Defense styles of pedophilic offenders.
This pilot study investigated the defense styles of pedophile sexual offenders. Interviews with 20 pedophiles and 20 controls were scored using the Defense Mechanisms Rating Scales. Results showed that pedophiles had a significantly lower overall defensive functioning score than the controls. Pedophiles used significantly fewer obsessional-level defenses but more major image-distorting and action-level defenses. Results also suggested differences in the prevalence of individual defenses where pedophiles used more dissociation, displacement, denial, autistic fantasy, splitting of object, projective identification, acting out, and passive aggressive behavior but less intellectualization and rationalization.


Protective Roles of Interferon-γ in Cardiac Hypertrophy Induced by Sustained Pressure Overload.
A clear understanding of the molecular mechanisms underlying hemodynamic stress-initiated cardiac hypertrophy is important for preventing heart failure. Interferon-γ (IFN-γ) has been suggested to play crucial roles in various diseases other than immunological disorders by modulating the expression of myriad genes. However, the involvement of IFN-γ in the pathogenesis of cardiac hypertrophy still remains unclear. In order to elucidate the roles of IFN-γ in pressure overload-induced cardiac pathology, we subjected Balb/c wild-type (WT) or IFN-γ-deficient (Ifng-/-) mice to transverse aortic constriction (TAC). Three weeks after TAC, Ifng-/- mice developed more severe cardiac hypertrophy, fibrosis, and dysfunction than WT mice. Bone marrow-derived immune cells including macrophages were a source of IFN-γ in hearts after TAC. The activation of PI3K/Akt signaling, a key signaling pathway in compensatory hypertrophy, was detected 3 days after TAC in the left ventricles of WT mice and was markedly attenuated in Ifng-/- mice. The administration of a neutralizing anti-IFN-γ antibody abrogated PI3K/Akt signal activation in WT mice during compensatory hypertrophy, while that of IFN-γ activated PI3K/Akt signaling in Ifng-/- mice. TAC also induced the phosphorylation of Stat5, but not Stat1 in the left ventricles of WT mice 3 days after TAC. Furthermore, IFN-γ induced Stat5 and Akt phosphorylation in rat cardiomyocytes cultured under stretch conditions. A Stat5 inhibitor significantly suppressed PI3K/Akt signaling activation in the left ventricles of WT mice, and aggravated pressure overload-induced cardiac hypertrophy. The IFN-γ/Stat5 axis may be protective against persistent pressure overload-induced cardiac hypertrophy by activating the PI3K/Akt pathway.


Choosing Wisely Campaign - Innovations in Cardiovascular Science and The United States Healthcare System.
The United States (US) is the third most expensive health care system in the world, but despite that, the US ranked last in the top 50 countries of the world when it comes to the performance measures, such as healthcare efficiency, life expectancy, health care costs, and gross domestic product (GDP) percentage. The spending health care cost keeps increasing and most of the healthcare costs go to waste. Due to this reason, it is therefore extremely important to focus on improving the quality and to bring the costs in appropriate control. To avoid this issue, the Choosing Wisely Campaign (CWC) came into being in 2012. The CWC encourages discussions between providers and patients regarding the care based on the evidence base, free from harm, duplicative or redundant tests/procedures that the patient already received, and whether medications, tests, or procedures are really necessary. Although diagnostic tests or procedures are highly valued for decision-making, unnecessary testing creates harmful health services and an economic impact on the healthcare system. The CWC has spread widely throughout the world but has many challenges which are limiting the CWC in further adoption and spread in the US. To overcome challenges in implementing and spreading the CWC, the government, physicians, social media, and mass media play an important role.


Weak acids produced during anaerobic respiration suppress both photosynthesis and aerobic respiration.
While photosynthesis transforms sunlight energy into sugar, aerobic and anaerobic respiration (fermentation) catabolizes sugars to fuel cellular activities. These processes take place within one cell across several compartments, however it remains largely unexplored how they interact with one another. Here we report that the weak acids produced during fermentation down-regulate both photosynthesis and aerobic respiration. This effect is mechanistically explained with an "ion trapping" model, in which the lipid bilayer selectively traps protons that effectively acidify subcellular compartments with smaller buffer capacities - such as the thylakoid lumen. Physiologically, we propose that under certain conditions, e.g., dim light at dawn, tuning down the photosynthetic light reaction could mitigate the pressure on its electron transport chains, while suppression of respiration could accelerate the net oxygen evolution, thus speeding up the recovery from hypoxia. Since we show that this effect is conserved across photosynthetic phyla, these results indicate that fermentation metabolites exert widespread feedback control over photosynthesis and aerobic respiration. This likely allows algae to better cope with changing environmental conditions.


Evaluating a Ward-based Foundation Year 1 (FY1) System in an Orthopaedic Setting.
Various models of hospital in-patient cover arrangements for junior doctors have been utilised in the United Kingdom. Some settings follow a team-based system for junior doctors and some a ward-based system. The aim of this study was to determine staff's satisfaction rates with regard to a ward-based system for Foundation Year 1 (FY1) doctors in relation to continuity of patient care and doctors' training. The Orthopaedic department of a District Teaching Hospital in the United Kingdom moved to a ward-based system for the FY1s from a previous team-based system. A questionnaire was administered to FY1s, nursing staff and senior doctors asking their satisfaction rates. 42 practitioners were questioned. They included 15 FY1s, 15 ward nurses and 12 senior doctors. 73.3% of FY1s were satisfied with the ward-based system with regard to continuity of patient care and 40% of them were very satisfied/satisfied with it with regard to achieving training objectives. All nurses, 66.7% of FY1s and 66.7% of senior doctors were very satisfied/satisfied with the ward-based system for achieving service provision (p=0.053). All nurses and 60% of FY1s preferred the ward-based system (p=0.017). All nurses and 66.7% of senior doctors rated the ward-based system as being much better/better than team-based at achieving service provision (p-0.028). 1. Our results suggest that a ward-based system for FY1s can be successfully implemented in an orthopaedic setting. 2. Ward-based system confers high satisfaction rates with regard to care provision and continuity of care. 3. Taking into account training needs and substitutes for structured team work would be an area for improvement.


Effects of aquatic walking exercise using a walker in a chronic stroke patient.
[Purpose] The aim of this study was to examine the usefulness of aquatic walking exercise using a walker for chronic stroke patients. We also examined the psychological effects on the study subject and the primary caregiver before and after aquatic walking exercise. [Subject and Methods] The subject was a 60-year-old male with bilateral paralysis after a cerebrovascular accident. The Fugl-Meyer Assessment (FMA) total score was 116 on the right and 115 on the left. The intervention combined aquatic and land walking exercise. A U-shaped walker was used for both water and land exercise. Continuous walking distance was the measure used to evaluate land walking ability. The psychological effects on the study subject and the primary caregiver were examined with the questionnaire. [Results] In aquatic walking, the mean time to walk 5 m showed an increase from the intervention after two months. After the aquatic walking and land walking combination, continuous walking distance also showed a prolonged trend. In the survey given to the main caregivers, improvements were observed. [Conclusion] Aquatic walking practice using a walker improved motivation in a chronic stroke patient, leading to improved walking ability, with a positive psychological influence on the participant and family caregiver.


Serological detection of St. Louis encephalitis virus and West Nile virus in equines from Santa Fe, Argentina.
St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) present ecological and antigenic similarities and are responsible for serious human diseases. In addition, WNV is a significant pathogen in terms of equine health. The purpose of our study was to analyse the seroprevalence of SLEV and WNV in equine sera collected in Santa Fe Province, Argentina. The seroprevalence determined using the plaque reduction neutralisation test was 12.2% for SLEV, 16.2% for WNV and 48.6% for a combination of both viruses. These results provide evidence of the co-circulation of SLEV and WNV in equines in Santa Fe.


Prospective Observational Study Evaluating Systemic Hormones and Corneal Crosslinking Effects in Keratoconus.
To evaluate associations between hormone levels and corneal parameters in patients with keratoconus (KC), before and after photooxidative corneal collagen crosslinking (CXL). Prospective, observational cohort study. Twenty-eight patients with KC who were scheduled for CXL at Aarhus University Hospital in Denmark. Androgen (dehydroepiandrosterone sulfate [DHEA-S]) and estrogen (estrone and estriol) plasma levels were measured and clinical assessments were performed before CXL and 2 to 3 months post-CXL, comparing the CXL eye with the control eye from the same participant. Associations between hormone levels and maximum corneal curvature (Kmax) and minimum central corneal thickness (CCtmin) before and after CXL. Corneal collagen crosslinking was associated with a 2% reduction in Kmax values in the CXL eye, post-CXL, from baseline (median, 56.8 diopters [D]; 95% confidence interval [CI], 50.4-60.3) to the second visit (55.7 D; 95% CI, 50.4-58.8; P < 0.001). Systemic DHEA-S levels were 5 to 6 orders of magnitude higher than estriol or estrone concentrations in plasma. Importantly, estriol levels, rather than DHEA-S or estrone levels, were more closely correlated with Kmax before CXL (Spearman's r = 0.55, P = 0.01). Post-CXL Kmax and CCtmin were not associated with DHEA-S, estrone, or estriol plasma levels at the same timepoint. This study provides supporting evidence based on a KC clinical population that systemic estrogen levels may influence corneal parameters (curvature and thickness) pre-CXL. Further studies evaluating the interplay between the therapeutic benefits of CXL and systemic hormone distributions are needed to determine if perturbation of the local corneal microenvironment influences endocrine function. The authors have no proprietary or commercial interest in any materials discussed in this article.


Intracellular magnetic labeling of lymphocytes for in vivo trafficking studies.
Lymphocyte adhesion and trafficking is difficult to observe in vivo over time. We used magnetic resonance imaging (MRI) to identify magnetically labeled lymphocytes in phantom experiments and in tissue. A method of lymphocyte labeling was developed that is based on fluid-phase endocytosis of nanometer-sized biocompatible superparamagnetic particles. The maximum cell uptake in culture was 0.11 ng Fe/cell corresponding to 5 x 10(6) particles/lymphocyte. Cells stably retained the label and were fully viable for at least 3 days. Labeled lymphocytes showed adhesion to human endothelial cells similar to unlabeled cells, indicating no effect of labeling on cell surface expression of adhesion proteins. No particle-mediated cytotoxicity could be observed. The detection threshold of MRI for detecting labeled lymphocytes in the current study was 2.5 x 10(6) cells/30 microL sampling volume. Following intravenous injection of labeled lymphocytes into rats, cells accumulated in spleen, lymph nodes and liver with a similar bio-distribution as unlabeled cells. Lymphocyte accumulation in the spleen resulted in MRI signal intensity changes readily detectable by MRI. These findings suggest that intracellular lymphocyte labeling with superparamagnetic particles is feasible, does not alter the viability or tissue distribution of labeled cells and allows the detection of labeled lymphocytes by MRI.


Papillary thyroid cancer, macrofollicular variant: the follow-up and analysis of prognosis of 5 patients.
Objective. The main aim of this study was to comparatively analyze the recurrence and prognosis of this rare variant with the literature by analyzing the follow-up data of 5 patients diagnosed with papillary cancer macrofollicular variant. Methods. The demographic data, radiological and pathological data, and prognostic data of 5 patients who underwent surgery for thyroid cancer and were diagnosed with papillary cancer macrofollicular variant pathologically were retrospectively analyzed. Results. The mean age of patients whose mean follow-up period was determined as 7.2 years was 41, and the male/female ratio was 4/1. All patients underwent total thyroidectomy. The pathology report of 2 patients (40%) revealed macrofollicular variant of papillary microcancer, and 3 patients papillary cancer macrofollicular variant. Central dissection was performed in one patient (20%) due to macroscopic pathologic lymph node and 4 metastatic lymph nodes were reported. Also, locoregional recurrence was present in 3 out of 5 patients (60%). Conclusions. Although an impression of earlier and increased risk of recurrence in papillary carcinoma with macrofollicular variant has been documented, more studies with extensive follow-up times and large populations are required.


A restructured nursing process model.
Nursing process has guided clinical nursing practice for more than 25 years. During this time, many changes have occurred in healthcare practices, delivery systems, and nursing. The cumulative effects of such changes show a need to restructure the basic nursing process model. The author presents a three-level differentiated nursing process model.


The role of mucoactive agents in the mechanically ventilated patient: a review of the literature.
The management of airway secretions in the mechanically ventilated patient is a routine task throughout all intensive care units. The current treatment strategies are primarily based on anecdotal experiences rather than statistical evidence. Areas covered: This review article evaluates the data from published trials surrounding mucoactive agents and their use in the critically ill patient population. We completed an extensive search through PUBMED and CINAHL via EBSCO, along with the Cochran library to find all trials using mucoactive agents in the critically ill patient population. Expert commentary: Overall, the role of mucoactive agents in the intensive care unit is a field within pulmonary critical care that is in need of evidence-based recommendations. We feel that there is great opportunity for investigators to evaluate different mucoactive therapies in this patient population and to determine their effect on clinical outcomes.


Acute effects of post-absorptive and postprandial moderate exercise on markers of inflammation in hyperglycemic individuals.
Systemic inflammation is involved in the development of several diseases, including cardiovascular disease and type 2 diabetes. It is known that vigorous exercise affects systemic inflammation, but less is known about exercise at lower intensities. Hyperglycemia can also entail pro-inflammatory responses; however, postprandial hyperglycemia is blunted if the meal is followed by exercise. Hypotheses were: (1) moderate physical exercise acutely affects levels of C-reactive protein (CRP) and serum soluble vascular cell adhesion molecule 1 (sVCAM-1) in hyperglycemic individuals and (2) the effect depends on whether the activity is performed in a post-absorptive or postprandial state. Twelve participants diagnosed with hyperglycemia, but not using anti-diabetic medication, underwent three test days in a randomized cross-over study; 1 control day without exercise, 1 day with 60 min of treadmill walking ending 30 min before breakfast, and 1 day with an identical bout of activity 30 min after the start of breakfast. Food intake was strictly standardized and venous blood for CRP, and sVCAM-1 analysis was sampled at standardized timepoints during the first 3.5 h after breakfast and once 24 h later. Merged data from the two exercise days showed that sVCAM-1 increased from baseline (4 ± 16 ng/mL) compared to the control condition (-28 ± 47 ng/mL, ES = 0.7, p = 0.024). There was no statistically significant difference in changes in sVCAM-1 levels between the two exercise test days. Exercise did not affect CRP values. Moderate exercise increases sVCAM-1 in hyperglycemic individuals, whereas it does not affect CRP.


A Case of Acute Leukemia Following Remission of COVID-19 Infection; an Urge to Search for a Probable Association.
Many aspects of Covid-19 infection, especially its complications and long-term health consequences are still unknown. Several reports concerning concomitant covid-19 infection and hematological disorders have been published recently. We aim to present a unique case of acute myeloid leukemia in a 61-year-old man with a previous history of covid-19 infection 40 days ago, with near complete resolution of signs and symptoms attributable to covid-19 infection. After 3 weeks, the patient presented again with progressive weakness, nausea, vomiting, and epigastric pain. No evidence of active covid-19 infection was observed. Instead, remarkable drop of hemoglobin and platelets relative to the values recorded in the discharge notes of the patient was observed. Further workup of the patient revealed evidence of acute leukemia and severe bone marrow involvement. We decided to present the current case as a concerning probable association.


Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure.
Renal failure causes alterations in thyroid hormone metabolism known as nonthyroidal illness syndrome. In the present study we have examined the effect of a low protein diet (LPD) on circulating levels of hormones of the pituitary-thyroid axis, and tumor necrosis factor alpha (TNF-alpha) in patients with chronic renal failure. Seventeen subjects with conservatively treated chronic renal failure (estimated creatinine clearance 39.5+/-11.1 mL/min) were studied before and after 8 wk of dietary intervention (0.6 g/kg of ideal body mass protein, 30% of calories derived from fat, 62% of calories derived from carbohydrates, and 10 mg/kg of phosphorus). Body fat and fat-free mass remained unchanged. Urea and TNF-alpha serum concentrations significantly decreased, whereas T3 and total and free T4 serum concentrations increased significantly. Triiodothyronine level after treatment correlated negatively with baseline urea level. Changes in T3, T4, and fT4 serum concentrations as well as calculated peripheral deiodinase activity correlated negatively with their baseline values. Alterations in TNF-alpha correlated positively with protein intake, whereas changes in T4 and T4/TSH were inversely related to vegetal protein intake. In conclusion, low protein, low phosphorus diet, which is often prescribed to patients with moderate impairment of renal function, exerts a beneficial effect on low T3 syndrome coexisting with renal failure. The effect of low protein diet on the pituitary-thyroid axis is dependent on the degree of renal functional impairment and LPD-induced decrease in TNF-alpha may also contribute to the observed effects of dietary treatment.


Polymorphous low-grade adenocarcinoma of the sublingual gland.
A case of polymorphous low-grade adenocarcinoma occurring in the sublingual gland is described, followed by a brief discussion on the differential diagnosis. This is the first case ever reported of this entity occurring in the sublingual gland. This paper brings into question the early belief that this tumor is restricted to intraoral minor salivary glands.


Analysis of the incidence of pelvic trauma in fatal automobile accidents.
Pelvic fractures are frequent complications of motor vehicle accidents, and motor vehicle accidents are the most common cause of pelvic fracture. Although pelvic fractures are associated with considerable morbidity and mortality, there has traditionally been no attempt to grade or classify pelvic fractures during postmortem examination. The authors performed a retrospective study of cases examined at the Jefferson County Coroner/Medical Examiner Office from 1994 to 1996, reviewing investigative reports and autopsy findings. Radiographs were examined for the presence and Tile type of pelvic fracture. Pelvic fractures were identified in 88 of 392 cases (23%). In most (89%), the pelvic fracture was readily classified according to Tile type on the basis of radiographs and the inferred mechanism of injury. This study indicates that current estimates of the mortality of pelvic fractures are low because of the exclusion of individuals who do not survive to hospitalization. Furthermore, pelvic fractures in rapidly fatal motor vehicle accidents tend to be more severe than fractures in individuals who have a significant interval of survival. The presence and classification of pelvic fractures may be readily determined by radiographs in most cases. The Tile classification scheme is easy to apply and has important implications in the comparison of study groups.


Plant Temperature Acclimation and Growth Rely on Cytosolic Ribosome Biogenesis Factor Homologs.
Arabidopsis (Arabidopsis thaliana) REI1-LIKE (REIL) proteins, REIL1 and REIL2, are homologs of a yeast ribosome biogenesis factor that participates in late cytoplasmic 60S ribosomal subunit maturation. Here, we report that the inhibited growth of the reil1-1 reil2-1 mutant at 10°C can be rescued by the expression of amino-terminal FLUORESCENT PROTEIN (FP)-REIL fusions driven by the UBIQUITIN10 promoter, allowing the analysis of REIL function in planta. Arabidopsis REIL1 appears to be functionally conserved, based on the cytosolic localization of FP-REIL1 and the interaction of native REIL1 with the 60S subunit in wild-type plants. In contrast to its yeast homologs, REIL1 also was present in translating ribosome fractions. Systems analysis revealed that wild-type Arabidopsis remodels the cytosolic translation machinery when grown at 10°C by accumulating cytosolic ribosome subunits and inducing the expression of cytosolic ribosomal RNA, ribosomal genes, ribosome biogenesis factors, and translation initiation or elongation factors. In the reil1-1 reil2-1 mutant, all processes associated with inhibited growth were delayed, although the plants maintained cellular integrity or acquired freezing tolerance. REIL proteins also were implicated in plant-specific processes: nonacclimated reil1-1 reil2-1 exhibited cold-acclimation responses, including activation of the DREB/CBF regulon. In addition, acclimated reil1-1 reil2-1 plants failed to activate FLOWERING LOCUS T expression in mature leaves. Therefore, in the wild type, REIL function may contribute to temperature perception by suppressing premature cold responses during growth at nonstressful temperatures. In conclusion, we suggest that Arabidopsis REIL proteins influence cold-induced plant ribosome remodeling and enhance the accumulation of cytosolic ribosome subunits after cold shift either by de novo synthesis or by recycling them from the translating ribosome fraction.


Effect of AC II, a herbal formulation on radiation-induced immunosuppression in mice.
A single dose of 6 Gy irradiation significantly reduced the total WBC count while in herbal formulation (AC II) treated groups it was found to be significantly increased. Similarly bone marrow cellularity and alpha-esterase positive cells, which were lowered by radiation, were partly restored in AC II treated groups. The data indicate that AC II can overcome the immunosuppression produced by irradiation.


Passage of pathogenic microorganisms through breathing system filters used in anaesthesia and intensive care.
Invasive ventilation poses a risk of respiratory infection that can be drug-resistant. One means of reducing transmission of infection is the use of a breathing system filter. Filters are intended to be used with dry gas. Current international standards do not require that filters prevent bacterial transfer when wet. It is not known whether microorganisms pass through wet filters, but theory predicts that this might occur. We tested six filters from three different manufacturers. We passed a suspension of microorganisms through the filters using the least pressure necessary, and incubated a sample of the filtrate on blood agar. All the filters tested allowed free passage of both Candida albicans and coagulase-negative staphylococci. The median (IQR [range]) pressure required for fluid to flow across the filter varied greatly between different filter types (20 (0-48 [0-138]) cmH(2)O). We conclude that even large microorganisms pass across moist breathing system filters in conditions that are found in clinical practice.


Complexity of translationally controlled transcription factor Sp3 isoform expression.
Sp3 is a ubiquitous transcription factor closely related to Sp1. Both proteins contain a highly conserved DNA-binding domain close to the C terminus and two glutamine-rich domains in the N-terminal moiety. Immunoblot analyses of Sp3 reveal a striking complex protein pattern of up to eight distinct species. This pattern is not observed in Sp3-deficient cell lines showing that all signals reflect Sp3 antigen. In this study, we have unraveled the complexity of Sp3 expression. We show that four isoforms of Sp3 that retain different parts of the N terminus are expressed in vivo. The four isoforms derive from alternative translational start sites at positions 1, 37, 856, and 907. An upstream open reading frame located at position -47 to -18 regulates expression of the two long isoforms. Unlike Sp1, none of the Sp3 isoforms is glycosylated. However, all four isoforms become SUMO-modified in vivo and in vitro specifically and exclusively at lysine residue 551. The transcriptional activity of the two long isoforms strongly depends on the promoter settings, whereas the small isoforms appear to be inactive. The transcriptional activity of all the Sp3 isoforms is regulated by SUMO modification. Our results demonstrate that Sp3 has many unique features and is not simply a functional equivalent of Sp1.


Causality Analysis of fMRI Data Based on the Directed Information Theory Framework.
This paper aims to conduct fMRI-based causality analysis in brain connectivity by exploiting the directed information (DI) theory framework. Unlike the well-known Granger causality (GC) analysis, which relies on the linear prediction technique, the DI theory framework does not have any modeling constraints on the sequences to be evaluated and ensures estimation convergence. Moreover, it can be used to generate the GC graphs. In this paper, first, we introduce the core concepts in the DI framework. Second, we present how to conduct causality analysis using DI measures between two time series. We provide the detailed procedure on how to calculate the DI for two finite-time series. The two major steps involved here are optimal bin size selection for data digitization and probability estimation. Finally, we demonstrate the applicability of DI-based causality analysis using both the simulated data and experimental fMRI data, and compare the results with that of the GC analysis. Our analysis indicates that GC analysis is effective in detecting linear or nearly linear causal relationship, but may have difficulty in capturing nonlinear causal relationships. On the other hand, DI-based causality analysis is more effective in capturing both linear and nonlinear causal relationships. Moreover, it is observed that brain connectivity among different regions generally involves dynamic two-way information transmissions between them. Our results show that when bidirectional information flow is present, DI is more effective than GC to quantify the overall causal relationship.


[CT-colonography with the 16-slice CT for the diagnostic evaluation of colorectal neoplasms and inflammatory colon diseases].
Comparison of the performance of virtual and conventional colonoscopy for the detection of colorectal polyps and inflammatory colon diseases using a 16-slice spiral CT scanner. Furthermore, presentation of the first experiences with a new three-dimensional reconstruction mode ("colon-dissection") that dissects the colonic wall like a pathologic-anatomic preparation to increase the sensitivity. Forty patients were studied using a 16-slice spiral CT (Lightspeed 16, General Electric Medical Systems, Milwaukee, Wisconsin 53201, USA). The examination was performed after standard oral preparation for colonoscopy. The colonic distension was achieved with room air and intravenous butylscopolamine. Images were obtained in supine and prone position using a detector configuration of 16 x 0.625 mm, pitch 1.7, rotation time 0.5 s, 160 mAs and 120 kV. Axial reconstruction with a slice thickness of 0.625 mm. The CT data were assessed by two radiologists on an Advantage Workstation (Volume Analysis 2, USA) using a software with the capabilities of axial, multiplanar and volume rendering, virtual endoscopy, and colon dissection. Conventional colonoscopy was used to determine the sensitivity. A total of 30 polyps were found in 8 patients and a carcinoma was detected in two patients. Colonography identified 4 polyps with a diameter of 10 mm or more, 6 polyps with a diameter of 5 mm to 9.9 mm, 11 polyps with a diameter of 3 to 4.9 mm and 9 polyps with a diameter of 3.0 mm or less. There were two false negative findings (one polyp of 3 mm and one of 4 mm had been overseen) and two false positive findings for polyps (polyps of 4 mm and 6 mm). The sensitivity and specificity for the detection of colonic polyps were 93% and 94% with the "colonic-dissection" mode, 87 % and 94 % with the "virtual-endoscopy" mode and 63 % and 97 % with multi-planar reconstruction, respectively. Depending on the diameter of the colonic polyps, the "colon-dissection" mode ("virtual-coloscopy") had a sensitivity and specificity of 100 % and 100 % for polyps with a diameter over 5.0 mm, 91 % and 82 % for polyps with a diameter from 3.0 to 4.9 mm and 89 % and 78 % for polyps with a diameter under 3.0 mm, respectively. Inflammatory colon diseases presented as thickening of the colon wall over 5 mm. Virtual colonoscopy with 16-slice spiral CT allows accurate detection of colonic polyps, including small polyps below a diameter of 3 mm. In comparison with the 2D- and 3D-"virtual-endoscopic" reconstruction, the 3D-reconstruction software "colon-dissection" achieves the highest sensitivity for the detection of colonic masses. Therefore, the combination of a 16-slice spiral CT and the "colon-dissection" reconstruction software provides a high resolution in the z-axis for detecting colonic masses and polyps down to a diameter of less than 2 mm, with a sensitivity of about 90 %. This sensitivity is much higher than the sensitivity achievable with 4-slice spiral CT and without "colon-dissection" mode. A thickened colon wall over 5 mm indicates inflammatory colon disease.


Acid induced gelation of soymilk, comparison between gels prepared with lactic acid bacteria and glucono-δ-lactone.
The objective of this work was to compare the gelation of soymilk particles induced by the acidification of a commercial starter culture with that resulting by addition of glucono-δ-lactone (GDL). Structure formation was followed using rheology, and the microstructure was observed by confocal microscopy. Acidification of lactic acid bacteria resulted in a higher gelation pH (pH 6.29±0.05) compared to that of a gel induced by GDL (pH 5.9±0.04). This difference was attributed to the longer time available for rearrangements of the soymilk particles in soymilk with starter cultures compared to the fast acidification by GDL. In spite of the earlier gelation pH, there were no observed differences in the final gel stiffness measured at pH 5.1, the value of tan δ, the frequency dependence and the linear viscoelastic range of the gels measured at the final pH. Microstructural observations also showed a similar protein network structure.


Synthesis of trifluoromethylated pyrazolidines by [3 + 2] cycloaddition.
A highly efficient [3 + 2] cycloaddition between trifluoromethylated N-acylhydrazones and nitroolefins in the presence of potassium hydroxide under phase transfer catalysis is developed to afford potentially bioactive trifluoromethylated pyrazolidines, which can be further transformed into trifluoromethylated pyrazoles in good yields.


Lessons for the stem cell discourse from the gene therapy experience.
The discovery of human embryonic stem cells has pointed to the potential use of these cells in developing new approaches to therapy for many major human diseases. While there is general agreement that such applications are possible and will require a great deal of additional basic and preclinical research, some discussions of the therapeutic applications of human embryonic stem cells have been characterized by the kinds of exaggerations and elevated expectations that characterized the field of human gene therapy a decade ago. In the case of gene therapy, public perception of and confidence in the field were damaged by the hype. Most unfortunate of all, the hopes of patients and their advocates were disappointed. The eventual success of a gene therapy approach, albeit one still plagued by serious adverse events, has come through scientific advance and careful clinical application. The probable eventual use of human embryonic stem cells for therapy of human disease will also require thorough basic and clinical research, but that goal is endangered by the current level of inaccurate representations and undeliverable promises.


Kinetic isotope effects implicate the iron-oxene as the sole oxidant in P450-catalyzed N-dealkylation.
Multiple oxidants have been implicated as playing a role in cytochrome P450-mediated oxidations. Herein, we report results on N-dealkylation, one of the most facile reactions mediated by P450 enzymes. We have employed the N-oxides of a series of para-substituted 13C2H2-labeled N,N-dimethylanilines to function as both substrates and surrogate oxygen atom donors for P450cam and P4502E1. Kinetic isotope effect profiles obtained using the N-oxide system were found to closely match the profiles produced using the complete NAD(P)H/NAD(P)-P450 reductase/O2 system. The results are consistent with oxidation occurring solely through an iron-oxene species.


In Vivo and In Vitro Anti-Arthritic Effects of Cardenolide-Rich and Caffeoylquinic Acid-Rich Fractions of Periploca forrestii.
Periploca forrestii Schltr. (P. forrestii) is a species used in Traditional Chinese Medicine (TCM) known as "Miao medicine", and has a long history of use in the treatment of rheumatism, rheumatoid arthritis (RA), and joint pain. The present study aimed to evaluate the anti-arthritis effects of the cardenolide-rich and caffeoylquinic acid-rich fractions (CDLFs and CQAFs) of P. forrestii in collagen-induced arthritic (CIA) rats, and defined the mechanisms of therapeutic action in MH7A cells treated with TNF-α. Serum rheumatoid factor (RF), TNF-α, IL-6, IL-1β, PGE₂, NO, SOD, and MDA were determined by ELISA or other commercially assay kits. Histopathological changes in ankle joint tissues were examined. The mRNA expressions of IL-1β, IL-6, COX-2, and iNOS in MH7A cells were measured by qRT-PCR assays. In addition, the expressions of iNOS, COX-2, and p65 proteins, and the phosphorylation of IκBα, p38, ERK1/2, and JNK proteins in MH7A cells were analyzed by Western blot. The results showed that CDLF and CQAF could suppress the paw swelling in CIA rats at different doses (125 mg/kg, 250 mg/kg, and 500 mg/kg). Histopathological examination suggests that the CDLF and CQAF significantly relieved the damage of the structure of the ankle joint in CIA rats. In addition, serum RF, TNF-α, IL-6, IL-1β, PGE₂, NO, and MDA were decreased, along with increased activity of serum SOD. Furthermore, CDLF and CQAF downregulated the expressions of IL-1β, IL-6, COX-2, iNOS, and p65, and inhibited the phosphorylation of IκBα, p38, ERK1/2, and JNK in MH7A cells treated with TNF-α. These findings demonstrated that both CDLF and CQAF exhibited anti-arthritic activity, which might be associated with their inhibitory effects on the NF-κB and MAPK signaling pathways.


Polyunsaturated fatty acid inhibition of fatty acid synthase transcription is independent of PPAR activation.
Polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3) families inhibit the rate of gene transcription for a number of hepatic lipogenic and glycolytic genes, e.g., fatty acid synthase (FAS). In contrast, saturated and monounsaturated fatty acids have no inhibitory capability. The suppression of gene transcription resulting from the addition of PUFA to a high carbohydrate diet: occurs quickly (< 3 h) after its addition to a high glucose diet; can be recreated with hepatocytes cultured in a serum-free medium containing insulin and glucocorticoids; can be demonstrated in diabetic rats fed fructose; and is independent of glucagon. While the nature of the intracellular PUFA inhibitor is unclear, it appears that delta-6 desaturation is a required step in the process. Recently, the fatty acid activated nuclear factor, peroxisome-proliferator activated receptor (PPAR) was suggested to be the PUFA-response factor. However, the potent PPAR activators ETYA and Wy-14643 did not suppress hepatic expression of FAS, but did induce the PPAR-responsive gene, acyl-CoA oxidase (AOX). Similarly, treating rat hepatocytes with 20:4 (n-6) suppressed FAS expression but had no effect on AOX. Thus, it appears that the PUFA regulation of gene transcription involves a PUFA-response factor that is independent from PPAR.


Effects of Tongue-Strengthening Exercise on Tongue Strength and Effortful Swallowing Pressure in Young Healthy Adults: A Pilot Study.
The purpose of this study was to investigate the effects of tongue-strengthening exercise (TSE) on tongue strength and effortful swallowing pressure in young healthy adults. Thirteen young healthy volunteers (six men, seven women; M age = 20.5 ± 0.5 years) performed 8 weeks of isometric TSE 3 days per week. A tongue pressure measurement device was used to measure maximum isometric tongue pressure (MITP) and conduct the TSE, and a tactile sensor system attached to the hard palate was used to measure effortful swallowing pressure. MITP and effortful swallowing pressure were measured at baseline, after 4 and 8 weeks of training, and at 4 and 8 weeks after the last training session to examine the detraining effects. The results indicated that both MITP and effortful swallowing pressure increased significantly from baseline to 8 weeks after training. Although the improved MITP significantly decreased at 4 and 8 weeks after training cessation, no detraining effect was observed for effortful swallowing pressure. TSE is an effective method for increasing tongue pressure in wide tongue-palate contact areas during effortful swallow. The effortful swallowing pressure gained with TSE appears to be maintained for at least eight nontraining weeks.


94 β-Decay Half-Lives of Neutron-Rich _{55}Cs to _{67}Ho: Experimental Feedback and Evaluation of the r-Process Rare-Earth Peak Formation.
The β-decay half-lives of 94 neutron-rich nuclei ^{144-151}Cs, ^{146-154}Ba, ^{148-156}La, ^{150-158}Ce, ^{153-160}Pr, ^{156-162}Nd, ^{159-163}Pm, ^{160-166}Sm, ^{161-168}Eu, ^{165-170}Gd, ^{166-172}Tb, ^{169-173}Dy, ^{172-175}Ho, and two isomeric states ^{174m}Er, ^{172m}Dy were measured at the Radioactive Isotope Beam Factory, providing a new experimental basis to test theoretical models. Strikingly large drops of β-decay half-lives are observed at neutron-number N=97 for _{58}Ce, _{59}Pr, _{60}Nd, and _{62}Sm, and N=105 for _{63}Eu, _{64}Gd, _{65}Tb, and _{66}Dy. Features in the data mirror the interplay between pairing effects and microscopic structure. r-process network calculations performed for a range of mass models and astrophysical conditions show that the 57 half-lives measured for the first time play an important role in shaping the abundance pattern of rare-earth elements in the solar system.


Identification of Saccharomyces cerevisiae GLY1 as a threonine aldolase: a key enzyme in glycine biosynthesis.
Determination of enzyme-specific activities revealed that GLY1 encodes a threonine aldolase (TA) in Saccharomyces cerevisiae. A knock-out mutant auxotrophic for glycine lacked detectable activity. After transformation with YEp24GLY1 glycine prototrophy was restored and TA-specific activity was 16-fold higher than in the wild type. Growth experiments using glucose as the sole carbon source showed that GLY1 is more important for glycine biosynthesis than SHM1 and SHM2 encoding alternative serine hydroxymethyltransferases. On ethanol as carbon source simultaneous disruption of GLY1, SHM1 and SHM2 did not lead to glycine auxotrophy because glycine biosynthesis proceeds via alanine glyoxylate aminotransferase.


Addressing Healthcare Professional Burnout: A Quality Improvement Intervention.
Burnout is a substantial phenomenon across healthcare settings, affecting more than half of healthcare professionals and leading to negative patient and health system outcomes. Infusion center professionals (ICPs) are at increased risk of burnout attributed to high patient volume and acuity levels. Strategies to address burnout have been developed and prioritized by the American Medical Association (AMA), the World Health Organization, and other organizations. This quality improvement project aimed to address perceived burnout, job-related stress, and job satisfaction among nurses, physician assistants, and medical assistants at a large pediatric hospital through integration of two infusion center (IC)-based staff engagement interventions. A pre- and post-test study design was used. Existing team huddles in the IC were modified based on the AMA STEPS Forward program recommendations to incorporate appreciative inquiry and recognition into team and department events. Peer recognition was tailored toward institutional core values. The Mini-Z Burnout survey was administered before and 3 months after implementation of both interventions. Pre- to post-intervention responses revealed a higher percentage of staff reporting no burnout (57.7% vs. 75%), low levels of job-related stress (58.8% vs. 65.5%), and satisfaction with current job (70.6% vs. 82.8%). Most participants agreed or strongly agreed that structured huddles (69%) and recognition events (82.8%) were beneficial and recommended continuation (65.5% and 82.8%, respectively). Open-ended responses regarding workplace stressors focused heavily on staffing and patient acuity. Project outcomes support the integration of tailored interventions to reduce burnout among pediatric ICPs. Organizational commitment to addressing burnout can provide incentive to scale up institution-wide staff engagement interventions. Further study is needed to assess the efficiency and effectiveness of such tailored interventions across diverse settings.


What's in a word? Case definitions in sexual health medicine.
In clinical medicine, establishing case definitions for diseases, including sexually transmitted infections, is often an inexact and arbitrary exercise. The definition is affected by the intended purpose, be it for disease surveillance, clinical care, service provision, research, or funding of services. A case must be defined precisely in order to monitor disease trends, detect outbreaks, and evaluate the effectiveness of interventions. The definition ensures consistent measurement of disease, specificity of reporting, and improves data standardization through time and across regions. The definition itself is one of the criteria used to evaluate the quality of a surveillance system. Designing definitions is fraught with problems relating to appropriate diagnostic criteria, sensitivity and specificity, context and relevance to current knowledge, and/or clinical practice. There is also the problem of reaching a consensus, especially for complex syndromes such as pelvic inflammatory disease.


Hepatitis B virus mutations associated with in situ expression of hepatitis B core antigen, viral load and prognosis in chronic hepatitis B patients.
In this retrospective study, we investigated the prevalence and significance of mutations in part of the hepatitis B virus (HBV) x gene, and tried to clarify their relationship with clinicopathological or histopathological characteristics and prognosis in patients with chronic hepatitis B (CHB). A total of 83 consecutive CHB patients (1986-1994) were chosen for the present study. Sequence analysis was performed using polymerase chain reaction (PCR) and the direct sequencing method. The histological activity index was described using Scheuer scores. Two-step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV DNA levels were determined by fluorescence quantitative real-time PCR. For the prognostic study, all the patients were followed up using clinical and laboratory data. Mutation at nt1726-1730 correlated significantly with decreased expression of HBcAg in situ (P = 0.006) and with lower HBV DNA levels in the liver (P = 0.004). In particular, the CTGAC mutation showed the strongest decrease of the viral load (P = 0.007). By contrast, nt1762/1764 mutation correlated with increased HBcAg (P = 0.005) and higher HBV DNA levels (P = 0.006). The mutants with the wild-type of nt1726-1730 or nt1762/1764 mutation were more prevalent in hepatocellular carcinoma (HCC) patients than in CHB patients. Although the mutations did not correlate with cirrhosis, the frequency of nt1762/1764 mutation in patients with hepatocarcinogenesis was significantly higher than in those without hepatocarcinogenesis (P = 0.011). Mutations at nt1726-1730 and nt1762/1764 are associated with in situ expression of HBcAg and viral load. Higher HBV DNA levels in the liver may be associated with hepatocarcinogenesis. Mutation at nt1762/1764 remarkably increases the risk of hepatocarcinogenesis.


The postoperative lean body mass loss at one month leads to a poor survival in patients with locally advanced gastric cancer.
Aims: We previously demonstrated that a loss of lean body mass loss at one month after gastrectomy was an independent risk factor for the continuation of adjuvant chemotherapy with S-1. However, it is unclear whether or not lean body mass loss after gastrectomy leads to a poor survival through poor compliance to adjuvant chemotherapy with S-1. Methods: The recurrence free survival (RFS) overall survival (OS) and were examined in 115 patients who underwent curative gastrectomy and were pathologically diagnosed with stage II or III gastric cancer and who received postoperative adjuvant chemotherapy with S-1 between May 2011 and September 2016. Results: The median follow-up period was 40.6 months. The RFS rates at 5 years after surgery were 57.8% in the lean body mass loss ≥5% group and 73.5% in the lean body mass loss <5% group. The univariate and multivariate analyses for the disease free survival (RFS) demonstrated that a lean body mass loss >5% was a significant risk factor. The OS rates at 5 years after surgery were 72.0% in the lean body mass loss ≥5% group and 77.3% in the lean body mass loss <5% group. The OS was slightly worse in the lean body mass loss ≥5% group than in the lean body mass loss <5% group (p=0.2062). Conclusions: The lean body mass loss at one month, which is closely associated with poor S-1 compliance, was an important risk factor for the RFS. A prospective cohort study is necessary to confirm whether or not the lean body mass loss affects the gastric cancer survival.


On the distribution of vaccine protection under heterogeneous response.
We assume that individuals in a vaccinated cohort respond heterogeneously and acquire a continuous spectrum of effective protection against an environmental exposure to infection that can be varying in time. The notion of dynamical invariants is applied to a proportional hazard model with an unvaccinated or placebo cohort as baseline. The hazard is expressed as a susceptibility factor times a measure of environmental exposure to infection. Using the time-evolving information for the aggregated vaccinated cohort and the unvaccinated cohort, it is possible to reconstruct the distribution of effective protection imparted by the vaccination at the beginning of observation. Efficacy is defined in terms of the hazard ratio at the beginning of observation.


Secondary Hyperparathyroidism in HIV-Infected Patients in Central Europe.
Secondary hyperparathyroidism (sHPT) might be a contributor to increased risk of osteoporosis in adult HIV patients but there is little data available on this issue in this particular population. The aim of the study was to investigate the prevalence of sHPT in an HIV-infected population with normal kidney function and to evaluate its risk factors in HIV patients. This cross-sectional study was carried out in a single HIV center in Germany using routine data from patients with normal kidney function attending the clinic between January 1st and December 31st, 2016. In total, 1263 patients were included [998 (79.0%) male, median age 48 (IQR 38-54) years]. In 214 patients (16.9%) elevated PTH levels with low or normal calcium levels were found. Multivariate logistic regression modeling showed significant associations with elevated PTH for African ethnicity [OR: 2.12 (95% CI: 1.42-3.16); p<0.001], low 25-hydroxyvitamin D levels [OR: 1.82 (95% CI: 1.32-2.51); p<0.001], low calcium levels [OR 1.69 (95% CI: 1.22-2.33); p=0.001], and use of tenofovir disoproxil fumarate [OR 2.33 (95% CI: 1.62-3.36); p<0.001]. Additional to common risk factors like vitamin D insufficiency and hypocalcemia, we found a significant association between the use of TDF and sHPT. Prospective data are needed to ascertain whether PTH-mediated bone loss is the underlying mechanism of TDF bone-toxicity. Additional screening of PTH even in HIV-infected patients with normal or low calcium levels may help to identify patients at increased risk of bone mineral density loss.


Cystic fibrosis and lung transplantation: ethical concerns.
Cystic fibrosis is a multisystem disorder affecting respiratory, digestive, integumentary, and reproductive systems. Despite the medical advancements treating cystic fibrosis, lung disease is the leading cause of morbidity and mortality in children and adults. A case study of a 21-year-old's struggle to undergo double lung transplantation is presented, and four ethical considerations are identified. An ethical decision-making model provides an avenue for discussing these concerns.


Sarcoid reactions in cystic duct carcinoma.
A diagnosis of sarcoidosis was evoked in a 61-year-old man on clinical and histologic bases. Nevertheless, a bile duct carcinoma was disclosed in association with the discovery of generalized sarcoid-like granulomas. This is only the third time that such an association has been described. HLA-B8, DR3, and DRw52 antigens were found, suggesting that altered immunologic mechanisms could play a role in the pathogenesis of this sarcoid-like reaction.


Response to polysaccharide vaccination amongst pediatric patients with common variable immunodeficiency correlates with clinical disease.
Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia and increased susceptibility to recurrent infections, autoimmunity and malignancies. We have previously shown that some pediatric patients with CVID can respond to meningococcal polysaccharide vaccine. Twelve pediatric cases with CVID were re-evaluated to determine whether bactericidal antibody responses or IgM memory B-cells correlate with the severity of disease resulting from the deficiency. We found that bronchiectasis and clinical manifestations of autoimmunity occur more commonly amongst non-responders to vaccine. In contrast, low populations of memory B-cells do not correlate with these sequelae. The results of this study could help pediatricians plan strategies for prevention of sequelae in children presenting with CVID.


Chromosomal localization of putative tumor-suppressor genes in several human cancers.
Restriction-fragment-length polymorphism analysis was performed on several different types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, stomach cancer, and small-cell lung carcinoma (SCLC), to determine the chromosomal loci of putative tumor-suppressor genes in each type of tumor because less of heterozygosity (LOH) is supposed to unmask the recessive mutation of tumor-suppressor gene in the remaining allele. Chromosomal loci showing frequent LOH differed among these tumors, suggesting that there are several tumor-suppressor genes in the human genome and that critical genes for the development of each type of tumor are different. In some cases LOH was observed in the early stage of tumor such as chromosome 3p loss in carcinoma of the uterine cervix, and in other cases it was observed only in the advanced stage of tumor such as chromosomes 4 and 16q loss in hepatocellular carcinoma. These results suggest that there are two different types of tumor-suppressor genes: one is the gene whose inactivation is responsible for malignant transformation of a normal cell and the other is the gene whose inactivation is responsible for the progression of a tumor cell. In SCLC, LOH at three different chromosomal loci, 3p, 13q, and 17p, was simultaneously observed in nearly 100% of tumors. It was observed even in stage I tumors and an untreated tumor, and it occurred prior to N-myc amplification. These results may imply that at least six genetic alterations are necessary to convert a normal cell into a fully malignant cancer cell in SCLC.


Head wave correlations in ambient noise.
Ambient ocean noise is processed with a vertical line array to reveal coherent time-separated arrivals suggesting the presence of head wave multipath propagation. Head waves, which are critically propagating water waves created by seabed waves traveling parallel to the water-sediment interface, can propagate faster than water-only waves. Such eigenrays are much weaker than water-only eigenrays, and are often completely overshadowed by them. Surface-generated noise is different whereby it amplifies the coherence between head waves and critically propagating water-only waves, which is measured by cross-correlating critically steered beams. This phenomenon is demonstrated both experimentally and with a full wave simulation.


Perinatal Complications in Diabetes Mellitus with Pregnancy: Comparison between Gestational Diabetes Mellitus (GDM) and Diabetes Mellitus Prior to Pregnancy.
Diabetes is alarmingly high among Bangladeshi people. But there have been very few studies assessing the effect of diabetes on perinatal outcomes, particularly comparing diabetes prior to pregnancy and gestational diabetes (GDM). This cross sectional observational study was conducted in the Department of Obstetrics & Gynaecology, BIRDEM Hospital, Dhaka, Bangladesh from September 2010 to February 2011. Pregnant women admitted in BIRDEM Hospital for delivery after 28 weeks of gestation were selected to assess perinatal complications of GDM and diabetes prior to pregnancy and to compare them after taking permission from institutional review board. Perinatal complications of 50 women with gestational diabetes, 50 pregnant women with diabetes prior to pregnancy, and 50 non diabetic pregnant women as control were studied after taking written consent and the outcomes between GDM, and mother with diabetes prior to pregnancy were compared. Perinatal outcomes including congenital anomalies, birth asphyxia, macrosomia, respiratory distress syndrome (RDS), hypoglycemia, hyperbilirubinaemia, and perinatal mortality were compared. Neonatal complications were significantly higher in both pregnancy with prior diabetes (74%) and gestational diabetes (58%) when compared with non diabetic control (24%). Leading neonatal complications were macrosomia, birth asphyxia, hyperbilirubinaemia, and hypoglycemia. Macrosomia was significantly higher in GDM than non diabetic group (10% vs. 0%, p=0.003). Frequency of birth asphyxia, hyperbilirubinaemia, and hypoglycemia were significantly higher in the infant of mother with prior diabetes (22%, 54%, & 22% respectively) and GDM (20%, 38%, 18% respectively) than that of non diabetic mother (6%, 20%, 0% respectively). Compared to GDM, mother with prior diabetes had more frequent hyperbilirubinaemia (38% vs. 54%, p=0.004) and hypoglycemia (18% vs. 22%, p=0.04). Women with diabetes had worse pregnancy outcomes compared to non-diabetic mothers. Pregnancy prior to diabetes is associated with more frequent complications than gestational diabetes.


Abnormal ventilation-perfusion scan due to swallowed DTPA aerosol and a paralyzed hemidiaphragm.
A case of ventilation-perfusion mismatch due to swallowed DTPA aerosol and a paralyzed hemidiaphragm is shown as a potential source of error in the evaluation of pulmonary embolus. This case emphasizes the importance of radiograph correlation in the interpretation of ventilation-perfusion images.


Analysis on professional identity and related factors among Chinese general practitioners: a National Cross-sectional Study.
Studies on professional identity and related factors among Chinese general practitioners (GPs) are unavailable. The objective of this study was to investigate the professional identity level of GPs in China and explore factors associated with GPs' perceptions of their professional identity. A multistage stratified random sampling method was used to collect data with a structured self-administered questionnaire from 3236 GPs working in community health service institutions (CHIs) in China between October, 2017 and February, 2018. Professional identity was measured by the 13 items scale. Descriptive statistics were calculated and groups' differences were estimated using nonparametric tests. Multiple linear stepwise regression analysis was used to analyze factors associated with professional identity among GPs. Based on a total score of 65 on the professional identity scale, the average score for GPs' professional identity was 51.23 (SD = 6.56). Multiple linear stepwise regression analysis showed that GPs who practiced in Central China, with an administrative responsibility, at a moderate or higher income level, who frequently worked overtime, had more occupational development opportunities, with a higher level of job satisfaction and older GPs had higher levels of professional identity. Professional identity level among GPs in China is high. Region, administrative responsibility, income level, working overtime, occupational development opportunities, age, and job satisfaction were significant predictors of professional identity.


Uncontrolled hypertension in patients with type 2 diabetes: What are the correlates?
Suboptimal blood pressure (BP) control in patients with type 2 diabetes is associated with adverse micro- and macrovascular complications. This study aimed to investigate the predictors of uncontrolled hypertension in an Iranian population with type 2 diabetes. This is a cross-sectional study of 2612 patients with type 2 diabetes, including 944 patients with hypertension. Controlled and uncontrolled hypertension were assessed. Multivariate logistic regression modeling was used to determined independent predictors of uncontrolled hypertension. Of 2612 patients with type 2 diabetes, 944 (36.1%) patients had hypertension. Of all patients with hypertension, 580 (61.4%) were still on monotherapy. Uncontrolled hypertension was detected in 536 participants (56.8%). Patients with uncontrolled hypertension had significantly higher body mass index (BMI) (29.8±4.8 vs. 28.6±4.6), waist circumference (99.11±10.95 vs. 96.68±10.92), pulse pressure (67.3±17.3 vs. 48.4±10.7), total cholesterol (177.1±45.5 vs. 164.3±40.5), non-HDL cholesterol (133.0±43.5 vs. 120.1±38.7), triglycerides (175.7±80.3 vs. 157.4±76.7), and Atherogenic Index of Plasma (AIP) (0.57±0.23 vs. 0.52±0.24) (p < .05 for all of them) compared to patients with controlled hypertension. Multivariate logistic regression analysis revealed that uncontrolled hypertension was significantly associated with BMI (p = .001), pulse pressure (p = .001), total cholesterol (p = .006), and non-HDL cholesterol (p = .009). In patients with triglycerides levels > 200 mg/dl non-HDL cholesterol had a significant correlation with uncontrolled hypertension (OR = 4.635, CI95%:1.781-12.064, p = .002). In conclusion, BMI, pulse pressure, total cholesterol, and non-HDL cholesterol are significant predictors of uncontrolled hypertension in patients with type 2 diabetes. Also, ineffective monotherapy, medical inertia and patients' non-compliance were other contributors to the uncontrolled hypertension.


Use of monoclonal antibodies in detection of melanoma-associated antigens in intact human tumors.
The use of antimelanoma monoclonal antibodies on tissue sections using a two-step indirect immunoperoxidase technique is reported. Antibodies 691-13-17 and 691-I5-Nu4B reacted with dysplastic nevus cells and all melanomas tested, but not with normal skin melanocytes, intradermal nevi, or lentigines. Antibody 691-13-17, directed against DR antigen, reacted also with Langerhan's cells, macrophages, and a subpopulation of lymphocytes. Antibody 691-I5-Nu4B reacted only with melanomas. The technique allows analysis of the expression of antigens by tumor cells in situ.


Matrix Metalloproteinase-9-Responsive Nanogels for Proximal Surface Conversion and Activated Cellular Uptake.
Here, we have exploited the heightened extracellular concentration of matrix metalloproteinase-9 (MMP-9) to induce surface-conversional properties of nanogels with the aim of tumor-specific enhanced cellular uptake. A modular polymeric nanogel platform was designed and synthesized for facile formulation and validation of MMP-9-mediated dePEGylation and generation of polyamine-type surface characteristics through peptide N-termini. Nanogels containing MMP-9-cleavable motifs and different poly(ethylene glycol) corona lengths (350 and 750 g/mol) were prepared, and enzymatic surface conversional properties were validated by MALDI characterization of cleaved byproducts, fluorescamine assay amine quantification, and zeta potential. The nanogel with a shorter PEG length, mPEG350-NG, exhibited superior surface conversion in response to extracellular concentrations of MMP-9 compared to that of the longer PEG length, mPEG750-NG. Confocal microscopy images of HeLa cells incubated with both fluorescein-labeled nanogels and DiI-encapsulated nanogels demonstrated greater uptake following MMP-9 "activation" for mPEG350-NG compared to its nontreated "passive" mPEG350-NG parent, demonstrating the versatility of such systems to achieve stimuli-responsive uptake in response to cancer-relevant proteases.


Endoscopic diagnosis and treatment of superficial non-ampullary duodenal epithelial tumors: A review.
The surface of the small bowel mucosa is covered more than any other section of the digestive canal; however, the overall prevalence of small bowel tumors of the whole gastrointestinal tract is evidently low. Owing to the improvement in endoscopic techniques, the prevalence of small bowel tumors has increased across multiple countries, which is mainly due to an increase in duodenal tumors. Superficial non-ampullary duodenal epithelial tumors (SNADETs) are defined as tumors originating from the non-ampullary region in the duodenum that share similarities and discrepancies with their gastric and colorectal counterparts in the pathogenesis and clinicopathologic characteristics. To date, white light endoscopy (WLE) remains the cornerstone of endoscopic diagnosis for SNADETs. Besides, narrow-band imaging (NBI) techniques and magnifying endoscopy (ME) have been widely used in the clinic and endorsed by multiple guidelines and consensuses for SNADETs' evaluation. Confocal laser endomicroscopy (CLE), endocytoscopy (ECS), and artificial intelligence (AI) are also up-and-coming methods, showing an exceptional value in the diagnosis of SNADETs. Similar to the endoscopic treatment for colorectal polyps, the choices for SNADETs mainly include cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and laparoscopic endoscopic cooperative surgery (LECS). However, owing to the narrow lumen, rich vascularity, weak muscle layer, abundant Brunner's gland, and the hardship of endoscope control, the duodenum ranks as one of the most dangerous operating areas in the digestive tract. Therefore, endoscopists must anticipate the difficulties in endoscopic maneuverability, remain aware of the increased risk of complications, and then select the appropriate treatment according to the advantages and disadvantages of each method.


Distinguishing Between Investigator Discriminability and Eyewitness Discriminability: A Method for Creating Full Receiver Operating Characteristic Curves of Lineup Identification Performance.
The conceptual frameworks provided by both the lineups-as-experiments analogy and signal detection theory have proven important to understanding how eyewitness lineups work. The lineups-as-experiments analogy proposes that when investigators use a lineup procedure, they are acting as experimenters and should therefore follow the same tried-and-true procedures that experimenters follow when executing an experiment. Signal detection theory offers a framework for distinguishing between factors that improve the trade-off between culprit and innocent-suspect identifications and factors that affect the frequency of suspect identifications. We integrate these two conceptual frameworks. We argue that an eyewitness lineup procedure is characterized by two simultaneous signal detection tasks. On one hand, the witness is tasked with determining whether the culprit is present in the lineup and identifying that person. On the other hand, the investigator knows which lineup member is the suspect and which lineup members are known-innocent fillers and is therefore tasked only with determining whether the suspect is the culprit. The investigator uses the witness's identification decision and associated level of confidence to decide whether the suspect is the culprit. We leverage this realization to demonstrate a method for creating full receiver operating characteristic curves for eyewitness lineup procedures.


[Impacts of Anthropogenic Emission Reduction and Meteorological Conditions on PM2.5 Pollution in Typical Cities of Beijing-Tianjin-Hebei in Winter].
This study used sampling analysis and a CAMx-PSAT coupling model to analyze the components, transmission, and source apportionment of PM2.5 in Beijing and Tangshan in January 2018. The results showed that in January 2018, water-soluble inorganic ions (WSⅡs) accounted for 49.59% and 39.13% of PM2.5 mass concentrations in Beijing and Tangshan, respectively. The ratios of NO3- to SO42- were 2.02 and 1.51, respectively, indicating that pollution in both cities was dominated by mobile sources. In Beijing and Tangshan, PM2.5 accounted for 48.74% and 30.67% of transmission, respectively. Regional transmissions were mainly contributed by neighboring areas, northwest masses, and southwest masses. However, the contribution of the southwest passage to pollution in the respective cities increased by 9.65% and 15.02% during pollution periods. The principal sources contributing to PM2.5 pollution in Beijing were mobile and dust sources. Secondary ions were more obviously affected by regional contributions, mobile and industrial sources had the most significant effect in Tangshan, and most particulate matter and sulfate were contributed by local emissions. From 2013 to 2018, the dominant component of WSⅡs changed from sulfate to nitrate while the main pollution sources changed from coal-fired and industrial sources to mobile and dust sources. Meanwhile, in January 2018, the meteorological factors were more favorable for pollution mitigation than in 2013. The meteorological impact of secondary ions is closely related to the lower relative humidity in 2018, compared to 2013.


The Effect of Color on the Use of Electronic Body Protectors in Taekwondo Matches.
This study investigated the relationship between the color protector and success in taekwondo combats in the qualification championships, when electronic body protectors were used. Moreover, it analyzed the confounding effect of a participant being a top-ranked athlete in the 2012 London Olympic Games, in a sample of 462 matches. Results from the entire sample showed a non-significant relationship between the combat outcome and the winner's color electronic protector. At the level of the tournament, the results showed a significant relationship between wearing a red electronic protector and winning the combat in the Asian and the European qualification tournaments. For gender and weight categories, there was no clear color effect. A significant association was, however, found between wearing red and winning the match in the female featherweight category. The inclusion of electronic body protectors and a counterbalanced seed-condition seem to be effective for controlling the effect of the protector's color on the outcomes of combats.


Locating Biobanks in the Canadian Privacy Maze.
Although Canada has not yet enacted any biobanking-specific privacy law, guidance and oversight are provided via various federal and provincial health and privacy-related laws as well as via ethics and policy documents. The primary policy document governing health research, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, provides the framework for the strong role of Research Ethics Boards in Canada, and limits research funding from Canada's three main federal funding agencies to those who agree to adhere to its policies. The broad consent model is gaining traction in Canada, although lack of legal and constitutional precedence for the broad consent or opt-out options makes this an evolving issue. In general, data is required to be coded; more specific security measures are outlined in guidelines that may be implemented by local policy. International sharing is allowed, and Canada meets the European Union's standards for receipt of data and samples.


Effect of chromium on bioenergetics and leukocyte dynamics following immunoactivation in lactating Holstein cows.
Activated immune cells are insulin sensitive and utilize copious amounts of glucose. Because chromium (Cr) increases insulin sensitivity and may be immunomodulatory, our objective was to evaluate the effect of supplemental Cr (KemTrace Cr propionate, 20 g/d; Kemin Industries Inc., Des Moines, IA) on immune system glucose utilization and immune system dynamics following an intravenous endotoxin challenge in lactating Holstein cows. Twenty cows (320 ± 18 d in milk) were randomly assigned to 1 of 4 treatments: (1) pair-fed (PF) control (PF-CON; 5 mL of saline; n = 5), (2) PF and Cr supplemented (PF-Cr; 5 mL of saline; n = 5), (3) lipopolysaccharide (LPS)-euglycemic clamp and control supplemented (LPS-CON; 0.375 µg/kg of body weight LPS; n = 5), and (4) LPS-euglycemic clamp and Cr supplemented (LPS-Cr; 0.375 µg/kg of body weight LPS; n = 5). The experiment was conducted serially in 3 periods (P). During P1 (3 d), cows received their respective dietary treatments and baseline values were obtained. At the initiation of P2 (2 d), either a 12-h LPS-euglycemic clamp was conducted or cows were PF to their respective dietary counterparts. During P3 (3 d), cows consumed feed ad libitum and continued to receive their respective dietary treatment. During P2, LPS administration decreased dry matter intake (DMI; 40%) similarly among diets, and by experimental design the pattern and magnitude of reduced DMI were similar in the PF cohorts. During P3, LPS-Cr cows tended to have decreased DMI (6%) relative to LPS-CON cows. Relative to controls, milk yield from LPS-challenged cows decreased (58%) during P2 and LPS-Cr cows produced less (16%) milk than LPS-CON cows. During P3, milk yield progressively increased similarly in LPS-administered cows, but overall milk yield remained decreased (24%) compared with PF controls. There were no dietary treatment differences in milk yield during P3. Circulating insulin increased 9- and 15-fold in LPS-administered cows at 6 and 12 h postbolus, respectively, compared with PF controls. Compared with LPS-CON cows, circulating insulin in LPS-Cr cows was decreased (48%) at 6 h postbolus. Relative to PF cows, circulating LPS binding protein and serum amyloid A from LPS-administered cows increased 2- and 5-fold, respectively. Compared with PF cows, blood neutrophil counts in LPS-infused cows initially decreased, then gradually increased 163%. Between 18 and 48 h postbolus, the number of neutrophils was increased (12%) in LPS-Cr versus LPS-CON cows. The 12-h total glucose deficit was 220 and 1,777 g for the PF and LPS treatments, respectively, but glucose utilization following immune activation was not influenced by Cr. In summary, supplemental Cr reduced the insulin response and increased circulating neutrophils following an LPS challenge but did not appear to alter the immune system's glucose requirement following acute and intense activation.


Phagocytic killing of Candida albicans by different murine effector cells.
Three major phagocytic populations in the mouse were tested in vitro for killing of Candida albicans by means of 51Cr release assay: early inflammatory peritoneal polymorphonuclear cells (PMN), unfractionated or adherent spleen cells and resident peritoneal macrophages (PEC). Considerable candidacidal activity was found in the early inflammatory neutrophil and adherent spleen cell populations. On the contrary, only limited activity was found to be associated with resident peritoneal macrophages. The phagocytic killing apparently involved multiple mechanisms.


Study of microleakage at Class I cavities prepared by Er:YAG laser using three types of restorative materials.
The purpose of this in vitro study were to investigate microleakage at class I cavities filled with amalgam, composite resin, or glass-ionomer after preparation by Er:YAG laser and to compare the results with those by a conventional method using an air turbine. There has been no report of a study of microleakage on class I cavities prepared by Er:YAG laser. Ninety-six extracted human premolar and molar teeth were used in this study. Forty-eight class I cavities were prepared by Er:YAG laser and 48 class I cavities by air turbine. After preparation, each of the 2 groups was further subdivided into 3 groups, respectively, and cavities in each of these subgroups were filled by 1 of 3 types of restorative materials. Microleakage at the restored cavities was assessed by the dye penetration method and scanning electron microscopy (SEM). Minimal or moderate leakage was evident at most of the composite resin or glass-ionomer restorations, whereas moderate or severe leakage was observed at most of the amalgam restorations as shown by the dye penetration method. There was significant difference among the 3 restorative materials (p < 0.05), but there was no significant difference in microleakage between the cavities prepared by Er:YAG laser and those by air turbine (p > 0.05). SEM evaluation demonstrated good adaptation with most of the composite resin or glass-ionomer restorations, but amalgam restorations showed slightly poorer adaptation. These results suggest that Er:YAG laser is useful for class I cavity preparation from the viewpoint of microleakage.


Identifying and validating a combined mRNA and microRNA signature in response to imatinib treatment in a chronic myeloid leukemia cell line.
Imatinib, a targeted tyrosine kinase inhibitor, is the gold standard for managing chronic myeloid leukemia (CML). Despite its wide application, imatinib resistance occurs in 20-30% of individuals with CML. Multiple potential biomarkers have been identified to predict imatinib response; however, the majority of them remain externally uncorroborated. In this study, we set out to systematically identify gene/microRNA (miRNA) whose expression changes are related to imatinib response. Through a Gene Expression Omnibus search, we identified two genome-wide expression datasets that contain expression changes in response to imatinib treatment in a CML cell line (K562): one for mRNA and the other for miRNA. Significantly differentially expressed transcripts/miRNAs post imatinib treatment were identified from both datasets. Three additional filtering criteria were applied 1) miRbase/miRanda predictive algorithm; 2) opposite direction of imatinib effect for genes and miRNAs; and 3) literature support. These criteria narrowed our candidate gene-miRNA to a single pair: IL8 and miR-493-5p. Using PCR we confirmed the significant up-regulation and down-regulation of miR-493-5p and IL8 by imatinib treatment, respectively in K562 cells. In addition, IL8 expression was significantly down-regulated in K562 cells 24 hours after miR-493-5p mimic transfection (p = 0.002). Furthermore, we demonstrated significant cellular growth inhibition after IL8 inhibition through either gene silencing or by over-expression of miR-493-5p (p = 0.0005 and p = 0.001 respectively). The IL8 inhibition also further sensitized K562 cells to imatinib cytotoxicity (p < 0.0001). Our study combined expression changes in transcriptome and miRNA after imatinib exposure to identify a potential gene-miRNA pair that is a critical target in imatinib response. Experimental validation supports the relationships between IL8 and miR-493-5p and between this gene-miRNA pair and imatinib sensitivity in a CML cell line. Our data suggests integrative analysis of multiple omic level data may provide new insight into biomarker discovery as well as mechanisms of imatinib resistance.


U.S. State Policy Contexts and Physical Health among Midlife Adults.
This study examines how state policy contexts may have contributed to unfavorable adult health in recent decades. It merges individual-level data from the 1993-2016 Behavioral Risk Factor Surveillance System (n=2,166,835) with 15 state-level policy domains measured annually on a conservative to liberal continuum. We examined associations between policy domains and health among adults ages 45-64 years and assess how much of the associations is accounted by adults' socioeconomic, behavioral/lifestyle, and family factors. A more liberal version of the civil rights domain was associated with better health. It was disproportionately important for less-educated adults and women, and its association with adult health was partly accounted by educational attainment, employment, and income. Environment, gun safety, and marijuana policy domains were, to a lesser degree, predictors of health in some model specifications. In sum, health improvements require a greater focus on macro-level factors that shape the conditions in which people live.


Detection of calprotectin and apoptotic activity in the colon of marmosets with chronic diarrhea.
The common marmoset (Callithrix jacchus) is used as a non-human primate laboratory animal. Marmoset wasting syndrome (MWS) is a disease endemic to captive colonies, and the pathogenesis is unclear. In the present study, marmosets with chronic bloody high-viscosity diarrhea, which is a contributing factor to MWS, were evaluated, and inflammation in the colon was found. Calprotectin is a surrogate marker of intestinal inflammation and induces apoptosis. Marmosets with chronic diarrhea exhibited higher levels of fecal calprotectin. Histochemical analyses showed high expression of calprotectin in the extravascular neutrophils and apoptosis in the chronic colitis lesions. No internal microbiological diseases were identified. Although the cause of chronic colitis was not identified, the marmoset could be a useful model of inflammatory bowel disease.


Defective monocyte accessory function due to surface sulphydryl (SH) oxidation in rheumatoid arthritis.
Low serum sulphydryl (SH) levels are a feature of active rheumatoid arthritis (RA). We have investigated whether a similar blockade of membrane SH groups on mononuclear cells modifies the function of these cells in this disease. Using pokeweed mitogen stimulated IgG synthesis as the assay system, we have found that the accessory cell function of peripheral blood monocytes is totally dependent on free SH groups on the cell surface. Monocytes from patients with active RA display poor accessory cell function when compared with healthy monocytes or with cells from patients treated with D-penicillamine. The poor function of the rheumatoid accessory cells may be corrected in vitro by 2-mercaptoethanol (2-ME). Addition of 2-ME to the culture system also enhances IgG synthesis by rheumatoid mononuclear cells to normal levels. We suggest that surface SH-dependent mechanisms are responsible, at least in part, for the depressed mononuclear cell functions of rheumatoid cells in vitro and may explain some effects of D-penicillamine therapy in rheumatoid patients.


Survey on status quo and development needs of research and innovation capabilities of young researchers at university-affiliated hospitals in China: a cross-sectional survey.
Researches in China on the innovation ability and development needs of young scientific research talents is not enough. The survey is aimed to shed light on the status quo, problems, and development needs of research and innovation capabilities among young researchers in terms of orientation, innovation atmosphere, platform support, training mechanisms, and training measures. From January to March 2022, a randomly-selected method was used to conduct a web-based self-made questionnaire survey on young talents in 6 university affiliated hospitals in 5 provinces in China. Intergroup comparisons were based on the chi-square test or Fisher' exact test. Overall, 586 usable responses had been collected, including 233 from full-time researchers and 353 from part-time researchers. 182 (31.06%) researchers believe that they have the ability to master innovative theories, tools and methods, 136 (23.21%) researchers choose "working alone". Compared with part-time research talents, the proportion of full-time research talents self-assessed as "very good" in scientific research innovation ability is higher (χ2=17.048, P<0.001). Full-time researchers had less knowledge about the relevant policies at their affiliation (χ2=3.190, P=0.074), were more likely to believe that the "talent management system" had a greater impact (χ2=4.906, P=0.027), and had higher expectations of "multiple incentive mechanisms" (χ2=10.312, P=0.001). In contrast, the proportion of part-time researchers who hoped that their affiliation would take measures such as "increasing financial investment" (χ2=9.049, P=0.003) and "strengthening external supports" (χ2=8.383, P=0.004) was significantly higher. Full-time and part-time scientific researchers have different requirements for capital investment, support for scientific research platforms, leadership demonstrations by senior peers, and a good atmosphere for scientific and technological innovation. Thus, it is important to promote innovation capacity-building among young researchers at university-affiliated hospitals (UAHs) by enhancing both talent training and introduction in a hierarchical, classified, multidimensional, and stepwise manner.


Surfactant-derived proteins as markers of alveolar membrane damage in heart failure.
In heart failure (HF) alveolar-capillary membrane is abnormal. Surfactant-derived proteins (SPs) and plasma receptor for advanced-glycation-end-products (RAGE) have been proposed as lung damage markers. Eighty-nine chronic HF and 17 healthy subjects were evaluated by echocardiography, blood parameters, carbon monoxide lung diffusion (DLCO) and cardiopulmonary exercise test. We measured immature SP-B, mature SP-B, SP-A, SP-D and RAGE plasma levels. Immature SP-B (arbitrary units), mature SP-A (ng/ml) and SP-D (ng/ml), but not mature SP-B (ng/ml) and RAGE (pg/ml) levels, were higher in HF than in controls [immature SP-B: 15.6 (13.1, 75th-25th interquartile range) Vs. 11.1 (6.4), p<0.01; SP-A, 29.6 (20.1) Vs. 18.3 (13.5), p = 0.01; SP-D: 125 (90) Vs. 78 (58), p<0.01]. Immature SP-B, SP-A, SP-D and RAGE values were related to DLCO, peak oxygen consumption, ventilatory efficiency, and brain natriuretic peptide (BNP), whereas plasma mature SP-B was not. The DLCO Vs. immature SP-B correlation was the strongest one. At multivariate analysis, RAGE was associated to age and creatinine, SP-A to DLCO and BNP, SP-D to BNP, mature SP-B to DLCO and creatinine, and immature SP-B only but strongly to DLCO. Immature SP-B is the most reliable biological marker of alveolar-capillary membrane function in HF.


AMG 580: a novel small molecule phosphodiesterase 10A (PDE10A) positron emission tomography tracer.
Phosphodiesterase 10A (PDE10A) inhibitors have therapeutic potential for the treatment of psychiatric and neurologic disorders, such as schizophrenia and Huntington's disease. One of the key requirements for successful central nervous system drug development is to demonstrate target coverage of therapeutic candidates in brain for lead optimization in the drug discovery phase and for assisting dose selection in clinical development. Therefore, we identified AMG 580 [1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one], a novel, selective small-molecule antagonist with subnanomolar affinity for rat, primate, and human PDE10A. We showed that AMG 580 is suitable as a tracer for lead optimization to determine target coverage by novel PDE10A inhibitors using triple-stage quadrupole liquid chromatography-tandem mass spectrometry technology. [(3)H]AMG 580 bound with high affinity in a specific and saturable manner to both striatal homogenates and brain slices from rats, baboons, and human in vitro. Moreover, [(18)F]AMG 580 demonstrated prominent uptake by positron emission tomography in rats, suggesting that radiolabeled AMG 580 may be suitable for further development as a noninvasive radiotracer for target coverage measurements in clinical studies. These results indicate that AMG 580 is a potential imaging biomarker for mapping PDE10A distribution and ensuring target coverage by therapeutic PDE10A inhibitors in clinical studies.


Prolonged epidural anaesthesia in a patient with Dupuytren's diathesis.
A patient with Dupuytren's diathesis experienced a prolonged sensory and motor block following epidural anaesthesia. It was postulated that this occurred secondary to fibrous changes within the epidural space.


Human C5a des Arg increases vascular permeability.
C5a were generated in human plasma by incubation with zymosan in the presence of a carboxypeptidase B inhibitor. The carboxypeptidase inhibitor was added to prevent cleavage of the carboxyl terminal arginine from C5a and enabled it to be purified on the basis of spasmogenic activity on the guinea-pig isolated ileum. When injected into rabbit skin, purified C5a induced marked plasma leakage over a 30-min period, but only if the substance was first mixed with a vasodilator substance such as prostaglandin (PG)E2. The responses to C5a + PGE2 did not appear to be related to anaphylatoxic, histamine-releasing activity because an antihistamine, mepyramine, had only a small effect on plasma leakage. Further, removal of the carboxyl terminal arginine by carboxypeptidase B abolished activity on the ileum but not in the skin. The observation that both human C5a and C5a des Arg were able to increase vascular permeability in vivo suggested a parallel with leukotactic activity in vitro. In support of this, no responses to C5a + PGE2 were obtained in rabbits depleted or circulating polymorphonuclear leukocytes. Thus, inflammatory edema resulting from extravascular complement activation may be dependent on 2 components: a leukocyte/endothelial cell interaction triggered by C5a, and the concomitant generation of a vasodilator, prostaglandin.


Single oral administration of captopril may not bring an improvement in screening of primary aldosteronism.
Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 19 cases with primary aldosteronism (PA) and 72 with essential hypertension (EHT) to differentiate the two disorders in the following conditions: after overnight recumbency (basal state) and after oral administration of captopril. Screening criteria were determined in order to pick up all of PA patients as positive. After the captopril administration, the specificity of a criterion based on the combination of PAC and PAC/PRA ratio was 93% and positive predictive value 79%. This criterion was superior to other conventional screening methods. However, higher specificity (97%) and positive predictive value (90%) were obtained from a combination criterion based on the basal PAC and PAC/PRA ratio. The single oral administration of captopril may not bring an improvement in the screening of PA.


Delayed hypoxic-ischemic leukoencephalopathy.
A 55-year-old female was found unconscious in a ventilated room. She recovered consciousness on the way to the emergency room. Her vital signs were stable. She presented with negativism and poor communication. Physical examination, routine tests, brain CT and electroencephalogram were normal. Urine toxicology was positive for benzodiazepines. Twelve days after, she presented with catatonia and immobility. Additional examinations, including cerebrospinal fluid (CSF) testing and brain CT, were again normal. Risperidone was administered, and psychotherapy intensified. In the third week, the condition worsened, with intense pyramidal signs and decerebration that led to a vegetative state. Brain MRI revealed diffuse leukoencephalopathy. Extensive metabolic and CSF studies were persistently negative. Brain biopsy was compatible with chronic cerebral hypoxia/anoxia. A diagnosis of delayed hypoxic-ischemic leukoencephalopathy was made. Supportive measures were intensified. She was discharged from the hospital after 4 months in a minimally conscious state and was capable of elementary communication and recognising faces.


Development cooperation in water and sanitation: is it based on the human rights framework?
The water and sanitation sector is verifiably receiving increased attention and funding through international development cooperation. Not least because of the way that it affects incentives and institutions in partner countries, development cooperation can have either positive or negative effects on human rights though. The consolidated frameworks for the human rights to water and sanitation is becoming linked to the international community's coordinated development efforts, as evidenced notably in the 2030 Agenda for Sustainable Development. However, a review of major funders' official policies for development cooperation in the sector suggests that many only partially endorse the frameworks for the human rights to water and sanitation. An observation of development cooperation flows to the sector allows the hypothesis to be advanced that worldwide inequalities in access to these services may be reduced through a full and clear application of the human rights framework in development cooperation activities. The article presents findings of this research and explores key stakes for development cooperation in the water and sanitation sector that are relevant for their ability to either negatively or positively contribute to the realization of human rights.


Regulation of pituitary tumor transforming gene (PTTG) expression and phosphorylation in thyroid cells.
Human pituitary tumor transforming gene (hPTTG) is a multifunctional proto-oncogene implicated in the initiation and progression of several tumors. Phosphorylation of hPTTG is mediated by cyclin-dependent kinase 2 (CDC2), whereas cellular expression is regulated by specificity protein 1 (SP1). The mechanisms underlying hPTTG propagation of aberrant thyroid cell growth have not been fully defined. We set out to investigate the interplay between hPTTG and growth factors, as well as the effects of phosphorylation and SP1 regulation on hPTTG expression and function. In our study, epidermal growth factor (EGF), TGFα, and IGF-1 induced hPTTG expression and phosphorylation in thyroid cells, which was associated with activation of MAPK and phosphoinositide 3-kinase. Growth factors induced hPTTG independently of CDC2 and SP1 in thyroid carcinoma cells. Strikingly, CDC2 depletion in TPC-1 cells resulted in enhanced expression and phosphorylation of hPTTG and reduced cellular proliferation. In reciprocal experiments, hPTTG overexpression induced EGF, IGF-1, and TGFα mRNAs in primary human thyrocytes. Treatment of primary human thyrocytes with conditioned media derived from hPTTG-transfected cells resulted in autocrine upregulation of hPTTG protein, which was ameliorated by growth factor depletion or growth factor receptor tyrosine kinase inhibitors. A transgenic murine model of thyroid targeted hPTTG overexpression (hPTTG-Tg) (FVB/N strain, both sexes) demonstrated smaller thyroids with reduced cellular proliferation and enhanced secretion of Egf. In contrast, Pttg(-/-) knockout mice (c57BL6 strain, both sexes) showed reduced thyroidal Egf mRNA expression. These results define hPTTG as having a central role in thyroid autocrine signaling mechanisms via growth factors, with profound implications for promotion of transformed cell growth.


The activities of progesterone receptor isoform A and B are differentially modulated by their ligands in a gene-selective manner.
It is known that progesterone receptor (PR) isoform A (PR-A) and isoform B (PR-B) may mediate different effects of progesterone. The objective of this study was to determine if the functions of PR isoforms also vary in response to different PR modulators (PRM). The effects of 7 synthetic PRM were tested in MDA-MB-231 cells engineered to express PR-A, PR-B, or both PR isoforms. The effects of progesterone were similar in cells expressing PR-A or PR-B in which it inhibited growth and induced focal adhesion. On the other hand, synthetic PRM modulated the activity of the PR isoforms differently. RU486, CDB4124, 17alpha-hydroxy CDB4124 and VA2914 exerted agonist activities on cell growth and adhesion via PR-B. Via PR-A, however, these compounds displayed agonist effect on cell growth but induced stellate morphology which was distinct from the agonist's effect. Their dual properties via PR-A were also displayed at the gene expression level: the compounds acted as agonists on cell cycle genes but exhibited antagonistic effect on cell adhesion genes. Introduction of ERalpha by adenoviral vector to these cells did not change PR-A or PR-B mediated effect of PRM radically, but it causes significant cell rounding and modified the magnitudes of the responses to PRM. The findings suggest that the activities of PR isoforms may be modulated by different PRM through gene-specific regulatory mechanisms. This raises an interesting possibility that PRM may be designed to be PR isoform and cellular pathway selective to achieve targeted therapy in breast cancer.


When does intent matter for memory? Bridging perspectives with Craik.
In his commentary, Craik (see record 2023-42323-002) argued that while intentional remembering might be effective for some populations and memory tasks, these are the exception, and that intent will not benefit memory if incidental encoding induces optimal processing. While we agree on many points, we maintain that in most situations the processes induced by the intention to remember are more effective than those induced by deep semantic processing alone. We show that effects of intent appear with a variety of tasks such as free recall, cued recall, source memory, item recognition, in both mixed and pure lists, and when studying individual words, word pairs, or word-image associations. Thus, the beneficial effects of intent generalize over tasks, list-compositions, and study materials. There are also little individual differences in the effect of intent in healthy young adults-most participants (86% out of 336 participants over six experiments) show a beneficial effect. We review evidence that the intent to remember strengthens item-context bindings in episodic memory, but that such effects could be masked and not measurable in subsequent memory tests, unless intrusions are taken into account. We agree that in principle incidental encoding could induce optimal processing, but we do not find the existing evidence convincing. We provide additional novel data that directly addresses Craik's (2023) concerns and we propose ways to further investigate how intention enhances memory. We conclude with a joint statement, coauthored by Craik and ourselves, that synthesizes our converging perspectives and current understanding of the impact of intent on memory. (PsycInfo Database Record (c) 2023 APA, all rights reserved).