[Psychosomatic health inventory: Basic psychosomatic documentation for quality assurance inpatient care].
Objectives: As part of the quality assurance of inpatient treatment, the severity of the disease and the course of therapy must be mapped. However, there is a high degree of heterogeneity in the implementation of basic diagnostics in psychosomatic facilities.There is a lack of scientifically based standardisation in determining the quality of outcomes. Methods: With the help of scientifically established test instruments, a resource-saving basic documentation instrument was developed. Many existing psychometric instruments were checked for test quality, costs and computer-supported application. Results: The Psychosomatic Health Inventory (gi-ps) consists of three basic modules with a total of 63 items: sociodemography, screening and psychosomatic health status.The latter is represented bymeans of construct-based recording on eight scales. Its collection at admission and discharge allows the presentation of the quality of outcomes.The development of a proprietary software solution with LimeSurvey enables the computer-based collection, evaluation, and storage of data. A list of test inventories for confirming diagnoses and predictors has been compiled, which are recommended for use in clinical routine. Discussion: With the gi-ps, a modular basic documentation instrument including the software solution is available to all interested institutions free of charge.


Anomalous Origins of Coronary Arteries From the Pulmonary Artery: A Comprehensive Review of Literature and Surgical Options.
Anomalous origins of coronary arteries from the pulmonary artery are rare malformations in which the coronary arteries originate from pulmonary artery sinuses or branches. The consequences are variable although, in most cases, these anomalies lead to severe coronary hypoperfusion and ventricular dysfunction. Surgical correction is indicated once the diagnosis is established due to high early mortality associated with the disease. In nearly all cases, the anomalous artery can be excised from its pulmonary origin, mobilized, and reimplanted directly into the ascending aorta using different surgical techniques. In rare circumstances, technical modifications must be used to restore a normal dual coronary perfusion. The emphasis of this article is to provide a collective review of surgical options published in the literature.


System dynamics modeling of transboundary systems: the bear river basin model.
System dynamics is a computer-aided approach to evaluating the interrelationships of different components and activities within complex systems. Recently, system dynamics models have been developed in areas such as policy design, biological and medical modeling, energy and the environmental analysis, and in various other areas in the natural and social sciences. The Idaho National Engineering and Environmental Laboratory, a multipurpose national laboratory managed by the Department of Energy, has developed a system dynamics model in order to evaluate its utility for modeling large complex hydrological systems. We modeled the Bear River basin, a transboundary basin that includes portions of Idaho, Utah, and Wyoming. We found that system dynamics modeling is very useful for integrating surface water and ground water data and for simulating the interactions between these sources within a given basin. In addition, we also found that system dynamics modeling is useful for integrating complex hydrologic data with other information (e.g., policy, regulatory, and management criteria) to produce a decision support system. Such decision support systems can allow managers and stakeholders to better visualize the key hydrologic elements and management constraints in the basin, which enables them to better understand the system via the simulation of multiple "what-if" scenarios. Although system dynamics models can be developed to conduct traditional hydraulic/hydrologic surface water or ground water modeling, we believe that their strength lies in their ability to quickly evaluate trends and cause-effect relationships in large-scale hydrological systems, for integrating disparate data, for incorporating output from traditional hydraulic/hydrologic models, and for integration of interdisciplinary data, information, and criteria to support better management decisions.


Suppression of gamma-oscillations in the dorsolateral prefrontal cortex following long interval cortical inhibition: a TMS-EEG study.
Gamma (gamma)-oscillations (30-50 Hz) represent important electrophysiological measures, which are generated through the execution of higher order cognitive tasks (eg, working memory) in the dorsolateral prefrontal cortex (DLPFC). By contrast, cortical inhibition (CI) refers to a neurophysiological process in which GABAergic inhibitory interneurons selectively suppress the activation of other neurons in the cortex. Recently, abnormalities in both CI and gamma-oscillations have been associated with various neuropsychiatric disorders including schizophrenia. Animal research suggests that suppression of gamma-oscillations is, in part, mediated through GABAergic inhibitory neurotransmission. However, no such evidence has been demonstrated in human, largely because of technological limitations. Recently, we reported on novel methods permitting the recording of CI from the DLPFC through transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG). The aim of this study was to examine the effects of GABAergic inhibitory neurotransmission on gamma-oscillations by combining TMS with EEG. Long interval cortical inhibition (LICI), a paired TMS paradigm, was used to index GABA(B) receptor mediated inhibitory neurotransmission in the motor cortex and DLPFC of healthy individuals. Gamma-oscillations were significantly inhibited by LICI (38.1+/-26.5%; p< or =0.013) in the DLPFC but not in the motor cortex. These results provide neurophysiological evidence to demonstrate gamma-oscillations are inhibited by LICI in the DLPFC but not in the motor cortex. Such specificity suggests that the modulation of gamma-oscillations may represent an important neurophysiological process that may, in part, be responsible for optimal DLPFC functioning in healthy human subjects.


The Plasmodium circumsporozoite protein, a novel NF-κB inhibitor, suppresses the growth of SW480.
The blocking of NF-κB activation is a promising strategy for the treatment of colorectal cancer. The circumsporozoite protein (CSP), a key component of the sporozoite stage of the malaria parasite, was recently reported to block NF-κB activation in hepatocytes. Thus, we investigated the effect of the CSP on the growth of the human colon cancer cell line, SW480. We demonstrated that transfection with a recombinant plasmid expressing CSP inhibited the proliferation of SW480 in a dose-dependent manner and induced the apoptosis of SW480. A NF-κB gene reporter assay showed that both the CSP and its nuclear localization signal (NLS) motif could equally suppress the activation of NF-κB following the stimulation with human recombinant TNF-α in the SW480. Furthermore, western blot analysis indicated that NLS did not affect the phosphorylation and degradation of IκB, but could sharply inhibit the nuclear translocation of NF-κB in TNF-α stimulated SW480. Hence, our data suggest that the CSP might be explored as a new NF-κB inhibitor for the treatment of colorectal cancer.


Comparison of the incidence of 5-azacytidine-induced exencephaly between MT/HokIdr and Slc:ICR mice.
The incidence of 5-azacytidine-induced exencephaly was compared between MT/HokIdr strain (MT) and Slc:ICR strain (ICR) mice. MT mice have a genetic predisposition for exencephaly, but ICR mice do not. Pregnant mice were given 5-azacytidine (1 mg/kg to 100 micrograms/kg) injected intraperitoneally on Day 7.5 of gestation (vaginal plug day = Day 0.5), and fetuses were observed for external malformations on Day 18.5 of gestation. One hundred micrograms/kg 5-azacytidine induced exencephaly in MT mice but not in ICR mice, and 1 mg/kg 5-azacytidine resulted in resorptions in MT mice but caused exencephaly in ICR mice. These results indicated that MT mice had 10-fold more sensitivity to 5-azacytidine than ICR mice. It seems likely that less than effective doses of teratogens for animals without genetic predispositions are still effective in inducing malformations in animals with a genetic predisposition for malformations. When 4-somite-stage embryos of both MT and ICR mice were cultured in rat serum supplemented with 5-azacytidine, 0.02 micrograms/ml 5-azacytidine induced the failure of closure of cephalic neural tube in MT embryos but not in ICR embryos, and 0.2 micrograms/ml 5-azacytidine induced severe growth retardation in MT embryos but in ICR embryos it only induced embryos with smaller heads and fewer somites than in control. These results indicated that MT mouse embryos in culture also had a 10-fold-increased sensitivity to 5-azacytidine compared with ICR mouse embryos, suggesting maternal effects play no significant role in their increased sensitivity to 5-azacytidine.


Comparison of PubMed, Scopus, Web of Science, and Google Scholar: strengths and weaknesses.
The evolution of the electronic age has led to the development of numerous medical databases on the World Wide Web, offering search facilities on a particular subject and the ability to perform citation analysis. We compared the content coverage and practical utility of PubMed, Scopus, Web of Science, and Google Scholar. The official Web pages of the databases were used to extract information on the range of journals covered, search facilities and restrictions, and update frequency. We used the example of a keyword search to evaluate the usefulness of these databases in biomedical information retrieval and a specific published article to evaluate their utility in performing citation analysis. All databases were practical in use and offered numerous search facilities. PubMed and Google Scholar are accessed for free. The keyword search with PubMed offers optimal update frequency and includes online early articles; other databases can rate articles by number of citations, as an index of importance. For citation analysis, Scopus offers about 20% more coverage than Web of Science, whereas Google Scholar offers results of inconsistent accuracy. PubMed remains an optimal tool in biomedical electronic research. Scopus covers a wider journal range, of help both in keyword searching and citation analysis, but it is currently limited to recent articles (published after 1995) compared with Web of Science. Google Scholar, as for the Web in general, can help in the retrieval of even the most obscure information but its use is marred by inadequate, less often updated, citation information.


[Oxygen transport function of blood in open heart surgery].
Complex intraoperative analysis of oxygen transporting function was performed in two groups of cardiosurgical patients operated on under ataralgesia (74 patients) and total intravenous anesthesia (49 patients). Heart performance, oxygen delivery (DO2) and O2 consumption (VO2) were the basic parameters reflecting O2 homeostasis at all stages of surgery. A decline in the cardiac output which is most frequent immediately before the beginning of cardiopulmonary bypass procedure leads to the disturbances in DO2. Metabolism maintenance in these conditions is due to increased O2 extraction from blood. According to the data of correlation analysis, a critical DO2 level, below which a decline of VO2, O2 debt and lactate accumulation are observed, is 350 ml/min/m2. Limited DO2 is more frequently encountered in patients operated on under ataralgesia using nitrous oxide. The use of drugs improving heart performance in the early postperfusion period is an effective technique of CPK damage correction in patients with decreased DO2, irrespective of the anesthesia technique. Dopamine administration at a dose of 5-7 micrograms/kg/min makes up for O2 debt, which is confirmed by positive changes in blood lactate.


Cytologic diagnosis of malignant melanoma.
Cytology in malignant melanoma of the skin is a useful method, which alone yields in many cases enough diagnostic informations for a therapeutical approach. It is of a special importance in cases with marked anisocytosis of cells and with large, sometimes polynuclear cells and with cells with melanotic pigment. In cases with middle-sized apigmented cells of epitheloid appearance it should be always completed by biopsy, which, in these cases predominates over cytology. Combination of both methods brings a more substantial elucidation of diagnosis.


Coronavirus Disease 2019 (COVID-19) Pandemic and Economic Impact.
In less than two decades, the world has experienced three outbreaks of deadly Coronaviruses, including the recent pandemic of Coronavirus Disease 2019 (COVID-19) in China. COVID-19 posed an emergency of international concerns, and cases have been reported in more than 200 countries/regions that resulted in health, lives, and economic losses. China's economic growth is projected to fall to 5.6% this year, the International Monetary Fund (IMF) projected that policy investment and tax policies to implement $3.3 trillion and contributes further $4.5 trillion. IMF forecasts grow from 3.7% of global gross domestic product (GDP) in 2019 to 9.9% in 2020. GDP ratio projected from 3.0% in 2019 to grow 10.7% in 2020, the US ratio expected to increase from 5.8% to 15.7%. France, Germany, Italy, Japan, and the United Kingdom (UK) each reported public sector funding programs totalling > 10% of their yearly GDP. There is a dire need for regional and international co-operation to extend hands to prevent further spreading of COVID-19.


An efficient stress-free strategy to displace stable bacterial plasmids.
A key stage in determining the phenotype(s) conferred by a plasmid is its displacement, or 'curing,' to create a plasmid-free strain. However, many plasmids are very stable, not only because they contain multiple replicons, but also because they can encode post-segregational killing systems that reduce the viability of plasmid-free segregants. We have developed an efficient curing strategy that involves combining key regions of the replicons and the post-segregational killing loci into an unstable cloning vector carrying sacB, which confers sensitivity to sucrose. Targeting plasmids of both the F family of Escherichia coli and the broad-host-range IncP-1 family, we demonstrated displacement of susceptible resident plasmids from all clones tested. Growth on sucrose allowed the isolation of many clones without either plasmid. This strategy is highly efficient and avoids the stress of inducing and surviving the effects of post-segregational killing systems or other lethal gene products.


Short-course monotherapy strategy for treating bacteremia in the critically ill.
Routine practice in the ICU of University College London (UCL) Hospitals is to use short course (5-6 days) monotherapy, unless contraindicated (e.g. endocarditis, osteomyelitis). The aim of this study is to assess our policy by monitoring the clinical response, relapse rate and patient outcome. A prospective observational study was carried out from February to July 2000. Clinically significant bacteraemia was identified by daily prospective surveillance of all positive blood cultures. On all the patients we recorded: 1) demographics; 2) antibiotic therapy (type, duration) and ACCP/SCCM sepsis criteria; 3) ICU support techniques (e.g. mechanical ventilation, intravascular catheter changes); 4) development of further bacteraemia or relapses. For all positive results, Gram stain, identification and antibiotic sensitivity patterns were noted. SPSS software was used for statistical analyses. Out of 713 admitted to the ICU over the study period, 84 (8.2%) patients experienced 102 bacteraemic episodes: 14 community-, 28 hospital- and 60 ICU-acquired (occurring in 49 patients). A total of 78 (76.4%) episodes [8 (57%) community-, 22 (79%) hospital- and 48 (80%) ICU-acquired] were treated with short course monotherapy. Moreover a low rate (23.8%) of death directly related to the bacteraemia and a satisfactory (72%) clinical response were recorded. ICU-acquired multidrug resistant Gram-negative bacteraemias (6.5%) and fungaemias (3%) were also uncommon. No patient discharged from the ICU, subsequently developed either bacteraemia relapse, or any long-term related complication. Short course antibiotic monotherapy strategy appears to provide a satisfactory clinical response, low relapse rate and no long-term infectious complications. Multicentre studies are warranted to confirm the efficacy of our practice.


[Cancer of the bladder occurring in occupational dye users: report of two cases].
Two cases of occupational dye users were found to have bladder tumors. Case 1 was a 32-year-old male, who had worked at the Yuzen process for the last 7 years. Multiple papillary tumors were seen on the whole wall of the bladder endoscopically and total cysto-urethrectomy and ileal conduit were performed. The pathological examination of the bladder tumors revealed non-invasive transitional cell carcinoma grade I--II. His post-operative course has been uneventful without any signs of tumor recurrence for 31 months. Case 2 was a 46-year-old male, who had worked at the throwing stained silk for the last 28 years. He suffered from severe hematuria for six months. A big egg-sized nonpapillary tumor on the posterior wall of the bladder was found and bilateral cutaneous-ureterostomy was performed but severe gross hematuria remained. Total cysto-urethrectomy was performed but the patient died of progressive disease 5 months later. The bladder tumor was a grade III invasive transitional cell carcinoma. The fact that process workers in the dye manufacturing industry have a high risk of bladder cancer has been well known and mass screening examination on them has been systematically performed. Though there is a higher relative risk of bladder cancer in occupational dye users, systematic screening examination has not been done. We emphasize the necessity for establishing systematic mass screening examination of occupational dye users for the early diagnosis of bladder cancer.


Optimization of water-soluble polysaccharides from stem lettuce by response surface methodology and study on its characterization and bioactivities.
Stem lettuce is widely consumed as a vegetable in China. It is also used as a traditional Chinese medicine for a long time. Up to now, no information is available for stem lettuce polysaccharide (SLP). In this study, extraction optimization, characterization, and antioxidant activity of SLP was investigated.The maximum SLP yield of 20.89% was obtained under the optimal extraction conditions as follows: extraction temperature 95°C, extraction time 3.3h and ratio of water to material 25mL/g. The sulfate content of SLP was 5.82% and the main monosaccharides were GalA, Gal, and Ara with a mole ratio of 49.2: 23.3: 22.9. FT-IR spectrum and HPGPC result further indicated that SLP is a sulfated polydisperse heterpolysaccharide. Congo-red test and AFM scan indicated that SLP might be branching and intertwining structure with triple helix conformation. Moreover, SLP exhibited potent antioxidant activity and α-amylase inhibitory activity, hence it could be used as a potential natural antioxidant and hypoglycemic agent in medicine or functional food fields.


The role of prostaglandin F2 alpha and oxytocin in the reproductive behavior of a marsupial, Bettongia gaimardi.
Bettongs give birth on the night that their large pouch young finally vacates the pouch. We have hypothesized that hormones associated with this birth are also involved in pouch vacation. Injections of prostaglandin F2 alpha (PGF2 alpha) caused contractions of the pouch. In a separate experiment PGF2 alpha caused pouch vacation; oxytocin had a similar effect but with a longer latency. In addition both hormones induced birth behavior in adult and immature females as well as in males. When a prostaglandin synthesis inhibitor (Finadyne) was given first, oxytocin failed to produce birth behavior or pouch vacation. This finding leads us to suggest that oxytocin exerts its behavioral effects via prostaglandin synthesis. These experiments are the first to demonstrate an effect by oxytocin on reproductive behavior in a marsupial.


[Influence of hiatal hernia of the diaphragm of the intensity of gastroesophageal reflux in children].
The aim of the study was to evaluate how the hiatal hernia acts on the gastroesophageal reflux (GER). We observed 52 children (31 boys, and 21 girls) aged from 2 months to 12 years (mean age 14,3 months), who were diagnosed as having GER by clinical symptoms and 24-hr oesophageal pH monitoring. All patients underwent barium radiological examination. According to the absence or presence of hiatal hernia diagnosed by barium radiology, subjects were divided into two groups: I- without hernia, II-with hernia. In both groups 24-hr oesophageal pH monitoring was analyzed. We found that patients with sliding hiatal hernia had significantly higher median percent total time when oesophageal pH was below 4, significantly higher median total number of reflux episodes and higher median time of duration of oesophageal episodes. Median number of episodes greater than five minutes did not significantly differ in both groups. We conclude that hiatal hernia increases the GER.


Integrated chemical and biological assessment of contaminant impacts in selected European coastal and offshore marine areas.
This paper reports a full assessment of results from ICON, an international workshop on marine integrated contaminant monitoring, encompassing different matrices (sediment, fish, mussels, gastropods), areas (Iceland, North Sea, Baltic, Wadden Sea, Seine estuary and the western Mediterranean) and endpoints (chemical analyses, biological effects). ICON has demonstrated the use of a framework for integrated contaminant assessment on European coastal and offshore areas. The assessment showed that chemical contamination did not always correspond with biological effects, indicating that both are required. The framework can be used to develop assessments for EU directives. If a 95% target were to be used as a regional indicator of MSFD GES, Iceland and offshore North Sea would achieve the target using the ICON dataset, but inshore North Sea, Baltic and Spanish Mediterranean regions would fail.


The many faces of postpartum depression.
To provide a profile of women suffering from major postpartum depression as assessed by the Postpartum Depression Screening Scale (PDSS). A secondary analysis conducted on a portion of the data collected from an earlier psychometric testing of the PDSS. Private practice in the San Francisco Bay Area of a marriage and family therapist specializing in perinatal mood disorders. One hundred thirty-three women who were diagnosed with major postpartum depression. Each mother completed the PDSS followed by a Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnostic interview. Seven dimensions of postpartum depression: sleeping/eating disturbances, anxiety/insecurity, emotional lability, mental confusion, loss of self, guilt/shame, and suicidal thoughts as measured by the PDSS. Scores on all seven dimensions of the PDSS were elevated. The three top dimensions were emotional lability, mental confusion, and anxiety/insecurity. The mean total PDSS score of 120 was well beyond the recommended cutoff score of 80 for a positive screen for major postpartum depression. Clinicians who come in contact with new mothers need to be alert to the range of possible symptoms that postpartum depressed mothers may experience so that these women are not left to suffer in silence.


[Blood lead content in the Viennese population (1982)].
The lead content of blood was determined in 213 cases of sudden death (accident victims) in the population of Vienna. The determinations were carried out by atomic absorption spectrometry (graphite furnace), similarly as in the case of the previous investigation in 1972. The mean value was now 242 micrograms/l, as compared with 261 micrograms/l in 1972. The difference was not statistically significant.


Variables Associated with Emotional Symptom Severity in Primary Care Patients: The Usefulness of a Logistic Regression Equation to Help Clinical Assessment and Treatment Decisions.
The aim of this study is to contribute to the evidence regarding variables related to emotional symptom severity and to use them to exemplify the potential usefulness of logistic regression for clinical assessment at primary care, where most of these disorders are treated. Cross-sectional data related to depression and anxiety symptoms, sociodemographic characteristics, quality of life (QoL), and emotion-regulation processes were collected from 1,704 primary care patients. Correlation and analysis of variance (ANOVA) tests were conducted to identify those variables associated with both depression and anxiety. Participants were then divided into severe and nonsevere emotional symptoms, and binomial logistic regression was used to identify the variables that contributed the most to classify the severity. The final adjusted model included psychological QoL (p < .001, odds ratio [OR] = .426, 95% CI [.318, .569]), negative metacognitions (p < .001, OR = 1.083, 95% CI [1.045, 1.122]), physical QoL (p < .001, OR = .870, 95% CI [.841, .900]), brooding rumination (p < .001, OR = 1.087, 95% CI [1.042, 1.133]), worry (p < .001, OR = 1.047, 95% CI [1.025, 1.070]), and employment status (p = .022, OR [.397, 2.039]) as independent variables, ρ2 = .326, area under the curve (AUC) = .857. Moreover, rumination and psychological QoL emerged as the best predictors to form a simplified equation to determine the emotional symptom severity (ρ2 = .259, AUC = .822). The use of statistical models like this could accelerate the assessment and treatment-decision process, depending less on the subjective point of view of clinicians and optimizing health care resources.


Exploratory Clinical Investigation of (4S)-4-(3-18F-Fluoropropyl)-L-Glutamate PET of Inflammatory and Infectious Lesions.
We explored system [Formula: see text] transporter activity and the detection of inflammatory or infectious lesions using (4S)-4-(3-(18)F-fluoropropyl)-l-glutamate ((18)F-FSPG) PET. In 10 patients with various inflammatory or infectious diseases, as many as 5 of the largest lesions were selected as reference lesions. (18)F-FSPG images were assessed visually and quantitatively. Expression levels of xCT, CD44, and surface markers of inflammatory cells were evaluated by immunohistochemistry. (18)F-FSPG PET detected all reference lesions. (18)F-FSPG uptake in sarcoidosis was significantly higher than that in nonsarcoidosis. The lesion-to-blood-pool SUV ratio for (18)F-FSPG was comparable to that for (18)F-FDG in sarcoidosis. In nonsarcoidosis, however, it was significantly lower. In 5 patients with available tissue samples, the SUVmax for (18)F-FSPG and CD163 were negatively correlated (ρ = -0.872, P = 0.054). (18)F-FSPG PET may detect inflammatory lesions when activated macrophages or monocytes are present, such as in sarcoidosis.


Social Return on Investment (SROI): An Innovative Approach to Sustainable Development Goals for Sexual and Reproductive Health Programming in sub-Saharan Africa.
Despite efforts, sub-Saharan Africa did not achieve many key Sexual and Reproductive Health (SRH) targets under the Millennium Development Goals. In the post 2015 era, the Sustainable Development Goals (SDGs) will frame decisions on donor priorities and resource allocations. Successfully addressing SRH challenges in sub-Saharan Africa have been blunted due to fragmentation of SRH interventions in planning and implementation, lack of coherence between policies and program implementation, resulting in poor program performance and lack of accountability. We suggest the Social Return on Investment (SROI) framework offers a strategic approach for sub-Saharan Africa in support of the implementation, monitoring and evaluation of SRH programs given its capacity to capture social and economic impacts, stakeholder participation, and sensitivity towards key human rights concerns relevant to SRH. SROI disrupts a -business as usual‖ approach for one that is systematic, participatory, and supportive of economic and human rights needs for success in the SDG era.


EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis.
Endothelial dysfunction links thrombotic microangiopathy to steroid-refractory graft-versus-host disease (GVHD) after allogeneic stem-cell transplantation. We aimed to assess if the simple formula-lactate dehydrogenase (U/L) × creatinine (mg/dL)/thrombocytes (109 cells per L)-termed the Endothelial Activation and Stress Index (EASIX), might be valuable for the prediction of death in patients with acute GVHD after allogeneic stem-cell transplantation. For this retrospective analysis, we analysed a training cohort (in Germany) and three validation cohorts (in Germany and the USA) of patients with acute GVHD who had received consecutive allogeneic stem-cell transplantation. The primary endpoint was prediction of overall survival when measured at acute GVHD onset (EASIX-GVHD). We validated the prognostic strength of EASIX-GVHD for overall survival and non-relapse mortality in the three independent cohorts by calculating the prediction error (integrated Brier score), and concordance index. In the total cohort of patients with acute GVHD (n=311), EASIX-GVHD predicted overall survival in univariable and multivariable models (univariate analysis, hazard ratio [HR] for a one-fold increase 1·16, 95% CI 1·12-1·20, p=0·0004). However, in the subpopulation of patients with myeloablative conditioning (n=72), EASIX-GVHD did not predict overall survival, which is probably attributable to thrombocytopenia at GVHD onset (73 × 109 cells per L [IQR 29·75-180·00] for myeloablative conditioning vs 160 × 109 cells per L [90·0-250·5] for reduced-intensity conditioning; p<0·0001). In patients who received reduced-intensity conditioning (n=239), EASIX-GVHD was a strong predictor of overall survival (HR for a two-fold change of 1·23, 95% CI 1·13-1·34; p<0·0001) and non-relapse mortality (cause-specific HR for a two-fold change of 1·24, 1·12-1·38; p<0·0001). Model validation for prediction of overall survival and non-relapse mortality by EASIX-GVHD was successful in two independent cohorts of adult patients with reduced-intensity conditioning (n=141, n=173) and in a cohort with mainly paediatric patients (n=89). In patients with reduced-intensity conditioning, EASIX-GVHD is a powerful predictor of survival after GVHD. EASIX-GVHD could be the future basis for development of risk-adapted GVHD treatment strategies. There was no external funding source for this study.


Gene expression analysis of the CD4+ T-cell clones derived from gingival tissues of periodontitis patients.
The function of T cells infiltrating periodontitis lesions is complex and has not been fully elucidated. Here, we established T-cell clones from the gingival tissues of periodontitis patients and examined their gene expression. A total of 57 and 101 T-cell clones were established by means of immobilized anti-CD3 antibody and IL-2 from gingival tissues and peripheral blood, respectively. The gingival T-cell clones were derived from three patients, and the peripheral blood T-cell clones from two of these patients and a further patient whose gingival T-cell clones were not established. Gingival tissues were also obtained from a further 19 periodontitis patients. The expression of cytokines and molecules related to both regulatory function and tissue destruction were examined by means of reverse-transcription polymerase chain reaction. All the gingival T-cell clones expressed mRNA for TGF-beta1, CTLA-4, and CD25, and all the T-cell clones from peripheral blood expressed IFN-gamma and TGF-beta1 mRNAs. Most but not all the T-cell clones from gingival tissues and peripheral blood expressed mRNA for IFN-gamma and, CD25 and CTLA-4, respectively. The frequency of T-cell clones and gingival tissues expressing FOXP3, a possible master gene for mouse CD4(+)CD25(+) regulatory T cells, was very high (97%, 93%, and 100% for gingival T-cell clones, peripheral blood T-cell clones, and gingival tissues, respectively). Whereas the frequency of IL-4-expressing T-cell clones was lower for gingival T-cell clones (70% vs. 87%), the frequency of the gingival T-cell clones expressing IL-10 and IL-17 was higher than peripheral blood T-cell clones (75% vs. 62% for IL-10, 51% vs. 11% for IL-17). A similar expression profile was observed for gingival T-cell clones compared with gingival tissue samples with the exception of IL-4 expression, where the frequency of positive samples was lower in the gingival tissues (70% vs. 11%). These results suggest that the individual T cells infiltrating gingival lesions can express mRNA for both Th1 and Th2 cytokines as well as regulatory cytokines simultaneously.


Understanding the dynamics behind the photoisomerization of a light-driven fluorene molecular rotary motor.
Light-driven molecular rotary motors derived from chiral overcrowded alkenes represent a broad class of compounds for which photochemical rearrangements lead to large scale motion of one part of the molecule with respect to another. It is this motion/change in molecular shape that is employed in many of their applications. A key group in this class are the molecular rotary motors that undergo unidirectional light-driven rotation about a double bond through a series of photochemical and thermal steps. In the present contribution we report a combined quantum chemical and molecular dynamics study of the mechanism of the rotational cycle of the fluorene-based molecular rotary motor 9-(2,4,7-trimethyl-2,3-dihydro-1H-inden-1-ylidene)-9H-fluorene (1). The potential energy surfaces of the ground and excited singlet states of 1 were calculated, and it was found that conical intersections play a central role in the mechanism of photo conversion between the stable conformer of 1 and its metastable conformer. Molecular dynamics simulations indicate that the average lifetime of the fluorene motor in the excited state is 1.40 +/- 0.10 ps when starting from the stable conformer, which increases to 1.77 +/- 0.13 ps for the reverse photoisomerization. These simulations indicate that the quantum yield of photoisomerization of the stable conformer is 0.92, whereas it is only 0.40 for the reverse photoisomerization. For the first time, a theoretical understanding of the experimentally observed photostationary state of 1 is reported that provides a detailed picture of the photoisomerization dynamics in overcrowded alkene-based molecular motor 1. The analysis of the electronic structure of the fluorene molecular motor holds considerable implications for the design of molecular motors. Importantly, the role of pyramidalization and conical intersections offer new insight into the factors that dominate the photostationary state achieved in these systems.


Design, synthesis, and activity of a novel series of factor Xa inhibitors: optimization of arylamidine groups.
A novel series of diaryloxypyridines have been designed as selective nanomolar factor Xa (fXa) inhibitors for use as anticoagulants. In this paper, we describe our efforts to identify an additional interaction and a replacement for the distal amidine group that binds in the S3/S4 pocket of fXa. Introduction of a hydroxyl group para to the proximal amidine group increases the potency vs fXa by 1-2 orders of magnitude, which is the result of a hydrogen bond to Ser195 of the catalytic triad. A methyl imidazoline and a dimethylamide are good alternatives for the second amidine. These substitutions have increased the selectivity vs the related serine proteases trypsin and thrombin. The synthesis, in vitro activity, and hypothetical modes of binding to fXa based on trypsin crystallographic data are outlined.


[Primary mucinous adenocarcinoma of the larynx: a case report].
Mucinous adenocarcinoma is most commonly found in the digestive tract,and the prognosis is poor.We present here a case of primary mucinous adenocarcinoma of the larynx, which is an extremely rare entity and very few have been reported in the literature.A 72-year-old male complained of intermittent hoarseness for over 2 months of duration.Fiberoptic laryngoscope showed negative result for tumor.While CT scan showed laryngeal space occupying lesion,and thyroid cartilage damage was observed.The patient underwent total laryngectomy.Histopathological examination and immunohistochemistry(IHC) analysis supported the diagnosis of mucinous adenocarcinoma.


Pregnancies following treatment by GnRH-a (Decapeptyl) and myomectomy in infertile women with uterine leiomyomata.
Uterine leiomyomata alone are an infrequent cause of infertility. We presumed that--since the smaller the uterine size at the time of myomectomy, the greater the chances of subsequent conception--diminishing the preoperative tumor size in infertile patients with large leiomyomata prior to myomectomy should be beneficial. Decapeptyl (D-Trp6-LHRH) depot 3.2 mg was administered for a period of 3-6 months to 23 infertile women. No causes of infertility were found in these patients except for uterine leiomyomata. In 10 of the 23 patients conservative myomectomy was added to Decapeptyl treatment. Following Decapeptyl treatment an average decrease in uterine volume of 57% (range: 22%-86%) was observed in all patients. In ten of the 23 patients conservative myomectomy was added to Decapeptyl treatment resulting in a further 16% decrease in uterine volume. Uterine regrowth following Decapeptyl and myomectomy was found to be significantly lower (P < 0.01) when compared with cases treated with Decapeptyl alone. Five of the ten patients treated by Decapeptyl and myomectomy achieved successful pregnancies and delivered. Among the women treated with Decapeptyl without myomectomy, only one patient conceived. From these findings it may be concluded that combined GnRH and myomectomy is the treatment of choice for infertile women with large uterine leiomyomata.


Excessive adiposity, metabolic health, and risks for genital human papillomavirus infection in adult women: a population-based cross-sectional study.
The role of excessive adiposity or its metabolic consequences in persistent HPV infection among general adult women remains unknown. Using data from the National Health and Nutrition Examination Survey (NHANES) in 2003-2010, we compared adult women's likelihood for any- or high-risk (HR) type HPV infection by degrees of excessive adiposity and metabolic health status. Any-type (41.1 % vs. 44.9 %, P = 0.045) or HR-type HPV prevalence (21.9 % vs. 25.4 %, P = 0.055) was comparable in women aged 20-59 years with or without central obesity. After adjusting for age, socioeconomic indicators, and lifetime sexual risks, centrally-obese women barely showed a different likelihood for any-type (aPR [adjusted prevalence ratio] = 0.91, P = 0.03) or HR-HPV infection (aPR = 0.92, P = 0.279). However, obesity (aPR = 0.76, P = 0.017) or centrally-obesity (aPR = 0.72, P = 0.003) was negatively correlated with HR-HPV infection in women reporting an early sex debut (<16 years; P for interaction <0.05). In the fasting subpopulation, obesity (aPR = 0.77, P = 0.016) or metabolically unhealthy obesity (aPR = 0.69, P = 0.018) was significantly correlated with a 23 % or 31 % reduced prevalence of HR-HPV infection. In contrary to findings for the general population, HR-HPV prevalence was decreased in a subgroup of women with obesity or central obesity. Possible explanations for such heterogeneity included less risky sexual behaviors, an altered immune milieu that promoted viral clearance, and increased access to healthcare resources due to other obesity-related co-morbidities in this subpopulation. Obesity or central obesity was not significantly associated with prevalent any-type or HR-type HPV infection among adult women in general. However, in certain subpopulations, excessive adiposity or its relevant metabolic dysfunction was negatively associated with HR-HPV infection.


Predictors of change in satisfaction with chewing ability: a 24-month study of dentate adults.
People's satisfaction with chewing ability is not determined entirely by their mechanical chewing function. Instead, it is a complex measure that embraces broad physical, social and psychological components. Using data from the Florida Dental Care Study, a prospective longitudinal study of oral health and dental care, this current study aimed to identify the longitudinal relationships between changes in satisfaction with chewing ability and changes in other dimensions of oral health and oral health-related quality of life (OHRQoL). A multidimensional conceptual model of oral health and OHRQoL was applied to guide the analysis. Most dentate people were satisfied with their chewing ability. However, changes in satisfaction with chewing ability were common: nearly 11-22% of subjects experienced improved satisfaction, depending on the interval; while about 12-18% of subjects experienced deteriorated satisfaction by the end of the interval. Changes in satisfaction with chewing ability were significantly associated with changes in other aspects of oral health and OHRQoL. Onset of certain oral health problems/conditions or constantly having such problems was associated with a lower probability of reporting improvement in satisfaction and a higher probability of experiencing deterioration. In contrast, recovery from certain oral health problems/conditions or not having such problems was associated with a higher probability of improvement and a lower probability of deterioration.


Poly(2-methyl-2-oxazoline)-b-poly(tetrahydrofuran)-b-poly(2-methyl-2-oxazoline) amphiphilic triblock copolymers: synthesis, physicochemical characterizations, and hydrosolubilizing properties.
Block copolymers assembled into micelles have gained a lot of attention to improve drug delivery. The recent drawbacks of the poly(ethylene oxide) blocks (PEO) contained in amphiphilic pluronics derivatives made of a central poly(propylene oxide) block surrounded by two PEO blocks were recently revealed, opening the way to the design of new amphiphilic block copolymers able to self-assemble in water and to entrap molecules of interest. Here, a family of p(methyloxazoline)-b-p(tetrahydrofuran)-b-p(methyloxazoline) triblock copolymers (called TBCP) is synthesized using cationic ring opening polymerization. Studies of micelle formation using dynamic light scattering, isothermal titration calorimetry (ITC), NMR diffusion-ordered spectroscopy (DOSY), and fluorescence experiments lead us to draw a relationship between copolymer structure and the physicochemical properties of the block copolymers (critical micellar concentration (CMC), Nagg, core diameter, shell thickness, etc.). The packing parameter of the block copolymers indicates the formation of a core-corona structure. Hydrosolubilizing properties of TBCPs were exemplified with curcumin selected as a highly insoluble drug model. Curcumin, a natural polyphenolic compound, has shown a large spectrum of biological and pharmacological activity, including anti-inflammatory, antimicrobial, antioxidant, and anticarcinogenic activities. An optimized formulation process reveals that the aggregation number is the parameter affecting drug encapsulation. Patch clamp experiments carried out to study the interaction of TBCP with the cell membrane demonstrate their permeation property suitable to promote the cellular internalization of curcumin.


Stabilizing the Inverted Phase of a WSe2/BLG/WSe2 Heterostructure via Hydrostatic Pressure.
Bilayer graphene (BLG) was recently shown to host a band-inverted phase with unconventional topology emerging from the Ising-type spin-orbit interaction (SOI) induced by the proximity of transition metal dichalcogenides with large intrinsic SOI. Here, we report the stabilization of this band-inverted phase in BLG symmetrically encapsulated in tungsten diselenide (WSe2) via hydrostatic pressure. Our observations from low temperature transport measurements are consistent with a single particle model with induced Ising SOI of opposite sign on the two graphene layers. To confirm the strengthening of the inverted phase, we present thermal activation measurements and show that the SOI-induced band gap increases by more than 100% due to the applied pressure. Finally, the investigation of Landau level spectra reveals the dependence of the level-crossings on the applied magnetic field, which further confirms the enhancement of SOI with pressure.


Germline mutation of ARF in a melanoma kindred.
Familial melanoma predisposition is associated with germline mutations at the CDKN2A/ARF locus in up to 40% of families. The exact role of the two proteins encoded by this complex locus in this predisposition is unclear. Most mutations affect either CDKN2A only or products of both genes. Recently a deletion affecting ARF-specific exon 1beta was reported in a family with melanoma and neural tumours. However, the possibility of this deletion also altering the CDKN2A transcript could not be excluded. More convincingly, a 16 base pair insertion in exon 1beta has been reported in an individual with multiple melanomas suggesting a direct role for ARF in melanoma predisposition. We report here a splice mutation in exon 1beta in a family with melanoma that results in ARF haploinsufficiency. The mutation was observed in a mother and daughter with melanoma. A sibling of the mother with breast cancer also had this mutation. Analysis of the melanoma from one individual revealed a 62 bp deletion in exon 3 of the wildtype allele and loss of the mutant allele; these somatic changes would affect both CDKN2A and ARF. These somatic events suggest that concomitant inactivation of both ARF and CDKN2A may be necessary for melanoma development and that mutations in ARF and CDKN2A possibly confer different levels of susceptibility to melanoma, with the former associated with lesser predisposition. In this situation, the events follow a 'three-hit' model as observed in tumours from FAP patients with an attenuated phenotype. Overall, the data suggest a direct role for ARF haploinsufficiency in melanoma predisposition and co-operation between ARF and CDKN2A in tumour formation, consistent with recent observations in Cdkn2a-specific knockout mice.


Intravascular ultrasound findings of coronary wall morphology in a child with Kawasaki disease.
Intravascular ultrasound (IVUS) imaging was performed to assess the coronary wall morphology in detail at 22 months after the onset of Kawasaki disease in a girl who had developed coronary aneurysms at 4 yr of age. The sites of persistent aneurysms demonstrated a dilated lumen with a marked symmetrical or asymmetrical thickening of the intima-media complex. This pathologic finding was also present in angiographically normal vessels near an aneurysm but with a mild thickening. Coronary artery calcification was observed at one site in the aneurysms. The sites of normal coronary artery far from an aneurysm showed normal intravascular ultrasound findings with no measurable intima-media complex. Our case indicates that the healing process may continue via cell proliferation, with extension to the proximity of the coronary aneurysms. IVUS is useful to evaluate the coronary wall morphology and may be valuable in the long-term follow-up of coronary lesions due to Kawasaki disease.


Impact of a Multifaceted Pharmacist-Led Intervention on Antimicrobial Stewardship in a Gastroenterology Ward: A Segmented Regression Analysis.
Irrational use of antimicrobial agents for gastrointestinal diseases deserves attention, but corresponding antimicrobial stewardship programs (ASPs) are generally not a priority for managers. We conducted this study to evaluate the effectiveness of multifaceted pharmacist-led (MPL) interventions in the gastroenterology ward (GW) to provide evidence for the efficacy of ASPs in a non-priority department. This was an interventional, retrospective study implemented in China. The MPL intervention lasting 1.5 years involved daily ward rounds with physicians, regular review of medical orders, monthly indicator feedback, frequent physician training, and necessary patient education. Data on all hospitalized adults receiving antibiotics was extracted from the hospital information system over a 36-month period from January 2016 to December 2018. Segmented regression analysis of interrupted time series was performed to evaluate the effect of the MPL interventions (started in July 2017) on antibiotic use and length of hospital stay, which was calculated monthly as analytical units. A total of 1763 patients receiving antibiotics were enrolled. Segmented regression models showed descending trends from the baseline in the intensity of antibiotic consumption (coefficient = -0.88, p = 0.01), including a significant decline in the level of change of the proportion of patients receiving combined antibiotics (coefficient = -9.91, p = 0.03) and average length of hospital stay (coefficient = -1.79, p = 0.00), after MPL interventions. The MPL interventions led to a temporary increase in the proportion of patients receiving antibiotics (coefficient = 4.95, p = 0.038), but this was part of a declining secular trend (coefficient = -0.45, p = 0.05). The MPL interventions led a statistically significant decline in the number of patients receiving antibiotics, the antibiotic consumption, and the average hospital stay post-intervention compared to the pre-intervention phase of the study. Health policymakers should actively practice MPL interventions by clinical pharmacists in ASPs in those departments that are not included in priority management.


Higher-order processes of excitation energy transfer in supramolecular complexes: Liouville space analysis of bridge molecule mediated transfer and direct photon exchange.
Long-range electronic excitation energy transfer is studied in the framework of a generalized master equation approach, which offers a systematic account for higher-order processes. Bridge molecule mediated transfer is confronted with the direct excitation energy exchange via photon emission and absorption. It is the central aim of this paper to present a systematic study of fourth-order rates, which describe both types of transfer processes characterized by the presence of intermediate states. While such a Liouville space formulation of rates is known from bridge mediated transfer, it is new for the case of photon mediated processes. In the former case, however, a novel approach to account for intermediate state relaxation is introduced. Finally and for illustration, some estimates are offered for the length dependence of the various discussed transfer rates.


Cardiac PACS: strategies for planning, integration & vendor selection.
Cardiologists are clamoring for better imaging techniques, the ability to view images from their office or home, and for the resulting improvement in efficiency which translates into increased profitability. The future is here; are you ready? Cardiac systems have developed into full-blown information management and digital imaging systems. Hospitals are moving aggressively to update their cardiac information systems and identifying the significant role the CIS (cardiac information system) plays in the selection process. It is important to plan the infrastructure of your cardiac PACS (picture archival communication system) and determine how it will integrate with the radiology PACS. Equally important is the integration potential with other hospital information systems such as the laboratory, pharmacy and billing, etc. Answers to these decision factors are provided in addition to information pertaining to the overall cardiac PACS planning process and vendor offerings.


Snell's Law for Spin Waves.
We report the experimental observation of Snell's law for magnetostatic spin waves in thin ferromagnetic Permalloy films by imaging incident, refracted, and reflected waves. We use a thickness step as the interface between two media with different dispersion relations. Since the dispersion relation for magnetostatic waves in thin ferromagnetic films is anisotropic, deviations from the isotropic Snell's law known in optics are observed for incidence angles larger than 25° with respect to the interface normal between the two magnetic media. Furthermore, we can show that the thickness step modifies the wavelength and the amplitude of the incident waves. Our findings open up a new way of spin wave steering for magnonic applications.


The Relationship Between Perceived Stress and Subjective Cognitive Decline During the COVID-19 Epidemic.
During the outbreak of the COVID-19 epidemic, fear of disease and its consequences, recommended lifestyle changes, and severe restrictions set by governments acted as stressors and affected people's mood, emotions, mental health, and wellbeing. Many studies conducted during this crisis focused on affective and physiological responses to stress, but few studies examined how the crisis affected cognition. The present cross-sectional study examined the relationship between physiological, affective, and cognitive responses to the epidemic. In an online survey conducted at the height of the first wave of the epidemic in Slovenia (April 15-25, 2020), 830 Slovenian residents aged 18-85 years reported the effects of stressors (confinement, problems at home, problems at work, lack of necessities, and increased workload), experienced emotions, generalized anxiety, perceived stress, changes in health, fatigue and sleep quality, and perceived changes in cognition during the epidemic. Risk factors for stress (neuroticism, vulnerability, general health, gender, and age) were also recorded. We hypothesized that stressors and stress risk factors will be related to subjective cognitive decline, with negative emotions, generalized anxiety, perceived stress, and physical symptoms acting as mediator variables. On average, the results showed a mild subjective cognitive decline during the epidemic. In structural equation modeling, 34% of its variance was predicted by the mediator variables, with negative emotions and physical symptoms having the largest contribution. Stress risk factors were predictably related to the four mediator variables. Among the stressors, confinement showed the strongest effect on the four mediator variables, implying the importance of thoughtful communication about necessary restrictive measures during emergency circumstances. The results of this study indicate that the possibility of altered cognitive function should be considered when planning work and study activities during the epidemic.


Backscattering properties of randomly oriented hexagonal hollow columns for lidar application.
The study of the optical properties of cirrus clouds is necessary to improve the accuracy of interpreting data from space lidars and ground-based lidar networks. Existing databases of backscattering properties do not include data on hollow columns. In this paper, the backscattering properties of randomly oriented hollow column ice crystal particles in cirrus at wavelengths of 355 nm, 532 nm, and 1064 nm have been investigated. The backscattering cross section (M11), depolarization ratio (δ), lidar ratio (S), and color ratio (χ) of randomly oriented hollow columns with sizes ranging from 10-316.23 µm are calculated within the framework of the physical optical approximation (PO). For the first time, we introduce the concept of modal hollow columns (MHC) suitable for mid-latitude regions, which simplifies the description of hollow ice crystals in nature. It is found that when the mixing proportion of MHC and solid columns (SC) reaches 50%, the mixing ratio can be distinguished by the lidar ratio for a wavelength of 1064 nm and by the χ(1064,532)-δ(532) relation.


MicroRNA miR-145-5p inhibits Phospholipase D 5 (PLD5) to downregulate cell proliferation and metastasis to mitigate prostate cancer.
Prostate cancer (PCa), a frequently detected malignant tumor, is the fifth leading global cancer mortality cause in men. Although research has improved the PCa survival rate, significantly reduced survival occurs among patients at the metastatic stage. MiRNAs, which are short non-coding proteins, are crucial for several biological roles, essential for PCa proliferation, differentiation, multiplication, and migration. The investigation aimed to explore miR-145-5p and PLD5 association and clarify their function in regulating proliferation in PCa cell lines.The study used PC-3, LNCaP, DU-145 PCa, and RWPE-1 non-cancerous cell line, PCa, and BPH tissue specimens, and nude mice to validate results. MiR-145-5p and PLD5 manifestation were assessed through RT-qPCR. PLD5 and miR-145 binding was determined through dual-luciferase reporter gene assays. Validation of cell proliferation, migration, and invasion was assessed through MTT, scratch wound, and transwell assays, respectively.The results indicated a downregulation of miR-145-5p level in PCa cell lines and tissues in comparison to the non-cancerous controls. PLD5 overexpression exerted a cancerous effect while mimicking of miR-145-5p reversed the PLD5-oncogenic effects and significantly inhibited PCa cells proliferation, migration, invasion, and metastasis.In conclusion, the study revealed that miR-145-5p upregulated apoptosis and repressed migration, invasion, and metastasis of PCa via direct PLD5 modulation.


Impact of Nuclear De Novo NAD+ Synthesis via Histone Dynamics on DNA Repair during Cellular Senescence To Prevent Tumorigenesis.
NAD+ synthesis is a fundamental process in living cells. The effects of local metabolite production on chromatin influence the epigenetic status of chromatin in DNA metabolism. We have previously shown that K5 acetylation of H2AX by TIP60 is required for the ADP ribosylation activity of PARP-1, for histone H2AX exchange at DNA damage sites. However, the detailed molecular mechanism has remained unclear. Here, we identified de novo NAD synthetase 1 (NAD syn1) as a novel binding partner to H2AX. The enzymatic activity of NAD syn1 is crucial for the ADP ribosylation activity of PARP-1 for the H2AX dynamics at sites of DNA damage. Inhibition of the NAD synthetase activity in the cell nucleus decreased the overall cellular NAD+ concentration, leading to cellular senescence. Accordingly, the acetylation-dependent H2AX dynamics and homologous recombination repair were suppressed, leading to increased tumorigenesis. Our findings have revealed the importance of de novo NAD+ production in the cell nucleus for protection against the decreased DNA repair capacity caused by cellular senescence and thus against tumorigenesis.


Stimuli-Responsive Self-Immolative Polymer Nanofiber Membranes Formed by Coaxial Electrospinning.
The first self-immolative polymer (SIP) nanofiber membrane is demonstrated in this report, in which the immolation can be triggered by external stimulus. Electrospun SIP/polyacrylonitrile (PAN) fibers provide depolymerization that is ∼25 times quicker and more responsive (i.e., immolation) than that of a cast film in the triggering condition. Depolymerization of SIP in the SIP/PAN blended fiber membrane results in the transition of the surface properties from hydrophobic (∼110°) to hygroscopic (∼0°). Triggered release of encapsulated functional molecules was demonstrated using coaxially electrospun fiber membrane made of a SIP/PAN blend sheath and polyvinylpyrrolidone/dye core. Coaxial fibers with the SIP/PAN sheath provide minimal release of the encapsulated material in nontriggering solution, while it releases the encapsulated material instantly when the triggering condition is met. Its versatility has been strengthened compared to that of non-SIP coaxial fibers that provide no triggering reaction by external stimulus.


A liquid phase affinity capture assay using magnetic beads to study protein-protein interaction: the poliovirus-nanobody example.
In this article, a simple, quantitative, liquid phase affinity capture assay is presented. Provided that one protein can be tagged and another protein labeled, this method can be implemented for the investigation of protein-protein interactions. It is based on one hand on the recognition of the tagged protein by cobalt coated magnetic beads and on the other hand on the interaction between the tagged protein and a second specific protein that is labeled. First, the labeled and tagged proteins are mixed and incubated at room temperature. The magnetic beads, that recognize the tag, are added and the bound fraction of labeled protein is separated from the unbound fraction using magnets. The amount of labeled protein that is captured can be determined in an indirect way by measuring the signal of the labeled protein remained in the unbound fraction. The described liquid phase affinity assay is extremely useful when conformational conversion sensitive proteins are assayed. The development and application of the assay is demonstrated for the interaction between poliovirus and poliovirus recognizing nanobodies(1). Since poliovirus is sensitive to conformational conversion(2) when attached to a solid surface (unpublished results), the use of ELISA is limited and a liquid phase based system should therefore be preferred. An example of a liquid phase based system often used in polioresearch(3,4) is the micro protein A-immunoprecipitation test(5). Even though this test has proven its applicability, it requires an Fc-structure, which is absent in the nanobodies(6,7). However, as another opportunity, these interesting and stable single-domain antibodies(8) can be easily engineered with different tags. The widely used (His)(6)-tag shows affinity for bivalent ions such as nickel or cobalt, which can on their turn be easily coated on magnetic beads. We therefore developed this simple quantitative affinity capture assay based on cobalt coated magnetic beads. Poliovirus was labeled with (35)S to enable unhindered interaction with the nanobodies and to make a quantitative detection feasible. The method is easy to perform and can be established with a low cost, which is further supported by the possibility of effectively regenerating the magnetic beads.


Human immune responses to porcine endogenous retrovirus-derived peptides presented naturally in the context of porcine and human major histocompatibility complex class I molecules: implications in xenotransplantation of porcine organs.
Porcine endogenous retroviruses (PERV) have been shown to infect human cells, raising concerns regarding safety of xenotransplantation. In patients exposed to porcine tissues, no PERV infection has been observed. This study was designed to develop human CD8+ cytotoxic T lymphocytes (CTL) against PERV-derived peptides presented in the context of human leukocyte antigen (HLA) or swine leukocyte antigen (SLA) class I molecules and to define dominant epitopes contributed by PERV. Human CD8+ CTL were generated against porcine aortic endothelial cells (PAEC). Peptides presented on SLA class I molecules were acid eluted and fractionated by reverse-phase high-performance liquid chromatography. Peptide fractions that restored lysis of acid-stripped PAEC were sequenced by tandem mass spectrometry. Human CD8+ CTL were generated against PERV envelope-derived peptides and PERV-infected human cells to identify immunodominant PERV-derived epitopes. We identified two peptides derived from retroviral transactivating regulatory protein (AHQDPLPEQP) and retroviral transcription factor (PQKPFVT) recognized by human CD8+ CTL in the context of SLA class I. Computer-assisted analysis identified nine PERV-envelope-derived 9-mer peptides with high affinity for the HLA-A2 molecule (Env-1-9). PERV-specific CD8+ CTL generated in vitro identified the immunodominant Env-5 peptide (303-311, KLFSLIQGA) and demonstrated HLA-A2-restricted cytotoxicity against PERV-infected human cells. Our results indicate that PERV-derived peptides are presented naturally on porcine and human major histocompatibility complex class I molecules. CD8+ CTL responses elicited against dominant SLA and HLA class I-restricted PERV-derived epitopes may play an important role in xenograft rejection and in containment of PERV infection of human cells after xenotransplantation.


Trans-dimensional joint inversion of seabed scattering and reflection data.
This paper examines joint inversion of acoustic scattering and reflection data to resolve seabed interface roughness parameters (spectral strength, exponent, and cutoff) and geoacoustic profiles. Trans-dimensional (trans-D) Bayesian sampling is applied with both the number of sediment layers and the order (zeroth or first) of auto-regressive parameters in the error model treated as unknowns. A prior distribution that allows fluid sediment layers over an elastic basement in a trans-D inversion is derived and implemented. Three cases are considered: Scattering-only inversion, joint scattering and reflection inversion, and joint inversion with the trans-D auto-regressive error model. Including reflection data improves the resolution of scattering and geoacoustic parameters. The trans-D auto-regressive model further improves scattering resolution and correctly differentiates between strongly and weakly correlated residual errors.


Idiopathic gingival fibromatosis: description of two cases.
Gingival fibromatosis is an enlargement localized or generalized of the gingival tissue characterized by an expansion and accumulation of the connective tissue, predominantly type I collagen, with occasional presence of increased number of cells, supposed fibroblastic proliferation. Gingival fibromatosis can be induced as a side effect of systemic drugs, such as phenytoin, cyclosporin, and nifedipine, or due to hereditary factors. However, in some cases, the gingival overgrowth is idiopathic. This paper reports two cases of idiopathic gingival fibromatosis and discusses the diagnosis, histopathological features, treatment and immunohistochemical evaluation of myofibroblasts of this condition. The tissues removed were fixed in formalin, and sections used for hematoxylin and eosin and Masson tricromic stain. To determine the presence of myofibroblasts, we performed immunohistochemistry against a-SMA protein. Histological examination revealed epithelial hyperplasia with long rete pegs and increase in the dense fibrous connective tissue. The Masson tricromic stain revealed wide bundles of collagen strongly stained. It was showed negative labeling to a-SMA. These results strongly suggest that myofibroblasts are not involved in gingival overgrowth in the cases of IGF reported. Future studies will be necessary to determine the pathogenesis of idiopathic gingival fibromatosis.


CT-optimized skin stroking delivered by hand or robot is comparable.
The aim of our study was to investigate whether a pleasant tactile stimulation which is manually produced is qualitatively comparable to an analogous tactile stimulation produced instead by a mechanical source. Thirty-one subjects [16 men, 15 women, 24.5 ± 2.6 years, mean, and standard deviation (SD)] were tested under four different conditions in a repeated measurements design. A pleasant caress-like brush stroke on the hairy skin of the forearm was either produced by a robot or by hand with three different velocities (0.3, 3, and 30 cm/s). In two conditions the subjects were informed about the stroke's source, whereas in two different conditions they were not. Subsequent to the stimulation, the subjects were asked to rate both pleasantness and intensity of each tactile sensation. Consistently, pleasantness ratings were very similar in both conditions. This was found across stimulus velocities and regardless of whether the subjects were informed about the source of the on-going stroke or not. In contrast, intensity ratings were significantly higher in the handheld condition for the two slower velocities, but not for the fastest one. As robot and human touch are highly comparable in terms of perceived pleasantness, handheld stimulation may be used in studies of touch hedonia where robot stimulation is not applicable (for instance in children or certain body parts).


Did we do it right?--an evaluation of the colour coding system for antenatal care in Malaysia.
Identification of pregnancies that are at greater than average risk is a fundamental component of antenatal care. The objective of this study was to assess the level of appropriate management and outcomes among mothers with hypertensive disorders of pregnancy, postdates and anemia in pregnancy, and to determine whether the colour coding system had any effect on the maternal mortality ratios. A retrospective follow-through study confined to users of government health services in Peninsular Malaysia was carried out in 1997. The study areas were stratified according to their high or low maternal mortality ratios. The study randomly sampled 1112 mothers out of 8388 mothers with the three common obstetric problems in the selected study districts. The study showed that the prevalence of anemia, hypertensive disorders in pregnancy and postmaturity among mothers with these conditions were according to known international standards. There was no significant difference in the colour coding practices between the high and low maternal mortality areas. Inappropriate referrals were surprisingly lower in the areas with high maternal mortality. Inappropriate care by diagnosis and by assigned colour code were significantly higher in the areas with high maternal mortality. The assigned colour code was accurate in only 56.1% of cases in the low maternal mortality areas and in 55.8% of the cases in the high maternal mortality areas and these two areas did not differ significantly in their accurate assignment of the colour codes. The colour coding system, as it exists now should be reviewed. Instead, a substantially revised system that takes cognisance of evidence in the scientific literature should be used to devise a more effective system that can be used by health care personnel involved in antenatal care to ensure appropriate level of care and referrals.


The estimation and partitioning of evapotranspiration in a coniferous plantation in subtropical China.
Accurate estimations of forest evapotranspiration (ET) and its components, transpiration (T) and evaporation (E), are important for deep understanding and predicting the responses of forest water cycles to climate change. In this study, the improved Shuttleworth-Wallace model (SWH) was applied to estimate ET, T, and E during 2003-2014 in a subtropical planation, and the modeled results were verified using in situ measurements by the eddy covariance technique, sap flow, and micro-lysimeter method. The study aimed to clarify whether it is feasible and reliable to use the SWH model to estimate and partition ET in forests. In addition, depending on the long-term data, the specific performances in modeling ET under different climatic backgrounds were investigated, and the underlying mechanisms were explored. The results verified that the SWH performed relatively well in the subtropical forest, and the modeled ET, T and E could track the seasonal variations, although overestimations were found in the peak seasons. However, the model was relatively weaker in estimating the interannual variabilities. It performed well in modeling ET in normal years but showed larger model residuals in years with obvious climatic anomalies. In the severe summer-drought (2003) and cold-spring (2005) years, the model greatly overestimated ET. It also overestimated ET in summer since 2010, which may be ascribed to the less dependency of ET on VPD induced by the more humid microclimate in forest accompanied with forest development. For the ET partitioning results, the modeled and measured E and T values were all in reasonable ranges. The possible reasons for underestimations (overestimations) of E and T by measurements (SWH model) were discussed. In this study, the data obtained using different methods and from different scales matched each other and could be cross validated, and the discussion on discrepancies would be beneficial for understanding the advantages and flaws of different methods and could be the basis for optimizing the measurement and model methods. In sum, this study verified that it is feasible to use the SWH model in forests and provided a basis for further improving and optimizing the modeled results under different climate backgrounds.


Verification of global cerebral ischaemia using scintigraphy.
The induction of global cerebral ischaemia in laboratory animals is difficult to accomplish and has been even more difficult to verify. Most reported verification methods suffer from lack of sensitivity or from being traumatic and highly invasive. We describe a non-traumatic global cerebral ischaemia verification technique which is quantitative, simple, and highly sensitive. Radioactive technetium-99m pertechnetate is injected intravenously during the ischaemic phase of an experiment and the appearance of radioactivity within the animal's head is quantitated using a gamma camera and nuclear medicine computer. Radioactivity levels below the visual perception threshold are readily measured, thus providing a high degree of confidence in assessing the partial or total nature of cerebral ischaemia.


Whose tradition? Which Enlightenment? What content? Engelhardt, Hauerwas, Capaldo, and the future of Christian bioethics.
The development of a content-full Christian bioethics requires an analysis of the particular contents and traditions which different Christians bring to morality. For Hauerwas, the content of Christian ethics is the speech and practices of the community. For Engelhardt, only a content-full tradition, such as the Orthodox tradition, will be able to arrive at closure on the moral issues presented by the contemporary practice of medicine. Capaldi calls, in contrast, for a Kantian society of autonomous self-legislators whose responsible freedom is grounded in a cosmic order that must be explicated and retrieved in particular practices. The manner in which we view our own traditions and the shortcomings of modernity determine the content that Christianity brings to bioethics.


Alarmins HMGB1, IL-33, S100A7, and S100A12 in Psoriasis Vulgaris.
Psoriasis vulgaris is a chronic autoimmune disease associated with systemic inflammation. Increased levels of numerous cytokines, chemokines, growth factors, and other molecules were found in the skin and in the circulation of psoriatic patients. Alarmins, also known as danger signals, are intracellular proteins, which are released to an extracellular space after infection or damage. They are the markers of cell destructive processes. The aim of the present study was to evaluate the suitability of selected alarmins (HMGB1, IL-33, S100A7, and S100A12) as potential biomarkers of severity of psoriasis and to explore possible relationships between these proteins for the purpose of better understanding their roles in the immunopathology of psoriasis. The serum levels of selected alarmins were measured in 63 psoriatic patients and 95 control individuals. The levels were assessed by the ELISA technique using commercial kits. The data were statistically processed with MedCalc version 19.0.5. In psoriatic patients, we found significantly increased levels of HMGB1 (p < 0.05), IL-33 (p < 0.01), S100A7 (p < 0.0001), and S100A12 (p < 0.0001). In addition, we found a significant relationship between HMGB1 and S100A7 (Spearman's rho = 0.276, p < 0.05) in the patients and significant relationship between HMGB1 and IL-33 in the controls (Spearman's rho = 0.416, p < 0.05). We did not find any relationship between observed alarmins and the disease severity. The alarmins HMGB1, IL-33, S100A7, and S100A12 were significantly elevated in the serum of patients, which states the hypothesis that they play specific roles in the immunopathology of psoriasis. However, we have not yet found a relationship between observed alarmins and the disease severity. The discovery of the relationship between HMGB1 and S100A7 is a novelty that should be studied in the future to further clarify its role and importance.


The helix-loop-helix protein Id-2 enhances cell proliferation and binds to the retinoblastoma protein.
Cell growth and differentiation are usually antagonistic. Proteins of the basic helix-loop-helix (bHLH) family bind DNA and play important roles in the differentiation of specific cell types. Id proteins heterodimerize with bHLH transcription factors, blocking their activation of lineage-specific gene expression and thereby inhibiting cellular differentiation. To examine the effect of Id-2 on cell proliferation, we overexpressed Id-2 in the human osteosarcoma cell line U2OS. Id-2 expression in U2OS reduced the serum requirement for growth and stimulated cellular proliferation by shortening the doubling time and increasing the percentage of cells in S phase. We demonstrated that Id-2 expression was able to reverse the inhibition of cellular proliferation and the block in cell cycle progression mediated by the product of the retinoblastoma tumor suppressor gene pRB. This effect was not associated with changes in the state of pRb phosphorylation in transfected cells. In vitro, unphosphorylated pRb from cell lysates specifically bound Id-2 but was not able to bind a mutated form of Id-2 lacking the HLH domain that also did not antagonize the growth arrest by pRb. In vitro-synthesized pRb containing mutations within the E1A/large T-binding pocket did not bind Id-2. However, wild-type pRb was able to bind to a region of Id-2 corresponding to only the HLH domain. In vivo, a physical association between Id-2 and pRb was seen in cross-linked extracts from SAOS-2 cells transfected with Id-2 and pRb. Our data identify a role for Id-2 in the regulation of cellular proliferation and suggest that the interaction between Id-2 and pRB is a molecular pathway over which synchronous changes in growth and differentiation are mediated in vivo.


Physiological Impact of Platelet Apheresis in Pigs: Oxygen Metabolism and Coagulation.
Platelet apheresis is a routine clinical practice, but the physiological impact on the donors has been incompletely characterized. This study measured the effects of platelet apheresis on hemodynamics, oxygen metabolism, and coagulation in pigs to assess its impact before employing the animals in experimental studies. Forty pigs (39.8 ± 0.6 kg) were anesthetized and catheterized with an apheresis catheter in the femoral vein. During the platelet apheresis process, blood was withdrawn from the pig to separate platelets, and the remaining red blood cells and plasma returned back to the pigs, using the Haemonetics MCS+9000 system. A total of 12 cycles of blood withdrawn and return were performed during the entire apheresis procedure to reduce platelet counts to a target of 50% of baseline. During the process, hemodynamics was recorded in each cycle. Blood samples were collected before and after apheresis to assess changes in oxygen metabolism and coagulation by prothrombin time, activated partial thromboplastin time (STA-R Evolution Stago), and using Rotem thrombelastometry, and platelet aggregation using a Chrono-Log 700 aggregometer. During each cycle of the apheresis, mean arterial pressure (MAP) was decreased and heart rate was increased by blood withdrawal, but both recovered after blood return. On the completion of the apheresis, platelet count decreased from baseline 345 ± 15 109/L to 141 ± 14 109/L and fibrinogen levels were reduced from 124 ± 5 to 99 ± 4 mg/dL (both p < 0.05). Although oxygen delivery remained unchanged, oxygen consumption was decreased from 4.0 ± 0.2 to 3.2 ± 0.0 mL O2/kg/min (p < 0.05). Rotem alpha (clotting speed) decreased from 79 ± 0 to 69 ± 1° and maximum clot firmness (MCF or clot strength) decreased from 71 ± 1 to 57 ± 1 mm (both p < 0.05). No changes were observed in prothrombin time or activated partial thromboplastin time. Platelet aggregation induced by arachidonic acid or collagen was decreased to 28 ± 6% or 71 ± 3% of baseline values (p < 0.05), respectively. Platelet apheresis caused significant fluctuations in hemodynamics, reduced oxygen consumption, in addition to the compromised platelet aggregation and clotting function expected. The observations warrant consideration in humans undergoing apheresis over extended periods.


Inherent biomechanical traits enable infective filariae to disseminate through collecting lymphatic vessels.
Filariases are diseases caused by arthropod-borne filaria nematodes. The related pathologies depend on the location of the infective larvae when their migration, the asymptomatic and least studied phase of the disease, comes to an end. To determine factors assisting in filariae dissemination, we image Litomosoides sigmodontis infective larvae during their escape from the skin. Burrowing through the dermis filariae exclusively enter pre-collecting lymphatics by mechanical disruption of their wall. Once inside collectors, their rapid and unidirectional movement towards the lymph node is supported by the morphology of lymphatic valves. In a microfluidic maze mimicking lymphatic vessels, filariae follow the direction of the flow, the first biomechanical factor capable of helminth guidance within the host. Finally, non-infective nematodes that rely on universal morpho-physiological cues alone also migrate through the dermis, and break in lymphatics, indicating that the ability to spread by the lymphatic route is an ancestral trait rather than acquired parasitic adaptation.


The phospholipase PNPLA7 functions as a positive indicator in human colorectal and gastric cancers.
Early diagnosis of gastrointestinal tumors remains a clinical challenge due to their insidious onset. Patatin-like phospholipase domain containing protein 7 (PNPLA7) has been shown to be associated with the occurrence and development of hepatocellular carcinoma. However, the expressions of PNPLA7 in colorectal and gastric cancers remain unclear. The online gene expression profiling interactive analysis and Kaplan-Meier Plotter databases were used for the analysis of the expression of PNPLA7 and the survival curve, respectively. The tumor tissues and their corresponding normal noncancerous tissues from colorectal cancer or gastric cancer patients were collected and quantitative real-time polymerase chain reaction assay was performed to evaluate the expression of related genes. PNPLA7 was significantly down-regulated in gastric and colorectal cancer tumor tissues compared to adjacent normal tissues. Receiver operating characteristic analysis showed that PNPLA7 could be used as a diagnostic marker for gastric and colorectal tumors. The overall survival of patients with high expression of PNPLA7 was also significantly higher than that of patients with low expression in stomach and rectum adenocarcinoma. Phospholipase PNPLA7 can be used as a positive diagnostic indicator for colorectal and gastric cancers.


Differential antiproliferative effects of combinations of recombinant interferons alpha and gamma on two murine tumor cell lines.
The in vitro antiproliferative effects of recombinant interferons (IFNs) alpha and gamma against the murine reticulum-cell sarcoma M5076 and the malignant melanoma B16 F10 were evaluated using the human hybrid IFN-alpha A/D (rHuIFN-alpha A/D), which is active on murine cells, and recombinant murine IFN gamma (rMuIFN-gamma). An isobologram analysis was used to evaluate the interactive antiproliferative effects of the recombinant IFNs on these two tumor cell lines. The data, in contrast to prior reports, indicate that rHuIFN-alpha A/D and rMuIFN-gamma interact in an additive rather than a synergistic manner against M5076 cells. When a similar analysis was performed on B16 F10 cells, synergy was obtained. Thus, either a synergistic or an additive antiproliferative effect can be obtained by combining IFN-alpha and IFN-gamma, depending upon the cell line used in the assay.


Calcium-Dependent Protein Kinase Family Genes Involved in Ethylene-Induced Natural Rubber Production in Different Hevea brasiliensis Cultivars.
Natural rubber latex production can be improved by ethylene stimulation in the rubber tree (Hevea brasiliensis). However, the expression levels of most functional proteins for natural rubber biosynthesis are not induced after ethylene application, indicating that post-translational modifications, especially protein phosphorylation, may play important roles in ethylene signaling in Hevea. Here, we performed a comprehensive investigation on evolution, ethylene-induced expression and protein-protein interaction of calcium-dependent protein kinases (CPKs), an important serine/threonine protein kinase family, in Hevea. Nine duplication events were determined in the 30 identified HbCPK genes. Expression profiling of HbCPKs in three rubber tree cultivars with low, medium and high ethylene sensitivity showed that HbCPK6, 17, 20, 22, 24, 28 and 30 are induced by ethylene in at least one cultivar. Evolution rate analysis suggested accelerated evolution rates in two paralogue pairs, HbCPK9/18 and HbCPK19/20. Analysis of proteomic data for rubber latex after ethylene treatment showed that seven HbCPK proteins could be detected, including six ethylene-induced ones. Protein-protein interaction analysis of the 493 different abundant proteins revealed that protein kinases, especially calcium-dependent protein kinases, possess most key nodes of the interaction network, indicating that protein kinase and protein phosphorylation play important roles in ethylene signaling in latex of Hevea. In summary, our data revealed the expression patterns of HbCPK family members and functional divergence of two HbCPK paralogue pairs, as well as the potential important roles of HbCPKs in ethylene-induced rubber production improvement in Hevea.


A meta-analysis of the existing knowledge of immunoreactivity against hepatitis C virus (HCV).
Approximately 3% of the world population is infected by HCV, which represents a major global health challenge. Almost 400 different scientific reports present immunological data related to T cell and antibody epitopes derived from HCV literature. Analysis of all HCV-related epitope hosted in the Immune Epitope Database (IEDB), a repository of freely accessible immune epitope data, revealed more than 1500 and 1900 distinct T cell and antibody epitopes, respectively. The inventory of all data revealed specific trends in terms of the host and the HCV genotypes from which sequences were derived. Upon further analysis we found that this large number of epitopes reflects overlapping structures, and homologous sequences derived from different HCV isolates. To access and visualize this information we developed a novel strategy that assembles large sets of epitope data, maps them onto reference genomes and displays the frequency of positive responses. Compilation of the HCV immune reactivity from hundreds of different studies, revealed a complex and thorough picture of HCV immune epitope data to date. The results pinpoint areas of more intense reactivity or research activities at the level of antibody, CD4 and CD8 responses for each of the individual HCV proteins. In general, the areas targeted by the different effector immune functions were distinct and antibody reactivity was positively correlated with hydrophilicity, while T cell reactivity correlated with hydrophobicity. At the sequence level, epitopes frequently recognized by both T cell and B cell correlated with low variability, and our analysis thus highlighted areas of potential interest for practical applications. The human reactivity was further analyzed to pinpoint differential patterns of reactivity associated with acute versus chronic infection, to reveal the apparent impact of glycosylation on T cell, but not antibody responses, and to highlight a paucity of studies involved antibody epitopes associated with virus neutralization.


Photochemical Water Splitting by Bismuth Chalcogenide Topological Insulators.
As one of the major areas of interest in catalysis revolves around 2D materials based on molybdenum sulfide, we have examined the catalytic properties of bismuth selenides and tellurides, which are among the first chalcogenides to be proven as topological insulators (TIs). We find significant photochemical H2 evolution activity with these TIs as catalysts. H2 evolution increases drastically in nanosheets of Bi2 Te3 compared to single crystals. First-principles calculations show that due to the topology, surface states participate and promote the hydrogen evolution.


Autoimmune correlation of rheumatoid arthritis and periodontitis.
Rheumatoid arthritis and periodontitis, both, chronic inflammatory diseases share certain common diagnostic, pathological, immunogenetic and therapeutic features. A recently discovered enzymatic mimicry between human and bacterial species is novel and it opens up a new terrain for therapeutic blockade in the management of rheumatoid arthritis.


Role of the density in the crossover region of o-terphenyl and poly(vinyl acetate).
The coupling between the reorientation of molecular probes and the density in one low-molar mass glass former [ o -terphenyl (OTP)] and one polymer [poly(vinyl acetate) (PVAc)] is studied in the Goldstein's crossover region where the structural (alpha) and the secondary (beta) relaxations bifurcate. The coupling is found to be strong in OTP and virtually absent in PVAc. The probes sense both the alpha and beta relaxations, and locate their splitting accurately. It is concluded that the density affects the relaxation occurring in the crossover region of OTP but not of PVAc at subnanometer length scales. The findings are compared with recent assessments of the role of the molecular packing close and above the glass transition temperature T(g).


Tissue levels of reduced folates in patients with colorectal carcinoma after infusion of folinic acid at various dose levels.
In patients with colorectal cancer (CRC), modulation of 5-fluorouracil (5-FU) by folinic acid (FA) improves response rate and overall survival compared with 5-FU alone. However, the optimal dose of FA is still debated. We investigated reduced folate pools in various tissues from patients with CRC without and after prior administration of FA. A total of 186 specimens (normal colorectal mucosa, primary colorectal tumor, normal liver, and liver metastases) from 86 consecutive patients with CRC were obtained and investigated for levels of reduced folates. Before surgery, patients did (n = 52) or did not (n = 34) receive FA as 15-minute i.v. infusion. FA-dose levels chosen were 20, 200, or 500 mg/m2. Tissue lysates were analyzed for reduced folate levels by means of the tritium release assay. In normal mucosa, combined pools of tetrahydrofolate and 5,10-methylenetetra-hydrofolate were significantly elevated at all FA dose levels compared with untreated controls. In primary tumor, only 200 and 500 mg/m2 FA resulted in a significant increase of reduced folates with highest values measured after 500 mg/m2 FA. In specimens from normal liver, folate levels did not increase after administration of FA. By contrast, in specimens from liver metastases, reduced folate levels were low without FA pretreatment compared with levels from normal liver samples. Infusion of 500 mg/m2 FA caused a significant increase of reduced folate levels in liver metastases. From a pharmacologic point of view, high-dose FA should be recommended for optimal modulation of 5-FU in patients with mCRC.


Conservation laws for collisions of branes and shells in general relativity.
We consider the collision of self-gravitating n-branes in a (n+2)-dimensional spacetime. We show that there is a geometrical constraint which can be expressed as a simple sum rule for angles characterizing Lorentz boosts between branes and the intervening spacetime regions. This constraint can then be reinterpreted as either energy or momentum conservation at the collision.


[Income inequality, corruption, and life expectancy at birth in Mexico].
To ascertain if the effect of income inequality on life expectancy at birth in Mexico is mediated by corruption, used as a proxy of social capital. An ecological study was carried out with the 32 Mexican federative entities. Global and by sex correlations between life expectancy at birth were estimated by federative entity with the Gini coefficient, the Corruption and Good Government Index, the percentage of Catholics, and the percentage of the population speaking indigenous language. Robust linear regressions, with and without instrumental variables, were used to explore if corruption acts as intermediate variable in the studied relationship. Negative correlations with Spearman's rho near to -0.60 (p < 0.05) and greater than -0.66 (p < 0.05) between life expectancy at birth, the Gini coefficient and the population speaking indigenous language, respectively, were observed. Moreover, the Corruption and Good Government Index correlated with men's life expectancy at birth with Spearman's rho -0.3592 (p < 0.05). Regressions with instruments were more consistent than conventional ones and they show a strong negative effect (p < 0.05) of income inequality on life expectancy at birth. This effect was greater among men. The findings suggest a negative effect of income inequality on life expectancy at birth in Mexico, mediated by corruption levels and other related cultural factors.


Nonlinear giant magnetoresistance in dual spin valves.
Giant magnetoresistance (GMR) arises from differential scattering of the majority and minority spin electrons by a ferromagnet (FM) so that the resistance of a heterostructure depends on the relative magnetic orientation of the FM layers within it separated by nonmagnetic spacers. Here, we show that highly nonequilibrium spin accumulation in metallic heterostructures results in a current-dependent nonlinear GMR which is not predicted within the present understanding of GMR. The behavior can be explained by allowing the scattering asymmetries in an ultrathin FM layer to be current dependent.


Neuroanatomical correlates to central deafness.
Our research experience with five centrally deaf patients showed that damage to various anatomical sites could result in central deafness. This finding was contrary to the commonly held notion that both Heschl's gyri must be severely damaged to yield central deafness. To discover whether lesions in various brain areas could cause central deafness, we reviewed 33 cases of central deafness reported in the literature which had sufficient radiological data to determine the anatomical regions involved. Both Heschl's gyri were involved in the majority of these cases, but there were definite exceptions. In these exceptional cases of central deafness, subcortical areas were involved (usually the internal capsule), as was the insula. Overall findings are discussed and recommendations are offered for the future study of centrally deaf patients.


Influence of a physical fitness course on menstrual cycle characteristics.
Exercise is commonly cited as a remedy for menstrual symptoms. The purpose of the present study was to evaluate the effect of a period of exercise on physical and psychological symptoms of menstruation, dysmenorrhea, oligomenorrhea and amenorrhea. Participants of the study were 250 students of Shiraz University who enrolled in a fitness course. The study design was semi-experimental with one group. Prior and after 12 weeks of a physical fitness program, our subjects completed questionnaires on menstrual distress. The physical fitness training program included physical fitness exercises (cardiovascular endurance, muscular endurance, agility, speed, strength; duration: 90 min, frequency: twice weekly, intensity: 50 to 70% of maximum heart rate). The t test was used for analysis of the data. Physical premenstrual symptoms (p = 0.005), psychological premenstrual symptoms (p = 0.019), dysmenorrhea (p = 0.0001) and oligomenorrhea (p = 0.034) were significantly reduced after the training program. There was no difference in the incidence of amenorrhea before and after the training program (p = 0.162). Our findings indicate that selected physical fitness exercises positively influenced menstrual symptoms.


Intellectual disabilities and developmental EEG transition to alpha band: a comment on Shibagaki, et al. (2006).
In 2006 Shibagaki, et al. estimated mean chronological age at which dominant EEG frequency reached alpha band in 11 children with intellectual disabilities (M age, 15 yr.). Consistent with previous studies, the results showed a delay in the critical age relative to healthy children and earlier maturation at posterior scalp sites, with the exception of several children who persistently showed EEG slower than alpha band. A flaw in the study might be that having only 2 children younger than 10 yr. was insufficient. A remaining problem for researchers would be to identify whether the developmental delay in EEG correlates with IQ in intellectually disabled children.


[A digital model for lumbar motion segment reconstruction and three-dimensional visualization].
To establish a digital model for reconstruction and three-dimensional visualization of lumbar motion segment from CT images. Based on 64 row spiral CT continuous 2-dimensional images of L4-L5 segments, the lumbar structure and various soft tissues were reconstructed with the Mimics software, followed by validation of this model using finite element analysis software. The established three-dimensional digital model of lumbar motion segment included two vertebral bodies, cortical bone, cancellous bone, endplate, annulus fibrosus, nucleus pulposus and 6 types of ligaments. The output result of the digital model can be used to for research of computer aided design, rapid rototyping and finite element analysis. The application of thin-layer CT and Dicom standard ensures more accurate digital model establishment, and Mimics software allows more convenient reconstruction of the human skeleton and various soft tissues to facilitate further research.