT) was 81.3% and was the same between the two groups. In multivariable analysis, extent of resection (p=0.034) and completion of CCRT (p=0.023) were statistically significant, independent prognostic factors only for PFS in all patients by Cox proportional hazards model. Age was not an independent prognostic factor. As for OS, there was no significant factor. Surgical resection and CCRT were well tolerated in elderly patients with glioblastoma, and maximal safe resection followed by timely CCRT could improve clinic-oncologic outcomes.


Correlates of HIV stigma in HIV-positive women.
We examined the variables associated with HIV stigma in HIV-positive women currently living in Ontario, Canada. Based on previous literature, we predicted that variables of social marginalization (e.g., ethnicity, income, education), medical variables (e.g., higher CD4 count, lower viral load), and increased psychological distress would be associated with higher perceived HIV stigma among HIV-positive women. One hundred fifty-nine HIV-positive women between the ages of 18 and 52 in Ontario completed self-report measures of the aforementioned variables. Women were recruited through 28 AIDS service organizations, eight HIV clinics, and two community health centers. In multiple regression analyses, for women born in Canada, lower educational level and higher anxiety were associated with higher HIV stigma. For women born outside of Canada, having been judged by a physician in Canada for trying to become pregnant was associated with higher HIV stigma. For HIV-positive women born outside of Canada, negative judgment by a physician regarding intentions to become pregnant should be addressed to reduce perceived HIV stigma and vice versa. Health care providers should be trained in the provision of sensitive and effective health care for women living with HIV, especially when providing reproductive health care.


A model-based analysis of a simplified beam-specific dose output in proton therapy with a single-ring wobbling system.
In radiation therapy, it is necessary to preset a monitor unit in an irradiation control system to deliver a prescribed absolute dose to a reference point in the planning target volume. The purpose of this study was to develop a model-based monitor unit calculation method for proton-beam therapy with a single-ring wobbling system. The absorbed dose at a calibration point per monitor unit had been measured for each beam-specific measurement condition without a patient-specific collimator or range compensator before proton therapeutic irradiation at Shizuoka Cancer Center. In this paper, we propose a simplified dose output model to obtain the output ratio between a beam-specific dose and a reference field dose, from which a monitor unit for the proton treatment could be derived without beam-specific measurements. The model parameters were determined to fit some typical data measured in a proton treatment room, called a Gantry 1 course. Then, the model calculation was compared with 5456 dose output ratios that had been measured for 150-, 190- and 220 MeV therapeutic proton beams in two treatment rooms over the past decade. The mean value and standard deviation of the difference between the measurement and the model calculation were respectively 0.00% and 0.27% for the Gantry 1 course, and -0.25% and 0.35% for the Gantry 2 course. The model calculation was in good agreement with the measured beam-specific doses, within 1%, except for conditions less frequently used for treatment. The small variation for the various beam conditions shows the high long-term reproducibility of the measurement and high degree of compatibility of the two treatment rooms. Therefore, the model was expected to assure the setting value of the dose monitor for treatment, to save the effort required for beam-specific measurement, and to predict the dose output for new beam conditions in the future.


Assessing the impact of changes in landuse and management practices on the diffuse pollution and retention of nitrate in a riparian floodplain.
In many European lowland rivers and riparian floodplains diffuse nutrient pollution is causing a major risk for the surface waters and groundwater to not achieve a good status as demanded by the European Water Framework Directive. In order to delimit the impact of diffuse nutrient pollution substantial and often controversial changes in landuse and management are under discussion. In this study we investigate the impact of two complex scenarios considering changes in landuse and land management practices on the nitrate loads of a typical lowland stream and the riparian groundwater in the North German Plains. Therefore the impacts of both scenarios on the nitrate dynamics, the attenuation efficiency and the nitrate exchange between groundwater and surface water were investigated for a 998.1 km(2) riparian floodplain of the Lower and Central Havel River and compared with the current conditions. Both scenarios target a substantial improvement of the ecological conditions and the water quality in the research area but promote different typical riparian landscape functions and consider a different grade of economical and legal feasibility of the proposed measures. Scenario 1 focuses on the optimisation of conservation measures for all natural resources of the riparian floodplain, scenario 2 considers measures in order to restore a good status of the water bodies mainly. The IWAN model was setup for the simulation of water balance and nitrate dynamics of the floodplain for a perennial simulation period of the current landuse and management conditions and of the scenario assumptions. The proposed landuse and management changes result in reduced rates of nitrate leaching from the root zone into the riparian groundwater (85% for scenario 1, 43% for scenario 2). The net contributions of nitrate from the floodplain can be reduced substantially for both scenarios. In case of scenario 2 a decrease by 70% can be obtained. For scenario 1 the nitrate exfiltration rates to the river drop even below the infiltration rates from the river, the riparian floodplain in that scenario represents a net sink for river derived nitrate. As the nitrate contributions from the investigated riparian floodplain represent only a small proportion of the total nitrate loads within the river (1% p.a.) the overall impact of the scenario measures on the nitrate loads at the river outlet remains small. However, during the ecologically most sensitive summer periods under current conditions nitrate contributions from the riparian groundwater of the Lower and Central Havel River (which covers only 5% of the area of the Havel catchment) represent more than 20% of the river loads. By the implementation of the investigated landuse changes within the research area the groundwater derived nitrate contributions could be halved to only 10% during summer baseflow conditions.


The unspecificity of the relationships between the invasive Pennisetum setaceum and mycorrhizal fungi may provide advantages during its establishment at semiarid Mediterranean sites.
The involvement of mutualistic plant-fungal interactions in invasion processes, especially in some climatic regions including semiarid areas, has not been sufficiently investigated. We compared the arbuscular mycorrhizal fungi (AMF) communities hosted by the invasive plant Pennisetum setaceum with those from the co-occurring native Hyparrhenia hirta at five Mediterranean semiarid locations with different edaphic characteristics. Illumina technology was used to investigate the AMF communities in the roots. The subsequent multivariate analysis showed that native and non-native host plants shared a similar AMF community, whereas the invaded locations differed in AMF communities harbored in the plant roots. The indicator species analysis revealed the absence of indicator virtual taxa for the fungal communities of the roots of native or invasive plants. In contrast, different numbers of indicator species were recorded in different sampling locations. According to the canonical correspondence analysis, the variability in the AMF communities between sampling sites was related to changes in soil total carbon, electrical conductivity, respiration, and protease and urease activities. These findings reveal the unspecificity of P. setaceum in relation to its association with the AMF community encountered in the invaded locations, which could have facilitated its successful establishment and spread.


Management of proximal cholangiocarcinomas by surgical resection and radiotherapy.
Ninety-six patients with proximal cholangiocarcinomas were managed surgically. Fifty-three patients (55 percent) were resected, 39 curatively (41 percent), and 43 (45 percent) underwent palliative stenting. The preoperative placement of Ring catheters and the operative use of silastic transhepatic biliary stents greatly facilitated the surgical management of these lesions. Sixty-three patients (66 percent) also received postoperative radiotherapy. Hospital mortality was 4 percent (four deaths). Hospital mortality was 2 percent after resection (1 of 53 patients) and 7 percent after palliative stenting (3 of 43 patients). All deaths resulted from sepsis. One, 3, 5, and 10-year survivals for the entire group were 49 percent, 12 percent, 5 percent, and 2 percent, respectively. One, 3, 5, and 10-year survivals in the resected group (66 percent, 21 percent, 8 percent, and 4 percent, respectively) were superior to those in the stented group (27 percent, 6 percent, 0 percent, and 0 percent, respectively). Radiotherapy appeared to significantly extend survival in those patients undergoing palliative stenting, but not in those undergoing resection. We conclude that surgical resection of proximal cholangiocarcinomas can be performed safely and that it significantly prolongs survival. Further improvement in long-term survival will depend on advances in adjuvant therapy.


Translabial ultrasound indices of failed pessary fittings in women with symptomatic pelvic organ prolapse.
To investigate translabial ultrasound (TLUS) parameters that may predict failed pessary fittings in women with symptomatic pelvic organ prolapse (POP). All participants in this retrospective study presented to the Pelvic Floor Disease Diagnosis and Treatment Center (Liaoning Province, China) between May 2018 and December 2020 seeking treatment for symptomatic POP. Each had chosen vaginal pessary as first-line treatment, undergoing TLUS in advance of placement. Participants were grouped by outcomes of pessary fittings as successful or failed. Group-wise demographic and clinical characteristics, including TLUS parameters, were then subjected to uni- and multi-variate logistic regression. A total of 373 women qualified for analysis, 255 (68.4%) achieved success, and were fitted with acceptable pessaries. Predictors of failed fittings included younger age (61.54 ± 10.25 y vs 64.72 ± 10.30 y; P = 0.006), premenopausal status (14.4% vs 5.9%; P = 0.006), sizeable hiatal circumference (20.36 ± 2.33 cm vs 19.70 ± 2.50 cm; P = 0.02) and hiatal area (HA) (29.67 ± 7.14 cm2 vs 27.27 ± 6.99 cm2; P = 0.003), levator ani muscle (LAM) avulsion (odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.62-6.46; P = 0.001), enterocele (OR = 2.51, 95% CI = 1.11-5.68; P = 0.03), and the inferiormost aspect of cervix situated below symphysis pubis (OR = 0.52, 95% CI = 0.29-0.95; P = 0.03). In multivariate logistic regression, younger age (OR = 0.98, 95% CI = 0.95-1.00; P = 0.04), sizeable HA on Valsalva (OR = 1.04, 95% CI = 1.01-1.08; P = 0.02), LAM avulsion (OR = 2.87, 95% CI = 1.32-6.25; P = 0.008), and enterocele (OR = 2.70, 95% CI = 1.12-6.50; P = 0.03) emerged as independent predictors of failed pessary fittings. Younger age, LAM avulsion, enterocele, and sizeable HA on Valsalva proved independently predictive of failed pessary fittings in women with symptomatic POP.


Clinical contextualization and the assessment of adverse events in HBOC trials.
Establishing an acceptable safety and efficacy profile for hemoglobin based oxygen carriers, HBOCs, is essential. Understanding the data that describes an HBOC "safety profile" requires consideration beyond counting "events" typically associated with intent to treat analysis. The imputation of causation from numerical counts alone, without clinical context, is an incomplete description of a complex situation. Clinical contextualization provides a greater understanding of the clinico-pathological processes involved. Generating alternative hypotheses for the origin of the events, apart from the drug, patient co-morbidities, situational and disease demands, could include protocol design, failure to provide mitigation strategies, patient management issues, or inadequate education of investigators. How clinical contextualization can provide insight for the interpretation of significant safety profile events is discussed in the context of a large phase III clinical trial where an appreciation of factors underlying the differences between intent to treat analysis and other approaches is discussed.


[Comparative inhibitory analysis of DNA biosynthesis catalyzed by retrovirus reverse transcriptase].
Comparative study of DNA biosynthesis inhibition, catalyzed by avian myeloblastose virus (AMV) reverse transcriptase (RT), human immunodeficiency virus (HIV) recombinant and native RT, has been performed. 3'-Azido-2',3'-dideoxythymidine 5'-triphosphate (AzTTP); 3'-azido-2',3'-dideoxythymidine 5'-methylenephosphonate-diphosphate: 3'-azido-2',3'-dideoxythymidine 5'-phosphate-phosponoacetate; 3'-azido-2',3'-dideoxythymidine 5'-phosphate-dibromomethylenephosphonate; 2',3'-O-isopropylidenecytidine 5'-methylenephosphonate-diphosphate (rC-IP-MPDP) were used as inhibitors. AzTTP proved to by the most active inhibitor (its activity against HIV RT is higher than against AMV RT), although not selective as the phosphonates; only rC-iP-MPDP has low selectivity.


A multi-centre investigation towards reaching a consensus on the immunohistochemical detection of ERbeta in archival formalin-fixed paraffin embedded human breast tissue.
Estrogen receptor (ER) alpha is a well-established independent prognostic factor in breast cancer whose presence determines the clinical implications of adjuvant endocrine therapy. A second receptor, ERb has been described, and a number of studies have examined its expression in breast tissue. However elucidation of the role played by ERb has been hampered by published immunohistochemical studies employing a variety of protocols and scoring systems such that inter-laboratory comparisons are difficult. Here we present a multi-centre study designed to critically evaluate inter-laboratory differences in methodology. Six UK and Irish centres participated in this study. A small series of breast cancers were stained using centre-specific laboratory protocols and scored using both centrespecific and standard scoring protocols. There was generally poor agreement as to what constituted a positive or negative case when centre-specific scoring systems were used with less than half of all cases in agreement. Concordance was improved when a standard scoring system was used but varied according to threshold for positivity employed and primary antibody. Our results emphasise the need for further studies addressing the role of ERb to be based on a wider consensus on criteria for positivity. Ideally this should be based on calibration against clinical outcome.


Dealing with difficult doctors.
Dealing with difficult doctors is not easy, and often many nurses shrink away from conflict situations because they are too intimidated to fight back. Unfortunately, despite years of study and comment, there is still a feeling that some doctors regard nurses as their hand-maidens. To explain this attitude as just a battle of feminine and masculine identity would be very short-sighted as studies have suggested that there is more to the nurse/doctor relationship than following a medical model of treatment.


Desquamative interstitial pneumonia: a case report.
Desquamative interstitial pneumonia is one of the rarest idiopathic interstitial pneumonias and the rarest form of smoking-related interstitial lung diseases. It was first described by Liebow in 1965. Histologically, it is characterized by the presence of eosinophilic macrophages uniformly filling airspaces which often contain a finely granular light-brown pigment that does not stain for hemosiderin. The alveolar walls are usually mildly thickened by fibrous tissue and infiltrated by a moderate number of lymphocytes. Our patient was a 56-year-old male, heavy smoker, with bilateral lung infiltrations of unknown etiology and several months of discomfort in the form of dry cough and shortness of breath. Lung function tests showed a moderate restrictive ventilation disorder and a severe reduction of diffusing capacity. Since bronchoscopic specimens did not reveal lung lesion etiology, an open lung biopsy of the lower left pulmonary lobe was performed, and based on the obtained surgical material the pathohistologically diagnosis of desquamative interstitial pneumonia was established. The patient was started on corticosteroid and immunosuppressive therapy, and he ceased smoking. At the last control examination, two years after the onset of symptoms, the patient was feeling well, and high-resolution computed tomography (HRCT) scan of the thorax showed regression of pathological changes. Although, as in our case, the majority of DIP patients improve on treatment, some patients still develop progressive irreversible fibrosis despite therapy.


Current state-of-the-art antiplatelet and anticoagulation therapy in diabetic patients with coronary artery disease.
Diabetes mellitus is a complex disease that leads to long-term damage to various organ systems. Among the numerous cardiovascular disease-related complications, thrombotic events frequently occur in patients with diabetes. Although guidelines exist for treating and preventing most diabetes-related co-morbidities, the evidence on antithrombotic therapy in primary and secondary prevention is limited due to the scarcity of randomized trials dedicated to patients with diabetes mellitus. Most of the available data are derived from studies that only included a small proportion of patients with diabetes. The present review provides an overview of the status of knowledge on antiplatelet and anticoagulation therapy in patients with diabetes, focusing on the risk-benefit balance of these therapies and future treatment strategies.


A quasi-3D Sb2S3/reduced graphene oxide/MXene (Ti3C2Tx) hybrid for high-rate and durable sodium-ion batteries.
Antimony sulfide (Sb2S3) is a promising anode material for sodium-ion batteries (SIBs) owing to its high theoretical capacity and superior reversibility. However, its cycling life and rate performance are seriously impeded by the inferior inherent electroconductibility and tremendous volume change in the charging/discharging processes. Herein, a quasi three-dimensional (3D) Sb2S3/RGO/MXene composite, with Sb2S3 nanoparticles (∼15 nm) uniformly distributed in the quasi-3D RGO/MXene architecture, was prepared by a toilless hydrothermal treatment. The RGO/MXene conductive substrate not only alleviates the volume expansion of Sb2S3, but also promotes electrolyte infiltration and affords highways for ion/electron transport. More importantly, the synergistic effects between RGO and Ti3C2Tx MXene are extremely favourable to maintain the integrity of the electrode during cycling. As a result, the Sb2S3/RGO/MXene composite exhibits a high reversible capacity of 633 mA h g-1 at 0.2 A g-1, outstanding rate capability (510.1 mA h g-1 at 4 A g-1) and good cycling performance with a capacity loss of 16% after 500 cycles.


[Topical treatment of localized edemas of mechanical or inflammatory origin with a novel antiedema ointment. A prospective study].
Following traumas, muscular or articular injuries it is common to observe lesions where edema is the main finding, with local pain leading to a muscular and/or articular limitation hindering the usual activity. In this study, a new anti-edema ointment with elevated saline concentration designed for the osmotic treatment of swelling has been evaluated. 21 subjects (mean age 34.2 yrs; range 6-73 yrs) have been enrolled and evaluated for the resolution of edema and restoration of the normal functional activity following the local application (3 times/daily) of the ointment until resolution for a maximum of 9 days (mean duration of treatment 5 days; range 2-9 days). After 2-3 days of application edema disappeared or was ameliorated in 13/21 cases, and in other 7/21 at 5-9 days of follow-up (p0.001 chi square for number of beneficial occurrences). Normal activity has been documented in 10/11 subjects in whom it was altered at enrollment. Local tolerability of the ointment has been optimal or good in the majority of patients, being represented only by local itching or erythema. The local application of the anti-edema ointment has allowed also a marked reduction in the use of acetaminophen or other anti-inflammatory treatments, that were infrequent and present only in 4/21 subjects. This study demonstrates that the local application of an anti-edema osmotic ointment allows to obtain a prompt resolution of the swelling coupled with a marginal use of anti-inflammatory therapies for the control of the local algic and inflammatory component of the disease.


[Nellix: New possibilities in the treatment of the aorto-iliac aneurysm - our initial experiences].
The Endologix developed an aortoiliac stent graft system that is different than the conventional implantation technique (Nellix, EVAS-endovascular aneurysm sealing system). The first implantation in Hungary has been performed in the beginning of 2016 at Heart and Vascular Center. Nellix: two endobags surrounding ballon-expandable covered stent (10 mm) with optional length, biocompatible polymer which is able to be injected into the endobags and a procedure-coordinating console. The instructions for use: aortic neck length: ≥10 mm, neck diameter: 18-32 mm, angulation: ≤60°, blood lumen diameter: ≤60 mm, aneurysm maximal diameter: >50 mm, common iliac artery (CIA) minimal and maximal diameter: ≥9 mm, ≤35 mm. Six elective implantations were performed at our clinic. The average age of the patients were: 68.33 ± 12.44 year, the rate of male was 100%. The reason of implantations was isolated infrarenal aortic aneurysm, CIA aneurysm or both. The average postoperative in-hospital stay were 5.17 ± 1.47 days. In the perioperative period fever and femoral wound healing problem developed in one patient respectively. The average follow-up period were 177.17 ± 96.91 days. There was no endoleak, graft-migration, aneurysm growth, reoperation or death. A stroke with left hemiparesis without residual symptoms developed in one case in the third week after the operation. Due to the new EVAS technology, according to 30-day and midterm results the system is able to be used in complicated anatomical situations with low perioperative mortality and morbidity, and it can decrease the incidence of endoleaks, graftmigration and aneurysm growth.


Clinicopathological profile of hepatic involvement in type-2 diabetes mellitus and its significance.
Involvement of liver as an organ complication in Type 2 Diabetes Mellitus (T2DM) is known. Studies are few about their baseline parameters from our country. Study the disease burden and clinicopathological profile of hepatic involvement in T2DM, find the associations with known risk factors and thus try to identify simple markers of advanced disease. A screened group of randomly selected 47 patients of T2DM without other liver diseases (viral, alcoholic, drug, autoimmune, etc.) was selected. Their clinical (age, sex, body mass index, family history, blood pressure), biochemical (transaminases, lipid profile), and hepatic ultrasonographic (USG) and histopathological (HPE) profiles were studied. Segregation was done according to the histological severity and duration of diabetes (< 5 yrs, 5-10 yrs, > 10 yrs). On histology, normalcy was maintained in 17%, only fatty change was present in 43%, nonalcoholic steatohepatitis (NASH) could be identified in 40% with more advanced disease in 23%. Prevalence of cirrhosis was low. Positive family history, hypertension, longer duration, female sex and increased body mass index were significantly associated with NASH; more advanced disease was associated with male sex only. Incident lipid profile and transaminases levels were non-contributory. In the early stage, USG detected abnormality correlated poorly with HPE. The burden of hepatopathy in T2DM is high; with improving cardiovascular mortality, a higher burden awaits us in the next decade or so. Naturally, it becomes imperative to the treating clinician for targeting this aspect of diabetic complication from the very beginning of therapy.


A molecular technique for detecting the liberation of intracellular zinc in cultured neurons.
We have previously reported that oxidative stimuli liberate Zn(2+) from metalloproteins, a phenomenon that can trigger neuronal cell death. Excessive intracellular Zn(2+) in many cell types triggers the expression of genes that encode metal binding proteins, such as metallothionein, via the activation and nuclear translocation of metal response element (MRE)-binding transcription factor-1 (MTF-1). Cd(2+) strongly induces nuclear translocation of MTF-1 in non-neuronal cells, but it does so by displacing Zn(2+) from its metal binding sites within the cell and increasing the intracellular concentration of this ion. Here, we describe the use of MRE-driven expression of a luciferase reporter gene as a sensitive molecular assay for detecting increases in intracellular zinc concentrations. MRE transactivation was induced in primary cortical neurons upon brief exposure to Zn(2+) or Cd(2+). Enhanced MRE transactivation was observed upon co-exposure of neurons to Cd(2+) together with NMDA, as this metal can permeate through the receptor channel. Luciferase expression was observed regardless of whether or not neurons had been co-transfected with an MTF-1-containing plasmid, suggesting the presence of an endogenous MTF-1-like protein. Indeed, RT-PCR revealed that MTF-1 mRNA is present in neurons. In contrast, MTF-1 deficient dko7 cells were only observed to have MRE transactivation when co-transfected with MTF-1. Our results indicate that Cd(2+) can effectively induce transactivation of MRE in neurons by liberating Zn(2+) from its intracellular binding sites.


Semiclassical mean-trajectory approximation for nonlinear spectroscopic response functions.
Observables in nonlinear and multidimensional infrared spectroscopy may be calculated from nonlinear response functions. Numerical challenges associated with the fully quantum-mechanical calculation of these dynamical response functions motivate the development of semiclassical methods based on the numerical propagation of classical trajectories. The Herman-Kluk frozen Gaussian approximation to the quantum propagator has been demonstrated to produce accurate linear and third-order spectroscopic response functions for thermal ensembles of anharmonic oscillators. However, the direct application of this propagator to spectroscopic response functions is numerically impractical. We analyze here the third-order response function with Herman-Kluk dynamics with the two related goals of understanding the origins of the success of the approximation and developing a simplified representation that is more readily implemented numerically. The result is a semiclassical approximation to the nth-order spectroscopic response function in which an integration over n pairs of classical trajectories connected by distributions of discontinuous transitions is collapsed to a single phase-space integration, in which n continuous trajectories are linked by deterministic transitions. This significant simplification is shown to retain a full description of quantum effects.


[Choice of second-line chemotherapy for advanced breast cancer based on the chemosensitivity assay by in vitro colony assay].
The efficacy of anticancer drugs and the development of drug resistance after chemotherapy for advanced breast cancer has been evaluated in vitro using the human tumor clonogenic assay (in vitro colony assay technique.) The rates of in vitro chemosensitivity to various anticancer drugs in untreated patients were similar or somewhat higher than the clinical efficacy reported for single clinical use of the drugs. The results of in vitro chemosensitivities to the drugs against previously treated patients showed decreased chemosensitivities to the drugs which had been used, especially adriamycin and mitomycin C. In contrast to this, in vitro chemosensitivities to 5-FU, methotrexate and L-PAM were unchanged after exposure to combination chemotherapy consisting of these drugs. This result suggests that the development of resistance to these drugs is minimal at the doses used in our protocol. The overall chemosensitivity rate for anthracyclines including adriamycin in vitro was only 5% (5/93) for previously treated patients, compared with 41% (35/83) for vinca alkaloids (p less than 0.005). This finding indicates that combination chemotherapy including vinca alkaloids is the appropriate selection for second line chemotherapy for advanced breast cancer patients who have been treated previously with adriamycin.


[MRI-diffusion weighted images of encephalopathy associated with human herpesvirus 6 infection].
Encephalopathy associated with human herpes virus 6 infection (HHV-6 encephalopathy) is not rare. The pathophysiology of HHV-6 encephalopathy has not been clearly established and diagnosis in the early stages is difficult. To elucidate the diagnostic value of MRI in the early stages of HHV-6 encephalopathy, we performed MRI including diffusion weighted imaging (DWI) on 6 patients. No abnormalities were found in the T1, T2 weighted images and fluid attenuated inversion recovery (FLAIR) images of any of the patients. DWI revealed an increase of signal in the subcortical white matter of the frontal lobes during the acute phase in all 6 patients. Follow-up MRI in two patients showed lesions expanded to the cortical regions, and disappearance of high signal-lesions followed by atrophy of the corresponding areas in 2 patients. To our knowledge, these findings have not previously been reported in acute encephalopathy and encephalitis and may be characteristic of HHV-6 encephalopathy. DWI may be a useful diagnostic procedure in the early stages of HHV-6 encephalopathy.


Rheumatoid arthritis and anemia: the impact of different anti-inflammatory therapies on hemoglobin levels. An observational study.
Rheumatoid Arthritis (RA) has been associated with anemia. The treatment of anemia in RA includes blood transfusions, erythropoietic agents and iron supplements. Our observations suggest that the treatment of the inflammatory disease is associated with an improvement of hemoglobin (Hgb) levels in RA patients. Record review, analyzing anemic RA patients and hemoglobin level changes after intensification of RA therapy. Three initial regimes were identified: corticosteroid (Prednisone), Disease Modifying Anti-rheumatic Drugs (DMARD's) plus Prednisone and for patients with no initial treatment with the initiation of Prednisone and or TNF a inhibitors (Etanercept). 8 female and 2 male patients with average age 59.7 + 14 years were selected. The results for the group treated with Prednisone initially N=4; showed a 0.9 g/dL increase in Hgb and Hct increase of 3% after addition of Etanercept. Those with DMARDs and corticosteroid regime had an Hgb and Hct increase of 1.2 g/dL and 3.5% after addition of Etanercept. The group with no initial treatment was further divided in two groups. The first was treated with Etanercept and the second was treated with Prednisone, resulting in average Hgb increases of 1.9 g/dl Hgb and 1.8 g/dL, and HCT increase 4% and 3.9% respectively. The global average change in Hgb was 1.3g/dL and HCT increase 3.2%. The intensity of treatment of RA including Etanercept and Prednisone improved cases of mild anemia in rheumatoid arthritis.


Impacts of selective logging on inbreeding and gene flow in two Amazonian timber species with contrasting ecological and reproductive characteristics.
Selective logging in Brazil allows for the removal of up to 90% of trees above 50 cm diameter of a given timber species, independent of a species' life history characteristics or how quickly it will recover. The genetic and demographic effects of selective logging on two Amazonian timber species (Dipteryx odorata Leguminosae, Jacaranda copaia Bignoniaceae) with contrasting ecological and reproductive characteristics were assessed in the same forest. Genetic diversity and gene flow were characterized by genotyping adults and seed sampled before and after logging, using hypervariable microsatellite markers. Overall, there were no short-term genetic impacts on the J. copaia population, with commercial application of current Brazilian forest management regulations. In contrast, for D. Odorata, selective logging showed a range of genetic impacts, with a 10% loss of alleles, and reductions in siring by pollen from trees within the 546-ha study area (23-11%) and in the number of pollen donors per progeny array (2.8-1.6), illustrating the importance of the surrounding landscape. Asynchrony in flowering between D. odorata trees led to trees with no breeding partners, which could limit the species reproduction and regeneration under current regulations. The results are summarized with other published studies from the same site and the implications for forest management discussed. The different types and levels of impacts associated with each species support the idea that ecological and genetic information by species, ecological guild or reproductive group is essential in helping to derive sustainable logging guidelines for tropical forests.


Dose response of luteinized porcine granulosa cells in vitro to prolactin: dependency on pre-exposure to human chorionic gonadotrophin.
This study examined the hypothesis that human chorionic gonadotrophin (hCG) increases prolactin (PRL) stimulation of the utilization of lipoprotein-borne cholesterol by pig luteinized granulosa cells in culture. These cells, which luteinize in culture, were harvested from 6-mm or greater diameter follicles and cultured in the presence of 1% fetal calf serum and 1 microgram/mL insulin for 48 h. On the third day, the media were replaced with fresh serum-free media, with the same dose of insulin, and on the following day (day 4) the media were replaced with serum- and insulin-free media. At this time (day 4) hCG was added to some cultures. On day 5, cells from the group with hCG and cells from the group without hCG were treated with graded doses of ovine PRL (0.1-3.0 micrograms/mL). To a second set of cells, likewise treated, 100 micrograms of porcine low density lipoprotein (LDL) was added. Two days later (day 7) media were sampled and replaced with media alone or media containing hormones and (or) LDL. On day 9 cultures were terminated. In the cells pre-exposed to hCG, PRL (1 microgram/mL) in the presence of LDL increased progesterone production 1.7-fold (p less than 0.01) on day 7 and 2.2-fold (p less than 0.01) on day 9. In the granulosa cells in culture pre-exposed to hCG, the effect of PRL on LDL utilization was dose dependent and saturable at 1 microgram/mL on days 7 and 9. We conclude that brief pretreatment of luteinized pig granulosa cells with hCG results in a dose-dependent PRL-induced utilization of LDL for progesterone synthesis.


Amalgam tattoo: a cause of sinusitis?
Little attention has been paid to the toxicity of silver amalgam fillings, which have been used over the centuries in Dentistry. Amalgam particles may accidentally and/or traumatically be embedded into the submucosal tissue during placement of a restoration and perpetuate in such area. This article presents a case of amalgam tattoo and investigates whether it is related to the patient's repeated episodes of sinusitis. The patient was a 46-year-old woman with a 2 mm diameter radiopaque lesion in the right oral mucosa detected on a panoramic radiograph and presented as a black macula clinically. A complete surgical resection was carried out. The histopathological examination revealed deposits of dark-brownish pigments lining the submucosal tissue with adjacent lymphocytic inflammatory infiltrate and multinucleated giant cells phagocyting pigments. There was a negative staining for both iron and melanin. One year after lesion removal, the patient reported that the sinusitis crises had ceased after repeated episodes for years. It may be speculated that the inflammatory process related to amalgam tattoo seems to lead to a local immune response that causes sinusitis because it enhances the human leukocyte antigen DR (HLA-DR) tissue expression.


Polypropylene Blend with Polyphenols through Dynamic Vulcanization: Mechanical, Rheological, Crystalline, Thermal, and UV Protective Property.
Tannin and lignin were blended with polypropylene (PP) through dynamic vulcanization technique. Their influence of mechanical property, crystallinity, thermal stability, as well as ultraviolet (UV) protection property on the PP matrix was investigated and compared with native tannin and lignin. According to our experimental results, tannin and lignin undergo dynamic vulcanization and were more compatible with the PP matrix. Besides, tannin and vulcanized tannin can perform as nucleating agents of PP because of their relatively small particle size. Moreover, vulcanized tannin/lignin have a better performance on the thermal stability of PP compared with native tannin/lignin, especially PP/vulcanized lignin blend. Furthermore, vulcanized tannin/lignin present better UV protective performance, concluded from fewer changes on surface morphology, carbonyl index, crystallinity, viscosity, and tensile property.


Filamentous aggregates of native titin and binding of C-protein and AMP-deaminase.
In solutions of high ionic strength, native titin-2, a large extractable fragment of the sarcomere matrix protein titin, appears as extremely long, flexible, and slender beaded strings. We report here that in solutions of lower ionic strength near neutral pH, titin-2 assembles into higher-order aggregates with surface projections. Solid phase binding assays show that two myosin-binding proteins, C-protein and AMP-deaminase, are also titin-binding proteins. Both proteins decorate titin aggregates, producing filaments of more uniform appearance. Numerical Fourier transforms of these decorated aggregates show approximately 12-nm periodicities. The interaction of titin with myosin-associated proteins such as C-protein may take part in the anchoring mechanism that prevents the stretching and extension of titin filaments in the A band.


A novel approach to quantifying surgical workflow in robotic-assisted lobectomy.
Understanding surgical workflow is critical for optimizing efficiencies and outcomes; however, most research evaluating workflow is impacted by observer subjectivity, limiting its reproducibility, scalability, and actionability. To address this, we developed a novel approach to quantitatively describe workflow within robotic-assisted lobectomy (RL). We demonstrate the utility of this approach by analysing features of surgical workflow that correlate with procedure duration. RL was deconstructed into 12 tasks by expert thoracic surgeons. Task start and stop times were annotated across videos of 10 upper RLs (5 right and 5 left). Markov Networks were used to estimate both the likelihood of transitioning from one task to another and each task-transition entropy (i.e. complexity). Associations between the frequency with which each task was revisited intraoperatively and procedure duration were assessed using Pearson's correlation coefficient. Entropy calculations identified fissure dissection and hilar node dissection as tasks with especially complex transitions, while mediastinal lymph node dissection and division of pulmonary veins were less complex. The number of transitions to three tasks significantly correlated with case duration (fissure dissection (R = 0.69, p = 0.01), dissect arteries (R = 0.59, p = 0.03), and divide arteries (R = 0.63, p = 0.03)). This pilot demonstrates the feasibility of objectively quantifying workflow between RL tasks and introduces entropy as a new metric of task-transition complexity. These innovative measures of surgical workflow enable detailed characterization of a given surgery and might indicate behaviour that impacts case progression. We discuss how these measures can serve as a foundation and be combined with relevant clinical information to better understand factors influencing surgical inefficiency.


An analysis of the mechanism by which gamma-aminobutyric acid depresses ventilation in the rat.
Intracerebroventricular administration of gamma-aminobutyric acid (GABA) or intraperitoneal injection of the GABA transaminase A inhibitor aminooxyacetic acid (AOAA) depressed ventilation in halothane-anesthetized rats. The depression was due to changes in both respiratory frequency (f) and tidal volume (VT) after GABA, whereas AOAA decreased only f. Intracerebroventricular GABA decreased inspiratory drive (VT/TI; intrapulmonary pressure at 100 ms) but did not change the bulbopontine setting of inspiratory duration (TI). Moreover, respiratory duty cycle (TI/TT) was decreased, and the ventilatory response to CO2 exposure was blunted. The ventilatory depression induced by GABA was reversed by the GABA antagonist bicuculline. The GABA content measured 45 min after AOAA administration was significantly increased in the whole brain, the hemispheres, striatum, and lower spinal cord regions. Whole-brain GABA content was significantly correlated to the changes in f, minute ventilation, TI, expiratory duration (TE), and total cycle duration. Furthermore, there was a significant negative correlation between brain stem GABA content and TI/TT but not VT/TI. In summary, GABA seems to interact with the central regulation of respiration at different levels in the brain. The main effect of increased endogenous concentrations of GABA is, however, a decrease in respiratory frequency due to a prolongation in TE.


Antisense directed at the Abeta region of APP decreases brain oxidative markers in aged senescence accelerated mice.
Amyloid beta-peptide (Abeta) is known to induce free radical-mediated oxidative stress in the brain. Free radical-mediated damage to the neuronal membrane components has been implicated in the etiology of Alzheimer's disease (AD). Abeta is produced by proteolytic processing of the amyloid precursor protein (APP). The senescence accelerated mouse prone 8 (SAMP8) strain was developed by phenotypic selection from a common genetic pool. The SAMP8 strain exhibits age-related deterioration in memory and learning as well as Abeta accumulation, and it is considered an effective model for studying brain aging in accelerated senescence. Previous research has shown that a phosphorothiolated antisense oligonucleotide directed against the Abeta region of APP decreases the expression of APP and reverses deficits in learning and memory in aged SAMP8 mice. Consistent with other reports, our previous study showed that 12-month-old SAMP8 mice have increased levels of oxidative stress markers in the brain compared with that in brains from 4-month-old SAMP8 mice. In the current study, 12-month-old SAMP8 mice were treated with antisense oligonucleotide directed against the Abeta region of APP, and the oxidative markers in brain were decreased significantly. Therefore, we conclude that Abeta may contribute to the oxidative stress found in aged SAMP8 mice that have learning and memory impairments. These results are discussed in reference to AD.


In vivo ossification of a scaffold combining β-tricalcium phosphate and platelet-rich plasma.
Tricalcium phosphate (TCP) and platelet-rich plasma (PRP) are commonly used in bone tissue engineering. The aim of the present study was to investigate a composite that combined TCP with PRP and assess its effectiveness in the treatment of bone defects. Cavity-shaped bone defects were established on the tibiae of 27 beagle dogs, and were repaired by pure β-TCP with bone marrow stromal cells (BMSCs), β-TCP/PRP with BMSCs and autogenic ilium. The samples were harvested at 4, 8 and 12 weeks, and bone regeneration was evaluated using X-ray radiography, immunocytochemical staining of osteocalcin (OCN), hematoxylin and eosin staining and reverse transcription-polymerase chain reaction analyses. Biomechanical tests of the scaffolds were performed at the 12th week after scaffold implantation. When using pure β-TCP as a scaffold, the scaffold-bone interface was clear and no material adsorption and bone healing was observed. Substantial bone regeneration was observed when the tibial defects were restored using β-TCP/PRP and autogenic ilium. Furthermore, the mRNA expression levels of OCN, alkaline phosphatase and collagen type I α1 were significantly higher in the animals with β-TCP/PRP scaffolds at 8 and 12 weeks following implantation compared with those in the animals with the pure β-TCP scaffolds. The maximum load and compressive strength of the β-TCP/PRP scaffolds were similar to those of the autogenic ilium; however, they were significantly higher than those of the pure β-TCP scaffold. Thus, the β-TCP/PRP composite may be used as a potential scaffold to carry in vitro cultured BMSCs to treat bone defects.


Inhibition of renal cancer cell growth by oncolytic adenovirus armed short hairpin RNA targeting hTERT gene.
RNA interference (RNAi) has been proved to be a powerful tool for gene knockdown purpose and holds a great promise for the treatment of cancer. Our previous study demonstrated that the reduction of hTERT expression by means of chemically synthesized siRNAs and shRNAs expressed from plasmid resulted in proliferation inhibition in human renal carcinoma cells. In this study, we constructed a novel oncolytic adenovirus-based shRNA expression system, ZD55-hTERT, and to explore ZD55-hTERT-mediated RNAi for hTERT gene silencing. Our results showed that ZD55-hTERT could induce silencing of hTERT gene effectively, allow for efficient tumor-specific viral replication and induce the apoptosis of tumor cells effectively in vitro and in nude mice. We conclude that combining shRNA gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and shRNA antitumor responses.


[Collagen fractions, obtained by water-salt extraction from animal fats].
Collagen fractions have been isolated by water-salt extraction from raw materials of animal origin (various tendon types or subcutaneous tissues of cattle, or porcine skin). Collagen fractions with maximum capacity for water and fat retention were isolated with high efficiency by water-salt solutions containing 1-10% sodium chloride at temperatures below 50 degrees C. The values of the effective constant of extraction rate (min-1) at pH 6.5, 9.0, and 12.0 were equal to (2.7 +/- 0.1) x 10(-3), (6.2 +/- 0.5) x 10(-3), and (15.4 +/- 0.7) x 10(-3), respectively. The optimum conditions found made it possible to isolate collagen those proteinaceous fractions that are of practical use in food industry.


A single base pair substitution on Chromosome 25 in zebrafish distinguishes between development and acute regulation of behavioral thresholds.
Behavioral thresholds define the lowest stimulus intensities sufficient to elicit a behavioral response. Establishment of baseline behavioral thresholds during development is critical for proper responses throughout the animal's life. Despite the relevance of such innate thresholds, the molecular mechanisms critical to establishing behavioral thresholds during development are not well understood. The acoustic startle response is a conserved behavior whose threshold is established during development yet is subsequently acutely regulated. We have previously identified a zebrafish mutant line ( escapist ) that displays a decreased baseline or innate acoustic startle threshold. Here, we identify a single base pair substitution on Chromosome 25 located within the coding sequence of the synaptotagmin 7a ( syt7a ) gene that is tightly linked to the escapist acoustic hypersensitivity phenotype. By generating animals in which we deleted the syt7a open reading frame, and subsequent complementation testing with the escapist line, we demonstrate that loss of syt7a function is not the cause of the escapist behavioral phenotype. Nonetheless, escapist mutants provide a powerful tool to decipher the overlap between acute and developmental regulation of behavioral thresholds. Extensive behavioral analyses reveal that in escapist mutants the establishment of the innate acoustic startle threshold is impaired, while regulation of its acute threshold remains intact. Moreover, our behavioral analyses reveal a deficit in baseline responses to visual stimuli, but not in the acute regulation of responses to visual stimuli. Together, this work eliminates loss of syt7a as causative for the escapist phenotype and suggests that mechanisms that regulate the establishment of behavioral thresholds in escapist larvae can operate largely independently from those regulating acute threshold regulation.


Stable learning of functional maps in self-organizing spiking neural networks with continuous synaptic plasticity.
This study describes a spiking model that self-organizes for stable formation and maintenance of orientation and ocular dominance maps in the visual cortex (V1). This self-organization process simulates three development phases: an early experience-independent phase, a late experience-independent phase and a subsequent refinement phase during which experience acts to shape the map properties. The ocular dominance maps that emerge accommodate the two sets of monocular inputs that arise from the lateral geniculate nucleus (LGN) to layer 4 of V1. The orientation selectivity maps that emerge feature well-developed iso-orientation domains and fractures. During the last two phases of development the orientation preferences at some locations appear to rotate continuously through ±180° along circular paths and referred to as pinwheel-like patterns but without any corresponding point discontinuities in the orientation gradient maps. The formation of these functional maps is driven by balanced excitatory and inhibitory currents that are established via synaptic plasticity based on spike timing for both excitatory and inhibitory synapses. The stability and maintenance of the formed maps with continuous synaptic plasticity is enabled by homeostasis caused by inhibitory plasticity. However, a prolonged exposure to repeated stimuli does alter the formed maps over time due to plasticity. The results from this study suggest that continuous synaptic plasticity in both excitatory neurons and interneurons could play a critical role in the formation, stability, and maintenance of functional maps in the cortex.


Differential effects of decisional and emotional forgiveness on distress and well-being: A three-wave study of Indonesian adults.
Research suggests that interpersonal forgiveness is beneficial to individual functioning, but few longitudinal studies have explored the independent contributions of decisional and emotional forgiveness to reducing different forms of distress and improving multidimensional well-being. In this three-wave (T1: December 2020; T2: January 2021; T3: February 2021) prospective study of predominantly young Indonesian adults (n = 595), we examined the associations of decisional and emotional forgiveness with three indicators of distress and 10 components of well-being. Applying the outcome-wide analytic template for longitudinal designs, our primary analysis involved estimating two sets of linear regression models (one set for decisional forgiveness and one set for emotional forgiveness) in which the outcomes were regressed on each interpersonal forgiveness process (one outcome at a time). Adjusting for a range of covariates (including prior values of decisional forgiveness, emotional forgiveness, and all 13 outcomes) assessed at T1, decisional forgiveness assessed at T2 was associated with an increase in seven components of well-being (i.e., life satisfaction, physical health, sense of purpose, promote good, delayed gratification, content with relationships, satisfying relationships) approximately 1 month later at T3. In contrast, emotional forgiveness assessed at T2 was associated with an increase in a single component of well-being (i.e., satisfying relationships) assessed at T3. Neither decisional nor emotional forgiveness assessed at T2 showed evidence of associations with any of the subsequent indicators of distress assessed at T3. Our findings suggest that, at least within a principally collectivistic cultural context such as Indonesia, decisional forgiveness in the aftermath of a transgression may have greater short-term benefits for well-being compared to emotional forgiveness. Implications of the findings for research and interventions are discussed.