Bacterial Leaf Infiltration Assay for Fine Characterization of Plant Defense Responses using the Arabidopsis thaliana-Pseudomonas syringae Pathosystem.
In the absence of specialized mobile immune cells, plants utilize their localized programmed cell death and Systemic Acquired Resistance to defend themselves against pathogen attack. The contribution of a specific Arabidopsis gene to the overall plant immune response can be specifically and quantitatively assessed by assaying the pathogen growth within the infected tissue. For over three decades, the hemibiotrophic bacterium Pseudomonas syringae pv. maculicola ES4326 (Psm ES4326) has been widely applied as the model pathogen to investigate the molecular mechanisms underlying the Arabidopsis immune response. To deliver pathogens into the leaf tissue, multiple inoculation methods have been established, e.g., syringe infiltration, dip inoculation, spray, vacuum infiltration, and flood inoculation. The following protocol describes an optimized syringe infiltration method to deliver virulent Psm ES4326 into leaves of adult soil-grown Arabidopsis plants and accurately screen for enhanced disease susceptibility (EDS) towards this pathogen. In addition, this protocol can be supplemented with multiple pre-treatments to further dissect specific immune defects within different layers of plant defense, including Salicylic Acid (SA)-Triggered Immunity (STI) and MAMP-Triggered Immunity (MTI).


Recent Developments in the Design of New Water-Soluble Boron Dipyrromethenes and Their Applications: An Updated Review.
Boron-dipyrromethene (BODIPY) and its derivatives play an important role in the area of organic fluorophore chemistry. Recently, the water-soluble boron-dipyrromethene dyes have increasingly received interest. The structural modification of the BODIPY core by incorporating different neutral and ionic hydrophilic groups makes it water-soluble. The important hydrophilic groups, such as quaternary ammonium, sulfonate, oligoethylene glycol, dicarboxylic acid, and sugar moieties significantly increase the solubility of these dyes in water while preserving their photophysical properties. As a result, these fluorescent dyes are utilized in aqueous systems for applications such as chemosensors, cell imaging, anticancer, biolabeling, biomedicine, metal ion detection, and photodynamic treatment. This review covers the most current developments in the design and synthesis of water-soluble BODIPY derivatives and their wide applications since 2014.


Blood collection procedures in hematology: knowledge and practice among laboratory personnel.
Blood collection is an important preanalytical component of haematological testing. This questionnaire based study was conducted on laboratory personnel to elicit their knowledge and practice regarding blood collection procedures for haematological testing. Questionnaire comprised of 37 multiple choice questions, of which 10 questions each were related to essential and desirable knowledge, 10 to practice and 7 to educational and job profile. Ninety four laboratory personnel participated in the study. Analysis was done on SPSS software. Percentages of unsatisfactory scores were 42.6%, 4.3%, 17% and 6% in the essential knowledge, desirable knowledge, practice and total scoring respectively. 91.5%, however, had a satisfactory total score. Importance needs to be given to blood collection procedures both, individually and collectively. The study highlights the deficient areas which need to addressed by all laboratorians. Such studies should also be conducted among nursing and resident staff- the other groups concerned with blood collection.


Reconstitution of the liver microsomal monooxygenase system in liposomes from dimyristoylphosphatidylcholine.
Different techniques to incorporate the essential isolated and purified enzymes of the hepatic endoplasmic reticulum into monolamellar dimyristoylphosphatidylcholine vesicles are compared with respect to structural and functional parameters of the reconstituted system. By use of gel penetrating chromatography on Sepharose 4B, dynamic light scattering and electron microscopy the structural properties of the reconstituted system were proved comparing the reduction of P-450 LM2 via the NADPH dependent reductase and by dithionite as well with the microsomal reduction rates and by studying the binding of benzphetamine to P-450 LM2 in soluble and liposomal form.


Behavioral and neuropathological characterization over the adult lifespan of the human tau knock-in mouse.
Tau is a microtubule-associated protein with a diverse functional repertoire linked to neurodegenerative disease. Recently, a human tau knock-in (MAPT KI) mouse was developed that may overcome many limitations associated with current animal models used to study tau. In MAPT KI mice, the entire murine Mapt gene was replaced with the human MAPT gene under control of the endogenous Mapt promoter. This model represents an ideal in vivo platform to study the function and dysfunction of human tau protein. Accordingly, a detailed understanding of the effects MAPT KI has on structure and function of the CNS is warranted. Here, we provide a detailed behavioral and neuropathological assessment of MAPT KI mice. We compared MAPT KI to wild-type (WT) C57BL/6j mice in behavioral assessments of anxiety, attention, working memory, spatial memory, and motor performance from 6 to 24 months (m) of age. Using immunohistological and biochemical assays, we quantified markers of glia (microglia, astrocytes and oligodendrocytes), synaptic integrity, neuronal integrity and the cytoskeleton. Finally, we quantified levels of total tau, tau isoforms, tau phosphorylation, and tau conformations. MAPT KI mice show normal cognitive and locomotor behavior at all ages, and resilience to mild age-associated locomotor deficits observed in WT mice. Markers of neuronal and synaptic integrity are unchanged in MAPT KI mice with advancing age. Glial markers are largely unchanged in MAPT KI mice, but glial fibrillary acidic protein is increased in the hippocampus of WT and MAPT KI mice at 24 m. MAPT KI mice express all 6 human tau isoforms and levels of tau remain stable throughout adulthood. Hippocampal tau in MAPT KI and WT mice is phosphorylated at serine 396/404 (PHF1) and murine tau in WT animals displays more PHF1 phosphorylation at 6 and 12 m. Lastly, we extended previous reports showing that MAPT KI mice do not display overt pathology. No evidence of other tau phosphorylation residues (AT8, pS422) or abnormal conformations (TNT2 or TOC1) associated with pathogenic tau were detected. The lack of overt pathological changes in MAPT KI mice make this an ideal platform for future investigations into the function and dysfunction of tau protein in vivo.


Prevalence of low automated platelet counts in cats: comparison with prevalence of thrombocytopenia based on blood smear estimation.
True thrombocytopenia is uncommon in cats; however, low platelet counts frequently are found using automated cell counters. Although this discrepancy is a well known problem, the prevalence of low automated platelet counts in feline blood samples has not been documented. We retrospectively compared the prevalence of low automated platelet counts with low blood smear-estimated platelet counts in feline blood samples. Results of blood sample analysis from 359 cats during a 1-year period at the University of Glasgow Veterinary Haematology Laboratory were examined. Smear estimates of platelet number were done in those cases in which records did not indicate adequate platelet numbers. Platelet counts obtained with an impedance counter (Minos Vet, Abx Hematologie) were <200X10(9) cells/L in 256 samples (71%) and <50X10(9) cells/L in 43 samples (12%). However, based on estimation of platelet numbers from blood smears, only 11 samples (3.1%) had platelet counts of <200X10(9) cells/L and 9 samples (2.5%) had counts of <50X10(9) cells/L. Four cats with thrombocytopenia estimated by blood smear evaluation had clinical signs of a bleeding disorder. Disorders associated with thrombocytopenia included neoplasia, cytotoxic chemotherapy, and infectious diseases. There was no evidence that delay due to mailing of samples was associated with lower automated platelet counts than would have been obtained on the day of sampling. The high prevalence of apparent thrombocytopenia in automated platelet counts was attributed to a combination of platelet aggregation and the impedance method of cell differentiation by size. Vigilance and careful examination of blood smears is required to identify the few cats with true thrombocytopenia.


Regional anesthesia for the management of limb injuries in space.
Traumatic injuries continue to present a threat to the success of current and future spaceflight missions. The magnitude of this threat will grow as the frequency of extravehicular activities is increased and missions venture beyond low Earth orbit and further away from terrestrial medical support. The capability to render definitive treatment to crewmembers who suffer a serious traumatic injury while in space is relatively limited at present. While some research has focused on the development of specific surgical techniques for the microgravity environment, little attention has been given to how one might practically provide anesthetic care for injured crewmembers expected to undergo these procedures. While many logistical and practical obstacles exist to the provision of general anesthesia in microgravity, regional anesthesia could be used to overcome many of these problems. A regional anesthetic capability for spaceflight missions could be developed with minimal modifications to existing terrestrial techniques and would provide the ability to manage a wide range of potential injuries while in orbit. The capability to provide reliable regional anesthesia could be further augmented and improved using a range of imaging technologies currently in development; it is expected that these devices would have a range of terrestrial applications, including the ability to provide immediate, safe, and reliable anesthetic care to patients in remote locations, or under austere conditions such as the combat environment.


Higher antiviral response of RIG-I through enhancing RIG-I/MAVS-mediated signaling by its long insertion variant in zebrafish.
As an intracellular pattern recognition receptor (PRR), the retinoic acid-inducible gene-I (RIG-I) is responsible for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). In the present study, an insertion variant of RIG-I with 38 amino acids inserted in the N-terminal CARD2 domain, as well as the typical type, named as RIG-Ia and RIG-Ib respectively were identified in zebrafish. RIG-Ia and RIG-Ib were all up-regulated following the infection of a negative ssRNA virus, the Spring Viremia of Carp Virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, indicating the RLR may have a role in the recognition of both viruses and bacteria. The over-expression of RIG-Ib in cultured fish cells resulted in significant increase in type I IFN promoter activity, and in protection against SVCV infection, whereas the over-expression of RIG-Ia had no direct effect on IFN activation nor antiviral response. Furthermore, it was revealed that both RIG-Ia and RIG-Ib were associated with the downstream molecular mitochondrial antiviral signaling protein, MAVS, and interestingly RIG-Ia when co-transfected with RIG-Ib or MAVS, induced a significantly higher level of type I IFN promoter activity and the expression level of Mx and IRF7, implying that the RIG-Ia may function as an enhancer in the RIG-Ib/MAVS-mediated signaling pathway.


Myosin isoform expression and smooth muscle cell heterogeneity in normal and atherosclerotic rabbit aorta.
Two monoclonal antimyosin antibodies, Western blotting experiments, and immunofluorescence procedures were used to investigate myosin isoform expression in normal and atherosclerotic aortas of adult rabbits. The SM-E7 antibody reacted with the two myosin heavy chain (MHC) isoforms of smooth muscle (SM) type (SM-MHC-1 and SM-MHC-2) expressed in the adult rabbit aorta. The NM-G2 antibody recognized an epitope shared by the nonmuscle (NM) myosin heavy chains (NM-MHC) present in fibroblasts, macrophages, lymphocytes, and platelets. Two smooth muscle cell (SMC) populations were identified in the medial layer of normal adult aorta, namely cells that contained SM myosin exclusively and cells that showed the coexistence of SM and NM myosin isoforms. The size of the cell population with double myosin isoform content increased markedly during experimental atherogenesis and represented by far the predominant SMC phenotype in the atherosclerotic plaque. Western blotting analysis performed on crude extracts from the atherosclerotic plaque showed the presence of SM-MHC-1 and NM-MHC isoforms in this tissue. Co-expression of SM and NM myosin at the molecular and the cellular level were found in aortic tissue during the early stages of development. These results indicate that in experimental atherosclerosis, the accumulation in the plaque of SMC with an "immature" pattern of myosin isoform expression is accompanied by similar modifications in the differentiation pattern of SMC of the underlying media.


Mucormycosis after allogeneic haematopoietic stem cell transplantation: a French Multicentre Cohort Study (2003-2008).
We conducted a nationwide retrospective study to evaluate clinical characteristics and outcome of mucormycosis among allogeneic haematopoietic stem cell transplant recipients. Twenty-nine patients were diagnosed between 2003 and 2008. Mucormycosis occurred at a median of 225 days after allogeneic haematopoietic stem cell transplant, and as a breakthrough infection in 23 cases. Twenty-six patients were receiving steroids, mainly for graft-versus-host disease treatment, while ten had experienced a prior post-transplant invasive fungal infection. Twenty-six patients received an antifungal treatment; surgery was performed in 12. Overall survival was 34% at 3 months and 17% at 1 year.


The effectiveness of low-level laser therapy on shoulder function in subacromial impingement syndrome.
To investigate the effectiveness of low-level laser therapy (LLLT) in addition to exercise programme on shoulder function in subacromial impingement syndrome (SAIS). Sixty-seven patients with SAIS were randomly assigned to either a group that received laser (n = 34) or a group that received placebo Laser (n = 26). Pain, functional assessment, disability and muscle strength of shoulder were assessed before and after a 3-week rehabilitation programme. Besides Laser or placebo Laser, superficial cold and progressive exercise programme were administered to both groups, 5 days a week, for 3 weeks. A progressive exercise programme that was done daily twice under supervision in clinic and at home was given to the patients. After the treatment, all outcome measurements had shown significant improvement except muscle strength in both the groups. When the parameters of the improvement were compared, there were no significant differences between the two groups after treatment. We concluded that there is no fundamental difference between LLLT and placebo LLLT when they are supplementing an exercise programme for rehabilitation of patients with shoulder impingement syndrome.


The Diagnosis and Treatment of Multiple Myeloma.
Multiple myeloma is a malignant disease of plasma cells with a worldwide incidence of 6-7 cases per 100 000 persons per year. It is among the 20 most common types of cancer in Germany. This review is based on pertinent publications up to December 2015 that were retrieved by a selective search of PubMed employing the terms "multiple myeloma" AND "therapy" OR "diagnostic." Systematic reviews, meta-analyses, randomized controlled trials, and treatment recommendations from Germany and abroad were considered. The diagnostic evaluation of multiple myeloma comprises thorough history-taking and physical examination, various laboratory tests including analysis of a 24-hour urine sample, a bone-marrow biopsy, and skeletal radiography. Systemic treatment should be administered only when organ damage has been diagnosed. The type of treatment to be given is chosen individually on the basis of the patient's age, comorbidities, and risk profile. High-dose therapy with autologous stem-cell transplantation remains the treatment of choice for patients under age 70 who are otherwise in good health. For patients who are not candidates for high-dose therapy or who have had a recurrence of multiple myeloma after prior high-dose therapy, there are a number of further conventional treatment options. Patients need not only systemic antineoplastic treatment, but also supportive treatment for the prevention of treatment-induced toxicity and myeloma-associated organ damage. Recent therapeutic advances have made the treatment of multiple myeloma both more complex and more costly. In particular, the median survival of patients with multiple myeloma has been markedly prolonged through the use of targeted drugs such as proteasome inhibitors and immune modulators.


Age-dependent overflow of endogenous norepinephrine from paraventricular hypothalamic nucleus of hypertensive rats.
The relationship between age and central noradrenergic neuronal activity of the paraventricular hypothalamic nucleus (PVH) was examined in 7- to 10-, 12- to 14-, and 30- to 36-wk-old Sprague-Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive rats (SHR). As an index of noradrenergic activity, endogenous norepinephrine (NE) overflow was assessed utilizing a miniaturized push-pull cannula assembly in unanesthetized freely moving rats. NE overlow under basal, 56 mM K+ stimulation, and in response to pressor/depressor drugs, were examined in all three strains at all ages. Significant increases in basal and K(+)-stimulated overflow of endogenous NE from the PVH were observed in all ages of SHR compared with normotensive controls with the greatest percent increase occurring during the development of hypertension in SHR. In addition, a reciprocal relationship exists with respect to blood pressure and overflow of NE from the PVH such that increases/decreases in blood pressure elicit decreases/increases in NE overflow in all strains at all ages examined. However, developing hypertensive SHR exhibited attenuated decreases in overflow of NE from the PVH compared with age-matched controls and established hypertensive SHR. These results suggest that noradrenergic pathways of the PVH contribute to the development and maintenance of arterial pressure hemostasis and that enhanced central noradrenergic neuronal activity is greatest during the development of hypertension in SHR.


Use of low level of continuous heat and Ibuprofen as an adjunct to physical therapy improves pain relief, range of motion and the compliance for home exercise in patients with nonspecific neck pain: A randomized controlled trial.
It has been well documented at heat reduces pain and increases healing by increasing blood flow in tissue. The purpose of this study was to see if the use of low level continuous heat (LLCH) and Ibuprofen used as a home therapy between physical therapy sessions at a clinic resulted in better therapy outcomes in people with chronic neck pain. Ninety-two patients with chronic nonspecific neck pain were randomly divided into 4 groups; LLCH group, LLCH with Ibuprofen (IP) group, sham LLCH with sham IP group, and controls. All subjects underwent 45 minutes of conventional physical therapy twice a week for 2 weeks. the neck disability index (NDI), subjective pain, range of motion (ROM), strength of the neck, and home exercise compliance were measured. Both LLCH and IP significantly reduced pain and NDI score, and increased ROM (p< 0.01). Home exercise compliance in LLCH and LLCH with IP group was significantly higher than the placebo and control groups (p < 0.05). The use of LLCH alone and LLCH with IP as an adjunct to conventional physical therapy for chronic neck pain significantly improved pain attenuation and it causes greater compliance for home.


Microbiota and Necrotizing Enterocolitis.
Necrotizing enterocolitis (NEC) is an acquired gastrointestinal inflammatory condition with significant mortality and morbidity in preterm very low birth weight infants. The interplay between toll-like receptors, bacterial endotoxins, developmentally regulated excessive proinflammatory responses of the immature innate immune system, hypoxia, ischemia, reperfusion, free radicals, and the presence of substrates and bacterial endotoxins is thought to play an important role in the pathogenesis of NEC. The association (cause?) of various microbes (bacteria, viruses, and fungi) with NEC has intrigued researchers for many years. Availability of newer molecular methods (e.g., 16S ribosomal RNA gene-specific primers/pyrosequencing of fecal DNA) is expected to improve our understanding of the role of gut microbiota in the pathogenesis of NEC. Recent studies employing such methods to assess fecal microbiota are reviewed. Current evidence suggests that dysbiosis of the gut microbiota precedes the development of NEC in preterm infants. Further research is required to understand the significance of changes in the gut microbiome over the early postnatal period including the relative abundance of Gammaproteobacteria and the paucity of strict anaerobic bacteria that precedes NEC in preterm infants. Assessing the reproducibility of previous findings in large prospective studies with standardized methodology (e.g. sample processing, PCR primer, and DNA extraction) is important.


Fertility after natural disaster: Hurricane Mitch in Nicaragua.
This investigation evaluates the effect of Hurricane Mitch on women's reproductive outcomes throughout Nicaragua. This research aim is achieved by analyzing a unique Nicaraguan Living Standards Measurement Study panel dataset that tracks women's fertility immediately before and at two time points after Hurricane Mitch, combined with satellite-derived municipality-level precipitation data for the 10-day storm period. Results show higher odds of post-disaster fertility in municipalities receiving higher precipitation levels in the immediate post-Hurricane Mitch period. However, fertility normalizes between disaster and non-disaster areas four to six years after the storm. These findings suggest that the disruptive effects of a natural disaster such as Hurricane Mitch can have an initial stimulative effect on fertility but the effect is ephemeral.


NMR analysis of the structure and metal sequestering properties of metallothioneins.
113Cd-NMR studies have been used to elucidate the structure of the metal-binding sites in mammalian and invertebrate ( Scylla serrata) metallothioneins (MTs). Chemical shift data have shown that all Cd ions are tetrahedrally coordinated to four cysteine thiolate ligands with single cysteinyl sulfurs bridging adjacent metals. Homonuclear decoupling experiments have shown that the 7 g-atoms of metal bound per mole of mammalian protein are located in a three- and a four-metal cluster while the 6 g-atoms of metal in the invertebrate MT are located in two three-metal clusters. The different metal binding affinities of the two mammalian clusters have been determined by 113Cd-NMR. The three-metal cluster prefers Cu greater than Zn greater than Cd whereas exactly the reverse order applies in the four-metal cluster. Proteolytic cleavage of the protein produced a 32-residue fragment which contained the four-metal cluster and demonstrated the presence of two separate domains in the protein. 500 MHz 1H-NMR has been employed to elucidate the arrangement of these metal clusters in the tertiary structure of the protein. The 1H resonances were assigned from their scalar and dipolar connectivities obtained from extensive one and two-dimensional NMR experiments. A specific application of 2D correlation spectroscopy ( COSY ) to the assignment of the 1H resonances in crab MT-1 is discussed. A molecular model, representing the three-dimensional solution structure of this protein, has been constructed based on an analysis of all these data. Detailed structural features of this model are discussed, with particular emphasis on their relationship to the function and evolution of the protein.


Managing change to improve outpatient care.
By establishing a quality circle and involving clients it is possible to improve many aspects of outpatient care in the multidisciplinary clinic. This article describes the ramifications of change within the multidisciplinary team and offers some suggestions for setting up similar groups in the inpatient, outpatient or community setting.


Intramedullary cysticercosis. Case report, literature review and comments on pathogenesis.
A 60-year-old woman developed progressive spastic crural paraplegia and global anesthesia and global anesthesia below T10, succumbing to urinary infection and bronchopneumonia 8 months after the onset of symptoms. At necropsy, the spinal cord was completely destroyed by a necrotic intramedullary cysticercus at T8. Six cysticerci were found in the brain. A review of the 17 published cases of intramedullary cysticercosis (including this one) showed this condition to be clinically indistinguishable from spinal cord tumours. The surgical prognosis was fair in 8 of 11 operated patients. The role of hematogenous and ventriculo-ependymal pathways in the pathogenesis of intramedullary cysticercosis was examined. The topographical distribution of intramedullary cysticerci (5 cervical, 12 thoracic, 2 lumbar, none sacral) was found to be statistically proportional to the blood flow to each of these regions; this favours the hematogenous route of infestation. The low spinal cord blood flow (100 times less than that to the brain), the type of vascularization of the cord (low calibre vessels under low pressure) and peculiarities of the cord tissue (such as its harder consistency) are all thought to be contributory factors accounting for the scarcity of intramedullary cysticerci. No evidence for an ependymal route of spread could be adduced.


Funipuncture for fetocide in late termination of pregnancy.
The most widely used method for fetocide in late termination of pregnancy for fetal abnormalities (TOPFA) consists of injecting of potassium chloride (KCl) into the fetal heart and is likely to be painful after 22 weeks of gestation. We studied ten consecutive women undergoing TOPFA between 22 and 38 weeks. This technique for fetocide consisted of a single umbilical vein puncture under ultrasound guidance with injections of sufentanil 5 microg followed by KCl 2 g. No electrocardiographic modifications could be observed and maternal plasma potassium levels did not show any significant variation throughout the procedure. Fetal umbilical phlebotomy for fetal analgesia followed by fetocide therefore appears to be a safe procedure for the mother and allows the fetus to die without pain when late termination of pregnancy (TOP) is indicated.


Sensory and motor evoked potentials in multiple system atrophy: a comparative study with Parkinson's disease.
Somatosensory evoked potentials (SEPs) to median nerve stimulation and motor evoked potentials to transcranial magnetic stimulation (TMS) of the motor cortex were studied in 15 patients with multiple system atrophy (MSA) and compared with matched groups of 20 patients with idiopathic Parkinson's disease (PD) and of 20 normal controls (NCs). No SEP latency or amplitude abnormalities were observed, and, in particular, the frontal N30 component was not significantly depressed. No differences in TMS threshold for evoking responses in relaxed or active thenar muscles were observed. The mean central motor conduction time was normal for the biceps brachii and opponens pollicis muscles and prolonged in the MSA group for the tibialis anterior muscle. Recording SEPs is not useful to differentiate MSA from PD, while the presence of central motor conduction abnormalities may bring into question the diagnosis of idiopathic PD.


High-velocity resistance training increases skeletal muscle peak power in older women.
Peak power declines more precipitously than strength with advancing age and is a reliable measure of impairment and a strong predictor of functional performance. We tested the hypothesis that a high-velocity resistance-training program (HI) would increase muscle power more than a traditional low-velocity resistance-training program (LO). Randomized controlled trial. University-based human physiology laboratory. Thirty women with self-reported dis-ability (aged 73 + 1, body mass index 30.1 + 1.1 kg/mn). We conducted a randomized trial comparing changes in skeletal muscle power and strength after 16 weeks of HI or LO. Training was performed three times per week, and subjects completed three sets (8-10 repetitions) of leg press (LP) and knee extension (KE) exercises at 70% of the one-repetition maximum (IRM). One-repetition maximum (1 RM) and peak power for KE and LP. LP and KE relative training force and total work were similar between groups (P > .05). However, HI generated significantly higher power during training sessions than LO for LP (3.7-fold greater, P < .001) and KE (2.1-fold greater, P < .001). Although LP and KE 1RM muscle strength increased similarly in both groups asa result of the training (P < .001), LP peak power increased significantly more in HI than in LO (267 W vs 139 W, P < .001). Furthermore, HI resulted in a significantly greater improvement in LP power at 40%, 50%, 60%,70%, 80%, and 90% of the 1 RM than did LO (P <.05). HI improved 1RM strength similarly and was more effective in improving peak power than was traditional LO in older women. Improvements in lower extremity peak power may exert a greater influence on age-associated reductions in physical functioning than other exercise interventions.


A rodent model for Wilms tumors: embryonal kidney neoplasms induced by N-nitroso-N'-methylurea.
Embryonal kidney cell tumors develop in rats given the alkylating agent N-nitroso-N'-methylurea as neonates. These tumors resemble the childhood Wilms tumors in their histopathology. Deletions and mutations in the Wilms tumor suppressor gene, WT1, are present in up to 6% of childhood nephroblastomas. To investigate the role of WT1 in rat kidney tumorigenesis, we studied the genetic alterations in WT1 and its target genes. Point mutations were found in WT1 cDNA in 7 of 18 kidney tumors. Mesenchymal tumors contained G-->A transition mutations in codons 128, 364, and 372, typical of the methylating action of N-nitroso-N'-methylurea on DNA. Each of the four nephroblastomas contained the same T-->A mutation at codon 111 of WT1, reflective of transversion mutagenesis by N-nitroso-N'-methylurea in vivo. Like Wilms tumors, mRNA levels of WT1, IGF2, Pax-2, and MK genes were higher than newborn kidney in the majority of the tumors. The histopathology of the rat kidney tumors and the genetic alterations are reminiscent of those observed in Wilms tumors, establishing this as a relevant model system for the human disease.


Iterative algorithm for absolute planarity calibration in three-flat test.
An iterative algorithm is presented to calibrate the shapes of the reference surfaces in three-flat test. Three measurements in three-flat test determine the even part of the flat surfaces. The odd part can be obtained by adding one or more rotation measurements and using analytical recovery algorithm. Here we present an iterative algorithm to obtain the odd part instead of special analytical recovery algorithm. The iterative algorithm is purely numerical, and only involved in data rotation operation. A simulation experiment proves the validity and high accuracy of the proposed algorithm method.


A gene cluster involved in degradation of substituted salicylates via ortho cleavage in Pseudomonas sp. strain MT1 encodes enzymes specifically adapted for transformation of 4-methylcatechol and 3-methylmuconate.
Pseudomonas sp. strain MT1 has recently been reported to degrade 4- and 5-chlorosalicylate by a pathway assumed to consist of a patchwork of reactions comprising enzymes of the 3-oxoadipate pathway. Genes encoding the initial steps in the degradation of salicylate and substituted derivatives were now localized and sequenced. One of the gene clusters characterized (sal) showed a novel gene arrangement, with salA, encoding a salicylate 1-hydroxylase, being clustered with salCD genes, encoding muconate cycloisomerase and catechol 1,2-dioxygenase, respectively, and was expressed during growth on salicylate and chlorosalicylate. A second gene cluster (cat), exhibiting the typical catRBCA arrangement of genes of the catechol branch of the 3-oxoadipate pathway in Pseudomonas strains, was expressed during growth on salicylate. Despite their high sequence similarities with isoenzymes encoded by the cat gene cluster, the catechol 1,2-dioxygenase and muconate cycloisomerase encoded by the sal cluster showed unusual kinetic properties. Enzymes were adapted for turnover of 4-chlorocatechol and 3-chloromuconate; however, 4-methylcatechol and 3-methylmuconate were identified as the preferred substrates. Investigation of the substrate spectrum identified 4- and 5-methylsalicylate as growth substrates, which were effectively converted by enzymes of the sal cluster into 4-methylmuconolactone, followed by isomerization to 3-methylmuconolactone. The function of the sal gene cluster is therefore to channel both chlorosubstituted and methylsubstituted salicylates into a catechol ortho cleavage pathway, followed by dismantling of the formed substituted muconolactones through specific pathways.


Adaptive behaviour and motor skills in children with upper limb deficiency.
The dysfunction of individuals with upper limb deficiencies affects their daily lives and social participation. To clarify the adaptive behaviours and motor skills of children with upper limb deficiencies. Cross-sectional survey. The subjects were 10 children ranging from 1 to 6 years of age with unilateral upper limb deficiencies at the level distal to the elbow who were using only cosmetic or passive prostheses or none at all. To measure their adaptive behaviour and motor skills, the Vineland Adaptive Behavior Scales, Second Edition was used. They were evaluated on the domains of communication, daily living skills, socialization and motor skills. We also examined the relationship of the scores with age. There were no statistically significant scores for domains or subdomains. The domain standard score of motor skills was significantly lower than the median scores of the domains and was negatively correlated with age. Children with upper limb deficiencies have individual weaknesses in motor skill behaviours, and these weaknesses increase with age. It may be helpful in considering approaches to rehabilitation and the prescription of prostheses to consider the characteristics and course of children's motor skill behaviours. Clinical relevance Even if children with unilateral upper limb deficiencies seem to compensate well for their affected limb function, they have or will experience individual weaknesses in motor skills. We should take this into consideration to develop better strategies for rehabilitation and prostheses prescriptions.


Neoplasms in persons treated with x-rays in infancy: fourth survey in 20 years.
The incidence of neoplastic disease was determined by a mail survey of 2,872 young adults given X-ray treatments in infancy and of their 5,005 nonirradiated siblings. Newly diagnosed benign and malignant neoplasms appeared more frequently in the irradiated subjects than in their siblings or the age- and sex-matched general population of upstate New York. Only thyroid neoplasms occurred in sufficient numbers to permit statistical analysis for the effects on incidence of sex, age, and dose, and of being in a high-risk group (sub-group C). Thyroid cancers developed earlier in life than did benign neoplasms, especially in boys; benign goiters occurred after smaller doses, predominantly in females. Females had a greater risk of developing thyroid cancer than males--2,3 times for females of all ages and 5 times for young adults. Except for young adult females, there was no definite age effect. The risk of cancer (but not of benign goiter) was proportional to the thyroid dose, with a linear risk coefficient of 2.5/year/million people exposed to 1 rad for the entire irradiated population and 4.0 for subgroup C. The high risk of thyroid cancer in subgroup C may be the result of the high percentage of Jews, who had a 3.4-fold greater risk than non-Jews. Young adult Jewish females had a 17-fold increased risk. An incidental observation was an apparent increased incidence of asthma and rare diseases with abnormal immunologic features in the irradiated population.


Two new meroterpenes from endophytic fungus A1 of Scyphiphora hydrophyllacea.
Two new meroterpenes, guignardone D (1) and guignardone E (2), were isolated from endophytic fungus A1 of Scyphiphora hydrophyllacea Gaertn. F. Their structures were established based on spectroscopic methods including 1D and 2D NMR (HMQC, (1)H-(1)H COSY, HMBC, and ROESY).


Radiation damage of optical fiber waveguides at long wavelengths.
Measurements of the radiation-induced optical attenuation at 1.3 microm and the induced absorption spectra (0.4-1.7 microm) of state-of-the-art pure synthetic silica and doped silica core optical fiber waveguides have been undertaken to characterize their radiation response at long wavelengths. It has been observed that radiation-induced absorption bands at long wavelengths can give rise to substantial induced losses at both 1.3 and 1.55 microm in some fibers, especially those doped with P or B; the ratio of the damage at 1.3 and 1.55 microm to that at 0.82 microm in these fibers has been found to be only ~0.29 and 0.71, respectively. In contrast, pure fused silica and binary Ge-doped silica core fibers have shown the greatest hardness at long wavelengths. Suggestions have been made for the optimum wavelengths and preferred fiber compositions to minimize the effects of nuclear radiation in fiber-optic communications systems operating at long wavelengths.


Effects of Ketorolac, Xylazine, and Bupivacaine Multimodal Analgesia on Goats.
The current study aimed to investigate the effect of some of the analgesic drugs, such as Xylazine, Ketorolac, and Bupivacaine alone/mixed, on analgesia scores in the local breed goats. This research was performed on 35 male and female local breed goats within the age range of 6-8 months with an average weight of 17±3 Kg. The animals were divided into seven groups (n=5). The first group received Xylazine at a dose of 0.1 mg/kg BW through intramuscular injection (IM), while the second group was administered Ketorolac at a dose of 2 mg/kg BW through IM. The third group was administered Bupivacaine at a dose of 2 mg/kg BW through subcutaneous injection (SC). The fourth group was administered ketorolac at a dose of 2 mg/kg BW through IM and after 1 h was administered xylazine at a dose of 0.1 mg/kg BW through IM. The fifth group was administered Bupivacaine at a dose of 2 mg/kg BW through SC and after 1 h was administered xylazine at a dose of 0.1 mg/kg BW through IM. The sixth group was administered a mixture of Bupivacaine and ketorolac at the dose of 2 mg/kg BW through SC and 2 mg/kg BW through IM, respectively. The seventh group was administered Bupivacaine at a dose of 2 mg/kg BW through SC and ketorolac at the dose of 2 mg/kg BW through IM simultaneously. After 1 h, the seventh group was administered xylazine at the dose of 0.1 mg/kg BW through IM. Analgesia scores were evaluated every 10 min from the starting point for 180 min to determine values, such as respiratory and heart rate as well as rectal temperature. Moreover, the analgesic degree was examined for the head, flanks, hind limb, forelimb, and tail every 10 min. The recorded data in the current study revealed that the seventh group had a higher analgesic effect, compared to the other groups depending on the analgesia of the head, tail, flank, forelimb, and hindlimb. In the end, the group that received the mixture or combination of Bupivacaine (2 mg/kg BW-SC) and ketorolac (2 mg/kg BW-IM) followed by the administration of xylazine at a dose of 0.1 mg/kg BW after 1 h had a short period of onset of analgesia and showed long analgesia time and more depth, compared to other groups and without ataxia.


Effect of sleep deprivation on emotional working memory.
The emotional dysregulation and impaired working memory found after sleep loss can have severe implications for our daily functioning. Considering the intertwined relationship between emotion and cognition in stimuli processing, there could be further implications of sleep deprivation in high-complex emotional situations. Although studied separately, this interaction between emotion and cognitive processes has been neglected in sleep research. The aim of the present study was to investigate the effect of 1 night of sleep deprivation on emotional working memory. Sixty-one healthy participants (mean age: 23.4 years) were either sleep deprived for 1 night (n = 30) or had a normal night's sleep (n = 31). They performed an N-back task with two levels of working memory load (1-back and 3-back) using positive, neutral and negative picture scenes. Sleep deprivation, compared with full night sleep, impaired emotional working memory accuracy, but not reaction times. The sleep-deprived participants, but not the controls, responded faster to positive than to negative and neutral pictures. The effect of sleep deprivation was similar for both high and low working memory loads. The results showed that although detrimental in terms of accuracy, sleep deprivation did not impair working memory speed. In fact, our findings indicate that positive stimuli may facilitate working memory processing speed after sleep deprivation.


Essential fatty acids, prostaglandins, and alcoholism: an overview.
Essential fatty acids (EFAs) are major structural components of the brain and through their effects on membrane properties can influence nerve conduction, transmitter release, and transmitter action. Prostaglandins (PGs) derived from EFAs have profound behavioral effects and are also able to modify conduction and transmitter function. Effects of alcohol on EFAs and PGs are therefore good candidates for explaining at least some of the actions of alcohol on brain function. Ethanol has three main known actions on EFA and PG metabolism: it reduces blood linoleic acid levels and induces or exaggerates EFA deficiency states; it blocks metabolism of linoleic acid to EFA metabolites which are known to be important in brain structure; and it enhances conversion of the linoleic acid metabolite, dihomo-gamma-linolenic acid, to PGE1. This review demonstrates that some of the short-term behavioral effects of ethanol and some of its long-term adverse effects on brain, liver, and other tissues may be partly explicable in terms of ethanol actions on EFA and PG metabolism. Modification of such metabolism by dietary and other means has already been shown to influence the effects of alcohol and alcohol withdrawal in both humans and animals. This promises to be a fruitful source of investigation with substantial implications for the understanding and treatment of alcoholism.


Thrombopoietin protects mice from mortality and myelosuppression following high-dose irradiation: importance of time scheduling.
Thrombopoietin is the major regulator of platelet production and a stimulator of multilineage hematopoietic recovery following irradiation. The efficacy of three different schedules of thrombopoietin administration was tested on blood cell counts, hematopoietic bone marrow progenitors, and 30-day animal survival in C57BL6/J mice receiving a total body irradiation, with doses ranging from 7 to 10 Gy. A single dose of murine thrombopoietin was injected 2 h before, 2 h after, or 24 h after irradiation. Thrombopoietin promoted multilineage hematopoietic recovery in comparison to placebo up to 9 Gy at the level of both blood cells and bone marrow progenitors, whatever the schedule of administration. The injection of thrombopoietin 2 h before or 2 h after irradiation equally led to the best results concerning hematopoietic recovery. On the other hand, thrombopoietin administration promoted 30-day survival up to 9 Gy with the highest efficacy obtained when thrombopoietin was injected either 2 h before or 2 h after irradiation. However, when its injection was delayed at 24 h, thrombopoietin had almost no effect on survival of 9 Gy irradiated mice. Altogether, our results show that the time schedule for thrombopoietin injection is of critical importance and when thrombopoietin is administered before or shortly after irradiation, it efficiently promotes mice survival to supra-lethal irradiation (up to 9 Gy) in relation with hematopoietic recovery.


A Comparison of Algorithms for Learning Hidden Variables in Bayesian Factor Graphs in Reduced Normal Form.
Bayesian-directed acyclic discrete-variable graphs are reduced to a simplified normal form made up of only replicator units (or equal constraint units), source, and single-input/single-output blocks. In this framework, the same adaptation algorithm can be applied to all the parametric blocks. We obtain and compare adaptation rules derived from a constrained maximum likelihood formulation and a minimum Kullback-Leibler divergence criterion using Karush-Kuhn-Tucker conditions. The learning algorithms are compared with two other updating equations based on localized decisions and on a variational approximation, respectively. The performance of the various algorithms is verified on synthetic data sets for various architectures. Factor graphs in reduced normal form provide an appealing framework for rapid deployment of Bayesian-directed graphs in the applications.


TRICARE; TRICARE retiree dental program (TRDP) basic benefit descriptions and administrative corrections. Final rule.
This final rule amends TRICARE Retiree Dental Program (TRDP) Basic benefit descriptions by replacing specific American Dental Association (ADA) dental procedure codes and nomenclature with general benefit categories and descriptions. This revision is necessary to keep the regulation current, since dental procedure codes are added, revised, and deleted on a regular basis. This final rule does not change or eliminate any benefits that are currently available under the TRDP program. This final rule also revises several incorrect, obsolete, or historical terms pertaining to the TRICARE program, and removes an inaccurate statement regarding appeals and grievances.


Prevalence of antibodies against alpha-fodrin in Sjögren's syndrome: comparison of 2 sets of classification criteria.
To compare the prevalence of antibodies against alpha-fodrin in Sjögren's syndrome (SS) classified according to San Diego and European Community Study Group (ESG) criteria. The prevalence and mean concentrations of IgA and IgG autoantibodies against alpha-fodrin were determined and compared in patients with SS classified either according to San Diego criteria or to criteria of the ESG by ELISA. IgA antibodies against alpha-fodrin were detected in 88% and IgG antibodies against alpha-fodrin in 64% and either of these antibodies in 93% of 85 patients classified according to San Diego criteria. Antibodies against Ro were present in 38% of these sera. IgA antibodies against alpha-fodrin were detected in 61%, IgG antibodies against alpha-fodrin in 51%, and any of these antibodies in 73% of 51 patients classified according to the ESG criteria. The mean concentrations of both IgA and IgG antibodies against alpha-fodrin that seem to correlate with disease activity were higher in patients classified according to the San Diego criteria. Antibodies against alpha-fodrin are detectable in almost all sera obtained from patients with SS classified according to the San Diego criteria and are significantly more prevalent than antibodies against Ro. The lower prevalence of the autoantibodies in patients classified according to the ESG criteria reflects the lower specificity of these criteria for SS.


Green fluorescent protein (GFP): is seeing believing and is that enough?
Intracellular compartmentalisation is a significant barrier to the successful nucleocytosolic delivery of biologics. The endocytic system has been shown to be responsible for compartmentalisation, providing an entry point, and trigger(s) for the activation of drug delivery systems. Consequently, many of the technologies used to understand endocytosis have found utility within the field of drug delivery. The use of fluorescent proteins as markers denoting compartmentalisation within the endocytic system has become commonplace. Several of the limitations associated with the use of green fluorescent protein (GFP) within the context of drug delivery have been explored here by asking a series of related questions: (1) Are molecules that regulate fusion to a specific compartment (i.e. Rab- or SNARE-GFP fusions) a good choice of marker for that compartment? (2) How reliable was GFP-marker overexpression when used to define a given endocytic compartment? (3) Can glutathione-s-transferase (GST) fused in frame with GFP (GST-GFP) act as a fluid phase endocytic probe? (4) Was GFP fluorescence a robust indicator of (GFP) protein integrity? This study concluded that there are many appropriate and useful applications for GFP; however, thought and an understanding of the biological and physicochemical character of these markers are required for the generation of meaningful data.


Saccade-related, long-lead burst neurons in the monkey rostral pons.
The paramedian pontine reticular formation contains the premotoneuronal cell groups that constitute the saccadic burst generator and control saccadic eye movements. Despite years of study and numerous investigations, the rostral portion of this area has received comparatively little attention, particularly the cell type known as long-lead burst neurons (LLBNs). Several hypotheses about the functional role of LLBNs in saccade generation have been proposed, although there is little information with which to assess them. To address this issue, I mapped and recorded LLBNs in the rostral pons to measure their discharge characteristics and correlate those characteristics with the metrics of the concurrent saccades. On the basis of their discharge and location, I identified three types of LLBNs in the rostral pons: excitatory (eLLBN), dorsal (dLLBN), and nucleus reticularis tegmenti pontis (nrtp) LLBNs. The eLLBNs, encountered throughout the pons, discharge for ipsilateral saccades in proportion to saccade amplitude, velocity, and duration. The dLLBNs, found at the pontomesencephalic junction, discharge maximally for ipsilateral saccades of a particular amplitude, usually <10 degrees , and are not associated with a particular anatomical nucleus. The nrtp LLBNs, previously described as vector LLBNs, discharge for saccades of a particular direction and sometimes a particular amplitude. The discharge of the eLLBNs suggests they drive motor neurons. The anatomical projections of the nrtp LLBNs suggest that their involvement in saccade production is less direct. The discharge of dLLBNs is consistent with a role in providing the "trigger" signal that initiates saccades.


Effects of dietary pectin and fat on the small intestinal contents and exocrine pancreas of rats.
The effects of dietary pectin and fat level on digestive enzyme activities in the pancreas and small intestine and on intestinal bile acid levels were investigated. In unfed rats, dietary pectin did not influence the pancreatic enzymes studied, but a higher level of corn oil in the diet lowered the amylase activity in the pancreas, increased pancreatic lipase activity and slightly lowered the chymotrypsin and trypsin activities. Diet did not change the dry weight of the pancreas. In the fed rats, dietary pectin increased the dry weight of the small gut wash plus the mucosal scraping. Dietary pectin increased the small intestinal lipase and chymotrypsin levels and at the low level of fat only, increased amylase and trypsin activities in the small intestine of fed rats. Intestinal lipase levels were higher and amylase levels lower in rats consuming the high level of corn oil. These results indicate that changes in dietary fat level led to changes in the amylase and lipase content of secreted pancreatic juice and that differences in absorption associated with diets containing pectin could be the result of increased material in the small intestine.


Lesions produced by the extravasation of urine from the upper urinary tract.
We present six cases which illustrate the spectrum of clinical features, macroscopic findings and light microscopic findings of urine extravasation from the upper urinary tract. The early lesions are characterized macroscopically by an oedematous, glistening or gelatinous appearance to the renal perihilar and peripelvic fat. Light microscopically there is lipolysis with associated foamy macrophages, multinucleate giant cells and lymphocytes. Immunohistochemical staining for Tamm-Horsfall protein is strongly positive in the extracellular space and in the foamy macrophages confirming urine extravazation. Later lesions are characterized by cicatrization of fibrous tissue around the renal pelvis and hydronephrosis. Microscopically there is relatively bland fibrosis with occasional lymphocytes and histiocytic cells. The late lesions are also characterized by extracellular deposits of weakly eosinophilic, granular or hyaline material, the so called 'urinary precipitates'. These deposits stain strongly with diastase PAS and weakly positive for Tamm-Horsfall protein. The staining of these urinary precipitates is analogous to renal tubular hyaline casts, thus supporting the theory that they are derived from uroproteins. We consider that these deposits are pathognomic of past urine extravasation.


An independent audit of electroconvulsive therapy patient information leaflets in Northern Ireland, Scotland and Wales.
To evaluate the accuracy of patient information leaflets about electroconvulsive therapy (ECT) used in Northern Ireland, Scotland and Wales, and their compliance with the principle of informed consent. To replicate an audit in England, Freedom of Information Act requests were sent to the 26 providers of ECT for their ECT patient information leaflet. These were scored, by two independent raters, on the same 40-item accuracy measure used in the England audit. The number of accurate statements (out of a possible 29) ranged from seven to 20, with a mean of 16.9. The most frequently omitted statements included: cardiovascular risks (mentioned by five leaflets), that it is not known how ECT works (3), risk of mortality (2), risks from multiple general anaesthetic procedures (2), how to access a legal advocate (2) and that that there is no evidence of long-term benefits (1). The leaflets made between six and nine inaccurate statements (out of 11) with a mean of 7.0. Nineteen minimised memory loss, blamed the memory loss on depression, claimed that ECT is the 'most effective treatment' and asserted it has very high response rates without mentioning similar placebo response rates. All 23 leaflets wrongly told patients that ECT saves lives. Electroconvulsive therapy information leaflets in these three nations are barely more accurate than those in England and do not comply with the ethical principle of informed consent. Patients and families across the UK are systematically being misled about the risks they are taking and the limited nature of ECT's benefits.


Probing Anisotropic Surface Properties of Molybdenite by Direct Force Measurements.
Probing anisotropic surface properties of layer-type mineral is fundamentally important in understanding its surface charge and wettability for a variety of applications. In this study, the surface properties of the face and the edge surfaces of natural molybdenite (MoS2) were investigated by direct surface force measurements using atomic force microscope (AFM). The interaction forces between the AFM tip (Si3N4) and face or edge surface of molybdenite were measured in 10 mM NaCl solutions at various pHs. The force profiles were well-fitted with classical DLVO (Derjaguin-Landau-Verwey-Overbeek) theory to determine the surface potentials of the face and the edge surfaces of molybdenite. The surface potentials of both the face and edge surfaces become more negative with increasing pH. At neutral and alkaline conditions, the edge surface exhibits more negative surface potential than the face surface, which is possibly due to molybdate and hydromolybdate ions on the edge surface. The point of zero charge (PZC) of the edge surface was determined around pH 3 while PZC of the face surface was not observed in the range of pH 3-11. The interaction forces between octadecyltrichlorosilane-treated AFM tip (OTS-tip) and face or edge surface of molybdenite were also measured at various pHs to study the wettability of molybdenite surfaces. An attractive force between the OTS-tip and the face surface was detected. The force profiles were well-fitted by considering DLVO forces and additional hydrophobic force. Our results suggest the hydrophobic feature of the face surface of molybdenite. In contrast, no attractive force between the OTS-tip and the edge surface was detected. This is the first study in directly measuring surface charge and wettability of the pristine face and edge surfaces of molybdenite through surface force measurements.


Tubercular serpiginous-like choroiditis.
Choroidal tuberculosis (TB) infection may present itself as a diffuse choroiditis that resembles serpiginous choroiditis, usually treated with immunossupressants. Recent studies have demonstrated that patients with serpiginous-like choroiditis and evidence of systemic or latent TB are best treated with antituberculosis treatment (ATT) in addition to the corticosteroid therapy. The authors present a case of a 58-year-old man with decreased vision in his left eye. His best-corrected visual acuity was 20/20 right eye and 20/200 left eye. Funduscopic examination revealed a diffuse choroiditis. Mantoux skin test showed an area of induration measuring 30×35 mm and the patient started ATT with complete resolution of retinal lesions after 2 weeks of treatment. His final visual acuity was 20/25 in the left eye with no recurrences over a follow-up of 6 months. The use of ATT in these patients is likely to reduce active inflammation and eliminate future recurrences.


Neuroprotection induced by Navβ2‑knockdown in APP/PS1 transgenic neurons is associated with NEP regulation.
Voltage‑gated sodium channel β2 (Navβ2), as an unconventional substrate of β‑site amyloid precursor protein cleaving enzyme 1, is involved in regulating the neuronal surface expression of sodium channels. A previous study demonstrated that knockdown of Navβ2 protected neurons and induced spatial cognition improvement by partially reducing pathological amyloidogenic processing of amyloid precursor protein (APP) in aged APP/presenilin 1 (PS1) transgenic mice. The present study aimed to investigate whether Navβ2 knockdown altered APP metabolism via regulation of the Aβ‑degrading enzyme neprilysin (NEP). APPswe/PS1ΔE9 mice (APP/PS1 transgenic mice with a C57BL/6J genetic background) carrying a Navβ2‑knockdown mutation (APP/PS1/Navβ2‑kd) or without Navβ2 knockdown (APP/PS1) were used for cell culture and further analysis. The present results demonstrated that in APP/PS1 mouse‑derived neurons, Navβ2 knockdown partially reversed the reduction in pathological APP cleavage, and the recovery of neurite extension and neuron area. Additionally, Navβ2 knockdown increased NEP activity and levels, and the levels of intracellular domain fragment binding to the NEP promoter. The present findings suggested that knockdown of Navβ2 reversed the APP/PS1 mutation‑induced deficiency in amyloid β degradation by regulating NEP.


The genome of epsilon15, a serotype-converting, Group E1 Salmonella enterica-specific bacteriophage.
The genome sequence of the Salmonella enterica serovar Anatum-specific, serotype-converting bacteriophage epsilon15 has been completed. The nonredundant genome contains 39,671 bp and 51 putative genes. It most closely resembles the genome of phiV10, an Escherichia coli O157:H7-specific temperate phage, with which it shares 36 related genes. More distant relatives include the Burkholderia cepacia-specific phage, BcepC6B (8 similar genes), the Bordetella bronchiseptica-specific phage, BPP-1 (8 similar genes) and the Photobacterium profundum prophage, P Pphipr1 (6 similar genes). epsilon15 gene identifications based on homologies with known gene families include the terminase small and large subunits, integrase, endolysin, two holins, two DNA methylase enzymes (one adenine-specific and one cytosine-specific) and a RecT-like enzyme. Genes identified experimentally include those coding for the serotype conversion proteins, the tail fiber, the major capsid protein and the major repressor. epsilon15's attP site and the Salmonella attB site with which it interacts during lysogenization have also been determined.


[Blood blister-like aneurysm on the posterior wall of the internal carotid artery causing subarachnoid hemorrhage: a case report].
We report a case of blood blister-like aneurysm(BBA)on the posterior wall of the internal carotid artery(ICA)causing subarachnoid hemorrhage(SAH). A 45-year-old man suffering from SAH(WFNS grade 5)was referred to our hospital. 3D-CT angiography showed a BBA on the posterior wall of the ICA. The aneurysm had been enlarged for a few days. Therefore we performed coil embolization. Four weeks after the operation, the aneurysm was found to have regrown. In the second operation the aneurysm was successfully treated by the ICA proximal occlusion with extracranial-intracranial bypass. Postoperative follow-up cerebral angiography detected no aneurysm. To our knowledge, BBA on the posterior wall of the ICA is rare. Radical surgery with bypass should be performed as soon as possible when the BBA is found to regrow. We discuss the clinical characteristics with a review of the literature.


Semisynthetic studies identify mitochondria poisons from botanical dietary supplements--geranyloxycoumarins from Aegle marmelos.
Bioassay-guided isolation and subsequent structure elucidation of a Bael tree Aegle marmelos lipid extract yielded two unstable acylated geranyloxycoumarin mixtures (1-2), six geranyloxycoumarins (3-8), (+)-9'-isovaleroxylariciresinol (9), and dehydromarmeline (10). In a T47D cell-based reporter assay, 1 and 2 potently inhibited hypoxia-induced HIF-1 activation (IC50 values 0.18 and 1.10 μgmL(-1), respectively). Insufficient material and chemical instability prevented full delineation of the fatty acyl side chain olefin substitution patterns in 1 and 2. Therefore, five fatty acyl geranyloxycoumarin ester derivatives (11-15) were prepared from marmin (3) and commercial fatty acyl chlorides by semisynthesis. The unsaturated C-6' linoleic acid ester derivative 14 that was structurally most similar to 1 and 2, inhibited HIF-1 activation with comparable potency (IC50 0.92 μM). The octanoyl (11) and undecanoyl (12) ester derivatives also suppressed HIF-1 activation (IC50 values 3.1 and 0.87 μM, respectively). Mechanistic studies revealed that these geranyloxycoumarin derivatives disrupt mitochondrial respiration, primarily at complex I. Thus, these compounds may inhibit HIF-1 activation by suppressing mitochondria-mediated hypoxic signaling. One surprising observation was that, while less potent, the purported cancer chemopreventive agent auraptene (8) was found to act as a mitochondrial poison that disrupts HIF-1 signaling in tumors.


The role of endoscopic retrograde cholangiopancreatography in choledochal cysts and/or abnormal pancreatobiliary junction in children.
Biliary cysts with an abnormal pancreatobiliary junction are one of the most common pancreatobiliary malformations. The main symptom is cholestasis; endoscopic retrograde cholangiopancreatography (ERCP) plays a key role in diagnosis. Retrospective evaluation of ERCP performed to diagnose abnormalities of the pancreatobiliary junction. We retrospectively evaluated ERCP performed to diagnose abnormalities of the pancreatobiliary junction, mainly choledochal cysts, in 112 children between 1990 and 2011. We performed 112 examinations of 50 children with abnormal pancreatobiliary junction and choledochal cysts (15 males and 35 females, average age: 5 years, range: 1 month - 15 years). Cysts were associated with a common channel in 37 (74%) cases, were not associated with a common channel in 9 (18%) cases, and in 3 (6%) cases the common channel lacked cysts. We performed endoscopic papilla sphincterotomy on 33 (66%) patients; endoscopic drainage was performed 62 times, including 17 patients without papilla sphincterotomy. In 15 (30%) cases, we only performed sphincterotomy. Extraction of lithiasis was done in 2 (4%) cases. Both ERCP and magnetic resonance cholangiopancreatography (MRCP) were performed on 13 patients. There was concordance of the choledochal cyst and of the type of cyst in both methods; however, common channels could not be observed by MRCP. There was 1 serious complication (perforation after sphincterotomy) and 11 (9%) mild adverse events. When performed at an expert centre, ECRP is a safe and reliable procedure for children with choledochal cysts and/or an abnormal pancreatobiliary junction. Endoscopic retrograde cholangiopancreatography remains a reasonable alternative because MRCP has a limited ability to diagnose the precise anomalies of the pancreatobiliary junction and has no therapeutic capabilities.


Augmentative and alternative communication services during the COVID-19 pandemic: impact on children, their families and service providers.
The closure of schools and healthcare facilities across the United States due to COVID-19 has dramatically changed the way that services are provided to children with disabilities. Little is known about how children who use augmentative and alternative communication (AAC), their families and their service providers have been impacted by these changes. This qualitative study sought to understand the perspectives of parents and speech-language pathologists (SLPs) on how COVID-19 has affected children, families, services providers and the delivery of AAC-related communication services. For the study, 25 parents and 25 SLPs of children who used aided AAC participated in semi-structured interviews, with data analyzed using qualitative thematic analysis. Parents and SLPs highlighted wide disparities in how children have been impacted, ranging from views of children making more progress with communication and language than before the pandemic to worries about regression. A complex system of factors and processes may explain these differences. COVID-19 will have lasting impacts on the lives of children with complex communication needs. This research highlights the crucial role of family-service provider partnerships and access to quality AAC services for children during the pandemic and into the future.


Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma.
Pancreatic ductal adenocarcinoma remains an extremely malignant tumor having a poor prognosis. The 5-year survival rate of PDAC is related to its stage (about 80% for stage I vs 20% for other stages). However, detection of PDAC in an early stage is difficult due to the lack of effective screening methods. In this study, we aimed to construct a novel metabolic model for stage-I PDAC detection, using both serum and tissue samples. We employed an untargeted technique, UHPLC-Q-TOF-MS, to identify the potential metabolite, and then used a targeted technique, GC-TOF-MS, to quantitatively validate. Multivariate and univariate statistics were performed to analyze the metabolomic profiles between stage-I PDAC and healthy controls, including 90 serum and 53 tissue samples. 28 patients with stage-I PDAC and 62 healthy controls were included in this study. A total of 10 potential metabolites presented the same expression levels both in serum and in tissue. Among them, a 2-metabolites-model (isoleucine and adrenic acid) for stage-I PDAC was constructed. The area under the curve (AUC) value was 0.93 in the discovery set and 0.90 in the independent validation set. Especially, the serum metabolite model had a better diagnostic performance than CA19-9 (AUC = 0.79). Pathway analysis revealed 11 altered pathways in both serum and tissue of stage-I PDAC. This study developed a novel serum metabolites model that could early separate stage-I PDAC from healthy controls.


Extending the color discrimination metric with consideration of illuminance level.
Color discrimination is a crucial dimension for the visual assessment of white light sources. In this Letter, we took full advantage of data comparability among Farnsworth-Munsell 100 Hue (FM-100) color vision tests and modified our recent proposed color discrimination metric [Opt. Lett.45, 6062 (2020)10.1364/OL.400422] to make it effective in quantifying the color discrimination capability of lighting under multiple illuminance levels. The updated metric was developed based on a meta-analysis of 100 sets of combined visual data derived from three groups of visual studies containing 29 FM-100 trials and its superiority was comprehensively validated by 140 sets of combined data from five groups of studies with 42 FM-100 trials.


An assessment of biological potency and molecular characteristics of different innovator and noninnovator interferon-beta products.
Approved innovator products and their noninnovator "copy" versions are likely to vary in their quality, eg, physicochemical characteristics and biological activity, with important implications for clinical efficacy and safety. Therefore, it is important to study and thoroughly evaluate the noninnovator products in comparison with approved products at the preclinical and clinical stages. We have obtained 4 noninnovator interferon (IFN)-β-1a products currently marketed in Latin America and Iran and compared these with approved IFN-β-1a products (Avonex and Rebif) obtained from the same geographical regions with respect to biological potency, estimated by in vitro bioassays, and molecular characteristics, assessed by immunoblotting and high-performance liquid chromatography. In this article, we present our data showing that the noninnovator IFN-β-1a products can vary considerably in their biological potency. In addition, we showed that all IFN-β-1a products formulated with human serum albumin contained variable amounts of higher-molecular-weight aggregates of IFN-β-1a and adducts with human serum albumin, these being more prevalent in 2 noninnovator IFN-β-1a products where biological potency was reduced compared with approved IFN-β-1a products. Additionally, significant lot-to-lot variability was observed for one of the noninnovator products. Taken together, the results of this study highlight the need for not only thorough in vitro characterization, but also preclinical and clinical assessment to ensure patient safety and efficacy.


Contribution of Open Mouth Technique in 18F-FDG PET/CT Imaging in Patients with Malignant Lip Neoplasm.
18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating head and neck cancers. However, localization and size evaluation in this region can be rough due to the multitude of the anatomic structures and physiologic uptakes. The aim of this study was to evaluate malignant lip lesions with the contribution of open mouth (OM) imaging technique at PET/CT. Fifty-six patients with malignant lip neoplasm underwent 18F-FDG PET/CT imaging. Each patient was imaged twice as whole-body PET/CT with routine closed mouth (CM) position; and OM head and neck image, standardized with a special device. Lesion maximum standard uptake value (SUVmax), localization, size, and involvement of lymph nodes were evaluated. Lesion localization was correctly detected in 100% of the OM images. Lesion size in PET/CT was compared with clinical, radiological (magnetic resonance imaging and CT) and/or histopathological results and the size measurement was coherent at 47.1% and 95.6% for CM and OM images, respectively. It was observed that OM acquisition did not contribute additionally in detecting regional lymph node metastasis. Forty-one PET/CT scans with CT artifacts due to dental amalgams were evaluated and 46.3% dimensional and 53.7% localization errors were detected in the CM position. There was no statistically significant difference between OM and CM SUVmax (p>0.05). We concluded that additional OM head and neck imaging is useful and necessary to accurately determine the localization and size of the tumor, thus enhancing the value of PET/CT in staging, treatment response assessment, and restaging of patients with malignant lip cancer with or without dental amalgam.


The genome of Salmacisia buchloëana, the parasitic puppetmaster pulling strings of sexual phenotypic monstrosities in buffalograss.
To complete its parasitic lifecycle, Salmacisia buchloëana, a biotrophic fungus, manipulates reproductive organ development, meristem determinacy, and resource allocation in its dioecious plant host, buffalograss (Bouteloua dactyloides; Poaceae). To gain insight into S. buchloëana's ability to manipulate its host, we sequenced and assembled the 20.1 Mb genome of S. buchloëana into 22 chromosome-level pseudomolecules. Phylogenetic analysis suggests that S. buchloëana is nested within the genus Tilletia and diverged from T. caries and T. walkeri ∼40 million years ago. We find that S. buchloëana contains a novel chromosome arm with no syntenic relationship to other publicly available Tilletia genomes and that genes on the novel arm are upregulated upon infection, suggesting that this unique chromosomal segment may have played a critical role in S. buchloëana's evolution and host specificity. Salmacisia buchloëana has one of the largest fractions of serine peptidases (1.53% of the proteome) and one of the highest GC contents (62.3%) in all classified fungi. Analysis of codon base composition indicated that GC content is controlled more by selective constraints than directional mutation and that S. buchloëana has a unique bias for the serine codon UCG. Finally, we identify three inteins within the S. buchloëana genome, two of which are located in a gene often used in fungal taxonomy. The genomic and transcriptomic resources generated here will aid plant pathologists and breeders by providing insight into the extracellular components contributing to sex determination in dioecious grasses.


An optimized protocol for rearing Fopius arisanus, a parasitoid of Tephritid fruit flies.
Fopius arisanus (Sonan) is an important parasitoid of Tephritid fruit flies for at least two reasons. First, it is the one of only three opiine parasitoids known to infect the host during the egg stage(1). Second, it has a wide range of potential fruit fly hosts. Perhaps due to its life history, F. arisanus has been a successfully used for biological control of fruit flies in multiple tropical regions(2-4). One impediment to the wide use of F. arisanus for fruit fly control is that it is difficult to establish a stable laboratory colony(5-9). Despite this difficulty, in the 1990s USDA researchers developed a reliable method to maintain laboratory populations of F. arisanus(10-12). There is significant interest in F. arisanus biology(13,14), especially regarding its ability to colonize a wide variety of Tephritid hosts(14-17); interest is especially driven by the alarming spread of Bactrocera fruit fly pests to new continents in the last decade(18). Further research on F. arisanus and additional deployments of this species as a biological control agent will benefit from optimizations and improvements of rearing methods. In this protocol and associated video article we describe an optimized method for rearing F. arisanus based on a previously described approach(12). The method we describe here allows rearing of F. arisanus in a small scale without the use of fruit, using materials available in tropical regions around the world and with relatively low manual labor requirements.


Vanillylamide-based propanolamine derivative displays alpha/beta-adrenoceptor blocking and vasodilating properties.
A propanolamine derivative with vanillylamide base, KMUP 880602, was first investigated under in vivo and in vitro conditions. IV KMUP 880602 (0.1, 0.5, 1.0, and 2.0 mg/kg) produced dose-dependent hypotensive and bradycardia responses in pentobarbital-anesthetized Wistar rats. KMUP 880602 also markedly inhibited both the tachycardia effects induced by (-)isoproterenol and arterial pressor responses induced by phenylephrine. In isolated guinea pig tissues, KMUP 880602 competitively antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses. The apparent pA2 values KMUP 880602 were 7.24 +/- 0.08 (right atria), 7.42 +/- 0.07 (left atria), and 6.24 +/- 0.06 (trachea). KMUP 880602 also produced a competitive antagonism of norepinephrine-induced contraction in the isolated rat aorta with pA2 values of 7.64 +/- 0.18. In the radioligand-binding assay, [3H]CGP-12177 binding to rat ventricle and lung tissues and [3H]prazosin binding to brain membranes were inhibited by KMUP 880602 with pKi values of 7.27, 6.08, and 8.25, respectively. In isolated rat thoracic aorta, the vasorelaxant effects of KMUP 880602 on phenylephrine-induced contractions were attenuated by pretreatment with tetraethylammonium (10-3 M) and charybdotoxin (10-7 M) but not by glibenclamide, 4-aminopyridine, and apamin. In conclusion, KMUP 880602 is an alpha/beta-adrenoceptor blocker, with selective beta1-adrenoceptor blocking and vascular smooth muscle relaxation activities. Particularly, the vasorelaxant effect of KMUP 880602 is partially mediated by the opening of charybdotoxin-sensitive K+ channel.


Contribution of retinoic acid receptor gamma to retinoid-induced craniofacial and axial defects.
Exogenous retinoic acid (RA) administered during mouse embryogenesis can alter the pattern of the axial skeleton during two developmental periods: an early window (7 to 8.5 days post-coitum; dpc) and a late window (9.5 to 11.5 dpc). Treatment during the early window results in vertebral homeotic transformations (predominantly posteriorizations) concomitant with rostral shifts in Hox gene expression, while treatment at the later window results in similar transformations without detectable alterations in Hox gene expression patterns. Mice null for retinoic acid receptor gamma (RAR gamma) exhibit axial defects, including homeosis of several vertebrae, therefore establishing a role for this receptor in normal axial specification RAR gamma null mutants are also completely resistant to RA-induced spina bifida, which occurs in wildtype embryos treated at 8.5-9.0 dpc, suggesting that this receptor specifically transduces at least a subset of the teratogenic effects of retinoids. To further investigate the role of RAR gamma in RA-induced defects during the early and late windows of retinoid-sensitive vertebral patterning, RAR gamma heterozygotes were intercrossed, pregnant females treated with vehicle or RA at 7.3, 10.5 or 11.5 dpc and full-term fetuses assessed for skeletal defects. Relative to wildtype littermates, RAR gamma null mutants treated at 7.3 dpc were markedly resistant to RA-induced embryolethality, craniofacial malformations, and neural tube defects. Furthermore, while RAR gamma null mutants were modestly resistant to certain vertebral malformations elicited by RA treatment at 7.3, they exhibited more pronounced resistance following treatment at 10.5 and 11.5 dpc. Moreover, several of the vertebral defects inherent to the RAR gamma null phenotype were abolished by RA treatment specifically at 10.5 dpc, suggesting that RAR alpha and/or RAR beta isoforms may substitute for certain RAR gamma functions, and that RAR gamma may elicit its normal effects on vertebral morphogenesis at this developmental stage.


Approaching a zero-waste strategy by reuse in New York City: Challenges and potential.
In New York City (NYC), the aspiring target of zero waste to landfills is robustly engaging the often poorly understood solid waste management technique of reuse. The reuse activities occurring in NYC are reported, accounting for the quantities of reuse of various products, such as furniture, appliances and automobile accessories, amongst others. The quantities of products are translated to reuse mass and net CO2-eq emissions saved as a consequence of reuse. This quantitative assessment employs the Reuse Impact Calculator (RIC), based on the Waste Reduction Model (WARM). The RIC is a novel calculator used to quantitatively assess the environmental impact of material reuse. It uses the information about the material to be reused from the WARM database and estimates the emissions and energy savings based on the product's final destination, that is, reuse, landfill, recycle or composting. A close monitoring of reuse activities in NYC shows 45 × 106 kg of reuse occurring for different products that would otherwise be directed to landfills. The net emissions reduced annually by reuse is approximately 122 × 106 kg of CO2-eq. This article compares the NYC reuse activities with that occurring in some select cities of the world. It is shown that the maximum recycle potential is saturated at 66%, and only auxiliary strategies like reuse can achieve the zero waste to landfill ambitions. Furthermore, this work discusses the role of reuse in the circular economy, wherein the resource utilization is maximized by increasing the shelf life of the product, and thereby enabling a maximum reuse potential.


Fluorescent DNA nanotags featuring covalently attached intercalating dyes: synthesis, antibody conjugation, and intracellular imaging.
We have synthesized fluorescent DNA duplexes featuring multiple thiazole orange (TO) intercalating dyes covalently attached to the DNA via a triazole linkage. The intercalating dyes stabilize the duplex against thermal denaturation and show bright fluorescence in the green region of the spectrum. The emission color can be changed to orange or red by addition of energy-accepting Cy3 or Cy5 dyes attached covalently to the DNA duplex. The dye-modified DNA duplexes were then attached to a secondary antibody for intracellular fluorescence imaging of centrosomes in Drosophila embryos. Bright fluorescent foci were observed at the centrosomes in both the donor (TO) and acceptor (Cy5) channels, because the energy transfer efficiency is moderate. Monitoring the Cy5 emission channel significantly minimized the background signal because of the large shift in emission wavelength allowed by energy transfer.


Multiwalled carbon nanotubes as efficient adsorbent for solid-phase extraction of chemical warfare agents and related chemicals from water.
Optimization of extraction and enrichment parameters of chemical warfare agents and their related chemicals from water are presented using multiwalled carbon nanotubes (MWCNTs) as solid-phase extractant. Selected analytes were O,O'-dialkyl alkylphosphonates, nerve agent and mustards. Extraction parameters, including sample volume, nature and volume of washing and eluting solvent, were optimized. Recoveries of analytes were determined by GC-MS and ranged from 81 to 104%. A comparison with C(18), hydrophilic-lipophilic balance and active carbon sorbents demonstrated the superiority of MWCNTs for non-toxic analogues of nerve agents. Optimized conditions involve 40 mg MWCNTs as the sorbent, 5.0 mL water as the washing solvent, 3 mL ethyl acetate as the eluent and sample loading of 10 mL water spiked at 0.1 μg/mL. The limits of detection (LOD) were achieved down to 1 and 0.05 ng/mL in full scan and selected ion-monitoring modes, respectively.


Guatemalans' practices for health promotion and the meaning of respect afforded them by health care providers.
This descriptive study, the second part of a multinational study of Central Americans and Mexicans, describes Guatemalans' practices for health promotion and wellness, disease and illness prevention, and the meaning of respect afforded them by health care providers. Understanding a person's beliefs and values when planning nursing and health care interventions helps the caregiver provide culturally acceptable care that improves clients' satisfaction and health status. Culturally respectful, acceptable, and appropriate care conserves the utilization of human, material, and financial resources. There were 25 participants in this sample. This study uses selected primary and secondary characteristics of culture and selected domains from the Purnell model for cultural competence as guides for questionnaire development, review of the literature, data analysis, and discussion of the findings.


Maternal knowledge of acute seizures.
To study maternal knowledge -of, and behavior during acute seizures. A cross sectional study conducted from September 2013 to January 2014 included consecutive mothers presenting at the Pediatric Neurology Clinics of King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. A structured 30-item questionnaire was designed to examine their demographics, knowledge, and behavior on acute seizures. A total of 92 mothers were interviewed and 41% witnessed at least one acute seizure in their affected child (range 1-15 years, mean 4.5). Up to 26% felt not knowledgeable at all regarding the acute care and management of seizure. Mothers with higher education (college or university degree) were more likely to feel very knowledgeable (19% versus 11%, p=0.02). Only 10% were aware of an antiepileptic drug that could be used at home to stop prolonged seizures, and 35% mentioned that they would wait for 15 minutes before taking the child to the emergency department. Most mothers (93%) wanted more information. Those who felt strongly regarding that (66%), were more likely to be younger (<27 years) (p=0.01), and have at least 3 out of 7 mismanagement decisions (p=0.003). Maternal level of knowledge and behavior during acute seizures needs improvement. Many mothers have significant misinformation, negative behavior, and poor management practices. Increased awareness and educational programs are needed.


Better to take one long or two quick looks? Independent processing of evidence from discrete visual presentations.
Should we prefer one long look to two quick looks of equal overall duration? The authors systematically compared conditions in which a circular letter array was available either for a single look of 2d ms duration (onset asynchrony [SOA] from target to mask) or for two separate looks of d ms each. On the basis of the geometry of the underlying psychometric function relating the SOA to the probability of target identification, separate activation models with peaked hazard functions predict that for short SOAs single long looks would lead to better identification performance and that this advantage decreases (and may turn into a disadvantage) with increasing SOA. These predictions were tested, confirmed, and extended in 5 letter-identification experiments that focused on the mechanism by which information extracted from single arrays is integrated across different looks.


Characterization of carotenoid biosynthetic pathway genes in the pea aphid (Acyrthosiphon pisum) revealed by heterologous complementation and RNA interference assays.
Carotenoids are involved in many essential physiological functions and are produced from geranylgeranyl pyrophosphate through synthase, desaturase, and cyclase activities. In the pea aphid (Acyrthosiphon pisum), the duplication of carotenoid biosynthetic genes, including carotenoid synthases/cyclases (ApCscA-C) and desaturases (ApCdeA-D), through horizontal gene transfer from fungi has been detected, and ApCdeB has known dehydrogenation functions. However, whether other genes contribute to aphid carotenoid biosynthesis, and its specific regulatory pathway, remains unclear. In the current study, functional analyses of seven genes were performed using heterologous complementation and RNA interference assays. The bifunctional enzymes ApCscA-C were responsible for the synthase of phytoene, and ApCscC may also have a cyclase activity. ApCdeA, ApCdeC, and ApCdeD had diverse dehydrogenation functions. ApCdeA catalyzed the enzymatic conversion of phytoene to neurosporene (three-step product), ApCdeC catalyzed the enzymatic conversion of phytoene to ζ-carotene (two-step product), and ApCdeD catalyzed the enzymatic conversion of phytoene to lycopene (four-step product). Silencing of ApCscs reduced the expression levels of ApCdes, and silencing these carotenoid biosynthetic genes reduced the α-, β-, and γ-carotene levels, as well as the total carotenoid level. The results suggest that these genes were activated and led to carotenoid biosynthesis in the pea aphid.


Neoadjuvant chemoradiotherapy for locally advanced rectal cancer: The debate continues.
Rectal carcinoma represents the 30% of all colorectal cancers, with about 40000 new cases/years. In the past two decades, the management of rectal cancer has made important progress, highlighting the main role of a multimodality strategy approach, combining surgery, radiation therapy and chemotherapy. Nowadays, surgery remains the primary treatment and neo-adjuvant chemoradiotherapy, based on fluoropyrimidine (5-FU) continuous infusion, is considered the standard in locally advanced rectal carcinoma. The aim is to reduce the incidence of local recurrence and to perform a conservative surgery. To improve these purposes different drugs combination have been tested in the neo-adjuvant setting. At American Society of Clinical Oncology 2014 an important abstract was presented focusing on the role of adding oxaliplatin to concomitant treatment, in patients with locally advanced rectal carcinoma. Rodel et al reported on the CAO/ARO/AIO-04 randomized phase III trial that compared standard treatment with 5-FU and radiation therapy, to oxaliplatin plus 5-FU in association with radiation therapy. The addition of oxaliplatin to the neo-adjuvant treatment has been shown to improve disease-free survival from 71.2% to 75.9% (P = 0.03). This editorial was planned to clarify the optimal treatment in patients with locally advanced rectal cancer, considering the results from CAO/ARO/AIO-04 study.


Correlation of digital health use and chronic pain coping strategies.
Digital health is an increasingly popular tool for patient engagement, having shown great success in arenas such as medication adherence, management of chronic conditions, and patient safety. Given the growth of chronic pain diagnoses, it is imperative to find new technologies to improve care for this particular population. Little research has catalogued the use of digital health in the chronic pain patient population. This manuscript's objective was to describe current patterns of digital health usage among chronic pain patients and how digital health use correlates with health care utilization and health outcomes. A cross-sectional survey was administered to patients with a self-identified chronic pain diagnosis participating in 'Patients Like Me'® (PLM), an organization that directly collects data from patients experiencing chronic health conditions, with emphasis on patient-centered outcomes and experiences interacting with the health care system. Validated measures of healthcare utilization, chronic pain management, and digital health use were adapted for the survey. Digital health was defined as the use of online sites, social media, and mobile phone applications before, during, or after healthcare utilization. Descriptive statistics, chi square tests, logistic regression, and linear regression were used as appropriate for analysis. Among 565 respondents (mean age 51.3, 87.2% female, 45.7% publicly insured), most participants (89.5%) reported some digital health use. Females and users below the age of 50 were more likely to use multiple forms of digital health. Healthcare utilization, education level, and race/ethnicity did not correlate with digital health use. Patients using more types of digital health reported significantly higher levels of pain coping skills in the realms of social support, relaxation, and exercise. Digital health use is common among a wide range of patients with chronic pain diagnoses. The use of multiple forms of digital health is associated with improved chronic pain coping mechanisms. Future work should explore the directional relationship between digital health tools and chronic pain coping skills, as well as which components of digital health have the most effect on chronic pain management and other patient-centered outcomes.


Pneumococcal conjugate vaccine: do not routinely vaccinate adults aged 65 years and older.
A randomised placebo-controlled trial of 13-valent pneumococcal conjugate vaccine was conducted in about 84 500 adults aged 65 years and older, with no particular risk factors. Four years on average after vaccination, there was no reduction in either mortality or the overall incidence of community-acquired pneumonia. It was necessary to vaccinate about 1000 individuals in order to prevent one case of vaccine-type pneumococcal pneumonia during the 4-year follow-up period.


Automated Glaucoma Screening and Diagnosis Based on Retinal Fundus Images Using Deep Learning Approaches: A Comprehensive Review.
Glaucoma is a chronic eye disease that may lead to permanent vision loss if it is not diagnosed and treated at an early stage. The disease originates from an irregular behavior in the drainage flow of the eye that eventually leads to an increase in intraocular pressure, which in the severe stage of the disease deteriorates the optic nerve head and leads to vision loss. Medical follow-ups to observe the retinal area are needed periodically by ophthalmologists, who require an extensive degree of skill and experience to interpret the results appropriately. To improve on this issue, algorithms based on deep learning techniques have been designed to screen and diagnose glaucoma based on retinal fundus image input and to analyze images of the optic nerve and retinal structures. Therefore, the objective of this paper is to provide a systematic analysis of 52 state-of-the-art relevant studies on the screening and diagnosis of glaucoma, which include a particular dataset used in the development of the algorithms, performance metrics, and modalities employed in each article. Furthermore, this review analyzes and evaluates the used methods and compares their strengths and weaknesses in an organized manner. It also explored a wide range of diagnostic procedures, such as image pre-processing, localization, classification, and segmentation. In conclusion, automated glaucoma diagnosis has shown considerable promise when deep learning algorithms are applied. Such algorithms could increase the accuracy and efficiency of glaucoma diagnosis in a better and faster manner.


Remarkable Improvement in the Mechanical Properties and CO2 Uptake of MOFs Brought About by Covalent Linking to Graphene.
Metal-organic frameworks (MOFs) are exceptional as gas adsorbents but their mechanical properties are poor. We present a successful strategy to improve the mechanical properties along with gas adsorption characteristics, wherein graphene (Gr) is covalently bonded with M/DOBDC (M=Mg(2+) , Ni(2+) , or Co(2+) , DOBDC=2,5-dioxido-1,4-benzene dicarboxylate) MOFs. The surface area of the graphene-MOF composites increases up to 200-300 m(2) g(-1) whereas the CO2 uptake increases by ca. 3-5 wt % at 0.15 atm and by 6-10 wt % at 1 atm. What is significant is that the composites exhibit improved mechanical properties. In the case of Mg/DOBDC, a three-fold increase in both the elastic modulus and hardness with 5 wt % graphene reinforcement is observed. Improvement in both the mechanical properties and gas adsorption characteristics of porous MOFs on linking them to graphene is a novel observation and suggests a new avenue for the design and synthesis of porous materials.


Sex-specific allelic transmission bias suggests sexual conflict at MC1R.
Sexual conflict arises when selection in one sex causes the displacement of the other sex from its phenotypic optimum, leading to an inevitable tension within the genome - called intralocus sexual conflict. Although the autosomal melanocortin-1-receptor gene (MC1R) can generate colour variation in sexually dichromatic species, most previous studies have not considered the possibility that MC1R may be subject to sexual conflict. In the barn owl (Tyto alba), the allele MC1RWHITE is associated with whitish plumage coloration, typical of males, and the allele MC1RRUFOUS is associated with dark rufous coloration, typical of females, although each sex can express any phenotype. Because each colour variant is adapted to specific environmental conditions, the allele MC1RWHITE may be more strongly selected in males and the allele MC1RRUFOUS in females. We therefore investigated whether MC1R genotypes are in excess or deficit in male and female fledglings compared with the expected Hardy-Weinberg proportions. Our results show an overall deficit of 7.5% in the proportion of heterozygotes in males and of 12.9% in females. In males, interannual variation in assortative pairing with respect to MC1R explained the year-specific deviations from Hardy-Weinberg proportions, whereas in females, the deficit was better explained by the interannual variation in the probability of inheriting the MC1RWHITE or MC1RRUFOUS allele. Additionally, we observed that sons inherit the MC1RRUFOUS allele from their fathers on average slightly less often than expected under the first Mendelian law. Transmission ratio distortion may be adaptive in this sexually dichromatic species if males and females are, respectively, selected to display white and rufous plumages.