Quality guidelines for endodontic treatment: consensus report of the European Society of Endodontology.
The assurance of the quality of a service rendered by a member of the dental profession is an essential feature of any system of peer review in dentistry. This document addresses two essential elements: (i) appropriateness of treatment modality and (ii) quality or level of treatment rendered. In revising these guidelines the European Society of Endodontology is responding to a public and professional need. In receiving care of a specialized nature such as endodontic treatment, patients need and deserve treatment that meets the standard of care generally given by competent practitioners. The European Society of Endodontology has the expertise and professional responsibility necessary to assist the dental profession by instituting guidelines on the standard of care in the special area of Endodontics. In accepting this responsibility the European Society of Endodontology formulated treatment guidelines that are intended to represent current good practice.


Effect of bombesin on basal and stimulated secretion of some pituitary hormones in humans.
The effect of bombesin (5 ng/kg/min X 2.5 h) on basal pituitary secretion as well as on the response to thyrotropin releasing hormone (TRH; 200 micrograms) plus luteinizing hormone releasing hormone (LHRH; 100 micrograms) was studied in healthy male volunteers. The peptide did not change the basal level of growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). On the contrary, the pituitary response to releasing hormones was modified by bombesin administration. When compared with control (saline) values, prolactin and TSH levels after TRH were lower during bombesin infusion, whereas LH and FSH levels after LHRH were higher. Thus bombesin affects in man, as in experimental animals, the secretion of some pituitary hormones.


Assessment of the preventive effects of Nd:YAG laser associated with fluoride on enamel caries using optical coherence tomography and FTIR spectroscopy.
This in vitro study characterized and monitored, by Optical Coherence Tomography (OCT) and Fourier Transformed Infrared Spectroscopy (FTIR), the effects of the association of acidulated phosphate fluoride gel (APF-gel) and Nd:YAG (neodymiun:yttrium-aluminum-garnet) laser, as sequencial treatments, in the prevention of incipient enamel caries lesions. 120 human enamel samples were randomized into 3 groups (n = 40): APF-gel (1.23% F-, 4 min.); Laser+APF (Nd:YAG laser irradiation-0.6W, 84.9J/cm2, 10Hz, followed by APF-gel); and APF+Laser (APF-gel followed by laser irradiation). The samples were subjected to a 15-day pH-cycling, evaluated by OCT (quantification of optical attenuation coefficient-OAC) and FTIR (analysis of carbonate and phosphate content) before treatments, after treatments, and on the 5th, 10th and 15th days of pH-cycling. The statistical analysis was performed (α = 5%). The Optical Attenuation Coefficient (OAC) assessed by OCT increases with the progression of demineralization, and the Laser+APF presented the highest values of OAC in 10th and 15th days of pH-cycling. Nd:YAG decreased the carbonate content after treatment regardless of the application order of the APF-gel, while APF-gel did not interfere in the composition of enamel. The carbonate content was also changed in the first 5 days of the pH-cycling in all groups. Nd:YAG laser irradiation before or after the application of APF-gel did not influence the appearance of incipient caries lesions, showing no synergistic effect. Regardless of the application order of the APF-gel, laser irradiation reduces the carbonate content of the enamel, which also changes during the demineralization process. However, irradiation before the application of APF-gel increased the speed of progression of the lesions, which positively impacts public health as it can prevent caries disease, even in high risk individuals. OCT and FTIR are suitable for assessing this effect.


Chronic subdural haematoma treated by craniotomy, durectomy, outer membranectomy and subgaleal suction drainage. Personal experience in 39 patients.
According to the CT and MRI appearances, 39 chronic subdural haematoma (CSDH) patients were suspected of having solid clots and/or a high likelihood of loculation. Craniotomy was planned from the start. Beside the better exposure, excision of the dura and outer membrane, assumed to be the source of haematoma fluid, this is an additional step to minimize the incidence of significant recollection. There were no additional operative or postoperative cranial and/or systemic complications when compared with other minor procedures. Two patients (5%) required once percutaneous tapping and aspiration. Accordingly, if a case is considered to be better managed with craniotomy, durectomy and outer membranectomy this is an easy and safe technique with minimal incidence of recollection, morbidity and mortality.


Effect of Glycocalyx on Drug Delivery Carriers Targeted to Endothelial Cells.
Animal models have shown that coupling ligands, targeted to endothelium surface receptors, with drug delivery carriers (DDC) can optimize the treatment of diseases by specific vascular delivery. The endothelium is exposed to hydrodynamic forces that modulate the expression of these cellular adhesion molecules (CAMs) and affect the structural and biological activity of endothelial cells (ECs). In order to investigate how delivery of targeted DDC can be optimized, we investigated carriers binding to flow adapted ECs under flow conditions. Comparison of live ECs to fixed cells from our previous experiments give insight into the effect of receptor motility on the cell surface as well as the effect of other factors such as glycocalyx (a protective layer of carbohydrates on the surface of cells) and actin remodeling. A flow chamber model is used to investigate how DDC size variation alters binding under flow conditions. Binding experiments were done with and without glycocalyx in order to elucidate its protective effect. Using fluorescence microscopy we determined the real time binding and rolling speeds of DDC under flow conditions. We also demonstrate the presence of glycocalyx and image actin filament remodeling. The binding of 1 µm carriers to ECs decreased after flow adaptation, in both non-activated and TNF-α activated ECs compared to non-flow adapted live cells. After removal of the glycocalyx by degrading enzymes binding increased in quiescent ECs, but only increased in activated cells after 2 hr of perfusion with particles. The binding with 100 nm carriers also decreased after flow adaptation but to a lesser extent and partially increased after enzyme degradation. These experiments give insight as to how tunable affinity parameters can be optimized to enhance therapeutic capabilities.


Evidence that carbon monoxide stimulates prostaglandin endoperoxide synthase activity in rat hypothalamic explants and in primary cultures of rat hypothalamic astrocytes.
Carbon monoxide (CO) shares with nitric oxide (NO) the ability to modulate the release of hypophysiotropic peptides from rat hypothalamic explants. While both gases are believed to act as neural messengers in the brain via the activation of soluble guanylyl cyclase, the latter is almost undetectable in the rat hypothalamus. NO has been shown to exert some of its biological actions through the modulation of prostaglandin endoperoxide synthase (PGHS) activity. We have, therefore, investigated whether CO also can use PGHS as a signaling pathway in the hypothalamus. Endogenous CO is produced in equimolar amounts with biliverdin (BV) by the catabolism of hemin through heme oxygenase (HO). Hemin, two inhibitors of HO, zinc-protoporphyrin-9 (ZnPP9) and tin-mesoporphyrin-9 (SnMP9), ferrous hemoglobin (Hb), indomethacin and dexamethasone (DEX) were used as pharmacological tools. Prostaglandin E2 (PGE2) released from rat hypothalamic explants or primary cultures of hypothalamic astrocytes was taken as a marker of PGHS activity. It was found that: (1) hemin evokes an increase in PGE2 release from hypothalamic explants; (2) this effect is counteracted by ZnPP9, SnMP9, Hb and indomethacin; (3) the metallo-porphyrins and indomethacin, but not Hb, are also able to inhibit basal PGE2 release from hypothalamic explants; and (4) dexamethasone does not inhibit, and even potentiates, the stimulatory effect of hemin on PGE2 release from hypothalamic astrocytes. The evidence presented here suggests that the catabolism of endogenous or exogenously added hemin is associated with an increase in PGE2 production in the rat hypothalamus. This effect can be attributed to the formation of CO, since the other end-product of HO, BV, does not enhance PGE2 release. Thus, at least some of the biological effects of CO at the hypothalamic level might be mediated by the activation of the PGHS pathway.


Use of Stem Cell Extracellular Vesicles as a "Holistic" Approach to CNS Repair.
Neurodegeneration is a hallmark of many diseases and disorders of the central nervous system (CNS). High levels of neuroinflammation are often associated with irreparable damage to CNS cells due to the dysregulation of signaling cascades that are unable to restore a homeostatic balance. Due to the inherent complexity of the CNS, development of CNS-related therapeutics has met limited success. While stem cell therapy has been evaluated in the context of CNS repair, the mechanisms responsible for their functional properties have not been clearly defined. In recent years, there has been growing interest in the use of stem cell extracellular vesicles (EVs) for the treatment of various CNS pathologies as these vesicles are believed to mediate many of the functional effects associated with their donor stem cells. The potency of stem cell EVs is believed to be largely driven by their biological cargo which includes various types of RNAs, proteins, and cytokines. In this review, we describe the characteristic properties of stem cell EVs and summarize their reported neuroprotective and immunomodulatory functions. A special emphasis is placed on the identification of specific biological cargo, including proteins and non-coding RNA molecules, that have been found to be associated with stem cell EVs. Collectively, this review highlights the potential of stem cell EVs as an alternative to traditional stem cell therapy for the repair of cellular damage associated with diverse CNS pathologies.


Comparison of extraperitoneal and transperitoneal pelvic lymph node dissection during minimally invasive radical prostatectomy.
Pelvic lymph node dissection (PLND) during radical prostatectomy (RP) has prognostic and possible therapeutic benefits. We assessed whether an extraperitoneal minimally invasive RP (MiRP) allows for standard-template PLND comparable to transperitoneal MiRP+PLND. A retrospective clinicopathologic study of 914 consecutive patients who underwent MiRP (laparoscopic or Da Vinci robot-assisted laparoscopic) with bilateral PLND by one surgeon (CPP) from 2001 to 2010 was performed. Low-risk patients generally received a limited dissection (external iliac nodes) when PLND was performed. Those with intermediate- and high-risk disease generally received a standard PLND (external iliac and obturator nodes). Patients were stratified into groups based on operative approach (extraperitoneal vs transperitoneal) for most analyses. Overall, 192 patients had transperitoneal MiRP+PLND, and 377 had extraperitoneal MiRP+PLND. The extraperitoneal group had higher body mass index (P=0.03), a higher percentage of low-risk (P=0.003), and a lower percentage of intermediate-risk disease (P=0.006). Lymph node yield (LNY) was higher with extraperitoneal PLND overall (6.5 vs 5.3, P=0.003). When stratified by risk category, LNY was greater in the extraperitoneal group for patients with low-risk disease only (6.6 vs 4.9, P=0.008). There was no difference in nodal yield in intermediate/high-risk patients receiving standard PLND by either the transperitoneal or extraperitoneal approach (6.0 vs 5.5, P=0.36 and 8.0 vs 5.8, P=0.14, respectively). Lymph node involvement was rare overall. Estimated blood loss and complication rates were comparable between operative approaches. The extraperitoneal MiRP approach does not compromise the oncologic efficacy or safety of routine PLND.


The ribosome receptors Mrx15 and Mba1 jointly organize cotranslational insertion and protein biogenesis in mitochondria.
Mitochondrial gene expression in Saccharomyces cerevisiae is responsible for the production of highly hydrophobic subunits of the oxidative phosphorylation system. Membrane insertion occurs cotranslationally on membrane-bound mitochondrial ribosomes. Here, by employing a systematic mass spectrometry-based approach, we discovered the previously uncharacterized membrane protein Mrx15 that interacts via a soluble C-terminal domain with the large ribosomal subunit. Mrx15 contacts mitochondrial translation products during their synthesis and plays, together with the ribosome receptor Mba1, an overlapping role in cotranslational protein insertion. Taken together, our data reveal how these ribosome receptors organize membrane protein biogenesis in mitochondria.


Development of Control Material for Exhaled Breath-Alcohol Testing and its Application.
Breath analyser tests are used worldwide to obtain proof of alcohol intoxication and often used in the conviction of traffic violators. These tests are conducted to quickly and painlessly determine the existing concentration of alcohol in arterial blood by measuring the amount of ethanol in exhaled breath, which can be identified with an electrochemical sensor.At present, the calibration and maintenance of analysers used for these tests are typically performed regularly but lack quality control. Consequently, test results may not be accurate because of calibration deterioration.The aim of this study was to develop and evaluate the uncertainty of control materials used in breath-alcohol testing at the Bangkok Metropolitan Police Station. Ethyl alcohol (99.99%; Certified Reference Material grade) diluted at three different concentrations was kept under design conditions. The concentrations were 28, 67, and 134 mg/dL, determined by performing headspace gas chromatography, and the uncertainty was set as ±1.3925, ±2.8736, and ±1.8231 mg/dL (±4.97%, ±4.29%, and ±2.72% for the concentrations, respectively), as per ISO Guide 35:2017. The total error percentages of the developed control materials were 4.97%, 4.29%, and 2.72% for concentrations of 28, 67, and 134 mg/dL, respectively. Each concentration of the materials was tested by using measurements from 70 breath-alcohol analysers belonging to the Bangkok Metropolitan Police Station. These control materials are applicable to quality assurance and standards tests and may help to ensure the accuracy of breath-alcohol testing in the future.


Managing Celiac Disease for Women: Implications for the Primary Care Provider.
Although many people have symptoms of celiac disease, it can take a while to diagnose. Villous atrophy may be present long before any gastrointestinal symptoms. An important point to acknowledge is that celiac disease could be identified earlier in some women with a positive family history. The disease also could be the cause of some women's reproductive problems. Primary care providers, using comprehensive history taking, are in the unique position to identify individuals who may have celiac disease, assist women in gaining knowledge about a gluten-free diet, order diagnostic testing, and refer to a gastroenterologist. The positive change in fertility with a simultaneous improvement of nutrient deficiencies shortly after adopting a gluten-free diet indicates a possible link between such nutrients and sex hormone function. High levels of homocysteine, which can negatively impact fertility, have also been linked to individuals with problems, such as celiac disease, that decrease vitamin B12 absorption. The purpose of this article is to review the literature and the evidence-based care guidelines for comprehensive screening, diagnostics, and pathophysiology of celiac disease, with a specific focus on the female reproductive system, anemia management, and gluten-free diet integration.


Antiestrogen Therapy Increases Plasticity and Cancer Stemness of Prolactin-Induced ERα+ Mammary Carcinomas.
Although antiestrogen therapies are successful in many patients with estrogen receptor alpha-positive (ERα+) breast cancer, 25% to 40% fail to respond. Although multiple mechanisms underlie evasion of these treatments, including tumor heterogeneity and drug-resistant cancer stem cells (CSC), further investigations have been limited by the paucity of preclinical ERα+ tumor models. Here, we examined a mouse model of prolactin-induced aggressive ERα+ breast cancer, which mimics the epidemiologic link between prolactin exposure and increased risk for metastatic ERα+ tumors. Like a subset of ERα+ patient cancers, the prolactin-induced adenocarcinomas contained two major tumor subpopulations that expressed markers of normal luminal and basal epithelial cells. CSC activity was distributed equally across these two tumor subpopulations. Treatment with the selective estrogen receptor downregulator (SERD), ICI 182,780 (ICI), did not slow tumor growth, but induced adaptive responses in CSC activity, increased markers of plasticity including target gene reporters of Wnt/Notch signaling and epithelial-mesenchymal transition, and increased double-positive (K8/K5) cells. In primary tumorsphere cultures, ICI stimulated CSC self-renewal and was able to overcome the dependence of self-renewal upon Wnt or Notch signaling individually, but not together. Our findings demonstrate that treatment of aggressive mixed lineage ERα+ breast cancers with a SERD does not inhibit growth, but rather evokes tumor cell plasticity and regenerative CSC activity, predicting likely negative impacts on patient tumors with these characteristics.Significance: This study suggests that treatment of a subset of ERα+ breast cancers with antiestrogen therapies may not only fail to slow growth but also promote aggressive behavior by evoking tumor cell plasticity and regenerative CSC activity. Cancer Res; 78(7); 1672-84. ©2018 AACR.


[Arrhythmias and conduction block in the newborns of mothers who had received long-term tocolytic therapy].
Serial electrocardiograms (ECGs) were studied prospectively in 48 newborns exposed in utero to prolonged tokolytic therapy to beta-sympathomimetics and in 30 newborns non-exposed in utero to beta-mimetics. Duration of exposure to tocolysis was at least 7 days, mean 51 +/- 36 days. The ECGs were made in 1-st and 3-rd day of life. The ECGs were estimated for duration the QT interval (as corrected QT-QTc) Cardiac event in 16 newborns from treated group and in 16 newborns from control group were examined in 1-st day of life on a Holter monitor. It was found that, the prolongation of QTc time, the ventricular extrasystole and the atrioventricular blocks second degree (Wenckenbach's period) were occurred more often in the newborns whose mother had taken beta-mimetic drugs then in the control group.


Collagen-PVA aligned nanofiber on collagen sponge as bi-layered scaffold for surface cartilage repair.
Researchers have made bi-layered scaffolds but mostly for osteochondral repairs. The anatomic structure of human cartilage has different zones and that each has varying matrix morphology and mechanical properties is often overlooked. Two bi-layered collagen-based composites were made to replicate the superficial and transitional zones of an articular cartilage. Aligned and random collagen-PVA nanofibers were electrospun onto a freeze-dried collagen sponge to make the aligned and random composites, respectively. The morphology, swelling ratio, degradation and tensile properties of the two composites were examined. Primary porcine chondrocytes were cultured on the composites for three weeks and their proliferation and secretion of glycosaminoglycan (GAG) and type II collagen were measured. The influences of the cell culture on the tensile properties of the composites were studied. The nanofiber layer remained adhered to the sponge after three weeks of cell culture. Both composites lost 30-35% of their total weight in a saline buffer after three weeks. The tensile strength and Young's modulus of both composites increased after three weeks of chondrocyte culture (p < 0.05). The aligned composite with extracellular matrix deposition had a Young's modulus (0.35 MPa) similar to that of articular cartilage reported in literature (0.36-0.8 MPa). The chondrocytes on both aligned and random composites proliferated and secreted similar amounts of GAG and type II collagen. They were seen embedded in lacunae after three weeks. The aligned composite may be more suitable for articular cartilage repair because of the higher tensile strength from the aligned nanofibers on the surface that can better resist wear.


Glycated Hemoglobin Value Combined with Initial Glucose Levels for Evaluating Mortality Risk in Patients with Ischemic Stroke.
Hyperglycemia is a marker of poor outcome in acute ischemic stroke (IS) patients. We aimed at evaluating the effect of combined HbA1c and first glucose measurement values on 3-month mortality prediction. In a prospective analysis, 1,317 first-ever IS patients with HbA1c values were classified by first glycemia value (<155, 155-199, ≥200 mg/dl). Three-month mortality was analyzed by glycemia category in nondiabetics, diabetics with good previous glucose control (PGC) (HbA1c <7%), and diabetics with poor PGC (HbA1c ≥7.0%). Mortality at 3 months was 13.1%, with no differences (p = 0.339) between non-diabetes mellitus (DM) (12.3%), good PGC-DM (12.4%), and poor PGC-DM (15.6%) patients. The unadjusted relative risk of 3-month mortality for patients with glucose ≥200 mg/dl was 3.76 (95% CI 1.48-9.56) in non-DM, 6.10 (95% CI 1.76-21.09) in good PGC-DM, and 1.44 (95% CI 0.77-2.69) in poor PGC-DM. Glycemia cutoffs most highly correlated with mortality increased as PGC declined: 107 mg/dl in non-DM, 152 mg/dl in good PGC-DM, and 229 mg/dl in poor PGC-DM patients. Glycemia correlated with stroke severity in nondiabetics and diabetic patients with good PGC, but not in those with poor PGC. HbA1c determination combined with first measured glucose value is useful to stratify mortality risk in IS patients: hyperglycemia is a poor prognostic marker in non-DM and DM patients with good PGC; results are inconsistent in poor PGC-DM patients. Our data suggest the relationship between hyperglycemia and poor outcome reflects stress response rather than a deleterious effect of glucose.


Association of Calcaneal Bone Marrow Lesions and Plantar Fascia Imaging Biomarkers With Chronic Plantar Heel Pain: A Case-Control Study.
To determine associations between chronic plantar heel pain (CPHP) and imaging biomarkers derived from magnetic resonance imaging (MRI) and ultrasonography. We compared 218 participants with CPHP with 100 age- and sex-matched population controls. We assessed imaging biomarkers on MRI (calcaneal bone marrow lesions [BMLs], plantar fascia [PF] signal and thickness, spurs, and fat pad signal) and B-mode/power Doppler ultrasound (PF thickness, echogenicity, and vascularity). Covariate data collected included demographic characteristics, disease history, clinical measures, and physical activity by accelerometry. Data were analyzed using multivariable conditional logistic regression. Plantar calcaneal BML size (mm2 , odds ratio [OR] 1.03 [95% confidence interval (95% CI) 1.02-1.05]), larger plantar spurs (OR for spurs >5 mm 2.15 [95% CI 1.13-4.10]), PF signal (OR for signal penetrating >50% of the dorsoplantar width 12.12 [95% CI 5.36-27.42]), PF thickness (mm, OR for MRI 3.23 [95% CI 2.36-4.43] and ultrasound OR 3.78 [95% CI 2.69-5.32]), and echogenicity (diffusely hypoechoic OR 7.89 [95% CI 4.02-15.48] and focally hypoechoic OR 24.92 [95% CI 9.60-64.69]) were independently associated with CPHP. PF vascularity was uncommon, occurring exclusively in cases (cases with signal n = 47 [22%]). Combining imaging biomarkers into 1 model, plantar BMLs and PF imaging biomarkers, but not fat pad signal or heel spurs, were independently associated with CPHP. Calcaneal BMLs and PF imaging biomarkers are associated with CPHP. Further research is required to understand whether these different markers represent distinct phenotypes of heel pain, and if so, whether there are specific treatment implications.


Reversible topological organization within a polytopic membrane protein is governed by a change in membrane phospholipid composition.
Once inserted, transmembrane segments of polytopic membrane proteins are generally considered stably oriented due to the large free energy barrier to topological reorientation of adjacent extramembrane domains. However, the topology and function of the polytopic membrane protein lactose permease of Escherichia coli are dependent on the membrane phospholipid composition, revealing topological dynamics of transmembrane domains after stable membrane insertion (Bogdanov, M., Heacock, P. N., and Dowhan, W. (2002) EMBO J. 21, 2107-2116). In this study, we show that the high affinity phenylalanine permease PheP shares many similarities with lactose permease. PheP assembled in a mutant of E. coli lacking phosphatidylethanolamine (PE) exhibited significantly reduced active transport function and a complete inversion in topological orientation of the N terminus and adjoining transmembrane hairpin loop compared with PheP in a PE-containing strain. Introduction of PE following the assembly of PheP triggered a reorientation of the N terminus and adjacent hairpin to their native orientation associated with regain of wild-type transport function. The reversible orientation of these secondary transport proteins in response to a change in phospholipid composition might be a result of inherent conformational flexibility necessary for transport function or during protein assembly.


Cu(I)-mediated reductive amination of boronic acids with nitroso aromatics.
[reaction: see text] A mild method for the reductive amination of aryl boronic acids with nitroso aromatic compounds is reported. This C-N bond formation is mediated by a stoichiometric amount of CuCl as both a catalyst and a reducing agent. Alternatively, 10% Cu(I)-3-methylsalicylate (CuMeSal) catalyzes the same reaction in the presence of either ascorbic acid or hydroquinone as the terminal reducing agent. Diarylamines bearing a variety of functional groups can be obtained in good yields.


Unexpectedly large enhancement of a severely constricted field with reversed Galilean telescopes.
A 25-year-old female presented with severely constricted visual fields secondary to stroke associated with mitral valve prolapse. Repeatably measured central fields of less than 4 degrees diameter showed an unexpected enlargement up to 20 to 40 degrees diameter, when fitted with reversed full field 1.3x and 1.7x Galilean telescopes. Although initial tests indicated no psychogenic component, fields of approximately 20 degrees diameter were eventually obtained through an imitation telescope made with 2 plano lenses. This technique may be useful in determining whether there is a psychogenic component to inexplicable field results in other patients.


Transmutation of human glutathione transferase A2-2 with peroxidase activity into an efficient steroid isomerase.
A major goal in protein engineering is the tailor-making of enzymes for specified chemical reactions. Successful attempts have frequently been based on directed molecular evolution involving libraries of random mutants in which variants with desired properties were identified. For the engineering of enzymes with novel functions, it would be of great value if the necessary changes of the active site could be predicted and implemented. Such attempts based on the comparison of similar structures with different substrate selectivities have previously met with limited success. However, the present work shows that the knowledge-based redesign restricted to substrate-binding residues in human glutathione transferase A2-2 can introduce high steroid double-bond isomerase activity into the enzyme originally characterized by glutathione peroxidase activity. Both the catalytic center activity (k(cat)) and catalytic efficiency (k(cat)/K(m)) match the values of the naturally evolved glutathione transferase A3-3, the most active steroid isomerase known in human tissues. The substrate selectivity of the mutated glutathione transferase was changed 7000-fold by five point mutations. This example demonstrates the functional plasticity of the glutathione transferase scaffold as well as the potential of rational active-site directed mutagenesis as a complement to DNA shuffling and other stochastic methods for the redesign of proteins with novel functions.


Synthesis of a Liquid Lignin-Based Methacrylate Resin and Its Application in 3D Printing without Any Reactive Diluents.
3D printing of bio-based and renewable polymers such as lignin has gained research attention during the last few decades. We report on the synthesis and characterization of a liquid lignin-based photopolymer and its application in additive manufacturing (AM). Wheat straw soda lignin is liquified in an oxyalkylation reaction with propylene oxide under alkaline conditions and modified with methacryloyl chloride to obtain a lignin-based methacrylate resin. Ninety percent of the functional hydroxyl groups are grafted during the synthesis. The photopolymerization efficiency was evaluated by real-time-NIR-photorheology experiments with two different photoinitiators, leading to double bond conversions (DBC) of ≥80%. 3D-printing experiments of the methacrylated lignin were performed with the hot lithography technology. For the first time, a light-curable lignin derivative with a lignin content of over 30% was successfully 3D printed via vat photopolymerization without any reactive diluents, which is a significant improvement over current state-of-the-art solutions. This outstanding result is a motivating proof of concept and a promising starting point for the in-depth evaluation of bio-based precursors as an alternative to nonrenewable derivatives for 3D printing.


Beer classification by means of a potentiometric electronic tongue.
In this work, an electronic tongue (ET) system based on an array of potentiometric ion-selective electrodes (ISEs) for the discrimination of different commercial beer types is presented. The array was formed by 21 ISEs combining both cationic and anionic sensors with others with generic response. For this purpose beer samples were analyzed with the ET without any pretreatment rather than the smooth agitation of the samples with a magnetic stirrer in order to reduce the foaming of samples, which could interfere into the measurements. Then, the obtained responses were evaluated using two different pattern recognition methods, principal component analysis (PCA), which allowed identifying some initial patterns, and linear discriminant analysis (LDA) in order to achieve the correct recognition of sample varieties (81.9% accuracy). In the case of LDA, a stepwise inclusion method for variable selection based on Mahalanobis distance criteria was used to select the most discriminating variables. In this respect, the results showed that the use of supervised pattern recognition methods such as LDA is a good alternative for the resolution of complex identification situations. In addition, in order to show an ET quantitative application, beer alcohol content was predicted from the array data employing an artificial neural network model (root mean square error for testing subset was 0.131 abv).


A Triaxial Applicator for the Measurement of the Electromagnetic Properties of Materials.
The design, analysis, and fabrication of a prototype triaxial applicator is described. The applicator provides both reflected and transmitted signals that can be used to characterize the electromagnetic properties of materials in situ. A method for calibrating the probe is outlined and validated using simulated data. Fabrication of the probe is discussed, and measured data for typical absorbing materials and for the probe situated in air are presented. The simulations and measurements suggest that the probe should be useful for measuring the properties of common radar absorbing materials under usual in situ conditions.


Lipoprotein-associated phospholipase A2, C-reactive protein, and coronary artery disease in individuals with type 1 diabetes and macroalbuminuria.
Given the paucity of data in type 1 diabetes concerning lipoprotein-associated phospholipase A( 2) (Lp-PLA(2)), we examined its prospective relationship with coronary artery disease (CAD), as well as the effect of modification by C-reactive protein (CRP) and haptoglobin genotype, in individuals with type 1 diabetes who are at an increased risk for CAD due to also having macroalbuminuria (n=96). Although Lp-PLA(2) activity was univariately predictive of CAD (HR=1.54 per SD, p=0.009), this relationship was not significant after covariate adjustment (p=0.59). There was a significant interaction between Lp-PLA(2) and CRP (p=0.02), i.e. those with both markers greater than the median level were more likely to have a CAD event than those persons with low levels of both (HR=2.89, p=0.06). When stratified by haptoglobin genotype, Lp-PLA(2) was predictive of CAD in persons with the 2/1 (HR=2.40, p=0.05), but not 2/2 (HR=0.66, p=0.27), genotype. The association between Lp-PLA(2) activity and CAD differs by CRP and haptoglobin genotype in this group of persons with type 1 diabetes and macroalbuminuria.


[Levels of alpha 1-antitrypsin in the blood of patients with chronic bronchitis].
Serum levels of alpha 1-antitrypsin were studied in 80 patients with chronic bronchitis. As a manifestation of the inflammatory response, nonsignificant increase was recorded compared to the group of healthy subjects. In discordance with literary data, no significant differences were found between bronchitics smokers and non-smokers. In 5 patients (6.2%), alpha 1-antitrypsin serum levels were below the lower limit of the reference range. The patients complained of cough, expectoration, and dyspnea. As a preventive measure, it is recommended to determine serum alpha 1-antitrypsin levels in smokers before they take up a job in a dusty environment and in bronchitics before inhalation treatment with proteolytic enzymes is administered. In alpha 1-antitrypsin deficit the value of substitution therapy in patients with emphysema is being emphasized.


Expression and phylogenetic analyses of the Gel/Gas proteins of Tuber melanosporum provide insights into the function and evolution of glucan remodeling enzymes in fungi.
The β(1,3)-glucanosyltransferases of the GH72 family are redundant enzymes that are essential for the formation and dynamic remodeling of the fungal wall during different stages of the life cycle. Four putative genes encoding glycosylphosphatidylinositol (GPI)-anchored β(1,3)-glucanosyltransferases, designated TmelGEL1, TmelGEL2, TmelGEL4 and TmelGAS4, have been annotated in the genome of Tuber melanosporum, an ectomycorrhizal fungus that also produces a hypogeous fruiting body (FB) of great commercial value (black truffle). This work focuses on the characterization and expression of this multigene family by taking advantage of a laser microdissection (LMD) technology that has been used to separate two distinct compartments in the FB, the hyphae and the asci containing the ascospores. Of the four genes, TmelGEL1 was the most up-regulated in the FB compared to the free-living mycelium. Inside the FB, the expression of TmelGEL1 was restricted to the hyphal compartment. A phylogenetic analysis of the Gel/Gas protein family of T. melanosporum was also carried out. A total of 237 GH72 proteins from 51 Ascomycotina and 3 Basidiomycota (outgroup) species were analyzed. The resulting tree provides insight into the evolution of the T. melanosporum proteins and identifies new GH72 paralogs/subfamilies. Moreover, it represents a starting point to formulate new hypotheses on the significance of the striking GH72 gene redundancy in fungal biology.


Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils.
Short chain fatty acids (SCFAs) are fermentation products of anaerobic bacteria. More than just being an important energy source for intestinal epithelial cells, these compounds are modulators of leukocyte function and potential targets for the development of new drugs. The aim of this study was to evaluate the effects of SCFAs (acetate, propionate and butyrate) on production of nitric oxide (NO) and proinflammatory cytokines [tumor necrosis factor α (TNF-α) and cytokine-induced neutrophil chemoattractant-2 (CINC-2αβ)] by rat neutrophils. The involvement of nuclear factor κB (NF-κB) and histone deacetylase (HDAC) was examined. The effect of butyrate was also investigated in vivo after oral administration of tributyrin (a pro-drug of butyrate). Propionate and butyrate diminished TNF-α, CINC-2αβ and NO production by LPS-stimulated neutrophils. We also observed that these fatty acids inhibit HDAC activity and NF-κB activation, which might be involved in the attenuation of the LPS response. Products of cyclooxygenase and 5-lipoxygenase are not involved in the effects of SCFAs as indicated by the results obtained with the inhibitors of these enzymes. The recruitment of neutrophils to the peritonium after intraperitoneal administration of a glycogen solution (1%) and the ex vivo production of cytokines and NO by neutrophils were attenuated in rats that previously received tributyrin. These results argue that this triglyceride may be effective in the treatment of inflammatory conditions.


Participative style of management in a family planning program.
In 1973, a small-scale project to involve family planning staff in program management was introduced in the Sangam primary health center in Andhra Pradesh by the Adminstrative Staff College of India, Hyderabad. Through group meetings, involving all levels of health center personnel, problem areas were identified and analysed and solutions sought. On the basis of recommendations made by the groups, a work plan was drawn up. Monthly review meetings were held to discuss progress in implementing the plan. The project was found to have a positive effect on staff morale and commitment, and program acceptance levels increased. In light of the success of the project at Sangam, a proposal has been submitted to the government to expand the project to other primary health centers in the district.


A Hopfield neural network for image change detection.
This paper outlines an optimization relaxation approach based on the analog Hopfield neural network (HNN) for solving the image change detection problem between two images. A difference image is obtained by subtracting pixel by pixel both images. The network topology is built so that each pixel in the difference image is a node in the network. Each node is characterized by its state, which determines if a pixel has changed. An energy function is derived, so that the network converges to stable states. The analog Hopfield's model allows each node to take on analog state values. Unlike most widely used approaches, where binary labels (changed/unchanged) are assigned to each pixel, the analog property provides the strength of the change. The main contribution of this paper is reflected in the customization of the analog Hopfield neural network to derive an automatic image change detection approach. When a pixel is being processed, some existing image change detection procedures consider only interpixel relations on its neighborhood. The main drawback of such approaches is the labeling of this pixel as changed or unchanged according to the information supplied by its neighbors, where its own information is ignored. The Hopfield model overcomes this drawback and for each pixel allows a tradeoff between the influence of its neighborhood and its own criterion. This is mapped under the energy function to be minimized. The performance of the proposed method is illustrated by comparative analysis against some existing image change detection methods.


Drug Development for Metastasis Prevention.
Metastatic disease is responsible for 90% of death from solid tumors. However, only a minority of metastasis-specific targets has been exploited therapeutically, and effective prevention and suppression of metastatic disease is still an elusive goal. In this review, we will first summarize the current state of knowledge about the molecular features of the disease, with particular focus on steps and targets potentially amenable to therapeutic intervention. We will then discuss the reasons underlying the paucity of metastatic drugs in the current oncological arsenal and potential ways to overcome this therapeutic gap. We reason that the discovery of novel promising targets, an increased understanding of the molecular features of the disease, the effect of disruptive technologies, and a shift in the current preclinical and clinical settings have the potential to create more successful drug development endeavors.


Independent Low-Rank Matrix Analysis-Based Automatic Artifact Reduction Technique Applied to Three BCI Paradigms.
Electroencephalogram (EEG)-based brain-computer interfaces (BCIs) can potentially enable people to non-invasively and directly communicate with others using brain activities. Artifacts generated from body activities (e.g., eyeblinks and teeth clenches) often contaminate EEGs and make EEG-based classification/identification hard. Although independent component analysis (ICA) is the gold-standard technique for attenuating the effects of such contamination, the estimated independent components are still mixed with artifactual and neuronal information because ICA relies only on the independence assumption. The same problem occurs when using independent vector analysis (IVA), an extended ICA method. To solve this problem, we designed an independent low-rank matrix analysis (ILRMA)-based automatic artifact reduction technique that clearly models sources from observations under the independence assumption and a low-rank nature in the frequency domain. For automatic artifact reduction, we combined the signal separation technique with an independent component classifier for EEGs named ICLabel. To assess the comparative efficiency of the proposed method, the discriminabilities of artifact-reduced EEGs using ICA, IVA, and ILRMA were determined using an open-access EEG dataset named OpenBMI, which contains EEG data obtained through three BCI paradigms [motor-imagery (MI), event-related potential (ERP), and steady-state visual evoked potential (SSVEP)]. BCI performances were obtained using these three paradigms after applying artifact reduction techniques, and the results suggested that our proposed method has the potential to achieve higher discriminability than ICA and IVA for BCIs. In addition, artifact reduction using the ILRMA approach clearly improved (by over 70%) the averaged BCI performances using artifact-reduced data sufficiently for most needs of the BCI community. The extension of ICA families to supervised separation that leaves the discriminative ability would further improve the usability of BCIs for real-life environments in which artifacts frequently contaminate EEGs.


Some remarks on the occurrence, host-specificity and validity of Myxobolus rotundus Nemeczek, 1911 (Myxozoa: Myxosporea).
Myxobolus rotundus Nemeczek, 1911 is a common and specific parasite of the common bream Abramis brama (L.). Small, round or ellipsoidal shaped plasmodia of this species develop in the gill and exhibit strong histotropism to the secondary gill lamellae with plasmodial development in their capillary network. M. rotundus is frequently found in mixed infection with M. bramae Reuss, 1906, a parasite of the afferent arteries of gill filaments. The round spores of M. rotundus resemble several other Myxobolus spp., but can be distinguished from these by their small subunit ribosomal RNA gene sequence (GenBank accession no. EU710583), which also differs from the sequence for 'M. rotundus' from the skin of Chinese goldfish Carassius auratus auratus (L.), which we suggest has been misidentified. The SSU rRNA gene sequence of M. rotundus myxospores from bream corresponded to Triactinomyxon type 4 actinospores (AY495707) isolated from Tubifex tubifex (Müller) by Hallett et al. (2005), and we infer from this that these are alternate life stages.


A high-resolution imaging x-ray crystal spectrometer for high energy density plasmas.
Adapting a concept developed for magnetic confinement fusion experiments, an imaging crystal spectrometer has been designed and tested for HED plasmas. The instrument uses a spherically bent quartz [211] crystal with radius of curvature of 490.8 mm. The instrument was tested at the Titan laser at Lawrence Livermore National Laboratory by irradiating titanium slabs with laser intensities of 10(19)-10(20) W/cm(2). He-like and Li-like Ti lines were recorded, from which the spectrometer performance was evaluated. This spectrometer provides very high spectral resolving power (E/dE > 7000) while acquiring a one-dimensional image of the source.


Water-soluble phenolic compounds produced from extractive ammonia pretreatment exerted binary inhibitory effects on yeast fermentation using synthetic hydrolysate.
Biochemical conversion of lignocellulosic biomass to liquid fuels requires pretreatment and enzymatic hydrolysis of the biomass to produce fermentable sugars. Degradation products produced during thermochemical pretreatment, however, inhibit the microbes with regard to both ethanol yield and cell growth. In this work, we used synthetic hydrolysates (SynH) to study the inhibition of yeast fermentation by water-soluble components (WSC) isolated from lignin streams obtained after extractive ammonia pretreatment (EA). We found that SynH with 20g/L WSC mimics real hydrolysate in cell growth, sugar consumption and ethanol production. However, a long lag phase was observed in the first 48 h of fermentation of SynH, which is not observed during fermentation with the crude extraction mixture. Ethyl acetate extraction was conducted to separate phenolic compounds from other water-soluble components. These phenolic compounds play a key inhibitory role during ethanol fermentation. The most abundant compounds were identified by Liquid Chromatography followed by Mass Spectrometry (LC-MS) and Gas Chromatography followed by Mass Spectrometry (GC-MS), including coumaroyl amide, feruloyl amide and coumaroyl glycerol. Chemical genomics profiling was employed to fingerprint the gene deletion response of yeast to different groups of inhibitors in WSC and AFEX-Pretreated Corn Stover Hydrolysate (ACSH). The sensitive/resistant genes cluster patterns for different fermentation media revealed their similarities and differences with regard to degradation compounds.


Thrombin Generation Decrease After LMWH Administration in an Antithrombin-Deficient Pregnant Woman With a Homozygous HBS II Mutation.
The cases of antithrombin (AT)-deficient pregnant women with a homozygous HBS II mutation are relatively rare and are accompanied by an increased thrombophilic risk, which is manifested by increased thrombin generation (TG). It is very difficult to ensure their prophylactic treatment during pregnancy. We aimed to determine the utility of the thrombin generation assay (TGA) and anti-factor Xa (anti-FXa) test to monitor the effects of a prophylactic dose of low-molecular-weight heparin (LMWH) in a 28-year-old woman with homozygous AT deficiency caused by mutation c.391C > T#, (p.Leu131Phe†) in the SERPINC1 gene and to compare the findings with those from a group of pregnant and non-pregnant women also treated with LMWH. TG monitoring was chosen due to severe AT deficiency that was manifested by low levels of anti-FXa activity when monitoring the efficacy of LMWH treatment. A significant decrease in TG was detected in all monitored groups (P < .05). There were no thrombotic complications during the whole pregnancy of the woman with AT deficiency. Consistent monitoring of TG with LMWH anticoagulant therapy administration during pregnancy together with AT administration before and after delivery may improve the overall condition of pregnant women and the quality of their care.


Reciprocal Trophic Interactions and Transmission of Blood Parasites between Mosquitoes and Frogs.
The relationship between mosquitoes and their amphibian hosts is a unique, reciprocal trophic interaction. Instead of a one-way, predator-prey relationship, there is a cyclical dance of avoidance and attraction. This has prompted spatial and temporal synchrony between organisms, reflected in emergence time of mosquitoes in the spring and choice of habitat for oviposition. Frog-feeding mosquitoes also possess different sensory apparatuses than do their mammal-feeding counterparts. The reciprocal nature of this relationship is exploited by various blood parasites that use mechanical, salivary or trophic transmission to pass from mosquitoes to frogs. It is important to investigate the involvement of mosquitoes, frogs and parasites in this interaction in order to understand the consequences of anthropogenic actions, such as implementing biocontrol efforts against mosquitoes, and to determine potential causes of the global decline of amphibian species.


Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head.
To measure quantitatively changes in lamina cribrosa (LC) cell and connective tissue structure in human glaucoma eyes. We studied 27 glaucoma and 19 age-matched non-glaucoma postmortem eyes. In 25 eyes, LC cross-sections were examined by confocal and multiphoton microscopy to quantify structures identified by anti-glial fibrillary acidic protein (GFAP), phalloidin-labeled F-actin, nuclear 4',6-diamidino-2-phenylindole (DAPI), and by second harmonic generation imaging of LC beams. Additional light and transmission electron microscopy were performed in 21 eyes to confirm features of LC remodeling, including immunolabeling by anti-SOX9 and anti-collagen IV. All glaucoma eyes had detailed clinical histories of open-angle glaucoma status, and degree of axon loss was quantified in retrolaminar optic nerve cross-sections. Within LC pores, the proportionate area of both GFAP and F-actin processes was significantly lower in glaucoma eyes than in controls (P = 0.01). Nuclei were rounder (lower median aspect ratio) in glaucoma specimens (P = 0.02). In models assessing degree of glaucoma damage, F-actin process width was significantly wider in glaucoma eyes with more damage (P = 0.024), average LC beam width decreased with worse glaucoma damage (P = 0.042), and nuclear count per square millimeter rose with worse damage (P = 0.019). The greater cell count in LC pores represented 92.3% astrocytes by SOX9 labeling. The results are consistent with replacement of axons in LC pores by basement membrane labeled by anti-collagen IV and in-migrating astrocytes. Alteration in LC structure in glaucoma involves migration of astrocytes into axonal bundles, change in astrocyte orientation and processes, production of basement membrane material, and thinning of connective tissue beams.


Bedazzled: A Blue and Black Ship, Dressed to Deceive.
The blue and black dress that "melted the Internet" is thought to have done so because its perceived color depended on people using different prior assumptions about discounting the illuminant. However, this is not the first monochromatic object to have confused the public. For a brief period during WWI, RMS Mauretania was dressed in (dazzle) camouflage shades of blue and black/grey, yet she is sometimes depicted by artists, modelers, and historians in a much showier dress of red, blue, yellow, green, and black. I raise the possibility that this originates from a case of public deception deriving from the momentary misperception of a playful artist who neglected to discount the illuminant, propagating the most (perhaps only) successful application of dazzle camouflage known.


Modification of Insect and Arachnid Behaviours by Vertically Transmitted Endosymbionts: Infections as Drivers of Behavioural Change and Evolutionary Novelty.
Vertically acquired, endosymbiotic bacteria such as those belonging to the Rickettsiales and the Mollicutes are known to influence the biology of their arthropod hosts in order to favour their own transmission. In this study we investigate the influence of such reproductive parasites on the behavior of their insects and arachnid hosts. We find that changes in host behavior that are associated with endosymbiont infections are not restricted to characteristics that are directly associated with reproduction. Other behavioural traits, such as those involved in intraspecific competition or in dispersal may also be affected. Such behavioural shifts are expected to influence the level of intraspecific variation and the rate at which adaptation can occur through their effects on effective population size and gene flow amongst populations. Symbionts may thus influence both levels of polymorphism within species and the rate at which diversification can occur.


Systematic review: Radiological and histological evidence of cochlear implant insertion trauma in adult patients.
Cochlear implantation (CI) has developed from its origins in the 1980s. Initially, CI was for profound bilateral hearing impairment. However, candidacy for CI have become more widespread in recent years with unilateral implantation and an emphasis on hearing preservation. Evidence supports full electrode insertion in an atraumatic fashion into the scala tympani (ST) provides optimal hearing outcomes. The main aim of this systematic review was to elucidate the degree of trauma associated with CI insertion. A systematic literature search was undertaken using PubMed Medline. A grading system described by Eshraghi was used to classify cochlear trauma. Both radiological and histological studies were included. Twenty one papers were identified which were relevant to our search. In total, 653 implants were inserted and 115 (17.6%) showed evidence of trauma. The cochleas with trauma had basilar membrane elevation in 5.2%, ruptured in 5.2%, the electrode passed from the ST to the SV in 84.4% and there was grade 4 trauma in 5.2%. The studies used a variety of histological and radiological methods to assess for evidence of trauma in both cadaveric temporal bones and live recipients. Minimizing cochlear trauma during implant insertion is important to preserve residual hearing and optimize audiological performance. An overall 17.6% trauma rate suggests that CI insertion could be improved with more accurate and consistent electrode insertion such as in the form of robotic guidance. The correlation of cochlea trauma with post-operative hearing has yet to be determined.


Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments.
Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the β4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.hCD46 lung function was consistently observed in association with either hEPCR (n = 15), hTBM (n = 4), or hEPCR.hTFPI (n = 11), but the loss of vascular barrier function in the xenograft and systemic inflammation in the recipient typically occurred within 24 h. Co-expression of hEPCR and hTBM (n = 11) and additionally blocking multiple pro-inflammatory innate and adaptive immune mechanisms was more consistently associated with survival >1 day, with one recipient surviving for 31 days. Combining targeted genetic modifications to the lung xenograft with selective innate and adaptive immune suppression enables prolonged initial life-supporting lung function and extends lung xenograft recipient survival, and illustrates residual barriers and candidate treatment strategies that may enable the clinical application of other organ xenografts.


Campus community gardens and student health: A case study of a campus garden and student well-being.
Objective The purpose of this study was to explore the relationship between working at a campus community garden and student volunteers' wellbeing. Participants: 76 undergraduate students at a large urban university in the San Francisco Bay area. Methods: A Web-based survey was conducted. Using an email mailing list of current and former garden volunteers, the study questionnaire was sent to survey participants multiple times to promote higher response rate. Results: Bootstrap regression revealed that both connectedness to nature and general health were significant predictors of a general well-being variable. Conclusions: University leaders might consider that campus natural spaces contribute to student success and may be among the few opportunities that urban college students have to engage with nature.


Label-free high-resolution 3-D imaging of gold nanoparticles inside live cells using optical diffraction tomography.
Delivery of gold nanoparticles (GNPs) into live cells has high potentials, ranging from molecular-specific imaging, photodiagnostics, to photothermal therapy. However, studying the long-term dynamics of cells with GNPs using conventional fluorescence techniques suffers from phototoxicity and photobleaching. Here, we present a method for 3-D imaging of GNPs inside live cells exploiting refractive index (RI) as imaging contrast. Employing optical diffraction tomography, 3-D RI tomograms of live cells with GNPs are precisely measured for an extended period with sub-micrometer resolution. The locations and contents of GNPs in live cells are precisely addressed and quantified due to their distinctly high RI values, which was validated by confocal fluorescence imaging of fluorescent dye conjugated GNPs. In addition, we perform quantitative imaging analysis including the segmentations of GNPs in the cytosol, the volume distributions of aggregated GNPs, and the temporal evolution of GNPs contents in HeLa and 4T1 cells.


Aryl hydrocarbon receptor activation inhibits regenerative growth.
There is considerable literature supporting the conclusion that inappropriate activation of the aryl hydrocarbon receptor (AHR) alters cellular signaling. We have established previously that fin regeneration is specifically inhibited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in adult zebrafish and have used this in vivo endpoint to evaluate interactions between AHR and growth-controlling pathways. Because there are experimental limitations in studying regeneration in adult animals, we have developed a larval model to evaluate the effect of AHR activation on tissue regeneration. Two-day-old zebrafish regenerate their amputated caudal fins within 3 days. Here, we demonstrate that TCDD specifically blocks regenerative growth in larvae. The AHR pathway in zebrafish is considerably more complex than in mammals, with at least three zebrafish AHR genes (zfAHR1a, zfAHR1b, and zfAHR2) and two ARNT genes (zfARNT1 and zfARNT2). Although it was presumed that the block in regeneration was mediated by AHR activation, it had not been experimentally demonstrated. Using antisense morpholinos and mutant fish lines, we report that zfAHR2 and zfARNT1 are the in vivo dimerization partners that are required for inhibition of regeneration by TCDD. Several pathways including fibroblast growth factor (FGF) signaling are essential for fin regeneration. Even though impaired FGF signaling and TCDD exposure both inhibit fin regeneration, their morphometric response is distinct, suggesting that the mechanisms of impairment are different. With the plethora of molecular and genetic techniques that can be applied to larval-stage embryos, this in vivo regeneration system can be further exploited to understand cross-talk between AHR and other signaling pathways.


Mobility of US Rural Primary Care Physicians During 2000-2014.
Despite considerable investment in increasing the number of primary care physicians in rural shortage areas, little is known about their movement rates and factors influencing their mobility. We aimed to characterize geographic mobility among rural primary care physicians, and to identify location and individual factors that influence such mobility. Using data from the American Medical Association Physician Masterfile for each clinically active US physician, we created seven 2-year (biennial) mobility periods during 2000-2014. These periods were merged with county-level "rurality," physician supply, economic characteristics, key demographic measures, and individual physician characteristics. We computed (1) mobility rates of physicians by rurality; (2) linear regression models of county-level rural nonretention (departure); and (3) logit models of physicians leaving rural practice. Biennial turnover was about 17% among physicians aged 45 and younger, compared with 9% among physicians aged 46 to 65, with little difference between rural and metropolitan groups. County-level physician mobility was higher for counties that lacked a hospital (absolute increase = 5.7%), had a smaller population size, and had lower primary care physician supply, but area-level economic and demographic factors had little impact. Female physicians (odds ratios = 1.24 and 1.46 for those aged 45 or younger and those aged 46 to 65, respectively) and physicians born in a metropolitan area (odds ratios = 1.75 and 1.56 for those aged 45 or younger and those aged 46 to 65, respectively) were more likely to leave rural practice. These flndings provide national-level evidence of rural physician mobility rates and factors associated with both county-level retention and individual-level departures. Outcomes were notably poorer in the most remote locations and those already having poorer physician supply and professional support. Rural health workforce planners and policymakers must be cognizant of these key factors to more effectively target retention policies and to take into account the additional support needed by these more vulnerable communities.


Generative Adversarial Network for Medical Images (MI-GAN).
Deep learning algorithms produces state-of-the-art results for different machine learning and computer vision tasks. To perform well on a given task, these algorithms require large dataset for training. However, deep learning algorithms lack generalization and suffer from over-fitting whenever trained on small dataset, especially when one is dealing with medical images. For supervised image analysis in medical imaging, having image data along with their corresponding annotated ground-truths is costly as well as time consuming since annotations of the data is done by medical experts manually. In this paper, we propose a new Generative Adversarial Network for Medical Imaging (MI-GAN). The MI-GAN generates synthetic medical images and their segmented masks, which can then be used for the application of supervised analysis of medical images. Particularly, we present MI-GAN for synthesis of retinal images. The proposed method generates precise segmented images better than the existing techniques. The proposed model achieves a dice coefficient of 0.837 on STARE dataset and 0.832 on DRIVE dataset which is state-of-the-art performance on both the datasets.


Photoimmunosuppression: a brief overview.
Exposure to ultraviolet radiation can lead to suppression of many adaptive immune responses, both to antigens encountered within a short period of the irradiation (primary) and to antigens previously encountered (memory). The pathways involved are complex and not completely elucidated. This brief review summarizes the information available currently regarding the multiple steps involved, with the aim of providing a general overview of the main aspects of photoimmunosuppression and its clinical consequences.


Impact of the spectral and spatial properties of natural light on indoor gas-phase chemistry: Experimental and modeling study.
The characteristics of indoor light (intensity, spectral, spatial distribution) originating from outdoors have been studied using experimental and modeling tools. They are influenced by many parameters such as building location, meteorological conditions, and the type of window. They have a direct impact on indoor air quality through a change in chemical processes by varying the photolysis rates of indoor pollutants. Transmittances of different windows have been measured and exhibit different wavelength cutoffs, thus influencing the potential of different species to be photolysed. The spectral distribution of light entering indoors through the windows was measured under different conditions and was found to be weakly dependent on the time of day for indirect cloudy, direct sunshine, partly cloudy conditions contrary to the light intensity, in agreement with calculations of the transmittance as a function of the zenithal angle and the calculated outdoor spectral distribution. The same conclusion can be drawn concerning the position within the room. The impact of these light characteristics on the indoor chemistry has been studied using the INCA-Indoor model by considering the variation in the photolysis rates of key indoor species. Depending on the conditions, photolysis processes can lead to a significant production of radicals and secondary species.


Use of an intraoperative sodium oxychlorosene-based infection prevention protocol to safely decrease postoperative wound infections after spine surgery.
Postoperative infection remains prevalent after spinal surgical procedures. Institutional protocols for infection prevention have improved rates of infection after spine surgery. However, prior studies have focused on only elective surgical patients. The aim of this study was to determine the efficacy of a multiinstitutional intraoperative sodium oxychlorosene-based infection prevention protocol for decreasing rate of infection after instrumented spinal surgery. A retrospective analysis was performed at two tertiary care institutions with level I trauma programs, and patients who underwent posterior instrumented spinal fusion between January 1, 2011, and May 31, 2019, were included. Postoperative deep wound infection rates were captured before and after implementation of a multiinstitutional infection prevention protocol. Possible adverse outcomes related to infection prevention techniques were also examined. In addition, consecutive patients treated from January 1, 2018, to May 31, 2019, were prospectively included in a database to collect preoperative and postoperative spine-specific quality of life measures and to assess the impact of postoperative infection on quality of life. A total of 5047 patients fit the inclusion criteria. Of these, 1043 patients underwent surgery prior to protocol implementation. The infection rate of this cohort (3.5%) decreased significantly after protocol implementation (1.2%, p < 0.001). Postoperative sterile seroma rates did not differ between the preprotocol and postprotocol groups (0.7% vs 0.7%, p = 0.5). In the 1031 patients who underwent surgery between January 2018 and May 2019, the fusion rate was 89.2%. Quality of life outcomes between patients with infection and those without infection were similar, although statistical power was limited owing to the low rate of infection. Notably, 2 of 10 patients who developed deep wound infection died of infection-related complications. An intraoperative sodium oxychlorosene-based infection prevention protocol helped to significantly decrease the rate of infection after spine surgery without negatively impacting other postoperative procedure-related metrics. Postoperative wound infection may be associated with higher-than-expected rate of postoperative mortality.


Negative regulation of bone morphogenetic protein/Smad signaling by Cas-interacting zinc finger protein in osteoblasts.
Bone morphogenetic protein (BMP) signaling regulates body axis determination, apoptosis, and differentiation of various types of cells including neuron, gut, and bone cells. However, the molecules involved in such BMP regulation of biological events have not been fully understood. Here, we examined the involvement of Cas-interacting zinc finger protein (CIZ) in the modulation of BMP2-induced osteoblastic cell differentiation. CIZ overexpression in osteoblastic MC3T3E1 cells suppressed BMP2-enhanced expression of alkaline phosphatase, osteocalcin, and type I collagen genes. Upstream analyses revealed that CIZ overexpression also suppressed BMP2-induced enhancement of the mRNA expression of Cbfa1, which is a critical transcription factor for osteoblastic differentiation. BMP-induced Smad1 and Smad5 activation of GCCG-mediated transcription was blocked in the presence of CIZ overexpression. CIZ overexpression alone in the absence of BMP2 moderately enhanced basal levels of Cbfa1 mRNA expression. CIZ overexpression also enhanced 1.8-kb Cbfa1 promoter activity in the absence of BMP2, whereas it suppressed the promoter activity in the presence of BMP2. Finally, CIZ overexpression suppressed the formation of mineralized nodules in osteoblastic cell cultures. These data indicate that CIZ is a novel type inhibitor of BMP/Smad signaling.


Two-dimensional radial laser scanning for circular marker detection and external mobile robot tracking.
This paper presents the use of an external fixed two-dimensional laser scanner to detect cylindrical targets attached to moving devices, such as a mobile robot. This proposal is based on the detection of circular markers in the raw data provided by the laser scanner by applying an algorithm for outlier avoidance and a least-squares circular fitting. Some experiments have been developed to empirically validate the proposal with different cylindrical targets in order to estimate the location and tracking errors achieved, which are generally less than 20 mm in the area covered by the laser sensor. As a result of the validation experiments, several error maps have been obtained in order to give an estimate of the uncertainty of any location computed. This proposal has been validated with a medium-sized mobile robot with an attached cylindrical target (diameter 200 mm). The trajectory of the mobile robot was estimated with an average location error of less than 15 mm, and the real location error in each individual circular fitting was similar to the error estimated with the obtained error maps. The radial area covered in this validation experiment was up to 10 m, a value that depends on the radius of the cylindrical target and the radial density of the distance range points provided by the laser scanner but this area can be increased by combining the information of additional external laser scanners.


Biomechanical analysis of articular-sided partial-thickness rotator cuff tear and repair.
Articular-sided partial-thickness rotator cuff tears are common injuries in throwing athletes. The superior shoulder capsule beneath the supraspinatus and infraspinatus tendons works as a stabilizer of the glenohumeral joint. To assess the effect of articular-sided partial-thickness rotator cuff tear and repair on shoulder biomechanics. The hypothesis was that shoulder laxity might be changed because of superior capsular plication in transtendon repair of articular-sided partial-thickness rotator cuff tears. Controlled laboratory study. Nine fresh-frozen cadaveric shoulders were tested by using a custom shoulder-testing system at the simulated late-cocking phase and acceleration phase of throwing motion. Maximum glenohumeral external rotation angle, anterior translation, position of the humeral head apex with respect to the glenoid, internal impingement area, and glenohumeral and subacromial contact pressures were measured. Each specimen underwent 3 stages of testing: stage 1, with the intact shoulder; stage 2, after creation of articular-sided partial-thickness tears of the supraspinatus and infraspinatus tendons; and stage 3, after transtendon repair of the torn tendons by using 2 suture anchors. Articular-sided partial-thickness tears did not significantly change any of the shoulder biomechanical measurements. In the simulated late-cocking phase, transtendon rotator cuff repair resulted in decreased maximum external rotation angle by 4.2° (P = .03), posterior shift of the humeral head (1.1-mm shift; P = .02), decreased glenohumeral contact pressure by 1.7 MPa (56%; P = .004), and decreased internal impingement area by 26.4 mm(2) (65%; P < .001) compared with values in the torn shoulder. In the acceleration phase, the humeral head shifted inferiorly (1.2-mm shift; P = .03 vs torn shoulder), and glenohumeral anterior translation (1.5-mm decrease; P = .03 vs torn shoulder) and subacromial contact pressure (32% decrease; P = .004 vs intact shoulder) decreased significantly after transtendon repair. Transtendon repair of articular-sided partial-thickness supraspinatus and infraspinatus tears decreased glenohumeral and subacromial contact pressures at time zero; these changes might lead to reduced secondary subacromial and internal impingements and consequently progression to full-thickness rotator cuff tear. However, repair of the tendons decreased anterior translation and external rotation and changed the positional relationship between the humeral head and the glenoid. Careful attention should be paid to shoulder laxity and range of motion when transtendon repair is chosen to treat articular-sided partial-thickness rotator cuff tears, specifically in throwing athletes.


Stereoselective synthesis of 2-deoxy-furanosides from 2,3-anhydro-furanosyl thioglycosides.
The stereocontrolled synthesis of 2-thiotolyl-furanosides from 2,3-anhydro-furanosyl thioglycosides through a rearrangement-glycosylation process is reported. The efficiency of this reaction is high, providing 70-95% yields of the products. Treatment of the resulting 2-deoxy-2-thiotolyl-glycosides with hydrogen and Raney nickel affords the corresponding 2-deoxy-furanosides with a 1,3-syn relationship.


Multiple twinning in cubic crystals: geometric/algebraic study and its application for the identification of the Sigma3(n) grain boundaries.
Multiple twinning in cubic crystals is represented geometrically by a three-dimensional fractal and algebraically by a groupoid. In this groupoid, the variant crystals are the objects, the misorientations between the variants are the operations, and the Sigma3(n) operators are the different types of operations (expressed by sets of equivalent operations). A general formula gives the number of variants and the number of Sigma3(n) operators for any twinning order. Different substructures of this groupoid (free group, semigroup) can be equivalently introduced to encode the operations with strings. For any coding substructure, the operators are expressed by sets of equivalent strings. The composition of two operators is determined without any matrix calculation by string concatenations. It is multivalued due to the groupoid structure. The composition table of the operators is used to identify the Sigma3(n) grain boundaries and to reconstruct the twin related domains in the electron back-scattered diffraction maps.


Reversal learning deficits in criminal offenders: Effects of psychopathy, substance use, and childhood maltreatment history.
Deficits in reinforcement learning are presumed to underlie the impulsive and incorrigible behavior exhibited by psychopathic criminals. However, previous studies documenting reversal learning impairments in psychopathic individuals have not investigated this relationship across a continuous range of psychopathy severity, nor have they examined how reversal learning impairments relate to different psychopathic traits, such as the interpersonal-affective and lifestyle-antisocial dimensions. Furthermore, previous studies have not considered the role that childhood maltreatment and substance use may have in this specific cognitive deficit. Using a standard reversal learning task in a sample of N = 114 incarcerated male offenders, we demonstrate a significant relationship between psychopathy severity and reversal learning errors. Furthermore, we show a significant interaction between psychopathy and childhood maltreatment, but not substance use, such that individuals high in psychopathy with an extensive history of maltreatment committed the greatest number of reversal learning errors. These findings extend the current understanding of reversal learning performance among psychopathic individuals, and highlight the importance of considering childhood maltreatment when studying psychopathy.


Adrenal scintigraphy in Cushing's syndrome caused by bilateral hyperplasia, adenoma or carcinoma.
The results of scintigraphy in 29 patients with Cushing's syndrome were evaluated. It was possible to separate bilateral hyperplasia from unilateral abnormality. In cases of unilateral abnormality correct localization of the tumour was accomplished and it was possible to visualize adrenocortical carcinoma. The many advantages of adrenal scintigraphy are listed and it is concluded that adrenal scintigraphy is the best means of investigation to differentiate between ACTH-dependent and ACTH-independent Cushing's syndrome.


Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling.
POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation (ChIP) assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks.


Clinical and Radiographic Success of Electrosurgical Pulpectomy in Primary Teeth.
A pulpectomy requires the swift extraction of the inflamed tissue. Moreover, the speed of treatment is especially important in the case of uncooperative children. Conventional pulpectomies, however, often require an extended treatment period, which can therefore cause problems with such patients. Electrosurgical methods have been applied to pulpotomies for a number of years. However, to the best of our knowledge, no studies to date have assessed its application to pulpectomies. The aim of this study was to compare clinical and radiographic success rates over a 6-month follow-up period between conventional and electrosurgical pulpectomies. A total of 50 children aged 4 to 8 years were enrolled in this randomized clinical trial. A pulpectomy of the first and second primary molar teeth was seen as the optimal treatment plan in all these patients. One group was treated using the conventional method (C group, 25 teeth) and the other with electrosurgery (ES group, 25 teeth). The patients were evaluated for the presence of pain, mobility, abscess, sinus tract, erythema, tenderness to percussion, internal and external root resorption, and radiolucency. Clinical and radiographic success rates and total working time were assessed. The Fisher's exact test and Mann-Whitney U-test were used for the statistical analysis. After 6 months of follow-up, the clinical and radiographic success rates were 90.5 and 85.7%, respectively, in the ES group, compared with 88.9 and 72.2%, respectively, in the C group. No statistically significant difference was observed between the two groups (p>0.05). Working time, however, was significantly shorter in the ES group (p<0.001). This suggests that pulpectomy with electrosurgery reduces treatment time, and is therefore quite useful in situations where duration of the treatment course is of crucial concern.


Outcomes in necrotizing soft tissue infections treated with therapeutic plasma exchange.
Treatment of necrotizing soft tissue infections (NSTIs) includes prompt surgical debridement and antibiotics, but despite standard care, the morbidity and mortality remain high. Since therapeutic plasma exchange (TPE) has been considered for treatment of severe sepsis, this study evaluates the efficacy of TPE for patients with NSTI. This is a retrospective study of patients with diagnosis of NSTI who received treatment with and without TPE over an 11-year period. The primary outcome was in-hospital mortality. Fifty-two patients with NSTI treated with TPE (TPE group) and 125 patients with NSTI not treated with TPE (non-TPE group) were assessed. Nineteen (36.5%) patients died in the TPE group, and 35 (28%) patients died in the non-TPE group. Within the TPE group, there was significant improvement in white blood cell (WBC) count and sodium levels 7 days after TPE treatment, but no improvement in creatinine. Inverse probability weighting based on propensity scores was used to compare survival in the TPE and non-TPE groups and demonstrated that TPE was associated with an increased odds of death (odds ratio, 2.8). A second analysis matched for six variables yielded 31 pairs and demonstrated no significant difference in mortality or length of stay. This study describes the largest series of patients with NSTIs treated with TPE and showed no evidence of clinical benefit. Further carefully designed studies with meaningful clinical endpoints would prove useful in assessing reproducibility and determining if there is a role for TPE in other forms of severe sepsis.


Clinical pharmacy cardiac risk service for managing patients with coronary artery disease in a health maintenance organization.
A clinical pharmacy service for managing the treatment of coronary artery disease in a health maintenance organization is described. Despite the proven benefits of aggressive risk factor modification for patients with coronary artery disease (CAD), there remains a treatment gap between consensus- and evidence-based recommendations and their application in patient care. In 1998, Kaiser Permanente of Colorado developed the Clinical Pharmacy Cardiac Risk Service (CPCRS) to focus on the long-term management of patients with CAD to improve clinical outcomes. The primary goals of the CPCRS are to increase the number of CAD patients on lipid-lowering therapy, manage medications shown to decrease the risk of future CAD-related events, assist in the monitoring and control of other diseases that increase cardiovascular risk, provide patient education and recommendations for nonpharmacologic therapy, and act as a CAD information resource for physicians and other health care providers. Using an electronic medical record and tracking database, the service works in close collaboration with primary care physicians, cardiologists, cardiac rehabilitation nurses, and other health care providers to reduce cardiac risk in the CAD population. Particular attention is given to dyslipidemia, blood pressure, diabetes mellitus, and tobacco cessation. Treatment with evidence-based regimens is initiated and adjusted as necessary. Over 11,000 patients are currently being followed by the CPCRS. A clinical pharmacy service in a large health maintenance organization provides cardiac risk reduction for patients with CAD and helps close treatment gaps that may exist for these patients.


Effect of increasing proportion of supplemental nitrogen from urea on intake and utilization of low-quality, tallgrass-prairie forage by beef steers.
Five Angus x Hereford steers with ruminal and duodenal fistulas were used in a 5 x 5 Latin square to determine effects of increasing the proportion of urea in supplemental degradable intake protein (DIP) on intake, fermentation, and digestion. Steers had ad libitum access to low-quality, tallgrass-prairie forage (2.4% CP, 76% NDF). Supplemental DIP (380 g/d) was from sodium caseinate and(or) urea and was balanced with cornstarch to provide a final supplement (approximately 939 g DM/d) that contained 40% CP. The percentages of supplemental DIP from urea were 0, 25, 50, 75, and 100%. Intake of forage OM was not affected (P > or = .30) by urea level. Ruminal and total tract digestibilities of OM and NDF generally responded in a quadratic manner (P < or = .09) to increasing urea, with the lowest values observed at the highest urea level. As a result, digestible OM intake (DOMI) declined (linear, P = .03) with increasing proportions of urea and tended (quadratic, P = .14) to exhibit the largest proportional decline at the highest urea level. The effects of increasing urea on duodenal N flow, microbial efficiency, ruminal contents, and fluid dilution rate were minimal. Ruminal ammonia N and molar percent acetate increased linearly (P < or = .02), whereas most other VFA (except propionate) decreased (P < or = .05) with increasing urea. In conclusion, although forage OM intake was not altered, OM digestion, NDF digestion, and DOMI were lowest when all supplemental DIP was supplied as urea. Changes in fermentation characteristics reflected the change in source of available nitrogen.


What have we learned from collaborative partnerships to concomitantly improve both education and health?
Collaborative partnerships are an essential means to concomitantly improve both education outcomes and health outcomes among K-12 students. We describe examples of contemporaneous, interactive, and evolving partnerships that have been implemented, respectively, by a national governmental health organization, national nongovernmental education and health organizations, a state governmental education organization, and a local nongovernmental health organization that serves partner schools. Each of these partnerships strategically built operational infrastructures that enabled partners to efficiently combine their resources to improve student education and health. To implement a Whole School, Whole Community, Whole Child Framework, we need to purposefully strengthen, expand, and interconnect national, state, and local collaborative partnerships and supporting infrastructures that concomitantly can improve both education and health.


Deep-RACE: Comprehensive Search for Novel ncRNAs Associated to a Specific Locus.
Deep-RACE (or RACEseq) is a recently described method (Olivarius et al. BioTechniques 46(2):130-132, 2009) that applies next-generation sequencing to the Rapid Amplification of cDNA End (RACE) protocol to define the 5' and 3' ends of RNA transcripts. Conventional mapping of 5' and 3' ends is achieved by manually cloning the PCR product of RACE followed by Sanger sequencing; this process can become costly and time-consuming when investigating multiple transcripts. High-throughput sequencing of the RACE products streamlines this process by eliminating the need to manually cut bands from an agarose gel and to clone each product individually. Importantly, in addition to these advantages, next-generation sequencing can detect low abundance fragments that would be difficult to extract from gel and clone for Sanger sequencing. For these reasons, Deep-RACE is an ideal protocol for the comprehensive study of noncoding transcripts from both intergenic regions of the genome and from within the loci of protein coding genes.


Efficient expression system for human antithrombin III in baby hamster kidney cells.
A DNA fragment carrying the enhancer of an immediate early gene of human cytomegalovirus (hCMV) was tested as a transcriptional control element by fusion downstream of a transcription unit for human antithrombin III (AT III) driven by the Simian virus (SV40) enhancer and promoter. Measurement of transient AT III expression in baby hamster kidney cells (BHK) shows that by the presence of the hCMV enhancer the synthesis of AT III is increased considerably (three to fourfold). The AT III expression vectors carrying the hCMV enhancer were used to establish stable BHK cell-lines by a new and fast G418/methotrexate selection protocol, which express up to 12 micrograms AT III/10(6) cells/24h after 40-50 days. The given system might be generally useful for the fast expression of recombinant proteins in mammalian cells, e.g. the screening of altered AT III molecules obtained by site directed mutagenesis.


Traditional mental health practitioners in Kwara State, Nigeria.
To assess the knowledge, practice and attitude of traditional mental health practitioners (TMHPs) in four Local Government Areas (LGAs) in Kwara State, Nigeria, on mental health care; to organise training sessions aimed at improving their knowledge base, practice and; to evaluate such training after allowing for a period of practice. STUDY DESIGN/INTERVENTION: Pre-training evaluation phase: TMHPs were assessed in the area of knowledge, attitude and practice of mental health, with the use of a questionnaire. They were then trained in the concepts of normality and abnormality, types of mental illness, treatment of mental illness including follow up, after-care, relapse prevention, other primary preventive measures, and some introductory talks on some sub-specialties of psychiatry, for example, child psychiatry, old age psychiatry, forensic psychiatry, drug and alcohol abuse and; after a free-practice period of two months, the TMHPs were again reassessed for the impact of the training. Pre-intervention phase: TMHPs could easily recognise most symptoms of mental illness except undue sadness. The TMHPs also expressed strong belief in the supernatural factor as a cause of mental illness. Some of them beat their patients for therapeutic reasons and; Post-intervention phase: there was a widening of the sense of recognition of TMHPs of important mental symptoms such as undue sadness, social withdrawal and elation. There was a better understanding of the aetiological concepts of mental illness. There was also a reduction in the habit of beating their patients as a form of treatment. The use of information, education and communication intervention techniques could lead to more positive and less hazardous forms of practice among TMHPs and; The high level of cooperation achieved in this study would indicate a bright chance for future collaborative activities between orthodox and traditional healthcare providers.


Transgenic strategy for demonstrating nuclear reprogramming in the mouse.
Totipotency can be restored to the nuclei of somatic cells by reprogramming the nucleus via the technique of nuclear transfer. As genes expressed in somatic cells differ from those expressed in early embryos, a change in gene expression must accompany nuclear reprogramming. In this study, nuclear reprogramming of somatic cell nuclei following nuclear transfer (NT) was demonstrated by the reactivation of developmentally regulated lacZ reporter genes. NT embryos were generated by direct injection of adult cumulus cell nuclei into mature mouse oocytes from which maternal chromosomes were subsequently removed. Cumulus cells were collected from transgenic mice which show developmentally regulated lacZ reporter gene expression as a result of integration and functional coupling of reporter gene expression with the endogenous Oct4 or COB54 genes. As both genes are transcriptionally silent in somatic cells but are expressed during early embryonic development, reactivation of reporter gene expression in cumulus cell-derived NT embryos was assessed as a means of monitoring nuclear reprogramming. The pattern of X-gal staining observed in individual NT embryos derived from both transgenic lines revealed that coordination of reactivation appeared to be specific for each gene, and that the timing of expression was consistent with that seen in control non-manipulated transgenic embryos. However, the staining in some NT embryos appeared to be diminished or absent. This reduction in staining may indicate a failure to reprogram gene expression in these embryos. Similar transgenic strategies employing lacZ vital stains, or alter-native reporters such as GFP, may facilitate real-time monitoring of reprogramming and a potential selection strategy to increase cloning efficiency through the identification and selection of reprogrammed, preimplantation stage NT embryos prior to embryo transfer.


Outcome of induction of labour in nulliparous women following replacement of Cervidil with Prostin.
This study at the Logan Hospital, Australia, compared the outcome of induction of labour (IOL) in nulliparous women following replacement of Cervidil with Prostin. Eighty-two nulliparous women were identified for this retrospective cohort study over a period of three months on either side of the changed practice. Forty-four women received Prostin and 38 received Cervidil. Baseline characteristics were similar amongst the groups including maternal age, mean gestational age, and modified Bishop's score at the commencement of IOL. The incidence of amniotomy, oxytocin augmentation of labour, and rate of epidural use did not differ significantly between the groups. The mean time to delivery (vaginally or abdominally) showed a significant difference, with women receiving Prostin delivering earlier than those having Cervidil (P = 0.018). Women receiving Prostin were more likely to have assisted vaginal delivery compared to the Cervidil group (P = 0.04).


OUTCOMES OF POSTERIOR SAGITTAL ANORECTOPLASTY FOR HIGH ANORECTAL MALFORMATION IN BENIN CITY, NIGERIA.
Surgical treatment for high anorectal malformations has evolved over the years with introduction of posterior sagittal anorectoplasty in the early 80s. Posterior sagittal anorectoplasty is being perfomed in many centres which necessitates a review of its outcomes in Benin City, Nigeria. To report a 10-year outcome and experience gained with posterior saggital anorectoplasty for children diagnosed with high anorectal malformation. A retrospective analyses of the records of all children with high anorectal malformation and managed with posterior sagittal anorectoplasty between April 2006 and March 2016 at the University of Benin Teaching Hospital. A total of 96 children were managed for anorectal malformation during the period. High anorectal malformation accounted for 33 (34.4%) cases, the intermediate 15 (15.6%) and the low types were 48 (50%). The 33 radiologically confirmed high type were19 males and 14 females with a male/female ratio of 1.3: 1. They were aged between 2 days and 4 years with a mean of 6.8 ± 3 months. A child each had additional prune belly syndrome, multiple limbs anomalies and unilateral undescended testis. Recto-bladder neck/recto-prostatic and recto-vaginal fistulae were recorded in 31 (94%) children. Five (15%) clinically stable neonates had primary posterior sagittal anorectoplasty without colostomy which was well tolerated. The majority, 28 (85%), had conventional posterior sagittal anorectoplasty that involves initial colostomy. Minor postoperative morbidities recorded in 10 (30.3%) children included superficial wound infection in 3 (9%), anal stenosis in 3 (9%) and fecal incontinence in 2 (6%) children which resolved on conservative treatment while 2 (6%) with rectal mucosal prolapse required refashioning. The functional clinical anal outcomes of posterior sagittal anorectoplasty recorded showed that the majority 18 (54.5%) of children were continent while 4 (12.1%) had voluntary bowel controls corresponding with their ages. Anal stenosis in the 3 and incontinence in the 2 children were the common anal dysfunctions recorded. The child with prune belly syndrome had breakdown of colostomy closure which resulted in the one (3%) death recorded. Anorectal malformation was common in this setting during this study with a large proportion of the children diagnosed with the high type and were managed with good outcome using posterior sagittal anorectoplasty.


Contributions of the anterolateral complex and the anterolateral ligament to rotatory knee stability in the setting of ACL Injury: a roundtable discussion.
Persistent rotatory knee laxity is increasingly recognized as a common finding after anterior cruciate ligament (ACL) reconstruction. While the reasons behind rotator knee laxity are multifactorial, the impact of the anterolateral knee structures is significant. As such, substantial focus has been directed toward better understanding these structures, including their anatomy, biomechanics, in vivo function, injury patterns, and the ideal procedures with which to address any rotatory knee laxity that results from damage to these structures. However, the complexity of lateral knee anatomy, varying dissection techniques, differing specimen preparation methods, inconsistent sectioning techniques in biomechanical studies, and confusing terminology have led to discrepancies in published studies on the topic. Furthermore, anatomical and functional descriptions have varied widely. As such, we have assembled a panel of expert surgeons and scientists to discuss the roles of the anterolateral structures in rotatory knee laxity, the healing potential of these structures, the most appropriate procedures to address rotatory knee laxity, and the indications for these procedures. In this round table discussion, KSSTA Editor-in-Chief Professor Jón Karlsson poses a variety of relevant and timely questions, and experts from around the world provide answers based on their personal experiences, scientific study, and interpretations of the literature. Level of evidence V.