A Perspective on Implementation of Technology-Driven Exergames for Adults as Telerehabilitation Services.
A major concern of public health authorities is to also encourage adults to be exposed to enriched environments (sensory and cognitive-motor activity) during the pandemic lockdown, as was recently the case worldwide during the COVID-19 outbreak. Games for adults that require physical activity, known as exergames, offer opportunities here. In particular, the output of the gaming industry nowadays offers computer games with extended reality (XR) which combines real and virtual environments and refers to human-machine interactions generated by computers and wearable technologies. For example, playing the game in front of a computer screen while standing or walking on a force plate or treadmill allows the user to react to certain infrastructural changes and obstacles within the virtual environment. Recent developments, optimization, and minimizations in wearable technology have produced wireless headsets and sensors that allow for unrestricted whole-body movement. This makes the virtual experience more immersive and provides the opportunity for greater engagement than traditional exercise. Currently, XR serves as an umbrella term for current immersive technologies as well as future realities that enhance the experience with features that produce new controllable environments. Overall, these technology-enhanced exergames challenge the adult user and modify the experience by increasing sensory stimulation and creating an environment where virtual and real elements interact. As a therapy, exergames can potentially create new environments and visualizations that may be more ecologically valid and thus simulate real activities of daily living that can be trained. Furthermore, by adding telemedicine features to the exergame, progress over time can be closely monitored and feedback provided, offering future opportunities for cognitive-motor assessment. To more optimally serve and challenge adults both physically and cognitively over time in future lockdowns, there is a need to provide long-term remote training and feedback. Particularly related to activities of daily living that create opportunities for effective and lasting rehabilitation for elderly and sufferers from chronic non-communicable diseases (CNDs). The aim of the current review is to envision the remote training and monitoring of physical and cognitive aspects for adults with limited mobility (due to disability, disease, or age), through the implementation of concurrent telehealth and exergame features using XR and wireless sensor technologies.


[Assay of myelin basic protein (MBP) antibody in the cerebrospinal fluid and serum of rabbits with experimental allergic encephalomyelitis (EAE) before and after sensitization].
The level of MBP antibody in the cerebrospinal fluid (CSF) and serum of 20 rabbits with EAE was determined with ELISA respectively before and after sensitization with MBP. The results showed that after sensitization the level of the antibody in CSF increased in accordance with the degree of severity of the EAE. While the increase of the serum was not parallel while the state of the disease. This study suggested that the determination of the level of MBP antibody might be of help in the diagnosis of demyelinative disease of the central nervous system and in monitoring the course and estimating the prognosis of the disease.


Symposium review: Understanding the role of the rumen microbiome in enteric methane mitigation and productivity in dairy cows.
Ruminants are one of the largest sources of global CH4 emissions. This enteric CH4 is exclusively produced by methanogenic archaea as a natural product during microbial fermentation in the reticulorumen. As CH4 formation leads to a gross energy loss for the ruminant host and is also an environmental issue, several CH4 mitigation approaches have been investigated, but results have been inconsistent, which may be partially attributed to a lack of understanding of the mechanistic basis of methanogenesis and the effect of inhibitors on individual methanogenic lineages and other fermenting microbes in the rumen. Methanogenic archaea are obligatory anaerobes that can reduce CO2, methanol, or methylamines or cleave acetate to form CH4. Although methanogens work toward a common goal of generating energy through the formation of CH4, individual methanogenic lineages differ in their physiological and metabolic capabilities, which can differentially affect H2 transactions and CH4 formation. Using advanced omic approaches, recent research has revealed that less abundant methanol-utilizing Methanosphaera and methylamine- and methanol-utilizing Methanomassiliicoccales lineages are positively correlated with CH4 emissions and may have a greater share in overall CH4 production compared with more abundant CO2-reducing methanogens than previously thought. These data imply that the diversity as well as the abundance of methanogens is important in CH4 formation, and that this diversity is influenced by H2 availability and interactions within and between H2-producing microbes in the rumen. These complex interactions between microbes and H2 are further influenced by variations in dietary, host, and environmental conditions. This review discusses critical knowledge gaps underlying methanogen diversity and its link to CH4 formation, formation of specific bacteria-archaeal cohorts, and how H2 production and utilization are regulated between these cohorts during normal and inhibited methanogenesis. Addressing these knowledge gaps has the potential to lead to the development of novel strategies or to complement existing strategies to effectively reduce CH4 formation while also improving productivity in dairy cows.


N-alkoxyacrylamides as substrates for enantioselective Diels-Alder reactions.
[reaction: see text] The use of N-alkoxyacrylamides as substrates for Lewis acid catalyzed Diels-Alder reactions has been examined. Enantioselectivities up to 92% ee have been achieved using very simple chiral Lewis acids prepared from triisobutylaluminum and 2,2-dimethyl-alpha,alpha,alpha',alpha'-tetra-1-naphthalenyl-TADDOL (1-NaphtTADDOL). The use of Yamamoto's Zn-BINOL, easily prepared from Et2Zn and 1,1'-bi-2-naphthol (BINOL), proved to be even more efficient, and enantioselectivities up to 96% ee were achieved.


Characterization of ferrihydrite-soil organic matter coprecipitates by X-ray diffraction and Mössbauer spectroscopy.
In soils and sediments ferrihydrite often precipitates from solutions containing dissolved organic matter, which affects its crystallinity. To simulate this process we prepared a series of 2-line ferrihydrite-organic matter coprecipitates using water extractable organic matter (OM) from a forest topsoil. The products were characterized byX-ray diffraction, Mössbauer spectroscopy, N2-gas adsorption and transmission electron microscopy. With increasing C/Fe ratios of the initial solution the d-spacings of the two major XRD peaks increased, while peak shoulders at 0.22 and 0.16 nm weakened. The asymmetry of the 0.26 nm peak decreased and disappeared at a C/Fe ratio of 0.78. The quadrupole splitting of the Mössbauer spectra at 300 K increased from 0.78 to 0.90 mm s(-1), the mean magnetic hyperfine field at 4.2 K dropped from 49.5 to 46.0 T, and the superparamagnetic collapse of the magnetic hyperfine splitting was shifted toward lower temperatures. These data reflect a strong interference of OM with crystal growth leading to smaller ferrihydrite crystals, increased lattice spacings, and more distorted Fe(O,OH)6 octahedra. Even small amounts of OM significantly change particle size and structural order of ferrihydrite. Crystallinity and reactivity of natural ferrihydrites will therefore often differ from their synthetic counterparts, formed in the absence of OM.


[Tolvaptan in a pediatric cardiorenal syndrome: What is its role?]
The cardiorenal syndrome has been defined as a situation in which therapy to relieve congestive symptoms of heart failure is limited by a decreased renal function. The resistance to conventional diuretic treatment makes difficult managing these patients. Tolvaptan, a selective vasopressin-2 receptor antagonist, has been used successfully in adults with this pathology but the experience with children is very limited. A five-year-old girl with renal failure waiting for a heart transplant is presented. Tolvaptan (0.1 mg/kg/day) was started at very low dosage, resulting in an excellent response. We analyzed the creatinine, urea, urine volume and sodium evolution. Renal function also improved. She could be discharged after four days of treatment (156 days of hospitalization) with ambulatory favourable follow-up until heart transplant. Tolvaptan should be considered in pediatric cases of conventional diuretic-resistant congestive heart failure, especially when complicated by kidney disease.


Breaking the bond: recent patents on bacterial adhesins.
Adhesins need to be exposed on the surface of pathogenic bacteria to properly interact with host tissues and allow establishment of the infection. This fact implies that, in theory, one could manage or avoid infection by controlling adhesins' function, and also by indirectly detecting bacteria through their surface-exposed adhesins. Besides, binding of anti-adhesin immunoglobulins on the bacterial surface tend to promote the opsonization of the pathogen. Therefore, bacterial adhesins represent a great target to develop new biopharmaceuticals, which may become commercially and medically important products. In this review, we will summarize the biological importance of bacterial adhesins, and also discuss some recent patents related to these molecules, as well as their use and possible new future developments in this area.


Protease resistance of syntaxin.SNAP-25.VAMP complexes. Implications for assembly and structure.
A stable ternary complex formed with vesicle-associated membrane protein 2 (VAMP2) and plasma membrane proteins syntaxin 1A and synaptosome-associated protein of 25 kDa (SNAP-25) is proposed to function in synaptic vesicle exocytosis. To analyze the structural characteristics of this synaptic protein complex, recombinant binary (syntaxin 1A.SNAP-25), recombinant ternary, and native ternary complexes were subjected to limited trypsin proteolysis. The protected fragments, defined by amino-terminal sequencing and mass spectrometry, included a carboxyl-terminal region of syntaxin 1A, the cytoplasmic domain of VAMP2, and amino- and carboxyl-terminal regions of SNAP-25. Furthermore, separate amino- and carboxyl-terminal fragments of SNAP-25, when combined with VAMP2 and syntaxin 1A, were sufficient for stable complex assembly. Analysis of ternary complexes formed with full-length proteins revealed that the carboxyl-terminal transmembrane anchors of both syntaxin 1A and VAMP2 were protected from trypsin digestion. Moreover, the stability of ternary complexes was increased by inclusion of these transmembrane domains. These results suggest that the transmembrane domains of VAMP2 and syntaxin 1A contribute to complex assembly and stability and that amino- and carboxyl-terminal regions of SNAP-25 may function as independent domains.


Rototranslational sum rules for electromagnetic hypershielding at the nuclei and related atomic Cartesian derivatives of the optical rotatory power.
Two molecular properties, the nuclear electromagnetic hypershielding (psi(gamma,alphabeta) ('I)) and the gradient of the electric dipole-magnetic dipole polarizability (nabla(Igamma)G(alphabeta) (')), have been calculated using the time-dependent Hartree-Fock method. Provided the Hellmann-Feynman theorem is satisfied, these quantities are equivalent and are related through the nabla(Igamma)G(alphabeta) (')=eZ(I)psi(gamma,alphabeta) ('I) relation, where Z(I) is the atomic number of atom I and e the magnitude of the electron charge. In such a case, the determination of the nuclear electromagnetic hypershielding presents the computational advantage over the evaluation of the gradient of G(alphabeta) (') of requiring only the knowledge of nine mixed second-order derivatives of the density matrix with respect to both electric and magnetic fields (D(alpha,beta)(-omega,omega)) instead of the 3N (N is the number of atoms) derivatives of the density matrix with respect to the Cartesian coordinates (D(Igamma)). It is shown here for the H(2)O(2) molecule that very large basis sets such as the aug-cc-pVQZ or the R12 basis are required to satisfy the Hellmann-Feynman theorem. These basis set requirements have been substantiated by considering the corresponding rototranslational sum rules. The origin dependence of the rototranslational sum rules for the gradient of G(alphabeta) (') has then been theoretically described and verified for the H(2)O(2) molecule.


Widespread occurrence and lateral transfer of the cyanobactin biosynthesis gene cluster in cyanobacteria.
Cyanobactins are small cyclic peptides produced by cyanobacteria. Here we demonstrate the widespread but sporadic occurrence of the cyanobactin biosynthetic pathway. We detected a cyanobactin biosynthetic gene in 48 of the 132 strains included in this study. Our results suggest that cyanobactin biosynthetic genes have a complex evolutionary history in cyanobacteria punctuated by a series of ancient horizontal gene transfer events.


Tonic pain reduces autonomic responses and EEG functional connectivity elicited by affective stimuli.
Most pain studies have focused on only two aspects of pain: the influence of pain on attentional processing and the modulation of pain perception by affective stimuli. However, the influence of tonic pain on the attentional processing of affective stimuli has not been studied. In this study, we investigated the effects of tonic pain on the attentional processing of affective stimuli, focusing on autonomic responses and their relationship with both EEG power and functional connectivity. Forty participants (20 men and 20 women) received tonically painful and nonpainful thermal stimulation while viewing blocks of pleasant, unpleasant, or neutral images. The galvanic skin conductance response (SCR), electrocardiographic activity, and electroencephalographic (EEG) activity in the delta and theta bands were recorded. Participants rated the unpleasantness of the pain at the end of each block. Typical affective SCR and heart rate (HR) patterns were found in the no-pain condition, but when the pain was delivered, these patterns disappeared. EEG power and functional connectivity results showed that tonic pain affected the delta band in the central region during pleasant and unpleasant image blocks. Our findings suggest that tonic pain captured attentional focus and reduced the cognitive resources available for processing affective stimuli, altering the emotional experience associated with pain.


The SPARC-related modular calcium binding protein 2 (SMOC2) gene polymorphism in primary glaucoma: a case-control study.
Primary glaucomas are among the most common eye diseases that may potentially result in bilateral blindness. Both genetics and environmental factors are reported to be involved in the etiology of primary glaucomas. Secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding protein 2 (SMOC2) is a matricellular glycoprotein encoded by the SMOC2 gene and known to regulate the expression of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), which play an important role in the pathogenesis of primary glaucomas. The frequencies of alleles and genotypes of SMOC2 variants were examined in 406 Saudi subjects, including primary open angle glaucoma (POAG, n=140) and primary angle closure glaucoma (PACG, n=64) patients and 202 matched healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotyping of SMOC2 polymorphism (rs13208776) revealed a significantly higher frequency of the heterozygous genotype GA (P<0.01) and a lower frequency of wild type GG genotype (P=0.05) in glaucoma patients compared to the controls. Upon stratification of the patients on the basis of types of glaucoma, PACG patients had a significantly higher frequency of GA genotype as compared to the controls (P<0.01), whereas there was no significant difference between the POAG patient and control groups in frequencies of SMOC2 alleles and genotypes. Further, there was no significant difference in frequency distribution of alleles and genotypes between male and female patients. This study indicates that the GA genotype of SMOC2 (G>A) polymorphism is significantly associated with PACG and may be a risk factor. However, further large-scale studies in the Saudi population as well as in other ethnic populations are needed to confirm this association.


Predictive value of anti-citrullinated peptide antibodies: a real life experience.
Rheumatoid Arthritis (RA) is an autoimmune destructive joint disease, characterized by the presence of rheumatoid factor and anti-citrullinated peptide antibodies. Anti-citrullinated peptide antibodies were recently defined as RA criterion with sensitivity and specificity of 50-80 and 75-95 %, respectively. However, in the general population, the predictive value of anti-citrullinated peptide antibodies is yet to be determined. Herein, we aim to determine the predictive value of anti-citrullinated peptide antibodies in real life as well as clinical and serological factors related to this value. Retrospective cross-sectional study of consecutive samples evaluated for anti-citrullinated peptide antibodies in a referral autoimmune laboratory. Demographic and clinical parameters at the time the sample was drawn were collected. During November 2011 through December 2013, a total of 215 anti-citrullinated peptide antibody tests were performed in our laboratory. Data were available for 140 samples of which only 28 samples were positive for anti-citrullinated peptide antibodies. Of the 140 patients tested, 18 were diagnosed with RA, of which 12 were positive and 6 were negative for anti-citrullinated peptide antibody test. Thus, in this cohort, anti-citrullinated peptide antibodies were positive in 20 % of samples with a positive predictive value (PPV) of 43 % and a negative predictive value of 95 %. In real life, only 20 % of anti-citrullinated peptide antibody tests referred to a tertiary center where found to be positive. The negative predictive value of this test is very high and may support the common use of anti-citrullinated peptide antibody test as an exclusion criterion in the process of evaluating a patient with rheumatic disease.


Cox Regression Models with Functional Covariates for Survival Data.
We extend the Cox proportional hazards model to cases when the exposure is a densely sampled functional process, measured at baseline. The fundamental idea is to combine penalized signal regression with methods developed for mixed effects proportional hazards models. The model is fit by maximizing the penalized partial likelihood, with smoothing parameters estimated by a likelihood-based criterion such as AIC or EPIC. The model may be extended to allow for multiple functional predictors, time varying coefficients, and missing or unequally-spaced data. Methods were inspired by and applied to a study of the association between time to death after hospital discharge and daily measures of disease severity collected in the intensive care unit, among survivors of acute respiratory distress syndrome.


Genome Sequence of Streptococcus agalactiae Strain H002, Serotype III, Isolated in China from a Pregnant Woman.
Here, we report the first whole-genome sequence of Streptococcus agalactiae strain H002, serotype III, isolated in China from a woman 32 weeks pregnant. This sequence represents an important addition to the published genomes and will promote comparative genomic studies of S. agalactiae spp. isolated from diverse regions, particularly when compared with Chinese strains.


Investigating the T regulatory cells and Sirtuin-I serum level in immunotherapy treated house dust mite allergic asthma patients.
House dust mite aeroallergens are predominant triggers of frequent asthma attacks among adults and children. The intensity of asthma and immune reaction necessitates treatment alternatives based on adjusting chosen immunity biomarkers to control the exacerbation of symptoms and establish long-term immune tolerance. In this study, we selected CD4+CD25+Foxp3+ regulatory T cells (Tregs), FOXP3, and Sirtuin-1 as they are known to have a potential role in the immune reaction in different allergic diseases. We investigated their interplay during HDM allergic asthma and its respective immunotherapy. Eighty-four subjects were divided into 3 groups; healthy controls (CT), HDM asthma patients without immunotherapy (WOIT), and HDM asthma patients treated with subcutaneous immunotherapy for 6 months before recruitment (WIT). They were enrolled according to the pulmonary function, skin prick tests, and HDM-specific IgE. CD4+ CD25+ and CD4+ CD25+ FOXP3+hi T cells Cell percentages, FOXP3 gene expression, and Sirtuin-1 (Sirt1) serum level were analyzed. We found that there is a significant difference between WOIT and WIT groups in the CD4+ CD25+ and CD4+ CD25+ FOXP3+hi T cell percentages. While there is no statistically significant difference between WOIT and WIT groups in FOXP3 level. On the controversy, the SIRT1 level in the CT group (4.53 ± 3.880) significantly decreased in the WOIT and WIT groups. This study revealed that both CD4 CD25 and CD4 CD25 high FOXP3 cell percentages increased in the WIT group and declined in the WOIT group. While, FOXP3 gene expression increased in both groups. In addition, the Sirt1 serum level showed some improvement in WIT group after a serious drop in the WOIT group comparing with the CT group. The modulation of these biomarkers for the remission and control of allergic asthma can be a prognostic outcome of immunotherapy which needs to be confirmed by larger scale studies.


Characterization of the yeast actin patch protein App1p phosphatidate phosphatase.
Yeast App1p is a phosphatidate phosphatase (PAP) that associates with endocytic proteins at cortical actin patches. App1p, which catalyzes the conversion of phosphatidate (PA) to diacylglycerol, is unique among Mg(2+)-dependent PAP enzymes in that its reaction is not involved with de novo lipid synthesis. Instead, App1p PAP is thought to play a role in endocytosis because its substrate and product facilitate membrane fission/fusion events and regulate enzymes that govern vesicular movement. App1p PAP was purified from yeast and characterized with respect to its enzymological, kinetic, and regulatory properties. Maximum PAP activity was dependent on Triton X-100 (20 mm), PA (2 mm), Mg(2+) (0.5 mm), and 2-mercaptoethanol (10 mm) at pH 7.5 and 30 °C. Analysis of surface dilution kinetics with Triton X-100/PA-mixed micelles yielded constants for surface binding (Ks(A) = 11 mm), interfacial PA binding (Km(B) = 4.2 mol %), and catalytic efficiency (Vmax = 557 μmol/min/mg). The activation energy, turnover number, and equilibrium constant were 16.5 kcal/mol, 406 s(-1), and 16.2, respectively. PAP activity was stimulated by anionic lipids (cardiolipin, phosphatidylglycerol, phosphatidylserine, and CDP-diacylglycerol) and inhibited by zwitterionic (phosphatidylcholine and phosphatidylethanolamine) and cationic (sphinganine) lipids, nucleotides (ATP and CTP), N-ethylmaleimide, propranolol, phenylglyoxal, and divalent cations (Ca(2+), Mn(2+), and Zn(2+)). App1p also utilized diacylglycerol pyrophosphate and lyso-PA as substrates with specificity constants 4- and 7-fold lower, respectively, when compared with PA.


Effectiveness of pre-emptive nerve block on opioid consumption in patients undergoing nasal surgery under general anaesthesia: A double-blinded randomised controlled study.
The efficacy of bilateral nasociliary and maxillary nerve blocks combined with general anaesthesia on intraoperative opioids consumption, emergence and recovery outcomes in adult patients is not well established. We conducted this study to test the hypothesis that the above blocks, combined with general anaesthesia, decrease the intraoperative opioid consumption following nasal surgery. In this prospective, double-blinded, randomised controlled study, 51 adult patients undergoing elective nasal surgery under general anaesthesia were randomised into one of two groups. Group A (n = 26) received bilateral nasociliary and maxillary nerve blocks with 12 mL of equal volumes of 0.5% bupivacaine and 2% lignocaine after induction of general anaesthesia. Group B (n = 25) did not receive any block (control group). The primary endpoint was the total intraoperative dose of fentanyl consumed. The secondary endpoints were the grade of cough, emergence agitation, the grade of post-operative nausea and vomiting, time to the first analgesia and time to post-anaesthesia care unit discharge. The mean total intraoperative fentanyl dose (μg) was significantly lower in group A than in group B (2.31 ± 11.76 vs. 41.20 ± 31.00, P = 0.00). The incidence of emergence agitation was lower in group A than group B (11.5% vs. 88%, P = 0.00). The time to the first analgesia was significantly longer in group A than group B (543.27 vs. 199.84 min, P = 0.017). The pre-emptive administration of bilateral nasociliary and maxillary nerve block for nasal surgery is an effective technique for reducing the intraoperative dose of fentanyl and emergence agitation.


Written in stone: memory and reconciliation intersecting the urban biosphere.
The article describes the process of planning the Memorial of Disappeared Detained Citizens in the City of Montevideo, Uruguay, the construction of which was completed in January 2003. It explores the role that memory, planning, and reconciliation carried out in the public realm can play in the context of an urban environment. It describes the procedures and involvement of different social agents in the achievement of a significant landmark where social healing is promoted in parallel to the materialization of the construction of the Memorial, the necessary interaction between the natural and the human dimensions, and how these relate to the city as a biosphere.


[The transport of colloidal gold-labelled albumin after its intra-abdominal administration in peritonitis].
We studied transportation of the colloidal gold labelled albumin 0.5-24 hours after intraabdominal administration of the tracer in normal rabbits and rabbits with experimental diffuse peritonitis (total 24 rabbits). Evacuation of foreign protein goes through the mesothelial stomata to the lymphatic vessels of diaphragm and further to the mediastinal lymph nodes. Sufficient amount of the tracer was captured by the phagocytes inside the lymph collectors. In case of peritonitis reticular cells of the lymph node displayed decreased capture of the tracer. This fact can be attributed to obstacles in the evacuation of the tracer from peritoneum and decreased phagocytic capacity of the reticular cells.


Vesicle numerical densities and cellular attenuation: comparisons between endothelium and epithelium of the alveolar septa in normal dog lungs.
The alveolar septa are divided into two anatomically distinct portions: The thin sides consist of capillary endothelium, alveolar epithelium, and their closely apposed (often fused) basal laminae; the thick sides are characterized by prominent interstitial spaces, containing fibrils and cells, which separate the respective basal laminae. Vesicle numerical densities are comparable (approximately 400 vesicles/ micron3 cytoplasm) in the endothelial and epithelial cells on both sides of the septa. Mean vesicle diameters, however, are substantially less in the epithelial cells on both the thin and thick sides. The extent of both endothelial and epithelial attenuation is significantly greater on the thin sides of the septa. Further, epithelial attenuation is more marked than endothelial attenuation on both sides of the septa. The attenuated cellular portions, possibly because of their extreme thinness, are void of vesicles but provide relatively short diffusion distances (20-30 nm) from vessel or alveolar lumen to the basal lamina. Whether these structural differences between endothelial and epithelial cells contribute to physiologic evidence that describes the endothelium as more permeable than the epithelium remains to be established.


CDMBE: A Case Description Model Based on Evidence.
By combining the advantages of argument map and Bayesian network, a case description model based on evidence (CDMBE), which is suitable to continental law system, is proposed to describe the criminal cases. The logic of the model adopts the credibility logical reason and gets evidence-based reasoning quantitatively based on evidences. In order to consist with practical inference rules, five types of relationship and a set of rules are defined to calculate the credibility of assumptions based on the credibility and supportability of the related evidences. Experiments show that the model can get users' ideas into a figure and the results calculated from CDMBE are in line with those from Bayesian model.


[Cigarette smoking further increases the risk of thrombosis in patients with mild hypertension].
Cigarette smoking and mild hypertension are well-recognized risk factors in the development of thrombotic vascular diseases. Enhanced platelet activity and reduced fibrinolytic activity has already been reported in patients with mild hypertension. This study demonstrated that cigarette smoking adds a further element of increased platelet activity to that already inherently present in hypertension: this could be an important factor promoting arterial thrombosis in hypertensive smokers.


[Structural mutations of chromosome mutations induced by heavy metal salts during aging in vivo and in vitro].
The cytogenetic effect of inorganic copper (CuSO4) and cadmium (CdCl2) salts was studied in cells of long-term (144-hour) human cultures (in vitro model of aging) and in elderly individuals (80-93 years old). Copper sulfate increased the incidence of aberrant cells both in elderly individuals (14.25 +/- 1.74%) and during in vitro aging (12.20 +/- 1.62%) (3.94 +/- 1.96% and 5.25 +/- 1.10% in the controls, respectively), whereas treatment with cadmium chloride did not induce any changes in the background index. Differences in the effect of the studied salts may be due to their different effects on chromatin modification.


Separability of tight and roaming pathways to molecular decomposition.
Recent studies have questioned the separability of the tight and roaming mechanisms to molecular decomposition. We explore this issue for a variety of reactions including MgH(2) → Mg + H(2), NCN → CNN, H(2)CO → H(2) + CO, CH(3)CHO → CH(4) + CO, and HNNOH → N(2) + H(2)O. Our analysis focuses on the role of second-order saddle points in defining global dividing surfaces that encompass both tight and roaming first-order saddle points. The second-order saddle points define an energetic criterion for separability of the two mechanisms. Furthermore, plots of the differential contribution to the reactive flux along paths connecting the first- and second-order saddle points provide a dynamic criterion for separability. The minimum in the differential reactive flux in the neighborhood of the second-order saddle point plays the role of a mechanism divider, with the presence of a strong minimum indicating that the roaming and tight mechanisms are dynamically distinct. We show that the mechanism divider is often, but not always, associated with a second-order saddle point. For the formaldehyde and acetaldehyde reactions, we find that the minimum energy geometry on a conical intersection is associated with the mechanism divider for the tight and roaming processes. For HNNOH, we again find that the roaming and tight processes are dynamically separable but we find no intrinsic feature of the potential energy surface associated with the mechanism divider. Overall, our calculations suggest that roaming and tight mechanisms are generally separable over broad ranges of energy covering most kinetically relevant regimes.


Older adults' descriptions of hope after a stroke.
This descriptive, qualitative study explored the phenomenon of hope and associated factors in older adults who have experienced a stroke. The research questions were (a) What are the patterns of hope manifested by older adults after a stroke? and (b) What are the factors associated with their patterns of hope after the stroke? Participants were a convenience sample of nine stroke survivors who were participating in a stroke support group. Patterns of hope they described were positive anticipation, active participation, forward moving process, inner sense/strength, faith in God, continuing to hope, relative comparison, life-sustaining realistic possibilities, connectedness, previous abilities, and mobility. Factors associated with hope patterning were family connectedness, spiritual connectedness, and goal achievement. Implications for nursing practice included the life-sustaining value of hope, benefits of stroke survivors telling their stories and knowing study results, the delicate balance between caregiver involvement and burden, and the influence of spirituality. Recommendations for further research focus on longitudinal investigations of stroke survivors' experiences, the relation between hope and stroke recovery, and outcome studies of stroke survivors who use hope-fostering strategies.


Feasibility study of the sterilization of pigskin used as wound dressings by neutral electrolyzed water.
Neutral electrolyzed water (NEW) is considered to be a high-level biodegradable disinfectant with sporicidal, bactericidal, and virucidal activity. It has also been reported to accelerate wound healing; thus, it is particularly attractive for the elimination or minimization of the microbial population of skin grafts to be used as wound dressings. Pigskins were sterilized with different concentrations of NEW and with different methods. The feasibility of pigskin sterilization by NEW was evaluated through microbiological analyses, viability assays, histologic assessments, contact cytotoxicity assays, and extract cytotoxicity assays. NEW has strong bactericidal effects on pigskin microorganisms, does not change skin graft histologic properties, and has no cytotoxicity; however, skin viability was significantly reduced after NEW treatment. Although NEW treatment is a very safe and effective method for nonviable pigskin dressing sterilization, to obtain a complete sterilization of pigskin grafts, available chlorine concentration of NEW as well as sterilization time and methods should be optimized.


Swine cysticercosis in the Karangasem district of Bali, Indonesia: An evaluation of serological screening methods.
A serological assessment was undertaken on pigs from the Kubu and Abang sub-districts of Karangasem on the island of Bali, Indonesia, where earlier studies had detected patients with cysticercosis. Antigens purified from Taenia solium cyst fluid by cation-exchange chromatography were used to evaluate antibody responses in the pigs and the serological tests were also evaluated using sera from pigs experimentally infected with T. solium eggs. A total of 392 serum samples from naturally exposed pigs were tested using an ELISA that could be read based on both a colour change perceptible by the naked eye and an ELISA based on absorbance values. Twenty six (6.6%) pigs were found seropositive by the naked-eye ELISA and were categorized into three groups: strongly positive (absorbance values >0.8, n=6), moderately positive (absorbance values between 0.2 and 0.8, n=7), and weakly positive (absorbance values <0.2, n=13). Necropsies performed on 11 strongly and moderately positive pigs revealed that six strongly positive pigs were infected either solely with T. solium cysticerci (n=3), or co-infected with both T. solium and Taenia hydatigena (n=3). Four moderately positive pigs were infected solely with T. hydatigena. No cysticerci were found in one pig that was moderately positive by the naked-eye ELISA. Two experimentally infected pigs became antibody positive by 6 weeks post-infection, whereas eight control pigs remained negative. An additional 60 pigs slaughtered at authorized abattoirs on Bali were tested using the same ELISA. All 60 pigs were seronegative with no evidence of Taenia infection at necropsy. The results confirm the presence of porcine cysticercosis on Bali and, while the serological responses seen in T. solium infected animals were much stronger than those infected with T. hydatigena, the diagnostic antigens are clearly not species specific. Further studies are necessary to confirm if it is possible to draw a cut off line for differentiation of pig infected with T. solium from those infected with T. hydatigena.


Implementation and Monitoring of a Gestational Trophoblastic Disease Management Program in a Tertiary Hospital in Morocco: Opportunities and Challenges.
Objective. Gestational Trophoblastic Disease (GTD) management requires clear guidelines for diagnosis, treatment, and follow-up. Unequal management skills among practitioners, inadequate treatment, irregular surveillance, and drop-out are common in resource-limited settings and can lead to life-threatening complications and morbidities. To address these challenges, we implemented a GTD Management Program at the National Center for Reproductive Health in Rabat, Morocco. Methods and Program Description. In-depth review of management protocols was carried out, and concise guidelines were developed, with targeted training for physicians. A physical space and a weekly fixed GTD consultation were set, and personalized follow-up was established for each patient. An electronic database documenting patients' surveillance was created, allowing immediate outreach in case of irregularities. Results. During the period from October 2013 to June 2016, 50 patients were included in this program. Patients' mean age was 33 years; 92% were illiterate and 82% had a low socioeconomic status. 68% had a positive evolution, while 32% developed gestational trophoblastic neoplasia, requiring 2 to 6 chemotherapy sessions. An average of 2.8 outreach reminders were necessary for each patient. 94% fully adhered to the program of care and completed properly their follow-up. Conclusion. Implementation and thorough monitoring of this program helped optimize patients' care, avoiding drop-outs and delays in diagnosing and treating complications.


New boron nitride structures B4N4: a first-principles random searching application.
The present investigation searched for new boron nitride (BN) polymorphs by means of first-principles simulations. The ab initio random structure searching strategy was implemented. The electronic and mechanical properties and equation of states of three new metastable BN crystal forms with equilibrium energies close to the most stable B4N4 form, c-BN, are presented. Results show either dynamically stable semiconductors or insulators, one of which is even slightly harder than c-BN. The equation of states is also presented and a phase transition is predicted.


SynBOLD-DisCo: Synthetic BOLD images for distortion correction of fMRI without additional calibration scans.
The blood oxygen level dependent (BOLD) signal from functional magnetic resonance imaging (fMRI) is a noninvasive technique that has been widely used in research to study brain function. However, fMRI suffers from susceptibility-induced off resonance fields which may cause geometric distortions and mismatches with anatomical images. State-of-the-art correction methods require acquiring reverse phase encoded images or additional field maps to enable distortion correction. However, not all imaging protocols include these additional scans and thus cannot take advantage of these susceptibility correction capabilities. As such, in this study we aim to enable state-of-the-art distortion correction with FSL's topup algorithm of historical and/or limited fMRI data that include only a structural image and single phase encoded fMRI. To do this, we use 3D U-net models to synthesize undistorted fMRI BOLD contrast images from the structural image and use this undistorted synthetic image as an anatomical target for distortion correction with topup. We evaluate the efficacy of this approach, named SynBOLD-DisCo (synthetic BOLD images for distortion correction), and show that BOLD images corrected using our approach are geometrically more similar to structural images than the distorted BOLD data and are practically equivalent to state-of-the-art correction methods which require reverse phase encoded data. Future directions include additional validation studies, integration with other preprocessing operations, retraining with broader pathologies, and investigating the effects of spin echo versus gradient echo images for training and distortion correction. In summary, we demonstrate SynBOLD-DisCo corrects distortion of fMRI when reverse phase encoding scans or field maps are not available.


Morbidity and mortality associated with polytrauma at a Nigerian tertiary hospital.
Polytrauma which is a leading cause of morbidity and mortality world-wide is associated with long hospital stay and loss of productivity. To determine the morbidity and mortality associated with polytrauma in an urban African tertiary hospital. This prospective study was carried out at the Lagos University Teaching Hospital (LUTH) between 1st November 2004 and 31st October 2006 All surviving patients with significant multiple injuries that presented at LUTH over the period were studied. Data were collected and analysed included age, gender, complications and outcomes. Two hundred and ninety-one patients with multiple trauma were studied excluding those brought in dead. Most (75.3%) of the patients were males. Ages were affected ranged from two years to 76 years with a mean of 32.2 +/- 16.4 years. The commonest complication was wound infection 24 (32.0%) followed by bedsores 12 (16.0%). Forty-two (14%) patients died. These deaths were associated with average high injury severity score of 37.2 +/- 12.0. Six patients had amputation and all of them had mangled extremity severity score greater than seven. Prolonged hospital stay was recorded among patients with fractures and spinal injuries, who had average stay of 71 days. Wound infection and high death rates among patients with high injury severity scores are the commonest complications in polytrauma as seen in this African teriary hospital.


Involvement of opioid, adenosine and 5-HT(3) receptors in antinociceptive effects of an ayurvedic polyherbal formulation.
The present study was undertaken to evaluate the antinociceptive effects of an ayurvedic polyherbal formulation in rats and mice employing the tail immersion test and acetic acid-induced writhing test, respectively. With the tail immersion method, rats received two different doses (270 and 405 mg/kg BW, p.o.) of a formulation, pethidine (5.4 mg/kg BW, p.o.) as a reference standard and the combination of the higher dose of the formulation with naloxone (2 mg/kg, i.p.), an opioid receptor antagonist, and caffeine (16 mg/kg, i.p.), used as an adenosine receptor antagonist. In the acetic acid-induced writhing test, mice received two different doses (390 and 585 mg/kg, BW, p.o.) of formulation, diclofenac sodium (15 mg/kg, BW, p.o.) as a reference standard and the combination of the higher dose of the polyherbal formulation with ondansetron (0.5 mg/kg, i.p.), a serotonin receptor antagonist. The polyherbal formulation (405 mg/kg) exhibited a significant (p < 0.01) antinociceptive effect using the tail immersion method. In the acetic acid-induced writhing test, the formulation showed significant (p < 0.01) dose-dependent activity. The antinociceptive effect of the polyherbal formulation apparently involved an opiate-like mechanism, since its antinociceptive action was attenuated by naloxone pretreatment. In addition, antinociceptive activity was attenuated by caffeine and reversed by ondansetron pretreatment. Our data suggest that the polyherbal formulation possessed centrally and peripherally mediated antinociceptive properties. The activity could be mediated through opioid, adenosine, and serotonin receptors and via inhibition of cyclo-oxygenase- and/or lipoxygenase-dependent pathways.


Human exposure to Bisphenol A and liver health status: Quantification of urinary and circulating levels by LC-MS/MS.
A selective and highly sensitive analytical methodology for determination of Bisphenol A in human plasma was developed and validated. The method was based on selective liquid/solid extraction, combined with liquid chromatography-electrospray ionization tandem mass spectrometry in the multiple reaction monitoring mode and negative ionization. The linearity of the detector response was verified in human plasma over the concentration range 0.100-200ngmL-1. The detection limit was 0.03ngmL-1 and the quantification limit was 0.100ngmL-1. The analytical features of the proposed in-house validated method were satisfactory: precision was <10% and recoveries were around 84-104%. The matrix effect was studied and compensated using deuterated labeled standard. The applicability of the proposed method was demonstrated analyzing human plasma samples from individuals affected by non-alcoholic fatty liver disease. Bisphenol A was detected above the detection limit in all samples. The data show a persistence of unconjugated Bisphenol A levels in plasma and indicate a chronic Bisphenol A exposure of the target organ, suggesting an association between liver health status and Bisphenol A exposure. The results from our study are valuable for further investigation with large sample size and longitudinal study designs, necessary to confirm the observed association.


A two-dimensional MXene potentiates a therapeutic microneedle patch for photonic implantable medicine in the second NIR biowindow.
Due to the refractory nature and recurrence of cancer, the related treatments are continuously updated and improved. Here, we designed a soluble polyvinylpyrrolidone (PVP) microneedle system loaded with a two-dimensional (2D) MXene (Nb2C nanosheets) for medical implantation and photothermal ablation of superficial tumors in the second near infrared biological window (NIR-II). In this system, 2D Nb2C nanosheets acted as high-performance photothermal nanoagents, and biocompatible PVP functioned as matrix material to maintain the structure of the needles. The microneedle system exhibited sufficient skin-penetration ability and distinctive dissolution behavior. After being inserted into the skin of the tumor site, it can be dissolved within a short period to release the loaded 2D Nb2C nanosheets. The temperature of the tumor site increased rapidly to almost 70 °C under the irradiation of a 1064 nm laser at a power density of 1 W cm-2, and this could provide sufficient conditions for photonic tumor ablation. After two weeks of treatment, the tumor growth was significantly suppressed, compared to that of the control group, and the survival rate of mice was clearly improved. In addition, the biocompatibility of the microneedle system was tested on mice, in which no significant toxicity or side effects were observed. Therefore, this kind of microneedle system with minimally invasive, safe and effective features is expected to be developed as an intriguing strategy for localized superficial cancer treatment.


Testing a digitally distributed method to recruit a network of community organizations to fight the consequences of the drug epidemic: A study in 13 American states.
To mitigate the opioid epidemic, a concerted effort to educate, prevent, diagnose, treat, and engage residents is required. In this study, a digitally distributed method to form a large network of organizations was tested with 99 counties in regions with high vulnerability to hepatitis C virus (HCV). The method involved a cascade of contacts going from email to phone calls, to videoconferencing and measuring the number of contacts required, amount of time taken, and the proportion of success at recruiting at least one community organization per county. A recruitment period of 5 months and 2118 contact attempts led to the recruitment of organizations from 73 out of our 99 target counties. Organizations belonging to health departments required more attempts and time to recruit but ultimately enrolled at higher rates than did other organizations such as coalitions and agencies. Organizations from counties more (vs. less) vulnerable to HCV outbreaks required more attempts to recruit and, using multiple recruitment methods (e.g., emails, phone calls, and Zoom meetings), improved enrollment success. Overall, this method proved to be successful at remotely engaging a large-scale network of communities with different levels of risk within a large geographic region.


The Effects of an Activity Promotion System on active living in overweight subjects with metabolic abnormalities.
The aim of this study is to examine the effects of Activity Promotion System (APs) on promoting physical activity (PA) for overweight subjects with metabolic abnormalities. We designed a six-month randomised controlled trial with a cross-over design, and recruited 53 subjects. Subjects in group A used APs with a wearable device measuring whole-day PA, including sleep time, sedentary, light, moderate and vigorous PA and a web-based feedback system in the first three months and followed by usual care with traditional health education in the next three months. Subjects in group B received the above programs in a reverse order. PA and metabolic profiles were measured prior to the intervention (T1), three months after the first intervention (T2), and six months after the other intervention (T3), respectively. An independent t test was used to test the differences between periods with and without Aps. This study found that the APs had short-term effects on decreasing sedentary time and increasing mild PA, total PA, daily step counts, and calories burnt. With regard to the secondary outcome measures of metabolic abnormalities, the results showed that APs had had no effect on metabolic abnormalities, except a borderline decreasing of waist circumference. Using this APs might be an effective approach to decrease sedentary time and increase PA for an overweight non-elderly adult population with only metabolic abnormalities. However, long-term studies with APs are needed to further confirm the effectiveness of this innovative Activity Promotion System.


Wide-Range Color Tuning of Narrowband Emission in Multi-resonance Organoboron Delayed Fluorescence Materials through Rational Imine/Amine Functionalization.
Establishing a simple and versatile design strategy to finely modulate emission colors while retaining high luminescence efficiency and color purity remains an appealing yet challenging task for the development of multi-resonance-induced thermally activated delayed fluorescence (MR-TADF) materials. Herein, we demonstrate that the strategic introduction of electron-withdrawing imine and electron-donating amine moieties into a versatile boron-embedded 1,3-bis(carbazol-9-yl)benzene skeleton enables systematic hypsochromic and bathochromic shifts of narrowband emissions, respectively. By this method, effective electroluminescence color tuning was accomplished over a wide visible range from deep-blue to yellow (461-571 nm), using the same MR molecular system, without compromising very narrow spectral features. Deep-blue to yellow organic light-emitting diodes with maximum external quantum efficiencies as high as 19.0-29.2 % and superb color purity could be produced with this family of color-tunable MR-TADF emitters.


Aromatization of 9,10-Dihydroacridine Derivatives: Discovering a Highly Selective and Rapid-Responding Fluorescent Probe for Peroxynitrite.
As part of an effort to develop generally applicable strategies for creating probes suitable for detecting important molecular and ionic species, the oxidative aromatization of nonfluorescent 9,10-dihydroacridine derivatives triggered by peroxynitrite (ONOO-) led to the identification of compound 2H, 9-phenyl-9,10-dihydroacridine-4-carboxylic acid, as a rapid-responding fluorescent probe capable of detecting ONOO- with an extraordinary selectivity. Adding a little more than 1 equiv of ONOO- to a solution of 2H resulted in over 100-fold fluorescence enhancement. In sharp contrast, treating 2H with excessive amounts of other oxidants that often interfere with the detection of ONOO- failed to lead to noticeable fluorescence increase. The reaction of ONOO- with 2H shows a similar efficiency in the pH range of 2-8. Low cytotoxicity was observed for 2H and its aromatized product. Bioimaging experiments revealed the promising potential of 2H as a new fluorescent probe for the selective detection of intracellular ONOO-.


[Prognostic value of DNA ploidy and nuclear morphometry in metastatic prostate cancer].
To assess the prognostic value of DNA ploidy and nuclear morphometry in metastatic prostate cancer after androgenic deprivation treatment. Fifty four patients with prostate cancer and bone metastases who had undergone androgenic suppression treatment were retrospectively studied. The deoxyribonucleic acid (DNA) content was analysed by flow cytometry. Nuclear morphometry characterized 14 nuclear descriptors. The study also included age, Gleason score, T classification, haematocrite, serum albumin, serum alkaline phosphatase, serum prostatic acid phosphatase and the amount of metastatic foci detected during radioisotope bone scan. Univariate survival analyses were performed and Cox's proportional hazards model was used to identify significant prognostic factors. To assess how the experimental factors improve the capacity of the classical factors for predicting the patients who reach median survival, logistic regression multivariate analysis was performed for the classical prognostic factors only and after added experimental variables (DNA content and Nuclear Area). The univariate survival analyses assigned a prognostic value to T category, level of albumin, alkaline phosphatase, Gleason score, bone scan, DNA ploidy and mean nuclear area. In the case of the Cox regression model only Gleason score, bone scan, mean nuclear area and DNA ploidy provided independent prognostic information. In logistic regression for classic prognostic factors only Gleason score is significant (sensibility 89.3%, specificity 64%). However, when the experimental factors are added, in addition to Gleason score, radioisotope bone scan and DNA ploidy are of prognostic value (sensibility 90% and specificity 72%). The study of DNA content and nuclear morphometry in the primitive tumor provides independent prognostic information in survival analysis for patients with metastatic prostate cancer. However, there is limited improvement with respect to the classical factors in predicting survival. This questions its utility in the daily clinical usage.


Efficacy and tolerability of controlled-release paroxetine.
Paroxetine controlled-release (CR) was developed with the objective of minimizing the occurrence and severity of selective serotonin reuptake inhibitor (SSRI)-associated adverse events, thereby improving clinical outcomes. Paroxetine CR delays the onset and controls the rate of absorption of medication. Multicenter controlled clinical trials have found lower rates of early-onset, treatment-associated nausea and lower dropout rates from adverse events in depressed patients treated with paroxetine CR compared with those treated with the conventional, immediate-release formulation. At the same time, clinical response and remission rates are favorable. Other studies have demonstrated the efficacy and tolerability of paroxetine CR in geriatric depression, panic disorder, and social anxiety disorder. The CR formulation of paroxetine appears to represent an effective pharmacokinetic approach to minimizing SSRI adverse events and thereby enhancing clinical outcomes.


Ultrafast Self-Induced X-Ray Transparency and Loss of Magnetic Diffraction.
Using ultrafast ≃2.5 fs and ≃25 fs self-amplified spontaneous emission pulses of increasing intensity and a novel experimental scheme, we report the concurrent increase of stimulated emission in the forward direction and loss of out-of-beam diffraction contrast for a Co/Pd multilayer sample. The experimental results are quantitatively accounted for by a statistical description of the pulses in conjunction with the optical Bloch equations. The dependence of the stimulated sample response on the incident intensity, coherence time, and energy jitter of the employed pulses reveals the importance of increased control of x-ray free electron laser radiation.


Isolation and identification of an endogenous inhibitor of enkephalin-degrading enzymes from bovine spinal cord.
We isolated a potent inhibitor of enkephalin-degrading enzymes from bovine spinal cord and determined its amino-acid sequence and inhibitory activity toward enkephalin-degrading enzymes. This new substance, designated spinorphin, is composed of a heptapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr). The inhibitory activity (IC50) of this new substance toward enkephalin-degrading enzymes, purified from monkey brain, was found to be 3.3 micrograms/ml against aminopeptidase, 1.4 micrograms/ml against dipeptidyl aminopeptidase, 2.4 micrograms/ml against angiotensin-converting enzyme, and 10 micrograms/ml against enkephalinase. This new substance did not show inhibitory activity toward enkephalin degrading enzymes purified from kidney and blood. Above results suggest that this substance is a new neuromodulator in the spinal cord.


[Results of treatment in osteosarcoma--chemotherapy with ADM and CDDP].
Malignant bone neoplasms contribute to about 7% of paediatric cancer. Within the last 20 years much has changed in cancer treatment. Neoadjuvant chemotherapy, as the first phase of comprehensive treatment, results in regression of the tumour and makes limb salvage surgery possible. An exact analysis of 36 patients with osteosarcoma of different localisation, treated at the National Research Institute of Mother and Child between 1991 and 1996 was carried out. Treatment was started with pre-operative adjuvant chemotherapy with ADM and CDDP, administrated during 6 weeks. The regimen and the length of administration depended on stage of disease and tumour reaction to chemotherapy. Amputations or limb salvage surgery was conducted as a second phase of therapy. Postoperative chemotherapy was given for 6 months. Tumour reaction to chemotherapy was described according to the Huvos scale - percentage map of necrosis and regression areas in the neoplastic tissue. The analysis shows good results after chemotherapy with ADM and CDDP.


Effects of Financial Incentives for Smoking Cessation on Mood and Anxiety Symptoms Among Pregnant and Newly Postpartum Women.
Financial incentives for smoking cessation increase smoking abstinence and decrease Beck Depression Inventory (BDI) scores among depression-prone pregnant and postpartum women. The present study is a secondary analysis using the Brief Symptom Inventory (BSI) to examine whether this treatment impacts a broader array of mood and anxiety symptoms. Participants (N = 253) were pregnant cigarette smokers who participated in four controlled clinical trials examining the efficacy of financial incentives for smoking cessation. Women were assigned to an intervention wherein they earned vouchers exchangeable for retail items contingent on smoking abstinence (Contingent, n = 143) or a control condition wherein they received comparable vouchers independent of smoking status (Noncontingent, n = 110). Participants were categorized as depression-prone (n = 105) or depression-negative (n = 148) based on self-reported history of depression and BDI scores at intake. A prior study demonstrated that financial incentives decreased depressive symptoms among depression-prone women in this sample. The present study examined whether those effects extended to a broader array of mood and anxiety symptoms using the BSI. Effects of treatment, time, and depression status were examined using repeated measures analyses of covariance. In addition to depressive symptoms, financial incentives reduced a multitude of BSI scores among depression-prone women, including the BSI global measure of distress and seven symptom subscales. Treatment effects were discernible by late pregnancy, peaked at 8 weeks postpartum, and dissipated by 24 weeks postpartum. In addition to reducing smoking, this financial incentives treatment appears to reduce a range of mood and anxiety symptoms among depression-prone pregnant and postpartum women. This study adds evidence that providing financial incentives contingent on smoking cessation lowers a broad array of psychiatric symptoms, as measured by the BSI, among depression-prone pregnant and newly postpartum women during a time of heightened risk for peripartum mood disorders.


Essential research projects of oral health science in Tokyo Dental College for the 21st century.
In this era of an aging society, no longer will it be sufficient for us to sit in small research units and concentrate on individual experiments. Tokyo Dental College must expand its abilities and develop new attitudes to meet society's evolving needs. The Search Eye 21 will provide us with new opportunities to identify such research goals and to unite coordinated efforts for the advancement of oral health science.


PacC and pH-dependent transcriptome of the mycotrophic fungus Trichoderma virens.
In fungi, environmental pH is an important signal for development, and successful host colonization depends on homeostasis. Surprisingly, little is known regarding the role of pH in fungal-fungal interactions. Species of Trichoderma grow as soil saprobes but many are primarily mycotrophic, using other fungi as hosts. Therefore, Trichoderma spp. are studied for their potential in biocontrol of plant diseases. Particularly in alkaline soil, pH is a critical limiting factor for these biofungicides, whose optimal growth pH is 4-6. Gaining an understanding of pH adaptability is an important step in broadening the activity spectrum of these economically important fungi. We studied the pH-responsive transcription factor PacC by gene knockout and by introduction of a constitutively active allele (pacCc). ΔpacC mutants exhibited reduced growth at alkaline pH, while pacCc strains grew poorly at acidic pH. In plate confrontation assays ΔpacC mutants showed decreased ability to compete with the plant pathogens Rhizoctonia solani and Sclerotium rolfsii. The pacCc strain exhibited an overgrowth of R. solani that was comparable to the wild type, but was unable to overgrow S. rolfsii. To identify genes whose expression is dependent on pH and pacC, we designed oligonucleotide microarrays from the transcript models of the T. virens genome, and compared the transcriptomes of wild type and mutant cultures exposed to high or low pH. Transcript levels from several functional classes were dependent on pacC, on pH, or on both. Furthermore, the expression of a set of pacC-dependent genes was increased in the constitutively-active pacCc strain, and was pH-independent in some, but not all cases. PacC is important for biocontrol-related antagonism of other fungi by T. virens. As much as 5% of the transcriptome is pH-dependent, and of these genes, some 25% depend on pacC. Secondary metabolite biosynthesis and ion transport are among the relevant gene classes. We suggest that ΔpacC mutants may have lost their full biocontrol potential due to their inability to adapt to alkaline pH, to perceive ambient pH, or both. The results raise the novel possibility of genetically manipulating Trichoderma in order to improve adaptability and biocontrol at alkaline pH.


Rom2-dependent phosphorylation of Elo2 controls the abundance of very long-chain fatty acids.
Sphingolipids are essential components of eukaryotic membranes, where they serve to maintain membrane integrity. They are important components of membrane trafficking and function in signaling as messenger molecules. Sphingolipids are synthesized de novo from very long-chain fatty acids (VLCFA) and sphingoid long-chain bases, which are amide linked to form ceramide and further processed by addition of various headgroups. Little is known concerning the regulation of VLCFA levels and how cells coordinate their synthesis with the availability of long-chain bases for sphingolipid synthesis. Here we show that Elo2, a key enzyme of VLCFA synthesis, is controlled by signaling of the guanine nucleotide exchange factor Rom2, initiating at the plasma membrane. This pathway controls Elo2 phosphorylation state and VLCFA synthesis. Our data identify a regulatory mechanism for coordinating VLCFA synthesis with sphingolipid metabolism and link signal transduction pathways from the plasma membrane to the regulation of lipids for membrane homeostasis.


Rate of Occult Cervical Lymph Node Involvement in Supraglottic Squamous Cell Carcinoma.
To assess the rate of cervical lymph node involvement in patients with supraglottic squamous cell carcinoma (SCC) with no lymph node in clinical assessments and radiological studies. Fifty-six patients who underwent elective dissection of the cervical lymph node of the second through fourth level were enrolled, and pathologic evaluation of the dissected lymph nodes was performed. Lymph node involvement and association between tumor grade, smoking and gender with lymph node involvement were assessed. The rate of the occult neck metastasis in this series was 37.5%. There was no statistically significant association between lymph node involvement and tumor grade, smoking, or gender. Based on the results of our study, we recommend elective bilateral neck dissection in all stages of N0 supraglottic SCC patients.


A Novel Natural Influenza A H1N1 Virus Neuraminidase Inhibitory Peptide Derived from Cod Skin Hydrolysates and Its Antiviral Mechanism.
In this paper, a novel natural influenza A H1N1 virus neuraminidase (NA) inhibitory peptide derived from cod skin hydrolysates was purified and its antiviral mechanism was explored. From the hydrolysates, novel efficient NA-inhibitory peptides were purified by a sequential approach utilizing an ultrafiltration membrane (5000 Da), sephadex G-15 gel column and reverse-phase high-performance liquid chromatography (RP-HPLC). The amino acid sequence of the pure peptide was determined by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) was PGEKGPSGEAGTAGPPGTPGPQGL, with a molecular weight of 2163 Da. The analysis of the Lineweacer⁻Burk model indicated that the peptide was a competitive NA inhibitor with Ki of 0.29 mM and could directly bind free enzymes. In addition, docking studies suggested that hydrogen binding might be the driving force for the binding affinity of PGEKGPSGEAGTAGPPGTPGPQGL to NA. The cytopathic effect reduction assay showed that the peptide PGEKGPSGEAGTAGPPGTPGPQGL protected Madin⁻Darby canine kidney (MDCK) cells from viral infection and reduced the viral production in a dose-dependent manner. The EC50 value was 471 ± 12 μg/mL against H1N1. Time-course analysis showed that PGEKGPSGEAGTAGPPGTPGPQGL inhibited influenza virus in the early stage of the infectious cycle. The virus titers assay indicated that the NA-inhibitory peptide PGEKGPSGEAGTAGPPGTPGPQGL could directly affect the virus toxicity and adsorption by host cells, further proving that the peptide had an anti-viral effect with multiple target sites. The activity of NA-inhibitory peptide was almost inactivated during the simulated in vitro gastrointestinal digestion, suggesting that oral administration is not recommended. The peptide PGEKGPSGEAGTAGPPGTPGPQGL acts as a neuraminidase blocker to inhibit influenza A virus in MDCK cells. Thus, the peptide PGEKGPSGEAGTAGPPGTPGPQGL has potential utility in the treatment of the influenza virus infection.


Photosensitization ability of a water soluble zinc(II)tetramethyltetrapyridinoporphyrazinium salt in aqueous solution and biomimetic reverse micelles medium.
The spectroscopic properties and the photodynamic activity of a highly water soluble zinc(II)tetramethyltetrapyridino[2,3-b:2',3'-g:2",3"-l:2"',3'''-q]porphyrazinium salt (ZnTM2,3PyPz) were investigated in aqueous homogeneous solution and in biomimetic reverse micelles medium bearing photooxidizable biological substrates. Absorption and fluorescence spectroscopic studies indicate that ZnTM2,3PyPz is dissolved as monomer in water and in n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate (AOT, 0.1 M)/water (W0 = 30) micellar system. Fluorescence quantum yields (phi F) of 0.29 and 0.27 were calculated for ZnTM2,3PyPz in water and in AOT micelles, respectively. Spectroscopic analysis at different AOT concentrations showed interaction between ZnTM2,3PyPz and AOT reverse micelles with a binding constant (Kb) of 1.7 x 10(3) M(-1). The photosensitization ability of ZnTM2,3PyPz was evaluated using 9,10-dimethylanthracene (DMA). Singlet molecular oxygen, O2(1 delta g), production yielded values of phi(delta) = 0.65 for ZnTM2,3PyPz in AOT micelles. Also, ZnTM2,3PyPz induced efficiently the decomposition of the amino acid L-tryptophan (Trp) and the nucleotide guanosine 5'-monophosphate (GMP) in both media. A value of approximately 3.6 x 10(7) s(-1) M(-1) was found for the second order rate constant of Trp (k(r)(Trp)) decomposition in the AOT system, which is near to that found in pure water. Moreover, ZnTM2,3PyPz formed stable complexes with GMP with a binding constant of K(GMP) = 1.0 x 10(3) M(-1). 1H NMR studies indicated that ZnTM2,3PyPz interacts mainly with the guanine moiety more than the sugar part of GMP. On the other hand, the photodynamic activity of ZnTM2,3PyPz produced decomposition of GMP. Quantification of GMP by HPLC indicates that the nucleotide is photooxidized with a k(obs)(GMP) = 2.6 x 10(-4) s(-1) in water. Photooxidation of GMP considerably increases in deuteriated water indicating that ZnTM2,3PyPz appears to perform its photosensitizing action via the intermediacy of O2(1delta g). Also, efficient sensitized decomposition was observed in micellar media resembling that in pure water. These results provide a better understanding of the effective photodynamic action produced by ZnTM2,3PyPz like a potential phototherapeutic agent for the treatment of neoplastic diseases by photodynamic therapy.


Are nurses able to assess fatigue, exertion fatigue and types of fatigue in residential home patients?
Are nurses able to assess fatigue, exertion fatigue and types of fatigue in residential home patients? Although fatigue is recognized as a subjective, generalized, extensive and disabling health care problem with a relatively high prevalence among the chronically ill, there have been no studies to show whether nurses caring for fatigued subjects are able to accurately assess the level of fatigue that exists in these patients. The aim of the present study is to investigate this issue. The following research questions are formulated: (1) To what degree do the assessments of fatigue and exertion fatigue given by nurses and patients agree? and (2) To what degree do the assessments of types of fatigue given by nurses and patients agree? The method adopted employed a correlational design approach applied to residential home patients and nurses. Data were gathered by questionnaire. Data collected from 44 selected patients and two assessors (nurses) for each patient are used in the analyses. Measurement instruments used are the Dutch fatigue scale (DUFS), the Dutch exertion fatigue scale (DEFS), types of fatigue and sociodemographic variables. Measurement correlations between the patients and the nurses, both for the DUFS and DEFS, showed fair agreement (fatigue and exertion fatigue) and slight agreement (types of fatigue). The main conclusion of this study is that nurses working in residential home care are unable, in comparison with the patients themselves, to accurately assess patient's fatigue (fair agreement), exertion fatigue (fair agreement) and types of fatigue (slight agreement).


Understanding and predicting distorted T- versus Y-geometries for neutral chromous complexes supported by a sterically encumbering beta-diketiminate ligand.
A series of three-coordinate Cr(II) complexes sharing the common molecular fragment "(nacnac)Cr" (nacnac(-) = [ArNC((t)Bu)](2)CH, Ar = 2,6-(i)Pr(2)C(6)H(3)) were prepared via salt metathesis with the dimer [(nacnac)Cr(mu-Cl)](2). Single-crystal X-ray diffraction studies revealed that the complexes (nacnac)Cr(L) (L = CH(2)(t)Bu, CH(3), CH(2)CH(3), SiH{2,4,6-Me(3)C(6)H(2)}(2), O{2,6-(i)Pr(2)C(6)H(3)}, N{CH(3)}(2)) represent a rare class of mononuclear, neutral chromium complexes with a three-coordinate high-spin chromous metal center. Depending on the nature of the third ligand, L(-), these complexes can adopt either distorted T-shaped or Y-shaped coordination geometries. Density functional theory calculations and molecular orbital analyses in combination with a detailed molecular fragment energy decomposition were used to establish an intuitive concept of the key electronic structure patterns that determine the coordination geometry of preference. The frontier orbitals of the (nacnac)Cr(II) fragment direct pi-donating ligands to adopt Y-shaped geometry, whereas ligands that are primarily sigma-donors prefer T-shaped coordination. The relationship between electronics at the metal center and coordination geometry was extended to include the putative neutral three-coordinate high-spin complexes of Sc(II) and Mn(II), which are predicted to both adopt Y-shaped geometry.


[A case report of an ectopic ureter in a patient treated for chronic prostatitis].
A male aged 20 had been treated for anal and lower abdominal pain after ejaculation for about 2 years under the diagnosis of chronic prostatis. Because of worsening of the pain, he was admitted to our hospital in September 24, 1991. On the rectal examination, a cystic tumor was palbable on the left side of the prostate. The left kidney was not detected by IVP and ultrasonography. CT revealed two retrovesical cystic lesions in the left side. Cystourethroscopy showed an absence of ureteral orifice and ureteral ridge on the left side. Left uretero-seminal vesiculectomy was performed on October 3rd, under the diagnosis of an ectopic ureter entering into the seminal vesicle or ejaculatory duct. Histopathologically, the left ectopic ureter entering into the lower portion of the seminal vesicle or ejaculatory duct and the left renal agenesis were diagnosed. It was remarkable that ureteral epithelium was not transitional but columnar epithelium.


Overexpression of Rictor protein and Rictor-H. pylori interaction has impact on tumor progression and prognosis in patients with gastric cancer.
Growing evidence indicates that Rictor (Rapamycin-insensitive companion of mTOR) is overexpressed across several malignancies and associated with poor survival. However, only limited data indicate that Rictor plays a role in gastric cancer (GC). We sought to explore the prognostic value of Rictor in GC and present interaction analysis between Rictor expression and H. pylori status regarding their effects over the prognosis of GC patient. 250 GC tissues and 124 lymph node metastases were collected for the detection of Rictor by immunohistochemistry. Cox regression model was used to assess the association between Rictor expression and patient prognosis. Functional experiments were examined in transfected cells using Rictor siRNA. Additive and multiplicative interactions of Rictor and H. pylori were evaluated. In this study, the positive rate of Rictor was 51.6% (129/150) in GC tissues. Multivariate analyses showed that Rictor was independent unfavorable predictor for OS (HR = 1.554, 95% CI = 1.076-2.244, P = 0.019) and DFS (HR = 1.556, 95% CI = 1.081-2.240, P = 0.017). Patients with upregulated Rictor in the primary tumor and lymph node metastases had the worst prognosis. We observed significant additive and multiplicative interactions between Rictor expression and H. pylori status for OS and DFS (P < 0.05). Our in vitro experiment showed that knockdown of Rictor could suppress cell proliferation, induce apoptosis and inhibit tumor migration and invasion. Our results demonstrate that Rictor, acting as an oncogene, might be a potential prognostic biomarker and therapeutic target in GC. We suggest that Rictor expression and H. pylori status may be a prognostic marker in gastric cancer.


Validation of Administrative Big Database for Colorectal Cancer Searched by International Classification of Disease 10th Codes in Korean: A Retrospective Big-cohort Study.
As the number of big-cohort studies increases, validation becomes increasingly more important. We aimed to validate administrative database categorized as colorectal cancer (CRC) by the International Classification of Disease (ICD) 10th code. Big-cohort was collected from Clinical Data Warehouse using ICD 10th codes from May 1, 2003 to November 30, 2016 at Seoul National University Bundang Hospital. The patients in the study group had been diagnosed with cancer and were recorded in the ICD 10th code of CRC by the National Health Insurance Service. Subjects with codes of inflammatory bowel disease or tuberculosis colitis were selected for the control group. For the accuracy of registered CRC codes (C18-21), the chart, imaging results, and pathologic findings were examined by two reviewers. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CRC were calculated. A total of 6,780 subjects with CRC and 1,899 control subjects were enrolled. Of these patients, 22 subjects did not have evidence of CRC by colonoscopy, computed tomography, magnetic resonance imaging, or positron emission tomography. The sensitivity and specificity of hospitalization data for identifying CRC were 100.00% and 98.86%, respectively. PPV and NPV were 99.68% and 100.00%, respectively. The big-cohort database using the ICD 10th code for CRC appears to be accurate.


Influence of minor deterioration of renal function after PCI on outcome in patients with ST-elevation myocardial infarction.
Our aim was to assess the possible impact of a deterioration of renal function (DRF) not fulfilling the criteria for acute kidney injury after percutaneous coronary intervention (PCI) on outcome in patients with ST-elevation myocardial infarction (STEMI) on 30-day and long-term outcomes. Data is lacking on the influence of DRF after PCI on outcome in patients with STEMI. The present study is an analysis of 2572 STEMI patients who underwent PCI. The group with DRF (1022 patients) and the group without DRF (1550 patients) were compared. Thirty-day and long-term all-cause mortality were observed. Data was analyzed using descriptive statistics. Similar mortality was observed in both groups at day 30 (4.2% patients with DRF died vs 3.2% without DRF; ns) but more patients had died in the DRF group (18.9% patients with DRF vs 14.0% without DRF; P = 0.001) by the end of the observation period. After adjustments, DRF did not independently predict long-term mortality. Age more than 70 years, bleeding, hyperlipidemia, renal dysfunction on admission, anemia on admission, diabetes, PCI of LAD, the use of more than 200 mL contrast, but not DRF after PCI, were identified as independent prognostic factors for increased long-term mortality. Renal dysfunction, bleeding, contrast >200 mL, hyperlipidemia, age >70 years, anemia, and PCI LAD predicted DRF. DRF identified patients at increased risk of higher long-term mortality but was not independently associated with mortality.


Pathways of glucose metabolism by rough and smooth variants of Bacillus stearothermophilus.
The radiorespirometric method was used to study the pathways of glucose metabolism in the rough and smooth variants of Bacillus stearothermophilus NCA 1518. The Embden-Meyerhof (EM) pathway was more active in the smooth variant than in the rough variant. The participation of the hexose monophosphate shunt (HMP) and EM pathways in the smooth variant was calculated as 4.2 and 95.8%, respectively. The rough variant utilized glucose via the EM pathway exclusively or in combination with a pathway other than the HMP pathway. The estimated efficiency of the tricarboxylic acid system in the rough and smooth variants was 81.3 and 4.9%, respectively.


The Effects of Aromatherapy on Intensive Care Unit Patients' Stress and Sleep Quality: A Nonrandomised Controlled Trial.
Stress has both physiological and psychological effects and can negatively impact patients' treatment and recovery. We examined whether the aromatherapy alleviated patients' stress and improved their sleep quality and provided data that can be utilized in clinical settings. This was a nonrandomised controlled experimental study. Participants included lucid adult patients who were admitted to the intensive care unit and had spent more than two nights there. The experimental treatment required participants to engage in deep breathing with essential oils as part of the aromatherapy. The control group was instructed to go to sleep without receiving the lavender aroma oil. The experimental group and control group showed a significant difference in perceived stress (F = 60.11, p < .001), objective stress index (F = 25.65, p < .001), systolic blood pressure (F = 9.09, p < .001), diastolic blood pressure (F = 2.47, p = .046), heart rate (F = 5.71, p < .001), and sleep quality (F = 109.46, p < .001). The results revealed that aromatherapy alleviated stress and improved sleep quality in intensive care unit patients after 2 days of the experimental treatment. These results demonstrate that aromatherapy affects stress and sleep quality, thus indicating its value in nursing interventions. This trial is registered with KCT0002344.


A Report of Two Patients with Darier Disease and Hidradenitis Suppurativa.
We report two unique cases of patients with Darier disease and hidradenitis suppurativa. Although it is unknown whether there is a connection between the two diseases, it is possible that an interaction between sarcoendoplasmic reticulum calcium transport ATPase and Notch homolog 1, translocation-associated (Drosophila) caused both diseases in these individuals.


Searching for information for presentations and publications.
Numerous information sources are available to the clinical nurse specialist preparing a presentation or writing a manuscript for publication. However, searching through this information to identify reputable sources and reliable data can be time consuming. Using a search plan that incorporates a timeline increases efficiency and helps visualize progress. A targeted search of biomedical databases, such as MEDLINE and PubMed, retrieves pertinent journal articles and avoids the "hit-and-miss" approach often used by novice speakers and authors. Information should be reviewed and organized soon after it is obtained so that more time can be spent writing and less time spent locating a specific reference or piece of information. The information can then be arranged in the order of the presentation or manuscript to facilitate the preparation process.


[Three-dimensional Ultrasound of the Pelvic Floor in Early Postpartum after First Delivery].
To dynamically observe the shape of levator hiatus and the mobility of bladder neck with three dimensional transperineal ultrasound, and then to evaluate female pelvic floor in early postpartum after delivery. 170 primiparae (the vaginal delivery group and the cesarean section group) and 35 nulliparous women were recruited, and three dimensional transperineal ultrasound were performed with standardized gynecological pelvic settings. Ultrasonic dynamic imaging information was obtained in the condition of resting, Valsalva maneuver and anal sphincter contraction, including two-dimensional midsagittal view and the three-dimensional axial plane in which some biometric measurements were determined. The anteroposterior diameters of levator hiatus were significantly greater on sphincter contraction in the vaginal delivery group than that in nulliparous group after the 6-8 weeks delivery, but the measurements of the levator hiatus within cesarean delivery group and nulliparous group did not show statistically significant differences (P > 0.05). The mobility of bladder neck was significantly greater on Valsalva maneuver in the vaginal delivery group than those in the other groups, while the backward motion of bladder neck was greater on Valsalva maneuver in the cesarean section group than that in nulliparous group. The incidence of postpartum stress urinary incontinence was greater in the vaginal delivery group (10/104) than that in the cesarean section group (4.5%, 3/66), but no statistically significant differences were observed (P > 0.05). The large difference of pelvic floor exists between vaginal delivery and cesarean delivery. The bladder neck decent and levator hiatus anteroposterior diameter may be relatively sensitive indicators in ultrasonic evaluation of pelvic floor muscle contraction, especially the latter may be adopted as an observation index to evaluate pelvic floor muscle recovery after delivery.


Encystment of parasitic freshwater pearl mussel (Margaritifera margaritifera) larvae coincides with increased metabolic rate and haematocrit in juvenile brown trout (Salmo trutta).
Gill parasites on fish are likely to negatively influence their host by inhibiting respiration, oxygen transport capacity and overall fitness. The glochidia larvae of the endangered freshwater pearl mussel (FPM, Margaritifera margaritifera (Linnaeus, 1758)) are obligate parasites on the gills of juvenile salmonid fish. We investigated the effects of FPM glochidia encystment on the metabolism and haematology of brown trout (Salmo trutta Linnaeus, 1758). Specifically, we measured whole-animal oxygen uptake rates at rest and following an exhaustive exercise protocol using intermittent flow-through respirometry, as well as haematocrit, in infested and uninfested trout. Glochidia encystment significantly affected whole-animal metabolic rate, as infested trout exhibited higher standard and maximum metabolic rates. Furthermore, glochidia-infested trout also had elevated levels of haematocrit. The combination of an increased metabolism and haematocrit in infested fish indicates that glochidia encystment has a physiological effect on the trout, perhaps as a compensatory response to the potential respiratory stress caused by the glochidia. When relating glochidia load to metabolism and haematocrit, fish with low numbers of encysted glochidia were the ones with particularly elevated metabolism and haematocrit. Standard metabolic rate decreased with substantial glochidia loads towards levels similar to those of uninfested fish. This suggests that initial effects visible at low levels of encystment may be countered by additional physiological effects at high loads, e.g. potential changes in energy utilization, and also that high numbers of glochidia may restrict oxygen uptake by the gills.


Leukocyte adhesion deficiency: molecular basis and functional consequences.
Leukocyte adhesion deficiency disease is characterized by a mutation in the gene encoding the beta-subunit shared by three adhesive heterodimers, LFA-1, Mac-1 (CR3) and p150,95 expressed by leukocytes. An absent or abnormal beta-subunit leads to defective expression of the three heterodimers. Severe and moderate phenotypes of the disease are defined by absent and low surface expression of the adhesion molecules. The disease causes an inability of phagocytic cells to adhere to endothelial cells and thereafter to migrate to sites of infections. Severe widespread life-threatening bacterial and fungal infections are the consequences of this abnormality. Cure of the disease can be effected by allogeneic bone marrow transplantation. T-lymphocyte adhesion to various cells is also impaired; its consequences are, however, limited because of the existence of other T-cell-adhesive pathways. Nevertheless, haploidentical bone marrow graft rejection does not occur in the severe phenotype, an indication for possible immunotherapy with LFA-1 specific monoclonal antibodies.


A new rapid and sensitive assay for detecting the T315I BCR-ABL kinase domain mutation in chronic myeloid leukaemia.
A significant minority of chronic myeloid leukaemia patients eventually develop resistance to imatinib, often as a result of point mutations within the BCR-ABL kinase domain. Second-line tyrosine kinase inhibitors (TKIs) are effective against mutations that confer imatinib resistance; however, the T315I BCR-ABL mutant has proved resistant to all available TKIs. An assay facilitating early identification of BCR-ABL(T315I) would therefore aid in identifying high-risk patients who may benefit from alternative therapy. This report describes the development of a sensitive T315I mutation detection methodology based on real-time PCR with self-probing fluorescent primers. The technique demonstrated complete concordance with direct sequencing, correctly identifying 34 T315I-positive samples from a total of 61 samples screened. In a limiting dilution assay, the mutated clone was detectable to a level of 1% of total cells. The data show that Scorpions PCR enables rapid screening for BCR-ABL(T315I) in chronic myeloid leukaemia patients and is appropriate for use in a clinical setting.


Bronchospasmolytic effects of salbutamol as powder inhalation in patients with reversible bronchial obstruction.
In a double-blind double-dummy crossover study, the effects of salbutamol dry powder inhaled from Salbutamol cyclocaps Pharbita 0.4 mg with the Pharbita inhaler and from a reference product were compared. On the first trial day, a single dose of one of the two preparations was administered, and 2 days later a single dose of the another preparation was administered, in random order. The effects on lung function (FEV1) were monitored from 15 to 360 min after administration. For both products the increase in FEV1 with reference to baseline values was statistically highly significant. There was no significant difference between the products.


Whats new in 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice?
2021 ESC Guidelines on cardiovascular disease prevention in clinical practice provides a comprehensive view on preventive cardiology. It presents strategies to reduce the burden of atherosclerotic cardiovascular disease (CVD), both at the individual level and at the population level. Healthy lifestyle and aggressive control of cardiovascular risk factors remain the cornerstone of prevention. Classification of individuals into risk groups based on their clinical characteristics followed by a stepwise treatment-intensification is a novel recommended approach. Updated risk charts - SCORE2 and SCORE2-OP - are intended for estimation of 10-year fatal and non-fatal CVD risk in apparently healthy individuals. Targets and goals for LDL cholesterol, blood pressure, and glycaemic control remain as recommended in recent ESC Guidelines.


Increased expression of IRF8 in tumor cells inhibits the generation of Th17 cells and predicts unfavorable survival of diffuse large B cell lymphoma patients.
The immunological pathogenesis of diffuse large B cell lymphoma (DLBCL) remains elusive. Searching for new prognostic markers of DLBCL is a crucial focal point for clinical scientists. The aim of the present study was to examine the prognostic value of interferon regulatory factor 8 (IRF8) expression and its effect on the development of Th17 cells in the tumor microenvironment of DLBCL patients. Flow cytometry, immunohistochemistry, and quantitative real-time PCR were used to detect the distribution of Th17 cells and related cytokines and IRF8 in tumor tissues from DLBCL patients. Two DLBCL cell lines (OCI-LY10 and OCI-LY1) with IRF8 knockdown or overexpression and two human B lymphoblast cell lines were co-cultured with peripheral blood mononuclear cells (PBMCs) in vitro to determine the effect of IRF8 on the generation of Th17 cells. Quantitative real-time PCR and Western blotting were used to investigate the involvement of retinoic acid receptor-related orphan receptor gamma t (RORγt) in the effect of IRF8 on Th17 cell generation. The survival of 67 DLBCL patients was estimated using the Kaplan-Meier method and log-rank analysis. The percentage of Th17 cells was lower in DLBCL tumor tissues than in PBMCs and corresponding adjacent benign tissues. Relative expression of interleukin (IL)-17A was lower, whereas that of interferon (IFN)-γ was higher in tumor tissues than in benign tissues. Co-culture with DLBCL cell lines inhibited the generation of Th17 cells in vitro. IRF8 upregulation was detected in DLBCL tumor tissues, and it was associated with decreased DLBCL patient survival. Investigation of the underlying mechanism suggested that IRF8 upregulation in DLBCL, through an unknown mechanism, inhibited Th17 cell generation by suppressing RORγt in neighboring CD4+ T cells. Tumor cells may express soluble or membrane-bound factors that inhibit the expression of RORγt in T cells within the tumor microenvironment. Our findings suggest that IRF8 expression could be a prognostic factor for DLBCL.


Statistics of unstable periodic orbits of a chaotic dynamical system with a large number of degrees of freedom.
For a simple model of chaotic dynamical systems with a large number of degrees of freedom, we find that there is an ensemble of unstable periodic orbits (UPOs) with the special property that the expectation values of macroscopic quantities can be calculated using only one UPO sampled from the ensemble. Evidence to support this conclusion is obtained by generating the ensemble by Monte Carlo calculation for a statistical mechanical model described by a space-time Hamiltonian that is expressed in terms of Floquet exponents of UPOs. This result allows us to interpret the recent interesting discovery that statistical properties of turbulence can be obtained from only one UPO [G. Kawahara and S. Kida, J. Fluid Mech. 449, 291 (2001); S. Kato and M. Yamada, Phys. Rev. E 68, 025302(R) (2003)].


[Segregation Analysis in Inherited Eye Disorders: An Academic Add-on or An Essential Effort?]
The knowledge of the genetic basis of many eye diseases is constantly increasing. Besides retinal degeneration, developmental defects of the anterior segment, cataracts, and the development of the basic structure are often associated with genetic defects. Moreover, a lot of genetic syndromes involve eye abnormalities. The impact of genetics has become more and more evident in ophthalmological practice. Although genetic counselling is usually carried out by human geneticists, the increasing availability of therapeutic options requires ophthalmologists to have some basic knowledge of the genetic causes and how to identify them. The first step in this regard is to recognise potential genetic eye disorders and to initiate an adequate genetic analysis to confirm the diagnosis. This review discusses possible and necessary investigations within the patient's family facing ophthalmologists after the genetic cause of an eye disease has been identified.


Overnight catheter drainage in children with poorly compliant bladders improves post-obstructive diuresis and urinary incontinence.
Overnight catheter drainage (OCD) has been suggested as a treatment for boys with valve bladder syndrome as well as those with polyuric renal failure. We report our experience using overnight catheter drainage in children with poorly compliant bladders. Between 1999 and 2004 OCD was initiated in 6 boys and 5 girls (median age 7.5 years) with poorly compliant bladders in whom aggressive daytime intermittent catheterization and anticholinergic use had failed. Etiologies of bladder dysfunction included posterior urethral valves in 1 case, The Hinman-Allen syndrome in 4, myelomeningocele in 2, neuroblastoma in 1, prune-belly syndrome in 1, transverse myelitis in 1 and sacral agenesis in 1. The amount of post-obstructive diuresis was calculated during urodynamics as the volume drained minus volume instilled divided by weight per hour. Other parameters evaluated included serum creatinine, degree of upper tract dilatation, and episodes of urinary tract infection (UTI) and incontinence. Median duration of OCD and followup was 28 months, respectively. One patient did not tolerate overnight drainage. Of 9 patients who were incontinent before OCD daytime urinary incontinence resolved in 6 and improved in 3. Recurrent febrile UTIs in 3 children were eliminated. Despite no change in serum creatinine with overnight drainage, 7 of 8 patients (88%) with upper tract dilatation improved on followup ultrasound. In select children with poorly compliant bladders OCD reduces diuresis, reduces the frequency of UTIs, improves upper tract dilatation and improves continence. Overnight drainage in conjunction with daytime clean intermittent catheterization may prove to be an alternative to bladder augmentation in select children with poorly compliant bladders and early stages of renal compromise.


Thiram modulates pro-inflammatory mediators in RAW 264.7 murine macrophage cells.
Thiram (TMTD) is a widely used dithiocarbamate pesticide and fungicide and is one of potent contact allergens. In the light of known properties, thiram is also considered to be used as an inhibitor of inflammation. To investigate whether known pro-oxidative properties of thiram might be involved in immunogenic mechanisms, we carried out an in vitro study aimed at analysis of reactive oxygen species (ROS) generation, activation of NF-κB, expression of iNOS and COX-2, production of NO, PGE2 and IL-1β in murine macrophage cells (RAW 264.7). The cells were treated by thiram alone (0.5 µg/mL; 2 μM and 2 µg/mL; 8 μM) or concomitantly with bacterial endotoxin (LPS; 1 μg/mL). LPS was used as an endotoxin that triggers changes characteristic for inflammatory state of the cell. TMTD increased ROS production, level of oxidized glutathione (GSSG) and activated NF-κB. The consequence of NF-κB activation was the increase of IL-1β and NO production characteristic for inflammation. However, we did not observe changes in PGE2 concentration. We observed expression of iNOS, COX-2 proteins and NO and PGE2 production in macrophages treated with thiram concomitantly with LPS lower than those in cells stimulated with LPS alone. Thiram (2 µg/mL) decreased NF-κB activation and production of LPS-induced IL-1β. In conclusion, we demonstrated changes induced by TMTD characteristic for inflammation. Hence, it can be supposed that they may participate in the elicitation phase of allergic contact dermatitis induced by thiram. However, when TMTD acts concomitantly with LPS, it decreases the intensity of inflammation state in RAW 264.7.