Influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses.
We have studied the influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. In a double-blind, placebo-controlled trial of immunotherapy in 40 adult hay fever sufferers, clinical improvement was accompanied by a decrease in the size of the late-phase skin response. When the immunotherapy-treated group was compared with the placebo group, analysis of skin biopsies obtained 24 h after intradermal allergen revealed a significant reduction in the number of infiltrating CD3+ (P = 0.04) and CD4+ (P = 0.009) cells and a trend for a decrease in EG2+ eosinophils (P = 0.08). Treatment did not influence allergen-induced recruitment of CD8+ cells, neutrophils, or macrophages. Unexpected increases in expression of CD25 (P = 0.006) and HLA-DR (P = 0.007) were observed in the actively treated group. In situ hybridization using a panel of riboprobes demonstrated "TH2-type" (IL-4, IL-5) cytokine mRNA responses in both groups of patients. In contrast, significant hybridization for IL-2 (8/16 patients, P = 0.02) and for interferon-gamma (6/16 patients, P = 0.04) was observed only in the actively treated group. These findings indicate that immunotherapy is associated with suppression of allergen-induced CD4+ T lymphocyte infiltration, but among the cells that are recruited, there is upregulation of CD25 and HLA-DR. At least in this model, immunotherapy does not appear to affect expression of TH2-pattern cytokines in response to allergen exposure, but expression of mRNA for Th1-type cytokines was enhanced in half of the patients. The results support the view that immunotherapy may possibly be working through induction of T cell tolerance.


Transcriptome analysis of testis reveals the effects of developmental exposure to bisphenol a or 17α-ethinylestradiol in medaka (Oryzias latipes).
Endocrine disrupting chemicals (EDCs) can induce abnormalities in organisms via alteration of molecular pathways and subsequent disruption of endocrine functions. Bisphenol A (BPA) and 17α-ethinylestradiol (EE2) are ubiquitous EDCs in the environment. Many aquatic organisms, including fish, are often exposed to varying concentrations of BPA and EE2 throughout their lifespan. Both BPA and EE2 can activate estrogenic signaling pathways and cause adverse effects on reproduction via alteration of pathways associated with steroidogenesis. However, transcriptional pathways that are affected by chronic exposure to these two ubiquitous environmental estrogens during embryonic, larval, and juvenile stages are not clearly understood. In the present study, we examined transcriptional alterations in the testis of medaka fish (Oryzias latipes) chronically exposed to a low concentration of BPA or EE2. Medaka were exposed to BPA (10 μg/L) or EE2 (0.01 μg/L) from 8 h post-fertilization (as embryos) to adulthood 50 days post fertilization (dpf), and transcriptional alterations in the testis were examined by RNA sequencing (RNA-seq). Transcriptomic profiling revealed 651 differentially expressed genes (DEGs) between BPA-exposed and control testes, while 1475 DEGs were found between EE2-exposed and control testes. Gene ontology (GO) analysis showed a significant enrichment of "intracellular receptor signaling pathway", "response to steroid hormone" and "hormone-mediated signaling pathway" in the BPA-induced DEGs, and of "cilium organization", "microtubule-based process" and "organelle assembly" in the EE2-induced DEGs. Pathway analysis showed significant enrichment of "integrin signaling pathway" in both treatment groups, and of "cadherin signaling pathway", "Alzheimer disease-presenilin pathway" in EE2-induced DEGs. Single nucleotide polymorphism (SNP) and insertion-deletion (Indel) analysis found no significant differences in mutation rates with either BPA or EE2 treatments. Taken together, global gene expression differences in testes of medaka during early stages of gametogenesis were responsive to chronic BPA and EE2 exposure.


Sexual Dimorphism and Hemispheric Asymmetry of Hippocampal Volumetric Integrity in Normal Aging and Alzheimer Disease.
Asymmetric atrophy of the hippocampus is an important clinical finding in normal aging and Alzheimer disease. In this study, we investigate the associations between the magnitude and asymmetry of hippocampal volumetric integrity and age, sex, and dementia severity. We have recently developed a rapid fully automatic algorithm to measure the hippocampal parenchymal fraction, an index of hippocampal volumetric integrity on structural MR imaging of the brain. We applied this algorithm to measure the hippocampal parenchymal fraction bilaterally on 775 MR imaging volumes scanned from 198 volunteers in a publicly available data base. All subjects were right-handed and older than 60 years of age. Subjects were categorized as cognitively healthy (n = 98), with mild cognitive impairment (n = 70), or with mild/moderate Alzheimer disease (n = 30). We used linear mixed-effects models to analyze the hippocampal parenchymal fraction and its asymmetry with respect to age, sex, dementia severity, and intracranial volume. After controlling for age, sex, and intracranial volume, we found that the magnitude of the hippocampal parenchymal fraction decreased and its asymmetry increased significantly with dementia severity. Also, hippocampal parenchymal fraction asymmetry was significantly higher in men after controlling for all other variables, but there was no sex effect on hippocampal parenchymal fraction magnitude. The magnitude of the hippocampal parenchymal fraction decreased and its asymmetry increased significantly with age in subjects who were cognitively healthy, but associations with age were different in nature in the mild cognitive impairment and Alzheimer disease groups. Hippocampal atrophy progresses asymmetrically with age in cognitively healthy subjects. Hippocampal parenchymal fraction asymmetry is significantly higher in men than women and in mild cognitive impairment/Alzheimer disease relative to cognitively healthy individuals.


Effect of lactulose on carbohydrate metabolism and diabetes mellitus.
Unabsorbable disaccharides, by reducing transit time and possibly glucose absorption, are expected to affect carbohydrate metabolism. To test the effects of a preparation containing fibre and lactulose in the form of biscuits on glucose and insulin levels in obesity. In 10 obese patients glucose and insulin were measured in the fasting state and in response to a meal during two consecutive days on a strictly controlled diet; on one day a total of 11 biscuits (10 g dietary fibre, 2 g raw fibre +8.2 g lactulose) were randomly substituted for an equicaloric part of a diet. Glucose and insulin in response to breakfast and to lunch were blunted by dietary fibre and lactulose, without any trend towards post-meal hypoglycaemia. Average day-time glucose decreased by 0.53 +/- SD 0.28 mmol/L, and insulin by 74.6 +/- 45.2 pmol/L. Plasma amino acids were higher during supplementation, ruling out malabsorption as a cause of glucose flattening. Because of the rationale of the preparation, good compliance of patients, and significant results in short-term experiments, the association of fibre and lactulose deserves more careful evaluation in long-term clinical studies.


Electromagnetic information transfer through aqueous system.
Several beneficial effects of the electromagnetic information transfer through aqueous system (EMITTAS) procedure have previously been reported in vitro. The clinical potential of this procedure has also started to be evaluated. Information flow in biological systems can be investigated through chemical and molecular approaches or by a biophysical approach focused on endogenous electrodynamic activities. Electromagnetic signals are endogenously generated at different levels of the biological organization and, likely, play an active role in synchronizing internal cell function or local/systemic adaptive response. Consequently, each adaptive response can be described by its specific electromagnetic pattern and, therefore, correlates with a unique and specific electromagnetic signature. A biophysical procedure synchronously integrating the EMITTAS procedure has already been applied for the treatment of articular pain, low-back pain, neck pain and mobility, fluctuating asymmetry, early-stage chronic kidney disease, refractory gynecological infections, minor anxiety and depression disorders. This clinical strategy involves a single treatment, since the EMITTAS procedure allows the patient to continue his/her own personal treatment at home by means of self-administration of the recorded aqueous system. A significant and long-lasting improvement has been reported, showing a potential beneficial use of this biophysical procedure in the management of common illnesses in an efficient, effective and personalized way. Data from recent studies suggest that aqueous systems may play a key role in providing the basis for recording, storing, transferring and retrieving clinically effective quanta of biological information. These features likely enable to trigger local and systemic self-regulation and self-regeneration potential of the organism.


A Bayesian network model for analysis of detection performance in surveillance systems.
Worldwide developments concerning infectious diseases and bioterrorism are driving forces for improving aberrancy detection in public health surveillance. The performance of an aberrancy detection algorithm can be measured in terms of sensitivity, specificity and timeliness. However, these metrics are probabilistically dependent variables and there is always a trade-off between them. This situation raises the question of how to quantify this tradeoff. The answer to this question depends on the characteristics of the specific disease under surveillance, the characteristics of data used for surveillance, and the algorithmic properties of detection methods. In practice, the evidence describing the relative performance of different algorithms remains fragmented and mainly qualitative. In this paper, we consider the development and evaluation of a Bayesian network framework for analysis of performance measures of aberrancy detection algorithms. This framework enables principled comparison of algorithms and identification of suitable algorithms for use in specific public health surveillance settings.


CONVERGENT EVOLUTION OF COURTSHIP SONGS AMONG CRYPTIC SPECIES OF THE CARNEA GROUP OF GREEN LACEWINGS (NEUROPTERA: CHRYSOPIDAE: CHRYSOPERLA).
Although traits of related species are likely to be similar due to common ancestry, mating signals are an exception. In singing insects, for example, song similarity has been documented only for allopatric or allochronic species pairs, and even then, not often. Where song similarity does occur, it has been logically attributed to the inheritance of ancestral traits rather than convergence. It is quite common for related, sympatric insect species to differ dramatically in calling song, which is predicted by evolutionary theory to maximize intraspecific mating success. Given that there are a limited number of ways to make sounds on anatomically similar organs and given that there would be no selective pressure for songs to differ in widely separated geographic areas, convergence in songs among related species living on different continents might be expected. Here we present the first well-documented case of such convergence, in a group of sibling, cryptic species characterized by substrate-borne vibrational mating songs. In this example from green lacewings of the carnea group of the genus Chrysoperla, a variety of statistical tests shows that one species in North America and another in Asia possess songs that are strikingly similar to each other. DNA data demonstrate that the species involved belong to divergent speciose lineages, and behavioral data demonstrate that the convergent songs are readily accepted by members of both species.


Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats.
Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. The adolescent stage marks a critical stage of brain development and maturation. Influences of agents on the brain at this stage may affect neuronal structural and functional attributes. To this end, the current experiment considered the effects of cannabis and caffeine on selected key neurotransmitters and enzymes in the brain tissues after regimented caffeine and cannabis treatment for 21 days. A total of 72 juvenile Wistar rats that were approximately 40 days old were divided into 6 groups A-F. The group A served as the control. Other groups were administered various dosages of caffeine or cannabis in distilled water, using oral gavages as follows: group B animals received 100 mg/kg body weight of caffeine, group C animals received 50 mg/kg body weight of caffeine, group D animals received 500 mg/kg body weight of cannabis, group E animals received 200 mg/kg body weight of cannabis, and group F received a low dose of cannabis (200 mg/kg body weight) plus a low dose of caffeine (50 mg/kg body weight). The animals were killed by cervical dislocation 24 h after the last administration. The brain tissues were excised and homogenized. The enzymes cytochrome C oxidase and glucose-6-phosphate dehydrogenase were assayed to observe tissue energy metabolism while the neurotransmitters gamma-amino butyric acid (GABA), glutamate, and dopamine were assayed to observe the effects of the psychoactive substances on their activities relative to mental activities. GABA, glutamate, and dopamine were generally higher in the treated groups of animals. The levels of G-6-PDH were higher in all treated animals' brains. Caffeine produced quite more significant effects relative to cannabis and the combination of both increased the level of G-6-PDH significantly. Results showed that caffeine and cannabis influenced the activities of the enzymes and neurotransmitters in the brain. Both stimulants altered brain chemistry relative to the tested enzymes and neurotransmitters.


Effect of orlistat on periostin, adiponectin, inflammatory markers and ultrasound grades of fatty liver in obese NAFLD patients.
Orlistat is recommended in the treatment of obesity, which is an independent risk factor for nonalcoholic fatty liver disease (NAFLD). The reported findings of orlistat in NAFLD are divisive. Recently, periostin is identified as an important regulatory molecule in the pathogenesis of obesity-induced fatty liver. Therefore, this study aimed to evaluate the potential effects of orlistat in the treatment of NAFLD. A 16-week prospective observational study was conducted, with obese NAFLD patient (n=77) receiving orlistat (120 mg capsules, three times a day) with hypocaloric diet or hypocaloric diet only. Grades of fatty liver were determined using ultrasound (US) echogenicity of liver; serum levels of periostin, adiponectin, tumor necrosis factor (TNF)-α and interleukin-6 were determined using ELISA kits at 0 and 16 weeks. Correlations of US grades of fatty liver with these biomarkers were also determined. Orlistat significantly reversed the US grades of fatty liver (P=0.016), decreased serum levels of periostin (P=0.030) and TNF-α (P=0.040), and increased serum adiponectin levels (P<0.001) when compared with hypocaloric diet only. Serum interleukin-6 levels were not found to be significantly different in both groups after the treatment. In the orlistat group, the degree of reduction in grades of fatty liver was found to be positively correlated with the changes in serum levels of periostin (rs=0.306, P=0.041) and adiponectin (rs=0.314, P=0.036), whereas the associations were insignificant with the change in serum levels of TNF-α (rs=0.053, P=0.729). Mild gastrointestinal side effects (20%) were reported in the orlistat group. In conclusion, orlistat is effective in the treatment of NAFLD patients without fibrosis. This study demonstrated a positive association between the reduction of fatty infiltration in the liver and the changes in serum levels of periostin and adiponectin in obese NAFLD patients.


Future directions for reductionistic research in gastric secretion and defense.
Our theme centers on the complex processes that constitute and regulate the function of the gastric mucosa. Although some investigators promote the critical importance of a given element, such as acid, blood flow, or mucus, it is clear that both gastric secretory function and mucosal defense and repair mechanisms are multifactorial and are regulated by redundant control circuits. While it is true that critical studies can be performed in vivo with intact mucosa, at the same time it is frequently difficult, using these methods, to define the specific cellular elements involved in the regulation of secretion, defense, and repair. We now recognize that ulcer disease does not occur simply when this balance is thrown off. To the contrary, ulcer disease commonly occurs when the normal mucosal mechanisms are perturbed by Helicobacter pylori-associated gastro-duodenitis or nonsteroidal anti-inflammatory drugs. In the absence of such perturbation, the redundancy of the regulatory mechanisms underlying gastric secretion and the multiple lines of defense and healing would render ulcer disease rare indeed.


Motion-defined contour processing in the early visual cortex.
From our daily experience, it is very clear that relative motion cues can contribute to correctly identifying object boundaries and perceiving depth. Motion-defined contours are not only generated by the motion of objects in a scene but also by the movement of an observer's head and body (motion parallax). However, the neural mechanism involved in detecting these contours is still unknown. To explore this mechanism, we extracellularly recorded visual responses of area 18 neurons in anesthetized and paralyzed cats. The goal of this study was to determine if motion-defined contours could be detected by neurons that have been previously shown to detect luminance-, texture-, and contrast-defined contours cue invariantly. Motion-defined contour stimuli were generated by modulating the velocity of high spatial frequency sinusoidal luminance gratings (carrier gratings) by a moving squarewave envelope. The carrier gratings were outside the luminance passband of a neuron, such that presence of the carrier alone within the receptive field did not elicit a response. Most neurons that responded to contrast-defined contours also responded to motion-defined contours. The orientation and direction selectivity of these neurons for motion-defined contours was similar to that of luminance gratings. A given neuron also exhibited similar selectivity for the spatial frequency of the carrier gratings of contrast- and motion-defined contours. These results suggest that different second-order contours are detected in a form-cue invariant manner, through a common neural mechanism in area 18.


Development of rat x mouse hybrid embryos produced by microsurgery.
Experimental production of hybrid embryos between Mus musculus L. and Rattus norvegicus L. was achieved by nuclear transplantation using both ovulated oocytes in metaphase II and pronuclear zygotes. Recipient egg-cells were of mouse origin in all cases. The developmental potential of hybrids was examined in vivo. Nucleo-cytoplasmic hybrids resulting from the introduction of rat metaphase II chromosomes into enucleated mouse oocytes, which were subsequently activated, were regularly blocked at the 1- or 2-cell stage. Nuclear (genetic) hybrids produced by transfer of a rat nucleus (in the form of metaphase II chromosomes or a pronucleus) into a nucleated mouse recipient (oocyte or zygote) were capable of development to the 5- to 8-cell stage. Transplantation of rat cytoplasm alone to intact metaphase II oocytes, followed by oocyte activation, generated cytoplasmic hybrids which developed to the morula stage. In control experiments (nuclear transfer between mouse oocytes or zygotes), a high proportion of embryos formed morulae and blastocysts. These results demonstrate that the rat nucleus is incapable of functioning in mouse cytoplasm, that introduction of the rat genome into intact mouse egg-cells impairs normal development, and that transfer of foreign (rat) cytoplasm into mouse egg-cells affects preimplantation development of manipulated embryos.


On the borders: surgeons and their activities in the Venetian State (1540-1640).
Through the biographies of a dynasty of practitioners who were active in some of the mountainous villages of the Venetian Terraferma the article brings to light unknown aspects of the professional world of surgeons. Their activities were profoundly influenced by the economic and geographic peculiarities of the territory where they lived and worked. Provincial towns and their territories offered professional opportunities both to licensed and to non-university trained practitioners. However, it was generally in small villages, especially those situated in border areas and part of the main commercial networks, that surgeons preferred to establish their practices, thus supplementing the medical services supplied by the town. Normally their knowledge was largely empirical and was transmitted from father to son. The apprenticeship-based training does not appear alternative to the academic education typical of learned practitioners: much evidence points to the existence of 'scientific autodidacts', self-taught practitioners who possessed and read medical texts or had attended academic courses, even if only in part. Practising surgery in this area was a highly mobile activity, stretching from the village to the neighbouring valleys, and even to areas outside the boundaries of the city and across the border of the Venetian state. Surgeons, furthermore, were able to transfer their skills and knowledge across a range of different occupations such as shoemakers, leather workers and tailors, a fact that confirms their close ties with the local artisan milieu.


Organophosphite Antioxidants in Indoor Dust Represent an Indirect Source of Organophosphate Esters.
Precise determination of organophosphate esters (OPEs) in the environment is crucial to estimating their potential toxicity effects on human health. Previous studies have mainly focused on OPEs from direct sources. This study explored a potential indirect source of OPEs: the oxidation of organophosphite antioxidants (OPAs). OPAs are frequently used to retard degradation in polymers through their oxidation to OPEs. In this work, five OPAs [tris(2-chloroethyl) phosphite, triphenyl phosphite, tris(2,4-di- tert-butylphenyl) phosphite, bis(2,4-di- tert-butylphenyl) pentaerythritol diphosphite, and trisnonylphenol phosphite] could be identified, with geometric mean (GM) concentrations from 2.46 to 70.4 ng/g, in indoor dust. Their oxidation products, triisodecyl phosphate (TiDeP), tris(2,4-di- tert-butylphenyl) phosphate (AO168═O), bis(2,4-di- tert-butylphenyl) pentaerythritol diphosphate (AO626═O2), and trisnonylphenol phosphate (TNPP), were found at significantly higher GM concentrations (30.5-3759 ng/g). Surprisingly, two novel oxidation products AO168═O (GM: 3759 ng/g) and TNPP (GM: 2185 ng/g) had higher concentrations than tris(2-chloroethyl) phosphate (GM: 1608 ng/g) and triphenyl phosphate (GM: 1827 ng/g), which are well-known OPEs. These four novel OPEs (TiDeP, TNPP, AO168═O, AO626═O2) contributed 54.1% to the total concentration of the eight OPEs. The present investigation demonstrates that oxidation of OPAs is an important indirect source of novel OPEs in indoor environments. This is the first detection of four OPAs and their newly identified OPE oxidation products in indoor dust.


[Two cases of stage IV gastric cancer treated by resection of the primary tumor after chemotherapy combined with trastuzumab].
We report 2 cases of stage IV gastric cancer in which the primary tumor was resected after chemotherapy combined with trastuzumab was administered. Case 1: A 57-year-old man who reported epigastric discomfort was diagnosed as having gastric cancer with Virchow's lymph node metastasis. Because his gastric cancer was human epidermal growth factor receptor( HER)-2-positive, he was treated with trastuzumab+capecitabine and CDDP( XP therapy). After 2 courses of this treatment, he underwent distal gastrectomy because of advanced pyloric stenosis. He was treated postoperatively with capecitabine+trastuzumab, and the residual lymph node shrank. Case 2: A 62-year-old man examined for weight loss was diagnosed as having gastric cancer with peritoneal metastases. Because his gastric cancer was HER2-positive, he was treated with trastuzumab+S-1 and CDDP( SP therapy). After 5 courses of this treatment, he underwent total gastrectomy because of advanced pyloric stenosis. He was treated postoperatively with trastuzumab+SP therapy, and his condition remained stable. Chemotherapy combined with trastuzumab could allow resection of the primary tumor and thereby improve the prognosis.


IL26, a Noncanonical Mediator of DNA Inflammatory Stimulation, Promotes TNBC Engraftment and Progression in Association with Neutrophils.
IL26 is a unique amphipathic member of the IL10 family of cytokines that participates in inflammatory signaling through a canonical receptor pathway. It also directly binds DNA to facilitate cellular transduction and intracellular inflammatory signaling. Although IL26 has almost no described role in cancer, our in vivo screen of inflammatory and cytokine pathway genes revealed IL26 to be one of the most significant inflammatory mediators of mammary engraftment and lung metastatic growth in triple-negative breast cancer (TNBC). Examination of human breast cancers demonstrated elevated IL26 transcripts in TNBC specimens, specifically in tumor cells as well as in Th17 CD4+ T cells within clinical TNBC specimens. IL26 did not have an autocrine effect on human TNBC cells, but rather its effect on engraftment and growth in vivo required neutrophils. IL26 enhanced mouse-derived DNA induction of inflammatory cytokines, which were collectively important for mammary and metastatic lung engraftment. To neutralize this effect, we developed a novel IL26 vaccine to stimulate antibody production and suppress IL26-enhanced engraftment in vivo, suggesting that targeting this inflammatory amplifier could be a unique means to control cancer-promoting inflammation in TNBC and other autoimmune diseases. Thus, we identified IL26 as a novel key modulator of TNBC metastasis and a potential therapeutic target in TNBC as well as other diseases reliant upon IL26-mediated inflammatory stimulation. SIGNIFICANCE: These findings identify IL26 as a unique, clinically relevant, inflammatory amplifier that enhances TNBC engraftment and dissemination in association with neutrophils, which has potential as a therapeutic target. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/15/3088/F1.large.jpg.


Influence of serogroup on the presentation, course, and outcome of invasive meningococcal disease in children in the Republic of Ireland, 1995-2000.
To test the hypothesis that the infecting meningococcal serogroup modulates the presentation, course, and outcome of invasive meningococcal disease (IMD), we performed a retrospective review of cases of IMD in 407 children from 2 tertiary referral centers and 2 regional centers in Ireland. Patients infected with serogroup C meningococci (n=104) were older than those infected with serogroup B (n=303; median, 2.5 vs. 1.5 years; P=.04); all other demographic and clinical parameters were similar for the 2 groups. Among serogroup B patients, mortality was 3.6% and morbidity was 10%; for serogroup C patients, mortality was 4.8% and morbidity was 12.5% (P=.81 and P=.76, respectively). Serogroup C-associated sequelae more often were multiple (P=.003). Despite the introduction of serogroup C conjugate vaccine into the routine immunization schedule of some countries, ongoing morbidity from IMD is anticipated, because group B disease was very similar to group C disease in this pediatric population.


Neuroprotective effect of G14-humanin on global cerebral ischemia/reperfusion by activation of SOCS3 - STAT3 - MCL-1 signal transduction pathway in rats.
Humanin (HN) has been identified to suppress neuron death. Gly14-HN (HNG), as a variant of HN, can decrease infarct volume after ischemia/reperfusion (I/R) injury. This study aimed to investigate the neuroprotective mechanism of HNG on global cerebral I/R (GI) in rats. Rats were randomly divided into 13 groups: Sham group, GI groups and HNG groups. Both GI group and HNG groups included six time points (1, 3, 6, 12, 24, and 72 h). At 24 h after reperfusion, Nissl staining was used to observe positive neurons, and p-STAT3, MCL-1, SOCS3, Bax and Caspase-3 in different groups were detected by immunohistochemistry. qRT-PCR and western blot were used to evaluate the expression of STAT3, p-STAT3, MCL-1, and SOCS3. The immunohistochemistry also showed a significant increase in Bax (0.29 ± 0.007 vs. 0.22 ± 0.007, P < 0.01) and Caspase-3 (0.24 ± 0.02 vs. 0.18 ± 0.006, P < 0.01) in GI group compared with Sham group, while Bax (0.26 ± 0.01 vs. 0.29 ± 0.008, P < 0.01) and Caspase-3 (0.20 ± 0.008 vs. 0.24 ± 0.02, P < 0.01) were significantly decreased by HNG-treatment compared with GI group. Along with immunohistochemistry, western blot and qRT-PCR indicated that the protein and mRNA levels of STAT3, MCL-1, and SOCS3 were up-regulated after administration of HNG at six time points after global cerebral I/R in rat. HNG might exert neuroprotective effects through alleviating apoptosis and activating of SOCS3 - STAT3 - MCL-1 signal transduction pathway. Highlights (1) Cerebral ischemia led to neuronal loss in hippocampal CA1 region of rats. (2) HNG had neuroprotective effects on ischemia/reperfusion rats. (3) The protective effect of HNG might be related to the SOCS3 - STAT3 - MCL-1 pathway.


Echocardiographic evaluation of ventricles during continuous positive airway pressure breathing.
Using M-mode and two-dimensional echocardiography, we have compared left and right ventricular dimensions at expiration and inspiration in a group of 12 healthy young volunteers during the following two distinct periods: 1) a control period with atmospheric pressure breathing, and 2) a continuous positive airway pressure (CPAP) period with 15 cmH2O end-expiratory pressure breathing. In 6 of the 12 subjects we also evaluated inferior vena caval size, using the same technique. Inspiratory decrease in left ventricular short-axis area (A), length (L), calculated volumes (V = 5/6 AL), and inspiratory increase in right ventricular short-axis diameter and long-axis area were evident at both control and CPAP periods. CPAP also produced a marked decrease in left and an increase in right ventricular dimensions during both expiration and inspiration and a significant decrease in calculated stroke output. An increase in vena caval size during CPAP breathing indirectly suggested a decrease in venous return, but the finding of an unchanged percent of inspiratory change of this vessel during CPAP indicated that the inspiratory augmentation of venous return was still present. On the other hand, the finding of an increased right ventricular size indicated that the right ventricle was afterloaded by CPAP; this probably could explain the observed reduction in calculated stroke output.


A follow-up study of the learning transfer process in further training of nursing staff.
The purpose of the study was to investigate whether the human and economic investment of resources in the further training of nursing and nursing assistants is justified. The study focused in particular on the transfer of knowledge from training course to working practice. It was carried out as a case study in Ringkøbing County, Denmark, during 1993/94. The population consisted of 49 nurses and 49 nursing assistants. The study showed that the participants took a keen interest in the courses. The learning process was found relevant by the nurses, but not by the nursing assistants. Neither group found that their expectations of getting more knowledge were satisfied. With respect to job-behaviour, the study confirmed the hypothesis that the practising of the content of the course will depend on the support and interest of the head of the department towards a goal-oriented development of competence and structure. If such support and interest is lacking, the course-participant will only change her own working practices, independent of the organizational structure.


Drug Delivery in Cancer Therapy, Quo Vadis?
The treatment of malignancies has undergone dramatic changes in the past few decades. Advances in drug delivery techniques and nanotechnology have allowed for new formulations of old drugs, so as to improve the pharmacokinetics, to enhance accumulation in solid tumors, and to reduce the significant toxic effects of these important therapeutic agents. Here, we review the published clinical data in cancer therapy of several major drug delivery systems, including targeted radionuclide therapy, antibody-drug conjugates, liposomes, polymer-drug conjugates, polymer implants, micelles, and nanoparticles. The clinical outcomes of these delivery systems from various phases of clinical trials are summarized. The success and limitations of the drug delivery strategies are discussed based on the clinical observations. In addition, the challenges in applying drug delivery for efficacious cancer therapy, including physical barriers, tumor heterogeneity, drug resistance, and metastasis, are discussed along with future perspectives of drug delivery in cancer therapy. In doing so, we intend to underscore that efficient delivery of cancer therapeutics to solid malignancies remains a major challenge in cancer therapy, and requires a multidisciplinary approach that integrates knowledge from the diverse fields of chemistry, biology, engineering, and medicine. The overall objective of this review is to improve our understanding of the clinical fate of commonly investigated drug delivery strategies, and to identify the limitations that must be addressed in future drug delivery strategies, toward the pursuit of curative therapies for cancer.


[Evaluation of the efficiency of activity of the liposomal form of isoniazid against different types of mycobacteria in vitro].
M. avium and three M. tuberculosis strains were used as an example to study the bacteriostatic activity of the liposomal form of isoniazid in the liquid nutrient medium by serial dilutions. Unlike isoniazid in solution, its liposomal form was found to suppress the multi plication of all study mycobacterial samples and diminishes their viability, but at different concentrations. The liposomes that did not contain the drug exerted an inhibitory effect only on the M. tuberculosis strains H37Rv and Erdman. It is suggested that the change in isoniazid sensitivity results from the effect of liposomal phospholipids on some mycobacterial enzymes. Electron microscopy indicated that the liposomal form of isoniazid is able to penetrate into the alveolar macrophageal cytoplasm of guinea pigs just 30 min after incubation.


Primary sequence determination of the most basic myonecrotic phospholipase A2 from the venom of Vipera russelli.
The most basic phospholipase A2 (PLA2), VRV-PL-VIIIa, was purified from (Sri Lankan) Vipera russelli venom. It is a major component of the venom, contributing over 40% to the whole venom PLA2 activity. The purity of VRV-PL-VIIIa was ascertained by electrophoresis and by reverse phase high-pressure liquid-chromatography (RP-HPLC). VRV-PL-VIIIa had an apparent mol. wt of 13,000 and was a single polypeptide. The protein was reduced, pyridylethylated and subjected to sequence analysis. The N-terminal amino acid sequence was established up to the 39th residue. Pyridylethylated VRV-PL-VIIIa was digested with endoprotease Glu-C, and several peptides were purified by RP-HPLC; six purified peptides were sequenced. The sequence of the C-terminal was established by sequencing a CNBr-produced peptide purified by RP-HPLC. Several peptides were also generated by digestion with endoprotease Asp-N. Two peptides were sequenced to obtain overlapping regions. The complete structure was deduced from sequences of overlapping peptides and through homology with other group II PLA2 sequences. Sequence homology was greatest with ammodytoxin A: 99 amino acid residues out of 121 occurred in identical positions. Myotoxin III of Bothrops asper showed 73% homology, 89 out of 121 residues. In agreement with the sequence data, polyclonal antiserum against VRV-PL-VIIIa cross-reacted in ELISA with ammodytoxin A and, to a lesser extent, with caudoxin.


[Multidisciplinary Management and Neurorehabilitation of Patients with Amyotrophic Lateral Sclerosis].
Patients with amyotrophic lateral sclerosis require comprehensive care with a multidisciplinary approach, which is individually adjusted to each patient. The goals of neurorehabilitation should be adjusted to the stage of disease. In early stages, physical therapy is focused on preserving and optimizing motor and respiratory function. At this stage, family should be involved to partake in desired activities and be informed regarding the natural course of the disease. In late stages, physical therapy is focused on preventing respiratory complications and contractures, and orthotics may also be recommended. The onset of dysarthria should trigger swallowing and pulmonary function testing. Swallowing maneuvers should be tried at the onset of symptoms, later feeding tubes or percutaneous gastrostomy tube is necessary. Noninvasive mechanical ventilation may delay the need of tracheostomy and invasive mechanical ventilation. The key objectives of multidisciplinary teams are to optimize medical care, facilitate communication, and thus to improve the quality of care and quality of life.


Ossification of the posterior longitudinal ligament in not only the cervical spine, but also other spinal regions: analysis using multidetector computed tomography of the whole spine.
A prospective cohort study. To evaluate ossification of the posterior longitudinal ligament (OPLL) of the whole spine in patients with cervical OPLL and to analyze which types of cervical OPLL were associated with the other lesions in the thoracic and/or lumbar spine. OPLL is most frequently seen in the cervical spine. The coexisting ossified lesions are sometimes observed in other spinal regions. However, coexisting OPLL in other spinal regions have not yet been precisely evaluated in patients with cervical OPLL. One hundred seventy-eight patients with a diagnosis of cervical OPLL whose plain radiographs were obtained were included. Computed tomographic images of the whole spine were obtained. The ossification index (OS index) was newly determined according to the sum of the levels of vertebral bodies and intervertebral discs with OPLL. The patients were divided into 2 groups, the group that had OPLL only in the cervical spine (C group) and the group that had OPLL in multilevel spinal regions other than the cervical spine (M group). Ninety-five (53.4%) had OPLL not only in the cervical spine, but also in other spinal regions. The M group had more females than the C group. The incidence of bridge formation in the cervical spine was higher in M group than in C group. More females had a high OS index. A positive correlation was found between the OS index of the cervical spine and the OS index of the thoracic and lumbar spine; however, the r value was small. This study demonstrated that more than half of the patients with cervical OPLL had coexisting OPLL in the thoracic and/or lumbar spine. We strongly recommend computed tomographic analysis of the whole spine for patients with radiographical evidence of OPLL in the cervical spine for the early detection of additional sites of ossification.


Effects of hyperbaric factors on lidocaine-induced apoptosis in spinal neurons and the role of p38 mitogen-activated protein kinase in rats with diabetic neuropathic pain.
The application of lidocaine can lead to nerve damage. Evidence suggests that patients with diabetic neuropathy are at a higher risk for neurotoxicity. In the present study, the successful induction of diabetic neuropathic pain (DNP) in rats via a high-sugar, high-fat diet and intraperitoneal injection of 1% streptozotocin was verified and pronounced tactile allodynia was observed. It was found that intrathecal injections of hyperbaric lidocaine produced motor blocks of longer durations in the DNP model rats than in nondiabetic rats, or in DNP model rats injected with isobaric lidocaine. Histology of the lumbar 4-5 spinal cord revealed a significant difference in neuropathology between the DNP and nondiabetic rats. Moreover, edematous neurons and TUNEL-positive cells were observed in the hyperbaric lidocaine group. It was also found that the inhibition of p38 mitogen-activated protein kinase (p38MAPK) played a neuroprotective role in response to hyperbaric lidocaine-induced apoptosis in DNP rats, which indicates that p38MAPK plays a key role in the regulation of hyperbaric lidocaine-induced apoptosis in DNP rats. These findings suggest that hyperbaric lidocaine can promote spinal cord neuronal apoptosis in rats with DNP. Furthermore, p38MAPK might play a key role in the regulation of hyperbaric lidocaine-induced apoptosis in rats with DNP.


Potential biomarkers for oral squamous cell carcinoma: proteomics discovery and clinical validation.
Oral squamous cell carcinoma (OSCC) is the worldwide concerned cancer. In spite of the advances in treatment, the 5-year survival rate has only increased subtly during the past two decades, which is largely due to the advanced stages of disease at diagnosis and the frequent development of relapse and second primary tumors. Therefore, the identification of underlying OSCC protein biomarker during cancer initiation and progression could aid the diagnosis and treatment of OSCC. In this review, recent researches on proteomics analysis of tissue, saliva, and serum for early detection and evaluation aggressiveness and occurrence of OSCC were summarized. The emphasis is placed on early detection by tissues, saliva, and serum of patients with histologically defined OSCC patients. Although lots of researches for searching OSCC protein biomarker have done, few common protein biomarkers have been detected. Low-redundant protein in tissues, saliva, and serum from OSCC may more accurately reflected the progression of OSCC, so novel approach for the depth research strategy and the sample choice for proteomics are of importance in OSCC biomarker discovery.


Morphological and molecular characterization, sexual reproduction, and pathogenicity of Setosphaeria rostrata isolates from rice leaf spot.
Setosphaeria rostrata, a common plant pathogen causing leaf spot disease, affects a wide range of plant species, mainly grasses. Fungi were isolated from brown spots on rice leaves throughout Peninsular Malaysia, and 45 isolates were identified as Setosphaeria rostrata The isolates were then characterized using morphological and molecular approaches. The mating type was determined using PCR amplification of the mating type alleles, and isolates of opposite mating types were crossed to examine sexual reproduction. Based on nuclear ribosomal DNA ITS1-5.8S-ITS2 region (ITS) and beta-tubulin (BT2) sequences, two phylogenetic trees were constructed using the maximum likelihood method; S. rostrata was clustered in one well-supported clade. Pathogenicity tests showed that S. rostrata isolates are pathogenic, suggesting that it is the cause of the symptoms. Mating-type analyses indicated that three isolates carried the MAT1-1 allele, and the other 42 isolates carried MAT1-2 After isolates with opposite mating types were crossed on Sach's medium and incubated for 3 wk, six crosses produced pseudothecia that contained eight mature ascospores, and 12 other crosses produced numerous pseudothecia with no ascospores. To our knowledge, this is the first report on S. rostrata isolated from leaf spots on rice.


Motorcyclists and pillion passengers with open lower-limb fractures: a study using TARN data 2007-2014.
Introduction We aimed to identify population demographics of motorcyclists and pillion passengers with isolated open lower-limb fractures, to ascertain the impact of the revised 2009 British Orthopaedic Association/British Association of Plastic Reconstructive and Aesthetic Surgeons joint standards for the management of open fractures of the lower limb (BOAST 4), in terms of time to skeletal stabilisation and soft-tissue coverage, and to observe any impact on patient movement. Methods Retrospective cohort data was collected by the Trauma Audit and Research Network (TARN). A longitudinal analysis was performed between two timeframes in England (pre-and post-BOAST 4 revision): 2007-2009 and 2010-2014. Results A total of 1564 motorcyclists and 64 pillion passengers were identified. Of these, 93% (1521/1628) were male. The median age for males was 30.5 years and 36.7 years for females. There was a statistically significant difference in the number of patients who underwent skeletal stabilisation (49% vs 65%, P < 0.0001), the time from injury to skeletal stabilisation (7.33 hours vs 14.3 hours, P < 0.0001) and the proportion receiving soft-tissue coverage (26% vs 43%, P < 0.0001). There was no difference in the time from injury to soft-tissue coverage (62.3 hours vs 63.7 hours, P = 0.726). The number of patients taken directly to a major trauma centre (or its equivalent) increased between the two timeframes (12.5% vs, 41%, P < 0.001). Conclusions Since the 2009 BOAST 4 revision, there has been no difference in the time taken from injury to soft-tissue coverage but the time from injury to skeletal stabilisation is longer. There has also been an increase in patient movement to centres offering joint orthopaedic and plastic care.


Are Residents Prepared for Surgical Cases? Implications in Patient Safety and Education.
In surgical education, the areas of focus and evaluation are skewed toward technical skill and operative knowledge; less emphasized is familiarity with the patient's medical history. The purposes of this study were to characterize how surgical trainees prepare for cases and to determine the comprehensiveness of their preparation. A 27-question survey was created through a web-based software program and distributed to all resident physicians and fellows in the Departments of Surgery, Neurosurgery, and Otolaryngology at our institution. Survey responses were collected anonymously and analyzed. Institutional review board exemption was obtained. This study was performed at Washington University in St. Louis, Missouri, at an institutional hospital setting. The survey was distributed to current surgical trainees at Washington University in St. Louis in the Departments of Surgery, Neurosurgery, and Otolaryngology. Further, 130 of 169 surgical residents and fellows completed the survey. Most respondents (96%) taught themselves case preparation. Only 57% of respondents reviewed the patients medical record before every surgery. Although most respondents (83%) felt they were prepared or very prepared from a patient-specific standpoint, only 24% felt that their handoff of a patient to on-call colleagues was comprehensive enough to include all pertinent aspects of a patient's history and expected perioperative course. From a technical perspective, most residents (63%) felt they were prepared or very prepared, and this level of comfort increased with postgraduate year; 76% of respondents would not feel comfortable telling their attending they were not adequately prepared. Although most trainees feel prepared or very prepared for cases from a patient-specific regard, only half review the patient's medical record before every surgery. Furthermore, almost all trainees have taught themselves how to prepare for surgery. This represents a critical gap in residency education and an opportunity to improve patient safety and quality of care.


Maximizing adherence and retention for women living with HIV and their infants in Kenya (MOTIVATE! study): study protocol for a randomized controlled trial.
Successful completion and retention throughout the multi-step cascade of prevention of mother-to-child HIV transmission (PMTCT) remains difficult to achieve. The Mother and Infant Visit Adherence and Treatment Engagement study aims to evaluate the effect of mobile text messaging, community-based mentor mothers (cMMs), or both on increasing antiretroviral therapy (ART) adherence, retention in HIV care, maternal viral load suppression, and mother-to-child HIV transmission for mother-infant pairs receiving lifelong ART. This study is a cluster randomized, 2 × 2 factorial, controlled trial. The trial will be undertaken in the western Kenyan counties of Migori, Kisumu, and Homa Bay. Study sites will be randomized into one of four groups: six sites will implement both text messaging and cMM, six sites will implement cMM only, six sites will implement text messaging only, and six sites will implement the existing standard of care. The primary analysis will be based on the intention-to-treat principle and will compare maternal ART adherence and maternal retention in care. This study will determine the impact of long-term (up to 12 months postpartum) text messaging and cMMs on retention in and adherence to ART among pregnant and breastfeeding women living with HIV in Kenya. It will address key gaps in our understanding of what interventions may successfully promote long-term retention in the PMTCT cascade of care. ClinicalTrials.gov, NCT02491177 . Registered on 11 March 2015.


Development and Validation of Clinical Whole-Exome and Whole-Genome Sequencing for Detection of Germline Variants in Inherited Disease.
- With the decrease in the cost of sequencing, the clinical testing paradigm has shifted from single gene to gene panel and now whole-exome and whole-genome sequencing. Clinical laboratories are rapidly implementing next-generation sequencing-based whole-exome and whole-genome sequencing. Because a large number of targets are covered by whole-exome and whole-genome sequencing, it is critical that a laboratory perform appropriate validation studies, develop a quality assurance and quality control program, and participate in proficiency testing. - To provide recommendations for whole-exome and whole-genome sequencing assay design, validation, and implementation for the detection of germline variants associated in inherited disorders. - An example of trio sequencing, filtration and annotation of variants, and phenotypic consideration to arrive at clinical diagnosis is discussed. - It is critical that clinical laboratories planning to implement whole-exome and whole-genome sequencing design and validate the assay to specifications and ensure adequate performance prior to implementation. Test design specifications, including variant filtering and annotation, phenotypic consideration, guidance on consenting options, and reporting of incidental findings, are provided. These are important steps a laboratory must take to validate and implement whole-exome and whole-genome sequencing in a clinical setting for germline variants in inherited disorders.


Integration of ER stress, oxidative stress and the inflammatory response in health and disease.
There has been much effort to define the molecular basis by which pathophysiological stimuli initiate and/or propagate the inflammatory response. Recent research endeavors on stress response from a cellular organelle called the endoplasmic reticulum (ER) shed new light on the understating of the molecular basis of the inflammatory response and its interaction with other intracellular stress signaling pathways. As a protein folding compartment and dynamic calcium store, the ER plays major roles in sensing cellular stress and mediating highly-specific signaling pathways termed Unfolded Protein Response (UPR). The UPR signaling emanating from the ER has been identified as one of the avenues leading to the inflammatory response. The integration of ER stress, oxidative stress, and the inflammatory response is critical to the pathogenesis of a variety of diseases. In this brief review, we discuss some representative evidence for the integration of ER stress, oxidative stress, and inflammation in health and disease.


The clinical manifestation and pathogenesis of enteritis associated with rotavirus and enterotoxigenic Escherichia coli infections in domestic animals.
Rotavirus and enterotoxigenic Escherichia coli (ETEC) are enteropathogens each capable of inducing diarrhoea in some animal species and man. Unstressed young animals develop an age-related resistance to infection with either rotavirus or ETEC which differs for each animal species. The effects of experimental infection of calves, lambs, foals and piglets with rotavirus and ETEC given either alone or in combination, have been examined. In general, dual infections tended to lengthen the period of age susceptibility and increase the severity of gastroenteritis, compared to infection with either agent alone. ETEC caused little or no pathological changes in the small intestine while rotavirus induced moderate inflammatory, morphological and physiological changes including reduced activity of membrane-bound digestive enzymes. In dual infections, mucosal lesions were more severe than those seen after rotavirus infection and ETEC proliferation in the lumen of the small intestine was greater than in animals infected with ETEC alone. Two distinct mechanisms of diarrhoea, presumably, were involved; net fluid hypersecretion into the lumen of the gut mediated by ETEC enterotoxin(s), and brush border maldigestion and malabsorption which was caused by rotavirus infection of the small intestine.


Kinetic and thermodynamic characterization of C-N bond rotation by N-methylacetohydroxamic acid in aqueous media.
Hydroxamic acids (HAs) perform tasks in medicine and industry that require bidentate metal binding. The two favored conformations of HAs are related by rotation around the C(=O)-N bond. The conformations are unequal in stability. Recently, we reported that the most stable conformation of a small secondary HA in water places the oxygen atoms anti to one another. The barrier to C-N bond rotation may therefore modulate metal binding by secondary HAs in aqueous media. We have now determined the activation barrier to C-N rotation from major to minor conformation of a small secondary HA in D2O to be 67.3 kJ/mol. The HA rotational barrier scales with solvent polarity, as is observed in amides, although the HA barrier is less than that of a comparable tertiary amide in aqueous solution. Successful design of new secondary HAs to perform specific tasks requires solid understanding of rules governing HA structural behavior. Results from this work provide a more complete foundation for HA design efforts.


A highly fluorescent simultaneous azo dye technique for demonstration of nonspecific alkaline phosphatase activity.
We describe a fluorescent histochemical technique for detection of nonspecific alkaline phosphatase (APase) in cells. The technique utilizes standard azo dye chemistry with naphthol AS-MX phosphate as substrate and fast red TR as the diazonium salt. The reaction product is a highly fluorescent red precipitate. Pre-implantation mouse embryos were used to establish optimal fixation and staining protocols and the specificity and sensitivity of the method. Fixation was in 4% paraformaldehyde for 1 hr, as glutaraldehyde induced autofluorescence of the cells. Maximal discriminable staining was detected after 15-20 min in the stain solution. The stain solution itself proved to be non-fluorescent, thus allowing visual observation of the progress of the staining reaction by fluorescence microscopy in its presence. To test the specificity of this fluorescent APase stain, a variety of cell types of known APase reactivity were stained by this protocol. Mouse lymphocytes and STO fibroblasts were negative, whereas F9 teratocarcinoma cells, intestinal epithelial cells, and rat fetal primordial germ cells were all found to be highly positive for APase activity, in agreement with published results on APase localization in these cells.


Genetic variability in the ITS and IGS regions of the ribosomal DNA of Acremonium cavaraeanum exhibiting antimicrobial activity.
Endophytic microorganisms represent promising alternatives for obtaining new drugs of biotechnological importance. In this study, the endophytic species Acremonium cavaraeanum (A1a) isolated from Cocos nucifera was cultivated for the production of secondary metabolites, and its extracts and fractions were evaluated by the dilution method (MIC). The EtOAc extracts and MeOH fractions were tested against Gram-positive and -negative bacteria, and had an MIC of 125 µg/mL when evaluated in the EtOAc extract (EBI). The EtOAc extract (EBII) had an MIC of 62.25 µg/mL for Staphylococcus aureus and an MIC between 125 and 250 µg/mL for Gram-negative bacteria. The methanolic fractions showed activity with MIC between 125 and 250 µg/mL for all bacteria tested. The IGS region of the rDNA repeat unit of genomic DNA was analyzed by PCR/RFLPs, including endonucleases PstI, BamHII, HinfI, and EcoRI. The physical maps showed different restriction sites for the 6 Acremonium sp isolates, and revealed 5 RFLP patterns. The results showed that isolates of the same Acremonium species exhibited variation in this specific region. The sequences of ITS1-5.8S-ITS2 regions were aligned by Clustal W using the neighbor joining method, which grouped the isolates into 5 distinct clusters. This study aimed to evaluate the genetic diversity of A. cavaraeanum crops exhibiting antibacterial activity. The results of this study indicate that different fungal genetic isolates have biotechnological potential for the production of active bio-compounds against several human pathogens.


Insulin mediators in man: effects of glucose ingestion and insulin resistance.
Insulin mediators (inositol phosphoglycans) have been shown to mimic insulin action in vitro and in intact mammals, but it is not known which mediator is involved in insulin action under physiological conditions, nor is it known whether insulin resistance alters the mediator profile under such conditions. We therefore investigated the effects of glucose ingestion on changes in the bioactivity of serum inositol phosphoglycan-like substances (IPG) in healthy men and insulin resistant (obese, non-insulin-dependent diabetic) men. Two classes of mediators were partially purified from serum before and after glucose ingestion. The first was eluted from an anion exchange resin with HCl pH 2.0, and bioactivity was determined by activation of pyruvate dehydrogenase in vitro. The second was eluted with HCl pH 1.3, and bioactivity was determined by inhibition of cyclic AMP-dependent protein kinase. In healthy men, the bioactivity of the pH 1.3 IPG was not altered by glucose ingestion, whereas bioactivity of the pH 2.0 IPG increased to approximately 120% of the pre-glucose ingestion value at 60-240 min post-glucose ingestion (p < 0.05 vs pre-glucose). There was no change in either IPG after glucose ingestion in the insulin-resistant group. These data suggest that the pH 2.0 IPG plays an important role in mediating insulin's effect on peripheral glucose utilization in man under physiological conditions. The data further show, for the first time, a defective change in the bioactivity of an insulin mediator isolated from insulin-resistant humans after hyperinsulinaemia, suggesting that inadequate generation/release of IPGs is associated with insulin resistance.


[On the origin of the horseshoe. A preliminary report (author's transl)].
The question of the origin of the horse-shoe is reconsidered and China is pointed out as the site of origin. The theory is put forward that the Mongolian people living north of China and having constant fights with the Chinese have learnt the horseshoes with nails from the Chinese and that the Huns on their travel westwards have brought this type of horseshoe to Europa. The theory is substantiated from authoritative sources. The Chinese ministry of agriculture and forestry has given the information that horseshoes with nails have been used here for more than 2000 years. The possibility exists -- however -- that the Mongolians having good knowledge of the treatment of various metals, have produced the first horseshoes and given the Chinese the knowledge of that procedure.


Structure of aplasmomycin.
A new antibiotic, aplasmomycin, was isolated from a broth cultivated with a marine isolate of actinomycete, and inhibits Gram-positive bacteria in vitro and Plasmodium berghei in vivo. It is a natural ionophore and the structure of the Ag-salt was solved by an X-ray crystallographic analysis. It has symmetric structure having boron in the centre of the molecule.


Antiapoptotic microenvironment of acute myeloid leukemia.
We showed previously that tumor-derived supernatant (TSN) from acute myeloid leukemia (AML) myeloblasts inhibits peripheral blood T cell activation and proliferation, rendering the T cells functionally incompetent. We show here that the AML TSN also significantly delays apoptosis of both resting and stimulated T cells, as judged by reduction in annexin V/propidium iodide staining. In addition, we show that this is not unique to T cells and that AML TSN inhibits apoptosis of peripheral B cells, neutrophils, and monocytes. Furthermore, it also enhances the survival of other AML myeloblasts with lower viability. Investigations into the mechanism demonstrate a reduction in the cleavage of procaspase-3, -8, and -9 and the caspase substrate, poly(ADP-ribose)polymerase (PARP). This may be due to Bcl-2, which is normally down-regulated in CD3/CD28-stimulated T cells, but is maintained in the presence of AML TSN. We conclude that AML cells generate an antiapoptotic microenvironment that favors the survival of malignant cells, but also inhibits apoptosis of other normal hemopoietic cells. Reversal of these immunosuppressive effects and restoration of normal immune responses in patients with AML would improve the success of immunotherapy protocols.


Bilateral transnasal vidian neurectomy in the management of chronic rhinitis.
Bilateral transnasal vidian neurectomy was performed on 276 patients between 1983 and 1991. The indications for operation were intractable vasomotor rhinitis, resistant allergic rhinitis and recurrent nasal polyposis. Two hundred and fifty-eight patients were contacted and long-term results showed that 88 per cent of the patients had an excellent result.


Effects of added chelated trace minerals, organic selenium, yeast culture, direct-fed microbials, and Yucca schidigera extract in horses: II. Nutrient excretion and potential environmental impact.
The objective of this study was to test the hypothesis that an equine diet formulated with chelated trace minerals, organic selenium, yeast culture, direct-fed microbials (DFM) and Yucca schidigera extract would decrease excretion of nutrients that have potential for environmental impact. Horses were acclimated to 100% pelleted diets formulated with (ADD) and without (CTRL) the aforementioned additives. Chelated sources of Cu, Zn, Mn, and Co were included in the ADD diet at a 100% replacement rate of sulfate forms used in the CTRL diet. Additionally, the ADD diet included organic selenium yeast, DFM, and Yucca schidigera extract. Ten horses were fed the 2 experimental diets during two 42-d periods in a crossover design. Total fecal and urine collection occurred during the last 14 d of each period. Results indicate no significant differences between Cu, Zn, Mn, and Co concentrations excreted via urine (P > 0.05) due to dietary treatment. There was no difference between fecal Cu and Mn concentrations (P > 0.05) based on diet consumed. Mean fecal Zn and Co concentrations excreted by horses consuming ADD were greater than CTRL (P < 0.003). Differences due to diet were found for selenium fecal (P < 0.0001) and urine (P < 0.0001) excretions, with decreased concentrations found for horses consuming organic selenium yeast (ADD). In contrast, fecal K (%) was greater (P = 0.0421) for horses consuming ADD, whereas concentrations of fecal solids, total N, ammonia N, P, total ammonia, and fecal output did not differ between dietary treatments (P > 0.05). In feces stockpiled to simulate a crude composting method, no differences (P > 0.05) due to diet were detected for particle size, temperature, moisture, OM, total N, P, phosphate, K, moisture, potash, or ammonia N (P > 0.05). Although no difference (P = 0.2737) in feces stockpile temperature due to diet was found, temperature differences over time were documented (P < 0.0001). In conclusion, the addition of certain chelated mineral sources, organic Se yeast, DFM, and Yucca schidigera extract did not decrease most nutrient concentrations excreted. Horses consuming organic selenium as part of the additive diet had lower fecal and urine Se concentrations, as well as greater fecal K concentrations.


Candida albicans endocarditis in a child with acute lymphoblastic leukemia: A dreaded complication of intensive chemotherapy.
Candida endocarditis is a rare entity during febrile neutropenia due to early introduction of empirical antifungal therapy. Early surgical intervention has diagnostic and therapeutic importance in Candida endocarditis. We report a case of Candida albicans endocarditis in a child with acute lymphoblastic leukemia on chemotherapy. The role of surgical intervention is discussed.


Psychological and behavioral differences between low back pain populations: a comparative analysis of chiropractic, primary and secondary care patients.
Psychological, behavioral and social factors have long been considered important in the development of persistent pain. Little is known about how chiropractic low back pain (LBP) patients compare to other LBP patients in terms of psychological/behavioral characteristics. In this cross-sectional study, the aim was to investigate patients with LBP as regards to psychosocial/behavioral characteristics by describing a chiropractic primary care population and comparing this sample to three other populations using the MPI-S instrument. Thus, four different samples were compared. A: Four hundred eighty subjects from chiropractic primary care clinics. B: One hundred twenty-eight subjects from a gainfully employed population (sick listed with high risk of developing chronicity). C: Two hundred seventy-three subjects from a secondary care rehabilitation clinic. D: Two hundred thirty-five subjects from secondary care clinics. The Swedish version of the Multidimensional Pain Inventory (MPI-S) was used to collect data. Subjects were classified using a cluster analytic strategy into three pre-defined subgroups (named adaptive copers, dysfunctional and interpersonally distressed). The data show statistically significant overall differences across samples for the subgroups based on psychological and behavioral characteristics. The cluster classifications placed (in terms of the proportions of the adaptive copers and dysfunctional subgroups) sample A between B and the two secondary care samples C and D. The chiropractic primary care sample was more affected by pain and worse off with regards to psychological and behavioral characteristics compared to the other primary care sample. Based on our findings from the MPI-S instrument the 4 samples may be considered statistically and clinically different. Sample A comes from an ongoing trial registered at clinical trials.gov; NCT01539863 , February 22, 2012.


[Anterior joints of the thoracic cage].
The chondro-sternal, interchondral, costo-chondral joints and the upper and lower sternal joints were studied in the thorax of 60 children and human adults. Chondro-sternal joints occur as frequent symphyses in the 5th, 6th and 7th joints or ellipsoid joints which are mainly found in the 2nd, 3rd and 4th joints. Diarthrosis frequency increases with age in every joint. An articular space appears particularly in the lower part of the 2nd, 3rd and 4th joints; in fewer cases a space is found in the upper part of the 5th, 6th and 7th joints. These partial spaces disappear with age and are replaced by spaces occupying the whole articulation. The first joint is a synchondrosis which does not vary with age. Interchondral joints are diarthrodial or trochoid joints from earliest childhood and their frequency increases with age. No direct articular contact was observed between the 9th and 10th costal cartilages. Costo-chondral joints are synarthrosis. The upper sternal joint, which is a synchondrosis in the child, may develop into a non-synovial cavity with age, or even turn into synostosis. The lower sternal joint is a synchondrosis which develops partially towards synostosis.


An Anti-Inflammatory PPAR-γ Agonist from the Jellyfish-Derived Fungus Penicillium chrysogenum J08NF-4.
An investigation of the jellyfish-derived fungus Penicillium chrysogenum J08NF-4 led to the isolation of two new meroterpene derivatives, chrysogenester (1) and 5-farnesyl-2-methyl-1-O-methylhydroquinone (2), and four known farnesyl meroterpenes. Docking analysis of 1 showed that it binds to PPAR-γ in the same manner as the natural PPAR-γ agonist amorfrutin B (7). Compound 1 activated PPAR-γ in murine Ac2F liver cells and increased nuclear PPAR-γ protein levels in murine RAW 264.7 macrophages. Because one of the main biological functions of PPAR-γ agonists is to suppress inflammatory response, an in vitro study was performed to explore the anti-inflammatory potency of 1 and the mechanism involved. In RAW 264.7 macrophages, 1 inhibited phosphorylation of the NF-κB p65 subunit and suppressed the expression of the pro-inflammatory mediators iNOS, NO, COX-2, TNF-α, IL-1β, and IL-6. We propose 1 suppresses inflammatory responses by activating PPAR-γ and subsequently downregulating the NF-κB signaling pathway, thus reducing the expressions of pro-inflammatory mediators.


Ultrastructure of peripheral blood lymphocytes in some degenerative central nervous system disease.
The ultrastructure of peripheral blood lymphocytes of 30 children with degenerative central nervous system diseases was analyzed. The affected children were divided into four groups. Lysosomal storage were characterized by the storage of membrane-bound inclusions in peripheral lymphocytes. Ceroidlipofuscinosis was manifested by the presence of curvilinear bodies. The appearance of abnormal mitochondria was found in mitochondrial encephalopathies. The tubuloreticular structures seen in lymphocytes of some unclassified cases suggested viral factors that acted in prenatal life. All findings confirm the role of peripheral lymphocytes analysis in the diagnosis of degenerative central nervous system diseases.


Implementation and evaluation of an opioid overdose education and naloxone distribution (OEND) program at a Veterans Affairs Medical Center.
In recognition of the importance of safe and effective pain management, the Department of Veterans Affairs and the Office of the Under Secretary for Health have encouraged implementation of opioid overdose education and naloxone distribution (OEND) programs at Veterans Affairs Medical Centers (VAMCs). An OEND program was developed in August 2015 and implemented in September 2015 at a VAMC which allowed for pharmacist-lead individual and group patient education. An OEND consult service was developed to streamline referrals of patients for naloxone education and distribution. At the conclusion of the class, participants were ordered a naloxone auto-injector or nasal spray kit. To evaluate the utility of this quality-improvement initiative, data was collected from September 2015 until May 2016. Examples of data collected included participant satisfaction with education, risk for accidental overdose, and number of naloxone kits dispensed to participants. Of a total of 243 consults placed, 71 individuals participated in OEND education. A large quantity of consults were discontinued due to patients no-showing education. Sixty-four consult referrals were identified to have a mental health diagnosis. Most participants who received education had a risk for accidental opioid overdose of 14%. Sixty-nine education participants were provided a naloxone kit. Based on the OEND class survey, participants felt that their knowledge of accidental opioid overdose increased and were generally satisfied with the education. OEND educated 30% of the Veterans referred into the program via the consult service, the majority of whom were at a relatively low risk for opioid overdose.


Does priming for mastery goals improve the performance of students with an entity view of ability?
There is evidence that an entity view of ability (where ability is viewed as a fixed entity that cannot be changed) is linked with social comparison goals and poor performance. On the other hand, an incremental view of ability (where ability is viewed as an acquirable skill) is linked with a mastery goal orientation and positive achievement outcomes. On these bases, the present study sought evidence that priming students with an entity view of ability to pursue mastery goals would result in improved performance. Participants were 48 students with an entity view of ability, and 48 students with an incremental view of ability. We used a 2 (views of ability: entity, incremental) x 2 (performance feedback: success, failure) x 2 (goal priming: mastery, social comparison) between-subjects factorial design to examine the effects of goal priming on performance for students with either an incremental or entity view of ability following either success or failure feedback. Prior to, and following, performance feedback, participants completed parallel measures of state anxiety. Participants were then primed for either social comparison goals prior to attempting to solve 16 Unicursal (tracing puzzle) tasks. Their performance on a subsequent set of Unicursal tasks was then examined. Finally participants completed a State Goals Scale assessing their degree of endorsement of social comparison/mastery goals whilst working on the Unicursal tasks. The performance of students with an incremental view of ability was comparable irrespective of whether they were initially exposed to success and failure feedback and irrespective of whether they were primed for mastery or social comparison goals. However the performance of students with an entity view of ability improved when they were primed for mastery relative to social comparison goals irrespective of whether they were initially exposed to success or failure. These findings confirm the performance-limiting consequences of social comparison goals for participants with an entity view of ability, suggesting benefits in encouraging these students to pursue mastery goals.


IMPACT OF A SERIOUS GAME FOR HEALTH ON CHRONIC DISEASE SELF-MANAGEMENT: PRELIMINARY EFFICACY AMONG COMMUNITY DWELLING ADULTS WITH HYPERTENSION.
Most Americans will acquire a chronic disease during their lifetime. One of the most prevalent chronic diseases that affect Americans is hypertension (HTN). Despite the known comorbidities and increased mortality rate associated with uncontrolled HTN, most community dwelling adults with HTN do not have sufficient blood pressure control Therefore, the aim of this article is to report the preliminary efficacy of a serious game for health to enhance blood pressure control among community dwelling adults with HTN. A nonprobability sample of 116 community dwelling adults with HTN participated in this nonblinded, randomized controlled trial. Participants were randomly assigned to: (1) an intervention arm that consisted of four exposures to a serious game for health known as eSMART-HD; or (2) an attentional control arm that compromised of four exposures to screen-based HTN education. The primary outcome measure for this trial was blood pressure reduction over a four month observational period. In this study, baseline characteristics and blood pressure measurements were similar between participants in each study arm. There was no significant between-group difference in blood pressure reduction over time. However, there were significant within-group reductions in systolic and diastolic blood pressures across time among favoring participants exposed to eSMART-HD. This study establishes the preliminary efficacy of eSMART-HD that can be easily administered to community dwelling adults and facilitate clinically significant reductions in systolic and diastolic blood pressures. Future studies should assess the influential components of this promising serious game for health (eSMART-HD) combined with medication management in larger and more diverse samples of community dwelling adults with HTN.


Weekly measurements accurately represent trends in resting energy expenditure in children undergoing hematopoietic stem cell transplantation.
Resting energy expenditure (REE) measurements are optimal for accurate assessment of energy requirements and precise provision of parenteral nutrients. We previously observed significant reduction in REE during a 4-week period in children undergoing hematopoietic stem cell transplantation (HSCT). The goal of this study was to determine if weekly REE measurements could accurately represent changes in REE in the peritransplant period compared with a more frequent standard of daily measurements. Data are presented from a previously described cohort of 37 children undergoing HSCT. We performed weekly indirect calorimetry on 25 patients; of those 25, we performed daily measurements on a convenience sample of 5 children. The time course of REE was analyzed in each sample by repeated measures regression. The REE trend of the 20 weekly participants was similar to that of the 5 daily participants, reaching about 80% of predicted REE at 4 weeks posttransplant, with an average decline of 3.4% per week during 4 weeks. The results suggest that weekly REE measurements accurately characterize REE changes 4 weeks after HSCT compared with daily measurements. Characterization of these trends using weekly measurements may help guide clinical and nutrition care of these patients.


Physiological and biochemical effect of neem and other Meliaceae plants secondary metabolites against Lepidopteran insects.
This review described the physiological and biochemical effects of various secondary metabolites from Meliaceae against major Lepidopteran insect pest including, Noctuidae and Pyralidae. The biochemical effect of major Meliaceae secondary metabolites were discussed more in this review. Several enzymes based on food materials have critical roles in nutritional indices (food utilization) of the insect pest population. Several research work has been referred and the effect of Meliaceae secondary metabolites on feeding parameters of insects by demonstrating food consumption, approximate digestibility of consumed food, efficiency of converting the ingested food to body substance, efficiency of converting digested food to body substance and consumption index was reviewed in detail. Further how the digestive enzymes including a-Amylases, α and β-glucosidases (EC 184.108.40.206), lipases (EC 3.1.1) Proteases, serine, cysteine, and aspartic proteinases affected by the Meliaceae secondary metabolites was reviewed. Further effect of Meliaceae secondary metabolites on detoxifying enzymes have been found to react against botanical insecticides including general esterases (EST), glutathione S-transferase (GST) and phosphatases was reviewed. Alkaline phosphatase (ALP, E.C.18.104.22.168) and acid phosphatase (ACP, E.C.18.104.22.168) are hydrolytic enzymes, which hydrolyze phosphomonoesters under alkaline or acid conditions, respectively. These enzymes were affected by the secondary metabolites treatment. The detailed mechanism of action was further explained in this review. Acethylcholine esterase (AChE) is a key enzyme that terminates nerve impulses by catalyzing the hydrolysis of neurotransmitter, acetylcholine, in the nervous system of various organisms. How the AChE activity was altered by the Meliaceae secondary metabolites reviewed in detail.


Gene expression profiling of rat livers after continuous whole-body exposure to low-dose rate of gamma rays.
To study gene expression modulation in response to continuous whole-body exposure to low-dose-rate gamma radiation and improve our understanding of the mechanism of this impact at the molecular basis. cDNA microarray method with complete pooling of samples was used to study expression changes in the transcriptome profile of livers from rats treated with prolonged low-dose-rate ionizing radiation (IR) relative to that of sham-irradiated rats. Of the 209 genes that were two-fold-up or down-regulated, 143 were known genes of which 27 were found in previous literatures to be modulated by IR. Remarkably, there were a significant number of differentially expressed genes involved in hepatic lipid metabolism. This study showed changes in transcriptome profile of livers from low-dose irradiated rats when compared with that of sham-irradiated ones. This study will be useful for studying the metabolic changes of human exposed for long term to cosmic ray such as in space and in polar regions.


Comparison of an improved polymerase chain reaction protocol and the indirect hemagglutination assay in the detection of Eperythrozoon suis infection.
The ability of an improved polymerase chain reaction (PCR) protocol to detect Eperythrozoon suis DNA in the blood of experimentally infected nonsplenectomized pigs was evaluated. The protocol utilizes previously described E. suis-specific primers and a proprietary DNA-releasing reagent in a 2-step amplification cycle followed by visualization of the 492-bp amplification product on agarose gels. This PCR protocol successfully amplified E. suis DNA in blood from all postinfection samples and from the preinfection samples of 2 pigs, indicating preexisting natural infections. Results of the indirect hemagglutination test on serum samples from these pigs revealed that only 1 pig developed detectable antibody titers to E. suis infection during the 43-day study; that pig was determined by PCR to have been infected naturally with E. suis prior to experimental inoculation. These results confirm previous reports of poor antibody response of young pigs to E. suis infection and demonstrate the potential of PCR as a valuable tool for the diagnosis and study of E. suis infection in pigs.


Pre-treatment maximum standardized uptake value predicts outcome after frontline therapy in patients with advanced stage follicular lymphoma.
The impact of pre-treatment maximum standardized uptake value (SUVmax) on the outcome of follicular lymphoma (FL) following specific frontline regimens has not been explored. We performed a retrospective analysis of 346 patients with advanced stage follicular lymphoma (FL) without histological evidence of transformation, and analyzed the impact of SUVmax on outcome after frontline therapy. Fifty-two (15%) patients had a SUVmax >18, and a large lymph node ≥6 cm was the only factor associating with SUVmax >18 on multivariate analysis (odds ratio 2.7, 95% confidence interval [CI]: 1.3-5.3, P=0.006). The complete response rate was significantly lower among patients treated with non-anthracycline-based regimens if SUVmax was >18 (45% vs 92%, P<0.001), but not among patients treated with R-CHOP (P=1). SUVmax >18 was associated with significantly shorter progression-free survival among patients treated with non-anthracycline-based regimens (77 months vs. not reached, P=0.02), but not among patients treated with R-CHOP (P=0.73). SUVmax >18 associated with shorter overall survival (OS) both in patients treated with R-CHOP (8-year OS 70% vs. 90%, P=0.02) and non-anthracycline-based frontline regimens (8-year OS 50% vs 85%, P=0.001). In conclusion, pre-treatment PET scan has prognostic and predictive value in patients with advanced stage FL receiving frontline treatment.


Malakoplakia mimicking carcinoma metastatic to lung.
Malakoplakia is a rare inflammatory disorder which infrequently involves sites outside of the lower genitourinary or gastrointestinal tract. We report a case of malakoplakia in which the patient presented with a left renal mass and bilateral pulmonary nodules suggestive of metastatic renal carcinoma. Postmortem cultures of the lesions grew E. coli; macrophages at both sites contained gram-negative bacilli and numerous Michaelis-Gutmann bodies. X-ray spectroscopic analysis of the bodies showed wide variation in calcium, phosphorus, and iron content, suggesting that Michaelis-Gutmann bodies were formed in part by the deposition of amorphous salts.


Role of hydrogen abstraction acetylene addition mechanisms in the formation of chlorinated naphthalenes. 1. A quantum chemical investigation.
The addition of chloroacetylene or tetrachlorovinylacetylene to 2,4,5-trichlorophenyl radicals, leading to the formation of tetra-, penta-, and hexachloronaphthalene congeners, has been explored at the M06-2X/6-311+G(3df,3p)//B3LYP/6-31G(d) level of theory. The accuracy of this method was justified by comparing the barriers of several pertinent reactions against energies from single point calculations at the B3LYP/cc-pVDZ, CCSD(T)/6-31G(d), and G2MS levels. Bittner-Howard and Frenklach hydrogen abstraction acetylene addition mechanisms were developed, as was a channel based on acetylene additions to chlorinated [4.2.0]octa-1,3,5-trien-7-yl congeners. While the latter channel exhibits relatively high C2HCl addition barriers and may be a minor growth channel at best, both the Bittner-Howard and Frenklach sequences appear facile. In all mechanisms, the additions of C2HCl leading to a β-chlorinated adduct is favored by ∼15 kJ mol(-1) relative to the α-chlorinated analogue, and the addition products typically access a variety of facile cyclization channels. The α-chlorinated product of C2HCl addition to 2,4,5-trichlorophenyl, however, undergoes a particularly rapid Cl-loss leading to 1-ethynyl-2,4,5-trichlorobenzene, effectively shutting down further growth. Generalization implies that α-chlorinated C6H5-CH═CH congeners do not participate in growth reactions. Addition of 2,4,5-trichlorophenyl to the C≡C bond of tetrachlorovinylacetylene and subsequent cyclization is found to be a facile route to hexachloronaphthalene formation and may be operative in fully chlorinated systems where the C6Cl5-CCl═CCl congeners cannot participate in the major growth processes.


[The current state of the evidence of malignant tumors of the eye and its adnexa (dg. C69) in the Slovak Republic and in the Czech Republic].
The area of ophthalmooncology includes not only intraocular tumors but also adnexal and extraocular tumors, relatively rare malignancies. To get valid data and to study the incidence, diagnosis and treatment is extremely difficult. The most frequently occurring intraocular tumor in adults is malignant melanoma, in children it is retinoblastoma. We present the results of the nationwide group of patients based on the diagnosis report C69 - Tumors of the eye and adnexa according to data of the National Cancer Registry in Slovak Republic. We monitor the incidence, distribution by age group, survival and staging. In the second part of the thesis analyzed data are compared with the data from Cancer Registry in the Czech Republic. After analyzing the data, we found that the incidence of intraocular tumors have been reported to be comparable with neighbouring countries. The classification of the disease in different stages due to TNM classifying in the report is below 50 % in Slovakia. The incidence observed in each year ranges from 0.6 to 1.0 per 100 000 inhabitants. Survival of patients with dg. C69 is comparable with other countries. The proportion of clinically defined stages of the disease is in the database of Slovakia lower than in the Czech Republic. The delay of inserting data of patients in the National Cancer Registry in Slovakia and the availability of data for analysis is currently unsatisfactory. In Slovakia are available data only up to year 2003, in Czech Republic up to year 2009.


[Research progress on the relationship between SLCO1B1 gene and neonatal jaundice].
Organic anion transporter 2 (OATP2) is an uptake transporter located on the basolateral membrane of human hepatocytes. It mediates the transportation of various organic solutes including bilirubin and impacts bilirubin metabolism. It is encoded by the gene of solute carrier organic anion transporter family member 1B1 and the gene variants that inhibit hepatic bilirubin uptake function may reduce the normal functional level of bilirubin elimination and result in neonatal hyperbilirubinemia. In recent years, some studies have indicated that variants of SLCO1B1 are associated with neonatal jaundice. This article reviews the research advance in SLCO1B1 with respect to the structure and function and the relationship between SLCO1B1 mutations and neonatal jaundice.


Reactive hypoglycemic tendency among arsonists.
A reactive hypoglycemic tendency during the glucose tolerance test was connected with fire-setting behavior. These hypoglycemic arsonists not only fulfilled the criteria for either intermittent explosive disorder or violent antisocial personality, but also those for borderline personality disorder. They seemed to differ from other arsonists in alcohol abuse and behavior during the fire-setting acts, and, in personality profile in MMPI, also differed from classical violent offenders with intermittent explosive disorder.


Idiopathic fibrosing pancreatitis causing obstructive jaundice in young adults: two case reports and literature review.
Chronic pancreatitis is uncommon in children and adolescents. A rare syndrome of idiopathic fibrosing pancreatitis has been reported in 28 patients, ages 4 months to 17 yr. We report two young adults with this syndrome who presented with obstructive jaundice. Both were seen in adult gastroenterology practice, and one is the oldest reported patient at age 20. We review the clinical features, diagnosis, and treatment of this disorder, which merits attention by adult gastroenterologists.


Autoimmune hepatitis as a complication of common variable immunodeficiency.
In common variable immunodeficiency (CVID) there is a deregulation of the immune system, which frequently leads to an increased risk of infections, but also to autoimmunity phenomena. Autoimmune hepatitis may develop at any time of CVID's evolution, but it is difficult to diagnose due to the frequent absence of autoantibodies and low levels of IgG. Early diagnosis is important because targeted treatment may allow disease improvement. We present a case of autoimmune hepatitis in a patient with CVID.


[Ethical problems in modern sexology].
The paper is focused on problems of sexual minorities. The authors discuss their position in society, terminological problems and in particular questions associated with ethical problems of treatment of paraphilics. The authors differentiate between essential, possible and not indicated therapeutic provisions. They also focus attention on ethical aspects of different types of treatment of sexual delinquents (surgical, pharmacological and psychotherapeutic methods), whereby they emphasize in particular the necessity to obtain the patient's informed consent. According to the authors skilled therapy gives a chance to reintegrate the paraphilic patient into society and to protect victims delinquent sexual behaviour.


Automatic detection of retinal anatomy to assist diabetic retinopathy screening.
Screening programmes for diabetic retinopathy are being introduced in the United Kingdom and elsewhere. These require large numbers of retinal images to be manually graded for the presence of disease. Automation of image grading would have a number of benefits. However, an important prerequisite for automation is the accurate location of the main anatomical features in the image, notably the optic disc and the fovea. The locations of these features are necessary so that lesion significance, image field of view and image clarity can be assessed. This paper describes methods for the robust location of the optic disc and fovea. The elliptical form of the major retinal blood vessels is used to obtain approximate locations, which are refined based on the circular edge of the optic disc and the local darkening at the fovea. The methods have been tested on 1056 sequential images from a retinal screening programme. Positional accuracy was better than 0.5 of a disc diameter in 98.4% of cases for optic disc location, and in 96.5% of cases for fovea location. The methods are sufficiently accurate to form an important and effective component of an automated image grading system for diabetic retinopathy screening.


Modeling Psychological Attributes in Psychology - An Epistemological Discussion: Network Analysis vs. Latent Variables.
Network Analysis is considered as a new method that challenges Latent Variable models in inferring psychological attributes. With Network Analysis, psychological attributes are derived from a complex system of components without the need to call on any latent variables. But the ontological status of psychological attributes is not adequately defined with Network Analysis, because a psychological attribute is both a complex system and a property emerging from this complex system. The aim of this article is to reappraise the legitimacy of latent variable models by engaging in an ontological and epistemological discussion on psychological attributes. Psychological attributes relate to the mental equilibrium of individuals embedded in their social interactions, as robust attractors within complex dynamic processes with emergent properties, distinct from physical entities located in precise areas of the brain. Latent variables thus possess legitimacy, because the emergent properties can be conceptualized and analyzed on the sole basis of their manifestations, without exploring the upstream complex system. However, in opposition with the usual Latent Variable models, this article is in favor of the integration of a dynamic system of manifestations. Latent Variables models and Network Analysis thus appear as complementary approaches. New approaches combining Latent Network Models and Network Residuals are certainly a promising new way to infer psychological attributes, placing psychological attributes in an inter-subjective dynamic approach. Pragmatism-realism appears as the epistemological framework required if we are to use latent variables as representations of psychological attributes.


From the determination of the accurate equilibrium structure of 1-methylthymine by gas electron diffraction and coupled cluster computations to the observation of methylation and flexibility effects in pyrimidine nucleobases.
1-Methylthymine is of particular interest because it can be considered as a simple model of thymidine, in which deoxyribose attaches to thymine precisely at the N1 atom. The structure of this molecule is still unknown and so far has been experimentally studied for the first time in this work. The semiexperimental equilibrium structural parameters (r(e)(se)/∠(e)(se)) of 1-methylthymine have been determined by the gas electron diffraction (GED) method, taking into account vibrational corrections calculated with the use of the anharmonic (cubic) MP2/cc-pVTZ force constants. The methyl torsion around the C–N bond has been treated as a large-amplitude motion. For the first time, the structure of this molecule has been optimized by the very time-consuming coupled-cluster method (CCSD(T)(ae)) with the triple-ζ (cc-pwCVTZ) basis set. The obtained results have been extrapolated to the quadruple-ζ basis set at the MP2 level. It has been revealed that the methylation of uracil, especially at the nitrogen atom, leads to an increase in the flexibility of the nucleobase as well as a noticeable deformation of the pyrimidine ring.


Evaluating the geometric and dosimetric impact of applying anisotropic CTV to PTV margins in image-guided post-prostatectomy radiation therapy.
Guidelines for clinical target volume (CTV) to planning target volume (PTV) margins in post-prostatectomy radiation therapy (PPRT) are varied and often not clearly defined. Assessment of appropriateness of margins is commonly measured on prevalence of geographic miss. Cone-beam CT (CBCT) images (n = 92) for 10 PPRT patients were incorporated to provide on-treatment information on the appropriateness of six different CTV expansion margins in terms of geographic miss and change in dose-volume statistics for CTV, rectum and bladder. Uniform margins included 10 mm, 5 mm, 10 mm + 5 mm posteriorly and 5 mm + 3 mm posteriorly. In addition, two anisotropic margins were evaluated by separating the superior and inferior portions of the CTV before expansion. Treatment plans were created for each PTV retrospectively. The frequency of geographic miss was the smallest for the large uniform expansions but resulted in the highest organ-at-risk (OAR) doses. Geographic miss in the smaller uniform and anisotropic PTVs was more prevalent but commonly to a small volume < 1% of CTV. When averaged over all CBCT fractions, V95% dose for all CTV margins remained > 99%. The anisotropic expansions generated smaller irradiated target volumes and consequently saw up to 7.3% reduction in bladder dose when compared with similar uniform expansion margins. Supplementing the incidence of geographic miss with dosimetric information on target coverage and OAR doses provides more informed assessment of the appropriateness of different CTV expansion margins. Our study extends the evaluation of anisotropic margins for PPRT.