Binding to retinoblastoma pocket domain does not alter the inter-domain flexibility of the J domain of SV40 large T antigen.
Simian Virus 40 uses the large T antigen (Tag) to bind and inactivate retinoblastoma tumor suppressor proteins (Rb), which can result in cellular transformation. Tag is a modular protein with four domains connected by flexible linkers. The N-terminal J domain of Tag is necessary for Rb inactivation. Binding of Rb is mediated by an LXCXE consensus motif immediately C-terminal to the J domain. Nuclear magnetic resonance (NMR) and small angle X-ray scattering (SAXS) were used to study the structural dynamics and interaction of Rb with the LXCXE motif, the J domain and a construct (N(260)) extending from the J domain through the origin binding domain (OBD). NMR and SAXS data revealed substantial flexibility between the domains in N(260). Binding of pRb to a construct containing the LXCXE motif and the J domain revealed weak interactions between pRb and the J domain. Analysis of the complex of pRb and N(260) indicated that the OBD is not involved and retains its dynamic independence from the remainder of Tag. These results support a 'chaperone' model in which the J domain of Tag changes its orientation as it acts upon different protein complexes.


Dependence of a cooling rate on structural and vibrational properties of amorphous silicon: A neural network potential-based molecular dynamics study.
Amorphous materials have variable structural order, which has a significant influence on their electronic, transport, and thermal properties. However, this difference in structure has rarely been investigated by atomistic modeling. In this study, a high-quality machine-learning-based interatomic potential was used to generate a series of atomic structures of amorphous silicon with different degrees of disorder by simulated cooling from the melt with different cooling rates (1011-1015 K/s). We found that the short- and intermediate-range orders are enhanced with decreasing cooling rate, and the influence of the structural order change is in excellent agreement with the experimental annealing process in terms of the structural, energetic, and vibrational properties. In addition, by comparing the excess energies, structure factors, radial distribution functions, phonon densities of states, and Raman spectra, it is possible to determine the corresponding theoretical model for experimental samples prepared with a certain method and thermal history.


Scrotal elephantiasis associated with hidradenitis suppurativa.
Hidradenitis suppurativa is a chronic relapsing infection of the apocrine sweat glands. Its association with penoscrotal lymphedema is not well recognized. A case of massive scrotal elephantiasis associated with chronic hidradenitis of the perineum and scrotum is described. A wide resection of the scrotal mass and perineum was performed, with reconstruction of the perineum and penis carried out using local skin flaps and split-thickness skin grafts. This one-stage treatment yielded an excellent cosmetic and functional outcome.


To Prime, or Not to Prime: That Is the Question.
Mitochondrial priming is regulated by the B-cell lymphoma 2 (BCL-2) family of proteins and determines a cell's "readiness" for apoptosis. A highly primed cell will undergo apoptosis more easily than an unprimed cell in response to apoptotic stimuli via the intrinsic apoptotic pathway. Priming can be measured via BH3 profiling, which uses BH3 peptides derived from the BH3 domain of pro-apoptotic BH3-only BCL-2 family members to provoke a response from viable mitochondria. BH3 profiling can be performed on tumor cells and can identify mechanisms a cell uses to evade apoptosis and anti-apoptotic dependency to the anti-apoptotic BCL-2 family members. Priming correlates with chemosensitivity of patients in multiple cancers. Therapeutics that enhances priming of patient tumor cells ex vivo could be used to aid therapeutic decisions for patients in the future.


Episodic intertrial learning of younger and older participants: effects of age of acquisition.
There is clear evidence of a deficit in episodic memory for older adults compared to younger adults. Using an intertrial technique previous research has investigated whether this deficit can be attributed to a decline in encoding or consolidation. On standard memory tests, these two aspects of memory function can be measured by examining the items forgotten or acquired across multiple learning trials. The present study assessed whether age deficits in episodic memory were affected by stimulus characteristics, specifically age of acquisition (AoA). A standard intertrial design was implemented whereby participants studied word lists over several study-test trials. The stimulus characteristics of AoA were manipulated using a pure-list technique. Our findings showed that older adults demonstrate an overall recall deficit which appeared to be a consequence of both an encoding deficit and consolidation weakness. Earlier-acquired words were recalled significantly better than later-acquired words and this was apparently due to both enhanced encoding and consolidation of earlier- over later-acquired words. The key finding is that older adults show a recall advantage for earlier- compared to later-acquired words over the entire experiment to a greater degree than younger adults.


Central nervous system opportunistic infections.
The spectrum of opportunistic infections occurring in association with human-immunodeficiency virus, type 1, is very broad. These infections develop most frequently in the setting of advanced immunosuppression. There is no part of the neuraxis that is immune to these complications and the concurrence of more than one infectious illness may always be considered. The neuroimaging features, when coupled with the clinical and laboratory findings, often suggest the correct diagnosis and enable the physician to initiate therapy.


Prevalence and consequences of concurrent dizziness on disability and quality of life in patients with long-lasting neck pain.
The purpose of this study was to examine the prevalence of concurrent dizziness in patients seeking treatment for neck pain at a secondary care clinic and examine how dizziness associates with physical function, disability, quality of life, and duration of neck pain. This was a cross-sectional study where patients referred for neck pain (n = 133) were recruited from an outpatient spine clinic and divided into: patients with and without dizziness. All patients were examined with posturography, global body examination-flexibility and cervical range of motion, and completed the Neck Disability Index (NDI) and RAND-12 health survey. Patients with concurrent dizziness completed the Vertigo Symptom Scale short form (VSSsf). Forty-three percent of the patients reported dizziness. Concurrent dizziness was associated with increased postural sway with eyes open (p < .001), eyes closed (p = .024), eyes open on foam (p = .010), eyes closed on foam (p = .003), higher disability on the NDI (β: 2.9, p = .009), RAND-12 physical (β: -4.3, p = .014) and mental subscales (β: -4.0, p = .014). A higher score on NDI was associated with higher score on the VSSsf (total score: r = 0.51, p < .001, anxiety: r = 0.52, p < .001, vertigo: r = 0.43, p = .02.). Dizziness is common among patients with long-lasting neck pain. It is associated with higher disability due to neck symptoms and general health-related quality of life. The findings highlight the importance of evaluating and addressing dizziness in patients with neck disorders.


Smokers who fail to identify smoking cessation as a health priority.
Smokers who identified smoking cessation as the primary activity they could undertake to improve their health were compared with smokers who did not identify smoking cessation. Examined factors included personal characteristics, health status, smoking attitudes and behaviors, and social factors. Subjects were 225 smokers who participated in a telephone survey of 853 randomly selected adults. Fifty-six percent of smokers did not identify smoking cessation as a priority. Nonidentifiers were more likely than identifiers to have minimal personal income, no paid employment, poor or fair health, dissatisfaction with their overall physical condition, less energy than others, little perceived control over their health, smoked fewer cigarettes per day, and reported no previous quit attempts. They were less likely to agree that they lacked the willpower to quit or that smoking helped them deal with stress. Smokers who fail to identify smoking cessation as a priority strategy for health improvement are unlikely to be exposed to workplace and social censures and should be targeted by health professionals.


Does salinity reduce growth in maize root epidermal cells by inhibiting their capacity for cell wall acidification?
The reduction in growth of maize (Zea mays L.) seedling primary roots induced by salinization of the nutrient medium with 100 millimolar NaCl was accompanied by reductions in the length of the root tip elongation zone, the length of fully elongated epidermal cells, and the apparent rate of cell production: Each was partially restored when calcium levels in the salinized growth medium were increased from 0.5 to 10.0 millimolar. We investigated the possibility that the inhibition of elongation growth by salinity might be associated with an inhibition of cell wall acidification, such as that which occurs when root growth is inhibited by IAA. A qualitative assay of root surface acidification, using bromocresol purple pH indicator in agar, showed that salinized roots, with and without extra calcium, produced a zone of surface acidification which was similar to that produced by control roots. The zone of acidification began 1 to 2 millimeters behind the tip and coincided with the zone of cell elongation. The remainder of the root alkalinized its surface. Kinetics of surface acidification were assayed quantitatively by placing a flat tipped pH electrode in contact with the elongation zone. The pH at the epidermal surfaces of roots grown either with 100 millimolar NaCl (growth inhibitory), or with 10 millimolar calcium +/- NaCl (little growth inhibition), declined from 6.0 to 5.1 over 30 minutes. We conclude that NaCl did not inhibit growth by reducing the capacity of epidermal cells to acidify their walls.


Patient blood management when blood is not an option: a report of two cases.
There are many patients who refuse to receive blood transfusions for religious or other reasons. Bloodless medicine and surgery are no longer new concept, but patients who refuse blood transfusion are still transferred to the bloodless center, regardless of patients' intention, for treatment. Here, we discuss the need for patient blood management when blood is not an option to treat them. Two patients of advanced age were transferred to our bloodless center due to refusal of transfusion. They are Jehovah's Witnesses and refused to receive blood transfusion despite life-threatening anemia and severe underlying diseases. Patient blood management protocols including iron supplementation, subcutaneous erythropoietin, folic acid and vitamin B were implemented to improve hematopoiesis, and supportive care was also performed to treat underlying diseases. Levels of Hemoglobin/Hematocrit and their symptom gradually improved about a week after treatment, and their condition had gradually stabilized. They were discharged safely. We treated patients of advanced age with severe underlying diseases and life-threatening anemia using patient blood management due to refusal of a blood transfusion. The patient blood management may be a useful alternative strategy, which meet the needs of patients who refuse blood transfusions as well as the need to reduce the use of blood products due to limited supply.


Prefrontal Cortex-Driven Dopamine Signals in the Striatum Show Unique Spatial and Pharmacological Properties.
Dopamine (DA) signals in the striatum are critical for a variety of vital processes, including motivation, motor learning, and reinforcement learning. Striatal DA signals can be evoked by direct activation of inputs from midbrain DA neurons (DANs) as well as cortical and thalamic inputs to the striatum. In this study, we show that in vivo optogenetic stimulation of prelimbic (PrL) and infralimbic (IL) cortical afferents to the striatum triggers an increase in extracellular DA concentration, which coincides with elevation of striatal acetylcholine (ACh) levels. This increase is blocked by a nicotinic ACh receptor (nAChR) antagonist. Using single or dual optogenetic stimulation in brain slices from male and female mice, we compared the properties of these PrL/IL-evoked DA signals with those evoked by stimulation from midbrain DAN axonal projections. PrL/IL-evoked DA signals are undistinguishable from DAN evoked DA signals in their amplitudes and electrochemical properties. However, PrL/IL-evoked DA signals are spatially restricted and preferentially recorded in the dorsomedial striatum. PrL/IL-evoked DA signals also differ in their pharmacological properties, requiring activation of glutamate and nicotinic ACh receptors. Thus, both in vivo and in vitro results indicate that cortical evoked DA signals rely on recruitment of cholinergic interneurons, which renders DA signals less able to summate during trains of stimulation and more sensitive to both cholinergic drugs and temperature. In conclusion, cortical and midbrain inputs to the striatum evoke DA signals with unique spatial and pharmacological properties that likely shape their functional roles and behavioral relevance.SIGNIFICANCE STATEMENT Dopamine signals in the striatum play a critical role in basal ganglia function, such as reinforcement and motor learning. Different afferents to the striatum can trigger dopamine signals, but their release properties are not well understood. Further, these input-specific dopamine signals have only been studied in separate animals. Here we show that optogenetic stimulation of cortical glutamatergic afferents to the striatum triggers dopamine signals both in vivo and in vitro These afferents engage cholinergic interneurons, which drive dopamine release from dopamine neuron axons by activation of nicotinic acetylcholine receptors. We also show that cortically evoked dopamine signals have other unique properties, including spatial restriction and sensitivity to temperature changes than dopamine signals evoked by stimulation of midbrain dopamine neuron axons.


Intracrine and myotrophic roles of 5α-reductase and androgens: a review.
Historically, the circulation was thought to be the primary source of androgens influencing skeletal muscle. However, a growing body of research indicates that skeletal muscle expresses several androgen-synthesizing enzymes, including 5α-reductase. The intramuscular expression of these enzymes suggests that skeletal muscle is capable of synthesizing bioactive androgens, which could induce myotrophic effects via intracrine action. The aim of this brief review is to discuss recent research related to the intracrine and myotrophic roles of androgens, with particular focus on 5α-reductase as a myotrophic mediator. Included in the review are 17 reviews and 58 original studies that were identified by a systematic review from MEDLINE and deemed particularly relevant to our purpose. Results are summarized to provide an overview of 5α-reductase as a mediator of the myotrophic effects of androgens. In particular, discussions are included regarding androgen biosynthesis and androgen signaling within skeletal muscle, the effects of exercise on intramuscular androgen biosynthesis, and clinical applications of androgens and of a new class of myotrophic agonists termed selective androgen receptor modulator. The ability of several peripheral tissues to synthesize bioactive androgens is well documented in the literature. Herein, we summarize newer studies that demonstrate that 1) skeletal muscle has the capability to synthesize both testosterone and dihydrotestosterone from dehydroepiandrosterone, which is present in abundance within the circulation, and 2) that exercise increases the expression of certain androgen-biosynthesizing enzymes within muscle. Intramuscularly synthesized androgens have the potential to influence skeletal muscle via intracrine action; however, their exact role in skeletal muscle development and maintenance requires further elucidation.


Phylogeny of the Paniceae (Poaceae: Panicoideae): integrating plastid DNA sequences and morphology into a new classification.
Included in the PACMAD clade of the family Poaceae (Panicoideae, Arundinoideae, Chloridoideae, Micrairoideae, Aristidoideae, Danthonioideae), the tribe Paniceae s.l. is one of the largest tribes of the subfamily Panicoideae, with more than 2000 species. This tribe comprises a huge morphological, cytological and physiological diversity represented by different inflorescence types, several basic chromosome numbers, and at least four major photosynthetic pathways. The tribe Paniceae has been the subject of molecular studies that have confirmed its paraphyly: two major clades were recognized based on their basic chromosome numbers (x = 9, x = 10). The x = 10 Paniceae clade is sister to the Andropogoneae-Arundinelleae s.s. clade (x = 10), while the combined x = 10 clade is sister to the x = 9 clade that contains the remaining genera of Paniceae. As a result of a recent realignment within the tribe in terms of the phylogenetic position of minor and major Paniceae genera, a reanalysis of the whole sampling is performed and new underrepresented taxa are discussed. A total of 155 genera, currently considered within subfamily Panicoideae, are represented here by almost all genera of Paniceae s.l., representatives of Andropogoneae and Arundinelleae s.s., and the endemic and small tribe Steyermarkochloeae; we also included specimens of subfamily Micrairoideae, tribes Isachneae and Eriachneae. The sampling includes as outgroups 18 genera of the PACMAD clade (excluding Panicoideae) and four genera from the BEP clade (Bambusoideae, Ehrhartoideae, Pooideae), rooting with Bromus inermis. A matrix with 265 taxa based on the combined evidence from ndhF plastid sequences (2074 bp) and 57 morphological characters was subjected to parsimony analyses. Jackknife resampling was used to calculate group support. Most clades are characterized by morphological, cytological, anatomical, and/or physiological characters. Major tribal changes are based on the basic chromosome number; the pantropical x = 9 clade is here recognized as Paniceae s.s., while the American x = 10 Paniceae s.l. is restricted to the reinstated tribe Paspaleae. The optimization of the photosynthetic pathway for the Paspaleae-Andropogoneae-Arundinelleae s.s. clade, including the monotypic Reynaudia, shows a plesiomorphic C4 state while the ancestral state for Paniceae s.s. is ambiguous. If Reynaudia were not included or placed elsewhere, the ancestral photosynthetic pathway for both the Paspaleae-Andropogoneae-Arundinelleae s.s. clade and the Paniceae s.s. would be unambiguously C3 . In order to explore character evolution further, the morphological characters were mapped onto one of the most parsimonious trees. A relationship between photosynthetic pathways and inflorescence morphology is suggested here for the first time. Based on the optimization of morphological characters and additional data, we propose names for almost all inner clades at the rank of subtribe with a few groups as incertae sedis. With this extensive sampling, we resolved the phylogenetic relationships and the assignation of synapomorphies, and improved the support in subtribe sorting; consequently a robust circumscription of the tribe Paniceae s.l. is proposed.


Sample size calculations for randomized clinical trials published in anesthesiology journals: a comparison of 2010 versus 2016.
Although every randomized clinical trial (RCT) needs participants, determining the ideal number of participants that balances limited resources and the ability to detect a real effect is difficult. Focussing on two-arm, parallel group, superiority RCTs published in six general anesthesiology journals, the objective of this study was to compare the quality of sample size calculations for RCTs published in 2010 vs 2016. Each RCT's full text was searched for the presence of a sample size calculation, and the assumptions made by the investigators were compared with the actual values observed in the results. Analyses were only performed for sample size calculations that were amenable to replication, defined as using a clearly identified outcome that was continuous or binary in a standard sample size calculation procedure. The percentage of RCTs reporting all sample size calculation assumptions increased from 51% in 2010 to 84% in 2016. The difference between the values observed in the study and the expected values used for the sample size calculation for most RCTs was usually > 10% of the expected value, with negligible improvement from 2010 to 2016. While the reporting of sample size calculations improved from 2010 to 2016, the expected values in these sample size calculations often assumed effect sizes larger than those actually observed in the study. Since overly optimistic assumptions may systematically lead to underpowered RCTs, improvements in how to calculate and report sample sizes in anesthesiology research are needed.


EDTA chelation therapy in the treatment of vascular disease.
Ethylenediamine tetraacetic acid (EDTA) chelation therapy has been used for decades for the treatment of vascular disease, alone or in combination with other treatments. This article includes a historic review of the research literature, current evidence of effectiveness, potential mechanisms of action of EDTA, and some brief case reports. The authors conclude that EDTA chelation therapy is a valuable therapeutic option for vascular disease, either alone or in conjunction with standard treatment protocols.


Potent, structurally constrained agonists and competitive antagonists of corticotropin-releasing factor.
Predictive methods, physicochemical measurements, and structure activity relationship studies suggest that corticotropin-releasing factor (CRF; corticoliberin), its family members, and competitive antagonists (resulting from N-terminal deletions) usually assume an alpha-helical conformation when interacting with the CRF receptor(s). To test this hypothesis further, we have scanned the whole sequence of the CRF antagonist [D-Phe12,Nle21,38]r/hCRF-(12-41) (r/hCRF, rat/human CRF; Nle, norleucine) with an i-(i + 3) bridge consisting of the Glu-Xaa-Xaa-Lys scaffold. We have found astressin [cyclo(30-33)[D-Phe12,Nle21,38,Glu30,Lys33]r/ hCRF(12-41)] to be approximately 30 times more potent than [D-Phe12,Nle21,38]r/hCRF-(12-41), our present standard, and 300 times more potent than the corresponding linear analog in an in vitro pituitary cell culture assay. Astressin has low affinity for the CRF binding protein and high affinity (Ki = 2 nM) for the cloned pituitary receptor. Radioiodinated [D-125I-Tyr12]astressin was found to be a reliable ligand for binding assays. In vivo, astressin is significantly more potent than any previously tested antagonist in reducing hypophyseal corticotropin (ACTH) secretion in stressed or adrenalectomized rats. The cyclo(30-33)[Ac-Pro4,D-Phe12,Nle21,38,Glu30,Lys33++ +]r/hCRF-(4-41) agonist and its linear analog are nearly equipotent, while the antagonist astressin and its linear form vary greatly in their potencies. This suggests that the lactam cyclization reinstates a structural constraint in the antagonists that is normally induced by the N terminus of the agonist.


[The role of a leukotriene receptor antagonist in the restoration of the nasal breathing in the patients presenting with polypous rhinosinusitis].
The present study was designed to investigate the clinical. laboratory, and morphological characteristics of the nasal obstruction process. It included 87 patients presenting with polypous rhinosinusitis. The dynamics of the serum leukotriene C4 (LTC4) level in the patients and the morphological changes in their polypous tissue suggested the existence of the pronounced exudative phase of allergic inflammation and provided a basis for the use of the leukotriene receptor antagonist in the form of the sodium montelucast tablets for the treatment of nasal obstruction.


Hemodynamic response in the unanesthetized rat: intrinsic optical imaging and spectroscopy of the barrel cortex.
Optical imaging spectroscopy was used to measure the hemodynamic response of somatosensory cortex to stimulation of the whiskers. Responses to brief puffs of air were compared in anesthetized and unanesthetized rats. The hemodynamic response was approximately four times larger in the unanesthetized animal than the corresponding anesthetized animal. In unanesthetized animals, a short-latency (approximately 400 milliseconds) short-duration (approximately 300 milliseconds) hemodynamic startle response was observed. General linear model analysis was used to extract this component from the time series, and revealed an underlying short-latency increase in deoxygenated hemoglobin in response to somatosensory stimulation. It is proposed that anesthesia can have a marked affect on the relation between changes in blood volume and blood flow. This work represents a step in the development of an experimental model that can be used to investigate fundamental neurologic processes in the awake-behaving rodent.


Ethylene Production by Chilled Cucumbers (Cucumis sativus L.).
Chilling at 2.5 C accelerated the synthesis of 1-aminocyclopropane-1-carboxylic acid (ACC) and C(2)H(4) production in cucumber fruit. Skin tissue contained higher levels of ACC and was more sensitive to chilling than was cortex tissue. Accumulation of ACC in chilled tissue was detected after 1 day of chilling and remained elevated even after C(2)H(4) production started to decline. These data suggest that ACC synthesis is readily stimulated by chilling, whereas the system that converts ACC to C(2)H(4) is vulnerable to chilling injury. Chilling-induced C(2)H(4) production was inhibited by amino-ethoxyvinylglycine, sodium benzoate, propyl gallate, 2,4-dinitrophenol, carbonyl cyanide m-chlorophenylhydrazone, and cycloheximide. The utilization of methionine for ACC formation and chilling-induced C(2)H(4) biosynthesis was established using l-[3,4-(14)C]methionine. Chilled tissue had a higher capacity to convert l-[3,4-(14)C]methionine to ACC and C(2)H(4) than did nonchilled tissue.


Lipocalin-2 increases fat oxidation in vitro and is correlated with energy expenditure in normal weight but not obese women.
The role of lipocalin-2 (Lcn2) was determined in regulating metabolism in cell, animal, and human models. Adipocytes were treated with recombinant lipocalin-2 (rLcn2) to determine the effect on lipid metabolism. rLcn2 was injected into mice to determine the effect on metabolism in vivo. To assess the relationship between Lcn2 and fat oxidation (FatOx) in humans, normal weight (NW) and obese (OB) women were given three separate high fat (HF) meals followed by indirect calorimetry. The relationship between postprandial Lcn2 with macronutrient metabolism and total energy expenditure (TEE) using Pearson correlations was determined. Lcn2 increased expression of genes involved in β-oxidation including peroxisome proliferator-activated receptor-δ in adipocytes, as well as (3) H labeled oleate β-oxidation. Lcn2 injected into chow-fed mice directly increased TEE by 18% after the first dark cycle (232 ± 1.4 cal vs. 341 ± 1.4 cal; PBS vs. Lcn2) and remained significantly elevated by 10% after the second dark cycle (296 ± 1.4 cal vs. 326 ± 1.4 cal; PBS vs. Lcn2). Lcn2 was correlated with TEE in all three HF meal challenges in NW but not OB females. Lipocalin-2 is a novel adipokine that promotes FatOx and TEE and its function may be impaired in obesity.


[Inhibition of arachidonic acid cascade by extract of rye pollen].
A standardized extract mainly from rye pollen (Cernilton N) was tested in vitro on the inhibition of prostaglandin and leukotrien synthesis. The determination of the prostaglandin and leukotrien synthesis from labelled arachidonic acid was done in microsomes of ram seminal vesicles resp. in rat basophilic leukemia cells (RBL-1 cells). The water soluble resp. the fat soluble extract fraction from the whole pollen extract were tested separately. The radio-TLC separation of the reaction metabolites showed a dose dependent inhibition of the cyclo-oxygenase and the 5-lipoxygenase activity by the fat soluble pollen extract fraction. The IC50-values are 0.005 mg/ml resp. 0.08 mg/ml and similar to those of the also tested diclofenac. The water soluble fractions showed no effect in this test system. According to these in vitro results and the clinical experience so far with the pollen extract its therapeutic efficacy on benign prostate diseases is best explainable by the anticongestive resp. anti-inflammatory effect of the fat soluble fraction. Due to the different actions of prostaglandins and leucotrienes also relaxant and antiproliferative effects were conceivable.


Effects of ryo-kan-kyomi-sin-ge-nin-to extract on degranulation of and histamine release from rat mast cells.
The effects of Ryo-kan-kyomi-sin-ge-nin-to (RKSG)) extract, a medicinal agent traditionally used in China and Japan for treatment of asthma, on the degranulation of and histamine release from rat mast cells were studied. At a concentration of 5 mg/ml RKSG, degranulation of mast cells stimulated either by antigen (DNP-Ascaris) or compound 48/80 was markedly suppressed. At a concentration of 1-5 mg/ml RKSG, histamine release from mast cells due to application of either antigen or compound 48/80 was inhibited in a dose-dependent fashion. These results suggest that RKSG may be useful for the treatment of type I allergy-related diseases.


Single-nucleotide polymorphisms and DNA methylation markers associated with central obesity and regulation of body weight.
Visceral fat is strongly associated with the development of specific obesity-related metabolic alterations. Genetic and epigenetic mechanisms seem to be involved in the development of obesity and visceral adiposity. The aims of this review are to identify the single-nucleotide polymorphisms related to central obesity and to summarize the main findings on DNA methylation and obesity. A search of the MEDLINE database was conducted to identify genome-wide association studies, meta-analyses of genome-wide association studies, and gene-diet interaction studies related to central obesity, and, in addition, studies that analyzed DNA methylation in relation to body weight regulation. A total of 8 genome-wide association studies and 9 meta-analyses of genome-wide association studies reported numerous single-nucleotide polymorphisms to be associated with central obesity. Ten studies analyzed gene-diet interactions and central obesity, while 2 epigenome-wide association studies analyzed DNA methylation patterns and obesity. Nine studies investigated the relationship between DNA methylation and weight loss, excess body weight, or adiposity outcomes. Given the development of new sequencing and omics technologies, significantly more knowledge on genomics and epigenomics of obesity and body fat distribution will emerge in the near future.


[Population-genetic characteristic of the rural population of southern Tajikistan].
The results of genetic and demographic study of the inhabitants in south Tadjikistan are presented. It had been shown that the population studied is a typical rural population of Middle Asia and is characterized by the extended reproductive capacity, homogeneity of national composition and a high proportion of consanguineous marriages. Genetic variation in blood groups (AB0, MN, Rh-D, P1), serum proteins and red cell enzyme systems (Tf, Gc, Hp, PGM1, PGD, EsD, AcP1) was examined. A comparative analysis of gene frequencies in the population studied and some other Middle Asia populations has been carried out.


Aneurysmal bone cysts and pathologic fracture associated with supernumerary ring chromosome 6 in two unrelated patients.
Small supernumerary ring chromosome 6 (sSRC[6]) is a rare chromosomal abnormality characterized by a broad clinical phenotype. The spectrum of this disorder can range from phenotypically normal to severe developmental delay and congenital anomalies. We describe two unrelated patients with small SRCs derived from chromosome 6 with a novel bone phenotype. Both patients presented with a complex bone disorder characterized by severe osteopenia, pathologic fractures, and cyst-like lesions within the bone. Imaging revealed decreased bone mineral density, mutiple multiloculated cysts and cortical thinning. Lesion pathology in both patients demonstrated a bland cyst wall with woven dysplastic appearing bone entrapped within it. In patient 1, array comparative genomic hybridization (CGH) detected a tandem duplication of region 6p12.3 to 6q12 per marker chromosome. Cytogenetic analysis further revealed a complex patient of mosaicism with some cell lines displaying either one or two copies of the marker indicative of both tetrasomy and hexasomy of this region. Patient 2 was mosaic for a sSRC that encompassed a 26.8 Mb gain from 6p21.2 to 6q12. We performed an in-depth clinical analysis of a phenotype not previously observed in sSRC(6) patients and discuss the potential influence of genes located within this region on the skeletal presentation observed.


Ketamine inhibits lung fluid clearance through reducing alveolar sodium transport.
Ketamine is a broadly used anaesthetic for analgosedation. Accumulating clinical evidence shows that ketamine causes pulmonary edema with unknown mechanisms. We measured the effects of ketamine on alveolar fluid clearance in human lung lobes ex vivo. Our results showed that intratracheal instillation of ketamine markedly decreased the reabsorption of 5% bovine serum albumin instillate. In the presence of amiloride (a specific ENaC blocker), fluid resolution was not further decreased, suggesting that ketamine could decrease amiloride-sensitive fraction of AFC associated with ENaC. Moreover, we measured the regulation of amiloride-sensitive currents by ketamine in A549 cells using whole-cell patch clamp mode. Our results suggested that ketamine decreased amiloride-sensitive Na+ currents (ENaC activity) in a dose-dependent fashion. These data demonstrate that reduction in lung ENaC activity and lung fluid clearance following administration of ketamine may be the crucial step of the pathogenesis of resultant pulmonary edema.


Different basal NAD levels determine opposite effects of poly(ADP-ribosyl)polymerase inhibitors on H2O2-induced apoptosis.
We have recently described that poly(ADP-ribosyl)-polymerase (PARP) inhibitors rescue U937 cells from apoptosis induced by 1 mM H2O2 oxidative stress; PARP activation leads to a reversible drop in NAD level, which could be blocked by PARP inhibitors (Nos-seri et al., 1994, Exp. Cell Res. 212, 367-373). A phenotypic variant of U937 is characterized by a lower basal NAD level (low NAD, LN U937, as opposed to the original high NAD, HN U937). In LN cells treatment with 1 mM H2O2, although activating PARP, does not lower NAD concentration; puzzlingly, PARP inhibitors increase (instead of decreasing, as occurs in HN cells) the extent of stress-induced apoptosis, leading to a reduced cell survival. NAD concentration could be increased in LN cells by adding nicotinamide (5-and 25-fold increase) to the culture medium. These cells (LN+) behaved as HN U937: oxidative stress induced a NAD drop, the extent of which is dependent on the cells' basal NAD level; moreover, PARP inhibitors could rescue LN+ cells from peroxide-induced apoptosis. H2O2-induced apoptosis is not triggered by NAD depletion, but instead it takes place only when NAD levels have been preserved or have recovered: on HN U937, peroxide doses (5 and 10 mM) which lead to necrosis induce an irreversible NAD drop, whereas apoptosis occurs only at lower doses, where NAD depletion is reversible; on LN cells NAD levels do not drop even upon 10 mM H2O2 treatment, and these cells die only by apoptosis; moreover, in HN cells apoptosis is not detectable until 8 h posttreatment, when NAD levels recover, whereas in LN cells, where NAD is always present, apoptosis begins to take place as early as 3 h after stress.


Intracellular transactivation of epidermal growth factor receptor by α1A-adrenoceptor is mediated by phosphatidylinositol 3-kinase independently of activation of extracellular signal regulated kinases 1/2 and serine-threonine kinases in Chinese hamster ovary cells.
Transactivation of epidermal growth factor receptor (EGFR) by α1-adrenoceptor (α1-AR) is implicated in contraction and hypertrophy of vascular smooth muscle (VSM). We examine whether all α1-AR subtypes transactivate EGFR and explore the mechanism of transactivation. Chinese hamster ovary (CHO) cells stably expressing one subtype of α1-AR were transiently transfected with EGFR. The transactivation mechanism was examined both by coexpression of a chimeric erythropoietin (EPO)-EGFR with an extracellular EPO and intracellular EGFR domain, and by pharmacologic inhibition of external and internal signaling routes. All three α1-AR subtypes transactivated EGFR, which was dependent on the increase in intracellular calcium. The EGFR kinase inhibitor AG1478 [4-(3'-chloroanilino)-6,7-dimethoxyquinazoline] abrogated α1A-AR and α1D-AR induced phosphorylation of EGFR, but both the inhibition of matrix metalloproteinases by GM6001 [(R)-N4-hydroxy-N(1)-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide] or blockade of EGFR by cetuximab did not. Stimulation of α1A-AR and α1D-AR also induced phosphorylation of EPO-EGFR chimeric receptors. Moreover, α1A-AR stimulation enhanced phosphorylation of extracellular signal regulated kinase (ERK) 1/2 and serine-threonine kinases (Akt), which were both unaffected by AG1478, indicating that ERK1/2 and Akt phosphorylation is independent of EGFR transactivation. Accordingly, inhibitors of ERK1/2 or Akt did not influence the α1A-AR-mediated EGFR transactivation. Inhibition of calcium/calmodulin-dependent kinase II (CaMKII), phosphatidylinositol 3-kinase (PI3K), and Src, however, did block EGFR transactivation by α1A-AR and α1D-AR. These findings demonstrate that all α1-AR subtypes transactivate EGFR, which is dependent on an intracellular signaling route involving an increase in calcium and activation of CaMKII, PI3K, and Src, but not the of ERK1/2 and Akt pathways.


Macrophages play a role in inflammatory transformation of colorectal cancer.
Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide, and it is also a typical inflammatory cancer. The function of macrophages is very important in the tissue immune microenvironment during inflammatory and carcinogenic transformation. Here, we evaluated the function and mechanism of macrophages in intestinal physiology and in different pathological stages. Furthermore, the role of macrophages in the immune microenvironment of CRC and the influence of the intestinal population and hypoxic environment on macrophage function are summarized. In addition, in the era of tumor immunotherapy, CRC currently has a limited response rate to immune checkpoint inhibitors, and we summarize potential therapeutic strategies for targeting tumor-associated macrophages.


EP receptor subtypes implicated in the PGE2-induced sensitization of polymodal receptors in response to bradykinin and heat.
1. Our previous studies, in which we used in vitro canine testispermatic nerve preparations, showed that prostaglandin E2 (PGE2) augments both bradykinin (BK)- and heat-induced discharges of polymodal receptors. However, the PGE2 concentration required to augment the BK responses were 100 times lower than those necessary for the heat responses, suggesting that different receptors are involved in these phenomena. We studied which receptors for E series of prostaglandins (EP receptors) were responsible, using the antagonist and agonists for three subtypes of EP receptors. 2. PGE2-induced augmentation of the BK responses was unaffected when treated with an antagonist for the EP1 receptor, AH6809. 3. An agonist for the EP3 receptor, M&B28767, at > or = 10 nM, significantly augmented the BK responses in a concentration-dependent manner that mimics the PGE2-induced effect. An agonist for the EP1 receptor, 17-phenyl trinor PGE2 (17-phen PGE2), at the high concentrations of 0.1 and 1 microM, augmented the BK responses in two and four of nine cases tested, respectively. However, this augmentation was not suppressed by the antagonist for the EP1 receptor, AH6809. In addition, an agonist for the EP2 receptor, butaprost, did not affect the BK responses even when applied at 10 microM. 4. In contrast, butaprost at > or = 10 nM significantly augmented the heat responses in a concentration-dependent manner. M&B28767 and 17-phen PGE2, respectively, augmented the heat responses at higher concentrations of 100 nM and 1 microM. 5. These results indicate that the EP3 and EP2 receptor subtypes are differentially implicated in the respective PGE2-induced augmentation of BK responses and heat responses of polymodal receptors.


Effective radiation dose, time, and contrast medium to measure fractional flow reserve.
This study sought to define the additional effective radiation dose, procedural time, and contrast medium needed to obtain fractional flow reserve (FFR) measurements after a diagnostic coronary angiogram. The FFR measurements performed at the end of a diagnostic angiogram allow the obtaining of functional information that complements the anatomic findings. In 200 patients (mean age 66 +/- 10 years) undergoing diagnostic coronary angiography, FFR was measured in at least 1 intermediate coronary artery stenosis. Hyperemia was achieved by intracoronary (n = 180) or intravenous (n = 20) adenosine. The radiation dose (mSv), procedural time (min), and contrast medium (ml) needed for diagnostic angiography and FFR were recorded. A total of 296 stenoses (1.5 +/- 0.7 stenoses per patient) were assessed. The additional mean radiation dose, procedural time, and contrast medium needed to obtain FFR expressed as a percentage of the entire procedure were 30 +/- 16% (median 4 mSv, range 2.4 to 6.7 mSv), 26 +/- 13% (median 9 min, range 7 to 13 min), and 31 +/- 16% (median 50 ml, range 30 to 90 ml), respectively. The radiation dose and contrast medium during FFR were similar after intravenous and intracoronary adenosine, though the procedural time was slightly longer with intravenous adenosine (median 11 min, range 10 to 17 min, p = 0.04) than with intracoronary adenosine (median 9 min, range 7 to 13 min). When FFR was measured in 3 or more lesions, radiation dose, procedural time, and contrast medium increased. The additional radiation dose, procedural time, and contrast medium to obtain FFR measurement are low as compared to other cardiovascular imaging modalities. Therefore, the combination of diagnostic angiography and FFR measurements is warranted to provide simultaneously anatomic and functional information in patients with coronary artery disease.


Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex.
Epileptic activity leads to rapid insertion of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) into the synapses of cortical and hippocampal glutamatergic neurons, which generally do not express them. The physiological significance of this process is not yet fully understood; however, it is usually assumed to be a pathological process that augments epileptic activity. Using whole-cell patch-clamp recordings in rat entorhinal cortex slices, we demonstrate that the timing of epileptiform discharges, induced by 4-aminopyridine and gabazine, is determined by the shunting effect of Ca2+-dependent slow conductance, mediated predominantly by K+-channels. The blockade of CP-AMPARs by IEM-1460 eliminates this extra conductance and consequently increases the rate of discharge generation. The blockade of NMDARs reduced the additional conductance to a lesser extent than the blockade of CP-AMPARs, indicating that CP-AMPARs are a more significant source of intracellular Ca2+. The study's main findings were implemented in a mathematical model, which reproduces the shunting effect of activity-dependent conductance on the generation of discharges. The obtained results suggest that the expression of CP-AMPARs in principal neurons reduces the discharge generation rate and may be considered as a protective mechanism.


Outcome of mechanical lithotripsy of bile duct stones in an unselected series of 704 patients.
This paper evaluates the potential benefit of non mechanical bile duct stone lithotripsy techniques. The efficacy, limitations and risks of mechanical lithotripsy as first choice procedure were studied. Endoscopic sphincterotomy was performed by Erlangen-type papillotomes, stone extraction by Olympus baskets and mechanical lithotripsy by the Wurbs-system. In an unselected series of 704 patients, everyone with common bile and hepatic duct stones (independent of size, number, location and stone consistency) was included in the study. Complete stone clearance by endoscopic sphincterotomy and basket extraction was possible in 87.6%. Additional mechanical lithotripsy led to a success rate of 98.4% and in combination with ESWL of 98.5%. In 11 patients without possibility of endoscopic stone removal (1.6%), 4 had no access transpapillary (B-II-situs or duodenal diverticulum), 5 anatomical problems (S-shaped common bile duct, intrahepatic stones or impacted stones in cystic duct orifice), and 2 refused further endoscopic interventions. Complication rate was 1.4% (thereof 1.1% successful treatment by endoscopic or surgical means), lethality rate 0.3%. A very high rate of stone clearance by standard endoscopic procedures is possible. In those patients where mechanical lithotripsy is not successful, other non-surgical lithotriptic procedures either cannot be applied because of anatomical reasons or if performed, the improvement in success rate is marginal.


Biochemical abnormalities in neonatal seizures.
Early diagnosis and appropriate treatment of biochemical abnormalities accompanying neonatal seizures is important for effective seizure control and to avoid further brain damage. The present study was carried out on 35 neonates to determine the frequency of various biochemical abnormalities in neonatal seizures. Diagnostic evaluation included estimation of levels of serum calcium, phosphorus, magnesium, sodium, potassium, zinc, and blood glucose. Two-thirds of the neonates with seizures had biochemical disturbances in their sera. A variety of abnormalities occurred in asphyxiated infants, including hyponatremia, hypoglycemia, hypocalcemia, and hypomagnesemia. Primary metabolic disorders accounted for one-forth of the cases of neonatal seizures, the most common being hypoglycemia, hypoglycemia/hypocalcemia, and hypocalcemia/hyperphosphatemia. Inappropriate intrauterine growth, inadequate feeding, and feeding with cow's milk were the main risk factors for primary metabolic seizures. Hyponatremia was a frequent finding in seizures resulting from brain damage like birth asphyxia, meningitis, and intracranial hemorrhage. No infant had hypernatremia, hyperkalemia, hypokalemia, or low serum zinc.


The dendritic cell mannose receptor mediates allergen internalization and maturation involving notch 1 signalling.
Dendritic cells (DCs) have been shown recently to play a key role in inducing and mediating T helper type 2 (Th2) responses associated with atopic disease. These responses are mediated in part by ligation to different Toll-like receptors (TLRs) and C-type lectins, e.g. the mannose receptor (MR), depending upon the DC subset involved and the respective microenvironments. Because ovalbumin (OVA) (which is structurally related to various allergens) can engage the MR, we can use OVA stimulation as a model for understanding the roles of both TLRs and the MR in allergic inflammatory responses. We examined TLR- and MR-mediated responses from mouse bone marrow-derived DCs in the context of antigen recognition and presentation in addition to examining the relationship between notch 1, TLRs and MR signalling pathways. This work demonstrated that OVA-mediated signalling up-regulated both TLR-2 and MR and that MR RNA interference (RNAi) but not TLR2 RNAi inhibited DC internalization of fluorescein isothiocyanate-OVA. Furthermore, MR RNAi inhibited OVA- and house dust mite allergen extract-induced DC maturation and MR RNAi and TLR2 RNAi influenced DC interleukin-12 production independently. Finally, we demonstrated that blocking notch 1 signalling inhibited both notch 1 and TLR-2 expression but not MR expression levels. However, MR RNAi inhibited the expression of MR, TLR-2 and notch 1. These results indicate that MR is the primary receptor mediating the internalization of environmental allergen glycoproteins. In addition, TLR-2 and notch 1 play important roles in DC maturation and antigen presentation and signals originating from the MR and TLR-2 receptors converge with the notch 1 signalling pathway.


Slowing of relaxation during fatigue in single mouse muscle fibres.
1. In the preceding paper we analysed the force decline in fatigue of isolated mouse muscle fibres. Using the same preparation and stimulation scheme we have now examined another aspect of muscle fatigue, namely slowing of relaxation. 2. Relaxation at the end of a tetanic contraction can usually be divided into two phases, an initial nearly linear force decline, followed by an exponential phase. We have analysed the initial phase in terms of decline rate and duration. In rested fibres the decline rate after a 350 ms tetanus was not affected by a 30% reduction of tetanic tension (obtained by decreasing the stimulation frequency). 3. Relaxation became gradually slower during fatiguing stimulation with a maximum reduction at the time when tetanic tension was reduced to about 75% of the original (end of phase 2, see preceding paper). At this time the decline rate of the linear phase had fallen to 55.2 +/- 2.9% (mean +/- S.E.M., n = 25) and its duration had increased to 151.3 +/- 14.2% of the control (unfatigued 350 ms, 70 Hz tetanus). 4. Short rest periods (duration = 10s), given at various times during fatiguing stimulation, resulted in a clear, but partial, normalization of the relaxation parameters; at the time of maximum slowing the mean decline rate increased from 50.3 to 58.7% and the duration decreased from 167.9 to 144.0% of the control (n = 14). 5. The influence of intracellular acidosis on relaxation was studied by exposing rested fibres to 30% CO2 instead of the normal 5%. This resulted in a decline rate of 43.0 +/- 2.6% and a duration of 221.1 +/- 13.1% of the control (n = 7). 6. In amphibian muscle relaxation is known to become gradually slower during a single, prolonged tetanus. The existence of such an effect also in the present preparation was studied by giving 'interrupted' tetani with a total duration of about 2 s. In rested fibres the mean rate of relaxation was found to fall from 140.9 to 71.8% (n = 11) of the control (end of 350 ms stimulation) with a time constant of about 0.5 s. Thus, a marked slowing during a long tetanus occurs also in mammalian muscle. 7. A distinct slowing of relaxation during prolonged tetani was observed also in the fatigued and in the acidified state. Under these two conditions the mean rate of relaxation fell from 87.0 to 34.0% (n = 3) and from 74.0 to 23.0% (n = 5) of the control, respectively, with time constants similar to that in the rested state.(ABSTRACT TRUNCATED AT 400 WORDS)


Genetics and bioethics: how our thinking has changed since 1969.
In 1969, the field of human genetics was in its infancy. Amniocentesis was a new technique for prenatal diagnosis, and a newborn genetic screening program had been established in one state. There were also concerns about the potential hazards of genetic engineering. A research group at the Hastings Center and Paul Ramsey pioneered in the discussion of genetics and bioethics. Two principal techniques have emerged as being of enduring importance: human gene transfer research and genetic testing and screening. This essay tracks the development and use of these techniques and considers the ethical issues that they raise.


Access to health and support services: perspectives of people living with a long-term traumatic spinal cord injury in rural and urban areas.
To examine the perspectives of persons living with traumatic spinal cord injuries (tSCI) on their access to health and support services. The specific aims were to identify the perceived gaps in access, classify the nature of the perceived gaps and compare differences in perceptions of access between urban and rural participants. Using a descriptive, qualitative approach, semi-structured interviews were conducted with 23 adults living with tSCI, 13 of whom had paraplegia. Ten participants resided in rural areas and 16 were male. Thematic analysis allowed for the identification of patterns, which were then categorized according to the dimensions of access. Opportunities to engage in health-promoting activities through a broad range of health and support services were at times limited, particularly by issues of affordability. In addition to core healthcare services, participants reported the need for complementary therapies, sports and leisure, peer support, equipment and mobility related services. Availability and accessibility of services was limited in some cases for rural participants, although rural residence conferred other valued benefits. Narratives of "not being heard" by providers were common. Maintaining health and well-being in people with tSCI demands access to both conventional health care and support services. Implications for Rehabilitation Access to both health and support services are important to maintaining the health and wellness of people with spinal cord injury. People with spinal cord injuries take an active role in coordinating their health, at times assuming various roles to compensate for perceived shortcomings of health care providers. Negotiating balances of power with gatekeepers in the health and insurance sectors was a key function of the coordinating role assumed by people with spinal cord injury. In order to effectively address the needs of this population, a coordinated interdisciplinary out-reach service, which includes peer support, must cross boundaries to engage sectors beyond traditional health care services, such as insurers and wellness providers.


Effect of relatives' intensive care unit diaries on post traumatic stress in patients and relatives (DRIP-study): A mixed methods study.
To explore the relationship between psychological distress and diary sharing in patients and relatives, by investigating: 1) diary usage, 2) diary perception and 3) symptoms of psychological stress. Convergent mixed methods study. Two intensive care units using patient diaries written by relatives with nurse guidance and shared with the patient after discharge. Self-reported scores of symptoms of posttraumatic stress, anxiety, depression and diary usage were crossed with qualitative description of diary usage and diary perception in 10 patients and 11 relatives. Most relatives expressed positive perceptions of diary usage; sharing the diary with the patient was related to fewer symptoms of posttraumatic stress. Patients had a positive perception of diary sharing, but symptoms of posttraumatic stress were unchanged. Reflecting on the tribulations of critical illness and later sharing reflections with the patient were related to lower rates of posttraumatic stress in relatives, suggesting that the act of writing and sharing a diary could have a protective effect. Delayed diary sharing did not have the same effect on patients but might enhance support between relatives and patients.


The prevalence of genetic disorders, birth defects and syndromes in central and eastern Kentucky.
Without an operative Birth Defects Registry, the state of Kentucky does not have a means of determining which of the nearly 6,000 syndromes and birth defects are the most common or the most rare, nor is there an ability to compare and contrast these data with data from other states. The authors reviewed 4,212 charts of patients evaluated between July 1981 and February 1995 by the Division of Genetics and Dysmorphology at the University of Kentucky Chandler Medical Center. Each patient's chart was categorized by diagnosis, and tables were generated to determine the most common diagnoses in the following groups: (1) multiple congenital anomaly syndromes, (2) teratogenic embryopathies, (3) chromosome anomalies, (4) isolated malformations, and (5) bone dysplasias. The most common multiple congenital anomaly syndromes were Down syndrome, Marfan syndrome, and trisomy 18. Fetal alcohol syndrome and infants of diabetic mothers were the most common embryopathies. Spina bifida (meningocele and myelomeningocele) was by far the most common isolated birth defect, followed by cleft lip/ palate and microcephaly. Achondroplasia was the most common bone dysplasia. These data support a number of previous assumptions including the universally high frequency of syndromes like Down syndrome and trisomy 18. The data also give credence to what was previously thought, but unproven, to be a high incidence of diabetic and alcohol embryopathies. The latter (fetal alcohol syndrome) has increased in frequency tremendously over the past 7 years. This is undoubtedly due in part to the overall increased awareness of the diagnosis in the medical community. However, it may also be due to the increased use of alcohol among Kentucky women. Other "rare" disorders, like diastrophic dysplasia, seem to be unusually the diagnosis in the medical community. However, it may also be due to the increased use of alcohol among Kentucky women. Other "rare" disorders, like diastrophic dysplasia, seem to be unusually the diagnosis in the medical community. However, it may also be due to the increased use of alcohol among Kentucky women. Other "rare" disorders, like diastrophic dysplasia, seem to be unusually


[Overweight and obesity in patients with severe mental illness].
Obesity is an increasing global problem. Individuals with severe mental illness (SMI) are no exception; on the contrary, these patients are more often obese than others and suffer from sequelae. Poor life style, poor socio-economic status and side effects to antipsychotics are well known contributors to obesity. Interventions targeting the individual have been tested with limited success. The healthcare systems and the communities have to rethink the integration of individuals with SMI as equal citizens in the society in order to prevent weight gain or for weight loss interventions to be successful.


Cognitive performance and aphasia recovery.
Objectives This study assessed cognitive performance of subjects with aphasia during the acute stage of stroke and evaluated how such performance relates to recovery at 3 months. Materials & methods Patients with aphasia following a left hemisphere stroke were evaluated during the first (baseline) and the fourth-month post onset. Assessment comprised non-verbal tests of attention/processing speed (Symbol Search, Cancelation Task), executive functioning (Matrix Reasoning, Tower of Hanoi, Clock Drawing, Motor Initiative), semantic (Camel and Cactus Test), episodic and immediate memory (Memory for Faces Test, 5 Objects Memory Test, and Spatial Span. Recovery was measured by the Token Test score at 3 months. The impact of baseline performance on recovery was evaluated by logistic regression adjusting for age, education, severity of aphasia and the Alberta Stroke Program Early CT (ASPECT) score. Results Thirty-nine subjects (with a mean of 66.5 ± 10.6 years of age, 17 men) were included. Average baseline cognitive performance was within normal range in all tests except in memory tests (semantic, episodic and immediate memory) for which scores were ≤-1.5sd. Subjects with poor aphasia recovery (N = 27) were older and had fewer years of formal education but had identical ASPECT score compared to those with favorable recovery. Considering each test individually, the score obtained on the Matrix Reasoning test was the only one to predict aphasia recovery (Exp(B)=24.085 p = 0.038). Conclusions The Matrix Reasoning Test may contribute to predict aphasia recovery. Cognitive performance is a measure of network disruption but may also indicate the availability of recovery strategies.


[Development of effervescent tablet of Chinese traditional medicine and its technology study].
Effervescent tablets which contain an effervescent mixture of a suitable organic acid and an alkali metal bicarbonate and/or carbonate can give out carbon dioxide when they meet water. The effervescent tablets for oral solution can be dissolved in cool water about 17-20 degrees C, therefore it is convenient to carry and use. It also has a good taste for patient with deodorizing agent added. The foam produced by external effervescent tablets is usually helpful in killing the local bacteria. The review displayed the main supplementary material, preparative technique and the study development of effervescent tablets of Chinese traditional medicine. Effervescent tablets that have been used to clinic were enumerated.


Lignans from the root of Rhodiola crenulata.
Rhodiola crenulata L. is an important species in genus Rhodiola widely used as a health food to reinforce immunity, improve memory and learning, scavenge active-oxygen species, and relieve altitude sickness. Eleven new lignans and a new benzonitrile compound, crenulatanoside A, were isolated from the roots of R. crenulata L. along with 25 known compounds, including 12 lignans. The structures of these compounds were elucidated by spectroscopic data and chemical evidence. Among them, compounds 1-4 and 5-7 were determined to be optical isomers of two 8-O-4' neolignan glycosides. Compounds 8-11 were aryl tetralin type lignans, and compounds 12 and 13 were dihydrobenzofuran neolignans. All of the isolated compounds were evaluated for their inhibitory activity against α-glucosidase. From the data obtained, compound 37 showed strong inhibitory activity against α-glucosidase with an IC(50) value of 96.8 μM.


Effect of recent hearing aid improvements on management of the hearing impaired.
Recent developments in hearing aid technology and earmold acoustics have improved the outlook for the hearing impaired. Advances involving the electric microphone, integrated circuit, and earmold/hearing aid coupling system have affected such features as compression amplification, filtering, and frequency characteristics of the amplified signal at the eardrum. The resulting changes in hearing aid fitting approaches are described, including factors which are considered in such fittings as in-the-ear, binaural, CROS and BICROS, with examples of difficult cases. Hearing aids are then discussed in the context of a broader rehabilitation strategy.


Kinetic and inhibition studies for the aerobic cometabolism of 1,1,1-trichloroethane, 1,1-dichloroethylene, and 1,1-dichloroethane by a butane-grown mixed culture.
Batch kinetic and inhibition studies were performed for the aerobic cometabolism of 1,1,1-trichloroethane (1,1,1-TCA), 1,1-dichloroethylene (1,1-DCE), and 1,1-dichloroethane (1,1-DCA) by a butane-grown mixed culture. These chlorinated aliphatic hydrocarbons (CAHs) are often found together as cocontaminants in groundwater. The maximum degradation rates (k(max)) and half-saturation coefficients (K(s)) were determined in single compound kinetic tests. The highest k(max) was obtained for butane (2.6 micromol/mg TSS/h) followed by 1,1-DCE (1.3 micromol/mg TSS/h), 1,1-DCA (0.49 micromol/mg TSS/h), and 1,1,1-TCA (0.19 micromol/mg TSS/h), while the order of K(s) from the highest to lowest was 1,1-DCA (19 microM), butane (19 microM), 1,1,1-TCA (12 microM) and 1,1-DCE (1.5 microM). The inhibition types were determined using direct linear plots, while inhibition coefficients (K(ic) and K(iu)) were estimated by nonlinear least squares regression (NLSR) fits to the kinetic model of the identified inhibition type. Two different inhibition types were observed among the compounds. Competitive inhibition among CAHs was indicated from direct linear plots, and the CAHs also competitively inhibited butane utilization. 1,1-DCE was a stronger inhibitor than the other CAHs. Mixed inhibition of 1,1,1-TCA, 1,1-DCA, and 1,1-DCE transformations by butane was observed. Thus, both competitive and mixed inhibitions are important in cometabolism of CAHs by this butane culture. For competitive inhibition between CAHs, the ratio of the K(s) values was a reasonable indicator of competitive inhibition observed. Butane was a strong inhibitor of CAH transformation, having a much lower inhibition coefficient than the K(s) value of butane, while the CAHs were weak inhibitors of butane utilization. Model simulations of reactor systems where both the growth substrate and the CAHs are present indicate that reactor performance is significantly affected by inhibition type and inhibition coefficients. Thus, determining inhibition type and measuring inhibition coefficients is important in designing CAH treatment systems.


Two improved algorithms with which to obtain contoured windows for fringe patterns generated by electronic speckle-pattern interferometry.
Fringe patterns generated by electronic speckle-pattern interferometry are full of high-spatial-frequency and high-contrast speckle noise. Filtering with contoured windows has proved to be an efficient approach to filtering out speckle noise while retaining the fringe patterns. Furthermore, with contoured windows the contoured correlation fringe pattern method can be used to derive smooth, normalized, consistent fringes. Contoured windows previously were determined by fringe orientation only, and this process generated accumulated errors. We propose two new algorithms with which to obtain the contoured windows according to the fringe intensity slope and the distance ratio to neighboring skeletons. These new techniques can determine contoured windows more precisely.


The impact of wood ice cream sticks' origin on the aroma of exposed ice cream mixes.
The effect of volatile compounds in white birch sticks obtained from four different geographical locations on the aroma of ice cream mix was investigated. Sensory evaluation, (specifically, a series of warmed-up paired comparisons) was conducted on stick-exposed ice cream mixes to determine whether aroma differences in those mixes could be detected. Batches of ice cream mix were exposed to the sticks and aged for 6 d at 4 degrees C and then assessed by the panelists by pairwise comparison. Findings suggest that differences in aroma of mixes that have been exposed to white birch sticks from four different geographical origins can be distinguished perceptually.


The Impact of Addition of Consolidation Chemotherapy to Standard Cisplatin-Based Chemoradiotherapy in Uterine Cervical Cancer: Matter of Distant Relapse.
Treatment of advanced uterine cervical cancer has advanced little in the last 15 years. Although two phase III trials showed survival benefit with the addition of consolidation chemotherapy (CT) after cisplatin-based chemoradiotherapy (RTCT), it is not considered standard of care. We aimed to evaluate the benefit of consolidation CT compared to no additional treatment in patients treated with RTCT. This is a retrospective study including 186 patients with FIGO stage IB2, IIA2, or IIB to IVB (paraaortic lymph nodes only) uterine cervical cancer who were treated with standard RTCT alone or RTCT followed by consolidation CT. Overall survival (OS), progression free survival (PFS), and the risk of distant and local relapses were compared between the two treatment groups. At 3 years OS was 91% versus 82.3% (p=0.027), PFS 84.3% versus 54.4% (p=0.047), and distant metastasis free survival (DMFS) 80.4% versus 62.5% (p=0.027) in favor of the consolidation CT group. Multivariate analysis confirmed the benefit of consolidation CT. There was no difference in locoregional free survival (LRFS). Positive lymph node was related to a higher risk of distant relapse. In the lymph node positive subgroup consolidation CT resulted in longer OS (p=0.050), PFS (p=0.014), and DMFS (p=0.022); in the lymph node negative subgroup there was no benefit from consolidation CT. Use of consolidation CT resulted in longer OS and PFS, mostly due to control of distant relapses. Patients at higher risk of distant relapse showed the greatest benefit. This data generates a hypothesis that could help to better select patients to consolidation CT.


A short form of the Recovery Assessment Scale-Domains and Stages: Development and validation among adults with anxiety disorders.
The Recovery Assessment Scale-Domains and Stages (RAS-DS) is a 38-item self-report instrument measuring recovery from serious mental illness. We explored the suitability of the RAS-DS for individuals with anxiety disorders. A parsimonious short form of the scale was developed. Participants with anxiety disorder symptoms (N = 295) completed the RAS-DS, DASS-21 and GAD-7. Confirmatory factor analysis supported the expected four-factor structure. Associations with related scales exhibited the expected pattern supporting construct validity in this population. The Recovery Assessment Scale-Short Form (RAS-SF) was derived by inspection of factor loadings and modification indices, yielding a 20-item scale with five items per subscale. Strong correlations between subscales confirmed the total score represented a valid overarching measure of recovery. The present study indicates that recovery is pertinent to individuals with anxiety disorders. Development of the short-form RAS-SF affords opportunity for routine measurement of recovery in populations with anxiety and other high prevalence conditions.


Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature.
In the current study, we report a 69-year-old female patient who was initially diagnosed with xanthogranulomatous pyelonephritis (XGPN) with nephrolithiasis and a peri-renal abscess. She presented to our department with right flank pain. Physical examination revealed right costovertebral angle knocking pain and computed tomography revealed dilated calyces and one staghorn stone over right kidney, with multiple abscess accumulations over the right peri-renal region. Right radical nephrectomy was performed using a transperitoneal flank approach, and pathology revealed squamous cell carcinoma (SCC) with concurrent XGPN. The patient was alive at 4 months post-operative follow-up. To the best of our knowledge, this is only the fifth case of renal SCC with concurrent XGPN reported in the English medical literature. Renal SCC with coexisting XGPN is an extremely rare presentation and only four cases have been previously reported in the English medical literature. A positive diagnosis for this rare combination of diseases was established, based on pathological and immunohistochemical examinations after radical nephrectomy. Poor prognosis has been reported in such cases. Malignancies should be considered in patients with a long-standing history of urolithiasis.


Distinct basal ganglia hyperechogenicity in idiopathic basal ganglia calcification.
We report a 67-year-old patient with idiopathic basal ganglia calcification (IBGC). He presented with progressive cognitive impairment, frontal lobe dysfunction, mild leg spasticity, and levodopa (L-dopa)-responsive parkinsonism. Transcranial sonography (TCS) revealed marked hyperechogenicity of the basal ganglia and periventricular spaces bilaterally. The detected signal alterations showed a fairly symmetric distribution and corresponded to the hyperintense calcifications depicted on the computer tomography brain scan. The combination of symmetric hyperechogenic areas adjacent to the lateral ventricles and of the basal ganglia may serve as an imaging marker characteristic of IBGC. Hyperechogenicity due to extended basal ganglia calcification as presented here is distinct from the pattern of hyperechogenicity caused by heavy metal accumulation, which is described to be less striking. In addition to atypical parkinsonian syndromes such as progressive supranuclear palsy and multiple system atrophy, IBGC is thus another differential diagnosis of parkinsonism with basal ganglia hyperechogenicity.


Visible light-induced selective hydrobromodifluoromethylation of alkenes with dibromodifluoromethane.
A visible light-induced selective hydrobromodifluoromethylation of alkenes using CF2Br2 was developed. This transformation proceeded smoothly in the presence of catalytic eosin Y at room temperature to give various hydrobromodifluoromethylated compounds with broad functional group tolerance.


Phenyl-Lactic Acid Is an Active Ingredient in Bactericidal Supernatants of Lactobacillus crispatus.
Lactobacillus crispatus is a well-established probiotic with antimicrobial activity against pathogens across several niches of the human body generally attributed to the production of bacteriostatic molecules, including hydrogen peroxide and lactic acid. Here, we show that the cell-free supernatants of clinical isolates of L. crispatus harbor robust bactericidal activity. We further identify phenyl-lactic acid as a bactericidal compound with properties and a susceptibility range nearly identical to that of the cell-free supernatant. As such, we hypothesize that phenyl-lactic acid is a key active ingredient in L. crispatus supernatant. IMPORTANCE Although Lactobacillus crispatus is an established commensal microbe frequently used in probiotics, its protective role in the bladder microbiome has not been clarified. We report here that some urinary isolates of L. crispatus exhibit bactericidal activity, primarily due to its ability to excrete phenyl-lactic acid into its environment. Both cell-free supernatants of L. crispatus isolates and phenyl-lactic acid exhibit bactericidal activity against a wide range of pathogens, including several that are resistant to multiple antibiotics.


The effects of aging on reaction time in a signal detection task.
The effects of aging on response time are examined in 2 simple signal detection tasks with young and older subjects (age 60 years and older). Older subjects were generally slower than young subjects, and standard Brinley plot analyses of response times showed typical results: slopes greater than 1 and (mostly) negative intercepts. R. Ratcliff, D. Spieler, and G. McKoon (2000) showed that the slopes of Brinley plots measure the relative standard deviations of the distributions of response times for older versus young subjects. Applying R. Ratcliff's (1978) diffusion model to fit the response times, their distributions, and response accuracy, it was found that the larger spread in older subjects' response times and their slowness relative to young subjects comes from a 50-ms slowing of the nondecision components of response time and more from conservative settings of response criteria.


Human nongastric H+-K+-ATPase: transport properties of ATP1al1 assembled with different beta-subunits.
To investigate whether nongastric H+-K+-ATPases transport Na+ in exchange for K+ and whether different beta-isoforms influence their transport properties, we compared the functional properties of the catalytic subunit of human nongastric H+-K+-ATPase, ATP1al1 (AL1), and of the Na+-K+-ATPase alpha1-subunit (alpha1) expressed in Xenopus oocytes, with different beta-subunits. Our results show that betaHK and beta1-NK can produce functional AL1/beta complexes at the oocyte cell surface that, in contrast to alpha1/beta1 NK and alpha1/betaHK complexes, exhibit a similar apparent K+ affinity. Similar to Na+-K+-ATPase, AL1/beta complexes are able to decrease intracellular Na+ concentrations in Na+-loaded oocytes, and their K+ transport depends on intra- and extracellular Na+ concentrations. Finally, controlled trypsinolysis reveals that beta-isoforms influence the protease sensitivity of AL1 and alpha1 and that AL1/beta complexes, similar to the Na+-K+-ATPase, can undergo distinct K+-Na+- and ouabain-dependent conformational changes. These results provide new evidence that the human nongastric H+-K+-ATPase interacts with and transports Na+ in exchange for K+ and that beta-isoforms have a distinct effect on the overall structural integrity of AL1 but influence its transport properties less than those of the Na+-K+-ATPase alpha-subunit.


Drosophila has a twitchin/titin-related gene that appears to encode projectin.
The sequences of twitchin and titin identify a superfamily of muscle proteins whose functions are not completely understood. In spite of their shared structural features, twitchin and titin appear to differ in function. Genetic and molecular evidence suggests that twitchin has a regulatory role in muscle contraction, whereas it has been proposed that titin has a structural function. We report here that Drosophila has a single-copy gene containing the two-motif amino acid sequence pattern that characterizes twitchin and titin. This gene appears to encode projectin, a muscle protein that is thought to play a structural role in asynchronous flight muscle but may have a role like that of twitchin in synchronous muscle. Thus Drosophila appears to be a case where the apparently diverged functions of twitchin and titin are encoded by a single gene.


Time-dependent energetic proton acceleration and scaling laws in ultraintense laser-pulse interactions with thin foils.
A two-phase model, where the plasma expansion is an isothermal one when laser irradiates and a following adiabatic one after laser ends, has been proposed to predict the maximum energy of the proton beams induced in the ultraintense laser-foil interactions. The hot-electron recirculation in the ultraintense laser-solid interactions has been accounted in and described by the time-dependent hot-electron density continuously in this model. The dilution effect of electron density as electrons recirculate and spread laterally has been considered. With our model, the scaling laws of maximum ion energy have been achieved and the dependence of the scaling coefficients on laser intensity, pulse duration, and target thickness have been obtained. Some interesting results have been predicted: the adiabatic expansion is an important process of the ion acceleration and cannot be neglected; the whole acceleration time is about 10-20 times of laser-pulse duration; the larger the laser intensity, the more sensitive the maximum ion energy to the change of focus radius, and so on.


Cytology of effusions in the coelom cavities.
oelom cavities (pleura, pericardium, peritoneum, tunica vaginalis testis) lined with mesothelial lining derived from the mesoderm, represent a frequent place of propagation of pathological processes both from the neighbourhood and primary. These are most often manifested by effusion, whose cytological examination contributes significantly to the diagnosis. Each larger amount of fluid in the coelom spaces is pathological. The primary task is, as a rule, the identification of tumour cells, more often of metastatic origin (with decreasing frequency (adenocarcinomas, melanoma, sarcomas) than primary (mesothelioma, primary lymphomas of coelom cavities). The differentiation of carcinoma or other tumour populations from mesothelial cells often requires, following careful morphological evaluation, the indication of complementary methods of staining, immunocytochemistry (in haematological malignancies, preferably in combination with flow cytometry) or methods of molecular pathology. Standardization is not yet advanced in this diagnostic area, however there is a consensus for a panel to distinguish between carcinoma and mesothelioma. Diagnosis is always generated via a summation of features. A good outcome requires adequate control of all three phases of the diagnostic process and a clear and unambiguous diagnosis, or differential diagnosis, formulation. Keywords: cytology of effusions - body cavity fluids - coelom cavities - carcinoma - reactive mesothelial cells - mesothelioma.


Insulin therapy for dogs and cats.
Management of diabetic dogs and cats requires a tremendous cooperative effort between the practitioner and the client. Consistency in the handling, availability, and formulations of the different insulins will improve client compliance. In addition to insulin therapy, successful management of the diabetic animal includes the client's perceptions of the animal's health, maintenance of the animal's body weight, consistency in water consumption, and monitoring serial blood glucose concentrations. Serial blood glucose determinations improve the practitioner's ability to identify and address problems associated with insulin therapy, and thereby delay or minimize the complications of long-term diabetes.


Trypsin inhibitor in mung bean cotyledons: purification, characteristics, subcellular localization, and metabolism.
Trypsin inhibitor was purified to homogeneity from seeds of the mung bean (Vigna radiata [L.] Wilczek). The protease inhibitor has the following properties: inhibitory activity toward trypsin, but not toward chymotrypsin; isoelectric point at pH 5.05; molecular weight of 11,000 to 12,000 (sodium dodecyl sulfate gel electrophoresis) or 14,000 (gel filtration); immunological cross-reactivity against extracts of black gram and black-eyed pea, but not against soybean; no inhibitory activity against vicilin peptidohydrolase, the principal endopeptidase in the cotyledons of mung bean seedlings.The trypsin inhibitor content of the cotyledons declines in the course of seedling growth and the presence of an inactivating factor can be demonstrated by incubating crude extracts in the presence of beta-mercaptoethanol. This inactivating factor may be a protease as vicilin peptidohydrolase rapidly inactivates the trypsin inhibitor. Removal of trypsin inhibitory activity from crude extracts by means of a trypsin affinity column does not result in an enhancement of protease activity in the extracts.The intracellular localization of trypsin inhibitor was determined by fractionation of crude extracts on isopycnic sucrose gradients and by cytochemistry with fluorescent antibodies. Both methods indicate that trypsin inhibitor is associated with the cytoplasm and not with the protein bodies where reserve protein hydrolysis occurs. No convincing evidence was obtained which indicates that the catabolism of trypsin inhibitor during germination and seedling growth is causally related to the onset of reserve protein breakdown.


Soy isoflavones reduce heat shock proteins in experimental atherosclerosis.
Soy isoflavones may affect several biochemical pathways like the synthesis of nitric oxide (*NO) and heat shock proteins (HSP) that are important factors for atherosclerosis development. The purpose of this study was to investigate the influence of soy isoflavones on the production of *NO and HSP60, HSP70 and HSC70 in experimental atherosclerosis. One group of rabbits (New Zealand) was fed an atherogenic diet containing 27 % casein (CAS) and another group was fed the same diet supplemented with soy isoflavones (5 mg/kg/day) (ISO). Blood samples were obtained monthly and after six months of feeding, the rabbits were sacrificed and the aortas were removed. The ISO group showed a significant reduction of cholesterol in LDL (36.2 %) and in aorta (36 %), as well as, an increase of HDL-cholesterol (2.1 times) in relation to the CAS group. The concentration of *NO metabolites (NOx) in blood plasma and the levels of reactive antibodies to HSC70 in blood plasma and to HSC70 and HSP70 in aortic tissue were significantly decreased in the ISO group. Isoflavones promoted a reduction of content of HSP60, HSP70 and HSC70 in aortic arch analyzed by immunohistochemistry. The isoflavone supplementation promoted a reduction of cholesterol content in aorta (62.2 %) (p < 0.05). Soy isoflavones reduced hypercholesterolemia, the production of HSP60, HSC70 and HSP70 and reactive antibodies to HSC70 in serum and to HSC70 and HSP70 in aorta, as well as, the cholesterol content in atherosclerotic lesions in rabbits fed a casein-based atherogenic diet.


Cosmic Coincidences: Investigations for Neutron Background Suppression.
Two experimental investigations were made in order to reduce background counts in neutron detectors. Each investigation relied upon the fact that neutron background is largely due to cosmic ray interactions with the air and ground. The first attempt was to look at neutron arrival times. Neutron events close in time were taken to have been of a common origin due to cosmic rays. The second investigation was similar, but based on coincident neutron/muon events. The investigations showed only a small effect, not practical for the suppression of neutron background.


Structural organization of xanthine crystals in the median ocellus of a member of the ancestral insect group Archaeognatha.
Biogenic purine crystals function in vision as mirrors, multilayer reflectors and light scatterers. We investigated a light sensory organ in a primarily wingless insect, the jumping bristletail Lepismachilis rozsypali (Archaeognatha), an ancestral group. The visual system of this animal comprises two compound eyes, two lateral ocelli, and a median ocellus, which is located on the front of the head, pointing downwards to the ground surface. We determined that the median ocellus contains crystals of xanthine, and we obtained insights into their function. To date, xanthine biocrystals have only been found in the Archaeognatha. We performed a structural analysis, using reflection light microscopy, cryo-FIB-SEM, microCT and cryo-SEM. The xanthine crystals cover the bottom of a bowl-shaped volume in the median ocellus, in analogy to a tapetum, and reflect photons to light-sensitive receptors that are spread in the volume without apparent order or preferential orientation. We infer that the median ocellus operates as an irregular multifocal reflector, which is not capable of forming images. A possible function of this organ is to improve photon capture, and by so doing assess distances from the ground surface when jumping by determining changes in the intensity and contrast of the incident light.


Senescence associated long non-coding RNA 1 regulates cigarette smoke-induced senescence of type II alveolar epithelial cells through sirtuin-1 signaling.
The primary aim of our study was to explore the mechanisms through which long non-coding RNA (lncRNA)-mediated sirtuin-1 (SIRT1) signaling regulates type II alveolar epithelial cell (AECII) senescence induced by a cigarette smoke-media suspension (CSM). Pharmacological SIRT1 activation was induced using SRT2104 and senescence-associated lncRNA 1 (SAL-RNA1) was overexpressed. The expression of SIRT1, FOXO3a, p53, p21, MMP-9, and TIMP-1 in different groups was detected by qRT-PCR and Western blotting; the activity of SA-β gal was detected by staining; the binding of SIRT1 to FOXO3a and p53 gene transcription promoters was detected by Chip. We found that CSM increased AECII senescence, while SAL-RNA1 overexpression and SIRT1 activation significantly decreased levels of AECII senescence induced by CSM. Using chromatin immunoprecipitation, we found that SIRT1 bound differentially to transcriptional complexes on the FOXO3a and p53 promoters. Our results suggested that lncRNA-SAL1-mediated SIRT1 signaling reduces senescence of AECIIs induced by CSM. These findings suggest a new therapeutic target to limit the irreversible apoptosis of lung epithelial cells in COPD patients.


[A case of malignant fibrous histiocytoma arising from the renal capsule].
A 62-year-old man was admitted with a chief complaint of general malaise. Computed tomography showed a large mass adjacent to the parenchyma of the left kidney. The mass was 17 x 13 x 12 cm in size. Preoperative diagnosis was left renal cell carcinoma and left radical nephrectomy was performed. Histopathologically, the tumor was diagnosed as malignant fibrous histiocytoma (MFH), and the tumor was considered to have arisen from the renal capsule. There has been no recurrence for 7 months postoperatively. We review 40 cases of MFH arising from the kidney or the renal capsule in the literature.


Good Clinical Approach: Delphi Consensus for the Use of Betahistine in Menière's Disease.
Menière's disease is a disorder of the inner ear that causes vertigo, tinnitus, fullness, and hearing loss. Several pharmacological treatments are available, but none of them has shown significant results. Betahistine has been largely used but its effect on the main symptoms of Menière's disease remains unclear. In order to improve clinical appropriateness and to reduce the heterogeneity of the therapeutic approaches for Menière's disease, we proposed a European Consensus Conference on Betahistine's prescription. A group of European experts in vestibular disorders completed a questionnaire, prepared by opinion leaders, on the use of betahistine in Menière's disease. The Delphi method was used as an iterative investigation method in order to increase and establish the consensus. While betahistine was considered useful to reduce the number of the vertigo attacks during the intercritical phase of the disease, its use during attacks was considered helpful only when associated with other drugs. Betahistine was not considered useful for preventing hearing loss. The experts support the use of betahistine during the intercritical phase of the disease to reduce the number and severity of vertigo episodes. They also defined the parameters for a good clinical approach to evaluate the efficacy of betahistine treatment for Menière's disease.


Evaluation of visual inspection with acetic acid and Lugol's iodine as cervical cancer screening tools in a low-resource setting.
In view of the failure of cytology screening programmes for cervical cancer in developing countries, the World Health Organization suggested unaided visual inspection of the cervix after an application of acetic acid (VIA) and Lugol's iodine (VILI) as alternative screening methods. Our study evaluates the effectiveness of VIA and VILI compared to Pap smear as screening methods for carcinoma of the cervix in a low-resource setting. Three hundred and twenty-eight women were subjected to a Pap smear test, VIA, VILI and colposcopy. The results were as follows: Pap smear test (20.83%, specificity 98.38%), VIA (55.5%, 71.39%) and VILI (86.84%, 48.93%). Although VIA and VILI are less specific in comparison to the Pap smear test, they are more sensitive in detecting pre-invasive lesions. Hence VIA and VILI can be used as cervical cancer screening tools in low-resource settings.


Development of a Korean Hyperthyroidism-Specific Health Status Scale.
The aims of this study were to develop a hyperthyroidism-specific health status scale of Korea (K-HHSS) and to verify its validity and reliability. A methodological study was performed with hyperthyroid patients to assess the following properties: content validity, item analysis, Cronbach's α, intraclass correlation coefficients, and confirmatory factor analysis. The data were obtained from 80 patients with hyperthyroidism given medical care at C university hospital in Seoul in 2017. The construct validity was supported by the item-analysis correlations ranging between 0.31 and 0.82. The internal consistency reliability was from 0.70 to 0.85, and the scale's stability was confirmed by intraclass correlation coefficients between 0.57 and 0.97. Construct reliability was 0.81 and the average variance extracted (AVE) was 0.72. These inclusion criteria resulted in the selection of 30 items in 7 categories. This scale will be useful as a limited health-measuring index for the nursing assessment of patients with hyperthyroidism in Korea.


[Employment of cross-border workers in the Federal Republic of Germany].
The author analyzes the cross-border movement of labor migrants in Germany. The impact of increased integration among European Community countries is considered, and the pressure of migration from neighboring Eastern European countries is discussed. "Employment of workers from border regions [provides the] possibility of meeting the labour demand in the region, of alleviating the pressure to migrate by legalizing inflows and of balancing the interests of employers and cross-border workers, thus avoiding some of the negative side-effects or social costs of traditional labour migration." (SUMMARY IN ENG AND FRE AND RUS)


Clinical experience with autobiotherapy of malignant tumor disease: a preliminary report.
It has been proposed that the elimination of excess scar tissue from the body is achieved by specialized killer cells, which are activated by vascular changes in the scar tissue. The malignant tumor is, according to this theory, considered to be a special type of excess scar tissue of fetal or near fetal age, the fetal blood supply of which prevents the activation of those specialized killer cells which were believed to eliminate excess scar tissue. Therefore, it is assumed that if the specialized killer cells of a malignant tumor patient are activated artificially, they would cause malignant tumor regression in vivo. This method of treatment is called autobiotherapy because it utilizes biological products from the patient to treat his own malignant tumor. Preliminary evidence is presented in support of autobiotherapy of malignant tumor disease.The peripheral leucocytes of 27 malignant tumor patients were activated separately by incubation in a serum-free medium containing the respective tumor cells or material. The effect of the injection of the activated leucocytes or their products, termed tumor leucocyte cultures (TLC), was studied in five patients with Kaposi sarcoma, five with carcinoma of the breast, four with carcinoma of the cervix, three with soft tissue sarcoma, two with carcinoma of the lung, two with carcinoma of the maxillary antrium, and a miscellaneous group of six patients. In 52 percent of cases, there was significant tumor regression. Tumor regression was most marked in patients with Kaposi sarcoma, carcinoma of the cervix, pharynx, and pancreas, one patient with a slow growing fibrosarcoma, one patient with a metastatic breast carcinoma, and also in one patient with myelogenous leukemia. However, not all the types of tumor studied responded satisfactorily to autobiotherapy. The reasons for the differences in response to autobiotherapy remain to be determined. Even so, the positive results obtained indicate that autobiotherapy is worthy of further research as an alternative in controlling malignant tumor disease.


Having faith: experiencing coronary artery bypass grafting.
Even though coronary artery bypass grafting (CABG) is a commonly performed procedure, it is perceived by the client as a life-threatening event. When one is faced with a crisis, spiritual issues become extremely important. The purposes of this qualitative study were to discover what the spiritual needs are for CABG clients and how these needs are met during hospitalization. Grounded theory methodology was used to accomplish these goals. Data were collected through semistructured interviews with 17 adults, ages 34 to 83, who were 4 to 7 days post-CABG. Initially, the interview questions centered around how they felt when told of the need for surgery and how spiritual issues entered into that decision. From these questions a pattern emerged that led to the development of specific research questions. The major findings were that spiritual needs centered around having faith in their decision making, in the hospital staff (especially the nurses), and an overwhelming faith in God. CABG is a time of great stress, a time of feeling "pulled apart" and fragmented. Clients need to feel a sense of wholeness, not only physically and psychologically, but also spiritually. Because nurses are with clients on a consistent basis, they are able to assess and identify spiritual needs and provide needed spiritual resources. If nurses are educated to meet these needs it may help clients become more aware that nurses care about them as human beings who have a variety of needs with which the nurse is willing to assist.


Identification and characterization of an immunophilin expressed during the clonal expansion phase of adipocyte differentiation.
Mouse 3T3-L1 cells differentiate into fat-laden adipocytes in response to a cocktail of adipogenic hormones. This conversion process occurs in two discrete steps. During an early clonal expansion phase, confluent 3T3-L1 cells proliferate and express the products of the beta and delta members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors. The cells subsequently arrest mitotic growth, induce the expression of the alpha form of C/EBP, and acquire the morphology of fully differentiated adipocytes. Many of the genes induced during the terminal phase of adipocyte conversion are directly activated by C/EBP alpha, and gratuitous expression of this transcription factor is capable of catalyzing adipose conversion in a number of different cultured cell lines. The genetic program undertaken during the clonal expansion phase of 3T3-L1 differentiation, controlled in part by C/EBP beta and C/EBP delta, is less clearly understood. To study the molecular events occurring during clonal expansion, we have identified mRNAs that selectively accumulate during this phase of adipocyte conversion. One such mRNA encodes an immunophilin hereby designated FKBP51. In this report we provide the initial molecular characterization of FKBP51.