Induction of RAC1 protein translation and MKK7/JNK-dependent autophagy through dicer/miR-145/SOX2/miR-365a axis contributes to isorhapontigenin (ISO) inhibition of human bladder cancer invasion.
Although our previous studies have identified that isorhapontigenin (ISO) is able to initiate autophagy in human bladder cancer (BC) cells by activating JNK/C-Jun/SESN2 axis and possesses an inhibitory effect on BC cell growth, association of autophagy directly with inhibition of BC invasion has never been explored. Also, upstream cascade responsible for ISO activating JNK remains unknown. Thus, we explored both important questions in the current study and discovered that ISO treatment initiated RAC1 protein translation, and its downstream kinase MKK7/JNK phosphorylation/activation, and in turn promoted autophagic responses in human BC cells. Inhibition of autophagy abolished ISO inhibition of BC invasion, revealing that autophagy inhibition was crucial for ISO inhibition of BC invasion. Consistently, knockout of RAC1 also attenuated induction of autophagy and inhibition of BC invasion by ISO treatment. Mechanistic studies showed that upregulation of RAC1 translation was due to ISO inhibition of miR-365a transcription, which reduced miR-365a binding to the 3'-UTR of RAC1 mRNA. Further study indicated that inhibition of miR-365a transcription was caused by downregulation of its transcription factor SOX2, while ISO-promoted Dicer protein translation increased miR-145 maturation, and consequently downregulating SOX2 expression. These findings not only provide a novel insight into the understanding association of autophagy induction with BC invasion inhibition by ISO, but also identify an upstream regulatory cascade, Dicer/miR145/SOX2/miR365a/RAC1, leading to MKK7/JNKs activation and autophagy induction.


Chromosome 7 translocation breakpoints in male carriers: clinical features and implications for genetic counseling.
Balanced reciprocal translocations are associated with reproductive failure. Some reciprocal translocation carriers exhibit azoospermia or oligozoospermia, and an association exists between these chromosomal abnormalities and recurrent abortion. Previous reports have indicated the involvement of chromosome 7 translocations in male infertility and recurrent miscarriage. A translocation breakpoint can occur within an important gene, interrupting its structure and leading to male infertility. However, clinical characteristics resulting from chromosome 7 translocation breakpoints have not been studied. Here, we report such breakpoints and their associated clinical features, to enable informed genetic counseling of carriers. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among these 82 individuals, 14 (17.07%) carried a chromosome 7 translocation, of which, five presented with pregestational infertility and clinical manifestations of oligozoospermia or necrospermia, while nine presented with gestational infertility (i.e., were able to conceive, but often resulting in miscarriage). Breakpoints at 7q31 and 7q36 were associated with pregestational infertility, whereas those at 7p10, 7q21.2, 7q22, and 7q32 were connected to gestational infertility. However, the breakpoint at 7p15 was associated with both. Chromosome 7 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the various molecular technologies available for assisted reproduction.


Kinship networks and child fostering in labor migration from Ilocos, Philippines to Italy.
"This paper is an attempt to analyze the process of contemporary overseas labor migration from a village in the Ilocos region in the Philippines to Italy. As such, it will seek to outline the basic characteristics of the process of migration and examine them in relation to the local social structure. It will demonstrate how the Ilocanos responded to new opportunities of migration by manipulating existing social relations. Particular attention will be given to the process of constructing kinship networks among the migrants and the practice of fosterage in the homeland community, both of which are considered as adaptive processes to the new migration opportunity."


Endocrine cell carcinoma of gall bladder.
Primary neuroendocrine carcinoma of the gall bladder is rare. We report a 70-year-old woman with a gall bladder mass and liver metastases; fine-needle aspiration cytology from these revealed neuroendocrine carcinoma. There was no evidence of any other primary site. The patient was treated symptomatically; she died within a month of discharge from hospital.


Plasma adrenomedullin levels in children with asthma: any relation with atopic dermatitis?
Asthma is a chronic, inflammatory disease of the airway, and adrenomedullin (ADM) may have some effects against bronchoconstriction. However, the role(s) of ADM in asthmatic children have not been evaluated yet. The aims of this study were to determine if there are any changes in plasma ADM levels during acute asthma attack, and to search for any association between allergen sensitivity and ADM level in asthmatic children. Twenty-seven children with acute asthma attack, ranging in age from 5 to 15 years were investigated and compared with 20 controls. Plasma ADM levels (ng/mL) were measured by ELISA method. No significant difference was found in ADM levels between the controls and patients in either the acute attack or remission period. Plasma ADM levels were significantly higher in the acute attack (p=0.043) compared to the remission period in patients who were considered as having a "severe attack" according to GINA (Global Initiative for Asthma) classification. There were statistically significant correlations between the patients' AlaTOP and Food Panel 7 levels and plasma ADM levels in the acute attack period (p=0.010, p=0.001, respectively). The ADM levels in patients with a history of atopic dermatitis were significantly higher in the acute attack period compared to those without a history of atopic dermatitis (p=0.007). We speculate that ADM may have a role in children with atopic dermatitis, and may also have a role in the immuno-inflammatory process of asthma.


Structure and thermorheology of concentrated pluronic copolymer micelles in the presence of laponite particles.
Small-angle neutron scattering and thermorheology techniques are used to investigate in detail the effect of laponite particles in aqueous solutions of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), PEO-PPO-PEO, block copolymers in the concentrated regime. At high polymer concentration or temperature, the micellar solutions exhibit a phase transition from fluid to crystal due to crowding of the micelles. The addition of laponite is found to disturb this phase transition. The adsorption of the copolymer unimers onto laponite in large amounts describes these findings. It is shown that the preferred adsorption of the copolymer chains results in a sufficient increase in free volume for the remaining micelles to yield the observed enhancement of the structural disorder.


Test-retest and Interrater Reliability of the Video Head Impulse Test in the Pediatric Population.
Determine reliability of horizontal and vertical video head impulse test (vHIT) and effect of maturation on angular vestibular ocular reflex (AVOR) gain estimations and peak head velocities of individual canals in typically developing children and adolescents. Reliability study. University research laboratory : Two normal adults mean age 51.5 ± 0.5 years and 28 typically developing children and adolescents mean age 10 ± 3.5 years (range, 4.33-17.25 years). Mean AVOR gain estimate and peak head impulse velocity for individual canals. In adult sample, mean AVOR gain estimates were 1.00 to 1.04 for lateral and 1.07 to 1.13 for vertical canals. In pediatric sample, mean AVOR gain estimates were 1.00 to 1.04 for lateral and 1.03 to 1.08 vertical canals. Mean AVOR gain intrarater reliability scores (intraclass correlation coefficient [ICC] ≥ 0.821 ≤ 0.945) and interrater reliability scores (ICC ≥ 0.800 ≤ 0.971) had good consistency. For each canal, across each age group, the range of percentage of trials with peak head velocities greater than 100 degrees/s was 32 to 49% right lateral, 31 to 49% left lateral, 0 to 11% right anterior, 3 to 4% left anterior, 1 to 7% right posterior, and 2 to 8% left posterior. Children aged less than 12 years, required 10 to 49% more trials compared with adults to obtain five valid, filtered trials. Adolescents required a similar number of trials compared with adults. In pediatric population, vHIT is a reliable clinical test to quantify individual canal function using high velocity head impulses. With children, it was difficult to acquire head impulse velocities of greater than 100 degrees/s especially in the plane of the vertical canals. These higher head velocities are required to reveal asymmetry in compensatory eye movements.


Interindividual differences in o,p'-DDD enantiomer kinetics examined in Göttingen minipigs.
Five minipigs were given a single oral dose of a racemic mixture of o,p'-DDD (30 mg kg(-1)b.w., EF=0.49). Blood plasma and subcutaneous adipose tissue were collected for analysis, at different time-points over 180 d. At the end of the experiment also liver, kidney and brain tissue were collected. Low concentrations of o,p'-DDD still remained after 180 d in plasma (mean 0.5+/-0.3 ng g(-1)f.w.) and in adipose tissue (mean 40+/-40 ng g(-1)f.w.). The mean concentrations in liver and kidney were 500+/-300 pg g(-1)f.w. and 90+/-50 pg g(-1)f.w., respectively. The enantiomers of o,p'-DDD were isolated by HPLC and the absolute configuration of the enantiomers were determined by X-ray crystallography and polarimetry as R-(+)-o,p'-DDD and S-(-)-o,p'-DDD. The enantiomer fractions (EFs) of o,p'-DDD were determined in plasma, adipose tissue and kidney using GC/ECD equipped with a chiral column. The EFs of o,p'-DDD in the individual minipigs showed large variability, ranging from 0.2 to 0.6 after 24h in plasma and from 0.2 to 0.7 after 90 d in adipose tissue. Hence in two of the minipigs, the S-(-)-o,p'-DDD enantiomer was dominating while the other enantiomer, R-(+)-o,p'-DDD was dominating in three minipigs. We propose that a yet not identified factor related to polymorphism, regulating the metabolism and/or elimination of the enantiomeric o,p'-DDD, is responsible for the differences in enantiomeric retention of the compound in the minipigs.


Increasing physician referrals.
The topic of enhancing physician referrals is not a new one. Studies on the subject date back to 1957. Today, there is an increased concern with methods to assure the viability of group practices and related or affiliated hospitals. Physician referral enhancement is one of a number of viable options that could help to assure a group practice's survival for the future and deserves renewed attention. Specifically, one should enhance physician communication.


On the extinction of radiation by a homogeneous but spatially correlated random medium: comment.
Some extinction laws for radiation transmitted through inhomogeneous random media were discussed by Kostinski [J. Opt. Soc. Am. A 18, 1929 (2001)] by means of a complicated use of concepts of statistical theory of fluids. We show that these extinction laws are readily obtained in terms of classical probability theory. The validity of exponential extinction laws for large observation distances (as compared with the size of inhomogeneities of a medium) is proven and emphasized. It is shown that Kostinski's results turn out to be applicable to small observation distances only, for which the concept of extinction law is hardly applicable.


Resin activation capture technology: libraries from stabilized acyl-pyridinium on solid support.
REsin Activation/Capture APproach or REACAP Technology, a novel approach to the synthesis of compound libraries, capitalizes on the formation and retention of a resin-bound reactive intermediate, which can be subsequently transformed into a stable, covalently attached molecule. Any unreacted "reactive intermediate" is quenched and removed from the resin upon work-up, leaving only the desired product on the solid support. In contrast to more traditional solid-supported chemistry that must address issues such as resin-loading, capping of unreactive functionalized moieties, and reaction yields, REACAP offers an attractive alternative with the focus more on the purity of the released products and less on yield. In an endeavor to generate truly non-peptide leads, we describe herein the synthesis of N-acyl-2-substituted-dihydro-4-pyridones, dihydro-4-pyridones, 4-ketopiperidines, tetrahydropyridines, and 2-acyl-3,7,8-substituted-5-oxo-2-azabicyclo[2.2.2]octane and triaza analogs using REACAP Technology.


An antifungal naphthoquinone, xanthones and secoiridoids from Swertia calycina.
A chemical and biological screening of 25 species of the Gentianaceae family has been undertaken. Both methanolic and dichloromethane extracts of Swertia calycina exhibited a strong antifungal activity against Cladosporium cucumerinum and Candida albicans. The compound responsible for this activity has been isolated and identified as 2-methoxy-1,4-naphthoquinone. It is the first naphthoquinone to be described in Gentianaceae species. LC-UV and LC-TSP-MS analysis of the crude extracts of Swertia calycina also allowed on-line identification of six known xanthones and secoiridoids.


Juvenile osteochondritis dissecans.
Juvenile osteochondritis dissecans is a diagnosis based on plain radiographic appearance. Although it is on occasion difficult to decide whether the observed radiographic abnormality represents osteochondritis dissecans or physiologic irregular ossification, 50% of children should evidence healing with nonoperative activity modification management. In those who fail this regimen, the majority require simple drilling of the lesion through intact articular cartilage.


Role of ROS signaling in differential hypoxic Ca2+ and contractile responses in pulmonary and systemic vascular smooth muscle cells.
Hypoxia causes a large increase in [Ca2+]i and attendant contraction in pulmonary artery smooth muscle cells (PASMCs), but not in systemic artery SMCs. The different responses meet the respective functional needs in these two distinct vascular myocytes; however, the underlying molecular mechanisms are not well known. We and other investigators have provided extensive evidence to reveal that voltage-dependent K+ (KV) channels, canonical transient receptor potential (TRPC) channels, ryanodine receptor Ca2+ release channels (RyRs), cyclic adenosine diphosphate-ribose, FK506 binding protein 12.6, protein kinase C, NADPH oxidase and reactive oxygen species (ROS) are the essential effectors and signaling intermediates in the hypoxic increase in [Ca2+]i in PASMCs and HPV, but they may not primarily underlie the diverse cellular responses in pulmonary and systemic vascular myocytes. Hypoxia significantly increases mitochondrial ROS generation in PASMCs, which can induce intracellular Ca2+ release by opening RyRs, and may also cause extracellular Ca2+ influx by inhibiting KV channels and activating TRPC channels, leading to a large increase in [Ca2+]i in PASMCs and HPV. In contrast, hypoxia has no or a minor effect on mitochondrial ROS generation in systemic SMCs, thereby causing no change or a negligible increase in [Ca2+]i and contraction. Further preliminary work indicates that Rieske iron-sulfur protein in the mitochondrial complex III may perhaps serve as a key initial molecular determinant for the hypoxic increase in [Ca2+]i in PASMCs and HPV, suggesting its potential important role in different cellular changes to respond to hypoxic stimulation in pulmonary and systemic artery myocytes. All these findings have greatly improved our understanding of the molecular processes for the differential hypoxic Ca2+ and contractile responses in vascular SMCs from distinct pulmonary and systemic circulation systems.


Prevalence of podoconiosis and its associated factors in Gamo zone, Southern Ethiopia, 2021.
Podoconiosis is a chronic non-infectious preventable disease. Though not fatal, it may cause social, economic and physical disability. Ethiopia is projected to bear one-fourth (25%) of the global burden of podoconiosis. Despite its huge economic impact and chronic morbidity and disability, podoconiosis seems to be neglected. Therefore, the aim of this study was to assess the prevalence of podoconiosis and its associated factors in Gamo zone, Southern Ethiopia. A community based cross sectional study was conducted among 683 household members. A multistage sampling method was used to select study participants. Binary logistic regression model was fitted to identify factors associated with podoconiosis. Odds ratio with 95% confidence interval was computed to determine the level of significance; in multivariable analysis, variables with a P value less than 0.05 were considered as statistically significant. The prevalence of podoconiosis was 6.2% (95%CI: 4.3-8%). The significantly contributed factors for the prevalence of podoconiosis were wealth index (AOR = 0.249, 95%CI = 0.073-0.845), number of shoes owned (AOR = 6.199, 95% CI = 1.281-29.98), times when individual do not wear shoes (AOR = 2.448, 95%CI = 1.041-5.754), soap utilization during foot washing (AOR = 2.773, 95%CI = 1.210-6.355) and family history of leg swelling (AOR = 4.69, 95%CI = 2.215-9.935). This study showed that there was significant burden of podoconiosis in the study area. Wealth index, times when individual do not wear shoes, number of shoes owned, soap utilization during foot washing, and family history of leg swelling were significantly associated with podoconiosis. It is recommended to practice secondary prevention which includes regular foot hygiene and wearing shoes, and the use of antiseptic soaks.


Fibroblastic rheumatism: a case without rheumatological symptoms.
Fibroblastic rheumatism is a rare syndrome characterized by the association of multiple cutaneous nodules with symmetric polyarthritis. We report on a patient who presented a 4-year history of pink to skin-coloured nodular lesions symmetrically localized at para-articular sites without evident rheumatological symptoms. Histopathology of a skin nodule led to the diagnosis of fibroblastic rheumatism showing a poorly circumscribed dermal proliferation of spindle and stellate fibroblast-like cells embedded in thickened collagen bundles with a marked reduction of elastic fibres. X-rays of both hands and feet showed metacarpophalangeal, metatarsalphalangeal and interphalangeal erosions, unexpected by patient history. This case of fibroblastic rheumatism appears unique in view of the absence of any clinical manifestation of polyarthritis at 7 years from appearance of skin lesions.


Successful lung transplant from donor after cardiac death: a potential solution to shortage of thoracic organs.
Lung transplant is an effective treatment for patients with end-stage lung disease but is limited because of the shortage of acceptable donor organs. Organ donation after cardiac death is one possible solution to the organ shortage because it could expand the pool of potential donors beyond brain-dead and living donors. We report the preliminary experience of Mayo Clinic with donation after cardiac death, lung procurement, and transplant.


Unidirectionally aligned copper hydroxide crystalline nanorods from two-dimensional copper hydroxy nitrate.
We were able to synthesize unidirectionally aligned copper hydroxide nanorods from two-dimensional copper hydroxide nitrate by anion exchange reaction using NaOH without any membrane or template. The structural conversion from Cu2(OH)3NO3 to Cu(OH)2 was confirmed by XRD and FT-IR data. The synthesized copper hydroxide nanorods showed unidirectionally aligned and tightly bound arrays on a hexagonal plate, leading to giant nanorod bundles.


LINC00665 sponges miR-641 to promote the progression of breast cancer by targeting the SNF2-related CREBBP activator protein (SRCAP).
The regulatory network of competing endogenous RNAs (ceRNA) exists widely in tumors and affects the expression of cancer-related genes, thus playing an important role in the development and prognosis of human tumors. In this research, we explored the role and mechanism of LINC00665 as a ceRNA in breast cancer. We analyzed the expression and targets of LINC00665 in breast cancer using bioinformatics, and detected their effects on breast cancer cells by CCK8, transwell, colony formation and flow cytometry assays. From our results, LINC00665 knockdown suppressed the proliferation, migration and invasion and induced the apoptosis through inactivating the AKT/mTOR signaling pathway in MCF7 and MDA-MB-231 cells. LINC00665 had five potential downstream target miRNAs (miR-542-3p, miR-624-5p, miR-641, miR-425-5p, and miR-30-3p). In dual-luciferase report gene assay, the fluorescence activity of cells transfected with miR-641 mimics decreased, and the expression of miR-641 decreased significantly after knocking down LINC00665. miR-641 mimics significantly inhibited cell proliferation and invasion in MCF7 and MDA-MB-231 cells. We detected five potential direct targets of miR-641 using qPCR (SRCAP, SIKE1, NADK, KHDC4, and HSPG2). SRCAP expression decreased significantly in miR-641 overexpression cells and the binding of SRCAP's 3'UTR and miR-641 was further confirmed by dual-luciferase report gene assay. SRCAP blocked the proliferation and invasion inhibition induced by miR-641 or si-LINC00665 in MCF7 and MDA-MB-231 cells. In conclusion, LINC00665 could promote the survival and metastasis of breast cancer cells through sponging miR-641 and targeting SRCAP. This research provided new potential targets for targeted therapy in human breast cancer.


Proposed coupling of an electron spin in a semiconductor quantum dot to a nanosize optical cavity.
We propose a scheme to efficiently couple a single quantum dot electron spin to an optical nano-cavity, which enables us to simultaneously benefit from a cavity as an efficient photonic interface, as well as to perform high fidelity (nearly 100%) spin initialization and manipulation achievable in bulk semiconductors. Moreover, the presence of the cavity speeds up the spin initialization process beyond the GHz range.


Upgrading of liquid fuel from the pyrolysis of biomass.
Pyrolysis of biomass was carried out in a fluidized bed unit (5 kg/h) with the objective of maximizing liquid yield. Liquid product formed in pyrolysis was separated into two phases: water phase and oil phase. The oil phase was upgraded by sulfided Co-Mo-P catalyst in an autoclave. Effects of reaction conditions on the product distribution were investigated, and optimal conditions were therefore concluded. Comparison was made by analysis between the raw oil phase and the upgraded liquid fuel. The significant difference between the raw pyrolytic oil and the upgraded oil was that the former was methanol-soluble while the latter was oil-soluble.


Biosynthesis of penicillin N and cephalosporin C. Antibiotic production and other features of the metabolism of Cephalosporium sp.
1. The production of penicillin N and cephalosporin C by two mutants of a Cephalosporium sp. has been studied with cultures grown in a chemically defined medium and with suspensions of washed mycelium in water or a buffered salt solution. 2. Antibiotic synthesis began at an early stage of growth and its rate per unit weight of mycelium appeared to pass its maximum as morphological changes were occurring in young hyphae. This rate subsequently declined, but rapid production could continue after net growth had ceased. 3. In a series of shake-flask fermentations in the growth medium, increases in the yield of penicillin N above the mean were correlated with much smaller increases in the yield of cephalosporin C and vice versa. 4. In suspensions of washed mycelium, moderate decreases in the efficiency of aeration increased the yield of penicillin N and decreased that of cephalosporin C. A similar result normally followed the addition of methionine to the suspension fluid, and in both cases there was usually an increase in the yield of the two antibiotics combined. 5. The apparent intracellular concentrations of the antibiotics were much lower than those attained extracellularly and also much lower than those of most of the amino acids in the intracellular pool. No detectable amount of [(14)C]penicillin N added to the extracellular fluid was found to enter the mycelium. 6. Very small amounts of peptide material whose behaviour was similar to that of the sulphonic acid of delta-(alpha-amino-adipoyl)cysteinylvaline on paper electrophoresis at pH1.8 were found in extracts of the mycelium that had been oxidized with performic acid. 6-Aminopenicillanic acid and 7-aminocephalosporanic acid were not detected. 7. Ultrasonic treatment of the mycelium resulted in rapid fragmentation of mycelial chains, rupture of many individual cells, and the liberation of amino acids and other substances into the medium. 8. Ultrasonically treated preparations synthesized penicillin N and cephalosporin C rapidly after a lag of 12hr. Antibiotic synthesis was accompanied by the growth of hyphae from swollen mycelial fragments and by the re-establishment of permeability barriers resulting in the uptake of amino acids from the medium.


[Mono- and dizygotic twins in forensic paternity testing in practice at the Department of Forensic Medicine (Silesian Academy of Medicine, Katowice) in the years 1996-2003].
Giving an opinion on disputable paternity, concerning monozygotic twins in practice at the Department of Forensic Medicine (Silesian Academy of Medicine, Katowice) demonstrated their ideal agreement according to examined genetic markers possible. Even the mutation, which was revealed using the RFLP-VNTR method was the same for both twin sisters. In the case of dizygotic twins a firm differentiation of paternity index and probability of paternity was proved. This was the consequence of independent features segregation in first, reductive meiotic division. While the rare, out-ladder allele 16 at the CSF1PO locus was transmitted to both twins: a daughter and a son by the putative father.


Mitochondria-Targeted Chimeric Peptide for Trinitarian Overcoming of Drug Resistance.
In this report, an amphiphilic mitochondria-targeted chimeric peptide-based drug delivery system (DDS) was designed to overcome drug resistance. In vitro studies revealed that chimeric peptide could encapsulate doxorubicin (DOX) with high efficacy and target tumor mitochondria, realizing controlled release of DOX and in situ photodynamic therapy (PDT) in mitochondria. Importantly, reactive oxygen species (ROS) during PDT significantly disrupted mitochondria, leading to a dramatic decrease of intracellular adenosine 5'-triphophate (ATP). As a result, ATP-dependent efflux of DOX was remarkably inhibited. Trinitarian therapeutic strategy was developed to ablation of drug-resistant cells, that is, (1) enhanced cellular uptake of hydrophobic DOX via encapsulation in DDS, (2) combined chemo-/photodynamic therapies, and (3) suppressed generation of intracellular ATP as well as drug efflux via in situ PDT in mitochondria. This trinitarian strategy may open a new window in the fabrication of subcellular organelle destructive DDS in overcoming drug resistance.


A transverse emittance and acceptance measurement system in a low-energy beam transport line.
A transverse beam emittance and acceptance measurement system has been developed to visualize the relationship between the injected beam emittance and the acceptance of a cyclotron. The system is composed of a steering magnet, two pairs of slits to limit the horizontal and vertical phase-space, a beam intensity detector just behind the slits for the emittance measurement, and a beam intensity detector in the cyclotron for the acceptance measurement. The emittance is obtained by scanning the slits and measuring the beam intensity distribution. The acceptance is obtained by measuring the distribution of relative beam transmission by injecting small emittance beams at various positions in a transverse phase-space using the slits. In the acceptance measurement, the beam from an ion source is deflected to the defined region by the slits using the steering magnet so that measurable acceptance area covers a region outside the injection beam emittance. Measurement tests were carried out under the condition of accelerating a beam of (16)O(6+) from 50.2 keV to 160 MeV. The emittance of the injected beam and the acceptance for accelerating and transporting the beam to the entrance of the extraction deflector were successfully measured. The relationship between the emittance and acceptance is visualized by displaying the results in the same phase-plane.


Raman spectroscopy of human skin for kidney failure detection.
The object of this paper is in vivo study of skin spectral-characteristics in patients with kidney failure by conventional Raman spectroscopy in near infrared region. The experimental dataset was subjected to discriminant analysis with the projection on latent structures (PLS-DA). Application of Raman spectroscopy to investigate the forearm skin in 85 adult patients with kidney failure (90 spectra) and 40 healthy adult volunteers (80 spectra) has yielded the accuracy of 0.96, sensitivity of 0.94 and specificity of 0.99 in terms of identifying the target subjects with kidney failure. The autofluorescence analysis in the near infrared region identified the patients with kidney failure among healthy volunteers of the same age group with specificity, sensitivity, and accuracy of 0.91, 0.84, and 0.88, respectively. When classifying subjects by the presence of kidney failure using the PLS-DA method, the most informative Raman spectral bands are 1315 to 1330, 1450 to 1460, 1700 to 1800 cm-1 . In general, the performed study demonstrates that for in vivo skin analysis, the conventional Raman spectroscopy can provide the basis for cost-effective and accurate detection of kidney failure and associated metabolic changes in the skin.


[Multiresistant pathogens--a challenge for clinicians].
Gram-negative pathogens are currently isolated frequently in invasive nosocomial infections and give rise to major therapeutic problems due to their resistance pattern. Metaanalyses of randomised controlled studies have demonstrated that an antibiotic combination treatment is not indicated in many cases. However, in critically ill patients (septic shock) and also in immunocompromised patients with previous intensive care as well as broad spectrum antibiotic treatment, a combination of antibiotics is recommended. This therapy should be based on the source of the infection, on local resistance data, on antibiotic pretreatment, on basic diseases of the patient and on current liver and renal functions. The start of therapy should be as fast as possible after collection of optimal materials for microbiological analysis. Dosage of selected antibiotics should be based on rational pharmacokinetic and pharmacodynamic parameters. A de-escalation of antibiotics is strongly recommended in all international guidelines based on the microbiological results and the clinical response of the patient. New antibiotics or therapeutic strategies against multiresistant Gram-negative pathogens will not be available in the next 5 to 10 years; therefore, it is absolute mandatory to use the currently still effective antibiotics, like carbapenems and polymyxins, very rationally and restrictively.


Genotypic Characterization of Virulence Factors in Escherichia coli Isolated from Patients with Acute Cystitis, Pyelonephritis and Asymptomatic Bacteriuria.
Urinary Tract Infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) are among the most common infections worldwide. It is well-documented that the pathogenesis of UPEC is mediated by the production of a wide variety of Virulence Factors (VFs). Thus, detection of these VFs and evaluation of their association with different clinical types of UTIs could help to understand the role of these factors in pathogenesis of UPEC isolates. To investigate the genotypic characteristics of UPEC isolates and to examine the relationship between VFs and different clinical symptoms of UTI. In this cross-sectional study conducted at Pasteur Institute of Iran, a total of 156 UPEC isolated from outpatients and inpatients (symptomatic and asymptomatic UTI patients) visiting general and private hospitals in Tehran, Iran between March 2014 and February 2015 were included. Among them, 49 patients experienced at least one episode of recurrent UTI. A Polymerase Chain Reaction (PCR) assay was developed to detect the presence of different VFs in the isolates. Moreover, Pulsed-Field Gel Electrophoresis (PFGE) was used to characterize clonal relationships among UPEC isolates. The prevalence of virulence genes ranged from 0% for cdtB to 100% for fimH. The papEF, hlyA and aer genes were found to be significantly more frequent in UPEC isolated from patients with pyelonephritis, while the afa gene, the only indicator of recurrent UTIs, was more prevalent in UPEC isolated from patients with cystitis. In the present study, 34 PFGE clonal groups were found in the UPEC genome. Our findings showed that from outpatients and patients with pyelonephritis, isolates were more virulent than those isolated from inpatients and cystitis patients, respectively. PFGE displayed a large diversity in the UPEC isolates that could be considered as an evolutionary strategy in the survival of the bacteria.


Independent monitor unit calculation for intensity modulated radiotherapy using the MIMiC multileaf collimator.
A self-consistent monitor unit (MU) and isocenter point-dose calculation method has been developed that provides an independent verification of the MU for intensity modulated radiotherapy (IMRT) using the MIMiC (Nomos Corporation) multileaf collimator. The method takes into account two unique features of IMRT using the MIMiC: namely the gantry-dynamic arc delivery of intensity modulated photon beams and the slice-by-slice dose delivery for large tumor volumes. The method converts the nonuniform beam intensity planned at discrete gantry angles of 5 degrees or 10 degrees into conventional nonmodulated beam intensity apertures of elemental arc segments of 1 degree. This approach more closely simulates the actual gantry-dynamic arc delivery by MIMiC. Because each elemental arc segment is of uniform intensity, the MU calculation for an IMRT arc is made equivalent to a conventional arc with gantry-angle dependent beam apertures. The dose to the isocenter from each 1 degree elemental arc segment is calculated by using the Clarkson scatter summation technique based on measured tissue-maximum-ratio and output factors, independent of the dose calculation model used in the IMRT planning system. For treatments requiring multiple treatment slices, the MU for the arc at each treatment slice takes into account the MU, leakage and scatter doses from other slices. This is achieved by solving a set of coupled linear equations for the MUs of all involved treatment slices. All input dosimetry data for the independent MU/isocenter point-dose calculation are measured directly. Comparison of the MU and isocenter point dose calculated by the independent program to those calculated by the Corvus planning system and to direct measurements has shown good agreement with relative difference less than +/-3%. The program can be used as an independent initial MU verification for IMRT plans using the MIMiC multileaf collimators.


Specialized scanning ion-conductance microscope for imaging of living cells.
A specialized scanning ion conductance microscope (SICM) for imaging living cells has been developed from a conventional patch-clamp apparatus, which uses a glass micropipette as the sensitive probe. In contrast with other types of scanning probe microscope, the SICM probe has significant advantages for imaging living cells: it is most suitable for imaging samples immersed in water solutions; and since the probe senses ion current and does not need physical contact with the sample during the scan, any preliminary preparation of cells (fixation or adherence to a substrate) is unnecessary. We have successfully imaged murine melanocytes in growth medium. The microscope images the highly convoluted surface structures without damaging or deforming them, and reveals the true, three-dimensional relief of the cells. This instrument has considerable ability to operate, potentially simultaneously, in applications as diverse as real-time microscopy, electrophysiology, micromanipulation and drug delivery.


[Therapeutic approach to acute otitis media in primary care in an urban area. Delayed antibiotic prescription evaluation].
Acute otitis media (AOM) is one of the most frequent causes of consultation and antibiotic prescription in pediatrics. The objective of this work is to evaluate the practice of delayed antibiotic prescription in AOM in pediatrics primary care. Observational, retrospective study, through reviewing of medical records in a primary care center of Aragon Community of children with OMA in which doctors perform delayed prescription. Logistic regression analyzes possibly related to antibiotic prescription factors. 1,390 episodes of AOM are analyzed in 696 patients. Immediate antibiotic prescription is performed in 67.6% (95% CI 65.1-70.0) of episodes, exclusive symptomatic in 13.7% (95% CI 11.9-15.6), and delayed antibiotic in 18.7% (95% CI 16.7-20.8), finally being given in 53.5% (95% CI 47.4-59.5) of these. Factors significantly related to final antimicrobial dispensation in delayed prescription are aged between 0 and 2 years (OR 1.89, 95% CI 1.25-2.87), bilaterality (OR 2.54, 95% CI 1.48-4.35), ear pain (OR 0.49, 95% CI 0.29-0.82), fever (OR 2.67, 95% CI 1.95-3.65), bulging (OR 3.63, 95% CI 2.50-5.29) and otorrhea (OR 25.98, 95% CI 12.75-52.92). The same factors have influence on global prescription of antibiotics. Amoxicillin (74.6%) is the most indicated antibiotic, followed by amoxicillin-clavulanic (17.0%). Delayed prescription in AOM seems to be useful to reduce antibiotics consumption, being necessary to advance in its implantation.


Access to Saturated Thiocyano-Containing Azaheterocycles via Selenide-Catalyzed Regio- and Stereoselective Thiocyanoaminocyclization of Alkenes.
An efficient route for the synthesis of saturated thiocyano-containing azaheterocycles by selenide-catalyzed regio- and stereoselective thiocyanoaminocyclization of alkenes is disclosed. The desired products were obtained in moderate to high yields under mild conditions. The generality of this method was elucidated by its efficient application in thiocyano oxycyclization of alkenes.


Clinical outcomes of high-risk labours monitored using fetal electrocardiography.
The aim of the study was to review clinical and laboratory outcomes of a cohort of fetuses monitored during high-risk labours, simultaneously by fetal electrocardiography (FECG) and routine cardiotocography (CTG). Eighty-three parturients from the Department of Obstetrics and Gynecology of Medical University were included in the clinical study. Inclusive criteria to the study group were: (i) singleton pregnancy at term (between 37 and 42 weeks' gestation), (ii) longitudinal fetal lying, (iii) more than 2500 g of estimated fetal weight, (iv) meconium-stained liquor, and (v) induction of labour due to fetal indications. Fetal outcome parameters analysed included Apgar scores at 1st, 5th and 10th minute after birth, cord artery acid-base assessment and lactate concentrations analysis. FECG was performed during labour, until the neonate was born, with the use of single spiral scalp electrode connected to the STAN S21 heart monitor. Immediately after delivery, arterial cord blood gas and venous cord blood lactate's concentrations were analysed. The sensitivity (100%), specificity (97%), negative predictive value (NPV) (100%) and positive predictive value (33%) were higher for FECG than for CTG. Moreover, several significant correlations between episodic/baseline T/QRS ratio rises and cord artery acid-base as well as lactate concentrations were demonstrated. Correlations between episodic/baseline T/QRS ratio rises and fetal outcome parameters indicate that observed changes in FECG reflect neonatal metabolic lactate acidosis. The high sensitivity, specificity and especially very high NPV are proof that FECG serves as a reliable method for electronic fetal monitoring during high-risk labours.


Correcting for a density distribution: particle size analysis of core-shell nanocomposite particles using disk centrifuge photosedimentometry.
Many types of colloidal particles possess a core-shell morphology. In this Article, we show that, if the core and shell densities differ, this morphology leads to an inherent density distribution for particles of finite polydispersity. If the shell is denser than the core, this density distribution implies an artificial narrowing of the particle size distribution as determined by disk centrifuge photosedimentometry (DCP). In the specific case of polystyrene/silica nanocomposite particles, which consist of a polystyrene core coated with a monolayer shell of silica nanoparticles, we demonstrate that the particle density distribution can be determined by analytical ultracentrifugation and introduce a mathematical method to account for this density distribution by reanalyzing the raw DCP data. Using the mean silica packing density calculated from small-angle X-ray scattering, the real particle density can be calculated for each data point. The corrected DCP particle size distribution is both broader and more consistent with particle size distributions reported for the same polystyrene/silica nanocomposite sample using other sizing techniques, such as electron microscopy, laser light diffraction, and dynamic light scattering. Artifactual narrowing of the size distribution is also likely to occur for many other polymer/inorganic nanocomposite particles comprising a low-density core of variable dimensions coated with a high-density shell of constant thickness, or for core-shell latexes where the shell is continuous rather than particulate in nature.


REVIEW OF DNA VACCINE APPROACHES AGAINST THE PARASITE TOXOPLASMA GONDII.
Toxoplasma gondii is an apicomplexan parasite that affects both humans and livestock. Transmitted to humans through ingestion, it is the second-leading cause of foodborne illness-related death. Currently, there exists no approved vaccine for humans or most livestock against the parasite. DNA vaccines, a type of subunit vaccine which uses segments of the pathogen's DNA to generate immunity, have shown varying degrees of experimental efficacy against infection caused by the parasite. This review compiles DNA vaccine efforts against Toxoplasma gondii, segmenting the analysis by parasite antigen, as well as a review of concomitant adjuvant usage. No single antigenic group was consistently more effective within in vivo trials relative to others.


Constrictive pericarditis localized to left ventricle presented with left pleural effusion: a case report.
An 18-year old woman presented with progressive dyspnea and cough. Physical examination revealed decreased breath sounds at the left hemithorax and distant heart sounds with no murmurs or rub. Electrocardiogram revealed low voltage. Chest X-ray showed unilateral left-sided pleural effusion with no cardiomegaly. Transthoracic echocardiogram showed thickened pericardium localized throughout the left ventricle impairing the diastolic filling. Doppler waveforms were suggestive of localized constrictive pericarditis. A computerized tomographic scan of the chest confirmed the presence of unilateral pleural effusion with thickened pericardium surrounding the left ventricle. The patient's symptoms and signs were related to localized constrictive pericarditis and improved following surgery.


beta-adrenergic modulation of maxi-K channels in vascular smooth muscle via Gi through a membrane-delimited pathway.
Direct modulation of large-conductance Ca2+-activated K+ (maxi-K) channel by receptor-associated G protein in rabbit mesenteric arterial smooth muscle cells was studied using the outside-out patch clamp technique. Applying a beta-adrenoceptor agonist (isoproterenol) increased maxi-K channel activity by 75%, and the effect was almost completely abolished by pretreating the cells with pertussis toxin but not with cholera toxin. When the antibody against Gi protein was present in the pipette solution the stimulatory effect of isoproterenol disappeared. These results suggest that beta-adrenoceptor stimulation increases maxi-K channel activity via a membrane-delimited pathway, probably through pertussis toxin-sensitive G protein (Gi).


Removing the center from computing: biology's new mode of digital knowledge production.
This article shows how the USA's National Institutes of Health (NIH) helped to bring about a major shift in the way computers are used to produce knowledge and in the design of computers themselves as a consequence of its early 1960s efforts to introduce information technology to biologists. Starting in 1960 the NIH sought to reform the life sciences by encouraging researchers to make use of digital electronic computers, but despite generous federal support biologists generally did not embrace the new technology. Initially the blame fell on biologists' lack of appropriate (i.e. digital) data for computers to process. However, when the NIH consulted MIT computer architect Wesley Clark about this problem, he argued that the computer's quality as a device that was centralized posed an even greater challenge to potential biologist users than did the computer's need for digital data. Clark convinced the NIH that if the agency hoped to effectively computerize biology, it would need to satisfy biologists' experimental and institutional needs by providing them the means to use a computer without going to a computing center. With NIH support, Clark developed the 1963 Laboratory Instrument Computer (LINC), a small, real-time interactive computer intended to be used inside the laboratory and controlled entirely by its biologist users. Once built, the LINC provided a viable alternative to the 1960s norm of large computers housed in computing centers. As such, the LINC not only became popular among biologists, but also served in later decades as an important precursor of today's computing norm in the sciences and far beyond, the personal computer.


Chronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis.
Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. In unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. In stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. In stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis.


Development of voltage-activated potassium currents in cultured cerebellar granule neurons under different growth conditions.
1. The functional expression of two potassium currents in cultured cerebellar granule cells was investigated with the whole cell patch-clamp technique in relation to development and growth condition. Cells were grown in medium containing different concentrations of potassium: 25 mM (K25) and 40 mM (K40), together referred to as "high K+"; 10 mM (K10) or "low K+"; and K10 with 100 microM N-methyl-D-aspartate (KNMDA). All conditions are known to influence maturation and survival of granule cells in culture. 2. At 2 days in vitro (DIV) the membrane capacitance, taken as index of membrane surface area, was the same for cells grown in each growth condition. At 7-9 DIV it had increased in each condition, but to a substantially larger extent in cells grown in KNMDA, K25, and K40 than in cells grown in K10. During development the input resistance only decreased in cells grown in KNMDA and high K+. 3. A delayed potassium current (IK) and a fast transient potassium current (IA) could both be recorded at 2 DIV in each growth condition, although a few neurons only expressed the IK. The IK was partially suppressed by tetraethylammonium (5 mM), whereas IA was predominantly sensitive to 4-aminopyridine (5 mM). 4. Normalized for cell capacitance, the specific IA conductance hardly changed during development in cells grown in high K+ and KNMDA. Cells in K10, however, displayed an IA with totally different properties in 23 of 24 cells; the specific IA conductance in these cells was considerably smaller at 7-9 DIV, suggesting a deletion of these channels during development.(ABSTRACT TRUNCATED AT 250 WORDS)


Comment on "Thermodynamic Self-Limiting Growth of Heteroepitaxial Islands Induced by Nonlinear Elastic Effect".
Making use of incontrovertible scaling arguments, here we demonstrate that the main findings of the recent Nano Letter paper Hu et al. ( Hu , H. , Niu , X. , and Liu , F. Nano Lett. 2016 , 16 , 3919 ) are incorrect and unphysical, that is, there is no self-limiting island growth due to nonlinear elastic effects, as claimed by Hu et al. We also note that the key concept of the paper by Hu et. al., that is, the island height dependence of the elastic strain field has already been published 10 years ago by Zinovyev , V. A. , Vastola , G. , Montalenti , F. , and Miglio , L. Surf. Sci. 2006 , 600 , 4777 , offering a correct and elaborate treatment even in a more generic sense, including also nonlinear elasticity effects consistently.


Adolescent health care in Brazil.
The period of youth and adolescence has been shown to have continuous demographic growth in the developing world. Young nations thus have to contend with the specific health needs of teenagers and young adults. This is illustrated by an analysis of the health-care needs of Brazilian adolescents. The issues highlighted here are adolescent morbidity and mortality, current delivery of adolescent health care, and future directions of adolescent programs in Brazil.


Prevention of restenosis after PTCA: role of calcium antagonists.
The recurrence of coronary obstruction after initially successful percutaneous transluminal coronary angioplasty (PTCA) represents a major problem of this interventional procedure at present. In the pathogenesis of restenosis the growth factor-dependent proliferation and migration of medial smooth muscle cells into the intima of the vessel wall may play a very important role. In experimental studies this process could be inhibited by calcium antagonists. However, the first two placebo-controlled clinical trials showed disappointing results: the restenosis rate was not decreased by the treatment with 10 mg of nifedipine four times daily or by the treatment with 90 mg of diltiazem three times daily. The influence of high-dose verapamil treatment [Isoptin RR (240 mg) twice daily] on the recurrence of coronary stenosis has been investigated by a recently completed double-blind, placebo-controlled trial, the verapamil angioplasty study (VAS). The VAS included 196 consecutive patients with at least one risk factor for restenosis after successful PTCA for stable angina pectoris (n = 75) or unstable angina pectoris/non-Q-wave infarction (n = 97). Eighty-eight percent of the patients underwent follow-up angiography at 4.3 +/- 2.3 months. The publication of detailed data of the VAS including restenosis rates in both clinical subgroups is being prepared.


Does simultaneous soft tissue augmentation around immediate or delayed dental implant placement using sub-epithelial connective tissue graft provide better outcomes compared to other treatment options? A systematic review and meta-analysis.
The clinical benefits of simultaneous implant placement and soft tissue augmentation using different treatment modalities are unclear. The current meta-analysis aimed to compare the effect of simultaneous soft tissue augmentation using subepithelial connective tissue graft (SCTG) around immediate or delayed dental implant placement with other treatment modalities on the peri-implant tissue health and esthetic. Up to May 2021, four databases (PubMed, EMBASE, Cochrane Central, and Google Scholar) were searched. Randomized control trials with follow-up >3 months, evaluating simultaneous implant placement (immediate or delayed) and soft tissue augmentation using SCTG compared with other treatment modalities were included. The predictor variables were SCTG versus no augmentation with/without guided bone regeneration (GBR) or other augmentation techniques (Acellular dermal matrix (ADM), Xenogeneic collagen matrix (XCM). The outcome variables were buccal tissue thickness (BTT), mid-buccal gingival level (MGL), marginal bone loss (MBL), and pink esthetic scores (PES). Cumulative mean differences (MD) and 95% confidence interval (CI) were estimated. Twelve studies were included. SCTG along with immediate implant placement (IIP) or delayed implant placement (DIP) showed a statistically significant improvement in BTT (Fixed; MD, 0.74; 95% CI, 0.51; 0.97), MGL (Fixed; MD, 0.5; 95% CI, 0.21; 0.80), PES (Fixed; MD, 0.79; 95% CI, 0.29; 1.29), and less MBL (Fixed; MD, -0.11; 95% CI, -0.14; -0.08) compared to no graft (P<0.05). A statistically insignificant differences in BTT (Random; MD, 0.62; 95% CI, -0.41; 1.65), MGL (Fixed; MD, -0.06; 95% CI, -0.23; 0.11), MBL (Fixed; MD, 0.36; 95% CI, -0.05; 0.77) and PES (Fixed; MD, 0.28; 95% CI, -0.10; 0.67) was observed when SCTG along with DIP was compared with no augmentation plus GBR. Similarly, no statistically significant difference was observed when comparing SCTG along with DIP with acellular dermal matrix (ADM) concerning BTT (MD:0.71, P = 0.18) and KMW (MD: 0.6, P = 0.19). There is a very low quality of evidence to provide recommendations on whether simultaneous dental implant placement (IIP or DIP) and soft tissue augmentation using SCTG is superior to no augmentation or is comparable to the other tissue augmentation materials in improving the quality and quantity of peri-implant tissues. Therefore, further, well-designed RCTs with larger sample sizes and long follow-up times are still needed.


Bicortical Laminar Screws for Posterior Fixation of Subaxial Cervical Spine: A Radiologic Analysis With Computed Tomography Images.
Retrospective radiological analysis. Translaminar screw (TLS) placement is one of the fixation techniques in the subaxial cervical spine. However, it can be difficult to use in small diameter of the lamina. This study proposed a novel bicortical laminar screw (BLS) and analyzed the related parameters using computed tomography (CT). Cervical CT images taken at our institution from January 2013 to March 2017 were used for measurement. On the axial images, the maximum screw length (MSL) and trajectory angle (TA) of BLS and TLS were measured, together with the distance from the midline (DM) to the BLS entry point and the lamina width (LW). On the parasagittal images, the height of the lamina (LH) was measured. MSL of BLS and TLS were 21.00 and 20.97 mm, 19.02 and 20.91 mm, 18.45 and 21.01 mm, and 20.00 and 21.01 mm in C3, C4, C5, and C6, respectively. TA of the BLS and TLS were 21.24° and 34.90°, 19.05° and 34.22°, 18.65° and 33.61°, and 18.30° and 34.51° at C3, C4, C5, and C6, respectively. DM were 6.44, 5.77, 5.68, and 6.03 at C3, C4, C5, and C6, respectively. LW and LH were 3.52 and 12.44 mm, 2.87 and 12.49 mm, 2.76 and 12.42 mm, and 3.18 and 13.30 mm at C3, C4, C5, and C6, respectively. We suggest that BLS fixation is a feasible alternative option for posterior fixation to the lamina of the subaxial cervical spine. It may be especially useful when pedicle screw, lateral mass screw, and TLS are not appropriate.


Structural evidence for a functional role of human tissue nonspecific alkaline phosphatase in bone mineralization.
The human tissue nonspecific alkaline phosphatase (TNAP) is found in liver, kidney, and bone. Mutations in the TNAP gene can lead to Hypophosphatasia, a rare inborn disease that is characterized by defective bone mineralization. TNAP is 74% homologous to human placental alkaline phosphatase (PLAP) whose crystal structure has been recently determined at atomic resolution (Le Du, M. H., Stigbrand, T., Taussig, M. J., Ménez, A., and Stura, E. A. (2001) J. Biol. Chem, 276, 9158-9165). The degree of homology allowed us to build a reliable TNAP model to investigate the relationship between mutations associated with hypophosphatasia and their probable consequences on the activity or the structure of the enzyme. The mutations are clustered within five crucial regions, namely the active site and its vicinity, the active site valley, the homodimer interface, the crown domain, and the metal-binding site. The crown domain and the metal-binding domain are mammalian-specific and were observed for the first time in the PLAP structure. The crown domain contains a collagen binding loop. A synchrotron radiation x-ray fluorescence study confirms that the metal in the metal-binding site is a calcium ion. Several severe mutations in TNAP occur around this calcium site, suggesting that calcium may be of critical importance for the TNAP function. The presence of this extra metal-binding site gives new insights on the controversial role observed for calcium.


Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM.
Recommendations for EEG monitoring in the ICU are lacking. The Neurointensive Care Section of the ESICM assembled a multidisciplinary group to establish consensus recommendations on the use of EEG in the ICU. A systematic review was performed and 42 studies were included. Data were extracted using the PICO approach, including: (a) population, i.e. ICU patients with at least one of the following: traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, stroke, coma after cardiac arrest, septic and metabolic encephalopathy, encephalitis, and status epilepticus; (b) intervention, i.e. EEG monitoring of at least 30 min duration; (c) control, i.e. intermittent vs. continuous EEG, as no studies compared patients with a specific clinical condition, with and without EEG monitoring; (d) outcome endpoints, i.e. seizure detection, ischemia detection, and prognostication. After selection, evidence was classified and recommendations developed using the GRADE system. The panel recommends EEG in generalized convulsive status epilepticus and to rule out nonconvulsive seizures in brain-injured patients and in comatose ICU patients without primary brain injury who have unexplained and persistent altered consciousness. We suggest EEG to detect ischemia in comatose patients with subarachnoid hemorrhage and to improve prognostication of coma after cardiac arrest. We recommend continuous over intermittent EEG for refractory status epilepticus and suggest it for patients with status epilepticus and suspected ongoing seizures and for comatose patients with unexplained and persistent altered consciousness. EEG monitoring is an important diagnostic tool for specific indications. Further data are necessary to understand its potential for ischemia assessment and coma prognostication.


Caring for families: double binds in neuroscience nursing.
Despite the proliferation of literature related to nurse-family relationships, little is known about such relationships in acute care neuroscience environments. A grounded theory study illuminated the experiences of nurses caring for families of patients with acquired brain injuries in the context of acute care hospital environments. Nurses, working in pressure-cooker-like environments, tried to meet information and emotional needs of families. During data analysis, a communication pattern emerged that impacted on nurses' experiences and relationships with families. This communication pattern, known as a double bind, contributed to a pattern of nursing that emerged and offers an explanation for the behaviours of the nurses in coping with family members. Nurses felt "damned if they did and damned if they didn't". To provide family-centred care, we need to fully understand the experiences of nurses caring for these families. This paper describes the concept of double bind and its application to neuroscience nursing.


Interphenylene 7-oxabicyclo[2.2.1]heptane thromboxane A2 antagonists. Semicarbazone omega-chains.
A series of chiral interphenylene 7-oxabicyclo[2.2.1]heptane semicarbazones 19-26 were prepared and evaluated for their in vitro thromboxane (TxA2) antagonistic activity and in vivo duration of action. The potency of 19-26 was found to highly dependent on the substitution pattern of the interphenylene ring and decreased in the order ortho greater than meta much greater than para. SQ 35,091 (25), [1S-(1 alpha,2 alpha,3 alpha,4 alpha)]-2-[[3-[[[(phenylamino) carbonyl]hydrazono]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]methyl] benzenepropanoic acid, was identified as a potent and long-acting TxA2 antagonist. In human platelet rich plasma SQ 35,091 inhibited arachidonic acid (800 microM) and U-46,619 (10 microM) induced aggregation with I50 values of 3 and 12 nM, respectively. In contrast, no inhibition of ADP (20 microM) induced aggregation was observed at greater than 1000 microM. Receptor binding studies with [3H]-SQ 29,548 showed SQ 35,091 was a competitive antagonist with a Kd value of 1.0 +/- 0.1 nM in human platelet membranes. In vivo SQ 35,091 (0.2 mg/kg po) showed extended protection (T50 = 16 h) from U-46,619 (2 mg/kg iv) induced death in mice. These compounds have for the first time demonstrated that a metabolically stable interphenylene alpha-sidechain can be introduced into a prostanoid-like series of TxA2 antagonists with the maintainance of potent antagonistic activity.


Socioeconomic differences in metabolic syndrome development: examining the mediating role of chronic stress using the Lifelines Cohort Study.
Metabolic syndrome (MetS) development strongly varies based on individuals' socioeconomic position (SEP), but to date, no studies have assessed the mediating role of perceived stress from long-term difficulties (chronic stress) in this association. The aim of this study is to examine the mediating role of chronic stress in the associations of the SEP measures education, occupational prestige and income, with MetS development, and whether associations between chronic stress and MetS are moderated by sex. We used an adult subsample (n = 53,216) from the Lifelines Cohort Study without MetS at baseline. MetS development was measured 3.9 years after baseline (follow-up), and defined according to National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATPIII) criteria. Direct associations between SEP, chronic stress and MetS development were estimated using multivariable logistic and linear regression analyses, and were adjusted for age, sex, the other SEP measures, and time between baseline and follow-up. The mediating percentages of chronic stress explaining the associations between SEP and MetS development were estimated using the Karlson-Holm-Breen method. Upon follow-up, 7.4% of the participants had developed MetS. Years of education and occupational prestige were inversely associated with MetS development. Chronic stress suppressed the association between education and MetS development (5.6%), as well as the association between occupational prestige and MetS development (6.2%). No effect modification of sex on the chronic stress-MetS pathway was observed. Chronic stress does not explain educational and occupational differences in developing MetS. In fact, individuals with more years of education or higher occupational prestige perceive more chronic stress than their lower SEP counterparts. Further, no difference between males and females was observed regarding the relationship between chronic stress and MetS development.


Recent progress in development and applications of second near-infrared (NIR-II) nanoprobes.
Optical probes for near-infrared (NIR) light have clear advantages over UV/VIS-based optical probes, such as their low levels of interfering auto-fluorescence and high tissue penetration. The second NIR (NIR-II) window (1000-1350 nm) offers better light penetration, lower background signal, higher safety limit, and higher maximum permitted exposure than the first NIR (NIR-I) window (650-950 nm). Therefore, NIR-II laser-based photoacoustic (PA) and fluorescence (FL) imaging can offer higher sensitivity and penetration depth than was previously available, and deeper lesions can be treated in vivo by photothermal therapy (PTT) and photodynamic therapy (PDT) with an NIR-II laser than with an NIR-I laser. Advances in creation of novel nanomaterials have increased options for improving light-induced bioimaging and treatment. Nanotechnology can provide advantages such as good disease targeting ability and relatively long circulation times to supplement the advantages of optical technologies. In this review, we present recent progress in development and applications of NIR-II light-based nanoplatforms for FL, PA, image-guided surgery, PDT, and PTT. We also discuss recent advances in smart NIR-II nanoprobes that can respond to stimuli in the tumor microenvironment and inflamed sites. Finally, we consider the challenges involved in using NIR-II nanomedicine for effective diagnosis and treatment.


Melanotic Neuroectodermal Tumor of Infancy: A Rare Case Report.
A rare case melanotic neuroectodermal tumor of infancy occurring in 2-year-old girl affecting left maxilla is described. Computed tomography showed benign expansile type of lesion affecting left maxilla. The lesion was surgically excised completely. Histopathology confirmed the diagnosis of melanotic neuroectodermal tumor. Four months' follow-up showed no recurrence.


Barriers and Facilitators to Performing Cardiopulmonary Resuscitation During Treatment in Outpatient Hemodialysis Clinics: A Qualitative Study.
Cardiac arrest is the leading cause of death among patients receiving hemodialysis, and major deficiencies exist in hemodialysis staff-provided cardiopulmonary resuscitation (CPR). Our study aimed to identify factors influencing CPR delivery in the outpatient hemodialysis clinic. Through content analysis of in-depth interviews with 10 staff members of a hemodialysis clinic, we identified three broad themes regarding barriers and facilitators to performing CPR in the hemodialysis clinic: 1) physical and environmental challenges regarding the layout of the clinic; 2) uncertainty about optimal in-clinic CPR procedures, particularly concerning patient positioning and dealing with the hemodialysis machine; and 3) benefit of continuous improvement programs, including hemodialysis-specific protocols, hands-on training, and pre-defined team roles. Our findings call for further investigation of optimal in-clinic resuscitation procedures to inform hemodialysis clinic CPR protocols and hemodialysis staff training.


Staged management of high-energy proximal tibia fractures.
High-energy proximal tibia fractures are complicated by soft tissue compromise and this may result in sub-optimal outcomes. There is a high association of open injuries, compartment syndromes, and vascular injuries with these bony disruptions. Surgical treatment of these injuries has been associated with significant complications such as infection, knee stiffness, malunion, loss of fixation, soft tissue failure, and amputations. The loss of fixation is an issue especially in the elderly, with failure associated with age more than sixty years, premature weight bearing, preoperative displacement, fracture fragmentation, and severe osteoporosis. The use of two-stage reconstruction for the treatment of distal tibia fractures has been successful in decreasing the complication rates, including wound compromise. The two stages involve: 1. stabilization of the injured limb with a bridging external fixator to allow the soft tissues to improve and recover and 2. definitive fixation for reconstruction of the articular surface and meta-diaphyseal fractures. The use of such a protocol has been proposed for high-energy proximal tibia fractures to decrease the high rate of soft tissue compromise associated with traditional open methods of treatment. The choice of definitive fixation may include plates, nails, or non-bridging external fixation.


First-line immunotherapy or angiogenesis inhibitor plus chemotherapy for HER2-altered NSCLC: a retrospective real-world POLISH study.
There have been no comprehensive large-scale studies that have evaluated the benefits of chemotherapy-based regimens in addressing HER2-altered advanced non-small-cell lung cancer (NSCLC) in a first-line setting. Data on HER2 alteration subtypes and concomitant alterations are also limited. Accordingly, our retrospective, real-world POLISH study assesses the efficacy of first-line chemotherapy alone (C) as well as combinations with immune checkpoint inhibitors (C + I) or angiogenesis inhibitors (C + A) for HER2-altered NSCLC; molecular features are also reported. HER2-altered NSCLC patients who received a first-line treatment between November 2015 and September 2021 were screened. Patients treated with C, C + I, or C + A were included in our final efficacy analysis. Progression-free survival (PFS) was compared between the subgroups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to evaluate concomitant alterations. A total of 293 patients were screened, with an identification of HER2 amplification and 37 distinct HER2 mutations, and 210 cases treated with C, C + I, or C + A were ultimately included. C + A achieved longer PFS than C (5.63 vs 4.03 months, hazard ratio: 0.64, 95% confidence interval [CI]: 0.46-0.88, p = 0.006). C + I did not improve median PFS compared to C + A or C (both p > 0.05), despite the programmed cell death ligand-1 (PD-L1) expression or tumor mutational burden. KEGG analysis revealed that concomitant upregulation of PI3 K/AKT pathway signaling was common in HER2-altered NSCLC. Chemotherapy plus angiogenesis inhibitors may yield a greater survival benefit than chemotherapy alone in a first-line setting for HER2-altered NSCLC, whereas an immune-based combination therapy may not be superior to a sole chemotherapy regimen. Activation of PI3 K/AKT signaling may mediate immunosuppression in HER2-altered NSCLC.


Spermatozoa of tapeworms (Platyhelminthes, Eucestoda): advances in ultrastructural and phylogenetic studies.
New data on spermiogenesis and the ultrastructure of spermatozoa of 'true' tapeworms (Eucestoda) are summarized. Since 2001, more than 50 species belonging to most orders of the Eucestoda have been studied or reinvestigated, particularly members of the Caryophyllidea, Spathebothriidea, Diphyllobothriidea, Bothriocephalidea, Trypanorhyncha, Tetraphyllidea, Proteocephalidea, and Cyclophyllidea. A new classification of spermatozoa of eucestodes into seven basic types is proposed and a key to their identification is given. For the first time, a phylogenetic tree inferred from spermatological characters is provided. New information obtained in the last decade has made it possible to fill numerous gaps in the character data matrix, enabling us to carry out a more reliable analysis of the evolution of ultrastructural characters of sperm and spermiogenesis in eucestodes. The tree is broadly congruent with those based on morphological and molecular data, indicating that convergent evolution of sperm characters in cestodes may not be as common as in other invertebrate taxa. The main gaps in the current knowledge of spermatological characters are mapped and topics for future research are outlined, with special emphasis on those characters that might provide additional information about the evolution of tapeworms and their spermatozoa. Future studies should be focused on representatives of those major groups (families and orders) in which molecular data indicate paraphyly or polyphyly (e.g. 'Tetraphyllidea' and Trypanorhyncha) and on those that have a key phylogenetic position among eucestodes (e.g. Diphyllidea, 'Tetraphyllidea', Lecanicephalidea, Nippotaeniidea).


The Slovenian version of the Oral Health Impact Profile Questionnaire (OHIP-SVN): translation and psychometric properties.
The aim of the study was to develop and to test the psychometric properties of the Slovenian version (OHIP-SVN) in the new cultural context. Construct validity was tested on 430 subjects, test-retest reliability on 60 subjects, internal consistency on 460 subjects, and responsiveness on 30 patients with a treatment demand (toothache). The significant association between the OHIP summary scores and the self-reported oral health (p < 0.001) confirmed the construct validity. The test-retest reliability showed high intraclass correlation coefficients and no significant differences between the two administrations (p > 0.05). The internal consistency showed high Cronbach's alpha (0.97). The responsiveness was confirmed by the statistically significant difference between the mean OHIP score at baseline and follow-up (p < 0.001) and by a considerable effect size in the patients with a treatment demand (0.515). The OHIP-SVN, as one of the first translation into one of the Slavic family of the languages proves that this instrument is suitable for the assessment of the Oral Health Related Quality of Life in Slovenia.


Molecular mechanisms of ion conduction in ClC-type chloride channels: lessons from disease-causing mutations.
The muscle Cl- channel, ClC-1, is a member of the ClC family of voltage-gated Cl- channels. Mutations in CLCN1, the gene encoding this channel, cause two forms of inherited human muscle disorders: recessive generalized myotonia congenita (Becker) and dominant myotonia (Thomsen). The functional characterization of these naturally occurring mutations not only allowed a better understanding of the pathophysiology of myotonia, it also provided important insights into the structure and function of the entire ClC channel family. This review describes recent experiments using a combination of cellular electrophysiology, molecular genetics, and recombinant DNA technology to study the molecular basis of ion permeation and selection in ClC-type chloride channels.


Surgical resection for pelvic retroperitoneal Castleman's disease: A case report and review literature.
Castleman's disease (CD) is a rare atypical lymphoproliferation disorder first reported in 1954. Clinically, CD is classified as unicentric or multicentric CD based on anatomical distribution. Unicentric CD primarily affects the mediastinum, and rarely affects the retroperitoneal location. The standard treatment for unicentric CD is complete surgical resection; however, this can be complicated by a high degree of attachment with other organs or hypervascularity. Preoperative angiography and embolization of the arteries that feed the problematic mass can reduce intraoperative bleeding in cases of CD with hypervascularity. In the present case report, a 44-year-old man who was found to have a pelvic retroperitoneal mass with calcification based on abdominal imaging results is discussed. Due to the hypervascularity of the mass, preoperative embolization was performed. The mass was completely resected without any complications. Additionally, a review of the literature on pelvic CD and preoperative embolization of CD was performed to provide an up-to-date reference on the management and outcomes of patients with CD.


Modulation of gastric and arterial pressure by nucleus tractus solitarius in rat.
By using L-glutamate as a physiological tool to selectively stimulate neurons in specific subnuclear regions of the nucleus tractus solitarius (NTS), we have sought to differentiate those regions that modulate cardiovascular activity from those that modulate gastric activity. Microinjections of L-glutamate (300 pmol/25 nl) into the dorsomedial NTS of alpha-chloralose-anesthetized rats elicited dose-dependent falls in arterial pressure (AP) of 37.5 +/- 7.7 Torr from a base line of 130 +/- 5.8 Torr and gastric pressure (GP) of 0.8 +/- 0.1 cmH2O and inhibited the usual 5-6 waves/min phasic activity. Microinjection into the ventromedial NTS did not affect AP but transiently lowered GP by 1.6 +/- 0.2 cmH2O and eliminated phasic waves. The GP changes were vagally mediated. Microinjections into the area postrema or the hypoglossal nucleus elicited neither AP nor GP changes. Microinjections in other NTS areas at the same rostral-caudal level did not alter GP consistently. This study suggests that local stimulation of neurons in a specific region of the NTS elicits vagally mediated alterations of tonic GP and phasic activity and that AP and GP can be influenced independently in the medial NTS region.


Modification of the T cell responsiveness to synthetic peptides by substituting amino acids on agretopes.
T cell receptors, major histocompatibility complex molecules, and antigens constitute tri-molecular complexes which induce T cell activation. T cells in I-Ab mice generate proliferative responses to a synthetic peptide composed of residues 43-58 of pigeon cytochrome c (p43-58) and its analogs with substitution at position 50 (50A, 50V, 50L, 50N, 50Q, 50K, and 50M). However, none of these peptides stimulate T cells in I-Ak mice. We substituted two residues at positions 46 and 54 of p43-58(50D), 50V, 50L, 50E, and 50K with two amino acids on agretopes of the I-Ak binding HEL52-61 peptide and immunized I-Ak mice with these newly synthesized peptides: 46D50D54R, 46D50V54R, 46D50L54R, 46D50E54R, and 46D50K54R. Apart from 46D50D54R, these peptides elicited T cell responses in I-Ak mice in an immunogen-specific manner, but did not stimulate those in I-Ab mice. Further, 46D50V54R inhibited competitively the responses of I-Ak restricted T cell hybridomas specific for 46D50E54R. These results demonstrate that the residues at positions 46 and 54 on the peptides act as an agretope and the residue at position 50 acts as an epitope in I-Ak mice, as in I-Ab mice, and provide the possibility of opening up a new method to prepare peptide antigens which induce T cell responses in each murine strain by introducing appropriate amino acids on agretopes.


Bioinspired Scene Classification by Deep Active Learning With Remote Sensing Applications.
Accurately classifying sceneries with different spatial configurations is an indispensable technique in computer vision and intelligent systems, for example, scene parsing, robot motion planning, and autonomous driving. Remarkable performance has been achieved by the deep recognition models in the past decade. As far as we know, however, these deep architectures are incapable of explicitly encoding the human visual perception, that is, the sequence of gaze movements and the subsequent cognitive processes. In this article, a biologically inspired deep model is proposed for scene classification, where the human gaze behaviors are robustly discovered and represented by a unified deep active learning (UDAL) framework. More specifically, to characterize objects' components with varied sizes, an objectness measure is employed to decompose each scenery into a set of semantically aware object patches. To represent each region at a low level, a local-global feature fusion scheme is developed which optimally integrates multimodal features by automatically calculating each feature's weight. To mimic the human visual perception of various sceneries, we develop the UDAL that hierarchically represents the human gaze behavior by recognizing semantically important regions within the scenery. Importantly, UDAL combines the semantically salient region detection and the deep gaze shifting path (GSP) representation learning into a principled framework, where only the partial semantic tags are required. Meanwhile, by incorporating the sparsity penalty, the contaminated/redundant low-level regional features can be intelligently avoided. Finally, the learned deep GSP features from the entire scene images are integrated to form an image kernel machine, which is subsequently fed into a kernel SVM to classify different sceneries. Experimental evaluations on six well-known scenery sets (including remote sensing images) have shown the competitiveness of our approach.


Adjunctive thrombectomy for acute myocardial infarction: A bayesian meta-analysis.
In available trials and meta-analyses, adjunctive thrombectomy in acute myocardial infarction (MI) improves markers of myocardial reperfusion but has limited effects on clinical outcomes. Thrombectomy devices simply aspirate thrombus or mechanically fragment it before aspiration. Simple aspiration thrombectomy may offer a distinct advantage. We identified 21 eligible trials (16 that used a simple aspiration thrombectomy device) involving 4299 patients with ST-segment elevation MI randomized to reperfusion therapy by primary percutaneous coronary intervention with or without thrombectomy. By using Bayesian meta-analysis methods, we found that thrombectomy yielded substantially less no-reflow (odds ratio [OR], 0.39; 95% credible interval [CrI], 0.18 to 0.69), more ST-segment resolution > or =50% (OR, 2.22; 95% CrI, 1.60 to 3.23), and more thrombolysis in myocardial infarction/myocardial perfusion grade 3 (OR, 2.50; 95% CrI, 1.48 to 4.41). There was no evidence for a decrease in death (OR, 0.94; 95% CrI, 0.47 to 1.80), death, recurrent MI, or stroke (OR, 1.07; 95% CrI, 0.63 to 1.92) with thrombectomy. Restriction of the analysis to trials that used simple aspiration thrombectomy devices did not yield substantially different results, except for a positive effect on postprocedure thrombolysis in myocardial infarction grade 3 flow (OR, 1.49; 95% CrI, 1.14 to 1.99). In this Bayesian meta-analysis, adjunctive thrombectomy improves early markers of reperfusion but does not substantially effect 30-day post-MI mortality, reinfarction, and stroke. The use of aspiration thrombectomy devices is not associated with a reduction in post-MI clinical outcomes. Thrombectomy is one of the rare effective preventive measures against no-reflow.


SC35 promotes splicing of the C5-V6-C6 isoform of CD44 pre-mRNA.
CD44 is a cell membrane glycoprotein that mediates the response of cells to their cellular microenvironment and regulates growth, survival, differentiation and motility. CD44 pre-mRNA contains 20 exons, 10 of which are alternatively spliced. Among the CD44 spliced variants, one of the V6 exon-containing isoforms, the V4-7 variant which contains variable exons 4, 5, 6 and 7, confers metastatic potential to non-metastatic cells. However, the splicing regulation of the V6 exon is not completely understood. SC35 is an arginine-serine rich protein that regulates alternative splicing of various pre-mRNAs. In the present study, we established a stable cell line which indicates inclusion or skipping of the V6 exon with the RFP or GFP signal. Using this stable cell line, we found that the V6 exon and flanking introns of CD44 pre-mRNA contained SC35 response elements that regulate V6 splicing. RT-PCR analyses of the endogenous CD44 splicing showed that SC35 promotes the production of the C5-V6-C6 isoform. shRNA knockdown of SC35 showed that reduced expression of SC35 decreased expression of the V6 exon-containing isoforms. Our results reveal a novel mechanism of CD44V6 splicing.


Frozen motion of gliding bacteria outlines inherent features of the motility apparatus.
High-resolution data of actively gliding wild-type bacteria of four different species and of four different gliding mutants of Myxococcus xanthus were obtained from scanning electron micrographs. By shock freezing and freeze drying, motility-associated surface patterns could be fixed and consequently distinct intermediate states of motion could be observed for the first time. It is shown that these topographic patterns are immediately lost when gliding motility is stopped by blocking the respiratory chain with potassium cyanide or sodium azide. From the surface topography, the mode of action of the gliding apparatus of all four bacterial species examined can be described as a twisted circularly closed 'band'. During gliding, groups of nodes of the supertwisted apparatus show evidence of travelling like waves along the trichomes. However, the spacing between the nodes is not constant but varies within a certain range. This indicates that they are flexibly modulated as a consequence of the gliding state of the individual trichome.


Ethylene Directly Inhibits Foliar Gas Exchange in Glycine max.
Gas exchange of individual attached leaves of soybean, Glycine max (L.) Merr cv Davis, was monitored during exposure to exogenous ethylene (C(2)H(4)) to test the hypothesis that the effects of C(2)H(4) on net photosynthesis (P(N)) and stomatal conductance to H(2)O vapor (g(s)) are direct and not mediated by changes in leaf orientation to light. Leaflets were held perpendicular to incident light in a temperature-controlled cuvette throughout a 5.5 hour exposure to 10 microliters per liter C(2)H(4). Declines in both P(N) and g(s) were evident within 2 hours and became more pronounced throughout the exposure period. In C(2)H(4) treated plants, P(N) and g(s) decreased to 80 and 62%, respectively, of the rates in control plants. Because epinastic movement of the leaflets was prohibited by the cuvette, the observed declines in P(N) and g(s) were a direct effect of C(2)H(4) rather than the result of reduced light interception caused by changing leaf angle.


[Prophylaxis and therapy of the acid aspiration syndrome].
The best prevention of the aspiration syndrome begins with early identification of any patient at risk. Reduction of gastric volume and elevation of gastric pH can be achieved by premedication with glycopyrrolate (0.3 mg i.m.) and preoperative administration of H2-receptor antagonists (150 mg ranitidine p.o. 6-8 h and 80 mg i.m./i.v. 60 min before induction). Transportation of stomach contents into the duodenum can further be accelerated by 10 mg metoclopramide i.v. 20-40 min before induction. Metoclopramide will also elevate lower esophageal sphincter tone. Rapid elevation of gastric pH can be achieved by oral administration of 15-30 ml 0.3 mol sodium citrate. Induction of anesthesia should be performed as a "rapid sequence induction". Manual compression of the esophagus (Sellick manoever) may prevent gastric regurgitation. In cases of pulmonary aspiration, consequent therapy has to be initiated as soon as possible to limit broncho-alveolar damage. After endotracheal intubation the upper respiratory tract should be cleared of stomach contents by suction. Further efforts should include artificial ventilation with a high FiO2 and low PEEP (5-10 cm H2O) as well as vigorous volume substitution to maintain cardiovascular stability. Corticosteroids (200 mg Hydrocortisone i.v. may have a beneficial effect if given within 5 min after aspiration. Severe bronchospasm may respond to aminophylline (5 mg/kg i.v. as an initial bolus) or inhalation of beta-adrenergics (terbutaline 0.75-1.5 mg/inh). Bronchial lavage will rather damage than improve broncho-alveolar integrity and cannot be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)


1,3-Dialkyltriazenes: reactive intermediates and DNA alkylation.
The reactions of calf thymus (ct) DNA with 1,3-dimethyltriazene (DMT), N-methyl-N-nitrosourea (MNU), 1,3-diethyltriazene (DET), N-ethyl-N-nitrosourea (ENU), and 1-ethyl-3-methyltriazene (MET) were studied as a function of concentration of the alkylating agents, of various buffers, and of ionic strength. The amount of alkylation at the 7- and O6-positions of guanine increased linearly with dose over a 10-fold concentration range. The slopes of the DMT and MNU curves were identical as were those of DET and ENU. These data suggest that both types of compounds alkylate DNA via a similar intermediate, presumably the corresponding alkanediazonium ion. MET methylates and ethylates DNA, the amount of each product being a function of the competitive formation of the two diazonium ions possible from MET. The MET product ratios could be reproduced by an appropriate mixture of DET and DMT. The alkylation of DNA by DMT and by MET is very sensitive to ionic strength, to the nature of the buffer, and to the identity of the salt used to balance ionic strength. In general, the reaction is favored by low ionic strength, by amine rather than oxy acid buffers, and by doubly charged inert anions. The alkylation of DNA is inversely proportional to the logarithm of the ionic strength over a wide range. The mutagenic activity of triazenes in Salmonella typhimurium is correlated very well with the ability of the triazenes to form adducts, particularly O6-guanine adducts.(ABSTRACT TRUNCATED AT 250 WORDS)


β-Catenin signaling positively regulates glutamate uptake and metabolism in astrocytes.
Neurological disorders have been linked to abnormal excitatory neurotransmission. Perturbations in glutamate cycling can have profound impacts on normal activity, lead to excitotoxicity and neuroinflammation, and induce and/or exacerbate impairments in these diseases. Astrocytes play a key role in excitatory signaling as they both clear glutamate from the synaptic cleft and house enzymes responsible for glutamate conversion to glutamine. However, mechanisms responsible for the regulation of glutamate cycling, including the main astrocytic glutamate transporter excitatory amino acid transporter 2 (EAAT2 or GLT-1 in rodents) and glutamine synthetase (GS) which catalyzes the ATP-dependent reaction of glutamate and ammonia into glutamine, remain largely undefined. Gain and loss of function for β-catenin in human progenitor-derived astrocyte (PDAs) was used to assess EAAT2 and GS levels by PCR, western blot, luciferase reporter assays, and chromatin immunoprecipitation (ChIP). Further, morpholinos were stereotaxically injected into C57BL/6 mice and western blots measured the protein levels of β-catenin, GLT-1, and GS. β-Catenin, a transcriptional co-activator and the central mediator of Wnt/β-catenin signaling pathway, positively regulates EAAT2 and GS at the transcriptional level in PDAs by partnering with T cell factor 1 (TCF-1) and TCF-3, respectively. This pathway is conserved in vivo as the knockdown of β-catenin in the prefrontal cortex results in reduced GLT-1 and GS expression. These studies confirm that β-catenin regulates key proteins responsible for excitatory glutamate neurotransmission in vitro and in vivo and reveal the therapeutic potential of β-catenin modulation in treating diseases with abnormal glutamatergic neurotransmission and excitotoxicity.


Evaluation of the effect of topical tacrolimus 0.03% versus cyclosporine 0.05% in the treatment of dry eye secondary to Sjogren syndrome.
To compare the effect of topical application of tacrolimus 0.03% eyedrops versus cyclosporine 0.05% in Sjogren syndrome subjects with severe dry eyes. A prospective single-blinded simply randomized controlled study. 60 Sjogren patients were randomized intoGroup A: 30 patients were instructed to put tacrolimus 0.03% eyedrops in one eye for 6 months and placebo eyedrops in the other eye, (N = 30, 44.9 ± 12.58 years).Group B: 30 patients were instructed to put cyclosporine 0.05% eyedrops in one eye for 6 months and placebo eyedrops in the other eye (N = 30, 49.4 ± 12.92 years).Main outcome measures: Patients were evaluated at day 0, 90, and 180 for Ocular Surface Disease Index Questionnaire (OSDI), frequency of use of artificial tears, average fluorescein tear break up time (TBUT), ocular surface staining scores, Schirmer I test, meibum quality, and expressibility scores. Upon comparing both eyedrops, the mean value of OSDI decrease was 38.25 ± 18.29% versus 31.69 ± 18.57% (p-value 0.09), SICCA score decrease was 2.97 ± 1.92 versus 2.27 ± 2.02 (p-value 0.124) the decrease in artificial tear substitute use was 3.90 ± 2.22 versus 3.63 ± 1.92 (p-value 0.616), increase in Schirmer I values were 4.10 ± 4.21 and 4.26 ± 2.00 (p-value 0.590) in eyes treated with tacrolimus and cyclosporine respectively. Neither of them affected meibum quality or expressibility scores. Both tacrolimus and cyclosporine significantly improved patient symptoms, frequency of artificial tears use and ocular surface staining compared to placebo-controlled eyes. However, no significant difference regarding the efficacy of both eyedrops at the end of 6 months treatment of severe dry eyes of Sjögren syndrome patients. ClinicalTrials.gov. Identifier: NCT03865888.


Inhibition of skin tumor promotion by restriction of fat and carbohydrate calories in SENCAR mice.
The purpose of this research was to compare the influence of calorie restriction by removal of fat with calorie restriction by removal of carbohydrate on the promotion of skin tumorigenesis in mice. Female SENCAR mice were initiated with 7,12-dimethylbenz(a)anthracene (10 nmol, single topical treatment) and fed calorie-restricted diets during and following promotion with 12-O-tetradecanoylphorbol-13-acetate (2 micrograms, topically, twice a week for 20 weeks). Control diet (American Institute of Nutrition-based formulation) was compared with a diet in which calories from fat and calories from carbohydrate were similar [balanced high fat (BHF)] in ad libitum-fed groups. Restricted animals were fed diets such that 35% of the calories from fat [high carbohydrate, calories restricted from fat (HCR)] or from carbohydrate (high fat, calories restricted from carbohydrate) were restricted, but other intake was equivalent to the BHF group. Results showed an inhibition of papilloma number in both restricted groups and the inhibition was greatest in the HCR mice. Larger papillomas were observed on mice in the control, BHF, and high-fat, calories restricted from carbohydrate diet groups than on mice in the HCR group. The pattern of carcinoma development was similar in the mice in the freely fed control and BHF groups. Restriction of calories from either fat or carbohydrate delayed the rate and reduced the incidence of carcinoma development. Carcinoma incidence did not differ between mice fed the high-fat, calories restricted from carbohydrate and HCR diets.


An ionic-chemical-mechanical model for muscle contraction.
The dynamic process underlying muscle contraction is the parallel sliding of thin actin filaments along an immobile thick myosin fiber powered by oar-like movements of protruding myosin cross bridges (myosin heads). The free energy for functioning of the myosin nanomotor comes from the hydrolysis of ATP bound to the myosin heads. The unit step of translational movement is based on a mechanical-chemical cycle involving ATP binding to myosin, hydrolysis of the bound ATP with ultimate release of the hydrolysis products, stress-generating conformational changes in the myosin cross bridge, and relief of built-up stress in the myosin power stroke. The cycle is regulated by a transition between weak and strong actin-myosin binding affinities. The dissociation of the weakly bound complex by addition of salt indicates the electrostatic basis for the weak affinity, while structural studies demonstrate that electrostatic interactions among negatively charged amino acid residues of actin and positively charged residues of myosin are involved in the strong binding interface. We therefore conjecture that intermediate states of increasing actin-myosin engagement during the weak-to-strong binding transition also involve electrostatic interactions. Methods of polymer solution physics have shown that the thin actin filament can be regarded in some of its aspects as a net negatively charged polyelectrolyte. Here we employ polyelectrolyte theory to suggest how actin-myosin electrostatic interactions might be of significance in the intermediate stages of binding, ensuring an engaged power stroke of the myosin motor that transmits force to the actin filament, and preventing the motor from getting stuck in a metastable pre-power stroke state. We provide electrostatic force estimates that are in the pN range known to operate in the cycle.