Comparative Analysis of Defense Responses in Chocolate Spot-Resistant and -Susceptible Faba Bean (Vicia faba) Cultivars Following Infection by the Necrotrophic Fungus Botrytis fabae.
In this study, resistance responses were investigated during the interaction of Botrytis fabae with two faba bean cultivars expressing different levels of resistance against this pathogen, Nubaria (resistant) and Giza 40 (susceptible). Disease severity was assessed on leaves using a rating scale from 1 to 9. Accumulation levels of reactive oxygen species (ROS), lipid peroxidation and antioxidant enzymes (superoxide dismutase, catalase and ascorbate peroxidase) were measured in leaf tissues at different times of infection. The expression profiles of two pathogenesis-related proteins (PRPs) encoded by the genes PR-1 and β-1,3-glucanase were also investigated using reverse transcription RT-PCR analysis. The accumulation of these defense responses was induced significantly in both cultivars upon infection with B. fabae compared with un-inoculated controls. The resistant cultivar showed weaker necrotic symptom expression, less ROS accumulation, a lower rate of lipid peroxidation and higher activity of the enzymatic ROS scavenging system compared with susceptible cultivar. Interestingly, ROS accumulated rapidly in the resistant leaf tissues and peaked during the early stages of infection, whereas accumulation was stronger and more intense in the susceptible tissues in later stages. Moreover, the response of the resistant cultivar to infection was earlier and stronger, exhibiting high transcript accumulation of the PR genes. These results indicated that the induction of oxidant/antioxidant responses and the accumulation of PRPs are part of the faba bean defense mechanism against the necrotrophic fungus B. fabae with a different intensity and timing of induction, depending on the resistance levels.


Genetic studies on the arrhythmia in acute myocardial infarction with special reference to serum free fatty acid level.
The serious arrhythmias have been regarded as one of the important complications in patients with acute myocardial infarction. Clinical and experimental observations were made of the arrhythmogenecity in acute myocardial infarction in special reference to the high free fatty acidemia (HFFA). The results obtained were as follows: (1) The incidence of arrhythmia in 35 patients with acute myocardial infarction, in whom the serum free fatty acid (FFA) value was measured, was 84.0%. (2) The serum FFA values of arrhythmic patients were significantly higher than those of patients without arrhythmia (P less than 0.001). (3) it was also revealed that the serum FFA values of patients with ventricular premature contraction (VPC) were significantly higher than those of non-arrhythmic patients (P less than 0.001). (4) each of the rate of incidence of VPC in total arrhthmic patients and the serum FFA value on the day of attack was significantly higher than that on the following days, respectively. (5) HFFA was experimentally produced in infaracted dog with the coronary ligation by the infusion of Intralipid and heparin and its effect on the ventricular fibrillation threshold (VFT) was observed. The VFT was markedly decreased promptly after the coronary ligation and a trend of natural recovery of the VFT was seen in a period later than 60 minutes after the coronary ligation. The recovery phase was significantly suppressed by the treatment producing HFFA (P less than 0.01). The deleterious effect of HFFA on the VFT was prevented by the treatment with glucose and insulin solution (GI solution) (P less than 0.02). From these results, it is postulated that HFFA in patients with acute myocardial infarction acts as an arrhythmogenic factor by lowering the VFT and GI solution prevents the occurrence of arrhythmia by lowering the serum FFA value.


Chemical and immunological characterizations of equine infectious anemia virus gag-encoded proteins.
The viral core proteins (p15, p26, p11, and p9) of equine infectious anemia virus (EIAV) (Wyoming strain) were purified by reverse-phase high-pressure liquid chromatography. Each purified protein was analyzed for amino acid content, N-terminal amino acid sequence, C-terminal amino acid sequence, and phosphoamino acid content. The results of N- and C-terminal amino acid sequence analysis of each gag protein, taken together with the nucleotide sequence of the EIAV gag gene (R. M. Stephens, J. W. Casey, and N. R. Rice, Science 231:589-594, 1986), show that the order of the proteins in the precursor is p15-p26-*-p11-p9, where a pentapeptide also found in the virus is represented by the asterisk. The data are in complete agreement with the predicted structure of the gag polyprotein and show the peptide bonds cleaved during proteolytic processing. The N-terminus of p15 is blocked to Edman degradation. The p11 protein is identical to the nucleic acid-binding protein of EIAV previously isolated (C. W. Long, L. E. Henderson, and S. Oroszlan, Virology 104:491-496, 1980). High-titer rabbit antiserum was prepared against each purified protein. These antisera were used to detect the putative gag precursor (Pr55gag) and intermediate cleavage products designated Pr49 (p15-p26-*-p11), Pr40 (p15-p26), and Pr35 (p26-*-p11) in the virus and in virus-infected cells. High-titer antisera to EIAV p15 and p26 showed cross-reactivity with the homologous protein of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus.


Hay fever treatment with budesonide and beclomethasone dipropionate twice daily - a clinical comparison.
Fifty-two patients with seasonal allergic rhinitis were admitted to a randomized clinical comparison between budesonide (Rhinocort) and beclomethasone dipropionate (Becotide Nasal). All patients were sensitive to birch pollen, which was confirmed by a skin prick test. The drugs were administered intranasally 200 micrograms b.i.d. Symptoms were assessed over four weeks starting with a run-in period of one week. Daily pollen counts were recorded throughout the trial and showed a rather mild birch pollen season. The patients diary cards revealed a beneficial therapeutic effect of the two drugs. No statistically significant differences between the drugs were seen except with regard to sneezing symptoms, where the Rhinocort-treated patients showed less symptoms (p less than 0.05). Side effects were few and transient with both drugs.


Pyrotinib treatment enhances the radiosensitivity in HER2-positive brain metastatic breast cancer patients.
Brain metastasis is a common cause of death in HER2-positive breast cancer patients. Currently, it is mainly treated by whole-brain radiotherapy. Pyrotinib is an irreversible pan-ErbB inhibitor, which has demonstrated promising tumor-suppressing activity and acceptable tolerance in previous phase trials. In the present study, we evaluated the efficacy of pyrotinib on HER2-positive brain metastatic breast cancer patients treated with whole-brain radiotherapy. A total of 20 such patients were separated into pyrotinib plus capecitabine and capecitabine-only groups in a 1:1 ratio. All patients met either the primary or secondary endpoints. Oral admission of pyrotinib together with radiotherapy can significantly increase the overall response rate, progression-free survival, time to progression and duration of response of HER2+ brain metastatic breast cancer patients, without causing extra adverse events. In addition, pyrotinib can enhance the radiosensitivity of in-vitro cultured HER2+ breast cancer cell lines. The outcome of our study suggests that pyrotinib might be an effective medication to enhance the tumor radiosensitivity of HER2-positive brain metastatic breast cancer patients.


Endovascular embolization of spontaneous rupture of isolated splenic artery dissection associated with hemosuccus pancreaticus: a case report.
Isolated splenic artery dissection (SAD) is extremely rare, life-threatening, and particularly difficult to diagnose. Moreover, SAD presenting as digestive hemorrhage has not been reported. A 44-year-old man presented with recurrent life-threatening hematochezia. Magnetic resonance and computed tomographic angiography showed isolated SAD with an intrapancreatic hematoma. Selective angiography confirmed the diagnosis of rupture of SAD. Hemosuccus pancreaticus was considered the potential mechanism of digestive hemorrhage. It was successfully managed by endovascular coil embolization. Isolated SAD is especially rare but fatal. Rupture of SAD should be considered in the differential diagnosis as a rare cause of digestive hemorrhage. Endovascular coil embolization is effective in treating ruptured SAD.


55-kd tumor necrosis factor receptor is expressed by human keratinocytes and plays a pivotal role in regulation of human keratinocyte ICAM-1 expression.
Tumor necrosis factor alpha (TNF alpha) is a potent modulator of human keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression. TNF alpha is known to exert its biologic effects by binding to specific cell-surface receptors. Two distinct TNF binding molecules, the 55-kd and the 75-kd TNF receptor (TNFR) recently have been found to be expressed by human cells. These two receptor types are independently regulated and differ markedly in their intracellular regions, indicating functional dichotomy. In order to gain further insight into the mechanisms underlying ICAM-1 regulation in human keratinocytes, in the present study, the receptor molecules mediating TNF alpha induced ICAM-1 upregulation in human keratinocytes was defined. Human keratinocyte TNFR expression was assessed using monoclonal antibodies that specifically recognize the 55-kd or the 75-kd TNFR. Using FACS analysis, normal (HNK) as well as transformed (KB) human keratinocytes were found to react with anti-55-kd TNFR, but not anti-75-kd TNFR antibodies. These immunofluorescence data were confirmed by Northern blot analysis revealing clearly detectable amounts of mRNA specific for the 55-kd TNFR in KB cells. Incubation of human keratinocytes with anti-55-kd TNFR antibodies at 37 degrees C for 24 h increased ICAM-1 expression in a TNF alpha-like fashion. Moreover, the well known synergistic effect of IFN gamma plus TNF alpha on keratinocyte ICAM-1 induction could be mimicked by stimulation of cells with IFN gamma plus anti-55-kd TNFR antibodies. Synergistic ICAM-1 induction was not associated with increased expression of the 55-kd TNFR in IFN gamma-stimulated human keratinocytes. These studies indicate that human keratinocytes express the 55-kd TNF receptor and that this surface molecule may play an important role in regulation of human keratinocyte ICAM-1 expression.


N4 -Hydroxycytidine/Molnupiravir Inhibits RNA-Virus Induced Encephalitis by Producing Mutated Viruses with Reduced Fitness.
A diverse group of RNA viruses including Rabies, Polio, La Crosse, West Nile, Zika, Nipah, Eastern and Western equine encephalitis, Venezuelan equine encephalitis, Japanese encephalitis, and tick-borne encephalitis viruses have the ability to gain access to and replicate in the central nervous system (CNS), causing severe neurological disease. Current treatment for these patients is generally limited to supportive care. To address the need for a generalizable antiviral, we utilized a strategy of mutagenesis to limit virus replication. We evaluated ribavirin (RBV), favipiravir (FAV) and N 4 -hydroxycytidine (NHC) against La Crosse virus (LACV) which is the primary cause of pediatric arboviral encephalitis cases in North America. NHC was more potent than RBV or FAV in neuronal cells. Oral administration of molnupiravir (MOV), the 5'-isobutyryl prodrug of NHC, decreased neurological disease development by 32% following intraperitoneal (IP) infection of LACV. MOV also reduced disease by 23% when virus was administered intranasally (IN). NHC and MOV produced less fit viruses by incorporating predominantly G-to-A or C-to-U mutations. Furthermore, NHC also inhibited two other orthobunyaviruses, Jamestown Canyon virus and Cache Valley virus. Collectively, these studies indicate that NHC/MOV has therapeutic potential to inhibit virus replication and subsequent neurological disease caused by this neurotropic RNA virus.


Assessment of Th17/Treg cells and Th cytokines in an improved immune thrombocytopenia mouse model.
The improved passive immune thrombocytopenia (ITP) mouse model has been extensively utilized for the study of ITP. However, how closely this model matches the human inflammation state and immune background is unclear. Our study aimed to explore the profile of Th cytokines and Th17/Treg cells in the model. We induced the ITP mouse model by dose-escalation injection of MWReg30. The serum levels of cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TGF-β1) were measured by enzyme-linked immunosorbent assay and the frequency of Th17 and Treg cells was measured by flow cytometry. The mRNA expression of Foxp3 and RORrt was measured by real-time PCR. The serum levels of cytokines IFN-γ, TGF-β1, IL-4, and IL-10 were significantly lower in ITP mice. The secretion of serum proinflammatory cytokines IL-2 and IL-17A and the percentage of Th17 cells showed no statistically significant increase. In ITP mice the frequency of Treg cells and mRNA expression of Foxp3 was significantly lower in splenocytes. Our data suggest that the improved passive ITP mouse model does not mimic the autoimmune inflammatory process of human ITP. Compared with human ITP, this model has a similar change in frequency of Treg cells, which may directly or indirectly result from antibody-mediated platelet destruction due to attenuated release of TGF-β.


Life-cycle effects of single-walled carbon nanotubes (SWNTs) on an estuarine meiobenthic copepod.
Single-walled carbon nanotubes (SWNT) are finding increasing use in consumer electronics and structural composites. These nanomaterials and their manufacturing byproducts may eventually reach estuarine systems through wastewater discharge. The acute and chronic toxicity of SWNTs were evaluated using full life-cycle bioassays with the estuarine copepod Amphiascus tenuiremis (ASTM method E-2317-04). A synchronous cohort of naupliar larvae was assayed by culturing individual larvae to adulthood in individual 96-well microplate wells amended with SWNTs in seawater. Copepods were exposed to "as prepared" (AP) SWNTs, electrophoretically purified SWNTs, or a fluorescent fraction of nanocarbon synthetic byproducts. Copepods ingesting purified SWNTs showed no significant effects on mortality, development, and reproduction across exposures (p < 0.05). In contrast, exposure to the more complex AP-SWNT mixture significantly increased life-cycle mortality, reduced fertilization rates, and reduced molting success in the highest exposure (10 mg x L(-1)) (p < 0.05). Exposure to small fluorescent nanocarbon byproducts caused significantly increased life-cycle mortality at 10 mg x L(-1) (p < 0.05). The fluorescent nanocarbon fraction also caused significant reduction in life-cycle molting success for all exposures (p < 0.05). These results suggest size-dependent toxicity of SWNT-based nanomaterials, with the smallest synthetic byproduct fractions causing increased mortality and delayed copepod development over the concentration ranges tested.


The fate of ribosomal RNA genes in spontaneous polyploid dogrose hybrids [Rosa L. sect. Caninae (DC.) Ser.] exhibiting non-symmetrical meiosis.
Dogroses represent an exceptional system for studying the effects of genome doubling and hybridization: their asymmetrical meiosis enables recombination in bi-parentally inherited chromosomes but prevents it in maternally inherited ones. We employed fluorescent in situ hybridization, genome skimming, amplicon sequencing of genomic and cDNA as well as conventional cloning of nuclear ribosomal DNA in two phylogenetically distinct pentaploid (2n = 5x = 35) species, Rosa canina and Rosa inodora, and their naturally occurring reciprocal hybrids, Rosa dumalis (5x) and Rosa agrestis (5x, 6x). Both progenitor species differed in composition, meiotic behaviour and expression of rDNA loci: R. canina (five 18S and 5-8 5S loci) was dominated by the Canina ribotypes, but R. inodora (four 18S loci and 7-8 5S loci) by the Rubiginosa ribotype. The co-localized 5S/18S loci occurred on either bivalent-forming (R. canina) or univalent-forming (R. inodora) chromosomes. Ribosomal DNA loci were additively inherited; however, the Canina ribotypes were dominantly expressed, even in genotypes with relatively low copy number of these genes. Moreover, we observed rDNA homogenization towards the paternally transmitted Canina ribotype in 6x R. agrestis. The here-observed variation in arrangement and composition of rDNA types between R. canina and R. inodora suggests the involvement of different genomes in bivalent formation. This results supports the hypothesis that the asymmetrical meiosis arose at least twice by independent ancient hybridization events.


[Cross-reacting antigens of human thymus myoid cells and stable L-forms of group A streptococci].
Indirect immunofluorescence has shown a similarity between the antigen components of group A streptococcus L-forms and human thymus myoid cells. An analogous antigen (or antigens) is present in the cytoplasmic membrane of human myocardial cell fibers. The depletion of antiserum to the streptococcal L-forms both by the culture of L-forms grown in meat or casein media and by the homogenate of the cardiac muscle leads to the inhibition of immunofluorescence. The depletion of serum by the homogenate of other tissues (liver) or by L-form culture does not virtually affect the immunofluorescence intensity. According to the authors' opinion, the similarity of antigens of group A streptococcus L-forms to the antigenic components of organ tissues is likely to be responsible for long-term persistence of the microorganisms under consideration and to favour, in some cases, the occurrence of autoantibodies. The latter circumstance might lead to pathological changes in organs containing cross-reacting antigens.


DNA double-strand breaks and hairpins in V(D)J recombination.
Several lines of evidence have suggested the existence of broken DNA molecules as intermediates in V(D)J recombination. These include sequence alterations at the recombined junctions and the presence of aberrant recombinants. More recently, broken DNA molecules have been directly detected in recombinationally active cells. The signal sequence ends have normal blunt-ended DNA breaks, but the coding ends have a hairpin (self-joined) structure that provides an explanation for the self-complementary P nucleotide insertions often found after V(D)J joining in the antigen receptor genes.


Observation of Steady Shear-Induced Nematic Ordering of Selenium Chain Moieties in Arsenic Selenide Liquids.
Structural anisotropy induced by steady shear and its mechanistic relation with shear thinning are investigated in AsxSe100-x glasses (5 ≤ x ≤ 30) quenched from parent liquids subjected to shear rates ranging between 0 and 104 s-1 using polarized Raman spectroscopy and two-dimensional X-ray diffraction. When taken together, the results demonstrate significant shear-induced partial alignment of -Se-Se-Se- chain moieties in the flow direction of the extruded fibers. This alignment is reminiscent of nematic liquid crystals where orientational order exists without positional order. The degree of this structural alignment in quenched glasses appears to be practically independent of the shear rate, although the parent liquids undergo shear thinning at the highest shear rates. It is conjectured that any causal relationship between structural alignment and shear thinning in the liquid may be masked in the glassy state by the postextrusion structural relaxation of the parent liquid.


Relationship violence among female and male college undergraduate students.
To assess prevalence of victimization and perpetration of relationship violence before and during college, to explore variations by gender, and to examine differences by relationship type. Anonymously surveyed students in 67 randomly chosen classes. Three urban college campuses. Nine hundred ten undergraduate college students aged 17 to 22 years. Self-reported victimization and perpetration of physical, emotional, and sexual violence; relationship to the victim or perpetrator. Most (57.1%) students were female, and 58.7% were white, 16.4% black, and 15.1% Asian. Of 910 participants, 407 (44.7%) experienced partner or nonpartner violence: 383 (42.1%) reported victimization and 156 (17.1%) reported perpetration. All victimization and perpetration rates were highest before college. Emotional violence was most common before college (21.1%); during college, sexual and emotional violence were equally common (12.0% and 11.8%, respectively). Women reported more victimization than men, but male victimization was considerable (27.2%). More men perpetrated sexual violence; more women perpetrated physical violence. More than half (130 of 227) of the violence experienced during college was partner related. Students experiencing partner violence during college were more likely to experience physical and emotional violence and were less likely to experience sexual violence. Relationship violence is prevalent among college students and frequently occurs before college. Emotional violence was most frequent before college; sexual and emotional violence were equally common during college. Women reported more victimization than men, but male victimization was common. Men perpetrated more sexual violence; women perpetrated more physical violence. Physical violence and emotional violence were most often committed by partners, while sexual violence was less likely to be partner related.


Pseudoseizures in children: a profile of 50 cases.
In contrast to adulthood hysterical disorders, childhood hysteria has not been accorded due recognition. Pseudoseizures are paroxysmal alterations in behavior that resemble epileptic seizures but are without any underlying organic cause. There is paucity of literature on pseudoseizures in children. In the present descriptive study of 2 years' duration, a series of consecutively seen 50 children with pseudoseizures is reported. After detailed history from parents, various socio-demographic and clinical variables were noted. Of 110 children seen with conversion disorder, 50 had pseudoseizures (45.5%). The average age was 8.2 years in boys and 9.4 years in girls. There were 28 girls (56.0%) and 22 boys (44.0%), and the majority of patients had the pseudoseizures for 1 to 3 months. When the mode of referral was studied, 52% were referred from pediatric outpatient department and the majority were referred to rule out comorbid psychiatric disorder. The fits mimicking generalized tonic-clonic seizures were most common and the duration of fits ranged from 10 to 35 minutes. The most common frequency of fits was 5 to 6 per week. The average duration of symptoms was 2.6 months in boys and 3.2 months in girls. Only 14 patients (28%) gave the history of having seen the fits in a relative or schoolmate. School phobia and the fear of examinations were the most common precipitating factors. Separation anxiety disorder, school phobia, and mood disorders were common comorbid diagnoses. The patients were put on appropriate drug treatment and/or psychotherapy for 3 months. Of 50 cases, 36 (72.0%) remitted, 10 (20.0%) showed a decrease in frequency of pseudoseizures, and 4 (8.0%) did not improve. With correct diagnosis and treatment, the children with pseudoseizures have a good outcome.


Independent Whole-Genome Duplications Define the Architecture of the Genomes of the Devastating West African Cacao Black Pod Pathogen Phytophthora megakarya and Its Close Relative Phytophthora palmivora.
Phytophthora megakarya and P. palmivora are oomycete pathogens that cause black pod rot of cacao (Theobroma cacao), the most economically important disease on cacao globally. While P. palmivora is a cosmopolitan pathogen, P. megakarya, which is more aggressive on cacao than P. palmivora, has been reported only in West and Central Africa where it has been spreading and devastating cacao farms since the 1950s. In this study, we reconstructed the complete diploid genomes of multiple isolates of both species using single-molecule real-time sequencing. Thirty-one additional genotypes were sequenced to analyze inter- and intra-species genomic diversity. The P. megakarya genome is exceptionally large (222 Mbp) and nearly twice the size of P. palmivora (135 Mbp) and most known Phytophthora species (∼100 Mbp on average). Previous reports pointed toward a whole-genome duplication (WGD) in P. palmivora In this study, we demonstrate that both species underwent independent and relatively recent WGD events. In P. megakarya we identified a unique combination of WGD and large-scale transposable element driven genome expansion, which places this genome in the upper range of Phytophthora genome sizes, as well as effector pools with 1,382 predicted RxLR effectors. Finally, this study provides evidence of adaptive evolution of effectors like RxLRs and Crinklers, and discusses the implications of effector expansion and diversification.


Multielement determination and speciation of major-to-trace elements in black tea leaves by ICP-AES and ICP-MS with the aid of size exclusion chromatography.
A multielement determination of major-to-trace elements in black tea leaves and their tea infusions was carried out by ICP-AES (inductively coupled plasma atomic emission spectrometry) and ICP-MS (inductively coupled plasma mass spectrometry). Tea infusions were prepared as usual tea beverage by brewing black tea leaves in boiling water for 5 min. About 40 elements in tea leaves and tea infusions could be determined over the wide concentration range in 8 orders of magnitude. The extraction efficiency of each element was estimated as the ratio of its concentration in tea infusions to that in tea leaves. From the experimental results for the extraction efficiencies, the elements in black tea leaves were classified into three characteristic groups: (i) highly-extractable elements (>55%): Na, K, Co, Ni, Rb, Cs and Tl, (ii) moderately-extractable elements (20-55%): Mg, Al, P, Mn and Zn, and (iii) poorly-extractable elements (<20%): Ca, Fe, Cu, Sr, Y, Zr, Mo, Sn, Ba and lanthanoid elements. Furthermore, speciation of major-to-trace elements in tea infusions was performed by using a combined system of size exclusion chromatography (SEC) and ICP-MS (or ICP-AES). As a result, many diverse elements were found to be present as complexes associated with large organic molecules in tea infusions.


Kinetics of CO ligation with nitric-oxide synthase by flash photolysis and stopped-flow spectrophotometry.
Interaction of CO with hemeproteins has physiological importance. This is especially true for nitric-oxide synthases (NOS), heme/flavoenzymes that produce .NO and citrulline from L-arginine (Arg) and are inhibited by CO in vitro. The kinetics of CO ligation with both neuronal NOS and its heme domain module were determined in the presence and absence of tetrahydrobiopterin and Arg to allow comparison with other hemeproteins. Geminate recombination in the nanosecond time domain is followed by bimolecular association in the millisecond time domain. Complex association kinetics imply considerable heterogeneity but can be approximated with two forms, one fast (2-3 x 10(6) M-1 s-1) and another slow (2-4 x 10(4) M-1 s-1). The relative proportions of the two forms vary with conditions. For the heme domain, fast forms dominate except in the presence of both tetrahydrobiopterin and Arg. In the holoenzyme, slow forms dominate except when both reagents are absent. Geminate recombination is substantial, approximately 50%, only when fast forms predominate. Stopped-flow mixing found dissociation constants near 0.3 s-1. These data imply an equilibrium constant such that very little CO should bind at physiological conditions unless large CO concentrations are present locally.


The role of perceived minority-group status in the conspiracy beliefs of factual majority groups.
Research suggests that minority-group members sometimes are more susceptible to misinformation. Two complementary studies examined the influence of perceived minority status on susceptibility to misinformation and conspiracy beliefs. In study 1 (n = 2140), the perception of belonging to a minority group, rather than factually belonging to it, was most consistently related with an increased susceptibility to COVID-19 misinformation across national samples from the USA, the UK, Germany and Poland. Specifically, perceiving that one belongs to a gender minority group particularly predicted susceptibility to misinformation when participants factually did not belong to it. In pre-registered study 2 (n = 1823), an experiment aiming to manipulate the minority perceptions of men failed to influence conspiracy beliefs in the predicted direction. However, pre-registered correlational analyses showed that men who view themselves as a gender minority were more prone to gender conspiracy beliefs and exhibited a heightened conspiracy mentality. This effect was correlationally mediated by increased feelings of system identity threat, collective narcissism, group relative deprivation and actively open-minded thinking. Especially, the perception of being a minority in terms of power and influence (as compared to numerically) was linked to these outcomes. We discuss limitations and practical implications for countering misinformation.


Determination of quaternary ammonium compounds by potentiometric titration with an ionic surfactant electrode: single-laboratory validation.
A potentiometric titration for determining the quaternary ammonium compounds (QAC) commonly found in antimicrobial products was validated by a single laboratory. Traditionally, QACs were determined by using a biphasic (chloroform and water) manual titration procedure. Because of safety considerations regarding chloroform, as well as the subjectivity of color indicator-based manual titration determinations, an automatic potentiometric titration procedure was tested with quaternary nitrogen product formulations. By using the Metrohm Titrando system coupled with an ionic surfactant electrode and an Ag/AgCl reference electrode, titrations were performed with various QAC-containing formulation products/matrixes; a standard sodium lauryl sulfate solution was used as the titrant. Results for the products tested are sufficiently reproducible and accurate for the purpose of regulatory product enforcement. The robustness of the method was measured by varying pH levels, as well as by comparing buffered versus unbuffered titration systems. A quantitation range of 1-1000 ppm quaternary nitrogen was established. Eight commercially available antimicrobial products covering a variety of matrixes were assayed; the results obtained were comparable to those obtained by the manual titration method. Recoveries of 94 to 104% were obtained for spiked samples.


Pseudarthrosis after four-level anterior cervical discectomy and fusion without posterior fixation.
Fusion rates and long-term outcomes are well established for anterior cervical discectomy and fusion (ACDF) of 3 levels or fewer, but there is a paucity of similar data on 4-level fusions. The authors evaluated long-term fusion rates and clinical outcomes after 4-level ACDF without supplemental posterior instrumentation. The authors retrospectively reviewed patients who underwent 4-level ACDF at a single institution with at least 1-year of radiological follow-up. Fusion was determined by measuring change in interspinous distance at each segment on dynamic radiographs or by the presence of bridging bone on CT scans at minimum 1-year follow-up. Clinical outcomes were assessed using Neck Disability Index and Short Form-36. A total of 63 patients (252 levels) met the inclusion criteria for the study, with a mean follow-up of 2.6 years. Complete radiographic fusion at all 4 levels was observed in 26 patients (41.3%). Of the 37 patients (58.7%) with radiographic pseudarthrosis, there was a mean of 1.35 nonfused levels. The fusion rate per level, however, was 80.2% (202/252 levels). The most common level demonstrating nonunion was the distal segment (C6-7), showing pseudarthrosis in 29 patients (46.8%), followed by the most proximal segment (C3-4) demonstrating nonunion in 9 patients (14.5%). The mean improvement in Neck Disability Index and Short Form-36 was 15.7 (p < 0.01) and 5.8 (p = 0.14), respectively, with improvement in both scores surpassing the minimum clinically important difference. One patient (1.6%) required revision surgery for symptomatic pseudarthrosis, and 5 patients (7.9%) underwent revision for symptomatic adjacent-segment disease. Patient-reported outcomes results are limited by the low rate of 1-year follow-up (50.8%), whereas reoperation data were available for all 63 patients. More than half of patients undergoing 4-level ACDF without posterior fixation demonstrated pseudarthrosis of at least 1 level-most commonly the distal C6-7 level. One patient required revision for symptomatic pseudarthrosis. Patient-reported outcomes showed significant improvements at 1-year follow-up, but clinical follow-up was limited. This is the largest series to date to evaluate fusion outcomes in 4-level ACDF.


A Case of Robotic Posterior Rectopexy for Full-thickness Rectal Prolapse.
We describe our experience with robotic posterior rectopexy for a patient with full-thickness rectal prolapse. To our knowledge, this is the first report of such a case in the literature. A 94-year-old woman presented with a history of gradually worsening rectal prolapse. On examination, we found that the rectum was completely prolapsed, and we observed a prolapsed intestinal tract. Surgery was indicated and robotic rectopexy was performed without intraoperative complications. The postoperative course was uneventful, and she was discharged 10 days after the operation. One year later, there were no signs of recurrence. Robotic surgery has become common in recent years. We used robotic surgery for rectopexy, including the suturing procedure. Suturing in robotic surgery is easier than that in laparoscopic surgery, and we demonstrated that robotic rectopexy could be safely and easily performed. The trial was registered in the UMIN clinical trial registry (number 000040378).


The Great Exhale: Using Breath Analysis to Detect Disease.
Your breath gives away a lot of information. Besides betraying that you've had garlic or onions for lunch, it also contains volatile organic compounds (VOCs) that provide quite telling biomarkers of disease. Building on the potential capability of VOCs to detect illness, the U.K. company Owlstone Medical is now developing a testing platform called Breath Biopsy [1] as a noninvasive diagnostic method and is collaborating with clinicians, researchers, and other biomedical companies around the world on its potential application for early detection of various cancers, respiratory illnesses, and immune diseases.


Robotic-assisted laparoscopic myomectomy: the feasibility in single-site system.
To evaluate the feasibility of robotic single-site myomectomy (RSSM). Medical records of 355 consecutive women who underwent robotic-assisted laparoscopic myomectomy were retrospectively reviewed. Clinical characteristics were compared between multi-site and single-site systems. After 1:1 propensity score matching for the total myoma number, largest myoma size, and total tumor weight (105 women in each group), surgical outcomes were also compared between the 2 systems. A total of 105 (29.6%) and 250 (70.4%) women underwent RSSM and robotic multi-site myomectomy (RMSM), respectively. RSSM was more commonly performed in women with lower body mass index (21.6 vs. 22.5 kg/m2, P=0.014), without peritoneal adhesions (7.6% vs. 24.8%, P<0.001), and less (2.6 vs. 4.6, P<0.001) and smaller (6.3 vs. 7.7 cm, P<0.001) myomas compared to RMSM. After propensity score matching, the largest myoma size (P=0.143), total myoma number (P=0.671), and tumor weight (P=0.510) were not significantly different between the 2 groups. Although the docking time was significantly longer in the RSSM group (5.1 vs. 3.8 minutes, P=0.005), total operation time was similar between RSSM and RMSM groups (145.9 vs. 147.3 minutes, P=0.856). Additionally, hemoglobin decrement was lower in the RSSM group than in the RMSM group (1.4 vs. 1.8 g/dL, P=0.009). No surgical complication was observed after RSSM, while 1 ileus and 2 febrile complications occurred in women that underwent RMSM (0% vs. 2.9%, P=0.246). Although RMSM is preferred for women with multiple large myomas in real clinical practice, RSSM seems to be a feasible surgical method for less complicated cases, and is associated with minimal surgical morbidity.


The caring concept, its behaviours and obstacles: perceptions from a qualitative study of undergraduate nursing students.
Developing caring competences is considered to be one of the most important aims of undergraduate nursing education and the role of clinical placement is recognised as special in this regard. Students' reflection on caring, their experience and obstacles in being caring is recommended as a key strategy in the process of teaching and studying the nursing discipline. Therefore, the aim of this study was to describe the concept of caring, its manifestations and possible obstacles while caring, as perceived by first-year nursing students before and after their first clinical placement. Qualitative content analysis of 15 Polish students' narratives written before and after their clinical experience in the form of text-diaries was undertaken. The findings revealed that students entered their nursing education with a deep humanistic vision of caring both on theoretical and practical levels and the first clinical placement has enriched this vision. Expressive caring was more appreciated by students than the instrumental one and their concept of caring was coherent with the caring behaviours as described in their narratives. Several internal and external obstacles for caring have been reported by students, indicating a specific tension between their ideal of caring and their practical experience of caring in the clinical reality.


Synthesis of Amides and Nitriles from Vinyl Azides and p-Quinone Methides.
A divergent synthesis of amides and nitriles from vinyl azides and p-quinone methides (p-QMs) was developed. The p-QMs could be activated by BF3-Et2O and then nucleophilically attacked by vinyl azides, leading to divergent rearrangement toward amides and nitriles.


[Cinnamaldehyde attenuates lipopolysaccharide induced inflammation and apoptosis in human umbilical vein endothelial cells].
Objective: To investigate the effect of cinnamaldehyde (CIN) on the inflammation and apoptosis on human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS), and to explore the potential mechanisms. Methods: HUVECs were divided in to 8 groups: blank control group, LPS group, LPS+(low, medium, high) dose CIN groups and (low, medium, high) CIN groups. Cell cytotoxicity was determined by trypan blue staining, mRNA expression of the inflammatory factors was determined by RT-PCR,apoptosis was determined by TUNEL staining,the signal pathway was determined by Western blot. Results: (1) Cell viability:compared with the control group,cell survival rate was significantly lower in the LPS group (P<0.01), while the survival rates were all significantly higher in the 3 LPS+CIN groups than in the LPS group (all P<0.01) in a concentration-dependent manner. (2) The mRNA expression of the inflammation factors: compared with the control group, mRNA expression of the inflammation factors were all increased in the LPS group (all P<0.01),while the effect of LPS could be significantly reversed by cotreatment with CIN in a concentration-dependent manner (all P<0.01). Compared with control group, the mRNA expression of the inflammation factors in the LPS group were all enhanced in a time-dependent manner (0,6,12,24 h),which could be significantly downregulated by cotreatment with LPS+CIN (high dose) in a time-dependent manner. (3) Cell apoptosis: compared with the control group, the apoptosis rate was significantly higher in the LPS group (P<0.01), while this effect could be significantly reversed by the cotreatment with CIN (high dose) (P<0.01). (4) Signaling pathway: compared with the control group, the phosphorylation of iκBα, p65 in HUVECs treated with LPS were rapidly up-regulated compared with their corresponding total proteins and the expression of TLR4 (all P<0.01), while the degree of p-iκBα/iκBα, p-p65/p65 and TLR4 could be significantly suppressed by cotreatment with CIN (high dose) (all P<0.01). Conclusion: CIN can attenuate LPS induced inflammation and apoptosis in HUVECs, possibly by inhibiting the activation of NF-κB signaling pathway.


The Myxobacterial Metabolite Soraphen A Inhibits HIV-1 by Reducing Virus Production and Altering Virion Composition.
Soraphen A is a myxobacterial metabolite that blocks the acetyl-coenzyme A carboxylase of the host and was previously identified as a novel HIV inhibitor. Here, we report that soraphen A acts by reducing virus production and altering the gp120 virion content, impacting entry capacity and infectivity. These effects are partially reversed by addition of palmitic acid, suggesting that inhibition of HIV envelope palmitoylation is one of the mechanisms of antiviral action.


Effectiveness of feedback with a smartwatch for high-quality chest compressions during adult cardiac arrest: A randomized controlled simulation study.
Previous studies have demonstrated the potential for using smartwatches with a built-in accelerometer as feedback devices for high-quality chest compression during cardiopulmonary resuscitation. However, to the best of our knowledge, no previous study has reported the effects of this feedback on chest compressions in action. A randomized, parallel controlled study of 40 senior medical students was conducted to examine the effect of chest compression feedback via a smartwatch during cardiopulmonary resuscitation of manikins. A feedback application was developed for the smartwatch, in which visual feedback was provided for chest compression depth and rate. Vibrations from smartwatch were used to indicate the chest compression rate. The participants were randomly allocated to the intervention and control groups, and they performed chest compressions on manikins for 2 min continuously with or without feedback, respectively. The proportion of accurate chest compression depth (≥5 cm and ≤6 cm) was assessed as the primary outcome, and the chest compression depth, chest compression rate, and the proportion of complete chest decompression (≤1 cm of residual leaning) were recorded as secondary outcomes. The proportion of accurate chest compression depth in the intervention group was significantly higher than that in the control group (64.6±7.8% versus 43.1±28.3%; p = 0.02). The mean compression depth and rate and the proportion of complete chest decompressions did not differ significantly between the two groups (all p>0.05). Cardiopulmonary resuscitation-related feedback via a smartwatch could provide assistance with respect to the ideal range of chest compression depth, and this can easily be applied to patients with out-of-hospital arrest by rescuers who wear smartwatches.


Differential tissue expression of enhanced green fluorescent protein in 'green mice'.
In order to clarify tissue expression of enhanced green fluorescent protein (EGFP) in 'green mice' from a transgenic line having an EGFP cDNA under the control of a chicken beta-actin promoter and cytomegalovirus enhancer, we studied the expression of EGFP in various organs and tissues from these 'green mice' by immunohistochemistry with anti- EGFP antibody in conjunction with direct observation for EGFP fluorescence using confocal laser scanning microscopy. On immunohistochemical examination and on direct observation by confocal laser scanning microscopy, the level of EGFP expression varied among organs and tissues. EGFP expression was diffusely and strongly observed in the skin, pituitary, thyroid gland, parathyroid gland, heart, gall bladder, pancreas, adrenals and urinary bladder. There was only sporadic and weak expression of EGFP in the epithelium of the trachea, bronchus of the lung, stratified squamous epithelium and gastric glands of the stomach, hepatic bile ducts of the liver, glomeruli and renal tubules of the kidney and endo-metrial glands of the uterus. Furthermore, EGFP was only demonstrated within the goblet and paneth cells in the colon and small intestine, the tall columnar cells in the ductus epididymis, and the leydig cells in the testis. In conclusion, our results show that EGFP is differentially expressed in organs and tissues of 'green mice', which indicates that 'green mice' may prove useful for research involving transplantation and tissue clonality.


Portable fibrobronchoscopic treatment for non-severe ischemic stroke-associated pneumonia patients with dysphagia: a pilot study.
To investigate the efficacy and safety of portable fibrobronchoscopy on the non-severe ischemic stroke-associated pneumonia (SAP) patients with dysphagia. A total of 86 non-severe ischemic SAP patients with dysphagia were randomly and equally divided into the treatment group and control group. The control group was given routine sputum suction, anti-infection drugs, and sputum-reducing drugs. The treatment group was treated with fiber-optic bronchoscopic sputum suction and alveolar lavage, and drug treatment same as the control group. The blood gases, inflammatory factors, clinical pulmonary infection score (CPIS), adverse reactions, and modified Rankin Scale (mRS) were compared. The blood gases, serum inflammatory factors including procalcitonin (PCT), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α), and CPIS in the treatment group were superior to those in control group (P < 0.05). No significant difference was found in the incidence of adverse reactions between the two groups (P > 0.05). The mRS scores of the treatment group were significantly lower than those of control group 3 months after discharge. Sputum suction and alveolar lavage with portable fibrobronchoscope can significantly improve the hypoxia and pulmonary infections, reduce the inflammatory response, and thus improve the prognosis, rendering suction and alveolar lavage with portable fibrobronchoscope as a safe and effective treatment for non-severe ischemic SAP patients with dysphagia.


Influence of ad Libitum Feeding of Piglets With Bacillus Subtilis Fermented Liquid Feed on Gut Flora, Luminal Contents and Health.
Some scholars caution that long-term ad libitum feeding with probiotic fermented food poses potential health risks to baby animals. We conducted a feeding experiment to investigate the influence of ad libitum feeding of pre-and post-weaned piglets with a Bacillus subtilis fermented diet on the gut microbiome, gut metabolomic profiles, bile acid metabolism, proinflammatory cytokines and faecal consistency. Compared with piglets fed a Bacillus subtilis-supplemented pellet diet, piglets fed the Bacillus subtilis fermented liquid diet had lower intestinal bacterial diversity (P > 0.05), higher intestinal fungal diversity (P > 0.05), more Firmicutes (P > 0.05), fewer Bacteroidetes, Actinobacteria and Proteobacteria (P > 0.05), higher concentrations of 3-hydroxypropionic acid (P < 0.05), orotic acid (P < 0.05), interleukin-6 (P < 0.01), lactic acid (P < 0.01), deoxycholic acid (P > 0.05) and lithocholic acid (P < 0.01) and a higher incidence of diarrhoea (P > 0.05). The data show that ad libitum feeding of piglets with a Bacillus subtilis fermented liquid diet during the suckling and early post-weaning periods promotes the growth of lactic acid bacteria, bile salt hydrolase-active bacteria and 7a-dehydroxylase-active bacteria in the intestinal lumen; disturbs the normal production of lactic acid, orotic acid and unconjugated bile acids; and increases circulating interleukin-6 levels and diarrhoea incidence.


The Adaptation and Standardization of the Teacher Version of the Child Behavior Profile: Turkish Boys aged 7-12.
This article reports on the adaptation and standardization of the teacher version of the Child Behavior Profile for boys aged 6-11 to Turkish boys aged 7-12. Data were, obtained from 48 referred and 294 nonreferred boys. Comparison of referred and nonreferred samples showed significant differences on all behaviour problem scores, except the 'Anxious' scale. The median of the Cronbach internal consistency of the scale scares was 0.75.


Monocyte procoagulant activity as a peripheral marker of clotting activation in cancer patients.
Peripheral blood monocytes generate the procoagulant tissue factor in vitro and in vivo in response to stimulation by a variety of agents. Monocytes from cancer patients generate significantly increased tissue factor and a quantitative relationship exists between the levels of monocyte tissue factor (MTF) and levels of circulating fibrinopeptide A (FPA), a marker of in vivo clotting activation. Furthermore, monocytes from cancer patients have a greater procoagulant response to stimulation by endotoxin in vitro, which appears independent of lymphocyte regulation. These findings suggest a priming process in vivo, and may reflect exposure of monocytes to tumor antigen(s) or components of the immune response to tumors.


Acupuncture prevents cognitive deficits and oxidative stress in cerebral multi-infarction rats.
The aim of this study is to investigate the effects of acupuncture on cognitive deficits and oxidative stress in cerebral multi-infarction rats. The results showed that acupunctural treatment attenuated memory impairment induced by cerebral multi-infarction, as evaluated by shortened escape latency and increased swimming time of rats with memory impairment in the target quadrant. The data additionally suggested that acupunctural treatment ameliorated oxidative injuries induced by cerebral multi-infarction by increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus. Further investigation by in situ hybridization and immunohistochemistry revealed that acupunctural treatment significantly increased the expression of CuZnSOD mRNA and protein in the hippocampus of the impaired rats. The findings demonstrate that acupuncture can exert beneficial effects on spatial memory and antioxidant status of cerebral multi-infarction rats.


Triradiate caecal fold: Is it a useful landmark for caecal intubation in colonoscopy?
To determine the frequency of identification of the triradiate fold during colonoscopy and evaluate its reliability as a marker of caecal intubation. One hundred consecutive patients undergoing colonoscopy in a tertiary hospital colorectal unit from May to September 2013 were studied. Video documentation of the caecum was recorded and shown to consultant colorectal surgeons on the unit. Each reviewer was asked through a series of questions to independently identify the triradiate fold. The main outcome was the frequency of visualisation of the triradiate fold in the caecum. The triradiate fold was seen on average in 18% of cases, but inter-observer agreement was poor. There were only four patients (4%) in which all reviewers agreed on the presence of a triradiate fold. In patients who had undergone previous appendicectomy, the appendiceal orifice was less frequently seen compared with patients who had not undergone appendicectomy. The triradiate fold is infrequently seen during colonoscopy and is therefore an unreliable landmark of caecal intubation.


Costs of Quality and Safety in Radiology.
With the movement toward at-risk population health management-related payment models, a core factor for the success and survival of health care organizations has become understanding and decreasing costs. In medical specialties such as radiology, understanding models for procedure-based costing will become increasingly important. Using bottom-up models for procedure-based costing, such as time-driven activity-based costing, is more advantageous than using the inaccurate ratio of costs to charges approach; however, these approaches are more resource intensive when compared to top-down approaches. Understanding the costs of quality is also important for creating an accounting and budgeting process that reflects the total cost of quality. The costs of quality are divided into two main categories: the cost of control (also referred to as the costs of conformance) and the costs of failure of control (also referred to as the costs of nonconformance). The costs of control are the expenditures that occur to ensure quality. The costs of noncontrol are the expenses that arise from the lack of quality and safety. The cost of control has two subcategories: prevention costs and appraisal costs. The cost of noncontrol also has two subcategories: internal failure costs and external failure costs. Adopting a mind-set that takes into account the costs of control, or the costs to ensure high-quality care, and the costs of noncontrol, or the hidden costs of poor-quality care, will be essential for successful health care organizations in the future. ©RSNA, 2018.


Augmented backward elimination: a pragmatic and purposeful way to develop statistical models.
Statistical models are simple mathematical rules derived from empirical data describing the association between an outcome and several explanatory variables. In a typical modeling situation statistical analysis often involves a large number of potential explanatory variables and frequently only partial subject-matter knowledge is available. Therefore, selecting the most suitable variables for a model in an objective and practical manner is usually a non-trivial task. We briefly revisit the purposeful variable selection procedure suggested by Hosmer and Lemeshow which combines significance and change-in-estimate criteria for variable selection and critically discuss the change-in-estimate criterion. We show that using a significance-based threshold for the change-in-estimate criterion reduces to a simple significance-based selection of variables, as if the change-in-estimate criterion is not considered at all. Various extensions to the purposeful variable selection procedure are suggested. We propose to use backward elimination augmented with a standardized change-in-estimate criterion on the quantity of interest usually reported and interpreted in a model for variable selection. Augmented backward elimination has been implemented in a SAS macro for linear, logistic and Cox proportional hazards regression. The algorithm and its implementation were evaluated by means of a simulation study. Augmented backward elimination tends to select larger models than backward elimination and approximates the unselected model up to negligible differences in point estimates of the regression coefficients. On average, regression coefficients obtained after applying augmented backward elimination were less biased relative to the coefficients of correctly specified models than after backward elimination. In summary, we propose augmented backward elimination as a reproducible variable selection algorithm that gives the analyst more flexibility in adopting model selection to a specific statistical modeling situation.


Rotational dynamics in supercooled water from nuclear spin relaxation and molecular simulations.
Structural dynamics in liquid water slow down dramatically in the supercooled regime. To shed further light on the origin of this super-Arrhenius temperature dependence, we report high-precision (17)O and (2)H NMR relaxation data for H(2)O and D(2)O, respectively, down to 37 K below the equilibrium freezing point. With the aid of molecular dynamics (MD) simulations, we provide a detailed analysis of the rotational motions probed by the NMR experiments. The NMR-derived rotational correlation time τ(R) is the integral of a time correlation function (TCF) that, after a subpicosecond librational decay, can be described as a sum of two exponentials. Using a coarse-graining algorithm to map the MD trajectory on a continuous-time random walk (CTRW) in angular space, we show that the slowest TCF component can be attributed to large-angle molecular jumps. The mean jump angle is ∼48° at all temperatures and the waiting time distribution is non-exponential, implying dynamical heterogeneity. We have previously used an analogous CTRW model to analyze quasielastic neutron scattering data from supercooled water. Although the translational and rotational waiting times are of similar magnitude, most translational jumps are not synchronized with a rotational jump of the same molecule. The rotational waiting time has a stronger temperature dependence than the translation one, consistent with the strong increase of the experimentally derived product τ(R) D(T) at low temperatures. The present CTRW jump model is related to, but differs in essential ways from the extended jump model proposed by Laage and co-workers. Our analysis traces the super-Arrhenius temperature dependence of τ(R) to the rotational waiting time. We present arguments against interpreting this temperature dependence in terms of mode-coupling theory or in terms of mixture models of water structure.


The cell shape proteins MreB and MreC control cell morphogenesis by positioning cell wall synthetic complexes.
MreB, the bacterial actin homologue, is thought to function in spatially co-ordinating cell morphogenesis in conjunction with MreC, a protein that wraps around the outside of the cell within the periplasmic space. In Caulobacter crescentus, MreC physically associates with penicillin-binding proteins (PBPs) which catalyse the insertion of intracellularly synthesized precursors into the peptidoglycan cell wall. Here we show that MreC is required for the spatial organization of components of the peptidoglycan-synthesizing holoenzyme in the periplasm and MreB directs the localization of a peptidoglycan precursor synthesis protein in the cytosol. Additionally, fluorescent vancomycin (Van-FL) labelling revealed that the bacterial cytoskeletal proteins MreB and FtsZ, as well as MreC and RodA, were required for peptidoglycan synthetic activity. MreB and FtsZ were found to be required for morphogenesis of the polar stalk. FtsZ was required for a cell cycle-regulated burst of peptidoglycan synthesis early in the cell cycle resulting in the synthesis of cross-band structures, whereas MreB was required for lengthening of the stalk. Thus, the bacterial cytoskeleton and cell shape-determining proteins such as MreC, function in concert to orchestrate the localization of cell wall synthetic complexes resulting in spatially co-ordinated and efficient peptidoglycan synthetic activity.


Mechanical QT and JT intervals by M-mode echocardiography: An extrapolation from the concurrent electrocardiographic tracings.
Congenital long QT syndrome (CLQTS) is a life-threatening ion channelopathy leading to syncope and sudden death. Early diagnosis during the prenatal period and timely intervention can prevent sudden cardiac death and catastrophic consequences of this genetic ion channelopathy. Fetal magnetocardiography and fetal electrocardiography (ECG) enable the measurement of fetal QT and JT intervals, but their inherently technically challenging and/or resource-intensiveness nature preclude their routine clinical application. On the other hand, the high-temporal resolution of M-mode echocardiography makes it a well-suited and widely available modality for the measurement of cardiac events. We aimed to investigate the mechanical counterparts of the electrical QT and JT intervals on M-mode echocardiographic images of the tricuspid, mitral and aortic valves, and aortic wall. We performed a prospective study on consecutive children referred to the outpatient pediatric cardiology clinic at a tertiary children's hospital. We defined M-mode echocardiographic landmark points on tracings of tricuspid annular planar systolic excursion, mitral and aortic valves, and aortic wall with simultaneous electrocardiographic recording. We measured the mean±SD of the absolute time difference and RR-adjusted time difference in cases with non-coincident ECG events and echocardiographic landmarks. Fifty healthy children were enrolled in the study. In 47 (94%) out of the 50 children, Q was coincident with the starting point of the tricuspid annular plane systolic excursion. In all children, the Q was coincident with the mid-point of the A-C line of the mitral valve. In 38 (76%) cases, there was a bump on the anterior wall of the aortic root immediately before the change in the slope of the aortic wall. This was coincident with the Q wave in 100% of cases. In all cases, the J point coincided with the point of acceleration of velocity on TAPSE. In all children, the J point coincided with the initial maximal opening of the aortic cusps. The end of the T wave occurred coincident with the peak of the tricuspid annular planar systolic excursion in 47 children (94%). In 48 children (96%), the end of the T wave coincided with the aortic cusps' closure point. Based on our findings, we propose to measure the averaged mechanical QT and JT intervals by using an angled M-mode tracing of the aortic and mitral valve in five consecutive beats in the parasternal long-axis view. This is the first study on mechanical QT and JT intervals in healthy children. The study opens the horizons into the in-utero diagnosis of congenital long QT syndrome by measuring fetal QT and JT intervals using the widely available M-mode echocardiography.


Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations.
Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ABCA3, are well-recognized causes of interstitial lung disease. Recessive mutations in ABCA3 were first attributed to fatal respiratory failure in full-term neonates, but they are also increasingly being recognized as a cause of respiratory disorders with less severe phenotypes in older children and also adults. Here, we report a 20-month-old boy with interstitial lung disease caused by two distinct ABCA3 mutations. Initial treatment with methylprednisolone was unsuccessful, but the additional administration of hydroxychloroquine was effective. The family history revealed that the patient's older brother had died of idiopathic interstitial lung disease at 6 months of age, suggesting a genetic etiology of the disease. Sequence analyses of SP-C and ABCA3 genes were performed using DNA samples from the patient himself, his parents, and his brother. These analyses revealed novel compound heterozygous mutations in the coding exons of ABCA3 in both the patient and his brother: c.2741A > G, of paternal origin, and c.3715_3716insGGGGGG, of maternal origin. Conclusion Since ABCA3 mutations seem to be a heterogeneous entity with various phenotypes, we recommend genetic testing for mutations in SP-C and ABCA3 genes to be considered in children with unexplained interstitial lung disease.


Effects of comorbid ADHD with learning disabilities on anxiety, depression, and aggression in adults.
ADHD and learning disabilities (LD) frequently coexist and there are indications that comorbidity may increase the risk of psychopathology. The current study examined the gender distribution and frequency of comorbidity and its impact on the prevalence of symptoms of anxiety, depression, and aggression in a clinic sample of 80 adults with ADHD, aged 18 to 58 years. More individuals were diagnosed with ADHD+LD than ADHD only, with no difference in this distribution according to gender. A factorial multivariate analysis of variance indicated that females with ADHD+LD displayed more cognitive depression than females with ADHD only and than males with ADHD+LD and ADHD only. However,individuals with ADHD only and individuals with ADHD+LD did not differ on overall anxiety, depression or aggression. Likewise, males and females did not differ on measures of psychopathology. This study lays the foundation for continued research into the characteristics and comorbidities of adults with ADHD.


Partitioning of 2-phenylethanol and limonene cosurfactants in C12E4.
Avoided level-crossing muon spin resonance (ALC-μSR) has been used to study the dynamics and local environment of spin probes formed by muonium (Mu) addition to 2-phenylethanol (PEA) and limonene (1-methyl-4-(1-methylethenyl)-cyclohexene) in an aqueous dispersion of the nonionic surfactant C12E4 (tetra(ethylene glycol) n-dodecyl ether). The spin probes derived from both cosurfactants reside within the micelles in the L1 phase and the bilayers in the Lα phase rather than in the aqueous region. The local polarity measured by the different isomers of the Mu adducts of PEA suggests there is a water gradient within the micelles and bilayers. Slow rotation of the micelles broadened the Δ1 resonances with increasing temperature in the L1 phase while narrower Δ1 resonances were observed in the Lα phase due to the rapid rotation of the spin probes around a preferred axis, which was wobbling within a cone.


Halitosis: a review of the literature on its prevalence, impact and control.
Halitosis is the offensive or disagreeable odour that may emanate from the mouth. In 80%-90% of cases, bacterial activities especially on the dorsum of the tongue are implicated. Current studies on halitosis accessed from electronic databases were appraised in the light of prevalence, impact and control of halitosis. Halitosis has a worldwide occurrence with a prevalence range of 22% to 50%. Due to the associated social and psychological effects, it should be taken seriously in all affected patients. Oral healthcare professionals ought to be well informed, because their office(s) are usually the first points of call for the affected patients.


Building a Tool Kit for Medical and Dental Students: Addressing Microaggressions and Discrimination on the Wards.
Microaggressions, subtle slights related to characteristics such as race, gender, or sexual orientation, in a clinical setting can sabotage the therapeutic alliance. Curricula tailored specifically towards medical students that raise awareness of microaggressions and aim to change behavior are absent. We created a 2-hour workshop to prepare preclinical medical and dental students to recognize and respond to microaggressions in clinical practice. The workshop consisted of a didactic portion describing microaggressions and strategies for responding to them and a case-based small-group portion to practice strategies. Participants completed electronic pre- and postworkshop surveys. Of 163 students participating in the workshop, 121 (74%) completed the preworkshop survey, 105 (64%) completed the postworkshop survey, and 81 (50%) completed both. Preworkshop, 48% reported female gender, and 36% reported underrepresented in medicine status. The majority (77%) had witnessed or experienced microaggressions in the clinical setting, and 69% reported very good or excellent familiarity with the concept of microaggressions. The curriculum appeared to significantly mitigate challenges associated with microaggressions, including reductions in perceived difficulty in identifying microaggressions (p < .001), being unsure what to do or say (p < .001), improvements in familiarity with institutional support systems (p < .001), and awareness of the clinical relevance of microaggressions (p < .001). Given the high self-reported prevalence of microaggressions in the clinical setting, students need the skills to respond. This innovative session improves readiness to address microaggressions by helping participants build and practice these skills in a supportive environment.


How to write an Interpretation.
Every day we interpret examination findings and clinical tests with the aim of coming to a diagnosis. But how well do we interpret these tests? Whether it is a traditional examination technique used by doctors for centuries or a new cutting edge biomarker, the diagnostic landscape shifts over time. The aim of interpretations is to produce a library of evidence-based resources directing the use of clinical tests including examination techniques. In this article we discuss how best to tackle writing an interpretation. Interpretations are succinct evidence-based summaries that draw together research findings to provide practical answers for clinicians.


Accurate guide wire of lag screw placement in the intertrochanteric fractures: a technical note.
Cephalomedullary fixations are commonly used in the treatment of intertrochanteric fractures. In clinical practice, one of the difficulties is when we exit the guide wire in a wrong position of femoral neck and insert near the hole again, the guide wire often flow into the previous track. This study develops a surgical technique to direct the guide wire to slip away the previous track and slip into a right position. When guide wire is exited to the cortex of femoral, we let the wire in and out at the cortical layer for several times to enlarge the entry hole. After that, electric drill is inverted, rubbed and entered slowly at a right angle. When guide wire encountered new resistance, the electric drill is turned back instantly. This technique can help trauma and orthopedic surgeons to obtain precision placement of the lag screw after the first try is failed.


A surveillance study of adenovirus infection in adult solid organ transplant recipients.
Little is known about adenovirus infections in adult organ transplant recipients. We prospectively assessed adenovirus infection in 263 transplant recipients using polymerase chain reaction (PCR) on plasma samples at regular intervals post-transplant. Adenovirus DNA was detected in 19 of 263 patients (7.2%). Viremia by transplant type was: liver (n = 10 of 121 [8.3%]), kidney (n = 6 of 92 [6.5%]) and heart (n = 3 of 45 [6.7%]). Time to viremia onset was within 10 days post-transplant (n = 4), on day 28 (n = 1), on day 100 (n = 7) and between months 6 and 12 (n = 7). At the time of viremia, 11 of 19 (58%) patients had no symptoms, 2 of 19 (10.5%) had gastrointestinal (GI) symptoms, 2 of 19 (10.5%) had respiratory symptoms and 4 patients (21%) had vague/non-specific symptoms. All patients recovered spontaneously. Only 1 of 19 (5%) patients had subsequent acute rejection. Adenovirus viremia is relatively common in adult liver, kidney and heart transplant recipients and most infections are asymptomatic, transient and self-limited. No serious clinical sequelae or effects on subsequent acute rejection were observed.


Estimating average annual percent change for disease rates without assuming constant change.
The annual percent change (APC) is often used to measure trends in disease and mortality rates, and a common estimator of this parameter uses a linear model on the log of the age-standardized rates. Under the assumption of linearity on the log scale, which is equivalent to a constant change assumption, APC can be equivalently defined in three ways as transformations of either (1) the slope of the line that runs through the log of each rate, (2) the ratio of the last rate to the first rate in the series, or (3) the geometric mean of the proportional changes in the rates over the series. When the constant change assumption fails then the first definition cannot be applied as is, while the second and third definitions unambiguously define the same parameter regardless of whether the assumption holds. We call this parameter the percent change annualized (PCA) and propose two new estimators of it. The first, the two-point estimator, uses only the first and last rates, assuming nothing about the rates in between. This estimator requires fewer assumptions and is asymptotically unbiased as the size of the population gets large, but has more variability since it uses no information from the middle rates. The second estimator is an adaptive one and equals the linear model estimator with a high probability when the rates are not significantly different from linear on the log scale, but includes fewer points if there are significant departures from that linearity. For the two-point estimator we can use confidence intervals previously developed for ratios of directly standardized rates. For the adaptive estimator, we show through simulation that the bootstrap confidence intervals give appropriate coverage.


Regenerative Therapy for Osteoarthritis: A Perspective.
Osteoarthritis (OA) is the most common type of arthritis and causes a significant deterioration in patients' quality of life. The high prevalence of OA as well as the current lack of disease-modifying drugs led to a rise in regenerative medicine efforts. The hope is that this will provide a treatment modality with the ability to alter the course of OA via structural modifications of damaged articular cartilage (AC). Regenerative therapy in OA starts with the concept that administered cells may engraft to a lesion site and differentiate into chondrocytes. However, recent studies show that cells, particularly when injected in suspension, rapidly undergo apoptosis after exerting a transient paracrine effect. If the injected stem cells do not lead to structural improvements of a diseased joint, the high cost of cell therapy for OA cannot be justified, particularly when compared with other injection therapeutics such as corticosteroids and hyaluronic acid. Long-term survival of implanted cells that offer prolonged paracrine effects or possible engraftment is essential for a successful cell therapy that will offer durable structural improvements. In this perspective review, the history and current status of regenerative therapy in OA are summarized along with the conceptual strategy and future directionsfor a successful regenerative therapy that can provide structural modifications in OA.


Monascin and ankaflavin-Biosynthesis from Monascus purpureus, production methods, pharmacological properties: A review.
Monascus purpureus copiously yields beneficial secondary metabolites , including Monascus pigments, which are broadly used as food additives, as a nitrite substitute in meat products, and as a colorant in the food industry. Monascus yellow pigments (monascin and ankaflavin) have shown potential antidiabetic, antibacterial, anti-inflammatory, antidepressant, antibiotic, anticancer, and antiobesity activities. Cosmetic and textile industries are other areas where it has established its potential as a dye. This paper reviews the production methods of Monascus yellow pigments, biosynthesis of Monascus pigments from M. purpureus, factors affecting yellow pigment production during fermentation, and the pharmacological properties of monascin and ankaflavin.


Morbidity and mortality of gastrectomy for cancer in Department of Veterans Affairs Medical Centers.
The purpose of this study was to define risk factors that predict 30-day morbidity and mortality after gastrectomy for cancer in Veterans Affairs (VA) Medical Centers. The VA National Surgical Quality Improvement Program prospectively collected data on 708 patients undergoing gastrectomy for cancer in 123 participating VA medical centers from 1991 to 1998. Independent variables included 68 preoperative patient characteristics and 12 intraoperative variables; the dependent variables were 21 defined adverse outcomes and death. Predictive models for 30-day morbidity and mortality were constructed by using stepwise logistic regression analysis. The 30-day morbidity rate was 33.3% (236 of 708). The overall 30-day mortality rate was 7.6% (54 of 708). Significant positive predictors of morbidity (P <.05) included current pneumonia, American Society of Anesthesiologists class IV (threat to life), partially dependent functional status, dyspnea on minimal exertion, preoperative transfusion, extended operative time, and increasing age. Significant positive predictors of mortality (P <.05) included do not resuscitate status, prior stroke, intraoperative transfusion, preoperative weight loss, preoperative transfusion, and elevated preoperative alkaline phosphatase level. Risk factors predicting morbidity and mortality rates at VA hospitals after gastrectomy for gastric cancer are reported by using a prospectively collected, multi-institutional database. Assigning relative weights to factors associated with adverse outcomes may help improve patient care.


A 1-year study of the epidemiology of hepatitis A virus in Tunisia.
This 1-year (September 2000 to August 2001) prospective study investigated the presence of hepatitis A virus (HAV) in the population of Monastir, Tunisia (86 serum samples), in the influents and effluents of two wastewater treatment plants, and in shellfish harvested in the coastal areas of Monastir, Bizerte and Sfax (January 2001 to May 2001). The virus was detected by RT-PCR using primers targeted at the VP3-VP1 region. An epidemic of HAV infection was observed during the winter months, with a peak in January. The presence of the virus was relatively constant in the influents and effluents of the wastewater treatment plants, and the virus was found in shellfish from the Monastir area during the months of January and February. The genotype IA strain was recovered most frequently from human serum and wastewater samples. The observation that the peak of the epidemic was during the winter months suggests that transmission of HAV is related to climatic factors and, presumably, to shellfish consumption.


The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells.
Chromosomal instability (CIN) is a major hallmark of human cancer and might contribute to tumorigenesis. Genes required for the normal progression of mitosis represent potential CIN genes and, as such, are important tumour suppressors. The Chk2 kinase and its downstream targets p53 and Brca1 are tumour suppressors that have been functionally linked to the DNA damage response pathway. Here, we report a function of Chk2, independent of p53 and DNA damage, that is required for proper progression of mitosis, and for the maintenance of chromosomal stability in human somatic cells. Depletion of Chk2 or abrogation of its kinase activity causes abnormal mitotic spindle assembly associated with a delay in mitosis, which promotes the generation of lagging chromosomes, chromosome missegregation and CIN, while still allowing survival and growth. Furthermore, we have identified Brca1 as a mitotic target of the Chk2 kinase in the absence of DNA damage. Accordingly, loss of BRCA1 or its Chk2-mediated phosphorylation leads to spindle formation defects and CIN. Thus, the CHK2-BRCA1 tumour suppressor pathway is required for chromosomal stability, which might contribute to their tumour suppressor function.


Estimating the global burden of scabies: what else do we need?
Scabies is one of the most common disorders identified in any estimate of global skin disease prevalence. Furthermore, quantifying its impact on individuals and societies has been problematic. There has been a lack of clear case definitions and laboratory tests. There have been few epidemiological studies, particularly those focusing on low-income countries, variation in prevalence within high-income countries, or estimates of the effect of scabies on health beyond the skin, such as renal disease or mental wellbeing. Economic studies are also lacking. However, the new strategy of integrating surveillance for skin Neglected Tropical Diseases may well produce advancements on these issues, in addition to providing an overarching structure for health improvement and disease control.


Synthesis of cysteinyl-tRNACys by a prolyl-tRNA synthetase.
The question of how cysteinyl-tRNA(Cys) is synthesized in organisms that lack a canonical cysteinyl-tRNA synthetase (CysRS) is an important open question in understanding protein synthesis. The prolyl-tRNA synthetase (ProRS) of wide ranging organisms has the ability to mis-activate cysteine without editing. This raises the question of whether the mis-activated cysteine can be charged to tRNA(Cys) to synthesize the correctly matched cys-tRNA(Cys), which may serve as an option in organisms that lack the conventional CysRS. Despite intense searches, such an activity has not been found. Here we show that the ProRS of the radiation-resistant bacterium Deinococcus radiodurans has the ability to charge cysteine to tRNA(Cys) and to retain the cognate pair cys-tRNA(Cys) stably without editing. The cysteinylation by D. radiodurans ProRS is not the major route for synthesis of cys-tRNA(Cys), however, because the organism encodes the conventional CysRS. Nonetheless, the synthesis of cys-tRNA(Cys) in vitro is important and it is unlike previously documented mis-charging of Methanocaldococcus jannaschii ProRS, which synthesizes cys-tRNA(Pro) but not cys-tRNA(Cys). We suggest that the cysteinylation activity of D. radiodruans ProRS may, in the presence of additional factors, offer one option to organisms that lack the conventional CysRS to synthesize cysteinyl-tRNA(Cys) in vivo.


Preventive Health Evaluation in Underserved Occupational Environment: A Cross-Sectional Study of its Practice, Facilitators, Barriers, and Benefits among Medical Practitioners in Nigeria.
The health of medical doctors (MDs) has been the focus of global concern in addition to the recently modified physician oath now called "The Modern Physician Pledge." As a member of human family, MDs are also prone to diseases they manage in healthcare environment. The study was aimed at describing the practice, facilitators, barriers, and benefits of preventive health evaluation (PHE) in a cross-section of medical practitioners in Nigeria. A cross-sectional study done on 178 MDs in Nigeria. Data collection was done using pretested, self-administered questionnaire that elicited information on practice, facilitators, barriers, and benefits of PHE. Self-rated health status was also studied. Practice of PHE was inquired in previous one year. The age of the respondents ranged from 25 to 72 (36 ± 10.2) years. There were 161 (90.5%) males. All the respondents were aware of PHE. One hundred and fifty-five (87.1%) respondents rated their overall health then as excellent; 142 (79.8%) rated their overall health compared to 6 months ago as excellent, while 169 (94.9%) rated their overall health compared to others of their age as excellent. Generally, in all ages and both sexes, the most common PHE was blood pressure (BP) measurements (100%). The commonest female sex-specific PHE was self-breast examinations (100%). Among the males, the most common male-specific PHE was testicular self-examinations (87.0%). The commonest facilitator and barrier were family history of hereditary diseases (100%) and financial restraints (82.0%), respectively. The most common benefit was early detection of diseases (100%). Awareness of PHE was 100% but didn't translate to comparative practice orientation. The most common general PHE was BP checks. The commonest female and male sex-specific PHE was self-breast and testicular examinations respectively. The predominant facilitator and barrier were family history of hereditary diseases and financial restraints. The most common benefit was early detection of diseases.


Clinical experience with the use of rhG-CSF in secondary autoimmune neutropenia.
This paper outlines the impact of granulocyte-colony stimulating factor (G-CSF) used as a single modality therapy in 17 patients with secondary autoimmune neutropenia (S-AIN) who had been treated a multiple number of times previously. Fifteen of these patients had demonstrable antineutrophil antibodies and two had cellular S-AIN with haemopoietic inhibitory T-cells present in the marrow. Prior to treatment, all had had problems with infection. All patients responded within 7 days of commencement of treatment. Provided G-CSF neutrophil counts were maintained above 1 x 109/l, no further infections occurred. This was achievable by using G-CSF administered as infrequently as once every 8 days. Eight of the 17 patients remained on G-CSF, although five switched to the glycosylated form because of side-effects. None have developed osteoporosis despite 47.29 patient years of total experience with G-CSF. In conclusion both glycosylated and nonglycosylated G-CSF can be used effectively in treating AIN on a long-term basis.


Clinical Updates on the Diagnosis and Management of Chronic Thromboembolic Pulmonary Hypertension.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a known sequela after acute pulmonary embolism (PE). It is a debilitating disease, and potentially fatal if left untreated. This review provides a clinically relevant overview of the disease and discusses the usefulness and limitations of the various investigational and treatment options. A PubMed search on articles relevant to PE, pulmonary hypertension, CTEPH, pulmonary endarterectomy, and balloon pulmonary angioplasty were performed. A total of 68 articles were found to be relevant and were reviewed. CTEPH occurs as a result of non-resolution of thrombotic material, with subsequent fibrosis and scarring of the pulmonary arteries. Risk factors have been identified, but the underlying mechanisms have yet to be fully elucidated. The cardinal symptom of CTEPH is dyspnoea on exertion, but the diagnosis is often challenging due to lack of awareness. The ventilation/perfusion scan is recommended for screening for CTEPH, with other modalities (eg. dual energy computed tomography pulmonary angiography) also being utilised in expert centres. Conventional pulmonary angiography with right heart catheterisation is important in the final diagnosis of CTEPH. Operability assessment by a multidisciplinary team is crucial for the management of CTEPH, as pulmonary endarterectomy (PEA) remains the guideline recommended treatment and has the best chance of cure. For inoperable patients or those with residual disease post-PEA, medical therapy or balloon pulmonary angioplasty are potential treatment options.


Time dependence of [3H]-vincristine accumulation by L1210 mouse leukemic cells. Effect of P-glycoprotein overexpression.
Overexpression of P-glycoprotein (P-GP) accompanied by multidrug resistance (MDR) to diverse groups of cytostatics was developed by long-term adaptation of mouse leukemic cell line L1210 to vincristine. Two resistant sublines of cells characterized by ID50 values for vincristine 1.05 mg/l (L1210/VCR-1) and 2.3 mg/l (L1210/VCR-2), respectively, were used. The sensitive parental cell line L1210 had the ID50 value for vincristine around 0.01 mg/l. Overexpression of P-GP induced by the adaptation procedure was found to be accompanied by an increase in the mean cell diameter from 10.28 +/- 1.60 microns (mean +/- SD, n = 122) for sensitive L1210 cells to 17.82 +/- 2.59 microns (n = 120) and 37.26 +/- 5.72 microns (n = 121) for L1210/VCR-1 and L1210/VCR-2 resistant cell sublines, respectively. Significant decrease in ability to accumulate [3H]-vincristine from cultivation medium was observed for both resistant cell sublines in comparison to sensitive cells. Accumulation of [3H]-vincristine by sensitive cells is secured only by passive diffusion of the drug across the plasma membrane. Contrary to that, active efflux of drug operating against its diffusion across the plasma membrane should be assumed as a factor influencing the [3H]-vincristine accumulation by resistant cells. Indeed, the time dependence of [3H]-vincristine accumulation by sensitive cells could be fitted using simple monoexponential kinetic dependence in contrast to biexponential kinetic dependences that are necessary for fitting [3H]-vincristine accumulation by both resistant cell sublines. Kinetic analysis of the experimental data indicates that accumulation of [3H]-vincristine by sensitive cells grows to a plateau reflecting probably the equilibrium of drug concentration in the intracellular and extracellular space. On the contrary, accumulation of [3H]-vincristine by both resistant cell sublines was stabilized after an initial growth on a considerably lower level than it was observed for the sensitive cells in the equilibrium.


Synthetic Covalent and Non-Covalent 2D Materials.
The creation of synthetic 2D materials represents an attractive challenge that is ultimately driven by their prospective uses in, for example, electronics, biomedicine, catalysis, sensing, and as membranes for separation and filtration. This Review illustrates some recent advances in this diverse field with a focus on covalent and non-covalent 2D polymers and frameworks, and self-assembled 2D materials derived from nanoparticles, homopolymers, and block copolymers.


Xeroderma Pigmentosum with Severe Neurological Manifestations/De Sanctis-Cacchione Syndrome and a Novel XPC Mutation.
Several genetic disorders caused by defective nucleotide excision repair that affect the skin and the nervous system have been described, including Xeroderma Pigmentosum (XP), De Sanctis-Cacchione syndrome (DSC), Cockayne syndrome, and Trichothiodystrophy. Cutaneous photosensitivity with an increased risk of skin malignancy is a common feature of these disorders, but clinical manifestations commonly overlap these syndromes. Several genes have been found to be altered in these pathologies, but we lack more genotype-phenotype correlations in order to make an accurate diagnosis. Very few cases of DSC syndrome have been reported in the literature. We present a case of a 12-year-old Colombian male, with multiple skin lesions in sun-exposed areas from the age of 3 months and a history of 15 skin cancers. He also displayed severe neurologic abnormalities (intellectual disability, ataxia, altered speech, and hyperreflexia), short stature, and microcephaly, which are features associated with DSC. Genetic testing revealed a novel germline mutation in the XP-C gene (c.547A>T). This is the first case of an XP-C mutation causing De Sanctis-Cacchione syndrome. Multigene panel testing is becoming more widely available and accessible in the clinical setting and will help rapidly unveil the molecular etiology of these rare genetic disorders.


HSPG modification by the secreted enzyme Notum shapes the Wingless morphogen gradient.
The secreted signaling protein Wingless acts as a morphogen to pattern the imaginal discs of Drosophila. Here we report identification of a secreted repressor of Wingless activity, which we call Notum. Loss of Notum function leads to increased Wingless activity by altering the shape of the Wingless protein gradient. When overexpressed, Notum blocks Wingless activity. Notum encodes a member of the alpha/beta-hydrolase superfamily, with similarity to pectin acetylesterases. We present evidence that Notum influences Wingless protein distribution by modifying the heparan sulfate proteoglycans Dally-like and Dally. High levels of Wingless signaling induce Notum expression. Thus, Wingless contributes to shaping its own gradient by regulating expression of a protein that modifies its interaction with cell surface proteoglycans.


A phenotypic small-molecule screen identifies an orphan ligand-receptor pair that regulates neural stem cell differentiation.
High-throughput identification of small molecules that selectively modulate molecular, cellular, or systems-level properties of the mammalian brain is a significant challenge. Here we report the chemical genetic identification of the orphan ligand phosphoserine (P-Ser) as an enhancer of neurogenesis. P-Ser inhibits neural stem cell/progenitor proliferation and self-renewal, enhances neurogenic fate commitment, and improves neuronal survival. We further demonstrate that the effects of P-Ser are mediated by the group III metabotropic glutamate receptor 4 (mGluR4). siRNA-mediated knockdown of mGluR4 abolished the effects of P-Ser and increased neurosphere proliferation, at least in part through upregulation of mTOR pathway activity. We also found that P-Ser increases neurogenesis in human embryonic stem cell-derived neural progenitors. This work highlights the tremendous potential of developing effective small-molecule drugs for use in regenerative medicine or transplantation therapy.


Why cure, why now?
Combination antiretroviral therapy (cART) is highly effective at preventing morbidity and mortality due to infection with human immunodeficiency virus (HIV), but does not eradicate the virus. Consequently, cART must be administered life-long. Recent progress has stimulated research towards a cure of HIV infection. Approaches under investigation include hematopoietic stem cell transplantation, latency reactivating agents, immune based therapies, and cell-based therapies. Each of these approaches carries potential risks that must be weighed against the availability of safe and effective cART. Balancing the risks and benefits of this research poses unique challenges to potential study participants, clinicians and investigators.


Community Engagement Framework for Community Assessment and Improvement Planning.
As the emphasis on community-based public health expands, academics and practitioners are challenged to include the community throughout assessment and improvement planning activities. The volatility of community-based government programs and the emergence of new initiatives further complicate community involvement. Many communities have grown tired of being participants, of strategies focused on assessments that never reach implementation or goals, and of being abandoned when funding ends. A framework that melds lessons learned from previous programs and existing models with Web-based resources and new initiatives provides insights for sustainable and agile community-based solutions. Other implications include ways to align multiple assessment and planning requirements through one framework. This article describes the components and distinctions of a community engagement framework for assessment and planning conceptualized through the experiences of public health practice and academic partners in South Carolina.


CE: Trauma-Informed Care in Nursing Practice.
Over the past 30 years, researchers have found that childhood trauma and its subsequent stress have a strong and cumulative effect on health in adulthood. Trauma in childhood often leads to mental health problems, skeletal fractures, and early death from conditions such as heart disease, cancer, lung disease, and liver disease. Compounding the effects of traumatic stress, health care systems often create a population of "never-served" persons who avoid health care settings because they've been subject to judgment and marginalization. Trauma-informed care (TIC) is a skill underutilized by health care providers and organizations, yet nurse ethics and respect for human rights require us to care for all patients equally without judgment, including those living with the stress of complex trauma. The TIC approach respects human rights and supports nursing ethics, promoting a welcoming, inclusive environment in health care systems and patient-provider relationships that eschews implicit and explicit bias toward patients, regardless of presentation or personal circumstances. TIC foundational principles guide the application of the nursing process using patient-centered care to create safety, the first principle in TIC. Here, the authors discuss the application of these core principles in nursing through a deidentified case study.


Synthetic diamonds as in vivo radiation detectors.
Synthetic diamonds with controlled amounts of impurity atoms can be manufactured so that, as thermoluminescent dosimeters, they can be made to have sensitivities at least as good as presently available commercial thermoluminescent dosimeters. They also exhibit, for radiations normally found in therapy situations, a linearity of response that extends from less than 0.01 Gy (1 rad) to over 10 Gy (1000 rad). Their physical size and form, crystals which can have volumes of less than 1 mm3, make them ideal candidates for in vivo monitoring of radiation fields, particularly electron fields where high-resolution measurements are essential for accurate isodose line determinations. Aspects of dose response from gamma-ray beams in relation to the type and concentrations of the impurity atoms within the diamond are discussed, and some experimental values for gamma, x-ray, and electron beams are presented.


Biologic scaffolds for musculotendinous tissue repair.
Traumatic injuries to the musculoskeletal system are common events and volumetric muscle loss (VML) is no longer a rare occurrence. Surgical intervention is typically the only option for restoration of partial function. Surgical intervention for VML however does not regenerate the lost tissue and typically results in alterations of both the anatomy and biomechanics at the site of injury. Non-traditional approaches to the restoration of functional musculoskeletal tissue, including those provided by tissue engineering and regenerative medicine strategies, become viable alternative therapies when the expected outcome is bleak. One such strategy involves the delivery of constructive cues and modulation of the micro-environmental niche via biologic scaffold materials. These materials ideally retain the native structure and composition of the extracellular matrix of the tissue from which they are derived. Some of the recent advances in the use of biologic scaffolds to target key stages of the musculotendinous repair process and promote the restoration of functional tissue are described herein.


The increase of the active form of hepatic glycogen phosphorylase in stressed rats.
In rats exposed to 400 revolutions (during 6 min and 40 sec) in rotating Noble-Collip drums essentially the same increase of the active form of hepatic glycogen phosphorylase as in animals studied 6 min and 40 sec after epinephrine (50 microgram/kg) or glucagon (100 microgram/kg), both i.v., was observed. However, in rats injured daily for 6 days, on day 7 this enzyme response was substantially blunted.