The effect on IVF outcome of small intramural fibroids not compressing the uterine cavity as determined by a prospective matched control study.
Several studies have reported that the presence of intramural fibroids affects conception following IVF. We attempted to corroborate or refute the conclusions relating to IVF and leiomyomas of the aforementioned studies. Women with small intramural leiomyomata (< or = 5 cm) discovered on initial pelvic sonographic studies performed in preparation for IVF were prospectively matched by age, with the next patient of the same age undergoing IVF who did not demonstrate fibroids (controls). Though no significant differences were found in outcome when comparing these two groups, there was a distinct trend for lower live delivery rates and higher miscarriage rates. These data support the conclusions of the only other prospective matched control study evaluating similar factors, i.e. that small intramural fibroids can negatively affect IVF outcome. Nevertheless, we think that a multicentre study should be conducted first before evaluating whether myomectomy improves outcome or not.


Facilitated Look-Back Analysis of Public Health Emergencies to Enhance Preparedness: A Brief Report of a Chemical Spill in Charleston, West Virginia.
To demonstrate how public health emergency systems can use health systems tools to analyze and learn from critical incidents, we employed a facilitated look-back approach to review the public response to a chemical spill in Charleston, West Virginia. We reviewed official reports, news articles, and other documents; conducted in-person interviews with key public health and emergency response officials and local community stakeholders; and organized a facilitated look-back meeting to identify root causes of the problems that were encountered. The primary response challenges were (1) public distrust stemming from scientific uncertainty about potential harms of chemicals involved in the spill and how this uncertainty was communicated and (2) communication within the public health system, broadly defined. We found that to address inherent uncertainty, health officials should acknowledge uncertainty and tell the public what is known and unknown, and what they are doing to get more information.


Using reflectometry to minimize the dependence of fluorescence intensity on optical absorption and scattering.
The total diffuse reflectance RT and the effective attenuation coefficient µeff of an optically diffuse medium map uniquely onto its absorption and reduced scattering coefficients. Using this premise, we developed a methodology where RT and the slope of the logarithmic spatially resolved reflectance, a quantity related to µeff, are the inputs of a look-up table to correct the dependence of fluorescent signals on the media's optical properties. This methodology does not require an estimation of the medium's optical property, avoiding elaborate simulations and their errors to offer accurate and fast corrections. The experimental demonstration of our method yielded a mean relative error in fluorophore concentrations of less than 4% over a wide range of optical property variations. We discuss how the method developed can be employed to improve image fidelity and fluorochrome quantification in fluorescence molecular imaging clinical applications.


1986 and beyond. Nursing's future.
Predicting the future is a risky effort for nursing administrators. What we can do is reevaluate our past and learn how the lessons of prior eras can help us understand the trends affecting health care and nursing and plan strategies for moving nursing forward. Specifically, to move forward we must effectively deal with our image, mechanism for educating students, attainment of public accountability and professional autonomy, political skills, and becoming more actively involved in research to document the value of nursing.


Pulmonary vasodilation with structurally altered pulmonary vessels and pulmonary hypertension.
To evaluate pulmonary vasodilation in a structurally altered pulmonary vascular bed, we gave endothelium-dependent (acetylcholine) and endothelium-independent [sodium nitroprusside, prostaglandin I2 (PGI2)] vasodilators in vivo and to isolated lobar pulmonary arteries from neonatal calves with severe pulmonary hypertension. Acetylcholine, administered by pulmonary artery infusion, decreased pulmonary arterial pressure from 120 +/- 7 to 71 +/- 6 mmHg and total pulmonary resistance from 29.4 +/- 2.6 to 10.4 +/- 0.9 mmHg.l-1.min without changing systemic arterial pressure (90 +/- 5 mmHg). Although both sodium nitroprusside and PGI2 lowered pulmonary arterial pressure to 86 +/- 4 and 96 +/- 4 mmHg, respectively, they also decreased systemic arterial pressure to 65 +/- 4 and 74 +/- 3 mmHg, respectively. Neither sodium nitroprusside nor PGI2 was as effective as acetylcholine at lowering total pulmonary resistance (18.0 +/- 3.6 and 19.1 +/- 2.2 mmHg.l-1.min, respectively). Right-to-left cardiac shunt through the foramen ovale was decreased by acetylcholine from 1.6 +/- 0.4 to 0.1 +/- 0.2 l/min but was not changed by sodium nitroprusside or PGI2. Isolated lobar pulmonary arteries from pulmonary hypertensive calves did not relax in response to acetylcholine, whereas isolated pulmonary arteries from age-matched control calves did relax in response to acetylcholine. Control and pulmonary hypertensive lobar pulmonary arteries relaxed equally well in response to sodium nitroprusside. We concluded that acetylcholine vasodilation was impaired in vitro in isolated lobar pulmonary arteries but was enhanced in vivo in resistance pulmonary arteries in neonatal calves with pulmonary hypertension.


Expression of Delta-like protein 4 in the human endometrium.
Activation of Delta-Notch signaling pathway promotes the development of the vascular system in embryo, normal adult tissues, and cancerous lesions. Delta and Notch genes are known to be expressed in endothelial cells, and little is known of their expression beyond the vascular system. The purpose of this study was to investigate whether Delta gene would be expressed in cells of the uterine endometrium. In this study, we found that the human endometrial cells expressed one of the Delta ligands, Delta-like 4 protein (Dll4). Dll4 was expressed in human endometrium in a spatiotemporal fashion. Immunohistochemistry studies showed the cytoplasm as well as membrane staining with apical localization both in the luminal and glandular epithelium and moderate diffuse staining in the cytoplasm of the stromal cells. Western blot analysis showed that the size of the endometrial Dll4 was identical to that in the human umbilical endothelial cells. The expression of Dll4 mRNA in human endometrial cells was quantitatively determined by real-time PCR. Dll4 mRNA expressed in the glandular epithelium showed large variations, and it was significantly elevated in the mid and late proliferative and early secretory endometrium. Endometrial stromal cells contained less Dll4 mRNA and had no clear correlation with the menstrual cycle. The effect of hormones was studied in the primary culture of isolated glandular epithelial and stromal cells. In glandular cells, estradiol had little effect, and medroxyprogesterone acetate significantly reduced the mRNAs compared with that of control. Relaxin induced the Dll4 mRNA. In stromal cells, both estradiol and medroxyprogesterone acetate reduced the Dll4 mRNA. To our knowledge, this is the first report of the expression of Dll4 in the endometrium. We propose that endometrial Dll4 may enhance the development of the endometrial microvascular system and facilitate the implantation of blastocyst in a fertile cycle.


Immunohistochemical patterns for alpha- and beta-catenin, E- and N-cadherin expression in ovarian epithelial tumors.
This study aims were to analyze and compare the E- and N-cadherin, beta- and alpha-catenin expression in benign and malignant epithelial neoplasms of the ovary, correlating with tumor staging, histological grade, and presence of metastases during evolution. Immunohistochemical reactions were performed on paraffin-embedded tissues and evaluated according to the number of positive, stained cellular structures and reaction intensity for each molecule. Information about histological type and grade, tumoral stage, and disease evolution was obtained from the patients' clinical records. Most of the carcinomas showed more intense beta-catenin reaction (P = 0.02). More than 50% of the endometrioid carcinomas showed increased beta-catenin expression, with a large number of positive cells and more intense staining, being the same also observed for most of the serous benign tumors (P < 0.01). E-cadherin membrane expression was frequently observed in carcinomas without metastasis, whereas cases with metastases in evolution were negative or showing E-cadherin expression only in the cytoplasm (P = 0.04). N-cadherin expression differed according to histological type and grade and alpha-catenin was also related to histological type, but these findings were not conclusive. Increased beta-catenin expression was more frequent in ovarian carcinomas, especially, but not only, in the endometrioid ones. The maintenance of E-cadherin expression in cellular membrane may be an independent marker of good prognosis in ovarian cancer. New studies about N-cadherin and alpha-catenin and their importance during ovarian carcinogenesis will be required.


Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
Glycosylation is one of the most common post-translational modifications to occur during protein biosynthesis, but remains poorly understood in insects. In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage. Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins. LC-MS/MS identified 149 larval and 303 pupal serum proteins in the Con A lectin-enriched fractions. GO analysis revealed that many serum proteins were involved in the proteolysis and carbohydrate metabolic process. 82 N-linked glycoproteins with at least one glycosylation site were identified. N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively. The N-glycan structures found in serum glycoproteins were mainly Man2FucGlcNAc2 (67.9%). Since storage protein 1 and transferrin had a relatively high abundance in the serum and could be significantly enriched by Con A lectin, their glycosylation was analyzed in detail. Glycoside hydrases, serine proteases and serpins were found to form three interacting glycoprotein networks using the website STRING. This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.


Multi-modal and multi-vendor retina image registration.
Multi-modal retinal image registration is often required to utilize the complementary information from different retinal imaging modalities. However, a robust and accurate registration is still a challenge due to the modality-varied resolution, contrast, and luminosity. In this paper, a two step registration method is proposed to address this problem. Descriptor matching on mean phase images is used to globally register images in the first step. Deformable registration based on modality independent neighbourhood descriptor (MIND) method is followed to locally refine the registration result in the second step. The proposed method is extensively evaluated on color fundus images and scanning laser ophthalmoscope (SLO) images. Both qualitative and quantitative tests demonstrate improved registration using the proposed method compared to the state-of-the-art. The proposed method produces significantly and substantially larger mean Dice coefficients compared to other methods (p<0.001). It may facilitate the measurement of corresponding features from different retinal images, which can aid in assessing certain retinal diseases.


A comparison of efficacy and safety of complementary and alternative therapies for children with asthma: A protocol for systematic review and meta analysis.
Bronchial Asthma is a chronic, hyperreactive inflammation of the airway that involves a variety of inflammatory cells. Due to the persistence of airway hyperresponsiveness, lung function is progressively damaged, making asthma more stubborn and difficult to heal. In recent years, the prevalence of childhood asthma is still on an increasing trend. Repeated asthma attacks not only affect children's life and learning, but also bring greater economic and mental burden to children's families, and even threaten children's lives. Traditional treatment methods such as oral western medicine, atomization therapy has obvious limitations, and the complementary and alternative therapy is an effective method to treat asthma in children. This study will evaluate the efficacy and safety of various complementary and alternative therapies for children with asthma by means of mesh meta-analysis. In order to provide the basis for clinical rational use. Use the computer to search the self-built database until January 2021, the China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journals Database, China Biomedical Literature Database, PubMed, Cochrance Library, EMBASE, Web of Science, Clinical Trials and other electronic databases to collect RCT studies on complementary and alternative therapies for for children with asthma. We will screen the relevant literature included in the systematic review/meta analysis. At the same time, Revman 5.3 software will be used for meta-analysis, and grade will be used to grade the quality of evidence in the network meta-analysis. This study will compare the efficacy and safety of different complementary and alternative therapies to treat childhood asthma, and evaluate and rank different interventions. The combined use of complementary and alternative therapies for childhood asthma on the basis of conventional basic treatment can improve clinical efficacy, reduce the occurrence of adverse reactions, improve the quality of life of children, and provide strong support for the rational use of clinicians. INPLASY202120005.


A Novel ESAT-6 Secretion System-Secreted Protein EsxX of Community-Associated Staphylococcus aureus Lineage ST398 Contributes to Immune Evasion and Virulence.
The ESAT-6 secretion system (ESS) has been reported to contribute to the virulence and pathogenicity of several Staphylococcus aureus strains such as USA300 and Newman. However, the role of the ESS in community-associated S. aureus (CA-SA) lineage ST398 in China is not well understood. By comparing the ess locus of ST398 with the published S. aureus sequence in the NCBI database, we found one gene in the ess locus encoding a novel WXG superfamily protein that is highly conserved only in ST398. LC-MS/MS and Western blot analysis revealed that this protein is a novel secreted protein controlled by the ST398 ESS, and we named the protein EsxX. Although EsxX was not under the control of the accessory gene regulator like many other virulence factors and had no influence on several phenotypes of ST398, such as growth, hemolysis, and biofilm formation, it showed important impacts on immune evasion and virulence in ST398. An esxX deletion mutant led to significantly reduced resistance to neutrophil killing and decreased virulence in murine skin and blood infection models, indicating its essential contribution to the evasion of innate host defense and virulence to support the pathogenesis of ST398 infections. The function of this novel secreted protein EsxX might help us better understand the role of the ESS in the virulence and epidemic success of the CA-SA lineage ST398.


Evaluation Intravenous Drip Cephazolin Prophylaxis of Breast Cancer Surgery Site Infection.
The efficacy of antibiotic prophylaxis for the prevention of surgical site infection (SSI) after breast cancer surgery remains uncertain. The authors of a recent Cochrane meta-analysis based on 15 randomized trials were unable to draw a definitive conclusion. The purpose of this study was to determine the effectiveness of prophylactic antibiotics for the prevention of SSI after breast cancer surgery and the risk factors for SSI. Breast cancer patients who underwent mastectomy at the authors' institution were enrolled in this study. All the patients give cephazolin by intravenous drip within 1 hour before surgery. Surgical site infection was defined using Centers for Disease Control criteria. Risk factors were abstracted from the electronic medical record. Pearson χ test, Student t test, and multivariable logistic regression were used for the analysis. Four hundred fifty-eight patients undergoing mastectomy were enrolled in this study, including 293 with intravenous drip cephazolin and 165 without. Among them, an overall SSI rate of 6.1% was observed; 4.2% of patients without prophylactic antibiotics developed SSI compared with 7.2% with antibiotics (P = 0.210). Factors associated with SSI were hypertension, diabetes, length of stay (d), age, and length of stay. Weight, duration of surgery, No. of drains, surgical procedure, and type of breast disease were not associated with increased SSI rates. Surgical site infection rates among patients who did and did not receive cephazolin after mastectomy had no significantly different. What is more, the authors should focus on advanced age, hypertension, diabetes, length of stay, and length of stay to decrease development of postoperative SSI rates.


Ovarian stimulation with buserelin/HMG/HCG: prospective randomized study of short versus long protocol.
The combined administration of the gonadotrophin-releasing hormone (GnRH) agonist buserelin and human menopausal gonadotrophin (HMG) was evaluated in 527 cycles (428 patients) of an assisted reproduction programme. All women were randomly allocated according to the ovulation induction protocol into two groups: group I (short protocol; 318 cycles) was given buserelin (1 mg/day) intranasally from cycle day 1 and HMG (2 ampoules/day) from day 3 until human chorionic gonadotrophin (HCG) administration: group II (long protocol; 209 cycles) was given buserelin (1 mg/day) intranasally from cycle day 1 for at least 14 days and then 2 ampoules HMG/day were added, increasing progressively according to the ovarian response. The number (mean +/- SEM) of follicles developed was higher in group II than in group I (9.1 +/- 0.4 versus 7.7 +/- 0.3, respectively; P < 0.05). More oocytes were retrieved in group II (8.4 +/- 0.5) than in group I (6.5 +/- 0.3) (P < 0.001), as well as more embryos (6.3 +/- 0.5 and 4.0 +/- 0.3, respectively; P < 0.001). Moreover, in group II there was a better correlation between oestradiol and the total follicular volume (r = 0.5391) on cycle day 0 compared with group I (r = 0.458), while oestradiol values were similar between the two groups. No differences were observed in the cancellation rate, fertilization rate and maturity of the oocytes between the two groups. The pregnancy rate per transfer was slightly better in group II (25.8%) than in group I (19.4%), but this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)


Endothelin receptor antagonism attenuates cardiomyocyte apoptosis after induction of ischemia in rats.
Apoptosis has recently been implicated as a process that may contribute to loss of cardiomyocytes and to adverse myocardial remodeling in congestive heart failure (CHF). We investigated to what extent myocardial ischemia and CHF lead to induction of apoptotic gene programs and loss of cardiomyocytes through apoptosis, and subsequently to what extent the beneficial effects of endothelin (ET) receptor antagonism after myocardial infarction (MI) could be attributed to reduction of apoptotic cell loss in the myocardium. Northern blot analysis, analysis of DNA fragmentation, and immunohistochemical analysis were performed after induction of MI in rats. After induction of MI, the mRNA levels of the pro-apoptotic genes FAS, BAX, P53, and CASPASE-1 were significantly increased in the non-ischemic region of the left ventricle (LV) with highest levels of expression in the peri-infarct area. High levels of FAS, BAX, P53, and CASPASE-1 mRNA were also observed in the infarcted region. Concomitantly, numerous TUNEL-positive cells and internucleosomal degradation of DNA were found in tissue from the peri-infarct area and in the infarcted zone, indicating apoptotic cell death. Treatment with bosentan, a mixed ET(A)/ET(B) receptor antagonist, during the first 24 h after induction of MI significantly reduced the area of TUNEL-positive myocardium in the ischemic region (64 +/- 2% of LV circumference in the vehicle group vs 55 +/- 2% of LV circumference in the bosentan group, p < 0.05). Consistently, bosentan also caused a similar reduction of infarct size. Our data demonstrate activation of pro-apoptotic genes and provide evidence of cardiomyocyte apoptosis in the viable peri-infarct area and in the infarcted region after MI in rats. Intervention with bosentan may attenuate cardiomyocyte cell loss through apoptosis in the area at risk after induction of ischemia.


Standard for Reporting Concentrations of Deuterium and Oxygen-18 in Natural Waters.
A standard, based on the set of ocean water samples used by Epstein and Mayeda to obtain a reference standard for oxygen-18 data, but defined relative to the National Bureau of Standards isotopic reference water sample, is proposed for reporting both deuterium and oxygen-18 variations in natural waters relative to the same water. The range of absolute concentrations of both isotopes in meteoric-waters is discussed.


Association of Genetic Variants in CYP3A4, CYP3A5, CYP2C8, and CYP2C19 with Tacrolimus Pharmacokinetics in Renal Transplant Recipients.
Our study aimed to investigate the pharmacogenetics of cytochrome P3A4 (CYP3A4), CYP3A5, CYP2C8, and CYP2C19 and their influence on TAC Pharmacokinetics (PKs) in short-term renal transplant recipients. A total of 105 renal transplant recipients were enrolled. Target Sequencing (TS) based on next-generation sequencing technology was used to detect all exons, exon/intron boundaries, and flanking regions of CYP3A4, CYP3A5, CYP2C8, and CYP2C19. After adjustment of Minor Allele Frequencies (MAF) and Hardy-Weinberg Equilibrium (HWE) analysis, tagger Single-nucleotide Polymorphisms (SNPs) and haplotypes were identified. Influence of tagger SNPs on TAC concentrations was analyzed. A total of 94 SNPs were identified in TS analysis. Nine tagger SNPs were selected, and two SNPs (rs15524 and rs4646453) were noted to be significantly associated with TAC PKs in short-term post-transplant follow-up. Measurement time points of TAC, body mass index (BMI), usage of sirolimus, and incidence of Delayed Graft Function (DGF) were observed to be significantly associated with TAC PKs. Three haplotypes were identified, and rs15524-rs4646453 was found to remarkably contribute to TAC PKs. Recipients carrying H2/H2 (GG-AA) haplotype also showed significantly high weight- and dose-adjusted TAC concentrations in posttransplant periods of 7, 14, and 30 days and 3 and 6 months. Two tagger SNPs, namely, rs15524 and rs4646453, are significantly related to the variability of TAC disposition, and TAC measurement time points, BMI, usage of sirolimus, and incidence of DGF contribute to this influence. Recipients carrying H2/H2 (GG-AA) haplotype in rs15524-rs4646453 may require a low dosage of TAC during 1-year follow-up posttransplant.


Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus.
Impairment of GABA-mediated inhibition is one of the main hypotheses invoked to explain seizure activity, both in experimental models and in human epilepsy. We have studied the distribution and the neurochemical characteristics of certain GABAergic circuits in the normal and epileptic human sclerotic hippocampal formation. We have focused our attention mainly on chandelier cells because, together with basket cells, they are considered to have powerful effects on spike generation. Chandelier cells represent a unique type of interneuron whose axon terminals (Ch-terminals) form synapses with the axon initial segments of cortical pyramidal cells and granular cells of the dentate gyrus. Different neurochemical subpopulations of chandelier cells have been identified by immunocytochemistry, mainly in the neocortex. Markers for Ch-terminals include the GABA transporter 1 (GAT-1), the polysialylated form of the cell-surface glycoprotein neural cell adhesion molecule (PSA-NCAM) and the calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB). In the normal hippocampal formation, GAT-1- and PV-immunoreactive (-ir) Ch-terminals were identified in the granular and polymorphic layers of the dentate gyrus, in the strata pyramidale and oriens of the CA fields, and in the pyramidal layer of the subicular complex. In addition, and in contrast to the hippocampus and dentate gyrus, subsets of Ch-terminals in the upper pyramidal layer of the normal subiculum express CB and PSA-NCAM. The sclerotic hippocampus of epileptic patients presented an impressive morphological and neurochemical reorganization of Ch-terminals and basket formations. This was apparent in the dentate gyrus and hippocampal formation, but not in the subiculum, which appeared to remain unaltered. Principally, numerous and more complex PV- and CB-ir Ch-terminals, as well as dense PV-ir basket formations, appeared in some hippocampal segments, whereas in other regions there was a lack of labelled elements. These changes varied considerably not only between different patients, but also within different hippocampal fields in a given patient. In general, the changes were not correlated with the clinical characteristics or degree of histopathological alterations observed in the patients, such as granular cell dispersion, neuron loss and proliferation of mossy fibres. However, some surviving neurons in the regions adjacent to the areas of neuron loss were consistently innervated by dense basket formations and complex Ch-terminals. These results indicate that, in the human epileptic hippocampus, GABAergic circuits are more highly modified than previously thought. When considered along with other extrahippocampal alterations, we suggest that these changes are important in the pathophysiology of temporal lobe epilepsy associated with hippocampal sclerosis.


Adjunctive use of ultraporous beta-tricalcium phosphate bone void filler in spinal arthrodesis.
Spinal fusion is one of the most common clinical indications for bone grafting. However, synthetic bone substitutes are needed to ameliorate limited availability, donor site morbidity, and potential disease transmission concerns associated with autograft and allograft. One new synthetic bone substitute, Vitoss (Orthovita, Malvern, Pa), is an ultraporous formulation of beta-tricalcium phosphate (beta-TCP). This study examines 50 patients who received ultraporous beta-TCP bone void filler as an adjunct to autogenous bone graft while undergoing spinal fusion procedures. All patients underwent decompressive laminectomy with bilateral posterolateral intertransverse fusion (PLITF) using bone graft mixed with ultraporous beta-TCP, with and without instrumentation. Some patients also underwent posterior lumbar interbody fusion (PLIF) using cages and bone graft. Thirty-two patients were studied for at least 5-7 months postoperatively. Of these patients, 100% demonstrated good consolidation on follow-up radiographs. The use of iliac crest bone graft (ICBG) was avoided entirely in 7 (14%) of the 50 patients, and 30% less ICBG volume was required on average in others. Only 3 patients (7%) had donor site-associated pain. Controlled studies are being conducted to support the clinical impression that ultraporous beta-TCP used as a bone void filler in spinal arthrodesis facilitates bone healing at both the spinal and donor operative sites, and contributes to less overall morbidity.


[Melioidosis is a rare diagnosis among returning travellers with fever].
The causative organism of melioidosis is Burkholderia pseudomallei, a Gram-negative bacterium endemic to Southeast Asia and Northern Australia. The clinical presentation varies, ranging from asymptomatic cases to rapidly progressive septicaemia and shock. Abscesses may be found in any internal organ. We describe an infrequent presentation of melioidosis with various symptoms, including haematuria and rectal pain. Perirectal and prostatic abscesses were found, the causative organism was identified and relevant treatment administered, resulting in a full recovery.


Sensing Qualia.
Accounting for qualia in the natural world is a difficult business, and it is worth understanding why. A close examination of several theories of mind-Behaviorism, Identity Theory, Functionalism, and Integrated Information Theory-will be discussed, revealing shortcomings for these theories in explaining the contents of conscious experience: qualia. It will be argued that in order to overcome the main difficulty of these theories the senses should be interpreted as physical detectors. A new theory, Grounded Functionalism, will be proposed, which retains multiple realizability while allowing for a scientifically based approach toward accounting for qualia in the natural world.


The G-->A single nucleotide polymorphism at the -308 position in the tumor necrosis factor-alpha promoter increases the risk for severe sepsis after trauma.
Clinical factors do not adequately explain why some patients develop severe sepsis after trauma and why others do not. We sought to determine whether genetic factors contribute to this risk. Patients admitted to a single Level I trauma center were enrolled and DNA was isolated from leukocytes. The risk for severe sepsis and for death associated with polymorphism in the tumor necrosis factor-alpha promoter was determined by multivariate analysis. One hundred fifty-two patients had a 24% incidence of severe sepsis and a 13% case fatality rate. The A-allele was most common at the -308 position (n = 35). A-allele carriage at this location was associated with an adjusted odds ratio of 4.6 (95% confidence interval, 1.9-10.9) for severe sepsis and of 2.1 (95% confidence interval, 0.6-7.3) for death. The A-allele at the -308 position in the tumor necrosis factor-alpha promoter increases the risk for severe sepsis and possibly for death after trauma.


[Chronic lumbago after unstable intertrochanteric femoral fracture: a new syndrome or sporadic feature of hip biomechanics after surgery? A case report].
Only in 2002, more than 86,000 hip fractures were registered in Italy in male and female patients over 45 years old, with 9% progression compared to 1999. In this paper, we report a clinic case of a patient experiencing working problems for a chronic back pain after an unstable extracapsular hip fracture. The patient, a 54 years old woman, factory worker, complaining of low back pain weeks after the hip fracture, was evaluated and scheduled for a computer tomography examination of the lumbar spine. The C.T. scans were evaluated to assess eventual evidence of disc problems and/or cross sectional changes in density and fibro-adipose degeneration of muscular body of the psoas muscle. Because back pain matched with the evidence of cross sectional changes in psoas density without any evidence of disc herniation, the patient was scheduled for aspecific back pain training. After a specific rehabilitation protocol the patient had 75% pain relief after four weeks. Age and diseases related changes are commonly seen in the lumbar spine, but the relationship between these changes and symptoms of back pain is not straightforward. Our case report suggest that back pain following extra capsular hip fracture may involve the psoas muscle. The prognosis might be favourable following a specific back training that is actually object of an ongoing controlled trial.


Collective effects in ciliar arrays.
Collective effects in one-dimensional ciliar arrays are studied analytically and numerically. A new phase oscillator description for ciliar motion is introduced which depends only on a single parameter. It allows the systematic study of hydrodynamic interactions between cilia exhibiting arbitrary beating patterns. It is shown that if the hydrodynamic interactions do not alter the beating pattern of the cilia no synchronization of ciliar motion occurs. This is in particular the case in arrays with low ciliar densities. But hydrodynamic interactions can lead to formation of a collective (metachronal) wave which is stable for periodic boundary conditions. In finite arrays free boundaries destroy this collective motion. The dispersion relation for metachronal waves is found to be non-universal, i.e., to depend crucially on the microscopic details of the ciliar beating pattern.


[Wilms' tumor in an adult patient: a case report].
A case of Wilms' tumor in an adult patient is presented. The tumor in adults is rather rare and has an unfavorable prognosis. A 39-year-old man bruised his left flank while skiing in February, 1983. He noticed severe left flank pain. The pain subsided after a week of rest. However, he complained of left abdominal mass and dull pain again, and consulted our outpatient clinic on May 21, 1983. Left transperitoneal nephrectomy was performed under a diagnosis of left injured renal tumor. Histological diagnosis was nephroblastoma. A combined chemotherapy of actinomycin D (ACD) and vincristine (VCR) was started after operation. A total of 10 mg of ACD and 14 mg of VCR was administered by the end of 1983. In March 1984, however, a local recurrence and pulmonary metastases of the tumor were detected by CT and chest films. Local RF-hyperthermia combined with irradiation, alpha-interferon or chemotherapy using cisplatin and adriamycin was given. The patient died of profound cachexia in December, 1984 after gradual deterioration of general conditions.


Side rail use and bed-related fall outcomes among nursing home residents.
To analyze the effect of physical restraint reduction on nighttime side rail use and to examine the relationship between bilateral side rail use and bed-related falls/injuries among nursing home residents. Secondary analysis of data collected in a longitudinal, prospective clinical trial designed to reduce restraint use. Three nonprofit nursing homes. To examine the first question regarding the effect of physical restraint reduction on side rail usage, we included all nursing home residents who survived a 1-year data collection period (n = 463). To answer the second research question concerning the relationship between side rail status and bed-related falls, subjects' side rail status for each of the four data collection periods was compared. The sample for this analysis includes only those with consistent side rail status (n = 319) for the four observations periods: either 0/1 side rail (n = 188) or 2 (bilateral) side rails (n = 131). Side rail and restraint status was directly observed by two research assistants, twice each night shift (10 p.m.-6 a.m.) for three nights at each of four data collection points. Nighttime fall-related outcome data were obtained from a review of nursing home incident reports during the entire 1-year data collection period (T1 through T4). Cognitive status was measured using the Folstein Mini-Mental State Examination. Functional and behavioral status was obtained using subscales of the Psychogeriatric Dependency Rating Scale. Over a 1-year period, there was an increase in the proportion of bilateral side rail use for all three nursing homes. Based on the multiple logistic regression analysis, there was no indication of a decreased risk of falls or recurrent falls with bilateral side rail use, controlling for cognition and functional and behavioral status (adjusted odds ratio (AOR) = 1.13, 95% confidence interval (CI) = 0.45,2.03). Similarly, bilateral side rail use did not reduce the risk of recurrent falls, controlling for cognition and functional status (AOR = 1.25, 95% CI = 0.33,4.67). Despite high usage of bilateral side rails, they do not appear to significantly reduce the likelihood of falls, recurrent falls, or serious injuries. Bed-related falls remain clinically challenging. The data from this study, coupled with increasing reports of side rail-related injuries and deaths, compel us to seek and empirically test alternative interventions to prevent bed-related falls.


Incorporation of rat prolactin into rat milk in vivo and in vitro.
Rat prolactin (11 i.u./mg) was continuously infused into the circulation of urethane-anaesthetized lactating rats for 35 min at doses of either 200 or 472 ng/min. The immunoreactive prolactin in both milk and plasma rose quickly during the first 20-25 min of infusion, then stabilized at similar levels over baseline (68 and 98 ng/ml for milk and plasma, respectively, with the 200 ng/min dose and 250 and 230 ng/ml, respectively, with the 472 ng/min dose). The concentration of prolactin in plasma fell after the infusion was stopped, whereas that in the milk either did not fall at all or fell slightly to a new stabilized level. There was a rapid and extensive loss in the immunoreactivity of prolactin added to milk when rat milk was incubated in vitro (37 degrees C for 1-120 min) with 600 ng/ml of extracted pituitary prolactin (NIAMDD RP-1) or unit equivalent amounts of prolactin obtained from pituitary culture media (secreted prolactin, supplied by C.S. Nicoll). Significantly greater amounts of added RP-1 prolactin were lost when it was incubated with milk obtained after 4 h than after 18 h of non-suckling. There was, however, no drop in endogenous immunoreactive milk prolactin levels (350-400 ng/ml) when rat milk was incubated with saline for 30 min. This suggests that milk prolactin obtained as a result of plasma transfer is different chemically from the milk prolactin resulting from the addition of either RP-1 or secreted prolactin to milk in vitro. Approximately 90% of 131I-labelled rat prolactin appeared in the trichloroacetic acid precipitable fraction after incubation (37 degrees C for 120 min) with milk obtained after 4 h of non-suckling in either the presence or absence of thiouracil (added to prevent binding of 131I or 131I-labelled fragments to milk protein). The recovery was slightly less when 131I-labelled prolactin was incubated with milk obtained after 18 h of non-suckling. These data suggest that prolactin is quickly transferred from plasma into milk in direct relation to the plasma concentration. Once there, much of it appears to be retained by the milk perhaps chemically or physically bound; there is little, if any, degradation of the hormone. We conclude that the lactating the mammary gland may function normally as an excretory organ for prolactin.


The vagotomy alleviates the anorectic effect of an excess amount of dietary leucine on rats fed a low-protein diet.
It is well known that large dose of leucine reduces the food intake and causes growth retardation in experimental animals when leucine is given with a low-protein diet. However, the mechanism for the anorectic effect of leucine has not yet been clarified. We demonstrate here that the anorectic effect of leucine was significantly reduced in a vagotomized rat.


Comparison of clinical trials with finasteride and dutasteride.
Finasteride selectively inhibits the Type 2 isoenzyme of 5alpha-reductase (5AR) (the enzyme responsible for converting testosterone to dihydrotestosterone [DHT]) whereas dutasteride inhibits both Type 1 and Type 2 5AR. General conclusions regarding the differences and similarities of these 2 agents, in terms of pharmacologic effect, safety, and efficacy, can be drawn from evaluation of short-term comparative trials and similar but non-comparative long-term trials. Dutasteride therapy reduces serum DHT significantly more than does finasteride. In men with benign prostatic hyperplasia (BPH), treatment with either agent results in similar prostate gland volume reduction, flow rate and symptom improvement, and similar reductions in long-term risk of BPH development in terms of symptom progression and acute urinary retention (AUR) and BPH-related surgery. There does not appear to be any clinically significant difference between the adverse event profiles of dutasteride and finasteride. Although weak evidence suggests a difference in the onset of clinical benefit, the available non-comparative trial data do not confirm this finding. Patients with symptomatic BPH who receive dutasteride or finasteride, either as monotherapy or combination therapy with alpha-blockers, can expect to experience significant prostate gland size reduction, improved symptoms, and reduced risk of progression in terms of long-term adverse outcomes.


Promising long-term outcome of gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule as salvage regimen for patients with previously heavily treated Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma.
The combination of gemcitabine (G), vinorelbine (V), and pegylated liposomal doxorubicin (D) has proved to be effective in relapsed Hodgkin's lymphoma (HL). Its efficacy in non-Hodgkin's lymphoma (NHL) remains to be discussed. We retrospectively evaluated the efficacy and toxicity of the dose-adjusted gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule in 35 heavily pretreated patients with relapsed and refractory aggressive NHL or HL. Treatment consisted of G: 800 mg/m(2) intravenous (i.v.) on day 1, V: 15 mg/m(2) i.v. on day 1; D: 20 mg/m(2) i.v. on day 1, repeated for 14 days. Patients responded to GVD proceeded to subsequent autologous stem cell transplantation. The objective response rate (ORR) was 48.6 %, with 31.4 % complete remission. A higher ORR was observed in patients with HL than in patients with NHL (80.0 vs. 36.0 %, P = 0.023). With a median follow-up of 26 months, the estimated median progression-free survival and overall survival were 5 (range 1-73 months) and 36 months (range 2-73 months), respectively. The estimated 5-year survival rate was 44.6 % (95 % confidence interval 28.1-61.1 %). Toxicities were mild (grade 3/4 neutropenia 34.3 %, thrombocytopenia 5.7 %). Our results suggest that the dose-adjusted GVD in 14-day schedule is effective and well tolerated in patients with refractory and relapsed HL and aggressive NHL. The potential long-term survival in NHL is promising.


Characterization of two long-chain fatty acid CoA ligases in the Gram-positive bacterium Geobacillus thermodenitrificans NG80-2.
The functions of two long-chain fatty acid CoA ligase genes (facl) in crude oil-degrading Geobacillus thermodenitrificans NG80-2 were characterized. Facl1 and Facl2 encoded by GTNG_0892 and GTNG_1447 were expressed in Escherichia coli and purified as His-tagged fusion proteins. Both enzymes utilized a broad range of fatty acids ranging from acetic acid (C(2)) to melissic acid (C(30)). The most preferred substrates were capric acid (C(10)) for Facl1 and palmitic acid (C(16)) for Facl2, respectively. Both enzymes had an optimal temperature of 60°C, an optimal pH of 7.5, and required ATP as a cofactor. Thermostability of the enzymes and effects of metal ions, EDTA, SDS and Triton X-100 on the enzyme activity were also investigated. When NG80-2 was cultured with crude oil rather than sucrose as the sole carbon source, upregulation of facl1 and facl2 mRNA was observed by real time RT-PCR. This is the first time that the activity of fatty acid CoA ligases toward long-chain fatty acids up to at least C(30) has been demonstrated in bacteria.


Optimization of time for neural stem cells transplantation for brain stroke in rats.
Despite encouraging data in terms of neurological outcome, stem cell based therapy for ischemic stroke in experimental models and human patients is still hampered by multiple as yet un-optimized variables, i.e., time of intervention, that significantly influence the prognosis. The aim of the present study was to delineate the optimum time for neural stem cells (NSCs) transplantation after ischemic stroke. The NSCs were isolated from 14 days embryo rat ganglion eminence and were cultured in NSA medium (neurobasal medium, 2% B27, 1% N2, bFGF 10 ng/mL, EGF 20 ng/mL and 1% pen/strep). The cells were characterized for tri-lineage differentiation by immunocytochemistry for tubulin-III, Olig2 and GFAP expression for neurons, oligodendrocytes and astrocyte respectively. The NSCs at passage 3 were injected intraventricularly in a rodent model of middle-cerebral artery occlusion (MCAO) on stipulated time points of 1 & 12 h, and 1, 3, 5 and 7 days after ischemic stroke. The animals were euthanized on day 28 after their respective treatment. dUTP nick end labeling (TUNEL) assay and Caspase assay showed significantly reduced number of apoptotic cells on day 3 treated animals as compared to the other treatment groups of animals. The neurological outcome showed that the group which received NSCs 3 days after brain ischemia had the best neurological performance. The optimum time for NSCs transplantation was day 3 after ischemic stroke in terms of attenuation of ischemic zone expansion and better preserved neurological performance.


Hand and upper extremity transplantation: an update of outcomes in the worldwide experience.
Hand/upper extremity transplantation is the most common form of vascularized composite allotransplantation performed to date. An Update of worldwide outcomes is reported. The authors summarize the international experience with 107 known transplanted hand/upper extremities in 72 patients. Data from published medical literature, national and international meetings, lay press reports, and personal communications were utilized to provide the most up-to-date summary. Although 24 losses (including four mortalities) are known, three of the four reported mortalities and eight of 24 limb losses were caused by multiple type vascularized composite allotransplantations (combined upper and lower limb or upper limb and face). Seven more losses were attributable to 15 patients in the early experience in China. In the United States and Western Europe, only three other non-acute graft losses have been reported, resulting in a patient survival rate for unilateral or bilateral hand transplantation in isolation of 98.5 percent and an overall graft survival rate of 83.1 percent. Published functional outcomes continue to demonstrate improvement in function and quality of life. The international experience supports the idea that, for properly selected individuals, hand and upper extremity transplantation should be considered an important treatment option.


Psychiatric nurses' knowledge, experience and attitudes towards clients with borderline personality disorder.
There is evidence in the literature to suggest that mental health care staffs' attitudes towards clients with borderline personality disorder (BPD) are less than favourable. This study reports on a survey of psychiatric nurses' knowledge, experience and attitudes towards care received by clients with a diagnosis of BPD. The questionnaire was sent to all clinical nurses (n = 157) working in a psychiatric service in Dublin, Ireland and received a response rate of 41.4% (n = 65). The results indicate that the majority of nurses have regular contact with clients with BPD and nurses on inpatient units reported more frequent contact than nurses in the community. Eighty per cent of nurses view clients with BPD as more difficult to care for than other clients and 81% believe that the care they receive is inadequate. Lack of services was cited as the most important factor contributing to the inadequate care and the development of a specialist service is reported as the most important resource to improve care.


Absolute Quantification of TGF-β Signaling Proteins Using Quantitative Western Blot.
Cell signaling governs the basic functions of cells by molecular interactions that involve of many proteins. The abundance of signaling proteins can directly influence cellular responses to external signal, contributing to cellular heterogeneity. Absolute quantification of proteins is important for modeling and understanding the complex signaling network. Here, we introduce how to measure the amount of TGF-β signaling proteins using quantitative immunoblotting. In addition, we discuss how to convert the measurements of protein abundance to the quantities of absolute molecules per cell. This method is generally applicable to the absolute quantification of other proteins.


High power tunable multiwavelength random fiber laser at 1.3 μm waveband.
Multiwavelength fiber lasers, especially those operating at optical communication wavebands such as 1.3 μm and 1.5 μm wavebands, have huge demands in wavelength division multiplexing communications. In the past decade, multiwavelength fiber lasers operating at 1.5 μm waveband have been widely reported. Nevertheless, 1.3 μm waveband multiwavelength fiber laser is rarely studied due to the lack of proper gain mechanism. Random fiber laser (RFL), owing to its good temporal stability and flexible wavelength tunability, is a great candidate for multiwavelength generation. Here, we reported high power multiwavelength generation at 1.3 μm waveband in RFL for the first time. At first, we employed a section of 10 km G655C fiber to provide Raman gains, as a result of which, 1.07 W multiwavelength generation at 1.3 μm waveband with an optical to signal noise ratio of ∼33 dB is demonstrated. By tuning the pump wavelength from 1055 nm to 1070 nm, tunable multiwavelength output covering the range of 1300-1330 nm can be achieved. Furtherly, we realized 4.67 W multiwavelength generation at 1.3 μm waveband by shortening the fiber length to 4 km. To the best of our knowledge, this is the highest output power ever reported for multiwavelength fiber lasers.


Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance.
Morphine tolerance remains an intractable problem, which hinders its prolonged use in clinical practice. Endoplasmic reticulum (ER) stress has been proved to play a fundamental role in the pathogenesis of Alzheimer's disease, diabetes, atherosclerosis, cancer, etc. In this study, we provide the first direct evidence that ER stress may be a significant driver of morphine tolerance. Binding immunoglobulin protein (BiP), the ER stress marker, was significantly upregulated in neurons in spinal dorsal horn in rats being treated with morphine for 7 days. Additionally, chronic morphine treatment resulted in the activation of three arms of unfolded protein response (UPR): inositol-requiring enzyme 1/X-box binding protein 1 (IRE1/XBP1), protein kinase RNA-like ER kinase/eukaryotic initiation factor 2 subunit alpha (PERK/eIF2α), and activating transcription factor 6 (ATF6). More importantly, inhibiting either one of the three cascades could attenuate the development of morphine tolerance. Taken together, our results suggest that ER stress in spinal cord might contribute to the development of morphine tolerance. These findings implicate a potential clinical strategy for preventing morphine tolerance and may contribute to expanding the morphine usage in clinic.


Basic reproduction number of epidemic models on sparse networks.
The basic reproduction number R_{0} is a standard indicator of infection control in epidemiology. Although R_{0} has been studied extensively for deterministic epidemic models, it has not been formulated accurately for models adopting network structures. Here, we extend a four-compartment model that includes commonly used epidemic models to a Markov process on networks. By examining the Markov process in detail, we derive a canonical formula for R_{0} involving two probability values. Numerical calculations show that the derived formula is a better approximation than the conventional formula when the network is very sparse. We propose this as a standard formula for controlling infections that can only be transmitted through intimate contact, where contacts between individuals can be described as a sparse network.


Transfer of cell-mediated immunity to Paracoccidioides brasiliensis in hamsters with dialysable leukocyte extracts.
Dialysable leukocyte extracts (DLE) were obtained from lymph nodes and spleen cells of hamsters immunized with Paracoccidioides brasiliensis (immune DLE) or from non-immunized hamsters (non-immune DLE). Sensitivity to P. brasiliensis antigen (PbAg) was transferred by immune DLE to normal recipient hamsters and could be detected by the macrophage migration inhibition (MIF) assay on day three and by a positive skin test to PbAg on day seven after DLE inoculation. This reactivity persisted for 120 days. The specificity of DLE was studied by inoculation of immune or non-immune DLE into normal hamsters and transfer was evaluated 7 days later by the MIF assay and by skin tests to PbAg, Candida albicans antigen (CaAg), sonically treated bacille Calmette-Guérin (BCG) (SBCG) and ovalbumin (OVA). The immune DLE recipients showed a reactivity to PbAg that was significantly stronger than that of the nonimmune DLE recipients although both groups of recipient animals showed reactivity to CaAg and SBCG. The results suggest that both DLE preparations contain a non-specific antigen augmenting factor. This factor may stimulate the minimal background response to the antigens in nonimmunized recipient hamsters.


Viral genome methylation as an epigenetic defense against geminiviruses.
Geminiviruses encapsidate single-stranded DNA genomes that replicate in plant cell nuclei through double-stranded DNA intermediates that associate with cellular histone proteins to form minichromosomes. Like most plant viruses, geminiviruses are targeted by RNA silencing and encode suppressor proteins such as AL2 and L2 to counter this defense. These related proteins can suppress silencing by multiple mechanisms, one of which involves interacting with and inhibiting adenosine kinase (ADK), a cellular enzyme associated with the methyl cycle that generates S-adenosyl-methionine, an essential methyltransferase cofactor. Thus, we hypothesized that the viral genome is targeted by small-RNA-directed methylation. Here, we show that Arabidopsis plants with mutations in genes encoding cytosine or histone H3 lysine 9 (H3K9) methyltransferases, RNA-directed methylation pathway components, or ADK are hypersensitive to geminivirus infection. We also demonstrate that viral DNA and associated histone H3 are methylated in infected plants and that cytosine methylation levels are significantly reduced in viral DNA isolated from methylation-deficient mutants. Finally, we demonstrate that Beet curly top virus L2- mutant DNA present in tissues that have recovered from infection is hypermethylated and that host recovery requires AGO4, a component of the RNA-directed methylation pathway. We propose that plants use chromatin methylation as a defense against DNA viruses, which geminiviruses counter by inhibiting global methylation. In addition, our results establish that geminiviruses can be useful models for genome methylation in plants and suggest that there are redundant pathways leading to cytosine methylation.


Radial alveolar count as a tool for the estimation of fetal age.
A total of 53 normal fetuses with a gestational age ranging from 15 up to 39 weeks was investigated and the radial alveolar count (RAC) was estimated as a parameter for lung maturation. Values lower than 2.0 could only be found in lungs of fetuses aged less than 18 weeks. Between 18 and 25 weeks of gestation, relatively constant levels of RAC were observed but with considerable interindividual variation. In fetuses with a gestational age of more than 25 and especially 30 weeks, a slight or rapid increase in RAC occurred respectively. Values lower than 3.0 were found up to a fetal age of less than 30 weeks and a RAC of more than 4.0 was only found in lungs of fetuses aged more than 30 weeks. Values exceeding 6.0 occurred only in fetuses at near full-term birth. Since the estimation of RAC overcomes the effects of varying degrees of alveolar collapse, such an analysis also seems to be useful for the determination for fetal age in cases of advanced putrefaction.


Membrane-initiated estrogen signaling via Gq-coupled GPCR in the central nervous system.
The last few decades have revealed increasing complexity and depth to our knowledge of receptor-mediated estrogen signaling. Nuclear estrogen receptors (ERs) ERα and ERβ remain the fundamental dogma, but recent research targeting membrane-bound ERs urges for a more expanded view on ER signaling. ERα and ERβ are also involved in membrane-delineated signaling alongside membrane-specific G protein-coupled estrogen receptor 1 (GPER1), ER-X, and the Gq-coupled membrane ER (Gq-mER). Membrane ERs are responsible for eliciting rapid responses to estrogen signaling, and their importance has been increasingly indicated in central nervous system (CNS) regulation of such functions as reproduction, energy homeostasis, and stress. While the Gq-mER signaling pathway is well characterized, the receptor structure and gene remains uncharacterized, although it is not similar to the nuclear ERα/β. This review will describe the current knowledge of this putative membrane ER and its selective ligand, STX, from its initial characterization in hypothalamic melanocortin circuitry to recent research exploring its role in the CNS outside of the hypothalamus.


Kaiso represses the expression of glucocorticoid receptor via a methylation-dependent mechanism and attenuates the anti-apoptotic activity of glucocorticoids in breast cancer cells.
Kaiso is a Pox Virus and Zinc Finger (POZ-ZF) transcription factor with bi-modal DNA-binding specificity. Here, we demonstrated that Kaiso expression is inversely correlated with glucocorticoid receptor (GR) expression in breast carcinomas. Knockdown of Kaiso increased GR expression, while overexpression of Kaiso inhibited GR expression in breast cancer cells. Furthermore, Kaiso repressed GR proximal promoter-reporter activity in a dose-dependent manner. Remarkably, ChIP experiments demonstrated that endogenous Kaiso was associated with the GR promoter sequence in a methylation-dependent manner. Since glucocorticoids inhibit chemotherapyinduced apoptosis and have been widely used as a co-treatment of patients with breast cancer, we assessed the role of Kasio in GR-mediated anti-apoptotic effects. We found that overexpression of Kaiso attenuated the anti-apoptotic effects of glucocorticoids in breast cancer cells. Our findings suggest that GR is a putative target gene of Kaiso and suggest Kaiso to be a potential therapeutic target in GC-combination chemotherapy in breast cancer. [BMB Reports 2016; 49(3): 167-172].


Bladder diverticulitis: a case report.
Bladder diverticulum, an outpouching of the mucosa through the muscular wall of the bladder, is a multifactorial disease process that can be either acquired or congenital. Although small diverticuli are usually asymptomatic, a large diverticulum may result in hematuria, urinary tract infection, acute abdomen due to its rupture, acute urinary retention, or neoplasm formation. We describe the case of an elderly gentleman who presented to the emergency department with abdominal pain and was ultimately diagnosed with bladder diverticulitis, a disease not previously described in the literature.


Theoretical prediction of the heats of formation of C2H5O* radicals derived from ethanol and of the kinetics of beta-C-C scission in the ethoxy radical.
Thermochemical parameters of three C(2)H(5)O* radicals derived from ethanol were reevaluated using coupled-cluster theory CCSD(T) calculations, with the aug-cc-pVnZ (n = D, T, Q) basis sets, that allow the CC energies to be extrapolated at the CBS limit. Theoretical results obtained for methanol and two CH(3)O* radicals were found to agree within +/-0.5 kcal/mol with the experiment values. A set of consistent values was determined for ethanol and its radicals: (a) heats of formation (298 K) DeltaHf(C(2)H(5)OH) = -56.4 +/- 0.8 kcal/mol (exptl: -56.21 +/- 0.12 kcal/mol), DeltaHf(CH(3)C*HOH) = -13.1 +/- 0.8 kcal/mol, DeltaHf(C*H(2)CH(2)OH) = -6.2 +/- 0.8 kcal/mol, and DeltaHf(CH(3)CH(2)O*) = -2.7 +/- 0.8 kcal/mol; (b) bond dissociation energies (BDEs) of ethanol (0 K) BDE(CH(3)CHOH-H) = 93.9 +/- 0.8 kcal/mol, BDE(CH(2)CH(2)OH-H) = 100.6 +/- 0.8 kcal/mol, and BDE(CH(3)CH(2)O-H) = 104.5 +/- 0.8 kcal/mol. The present results support the experimental ionization energies and electron affinities of the radicals, and appearance energy of (CH(3)CHOH+) cation. Beta-C-C bond scission in the ethoxy radical, CH(3)CH2O*, leading to the formation of C*H3 and CH(2)=O, is characterized by a C-C bond energy of 9.6 kcal/mol at 0 K, a zero-point-corrected energy barrier of E0++ = 17.2 kcal/mol, an activation energy of Ea = 18.0 kcal/mol and a high-pressure thermal rate coefficient of k(infinity)(298 K) = 3.9 s(-1), including a tunneling correction. The latter value is in excellent agreement with the value of 5.2 s(-1) from the most recent experimental kinetic data. Using RRKM theory, we obtain a general rate expression of k(T,p) = 1.26 x 10(9)p(0.793) exp(-15.5/RT) s(-1) in the temperature range (T) from 198 to 1998 K and pressure range (p) from 0.1 to 8360.1 Torr with N2 as the collision partners, where k(298 K, 760 Torr) = 2.7 s(-1), without tunneling and k = 3.2 s(-1) with the tunneling correction. Evidence is provided that heavy atom tunneling can play a role in the rate constant for beta-C-C bond scission in alkoxy radicals.


Antifungal Activity of Decyl Gallate against Several Species of Pathogenic Fungi.
This work aims to demonstrate that the gallic acid structure modification to the decyl gallate (G14) compound contributed to increase the antifungal activity against several species of pathogenic fungi, mainly, Candida spp., Cryptococcus spp., Paracoccidioides spp., and Histoplasma capsulatum, according to standardized microdilution method described by Clinical Laboratory Standard Institute (CLSI) documents. Moreover this compound has a particularly good selectivity index value, which makes it an excellent candidate for broad-spectrum antifungal prototype and encourages the continuation of subsequent studies for the discovery of its mechanism of action.


[Lactic acid bacteria and health: are probiotics safe for human?].
The effect of Lactobacillus and Bifidobacterium on human health has been examined for many years. Numerous in vivo and in vitro studies have confirmed the beneficial activity of some exogenous lactic acid bacteria in the treatment and prevention of rotaviral infection, antibiotic-associated diarrhea, inflammatory bowel disease and other gastrointestinal disorders. Probiotics support the action of the intestinal microflora and exhibit a favorable modulatory effect on the host's immune system. However, it should be remembered that relatively harmless lactobacilli can occasionally induce opportunistic infections. Due to reaching almost 20x10(12) probiotic doses per year which contain live cultures of bacteria, it is essential to monitor the safety aspect of their administration. In recent years, infections caused by Lactobacillus and Bifidobacterium made up 0.05% to 0.4% of cases of endocarditis and bacteremia. In most cases, the infections were caused by endogenous microflora of the host or bacterial strains colonizing the host's oral cavity. According to a review of cases of infections caused by bacteria of the genus Lactobacillus from 2005 (collected by J.P. Cannot'a), 1.7% of infections have been linked directly with intensive dairy probiotic consumption by patients. Additionally, due to the lack of a precise description of most individuals' eating habits, the possible effect of probiotics on infection development definitively should not be ruled out. The present paper describes cases of diseases caused by lactic acid bacteria, a potential mechanism for the adverse action of bacteria, and the possible hazard connected with probiotic supplementation for seriously ill and hospitalized patients.


A strong pelvic floor: how nurses can spread the word.
The pelvic floor contains muscles that support continence, sexual functioning, childbirth and more. Yet, few people even know these muscles exist or how important they are to overall health and well-being. This article explains in detail the anatomy, functions and importance of the pelvic floor musculature (PFM) and how nurses can educate and empower women of all ages about its important role in many aspects of their health and well-being. Accompanying this article is a patient education page with specific instructions on how to exercise the PFM.


Bile acids. LI. Formation of 12alpha-hydroxyl derivatives and companions from 5 alpha-sterols by rabbit liver microsomes.
A comparison of the activity of rabbit liver microsomes fortified with 0.1 mM NADPH to promote 12alpha-hydroxylation over 60 minutes with appropriate sterols provided the following relative order of activities: kalpha-cholestane-3alpha, 7alpha-diol, 100; 7alpha-hydroxy-5alpha-cholestane-3one, 76; 7alpha-hydroxycholest-4-en-3-one, 64; 5alpha-cholestane-3-3beta, 7alpha-diol, 26; allochendoexycholate, 22. If the more polar products formation. Investigation by gas-liquid chromatography-mass spectrometry of the nature of these more polar products derived form 5alpha-cholestane-3alpha, 7alpha-diol showed that a series of tetrols was dormed; i.e., 5alpha-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol as the major product and lesser amounts of 5alpha-cholestane-3alpha, 7alpha, 12alpha, 24- and 3alpha, 7alpha, 12alpha, 23tetrols. No significant amount of 26-hydroxylated product was formed.


Nanoemulsified Carvacrol as a Novel Washing Treatment Reduces Escherichia coli O157:H7 on Spinach and Lettuce.
Fresh produce continues to be the main source of foodborne illness outbreaks in the United States, implicating bacterial pathogens such as Escherichia coli O157:H7 (EHEC). The efficacy of nanoemulsified carvacrol (NCR) as a washing treatment in reducing EHEC on fresh produce was investigated. Fresh baby spinach, romaine lettuce, and iceberg lettuce leaves (2.5-cm-diameter cores) were spot inoculated with a five-strain cocktail of nalidixic acid-resistant EHEC at ∼6 log CFU/cm2. After air drying for 1 h, 20 pieces of each inoculated produce leaf were immersed in water-based treatment solutions (200 mL per group), including water alone, 25 or 50 ppm of free chlorine, and 0.25 or 0.75% NCR for 2 min. Inoculated produce leaves without any treatment served as baseline. Produce leaves were stored at 10°C, and surviving EHEC populations were enumerated on days 0, 2, 7, and 14. The viability of EHEC following NCR treatments on the fresh produce was visualized under a fluorescence microscope. NCR treatment at 0.75% immediately reduced EHEC populations on iceberg lettuce by 1.3 log CFU/cm2 as compared with the produce treated with water alone (P < 0.05). Antimicrobial activity of NCR against EHEC was comparable to chlorine treatments on day 0 for all produce (P > 0.05). After 14 days of storage at 10°C, populations of EHEC on 0.75% NCR-treated romaine lettuce were reduced by 2.3 log CFU/cm2 compared with the recovery from 50 ppm of chlorine-treated samples (P < 0.05). Microscopic images revealed that EHEC cells were observed to be clustered on the baseline samples, indicating the development of cell aggregation, compared with the scattered cells seen on NCR-treated leaf surfaces. Treatments with NCR did not significantly affect the color of the fresh produce leaves during 14 days of storage at 10°C. Results of this study support the potential use of NCR as a water-soluble natural antimicrobial wash treatment for controlling EHEC on fresh produce.


Adaptive Alignment of Plasticity With Genetic Variation and Selection.
Theoretical research has outlined how selection may shape both genetic variation and the expression of phenotypic plasticity in multivariate trait space. Specifically, research regarding the evolution of patterns of additive genetic variances and covariances (summarized in matrix form as G) and complementary research into how selection may shape adaptive plasticity lead to the general prediction that G, plasticity, and selection surfaces are all expected to align with each other. However, less well discussed is how this prediction might be assessed and how the modeled theoretical processes are expected to manifest in actual populations. Here, we discuss the theoretical foundations of the overarching prediction of alignment, what alignment mathematically means, how researchers might test for alignment and important caveats to this testing. The most important caveat concerns the fact that, for plasticity, the prediction of alignment only applies to cases where plasticity is adaptive, whereas organisms express considerable plasticity that may be neutral or even maladaptive. We detail the ramifications of these alternative expressions of plasticity vis-à-vis predictions of alignment. Finally, we briefly highlight some important interpretations of deviations from the prediction of alignment and what alignment might mean for populations experiencing environmental and selective changes.


Electron microscopic features of experimental choroidal neovascularization.
We produced choroidal neovascularization in the rhesus monkey by diminishing the blood supply to the inner retina and producing defects in Bruch's membrane by photocoagulation. The neovascular fronds which developed either infiltrated the subretinal space or proliferated through necrotic and gliotic retina into the vitreous cavity. Sequential electron microscopic sections of neovascular fronds in the subretinal space demonstrated that the advancing capillary sprouts were composed of primitive endothelial tubes surrounded by pericytes and enmeshed in a loose basement-membrane-like substance. More mature capillaris and displayed endothelial fenestrations and endothelial-pericyte membranous contacts. Large neovascular fronds developed major feeding vessels that closely resembled normal small choroidal arteries and veins. Retinal pigment epithelial cells in various guises were in constant association with proliferating neovascular networks.


Clinical assessment of spatiotemporal gait parameters in patients and older adults.
Spatial and temporal characteristics of human walking are frequently evaluated to identify possible gait impairments, mainly in orthopedic and neurological patients, but also in healthy older adults. The quantitative gait analysis described in this protocol is performed with a recently-introduced photoelectric system (see Materials table) which has the potential to be used in the clinic because it is portable, easy to set up (no subject preparation is required before a test), and does not require maintenance and sensor calibration. The photoelectric system consists of series of high-density floor-based photoelectric cells with light-emitting and light-receiving diodes that are placed parallel to each other to create a corridor, and are oriented perpendicular to the line of progression. The system simply detects interruptions in light signal, for instance due to the presence of feet within the recording area. Temporal gait parameters and 1D spatial coordinates of consecutive steps are subsequently calculated to provide common gait parameters such as step length, single limb support and walking velocity, whose validity against a criterion instrument has recently been demonstrated. The measurement procedures are very straightforward; a single patient can be tested in less than 5 min and a comprehensive report can be generated in less than 1 min.


Smoking and aging. Clinical implications. Part I: Health and consequence.
Smoking is the number one preventable cause of disability and mortality in older adults. In the past few decades there has been an enhanced focus on smoking behaviors and smoking cessation, however, the older smoker has been excluded. Even though nonsmoking status can provide older smokers with a chance for increased quality as well as quantity of life, they are asked less often to quit, given fewer resources, and provided less guidance than younger smokers. There is limited knowledge about how to design and deliver interventions for smoking cessation among older adults. The explanation for the absence of an empirical and clinical focus on smoking cessation for the older adult is in part because of the belief in myths rather than reality. These beliefs about the health consequences of smoking behaviors and the benefits of smoking cessation for older smokers are held by older adults and their health care providers. However, the truth is that older adults can stop smoking, and the benefits are vast.


Identification of Capsid/Coat Related Protein Folds and Their Utility for Virus Classification.
The viral supergroup includes the entire collection of known and unknown viruses that roam our planet and infect life forms. The supergroup is remarkably diverse both in its genetics and morphology and has historically remained difficult to study and classify. The accumulation of protein structure data in the past few years now provides an excellent opportunity to re-examine the classification and evolution of viruses. Here we scan completely sequenced viral proteomes from all genome types and identify protein folds involved in the formation of viral capsids and virion architectures. Viruses encoding similar capsid/coat related folds were pooled into lineages, after benchmarking against published literature. Remarkably, the in silico exercise reproduced all previously described members of known structure-based viral lineages, along with several proposals for new additions, suggesting it could be a useful supplement to experimental approaches and to aid qualitative assessment of viral diversity in metagenome samples.


Testing the sensitivity and specificity of the fluorescence microscope (Cyscope) for malaria diagnosis.
Early diagnosis and treatment of malaria are necessary components in the control of malaria. The gold standard light microscopy technique has high sensitivity, but is a relatively time-consuming procedure especially during epidemics and in areas of high endemicity. This study attempted to test the sensitivity and specificity of a new diagnostic tool - the Cyscope fluorescence microscope, which is based on the use of Plasmodium nucleic acid-specific fluorescent dyes to facilitate detection of the parasites even in low parasitaemia conditions due to the contrast with the background. In this study, 293 febrile patients above the age of 18 years attending the malaria treatment centre in Sinnar State (Sudan) were interviewed using a structured questionnaire. Finger-prick blood samples were also collected from the participants to be tested for malaria using the hospital's microscope, the reference laboratory microscope, as well as the Cyscope microscope. The results of the investigations were then used to calculate the sensitivity, specificity, and positive and negative predictive values of the Cyscope microscope in reference to gold standard light microscopy. The sensitivity was found to be 98.2% (95% CI: 90.6%-100%); specificity = 98.3% (95% CI: 95.7% - 99.5%); positive predictive value = 93.3% (95% CI: 83.8% - 98.2%); and negative predictive value = 99.6% (95% CI: 97.6% - 100%). In conclusion, the Cyscope microscope was found to be sensitive, specific and provide rapid, reliable results in a matter of less than 10 minutes. The Cyscope microscope should be considered as a viable, cheaper and time-saving option for malaria diagnosis, especially in areas where Plasmodium falciparum is the predominant parasite.


Mild serotonin syndrome associated with concurrent linezolid and fluoxetine.
A case of serotonin syndrome that developed during concurrent linezolid and fluoxetine is presented. A 23-year-old white male patient was originally admitted to receive intravenous chemotherapy for acute myelogenous leukemia. He had a history of intravenous amphetamine abuse, hepatitis B virus infection, hepatitis C virus infection, depression, and bipolar disorder. The patient's routine medications before admission included methadone, fluoxetine, voriconazole, transdermal nicotine patch, lorazepam, and quetiapine. The patient developed persistent neutropenia and complications from chemotherapy, including mild mucositis. Despite treatment with levofloxacin, acyclovir, and voriconazole, the patient developed high fevers. Levofloxacin was discontinued and aztreonam and vancomycin were started. After a blood culture revealed that the bacteria were likely vancomycin resistant, vancomycin was discontinued and linezolid was initiated. Nine hours later, the patient began complaining of severe pain in his abdomen. After a total of four doses of linezolid, the patient reported further discomfort. Two days after linezolid initiation, a health care team member identified the interaction between fluoxetine and linezolid as the cause of the patient's symptoms, and linezolid was discontinued. All symptoms resolved within 48 hours. While resolution generally occurs within 24-48 hours after discontinuing the offending agent, the time to resolution may be delayed if the agent has a long half-life or active metabolites, in which case admission to an intensive care unit is recommended. Cyproheptadine and chlorpromazine may also be used to treat symptoms. Serotonin syndrome developed in a patient taking concurrent linezolid and fluoxetine.


The Effectiveness of Endovenous Thermal Ablation for the Knee Symptoms of the Osteoarthritis with Varicose Veins.
Patients with varicose veins of the lower extremities with osteoarthritis of the knee often experience improvement in knee joint symptoms after endovascular treatment. We considered that it was important to decide the operation indication of lower extremity varices, to know the correlation between the two diseases in the treatment of varicose veins. To investigate the postoperative improvement of knee symptoms related to varicose veins with knee osteoarthritis, we conducted a questionnaire survey for a total of 12 months, from December 2014 to May 2015 and from October 2018 to March 2019. The participants were 35 patients (7 men and 28 women) with varicose veins complicated with knee osteoarthritis. We classified knee osteoarthritis according to a grading scale and compared the improvement of knee symptoms after endovenous thermal ablation. The higher the knee grade, the lower the degree of improvement. However, the improvement was observed in all knee osteoarthritis grades, and as a whole, 25 patients (71.4%) have experienced improvement of subjective symptoms. For patients with knee osteoarthritis, we strongly recommend surgical treatment of the varicose veins regardless of the progression of knee grade. (This is a translation of Jpn J Phlebol 2019; 30(3): 279-283.).


Serotonergic transcription of human FEV reveals direct GATA factor interactions and fate of Pet-1-deficient serotonin neuron precursors.
Altered expression of the human FEV (fifth Ewing variant) ETS transcription factor gene impacts the level of CNS serotonin (5-HT) neuron gene expression and maternal nurturing. However, the regulatory mechanisms that determine FEV expression are poorly understood. Here, we investigated the cis-regulatory control of FEV to begin to identify the upstream transcription factors that restrict FEV expression to 5-HT neurons. We find that sequences extending only 275 bp upstream of the FEV 5' untranslated region are sufficient to direct FEV transgene expression to embryonic 5-HT neurons, although sequences farther upstream are required for maintenance in adult 5-HT neurons. Two highly conserved consensus GATA factor binding sites within the 275 bp region interact with GATA factors in vitro. Chromatin immunoprecipitations with embryonic hindbrain demonstrated Gata-2 interactions with the orthologous mouse Pet-1 ETS cis-regulatory region. Mutagenesis of GATA sites revealed that one or the other site is required for serotonergic FEV transgene expression. Unexpectedly, FEV-LacZ transgenes enabled determination of 5-HT neuron precursor fate in the adult Pet-1(-/-) dorsal and median raphe nuclei and thus provided additional insight into FEV/Pet-1 function. Comparable numbers of FEV-LacZ-positive cells were detected in Pet-1(+/-) and Pet-1(-/-) adult dorsal raphe nuclei, indicating that the majority of mutant serotonergic precursors are not fated to apoptosis. However, B7 dorsal raphe cells were aberrantly distributed, suggesting a role for FEV/Pet-1 in their midline organization. Our findings identify a direct transcriptional interaction between Gata-2 and FEV and a unique marker for new insight into FEV/Pet-1 function in 5-HT neuron development.


Echocardiography during treadmill exercise testing for evaluation of pulmonary artery systolic pressure: advantages of the method.
Determination of pulmonary artery systolic pressure by Doppler echocardiography (based on the pressure gradient between the right ventricle and right atrium - DeltaP RV/RA) or by right heart catheterization is useful in evaluating the severity and prognosis of cardiac disease. The aim of the study was to evaluate DeltaP RV/RA non-invasively during treadmill exercise in patients with tricuspid regurgitation and without coronary artery disease. Of a total of 149 patients referred to our echo laboratory, we completed the study in 142 (95%), of whom 120 were women, mean age 52+/-13 years (23 to 82). We studied 68 patients with valvular heart disease (of whom 56 had mitral valve stenosis and sinus rhythm on ECG), 42 with systemic sclerosis, 10 with severe pulmonary hypertension, 12 with a history of pulmonary embolism and 10 healthy controls. The DeltaP RV/RA was determined from the tricuspid regurgitation jet using continuous wave Doppler in left lateral decubitus (LLD) before exercise testing (BLLD), in a standing position (SP), at peak workload (PW) before termination of the test, and in the first 60 seconds of the recovery period in LLD (RLLD). The DeltaP RV/RA in BLLD was 36+/-21 mmHg (range 18 to 147); the SP [symbol: see text]P RV/RA was 32+/-24 mmHg (range 12 to 137), p<0.001 vs. BLLD DeltaP RV/RA; the PW DeltaP RV/RA was 58+/-26 mmHg (range 28 to 177), p<0.0001 vs. SP DeltaP RV/RA; and the RLLD DeltaP RV/RA was 47+/-25 mmHg (range 20 to 152), p<0.001 vs. PW DeltaP RV/RA. The differences between PW DeltaP RV/RA and RLLD DeltaP RV/RA changed therapeutic decisions in 10 patients (18%) with mitral stenosis, and modified the management of 13 patients (30%) with systemic sclerosis (who then underwent right heart catheterization). Echocardiography during treadmill exercise testing was feasible in most patients. The DeltaP RV/RA decreases in response to the standing position. The DeltaP RV/RA rises considerably with exercise in the majority of patients and is significantly higher at peak workload than in the recovery period. The differences between PW DeltaP RV/RA and RLLD DeltaP RV/RA influenced patient management.


Natural inhibitors of cholinesterases: implications for adverse drug reactions.
Acetylcholinesterase and butyrylcholinesterase are two closely related enzymes important in the metabolism of acetylcholine and anaesthetic drugs, including succinylcholine, mivacurium, and cocaine. The solanaceous glycoalkaloids (SGAs) are naturally occurring steroids in potatoes and related plants that inhibit both acetylcholinesterase and butyrylcholinesterase. There are many clinical examples of direct SGA toxicity due to cholinesterase inhibition. The aim of this study was to review the hypotheses that (1) SGAs may be the evolutionary driving force for atypical butyrylcholinesterase alleles and that (2) SGAs may adversely influence the actions of anaesthetic drugs that are metabolized by acetylcholinesterase and butyrylcholinesterase. The information was obtained by Medline search and consultation with experts in the study of SGAs and cholinesterases. The SGAs inhibit both acetylcholinesterase and butyrylcholinesterase in numerous in vitro and in vivo experiments. Although accurate assays of SGA levels are difficult, published data indicate human serum SGA concentrations at least ten-fold lower than required to inhibit acetylcholinesterase and butyrylcholinesterase in vitro. However, we review evidence that suggests the dietary ingestion of SGAs can initiate a cholinergic syndrome in humans. This syndrome appears to occur at SGA levels lower than those which interfere with anaesthetic drug catabolism. The world distribution of solanaceous plants parallels the distribution of atypical alleles of butyrylcholinesterase and may explain the genetic diversity of the butyrylcholinesterase gene. Correlative evidence suggests that dietary SGAs may be the driving force for atypical butyrylcholinesterase alleles. In addition, SGAs may influence the metabolism of anaesthetic drugs and this hypothesis warrants experimental investigation.


Respiratory infections following haemopoietic stem cell transplantation in children.
Disorders of the respiratory system are well recognised following the administration of chemotherapy schedules; although respiratory complications may occur following less intensive regimens, they are most frequently seen following the administration of high dose chemotherapy with or without radiotherapy which is used in preparation for haemopoietic stem cell transplantation (SCT). In this setting, respiratory complications may occur in up to 50% of patients and account for over 40% of all deaths; those patients who require admission to intensive care (ICU) requiring intubation and mechanical ventilation have a particularly poor prognosis, with less than 10% becoming long-term survivors.


Long-Term Outcomes in Children Diagnosed with Autism Spectrum Disorders in India.
We investigated long-term outcomes in children with diagnosis of autism spectrum disorders based on Childhood Autism Rating Scale (CARS score). Information about outcomes such as speech, friendships and activities of daily living (ADLs) was collected through telephone-based interviews. Gilliam Autism Rating Scale-2 and Vineland Social Maturity Scale were used to assess level of functioning at follow-up. Parents of 80 [67 males, mean age 12 (3) years] children participated in the interview, 23 attended follow-up assessment. Sixty-four (80%) were verbal, 34 (42.5%) had need-based speech, 20 (25%) had friends and 37 (46%) had achieved age-appropriate ADLs. Median total follow-up period was 10 years. Lower disease severity, parent participation and higher maternal education were associated with better outcomes.


INFORMATIONAL STRESS AS A DEPRESSION INDUCING FACTOR (EXPERIMENTAL STUDY).
Chronic psychogenic stress represents the major initiating agent of psychoneural diseases including depression. We used informational stress model for the purpose of modelling chronic psychogenic stress and depression. The aim of the research was to study behavior of dominant and submissive rats at different stages of informational stress and during depression state. In order to study anxiety and depressive behavior of rats we used "forced swim", "elevated cross maze" and "open-field" tests. The obtained results showed that chronic stressing procedure performed on rats by using the mentioned "informational" stress model led to the development of depression both in dominant and submissive rats. Stressing procedure caused sharp increase of serotonin concentration in hypothalamus of dominant and submissive rats. Under behavioral depression background, sharp increase of serotonin concentration in hypothalamus has been revealed which is caused by the peculiarities of stress model (by uncontrollable stressor. Specifically, by inevitable electric painful irritation).


How far in-silico computing meets real experiments. A study on the structure and dynamics of spin labeled vinculin tail protein by molecular dynamics simulations and EPR spectroscopy.
Investigation of conformational changes in a protein is a prerequisite to understand its biological function. To explore these conformational changes in proteins we developed a strategy with the combination of molecular dynamics (MD) simulations and electron paramagnetic resonance (EPR) spectroscopy. The major goal of this work is to investigate how far computer simulations can meet the experiments. Vinculin tail protein is chosen as a model system as conformational changes within the vinculin protein are believed to be important for its biological function at the sites of cell adhesion. MD simulations were performed on vinculin tail protein both in water and in vacuo environments. EPR experimental data is compared with those of the simulated data for corresponding spin label positions. The calculated EPR spectra from MD simulations trajectories of selected spin labelled positions are comparable to experimental EPR spectra. The results show that the information contained in the spin label mobility provides a powerful means of mapping protein folds and their conformational changes. The results suggest the localization of dynamic and flexible regions of the vinculin tail protein. This study shows MD simulations can be used as a complementary tool to interpret experimental EPR data.


Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation.
Silicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO2). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol trafficking. Lysosomal cholesterol has been demonstrated to regulate LMP while cationic amphiphilic drugs (CADs) reduce cholesterol trafficking from lysosomes and promote endolysosomal cholesterol accumulation as seen in Niemann Pick disease. Using a bone marrow derived macrophage (BMdM) model, four CADs were examined for their potential to reduce cSiO2-induced inflammation. Here we found that FDA-approved CAD drugs imipramine, hydroxychloroquine, fluvoxamine, and fluoxetine contributed to reduced LMP and IL-1β release in cSiO2 treated BMdM. These drugs inhibited lysosomal enzymatic activity of acid sphingomyelinase, decreased lysosomal proteolytic function, and increased lysosomal pH. CADs also demonstrated a significant increase in lysosomal-associated free cholesterol. Increased lysosomal cholesterol was associated with a significant reduction in cSiO2 induced LMP and IL-1β release. In contrast, reduced lysosomal cholesterol significantly exacerbated cSiO2-induced IL-1β release and reduced the protective effect of CADs on IL-1β release following cSiO2 exposure. Taken together, these results suggest that CAD modification of lysosomal cholesterol may be used to reduce LMP and cSiO2-induced inflammation and could prove an effective therapeutic for silicosis and other particle-caused respiratory diseases.


[A case of anaphylactic shock caused by granisetron].
A 60-year-old man suffered from inoperable recurrent undifferentiated thyroid cancer and was scheduled to undergo chemotherapy. He had no known allergy to medications. In the first regimen, he was given IV granisetron and betamethasone before IV 120 mg paclitaxel was administered. Five minutes after the paclitaxel infusion, he developed anaphylactic shock of hypotension, dyspnea, and flushing. He was treated by steroid and recovered. In the second regimen one week later, he was scheduled to be treated by other antineoplastic medication instead of paclitaxel for fear of anaphylaxis. Prechemotherapy the same as the first regimen, granisetron and betamethasone, were given,but he developed the same anaphylaxis before the antineoplastic medication was given. He was thus thought to develop anaphylaxis due to the granisetron itself. Anaphylaxis caused by granisetron has not yet been reported, and this experience prompted us to report this case.


The influences of casein phosphopeptides on metabolism of ectopic bone induced by decalcified bone matrix implantation in rats.
The effect of casein phosphopeptides (CPP) on bone metabolism was studied in the ectopic bone induced by the implantation of decalcified bone matrix in rats. Forty-two Wistar male rats of 7 weeks old were fed low calcium diets (0.39% of calcium) with or without supplying 0.50% of CPP, or a control diet (0.91% of calcium) without CPP supplementation. After a 1-week preliminary period, each rat was subcutaneously implanted with 30 mg of demineralized bone matrix powder. Fourteen and 21 days after the implantation, the implants were harvested from 7 rats of each group. Calcium content in the graft was not significantly different among all groups on day 14. Subsequently, the content of calcium rapidly increased in the grafts irrespective of diets given. However, the graft of the CPP- group contained less calcium than the other groups and the calcium content was more in the control rats compared to the CPP+ animals on day 21. Alkaline phosphatase activity (an index of bone and cartilage calcification) was lower in the control group than in the CPP+ group on day 14. The enzyme activity subsequently decreased in the control group but the activity was not changed in the other groups. As a result, the activity of alkaline phosphatase was lower in the control animals than in the other rats on day 21. Tartrate-resistant cap phosphatase activity (an index of bone resorption) was higher in the CPP--group compared to the control on day 14. On day 21, the activity was higher in the CPP--group compared to the others.(ABSTRACT TRUNCATED AT 250 WORDS)


[25-hydroxy vitamin D deficiency with reduction of intestinal calcium absorption and bone density in chronic alcoholism].
Plasma levels of 25-hydroxycalciferol (25-OH-D), 47-calcium intestinal absorption, bone mineral content and the biologic parameters of phospho-calcium metabolism were studied in 30 chronic alcoholics, 15 with Laennec's cirrhosis (group A) and 15 without (group B). These patients were compared with 27 normal subjects. In group A, the mean 25-OH-D plasma level was 23.7 +/- SD 18.5 microgram/l and in group B 35.2 +/- SD 21.8 microgram/l. These mean levels were lower than those of the control group, which were 57.2 +/- SD 22.5 microgram/l (p less than 0.001). The mean value of the 47Ca intestinal absorption, measured as the percentage of the ingested dose per litre of plasma and multiplied by the body weight, was also significantly lower in group A, which was 140 +/- SD 47 (p less than 0.01), and in group B, which was 145 +/- SD 69 (p less than 0.05), compared with the normal subjects whose average was 182 +/- SD 45.6. Similarly, the total plasma calcium was low: 1.99 +/- SD 0.24 mmol/l in all the alcoholics, while that of the control group was 2.22 +/- SD 0.18 mmol/l (p less than 0.001). For the 30 chronic alcoholics there was a positive correlation between 25-OH-D and 47Ca intestinal absorption, (r = 0.484; p less than 0.004). This suggests that in chronic alcoholism the deficiency of 25-OH-D induces a diminution of the intestinal absorption of calcium which, in the long term, can result in bone demineralization evidenced in the patients studied by a bone mineral content lower than normal (p less than 0.001).


Dispersing molecular cobalt in graphitic carbon nitride frameworks for photocatalytic water oxidation.
The development of water oxidation catalysts (WOCs) to cooperate with light-energy transducers for solar energy conversion by water splitting and CO2 fixation is a demanding challenge. The key measure is to develop efficient and sustainable WOCs that can support a sustainable photocatalyst to reduce over-potentials and thus to enhance reaction rate of water oxidation reaction. Cobalt has been indentified as active component of WOCs for photo/electrochemical water oxidation, and its performance relies strongly on the contact and adhesion of the cobalt species with photoactive substrates. Here, cobalt is homogeneously engineered into the framework of pristine graphitic carbon nitride (g-C3 N4 ) via chemical interaction, establishing surface junctions on the polymeric photocatalyst for the water oxidation reaction. This modification promotes the surface kinetics of oxygen evolution reaction by the g-C3 N4 -based photocatalytic system made of inexpensive substances, and further optimizations in the optical and textural structure of Co-g-C3 N4 is envisaged by considering ample choice of modification schemes for carbon nitride materials.


ACUTE INFLAMMATION AND TISSUE MAST CELLS IN ADRENALECTOMIZED RATS WITH CUTANEOUS MUCORMYCOSIS.
The effects of the absence of adrenal tissues on the inflammatory reaction and on the relationship of the tissue mast cells to the inflammatory process have been studied histologically in rats with cutaneous Rhizopus oryzae infection. Degranulation and regranulation of the tissue mast cells at the site of injury have been found to correlate respectively with the onset and subsidence of the exudative cellular phase of inflammation. In the adrenalectomized animals regranulation of these cells and correspondingly termination of the exudative phase are delayed. In the lesions of these rats the numbers of eosinophiles are increased. The proliferative cellular processes of inflammation, although delayed in onset, progress in essentially normal manner but result in some increased collagen deposition. The lack of adrenal secretions does not enhance fungus proliferation and is not associated with spread of the infection. In the present experiments the effectiveness of inflammation does not differ in normal and adrenalectomized rats.