Gypsum compatibility of antimicrobial alginates after spray disinfection.
This investigation examined the gypsum compatibility of two antimicrobial alginates after spray disinfection. Subjective compatibility evaluations were compared with objective quantitative profilometer readings of gypsum cast surface roughness. COE Hydrophilic Gel Alginate, Jeltrate Plus, Antimicrobial Alginate, and their nonantimicrobial counterparts, Coe Alginate and Jeltrate Plus, were used in this study. After spray disinfection with water (control), Alcide LD, Biocide, OMC II, and 0.5% NaOCI, impressions of the American National Standards Institute/American Dental Association (ANSI/ADA) specification no. 18 detail reproduction die and impressions made simultaneously of a smooth glass die were cast in Microstone, Silky-Rock, and Die-Keen. Five specimens were made for each alginate/disinfectant/gypsum combination for a total of 300 samples each for both the subjective and objective analyses. For the subjective analysis of gypsum compatibility, the specimens made from the ANSI/ADA specification no. 18 test die were evaluated by using a 1-to-4 visual rating system at magnification x12. For the objective analysis, the arithmetic average surface roughness of each specimen made from the smooth glass die was recorded three times with a 200-mg skidless stylus instruments. The results of the ANSI/ADA specification no. 18 testing for gypsum compatibility showed that 11 of 60 possible combinations did not pass the test. All impressions made with nonantimicrobial COE Alginate passed the test regardless of the disinfectant/gypsum combination. The results of the three-factor analysis of variance for the subjective and objective analyses showed significant interactions between alginates, disinfectants, and stones at the P < .05 level. To further delineate these differences, unpaired t tests (P < .05) within brands for each disinfectant/gypsum combination were performed. The addition of 1% chlorhexidine diacetate to COE Hydrophilic Gel Alginate has decreased its compatibility with the dental stones and disinfectants tested when compared with its nonantimicrobial counterpart. In terms of gypsum compatibility, the nonantimicrobial COE Alginate was compatible with all disinfectant and gypsum combinations tested. The addition of 1.70% didecyldimethyl ammonium chloride to Jeltrate Plus Antimicrobial Alginate has increased its compatibility with all the dental stones tested. A strong positive correlation (r = 0.7398) was found between visual gypsum compatibility evaluation scores and surface roughness of gypsum casts.


KRAS Mutation Testing on Endoscopic Ultrasound-Guided Fine-Needle Aspiration Samples Improves the Diagnostic Accuracy of Pancreatic Cancer.
Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology was one of the investigations for pancreatic masses. While the specificity approached 100%, its sensitivity remained low because of high rate of indeterminate and false-negative results. Meanwhile, KRAS gene was frequently mutated in up to 90% of pancreatic ductal adenocarcinoma and its precursor lesions. This study aimed to determine whether KRAS mutation analysis could improve the diagnostic sensitivity in EUS-FNA samples for pancreatic adenocarcinoma. The EUS-FNA samples from patients with a pancreatic mass obtained between January 2016 and December 2017 were reviewed retrospectively. The cytology results were classified as malignant, suspicious for malignancy, atypical, negative for malignancy, and nondiagnostic. KRAS mutation testing was performed using polymerase chain reaction followed by Sanger sequencing. A total of 126 EUS-FNA specimens were reviewed. The overall sensitivity and specificity by cytology alone were 29% and 100%, respectively. When KRAS mutation testing was performed in cases with indeterminate and negative cytology, the sensitivity increased to 74.2%, and the specificity remained at 100%. KRAS mutation analysis, especially when performed in cytologically indeterminate cases, improves the diagnostic accuracy for pancreatic ductal adenocarcinoma. This may reduce the need to repeat invasive EUS-FNA for diagnosis.


Recent Advances of Upconversion Nanomaterials in the Biological Field.
Rare Earth Upconversion nanoparticles (UCNPs) are a type of material that emits high-energy photons by absorbing two or more low-energy photons caused by the anti-stokes process. It can emit ultraviolet (UV) visible light or near-infrared (NIR) luminescence upon NIR light excitation. Due to its excellent physical and chemical properties, including exceptional optical stability, narrow emission band, enormous Anti-Stokes spectral shift, high light penetration in biological tissues, long luminescent lifetime, and a high signal-to-noise ratio, it shows a prodigious application potential for bio-imaging and photodynamic therapy. This paper will briefly introduce the physical mechanism of upconversion luminescence (UCL) and focus on their research progress and achievements in bio-imaging, bio-detection, and photodynamic therapy.


Microsurgical testis biopsy: a novel technique for retrieval of testicular tissue.
In vitro fertilization with intracytoplasmic sperm injection has resulted in a dramatic increase in the need for diagnostic and therapeutic testis biopsies. We developed a microsurgical testis biopsy technique which allows identification of testicular vessels and individual seminiferous tubules. We compare the results of this technique to our prior series of nonmicroscopic biopsies. A retrospective study of 226 consecutive patients who had undergone open testes biopsy with or without an operating microscope was performed. Between 1988 and 1994 standard open testis biopsy was performed without a microscope in 119 patients and a single sample of testicular tissue was taken. After 1994 microsurgical biopsy was performed under 6 to 25x magnification in 107 patients, nearly half of whom had multiple biopsies of each testis. The complication rates of the 2 procedures were compared. Scrotal hematoma required surgical drainage in 3 of the 119 standard testis biopsy cases and testis atrophy was noted in 1, for a total complication rate of 3.4%. There were no episodes of clinically detectable testicular atrophy or scrotal hematoma requiring surgical drainage in the 107 microsurgical biopsy cases (p<0.05). In 2 men the microscope allowed identification of larger tubules that contained sperm. Use of the operating microscope for testicular biopsy allows identification and avoidance of testicular vessels, minimizing complications. It also may allow selection of seminiferous tubules more likely to contain sperm.


[Mediator aspects of the inflammatory process].
Signal sequences of inflammation and regeneration are presented. The number of factors such as sensor neuropeptides, lipid mediators, interleukins and factors of growth are shown to participate in the initiation and regulation of inflammation. These factors are produced in a certain sequence by various structures: cells-object of damage, opsonocytophagic and immune cells, connective tissue cells. This results in the stimulation of adhesion proteins, processes of migration, chemotaxis, interaction with components of the intercellular matrix and parenchyma cells of the viscera. Fibroblast is considered to be the central figure in the resolution of inflammation and its chronization. The regulation of the process occurs with the help of autocrine regulation and apoptosis of functionally exhausted cells.


Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing.
Even though the mother and the fetus of placental mammals are immunologically non-self with respect to one other, mutual exchange of small numbers of cells between them is known to occur. Maternal cells entering the fetus, called maternal microchimeric cells (MMc cells), are thought to be involved in different physiological phenomena, such as establishing immune tolerance, tissue repair, and the pathogenesis or deterioration of some inflammatory diseases and congenital malformations. While specific MMc cell types have been reported as associated with these phenomena, the contribution of MMc cells to these different outcomes remains unknown. As one possibility, we hypothesized that different embryos have differing repertoires of MMc cell types, leading to or biasing embryos toward different fates. To date, no studies have succeeded in identifying the MMc cell type repertoire of a single embryo. Accordingly, here, we isolated MMc cells from whole mouse embryos, determined their types, and analyzed their MMc cell type variability. By combining our previously established, whole-embryonic MMc isolation method with single-cell RNA sequencing, we successfully estimated the cell type repertoires of MMc cells isolated from 26 mouse embryos. The majority of MMc cells were immune-related cells, such as myeloid cells and granulocytes. We also detected stem cell-like MMc cells expressing proliferation marker genes and terminally differentiated cells. As hypothesized, we noted statistically significant inter-individual variation in the proportion of immune-related cells in the different embryos. We here successfully estimated MMc cell types in individual whole mouse embryos. The proportion of immune-related cells significantly differed among the individual embryos, suggesting that the variations are one of the potential mechanisms underlying the differing MMc-related physiological phenomena in offspring. These findings provide insight into cell-level epigenetics by maternal cells.


Studies on the polymorphism of carbromal.
Specimens of carbromal obtained by crystallization from various solvents were analyzed. After a 9-month storage period, the occurrence of three polymorphic forms (I, II and III) was ascertained. The metastable form III obtained by crystallization from dimethylformamide showed a reasonably high stability. Preliminary pharmacological tests revealed clear-cut differences in the therapeutic effect between a commercial specimen and the polymorphic modification III. The results presented here indicate the importance of polymorphism of carbromal for medicinal use.


Adrenergic activation of electrogenic K+ secretion in guinea pig distal colonic epithelium: desensitization via the Y2-neuropeptide receptor.
Adrenergic activation of electrogenic K+ secretion in isolated mucosa from guinea pig distal colon was desensitized by peptide-YY (PYY). Addition of PYY or neuropeptide-Y (NPY) to the bathing solution of mucosae in Ussing chambers suppressed the short-circuit current (Isc) corresponding to electrogenic Cl- secretion, whether stimulated by epinephrine (epi), prostaglandin-E2 (PGE2), or carbachol (CCh). Neither peptide markedly inhibited the large transient component of synergistic secretion (PGE2 + CCh). Sustained Cl- secretory Isc was inhibited approximately 65% by PYY or NPY, with IC50s of 4.1 +/- 0.9 nM and 9.4 +/- 3.8 nM, respectively. This inhibition was eliminated by BIIE0246, an antagonist of the Y2-neuropeptide receptor (Y2-NpR), but not by Y1-NpR antagonist BVD10. Adrenergic sensitivity for activation of K+ secretion in the presence of Y2-NpR blockade by BIIE0246 was (EC50s) 2.9 +/- 1.2 nM for epi and 13.3 +/- 1.0 nM for norepinephrine, approximately fourfold greater than in the presence of PYY. Expression of mRNA for both Y1-NpR and Y2-NpR was indicated by RT-PCR of RNA from colonic mucosa, and protein expression was indicated by immunoblot. Immunoreactivity (ir) for Y1-NpR and Y2-NpR was distinct in basolateral membranes of columnar epithelial cells in the crypts of Lieberkühn as well as intercrypt surface epithelium. Adrenergic nerves in proximity with crypts were detected by ir for dopamine-beta-hydroxylase, and a portion of these nerves also contained NPY(ir). BIIE0246 addition increased secretagog-activated Isc, consistent with in vitro release of either PYY or NPY. Thus PYY and NPY were able to suppress Cl- secretory capacity and desensitize the adrenergic K+ secretory response, providing a direct inhibitory counterbalance against secretory activation.


Effect of Different Doses of Acetylsalicylic Acid on the Antithrombotic Activity of Clopidogrel in a Mouse Arterial Thrombosis Model.
Objective- Dual-antiplatelet therapy with acetylsalicylic acid and a P2Y12 antagonist, such as clopidogrel, is the standard of care for acute coronary syndromes. However, the drugs have divergent effects on the formation of cAMP, an inhibitory second messenger. Thus, by inhibiting the synthesis of prostacyclin, acetylsalicylic acid reduces cAMP formation, whereas clopidogrel potentiates it. Therefore, with higher doses of acetylsalicylic acid, the potentiation of cAMP production by clopidogrel may be attenuated, which could limit the antithrombotic potential of the drug combination. The purpose of this study was to examine this possibility in vivo. Approach and Results- Mice were given oral acetylsalicylic acid at varying doses, oral clopidogrel (5 mg/kg body weight), or both. At doses of 0.15 and 0.6 mg/kg, acetylsalicylic acid inhibited arachidonic acid-induced platelet aggregation, but only 0.6 mg/kg acetylsalicylic acid, or higher, decreased the plasma levels of 6-keto-prostaglandin-F1α, the stable metabolite of prostacyclin. When given with clopidogrel, laser injury-induced arterial thrombi were significantly larger with the 0.6 mg/kg dose of acetylsalicylic acid than with the 0.15 mg/kg dose. Thrombi in mice treated with clopidogrel and the 0.15 mg/kg dose of acetylsalicylic acid were smaller than in mice treated with clopidogrel alone, suggesting that acetylsalicylic acid can add to the antithrombotic effect of clopidogrel but that higher doses of acetylsalicylic acid blunt the antithrombotic effect of clopidogrel. Conclusions- These findings support the use of lower, prostacyclin-preserving, doses of acetylsalicylic acid in conjunction with clopidogrel.


Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease.
Despite convenience, accessibility, and strong correlation to severity of Alzheimer disease (AD) pathology, medial temporal lobe atrophy (MTA) has not been used as a criterion in the diagnosis of prodromal and probable AD. Using a newly validated visual rating system, mean MTA scores of three bilateral medial temporal lobe structures were compared for subjects with no cognitive impairment (NCI) (n = 117), nonamnestic mild cognitive impairment (MCI) (n = 46), amnestic MCI (n = 45), and probable AD (n = 53). Correlations between MTA scores and neuropsychological test scores at baseline, and predictors of change in diagnosis at 1-year follow-up were evaluated. With NCI as the reference group, a mean MTA cut score of 1.33 yielded an optimal sensitivity/specificity of 85%/82% for probable AD subjects and 80%/82% for amnestic MCI subjects. MTA and Clinical Dementia Rating Sum of Boxes scores at baseline were independent and additive predictors of diagnosis at baseline, and of transition from NCI to MCI or from MCI to dementia at 1-year follow-up. Medial temporal lobe atrophy (MTA) scores 1) distinguish probable Alzheimer disease (AD) and amnestic mild cognitive impairment (MCI) subjects from nonamnestic MCI and no cognitive impairment (NCI) subjects, 2) help predict diagnosis at baseline, and 3) predict transition from NCI to MCI and from MCI to probable AD. MTA scores should be used as a criterion in the clinical diagnosis of AD.


ΔNp63α Silences a miRNA Program to Aberrantly Initiate a Wound-Healing Program That Promotes TGFβ-Induced Metastasis.
Primary cancer cell dissemination is a key event during the metastatic cascade, but context-specific determinants of this process remain largely undefined. Multiple reports have suggested that the p53 (TP53) family member p63 (TP63) plays an antimetastatic role through its minor epithelial isoform containing the N-terminal transactivation domain (TAp63). However, the role and contribution of the major p63 isoform lacking this domain, ΔNp63α, remain largely undefined. Here, we report a distinct and TAp63-independent mechanism by which ΔNp63α-expressing cells within a TGFβ-rich microenvironment become positively selected for metastatic dissemination. Orthotopic transplantation of ΔNp63α-expressing human osteosarcoma cells into athymic mice resulted in larger and more frequent lung metastases than transplantation of control cells. Mechanistic investigations revealed that ΔNp63α repressed miR-527 and miR-665, leading to the upregulation of two TGFβ effectors, SMAD4 and TβRII (TGFBR2). Furthermore, we provide evidence that this mechanism reflects a fundamental role for ΔNp63α in the normal wound-healing response. We show that ΔNp63α-mediated repression of miR-527/665 controls a TGFβ-dependent signaling node that switches off antimigratory miR-198 by suppressing the expression of the regulatory factor, KSRP (KHSRP). Collectively, these findings reveal that a novel miRNA network involved in the regulation of physiologic wound-healing responses is hijacked and suppressed by tumor cells to promote metastatic dissemination. Cancer Res; 76(11); 3236-51. ©2016 AACR.


Physiological Adaptations to Sugar Intake: New Paradigms from Drosophila melanogaster.
Sugars are important energy sources, but high sugar intake poses a metabolic challenge and leads to diseases. Drosophila melanogaster is a generalist fruit breeder that encounters high levels of dietary sugars in its natural habitat. Consequently, Drosophila displays adaptive responses to dietary sugars, including highly conserved and unique metabolic adaptations not described in mammals. Carbohydrate homeostasis is maintained by a network comprising intracellular energy sensors, transcriptional regulators, and hormonal and neuronal mechanisms that together coordinate animal behavior, gut function, and metabolic flux. Here we give an overview of the physiological responses associated with sugar intake and discuss some of the emerging themes and applications of the Drosophila model in understanding sugar sensing and carbohydrate metabolism.


Association between sequevar and antibiotic treatment outcome in patients with Mycobacterium abscessus complex infections in Japan.
Macrolide susceptibility differs between subspecies in the Mycobacterium abscessus complex, likely due to differences in erm(41) sequevars. Patients with M. abscessus complex infection generally show poor clinical outcomes in response to antibiotic treatment. Here, the association between genotype and treatment outcome was investigated. We collected 69 isolates from 35 patients with non-cystic fibrosis bronchiectasis: 24 had M. abscessus complex lung disease and non-cystic fibrosis bronchiectasis, and 11 were colonized. Outcome analysis was performed in the 24 infected patients. Molecular analyses, including erm(41) and rrl sequencing, and variable-number tandem-repeat (VNTR) analysis of 69 isolates, from 24 infected and 11 colonized patients, were performed to elucidate the influence of genotype on antibiotic susceptibility. Among the 24 patients, 18 (14 infected with M. abscessus subsp. abscessus and 4 with M. abscessus subsp. massiliense) showed unfavourable outcomes; six (three infected with M. abscessus subsp. abscessus and three with M. abscessus subsp. massiliense) exhibited favourable outcomes. Patients with unfavourable outcomes showed acquired clarithromycin resistance (33.3 vs 0 %), mixed sequevars (38.9 vs 16.7 %) and differing VNTR patterns between initial and serial isolates (33.3 vs 16.7 %). In contrast, in the 11 colonized patients, M. abscessus subsp. abscessus C28 (sequevar 02) and M. abscessus subsp. massiliense were the most prevalent subspecies. Patients infected with multiple sequevars and genotypes were more likely to exhibit treatment failure and/or recurrence. The precise identification of subspecies and analyses of mycobacterial characteristics may help to predict treatment outcomes in patients with M. abscessus complex lung disease.


The effects of pastoral intensification on the feeding interactions of generalist predators in streams.
Land-use change can alter trophic interactions with wide-ranging functional consequences, yet the consequences for aquatic food webs have been little studied. In part, this may reflect the challenges of resolving the diets of aquatic organisms using classical gut contents analysis, especially for soft-bodied prey. We used next-generation sequencing to resolve prey use in nearly 400 individuals of two predatory invertebrates (the Caddisfly, Rhyacophila dorsalis, and the Stonefly Dinocras cephalotes) in streams draining land with increasingly intensive livestock farming. Rhyacophila dorsalis occurred in all streams, whereas D. cephalotes was restricted to low intensities, allowing us to test whether: (i) apparent sensitivity to agriculture in the latter species reflects a more specialized diet and (ii) diet in R. dorsalis varied between sites with and without D. cephalotes. DNA was extracted from dissected gut contents, amplified without blocking probes and sequenced using Ion Torrent technology. Both predators were generalists, consuming 30 prey taxa with a preference for taxa that were abundant in all streams or that increased with intensification. Where both predators were present, their diets were nearly identical, and R. dorsalis's diet was virtually unchanged in the absence of D. cephalotes. The loss of D. cephalotes from more intensive sites was probably due to physicochemical stressors, such as sedimentation, rather than to dietary specialization, although wider biotic factors (e.g., competition with other predatory taxa) could not be excluded. This study provides a uniquely detailed description of predator diets along a land-use intensity gradient, offering new insights into how anthropogenic stressors affect stream communities.


Regulation of pollen tube growth by Rac-like GTPases.
Plant Rac-like GTPases have been classified phylogenetically into two major groups-class I and class II. Several pollen-expressed class I Rac-like GTPases have been shown to be important regulators of polar pollen tube growth. The functional participation by some of the class I and all of the class II Arabidopsis Rac-like GTPases in pollen tube growth remains to be explored. It is shown that at least four members of the Arabidopsis Rac GTPase family are expressed in pollen, including a class II Rac, AtRac7. However, when over-expressed as fusion proteins with GFP, both pollen- and non-pollen-expressed AtRacs interfered with the normal pollen tube tip growth process. These observations suggest that these AtRacs share similar biochemical activities and may integrate into the pollen cellular machinery that regulates the polar tube growth process. Therefore, the functional contribution by individual Rac GTPase to the pollen tube growth process probably depends to a considerable extent on their expression characteristics in pollen. Among the Arabidopsis Racs, GFP-AtRac7 showed association with the cell membrane and Golgi bodies, a pattern distinct from all previously reported localization for other plant Racs. Over-expressing GFP-AtRac7 also induced the broadest spectrum of pollen tube growth defects, including pollen tubes that are bifurcated, with diverted growth trajectory or a ballooned tip. Transgenic plants with multiple copies of the chimeric Lat52-GFP-AtRac7 showed severely reduced seed set, probably many of these defective pollen tubes were arrested, or reduced in their growth rates that they did not arrive at the ovules while they were still receptive for fertilization. These observations substantiate the importance of Rac-like GTPases to sexual reproduction.


Synthesis of Cyclic and Acyclic Pyrimidine Nucleosides Analogues with Anticipated Antiviral Activity.
A convenient method for preparation of cyclic and acyclic nucleosides was achieved by alkylation of 6-(2,4-dichlorophenoxymethyl) pyrimidine-2,4-dione (1) with a variety of acyclic and cyclic activated sugar analogues, namely (2-acetoxyethoxy)methyl acetate (3), 2-(acetoxymethoxy)propane-1,3-diyl dibenzoate (4), benzyloxymethyl acetate (5), 2-acetoxy-5-(benzoyloxymethyl)tetrahydrofuran-3,4-diyl dibenzoate (12), 5-chloro-2-((4-chlorobenzoyloxy)methyl) tetrahydrofuran-3-yl 4-chlorobenzoate (13) and 2-(acetoxymethyl)-6-bromotetrahydro-2H-pyran-3,4,5-triyl triacetate (14), respectively. Deprotection of the synthesized nucleosides was achieved by using methanolic ammonia. The structures of the newly synthesized nucleoside analogues were fully characterized by analytical methods (mass spectrometry, 1H NMR, 13C NMR, and elemental analysis).


The effects of the SUN project on teacher knowledge and self-efficacy regarding biological energy transfer are significant and long-lasting: results of a randomized controlled trial.
Biological energy flow has been notoriously difficult to teach. Our approach to this topic relies on abiotic and biotic examples of the energy released by moving electrons in thermodynamically spontaneous reactions. A series of analogical model-building experiences was supported with common language and representations including manipulatives. These materials were designed to help learners understand why electrons move in a hydrogen explosion and hydrogen fuel cell, so they could ultimately understand the rationale for energy transfer in the mitochondrion and the chloroplast. High school biology teachers attended a 2-wk Students Understanding eNergy (SUN) workshop during a randomized controlled trial. These treatment group teachers then took hydrogen fuel cells, manipulatives, and other materials into their regular biology classrooms. In this paper, we report significant gains in teacher knowledge and self-efficacy regarding biological energy transfer in the treatment group versus randomized controls. Significant effects on treatment group teacher knowledge and self-efficacy were found not only post-SUN workshop but even 1 yr later. Teacher knowledge was measured with both a multiple-choice exam and a drawing with a written explanation. Teacher confidence in their ability to teach biological energy transfer was measured by a modified form of the Science Teaching Efficacy Belief Instrument, In-Service A. Professional development implications regarding this topic are discussed.


Gender Specific Re-organization of Resting-State Networks in Older Age.
Advancing age is commonly associated with changes in both brain structure and function. Recently, the suggestion that alterations in brain connectivity may drive disruption in cognitive abilities with age has been investigated. However, the interaction between the effects of age and gender on the re-organization of resting-state networks is not fully understood. This study sought to investigate the effect of both age and gender on intra- and inter-network functional connectivity (FC) and the extent to which resting-state network (RSN) node definition may alter with older age. We obtained resting-state functional magnetic resonance images from younger (n = 20) and older (n = 20) adults and assessed the FC of three main cortical networks: default mode (DMN), dorsal attention (DAN), and saliency (SN). Older adults exhibited reduced DMN intra-network FC and increased inter-network FC between the anterior cingulate cortex (ACC) and nodes of the DAN, in comparison to younger participants. Furthermore, this increase in ACC-DAN inter-network FC with age was driven largely by male participants. However, further analyses suggested that the spatial location of ACC, bilateral anterior insula and orbitofrontal cortex RSN nodes changed with older age and that age-related gender differences in FC may reflect spatial re-organization rather than increases or decreases in FC strength alone. These differences in both the FC and spatial distribution of RSNs between younger and older adults provide evidence of re-organization of fundamental brain networks with age, which is modulated by gender. These results highlight the need to further investigate changes in both intra- and inter-network FC with age, whilst also exploring the modifying effect of gender. They also emphasize the difficulties in directly comparing the FC of RSN nodes between groups and suggest that caution should be taken when using the same RSN node definitions for different age or patient groups to investigate FC.


[The optimization of the net structure of curative preventive institutions in rural municipal area].
The article considers the issue of optimization of structure of the medical institutions network of the municipal unit in rural area based on the enhancement of planning of amount of poly-clinical and hospital care. The planned normative indicators have to be considered in concordance with the state guarantees program, characteristics of composition and structure of population, settlement of inhabitants in the region, morbidity and other factors. The results of study are assumed as a basis for the adjustment of factual amount of medical care consumption considering real population needs.


Uncollimated gamma camera measurements at two metres to the patient provide a practical and statistically robust method for SeHCAT retention calculation.
[75Se]tauroselcholic acid (SeHCAT) retention studies may be performed using a collimated or uncollimated (intrinsic) gamma camera, with trade-offs between counting sensitivity, collision risk, and stray source influence. In this work, we evaluate the uncertainty in SeHCAT studies performed in 'outer room' mode, where the patient sits or stands two metres away from the uncollimated camera face. 768 SeHCAT studies performed at the Royal Free Hospital were analysed retrospectively, and in all cases, the absolute uncertainty was found to be well within the clinically acceptable limit of ±1 percentage point at 15% retention. The mean counting sensitivity was found to be 1.64 cps/kBq, which is higher than collimated counting but lower than uncollimated counting with the patient on the couch. Seeing as the outer room method does not require patients to transfer onto the couch it may provide savings in setup time which may offset the necessarily longer acquisition time. Because the patient does not come into close proximity to the unprotected camera face the risk of collision is also reduced. Spectra from a SeHCAT capsule in a water-filled torso phantom were used to examine the potential impact of modifying the energy windows. We recommend adopting a wide central photopeak and downscatter window (160-296 keV) plus a lower photopeak window (111-159 keV), which may provide significant improvements in sensitivity. This improved sensitivity could be used to reduce the acquisition time, which is of particular interest in the context of increasing numbers of referrals for SeHCAT retention tests.


[Specific cytotoxicity of recombinant interleukin 6-pseudomonas exotoxin fusion protein (IL6-PE40) on LT12 leukemic cells expressing high levels of interleukin 6 receptor (IL6R)].
An acute promyelocytic leukemic cell line LT12 was transduced with IL6R cDNA by electroporation. The resultant LT12-IL6R+ leukemic cells expressed more than 1000 IL6R per cell. The effect of the recombinant IL6-PE40 on both the LT12-IL6R+ cells and the IL6R- parental cells (LT12-IL6R-) was studied by leukemic progenitor colony (CFU-L) formation and 3H-TdR incorporation assays. It was found that IL6-PE40 at concentrations ranging from 1 to 1,000 ng/ml inhibited CFU-L formation and DNA synthesis of LT12-IL6R+ cells in a dose-dependent manner. No inhibition was seen at the same concentration range in LT12-IL6R- cells. At concentrations of 250-1000ng/ml, IL6-PE40 led to only 40% inhibition of DNA synthesis in LT12-IL6R- cells. Inasmuch as rIL6 at the same concentrations had no significant effect on both IL6R+ and IL6R- cells, we concluded it is IL6-PE40 that exerts its highly specific killing on leukemic cells expressing high levels of IL6R.


Brain Structural Effects of Antidepressant Treatment in Major Depression.
Depressive disorder is a very frequent and heterogeneous syndrome. Structural imaging techniques offer a useful tool in the comprehension of neurobiological alterations that concern depressive disorder. Altered brain structures in depressive disorder have been particularly located in the prefrontal cortex (medial prefrontal cortex and orbitofrontal cortex, OFC) and medial temporal cortex areas (hippocampus). These brain areas belong to a structural and functional network related to cognitive and emotional processes putatively implicated in depressive symptoms. These volumetric alterations may also represent biological predictors of response to pharmacological treatment. In this context, major findings of magnetic resonance (MR) imaging, in relation to treatment response in depressive disorder, will here be presented and discussed.


Laboratory-Based and Point-of-Care Testing for MSSA/MRSA Detection in the Age of Whole Genome Sequencing.
Staphylococcus aureus is an opportunistic pathogen of animals and humans that is capable of both colonizing and infecting its eukaryotic host. It is frequently detected in the clinical microbiology routine laboratory. S. aureus is capable of acquiring antibiotic resistance traits with ease and, given its rapid global dissemination, resistance to meticillin in S. aureus has received extensive coverage in the popular and medical press. The detection of meticillin-resistant versus meticillin-susceptible S. aureus (MRSA and MSSA) is of significant clinical importance. Detection of meticillin resistance is relatively straightforward since it is defined by a single determinant, penicillin-binding protein 2a', which exists in a limited number of genetic variants carried on various Staphylococcal Cassette Chromosomes mec. Diagnosis of MRSA and MSSA has evolved significantly over the past decades and there has been a strong shift from culture-based, phenotypic methods toward molecular detection, especially given the close correlation between the presence of the mec genes and phenotypic resistance. This brief review summarizes the current state of affairs concerning the mostly polymerase chain reaction-mediated detection of MRSA and MSSA in either the classical laboratory setting or at the point of care. The potential diagnostic impact of the currently emerging whole genome sequencing (WGS) technology will be discussed against a background of diagnostic, surveillance, and infection control parameters. Adequate detection of MSSA and MRSA is at the basis of any subsequent, more generic antibiotic susceptibility testing, epidemiological characterization, and detection of virulence factors, whether performed with classical technology or WGS analyses.


Patterns of Atypical Functional Connectivity and Behavioral Links in Autism Differ Between Default, Salience, and Executive Networks.
Autism spectrum disorder (ASD) is characterized by atypical brain network organization, but findings have been inconsistent. While methodological and maturational factors have been considered, the network specificity of connectivity abnormalities remains incompletely understood. We investigated intrinsic functional connectivity (iFC) for four "core" functional networks-default-mode (DMN), salience (SN), and left (lECN) and right executive control (rECN). Resting-state functional MRI data from 75 children and adolescents (37 ASD, 38 typically developing [TD]) were included. Functional connectivity within and between networks was analyzed for regions of interest (ROIs) and whole brain, compared between groups, and correlated with behavioral scores. ROI analyses showed overconnectivity (ASD > TD), especially between DMN and ECN. Whole-brain results were mixed. While predominant overconnectivity was found for DMN (posterior cingulate seed) and rECN (right inferior parietal seed), predominant underconnectivity was found for SN (right anterior insula seed) and lECN (left inferior parietal seed). In the ASD group, reduced SN integrity was associated with sensory and sociocommunicative symptoms. In conclusion, atypical connectivity in ASD is network-specific, ranging from extensive overconnectivity (DMN, rECN) to extensive underconnectivity (SN, lECN). Links between iFC and behavior differed between groups. Core symptomatology in the ASD group was predominantly related to connectivity within the salience network.


[Problems and perspectives of radiotherapy of non-tumor diseases].
The experience of the world leading hospitals confirms the high efficacy and appropriateness of radiation therapy of nontumorous diseases. The authors consider the general principles of the organization of radiotherapeutic service, discuss reasons that have led to a decrease in the use of this method for therapy of nontumorous diseases in this country. They also emphasize the fact that radiation therapy must have its place among therapeutic modalities used for nontumorous diseases.


Effects of nicotinamide on cardiac contraction force and slow inward current.
The effects of nicotinamide (Nic) on cardiac contraction force and on slow inward current (Isi) in guinea pigs were studied with atrial strips and voltage clamp techniques. Verapamil (Ver), MnCl2, nifedipine (Nif), and propranolol (Pro) depressed markedly the positive inotropic effect induced by Nic in a noncompetitive manner. The pD2 values of Ver, MnCl2, Nif, and Pro were 6.19, 3.41, 5.00, and 6.43, respectively. The action of Nic was reduced by a low Ca2+ Tyrode solution and disappeared in a Ca(2+)-free solution. Nic 33 mmol.L-1 elevated the Isi from 6.5 +/- 1.3 microA to 10.3 +/- 2.2 microA. The results suggest that Nic promotes the Ca2+ influx and its site of action is different from that of both Pro and the calcium antagonists.


Ewing's sarcoma family of tumors: current management.
Ewing's sarcoma is the second most frequent primary bone cancer, with approximately 225 new cases diagnosed each year in patients less than 20 years of age in North America. It is one of the pediatric small round blue cell tumors, characterized by strong membrane expression of CD99 in a chain-mail pattern and negativity for lymphoid (CD45), rhabdomyosarcoma (myogenin, desmin, actin) and neuroblastoma (neurofilament protein) markers. Pathognomonic translocations involving the ews gene on chromosome 22 and an ets-type gene, most commonly the fli1 gene on chromosome 11, are implicated in the great majority of cases. Clinical presentation is usually dominated by local bone pain and a mass. Imaging reveals a technetium pyrophosphate avid lesion that, on plain radiograph, is destructive, diaphyseal and classically causes layered periosteal calcification. Magnetic resonance best defines the extent of the lesion. Biopsy should be undertaken by an experienced orthopedic oncologist. Approximately three quarters of patients have initially localized disease. About two thirds survive disease-free. Management, preferably at a specialist center with a multi-disciplinary team, includes both local control-either surgery, radiation or a combination-and systemic chemotherapy. Chemotherapy includes cyclic combinations, incorporating vincristine, doxorubicin, cyclophosphamide, etoposide, ifosfamide and occasionally actinomycin D. Topotecan in combination with cyclophosphamide has shown preliminary activity. Patients with initially metastatic disease fare less well, with about one quarter surviving. Studies incorporating intensive therapy followed by stem cell infusion show no clear benefit. New approaches include anti-angiogenic therapy, particularly since vascular endothelial growth factor is an apparent downstream target of the ews-fli1 oncogene.


Development of High-Risk Geriatric Polypharmacy Electronic Clinical Quality Measures and a Pilot Test of EHR Nudges Based on These Measures.
Inappropriate polypharmacy, prevalent among older patients, is associated with substantial harms. To develop measures of high-risk polypharmacy and pilot test novel electronic health record (EHR)-based nudges grounded in behavioral science to promote deprescribing. We developed and validated seven measures, then conducted a three-arm pilot from February to May 2019. Validation used data from 78,880 patients from a single large health system. Six physicians were pre-pilot test environment users. Sixty-nine physicians participated in the pilot. Rate of high-risk polypharmacy among patients aged 65 years or older. High-risk polypharmacy was defined as being prescribed ≥5 medications and satisfying ≥1 of the following high-risk criteria: drugs that increase fall risk among patients with fall history; drug-drug interactions that increase fall risk; thiazolidinedione, NSAID, or non-dihydropyridine calcium channel blocker in heart failure; and glyburide, glimepiride, or NSAID in chronic kidney disease. Physicians received EHR alerts when renewing or prescribing certain high-risk medications when criteria were met. One practice received a "commitment nudge" that offered a chance to commit to addressing high-risk polypharmacy at the next visit. One practice received a "justification nudge" that asked for a reason when high-risk polypharmacy was present. One practice received both. Among 55,107 patients 65 and older prescribed 5 or more medications, 6256 (7.9%) had one or more high-risk criteria. During the pilot, the mean (SD) number of nudges per physician per week was 1.7 (0.4) for commitment, 0.8 (0.5) for justification, and 1.9 (0.5) for both interventions. Physicians requested to be reminded to address high-risk polypharmacy for 236/833 (28.3%) of the commitment nudges and acknowledged 441 of 460 (95.9%) of justification nudges, providing a text response for 187 (40.7%). EHR-based measures and nudges addressing high-risk polypharmacy were feasible to develop and implement, and warrant further testing.


Oocyte retrieval in an IVF program. A comparison of laparoscopic and transvaginal ultrasound-guided follicular puncture.
From 1 April 1986 to 20 May 1987, 160 oocyte retrievals were performed in our IVF program. 80 oocyte retrievals were done by laparoscopy under general anaesthesia and 80 under light sedation and local analgesia using transvaginal ultrasound guided follicle puncture. More oocytes were recovered with the ultrasound procedure than with laparoscopy, 616 versus 478. The fertilization rate was higher when the oocytes were collected with the ultrasound procedure, vis-à-vis laparoscopy, 70.6% versus 59.6%. The number of embryos transferred was greater in the former than in the latter group, 300 versus 182. There were 13 clinical pregnancies in the laparoscopy group versus 17 in the ultrasound group. There were no serious complications in either group. Transvaginal ultrasound guided follicle aspiration is a safe and simple procedure.


Temporal effects of prescribed burning on terpene production in Mediterranean pines.
Prescribed burning is used to reduce fuel hazard but underburning can damage standing trees. The effect of burning on needle terpene storage, a proxy for secondary metabolism, in fire-damaged pines is poorly understood despite the protection terpenes confer against biotic and abiotic stressors. We investigated variation in needle terpene storage after burning in three Mediterranean pine species featuring different adaptations to fire regimes. In two pure-stands of Pinus halepensis Mill. and two mixed-stands of Pinus sylvestris L. and Pinus nigra ssp. salzmanni (Dunal) Franco, we compared 24 h and 1 year post-burning concentrations with pre-burning concentrations in 20 trees per species, and evaluated the relative contribution of tree fire severity and physiological condition (δ13C and N concentration) on temporal terpene dynamics (for mono- sesqui- and diterpenes). Twenty-four hours post-burning, monoterpene concentrations were slightly higher in P. halepensis than at pre-burning, while values were similar in P. sylvestris. Differently, in the more fire-resistant P. nigra monoterpene concentrations were lower at 24 h, compared with pre-burning. One year post-burning, concentrations were always lower compared with pre- or 24 h post-burning, regardless of the terpene group. Mono- and sesquiterpene variations were negatively related to pre-burning δ13C, while diterpene variations were associated with fire-induced changes in needle δ13C and N concentration. At both post-burning times, mono- and diterpene concentrations increased significantly with crown scorch volume in all species. Differences in post-burning terpene contents as a function of the pine species' sensitivity to fire suggest that terpenic metabolites could have adaptive importance in fire-prone ecosystems in terms of flammability or defence against biotic agents post-burning. One year post-burning, our results suggest that in a context of fire-induced resource availability, pines likely prioritize primary rather than secondary metabolism. Overall, this study contributes to the assessment of the direct and indirect effects of fire on pine terpene storage, providing valuable information about their vulnerability to biotic and abiotic stressors throughout time.


Acute hemorrhagic leukoencephalitis in patients with acute myeloid leukemia in hematologic complete remission.
The authors describe the cases of three patients affected by acute myeloid leukemia, in complete remission, who rapidly developed neurologic symptoms leading to death. Neither clinical characteristics, nor radiological or microbiological procedures, allowed an etiological diagnosis of the neurologic syndrome. Post-mortem examination of the brain showed both macroscopic and microscopic findings compatible with acute hemorrhagic leukoencephalitis. The difficulty in distinguishing this entity from other CNS disease-related complications (e.g. leukemia infiltration, drug toxicity, hemorrhages) should not lead to an underestimation of the true incidence of this complication. We believe that with more attention to the possibility of this complication there would probably be both a greater possibility of collecting clinical informations about the real impact of this dramatic disease and a stronger hope of finding the right treatment for it.


Aggressive angiomyxoma of the vulva.
A case of aggressive angiomyxoma (AAM) of the vulva is presented. The tumor presented as a slowly growing polypoid mass in the right labium minus near the clitoris. The tumor was treated by wide local excision. The microscopic appearance was that of spindle-shaped neoplastic cells widely separated by a loose myxoid stroma rich in collagen fibers, hyaluronic acid, and prominent irregular-shaped blood vessels. Aggressive angiomyxoma of the vulva must be distinguished from the more common benign and malignant myxoid tumors including myxoma, myxoid liposarcoma, myxoid variant of malignant fibrous histiocytoma, sarcoma botryoides, nerve sheath myxoma, and other soft tissue tumors with secondary myxoid changes. Local recurrence of AAM may be avoided by wide local excision.


[Predictive factors of response to electronarcosis].
There is an international consensus on the indications of electroconvulsive treatment (ECT): they result in particular from the limitations of antidepressant drug treatment. Even though the global effect of ECT is considered as satisfactory, 10 to 20% of depressed patients eligible for ECT are treatment refractory. This warrants a search for factors predicting efficacy or lack of efficacy of ECT. Predicting factors prior to ECT: Usual clinical criteria, such as the presence of delusional thoughts, are generally classified with endogenous signs of depression. Among biological criteria, EEG data, tests assessing reactivity of autonomous nervous system, plasma measures of catecholamines, calcium and cortisol do not seem relevant parameters. Dexamethasone suppression test and stimulation of TSH by TRH have no more predictive value. Predictive indices during treatment: Empirically clinicians identified a sequence in the response of depressive symptoms, although no conclusion can be drawn from these clinical impressions. Among biological factors some authors stress the importance of the epileptogenic threshold and of measuring plasma levels of peptides released by the posterior lobe of hypophysis. Such data have to be confirmed and their physiopathological value better understood. Actually some parameters representing good therapeutic practices are valued by physicians using ECT: sufficient duration of electrical crisis, total seizure time during the series of electroshocks. Those conceptions are close to the classical emphasis on the adequate number of ECTs and to the discussion on the comparative efficacy of unilateral and bilateral ECT. After ECT most authors shift to antidepressants, although data about medium and long term outcome prediction with this approach are also lacking.


Prediction of psychosis across protocols and risk cohorts using automated language analysis.
Language and speech are the primary source of data for psychiatrists to diagnose and treat mental disorders. In psychosis, the very structure of language can be disturbed, including semantic coherence (e.g., derailment and tangentiality) and syntactic complexity (e.g., concreteness). Subtle disturbances in language are evident in schizophrenia even prior to first psychosis onset, during prodromal stages. Using computer-based natural language processing analyses, we previously showed that, among English-speaking clinical (e.g., ultra) high-risk youths, baseline reduction in semantic coherence (the flow of meaning in speech) and in syntactic complexity could predict subsequent psychosis onset with high accuracy. Herein, we aimed to cross-validate these automated linguistic analytic methods in a second larger risk cohort, also English-speaking, and to discriminate speech in psychosis from normal speech. We identified an automated machine-learning speech classifier - comprising decreased semantic coherence, greater variance in that coherence, and reduced usage of possessive pronouns - that had an 83% accuracy in predicting psychosis onset (intra-protocol), a cross-validated accuracy of 79% of psychosis onset prediction in the original risk cohort (cross-protocol), and a 72% accuracy in discriminating the speech of recent-onset psychosis patients from that of healthy individuals. The classifier was highly correlated with previously identified manual linguistic predictors. Our findings support the utility and validity of automated natural language processing methods to characterize disturbances in semantics and syntax across stages of psychotic disorder. The next steps will be to apply these methods in larger risk cohorts to further test reproducibility, also in languages other than English, and identify sources of variability. This technology has the potential to improve prediction of psychosis outcome among at-risk youths and identify linguistic targets for remediation and preventive intervention. More broadly, automated linguistic analysis can be a powerful tool for diagnosis and treatment across neuropsychiatry.


Interaction of Zygomycetes with innate immune cells reconsidered with respect to ecology, morphology, evolution and infection biology: a mini-review.
Zygomycetes are saprophytic fungi found ubiquitously in nature. Generally, fungi are considered as the most common microbes encountered by mammalian hosts due to its ubiquity in nature. Among the fungi, the Zygomycetes represent the most basal terrestrial lineage which can cause infections in humans. They comprise two orders, the Mucorales and the Entomophthorales, which contain human pathogenic species. Members of the Mucorales are responsible for mucormycosis; the second most common mould fungi infection in the world and infection with members of the Entomophthorales can result in basidiobolomycosis and conidiobolomycosis. However, the infection does not occur frequently as we have efficient barriers from immune system against the fungal invasion. In this review, a summary is provided on the current literature available on innate immune cells such as polymorphonuclear leucocytes, macrophages, etc. and their interaction with zygomycetes.


Comparative physiological and metabolomic analyses reveal mechanisms of Aspergillus aculeatus-mediated abiotic stress tolerance in tall fescue.
Aspergillus aculeatus has been shown to stimulate plant growth, but its role in plants abiotic stress tolerance and the underlying mechanisms are not fully documented. In this study, we investigated the mechanisms of A.aculeatus-mediated drought, heat and salt stress tolerance in tall fescue. The results showed that A.aculeatus inoculation improved drought and heat stress tolerance in tall fescue as observed from its effect on turf quality (TQ) and leaf relative water content (LWC). In the same stress conditions, A.aculeatus alleviated reactive oxygen species (ROS) induced burst and cell damage, as indicated by lower H2O2, electrolyte leakage (EL) and malondialdehyde (MDA) levels. Additionally, the A.aculeatus inoculated plants exhibited higher photosynthetic efficiency than uninoculated plants under drought, heat and salt stress conditions. The fungus reduced the uptake of Na+, and inoculated plants showed lower Na+/K+, Na+/Ca2+and Na+/Mg2+ ratios compared to uninoculated ones under salt stress. Furthermore, comparative metabolomic analysis showed that A.aculeatus exclusively increased amino acid (such as proline and glycine) and sugar (such as glucose, fructose, sorbose, and talose) accumulation under drought and heat stress. However, there were no differences between inoculated and uninoculated plants except for changes in H2O2 level, Na+ in the root and photosynthetic efficiency under salt stress. Taken together, this study provides the first evidence of the protective roles of A.aculeatus in the tall fescue response to abiotic stresses, partially via protection of photosynthesis and modulation of metabolic homeostasis.


Microbial Contamination During Long-term Ex Vivo Normothermic Machine Perfusion of Human Livers.
Normothermic machine perfusion permits the ex vivo preservation of human livers before transplantation. Long-term perfusion for days-to-weeks provides the opportunity for enhanced pretransplant assessment and potential regeneration of organs. However, this risks microbial contamination and infection of the recipient if the organ is transplanted. An understanding of perfusate microbial contamination is required to inform infection control procedures and antimicrobial prophylaxis for this technology. We modified a liver perfusion machine for long-term use by adding long-term oxygenators and a dialysis filter. Human livers that were not suitable for transplantation were perfused using a red-cell-based perfusate under aseptic and normothermic conditions (36 °C) with a goal of 14 d. Cephazolin was added to the perfusate for antimicrobial prophylaxis. Perfusate and bile were sampled every 72 h for microbial culture. Eighteen partial human livers (9 left lateral segment grafts and 9 extended right grafts) were perfused using our perfusion system. The median survival was 7.2 d. All organs surviving longer than 7 d (9/18) had negative perfusate cultures at 24 and 48 h. Half of the grafts (9/18) became culture-positive by the end of perfusion. Microbial contaminants included Gram-negative (Pseudomonas species, Proteus mirabilis, Stenotrophomonas maltophilia) and Gram-positive bacteria (Staphylococcus epidermidis, Enterococcus faecalis, and Bacillus species) as well as yeast (Candida albicans). Microbial contamination of perfusate is common during long-term perfusion of human livers with both exogenous and endogenous sources. Enhanced infection control practices and review of targeted antimicrobial prophylaxis are likely to be necessary for translation into the clinical arena.


Eel ventricular natriuretic peptide: cDNA cloning and mRNA expression.
Ventricular natriuretic peptide (VNP), a newly discovered type of cardiac natriuretic peptide identified in eels, has a unique amino acid sequence and biological activity compared with other members of the natriuretic peptide family. We have cloned a cDNA encoding the eel VNP precursor from a cDNA library of eel ventricles and determined its sequence. Sequence analysis showed that the preproVNP consists of 150 amino acid residues containing a signal sequence of 22 amino acid residues at its N terminus and mature VNP(1-36) at its C terminus. Comparison with two types of mammalian cardiac natriuretic peptides (A and B type natriuretic peptides; ANP and BNP) revealed that VNP showed greater overall sequence identity to ANP than to BNP at both the cDNA and amino acid sequence levels. Since VNP cDNA lacks the repetitive ATTTA sequence in the 3' non-coding region, which is a characteristic common to all BNP cDNAs sequenced to date, VNP may differ from BNP. While mRNA for eel ANP was detected only in the atrium, that for eel VNP was more abundant in the ventricle than in the atrium. Thus VNP is regarded as the first truly ventricular hormone in terms of synthesis and storage. Southern blot analysis indicated that VNP is also present in the quail, which belongs to a taxon where BNP has already been identified.


Flunisolide intranasal spray in the treatment of perennial rhinitis.
A flunisolide-containing intranasal spray and matching placebo were used in an eight-week, double-blind parallel study in 67 patients with perennial rhinitis. Seventeen patients who did not benefit from treatment with the placebo then switched to flunisolide for a six-week open trial. Flunisolide-treated patients showed greater improvement in both duration and severity of symptoms, as well as a greater preference for flunisolide; 75% of patients either had "mild" symptoms or were asymptomatic and 67% stated that they experienced "substantial" or "total" control of symptoms. No serious side effects were encountered. Chief side effects in both drug and placebo groups were brief, mild, nasal burning and stinging on spray application. The drug exhibited no adverse effects on adrenal function (morning plasma cortisol levels).


[Analysis of the enzyme terminal deoxyribonucleotidyl transferase in lymphoma and leukemia cells].
This work analyses the presence of terminal deoxynucleotidyl transferase (TdT) in neoplastic lymphoid cells from a series of malignant lymphomas and in leukemic cells from blood or bone marrow of patients with lymphoproliferative diseases. The studied cases were 63 patients with acute leukemias, 26 patients with chronic leukemias, 85 patients with lymphomas and 14 normal controls. The presence of TdT in the neoplastic cells was determined by optimized assays of enzymatic activity or by immunofluorescence test for TdT positive blasts. The fluorescence tests made use of anti-TdT antibodies specifically absorbed on cells containing the enzyme and then revealed by a second fluorescent antibody. Appreciable amounts of TdT were found in the white cells of blood or bone marrow from the following 25 out of 35 acute lymphoblastic leukemias (ALL) with modulations in the different phenotypes; 13 out of 14 acute undifferentiated leukemias (AUL); and 9 out of 15 blastic crises in chronic myelogenous leukemia (CMLbc). The enzyme was present in 12 out of 14 lymphomas of lymphoblastic type (LL); 2 B lymphoblastic lymphomas did not show any TdT positivity. The highest levels of TdT were detected in cells classified as immature lymphoblast or in their precursors. TdT was absent from normal lymph nodes from leukocytes of chronic lymphocytic leukemia (CLL) and chronic (CML) and acute myelogenous leukemia (AML). 2 out of 14 cases of AML showed a border-line positivity. A definite correlation between concentrations of enzymatic activity and percentage of immunofluorescent cells could not be established. We did not find a precise correlation between the TdT content of lymphoid blasts and other clinical prognostic indices.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of the compliance with antiemetic guidelines for prevention of chemotherapy-induced nausea and vomiting in patients with hematologic malignancy.
To assess compliance with the Japanese antiemetic guidelines for chemotherapy-induced nausea and vomiting (CINV), the frequencies of CINV occurrence and use of antiemetic rescue medications were examined in patients with hematological malignancy. A total of 40 patients with hematologic malignancy were eligible in this study. This study was performed in the Department of Hematology, Kyushu University Hospital, as a subgroup analysis from a nationwide, multicenter prospective cohort study conducted by the CINV Study Group of Japan. In the patients with hematological malignancy, the guideline compliance rate was 45 %. Five patients (22.7 %) experienced vomiting during the observation period after receiving non-guideline-consistent antiemetic prophylaxis, whereas no patient experienced vomiting after receiving guideline-consistent antiemetic prophylaxis. The study was not sufficiently powered to reach a statistical significance in its frequency of occurrence between the compliance and non-compliance groups. In the entire study period, 8 out of 40 patients required rescue medication, but there was no association between the status of compliance and the antiemetic guidelines. A total of 22 (55.0 %) patients achieved complete response, which was defined as no vomiting and no use of antiemetic rescue medication, during the study period. The rate of compliance with the prophylactic antiemetic treatment guidelines seemed to be low in patients with hematological malignancy, although the status of the guideline compliance did not always influence the antiemetic effects.


Three-step-in-one synthesis of supercapacitor MWCNT superparamagnetic magnetite composite material under flow.
Composites of multi-walled carbon nanotubes (MWCNTs) and superparamagnetic magnetite nanoparticles, Fe3O4@MWCNT, were synthesized in DMF in a vortex fluidic device (VFD). This involved in situ generation of the iron oxide nanoparticles by laser ablation of bulk iron metal at 1064 nm using a pulsed laser, over the dynamic thin film in the microfluidic platform. The overall processing is a three-step in one operation: (i) slicing MWCNTs, (ii) generating the superparamagnetic nanoparticles and (iii) decorating them on the surface of the MWCNTs. The Fe3O4@MWCNT composites were characterized by transmission electron microscopy, scanning transmission electron microscope, TG analysis, X-ray diffraction and X-ray photoelectron spectroscopy. They were used as an active electrode for supercapacitor measurements, establishing high gravimetric and areal capacitances of 834 F g-1 and 1317.7 mF cm-2 at a scan rate of 10 mV s-1, respectively, which are higher values than those reported using similar materials. In addition, the designer material has a significantly higher specific energy of 115.84 W h kg-1 at a specific power of 2085 W kg-1, thereby showing promise for the material in next-generation energy storage devices.


The influence of vgll3 genotypes on sea age at maturity is altered in farmed mowi strain Atlantic salmon.
In Atlantic salmon in the wild, age at maturity is strongly influenced by the vgll3 locus. Under farming conditions, light, temperature and feeding regimes are known significantly advance or delay age at maturity. However, the potential influence of the vgll3 locus on the maturation of salmon reared under farming conditions has been rarely investigated, especially in females. Here, we reared domesticated salmon (mowi strain) with different vgll3 genotypes under standard farming conditions until they matured at either one, two or more than two sea winters. Interestingly, and in contrast to previous findings in the wild, we were not able to identify a link between vgll3 and age at maturity in females when reared under farming conditions. For males however, we found that the probability of delaying maturation from one to two sea winters was significantly lower in fish homozygous for the early allele compared to homozygous fish for the late allele, while the probability for heterozygous fish was intermediate. These data also contrast to previous findings in the wild where the early allele has been reported as dominant. However, we found that the probability of males delaying maturation from two to three sea winters was regulated in the same manner as the wild. Collectively, our data suggest that increased growth rates in mowi salmon, caused by high feed intake and artificial light and temperature regimes together with other possible genetic/epigenetic components, may significantly influence the impact that the vgll3 locus has on age at maturity, especially in females. In turn, our results show that the vgll3 locus can only to a large extent be used in selective breeding to control age at maturation in mowi males. In summary, we here show that in contrast to the situation in wild salmon, under farming conditions vgll3 does not seem to influence age at maturity in mowi females whereas in mowi males, maturing as one or two sea winters it alters the early allele effect from dominant to intermediate.


A domain of murine retrovirus surface protein gp70 mediates cell fusion, as shown in a novel SC-1 cell fusion system.
Virus-induced cell fusion of the fusion-from-without type was observed in SC-1 cells infected with Moloney murine leukemia virus when grown in NIH 3T3 cells. Replication-competent virus mutants with altered surface protein gp70 were examined. Fusion mutations were found in the proline-rich region of gp70. They acted on a step after binding and before or during endocytosis. The fusion mutants had an altered gp70 isomer pattern, presumably caused by different glycosylation. Other mutants with deleted glycans were analyzed, and some which also showed defective fusion were found. The interrelationship of the proline-rich region, glycosylation, and fusion is discussed.


Characteristics of d-Tryptophan as an Antibacterial Agent: Effect of Sodium Chloride Concentration and Temperature on Escherichia coli Growth Inhibition.
We previously reported that d-tryptophan exhibits adverse effects on bacterial physiology under osmotic stress. However, the mechanism by which d-tryptophan acts as an inhibitor and/or incompatible solute for bacterial growth has not yet been investigated in detail. In this study, we aimed to determine how osmotic pressure and temperature affect the antimicrobial effect of d-tryptophan. Even at the same level of osmotic pressure, d-tryptophan in conjunction with sodium chloride (NaCl) had a stronger inhibitory effect on the growth of Escherichia coli than that obtained by incubation with potassium chloride (KCl) and sucrose. Because d-tryptophan with NaCl showed the strongest inhibitory effect, we determined the optimum concentration combination of d-tryptophan and NaCl. The growth inhibition boundary conditions as a function of d-tryptophan and NaCl concentrations were determined by a logistic regression model. We found that the minimum level of NaCl for E. coli growth inhibition was 2.5% (w/v) together with 40 mM d-tryptophan. Moreover, the higher the NaCl concentration, the lower the concentration of d-tryptophan that was needed to inhibit bacterial growth. The logistic regression model that we developed enabled us to predict the concentrations required to inhibit bacterial growth. Furthermore, we examined the effect of incubation temperatures ranging from 15 to 46°C on the antimicrobial effect of d-tryptophan. The higher the reaction temperature, the more rapid the decrease of viable E. coli that was observed. This trend is likely attributable to activation of physiological metabolism under the optimum growth temperature. Together, our findings should make a significant contribution to the development of a novel bacterial growth control strategy using d-tryptophan.


Role of Ca2+ in H+ transport by rabbit gastric glands studied with A23187 and BAPTA, an incorporated Ca2+ chelator.
The role of Ca2+ in stimulation of H+ gastric secretion by cAMP-dependent and -independent secretagogues was studied in isolated rabbit glands using Ca2+ ionophore, A23187, and an intracellular Ca2+ chelator (BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) incorporated as its acetoxymethyl ester (BAPTA-AM). Acetylcholine (ACh), tetragastrin (TG), histamine and forskolin induced a transitory increase of intracellular Ca2+ concentration, [Ca2+]i, measured in gastric glands loaded with Ca2+-sensitive dye fura-2, and provoked an acid secretory response evaluated with aminopyrine accumulation ratio (AP ratio). The Ca2+-ionophore A23187 also induced an increase in [Ca2+]i and in AP ratio. cAMP-dependent secretagogues were more potent stimulants of acid secretion than cAMP-independent secretagogues. cAMP analogue, 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BR-cAMP) induced an increase in AP ratio without modifying [Ca2+]i. BAPTA-AM (5-25 microM) induced a transient decrease of resting [Ca2+]i which returned to basal level due to extracellular Ca2+ entry. Increases in [Ca2+]i produced by ACh and TG were abolished by BAPTA and those produced by Ca2+ ionophore A23187 were partially buffered. BAPTA inhibited in a dose-dependent manner H+ secretion induced by cholinergic and gastrinergic stimulants in the presence of cimetidine. A23187 increased the AP ratio to values similar to those obtained with ACh or TG and was not inhibited by BAPTA. BAPTA partially inhibited (40%) the increase in AP ratio induced by forskolin and histamine inspite of the complete inhibition of the Ca2+ response. BAPTA did not inhibit the response to 8-BR-cAMP. BAPTA inhibition of forskolin stimulation was reversed by A23187 and the response was potentiated. These results indicate that ACh and TG response are completely dependent on an increase of [Ca2+]i. The response to cAMP-dependent agonists histamine and forskolin depend both on Ca2+ and cAMP. For forskolin stimulation the response may be the result of a potentiation between Ca2+ and cAMP.


I guideline for cardiopulmonary resuscitation and emergency cardiovascular care -- Brazilian Society of Cardiology: executive summary.
Despite advances related to the prevention and treatment in the past few years, many lives are lost to cardiac arrest and cardiovascular events in general in Brazil every year. Basic Life Support involves cardiovascular emergency treatment mainly in the pre-hospital environment, with emphasis on the early recognition and delivery of cardiopulmonary resuscitation maneuvers focused on high-quality thoracic compressions and rapid defibrillation by means of the implementation of public access-to-defibrillation programs. These aspects are of the utmost importance and may make the difference on the patient's outcomes, such as on hospital survival with no permanent neurological damage. Early initiation of the Advanced Cardiology Life Support also plays an essential role by keeping the quality of thoracic compressions; adequate airway management; specific treatment for the different arrest rhythms; defibrillation; and assessment and treatment of the possible causes during all the assistance. More recently, emphasis has been given to post-resuscitation care, with the purpose of reducing mortality by means of early recognition and treatment of the post-cardiac arrest syndrome. Therapeutic hypothermia has provided significant improvement of neurological damage and should be performed in comatose individuals post-cardiac arrest. For physicians working in the emergency department or intensive care unit, it is extremely important to improve the treatment given to these patients by means of specific training, thus giving them the chance of higher success and of better survival rates.


Identification and Clinical Significance of Pancreatic Cancer Stem Cells and Their Chemotherapeutic Drug Resistance.
Pancreatic cancer ranks in the 10th-11th position among cancers affecting men in Taiwan, besides being a rather difficult-to-treat disease. The overall 5-year survival rate of pancreatic cancer is only 5-10%, while that of resectable pancreatic cancer is still approximately 15-20%. Cancer stem cells possess intrinsic detoxifying mechanisms that allow them to survive against conventional therapy by developing multidrug resistance. This study was conducted to investigate how to overcome chemoresistance and its mechanisms in pancreatic cancer stem cells (CSCs) using gemcitabine-resistant pancreatic cancer cell lines. Pancreatic CSCs were identified from human pancreatic cancer lines. To determine whether CSCs possess a chemoresistant phenotype, the sensitivity of unselected tumor cells, sorted CSCs, and tumor spheroid cells to fluorouracil (5-FU), gemcitabine (GEM), and cisplatin was analyzed under stem cell conditions or differentiating conditions. Although the mechanisms underlying multidrug resistance in CSCs are poorly understood, ABC transporters such as ABCG2, ABCB1, and ABCC1 are believed to be responsible. Therefore, we measured the mRNA expression levels of ABCG2, ABCB1, and ABCC1 by real-time RT-PCR. Our results showed that no significant differences were found in the effects of different concentrations of gemcitabine on CSCs CD44+/EpCAM+ of various PDAC cell line cultures (BxPC-3, Capan-1, and PANC-1). There was also no difference between CSCs and non-CSCs. Gemcitabine-resistant cells exhibited distinct morphological changes, including a spindle-shaped morphology, the appearance of pseudopodia, and reduced adhesion characteristics of transformed fibroblasts. These cells were found to be more invasive and migratory, and showed increased vimentin expression and decreased E-cadherin expression. Immunofluorescence and immunoblotting experiments demonstrated increased nuclear localization of total β-catenin. These alterations are hallmarks of epithelial-to-mesenchymal transition (EMT). Resistant cells showed activation of the receptor protein tyrosine kinase c-Met and increased expression of the stem cell marker cluster of differentiation (CD) 24, CD44, and epithelial specific antigen (ESA). We concluded that the expression of the ABCG2 transporter protein was significantly higher in CD44+ and EpCAM+ CSCs of PDAC cell lines. Cancer stem-like cells exhibited chemoresistance. Gemcitabine-resistant pancreatic tumor cells were associated with EMT, a more aggressive and invasive phenotype of numerous solid tumors. Increased phosphorylation of c-Met may also be related to chemoresistance, and EMT and could be used as an attractive adjunctive chemotherapeutic target in pancreatic cancer.


[Expression of the db (diabetes) gene in mice with hereditary load by generalized autoimmune pathology].
A model of genetically determinate diabetes mellitus in hybrid db/db mice with hereditary load by generalized autoimmune pathology has been described. The data on the character of hormonal-metabolic disturbances permit a conclusion on more serious course of diabetes mellitus in mice (C57Bl/Ks x NZB)F2 db/db as against (C57BL/Ks x NZW)F2 db/db, that is correlated with expression of autoimmune pathology in parent lines of New Zealand mice NZB and NZW. It is stated that diabetic syndrome in males proceeds in more serious form than in females.


Mangiferin inhibits high-fat diet induced vascular injury via regulation of PTEN/AKT/eNOS pathway.
Mangiferin (MAN), a naturally occurring polyphenol commonly found in mango and papaya. However, little is known its anti-vascular injury effects and the underlying mechanisms. This paper investigated the anti-vascular injury effect of MAN and the mechanisms in high-fat diet (HFD)-induced C57BL/6J mice and oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs). The levels of plasma lipid, inflammatory factors and nitric oxide (NO) in mice were evaluated. The expression levels of PI3K, AKT, eNOS, PTEN and their phosphorylated proteins were measured by western blots. In addition, the PTEN-siRNA HUVECs were also used. The result showed that MAN markedly decreased the plasma lipid, inflammatory level in HFD-induced vascular injury mice respectively. Furthermore, MAN alleviate ox-LDL-stimulated dysfunction of HUVECs, restored the diminished NO release, decreased the ROS generation, significantly increased the expression of p-Akt, p-eNOS, and decreased the expression of PTEN, but have no effect on PI3K. However, the protective effects of MAN were significantly reduced by co-treatment with PI3K inhibitor or abolished by eNOS inhibitor. In addition, MAN has no protective effect on ox-LDL induced PTEN-siRNA HUVECs injury. Collectively, MAN appeared to alleviate ox-LDL-stimulated dysfunction of HUVECs via the PTEN/Akt/eNOS signaling pathway, thus decrease vascular injury in HFD-administrated mice.


Pathogenesis of ascites tumor growth: fibrinogen influx and fibrin accumulation in tissues lining the peritoneal cavity.
In the immediately preceding paper, we demonstrated that the microvasculature supplying peritoneal lining tissues of mice bearing either of two transplantable ascites carcinomas was hyperpermeable to circulating macromolecules. Solid tumors have been shown to exhibit similar levels of microvascular hyperpermeability, leading to extravasation of plasma proteins, including fibrinogen which clots on extravasation to form an extravascular fibrin gel. To determine whether similar extravasation and clotting of plasma fibrinogen occurred in ascites tumors, we used 125I-labeled fibrinogen (125I-F) as a tracer to measure inflow of fibrinogen into the peritoneal cavities, and influx and accumulation of fibrinogen/fibrin in the peritoneal lining tissues (peritoneal wall, mesentery, and diaphragm) of mice bearing syngeneic TA3/St or MOT ascites tumors. The percentage of circulating 125I-F that extravasated into the peritoneal cavity was increased from 10- to 50-fold in mice bearing either ascites tumor. Influx into the peritoneal walls of ascites tumor-bearing mice was 3-7 times that of control mice and became maximal on day 8 (TA3/St) and day 15 (MOT). Accumulation of 125I-F in ascites fluid and peritoneal lining tissues was also increased substantially in mice bearing these ascites tumors, reaching maximal values on days 7-8 (TA3/St) and 19-29 (MOT) at levels 2- to 3-fold (peritoneal wall) and 33- to 148-fold (ascites fluid) above control levels. Significant amounts of the 125I-F that accumulated in the peritoneal lining tissues of ascites tumor-bearing animals were insoluble in 3 M urea, consistent with clotting of 125I-F to cross-linked fibrin. Autoradiographs of SDS-PAGE gels performed on extracts of peritoneal lining tissues of both ascites tumors revealed the characteristic signature of cross-linked fibrin, i.e., gamma-gamma dimers and alpha-polymers. Fibrin was also identified in peritoneal lining tissues of both ascites tumors by immunohistochemistry. Taken together, these data indicate that fibrinogen, like other circulating macromolecules, extravasates into the peritoneal cavity and peritoneal lining tissues of ascites tumor-bearing mice and does so with kinetics similar to those of other macromolecular tracers we have studied. Moreover, a portion of the fibrinogen that extravasated into peritoneal lining tissues clotted to form a cross-linked fibrin meshwork which trapped tumor cells and favored their attachment to the peritoneal surface. By analogy with solid tumors, such fibrin deposits may also be expected to have a role in initiating angiogenesis and the generation of mature tumor stroma.


Is research into ethnicity and health racist, unsound, or important science?
Much historical research on race, intelligence, and health was racist, unethical, and ineffective. The concepts of race and ethnicity are difficult to define but continue to be applied to the study of the health of immigrant and ethnic minority groups in the hope of advancing understanding of causes of disease. While a morass of associations has been generated, race and ethnicity in health research have seldom given fundamental new understanding of disease. Most such research is "black box epidemiology." Researchers have not overcome the many conceptual and technical problems of research into ethnicity and health. By emphasising the negative aspects of the health of ethnic minority groups, research may have damaged their social standing and deflected attention from their health priorities. Unless researchers recognise the difficulties with research into ethnicity and health and correct its weaknesses, 20th century research in this subject may suffer the same ignominious fate as that of race science in the 19th century.


Correlation of environmental carbaryl measurements with serum and urinary 1-naphthol measurements in a farmer applicator and his family.
In exposure or risk assessments, both environmental and biological measurements are often used. Environmental measurements are an excellent means for evaluating regulatory compliance, but the models used to estimate body burden from these measurements are complex. Unless all possible routes of exposure (i.e., inhalation, dermal absorption, ingestion) are evaluated, exposure to a toxicant can be underestimated. To circumvent this problem, measurements of the internal dose of a toxicant in blood, serum, urine, or tissues can be used singularly or in combination with environmental data for exposure assessment. In three separate laboratories, carbaryl or its primary metabolite, 1-naphthol, was measured in personal air, dermal samples, blood serum, and urine from farmer applicators and their families. The usefulness of both environmental and biological data has been demonstrated. For the farmer applicator, the environmental levels of carbaryl would have been sufficient to determine that an exposure had occurred. However, biological measurements were necessary to determine the absorbed dose of each member of the applicator's family. In addition, a correlation between serum and urinary 1-naphthol measurements has been shown; therefore, either matrix can be used to accurately evaluate occupational carbaryl exposure.


Microinjection of a 19-kDa guanine nucleotide-binding protein inhibits maturation of Xenopus oocytes.
ADP-ribosylation factors (ARFs) are 19-21-kDa proteins purified from bovine brain that bind guanosine 5'-triphosphate (GTP). They exhibit GTP-dependent activity as activators of cholera toxin-catalyzed ADP-ribosylation of the alpha-subunit of the stimulatory guanine nucleotide-binding protein of the adenylyl cyclase system (Gs alpha). ARF, which interacts directly with the catalytic subunit of cholera toxin, has no known physiologic role. Intracellular microinjection of ARF was employed to investigate the effect of ARF on progesterone- and insulin-stimulated maturation of Xenopus oocytes. Maturation was inhibited by injection of ARF 3-8 h before exposure of oocytes to progesterone or insulin. ARF inhibition was dependent on progesterone concentration but not on insulin concentration. Inhibition was enhanced by concomitant injection of GTP and to a greater extent by guanosine 5'-O-(thiotriphosphate) (GTP gamma S) which, in the absence of ARF, inhibited somewhat at early time points. The demonstration of this effect of ARF on both progesterone- and insulin-stimulated oocyte maturation may provide a clue to the physiologic role of this guanine nucleotide-binding protein.


Adding emollient bath additives to standard eczema management for children with eczema: the BATHE RCT.
Childhood eczema is very common. Treatment often includes emollient bath additives, despite there being little evidence of their effectiveness. To determine the clinical effectiveness and cost-effectiveness of emollient bath additives in the management of childhood eczema. Pragmatic, randomised, open-label, multicentre superiority trial with two parallel groups. Ninety-six general practices in Wales, the west of England and southern England. Invitation by personal letter or opportunistically. Children aged between 12 months and 12 years fulfilling the UK Diagnostic Criteria for Atopic Eczema. Children with inactive or very mild eczema (a score of ≤ 5 on the Nottingham Eczema Severity Scale) were excluded, as were children who bathed less than once per week or whose parents/carers were not prepared to accept randomisation. The intervention group were prescribed bath additives by their usual clinical team and were asked to use them regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued standard eczema management, including regular leave-on emollients and topical corticosteroids (TCSs) when required. The primary outcome was eczema control measured by Patient Oriented Eczema Measure [POEM, 0 (clear) to 28 (severe)] weekly for 16 weeks. The secondary outcomes were eczema severity over 1 year (4-weekly POEM), number of eczema exacerbations, disease-specific quality of life (QoL) (Dermatitis Family Impact Questionnaire), generic QoL (Child Health Utility-9 Dimensions) and type and quantity of topical steroid/calcineurin inhibitors prescribed. Children were randomised (1 : 1) using online software to either bath additives plus standard eczema care or standard eczema care alone, stratified by recruiting centre, and there was open-label blinding. From December 2014 to May 2016, 482 children were randomised: 51% were female, 84% were white and the mean age was 5 years (n = 264 in the intervention group, n = 218 in the control group). Reported adherence to randomised treatment allocation was > 92% in both groups, with 76.7% of participants completing at least 12 (80%) of the first 16 weekly questionnaires for the primary outcome. Baseline POEM score was 9.5 [standard deviation (SD) 5.7] in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. Average POEM score over the first 16 weeks was 7.5 (SD 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group, with no statistically significant difference between the groups. After controlling for baseline severity and confounders (ethnicity, TCS use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additive group were 0.41 points higher than in the bath additive group (95% confidence interval -0.27 to 1.10), which is well below the published minimal clinically important difference of 3 points. There was no difference between groups in secondary outcomes or in adverse effects such as redness, stinging or slipping. Simple randomisation resulted in an imbalance in baseline group size, although baseline characteristics were well balanced between groups. This trial found no evidence of clinical benefit of including emollient bath additives in the standard management of childhood eczema. Further research is required on optimal regimens of leave-on emollients and the use of emollients as soap substitutes. Current Controlled Trials ISRCTN84102309. This project was funded by the NIHR Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 22, No. 57. See the NIHR Journals Library website for further project information.


Pathophysiologic effects of biliary shockwave lithotripsy in a canine model.
At least 10 extracorporeal shockwave lithotripters are under investigation in the United States for treatment of biliary stone disease. Few reports, however, have documented the potential side effects of this new treatment method. In this study, we performed a series of acute and chronic studies in dogs exposed to varying numbers of shockwaves directed at the gallbladder wall via a transthoracic or transabdominal targeting approach. When shockwaves were directed transthoracically, pulmonary hemorrhagic contusions were found which were sometimes large in size. When a transabdominal approach was used, however, only focal areas of hemorrhage were found in the gallbladder wall and adjacent liver with no alterations in postlithotripsy pancreatic or liver enzymes, and normal cholecystokinin-octapeptide stimulated oral cholecystograms were obtained 6 days after treatment. Biliary shockwaves appear to cause few side effects under normal conditions but should be used with caution in patients with potential bleeding disorders. Until further studies are performed, lung tissue should be avoided in the shockwave beam path during treatment.


For better or worse? Coregulation of couples' cortisol levels and mood states.
Although a majority of adults live with a close relationship partner, little is known about whether and how partners' momentary affect and physiology covary, or "coregulate." This study used a dyadic multilevel modeling approach to explore the coregulation of spouses' mood states and cortisol levels in 30 married couples who sampled saliva and reported on mood states 4 times per day for 3 days. For both husbands and wives, own cortisol level was positively associated with partner's cortisol level, even after sampling time was controlled. For wives, marital satisfaction weakened the strength of this effect. Partner's negative mood was positively associated with own negative mood for both husbands and wives. Marital satisfaction fully moderated this effect, reducing the strength of the association between one's own and one's partner's negative mood states. Spouses' positive moods were not correlated. As expected, within-couple coregulation coefficients were stronger when mood and cortisol were sampled in the early morning and evening, when spouses were together at home, than during the workday. The results suggest that spouses' fluctuations in negative mood and cortisol levels are linked over several days and that marital satisfaction may buffer spouses from their partners' negative mood or stress state.


[Congenital paralysis of the vocal cords: a review of 14 cases].
Were performed 220 direct laryngoscopys and bronchoscopys, from 1981 to 1990, in newborns and infants that showed as a main finding: stridor, voice change or aspiration syndromes. Fourteen (20.28%) of the 69 congenital laryngeal anomalies were vocal cord paralysis: 13 (92.8%) unilateral paralysis and 1 (7.2%) bilateral paralysis. Eleven (84.6%) of the 13 unilateral paralysis were left and 2 (15.4%) were right. The vocal cord position was noted to be median or paramedian in 13 (92.8%) patients. The etiology was idiopathic in 11 (78.5%) of the cases. The bilateral paralysis required tracheotomy and in the unilateral paralysis wasn't necessary it.


GLP-1 receptor agonist liraglutide protects cardiomyocytes from IL-1β-induced metabolic disturbance and mitochondrial dysfunction.
Cardiac inflammation plays a critical role in the development of heart failure. Inflammation-induced oxidative stress contributes to aberrant cardiac metabolism and mitochondrial function. GLP-1 receptor agonists (GLP-1 RAs) are a type of blood glucose-lowering agent typically used in the treatment of type 2 diabetes. Recent studies have convincingly shown that GLP-1 RAs possess beneficial effects in diabetes-related cardiovascular complications. Liraglutide is a commonly used long-acting agonist that shows promising cardioprotective benefits. In this study, we investigated the protective role of Liraglutide in cultured cardiomyocytes. We found that HL-1 cardiomyocytes moderately expressed the GLP-1 receptor, and co-treatment with Liraglutide ameliorated IL-1β-induced cellular ROS production and NADPH oxidase (NOX)-4 expression. Furthermore, we found that Liraglutide protected cardiomyocytes from IL-1β-induced decreased mitochondrial membrane potential and reduced ATP production. Seahorse analysis revealed that Liraglutide mitigated IL-1β-induced reduced basal and maximum respiration rates as well as spare respiration capacity. Additionally, we found that Liraglutide alleviated IL-1β-induced aberrant triglyceride accumulation and adiponectin secretion. Mechanistically, we showed that Liraglutide ameliorated IL-1β-induced phosphorylation of AMPK and ACC as well as the reduction in PGC-1α, CPT-1, and DGAT1. Finally, through the study we demonstrated that the blockage of AMPK activity by Compound C abolished the ameliorative effect of Liraglutide on IL-1β-induced repressed ATP production and triglyceride accumulation, indicating that the action of Liraglutide was dependent on AMPK activation. In conclusion, this study revealed the molecular mechanism of Liraglutide protection in cultured cardiomyocytes. The GLP-1 RA Liraglutide could have therapeutic implications by modulating cardiac inflammation.


Lung Function in Very Low Birth Weight Adults.
Lung function attained in young adulthood is 1 of the strongest predictors of obstructive airways disease in later life. Adults born preterm at very low birth weight (VLBW; <1500 g) who have experienced bronchopulmonary dysplasia (BPD) have reduced lung function. We studied the association of lung function in young adulthood with preterm birth at VLBW and with BPD and other prenatal and neonatal conditions. We performed spirometry for 160 VLBW subjects (29 with BPD according to Northway criteria) aged 18 to 27 years and 162 term control subjects group-matched for gender, age, and birth hospital. Lung function was expressed as z scores according to the Global Lung Function Initiative standards. Forced expiratory volume in 1 second z score was 1.41 units (95% confidence interval [CI]: 0.89 to 1.94) lower in BPD-VLBW subjects and 0.39 units (95% CI: 0.08 to 0.69) in non-BPD VLBW subjects compared with control subjects. Corresponding differences for forced expiratory volume in 1 second/forced vital capacity were 1.52 (95% CI: 0.99 to 2.05) and 0.51 (95% CI: 0.21 to 0.81), respectively. Maternal smoking in pregnancy predicted poorer airflow in all groups; this finding was strongest in the BPD-VLBW group. Lung function was unrelated to fetal or postnatal growth or to neonatal respiratory distress syndrome. Young adults born at VLBW have reduced airflow. The outcome is stronger in those who have a history of BPD but is present among those with no such history. This finding suggests an increased risk of later obstructive airways disease in adults born at VLBW.


Focality-Oriented Selection of Current Dose for Transcranial Direct Current Stimulation.
Background: In transcranial direct current stimulation (tDCS), the injected current becomes distributed across the brain areas. The objective is to stimulate the target region of interest (ROI) while minimizing the current in non-target ROIs (the 'focality' of tDCS). For this purpose, determining the appropriate current dose for an individual is difficult. Aim: To introduce a dose-target determination index (DTDI) to quantify the focality of tDCS and examine the dose-focality relationship in three different populations. Method: Here, we extended our previous toolbox i-SATA to the MNI reference space. After a tDCS montage is simulated for a current dose, the i-SATA(MNI) computes the average (over voxels) current density for every region in the brain. DTDI is the ratio of the average current density at the target ROI to the ROI with a maximum value (the peak region). Ideally, target ROI should be the peak region, so DTDI shall range from 0 to 1. The higher the value, the better the dose. We estimated the variation of DTDI within and across individuals using T1-weighted brain images of 45 males and females distributed equally across three age groups: (a) young adults (20 ≤ x ˂ 40 years), (b) mid adults (40 ≤ x ˂ 60 years), and (c) older adults (60 ≤ x ˂ 80 years). DTDI's were evaluated for the frontal montage with electrodes at F3 and the right supraorbital for three current doses of 1 mA, 2 mA, and 3 mA, with the target ROI at the left middle frontal gyrus. Result: As the dose is incremented, DTDI may show (a) increase, (b) decrease, and (c) no change across the individuals depending on the relationship (nonlinear or linear) between the injected tDCS current and the distribution of current density in the target ROI. The nonlinearity is predominant in older adults with a decrease in focality. The decline is stronger in males. Higher current dose at older age can enhance the focality of stimulation. Conclusion: DTDI provides information on which tDCS current dose will optimize the focality of stimulation. The recommended DTDI dose should be prioritized based on the age (>40 years) and sex (especially for males) of an individual. The toolbox i-SATA(MNI) is freely available.


Small isolated paraspinal arteriovenous fistula.
We report a case of a small, isolated paraspinal arteriovenous fistula (AVF) that arose in an adult without obvious trauma. The fistula, despite its extraspinal location and small size, caused hypertension of the intrathecal venous system and produced symptoms that were similar to those of spinal dural AVF. Detecting such a small lesion is difficult, but contrast-enhanced MR imaging can prove helpful in this regard.


[Organ failure due to hypoxemia, and effects of oxygen therapy--effects of hypoxemia on pulmonary hemodynamics, and improvement with oxygenation].
To investigate pulmonary hemodynamics in patients with chronic respiratory failure, we performed right heart catheterization and also examined the effects of oxygen inhalation. Thirty-three patients were studied. Their mean age was 65 +/- 10 years, and FEV1.0% and PaO2 on room air were 47 +/- 16% and 63 +/- 14 mmHg, respectively. mPAP was 27 +/- 10 mmHg, and 26 (78%) had pulmonary hypertension. Although PVR was abnormally high, CI and PCWP were within normal limits. PaO2 was significant Significantly correlated with mPAP and PVR. Although oxygen inhalation (28%) for 30 minutes significantly changed PaO2, PaCO2, and PvO2, it did not significantly affect mPAP, PVR, CI, or PCWP. These results suggest that short-term oxygen inhalation does not affect pulmonary hemodynamics in patients with chronic respiratory failure. Radionuclid ventriculography was also done to evaluate cardiac function in 16 patients before and after home oxygen therapy (HOT). Both right ventricular ejection fraction (RVEP) and left ventricular ejection fraction (LVEF) were significantly increased by HOT, and the significant correlation between RVEF and LVEF that had been observed before HOT disappeared. These results suggest cardiac function improved and that the interdependence between the right and left ventricle was eliminated by HOT.