Munc18-1 regulates first-phase insulin release by promoting granule docking to multiple syntaxin isoforms.
Attenuated levels of the Sec1/Munc18 (SM) protein Munc18-1 in human islet β-cells is coincident with type 2 diabetes, although how Munc18-1 facilitates insulin secretion remains enigmatic. Herein, using conventional Munc18-1(+/-) and β-cell specific Munc18-1(-/-) knock-out mice, we establish that Munc18-1 is required for the first phase of insulin secretion. Conversely, human islets expressing elevated levels of Munc18-1 elicited significant potentiation of only first-phase insulin release. Insulin secretory changes positively correlated with insulin granule number at the plasma membrane: Munc18-1-deficient cells lacked 35% of the normal component of pre-docked insulin secretory granules, whereas cells with elevated levels of Munc18-1 exhibited a ∼20% increase in pre-docked granule number. Pre-docked syntaxin 1-based SNARE complexes bound by Munc18-1 were detected in β-cell lysates but, surprisingly, were reduced by elevation of Munc18-1 levels. Paradoxically, elevated Munc18-1 levels coincided with increased binding of syntaxin 4 to VAMP2 at the plasma membrane. Accordingly, syntaxin 4 was a requisite for Munc18-1 potentiation of insulin release. Munc18c, the cognate SM isoform for syntaxin 4, failed to bind SNARE complexes. Given that Munc18-1 does not pair with syntaxin 4, these data suggest a novel indirect role for Munc18-1 in facilitating syntaxin 4-mediated granule pre-docking to support first-phase insulin exocytosis.


Nitrogen Sources Inhibit Biofilm Formation by Xanthomonas oryzae pv. oryzae.
Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight, which results in severe economic damage to rice farms. Xoo produces biofilms for pathogenesis and survival both inside and outside the host. Biofilms, which are important virulence factors, play a key role in causing the symptoms of Xoo infection. In the present study, we investigated the nutritional conditions for biofilm formation by Xoo. Although Xoo biofilm formation may be initiated by interactions with the host, Xoo biofilm cannot mature without the support of favorable nutritional conditions. Nitrogen sources inhibited Xoo biofilm formation by overwhelming the positive effect that cell growth has on it. However, limited nutrients with low amino acid concentration supported biofilm formation by Xoo in the xylem sap rather than in the phloem sap of rice.


Different effects of immune stimulation on chronic unpredictable mild stress-induced anxiety- and depression-like behaviors depending on timing of stimulation.
Stressful life events are thought to be triggering factors of numerous neuropsychiatric disorders, including anxiety and depression. However, the interactions between chronic unpredictable mild stress (CUMS) and immune stimulation have not been thoroughly investigated. In the present study, we evaluated the effects of lipopolysaccharide (LPS) challenge at different time points on CUMS-induced anxiety- and depression-like behaviors. At 1 day before, 18 or 35 days following the initial of CUMS, mice were intraperitoneally given a single LPS (0.1 mg/kg). Neurobehavioral and biochemical studies were performed at the indicated time points. LPS challenge had different effects on CUMS-induced anxiety- and depression-like behaviors depending on the timing of stimulation. When given 1 day before CUMS, LPS restored brain-derived neurotrophic factor level and reversed anxiety- and depression-like behaviors. When given at 18 days after the initial of CUMS, LPS seemed to promote the immune response and even induce a slight exacerbation of neurobehavioral performance, although the difference did not reach statistical significance. Intriguingly, when given at the end of CUMS, LPS reversed some of the anxiety- and depression-like behavior. Taken together, our study highlights the complex interaction between stress and immune challenge, suggesting therapies that modulate immune responses should be tailored to the immune status of the individual.


The effect of missing data and imputation on the detection of bias in cognitive testing using differential item functioning methods.
Item response theory (IRT) methods for addressing differential item functioning (DIF) can detect group differences in responses to individual items (e.g., bias). IRT and DIF-detection methods have been used increasingly often to identify bias in cognitive test performance by characteristics (DIF grouping variables) such as hearing impairment, race, and educational attainment. Previous analyses have not considered the effect of missing data on inferences, although levels of missing cognitive data can be substantial in epidemiologic studies. We used data from Visit 6 (2016-2017) of the Atherosclerosis Risk in Communities Neurocognitive Study (N = 3,580) to explicate the effect of artificially imposed missing data patterns and imputation on DIF detection. When missing data was imposed among individuals in a specific DIF group but was unrelated to cognitive test performance, there was no systematic error. However, when missing data was related to cognitive test performance and DIF group membership, there was systematic error in DIF detection. Given this missing data pattern, the median DIF detection error associated with 10%, 30%, and 50% missingness was -0.03, -0.08, and -0.14 standard deviation (SD) units without imputation, but this decreased to -0.02, -0.04, and -0.08 SD units with multiple imputation. Incorrect inferences in DIF testing have downstream consequences for the use of cognitive tests in research. It is therefore crucial to consider the effect and reasons behind missing data when evaluating bias in cognitive testing.


Percutaneous trans-hepatic rescue and neo-creation of a post-surgical complete hepaticojejunostomy dehiscence.
Biliary leakage complicating hepaticojejunostomy is a therapeutic dilemma for surgeons, gastroenterologist, and interventional radiologist. It is a major cause of postoperative morbidity. Percutaneous biliary intervention techniques have been developed for treating benign post-surgical biliary disease in patients not having severely compromised clinical conditions. Interventional radiology manoeuvres are especially indicated as the first line of treatment if endoscopic procedures are unfeasible for patients due to postsurgical anatomical modifications. We present a case of post-surgical complete hepaticojejunostomy dehiscence that was treated totally by percutaneous techniques with trans-hepatic rescue and hepaticojejunostomy neo-creation.


Dithiooxamide modified glassy carbon electrode for the studies of non-aqueous media: electrochemical behaviors of quercetin on the electrode surface.
Electrochemical oxidation of quercetin, as an important biological molecule, has been studied in non-aqueous media using cyclic voltammetry, electrochemical impedance spectroscopy and scanning electron microscopy. To investigate the electrochemical properties of quercetin, an important flavonoid derivative, on a different surface, a new glassy carbon electrode has been developed using dithiooxamide as modifier in non-aqueous media. The surface modification of glassy carbon electrode has been performed within the 0.0 mV and +800 mV potential range with 20 cycles using 1 mM dithioxamide solution in acetonitrile. However, the modification of quercetin to both bare glassy carbon and dithiooxamide modified glassy carbon electrode surface was carried out in a wide +300 mV and +2,800 mV potential range with 10 cycles. Following the modification process, cyclic voltammetry has been used for the surface characterization in aqueous and non-aqueous media whereas electrochemical impedance spectroscopy has been used in aqueous media. Scanning electron microscopy has also been used to support the surface analysis. The obtained data from the characterization and modification studies of dithioxamide modified and quercetin grafted glassy carbon electrode showed that the developed electrode can be used for the quantitative determination of quercetin and antioxidant capacity determination as a chemical sensor electrode.


GrTEdb: the first web-based database of transposable elements in cotton (Gossypium raimondii).
Although several diploid and tetroploid Gossypium species genomes have been sequenced, the well annotated web-based transposable elements (TEs) database is lacking. To better understand the roles of TEs in structural, functional and evolutionary dynamics of the cotton genome, a comprehensive, specific, and user-friendly web-based database, Gossypium raimondii transposable elements database (GrTEdb), was constructed. A total of 14 332 TEs were structurally annotated and clearly categorized in G. raimondii genome, and these elements have been classified into seven distinct superfamilies based on the order of protein-coding domains, structures and/or sequence similarity, including 2929 Copia-like elements, 10 368 Gypsy-like elements, 299 L1 , 12 Mutators , 435 PIF-Harbingers , 275 CACTAs and 14 Helitrons . Meanwhile, the web-based sequence browsing, searching, downloading and blast tool were implemented to help users easily and effectively to annotate the TEs or TE fragments in genomic sequences from G. raimondii and other closely related Gossypium species. GrTEdb provides resources and information related with TEs in G. raimondii , and will facilitate gene and genome analyses within or across Gossypium species, evaluating the impact of TEs on their host genomes, and investigating the potential interaction between TEs and protein-coding genes in Gossypium species. http://www.grtedb.org/.


Incorporating PARP-inhibitors into clinical routine: A tailored treatment strategy to tackle ovarian cancer.
DNA repair mechanisms play a key role in oncogenesis and cancer progression in women with BRCA mutation-positive (BRCAm) ovarian cancer (OC). The BRCA1/2 and poly(ADP-ribose) polymerase (PARP) proteins are considered the foremost mediators among the various components of double-strand and single-strand repair, respectively. A series of new therapeutic drugs that target PARP have been developed for BRCAm OC. This class of agents provokes tumour-specific cytotoxicity with minimal side effects by inducing synthetic lethality, of which they are the first clinical example. The European Medicines Agency granted accelerated licensing approval for the first-in-class-drug that inhibits PARP, olaparib (Lynparza™, AstraZeneca). Olaparib can be used as a monotherapeutic maintenance treatment in patients with platinum-sensitive relapsed (germline and/or somatic) BRCAm high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer responsive to platinum-based chemotherapy. Seen in light of these recent events, this review article will focus on (a) how PARP-inhibitors exploit cancer-specific defects in the homologous recombination repair apparatus and (b) how BRCA testing is implemented in routine clinical care.


The redox regulation of PI 3-kinase-dependent signaling.
Signal transduction via PI 3-kinases plays an important role in regulating the cellular processes of cell growth, survival, proliferation, and motility. The stimulated generation of reactive oxygen species is a necessary component of the signal transduction mechanisms by which many growth factors and cytokines activate this signaling pathway and elicit their cellular responses. Evidence now supports the oxidative inactivation of both tyrosine phosphatases acting upstream of PI 3-kinase, and of the lipid phosphatase PTEN as components of the normal stimulated regulation of PI 3-kinase signaling. However, the effects of chronic oxidative stress appear rather different, particularly a proposed role for nitrosylation of Akt and other targets leading to inhibition of PI 3-kinase signaling during diabetic insulin resistance in muscle. Recently, evidence has also begun to emerge, indicating that physiological redox signaling may display the same tight spatial and temporal specificity as seen with many other signal transduction systems in terms of targeting individual proteins for modification, and of enzymatic reversal mechanisms. This review will focus upon the details of these and other roles for reactive oxygen and nitrogen species in the regulation of PI 3-kinase signaling, both during acute stimulation and chronic oxidative stress, and the evidence for their significance.


Percutaneous internal carotid artery angioplasty with stenting: early and long-term results.
Cerebro-vascular accidents are the third most common cause of death. The most frequent localisation of lesions responsible for stroke are bifurcation of the common carotid artery or the proximal internal carotid artery (ICA). Surgical carotid endarterectomy (CEA) and carotid artery stenting (CAS) are the non-pharmacological methods used to treat carotid artery stenosis. To assess the efficacy and safety of CAS of ICA. CAS was performed in 75 patients (49 males, 26 females) with a mean age of 65.2+/-9.1 years. Twenty (26.7%) patients underwent CAS with the use of the central nervous system (CNS) protective devices. The immediate, mid-term, and long-term results were analysed. In total, 84 stents were implanted to 80 ICA in 73 patients. In two patients stent implantation was not possible. In 7 (9%) patients with a stenosis of both ICA, a bilateral procedure was performed. In two patients concomitant dilatations of the vertebral artery, and in the other two - of subclavian artery, were performed. In 38 patients coronary angiography was performed directly before CAS; one patient underwent coronary angioplasty. In 20 patients protective CNS devices were used. During the procedure four patients developed ischaemic stroke on the side of CAS. In one patient neurological symptoms completely disappeared within 48 hours. The type of technique used during CAS did not influence the frequency of ischaemic complications. Four patients developed hyperperfusion syndrome which disappeared after a few days. There were fire deaths during follow-up: three due to myocardial infarction (MI), one - after urgent CABG, and one due to pulmonary embolism. There were no deaths due to stroke. No new ischaemic changes in CNS nor significant changes in the neurological status, using the UNSS or Barthel scales, were observed. Asymptomatic restenosis was documented in six patients whereas one patient developed symptomatic restenosis due to stent deformation. Percutaneous angioplasty of an internal carotid artery carries a risk not exceeding that of surgical endarterectomy. In our study, a one-year follow-up revealed a minor risk of ischaemic stroke. Percutaneous angioplasty with the use of protective devices should be tested in larger groups of patients in order to establish the real clinical usefulness and improved safety of this technique.


Comparison of buffering capacity in patients on hemodialysis and continuous ambulatory peritoneal dialysis.
A standard acid loading test was used to assess the buffering capacity in 9 hemodialysis (HD) and 25 continuous ambulatory peritoneal dialysis (CAPD) patients. There was a significant increase in H+ concentration and a decrease in plasma bicarbonate levels after the acid loading in all patients; however, PaCO2 did not change significantly. CAPD patients tolerated the acid load better, at least in the first 2 h, than HD patients. The brief duration of experiments did not allow us to observe differences, if any, in the recovery rates between HD and CAPD patients. CAPD patients tolerated the acid load equally, whether studied with or without fresh dialysate in the peritoneal cavity. Their tolerance to the acid load did not change with an increasing duration of the CAPD therapy. Baseline values and acid tolerance curves were similar in CAPD patients on regular Dianeal (lactate 35 mEq/l) and Dianeal PD2 (lactate 40 mEq/l). It is concluded that the buffering capacity is marginally higher in CAPD than in HD patients, although the baseline acid-base parameters were essentially identical.


[The results of patients follow up at Gaziantep Number II Dispensary of Tuberculosis Control in the year 2004].
In this study, the aim was to investigate the performance of number-II Dispensary of Tuberculous Control (DTC) in Gaziantep in 2004. The patients diagnosed to have tuberculosis between 2004 January 1st and 2004 December 31st were included. The patients registries were evaluated retrospectively. The mean age of the patients was 28.92+/-14.43 years (ranged between 1-68), 70.5% of the cases were male, and 72.5% of the cases were between 15-44 years old. Forty-two (82.3%) of the cases had the diagnosis of lung tuberculosis. 47% of them did not have any health insurance. The symptoms detected in the patients were cough, night sweats, sputum and hemoptysis respectively. There was no symptom registry in ten patients (19.6%). Sputum analysis to detect acid-fast bacilli (AFB) was done in 18 patients (19.6%). AFB was perfomed in 3.9% of the patients following two-months of therapy, and in 1.9% of the patients at the end of the therapy. Diagnostic tuberculous culture was performed in only one patient (1.9%). There was no tuberculous culture performed neither at the second month nor at the end of the therapy course. AFB was found to be positive in direct or concentrated sputum samples in eight (44.4%) of the patients. All the patients were evaluated with radiographies. The eritrocyte sedimentation rate was measured in 33.3%, 9.8%, and 15.6% of the patients before the therapy, at the end of the two months of therapy, and at the end of the therapy, respectively. The diagnosis was established with radiology clinical findings in 34 patients (66.6%). Directly observed therapy was performed in one patient (1.9%). The cure rate among smear positive patients was 12.5%, and the 100% of the patients were completed the therapy. There exists many problems with tuberculosis "warfare" and we believe the solution lies in DOTS.


Previous cytomegalovirus infection and restenosis after aggressive angioplasty with provisional stenting.
The aim of this study was to determine the impact of previous with cytomegalovirus (CMV) on restenosis after aggressive angioplasty with provisional stenting. We prospectively studied 78 consecutive patients scheduled for 6-month follow-up coronary angiography as part of the SIPS study. Anti-CMV IgG and IgM antibodies were measured on admission. Anti-CMV IgG positive and anti-CMV IgG negative patients had similar minimal lumen diameter (MLD) in the target vessel before (0.68 +/- 0.49 mm vs 0.71 +/- 0.52 mm, P = 0.84) and directly after the intervention (2.50 +/- 0.60 mm vs 2.57 +/- 0.52 mm, P = 0.58). After 6 months, however, the MLD was significantly smaller in CMV-positive as compared to CMV-negative patients (1.57 +/- 0.82 mm vs 2.00 +/- 0.83 mm, P < 0.03). Net lumen gain at 6 months was significantly lower in CMV-positive patients (0.89 +/- 0.79 mm vs 1.30 +/- 0.87 mm, P < 0.04) and the rate of clinically relevant restenosis was significantly higher (31% vs 7%, P < 0.02). In a multivariate logistic regression model, CMV seropositivity was an independent predictor of restenosis (odds ratio 5.7 (95% CI 1.2-30.3, P = 0.04). Six months after aggressive coronary angioplasty with provisional stenting, patients with prior CMV infection had a smaller MLD and a higher restenosis rate. CMV seropositivity was a strong independent predictor of restenosis.


Peptide Variant Detection by a Living Yeast Biosensor via an Epitope-Selective Protease.
We previously demonstrated that we could hijack the fungal pheromone signaling pathway to provide a living yeast biosensor where peptide biomarkers were recognized by G-protein-coupled receptors and engineered to transcribe a readout. Here, we demonstrated that the protease could be reintroduced to the biosensor to provide a simple mechanism for distinguishing single-amino-acid changes in peptide ligands that, otherwise, would likely be difficult to detect using binding-based assays. We characterized the dose-response curves for five fungal pheromone G-protein-coupled receptors, peptides, and proteases-Saccharomyces cerevisiae, Candida albicans, Schizosaccharomyces pombe, Schizosaccharomyces octosporus, and Schizosaccharomyces japonicus. Alanine scanning was carried out for the most selective of these-S. cerevisiae and C. albicans-with and without the protease. Two peptide variants were discovered, which showed diminished cleavage by the protease (CaPep2A and CaPep2A13A). Those peptides were then distinguished by utilizing the biosensor strains with and without the protease, which selectively cleaved and altered the apparent concentration of peptide required for half-maximal activation for 2 peptides-CaPep and CaPep13A, respectively-by more than one order of magnitude. These results support the hypothesis that the living yeast biosensor with a sequence-specific protease can translate single-amino-acid changes into more than one order of magnitude apparent shift in the concentration of peptide required for half-maximal activation. With further engineering by computational modeling and directed evolution, the biosensor could likely distinguish a wide variety of peptide sequences beyond the alanine scanning carried out here. In the future, we envision incorporating proteases into our living yeast biosensor for use as a point of care diagnostic, a scalable communication language, and other applications.


Radioimmunoassay of laminin in serum and its application to cancer patients.
In this sensitive radioimmunoassay for laminin fragment P1 (purified from pepsin extracts of human placenta), monovalent antibody fragments obtained from rabbit antisera against the laminin component are used. The inhibition assay showed a low intra- and interassay variability, and the inhibition curves for various serum samples had parallel slopes. Molecular-sieve chromatography demonstrated heterogeneity of the laminin antigen in serum. For quantification we defined arbitrary units based on the amount of antigenic material present in normal human serum. Sera from 361 tumor patients showed increased values in about half of the cases. Correlation with increased concentration of carcinoembryonic antigen was poor (r = 0.259). The assay may be useful for diseases involving basement-membrane metabolism.


Investigating the Impact of Electrolyte Flow Velocity on the Resistivity of Vanadium Redox Batteries: A Theoretical Analysis and Experimental Data Comparison.
The influence of electrolyte velocity over the ion-exchange membrane surface on ion and vanadium redox batteries' conductivity was formalized and quantified. The increase in electrolyte velocity dramatically improves proton conductivity, resulting in improved battery efficiency. An analysis of conductivity was carried out using a math model considering diffusion and drift ion motion together with their mass transport. The model is represented by the system of partial differential together with algebraic equations describing the steady-state mode of dynamic behavior. The theoretical solution obtained was compared qualitatively with the experimental results that prove the correctness of the submitted math model describing the influence of the electrolyte flow on the resistance of the vanadium redox battery. The presented theoretical approach was employed to conduct a parametric analysis of flow batteries, aiming to estimate the impact of electrolyte velocity on the output characteristics of these batteries.


Addition of Chloroprene Grignards to Aromatic Aldehydes: Synthesis of Homoallenyl Alcohols.
A general procedure for the one-pot synthesis of racemic homoallenyl alcohols from the corresponding aldehyde and chloroprene-derived Grignards is described. Employing bis[2-dimethylaminoethyl]ether (BDMAEE) as an additive at low temperatures shifts the selectivity of the chloroprene Grignard addition to aldehydes such that it is almost exclusive toward allene formation. In a set of follow-up experiments, simple and more elaborate methods for further derivatization have been demonstrated, allowing quick access to more complex structures.


Multi-Layered Filtration Framework for Efficient Detection of Network Attacks Using Machine Learning.
The advancements and reliance on digital data necessitates dependence on information technology. The growing amount of digital data and their availability over the Internet have given rise to the problem of information security. With the increase in connectivity among devices and networks, maintaining the information security of an asset has now become essential for an organization. Intrusion detection systems (IDS) are widely used in networks for protection against different network attacks. Several machine-learning-based techniques have been used among researchers for the implementation of anomaly-based IDS (AIDS). In the past, the focus primarily remained on the improvement of the accuracy of the system. Efficiency with respect to time is an important aspect of an IDS, which most of the research has thus far somewhat overlooked. For this purpose, we propose a multi-layered filtration framework (MLFF) for feature reduction using a statistical approach. The proposed framework helps reduce the detection time without affecting the accuracy. We use the CIC-IDS2017 dataset for experiments. The proposed framework contains three filters and is connected in sequential order. The accuracy, precision, recall and F1 score are calculated against the selected machine learning models. In addition, the training time and the detection time are also calculated because these parameters are considered important in measuring the performance of a detection system. Generally, decision tree models, random forest methods, and artificial neural networks show better results in the detection of network attacks with minimum detection time.


The importance of bacterial membrane composition in the structure and function of aurein 2.2 and selected variants.
For cationic antimicrobial peptides to become useful therapeutic agents, it is important to understand their mechanism of action. To obtain high resolution data, this involves studying the structure and membrane interaction of these peptides in tractable model bacterial membranes rather than directly utilizing more complex bacterial surfaces. A number of lipid mixtures have been used as bacterial mimetics, including a range of lipid headgroups, and different ratios of neutral to negatively charged headgroups. Here we examine how the structure and membrane interaction of aurein 2.2 and some of its variants depend on the choice of lipids, and how these models correlate with activity data in intact bacteria (MICs, membrane depolarization). Specifically, we investigated the structure and membrane interaction of aurein 2.2 and aurein 2.3 in 1:1 cardiolipin/1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (CL/POPG) (mol/mol), as an alternative to 1:1 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)/POPG and a potential model for Gram positive bacteria such as S. aureus. The structure and membrane interaction of aurein 2.2, aurein 2.3, and five variants of aurein 2.2 were also investigated in 1:1 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE)/POPG (mol/mol) lipids as a possible model for other Gram positive bacteria, such as Bacillus cereus. Solution circular dichroism (CD) results demonstrated that the aurein peptides adopted α-helical structure in all lipid membranes examined, but demonstrated a greater helical content in the presence of POPE/POPG membranes. Oriented CD and ³¹P NMR results showed that the aurein peptides had similar membrane insertion profiles and headgroup disordering effects on POPC/POPG and CL/POPG bilayers, but demonstrated reduced membrane insertion and decreased headgroup disordering on mixing with POPE/POPG bilayers at low peptide concentrations. Since the aurein peptides behaved very differently in POPE/POPG membrane, minimal inhibitory concentrations (MICs) of the aurein peptides in B. cereus strain C737 were determined. The MIC results indicated that all aurein peptides are significantly less active against B. cereus than against S. aureus and S. epidermidis. Overall, the data suggest that it is important to use a relevant model for bacterial membranes to gain insight into the mode of action of a given antimicrobial peptide in specific bacteria.


Human papilloma virus--role in precancerous and cancerous oral lesions of tobacco chewers.
Human papilloma viruses (HPV), members of the papillomaviridae family, infects squamous epithelial cells of cevix, lower genitalia, and oral cavity. The association of HPV with oropharyngeal carcinogenesis is well documented.The incidence of oral cancer ranks second in Karachi South in both genders according to World Health Organization (WHO) statistics. This is attributed to the popularity of chewable tobacco products among the general population. Studies on Gutka-eaters in a set population of Karachi showed high frequency of HPV (17%) and high prevalence of HPV in squamous cell carcinoma in Pakistani patients (68%). The exposure of oral mucosa to chewable tobacco causes abrasions making it susceptible to HPV. This review strives to summarise the role of HPV in chewable tobacco-related precancerous and cancerous lesions. The literature of about a decade was retrieved from Google and pubMed with the under mentioned key words. It was found that the use of chewable tobacco products, especially Gutka, may increase the risk of oral squamous cell carcinoma (OSCC).


Clinicopathological aspects of primary mucosa-associated lymphoid tissue lymphoma of the salivary gland: A retrospective single-center analysis of 72 cases.
Salivary gland extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) is uncommon and has not been studied extensively. We aimed to investigate the features of clinicopathological and molecular changes of salivary MALT lymphoma. Seventy-two cases of primary salivary MALT lymphoma that had clinicopathological information available were utilized in this study. MALT1 gene translocation, trisomy 3, and trisomy 18 were detected by interphase fluorescence in situ hybridization (FISH). The data were analyzed using SPSS 17.0 software package. The ratio of male to female was 1:2.8, and the median age was 57.0 years. 12.5% (9/72) of the patients presented with multiple swellings. Among the others with solitary mass, the parotid gland was involved most frequently (47/63,74.6%), followed by the palate (7/63, 11.1%). 34.7% of patients had an autoimmune disease, with Sjögren syndrome (SS) being the most common. Among the 70 cases successfully performed, it was identified that trisomy 3 was the most frequent molecular change (41/70, 58.6%), followed by trisomy 18 (7/70, 10%) and MALT1 translocation (5/70, 7.1%). The tumor tissue tended to exhibit trisomy 3 in patients without SS (p = 0.038). The 5-year overall survival was 94.1%, and the 5-year disease-free survival was 85.3% (mean follow-up time: 104.7 months). The patients without SS and trisomy 18 had a prolonged recurrence-free survival (p = 0.015, p = 0.001 respectively). Salivary gland MALT lymphoma is associated with autoimmune diseases, and trisomy 3 is the most common genetic change. Trisomy 18 can be used to predict the possibility of tumor relapse.


Seasonal changes in serum calcium, PTH and vitamin D levels in patients with primary hyperparathyroidism.
Seasonal variations of 25-hydroxyvitamin D, PTH and calcium levels are not well characterized in primary hyperparathyroidism (PHPT). Our objectives were to characterize seasonal changes in these parameters in PHPT patients, and to assess whether these seasonal changes affect clinical decision making. This is a retrospective study based on the electronic medical records of Clalit Health service in the south of Israel between 2000 and 2012. Patients 18years and older with PHPT (PTH>upper limit of norm (ULN) and serum calcium>10.5mg%) were included. Patients with renal failure or on Thiazide diuretics were excluded. All serum levels of calcium, PTH and 25-hydroxyvitamin D were collected and then stratified according to season. 792 patients were classified as PHPT (72.2% female) and had a total of 2659 PTH tests, 1395 25-hydroxyvitamin D tests and 7426 calcium test. Fifty six percent of 25-hydroxyvitamin D levels were <50nmol/L. Seasonality was demonstrated in all three parameters: mean 25-hydroxyvitamin D was 13% higher in the summer compared to the winter (P<0.001), median PTH values showed opposite trend with a fall of about 8.4% in summer compared to winter (P<0.001). Calcium levels were higher during the autumn with a rise of about 0.2mg/dL in the mean calcium levels compared to spring and summer (P<0.001). The odds ratio of calcium level above 11.5mg/dL is highest in the autumn (OR=1.275, P=0.018). We show seasonal variation in serum 25-hydroxyvitamin D, PTH, and calcium levels in patients with PHPT. These seasonal variations cause transition to pathological values that may influence diagnosis and treatment of PHPT patients.


Roles for both FtsA and the FtsBLQ subcomplex in FtsN-stimulated cell constriction in Escherichia coli.
Escherichia coli FtsN is a bitopic membrane protein that is essential for triggering active cell constriction. A small periplasmic subdomain ((E) FtsN) is required and sufficient for function, but its mechanism of action is unclear. We isolated extragenic (E) FtsN*-suppressing mutations that restore division in cells producing otherwise non-functional variants of FtsN. These mapped to the IC domain of FtsA in the cytoplasm and to small subdomains of the FtsB and FtsL proteins in the periplasm. All FtsB and FtsL variants allowed survival without (E) FtsN, but many then imposed a new requirement for interaction between the cytoplasmic domain of FtsN ((N) FtsN) and FtsA. Alternatively, variants of FtsA, FtsB or FtsL acted synergistically to allow cell division in the complete absence of FtsN. Strikingly, moreover, substitution of a single residue in FtsB (E56) proved sufficient to rescue ΔftsN cells as well. In FtsN(+) cells, (E) FtsN*-suppressing mutations promoted cell fission at an abnormally small cell size, and caused cell shape and integrity defects under certain conditions. This and additional evidence support a model in which FtsN acts on either side of the membrane to induce a conformational switch in both FtsA and the FtsBLQ subcomplex to de-repress septal peptidoglycan synthesis and membrane invagination.


Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor.
PKI-402 is a selective, reversible, ATP-competitive, equipotent inhibitor of class I phosphatidylinositol 3-kinases (PI3K), including PI3K-alpha mutants, and mammalian target of rapamycin (mTOR; IC(50) versus PI3K-alpha = 2 nmol/L). PKI-402 inhibited growth of human tumor cell lines derived from breast, brain (glioma), pancreas, and non-small cell lung cancer tissue and suppressed phosphorylation of PI3K and mTOR effector proteins (e.g., Akt at T308) at concentrations that matched those that inhibited cell growth. In MDA-MB-361 [breast: Her2(+) and PIK3CA mutant (E545K)], 30 nmol/L PKI-402 induced cleaved poly(ADP-ribose) polymerase (PARP), a marker for apoptosis. In vivo, PKI-402 inhibited tumor growth in MDA-MB-361, glioma (U87MG), and lung (A549) xenograft models. In MDA-MB-361, PKI-402 at 100 mg/kg (daily for 5 days, one round) reduced initial tumor volume of 260 mm(3) to 129 mm(3) and prevented tumor regrowth for 70 days. In MDA-MB-361 tumors, PKI-402 (100 mg/kg, single dose) suppressed Akt phosphorylation (at T308) and induced cleaved PARP. Suppression of phosphorylated Akt (p-Akt) was complete at 8 hours and still evident at 24 hours. Cleaved PARP was evident at 8 and 24 hours. In normal tissue (heart and lung), PKI-402 (100 mg/kg) had minimal effect on p-Akt, with no detectable cleaved PARP. Preferential accumulation of PKI-402 in tumor tissue was observed. Complete, sustained suppression of Akt phosphorylation may cause tumor regression in MDA-MB-361 and other xenograft models. We are testing whether dual PI3K/mTOR inhibitors can durably suppress p-Akt, induce cleaved PARP, and cause tumor regression in a diverse set of human tumor xenograft models. Mol Cancer Ther; 9(4); 976-84. (c)2010 AACR.


Sarcomatous Nodules Associated with Mucinous Neoplasms of Ovary: A Report of Two Cases.
Ovarian mucinous neoplasms (benign/borderline/malignant), one of the common surface epithelial tumours of ovary, at times can be associated with mural nodules. These mural nodules can either be sarcomatous, sarcoma like or anaplastic carcinomatous. The nodules can be single or multiple and appear solid, white to brown in color. Sarcomatous nodules tend to occur in older patients and microscopically are poorly circumscribed, comprising of a population of pleomorphic spindled cells. Two cases of sarcomatous nodules associated with ovarian mucinous neoplasm are being presented here.


The human papillomavirus vaccination: a review of the cost-effectiveness studies.
The Human Papillomavirus (HPV) is one of the most common sexually transmitted viruses, its infection with certain subtypes is the primary cause of cervical cancer. Several countries conducted specific cost-effectiveness evaluations toward HPV vaccination. The constant growth of healthcare demand, in an economic context characterized by limited resources, requires that the decision-making process be based on the comparison of alternative choices. This study offers an overview of the published cost-effectiveness studies about HPV vaccination. The research was performed on the scientific databases MEDLINE and SCOPUS in order to find out journal articles focused on cost-effectiveness of the HPV vaccination. The rational for any exclusion criteria of data in the search is mainly due to lack of relevance to cost-effectiveness information. The literature results were presented according to different groups of countries worldwide. A total of 24 articles were finally retrieved. In spite of the different models and assumptions, most studies showed the cost-effectiveness of vaccination; only two studies considered the vaccination as not cost effective. HPV vaccination may determine a cost reduction for country-specific National Health Systems. However, the cost-effectiveness of universal HPV vaccination still remains an open debate. It is important that economic analysis of universal HPV vaccination adopts large perspectives than is the case with the existing literature, focusing on the critical issues that still exist in many areas. Reducing cost, increasing duration of efficacy, and integrating vaccines into existing screening and treatment procedures in a cost-effective manner are of crucial importance even as they are a major challenge.


Reference values of gastric intramucosal pH in children.
To determine the reference values of gastric intramucosal pH (pHi) by tonometry in paediatric patients, we studied 17 children (nine males, eight females) with no systemic or gastrointestinal disease, aged six months to 12 years undergoing minor reconstructive surgery. Following anaesthetic induction a sigmoid tonometry catheter was inserted (Tonometrics, Inc.) into the stomach of the patients under direct vision. All children were normoventilated and were haemodynamically stable. After an equilibration period of 30 min, gastric pHi was calculated by applying the Henderson-Hasselbalch equation on the PCO2 obtained with the tonometer and the bicarbonate from the arterial blood gas analysis. The mean gastric pHi in our patients was 7.35 +/- 0.06 (SD). The normal pHi in the general population is estimated to be 7.31-7.40, with a confidence interval of 99%. No correlation was found between pHi and arterial pH, bicarbonate or base excess. Under conditions of normal ventilation and haemodynamic stability, healthy children during general anaesthesia have gastric intramucosal values similar to those of adults.


Impaired diastolic function in naïve untreated human immunodeficiency virus infected patients.
To evaluate cardiac function and structure in untreated human immunodeficiency virus (HIV) patients without clinical evidence of cardiovascular disease. Fifty-three naïve untreated HIV-infected patients and 56 healthy control subjects underwent clinical assessment, electrocardiography (ECG) and echocardiography, including tissue doppler imaging. Moreover, a set of laboratory parameters was obtained from all subjects, including HIV-RNA plasma levels, CD4 cell counts and tumor necrosis factor-α levels. The two groups showed normal ECG traces and no differences regarding systolic morphologic parameters. In contrast, a higher prevalence of left ventricular diastolic dysfunction (abnormal relaxation or pseudonormal filling pattern) was found in the HIV patients (36% vs 9% in patients and controls, respectively, P <0.001). Subclinical cardiac abnormalities appear in an early stage of the HIV infection, independent of antiretroviral therapy. The data suggest that HIV per se plays a role in the genesis of diastolic dysfunction.


[Scleroderma as a paraneoplastic syndrome of ductal carcinoma of the prostate].
We report on a patient with ductal carcinoma of the prostate. A few months earlier, the patient had presented with disabling scleroderma that progressed rapidly and compromised multiple organs. The findings that led us to suspect a paraneoplastic syndrome are discussed and the recent literature on scleroderma and cancer is briefly reviewed.


Alcalase Enzymolysis of Red Bean (adzuki) Ferritin Achieves Nanoencapsulation of Food Nutrients in a Mild Condition.
Classical methods to fabricate ferritin-nutrients shell-core nanoparticles usually apply extremely acid/alkaline pH transition, which may cause the activity loss of nutrients or the formation of insoluble aggregates. In this work, we prepared an extension peptide (EP) deleted red bean (adzuki) ferritin (apoRBFΔEP) by Alcalase 3.0T enzymolysis. Such enzymolysis could delete the EP domain and remain the typical shell-like structure of the ferritin. Meanwhile, the α-helix content of apoRBFΔEP was decreased by 5.5%, and the transition temperature (Tm) was decreased by 4.1 °C. Interestingly, the apoRBFΔEP can be disassembled into subunits under a benign condition at pH 4.0 and is assembled to form an intact cage protein when the pH was increased to 6.7. By using this novel route, the epigallocatechin gallate (EGCG) molecules were successfully encapsulated into the apoRBFΔEP cage with an encapsulation ratio of 11.6% (w/w), which was comparable with that by the traditional pH 2.0 transition. The newly prepared EGCG-loaded apoRBFΔEP exhibited a similarly protective effect on the EGCG upon simulated gastrointestinal tract and thermal treatment as compared with the control. In addition, the EGCG-loaded apoRBFΔEP could significantly relieve the ferritin association induced by pH transition, which was superior to traditional method. The thinking of this work will be especially suitable for encapsulating pH-sensitive molecules based on ferritin in a benign condition.


Hyperperfusion on magnetic resonance imaging in acute chemotherapy-related leukoencephalopathy.
Acute chemotherapy-related leukoencephalopathy can present similar to acute stroke with symptoms including aphasia, dysarthria, and hemiplegia. Differentiation based on clinical appearance is challenging, and physicians must distinguish between the 2 conditions rapidly to institute appropriate therapies. An 8-year-old male with acute lymphoblastic leukemia receiving chemotherapy, including intrathecal methotrexate, presented to our emergency center with 2 hours of expressive aphasia and flaccid right hemiplegia. Emergent magnetic resonance imaging (MRI) was obtained, demonstrating diffusion restriction within bilateral corona radiata and centrum semiovale. Magnetic resonance perfusion revealed mildly increased perfusion, a finding inconsistent with ischemic stroke and previously unreported in acute chemotherapy-related leukoencephalopathy without necrosis. This increased perfusion conclusively eliminated stroke from the clinical differential. Magnetic resonance perfusion imaging proved valuable to rapidly distinguish acute chemotherapy-related leukoencephalopathy from ischemia, and the evaluation of perfusion alterations in this disorder may provide further insight into the pathophysiology of this entity.


Conductive Hydrogel Electrodes for Delivery of Long-Term High Frequency Pulses.
Nerve block waveforms require the passage of large amounts of electrical energy at the neural interface for extended periods of time. It is desirable that such waveforms be applied chronically, consistent with the treatment of protracted immune conditions, however current metal electrode technologies are limited in their capacity to safely deliver ongoing stable blocking waveforms. Conductive hydrogel (CH) electrode coatings have been shown to improve the performance of conventional bionic devices, which use considerably lower amounts of energy than conventional metal electrodes to replace or augment sensory neuron function. In this study the application of CH materials was explored, using both a commercially available platinum iridium (PtIr) cuff electrode array and a novel low-cost stainless steel (SS) electrode array. The CH was able to significantly increase the electrochemical performance of both array types. The SS electrode coated with the CH was shown to be stable under continuous delivery of 2 mA square pulse waveforms at 40,000 Hz for 42 days. CH coatings have been shown as a beneficial electrode material compatible with long-term delivery of high current, high energy waveforms.


Surface force confinement cell for neutron reflectometry studies of complex fluids under nanoconfinement.
In this paper, we describe the construction of a new neutron surface force confinement cell (NSFCC). The NSFCC is equipped with hydraulically powered in situ, temporally stable, force control system for simultaneous neutron reflectometry studies of nanoconfined complex fluid systems. Test measurements with deuterated toluene confined between two opposing diblock copolymer (polystyrene+poly 2-vinylpyridine) coated quartz substrates demonstrate the capabilities of the NSFCC. With increasing hydraulically applied force, a series of well-defined decreasing separations were observed from neutron reflectivity measurements. No noticeable changes in the hydraulic pressure used for controlling the surface separation were observed during the measurements, demonstrating the high stability of the apparatus. This newly designed NSFCC introduces a higher level of control for studies of confinement and consequent finite size effects on nanoscale structure in a variety of complex fluid and soft condensed matter systems.


Inhibitory effect of rhynchophylline on human ether-a-go-go related gene channel.
We studied the effects of Chinese traditional medicine rhynchophylline (Rhy) on human ether-a-go-go related gene (HERG) channel and characterized the electrophysiological properties of Rhy's pharmacological effect on HERG channel using Xenopus oocytes. Xenopus oocytes were injected with either 23 nl (5.75 ng) HERG cRNA or 23 nl distilled water. Xenopus oocytes were randomly assigned to receive one of the following different concentrations of Rhy: (1) control, (2)10 mumol/L Rhy, (3)100 mumol/L Rhy, (4) 500 mumol/L Rhy, (5) 1 000 mumol/L Rhy, (6) 10 000 mumol/L Rhy. Cell currents were recorded in oocytes. The peak tail currents of HERG channel were inhibited by Rhy. The inhibition was in a dose-dependent manner [IC(50)=(773.4 +/- 42.5) mumol/L]. Experiment with 100 mumol/L Rhy indicated that the degree of HERG blockade showed some voltage dependence (within -40 mV to -20 mV ). Kinetic analyses revealed that Rhy decreased the rate of channel activation. The findings indicate that Rhy inhibits HERG encoded potassium channels. It may underline the molecular mechanism of myocardial electrophysiological characteristics associated with this drug.


Biological effects of estradiol-17 beta in postmenopausal women: oral versus percutaneous administration.
To determine whether the route of administration or the type of estrogen used in estrogen replacement therapy (ERT) is more important in avoiding effects on hepatic function, 24 postmenopausal women were studied before and at the end of 2 months of oral or percutaneous administration of the same estrogen, estradiol-17 beta (E2). The treatments studied were oral micronized E2, 2 mg/day (9 women); oral E2 valerate, 2 mg/day (5 women), and percutaneous E2, 3 mg/day (10 women). Specific plasma biological and biochemical markers of estrogenic action were evaluated, namely, E2, estrone (E1), LH, FSH, sex steroid binding protein (SBP), renin substrate, antithrombin activity, and lipoproteins (high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein triglycerides). Both oral and percutaneous administration of E2 increased plasma E2 levels up to midfollicular values and decreased LH and FSH levels into the same range. Oral administration of E2 led to substantial increases in plasma E1, SBP, renin substrate, and VLDL levels, whereas AT decreased significantly. Percutaneous administration of E2 led to a physiological plasma E1/E2 ratio and did not induce any change in hepatic proteins. These data suggest that the route of administration of E2 determines the biochemical response to ERT in postmenopausal women. SBP is the most sensitive marker of the liver action of estrogen, and triglycerides also are simple and useful markers for this effect. Percutaneous E2 therapy is an effective method of ERT, and has no measurable effects on hepatic markers of estrogen action.


Horizontal diplopia following upper blepharoplasty.
Diplopia is an infrequent complication after blepharoplasty. Most of the cases are in its vertical form due to trauma of the extraocular muscles. In this article, we present a case of horizontal diplopia following cosmetic upper blepharoplasty; we review the literature on this unexpected complication and offer some recommendations to avoid it.


Students' experiences and perceptions of interprofessional education during rural placement: A mixed methods study.
Interprofessional collaboration is key to addressing the complexity of contemporary health care, therefore it is imperative that students from different disciplines have access to interprofessional education to equip them with the requisite skills and attributes. While interprofessional education promotes a person-centred approach and mutual recognition of one another's contributions to health outcomes, interprofessional education in Australian universities is fragmented and presents challenges that can be addressed through clinical placements. This article reports student perceptions and readiness for interprofessional education in the rural clinical learning environment in one region of Australia. A mixed methods approach. Rural clinical learning environments in one geographic area in Victoria, Australia. 60 undergraduate healthcare students from allied health, medicine, nursing and midwifery. A survey incorporating Readiness for Interprofessional Learning Scale, Interdisciplinary Education Perception Scale and focused interprofessional questions. Qualitative data were collected via survey comments, interviews and focus groups. Students had numerous opportunities for interprofessional education, to observe role modelling in the workplace and considered that learning with other professions would help them become more effective members of the health care team. Students valued learning about collaborative practice, the roles of other professions and identified activities that enhanced interprofessional engagement. This study provides important insights regarding students' perceptions and readiness for interprofessional education. These results demonstrate that there are numerous opportunities to embed interprofessional education within the rural clinical learning environment and offer new insights into students' experiences and preferences for potential activities. These findings may resonate with others implementing interprofessional education in the workplace and guide facilitators in planning activities for students. Factors influencing differences in attitudes towards interprofessional education and how students acquire an understanding of their professional or disciplinary role warrant further study.


An additional bone in the carpal region of raptorial birds.
In a series of 4 species of owls and 12 species of diurnal raptors, an additional bone was present bilaterally in the area of the carpus. Designating the bone as an "additional bone of the raptorial carpal region" is suggested pending appropriate embryological studies to determine the origin of the bone. Generally, the bone was present in owls and in diurnal raptors with relatively short, rounded wings, but was absent in species with longer, more tapered wings. The bone lies at the cranial edge of the carpal area near the radial carpal bone, and is fixed to the surrounding skeleton by ligaments. The tendon of the tensor patagium longus muscle has one slip that attaches to the additional bone and another that passes over its craniodorsal surface en route to insertion. Awareness of the occurrence of this bone in some raptors, but not others, is essential in clinical evaluation of wing injuries, as well as in forming a prognosis for the return to soundness, the potential for release, and, therefore, the life of an injured raptor.


Six-pack holographic imaging for dynamic rejection of out-of-focus objects.
Six-pack holography is adapted to reject out-of-focus objects in dynamic samples, using a single camera exposure and without any scanning. By illuminating the sample from six different angles in parallel using a low-coherence source, out-of-focus objects are laterally shifted in six different directions when projected onto the focal plane. Then pixel-wise averaging of the six reconstructed images creates a significantly clearer image, with rejection of out-of-focus objects. Dynamic imaging results are shown for swimming microalgae and flowing microbeads, including numerical refocusing by Fresnel propagation. The averaged images reduced the contribution of out-of-focus objects by up to 83% in comparison to standard holograms captured using the same light source, further improving the system sectioning capabilities. Both simulation and experimental results are presented.


Geniospasm: hereditary chin trembling.
Geniospasm is a hereditary disorder characterized by episodic, usually stress-induced involuntary trembling of the chin. Nineteen families from Europe and the U.S.A. suffering from this disorder have been described since 1894. We present three cases from two newly detected families. There was no evidence of any other nervous system abnormality, although abnormal EEG, sleep disorders, and involvement of other facial muscles have been described in rare cases. Geniospasm is transmitted as an autosomal-dominant trait with high penetrance. It must be differentiated from facial myokymia, palatal tremor, and essential tremor affecting facial muscles. Neurophysiological and molecular mechanisms of this peculiar disorder are unknown.


Species of Dirhinus Dalman, 1818 (Hymenoptera: Chalcididae, Dirhininae) from Saudi Arabia: new species and a new record.
The species of chalcidid wasps of Dirhinus Dalman, 1818 (Hymenoptera: Chalcididae) from Saudi Arabia are reviewed. Seven species are reported from Al Bahah, Asir, Jazan and Riyadh regions, of which three have hitherto been recorded: D. (Dirhinus) anthracia Walker, 1846, D. (Dirhinus) himalayanus Westwood, 1836 and D. (Dirhinus) wohlfahrtiae Ferrière, 1935. One species D. (Dirhinus) claviger Bouček Narendran, 1981 is recorded for the first time from Saudi Arabia (Asir). Additionally, three new species: D. (Dirhinus) asirensis sp. nov. (Asir), D. (Dirhinus) sculpturatus sp. nov. (Al Bahah, Asir and Riyadh) and D. (Pareniaca) transversus sp. nov. (Al Bahah, Asir and Jazan) are described and illustrated. An illustrated key to females of the species of Dirhinus from Saudi Arabia is provided.


Risk factors for osteoarthritis and contributing factors to current arthritic pain in South Korean older adults.
Although previous studies have focused on risk factors for osteoarthritis, there is some debate on this issue. Furthermore, associated factors with arthritic symptom (arthralgia) have not been sufficiently investigated, despite its clinical importance in the management of osteoarthritis. This study was performed to examine the risk factors for osteoarthritis and the contributing factors to current arthritic pain in older adults. The Fourth Korean National Health and Nutrition Examination Surveys was conducted in 2009. Therein, 720 males and 1008 females aged 65 years and older were included. Comprehensive data on habitual, socioeconomic, medical, nutritional, and psychological factors were collected along with the presence of osteoarthritis and arthritic pain. After univariate analysis, binary logistic regression analysis was performed to identify risk factors for osteoarthritis and contributing factors to current arthritic pain. Age (p=0.005), female gender (p<0.001), higher body mass index (BMI) (p<0.001), and osteoporosis (p<0.001) were significant risk factors for osteoarthritis, while higher education level (p=0.025) was a protective factor for osteoarthritis. Higher BMI (p=0.047), lack of weekly moderate intensity activity (p<0.001), and unfavorable subjective health status (p<0.001) were significant factors contributing to current arthritic pain among subjects with osteoarthritis. Both osteoarthritis and current arthritic pain adversely affected health related quality of life. Higher BMI, lack of weekly moderate intensity activity, and unfavorable subjective health status were significant factors contributing to current arthritic pain. More attention needs to be paid to psychiatric effects on osteoarthritis and joint related pain.


Size-specific dose estimates in chest, abdomen, and pelvis CT examinations of pediatric patients.
Size-specific dose estimates (SSDEs) are the latest focus of interest among medical physicists studying radiation dose to the patient in computed tomography (CT). This study aims to make conversions from CTDIvol to SSDE and investigate the relationship between mean SSDE (SSDE) and central SSDE (SSDEcenter) values for pediatric patients of different age groups undergoing chest, abdomen, and pelvis scans. In this retrospective study, we examined 105 consecutive pediatric CT exams of chest, abdomen, and pelvis (CAP) classified in 3 separate groups according to age: 0-5 years, 6-10 years, and 11-16 years. A MATLAB program was developed to determine SSDE values for each patient along 6 subregions: chest, abdomen, pelvis, chest and abdomen, abdomen and pelvis, and CAP. SSDE values derived over the slice at the center of each scan range (SSDEcenter) were also recorded. SSDE and corresponding SSDEcenter results were compared for each age group. Root mean square differences (RMSD) between SSDE and SSDEcenter values ranged between 0.13 mGy and 2.1 mGy through all groups and subregions, corresponding to 1.2% and 11%, respectively. In pediatric CT exams involving CAP region, CTDIvol and the water equivalent diameter at the middle of the scan range can be used to provide a reasonable estimate of mean SSDE with an RMSD of 11% at most.


Emergence of Rhino-Orbito-Cerebral Mucormycosis in Peru: Impact of the COVID-19 Pandemic.
Introduction Mucormycosis is an invasive fungal infection caused by Mucorales that has been increasingly recognized over the years, particularly during the COVID-19 pandemic. Nevertheless, in Peru, there has been limited research on this disease. This study seeks to provide insights into the demographics, clinical presentations, treatment, and outcomes of patients with mucormycosis, before and during the COVID-19 pandemic. Materials and methods We conducted a retrospective case series by reviewing the medical records of Peruvian patients hospitalized at a referral medical center between 2017 and 2021. The selection criteria included patients aged 18 years or older with clinical features of rhino-orbito-cerebral mucormycosis supported by radiological imaging. We extracted data related to risk factors for mucormycosis infection, clinical presentation, management, and hospitalization. Data analysis was performed using Stata software (StataCorp LLC, College Station, Texas, USA) to compare patient groups before and during the COVID-19 pandemic. Results Nineteen cases met our selection criteria: 11 men and eight women with an average age of 57.6 ± 10.6 years. All 19 patients had type 2 diabetes mellitus as comorbidity, with 13 cases exhibiting uncontrolled diabetes. Six patients presented before the COVID-19 pandemic, while 13 during its course. Within the group of patients diagnosed during the pandemic, nine were diagnosed with SARS-CoV-2 infection. Regarding the site of mucormycosis infection, the paranasal sinuses were predominantly involved. Survival analysis indicated that patients who developed mucormycosis during the COVID-19 pandemic, those with uncontrolled diabetes, or those who did not undergo surgery had lower probabilities of survival. Conclusion Mucormycosis is a rare infection associated with high mortality and morbidity with increased frequency during the COVID-19 pandemic. Early diagnosis, timely administration of antifungal treatment, surgery, and effective management of comorbidities can have life-saving implications. Unfortunately, despite the availability of various diagnostic tests and less toxic antifungal options such as liposomal amphotericin-B, such resources are not accessible in Peru's national hospitals.


Total Synthesis of Microcystin-LF and Derivatives Thereof.
Microcystins (MCs) are highly toxic natural products which are produced by cyanobacteria. They can be released to the water during harmful algal blooms and are a serious threat to animals and humans. Described is the total synthesis of the cyanotoxin microcystin-LF (MC-LF, 1a) and two derivatives thereof. Deuterated derivative 1b is of interest as an internal standard during MC quantification in biological samples by mass spectrometry and alkyne-labeled 1c can be employed for toxin derivatization by click chemistry with an azide-containing reporter molecule or as an activity-based probe to identify interaction partners. Application of tert-butyl ester protecting groups for erythro-β-d-methylaspartic acid and γ-d-glutamic acid were key for an isomerization-free synthesis. The analytical data of synthetic MC-LF were identical to those of an authentic sample of the natural product. All derivatives 1a-c were determined to be potent inhibitors of protein phosphatase-1 with similar activity.


"Making a connection": BSN students' perceptions of their reminiscence experiences with older adults.
The projected increase in the diversity of the older adult population in the United States has generated a demand for nurses prepared to care for older adults from different cultural backgrounds. Nurse educators are challenged to develop innovative experiences to help prepare students who are competent in gerontological nursing and sensitive to cultural differences. The purpose of this study was to examine baccalaureate nursing students' perceptions of their reminiscence experiences with older adults. Forty-one nursing students who participated in a reminiscence education program during their clinical practicum completed an open-ended questionnaire. Data were analyzed, and three major themes emerged: "Making a Connection," "Seeing the World Through Their Eyes," and "Benefits of Reminiscence." Results indicate that implementing reminiscence education programs in clinical experiences can help students develop gerontological nursing skills, increase their cultural sensitivity, and improve their care of older adults.


The fetal sheep lung does not respond to cortisol infusion during the late canalicular phase of development.
The prepartum surge in plasma cortisol concentrations in humans and sheep promotes fetal lung and surfactant system maturation in the support of air breathing after birth. This physiological process has been used to enhance lung maturation in the preterm fetus using maternal administration of betamethasone in the clinical setting in fetuses as young as 24 weeks gestation (term = 40 weeks). Here, we have investigated the impact of fetal intravenous cortisol infusion during the canalicular phase of lung development (from 109- to 116-days gestation, term = 150 ± 3 days) on the expression of genes regulating glucocorticoid (GC) activity, lung liquid reabsorption, and surfactant maturation in the very preterm sheep fetus and compared this to their expression near term. Cortisol infusion had no impact on mRNA expression of the corticosteroid receptors (GC receptor and mineralocorticoid receptor) or HSD11B-2, however, there was increased expression of HSD11B-1 in the fetal lung. Despite this, cortisol infusion had no effect on the expression of genes involved in lung sodium (epithelial sodium channel -α, -β, or -γ subunits and sodium-potassium ATPase-β1 subunit) or water (aquaporin 1, 3, and 5) reabsorption when compared to the level of expression during exposure to the normal prepartum cortisol surge. Furthermore, in comparison to late gestation, cortisol infusion does not increase mRNA expression of surfactant proteins (SFTP-A, -B, and -C) or the number of SFTP-B-positive cells present in the alveolar epithelium, the cells that produce pulmonary surfactant. These data suggest that there may be an age before which the lung is unable to respond biochemically to an increase in fetal plasma cortisol concentrations.


[MONITORING UNITS IN DEPARTMENTS OF INTERNAL MEDICINE: FREQUENCY, IMPACT AND SATISFACTION].
Due to increasing numbers of elderly, seriously ill patients and shortage of ICU beds, many hospitals have established monitoring units (MU) in their medical departments. (1) To assess the national prevalence of MUs in medical departments; (2) to determine the outcome of consecutively admitted MU patients; (3) to evaluate patient/ family satisfaction with care. The case control study included all 123 patients hospitalized in the MU during a 5-month period, compared with two control groups: (1) 123 patients admitted to medical departments, matched at a ratio of 1:1 by gender, age±10 years and mechanical ventilation; (2) all 52 medical patients treated in the ICU. The main endpoint was 28-day survival. A total of 76/99 (77%) directors of medical departments in Israel responded: 70 (92%) reported the presence of a MU, 64 (92%) have 5-7 beds and 47 (67%) have one nurse per shift. Baseline characteristics of enrolled MU and medical department patients were similar, although 52 medical ICU patients were younger (56±21 vs. 73±14, p<0.001) and had a lower incidence of kidney failure (11.5% vs. 41.5%, p<0.001). The predicted mortality rates were higher for MU patients compared to medical department patients, but 28-day survival rates were similar (64-70%, NS). The questionnaire showed high rates of satisfaction (from 0=low to 5=high): highest with MU care: (4.79±0.48), followed by ICU (4.41±1.06) and lowest for medical department nursing care (4.27±0.84)(p=0.017). Monitoring units are ubiquitous in Israeli hospitals and contribute to survival and satisfaction with care.


Radiographic Hip Anatomy Correlates With Range of Motion and Symptoms in National Hockey League Players.
Hip disorders in athletes have been increasingly recognized. To characterize radiographic hip anatomy for National Hockey League (NHL) players and correlate it with hip range of motion and hip symptoms and/or surgery. Cross-sectional study; Level of evidence, 3. Fifty-nine professional hockey players (118 hips) with 1 NHL organization (mean age, 24.2 years; range, 18-36) prospectively underwent history and physician examination by 2 independent orthopaedic surgeons. Current or previous groin and/or hip pain or surgery was noted. Anteroposterior (AP) pelvis and bilateral Dunn lateral radiographs were obtained for all players with assessment of hip morphology by 2 blinded independent orthopaedic surgeons. Good to very good reliability of radiographic assessments was noted (intraclass correlation coefficients = 0.749-0.958). Sixty-four percent of athletes had a positive crossover sign, while 86% and 60% had a positive posterior wall sign and a prominent ischial spine sign, respectively. Twenty-one percent of hips demonstrated dysplastic acetabular features (lateral center edge angle <25°). Eighty-five percent and 89% of hips demonstrated cam-type morphology based on alpha angle (>50° Dunn lateral) and head-neck offset, respectively. Good to very good reliability was noted for ROM assessments (intraclass correlation coefficient >0.69). Mean hip flexion was 107.4º ± 6.7º, and mean hip internal rotation was 26.1º ± 6.6º. Thirty-one percent of hips had a history of hip-related pain and/or surgery. Higher AP, Dunn lateral, and maximal alpha angles correlated with decreased hip internal rotation ( P = .004). Greater AP alpha angle correlated with decreased hip extension/abduction ( P = .025), and greater Dunn lateral and maximal alpha angle correlated with decreased hip flexion/abduction ( P = .001). A positive posterior wall sign correlated with increased straight hip abduction, while other radiographic acetabular parameters were not predictive of range of motion. Only decreased hip external rotation and total arc of motion correlated with an increased risk for current or prior hip symptoms or surgery ( P < .001). Hip anatomy in NHL players is characterized by highly prevalent cam-type morphology (>85%) and acetabular retroversion (>60%). In addition, acetabular dysplasia (21%) was relatively common. Greater cam-type morphology correlated with decreased hip range of motion, and a positive crossover sign correlated with increased hip abduction. Decreased hip external rotation and total arc of motion were predictive of hip-related pain and/or surgery.


Compound spatial sonography of the thyroid gland: evaluation of freedom from artifacts and of nodule conspicuity.
The purpose of this study was to compare compound spatial sonography with conventional sonography of the thyroid gland with respect to freedom from sonographic artifacts and conspicuity of thyroid nodules. A prospective study was performed on 50 thyroid nodules (in 43 patients). Each nodule was examined using compound spatial sonography and conventional sonography. The sonographic techniques were then compared with respect to freedom from sonographic artifacts and thyroid nodule conspicuity. For freedom from artifacts, compound spatial sonography was superior in 45 cases (90%), and conventional sonography was superior in five cases (10%). Statistical analysis showed that compound spatial sonography was superior to conventional sonography for freedom from artifacts (p < 0.001). For thyroid nodule conspicuity, compound spatial sonography was superior in 37 cases (74%), and conventional sonography was superior in 13 cases (26%). Statistical analysis showed that compound spatial sonography was superior to conventional sonography for thyroid nodule conspicuity (p < 0.001). Compound spatial sonography of the thyroid displays greater freedom from artifacts and better nodule conspicuity than does conventional sonography.


Tuna pepsin: characteristics and its use for collagen extraction from the skin of threadfin bream (Nemipterus spp.).
Pepsin from the stomach of albacore tuna, skipjack tuna, and tongol tuna was characterized. Pepsin from all tuna species showed maximal activity at pH 2.0 and 50 degrees C when hemoglobin was used as a substrate. Among the stomach extract of all species tested, that of albacore tuna showed the highest activity (40.55 units/g tissue) (P < 0.05). Substrate-Native-PAGE revealed that pepsin from albacore tuna and tongol tuna consisted of 2 isoforms, whereas pepsin from skipjack tuna had only 1 form. The activity was completely inhibited by pepstatin A, while EDTA (ethylenediaminetetraacetic acid), SBTI (soybean trypsin inhibitor), and E-64 (1-(L-trans-epoxysuccinyl-leucylamino)-4-guanidinobutane) exhibited negligible effect. The activity was strongly inhibited by SDS (sodium dodecyl sulfate) (0.05% to 0.1%, w/v). Cysteine (5 to 50 mM) also showed an inhibitory effect in a concentration dependent manner. ATP, molybdate, NaCl, MgCl(2), and CaCl(2) had no impact on the activity. When tuna pepsin (10 units/g defatted skin) was used for collagen extraction from the skin of threadfin bream for 12 h, the yield of collagen increased by 1.84- to 2.32-fold and albacore pepsin showed the comparable extraction efficacy to porcine pepsin. The yield generally increased with increasing extraction time (P < 0.05). All collagen obtained with the aid of tuna pepsin showed similar protein patterns compared with those found in acid-solubilized collagen. Nevertheless, pepsin from skipjack tuna caused the degradation of alpha and beta components. All collagens were classified as type I with large portion of beta-chain. However, proteins with molecular weight (MW) greater than 200 kDa were abundant in acid-solubilized collagen.


Occupational Therapy Practice: Time From Stroke Onset to Outpatient Upper Limb Rehabilitation.
Upper limb stroke rehabilitation has been understudied in usual occupational therapy. The study's purpose was to describe the timing and amount of usual occupational therapy in the stroke population for hospital-based outpatient upper limb rehabilitation. A multi-site study of timing and amount of occupational therapy was calculated for mild and moderate upper limb stroke impairments using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE). Mild stroke participants (n = 58) had a mean of 164.25 days, and the moderate stroke participants (n = 64) had a mean of 106.75 days from the date of stroke onset to first treatment which was significantly different (p = .047). There were no significant differences in the amount of therapy between mild or moderate stroke patients. Mild stroke patients experience a longer delay in receiving outpatient occupational therapy compared with moderate impairments which may be attributed to the subtlety of the impairments that impact participation in daily activities.


[Structural Equation Modeling of Self-Management in Patients with Hemodialysis].
The purpose of this study was to construct and test a hypothetical model of self-management in patients with hemodialysis based on the Self-Regulation Model and resource-coping perspective. Data were collected from 215 adults receiving hemodialysis in 17 local clinics and one tertiary hospital in 2016. The Hemodialysis Self-management Instrument, the Revised Illness Perception Questionnaire, Herth Hope Index and Multidimensional Scale of Perceived Social Support were used. The exogenous variable was social context; the endogenous variables were cognitive illness representation, hope, self-management behavior, and illness outcome. For data analysis, descriptive statistics, Pearson correlation analysis, factor analysis, and structural equation modeling were performed. The hypothetical model with six paths showed a good fitness to the empirical data: GFI=.96, AGFI=.90, CFI=.95, RMSEA=.08, SRMR=.04. The factors that had an influence on self-management behavior were social context (β=.84), hope and cognitive illness representation (β=.37 and β=.27) explaining 92.4% of the variance. Self-management behavior mediated the relationship between psychosocial coping resources and illness outcome. This research specifies a more complete spectrum of the self-management process. It is important to recognize the array of clinical resources available to support patients' self-management. Healthcare providers can facilitate self-management through collaborative care and understanding the ideas and emotions that each patient has about the illness, and ultimately improve the health outcomes. This framework can be used to guide self-management intervention development and assure effective clinical assessment.


Real-time measurement of alveolar size and population using phase contrast x-ray imaging.
Herein a propagation-based phase contrast x-ray imaging technique for measuring particle size and number is presented. This is achieved with an algorithm that utilizes the Fourier space signature of the speckle pattern associated with the images of particles. We validate this algorithm using soda-lime glass particles, demonstrating its effectiveness on random and non-randomly packed particles. This technique is then applied to characterise lung alveoli, which are difficult to measure dynamically in vivo with current imaging modalities due to inadequate temporal resolution and/or depth of penetration and field-of-view. We obtain an important result in that our algorithm is able to measure changes in alveolar size on the micron scale during ventilation and shows the presence of alveolar recruitment/de-recruitment in newborn rabbit kittens. This technique will be useful for ventilation management and lung diagnostic procedures.


Wafer Scale Fabrication of Dense and High Aspect Ratio Sub-50 nm Nanopillars from Phase Separation of Cross-Linkable Polysiloxane/Polystyrene Blend.
We demonstrated a simple and effective approach to fabricate dense and high aspect ratio sub-50 nm pillars based on phase separation of a polymer blend composed of a cross-linkable polysiloxane and polystyrene (PS). In order to obtain the phase-separated domains with nanoscale size, a liquid prepolymer of cross-linkable polysiloxane was employed as one moiety for increasing the miscibility of the polymer blend. After phase separation via spin-coating, the dispersed domains of liquid polysiloxane with sub-50 nm size could be solidified by UV exposure. The solidified polysiloxane domains took the role of etching mask for formation of high aspect ratio nanopillars by O2 reactive ion etching (RIE). The aspect ratio of the nanopillars could be further amplified by introduction of a polymer transfer layer underneath the polymer blend film. The effects of spin speeds, the weight ratio of the polysiloxane/PS blend, and the concentration of polysiloxane/PS blend in toluene on the characters of the nanopillars were investigated. The gold-coated nanopillar arrays exhibited a high Raman scattering enhancement factor in the range of 108-109 with high uniformity across over the wafer scale sample. A superhydrophobic surface could be realized by coating a self-assembled monolayers (SAM) of fluoroalkyltrichlorosilane on the nanopillar arrays. Sub-50 nm silicon nanowires (SiNWs) with high aspect ratio of about 1000 were achieved by using the nanopillars as etching mask through a metal-assisted chemical etching process. They showed an ultralow reflectance of approximately 0.1% for wavelengths ranging from 200 to 800 nm.


American College of Rheumatology quality indicators for rheumatoid arthritis: benchmarking, variability, and opportunities to improve quality of care using the electronic health record.
To measure how rheumatologists across our health system performed with the American College of Rheumatology (ACR) quality indicators (QIs) for rheumatoid arthritis (RA) and methotrexate (MTX) drug safety, and to develop opportunities for improvement. An electronic health record (EHR) review of 1,062 unique RA patients seen by 15 rheumatologists in a 1-year period was performed. Percentage of each QI met, reasons why the metric was not met, and performance of rheumatologists based on years of experience were evaluated. The percentage met was high for QI-2 (RA disease-modifying antirheumatic drug use; 94%), QI-3 (intervention if RA worse; 85%), and QI-4 (MTX risks discussion; 87%). Percentage met was lower for QI-1 (RA core data set; 69%), QI-5 (MTX baseline studies; 41%), and QI-6 (MTX followup studies; 46%). QI-1 and QI-5 were low due to most physicians missing a single test, and QI-6 was low because of few physicians driving the percentage down. Better QI performance was seen in rheumatologists with <or=10 years versus >10 years of experience for QI-1 (90% versus 64%; odds ratio [OR] 4.21, P = 0.004) and QI-3 (96% versus 82%; OR 4.47, P = 0.019). EHR chart review for this population required 179.3 hours. Measurement allows us to better understand the quality of care that we deliver. In this systematic benchmarking of the ACR QIs in a large RA cohort, performance was excellent in RA treatment-related QIs. Significant variability was noted in RA and MTX monitoring measures, which can be addressed using process redesign techniques.


Competing Risks Analysis of Cancer-associated Recurrent Thrombosis, Major Bleeds, and Death in a Geriatric Cohort.
Background: Individuals with cancer are at an increased risk of venous thromboembolism (VTE). There is a continued increased risk of recurrent VTE after the initial event as well as increased bleed risk related to VTE treatment. Objectives: This study sought to observe the incidence of recurrent VTE, major bleeding, and death in a geriatric oncology population during treatment for a cancer-associated VTE. Methods: We utilized an insurance claims database of Medicare Advantage beneficiaries 65 and older. The index VTE was identified and individuals were followed up to 180 days to observe an outcome event. Treatment groups were classified among those receiving warfarin, low-molecular weight heparins (LMWH), vena cava (VC) filters with or without anticoagulation, or no treatment. Treatment groups were compared on baseline demographic and clinical characteristics and an inverse probability of treatment weight was used to balance these factors between the groups. A competing risks, time-to-event analysis was performed including treatment only models as well as adjusted models with additional covariates. Causespecific hazards ratios (HRs) and their 95% confidence intervals were reported. Results: Treatment groups differed on baseline variables including age, comorbidities, and tumor sites. After balancing the treatment groups on baseline characteristics, those receiving LMWHs had no difference in recurrent VTE compared to warfarin but had less than half the risk of major bleeding (HR=0.48 [0.27-0.85]). Those receiving VC filters had increased risk of all outcome events relative to warfarin. Conclusions: Patients over the age of 65 with cancer are at a high risk of experiencing recurrent VTE and major bleeding during treatment for a cancer-associated VTE. These results are consistent with United States guidelines which recommend LMWHs over warfarin for treatment and secondary prevention of VTE.


Color discrimination ellipses of trichromats measured with transient and steady state visual evoked potentials.
The purpose of this work is to investigate the use of different forms of visual evoked potentials (VEPs) to measure color discrimination thresholds and to plot color discrimination ellipses (MacAdam, 1942). Five normal trichromats (24.5 +/- 2.6 years-old) were monocularly tested. Stimuli consisted of sinusoidal isoluminant chromatic gratings made from chromaticity pairs located along four different color directions radiating from one reference point of the CIE 1976 chromaticity diagram (u' = 0.225; v' = 0.415). Heterochromatic flicker photometry (HFP) was used to obtain the isoluminance condition for every subject and for all chromaticity pairs. VEPs were elicited using two cycles per degree grating stimuli at three different temporal configurations: transient, onset (300 ms)/offset (700 ms), 1 Hz fundamental frequency; steady-state, onset (50 ms)/offset (50 ms), 10 Hz fundamental frequency; and steady-state pattern reversal at 5 Hz fundamental frequency (10 Hz phase reversal). VEP amplitude was measured using transient VEP N1-P1 components and steady state VEP first (10 Hz) and second (20 Hz) harmonics. VEP amplitude was plotted as a function of chromatic distance in the CIE 1976 color space and the data points were extrapolated to zero amplitude level to obtain chromatic discrimination thresholds. The results were compared with psychophysical measurements performed using the same stimulus configurations and with the pseudoisochromatic method of Mollon-Reffin (one-way ANOVA). For all subjects and all stimulation methods, the ellipses showed small sizes, low ellipticities, and were vertically oriented. Despite some consistent differences in the results obtained with different procedures, there was no statistical difference between ellipses obtained electrophysiologically and psychophysically. For steady state VEPs, ellipses obtained from second harmonic amplitudes were larger and more elongated in the tritan direction than those obtained with first harmonic amplitudes.


Genetic analysis of developmental mechanisms in hydra. XII. Analysis of chimaeric hydra produced from a normal and a slow-budding strain (L4).
Chimaeric hydra strains were produced from a normal strain (105) and a naturally-occurring mutant strain (L4) which has a large polyp size, a low budding rate and a high head-inhibition potential. Various properties of the chimaeras were then examined and compared to those of the two parental strains. Hydra tissue consists of three cell lineages: the ectodermal epithelial, the endodermal epithelial and the interstitial cell lineages. Using the methods recently developed by Marcum & Campbell (1978b) and by Wanek & Campbell (1982), six chimaeric strains were produced which contained six different combinations of the three cell lineages from 105 and L4. Evidence obtained from the comparison of the chimaeras and their parental strains indicates that the ectodermal epithelial cell lineage in L4 is primarily responsible for the large polyp size and the low budding rate of this strain, whereas the endodermal epithelial cell lineage is largely, and the interstitial cell lineage is also partially, responsible for the high head-inhibition potential in L4. This suggests that the mechanisms determining the occurrence and location of bud formation and the mechanisms determining the inhibition potential levels are not related to each other (cf. Takano & Sugiyama, 1983; Bode & Bode, 1983). Evidence was also obtained which suggests that the levels of the head-activation and head-inhibition potentials in the chimaeras are determined independent of each other, apparently without the cross-catalytic relationship between them assumed in the Gierer-Meinhardt model (Gierer & Meinhardt, 1972; Meinhardt & Gierer, 1974).


Reactive ballistic deposition of alpha-Fe2O3 thin films for photoelectrochemical water oxidation.
We report the preparation of alpha-Fe2O3 electrodes using a technique known as reactive ballistic deposition in which iron metal is evaporatively deposited in an oxygen ambient for photoelectrochemical (PEC) water oxidation. By manipulating synthesis parameters such as deposition angle, film thickness, and annealing temperature, we find that it is possible to optimize the structural and morphological properties of such films in order to improve their PEC efficiency. Incident photon to current conversion efficiencies (IPCE) are used to calculate an AM1.5 photocurrent of 0.55 mA/cm(2) for optimized films with an IPCE reaching 10% at 420 nm in 1 M KOH at +0.5 V versus Ag/AgCl. We also note that the commonly observed low photoactivity of extremely thin hematite films on fluorine-doped tin oxide substrates may be improved by modification of annealing conditions in some cases.


Paradoxical (REM) sleep deprivation in mice using the small-platforms-over-water method: polysomnographic analyses and melanin-concentrating hormone and hypocretin/orexin neuronal activation before, during and after deprivation.
Studying paradoxical sleep homeostasis requires the specific and efficient deprivation of paradoxical sleep and the evaluation of the subsequent recovery period. With this aim, the small-platforms-over-water technique has been used extensively in rats, but only rare studies were conducted in mice, with no sleep data reported during deprivation. Mice are used increasingly with the emergence of transgenic mice and technologies such as optogenetics, raising the need for a reliable method to manipulate paradoxical sleep. To fulfil this need, we refined this deprivation method and analysed vigilance states thoroughly during the entire protocol. We also studied activation of hypocretin/orexin and melanin-concentrating hormone neurones using Fos immunohistochemistry to verify whether mechanisms regulating paradoxical sleep in mice are similar to those in rats. We showed that 48 h of deprivation was highly efficient, with a residual amount of paradoxical sleep of only 2.2%. Slow wave sleep and wake quantities were similar to baseline, except during the first 4 h of deprivation, where slow wave sleep was strongly reduced. After deprivation, we observed a 124% increase in paradoxical sleep quantities during the first hour of rebound. In addition, 34% of hypocretin/orexin neurones were activated during deprivation, whereas melanin-concentrated hormone neurones were activated only during paradoxical sleep rebound. Corticosterone level showed a twofold increase after deprivation and returned to baseline level after 4 h of recovery. In summary, a fairly selective deprivation and a significant rebound of paradoxical sleep can be obtained in mice using the small-platforms-over-water method. As in rats, rebound is accompanied by a selective activation of melanin-concentrating hormone neurones.


Ethics support for GPs: what should it look like?
INTRODUCTION Ethics support services for hospital clinicians have become increasingly common globally but not as yet in New Zealand. However, an initiative to change this is gathering momentum. Its slogan 'Clinical ethics is everyone's business' indicates that the aim is to encompass all of health care, not just the hospital sector. General Practitioners (GPs) deal with ethical issues on a daily basis. These issues are often quite different from ethical issues in hospitals. To make future ethics support relevant for primary care, local GPs were interviewed to find out how they might envisage ethics support services that could be useful to them. METHODS A focus group interview with six GPs and semi-structured individual interviews with three GPs were conducted. Questions included how they made decisions on ethical issues at present, what they perceived as obstacles to ethical reflection and decision-making, and what support might be helpful. FINDINGS Three areas of ethics support were considered potentially useful: Formal ethics education during GP training, access to an ethicist for assistance with analysing an ethical issue, and professional guidance with structured ethics conversations in peer groups. CONCLUSION The complex nature of general practice requires GPs to be well educated and supported for handling ethical issues. The findings from this study could serve as input to the development of ethics support services. KEYWORDS General practice; primary care; ethics; support; education.


Ulcerative colitis and colon cancer.
Chronic ulcerative colitis is an idiopathic inflammatory disease of the colon associated with an increased incidence of colorectal cancer. Colonoscopy with biopsy for mucosal dysplasia (precancer) can identify individuals with ulcerative colitis who are at increased risk for colorectal cancer. Identification of high-risk individuals can be used to guide clinical decisions regarding the timing and appropriateness of prophylactic colectomy.


Prevalence of Clonorchis sinensis Metacercariae in Fish from Water Systems of Seomjin-gang (River).
The prevalence of Clonorchis sinensis metacercariae (CsMc) was examined in freshwater fish from the water systems of Seomjin-gang (River), the Republic of Korea. Total 1,604 fish from 7 local sites of Seomjin-gang were examined by artificial digestion methods. The metacercariae of C. sinensis were detected in 102 (39.8%) out of 256 fish (14 species) from the upper reaches of Seomjin-gang, i.e., Osucheon (22.3% in 6 fish species) in Imsil-gun, and Seomjin-gang (63.9% in 9 fish species) in Sunchang-gun, Jeollabuk-do. Their average density was 9.0 per infected fish. They were also found in 132 (48.0%) out of 275 fish (12 spp.) from the middle reaches of Seomjin-gang, i.e., Songdaecheon (58.9% in 4 fish species) in Namwon-si, Jeollabuk-do, and Seomjin-gang (45.2% in 10 fish species) in Gokseong-gun, Jeollanam-do. Their average density was 21.0 per infected fish. CsMc were detected in 77 (56.6%) out of 136 fish (11 species) from the lower reaches of Seomjin-gang, i.e., Seomjin-gang (73.3% in 11 fish species) in Gurye-gun, Jeollanam-do, and Namsancheon (8.6% in 1 fish species) in Hadong-gun, Gyeongsangnam-do. Their average density was 64.9 per infected fish. The metacercariae of Metorchis orientalis were also detected in 6 fish species from 4 sites of Seomjin-gang. Conclusively, it has been confirmed that CsMc are more or less prevalent in fish from some water systems of Seomjin-gang in Korea.


Diagnosis of hepatic glycogenosis in poorly controlled type 1 diabetes mellitus.
Hepatic glycogenosis (HG) in type 1 diabetes is a underrecognized complication. Mauriac firstly described the syndrome characterized by hepatomegaly with altered liver enzymes, growth impairment, delay puberty and Cushingoid features, during childhood. HG in adulthood is characterized by the liver disorder (with circulating aminotransferase increase) in the presence of poor glycemic control (elevation of glycated hemoglobin, HbA1c levels). The advances in the comprehension of the metabolic pathways driving to the hepatic glycogen deposition point out the role of glucose transporters and insulin mediated activations of glucokinase and glycogen synthase, with inhibition of glucose-6-phosphatase. The differential diagnosis of HG consists in the exclusion of causes of liver damage (infectious, metabolic, obstructive and autoimmune disease). The imaging study (ultrasonography and/or radiological examinations) gives information about the liver alterations (hepatomegaly), but the diagnosis needs to be confirmed by the liver biopsy. The main treatment of HG is the amelioration of glycemic control that is usually accompanied by the reversal of the liver disorder. In selected cases, more aggressive treatment options (transplantation) have been successfully reported.


Cloning and expression analysis of a Toll-like receptor 21 (TLR21) gene from turbot, Scophthalmus maximus.
Toll-like receptor 21 (TLR21) is a non-mammalian TLR recognizing unmethylated CpG DNA and considered as a functional homolog of mammalian TLR9. In the present study, a TLR21 gene was cloned from turbot, Scophthalmus maximus, its immune responsive expression was subsequently studied in vivo. The turbot (Sm)TLR21 gene is an intronless gene with a length of 3527 bp and encodes a peptide of 984 amino acids. The deduced protein possesses a signal peptide sequence, a leucine-rich repeat (LRR) domain composed of 16 LRR motifs, a transmembrane (TM) region and a Toll/interleukin-1 receptor (TIR) domain. Phylogenetic analysis grouped it with other teleost TLR21s. Quantitative real-time PCR (qPCR) analysis demonstrated the constitutive expression of SmTLR21 mRNA in all twelve examined tissues with higher levels in the lymphomyeloid-rich tissues like spleen and head kidney. Further, upon stimulation with polyinosinic: polycytidylic acid [poly(I:C)], turbot reddish body iridovirus (TRBIV) and CpG oligodeoxynucleotides (CpG-ODN) 2395, the SmTLR21 mRNA expression was up-regulated in the gills, head kidney, spleen and muscle. The maximum increases of SmTLR21 transcript levels ranged from 1.3 to 8.1-fold and appeared at 3 h to 5 day post-injection depending on different organs and stimuli. These findings suggest that SmTLR21 may play an important role in the immune responses to the infections of a broad range of pathogens that include RNA and DNA viruses and bacteria.


Innovation in Urology: Three Dimensional Printing and Its Clinical Application.
Three-dimensional (3D) printing allows rapid prototyping of novel equipment as well as the translation of medical imaging into tangible replicas of patient-specific anatomy. The technology has emerged as a versatile medium for innovation in medicine but with ever-expanding potential uses, does 3D printing represent a valuable adjunct to urological practice? We present a concise systematic review of articles on 3D printing within urology, outlining proposed benefits and the limitations in evidence supporting its utility. We review publications prior to December 2019 using guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Of 117 identified articles, 67 are included highlighting key areas of research as the use of patient-specific models for patient education, surgical planning, and surgical training. Further novel applications included printed surgical tools, patient-specific surgical guides, and bioprinting of graft tissues. We conclude to justify its adoption within standard practice, further research is required demonstrating that use of 3D printing can produce; direct and measurable improvements in patient experience, consistent evidence of superior surgical outcomes or simulation which surpasses existing means' both in fidelity and enhancement of surgical skills. Although exploration of 3D printing's urological applications remains nascent, the seemingly limitless scope for innovation and collaborative design afforded by the technology presents undeniable value as a resource and assures a place at the forefront of future advances.