Immunohistochemical analysis of sox9 in ovarian Sertoli cell tumors and other tumors in the differential diagnosis.
The distinction of ovarian Sertoli cell tumor from other tumors in the histological differential diagnosis, particularly endometrioid carcinoma and carcinoid tumor, may be difficult. Many immunohistochemical markers have been studied for this differential diagnosis, but currently available markers are neither 100% sensitive nor specific. Sox9 is a transcription factor involved in Sertoli cell differentiation in the testis. The role that this molecule plays in the pathogenesis of ovarian Sertoli cell tumors and the potential use as an immunohistochemical marker for differential diagnosis have not been investigated. Immunohistochemical staining for Sox9 was performed in 152 ovarian tumors: pure Sertoli cell tumor (n = 36), endometrioid borderline tumor (n = 38), well-differentiated endometrioid carcinoma (n = 26), sertoliform endometrioid carcinoma (n = 13), and carcinoid tumor (n = 39). Nuclear expression was considered positive. Extent and intensity of staining were semiquantitatively scored. In addition, immunohistochemical composite scores in positive cases (ranging from 1 to 12) were calculated based on the extent score multiplied by the intensity score. Sox9 was expressed in 44% of Sertoli cell tumors, 55% of endometrioid borderline tumors, 65% of well-differentiated endometrioid carcinomas, 39% of sertoliform endometrioid carcinomas, and 10% of carcinoid tumors. The mean Sox9 immunohistochemical composite scores in positive cases were 6.3 for Sertoli cell tumor, 5.3 for endometrioid borderline tumor, 8.0 for well-differentiated endometrioid carcinoma, 2.8 for sertoliform endometrioid carcinoma, and 6.8 for carcinoid tumor. The differences in the mean Sox9 composite scores between Sertoli cell tumor and the other tumor categories were not statistically significant (p values ranged from 0.092 to 0.523). We conclude that Sox9 is variably expressed in ovarian Sertoli cell tumor and other tumors that are in the differential diagnosis and, thus, is not helpful for immunohistochemical distinction. Understanding the role of Sox9 in the pathogenesis of ovarian Sertoli cell tumor requires further study.


Molecular sieve in renal glomerular and tubular basement membranes as revealed by electron microscopy.
Bovine glomerular basement membrane (GBM) was isolated and purified according to a modification of Spiro's method. Rat and bovine tubular basement membranes (TBM) were isolated and purified by sonic disruption or by the method of Carlson et al. Electron microscopic studies on the ultrastructure of GBM and TBM were performed after negative staining with 1% phosphotungstic acid solution, pH 7.3. When negatively stained, GBM and TBM were seen as fragments varying in size. The surface of the membranes showed a characteristic felt-like or spongy appearance. At higher magnification, GBM and TBM showed a fine meshwork composed of strands and pores which three-dimensionally resembled a crystal lattice. Pores were fairly uniform in size and shape. They were round, oval or polygonal in shape. Some of the pores were elongated to form short straight or bent channels. Strands were also uniform in diameter and surrounded a pore or channel. For an average of 50 pores, the long dimension was 3.1 +/- 0.6 nm and the short dimension 2.5 +/- 0.3 nm in bovine GBM, 3.8 +/- 1.2 and 2.5 +/- 0.7 nm in bovine TBM, and 4.9 +/- 1.5 and 2.8 +/- 0.6 nm in rat TBM, respectively. The strand was 1.8 +/- 0.3 nm in diameter in bovine GBM, 2.5 +/- 0.6 nm in bovine TBM and 3.7 +/- 0.7 nm in rat TBM for an average of 50 strands. The diameters of the pores were less than or close to the short axis of an albumin molecule. It was concluded that renal GBM and TBM were molecular sieves composed of pores and strands.


Double metal cyanides as heterogeneous Lewis acid catalysts for nitrile synthesis via acid-nitrile exchange reactions.
A series of transition metal-based double metal cyanides (DMCs) were studied as catalysts for the synthesis of nitriles via acid-nitrile exchange reaction. The best nitrile yields were obtained with Co3[Co(CN6)]2 DMC, which proved to be a versatile, stable, reusable and highly active catalyst, exhibiting an activity comparable to that of homogeneous Lewis acid catalysts.


Efficacy, effectiveness and side effects of medications used to prevent fractures.
There is an increasing number of effective therapies for fracture prevention in adults at risk of osteoporosis. However, shortcomings in the evidence underpinning our management of osteoporosis still exist. Evidence of antifracture efficacy in the groups of patients who most commonly use calcium and vitamin D supplements is lacking, the safety of calcium supplements is in doubt, and the safety and efficacy of high doses of vitamin D give cause for concern. Alendronate, risedronate, zoledronate and denosumab have been shown to prevent spine, nonspine and hip fractures; in addition, teriparatide and strontium ranelate prevent both spine and nonspine fractures, and raloxifene and ibandronate prevent spine fractures. However, most trials provide little information regarding long-term efficacy or safety. A particular concern at present is the possibility that oral bisphosphonates might cause atypical femoral fractures. Observational data suggest that the incidence of this type of fracture increases steeply with duration of bisphosphonate use, resulting in concern that the benefit-risk balance may become negative in the long term, particularly in patients in whom the osteoporotic fracture risk is not high. Therefore, reappraisal of ongoing use of bisphosphonates after about 5 years is endorsed by expert consensus, and 'drug holidays' should be considered at this time. Further studies are needed to guide clinical practice in this area.


[Changes in serum chromogranin A and urotensin II levels in children with chronic heart failure].
To examine the changes in serum chromogranin A (CgA) and urotensin II (U II) levels in children with chronic heart failure (CHF) and their clinical significance. A total of 58 children with CHF, among whom 17 had endocardial fibroelastosis (EFE) and 41 had dilated cardiomyopathy (DCM), were selected as CHF group, and 20 healthy children were selected as control group. Serum levels of CgA and U II were measured using enzyme-linked immunosorbent assay, and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined by bi-directional lateral flow immunoassay. Ventricular remodeling indices were measured using echocardiography. The correlation between serum CgA and U II levels and ventricular remodeling was evaluated by Pearson correlation or Spearman's rank correlation analysis. There were no significant differences in serum CgA and NT-proBNP levels between children with grade II heart function and the control group (P>0.05). However, the serum CgA and NT-proBNP levels gradually increased as the heart function grade increased, and were significantly higher in grade III and IV children compared to those in the control group (P<0.05). U II levels were lower in children with grade II, III, or IV heart function than those in the control group (P<0.05), and significantly decreased with the aggravation of CHF (P<0.05). There were no significant differences in CgA and U II levels between patients with EFE and DCM (P>0.05). Serum CgA concentration was positively correlated with left ventricular mass index (LVMI), NT-proBNP, and cardiac function classification (r=0.279, 0.649, and 0.778 respectively; P<0.05), but was negatively correlated with left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and U II (r=-0.369, -0.322, and -0.718 respectively; P<0.05). Serum U II concentration was negatively correlated with NT-proBNP and cardiac function classification (r=-0.472 and -0.591 respectively; P<0.05), but was not correlated with LVMI, LVEF, and LVFS (P>0.05). CgA may play a role in ventricular remodeling in children with CHF. Serum CgA and U II may serve as a reference for the diagnosis and functional classification of heart failure.


Midterm results of free internal thoracic artery grafting for myocardial revascularization.
This study investigated the midterm results after free internal thoracic artery (FITA) grafting for coronary artery bypass grafting. Between 1988 and 1995, coronary artery bypass grafting and postoperative graft angiography were performed in 337 patients, of whom 56 patients were treated with 57 FITA grafts. We examined the postoperative graft patency of FITA grafts compared with in situ internal thoracic artery (IITA) grafts, and the late results in the patients receiving at least one FITA graft (FITA group) were compared with those in the patients receiving only IITA graft (IITA group). The early postoperative graft patency rate was 93.2% for the FITA grafts and 96.0% for the IITA grafts (not significant [NS]). Patients underwent sequential graft angiography at 29.5 months postoperatively (25 FITA and 89 IITA). The late graft patency rate was 100% and 92.1%, respectively (not significant). The cardiac death-free survival rate at 5 years was 93.5% in the FITA group and 96.6% in the IITA group (not significant), and the angina-free survival rate at 5 years was 80.6% and 83.2%, respectively (not significant). The FITA provides late results comparable with those attained with IITA.


Downregulated MTAP expression in myxofibrosarcoma: A characterization of inactivating mechanisms, tumor suppressive function, and therapeutic relevance.
Myxofibrosarcomas are genetically complex and involve recurrently deleted chromosome 9p, for which we characterized the pathogenically relevant target(s) using genomic profiling. In 12 of the 15 samples, we detected complete or partial losses of 9p. The only aggressiveness-associated, differentially lost region was 9p21.3, spanning the potential inactivated methylthioadenosine phosphorylase (MTAP) that exhibited homozygous (4/15) or hemizygous (3/15) deletions. In independent samples, MTAP gene status was assessed using quantitative- and methylation-specific PCR assays, and immunoexpression was evaluated. We applied MTAP reexpression or knockdown to elucidate the functional roles of MTAP and the therapeutic potential of L-alanosine in MTAP-preserved and MTAP-deficient myxofibrosarcoma cell lines and xenografts. MTAP protein deficiency (37%) was associated with MTAP gene inactivation (P < 0.001) by homozygous deletion or promoter methylation, and independently portended unfavorable metastasis-free survival (P = 0.0318) and disease-specific survival (P = 0.014). Among the MTAP-deficient cases, the homozygous deletion of MTAP predicted adverse outcome. In MTAP-deficient cells, MTAP reexpression inhibited cell migration and invasion, proliferation, and anchorage-independent colony formation and downregulated cyclin D1. This approach also attenuated the tube-forming abilities of human umbilical venous endothelial cells, attributable to the transcriptional repression of MMP-9, and abrogated the susceptibility to L-alanosine. The inhibiting effects of MTAP expression on tumor growth, angiogenesis, and the induction of apoptosis by L-alanosine were validated using MTAP-reexpressing xenografts and reverted using RNA interference in MTAP-preserved cells. In conclusion, homozygous deletion primarily accounts for the adverse prognostic impact of MTAP deficiency and confers the biological aggressiveness and susceptibility to L-alanosine in myxofibrosarcomas.


Dynamical modelling of viral infection and cooperative immune protection in COVID-19 patients.
Once challenged by the SARS-CoV-2 virus, the human host immune system triggers a dynamic process against infection. We constructed a mathematical model to describe host innate and adaptive immune response to viral challenge. Based on the dynamic properties of viral load and immune response, we classified the resulting dynamics into four modes, reflecting increasing severity of COVID-19 disease. We found the numerical product of immune system's ability to clear the virus and to kill the infected cells, namely immune efficacy, to be predictive of disease severity. We also investigated vaccine-induced protection against SARS-CoV-2 infection. Results suggested that immune efficacy based on memory T cells and neutralizing antibody titers could be used to predict population vaccine protection rates. Finally, we analyzed infection dynamics of SARS-CoV-2 variants within the construct of our mathematical model. Overall, our results provide a systematic framework for understanding the dynamics of host response upon challenge by SARS-CoV-2 infection, and this framework can be used to predict vaccine protection and perform clinical diagnosis.


Central Demyelinating Diseases after Vaccination Against Hepatitis B Virus: A Disproportionality Analysis within the VAERS Database.
Hepatitis B (HB) vaccination programs were set up worldwide in the early 1990s. Despite their major focus on reducing the burden of HB infection, they have seldom achieved the targeted population coverage in most countries, including the USA, with around 24.5% of adults being vaccinated against HB. Among proposed reasons for this is the persisting doubt about a possible link between HB vaccination and the occurrence of cases of multiple sclerosis (MS). Our objective was to evaluate a potential safety signal between MS and HB vaccination. We conducted a disproportionality analysis (DPA) using the cases reported to the Vaccine Adverse Event Reporting System (VAERS). We calculated the proportional reporting rate (PRR) and reporting odds ratio (ROR) of MS having occurred within the 120 days following HB immunization in adults aged 19-49 years when compared with other vaccines using the reports recorded in the VAERS database. Both ratios were estimated globally and then according to the origin of reports (USA vs. non-USA). We then performed a sensitivity analysis using a broader category of demyelinating events. MS cases following HB vaccination were more likely to originate from outside the USA and to be reported before 2000 than those associated with other immunizations. All computed ratios were found to be statistically significant, with PRRs ranging from 3.48 to 5.56 and RORs ranging from 3.48 to 5.62. When considering the geographical origin, similar RORs were obtained for both US and non-US cases. In VAERS, MS cases were up to five times more likely to be reported after an HB vaccination than after any other vaccination. Since DPA is mainly suited for hypothesis generation, further studies evaluating the nature of the link between MS and HB vaccination would be of considerable importance.


Permeation of long-chain fatty acid into adipocytes. Kinetics, specificity, and evidence for involvement of a membrane protein.
This study extends our earlier work (Abumrad, N. A., Perkins, R.C., Park, J.H., and Park, C.R. J. Biol. Chem. 256, 9183-9191) which showed that oleate permeates the plasma membrane of the rat adipocyte principally by a transport process with the characteristics of facilitated diffusion. In the present study, fatty acid (FA) transport is characterized with regard to its specificity and susceptibility to inhibition by protein modifiers. The kinetics of competitive inhibition for transport of oleate and stearate are shown under conditions where complications due to competition for binding of FAs to the albumin in the medium are minimized. Stearate inhibits influx of tracer oleate with a Ki that closely approximates its Km and, conversely, oleate inhibits similarly the influx of tracer stearate. Specificity of the FA transport system is shown in studies using a variety of natural FAs of different chain length, or FA analogues. Oleate (Km = 0.06 microM), stearate (Km = 0.16 microM), linoleate (Km = 0.22 microM), palmitate, (Km = 0.2 microM), and laurate (Km = 1.5 microM) are good substrates, but octanoate is not transported. An oxazolidine ring on C-5 but not on C-16 of stearate blocks binding to the transporter. Methylation of the carboxyl function but not alpha-bromination inhibits transport. These studies suggest that a FA must have a hydrocarbon chain of at least nine carbons and a free carboxyl function to be recognized by the transporter. FA transport does not require Na or ATP. Pronase but not trypsin treatment of intact cells reduces fatty acid influx. Transport is insensitive to maleimides. It is strongly and irreversibly blocked by pretreatment of the cells with the stilbene compounds, 4,4'-diisothiocyanostilbene-2,2'-disulfonate and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, but only slightly inhibited by dipyridamole. Polyacrylamide gel electrophoresis of plasma membrane proteins from cells treated with [3H] 4,4'-diisothiocyanostilbene-2,2'-disulfonate shows a peak of radioactivity at about Mr = 85,000. When cells are incubated in various concentrations of this agent, the counts recovered in the peak reach a maximum coincident with maximum inhibition of transport. We conclude that permeation of the plasma membrane of the adipocyte by long-chain FAs at physiological concentrations is mediated by a protein transporter with distinct specificity requirements.


Identifying Circulating and Lung Tissue Cytokines Associated with Thoracic Irradiation and AEOL 10150 Treatment in a Nonhuman Primate Model.
Inflammatory cytokines have been suggested to play important roles in radiation-induced lung injury (RILI). Identifying significantly changed circulating and tissue cytokines after thoracic irradiation will aid in deciphering the mechanism of RILI and identifying potential biomarkers to predict clinical outcome. Herein, the levels of 24 cytokines were measured in serial plasma samples and lung tissue samples collected from a pilot study where nonhuman primates (NHPs) received 11.5 Gy whole thoracic lung irradiation (WTLI) and were then treated with or without a medical countermeasure, AEOL 10150 [a superoxide dismutase (SOD) mimetic]. Seven plasma cytokines (i.e., IP-10, MCP-1, IL-12, IL-15, IL-16, IL-7 and IL-6) were found to be significantly changed at different time points due to WTLI. Plasma IP-10 and MDC were significantly changed between the vehicle group and the drug group. The levels of IP-10, MCP-1, MIP-1α, TARC, IL-17, TNF-β and IL-6 were significantly elevated in the lung tissue lysates of NHPs that received WTLI versus radiation-naïve NHPs. The terminal plasma concentrations of IP-10, MDC, TARC, IL-12, IL-15 and IL-6 were significantly correlated with their levels in the lung tissue. The levels of four cytokines (MCP-4, IL-17, TNF-β and IL-2) at early time points (≤8 weeks postirradiation) were significantly correlated with their terminal plasma levels, respectively. Statistical analysis indicated that circulating cytokines could be discriminatory predictors of AEOL 10150 treatment. Taken together, our data suggested that the cytokine profiles were significantly changed after WTLI as well as mitigator treatment, and that the plasma cytokine profiles could potentially be used to distinguish vehicle or mitigator treatment after WTLI in a NHP model.


The relationship between coronary artery calcification and renal function in nondialyzed patients.
Coronary artery calcification (CAC) has been described in individuals with chronic kidney disease (CKD), and its presence is associated with an increased risk of cardiovascular death. However, it is unclear whether there is an independent relationship between renal function and CAC. Therefore, we evaluated the association between renal function and CAC. We retrospectively reviewed 870 Korean patients who had undergone computed tomographic coronary angiography. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study formula with an ethnic factor for the Korean population. The CKD stages were classified using estimated GFR (eGFR) and proteinuria. The mean age of the participants was 56.8±11.8 years, and the mean eGFR was 89.4±16.5 mL/min/1.73 m². Hypertension and diabetes were noted in 41.5 and 17.0% of patients, respectively. There were 584 and 286 patients with no CAC and with CAC, respectively. After adjusting for confounding variables, late stage CKD was associated with CAC [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.05-7.46]. However, early stage CKD was not associated with CAC (OR 1.61, 95% CI 0.92-2.82). Diabetes was an independent risk factor of CAC (OR 2.06, 95% CI 1.36-3.13). There was no significant association between proteinuria and CAC (OR 1.65, 95% CI 0.96-2.85). CAC is related to late stage CKD in nondialyzed patients. These findings emphasize that individuals with CAC should be considered a high-risk population for decreased renal function.


Enhanced aqueous photochemical reaction rates after freezing.
Sunlit snow/ice is known to play an important role in the processing of atmospheric species, including photochemical production of NO(x), HONO, molecular halogens, alkyl halides, and carbonyl compounds, among others. It has been shown that a liquid-like (quasi-liquid or disordered) layer exists on the surface of pure ice and that this quasi-liquid layer is also found on the surface of ambient snow crystals and ice at temperatures similar to polar conditions. However, it is unclear what role the liquid-like fractions present in and on frozen water play in potential photochemical reactions, particularly with regard to organic substrates. Here, we report a detailed study of enhanced rates of photochemical nucleophilic substitution of p-nitroanisole (PNA) with pyridine, a well-characterized and commonly used actinometer system. Reaction rates were enhanced by a factor of up to approximately 40 when frozen at temperatures between 236 and 272 K. Reaction rates were dependent on temperature and solute concentration, both variables that control the nature of the liquid-like fraction in frozen water. The results obtained indicate that a major portion of the organic solutes is excluded to the liquid-like layer, significantly impacting the rate of the photochemical nucleophilic substitution reaction studied here. Also, the direct comparison of liquid-phase kinetics to reactions occurring in frozen water systems is drawn into question, indicating that a simple extrapolation of liquid-phase mechanisms to snow/ice may not be valid for certain reactions.


The additional therapeutic effect of group music therapy for schizophrenic patients: a randomized study.
Schizophrenia is one of the most serious mental disorders. Music therapy has only recently been introduced as a form of treatment. The aim of this study was to examine the effect of music therapy for schizophrenic in-patients needing acute care. Thirty-seven patients with psychotic disorders were randomly assigned to an experimental group and a control group. Both groups received medication and treatment indicated for their disorder. Additionally, the experimental group (n = 21) underwent group music therapy. Significant effects of music therapy are found in patients' self-evaluation of their psychosocial orientation and for negative symptoms. No differences were found in the quality of life. Musical activity diminishes negative symptoms and improves interpersonal contact. These positive effects of music therapy could increase the patient's abilities to adapt to the social environment in the community after discharge from the hospital.


Human carcinogenesis and alcohol in hepato-gastroenterology.
Alcohol consumption is one of the top-10 risks for worldwide burden of disease. The International Agency for Research for Cancer affirmed that there was evidence for the carcinogenicity of ethanol in animals and classified alcohol consumption as carcinogenic for humans. Alcohol consumption causes cancers of the oral cavity, pharynx, larynx, oesophagus, colorectum, liver, pancreas and female breast. Most alcohol-induced diseases increases in a linear fashion as intake increases: oral, oesophagus and colon cancer fall into this pattern: very little is known about safe margins of alcohol consumption. Given the linear dose-response relation between alcohol intake and risk of cancer, control of heavy drinking remains the main target for cancer control. European Code Against Cancer recommends keeping daily consumption within two drinks (20 g [corrected] of alcohol/day) for man and one drink for women and US Department of Health and Human Services suggest as a low risk, a maximum of 10 g [corrected] of alcohol a day in man and half of this in women.


Ethos: The heart of ethics and health.
Ethics in nursing care are traditionally discussed in terms of moral norms or principles. When taking an ontological approach to ethics, ethics is about ethos. Ethos involves both an internal and an external side of ethics. Considering ethics and health from an ontological perspective can provide a different understanding of ethics and health in caring and nursing. The aim of this study is to deepen the ontological understanding of ethics and health in caring and nursing. The research question is as follows: What is the ontology of health and ethics in caring and nursing? The study follows a hermeneutical design inspired by Gadamer. Participants and research context: essays about ethics and health were gathered from PhD students in nursing and caring sciences. The research follows Responsible conduct of research guidelines provided by the Finnish Advisory Board on Research Integrity. An ethos with the values of freedom and responsibility seem to ontologically be important for ethics and health. These values allow a movement between the internal and the external sides of ethics that is important for health. The ethos of freedom and responsibility that is essential for ethics and health can provide the current ethical debate a new starting point that previous research asks for. Ontologically, an ethos of freedom and responsibility is essential for ethics and health in nursing and caring.


Ligand Dynamics Time Scales Identify the Surface-Ligand Interactions in Thiocyanate-Capped Cadmium Sulfide Nanocrystals.
The nanocrystal surface, which acts as an interface between the semiconductor lattice and the capping ligands, plays a significant role in the attractive photophysical properties of semiconductor nanocrystals for use in a wide range of applications. Replacing the long-chain organic ligands with short inorganic variants improves the conductivity and carrier mobility of nanocrystal-based devices. However, our current understanding of the interactions between the inorganic ligands and the nanocrystals is obscure due to the lack of experiments to directly probe the inorganic ligands. Herein, using two-dimensional infrared spectroscopy, we show that the variations in the inorganic ligand dynamics within the heterogeneous nanocrystal ensemble can identify the diversities in the inorganic ligand-nanocrystal interactions. The ligand dynamics time scale in SCN- capped CdS nanocrystals identifies three distinct ligand populations and provides molecular insight into the nanocrystal surface. Our results demonstrate that the SCN- ligands engage in a dynamic equilibrium and stabilize the nanocrystals by neutralizing the surface charges through both direct binding and electrostatic interaction.


Oral pharmacokinetics of fluazifop-butyl in human volunteers.
1. Fluazifop-butyl, the active ingredient of FUSILADE, a selective herbicide, was administered orally to three male volunteers at a dose level of 0.07 mg kg-1 body weight. Over a period of 6 d between 80 and 93% of the dose was excreted in urine as the metabolite fluazifop, the majority within the first 24 h. Peak plasma concentrations of fluazifop occurred 1-2.5 h after administration. 2. The elimination of fluazifop from plasma and urine can be described by a one-compartment pharmacokinetic model and the elimination half-life was estimated from blood and urine data to be within the range 9-37 h. Fluazifop was found to bind to serum proteins. 3. The study indicates that the amount of fluazifop-butyl absorbed in exposed persons can be assessed by measuring fluazifop concentrations in urine.


Evolution of power law distributions in science and society.
Power law distributions have been observed in numerous physical and social systems; for example, the size distributions of particles, aerosols, corporations, and cities are often power laws. Each system is an ensemble of clusters, comprising units that combine with or dissociate from the cluster. Constructing models and investigating their properties are needed to understand how such clusters evolve. To describe the growth of clusters, we hypothesize that a distribution obeys a governing population dynamics equation based on a reversible association-dissociation process. The rate coefficients are considered to depend on the cluster size as power expressions, thus providing an explanation for the asymptotic evolution of power law distributions.


Fasudil hydrochloride hydrate, a Rho-kinase inhibitor, suppresses 5-hydroxytryptamine-induced pulmonary artery smooth muscle cell proliferation via JNK and ERK1/2 pathway.
Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) plays a critical role in the development of pulmonary artery hypertension, and inhibition of PASMC proliferation has been shown to be beneficial to patients with this disease. Recent studies indicate that Rho/ROCK is critically involved in the proliferation of smooth muscle cells. However, the signal transduction of Rho/ROCK and its downstream signaling are not fully understood. In the present study, we investigated the antiproliferation effect of fasudil hydrochloride hydrate, a Rho-kinase inhibitor, on rat PASMC proliferation, and the possible relation of Rho/ROCK to ERK, JNK pathways. The results indicate that fasudil effectively inhibited 5-HT-induced PASMC proliferation, as evaluated by MTT assay and protein expression of proliferating cell nuclear antigen. Flow cytometry analysis showed that fasudil markedly blocked 5-HT-induced cell-cycle progression by arresting the cells in the G(0)/G(1) phase. Consistently, 5-HT-induced ROCK-1 mRNA expression and MYPT-1 phosphorylation were markedly suppressed by fasudil. In addition, fasudil significantly decreased 5-HT-induced JNK activation, ERK translocation to the nucleus and subsequent c-fos and c-jun expression. Taken together, these results indicate that Rho/ROCK is essential for PASMC proliferation produced by 5-HT. Fasudil effectively suppressed 5-HT-induced PASMC proliferation and cell-cycle progression, which was associated with inhibition of JNK activation, ERK translocation to nucleus and subsequent c-fos and c-jun expression.


Severe uropathy and normal amniotic fluid volume in a male fetus: sonographic surveillance leading to the diagnosis of megacystis-microcolon-intestinal hypoperistalsis syndrome.
The widespread use of sonography as a screening tool for fetal anomalies has facilitated prenatal detection of several fetal conditions characterized by urinary tract dilatation. These conditions are more common in male fetuses and are generally a result of an anatomic defect causing obstruction along the urinary tract system. Although the prognosis of these conditions largely depends on the specific anomaly, several poor prognostic factors have been described. These factors include detection at an early gestational age, bilateral marked dilatation, a persistently obstructed bladder, oligohydramnios causing pulmonary hypoplasia, and the presence of associated fetal or chromosomal anomalies. We report a case in which a male fetus at 14 weeks' gestation had a diagnosis of rapidly progressing bilateral hydronephrosis, massive bladder dilatation, hydroureter, and a surprisingly normal amniotic fluid volume. Serial sonographic surveillance assisted us in obtaining the correct diagnosis, which was important for adequately consulting the patient regarding the fetal prognosis in the affected index pregnancy as well as the likelihood of recurrence in future gestations.


[Clinical medicinal engineering support in disaster relief medicine].
Disaster Relief Medicine (DRM), a newly developed science, not only crosses Emergency Service and Critical Health Care, but also relates to other various fields such as Nursing, Clinical examination and Clinical Medicinal Engineering etc, all of which require competent Clinical Medicinal Engineers. Thus, a key subject of Clinical Engineering is to provide quality support to medical equipments, and to offer engineers educational training on this diverse science, in order to improve their professional and managerial skills. Based on DRM characteristics, specifically, based on our first hand experience during disaster relief effort in Wen-Chuan Earthquake, we documents our thoughts and discussion over the issues we found in above areas as listed in the article below.


Rapid plasmid analysis for identification of Edwardsiella ictaluri from infected channel catfish (Ictalurus punctatus).
Eighteen different strains of Edwardsiella ictaluri isolated from infected channel catfish (Ictalurus punctatus) were screened to determine whether plasmid DNA was present. Two plasmids of 5,700 and 4,900 base pairs were identified. Restriction enzyme analysis showed that each of the strains harbored these same two plasmids. Restriction maps of the separated plasmids indicated that these plasmids were not closely related to each other. A rapid screening technique was developed that would allow the presence of these plasmids from either broth cultures or single colonies of E. ictaluri to be determined within 2 to 3 h by agarose gel electrophoresis. These results suggest that plasmid fingerprinting of E. ictaluri should become a useful tool in the presumptive identification of this bacterium from infected channel catfish.


Partial characterization of procollagen messenger ribonucleic acid in a murine chondrosarcoma.
Cells from a rat chondrosarcoma in primary suspension culture were used for labeling studies and isolation of RNA. With extended labeling, a distinct fraction of poly(A+)RNA sedimented in the region of 26S on denaturing sucrose gradients. Similar profiles were obtained with labeled poly(A+)RNA isolated from normal cartilage tissues, as well as from chondrocytes in culture. This mRNA coded for collagenous protein when translated in a cell-free system derived from wheat germ. Among the polypeptides synthesized in vitro, one distinctive component of approximately 150,000 daltons was detected by gel electrophoresis. Polypeptides of identical size, sensitive to bacterial collagenase, were also synthesized in vitro by polysomes isolated from the chondrosarcoma.


Fusion protein between protein ZZ and red fluorescent protein DsRed and its application to immunoassays.
In the present study, a red fluorescent protein (DsRed) from the coral Discosoma was fused to the C-terminus of protein ZZ, a synthetic artificial IgG-Fc-fragment-binding protein derived from the B-domain of staphylococcal Protein A. The chimaeric protein, tagged with six histidine residues at the N-terminus, was expressed in Escherichia coli and easily purified by one-step Ni2+-chelating affinity chromatography. Its fluorescence and IgG-binding activities were validated using fluorescence-spectrum analysis, ELISA and dot-blot analysis. Furthermore, in subsequent dot-blotting immunoanalysis of glutathione S-transferase and tumour necrosis factor-alpha, and immunofluorescent microscopy assay of interferon regulatory factor 3, the chimaeric protein enabled effective detection of target molecules. Compared with fluorescence-conjugated antibodies, ZZ-DsRed is less susceptible to photobleaching and easy to produce. In addition, unlike HRP (horseradish peroxidase)-conjugated antibodies, using ZZ-DsRed needs no addition of a chromogenic reagent. Our results indicate that ZZ-DsRed shows a wide and promising application potential in immunological detection as a substitute for fluorescent or HRP-conjugated anti-IgGs.


miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma.
Abnormal expression of miRNAs is closely related to a variety of human cancers. The purpose of this study is to identify new tumor suppressor miRNA and elucidate its physiological function and mechanism in renal cell carcinoma (RCC). The expression of miR-145 in 45 RCC and adjacent normal tissues was performed by quantitative RT-PCR. Cell proliferation, migration, invasion, apoptosis and cycle assays were carried out for functional analysis after miR-145 transfection. Two target genes of miR-145 were identified by luciferase reporter assay. The altered expression of 84 epithelial to mesenchymal transition (EMT)-related genes after miR-145 transfection was detected by RT(2) Profiler EMT PCR array. The expression of miR-145 was downregulated in RCC compared to their normal adjacent tissues. Restoring miR-145 expression in RCC cell lines dramatically suppressed cell proliferation, migration and invasion, and induced cell apoptosis and G2-phase arrest. We further validated those miR-145 targets two oncogenes, ANGPT2 and NEDD9 in RCC. In addition, miR-145 was found to regulate numerous genes involved in the EMT. These findings demonstrate that miR-145 functions as tumor suppressor in RCC, suggesting that miR-145 may be a potential therapeutic target for RCC.


Connectivity in ictal single photon emission computed tomography perfusion: a cortico-cortical evoked potential study.
Subtraction ictal and interictal single photon emission computed tomography can demonstrate complex ictal perfusion patterns. Regions with ictal hyperperfusion are suggested to reflect seizure onset and propagation pathways. The significance of ictal hypoperfusion is not well understood. The aim of this study was to verify whether ictal perfusion changes, both hyper- and hypoperfusion, correspond to electrically connected brain networks. A total of 36 subtraction ictal and interictal perfusion studies were analysed in 31 consecutive medically refractory focal epilepsy patients, evaluated by stereo-electroencephalography that demonstrated a single focal onset. Cortico-cortical evoked potential studies were performed after repetitive electrical stimulation of the ictal onset zone. Evoked responses at electrode contacts outside the stimulation site were used as a measure of connectivity. The evoked responses at these electrodes were compared to ictal perfusion values noted at these locations. In 67% of studies, evoked responses were significantly larger in hyperperfused compared to baseline-perfused areas. The majority of hyperperfused contacts also had significantly increased evoked responses relative to pre-stimulus electroencephalogram. In contrast, baseline-perfused and hypoperfused contacts mainly demonstrated non-significant evoked responses. Finally, positive significant correlations (P < 0.05) were found between perfusion scores and evoked responses in 61% of studies. When the stimulated ictal onset area was hyperperfused, 82% of studies demonstrated positive significant correlations. Following stimulation of hyperperfused areas outside seizure onset, positive significant correlations between perfusion changes and evoked responses could be seen, suggesting bidirectional connectivity. We conclude that strong connectivity was demonstrated between the ictal onset zone and hyperperfused regions, while connectivity was weaker in the direction of baseline-perfused or hypoperfused areas. In trying to understand a patient's epilepsy, one should consider the contribution of all hyperperfused regions, as these are likely not random, but represent an electrically connected epileptic network.


Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain.
Disc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation. This study evaluated the association of single nucleotide variants (SNVs) of the candidate genes of the aggrecan metabolic pathway with the severity of lumbar disc herniation in patients with chronic mechanical low back pain. In addition, we assessed the in-silico functional analysis of the significant SNVs and association of their haplotypes with the severity of lumbar disc herniation. A descriptive cross sectional study was carried out on 106 patients. Severity of disc herniation and disc degeneration were assessed on T2-weighted mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform. Multivariable linear regression analysis was carried out using PLINK 1.9 software adjusting for age, gender, body mass index and severity of disc degeneration. Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster) were used for in-silico functional analysis. Mean age was 52.42 ± 9.42 years and 69.8% were females. The mean severity of disc herniation was 2.81 ± 1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994, rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were associated with the severity of lumbar disc herniation. However, only the rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic by in-silico functional analysis. SNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation.


SEC7 encodes an unusual, high molecular weight protein required for membrane traffic from the yeast Golgi apparatus.
Saccharomyces cerevisiae with mutations at the sec7 locus are pleiotropically deficient in protein transport within the Golgi apparatus and proliferate a large array of Golgi cisternae at a restrictive growth temperature (37 degrees C). The SEC7 gene and its product (Sec7p) have been evaluated by molecular cloning and sequence analysis. Two genes that allow sec7 mutant cells to grow at 37 degrees C are represented in wild-type yeast DNA libraries. A single copy of the authentic SEC7 gene permits growth of mutant cells, whereas the other gene suppresses growth deficiency only when expressed from a multicopy plasmid. The SEC7 gene is contained on a 8.4-kilobase pair SphI restriction fragment, portions of which hybridize to a single 6-kilobase pair mRNA. The gene is essential for yeast vegetative growth. DNA sequence analysis of this region detects a single open reading frame with the potential to encode a 2008-amino acid-long hydrophilic protein of 230 kDa. Putative Sec7p contains an unusual, highly charged acidic domain of 125 amino acids with 29% glutamate, 18% aspartate, and 21% serine. Within this region, stretches of 14 consecutive glutamate residues and 13 consecutive glutamates/aspartates are predicted. This domain in Sec7p may serve a structural role to interact with lipids or proteins on the cytoplasmic surface of the Golgi apparatus.


Preoperative antisepsis: critiquing a research article.
A critique of a research article on preoperative skin antisepsis was undertaken using a recognised framework. This critique drew out issues which may be of use for clinicians in making a judgement regarding implementing change into their clinical practice.


Alkali-Metal-Mediated Magnesiations of an N-Heterocyclic Carbene: Normal, Abnormal, and "Paranormal" Reactivity in a Single Tritopic Molecule.
Herein the sodium alkylmagnesium amide [Na4Mg2(TMP)6(nBu)2] (TMP=2,2,6,6-tetramethylpiperidide), a template base as its deprotonating action is dictated primarily by its 12 atom ring structure, is studied with the common N-heterocyclic carbene (NHC) IPr [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]. Remarkably, magnesiation of IPr occurs at the para-position of an aryl substituent, sodiation occurs at the abnormal C4 position, and a dative bond occurs between normal C2 and sodium, all within a 20 atom ring structure accommodating two IPr(2-). Studies with different K/Mg and Na/Mg bimetallic bases led to two other magnesiated NHC structures containing two or three IPr(-) monoanions bound to Mg through abnormal C4 sites. Synergistic in that magnesiation can only work through alkali-metal mediation, these reactions add magnesium to the small cartel of metals capable of directly metalating a NHC.


Improving Analgesic Efficacy and Safety of Thoracic Paravertebral Block for Breast Surgery: A Mixed-Effects Meta-Analysis.
While most trials of thoracic paravertebral nerve blocks (TPVB) for breast surgery show benefit, their effect on postoperative pain intensity, opioid consumption, and prevention of chronic postsurgical pain varies substantially across studies. Variability may result from use of different drugs and techniques. To examine the use of TPVB in breast surgery, and to determine which method(s) provide optimal efficacy and safety. Mixed-Effects Meta-Analysis. We conducted a systematic review of randomized trials comparing TPVB to no intervention using random-effects models. To evaluate the contributions of various techniques, clinical approaches were included as moderators in mixed-effects models. A total of 24 randomized controlled trials (RCTs) with 1,822 patients were included. Use of TPVB decreased postoperative pain scores at rest and movement at the first 2, 24, 48, and 72 hours. TPVB modestly decreased intraoperative and postoperative opioid consumption, reduced nausea and vomiting, and shortened hospitalization, but to a probably clinically irrelevant degree. Blocks also appeared to reduce the incidence of chronic postsurgical pain at 6 months. Adding fentanyl to the TPVB improved pain at rest (at 24, 48, and 72 hours) and movement (at 24 and 72 hours). Multilevel blocks provided better postoperative pain control, but only during movement (at 2, 48, and 72 hours). Fewer procedural complications (especially hypotension, epidural spread, and Horner's syndrome) occurred when anatomical landmarks were supplemented with ultrasound guidance. The number of studies available was limited in the meta-analytic model of incidence of chronic post-surgical pain. TPVB reduces postoperative pain and opioid consumption, and has a limited beneficial effect on the quality of recovery. From all the techniques that were evaluated, only the addition of fentanyl, and performing multilevel blocks were associated with improved acute analgesia. TPVB may reduce chronic postsurgical pain at 6 months.


Simplified skeletal maturity scoring system: learning curve and methods to improve reliability.
Retrospective radiographical review by 5 independent observers. To validate the intra- and interobserver reliability of the simplified skeletal maturity scoring (SSMS) system in a large cohort for each stage and for the overall cohort. The SSMS has been used to successfully predict curve progression in idiopathic scoliosis. A total of 275 patients with scoliosis (8-16 yr) with 1 hand radiograph were included from 2005 to 2011. Five participants independently scored images on 2 separate occasions using the SSMS (stage, 1-8). Observers (listed in order of increasing SSMS experience) included orthopedic surgery resident, clinical fellow (CF), research fellow, and senior faculty. Intraobserver agreement between the 2 sets of scores was estimated using the Pearson and Spearman rank correlation coefficients. Interobserver agreement was estimated with the unweighted Fleiss κ coefficient for the overall cohort and for junior (orthopedic surgery resident, CF, research fellow) versus senior faculty. Intrarater reliability for orthopedic surgery resident, CF, research fellow, senior faculty was 0.956, 0.967, 0.986, 0.991, and 0.998, respectively (Spearman). Intrarater agreement improved with greater familiarity using the SSMS. The inter-rater reliability for junior faculty (κ = 0.65), senior faculty (κ = 0.652), and the overall group (κ = 0.66) indicated agreement between all observers but no improved inter-rater agreement with experience. However, 98% of disagreements occurred only within 1 stage. Stages 2, 3, and 4 accounted for most of the variability; stage 3 was the most commonly scored stage, corresponding to peak growth velocity. The SSMS has excellent intraobserver agreement with substantial interobserver agreement. Intraobserver--but not interobserver agreement--improves with familiarity using the SSMS. Expectancy bias may contribute to a higher likelihood of assigning an SSMS 3. Discrepancies when classifying stages 2 to 4 may be resolved by improved descriptions of epiphyseal capping in stages 2 and 3. 2.


Study protocol for evaluating Brown Buttabean Motivation (BBM): a community-based, Pacific-driven approach to health.
Buttabean Motivation (BBM) is a Pacific-led organisation which aims to reduce obesity amongst Pacific and Māori people in New Zealand enabling them to choose a healthy and active life-style for the duration of their lives, their children, their wider family and the community. BBM offers a holistic approach to weight loss, recognising that mental health, family and cultural factors all play essential and critical role in nutrition and physical activity patterns. This study aims to evaluate the effectiveness of BBM for sustained health and wellbeing outcomes among its predominantly Pacific and Māori participants for both general BBM members and those with morbid obesity attending the 'From the Couch' programme. Quasi-experimental pre-post quantitative cohort study design with measured or self-reported weight at various time intervals for both cohorts. Weight will be analysed with general linear mixed model for repeated measures, and compared with a prediction model generated from the literature using a mixed method meta-analysis. The secondary outcome is change in pre- and post scores of Māori scale of health and well-being, Hua Oranga. Multiple studies have shown that many diet and physical activity programmes can create short-term weight loss. The fundamental question is whether BBM members maintain weight loss over time. In New Zealand, Pacific and Māori engagement in health enhancing programmes remains an important strategy for achieving better health and wellbeing outcomes, and quality of life. Internationally, the collectivist cultures of indigenous and migrant and minority populations, living within dominant individualist western ideologies, have much greater burdens of obesity. If BBM members demonstrate sustained weight loss, this culturally informed community-based approach could benefit to other indigenous and migrant populations. Australian New Zealand Clinical Trial Registry ACTRN12621000931875 (BBM general members) First submitted 10 May 2021, registration completed 15 July 2021. ACTRN12621001676808 7 (From the Couch) First submitted 28 October 2021, registration completed 7 December 2021.


[The Bridge between Pediatric and Adult Neurology].
Pediatric and adult departments are differentiated based on a cutoff age of approximately 15-17 years. In clinical neurology, there are certain disorders and related problems that overlap these age-determined boundaries. In this review, the following three themes are discussed. (1) Manual dexterity: Considering motor skills through the developmental stages of a child and manual impairment due to localized brain damage in adults, manual dexterity has been reviewed extensively from the perspective of cortical association areas. (2) Hepatolenticular degeneration: Wilson's disease (children) and Westphal-Strümpell pseudosclerosis (adults) are compared and assessed based on the age of onset to identify differences in clinical symptoms and pathological findings. (3) Hirayama disease: This disease has been identified as an adult neurological disorder. Since the onset of Hirayama disease occurs around puberty in children and adolescents, it provides a connecting link between pediatric and adult neurology.


A new indicator for the measurement of change with ordinal scores.
Studies on how to better measure change have been published at least since the third decade of the last century, but no general indicator or strategy of measurement is currently agreed upon. The aim of this study is to propose a new indicator, the indicator of positive change, as an option for the assessment of change when ordinal scores are used in pretest and posttest designs. The basic idea is to measure the proportion of possible (positive) change inside a group that can be attributed to an intervention. The approach is based on the joint distribution of the before and after scores (differences), represented by the cells (i, j) of a contingency table m × m (m is the number of classes of the ordinal measurement scale; i and j are the lines and columns of the table, respectively). By convention, higher classes are the most unfavorable on the scale such that subjects that improve "migrate" from the higher to the lower classes as a result of an intervention and vice versa. The introduced indicator offers a new strategy for the analysis of change when dealing with repeated measurements of the same subject, assuming that the measured variable is ordinal (e.g., clinician-rating scales). The presented approach is easily interpretable and avoids the problems that arise, for instance, in those cases where a large concentration of high/low scores is present at the baseline.


An Investigation Into Interpersonal and Peripersonal Spaces of Chinese People for Different Directions and Genders.
This study explores the interpersonal space (IPS) and peripersonal space (PPS) of Chinese people and evaluates the relationship between the two spaces for different directions and genders. Seventy-one participants were recruited for this study. Participants were required to determine their IPS in eight directions (0°, 45°, 90°, 135°, 180°, 225°, 270°, 315°) when approached by male or female confederates in the comfort distance task. Each participant was also asked to judge their PPS in five directions (0°, 45°, 90°, 270°, 315°) following the same procedure. Results showed that their IPS was significantly influenced by direction (p < 0.05), with the largest distance in the front (0°) and the closest distance in the rear (135°, 180°, 225°), indicating non-circular IPS among Chinese subjects. Moreover, the PPS on the right side (90°) was larger than in other directions (0°, 45°, 270°, 315°). Participants maintained larger IPS than PPS in the front, but the IPS was closer than PPS on the right and left sides. When facing a female confederate, larger IPS was preferred than PPS, whereas the opposite held true when facing a male confederate. Comparison of participants' arm length and PPS showed that the reachability distance was overestimated in the front but underestimated laterally. The findings of this study can be applied to environmental design, space utilization, and social interaction.


Concentration dependence of active potassium transport in the human red blood cell in the presence of inhibitors.
The active potassium influx in the human red blood cell is inhibited by strophanthidin, ethacrynic acid, and MK-870 (a new diuretic), and the degree of inhibition is greater at low concentrations of extracellular potassium than at high. In the case of ethacrynic acid, potassium appears to diminish the rate of combination of the drug with the transport system. The kinetic behavior of the active potassium influx in the presence of the inhibitors strophanthidin and ethacrynic acid is consistent with a model in which the binding of potassium at one of the potassium-sensitive sites in the transport system reduces the affinity of the system for the drug, and binding of a second potassium ion further reduces the affinity. It is not possible to distinguish between the sites on the basis of the studies presented here.


Beyond the Complement Cascade: Insights into Systemic Immunosenescence and Inflammaging in Age-Related Macular Degeneration and Current Barriers to Treatment.
Landmark genetic studies have revealed the effect of complement biology and its regulation on the pathogenesis of age-related macular degeneration (AMD). Limited phase 3 clinical trial data showing a benefit of complement inhibition in AMD raises the prospect of more complex mediators at play. Substantial evidence supports the role of para-inflammation in maintaining homeostasis in the retina and choroid. With increasing age, a decline in immune system regulation, known as immunosenescence, has been shown to alter the equilibrium maintained by para-inflammation. The altered equilibrium results in chronic, sterile inflammation with aging, termed 'inflammaging', including in the retina and choroid. The chronic inflammatory state in AMD is complex, with contributions from cells of the innate and adaptive branches of the immune system, sometimes with overlapping features, and the interaction of their secretory products with retinal cells such as microglia and retinal pigment epithelium (RPE), extracellular matrix and choroidal vascular endothelial cells. In this review, the chronic inflammatory state in AMD will be explored by immune cell type, with a discussion of factors that will need to be overcome in the development of curative therapies.


A case of interstitial pneumonitis associated with natural alpha-interferon therapy for myelofibrosis.
A 55-year-old man with myelofibrosis was treated with natural alpha-interferon with a good hematologic response. Initially, he had anemia, leukocytosis, thrombocytosis and hepatospleomegaly. A bone marrow biopsy showed replacement with fibrosis with an increase in megakaryocytes. Natural alpha-interferon (alpha-IFN) was started at a dose of 3 x 10(6) units/day. The leukocyte and platelet counts gradually normalized, and the liver and spleen decreased in size. However, the patient complained of a dry cough and dyspnea on the 61st treatment day, when the accumulated dose of alpha-IFN treatment had reached 1.8 x 10(8) units. He subsequently developed acute respiratory failure (PaO2 < 60 mm Hg) with bilateral lung infiltrations, suggesting the occurrence of interstitial pneumonitis associated with alpha-interferon therapy. Immediately, the alpha-interferon was discontinued and high-dose methylprednisolone (1.5 g/day) was administered for 3 days. This treatment was followed by oral prednisone therapy. Steroid therapy brought about gradual improvement as suggested by a repeat radiograph. Since high levels of fibrogenic cytokines, such as PDGF and TGF-beta, have been reported in patients with myelofibrosis, it is necessary to pay attention to interstitial pneumonia as a complication in alpha-IFN therapy for myelofibrosis.


Treatment challenges and outcomes for pediatric intracranial ependymoma at a single institution in Iran.
The scarcity of information on pediatric ependymoma in Iran motivated this study. Our main objectives were to determine outcomes, identify clinical management challenges at a nongovernment hospital in Iran, and devise guidelines for improving care. A retrospective chart review was performed for pediatric patients with ependymoma who were younger than 15 years and treated at MPCTRC between 2007 and 2015. Records included patient demographics, treatment regimens used, duration of follow-up, and outcomes. Clinical outcomes [ie, 3-year overall survival (OS) and progression-free survival (PFS)] were determined based on the age at diagnosis (younger or older than 3 years) by using the Kaplan-Meier method. In total, 73 eligible patients were enrolled; 20 patients were in the younger group, and 53 were in the older group. The majority (91.8%, n = 67) of patients underwent initial gross-total or partial surgical resection, and 6 (8.2%) had a biopsy. Twenty-one patients experienced ependymoma recurrence. The median time to relapse was 1 year. The median duration of follow-up and PFS were 25 and 17 months, respectively. The 3-year OS and PFS were 61% and 59.5%, respectively. At the time of this project, 27 patients had died, and 35 were alive with no evidence of disease. Our study demonstrated inferior outcomes of Iranian children with ependymoma. To improve our care for these children, a paradigm shift must occur that includes radiation therapy as standard of care, second-look surgery, a multidisciplinary team approach, and potentially twinning initiatives.


Development of an in situ simulation-based continuing professional development curriculum in pediatric emergency medicine.
Continuing professional development (CPD) activities delivered by simulation to independently practicing physicians are becoming increasingly popular. At present, the educational potential of such simulations is limited by the inability to create effective curricula for the CPD audience. In contrast to medical trainees, CPD activities lack pre-defined learning expectations and, instead, emphasize self-directed learning, which may not encompass true learning needs. We hypothesize that we could generate an interprofessional CPD simulation curriculum for practicing pediatric emergency medicine (PEM) physicians in a single-center tertiary care hospital using a deliberative approach combined with Kern's six-step method of curriculum development. From a comprehensive core list of 94 possible PEM clinical presentations and procedures, we generated an 18-scenario CPD simulation curriculum. We conducted a comprehensive perceived and unperceived needs assessment on topics to include, incorporating opinions of faculty PEM physicians, hospital leadership, interprofessional colleagues, and expert opinion on patient benefit, simulation feasibility, and value of simulating the case for learning. To systematically rank items while balancing the needs of all stakeholders, we used a prioritization matrix to generate objective "priority scores." These scores were used by CPD planners to deliberately determine the simulation curriculum contents. We describe a novel three-step CPD simulation curriculum design method involving (1) systematic and deliberate needs assessment, (2) systematic prioritization, and (3) curriculum synthesis. Of practicing PEM physicians, 17/20 responded to the perceived learning needs survey, while 6/6 leaders responded to the unperceived needs assessment. These ranked data were input to a five-variable prioritization matrix generating priority scores. Based on local needs, the highest 18 scoring clinical presentations and procedures were selected for final inclusion in a PEM CPD simulation curriculum. An interim survey of PEM physician (21/24 respondents) opinions was collected, with 90% finding educational value with the curriculum. The curriculum includes items not identified by self-directed learning that PEM physicians thought should be included. We highlight a novel methodology for PEM physicians that can be adapted by other specialities when designing their own CPD simulation curriculum. This methodology objectively considers and prioritizes the needs of practicing physicians and stakeholders involved in CPD.


The relationship of disability and employment for veterans from the 2010 Medical Expenditure Panel Survey (MEPS).
Veterans with disabilities, especially those with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) have difficulty obtaining and maintaining competitive employment. To determine if there are significant differences in employment between veterans with and without disability, between veterans with a disability and nonveterans with a disability, and to investigate the association of veteran status and disability with employment. Chi square analyses were conducted on data obtained from the 2010 Medical Expenditure Panel Survey to determine if significant differences in employment occurred between veterans with disabilities, veterans without disabilities and nonveterans with disabilities. Multivariate regression analyses were used to determine how veteran status and disability are associated with employment. Significant differences in employment were found between veterans with and without a disability; however, no significant differences existed in employment between veterans and nonveterans with a disability. Multivariate analysis showed that veteran status (aOR=1.80), having any disability (aOR=7.29), social disability (aOR=3.47) or a cognitive disability (aOR=3.16) were associated with not being employed. Veterans with disabilities are more likely not to be employed than veteran populations without disabilities. Veterans; however have unique disabilities, different than nonveterans with disabilities, that need to be addressed, such as social and cognitive disabilities resulting from TBI and PTSD. Future research should focus on evaluating the effectiveness of employment programs and policies designed to address the unique issues faced by veterans with disabilities.


Loss to follow-up among children and adolescents growing up with HIV infection: age really matters.
Globally, increasing numbers of HIV-infected children are reaching adolescence due to antiretroviral therapy (ART). We investigated rates of loss-to-follow-up (LTFU) from HIV care services among children as they transition from childhood through adolescence. Individuals aged 5-19 years initiated on ART in a public-sector HIV clinic in Bulawayo, Zimbabwe, between 2005 and 2009 were included in a retrospective cohort study. Participants were categorized into narrow age-bands namely: 5-9 (children), 10-14 (young adolescents) and 15-19 (older adolescents). The effect of age at ART initiation, current age (using a time-updated Lexis expansion) and transitioning from one age group to the next on LTFU was estimated using Poisson regression. Of 2273 participants, 1013, 875 and 385 initiated ART aged 5-9, 10-14 and 15-19 years, respectively. Unlike those starting ART as children, individuals starting ART as young adolescents had higher LTFU rates after moving to the older adolescent age-band (Adjusted rate ratio (ARR) 1.54; 95% CI: 0.94-2.55) and similarly, older adolescents had higher LTFU rates after transitioning to being young adults (ARR 1.79; 95% CI: 1.05-3.07). In older adolescents, the LTFU rate among those who started ART in that age-band was higher compared to the rate among those starting ART at a younger age (ARR = 1.70; 95% CI: 1.05, 2.77). This however did not hold true for other age-groups. Adolescents had higher rates of LTFU compared to other age-groups, with older adolescents at particularly high risk in all analyses. Age-updated analyses that examine movement across narrow age-bands are paramount in understanding how developmental heterogeneity in children affects HIV outcomes.


Immune Checkpoint Inhibitor Therapy as an Eye-Preserving Treatment for Locally Advanced Conjunctival Melanoma.
The authors present 2 patients with locally advanced conjunctival melanoma for whom definitive surgery would mean an orbital exenteration with its associated inherent total visual loss and major facial disfigurement. Instead both patients were treated with immune checkpoint inhibitor therapy. In 1 patient neoadjuvant pembrolizumab was used for approximately 12 months and the patient experienced near-total clinical resolution of the conjunctival melanoma. Multiple surgical biopsies of very small residual pigmentation showed pigmented macrophages and a complete pathologic response. In the second patient who presented with a locally advanced and metastatic conjunctival melanoma, significant shrinkage of conjunctival mass was observed after treatment with a combination of ipilimumab and nivolumab for 5 months, and this allowed preservation of the eye and ocular function.


Psychological abuse and its characteristic correlates among elderly Taiwanese.
This study examined the prevalence of psychological abuse and identified individual characteristics associated with different levels of psychological abuse in a group of randomly selected elderly Taiwanese. A cross-sectional design was performed that utilized a descriptive-correlational approach. Data for this study were gathered from several communities in southern Taiwan. The sample comprised 195 elderly Taiwanese aged 60 years or older, capable of verbal communication, and partially dependent on a caregiver. The Psychological Elder Abuse Scale (PEAS), the Short Portable Mental State Questionnaire (SPMSQ), and the Barthel's Index were used for data collection. The findings demonstrated that the PEAS score range was 0-24 (mean 6.32 +/- 4.6). Moreover, 44 subjects (22.6%) had scores of ten or greater. The most frequently reported indicators in the PEAS were "wishes to see family members unfulfilled" and "economic dependence on others". The analytical results also showed that the SPMSQ and Barthel's Index scores were strongly related to the PEAS score (p < 0.001), indicating psychological abuse appeared higher among elderly people with lower cognitive and physical functioning. The findings of this study are crucial in developing a national system for protecting the elderly, and a continuing educational plan is required for enforcing communication between caregivers and elders.


Comparative evaluation of uniplex, nested, semi-nested, multiplex and nested multiplex PCR methods in the identification of microbial etiology of clinically suspected infectious endophthalmitis.
This study is aimed to determine the utility of various polymerase chain reaction (PCR) methods in vitreous fluids (VFs) for detecting the infectious genomes in the diagnosis of infectious endophthalmitis in terms of sensitivity and specificity. This prospective and consecutive analysis included a total of 66 VFs that were submitted for the microbiological evaluation, which were obtained from 66 clinically diagnosed endophthalmitis patients presented between November 2010 and October 2011 at the tertiary eye care referral centre in South India. Part of the collected VFs were subjected to cultures and smears, and the remaining parts were utilized for five PCR methods: uniplex, nested, semi-nested, multiplex and nested multiplex after extracting DNA, using universal eubacterial and Propionibacterium acnes species-specific primer sets targeting 16S rRNA gene in all bacteria and P. acnes, and panfungal primers, targeting 28S rRNA gene in all fungi. Of the 66 VFs, five (7.5%) showed positive results in smears, 16 (24%) in cultures and 43 (65%) showed positive results in PCRs. Among the 43 positively amplified VFs, 10 (15%) were positive for P. acnes genome, one for panfungal genome and 42 (62%) for eubacterial genome (including 10 P. acnes positives). Among 42 eubacterial-positive VFs, 36 were positive by both uniplex (first round) and multiplex (first round) PCRs, while nested (second round) and nested multiplex (second round) PCRs produced positive results in 42 and 41 VFs, respectively. Of the 43 PCR-positive specimens, 16 (37%) had positive growth (15 bacterial and one fungal) in culture. Of 50 culture-negative specimens, 27 (54%) were showed positive amplification, of which 10 were amplified for both P. acnes and eubacterial genomes and the remaining 17 were for eubacterial genome alone. Nested PCRs are superior than uniplex and multiplex PCR. PCRs proved to be a powerful tool in the diagnosis of endophthalmitis, especially for detecting uncultured microbes.


Epilepsy surgery in patients with bilateral temporal lobe seizures: a systematic review.
We explored the association between magnetic resonance imaging (MRI) lesion, degree of seizure laterality on intracranial electroencephalography (iEEG), and seizure outcome in patients with ambiguous or presumed bilateral temporal lobe epilepsy (BiTLE) on scalp EEG. We systematically reviewed the literature using Embase and MEDLINE up to May 31, 2012. Patients with bilateral iEEG, temporal lobe surgery, and follow-up ≥1 year were included. We undertook three separate analyses on patients whose scalp EEG showed ambiguous onset or BiTLE (1) group data of those whose iEEG demonstrated unilateral TLE, (2) group data of those whose iEEG demonstrated BiTLE, (3) individual patient analysis in those with BiTLE for whom iEEG seizure laterality data were provided. Of 1,403 patients with ambiguous or presumed BiTLE on scalp EEG, 1,027 (73%) proved to have unilateral TLE on iEEG and contributed to the first analysis. Of these, 58% had Engel class I and 9% Engel class II outcomes. Of 132 patients in the second analysis (true BiTLE), Engel class I and II outcomes were achieved in 23% and 14%, respectively. Of 41 patients in the third analysis, 66% and 2% had Engel class I and II outcomes, respectively. The median proportion of seizures ipsilateral to the resection on iEEG did not differ between BiTLE patients with Engel class I-II (76%) and Engel III-IV (78%) outcomes (p = 0.87). Patients with ambiguous or independent bitemporal seizure onset on scalp EEG achieved good surgical outcomes. Overall, a significantly higher proportion of patients achieved good outcomes when iEEG showed unilateral TLE (67%) than when it showed true BiTLE (45%). However, the degree of seizure lateralization in those with BiTLE was not associated with seizure outcome, and it has a limited role in selecting the side of surgery.


Suppression of AGO2 by miR-132 as a determinant of miRNA-mediated silencing in human primary endothelial cells.
The abundance of miR-132 ranges from constitutively high in the brain where it is necessary for neuronal development and function, to inducible expression in haematopoietic and endothelial cells where it controls angiogenesis and immune activation. We show that expression of AGO2, a protein central to miRNA-mediated gene silencing and miRNA biogenesis, is negatively regulated by miR-132. Using HeLa cells, we demonstrate that miR-132 interacts with the AGO2 mRNA 3'UTR and suppresses AGO2 expression and AGO2-dependent small RNA-mediated silencing. Similarly, miR-132 over-expression leads to AGO2 suppression in primary human dermal lymphatic endothelial cells (HDLECs). During phorbol myristate acetate (PMA)-activation of HDLECs, miR-132 is induced in a CREB-dependent manner and inhibition of miR-132 results in increased AGO2 expression. In agreement with the role of AGO2 in maintenance of miRNA expression, AGO2 suppression by miR-132 affects the steady state levels of miR-221 and miR-146a, two miRNAs involved in angiogenesis and inflammation, respectively. Our data demonstrate that the miRNA-silencing machinery is subject to autoregulation during primary cell activation through direct suppression of AGO2 by miR-132.


Coping with data in an ethnographic study.
Traditionally, and as described in other articles in this issue, ethnography is a form of study pioneered by anthropologists.They examine the societies and customs of peoples far removed from Western culture, through their families, lives, education, socialisation, religion, language and so on.They study for long periods of time during which they theorise about aspects of the culture and its meaning to the individuals within it. The researchers often keep diaries which form the basis of their later writings.


Two-component relativistic hybrid density functional computations of nuclear spin-spin coupling tensors using Slater-type basis sets and density-fitting techniques.
Computations of indirect nuclear spin-spin coupling constants using two-component relativistic density functional theory with a hybrid functional are reported. The program implementation makes use of a Slater-type orbital expansion of the molecular orbitals and the zeroth-order regular approximation for the treatment of relativistic effects. Exact exchange terms in the Kohn-Sham response kernel were computed using a fitting procedure. Computations with the PBE0 hybrid functional were carried out for heavy-atom-ligand-one-bond couplings in PbH(4), Pb(CH(3))(2)H(2), Pb(CH(3))(3)H, three platinum complexes, the interhalogen diatomics such as ClF, ClBr, ClI, BrF, BrI, IF, and the series Tl-X with X=F, Cl, Br, I. The hybrid functional computations performed very well. In particular, for the isotropic coupling and the coupling anisotropy of Tl-X, the PBE0 hybrid functional yielded considerably improved agreement with experiment.


Triple, double- and single-incision laparoscopic cholecystectomy: a prospective study.
Advances in laparoscopic techniques have enabled complicated intra-abdominal surgical procedures to be made with less trauma and a better cosmetic appearance. The techniques have been developed by decreasing the number of incisions in conventional laparoscopic procedures in order to increase patient satisfaction. The aim of this study was to compare the results of cholecystectomies made with 3, 2 or a single incision. A total of 95 cholecystectomy patients from Elbistan State Hospital and Suleyman Demirel University Hospital between 2011 and 2013 were prospectively evaluated. The patients were separated into 3 groups as triple incision laparoscopic cholecystectomy (TILC), double incision laparoscopic cholecystectomy (DILC) and single incision laparoscopic cholecystectomy (SILC). Patients were evaluated in respect of demographic characteristics, operation time, success rate, analgesia requirement, length of hospital stay and patient satisfaction. Successful procedures were completed in 40 TILC, 40 DILC and 15 SILC cases. Transfer to open cholecystectomy was not required in any case. The mean duration of operation was 71 mins (range, 55-120 mins) for SILC cases, 45 mins (range, 32-125 mins) for DILC cases and 42 mins (range, 29-96 mins) for TILC cases. The mean time for the SILC cases was statistically significantly longer than the other two groups (p < 0.000). At a comparable level with DILC and TILC, single incision laparosccopic cholecystectomy is a method which can be used without incurring any extra costs or requiring additional instrumentation or training and which has good cosmetic results and a low requirement for analgesia.


[Pulmonary vein stenosis after radio frequency ablation].
Physicians should be alert to the occurrence of respiratory symptoms after radio frequency ablation for the treatment of atrial fibrillation. Pulmonary veins stenosis could appear with an incidence of between 1 and 3% during the two years following the procedure. We present the case of a 41 year-old-male patient admitted with a three weeks old hemoptysis and thoracodinia and a prior history of a radiofrequency ablation procedure performed six months earlier. The angiotomography was not compatible with the diagnosis of pulmonary embolism and the angio-MRI detected hypoperfusion of the left upper pulmonary lobe. Consequently pulmonary veins angiotomography was requested, showing upper pulmonary lobe vein stenosis. An hemodynamic study with vein expansion and stent placement was successfully performed.


Evaluation of nitric oxide production by Leishmania infantum-infected dog macrophages.
Protozoa of the genus Leishmania (L.) infect reticuloendothelial cells of several mammalian species, including dogs, in which they often give rise to a chronic, not self-healing visceral disease. Since the parasitocidal mechanism of macrophages towards Leishmania in dog has not yet been well investigated, in this work we have evaluated in Leishmania infantum-infected macrophage cultures from 10 healthy dogs, killing capacity and nitric oxide (NO) production, in terms of nitrite (NO2) levels. Parallel experiments were performed on macrophages stimulated with both Concanavalin A (ConA)-activated PBMC supernatants and Salmonella typhimurium lipopolysaccharide (LPS), and in the same conditions, but in the presence of the NO synthase inhibitor L-N monomethylarginine (L-NMMA). In L. infantum-infected macrophages, nitric oxide production was observed at a concentration significantly higher after stimulation with both Con A-activated PBMC supernatants and LPS than that observed in uninfected cells cultured in medium alone, or infected cells unstimulated or stimulated by PBMC supernatants or LPS alone, respectively. Moreover, NO production was abolished in the presence of the NO synthase inhibitor L-NMMA. Finally, killing of Leishmania by macrophages was significantly reduced in the presence of L-NMMA.


[Effect of Recombinant Super-compound Interferon (rSIFN-co) on Proliferation and Apoptosis of Human Pulmonary Adenocarcinoma Cell A549].
To investigate the effect of recombinant super-compound interferon (rSIFN-co) on the proliferation and apoptosis of pulmonary adenocarcinoma cell line A549. Screening tests were conducted to determine the concentrations of rSIFN-co that have a significant impact on A549 and the optimal concentration and duration for the test of rSIFN-co combined with Cisplatin. A549 cells were treated with rSIFN-co, Infergen, rSIFN- co+ Cisplatin, Infergen + Cisplatin, and Cisplatin, respectively, and compared with those cultured in normal medium. The viable A549 cells from Day 1 to Day 7 were detected by MTT assay. Cell apoptosis was detected by flow cytometry (FCM). Apoptosis-associated proteins, Fas and Bcl-2 were detected by immunofluoroscence at 48 h. Effective concentrations of rSIFN-co ranged from 1 to 64 µg/mL, and a minimal of 2 µg/mL Cisplatin was needed. The optimal test condition was set at 5 µg/mL rSIFN-co combined with 2 µg/mL Cisplatin for a duration of 48 h. rSIFN-co demonstrated a stronger inhibiting effect on cell proliferation than Infergen. The inhibiting efficiency of rSIFN-co+Cisplatin was also stronger than that of Infergen+Cisplatin. Apoptosis of A549 cells induced by rSIFN-co was also more significant than that of Infergen (P = 0.000). Cells treated with rSIFN- co+ Cisplatin has a higher apoptosis rate than those treated with rSIFN-co (P = 0.004) or Cisplatin (P = 0.023). rSIFN-co increased the expression of Fas and decreased the expression of Bcl-2. Cells treated with rSIFN-co showed lower fluoroscence intensity of Bcl-2 than those treated with Infergen (P < 0.05). rSIFN-co inhibits the proliferation of A549 and its effect is stronger than that of Infergen. Cisplatin can further enhance the inhibiting effect of rSIFN-co. The inhibiting efficiency may be associated with the expression of apoptosis-related genes.


Endoscopic sclerotherapy: a risk factor for splanchnic venous thrombosis.
Endoscopic sclerotherapy has been widely advocated as primary therapy for patients surviving hemorrhage from esophageal varices. The potential for endoscopic sclerotherapy to limit subsequent surgical options remains unclear. The following study was undertaken to assess the endoscopic sclerotherapy-related incidence of splanchnic venous thrombosis in patients undergoing surgery for variceal bleeding. We retrospectively identified 27 patients who underwent portosystemic shunting after an episode of variceal hemorrhage documented by endoscopic examination. Eleven patients underwent endoscopic sclerotherapy before portosystemic surgery for shunting. Among the patients undergoing prior endoscopic sclerotherapy, 6/11 had partial splanchnic venous thrombosis at surgery compared with 2/16 in the non-endoscopic sclerotherapy group. This difference was statistically significant. Only one of the eight patients with splenic or portal vein thrombosis detected at surgery showed signs of the condition when an angiograph was performed. Endoscopic sclerotherapy appears to impose a significant risk for splanchnic venous thrombosis. This complication, not reliably detected by angiographic means, may limit the operative options and long-term outcomes of patients in whom endoscopic sclerotherapy fails.


Assessment of dangerousness in clinical practice.
Physicians, especially psychiatrists, face the daunting task of assessing the risk of dangerousness in clinical settings. This article reviews the research on mental illness and violence and identifies the specific psychiatric symptoms that have been associated with an increased risk of violence.


Improving quality of life and physical health in patients with schizophrenia: A 30-month program carried out in a real-life setting.
Patients with schizophrenia experience low quality of life (QoL) and poor physical health, which is explained, in part, by unhealthy lifestyle, tobacco smoking, poor diet and sedentary behavior. To measure QoL and physical health in patients with schizophrenia and to quantify associations between QoL and physical health. This was a naturalistic longitudinal 30-month follow-up study including individual guidance, group sessions and treatment as usual. We included 190 patients. QoL was low among newly diagnosed patients. Higher body mass index was significantly associated with lower QoL. Newly diagnosed male patients showed lower QoL compared with females. Newly diagnosed patients experienced worsened health during the study period. In contrast, long-term schizophrenic patients started with worse physical health but improved with regard to weight, waist circumferences, intake of fast food and soft drinks, and light physical activity level. Newly diagnosed patients improved their QoL ( p = .056), and the psychological domain improved by 8.0 points ( p = .003). The number of interventions was positively associated with QoL. Patients with schizophrenia presented with low QoL and elevated risk factors for poor physical health. The intervention added onto 'treatment as usual' improved some risk factors for poor physical health among long-term patients. The number of interventions had an elevating effect on QoL in patients.


Medicine vs. prayer: the case of Kara Neumann.
Religious beliefs and the use of complementary and alternative medicine can help or hinder health care and the well being of children, who are often unable to make informed decisions for themselves, but instead, depend on their parents or caregivers to make health care decisions for them. Tragically, this can sometimes result in prolonged suffering and death when parents or caregivers refuse treatment due to their own personal beliefs. This two-part article explores the case of Kara Neumann, an 11-year-old girl who died after her parents denied her medical care in lieu of prayer to cure her "spiritual attack," and the role pediatric nurses can play in educating patients and their families.


High Phase Stability in CsPbI3 Enabled by Pb-I Octahedra Anchors for Efficient Inorganic Perovskite Photovoltaics.
CsPbI3 inorganic perovskite has exhibited some special properties particularly crystal structure distortion and quantum confinement effect, yet the poor phase stability of CsPbI3 severely hinders its applications. Herein, the nature of the photoactive CsPbI3 phase transition from the perspective of PbI6 octahedra is revealed. A facile method is also developed to stabilize the photoactive phase and to reduce the defect density of CsPbI3 . CsPbI3 is decorated with multifunctional 4-aminobenzoic acid (ABA), and steric neostigmine bromide (NGBr) is subsequently used to further mediate the thin films' surface (NGBr-CsPbI3 (ABA)). The ABA or NG cation adsorbed onto the grain boundaries/surface of CsPbI3 anchors the PbI6 octahedra via increasing the energy barriers of octahedral rotation, which maintains the continuous array of corner-sharing PbI6 octahedra and kinetically stabilizes the photoactive phase CsPbI3 . Moreover, the added ABA and NGBr not only interact with shallow- or deep-level defects in CsPbI3 to significantly reduce defect density, but also lead to improved energy-level alignment at the interfaces between the CsPbI3 and the charge transport layers. Finally, the champion NGBr-CsPbI3 (ABA)-based inorganic perovskite solar cell delivers 18.27% efficiency with excellent stability. Overall, this work demonstrates a promising concept to achieve highly phase-stabilized inorganic perovskite with suppressed defect density for promoting its optoelectronic applications.


Synthesis and bioassay of racemic and chiral trans-alpha-necrodyl isobutyrate, the sex pheromone of the grape mealybug Pseudococcus maritimus.
A concise synthesis of the racemic form of the female-produced pheromone of the grape mealybug was developed. The synthesis was readily adapted to production of both enantiomers of the pheromone via lipase-catalyzed kinetic resolution of an intermediate in the synthesis. Replicated field trials revealed that, contrary to a preliminary report, the (R,R)- rather than the (S,S)-enantiomer is the attractive stereoisomer. Lithium aluminum hydride reduction of the insect-produced compound to alpha-necrodol followed by analysis on a chiral stationary phase GC column showed that the insect-produced material was actually an 85:15 mixture of the (R,R)- and (S,S)-enantiomers. The racemic form of the pheromone was highly attractive to male mealybugs, and in one of two field bioassays, the racemic material was significantly more attractive than the pure (R,R)-enantiomer, suggesting that the (S,S)-enantiomer might act synergistically.


[Outcome of bortezomib plus chemotherapy with or without stem cell transplantation for treatment of multiple myeloma].
To investigate the efficacy and adverse reaction of bortezomib plus chemotherapy with or without stem cell transplantation (SCT) for treatment of multiple myeloma (MM). Thirty-one MM patients were treated with bortezomib plus dexamethasone or thalidomide or DTPACE, followed by SCT. Response to bortezomib was evaluated according to the European Blood and Marrow Transplantation (EBMT) criteria. Adverse events were graded according to the WHO criteria. 1) 5 discontinued the bortezomib therapy because of acute renal failure or acute tumor lysis syndrome and 3 died. In 26 evaluable patients received 99 courses of therapy. The overall response rate (ORR) to bortezomib was 80.8%, and was 100.0% in 15 newly diagnosed patients and 54.6% in 11 relapsed/refractory patients. All of the 6 newly diagnosed patients treated with bortezomib plus DTPACE followed by SCT achieved CR. 2) In 7 newly diagnosed patients completed 8 cycles bortezomib treatment, the diseases were improved more and more with the courses of treatment. Chromosome 13 deletion did not exert a negative impact on response. 3) 6 of 7 patients completed 8 cycles treatment without SCT relapsed in 1-3 month after discontinued therapy; only 1 of 6 such patients received SCT relapsed with the rest keeping on CR at 6-11 month follow-up. 4) The most common adverse events were 1-2 grade and tolerable 3 patients had to reduce the bortezomib dosage because of peripheral neuropathy or sinus bradycardia. Bortezomib in combination with chemotherapy with or without SCT is an effective therapy with manageable toxicities for MM patients.


Nuclear magnetic resonance based metabolomic differentiation of different Astragali Radix.
Astragali Radix (AR) is one of the most popular herbal medicines in traditional Chinese medicine (TCM). Wild AR is believed to be of high quality, and substitution with cultivated AR is frequently encountered in the market. In the present study, two types of ARs (wild and cultivated) from Astragalus membranaceus (Fisch.) Bge. and A. membranaceus var. mongholicus (Bge.) Hsiao, growing in different regions of China, were analyzed by NMR profiling coupled with multivariate analysis. Results showed that both could be differentiated successfully and cultivation patterns or growing years might have greater impact on the metabolite compositions than the variety; the metabolites responsible for the separation were identified. In addition, three extraction methods were compared and the method (M1) was used for further analysis. In M1, the extraction solvent composed of water, methanol, and chloroform in the ratio of 1 : 1 : 2 was used to obtain the aqueous methanol (upper layer) and chloroform (lower layer) fractions, respectively, showing the best separation. The differential metabolites among different methods were also revealed. Moreover, the sucrose/glucose ratio could be used as a simple index to differentiate wild and cultivated AR. Meanwhile, the changes of correlation pattern among the differential metabolites of the two varieties were found. The work demonstrated that NMR-based non-targeted profiling approach, combined with multivariate statistical analysis, can be used as a powerful tool for differentiating AR of different cultivation types or growing years.


Stem cell factor promotes in vitro ovarian follicle development in the domestic cat by upregulating c-kit mRNA expression and stimulating the phosphatidylinositol 3-kinase/AKT pathway.
In the present study we examined the effects of stem cell factor (SCF; 50 vs 100ngmL-1) alone or in combination with epidermal growth factor (EGF; 100ngmL-1) on: (1) the in vitro viability and growth of cat follicles within ovarian cortices; (2) phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) phosphorylation; and (3) c-kit and FSH receptor (FSHr) mRNA expression. At 100ngmL-1, SCF increased (P≤0.05) the percentage and size of secondary follicles after 14 days of in vitro culture and sustained AKT phosphorylation after 3 days incubation. EGF suppressed this beneficial effect and reduced (P≤0.05) the percentage of structurally normal follicles and FSHr expression when combined with 100ngmL-1 SCF. Expression of c-kit mRNA was higher (P≤0.05) in the presence of 100ngmL-1 SCF compared with fresh follicles and cohorts cultured under other conditions. A c-kit inhibitor suppressed follicle growth and reduced AKT phosphorylation. Collectively, the results demonstrate that SCF promotes cat follicle development by upregulating c-kit mRNA expression and AKT phosphorylation. EGF suppresses the stimulating effect of SCF, leading to downregulation of FSHr expression.


Theoretical study on the generation of a low-noise plasmonic hotspot by means of a trench-assisted circular nano-slit.
We propose a novel trench-assisted circular metal nano-slit (CMNS) structure implementable on a fiber platform for the generation of a low-noise cylindrical surface plasmon (CSP) hotspot. We design trench structures based on a multi-pole cancellation method in order that a converging surface plasmon signal is well separated from co-propagating non-confined diffracted light (NCDL) at the hotspot location. In fact, the secondary radiation by the quasi-pole oscillation at the edge of the trench cancels the primary NCDL, thereby enhancing the signal-to-noise ratio (SNR) of the CSP hotspot. In particular, we investigate two types of trench structures: a rectangular-trench (RT) structure and an asymmetric-parabolic-trench (APT) structure, which are considered for the sake of the simplicity of fabrication and of the maximal enhancement of the SNR, respectively. In comparison with a conventional CMNS having no trenches, we highlight that the mean SNR of the CSP hotspot is enhanced by 6.97 and 11.89 dB in case of the optimized RT and APT CMNSs, respectively. The proposed schemes are expected to be useful for increasing the SNR of plasmonic devices that are interfered by NCDL, such as various types of nano-slits for generating high-resolution plasmonic signals, for example.


A periodontal probe that measures to one tenth millimeter.
A periodontal probe has been developed which utilizes a vernier gauge to permit direct measurement to one-tenth millimeter. This configuration eliminates the need for multiple step measurements using stents or calipers. The probe can be sterilized easily to make measurements during surgical procedures. The probe should prove useful in clinical research, minor tooth movement and patient treatment documentation.


A Case of Pyelonephritis in an Anuric Patient with End-Stage Renal Disease on Hemodialysis.
Urinary tract infections are common sources of infections requiring antibiotic use worldwide. Chronic kidney disease (CKD) patients, especially those with minimal urine output are challenging when it comes to antibiotic stewardship given the scarcity of cases in the literature. It is further complicated by the fact that end-stage renal disease (ESRD) patients are found to have asymptomatic pyuria and its clinical significance for bacterial infection is yet to be determined. In this case, we report a patient who presented with non-specific symptoms including fever, cough, chills, diarrhea, nausea and was found to have left-sided perinephric stranding on CT scan of the abdomen. The patient also had a fever of 104.6 F which we attributed to left-sided pyelonephritis given the high sensitivity of such findings on CT scan. In this report, we explored the literature for the incidence and management of pyelonephritis in ESRD patients who are anuric.


Lung epithelial cells and type II pneumocytes of donor origin after allogeneic hematopoietic stem cell transplantation.
In the present investigation, we determined whether donor epithelial lung cells might be detected after allogeneic hematopoietic stem cell transplantation (HSCT). Lung-tissue specimens were obtained at autopsy from four female patients, two with male donors, after nonmyeloablative HSCT. Immunohistochemical staining for cytokeratin was used to identify lung epithelial cells. The tissue sections were analyzed for the presence of donor-derived lung epithelial cells with the use of fluorescence in situ hybridization of XY-positive cells. All patients showed almost complete donor chimerism in all cell lineages after HSCT with polymerase chain reaction of minisatellites. In the two positive controls, between 2% and 6% Y-chromosome-positive epithelial lung cells were detected in each section. Surfactant-positive male epithelial cells were also detected, indicating engraftment of type II pneumocytes. In the two negative controls, no Y-chromosome-positive cells were detected. Circulating donor stem cells may differentiate into lung epithelial cells after allogeneic HSCT.