A high-throughput screening to identify small molecules that suppress huntingtin promoter activity or activate huntingtin-antisense promoter activity.
Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of huntingtin (HTT). While there are currently no disease-modifying treatments for HD, recent efforts have focused on the development of nucleotide-based therapeutics to lower HTT expression. As an alternative to siRNA or oligonucleotide methods, we hypothesized that suppression of HTT expression might be accomplished by small molecules that either (1) directly decrease HTT expression by suppressing HTT promoter activity or (2) indirectly decrease HTT expression by increasing the promoter activity of HTT-AS, the gene antisense to HTT that appears to inhibit expression of HTT. We developed and employed a high-throughput screen for modifiers of HTT and HTT-AS promoter activity using luminescent reporter HEK293 cells; of the 52,041 compounds tested, we identified 898 replicable hits. We used a rigorous stepwise approach to assess compound toxicity and the capacity of the compounds to specifically lower huntingtin protein in 5 different cell lines, including HEK293 cells, HD lymphoblastoid cells, mouse primary neurons, HD iPSCs differentiated into cortical-like neurons, and HD hESCs. We found no compounds which were able to lower huntingtin without lowering cell viability in all assays, though the potential efficacy of a few compounds at non-toxic doses could not be excluded. Our results suggest that more specific targets may facilitate a small molecule approach to HTT suppression.


INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 1 PREDICTS INSULIN SENSITIVITY AND INSULIN AREA-UNDER-THE-CURVE IN OBESE, NONDIABETIC ADOLESCENTS.
To compare fasting insulin-like growth factor binding protein 1 (IGFBP-1) to other fasting indices as a surrogate marker of insulin sensitivity and resistance calculated from a 3-hour oral glucose tolerance test (oGTT). Fasting IGFBP-1 and oGTT were performed at 0 (n = 77), 52 (n = 54), and 100 (n = 38) weeks in a study investigating metformin treatment of obesity in adolescents. Insulin area-under-the-curve (IAUC) and the composite insulin sensitivity index (CISI) calculated from the oGTT were compared to fasting IGFBP-1, homeostasis model assessment-insulin resistance, and corrected insulin release at the glucose peak (CIRgp). IGFBP-1 and the ratio of IGFBP-1 to fasting insulin were significantly correlated with indices based on timed sampling, including IAUC, CISI, and CIRgp. In addition, a significant effect of IGFBP-1, but not IGFBP-1 to insulin at time zero, was observed for IAUC and CISI. Our results indicate that fasting IGFBP-1 may be a useful marker of insulin sensitivity and secretion.


What mental health teams want in their leaders.
The authors present the findings of the first phase of a 3-year study developing a skills training curriculum for mental health team leaders. A factor model empirically generated from clinical team members was compared to Bass' (1990) Multifactor Model of Leadership. Members of mental health teams generated individual responses to questions about effective leaders. Results from this survey were subsequently administered to a sample of mental health team members. Analysis of these data yielded six factors: Autocratic Leadership, Clear Roles and Goals, Reluctant Leadership, Vision, Diversity Issues, and Supervision. Additional analyses suggest Bass' Multifactor Model offers a useful paradigm for developing a curriculum specific to the needs of mental health team leaders.


Participation of the thalamic CM-Pf complex in attentional orienting.
The centre médian-parafascicular (CM-Pf) complex is located at the posterior intralaminar nuclei of the thalamus and forms part of the nonspecific thalamocortical projection system and the internal circuit of the basal ganglia. However, the functional roles of this complex remain to be fully elucidated. Here we have examined whether the CM-Pf complex is involved in the process of covert attention. We trained two macaque monkeys to perform a task in which a visual target stimulus for button release appeared at either the same location as the preceding visual instruction cue (a "validly cued target") or a location on the opposite side (an "invalidly cued target"). Reaction times (RTs) to a validly cued target were significantly shorter than those to an invalidly cued target, leading to a "validity effect" of about 20 ms. We recorded the activity of 97 neurons in the CM-Pf while the monkeys performed the attention task with the hand that was contralateral to the neuronal recording. Seventy CM-Pf neurons showed task-related activity after the appearance of either the instruction cue or the target stimulus: 33 neurons responded with a prominent short-latency facilitation (SLF), whereas 37 responded with a short-latency suppression followed by a long-latency facilitation (LLF). Most of the SLF neurons responded preferentially to a cue appearing on the contralateral side (76%) and to an invalidly cued target appearing on the contralateral side (61%). In contrast, LLF neurons showed a short-latency suppression after the cue stimulus, regardless of whether the cue appeared on the contra- or ipsilateral side (84%). Inactivating the CM-Pf complex by local injection (1 microl) of the GABA(A) receptor agonist muscimol (1-5 microg/microl) resulted in a significant increase in the RT to a validly cued target presented on the contra- but not the ipsilateral side. In contrast, inactivating the CM-Pf complex did not affect RTs to invalidly cued targets on either the contra- or the ipsilateral side. Thus the validity effect was abolished only on the contralateral side. We conclude that the CM-Pf complex plays a specific and essential role in the process of attentional orienting to external events occurring on the contralateral side, probably through the projection of primary outputs to the striatum, which is involved in the action-selection mechanisms of the basal ganglia.


Genetic factors in suicide: reassessment of adoption studies and individuals' beliefs about adoption study findings.
Based on multifaceted evidence (family, twin, adoption, molecular genetic, geographic, immigrant, and surname studies of suicide), the genetics of suicide is increasingly recognized. However, a comprehensive, stand-alone review of adoption studies in this area is unavailable, nor are there data on what people actually believe about adoption study findings. To reassess the available adoption studies of suicide and to provide novel data on beliefs relating to these. Key findings of the 3 existing adoption studies of suicide were reviewed and subjected to a meta-analysis. Beliefs pertaining to these were analyzed in 10 samples (total N = 1379) of different types (medical and psychology students, general population) from 6 countries. The combined evidence from adoption studies clearly supported genetic factors in suicide. Critical tests showed that suicide runs in the biological families of suicided (as well as schizophrenic or affectively ill) adoptees, but not in those of demographically matched healthy control adoptees alive (relative risk RR = 8.38, p = 0.0002). Individuals' beliefs about the plausibility of these findings were inconsistent and self-contradictory. Particularly, it was widely disbelieved that adoptees' risk of suicide resembles the one of their biological, not their adoptive, relatives (which is the case). Despite demonstrating a significant genetic effect, the evidence base from adoption studies of suicide is narrow. To broaden the evidence remains an important research agenda. Gaps in and deficiencies of this specific literature as well as general limitations of adoption study designs are discussed.


Trace analyses of arsenic in drinking water by inductively coupled plasma mass spectrometry: high resolution versus hydride generation.
A magnetic sector inductively coupled plasma mass spectrometer (ICPMS) was applied to the determination of arsenic in drinking water samples using standard liquid sample introduction in the high-resolution mode (M/delta M = 7800) and hydride generation in the low-resolution mode (M/delta M = 300). Although high mass resolution ICPMS allowed the spectral separation of the argon chloride interference, the accompanying reduction in sensitivity at high resolution compromised detection and determination limits to 0.3 and 0.7 microgram/L, respectively. Therefore, a hydride generation sample introduction method, utilizing a new membrane gas-liquid separator design, was developed to overcome the chloride interference. Due to the high transport efficiency and the 50-100 times higher sensitivity at M/delta M = 300, the HG-ICPMS method resulted in an over 2000-fold increase in relative sensitivity. The routine detection and quantification limits were 0.3 and 0.5 ng/L, respectively. The results for both methods applied to the analysis of over 400 drinking water samples showed very good agreement at concentrations above 1 microgram/L. For concentrations between 0.01 and 1 microgram/L, only HG-ICPMS provided accurate quantitative results. Membrane desolvation, mixed-gas plasmas, and the addition of organic solvents for the reduction of the ArCl+ interference were also investigated and evaluated for trace As determination.


[Association between echocardiography derived right ventricular function parameters with cardiac magnetic resonance derived right ventricular ejection fraction and 6-minute walk distance in pulmonary hypertension patients].
To explore the association between transthoracic echocardiography (TTE) derived right ventricular (RV) function parameters with cardiovascular magnetic resonance imaging (CMR) derived RV ejection fraction (RVEF) and 6 minute walk distance (6MWD) in pulmonary hypertension (PH) patients. A total of 40 PH patients (37 pulmonary artery hypertension (PAH) and 3 chronic thromboembolic pulmonary hypertension (CTEPH)) hospitalized in our department between March 2011 and March 2013 were enrolled in this study. PH diagnosis was established by right heart catheterization and TTE, CMR and 6MWT were performed within one week post TTE examination. TTE parameters included: tricuspid annular peak systolic excursion (TAPSE), isovolumic contraction acceleration (IVA), peak systolic velocity (S') at the lateral tricuspid annulus derived from tissue Doppler imaging, RV myocardial performance index (MPI) and RV fractional area change (FAC). RVEF was obtained from CMR. S' (r = 0.69, P < 0.001), TAPSE (r = 0.65, P < 0.001), FAC (r = 0.62, P < 0.001), IVA (r = 0.43, P = 0.006), MPI (r = -0.38, P < 0.05) correlated significantly with RVEF obtained from CMR. The best parameter to detect RVEF ≤ 20% was S' < 8.79 cm/s (area under the ROC curve was 0.92 (95% CI: 0.72-0.84), sensitivity 0.91, and specificity 0.80) . No correlation was found between TTE parameters and 6MWD and between RVEF obtained from CMR and 6MWD. S', derived from tissue Doppler imaging correlates best with RVEF obtained from CMR and may facilitate simple and quantitative assessment of RV function. The best parameter to detect RVEF ≤ 20% is S' < 8.79 cm/s.


"They don't leave you on your own:" a qualitative study of the home care of chronically ill children.
Learning to cope with a chronic illness is a process often demanding professional help that extends beyond the time spent in the hospital. Using interviews, this qualitative study describes the subjective experiences of five families with children who are chronically ill and the experiences of the two head nurses at External Care Services (EPD) in Berlin, Germany, an institution focused exclusively on home care for children. The positive experiences expressed by parents reflect the patient-oriented understanding of caring developed by the EPD, which strives for the qualified instruction of families and the building of caring relationships. As a result of the care offered by the EPD, many children are spared the repeated hospitalizations that so hinder the normalization of family life and impede family health.


Influence of patient characteristics on assessment of diabetes self-management support.
Factors contributing to patient-reported experiences of diabetes self-management support are not understood well, particularly over time. The aim of the study was to identify the contribution of patient characteristics to patient-reported quality of SMS. Using secondary data from a prospective clinical trial (n = 339) comparing three approaches of providing diabetes self-management support (Group Medical Visits, Automated Telephone Support, and Usual Care) in a diverse, underserved population, the influence of patient characteristics (e.g., age, gender, income, and health status) was examined on Patient Assessment of Chronic Illness Care ratings. At baseline, older age (p = .014), being female (p = .038), and having lower income (p = .001) were associated with lower ratings. Income and interactions involving income combined explained 12% of the variance in baseline ratings. Compared with White patients, African American and Asian patients tended to have higher baseline ratings (p = .076 and p = .045, respectively). Race or ethnicity influenced perceptions throughout the trial, explaining 5% of the variance at baseline and 2% of the variance in 1-year changes in Patient Assessment of Chronic Illness Care ratings. As expected, over 1 year, ratings increased more for patients in both intervention groups compared with the control group (p < .001). Ratings of healthcare quality are influenced by patient characteristics independent of the nature of the care provided. Understanding more precisely how these differences are associated with differences in clinical processes will be particularly important for efforts aiming to integrate patient-reported measures into assessments of healthcare quality during routine clinical care and clinical trials.


[The urological spiral. A real alternative to the indwelling catheter? Experience in 23 patients].
Our experiences are reported with the "intraprostatic spiral" in 23 high-risk patients with prostatic adenoma. The intraprostatic spiral was used only in selected patients for medical indications. Patients confined to bed as well as those with detrusor instability or secondary dilatation of the upper urinary tract were excluded. 14 of our patients (60.8%) showed excellent voiding ability, without residual urine and all of them were fully satisfied with the functioning of the prostatic spiral. The longest indwelling time in this group is now about 36 months. 9 of 23 patients (39.2%) were not satisfied with their prostatic spiral. In all of them, the spiral had to be removed later on. Urinary stress incontinence was the main reason for removal. Two thirds of the patients who were not satisfied with the functioning of the prostatic spiral, had a marked decrease in detrusor function. This is a major reason for unsatisfying prostatic spiral function. On average, the prostatic spirals had to be exchanged after 15-18 months because of incrustation. Nearly all patients (21 of 23) showed asymptomatic bacteriuria.


Financing home health-care products and services.
Factors affecting growth of the home health-care (HHC) industry are identified, basic principles of HHC product and service reimbursement are reviewed, and third-party payer coverage criteria and payment methods for HHC products and services are discussed. Reimbursement for HHC services has suffered from the absence of a financing mechanism for long-term care. Providers of HHC services are burdened by the laborious process of obtaining favorable coverage determinations for short-term-care patients when home care substitutes for institutional care. When home care is covered benefit, there is often a complex mix of confusing coverage rules, coverage criteria that differ among public and private payers, and interpretations of coverage criteria that differ among local carrier personnel. Private financing obstacles and federal budget deficits will deter the development of an adequate financing mechanism for HHC. The growth of health-maintenance organizations and competitive medical plans will help to reduce reimbursement complexity. Long-term changes in HHC financing may become less important if capitation payment is successful.


Surgical resection for metastatic neoplasms of the lung: experience at the University of Minnesota Hospitals.
Pulmonary resection for metastatic disease in 167 patients undergoing 207 thoracotomies resulted in a cumulative survival rate of 29% at five years and 20% at 10 years, with an operative mortality of 0.6%. The most favorable prognosis was associated with testicular and renal cell carcinomas and sarcomas. Less favorable tumors were malignant melanoma, carcinoma of the colon and rectum, and cervix uteri. A significant factor influencing survival was duration of disease-free interval with a 50% five-year survival rate in patients whose primary tumor was treated over five year ago. Patients with multiple pulmonary metastases had a five-year survival rate of 27% vs. 22% of patients with solitary metastases. Of 23 patients with tumor extending to the chest wall, diaphragm, or pleura, only two survived five years. Of 26 patients with mediastinal involvement none survived two years.


Technical pitfalls of transcervical extended mediastinal lymphadenectomy--how to avoid them and to manage intraoperative complications.
Transcervical extended mediastinal lymphadenectomy (TEMLA), introduced by our team in 2004, is a new technique for the preoperative staging of non-small cell lung cancer (NSCLC). The aim of TEMLA is to maximally accurately stage and possibly to improve late results of treatment of NSCLC. Operative techniques include a collar incision in the neck, elevation of the sternal manubrium with a special retractor, bilateral visualization of the laryngeal recurrent and vagus nerves, and dissection of all mediastinal nodal stations except for the pulmonary ligaments nodes (station 9, according to the Mountain-Dresler map). Generally, the mediastinal pleura are not violated, and no drain is left in the mediastinum. In this article, some important steps the facilitating safe and straightforward performance of TEMLA are presented, and methods of managing intraoperative complications is discussed.


Role of Spin Polarization and Dynamic Correlation in Singlet-Triplet Gap Inversion of Heptazine Derivatives.
The new generation of proposed light-emitting molecules for organic light-emitting diodes (OLEDs) has raised considerable research interest due to its exceptional feature─a negative singlet-triplet (ST) gap violating Hund's multiplicity rule in the excited S1 and T1 states. We investigate the role of spin polarization in the mechanism of ST gap inversion. Spin polarization is associated with doubly excited determinants of certain types, whose presence in the wave function expansion favors the energy of the singlet state more than that of the triplet. Using a perturbation theory-based model for spin polarization, we propose a simple descriptor for prescreening of candidate molecules with negative ST gaps and prove its usefulness for heptazine-type molecules. Numerical results show that the quantitative effect of spin polarization decreases linearly with the increasing highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) exchange integral. Comparison of single- and multireference coupled-cluster predictions of ST gaps shows that the former methods provide good accuracy by correctly balancing the effects of doubly excited determinants and dynamic correlation. We also show that accurate ST gaps may be obtained using a complete active space model supplemented with dynamic correlation from multireference adiabatic connection theory.


Regional cerebral blood flow during volitional expiration in man: a comparison with volitional inspiration.
1. Positron emission tomographic (PET) imaging of regional cerebral blood flow (rCBF), using a new 3-dimensional technique of data collection, was used to identify areas of neuronal activation associated with volitional inspiration and separately with volitional expiration in five normal male subjects. A comparison of the activated areas was also undertaken to isolate regions specific for one or other active task. 2. Scans were performed during intravenous infusion of H2(15)O under conditions of (a) volitional inspiration with passive expiration, (b) passive inspiration with volitional expiration and (c) passive inspiration with passive expiration. Four measurements in these three conditions were performed in each subject. Breathing pattern was well matched between conditions. 3. Regional increases in brain blood flow, due to increased neural activity associated with either active inspiration or active expiration, were derived using a pixel by pixel comparison of images obtained during the volitional and passive ventilation phases. Data were pooled from all runs in all subjects and were then processed to detect statistically significant (P < 0.05) increases in rCBF comparing active inspiration with passive inspiration and active expiration with passive expiration. 4. During active inspiration significant increases in rCBF were found bilaterally in the primary motor cortex dorsally just lateral to the vertex, in the supplementary motor area, in the right lateral pre-motor cortex and in the left ventrolateral thalamus. 5. In active expiration significant increases in rCBF were found in the right and left primary motor cortices dorsally just lateral to the vertex, the right and left primary motor cortices more ventrolaterally, the supplementary motor area, the right lateral pre-motor cortex, the ventrolateral thalamus bilaterally, and the cerebellum. 6. Using this modified and more sensitive PET technique, these findings essentially replicate those for volitional inspiration obtained in a previous study. For volitional expiration the areas activated are more extensive, but overlap with those involved in volitional inspiration. 7. The technique used has been successful in demonstrating the regions of the brain involved in the generation of volitional breathing, and probably in the volitional modulation of automatic breathing patterns such as would be required for the production of speech.


The patient with schizophrenia and his father. The father's role and personality traits in the dynamics of the family with a son suffering from schizophrenia.
The role of the father in the onset and development of schizophrenic disorder/disturbance is very often secondary as compared to that of the mother. This study deals with the father's sphere in the family with a patient/son suffering from schizophrenia, the traits of his personality and his relationship with his son/patient, and with his wife/the mother of the patient. The methods applied were clinical interview, structured interview and semantic differential. The following statistical procedures were used: correlation, componential, discriminative, factor and quasicanonical analyses. The results include some characteristic excerpts from clinical interviews with patients/sons and their fathers, projective perception of current family relationships, quasicanonical analysis of the father's, mother's and son's experiences of the patient's/son's early childhood, and the projective view of the father. Among the conclusions reached, the phenomenon of "dead father" is emphasized as one of the main factors in the onset and development of schizophrenic disorder/disturbance.


Assessment of the effects of contingent histamine injections on the reinforcing effectiveness of cocaine using behavioral economic and progressive-ratio designs.
Recent research has demonstrated that the drug, histamine, can function as a punisher of cocaine self-administration. However, little is known about how drug punishers affect the maximum reinforcing effectiveness of drugs as reinforcers. The goal of the present study was to determine if histamine, when self-administered as a mixture with cocaine, could reduce cocaine's maximum reinforcing effectiveness using two procedures designed for measuring reinforcing effectiveness. In the first experiment, rhesus monkeys were allowed to self-administer cocaine (0.1 mg/kg/inj) alone or as a mixture with histamine (0.012-0.05 mg/kg/inj) in a behavioral economic design. In the second experiment, monkeys were allowed to self-administer cocaine alone (0.006-0.56 mg/kg/inj) or as a mixture with histamine (0.025-0.1 mg/kg/inj) under a progressive-ratio schedule of reinforcement. In Experiment 1, histamine decreased the reinforcing effectiveness of cocaine in a dose-dependent manner as evidenced by increases in cocaine's demand elasticity with increases in histamine dose. In Experiment 2, histamine decreased cocaine's potency and effectiveness as a reinforcer in a dose-dependent manner as indicated by rightward and downward shifts, respectively, in the dose-response functions. The reinforcing effectiveness of cocaine can be reduced by contingent self-administration of histamine. These results indicate that combining drug punishers with drug reinforcers reduces the maximum reinforcing effect of the drug reinforcer, which suggests a use for drug punishers as a deterrent to drug abuse (e.g., as mixtures with prescription medications with abuse potential).


Vascularity in the reptilian spectacle.
Vascularization of the spectacle or brille of the reptile was demonstrated by biomicroscopy, histology, fluorescein (in vivo), and Microfil silicone rubber (in situ) injections. This unusual vascularity provides new evidence for reassessment of the origin and development of this structure, and a useful tool with which to do so.


Allosteric hammerhead ribozyme TRAPs.
A new mode of allosteric regulation of nucleic acid enzymes is described and shown to operate effectively with hammerhead ribozymes. In the "TRAP" design (for targeted ribozyme-attenuated probe), a 3' terminal "attenuator" anneals to conserved bases in the catalytic core to form the "off" state of the ribozyme. Binding of RNA or DNA to an antisense sequence linking the ribozyme and attenuator frees the core to fold into an active conformation, even though the antisense sequence itself does not interfere with the ribozyme. TRAP hammerheads based on the previously characterized HH8 ribozyme were shown to be activated more than 250-fold upon addition of the sense strand. RNA oligonucleotides were more effective activators than DNA oligos, consistent with the known relative helix stabilities (RNA-RNA > RNA-DNA). Oligonucleotides that directly paired with the attenuator gave up to 1760-fold activation. The magnitude of the activation was greater when the oligo was added prior to folding than if it was added during the cleavage reaction. The TRAP design requires no prior knowledge of (deoxy)ribozyme structure beyond identification of the essential core. Thus, this approach should be readily generalizable to other systems for biomedicine, sensor technology, and additional applications.


Dietary and lifestyle practices of Hmong in California.
As Hmong adapt to life in Fresno, California, their dietary and lifestyle patterns are examined. Data on tobacco and alcohol use, dietary practices, and socio-demographic variables were collected from a convenience sample, stratified by age and sex. The 248 participants were interviewed. Descriptive analyses reveal that more than 63% of Hmong adults were either overweight or obese. Only 57% could speak English fluently, and 71% were economically impoverished. Hmong do not consume tobacco and alcoholic products excessively. Rice, chicken, beef, and eggs were the most frequently identified food items. Fruits and vegetables were also identified. Low alcohol and tobacco consumption may offer Hmong some protection against certain diseases. However, low socioeconomic status and rapid urbanization may have resulted in a shift from a high-energy expenditure lifestyle and high fiber diets to a sedentary lifestyle with high saturated fat food diets, which may be detrimental to the health of many Hmong.


Thermally stimulated relaxations in DNA.
The thermally stimulated depolarization current (TSDC) measurements in frozen aqueous solutions, gels and solid layers of NaDNA show typically up to three dipolar overlapping peaks in the low-temperature range of 80-150 K. Up to four discrete relaxation peaks have been observed at higher temperatures above 150 K. The low-temperature TSDC peaks are due to the dipolar relaxations of free and loosely bound water which crystallizes. Part of bound water especially in the first hydration shell of DNA molecule is at low temperatures in the form of glass. The transition of this glass from solidlike behavior to liquidlike behavior observed mainly in gels and solid samples is associated with a previously founded TSDC relaxation peak. The peak is at its maximum at 165-250 K depending on the sample humidity. Existence of this relaxation in the samples with water contents in a broad range confirms, that the slowly relaxing shell (minimally 5-7 water molecules/nucleotide) closely associated with DNA double helix retains its characteristics. Also another peak of the high-temperature band at 180-205 K which was observed in the samples at hydration 2-1800 g H2O/g dry NaDNA is due to a relaxation in the sample volume. At the highest temperatures relax the space charges trapped at the electrodes.


The Psa fimbriae of Yersinia pestis interact with phosphatidylcholine on alveolar epithelial cells and pulmonary surfactant.
The pH 6 antigen (Psa) of Yersinia pestis consists of fimbriae with adhesive properties of potential importance for the pathogenesis of plague, including pneumonic plague. The Psa fimbriae mediate bacterial binding to human alveolar epithelial cells. The Psa fimbriae bound mostly to one component present in the total lipid extract from type II alveolar epithelial cells of the cell line A549 separated by thin-layer chromatography (TLC). The Psa receptor was identified as phosphatidylcholine (PC) by TLC using alkali treatment, molybdenum blue staining, and Psa overlays. The Psa fimbriae bound to PC in a dose-dependent manner, and binding was inhibited by phosphorylcholine (ChoP) and choline. Binding inhibition was dose dependent, although only high concentrations of ChoP completely blocked Psa binding to PC. In contrast, less than 1 muM of a ChoP-polylysine polymer inhibited specifically the adhesion of Psa-fimbriated Escherichia coli to PC, and type I (WI-26 VA4) and type II alveolar epithelial cells. These results indicated that the homopolymeric Psa fimbriae are multimeric adhesins. Psa also bound to pulmonary surfactant, which covers the alveolar surface as a product of type II alveolar epithelial cells and includes PC as the major component. The observed dose-dependent interaction of Psa with pulmonary surfactant was blocked by ChoP. Interestingly, surfactant did not inhibit Psa-mediated bacterial binding to alveolar cells, suggesting that both surfactant and cell membrane PC retain Psa-fimbriated bacteria on the alveolar surface. Altogether, the results indicate that Psa uses the ChoP moiety of PC as a receptor to mediate bacterial binding to pulmonary surfactant and alveolar epithelial cells.


In Silico Characterization of RNASEH2A Pathogenic Variants and Identification of Novel Splice Site Donor Variant c.549+1G>T in Indian Population.
Background Aicardi-Goutieres syndrome (AGS) is a genetic disorder that has variable manifestations including neurological, immunological, and sometimes other system involvement in various combinations. Considering the high genetic and clinical diversity of AGS and the importance of RNASEH2 complex in the biological system, it is important to take a systematic approach to delineate the genetic diagnosis and impact of missense mutations. Methods Clinical targeted gene sequencing followed by Sanger validation was performed in an individual with the clinical features of AGS. Protein modeling studies of all the reported RNASEH2A missense variants till date were performed using freely available web servers BioGrid, ShinyGO. Protein structures were visualized using Pymol. Results and discussion We identified a novel homozygous splice site donor variant c.549+1G>T in RNASEH2A. Furthermore protein-interactome studies identifiedpotential genetic interactors that include RNASEH2A, RNASEH2B, TYMS, RNASEH2C, RPA1, ORC3, ORC2, CDC6, PCNA, LIG1, PRIM1, RFC2, DUT, GINS1, MCM7, FEN1, MCM4, GINS2, CDK4, and MCM5. Identified genes were mapped to specific pathways using SHINY GO. DNA replication and cell cycle, centrosome cycle, post-replication repair, nucleic acid and metabolic process, cellular response to stress, DNA metabolic process, nucleic acid phosphodiester bond hydrolysis, RNA phosphodiester bond hydrolysis, and DNA biosynthetic process were identified as the linked pathways with the prioritized genes. Conclusion In conclusion, a sophisticated genotype and phenotype correlation followed by linking the genes to the key biological pathways opens new avenues to understand disease pathology and plan for therapeutic interventions.


Two polydimethylsiloxane rod extraction methods for the sensitive determination of phenolic compounds in water samples.
Simple, precise, and low-cost methods for the simultaneous determination of phenolic endocrine disrupting compounds such as bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water samples were developed. The Direct, in situ derivatization methods are based on polydimethylsiloxane rod extraction followed by liquid desorption and chromatographic analysis by liquid chromatography and diode array detection. Several parameters affecting the extraction and desorption of the phenolic compounds and their acetylated derivates were studied, as well as the chromatographic and detection conditions. For the direct method, determination coefficients (r(2) ) > 0.990 and LODs in the 0.6-2 μg/L range were obtained for all compounds except bisphenol A (9.5 μg/L). With the derivatization-based method, based on in situ acetylation, lower limits of detection (0.3-0.9 μg/L) were obtained for all the compounds with r(2) > 0.988 and RSDs in the 2-9% range. The developed methods were applied to the analysis of spiked water samples obtaining recoveries of between 60.2 and 131.7% for the direct method, and of between 76.6 and 108.2% for the derivatization-based method. The results demonstrate the feasibility of using these two methods for determining bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water.


Fibromatosis-like metaplastic carcinoma of the breast: Two case reports.
Fibromatosis-like metaplastic carcinoma is classified as a rare type of metaplastic carcinoma of the breast by the 2012 WHO pathological and genetic classification criteria for breast tumors, which takes hyperplastic spindle cells as the main component and is often misdiagnosed as benign stromal proliferative lesions or benign mesenchymal tumors of the breast because of its mild morphology. Here, we collected the clinical data of 2 cases of fibromatosis-like metaplastic carcinoma of the breast and performed pathomorphological observation and immunohistochemical staining of the surgically resected specimens. According to the clinical features, imaging features, immunophenotype, diagnosis and differential diagnosis of 2 cases of fibromatosis-like metaplastic carcinoma of the breast, it was further differentiated. Case 1: A 56-year-old postmenopausal female was admitted due to "right breast mass for over 1 year and local ulceration for over 1 mo". Physical examination showed a mass with a diameter of 4.5 cm × 5.5 cm palpable at 2.5 cm from the nipple at 1 o'clock in the right breast. The skin on the surface of the mass ruptured about 3 cm, with a small amount of exudation and bleeding, less clear boundary, hard texture, fair activity, without obvious tenderness. No obvious abnormality was palpable in the left breast. No enlarged lymph nodes were palpable in the bilateral axillae and bilateral supraclavicular region. After removing the mass tissue, it was promptly sent to the pathology department for examination. Case 2: Female, 52-years-old, premenopausal, admitted due to "right breast mass for more than 3 mo". Physical examination showed a 4.0 cm × 4.0 cm diameter mass palpable at 2.0 cm of the nipple in the lower outer 7 o'clock direction of the right breast, with less clear boundary, hard texture, fair activity, no significant tenderness, no palpable significant abnormalities in the left breast, and no palpable enlarged lymph nodes in the bilateral axillae and bilateral supraclavicular region. The mass was resected and sent for pathological examination. Postoperative pathological examination revealed fibromatosis-like metaplastic carcinoma of the breast in both patient 1 and patient 2. No systemic therapy and local radiotherapy were performed after surgery, and no tumor recurrence or metastasis was observed. Fibromatosis-like metaplastic carcinoma of the breast is a rare subtype of metaplastic carcinoma that is often misdiagnosed, and the diagnosis relies on medical history collection, complete sampling, and full use of immunohistochemical assessment. The risk of lymph node and distant metastasis is low, and the current treatment is based on complete surgical resection. The efficacy of systemic radiotherapy and chemotherapy is not clear.


Analysis of Mitochondrial Dimensions and Cristae Structure in Pluripotent Stem Cells Using Transmission Electron Microscopy.
Dynamic alterations to mitochondrial structure and function regulate cell fate decisions and underlie multiple age-related and genetic diseases that are modeled using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Transmission electron microscopy (TEM) can be used to obtain high-resolution micrographs of mitochondria, but mitochondrial ultrastructure is easily distorted during specimen processing. This unit describes a method that preserves mitochondrial membrane structure from adherent ESC cultures for TEM sample preparation. This procedure is useful for assessing ultrastructural changes to mitochondria during differentiation, reprogramming, or experimental manipulation of ESC metabolism. We provide comprehensive protocols for: (1) preparation of ESC cultures for TEM; (2) retrieval of thin sections from individual ESCs; and (3) contrast staining and morphometric analysis of mitochondria and cristae. This unit also describes an alternative procedure for samples with low cell numbers and a supporting protocol for morphometric image analysis. Collectively, these protocols allow for the observation and quantitative analysis of mitochondria in ESCs. © 2018 by John Wiley & Sons, Inc.


Hypertension as a predictor of adverse cardiac events in patients with borderline fractional flow reserve.
The cut-off value myocardial fractional flow reserve (FFRmyo) < 0.75 identifies patients with clinically significant coronary stenosis. Normally PCI is deferred with a FFRmyo > or = 0.75. Other clinical characteristics may affect such treatment decision. Therefore, we studied the association between baseline characteristics and clinical outcomes in an unselected patient cohort with coronary artery disease, with intermediate coronary stenosis, initially referred for PCI, but in whom the intervention was deferred on the basis of FFRmyo > or = 0.75. Angiographic analysis and follow-up were performed in 152 patients with stable or unstable angina pectoris with intermediate coronary stenosis severity and normal left ventricular function. A major adverse cardiac event (MACE) was defined as postprocedural acute myocardial infarction (AMI), target vessel revascularization (TVR) and verified cardiac death. More adverse cardiac events occurred in patients with 0.75 < or = FFRmyo < 0.80 (24/30) compared with FFRmyo > or = 0.80 (9/97) (P < 0.001). Hypertension, diabetes and hyperlipidaemia were significantly associated with the occurrence of MACE in the univariate analyses. Logistic regression analyses showed that only hypertension remained as a significant independent predictor of MACE for patients with 0.75 < or = FFRmyo < 0.80 (P < 0.10). In an unselected patient population with coronary artery disease, a FFRmyo cut-off value of 0.8 should be used in hypertensive patients to discriminate between clinically significant coronary stenosis.


Understanding self-assembled amphiphilic peptide supramolecular structures from primary structure helix propensity.
Small amphiphilic peptides are attractive building blocks to design biocompatible supramolecular structures via self-assembly, with applications in, for example, drug delivery, tissue engineering, and nanotemplating. We address the influence of systematical changes in the amino acid sequence of such peptides on the self-assembled macromolecular structures. For cationic-head surfactant-like eight-residue peptides, the apolar tail amino acids were chosen to systematically vary the propensity to form an alpha-helical secondary structure while conserving the overall hydrophobicity of the sequence. Characterization of the supramolecular structures indicates that for short peptides a beta-sheet secondary structure correlates with ribbonlike assemblies while random-coil and alpha-helical secondary structures correlate with assembly of rods.


Dermatologic management of oncotherapy side effects: A proposed algorithm.
Since the introduction of the first chemotherapeutic regimens for the treatment of oncological disease, hundreds of drugs have been approved for cancer treatment and many more are under investigation. The development of newer drugs such as target therapies, immuno-oncotherapies, and hormonal therapies has increased in specificity with the development of smaller molecules and more selective targets. Cutaneous side effects are now well known for both standard chemotherapy and targeted therapies. The correct diagnosis and management of these effects are of vital importance both to optimize therapeutic success rates and to reduce the patient's suffering. In fact, the appearance of a cutaneous adverse event can be responsible for a reduction in drug dosage or worse its suspension. In order to achieve this objective, we propose a management algorithm, based on three different steps, before, during, and after the oncological treatments, respectively. Our proposal underlines the importance of correct skin care measures to limit or reduce the severity of side effects.


Body temperatures of Manis pentadactyla and Manis javanica.
Body temperature is an important parameter for assessing animal health and physiological function. An iButton thermometer was used to measure the body temperatures of three Chinese pangolins (Manis pentadacyla) and three Sunda pangolins (M. javanica). The body temperature of Chinese pangolins was 33.2 ± 0.95°C (30.6-34.2°C, n = 3) and that of Sunda pangolins was 32.8 ± 0.48°C (31.7-34.2°C, n = 3). The daily variation in body temperature was 1.0-2.9°C in three Chinese pangolins and 1.2-1.9°C in three Sunda pangolins. The body temperature of Sunda pangolins tended to rise at night, with the highest body temperatures occurring mostly at night. This study provides valuable body temperature data for Chinese and Sunda pangolins and lays the foundation for future research on their mechanisms of body temperature regulation.


A three-dimensional CuII-WIV bimetallic porous assembly containing a zigzag ladder structure.
The asymmetric unit of the three-dimensional Cu(II)-W(IV) polymeric assembly [Cu(en)(2)][Cu(en)][W(CN)(8)].4H(2)O](n) (en is ethylenediamine, C(2)H(8)N(2)) or [Cu(2)W(CN)(8)(C(2)H(8)N(2))(3)].4H(2)O](n), which can be named as polymeric bis(ethylenediamine)copper(II) (ethylenediamine)copper(II) octacyanotungstate(IV) tetrahydrate or penta-micro-cyano-tricyanotris(ethylenediamine)dicopper(II)tungsten(IV) tetrahydrate, consists of two half [Cu(en)(2)](2+) cations (Cu(2+) on inversion centres), a [Cu(en)](2+) cation and a [W(CN)(8)](4-) ion, together with four water molecules. The latter Cu(II) site is coordinated by five N atoms from an en ligand and by three cyanides in a distorted square-pyramidal geometry. The Cu(II) atoms of the two [Cu(en)(2)](2+) cations reside in an elongated octahedral coordination environment, and one of them is localized at a centre of inversion. The W atom is coordinated by eight cyano groups in an irregular square antiprism. Five of these act as bridging units connecting the W and the three Cu atoms, to form an infinite three-dimensional porous network containing a zigzag ladder structure.


Mutual Protein-Ligand Conformational Selection Drives cGMP vs. cAMP Selectivity in Protein Kinase G.
Protein kinase G (PKG) is a major receptor of cGMP, and controls signaling pathways distinct from those regulated by cAMP. However, the contributions of the two substituents that differentiate cGMP from cAMP (i.e. 6-oxo and 2-NH2) to the cGMP-versus-cAMP selectivity of PKG remain unclear. Here, using NMR to map how binding affinity and dynamics of the protein and ligand vary along a ligand double-substitution cycle, we show that the contributions of the two substituents to binding affinity are surprisingly non-additive. Such non-additivity stems primarily from mutual protein-ligand conformational selection, whereby not only does the ligand select for a preferred protein conformation upon binding, but also, the protein selects for a preferred ligand conformation. The 6-oxo substituent mainly controls the conformational equilibrium of the bound protein, while the 2-NH2 substituent primarily controls the conformational equilibrium of the unbound ligand (i.e. syn versus anti). Therefore, understanding the conformational dynamics of both the protein and ligand is essential to explain the cGMP-versus-cAMP selectivity of PKG.


Quantitative analysis of the coverage density of Br- ions on Pd{100} facets and its role in controlling the shape of Pd nanocrystals.
We report an approach based on a combination of inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy for quantitative analysis of the role played by Br(-) ions in the synthesis of Pd nanocrystals. The Br(-) ions were found to adsorb onto Pd{100} facets selectively with a coverage density of ca. 0.8 ion per surface Pd atom. The chemisorbed Br(-) ions could be removed via desorption at an elevated temperature under reductive conditions. They could also be gradually released from the surface when Pd cubic seeds grew into cuboctahedrons and then octahedrons. On the basis of the coverage density information, we were able to estimate the minimum concentration of Br(-) ions needed for the formation of Pd nanocubes with a specific size. If the concentration of Br(-) ions was below this minimum value, not all of the {100} facets could be stabilized by the capping agent, leading to the formation of nanocubes with truncated corners. The quantitative analysis developed in this study is potentially extendable to other systems involving chemisorbed capping agents.


Assembly of Submicron Sized Ag, Co, and Ni Particles Into Thin Films at Liquid/Liquid Interfaces.
Submicron sized particles of Ag, Co and Ni were synthesised by reducing metal salts in ethylene glycol (EG) in the presence of polyvinylpyrrolidone (PVP). These particles on dispersion in water when held in contact with a toluene layer were found to assemble into dense films extending over large areas at the interface between the two liquids. The effect of reaction conditions (solvent, precursor concentration, temperature) on the synthesis and assembly of the particles was studied. The characteristics of the interfacial deposits and the particulate dispersions were studied by scanning electron microscopy (SEM), X-ray diffraction (XRD), ultraviolet-visible (UV-Vis) spectroscopy and dynamic light scattering (DLS).


The role of Taiwan's National Health Insurance program in influencing adequate prenatal care.
This paper reviews achievements in the utilization of prenatal care by pregnant women in Taiwan by analysing the 1989 and 1996 National Maternal and Infant Health Survey data. More precisely, it identifies and examines the programmatic and non-programmatic factors that influence prenatal care utilization, thus determining the areas that require further attention from the programe. Logistic regression results show that the adequacy of prenatal care use was significantly associated with the implementation of the National Health Insurance (NHI). A higher likelihood of adequate care utilization was found among women who were married or employed, had a higher level of education, had more experience with regard to pregnancy and were at higher risk in terms of obstetrics. The effect of facility choice showed variations after the implementation of the NHI programme. Prior to NHI, no differences were noted between the use of clinics and hospitals. After the implementation of NHI, on the other hand, women who received most of their care from clinics had a higher likelihood of receiving more adequate prenatal care than those who received care from hospitals. Regional differences in seeking adequate prenatal care were also evident. Mothers who were living in southern areas were less likely to receive adequate prenatal care despite the implementation of NHI. The Bureau of NHI, therefore, still needs to work on mechanisms to ensure that more attention is given to the distribution of its medical resources and that additional health care accessibility is provided to pregnant women in these areas.


Reduced cardiovascular risks in women with endometriosis or polycystic ovary syndrome carrying a common functional IGF1R variant.
Is the increased future cardiovascular risk seen in women with endometriosis or polycystic ovary syndrome (PCOS) mitigated by functional insulin-like growth factor-1 receptor (IGF1R) single-nucleotide polymorphism (SNP) rs2016347 as previously shown in women with hypertensive disorders of pregnancy? This cohort study found that women with endometriosis or PCOS who carry a T allele of IGF1R SNP rs2016347 had a reduced future risk of developing cardiovascular disease (CVD) and associated risk factors, with risk reduction dependent on cohort era. Women with endometriosis or PCOS have been shown to have an increased future risk of CVD and associated risk factors with limited predictive ability. This retrospective cohort study took place in the Nurses' Health Study 2 (NHS2), which enrolled 116 430 participants in 1989 who were followed through 2015. The study population was analyzed in its entirety, and subdivided into entry (pre-1989) and after entry (post-1989) exposure cohorts. All NHS2 participants were eligible for inclusion in the study, 9599 (8.2%) were excluded for missing covariates. The NHS2 enrolled female registered nurses from 14 different states who ranged in age from 25 to 42 years at study entry. Data were collected from entry and biennial questionnaires, and analysis conducted from November 2020 to June 2021. Cox proportional hazard models were used to assess risk of CVD, hypertension (HTN), hypercholesterolemia (HC) and type 2 diabetes, both with and without genotyping for rs2016347. While women without endometriosis or PCOS, as a whole, demonstrated no impact of genotype on risk in either cohort, women with endometriosis carrying a T allele had a lower risk of CVD (hazard ratio (HR), 0.48; 95% CI, 0.27-0.86, P = 0.02) and HTN (HR, 0.80; 95% CI, 0.66-0.97, P = 0.03) in the pre-1989 cohort, while those in the post-1989 cohort had a decrease in risk for HC (HR, 0.76; 95% CI, 0.62-0.94, P = 0.01). Women with PCOS in the post-1989 cohort showed a significant protective impact of the T allele on HTN (HR, 0.44; 95% CI, 0.27-0.73, P = 0.002) and HC (HR, 0.62; 95% CI, 0.40-0.95, P = 0.03). Data on specific endometriosis lesion locations or disease stage, as well as on PCOS phenotypes were lacking. In addition, data on systemic medical treatments beyond the use of oral contraceptives were missing, and these treatments may have confounded the results. These findings implicate systemic dysregulation of the insulin-like growth factor-1 axis in the development of HTN, HC and clinical CVD in endometriosis and PCOS, suggesting a common underlying pathogenetic mechanism. The NHS2 infrastructure for questionnaire data collection was supported by National Institute of Health (NIH) grant U01CA176726. This work was also supported in part by NIH and National Cancer Institute grant U24CA210990; as well, research effort and publication costs were supported by the Elizabeth MA Stevens donor funds provided to the Buck Institute for Research on Aging. The authors declare they have no conflicts of interest. N/A.


The characteristics of HPV integration in cervical intraepithelial cells.
Cervical cancer is one of the most common malignant tumors in gynecology. Deploying HIVID, a cost-effective technique to detect HPV integration sites, our team had studied the characteristics of HPV integrations in cervical exfoliated cells. Our results indicated that both the sample proportion and the number of HPV integrations gradually increased following the development of cervical lesion. Meanwhile, our data also revealed that there were recurrent genes integrated by HPV in cervical exfoliated cells. Collectively, the HPV integration breakpoints were highly enriched in the intron and promoter regions. Intriguingly, the gene pathway analysis indicated that the HPV-integrated genes were strongly inclined to pathways of metabolism of xenobiotics by cytochrome P450, chemical carcinogenesis and steroid hormone biosynthesis. In conclusion, this study unveiled the HPV integration patterns and the associated recurrent genes in cervical epithelial exfoliated cells. Altogether, our data suggested that the HPV integrations in cervical exfoliated cells might have vital clinical significance, and probably also diagnostic and/or prognostic values in future clinical applications.


[Azoospermia factor and male infertility].
Azoospermia factor (AZF) microdeletions of the Y chromosome, which occur in 1 - 55% of infertile men, are closely associated with severe spermatogenic failure and represent the most frequent molecular genetic causes of azoospermia and severe oligozoospermia. Researches on AZF and its related genes, approaching the mechanisms of spermatogenic failure at the molecular level, are of great significance for the diagnosis, treatment and prognosis of male infertility. The detection of AZF microdeletions can provide scientific basis for correct diagnosis and reasonable therapy. This article outlines the structure and functional characteristics of AZF, as well as its relationship with male infertility, cryptorchidism, varicocele, Klinefelter syndrome, seminoma, and recurrent abortion.


A randomized study of surgical site infiltration with bupivacaine or ketamine for pain relief in children following cleft palate repair.
Wound infiltration with ketamine reduces postoperative pain after tonsillectomy by NMDA receptor blockade and local anesthetic effect. To evaluate the postoperative analgesia after surgical site infiltration with bupivacaine or ketamine in children undergoing cleft palate surgery. After institutional ethics committee approval and parental consent, 50 ASA-1 children of age 1-6 years undergoing palatoplasty were included in this prospective randomized double-blind study. A standardized technique of general anesthesia was used. The surgical site was infiltrated with either 2 mg·kg(-1) of bupivacaine (Group B) or 0.5 mg·kg(-1) of ketamine (Group K). Pain (Children Hospital Eastern Ontario Pain Score), sedation, dysphagia, nausea, vomiting, and sleep pattern were assessed postoperatively up to 24 h. CHEOPS scores were similar in both the groups up to 12 h but were lower with ketamine compared with bupivacaine at 24 h postoperatively (P = 0.01). Fewer children required rescue analgesics in Group K (28%) than in Group B (64%; P < 0.01). The time to first rescue analgesic and the amount of analgesics used in 24 h were similar in the two groups. Fewer children suffered from dysphagia in Group K (52%) than in Group B (88%; P < 0.01). More children in Group B had disturbed sleep than in Group K at 6 (88% vs 56%; P = 0.012) and 12 h (60% vs 24%; P = 0.01) postoperatively. None of the children had deep sedation, desaturation or respiratory depression. Surgical site infiltration with either bupivacaine or ketamine provides adequate analgesia and is devoid of major side effects. Ketamine is superior to bupivacaine in terms of requirement of rescue analgesic, peaceful sleep pattern and early resumption of feeding.


Effect of microorganisms isolated from the upper gut of malnourished children on intestinal sugar absorption in vivo.
The effect of microorganisms isolated from the upper gastrointestinal tract of malnourished children on intestinal sugar absorption was studied in rats in vivo. Pure cultures of organisms were grown overnight in a nutrient broth and the resultant supernatant fluid which contained microorganisms in similar numbers to those found in the patients was used as the basic solution for jejunal perfusions which were done in anesthetized adult Wistar rats. The substrate used was arbutin (p-hydroxphenyl-beta-glucoside), a recognized marker of intestinal active sugar transport. Of the gram-positive cocci studied, only the saprophyte, Staphylococcus saprophyticus, did not adversely affect the intestinal absorption of arbutin. The only gram-positive rod studied, a lactobacillus, also significantly inhibited arbutin absorption. Of the Enterobacteriaciae studied, Salmonella paratyphi B, a Shigella and Proteus sp. did not affect arbutin absorption. All the species of Escherichia coli studied, including a nonpathogenic variety, inhibited absorption. Klebsiella sp. and Pseudomonas sp. were also effective. Of the Candida sp., C. albicans and C. parapsilosis were inhibitory while C. tropicalis was not. These results suggest that microorganisms not generally considered enteropathogenic may adversely affect intestinal function when present in the lumen of the gut in excessive numbers and contribute to the production of diarrhea in children with malnutrition.


Efficacy of etanercept for the treatment of psoriasis: an overview of the Italian clinical experience from the real-life setting and independent studies.
Etanercept is a dimeric fusion protein consisting of the extracellular portion of tumor necrosis factor (TNF) p75 receptor and human IgG1 Fc fragment, which, similarly to the physiological soluble TNF receptor, is capable of binding TNF-α and lymphotoxin. The mechanism of action of etanercept in psoriatic disease and other approved indications is mediated by the neutralization of soluble TNF-α leading to a modulation of the immune response. Clinical trials have provided robust evidence supporting the sustained efficacy and safety of etanercept in psoriasis, as both intermittent and continuous therapy. The aim of this manuscript was to review the efficacy profile of etanercept in psoriasis according to the clinical experience gained by Italian dermatological centers and derived from the available publications on this topic. Everyday practice confirms that etanercept is a valuable and flexible therapeutic tool for the management of high-need psoriasis patients.


Increasing the antibacterial activity of gentamicin in combination with extracted polyphosphate from Bacillus megaterium.
The aim of this research was production of polyphosphate (poly P) and study on its antibacterial effects. Poly P granules in the cells were observed with the help of Albert staining and extracted by Mussig-Zufika method. Thin layer chromatography and nuclear magnetic resonance spectroscopy ((31) P NMR) were used to characterize properties of these granules. Relation of phosphorus consumption and poly P production with growth was determined by the vanado-molybdate colorimetric method. Among the 60 strains of bacteria isolated from the environmental samples, strain G11 showed ability for the formation of high levels of poly P. Phylogenetic analysis showed that this isolate had 98% similarity with Bacillus megaterium. 16S rRNA sequence of isolate was deposited in GenBank with accession number JX115009. The average poly P chain length was 10·5 in this bacterium. The antimicrobial activity of bacterial extracted poly P was much better than chemical poly P, and its interaction with gentamicin increased the activity of this drug. The best synergistic activity of this interaction was observed for Corynebacterium glutamicum and Pseudomonas aeruginosa species. The highest adsorption of phosphorus occurred in stationary phase of growth curve, and then the amount of phosphorus increased in medium by degradation of stored poly P. In this study, we isolated a high-level producer bacterium of poly P and extracted poly P by chemical treatment. In addition, we compared antimicrobial activity of chemical poly P with bacterial poly P and its interaction with gentamicin against both Gram-positive and Gram-negative bacteria. Many studies have shown that bacteria are becoming resistant to gentamicin sulphate. In this study, we approved that Acinetobacter baumannii, a pathogenic gentamicin-resistant bacterium, is sensitive to bacterial poly P, and thus, this poly P can be substituted for gentamicin in treatment.


Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies.
We report five of 38 patients with stiff person syndrome (SPS), who also had cerebellar disease, gait ataxia, dysarthria, and oculomotor dysfunction (SPS-Cer). Cerebellar manifestations either preceded SPS or occurred concurrently. Brain MRI was normal. The intrathecal production of glutamic acid decarboxylase antibodies was elevated. Gamma-aminobutyric acid-enhancing drugs and immunotherapies improved only the stiffness. SPS-Cer is a distinct subset of SPS causing a more severe and complex clinical phenotype.


Psychosocial Stress and Risk of Myocardial Infarction: A Case-Control Study in Belgrade (Serbia).
The purpose of this study was to investigate which psychosocial risk factors show the strongest association with occurrence of myocardial infarction (MI) in the population of Belgrade in peacetime, after the big political changes in Serbia. A case-control study was conducted involving 154 consecutive newly diagnosed patients with MI, and 308 controls matched by gender, age, and place of residence. According to conditional logistic regression analysis, after adjustment for conventional coronary risk factors, the odds ratios (95% confidence intervals) for work-related stressful events, financial stress, deaths and diseases, and general stress were 3.78 (1.83-7.81), 3.80 (1.96-7.38), 1.69 (1.03-2.78), and 3.54 (2.01-6.22), respectively. Among individual stressful life events, the following were independently related to MI: death of a close family member, 2.21 (1.01-4.84); death of a close friend, 42.20 (3.70-481.29); major financial problems, 8.94 (1.83-43.63); minor financial problems, 4.74 (2.02-11.14); changes in working hours, 4.99 (1.64-15.22); and changes in working conditions, 30.94 (5.43-176.31). During this political transition period , stress at work, financial stress, and stress in general as they impacted the population of Belgrade, Serbia were strongly associated with occurence of MI.


Effects of tibiofemoral compression on ACL forces and knee kinematics under combined knee loads.
Injuries to the anterior cruciate ligament (ACL) can occur during landing from a jump or changing direction during a cutting maneuver. In these instances, the knee is subjected to combined forces and moments as it flexes under tibiofemoral compression force (TCF). We hypothesized that TCF would increase ACL forces and tibiofemoral motions under isolated and combined modes of loading relevant to knee injury. ACL force and knee kinematics were recorded in human cadaveric specimens during knee flexion from 0° to 50° under the following test conditions (alone and in combination): 2 N-m internal tibial torque (IT), 5 N-m valgus moment (VM), and 45N anterior tibial force (AF). Knees were tested with 25N (baseline), 250N, and 500N TCF. ACL force increased with knee flexion during all tests. As the knee was flexed, VM produced a coupled internal tibial rotation, and IT produced a coupled valgus rotation. ACL forces with IT + VM were significantly higher than with IT alone (beyond 10° flexion) or VM alone (at all flexion angles). Increasing the level of TCF above baseline did not significantly change valgus or tibial rotations for any loading condition, but did significantly increase anterior tibial translation (ATT) at all flexion angles and ACL force at flexion angles beyond 5° to 15°. Addition of AF to tests with IT + VM significantly increased ATT and ACL force without significantly altering internal and valgus rotations. The mechanism of high ACL force generation from increased TCF was related to ATT and not internal or valgus rotations of the tibia. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.


[Quantitative changes of rat's alpha 2 macroglobulin concentration by influence of carbon tetrachloride (author's transl)].
We examined the influence of carbon tetrachloride on the rat liver by means of some biological parameters (body mass, GPT-activity, time of hexobarbital narcosis, aminophenazone demethylation) in comparison to the relative concentration of alpha 2 AP under conditions of a long time experiment (8 weeks). The results show, that merely the alpha 2 AP is altered significant in test groups after 1 d of treatment in comparison to the other parameters. Afterwards, under lasting carbon tetrachloride influence the macroglobulin decreases below normal levels. The potential diagnostic value of the alpha 2 AP for toxicological examinations is discussed.


Craniopagus, Laleh and Ladan twins, sagital sinus.
Adult craniopagus twins aged 29 years who succumbed to the surgical separation are being presented posthumously. Neuroimaging studies had revealed a total type 3 craniopagus with a common superior sagittal sinus beginning at its distal half and draining into a common Torcular Herophili. In July 2003, neurosurgeons at Singapore embarked on the mission to tackle the separation of the most complex and challenging adult craniopagus of the present millennium, unfortunately ending up with devastating results. The authors intend to expand upon their life style, shared intracranial structures, the potential risks of a one-stage procedure as carried out in this case and finally offer some suggestions in tackling such rare and complex cases in neurosurgery.


[Effects of xianggui pill on cytokine in endometriosis model rat].
To study the adjustment of Xianggui pill on the cytokine of endometriosis model rat, and investigate the mechanism of Xianggui pill on the treatment of endometriosis. To set up endometriosis model by rat self-endometria transplantation, drench sodium chloride, Xianggui pill elixation or Danazol after grouping, and to detect the contents of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) by ELISA. The contents of IL-8, TNF-alpha in the peripheral blood and peritoneal fluid of model group were higher than that of the blank group; The quality of allotopia growth intima tissue, the quantity of macrophage in peritoneal fluid and the contents of IL-8, TNF-alpha in the Xianggui pill group and Danazol group were all lower than those of the model group; but there was no significant difference of each target between the Xianggui pill group and Danazol group. Xianggui pill can restrain significantly the growth of allotopia intima tissue, and has apparently adjustment to the cytokine.


Hydrogen Bonds as Stability-Controlling Elements of Spherical Aggregates of ZnO Nanoparticles: A Joint Experimental and Theoretical Approach.
The effects of various organic additives, such as diethanolamine (DEA) and ethanolamine (EA), and variations in aging times on the formation and stability mechanisms of spherical aggregates of ZnO nanoparticles (NPs) prepared by using solvothermal synthesis were studied. The experimental results of the structural, morphological and optical properties monitored by using X-ray diffraction, field-emission scanning electron microscopy (FE-SEM) and UV-Vis spectroscopy were supported by quantum chemical calculations at the level of density functional theory (DFT). Understanding the mechanism of spherical ZnO aggregate formation and its stability by mimicking the processes at the computer level was achieved through theoretical simulations of the ZnO surface/additive interactions using (ZnO)36-DEA and (ZnO)36-EA models. The fine-tuned spherical aggregation of ZnO nanoparticles was driven by various interactions, in particular, strong O-H∙∙∙O and weak N-H∙∙∙O hydrogen bonds as controlling interactions. The calculated negative free release energy, ∆G*INT, indicates that the ZnO surface/additive interaction in diethanolamine media is a spontaneous exergonic process (∆G*INT = -7.73 kcal mol-1), whereas, in ethanolamine media, it is an unfavorable, slightly endergonic process (∆G*INT > 0). The presence of two strong O-H∙∙∙O hydrogen bonds and, at the same time, a weaker N-H∙∙∙O hydrogen bond is the key factor for the very good and long-term aggregate stability of ZnO NPs in DEA media. This integrated experimental-theoretical study highlights the stability and compactness of spherical ZnO aggregates of ZnO NPs, prepared in the presence of diethanolamine compared to ethanolamine media, and provides a promising method and flexible design of ZnO nanomaterials to improve their adsorptive and optical properties.


The cellular expression of antiangiogenic factors in fetal primate macula.
To characterize the cellular expression patterns of antiangiogenic factors differentially regulated in the fetal human macula. RNA was extracted from macular, nasal, and surround biopsies of three human fetal retinas at midgestation. Relative levels of expression of pigment epithelium-derived factor (PEDF), brain natriuretic peptide (BNP), collagen type IValpha2 (COL4A2), and natriuretic peptide receptors A and C (NPRA and NPRC) were determined with quantitative PCR. Cellular expression of PEDF and BNP was investigated by in situ hybridization on retinal sections from monkeys aged between fetal day 55 and 11 years. BNP, COL4A2, and NPRA proteins were localized by immunohistochemistry. Labeling was imaged and quantified by confocal microscopy and optical densitometry. Quantitative PCR confirmed higher levels of PEDF and BNP and lower levels of COL4A2 in the macula at midgestation. PEDF mRNA was detected in ganglion cells (GCs) and the pigment epithelium (RPE). BNP mRNA was detected in GCs and macroglia, although BNP immunoreactivity (IR) was predominantly perivascular. COL4A2-IR was detected in large blood vessels and NPRA-IR on the retinal vascular endothelium, GC axons in fetal retinas, and cone axons at all ages. Optical densitometry showed a graded expression of PEDF and BNP at all ages, with highest levels of expression in GCs in the developing fovea. Because the retinal vessels initially form in the GC layer, it is likely that PEDF has a key role in defining and maintaining the foveal avascular area. The precise role of BNP is unclear, but it may include both antiangiogenic and natriuretic functions.


The Evolving Dilemma of Factor XI in Pregnancy: Suggestions for Management.
A case of a patient with severe factor XI (FXI) deficiency who presented for her seventh labor and delivery is presented. The nature of FXI deficiency, its prevalence, and issues related to genetic screening are discussed. Published literature on the topic is reviewed, including criteria that were developed to assess bleeding, laboratory tools used to estimate bleeding risk, and available treatments. Within the context of this challenging clinical dilemma, specific recommendations are provided for the antepartum, intrapartum, and postpartum stages of pregnancy. These include recommendations that take into account both FXI levels and history of any abnormal bleeding. While there are effective treatments available, it is important to consider that institutional multidisciplinary protocols are needed to manage this complex disorder. More work is needed to define the best management protocols.


Regulation and Function of RFRP-3 (GnIH) Neurons during Postnatal Development.
RFamide-related peptide-3 (RFRP-3) [mammalian ortholog to gonadotropin-inhibiting hormone (GnIH)] potently inhibits gonadotropin secretion in mammals. Studies of RFRP-3 immunoreactivity and Rfrp expression (the gene encoding RFRP-3) in mammalian brains have uncovered several possible pathways regulating RFRP-3 neurons, shedding light on their potential role in reproduction and other processes, and pharmacological studies have probed the target sites of RFRP-3 action. Despite this, there is currently no major consensus on RFRP-3's specific endogenous role(s) in reproductive physiology. Here, we discuss the latest evidence relating to RFRP-3 neuron regulation and function during development and sexual maturation, focusing on rodents. We highlight significant changes in RFRP-3 and Rfrp expression, as well as RFRP-3 neuronal activation, during key stages of postnatal and pubertal development and also discuss recent evidence testing the requisite role of RFRP-3 receptors for normal pubertal timing and developmental LH secretion. Interestingly, some findings suggest that endogenous RFRP-3 signaling may not be necessary for the puberty timing, at least in some species, forcing new hypotheses to be generated regarding this peptide's functional significance to sexual maturation and development.


The genus Epeolus Latreille, 1802 (Hymenoptera, Apidae) in Central Asia.
Available information about bees of the genus Epeolus in Central Asia is summarized. Twenty species are currently known from this area. Two new species are described: E.albus Astafurova & Proshchalykin, sp. nov. and E.pesenkoi Astafurova, sp. nov. Two species are newly recorded from Central Asia: E.asiaticus Astafurova & Proshchalykin, 2022 and E.nudiventris Bischoff, 1930. The hitherto unknown male of E.mikhailovi Astafurova & Proshchalykin, 2021 is described, and lectotypes are designated for E.ruficornis Morawitz, 1875 and E.vinogradovi Popov, 1952.


Cryptocapsinepoxide-type carotenoids from red mamey, Pouteria sapota.
New carotenoids, cryptocapsin-5,6-epoxide, 3'-deoxycapsanthin-5,6-epoxide, and cryptocapsin-5,8-epoxides, have been isolated from the ripe fruits of red mamey (Pouteria sapota). Cryptocapsin-5,6-epoxide was prepared by partial synthesis via epoxidation of cryptocapsin, and the (5R,6S)- and (5S,6R)-stereoisomers were identified by HPLC-ECD analysis. Spectroscopic data of the natural (anti) and semisynthetic (syn) derivatives obtained by acid-catalyzed rearrangement of cryptocapsin-5,8-epoxide stereoisomers were compared for structural elucidation. Chiral HPLC separation of natural and semisynthetic samples of cryptocapsin-5,8-epoxides was performed, and HPLC-ECD analysis allowed configurational assignment of the separated stereoisomers.


[A rare cause of recurrent laryngeal nerve palsy].
Aneurysm of the cervical carotid artery is rare and usually presents with ischemic symptoms as opposed to local mass effect. The authors report a case of recurrent laryngeal nerve palsy secondary to mass effect from a cervical internal carotid artery aneurysm.


Splay bend elasticity of a bent-core nematic liquid crystal.
We measured the splay (K11) and bend (K33) elastic constants in the nematic phase of a bent-core liquid crystal. In the vicinity of the nematic-isotropic transition temperature K33 is proportional to the square of the order parameter. In the nematic range K11 increases monotonically with decreasing temperature, whereas K33 is practically independent of temperature and is smaller than K11 . K33 exhibits a pretransitional slow divergence toward the transition temperature to the smectic phase and becomes slightly larger than K11. The small K33 is explained on the basis of strong coupling of the bent shape of the molecules with the bend distortion.


Infections in the monogenic autoimmune syndrome APECED.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the Autoimmune Regulator (AIRE) gene, which impair the thymic negative selection of self-reactive T-cells and underlie the development of autoimmunity that targets multiple endocrine and non-endocrine tissues. Beyond autoimmunity, APECED features heightened susceptibility to certain specific infections, which is mediated by anti-cytokine autoantibodies and/or T-cell driven autoimmune tissue injury. These include the 'signature' APECED infection chronic mucocutaneous candidiasis (CMC), but also life-threatening coronavirus disease 2019 (COVID-19) pneumonia, bronchiectasis-associated bacterial pneumonia, and sepsis by encapsulated bacteria. Here we discuss the expanding understanding of the immunological mechanisms that contribute to infection susceptibility in this prototypic syndrome of impaired central tolerance, which provide the foundation for devising improved diagnostic and therapeutic strategies for affected patients.


Anti-idiotypic antibodies derived against C8, C9 and perforin bind homologous restriction factor.
A pore-forming protein (PFP/perforin/cytolysin), stored in the cytoplasmic granules of cytolytic lymphocytes, lyses a variety of target cells but not the cytolytic lymphocytes. In the complement (C) system, a C8-binding protein (C8bp) or homologous restriction factor (HRF) has been described that protects cells against lysis mediated by homologous C. C8bp/HRF is known to bind to C8 and C9 and has also been suggested to protect lymphocytes against perforin-mediated lysis. Here, using an anti-idiotypic antibody approach, several polyclonal antisera were raised against IgGs that are specific for mouse perforin, and human C8 and C9. These anti-idiotypic antisera were shown to react against an overlapping epitope(s) on C8bp/HRF as indicated by the following evidence: (i) all three types of antisera reacted against partially purified C8bp/HRF and against a 65 kDa protein band in cell lysates; reactivity was only observed against disulfide-reduced antigens; (ii) the three antibodies react with a protein band in normal erythrocytes (E) but not with type III E of patients with paroxysmal nocturnal hemoglobinuria or with a mutant B lymphoblastoid cell line, both of which cell types are known to be deficient in C8bp/HRF; and (iii) the three antibodies compete with each other for binding to C8bp/HRF. Type III E and the C8bp/HRF-deficient mutant lymphoblastoid cell line, however, are as susceptible to perforin-mediated lysis as type I E and wild-type lymphoblastoid cell line, respectively, indicating that C8bp/HRF does not play a role in protecting cells against perforin-mediated lysis. These paradoxical findings suggest that perforin may share with C8 and C9 the same domain(s) that bind to C8bp/HRF and yet, unlike C8 and C9, perforin is not inactivated by this type of putative interaction. Since C8 and C9 are now readily available, the anti-idiotypic approach described here provides a convenient protocol for production of antisera specific for C8bp/HRF.


Biomimetic layer-by-layer templates for calcium phosphate biomineralization.
Carboxylated, sulfated and/or phosphorylated surfaces are admitted as potential optimal templates for biomimetic deposition of calcium phosphate (CaP) coatings in view of improving implants' osseointegration. Layer-by-layer films were built up consisting of anionic chondroitin sulfate (ChS), a biological carboxylated and sulfated polysaccharide and cationic poly(l-lysine) (PLL). The films were used as soft matrices to immobilize a model phosphoprotein, phosvitin (PhV). The respective roles of ChS, PLL and PhV terminal layers on the heterogeneous nucleation kinetics and the structure of CaP deposits obtained from supersaturated solutions were inspected. Critical supersaturation ratios and induction times preceding heterogeneous nucleation were precisely determined and interpreted within the framework of classical nucleation theory in order to derive the effective interfacial energies of CaP crystals. It was found that the potency of terminal layers toward CaP nucleation increased in the order: PLL<ChS<PhV. Beyond a supersaturation threshold, PhV-terminated films exerted unique influence on the nucleation kinetics, maintaining the induction time at a constant value owing to conformational change of the PhV molecules upon calcium bridging. Promisingly, all films templated the deposition of thin (a few micrometer thick) uniform coatings of octacalcium phosphate and possibly hydroxyapatite, the two most relevant biological phases of CaP.


Gills are needed for ionoregulation before they are needed for O(2) uptake in developing zebrafish, Danio rerio.
A variation on the classic ablation method was used to determine whether O(2) uptake or ionoregulation is the first to shift from the skin to the gills in developing zebrafish, Danio rerio. Zebrafish larvae, ranging in age from 3 to 21 days postfertilization, were prevented from ventilating their gills and forced to rely on cutaneous processes by exposing them to one of two anaesthetics (tricaine methanesulphonate or phenoxyethanol) or by embedding their gills in agar. They were then placed in solutions designed to compensate selectively for impaired O(2) uptake (42% O(2)), impaired ionoregulatory capacity (50% physiological saline) or impairment of both functions (42% O(2)+50% physiological saline). Survival under these conditions was compared with that in normoxic (21% O(2)) fresh water. Neither hyperoxia nor 50% physiological saline had any significant effect on the survival of newly hatched larvae (3 days postfertilization), suggesting that at this stage cutaneous exchange was sufficient to satisfy both ionoregulatory and respiratory requirements. At 7 days postfertilization, the skin still appeared capable of satisfying the O(2) requirements of larvae but not their ionoregulatory requirements. Physiological saline significantly improved survival at 7 days postfertilization; hyperoxia did not. At 14 days postfertilization, both hyperoxia and 50% saline significantly improved survival, indicating that at this stage gills were required for O(2) uptake as well as for ionoregulation. At 21 days postfertilization, only hyperoxia significantly improved survival. By this stage, larvae apparently are so dependent on gills for O(2) uptake that they suffocate before the effects of ionoregulatory impairment become apparent. Thus, it would appear that in zebrafish it is the ionoregulatory capacity of the skin not its ability to take up O(2) that first becomes limiting. This raises the possibility that ionoregulatory pressures may play a more important role in gill development than is generally appreciated.


[Clinically multi-central randomized controlled study on scalp electroacupuncture for treatment of vascular dementia].
To provide reliable evidence for acupuncture treatment of vascular dementia (VD). Multi-central randomized controlled trial method was adopted and 270 cases enrolled were randomly assigned to an acupuncture-medicine group, an electroacupuncture group and a medication group. The acupuncture-medicine group were treated by scalp electroacupuncture on Sishencong (EX-HN 1), Baihui (GV 20), Shenting (GV 24), Fengchi (GB 20) and oral administration of Nimodipine; the electroacupuncture group were treated with scalp electroacupuncture; the medication group were treated with simple oral administration of Nimodipine. They were treated for 6 weeks. Mini-mental state scale (MMSE), ability of daily life-rating scale (ADL-R) and P300 were detected before and after treatment. The total effective rate for cognition improvement was 86.59% in the acupuncture-medicine group, 82.05% in the electroacupuncture group and 43.21% in the medication group, the electroacupuncture group and the acupuncture-medicine group being better than the medication group; and their total effective rates for improvement of ability of daily life were 59.76%, 65.38% and 32.10%, respectively, the electroacupuncture group and the acupuncture-medicine group being better than the medication group. Scores for MMSE and ADL-R and P300 examination indicated that there were significant differences as the acupuncture-medicine group and the electroacupuncture group compared with the medication group (P < 0.01). Scalp electroacupuncture or scalp electroacupuncture combined with oral administration of Nimodipine has a better therapeutic effect in improvement of recognition function and the ability of life activity than simple oral administration of Nimodipine with a higher safety.


Anti-toxoplasmosis effects of oleuropein isolated from Fraxinus rhychophylla.
Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii, with very few therapeutic treatment options. Typically, the choices for treatment are pyrimethamine and sulfadiazine, however their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound oleuropein isolated from Fraxinus rhynchophylla showed anti-T. gondii effects in vitro and in vivo. In Madin-Darby bovine kidney cells, the selectivity of oleuropein was 8.9, which was higher than sulfadiazine and pyrimethamine (3.8 and 2.5, respectively). In infected mice, the inhibition ratio of T. gondii in the peritoneal cavity was 55.4% compared to the negative control group after treatment with 300 mg/kg oleuropein. In addition, inhibitory effects on granuloma, apoptosis, necrosis and cyst-formation were shown in sections of spleen and liver. Oleuropein is therefore a potentially useful anti-T. gondii candidate for clinical application.


Steep-Slope Threshold Switch Enabled by Pulsed-Laser-Induced Phase Transformation.
Super-steep two-terminal electronic devices using NbO2, which abruptly switch from insulator to metal at a threshold voltage (Vth), offer diverse strategies for energy-efficient and high-density device architecture to overcome fundamental limitation in current electronics. However, the tight control of stoichiometry and high-temperature processing limit practical implementation of NbO2 as a component of device integration. Here, we demonstrate a facile room-temperature process that uses solid-solid phase transformation induced by pulsed laser to fabricate NbO2-based threshold switches. Interestingly, pulsed laser annealing under a reducing environment facilitates a two-step nucleation pathway (a-Nb2O5 → o-Nb2O5-δ → t-NbO2) of the threshold-enabled NbO2 phase mediated by oxygen vacancies in o-Nb2O5-δ. The laser-annealed devices with embedded NbO2 crystallites exhibit excellent threshold device performance with low off-current and high on/off current ratio. Our strategy that exploits the interactions of pulsed lasers with multivalent metal oxides can guide the development of a rational route to achieve NbO2-based threshold switches that are compatible with current semiconductor fabrication technology.


[An overview of the evaluation of nursing graduation courses].
This study aimed, starting from the index of adherence of the Pedagogical Projects of the Undergraduate Nursing Courses to the National Curriculum Rules for these Courses, to analyze qualitatively potentialities and weak points of the courses. It is a descriptive, comparative study, between the present data in the PP/UNC and the proposed in the NCR/UNC, having as basis the reports of the evaluation processes conducted by the INEP/MEC. The sample was composed by the reports used for approval and reapproval, conducted in the period from 2002 through 2006, concerning 12 undergraduate courses. One analyzed 8 courses located in the superior part and 4 in the inferior. The study revealed strong and weak points of the courses in the three dimensions of the evaluation reports, and shows needs in the colleges/courses to search for a better use of the epistemologic bases present in the NCR/UNC and proposed in the PP/UNC.


Adsorption of water molecules on partially oxidized graphite surfaces: a molecular dynamics study of the competition between OH and COOH sites.
In this paper, molecular dynamic simulations are used to study the adsorption of water molecules on partially oxidized graphite surfaces containing COOH and OH sites. More specially, the competition between the OH and COOH sites with respect to water adsorption is characterized at three different temperatures (200, 250 and 300 K). The simulations show a strong preferential clustering of the water molecules around the COOH sites irrespective of the temperature. The present results also show that the OH sites can influence the water adsorption process at high temperature, if their local density on the surface is sufficiently large. In this situation, the dynamics of the adsorption process is shown to depend on the distribution of these OH sites on the surface. These results give insights into the water adsorption mechanisms on oxidized graphite surfaces constituting, for example, black carbons or soot particles emitted by aircraft.


Point-of-Care Testing for Infectious Diseases: Past, Present, and Future.
Point-of-care (POC) diagnostics provide rapid actionable information for patient care at the time and site of an encounter with the health care system. The usual platform has been the lateral flow immunoassay. Recently, emerging molecular diagnostics have met requirements for speed, low cost, and ease of use for POC applications. A major driver for POC development is the ability to diagnose infectious diseases at sites with a limited infrastructure. The potential use in both wealthy and resource-limited settings has fueled an intense effort to build on existing technologies and to generate new technologies for the diagnosis of a broad spectrum of infectious diseases.


Sarcoidosis and MIF gene polymorphism: a case-control study in an Irish population.
Macrophage migration inhibitory factor is a key pro-inflammatory mediator. A 5-CATT repeat functional polymorphism within the promoter of the gene was previously associated with the lowest promoter activity. It was hypothesised that patients exhibiting a 5-CATT allele would have a less aggressive inflammatory response with an associated less severe clinical phenotype in sarcoidosis. Irish Caucasian sarcoidosis patients (n = 173) followed up for 1-39 yrs and a control group (n = 166) were genotyped for the CATT repeat polymorphism. Disease severity at the time of diagnosis and at the time of elaboration of the present study was assessed by the presence of thoracic and extrathoracic symptoms, erythema nodosum, radiographic interstitial changes (chest radiograph score equal to stage II or greater, or high-resolution computed tomography confirmed), pulmonary function tests, steroid use, erythrocyte sedimentation rate, C-reactive protein and angiotensin-converting enzyme levels. In the Irish population studied, no evidence was found of a significant association between either sarcoidosis susceptibility and disease severity and the 5-CATT repeat functional polymorphism in the macrophage migration inhibitory gene. The present study found no significant association between the 5-CATT repeat macrophage migration inhibitory factor gene polymorphism and sarcoidosis, and did not support the overriding role for macrophage migration inhibitory factor in driving sarcoidosis pathogenesis.


Correlation coefficients of three self-perceived orthodontic treatment need indices.
To determine patient orthodontic treatment need, appropriate self-perceived indices are required. The aim of this study was to assess the sensitivity and specificity of esthetic component (AC) of the index of orthodontic treatment need (IOTN), oral esthetic subjective index scale (OASIS), and visual analog scale (VAS) through dental health component (DHC) IOTN as a normative index to determine the more appropriate self-perceived index among young adults. In this cross-sectional study, a sample of 993 was randomly selected from freshman students of Isfahan University. Those with a history of orthodontic treatment or current treatment were excluded. DHC was evaluated by two inter- and intra-calibrated examiners. Data for AC, OASIS, and VAS were collected through a questionnaire completed by students. Descriptive statistics, Mann-Whitney U-test, and Spearman correlation test, were used for data analyses. Sensitivity, specificity, positive and negative predictive values of self-perceived indices were calculated through DHC. Sensitivity of AC, OASIS, and VAS for evaluating definite orthodontic treatment need was calculated at 15.4%, 22.3%, and 44.6%, respectively. Specificity of these indices for evaluating definite orthodontic treatment need was calculated at 92.7%, 90.5%, and 76.2% percent, respectively. All self-perceived indices had a significant correlation with together and with DHC (P < 0.01). Among demographic factors, there was weak but significant correlation only between mother's educational level and VAS (P < 0.01). Due to the sensitivity and specificity of the three self-perceived indices, these indices are not recommended for population screening and should be used as adjuncts to a normative index for decision-making in orthodontic treatment planning.


[Maternal experiences in the reality of having an autistic son: an understanding for nursing].
This study has as objective to describe the experience of being mother of an autistic child. A qualitative approach was accomplished according to the phenomenological concepts of Martin Heidegger. Fourteen mothers of autistic children had been interviewed, with semi-structured questions, tape-recorded and transcribed integrally. The local of data collection was the AMA-PI with data produced in May, 2006. The analysis revealed that mothers who live the facticity of having an autistic child is permeated by negative feelings, faith and solitudeness. Mothers also leave their daily life to live their children's daily live. When assuming their existential condition - to be -in the world and to be mother of a autistic child, they begin to understand how to be capable to fight for their children's well-being, without complaints, demonstrating self-denial, patience and concern.


The antifungal activity of the peptide, periplanetasin-2, derived from American cockroach Periplaneta americana.
The cockroach, which is a household insect, is an established model organism in research. Periplanetasin-2, derived from the American cockroach Periplaneta americana, exerted potent antifungal effect against pathogenic fungi without causing hemolysis. Periplanetasin-2 induced oxidative stress by generation of reactive oxygen species (ROS) and lipid peroxidation. Periplanetasin-2 also caused apoptosis by exposure of phosphatidylserine and fragmentation of DNA, exerted in a concentration-dependent manner. Hence, we investigated the mitochondrial apoptotic mechanism of periplanetasin-2 in Candida albicans After treatment with periplanetasin-2, we observed mitochondrial depolarization and calcium accumulation. Moreover, we observed a decrease in cytosolic glutathione, and an increase in mitochondrial glutathione, indicating that periplanetasin-2 induced oxidative stress and high ROS production in the mitochondria. Because of this mitochondrial dysfunction, cytochrome c was released from the mitochondria into the cytosol, and caspase was activated in a time-dependent manner. In summary, the antifungal peptide periplanetasin-2 activates apoptotic signals in the mitochondria by induction of oxidative stress.


Mutations that increase the affinity of a translational repressor for RNA.
The coat protein of the RNA bacteriophage MS2 is a specific RNA binding protein that represses translation of the viral replicase gene during the infection cycle. As an approach to characterizing the RNA-binding site of coat protein we have isolated a series of coat mutants that suppress the effects of a mutation in the translational operator. Each of the mutants exhibits a super-repressor phenotype, more tightly repressing both the mutant and wild-type operators than does the wild-type protein. The variant coat proteins were purified and subjected to filter binding assays to determine their affinities for the mutant and wild-type operators. Each protein binds the operators from 3 to 7.5-fold more tightly than normal coat protein. The amino acid substitutions seem to extend the normal binding site by introducing new interactions with RNA.


Fetomaternal alloimmunization with antenatal glomerulopathies.
Fetomaternal alloimmunization with antenatal glomerulopathies (FMAIG) is a recently described alloimmune disorder, which results from maternal antibodies that cross the placenta, bind to fetal glomerular podocytes, and mediate renal disease. The pathogenic antibodies are directed against neutral endopeptidase (NEP). The infant's mother is NEP-deficient and thus she becomes immunized during pregnancy against NEP expressed by placental cells. Because future pregnancies in NEP-immunized mothers are at high risk for the fetus, detection of anti-NEP antibodies in pregnant mothers and antigen-driven therapies including induction of mucosal tolerance, are urgently needed. This ideally requires identification of the pathogenic epitopes born by the antigen. We have recently characterized two linear B cell epitopes on the NEP that are specifically recognized by the mother's antibodies. The identification of these B cell epitopes is useful for diagnostic tests and may lead to future development of new therapeutic approaches based on peptide-specific immune intervention.


Is the implicit association test immune to faking?
One of the main advantages of measures of automatic cognition is supposed to be that they are less susceptible to faking than explicit tests. It is an empirical question, however, to what degree these measures can be faked, and the response might well differ for different measures. We tested whether the Implicit Association Test (IAT, Greenwald, McGhee, & Schwartz, 1998) cannot be faked as easily as explicit measures of the same constructs. We chose the Big-Five dimensions conscientiousness and extraversion as the constructs of interest. The results show, indeed, that the IAT is much less susceptible to faking than questionnaire measures are, even if no selective faking of single dimensions of the questionnaire occurred. However, given limited experience, scores on the IAT, too, are susceptible to faking.