Leading a multigenerational nursing workforce: issues, challenges and strategies.
Today's nursing workforce is made up of staff and nursing leaders from four different generational cohorts. Generational diversity, including workforce differences in attitudes, beliefs, work habits, and expectations, has proven challenging for nursing leaders. The purpose of this article is to assist nursing leaders to reframe perceptions about generational differences and to view these differences in attitudes and behaviors as potential strengths. Developing the skill to view generational differences through a different lens will allow the leader to flex their leadership style, enhance quality and productivity, reduce conflict, and maximize the contributions of all staff. This article provides an overview of the generational cohorts and presents strategies which nursing leaders can use to coach and motivate, communication with, and reduce conflict for each generational cohort of nurses.


[Dyskinesia in Parkinson's disease: an update on new neuroimaging methods and treatment possibilities].
Levodopa-induced dyskinesia (LID) represents a severe adverse effect of long-term treatment of Parkinson's disease with levodopa. Neuroimaging studies have contributed to our understanding of LID and may help to identify patients at risk of developing LID. Amantadine can be used for the treatment of LID, and novel drugs are under development. Deep brain stimulation of the subthalamic nucleus and globus pallidus internus alleviates LID, the former indirectly by reducing levodopa intake, the latter through direct effects. Repetitive transcranial magnetic stimulation has been shown to transiently improve LID.


Acute myeloid leukemia is a disease associated with HLA-C3.
We aimed to observe human leukocyte antigen (HLA) associations with human acute myeloid leukemia (AML) in a large population, in order to investigate the roles of HLA in leukemogenesis. Furthermore, we examined the HLA association according to morphological, cytogenetic, immunological, and clinical classifications. We performed HLA genotyping, bone marrow studies, cytogenetic analyses, and fluorescence-activated cell sorting analyses. A clinical outcome database was constructed, and the HLA frequency, gene frequency, relative risk (RR), linkage disequilibrium, and the 2-locus and 3-locus haplotype frequency using the Mattiuz formula were calculated. For the healthy controls, Korean HLA data published by Park and co-workers were used. AML was found to be associated with HLA-C3 (RR = 1.46; p < 0.001). In the French-American-British (FAB) classification, acute myelomonocytic leukemia (AML-M4) was associated with HLA-C3 (47.2 vs. 74.1%; RR = 3.13; p = 0.005), in cytogenetic classification, del(9), which is frequently observed in AML-M4, was also associated with HLA-C3 (47.2 vs. 100%; RR = 13.43; p = 0.024), and in clinical classification, incomplete remission was associated with HLA-C3 as well (47.2 vs. 63.2%; RR = 1.92; p = 0.002). No correlations between AML and immunological classifications were observed. Moreover, and in terms of 2-locus haplotypes, AML was found to be associated with HLA-C3/B62 (HLA-C3 gene frequency 0.3415; HLA-B62 gene frequency 0.1361; linkage disequilibrium 0.0136; haplotype frequency 4.15 vs. 6.0%; p < 0.05). In clinical classification, incomplete remission (linkage disequilibrium 0.0136; haplotype frequency 4.15 vs. 13.6%; p = 0.013) and relapse (linkage disequilibrium 0.0136; haplotype frequency 4.15 vs. 71.0%; p = 0.044) were associated with HLA-C3/B62, whereas no association was observed for FAB, cytogenetic and immunological classifications. No association was observed for the 3-locus haplotype. The HLA-C3 antigen and the 2-locus haplotype are associated with AML.


Outcomes of completion lobectomy long after segmentectomy.
Completion lobectomy long after segmentectomy in the same lobe is extremely difficult because of severe adhesions around hilar structures, especially in cases involving video-assisted thoracoscopic surgery (VATS) completion lobectomy. We report and compare the surgical outcomes of patients who underwent VATS or thoracotomy completion lobectomy long after radical segmentectomy for lung cancer. We retrospectively evaluated the surgical outcomes of completion lobectomies performed at our institute long after radical segmentectomies for lung cancer in the same lobe. The efficacy and safety of VATS completion lobectomy was compared to that of thoracotomy completion lobectomy. Ten of 228 patients who underwent radical segmentectomy for lung cancer between 2009 and 2018 underwent completion lobectomy at least a month after segmentectomy; five patients underwent VATS completion lobectomy. None of the patients underwent VATS left upper completion lobectomy, and conversion to thoracotomy was required in one patient. There were no significant differences between VATS and thoracotomy completion lobectomies in the median operative times (VATS 295 min, thoracotomy 339 min, p = 0.55), intraoperative blood loss volumes (VATS 350 mL, thoracotomy 500 mL, p = 0.84), intervals between initial segmentectomy and completion lobectomy (VATS 40 months, thoracotomy 48 months, p = 0.55), and number of patients with pulmonary artery injury (VATS 1, thoracotomy 2, p = 0.49). There was no operation-related mortality. VATS completion lobectomy long after segmentectomy for lung cancer could be performed without fatal complications unless severe adhesions are observed around each main pulmonary artery.


Pediatric cyanide intoxication and death from an acetonitrile-containing cosmetic.
Two cases of pediatric accidental ingestion of an acetonitrile-containing cosmetic are reported. One of the children, a 16-month-old boy, was found dead in bed the morning after ingesting the product. No therapy had been undertaken, as the product was mistakenly assumed to be an acetone-containing nail polish remover. The second child, a 2-year-old boy, experienced signs of severe cyanide poisoning, but survived with vigorous supportive care. Both children had blood cyanide levels in the potentially lethal range. The observed delayed onset of severe toxic reactions supports the proposed mechanism of acetonitrile conversion to inorganic cyanide via hepatic microsomal enzymes. Physicians and poison centers should be alerted to the existence of this highly toxic product, sold for removal of sculptured nails and likely to be confused with the less toxic acetone-containing nail polish removers. We urge regulatory agencies to reconsider the wisdom of marketing a cosmetic that poses such an extreme health hazard.


Halitosis as a symptom of gastroenterological diseases.
Bad breath is a clinical symptom encountered by doctors of various specialties in their daily practice. The symptom causes lower self-esteem and a negative perception of the patient by society, and consequently personal and social isolation. Bad breath can be an early manifestation of many systemic diseases. Because its causes are numerous, it is important to properly diagnose the condition and apply the appropriate treatment. The aim of the study was to present the gastroenterological aspect of halitosis on the basis of available literature reports.


Endoparasites of exotic ungulates from the Giraffidae and Camelidae families kept ex situ.
Giraffes and camels are popular attractions at zoological gardens. In order to present the diversity of parasites infecting exotic ungulates from zoos, faecal samples from three giraffes and six camels from both the Silesian Zoological Garden in Chorzów, and Kraków Zoological Garden, were examined. The research was carried out over a ten-month period in 2013 and 2014. In total, 100 faecal samples from 18 animals were analysed with the use of the McMaster method. Moreover, coccidian oocysts were incubated to investigate their development and larvoscopic examination was conducted to detect the presence of nematode species. Giraffes were infected with coccidia from the genus Eimeria, and gastrointestinal nematodes from the Strongylida order, and Trichuris and Aonhotheca genera. One male giraffe was uninfected. The level of infection in giraffes was low when compared to camels kept in both of the zoos. Limited contact with other animal species contributed greatly to the lower level of infection in camels from Kraków Zoo than those from Chorzów, which were kept in the same enclosure as alpacas and Shetland ponies.


Neuroprotective effects of hemicraniectomy in malignant middle cerebral artery infarctions: experimental study.
Despite optimal medical therapy the mortality rate approaches 50% in MCA infarctions. Although recent studies have been showed life-saving effect of hemicraniectomy; there are a few data available in regard to neuroprotection effect of decompressive craniectomy (DC). We induced a malignant cerebral ischemia model by intraluminal permanent middle cerebral artery occlusion (MCAo) in male rats for defining the neuroprotective effects of early DC on brain-blood barrier (BBB) molecular changes, infarct size and cerebral edema. A total of 48 male Spraque-Dawley rats were allocated to 4 groups; sham (N.=9), control (N.=9), experiment 1 (N.=15), experiment 2 (N.=15). DC was performed by creating a bone flap, after MCAo at 4 and 24 hours. After 28 hours of survival, all animals were sacrificed. Infarction volumes were calculated from TTC (2,3,5-triphenyl-2H-tetrazolium chloride)-stained brain sections. In all groups, cerebral edema was quantified as a change in the percentage of brain water content. Western Blot was used to analyze the expression of tight junction protein claudin-5 and occludin. Brain water content was calculated 75.18±0.75% in the early DC group and 77.76±0.71% in the late DC group. No significant difference was found between experiment groups (P=0.178). In the early DC group; occludin and claudin-5 were significantly expressed at higher levels compared to late DC group (occluding, P=0.013; claudin-5, P=0.034). At early DC group (73.38±23.11 mm3) the final infarct volumes were significantly smaller than in the late DC group (377.18±39.23 mm3) (P=0.013). The study results supported the neuroprotective effects of early DC in malignant MCA infarcts.


Complex bacterial infections pre- and posttransplant.
Infections complications following lung transplantation are associated with significant morbidity and mortality. Management of infections is most challenging in patients with cystic fibrosis (CF), but all lung transplant recipients are at heightened risk for opportunistic infections. Particularly in CF, pretransplant infections with PSEUDOMONAS AERUGINOSA, other highly resistant bacteria (e.g., STENOTROPHOMONAS, BURKHOLDERIA), and mycobacteria play a major role in recipient selection and post-lung transplant outcomes. Understanding the clinical impact and management strategies for each of these different pathogens is critical to maximizing the benefit of lung transplantation. In the review, we discuss each of these infections both as pretransplant risk factors as well as posttransplant pathogens and the individual issues that arise with each infection.


Psoriatic spondylitis: a clinical, radiological, and scintiscan survey.
Thirty-three per cent of patients with psoriatic spondyloarthropathy referred to a rheumatic disease unit were found to have radiological sacroiliitis. The majority of these patients had definite or probable spondylitis according to the New York criteria. Abnormal sacroiliac uptake of 99mTcPP on bone scan correlated well with the radiological finding of sacroiliitis. In addtion, eight patients with normal radiographs had an abnormal uptake of radionuclide over the sacroiliac joints, indicating sacroiliitis. Patients with sacroiliitis tended to have more severe psoriasis. Sacroiliitis occurred in association with all of the patterns of peripheral joint involvement which may occur in psoriatic arthritis. Although the HLA antigen B27 was present in only 21 percent of the total group and in 33 percent of those with sacroiliitis, 8 out of 10 with this antigen had sacroiliitis.


Whole-Genome Profiling of a Novel Mutagenesis Technique Using Proofreading-Deficient DNA Polymerase δ.
A novel mutagenesis technique using error-prone DNA polymerase δ (polδ), the disparity mutagenesis model of evolution, has been successfully employed to generate novel microorganism strains with desired traits. However, little else is known about the spectra of mutagenic effects caused by disparity mutagenesis. We evaluated and compared the performance of the polδMKII mutator, which expresses the proofreading-deficient and low-fidelity polδ, in Saccharomyces cerevisiae haploid strain with that of the commonly used chemical mutagen ethyl methanesulfonate (EMS). This mutator strain possesses exogenous mutant polδ supplied from a plasmid, tthereby leaving the genomic one intact. We measured the mutation rate achieved by each mutagen and performed high-throughput next generation sequencing to analyze the genome-wide mutation spectra produced by the 2 mutagenesis methods. The mutation frequency of the mutator was approximately 7 times higher than that of EMS. Our analysis confirmed the strong G/C to A/T transition bias of EMS, whereas we found that the mutator mainly produces transversions, giving rise to more diverse amino acid substitution patterns. Our present study demonstrated that the polδMKII mutator is a useful and efficient method for rapid strain improvement based on in vivo mutagenesis.


Pathogenicity of basidiospores of Filobasidiella neoformans var. neoformans.
Basidiospores of Filobasidiella neoformans var. neoformans (progeny of Cryptococcus neoformans MT 100.1 x VR 45980) were able to induce cryptococcosis in Swiss albino mice if inoculated by intraperitoneal injection, nasal instillation or nasal spraying. The latter method, with the aid of a jet nebulizer, was first adopted to imitate the natural entrance of infectious particles. Using this method the small number of basidiospores (7 x 10(3)) could induce cryptococcosis in mice, while the higher number of the parental laboratory-grown yeast cells (1.5 x 10(6)) did not produce infections. By nasal instillation Cyclophosphamide (Cy)-treated mice were more susceptible to the basidiospores, showing 80% cryptococcosis (eight of 10). Seven of the eight infected mice had disseminated cryptococcosis. Immunocompetent mice were more resistant to basidiospore infection than Cy-treated mice, as 40% of that group developed only pulmonary cryptococcosis; none had disseminated infection. Thus, we propose that basidiospores are one form of the infectious propagules of F. neoformans var. neoformans which can cause cryptococcosis, particularly in immunocompromised people.


Foam-in-vein: A review of rheological properties and characterization methods for optimization of sclerosing foams.
Varicose veins are chronic venous defects that affect >20% of the population in developed countries. Among potential treatments, sclerotherapy is one of the most commonly used. It involves endovenous injection of a surfactant solution (or foam) in varicose veins, inducing damage to the endothelial layer and subsequent vessel sclerosis. Treatments have proven to be effective in the short-term, however recurrence is reported at rates of up to 64% 5-year post-treatment. Thus, once diagnosed with varicosities there is a high probability of a permanently reduced quality of life. Recently, foam sclerotherapy has become increasingly popular over its liquid counterpart, since foams can treat larger and longer varicosities more effectively, they can be imaged using ultrasound, and require lower amounts of sclerosing agent. In order to minimize recurrence rates however, an investigation of current treatment methods should lead to more effective and long-lasting effects. The literature is populated with studies aimed at characterizing the fundamental physics of aqueous foams; nevertheless, there is a significant need for appropriate product development platforms. Despite successfully capturing the microstructural evolution of aqueous foams, the complexity of current models renders them inadequate for pharmaceutical development. This review article will focus on the physics of foams and the attempts at optimizing them for sclerotherapy. This takes the form of a discussion of the most recent numerical and experimental models, as well as an overview of clinically relevant parameters. This holistic approach could contribute to better foam characterization methods that patients may eventually derive long term benefit from.


Family and community influences on the social and sexual lives of Latino gay men.
The purpose of this study was to explore the effect of family and community on the social and sexual lives of a group of Latino gay men living in a metropolitan area. A secondary analysis of four focus groups with 28 Latino gay men was conducted. Families had a difficult time acknowledging and supporting participants' homosexuality. Participants experienced racism, discrimination, and physical and verbal abuse as a result of their ethnicity and homosexuality. These negative effects contributed to their marginalization and made them vulnerable to depression and suicide. Health care professionals should be aware of the effect of family and culture on the social and sexual lives of Latino gay men so that they can intervene and direct the client to the services needed to manage depression, suicidal ideation, and high-risk sexual behavior.


Traumatic brain injury: special problem, special care.
External physical insult, an accidental blow, acceleration followed by rapid deceleration, or explosive blasts can cause traumatic brain injury (TBI). During the last few years, experts have realized that even mild blows to the head can cause lasting damage. Better understanding of how TBI occurs has improved the probability of survival for those with the most serious injuries. Graded using the Glasgow Coma Scale, TBI may leave its sufferers awake, in periods of alertness interspersed with cognitive confusion, or deep in coma. Falls recently displaced motor vehicle accidents as the leading cause of TBI. Elders are at high risk for falls and TBI, and they may be unaware of possible lasting complications. Pharmacologic therapies for patients who have suffered TBI are, by necessity, individualized.


Synthesis of Alternating Polyisocyanate Copolymers by Anionic Polymerization for Mimicking Amphiphilic Helical Peptides.
The amphiphilic conformation of α-helical peptides has important biological functions, such as ion transport, antifreeze, and innate immunity, which can be mimicked by alternating polyisocyanate copolymers. We synthesized poly(allyl isocyanate-alt-(S)-(-)-α-methylbenzyl isocyanate (P(AIC-alt-SMBIC)) and ammonium-containing P(AIC-alt-SMBIC) (N-P(AIC-alt-SMBIC)), ensuring the amphiphilic helical conformation. The benzyl group of SMBIC plays an important role in alternating copolymerization with its steric and electron-withdrawing effects, while AIC provides an alkene group capable of introducing a customized functional group. The P(AIC-alt-SMBIC) with predominantly alternating sequence was acquired at fSMBIC /fAIC =8 with a controlled molecular weight and narrow dispersity. N-P(AIC-alt-SMBIC)s were synthesized from thiol-ene radical addition with P(AIC-alt-SMBIC).


Construction and partial characterization of a Corynebacterium pseudotuberculosis bacterial artificial chromosome library through genomic survey sequencing.
Corynebacterium pseudotuberculosis is a gram-positive bacterium that causes caseous lymphadenitis in sheep and goats. However, despite the economic losses caused by caseous lymphadenitis, there is little information about the molecular mechanisms of pathogenesis of this bacterium. Genomic libraries constructed in bacterial artificial chromosome (BAC) vectors have become the method of choice for clone development in high-throughput genomic-sequencing projects. Large-insert DNA libraries are useful for isolation and characterization of important genomic regions and genes. In order to identify targets that might be useful for genome sequencing, we constructed a C. pseudotuberculosis BAC library in the vector pBeloBAC11. This library contains about 18,000 BAC clones, with inserts ranging in size from 25 to 120 kb, theoretically representing a 390-fold coverage of the C. pseudotuberculosis genome (estimated to be 2.5-3.1 Mb). Many genomic survey sequences (GSSs) with homology to C. diphtheriae, C. glutamicum, C. efficiens, and C. jeikeium proteins were observed within a sample of 215 sequenced clones, confirming their close phylogenetic relationship. Computer analyses of GSSs did not detect chimeric, deleted, or rearranged BAC clones, showing that this library has low redundancy. This GSSs collection is now available for further genetic and physical analysis of the C. pseudotuberculosis genome. The GSS strategy that we used to develop our library proved to be efficient for the identification of genes and will be an important tool for mapping, assembly, comparative, and functional genomic studies in a C. pseudotuberculosis genome sequencing project that will begin this year.


An optometric purview of intraorbital meningioma.
A 34-year-old black male presented with marked unilateral proptosis and pain in the left eye. Visual acuities were OD 6/7.5 (20/25) and OS 6/120 (20/400). His left eye was exophthalmic , had a Marcus Gunn pupil, and exposure keratitis. Sectorial pallor and a decreased Kestenbaum count were evident on the left optic nerve head. A tentative diagnosis of orbital meningioma was made and later confirmed. Optometric management of the patient, including appropriate screening tests and referrals, are discussed.


Peripartum cardiomyopathy in a patient treated for acute myeloid leukemia.
Peripartum cardiomyopathy usually presents with systolic heart failure during the last months of pregnancy and up to five months postpartum. The disease is rare and can be fatal. We report a 30-year-old female who was diagnosed with acute myeloid leukemia, with maturation and cytogenetic finding of t(8;21)(q22;q22),del(9)(q22) in January 2004. She was treated with chemotherapy and achieved complete remission that lasts to date. She became pregnant and delivered a healthy newborn with caesarean section in 2009. Seven months later, she again became pregnant and delivered the second child with caesarean section in January 2011. Seven days after delivery she developed symptoms and signs of heart failure. Electrocardiogram showed sinus rhythm, low voltage and negative T-waves in inferior and lateral leads. Echocardiography revealed global left ventricular dysfunction with ejection fraction of 15%, with mobile thrombotic mass of 12 mm attached to the left ventricle wall. She was treated with both unfractionated and low-molecular heparin, diuretics, cardiotonics, and beta-blockers. Within six following weeks left ventricle systolic function improved up to 25-30%. The full clinical recovery was achieved in September 2013, resulting in absence of heart failure and left ventricular ejection fraction of 54%. Peripartum cardiomyopathy is a rare condition. The cause of cardiomyopathy is unknown, but it is believed that it could be triggered by various conditions and risk factors. Although the patient was treated with cardiotoxic drugs (doxorubicin and mitoxantrone) in permitted doses, they could have been contributory factors of myocardial damage. Close monitoring of cardiac function in the peripartal period might be beneficial in patients treated with cardiotoxic drugs.


Communities of solutions in single solution clusters of a random K-satisfiability formula.
The solution space of a K-satisfiability (K-SAT) formula is a collection of solution clusters, each of which contains all the solutions that are mutually reachable through a sequence of single-spin flips. Knowledge of the statistical property of solution clusters is valuable for a complete understanding of the solution space structure and the computational complexity of the random K-SAT problem. This paper explores single solution clusters of random 3- and 4-SAT formulas through unbiased and biased random-walk processes and the replica-symmetric cavity method of statistical physics. We find that the giant connected component of the solution space has already formed many different communities when the constraint density of the formula is still lower than the solution space clustering transition point. Solutions of the same community are more similar with each other and more densely connected with each other than with the other solutions. The entropy density of a solution community is calculated using belief propagation and is found to be different for different communities of the same cluster. When the constraint density is beyond the clustering transition point, the same behavior is observed for the solution clusters reached by several stochastic search algorithms. Taking together, the results of this work suggest a refined picture on the evolution of the solution space structure of the random K-SAT problem; they may also be helpful for designing heuristic algorithms.


[Idiopathic nephrotic syndrome and food hypersensitivity. Value of an exclusion diet].
A case of idiopathic nephrotic syndrome (INS) evolving since more than 7 years with 4 successive corticosensitive relapses is reported. At the time of a 5th relapse corticosteroid treatment was refused by the parents and evolution went on without any spontaneous tendency to remission. Three months later, allergy tests detected various sensitizations, especially for food allergens. An antiallergic treatment including dietary exclusions induced a complete and durable remission. Five similar cases are reported. These facts, compared to data from the literature, indicate the possible role of food hypersensitivity in INS. Its mechanism has been discussed; the possible part of a lymphocyte activation has been emphasized.


Gastric squamous metaplasia observed by image-enhanced endoscopy.
A 61-year-old Helicobacter pylori-positive female with gastroesophageal reflux disease has undergone surveillance endoscopy every year for 13 years at Tokyo Medical University Hospital. At the first surveillance in 2009, conventional white light endoscopy showed a 10-mm whitish slightly depressed lesion at the lesser curvature of the gastric cardia. This lesion gradually increased in size to 15 mm over the 13-year observational period. Indigo carmine chromoendoscopy, narrow band imaging, and texture and color enhancement imaging in both mode 1 and mode 2 clearly emphasized the presence of a depressed whitish mucosa around the gastric mucosa compared with white light imaging. None of the three image-enhanced endoscopy techniques showed any abnormality in the vascular or structural pattern. Pathological findings showed squamous epithelium without atypia and revealed no evidence of malignancy in the stomach. We thus report a case of gastric squamous metaplasia without gastric neoplastic lesion in the gastric cardia whose lesions were endoscopically observed to change the size for more than 10 years and whose lesions were endoscopically evaluated with a texture and color enhancement imaging mode 1 and mode 2 and narrow band imaging.


HepaRG culture in tethered spheroids as an in vitro three-dimensional model for drug safety screening.
Conventional two-dimensional (2D) monolayer cultures of HepaRG cells allow in vitro maintenance of many liver-specific functions. However, cellular dedifferentiation and functional deterioration over an extended culture period in the conventional 2D HepaRG culture have hampered its applications in drug testing. To address this issue, we developed tethered spheroids of HepaRG cells on Arg-Gly-Asp (RGD) and galactose-conjugated substratum with an optimized hybrid ratio as an in vitro three-dimensional (3D) human hepatocyte model. The liver-specific gene expression level and drug metabolizing enzyme activities in HepaRG-tethered spheorids were markedly higher than those in 2D cultures throughout the culture period of 7 days. The inducibility of three major cytochrome P450 (CYP) enzymes, namely CYP1A2, CYP2B6 and CYP3A4, was improved in both mRNA and activity level in tethered spheroids. Drug-induced cytotoxic responses to model hepatotoxins (acetaminophen, chlorpromazine and ketoconazole) in tethered spheroids were comparable to 2D cultures as well as other studies in the literature. Our results suggested that the HepaRG-tethered spheroid would be an alternative in vitro model suitable for drug safety screening.


Removing barriers to care among persons with psychiatric symptoms.
Many persons with serious psychiatric conditions who could benefit from available treatments do not receive care, and the barriers are generally understood to be limited knowledge, inadequacies in insurance coverage, and stigma. Sophisticated approaches are needed to realistically eliminate these and other barriers. Public policy should focus on criteria for need for care and encourage interventions that facilitate treatment when it can be helpful. Appropriate insurance coverage is indispensable, and achieving mental health parity will require careful management of care. Policymakers must help to create a trustworthy management structure that is inclusive, that develops and disseminates models of best practice, that encourages evidence-based decision processes, and that ensures continuing dialogue and procedural fairness in managed care decision making.


Sebnif: an integrated bioinformatics pipeline for the identification of novel large intergenic noncoding RNAs (lincRNAs)--application in human skeletal muscle cells.
Ab initio assembly of transcriptome sequencing data has been widely used to identify large intergenic non-coding RNAs (lincRNAs), a novel class of gene regulators involved in many biological processes. To differentiate real lincRNA transcripts from thousands of assembly artifacts, a series of filtering steps such as filters of transcript length, expression level and coding potential, need to be applied. However, an easy-to-use and publicly available bioinformatics pipeline that integrates these filters is not yet available. Hence, we implemented sebnif, an integrative bioinformatics pipeline to facilitate the discovery of bona fide novel lincRNAs that are suitable for further functional characterization. Specifically, sebnif is the only pipeline that implements an algorithm for identifying high-quality single-exonic lincRNAs that were often omitted in many studies. To demonstrate the usage of sebnif, we applied it on a real biological RNA-seq dataset from Human Skeletal Muscle Cells (HSkMC) and built a novel lincRNA catalog containing 917 highly reliable lincRNAs. Sebnif is available at http://sunlab.lihs.cuhk.edu.hk/sebnif/.


Cytochrome P450-catalyzed degradation of nicotine: fundamental parameters determining hydroxylation by cytochrome P450 2A6 at the 5'-carbon or the n-methyl carbon.
The oxidation of (2'S)-nicotine in the active site of human cytochrome P450 2A6 has been subjected to a detailed analysis by theoretical quantum mechanical/molecular mechanical (QM/MM) calculations linked with a theoretical and experimental study of the associated isotope effects. The study has focused on seeking an explanation as to why oxidation at the 5'-carbon position (A) is favored over oxidation at the methyl carbon (CMe) position (B). It is deduced that the choice of hydrogen for abstraction is not determined by geometric features of the active site, but by the lower energy barrier associated with 5' oxidation. N-Demethylation leading to N-hydroxymethylnornicotine requires ca. 6.5 kcal/mol more energy to transfer a hydrogen atom than is required for oxidation on the carbon 5'. Neither protonation of the pyrrolidine nitrogen (N1') nor inclusion of a water molecule in the reaction process influences the balance between the two oxidation pathways. In both cases, the hydrogen transfer step is rate limiting. An analysis of the calculated kinetic isotope effects indicates that the presence of a (2)H in either the C5' or the CMepositions has a significant effect on the reaction kinetics. However, the experimental values of around 2.2-2.6 are considerably lower than those predicted by theoretical calculations (9.3 and 6.9 for C5' or the CMe positions, respectively, in the LS state of Cpd I), typical of the masking commonly found for CYP450 reactions. The fact that similar values are found for cotinine formation from both substrates, however, may indicate that the measured value is not that for H-abstraction but, rather, is a combined value for (2)H influence on electronic redistribution between iminium states of the pyrrolidine ring. This is the first time that oxidation at the C5' or the CMe positions has been directly compared and that isotope effects have been obtained for this reaction in a human cytochrome P450 reaction.


[Determination of lecithin: cholesterol acyltransferase activity by a radioisotopic assay (author's transl)].
A method for determining Lecithin: Cholesterol Acyltransferase (LCAT) activity is presented. Trace amounts of labelled cholesterol are added to innactivated homologous substrate from a pool of normal serum. LCAT activity is determined measuring the cholesterol esterification, and is expressed as micrograms of cholesterol esters formed per milliliter plasma per hour. LCAT time-course, reproducibility, activity after serum storage at 4 degrees C, and normal values from 20 healthy subjects are studied.


Anti-A and anti-B isohemagglutinins in the course of children's leukemias.
The changes in titres of isohemagglutinins anti-A and anti-B were followed up in 48 leukemic children during relapses and remissions. The levels of titres were compared 1. with levels in healthy children in the same age group, 2. in the different phases of disease in the same child. Compared with healthy children, a higher frequency of low isohemagglutinin levels was found in the phases of the exacerbation of malignancy, no changes were observed in remissions. In some children a quite evident fluctuation of isohemagglutinin titres in relation to the phases of the malignant disease was found. The depression of blood group isohemagglutinins in the phases of activation of the malignant process is considered as a partial defect in IgM, analogical to the so called normoglobulinemic defect of the antibodies.


High-quality-draft genome sequence of the fermenting bacterium Anaerobium acetethylicum type strain GluBS11T (DSM 29698).
Anaerobium acetethylicum strain GluBS11T belongs to the family Lachnospiraceae within the order Clostridiales. It is a Gram-positive, non-motile and strictly anaerobic bacterium isolated from biogas slurry that was originally enriched with gluconate as carbon source (Patil, et al., Int J Syst Evol Microbiol 65:3289-3296, 2015). Here we describe the draft genome sequence of strain GluBS11T and provide a detailed insight into its physiological and metabolic features. The draft genome sequence generated 4,609,043 bp, distributed among 105 scaffolds assembled using the SPAdes genome assembler method. It comprises in total 4,132 genes, of which 4,008 were predicted to be protein coding genes, 124 RNA genes and 867 pseudogenes. The G + C content was 43.51 mol %. The annotated genome of strain GluBS11T contains putative genes coding for the pentose phosphate pathway, the Embden-Meyerhoff-Parnas pathway, the Entner-Doudoroff pathway and the tricarboxylic acid cycle. The genome revealed the presence of most of the necessary genes required for the fermentation of glucose and gluconate to acetate, ethanol, and hydrogen gas. However, a candidate gene for production of formate was not identified.


Controlled Surface Modification to Revive Shallow NV- Centers.
Near-surface negatively charged nitrogen vacancy (NV) centers hold excellent promise for nanoscale magnetic imaging and quantum sensing. However, they often experience charge-state instabilities, leading to strongly reduced fluorescence and NV coherence time, which negatively impact magnetic imaging sensitivity. This occurs even more severely at 4 K and ultrahigh vacuum (UHV, p = 2 × 10-10 mbar). We demonstrate that in situ adsorption of H2O on the diamond surface allows the partial recovery of the shallow NV sensors. Combining these with band-bending calculations, we conclude that controlled surface treatments are essential for implementing NV-based quantum sensing protocols under cryogenic UHV conditions.


Case report: severe course of encephalitis of unknown origin.
The exact cause of encephalitis is still unclear in many cases, although the common etiological factors of this process are viruses such as herpes simplex virus and rabies virus, and also bacteria, fungi, parasites, several medicines and autoimmune diseases. Herein, we report a case of a 56-year-old man with a history of amnestic syndrome, impaired consciousness, somnolence throughout the day, headache, dizziness and hypertension, who was admitted to hospital with suspected neurological disease, and imaging features that were consistent with encephalitis of unknown etiology. Methods which were used to examine patient: cerebrospinal fluid testing, PCR examinations for viruses, testing of antibodies against surface antigens, magnetic resonance imaging of the head, psychiatric consultation, oncology consultation. The objective of this study is to demonstrate a case about an uncommon neurologic condition, which every clinician might meet in clinical practice. In this type of cases, the use of steroids such as dexamethasone and methylprednisolone might lead to a full recovery.


[Prevalence of discrepant lipid levels in Curaçao].
To assess the prevalence of lipid risk factors in Curaçao and to investigate possible interactions with socioeconomic and demographic variables. Cross-sectional population-based study. Public Health Laboratory and Public Health Service, Curaçao, Netherlands Antilles. In a random sample of persons aged 18 years and over from the population of Curaao, serum levels were measured of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and, in a smaller number of samples, of lipoprotein(a) (Lp(a)). The findings were in persons between 20 and 60 years compared with those reported for a random sample from the Netherlands. Multiple regression analysis was used to study the relationship between the total cholesterol values found and various socio-economic variables (age, sex, education, place of residence, race). Among persons aged 20-59 years serum cholesterol levels were > 6.5 mmol/l in 30 of the 288 male participants (11%) and in 42 of the 427 female participants (10%). Fifty-three of the males (18%) had HDL cholesterol levels < 0.9 mmol/l as against 31 of the females (7%). The distributions of both total cholesterol and HDL cholesterol levels was better in Curaao than in the Netherlands, among males aged 20-29 years and males and females over 40 years of age. The median Lp(a) concentration of the 225 participants of Curaao in whom it was measured was 250 mg/l, as against 80 mg/l in the Dutch group. More advanced age, female sex, higher educational level, negroid race and residence in the 'East District' were correlated with a higher serum level of total cholesterol. Both total cholesterol and HDL cholesterol concentrations were favourable in Curaçao compared with the Netherlands, especially in the elderly population.


Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis.
Morphine is widely used for relieving cancer pain in patients with advanced cancer. However, whether morphine can suppress or promote the progression of cancer in breast cancer patients receiving morphine analgesia remains unclear. Therefore, we used an in vitro model treated with morphine and naloxone to investigate the effects of morphine on breast cancer cell line MCF-7. MCF-7 cells were cultured with different concentrations (0.01 to 10 µM) of morphine at 12th, 24th, 36th, 48th, 60th and 72nd hours. Then, cell viability was measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In addition, cell proliferation was conducted by colony formation assay. In this study, we have found that morphine (0.01 to 10 µM) could significantly reduce the cell vitality, growth and colony formation rate of MCF-7 cells, which has a certain relationship with cell cycle progression arrested at the G0/G1 and G2/M phase and MCF-7 cells apoptosis. Moreover, naloxone along with morphine could not reverse these effects, which indicates that the inhibition of MCF-7 breast cancer cell growth and proliferation by morphine could be its independent effect, not associated with opioid receptors. Morphine can inhibit cell growth by blocking the cell cycle and promote apoptosis in MCF-7 cells. Hence, morphine may be unable to promote the progression of cancer in breast cancer patients receiving morphine analgesia.


That looks easy! Evidence against the benefits of an easier criterion of success for enhancing motor learning.
OPTIMAL theory predicts providing learners with a relatively easier criterion of success during practice enhances motor learning through increased self-efficacy, perceptions of competence, and intrinsic motivation. However, mixed results in the literature suggest this enhancement effect may be moderated by the number of successes achieved by learners practicing with the difficult criterion. To investigate this possibility, we manipulated quantity of practice to affect the absolute number of successes achieved by learners practicing with different success criteria. Eighty participants were divided into four groups and performed 50 or 100 trials of a mini-shuffleboard task. Groups practiced with either a large or a small zone of success surrounding the target. Learning was assessed 24 h after acquisition with retention and transfer tests. In terms of endpoint accuracy and precision, there were no learning or practice performance benefits of practicing with an easier criterion of success, regardless of the number of trials. This absence of a criterion of success effect was despite the efficacy of our manipulation in increasing the number of trials stopping within the zone of success, self-efficacy, perceptions of competence, and, for participants with 100 trials, intrinsic motivation. An equivalence test indicated that the effect of criterion of success was small, if existent. Moreover, at the individual level, intrinsic motivation did not predict posttest or acquisition performance. There were no benefits of easing the criterion of success on pressure, effort, accrual of explicit knowledge, or conscious processing. These data challenge key tenets of OPTIMAL theory and question the efficacy of easing criterion of success for motor learning.


ERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer.
Platinum-based therapy is pivotal to the treatment of advanced non-small cell lung Cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. We sought to determine the influence of ERCC1 mRNA expression in advanced NSCLC on chemotherapy response, toxicity, and survival after platinum-based chemotherapy. Patients randomized to a phase III trial of platinum-based chemotherapy were eligible for inclusion. Formalin-fixed paraffin-embedded tumor biopsies were retrieved for mRNA extraction and purification before quantitative real-time polymerase chain reaction analysis using Taqman technology. Expression data were correlated with treatment response, toxicity, and overall survival. Sixty-six patients were enrolled. No statistically significant relationship existed between ERCC1 mRNA expression and response to chemotherapy (p = 0.794) or hematological toxicity. No statistically significant difference in median survival was demonstrated according to ERCC1 expression (high expression, 415 days, 95% confidence interval [95%CI]: 197-633 days; low expression, 327 days [95%CI: 211-433 days]; p = 0.801). High ERCC1 mRNA expression was associated with a hazard ratio for death of 0.96 (95% CI 0.919-1.004; p = 0.08). In contrast to recent publications, ERCC1 mRNA expression in our study did not favor a prognostically better outcome after platinum-based chemotherapy in advanced NSCLC. We explore potential reasons for this, including the need for cautious interpretation of mRNA expression data from archival materials and highlight the need for additional translational research linking gene expression with a promising ERCC1 polymorphism.


Formation of a N/O/F-Rich and Rooflike Cluster-Based Highly Stable Cu(I/II)-MOF for Promising Pipeline Natural Gas Upgrading by the Recovery of Individual C3H8 and C2H6 Gases.
Due to the ultralow amounts of C3H8 and C2H6 gases, to design and synthesize water-stable MOFs that are promising for real-world efficient pipeline natural gas (NG) upgrading by the recovery of individual C3H8 and C2H6 gases is still a great challenge. Here, a N/O/F heteroatom-rich and rooflike [Cu(II)4Cu(I)2(COO)4(tetrazolyl)6] cluster-based ultra-microporous tsi-MOF (SNNU-Bai68) was afforded as a multiple heteroatom-rich and curved-surface-shaped cluster-based ultra-microporous MOF and the first porous MOF based upon such rooflike [Cu(II)xCu(I)y(tetrazolyl)z](2x+y-z)+ cluster. In SNNU-Bai68, the rooflike cluster was further assembled into a 1D chain secondary building block (SBB), which led to a high density of accessible potential adsorptive sites. Very interestingly, it exhibited the most promising balance of high gas adsorption uptakes at 0.01, 0.03, and 0.05 bar, high C3H8/CH4, C3H8/C2H6, and C2H6/CH4 adsorption selectivities, moderate adsorption enthalpies, and high water and chemical stability for pipeline natural gas upgrading by the recovery of individual C3H8 and C2H6 gases, which was further confirmed by the breakthrough experiments of the gas mixtures with/without 74% RH. Furthermore, the SC-XRD and GCMC studies revealed that the successful separation of C3H8, C2H6, and CH4 gases in SNNU-Bai68 is due to different synergistic effects of H-bonds between the frameworks at three adsorptive sites around each rooflike cluster and those different gas molecules, which were initially described systematically by the number of H atoms from the gas molecules, the total number of H-bonds within the synergistic H-bonds, and the binding energy of the framework at an adsorption site toward the gas molecules. In addition, this work may provide a method for the construction of a multiple heteroatom-rich and curved-surface-shaped cluster-based ultra-microporous MOF as a novel approach to build MOFs with polar pore surfaces, suitable pore sizes, and unique pore shapes to maximize the synergistic H-bonds between the framework and guests.


Extended-release Formulation of Minocycline in the Treatment of Moderate-to-severe Acne Vulgaris in Patients Over the Age of 12 Years.
Oral antibiotics continue to play an important role in the treatment of moderate-to-severe acne. Minocycline is widely used in moderate-to-severe acne. Minocycline has anti-inflammatory properties, activity against Propionibacterium acnes and lipophilicity. An extended-release formulation of minocycline has been introduced. Extended-release minocycline is not bioequivalent to nonmodified release minocycline products and exhibits dose-proportional pharmacokinetics. Food or dairy products did not influence absorption. Efficacy is not dose-dependent, while the incidence of acute vestibular adverse events increases with dose suggesting an optimal dose of 1mg/kg. In two Phase 3 clinical trials, mean percent improvement in inflammatory lesions after 12 weeks of treatment with extended-release minocycline was 43.1 and 45.8 percent compared to 31.7 and 30.8 percent with placebo (P=0.001 and P<0.001, respectively) while the incidence of acute vestibular adverse events was comparable to placebo.


Gene-based analysis of rare and common variants to determine association with blood pressure.
Systolic blood pressure and diastolic blood pressure are known risk factors for cardiovascular diseases and understanding their genetic basis will have important public health implications. For rare variants, it is extremely challenging to make statistical inference for single-maker tests. Therefore, joint analysis of a set of variants has been proposed. In this paper, we applied recently proposed methods "test for testing the effect of an optimally weighted combination of variants" and "variable weight-TOW" to determine genetic regions that are associated with blood pressure. Then least absolute shrinkage and selection operator, as well as sparse partial least square methods, were used to identify significant markers within a gene or in intergenic regions. We investigated the effect of rare variants and common variants, and their combined effect.


IRISIN AND CHEMERIN LEVELS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.
Changes in the secretion of signaling molecules that originates from adipose tissue and inflammation draw attention in the pathogenesis of type 2 DM. Chemerin, one of the signaling molecules of adipose origin, and irisin, defined as the Renaissance of the metabolism, are among these molecules. This cross-sectional study was planned in order to compare the values of serum irisin and chemerin levels in patients newly diagnosed with T2DM and in healthy subjects. The study included 41 patients newly diagnosed with T2DM and 49 healthy individuals. The chemistry parameters were analyzed with a biochemistry autoanalyzer, and hormonal parameters were analyzed with an immunoassay analyzer. Plasma irisin and chemerin levels were measured using the enzyme-linked immunosorbent assay method. There was a significant difference between the groups in terms of glucose, HbA1C, Insulin, HOMA-IR and lipid panel results. Irisin levels in the group of patients newly diagnosed with T2DM were lower than in the control group. Chemerin levels in the group of patients newly diagnosed with T2DM were higher than in the control group. Consequently, diabetes-dependent changes in chemerin and irisin concentrations suggest that these two hormones have a role in the pathophysiology of DM. Further studies are required to understand the complex structure of the signaling pathways of chemerin and irisin molecules as well as the physiological importance of these molecules as metabolism regulators especially in humans.


Lineage-specific expansion and loss of tyrosinase genes across platyhelminths and their induction profiles in the carcinogenic oriental liver fluke, Clonorchis sinensis.
Tyrosinase provides an essential activity during egg production in diverse platyhelminths by mediating sclerotization of eggshells. In this study, we investigated the genomic and evolutionary features of tyrosinases in parasitic platyhelminths whose genomic information is available. A pair of paralogous tyrosinases was detected in most trematodes, whereas they were lost in cyclophyllidean cestodes. A pseudophyllidean cestode displaying egg biology similar to that of trematodes possessed an orthologous gene. Interestingly, one of the paralogous tyrosinases appeared to have been multiplied into three copies in Clonorchis sinensis and Opisthorchis viverrini. In addition, a fifth tyrosinase gene that was minimally transcribed through all developmental stages was further detected in these opisthorchiid genomes. Phylogenetic analyses demonstrated that the tyrosinase gene has undergone duplication at least three times in platyhelminths. The additional opisthorchiid gene arose from the first duplication. A paralogous copy generated from these gene duplications, except for the last one, seemed to be lost in the major neodermatans lineages. In C. sinensis, tyrosinase gene expressions were initiated following sexual maturation and the levels were significantly enhanced by the presence of O2 and bile. Taken together, our data suggest that tyrosinase has evolved lineage-specifically across platyhelminths related to its copy number and induction mechanism.


Energetics of Helicobacter pylori and its implications for the mechanism of urease-dependent acid tolerance at pH 1.
In the presence of urea the neutrophilic human pathogen Helicobacter pylori survives for several hours at pH 1 with concomitant cytoplasmic pH homeostasis. To study this effect in detail, the transmembrane proton motive force and cytoplasmic urease activity of H. pylori were determined at various pH values. In the absence of urea, the organism maintained a close-to-neutral cytoplasm and an internally negative membrane potential at external pH values greater than 4 to 5. In the presence of urea, H. pylori accomplished cytoplasmic pH homeostasis down to an external pH of 1.2. At this external pH, the cytoplasmic pH was 4.9 and the membrane potential was slightly negative inside. The latter finding is in contrast to the situation in acidophiles, which develop inside-positive membrane potentials under similar conditions. Measurements of the time course of the membrane potential confirmed that addition of urea to the cells led to hyperpolarization. Most likely, this effect was due to electrogenic export of ammonium cations from the cytoplasm. The urease activity of intact cells increased nearly exponentially with decreasing external pH. This activation was not due to enhanced gene expression at low external pH values. In cell extracts the pH optimum of urease activity was dependent on the buffer system and was about pH 5 in sodium citrate buffer. Since this is the cytoplasmic pH of the cells at pH 1 to 2, we propose that cytoplasmic pH is a factor in the in vivo activation of the urease at low external pH values. The mechanism by which urease activity leads to cytoplasmic pH homeostasis in H. pylori is discussed.


Design and synthesis of isocyanide ligands for catalysis: application to Rh-catalyzed hydrosilylation of ketones.
New isocyanide ligands with meta-terphenyl backbones were synthesized. 2,6-Bis[3,5-bis(trimethylsilyl)phenyl]-4-methylphenyl isocyanide exhibited the highest rate acceleration in rhodium-catalyzed hydrosilylation among other isocyanide and phosphine ligands tested in this study. 1H NMR spectroscopic studies on the coordination behavior of the new ligands to [Rh(cod)2]BF4 indicated that 2,6-bis[3,5-bis(trimethylsilyl)phenyl]-4-methylphenyl isocyanide exclusively forms the biscoordinated rhodium-isocyanide complex, whereas less sterically demanding isocyanide ligands predominantly form tetracoordinated rhodium-isocyanide complexes. FTIR and 13C NMR spectroscopic studies on the hydrosilylation reaction mixture with the rhodium-isocyanide catalyst showed that the major catalytic species responsible for the hydrosilylation activity is the Rh complex coordinated with the isocyanide ligand. DFT calculations of model compounds revealed the higher affinity of isocyanides for rhodium relative to phosphines. The combined effect of high ligand affinity for the rhodium atom and the bulkiness of the ligand, which facilitates the formation of a catalytically active, monoisocyanide-rhodium species, is proposed to account for the catalytic efficiency of the rhodium-bulky isocyanide system in hydrosilylation.


HER-2, gp100, and MAGE-1 are expressed in human glioblastoma and recognized by cytotoxic T cells.
It has recently been demonstrated that malignant glioma cells express certain known tumor-associated antigens, such as HER-2, gp100, and MAGE-1. To further determine the possible utilization of these antigens for glioma immunotherapy and as surrogate markers for specific tumor antigen cytotoxicity, we characterized the presence of mRNA and protein expression in 43 primary glioblastoma multiforme (GBM) cell lines and 7 established human GBM cell lines. HER-2, gp100, and MAGE-1 mRNA expression was detected in 81.4%, 46.5%, and 39.5% of the GBM primary cell lines, respectively. Using immunoreactive staining analysis by flow cytometry, HER-2, gp100, and MAGE-1 protein expression was detected in 76%, 45%, and 38% of the GBM primary cell lines, respectively. HLA-A1-restricted epitope specific for MAGE-1 peptide (EADPTGHSY) CTL clone B07 and HLA-A2-restricted epitope specific for HER-2 peptide (KIFGSLAFL) CTL clone A05 and gp100 peptide (ITDQVPFSV) CTL clone CK3H6 were used in this study. The specificity of CTL clone was verified by HLA/peptide tetramer staining. Three CTL clones could efficiently recognize GBM tumor cells in an antigen-specific and MHC class I-restricted manner. IFN-gamma treatment can dramatically increase MHC class I expression of GBM tumor cells and significantly increase CTL recognition of tumor cells. Treatment with the DNA hypomethylating agent 5-aza-2'-deoxycytidine induced and up-regulated the mRNA expression of MAGE-1 and epitope presentation by autologous MHC. These data indicate that HER-2, gp100, and MAGE-1 could be used as tumor antigen targets for surrogate assays for antigen-specific CTLs or to develop antigen-specific active immunotherapy strategies for glioma patients.


Machine learning-based segmentation of the rodent hippocampal CA2 area from Nissl-stained sections.
The hippocampus is a center of learning, memory, and spatial navigation. This region is divided into the CA1, CA2, and CA3 areas, which are anatomically different from each other. Among these divisions, the CA2 area is unique in terms of functional relevance to sociality. The CA2 area is often manually detected based on the size, shape, and density of neurons in the hippocampal pyramidal cell layer, but this manual segmentation relying on cytoarchitecture is impractical to apply to a large number of samples and dependent on experimenters' proficiency. Moreover, the CA2 area has been defined based on expression pattern of molecular marker proteins, but it generally takes days to complete immunostaining for such proteins. Thus, we asked whether the CA2 area can be systematically segmented based on cytoarchitecture alone. Since the expression pattern of regulator of G-protein signaling 14 (RGS14) signifies the CA2 area, we visualized the CA2 area in the mouse hippocampus by RGS14-immunostaining and Nissl-counterstaining and manually delineated the CA2 area. We then established "CAseg," a machine learning-based automated algorithm to segment the CA2 area with the F1-score of approximately 0.8 solely from Nissl-counterstained images that visualized cytoarchitecture. CAseg was extended to the segmentation of the prairie vole CA2 area, which raises the possibility that the use of this algorithm can be expanded to other species. Thus, CAseg will be beneficial for investigating unique properties of the hippocampal CA2 area.


Hematological parameters in Bufo arenarum injected with sublethal dose of lead acetate.
Lead has been recognized as a high risk toxic for most organisms including human. The effects of Pb in non-mammalian vertebrates are poorly known, particularly in anuran amphibians. The purpose of this study was to determine the effect of this metal on some hematological parameters of adult Bufo arenarum. It was found that all parameters remained unaltered within normal ranges, with the exception of reticulocyte counts which was significantly increased compared to the in controls (3.7% vs. 0.2%). It is suggested that the selective change found in reticulocyte count might be considered as an early response of a biomarker to sublethal exposition of Bufo arenarum to lead.


Disseminated Kaposi's sarcoma in a patient with acquired ichthyosis.
An elderly black male with Kaposi's sarcoma of the skin and lymph nodes is presented. The patient developed several violaceous papules involving the nose, which suggested a diagnosis of sarcoidosis clinically but proved to be Kaposi's sarcoma on biopsy. His clinical course was complicated by the development of acquired ichthyosis. The prognosis and treatment of generalized Kaposi's sarcoma is discussed.


Association and dissociation of a protease and its inhibitor on the surface of lung squamous cell carcinoma cells.
Squamous cell carcinoma cells possess a cell surface protease, referred to as guanidinobenzoatase (GB). GB is a plasminogen-activator-like enzyme which can be located by the fluorescent probe 9-amino acridine in frozen sections. Fluorescence microscopy has been used to study the inhibition of this GB, the displacement of inhibitor from GB, the displacement of GB from the cell surface receptor and the preparation of both active GB and inhibitor, obtained from these frozen sections of tumour tissue.


Psoas abscess caused by non-typhoid Salmonella in a patient with severe aplastic anemia.
The clinical spectrum of infections caused by non-typhoid Salmonella spp. includes gastroenteritis, enteric fever, bacteremia, and extraintestinal localized complications, especially in immunocompromised hosts. Here we report a patient with severe aplastic anemia developing left iliopsoas abscess caused by non-typhoid Salmonella (NTS), which was successfully treated by prolonged antibiotic treatment and repeated debridement. Our data indicate that aplastic anemia is a risk factor for infection caused by NTS.


Microgel particles at the fluid-fluid interfaces.
Microgels are colloidal gel particles that consist of chemically cross-linked three-dimensional polymer networks. They are able to dramatically swell or shrink in response to a variety of external stimuli such as temperature, pH, ionic strength, electric field, and enzyme activities. Very recently, microgel particles were employed as stabilizers for emulsions. Being soft, porous and stimuli sensitivity, it has been shown that emulsions stabilized by these microgel particles can offer an unparalleled degree of control on emulsions' stability, well beyond what can be achieved by using small molecular surfactants or conventional solid colloidal particles. In this feature article, we review recent studies where microgel particles were employed as emulsion stabilizers, focusing on the behavior of microgel particles at the liquid-liquid interfaces. We also highlight that emulsions stabilized by soft microgel particles can serve as a template for the fabrication of novel functional materials which will have a great potential to be applied in a variety of applications.


The meaning of menarche: A cross-cultural semantic network analysis.
The psychological meaning of menarche was explored in 102 college students from Mexico and the United States. The Natural Semantic Networks Technique was used and participants were asked to respond to the prompt "My first period was …" The strongest components of the Mexican women's semantic network were scary, confusing, and unexpected; the strongest components of the American women's semantic network were unexpected, annoying, and painful. Only the Americans listed positive words (i.e., nice). The Mexicans' network contained the most negative words (i.e., dirty). The results suggest a need for better education and greater social support, especially in Mexico.


Physicians' acquaintance with a new procedure results in higher patient referral: experience of Kosovo in coronary angiography.
The first coronary angiography in Kosovo was completed in 2003. We analyzed coronary angiographies performed in our center from October 2003 until October 2009 divided into two 3-year periods. to compare the number of coronary angiographies completed in the two periods; to evaluate the prevalence of normal coronary angiographies diagnosed in the first period compared to the second period; and to assess the prevalence of advanced coronary artery disease in the first three years compared to the last three years. This was a prospective angiography study that included 1,139 patients. The first group had 422 patients, who underwent the angiography procedure during the first three years, and the second group had 717 patients that went through the procedure during the last three years. In the first year, 109 coronary angiographies were completed, followed by 137, 176, 213, 218 and 286 (P<0.001) procedures in the subsequent years. In the first period, a normal or near-normal coronary artery profile was found in 27% of patients, while this figure rose to approximately 39% in the second period (P=0.004). Advanced coronary artery disease was found in 45% of the patients who underwent coronary angiography during the first three years, whereas this figure was only 24% of cases during the second period (P<0.001). We believe that the availability of specialized resources and the physicians' familiarity with coronary angiography in our country influenced their decision to refer more patients for this procedure.


Urinary GGT/creatinine ratio and fractional excretion of electrolytes in diarrhoeic calves.
The aim of this study was to monitor renal function in diarrhoeic calves and to determine the effectiveness of an applied fluid therapy. A total of 28 diarrhoeic (n = 18) and healthy (n = 10) Holstein-Friesian calves of different sexes, between 1 and 30 days of age, were used. Blood and urine samples were obtained from diarrhoeic calves before the treatment and then three more times at 24-h intervals during the treatment. From healthy calves, samples were taken only once. Therapy was started by the intravenous administration of 8.4% sodium bicarbonate and 0.9% sodium chloride solutions for the first 24 h, followed by the oral application of a commercial electrolyte solution (sodium chloride 3.5 g, trisodium citrate 2.9 g, potassium chloride 1.5 g and glucose anhydrous 20 g in 1 litre H2O) up to the 48th h of therapy. Before the therapy, the average levels of pH (7.10 +/- 0.12), bicarbonate (HCO3-) (16.48 +/- 3.80 mmol/l), base deficit (-12.65 +/- 5.97 mmo/l) and fractional excretion (FE) of sodium (0.16 +/- 0.11%) and potassium (15.07 +/- 8.56%) were significantly lower while serum urea (17.48 +/- 10.32 mmol/l) and creatinine (Cr) concentrations (169.72 +/- 98.12 micromol/l), haematocrit levels (45.13 +/- 13.60%) and urinary gamma glutamyl transferase (GGT)/Cr ratio (8.6 +/- 4.3 x 1/10(3) U/micromol) were significantly higher in diarrhoeic calves than in healthy calves. Alterations in parameters indicating the presence of renal dysfunction were normalised in the diarrhoeic calves that survived (83.3%). Three calves with severe metabolic acidosis and azotaemia died at the beginning of therapy. It was concluded that the FE of Na and K (FENa, FEK) and urine GGT/Cr ratio may have an important role in assessing renal function in diarrhoeic calves and in evaluating the effectiveness of an applied fluid therapy.


Effectiveness of prehospital continuous positive airway pressure in the management of acute pulmonary edema.
To compare the effectiveness of continuous positive airway pressure (CPAP) with standard pharmacologic treatment in the management of prehospital acute pulmonary edema. Using a nonrandomized control group design, all consecutive patients presenting to two participating emergency medical services (EMS) systems with a field impression of acute pulmonary edema between July 1, 2004, and June 30, 2005, were included in the study. The control EMS system patients received standard treatment with oxygen, nitrates, furosemide, morphine, and, if indicated, endotracheal intubation. The intervention EMS system patients received CPAP via face mask at 10 cm H2O in addition to standard therapy. Ninety-five patients received standard therapy, and 120 patients received CPAP and standard therapy. Intubation was required in 8.9% of CPAP-treated patients compared with 25.3% in the control group (p = 0.003), and mortality was lower in the CPAP group than in the control group (5.4% vs. 23.2%; p = 0.000). When compared with the control group, the CPAP group had more improvement in respiratory rate (-4.55 vs. -1.81; p = 0.001), pulse rate (-4.77 vs. 0.82; p = 0.013), and dyspnea score (-2.11 vs. -1.36; p = 0.008). Using logistic regression to control for potential confounders, patients receiving standard treatment were more likely to be intubated (odds ratio, 4.04; 95% confidence interval, 1.64 to 9.95) and more likely to die (odds ratio, 7.48; 95% confidence interval, 1.96 to 28.54) than those receiving standard therapy and CPAP. The prehospital use of CPAP is feasible, may avert the need for endotracheal intubation, and may reduce short-term mortality.


Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae.
Olfactory dysfunction (OD) commonly accompanies coronavirus disease 2019 (COVID-19). We investigated the kinetics of OD resolution following SARS-CoV-2 infection (wild-type and alpha variant) and its impact on quality of life, physical and mental health. OD prevalence was assessed in an ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and an observational cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up). Co-occurrence of OD with other symptoms and effects on quality of life, physical and mental health were analyzed by multi-dimensional scaling, association rule mining and semi-supervised clustering. Both in the ambulatory COVID-19 survey study (72%) and the observational ambulatory and hospitalized cohort (41%) self-reported OD was frequent during acute COVID-19. Recovery from self-reported OD was slow (survey: median 28 days, observational cohort: 90 days). By clustering of the survey data, we identified a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorders (median recovery: 90 days) but low frequency of post-acute fatigue, respiratory or neurocognitive symptoms. This smell and taste disorder cluster was characterized by a high rating of physical performance, mental health, and quality of life as compared with convalescents affected by prolonged fatigue or neurocognitive complaints. Our results underline the heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype is characterized by good clinical, physical, and mental recovery and may pose a minor challenge for public health. ClinicalTrials.gov: NCT04661462 (survey study), NCT04416100 (observational cohort).


Periostin-integrin interaction regulates force-induced TGF-β1 and α-SMA expression by hPDLSCs.
Periostin (PN), a major matricellular periodontal ligament (PDL) protein, modulates the remodeling of the PDL and bone, especially under mechanical stress. This study investigated the requirement of PN-integrin signaling in force-induced expression of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) in human PDL stem cells (hPDLSCs). Cells were stimulated with intermittent compressive force (ICF) using computerized controlled apparatus. Cell migration was examined using in vitro scratch assay. The mRNA expression was examined using real-time polymerase chain reaction. The protein expression was determined using immunofluorescent staining and western blot analysis. Stimulation with ICF for 24 h increased the expression of PN, TGF-β1, and α-SMA, along with increased SMAD2/3 phosphorylation. Knockdown of POSTN (PN gene) decreased the protein levels of TGF-β1 and pSMAD2/3 upon force stimulation. POSTN knockdown of hPDLSCs resulted in delayed cell migration, as determined by a scratch assay. However, migration improved after seeding these knockdown cells on pre-PN-coated surfaces. Further, the knockdown of αVβ5 significantly attenuated the force-induced TGF-β1 expression. Our findings indicate the importance of PN-αVβ5 interactions in ICF-induced TGF-β1 signaling and the expression of α-SMA. Findings support the critical role of PN in maintaining the PDL's tissue integrity and homeostasis.


Comparative Effectiveness of eConsent: Systematic Review.
Providing informed consent means agreeing to participate in a clinical trial and having understood what is involved. Flawed informed consent processes, including missing dates and signatures, are common regulatory audit findings. Electronic consent (eConsent) uses digital technologies to enable the consenting process. It aims to improve participant comprehension and engagement with study information and to address data quality concerns. This systematic literature review aimed to assess the effectiveness of eConsent in terms of patient comprehension, acceptability, usability, and study enrollment and retention rates, as well as the effects of eConsent on the time patients took to perform the consenting process ("cycle time") and on-site workload in comparison with traditional paper-based consenting. The systematic review was conducted and reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Ovid Embase and Ovid MEDLINE were systematically searched for publications reporting original, comparative data on the effectiveness of eConsent in terms of patient comprehension, acceptability, usability, enrollment and retention rates, cycle time, and site workload. The methodological validity of the studies that compared outcomes for comprehension, acceptability, and usability across paper consent and eConsent was assessed. Study methodologies were categorized as having "high" validity if comprehensive assessments were performed using established instruments. Overall, 37 publications describing 35 studies (13,281 participants) were included. All studies comparing eConsenting and paper-based consenting for comprehension (20/35, 57% of the studies; 10 with "high" validity), acceptability (8/35, 23% of the studies; 1 with "high" validity), and usability (5/35, 14% of the studies; 1 with "high" validity) reported significantly better results with eConsent, better results but without significance testing, or no significant differences in overall results. None of the studies reported better results with paper than with eConsent. Among the "high" validity studies, 6 studies on comprehension reported significantly better understanding of at least some concepts, the study on acceptability reported statistically significant higher satisfaction scores, and the study on usability reported statistically significant higher usability scores with eConsent than with paper (P<.05 for all). Cycle times were increased with eConsent, potentially reflecting greater patient engagement with the content. Data on enrollment and retention were limited. Comparative data from site staff and other study researchers indicated the potential for reduced workload and lower administrative burden with eConsent. This systematic review showed that compared with patients using paper-based consenting, patients using eConsent had a better understanding of the clinical trial information, showed greater engagement with content, and rated the consenting process as more acceptable and usable. eConsent solutions thus have the potential to enhance understanding, acceptability, and usability of the consenting process while inherently being able to address data quality concerns, including those related to flawed consenting processes.


Experimental demonstration of weak-light inter-spacecraft clock jitter readout for TianQin.
The space-based gravitational wave detection mission, TianQin, requires high-level synchronization between independent clocks of all spacecrafts to extract the gravitational wave signals. It is necessary to measure the inter-spacecraft relative clock jitter based on laser phase-sideband clock transfer. The main challenge is the tracking and locking of clock sideband beatnote signals with low signal-to-noise ratio and frequency variation. In this paper, a systematic scheme of inter-spacecraft clock jitter readout is reported. The requirement of the clock transfer link for TianQin based on the time-delay interferometry algorithm is derived. A bi-directional laser interferometer system with a transmission optical power below 1 nW and a time delay of ∼50 µs is built up to demonstrate the weak-light clock transfer. In this scheme, frequency modulation is performed on the laser to simulate the inter-spacecraft Doppler frequency shift and its variation. Based on electrical and optical clock transfer comparison experiments, it is demonstrated that the GHz frequency synthesizer is the main noise source below the 50 mHz frequency range. The residual clock jitter noise introduced by the optical transfer link is below 40 fs/Hz1/2 above the 6 mHz frequency range, and the fractional frequency instability is less than 6.7 × 10-17 at 1000 s, which meets the requirement of the TianQin mission. Ultimately, The carrier phase measurement accuracy reaches 1 × 10-4 cycles/Hz1/2 above 6 mHz after differential clock noise correction using measured clock jitter.


Incorporation of Fly Ash in Flame-Retardant Systems of Biopolyesters.
The incorporation of fly ash in polybutyl succinate (PBS) and polybutyl adipate terephtalate (PBAT) in the partial replacement of ammonium polyphosphate and/or melamine polyphosphate is evaluated in the present work. Furthermore, the influence of the surface modification of fly ash with two silanes and titanate coupling agents was also studied. Cone calorimeter experiments, pyrolysis combustion flow calorimeters (PCFCs), and UL94V tests were used to assess the fire performance of the composites. Scanning electronic microscopy, X-microanalysis, and X-ray diffractometry analysis were carried out on cone calorimeter residues in order to access the fire-retardant mode of action. The formation of new components due to the presence of fly ash was highlighted by X-ray diffractometry, indicating the synergistic effects between the flame-retardant system and fly ash. The X-microanalysis results showed that the main fraction of initial phosphorous is present in the cone calorimeter residue, indicating that the proposed system acts in a condensed phase.


Feeding schemes and C/N ratio of a laboratory-scale step-fed sequencing batch reactor for liquid swine manure treatment.
This study was undertaken to investigate the effect of two split feeding schemes (600 mL/200 mL and 400 mL/400 mL, designated as FS1 and FS2, respectively) on the performance of a step-fed sequencing batch reactor (SBR) in treating liquid swine manure for nutrient removal. The SBR was run on an 8-h cycle with a repeated pattern of anaerobic/anoxic/aerobic phases in each cycle and the two feedings always occurred at the beginning of each anaerobic phase. A low-level aeration was used (1.0 L/m3.sec) for the anoxic/aerobic phase to facilitate nitrification and phosphorus uptake while reducing the energy consumption. The results showed that FS1 reduced NH4+-N by 98.7% and FS2 by 98.3%. FS1 had 12.3 mg/L NO3-N left in the effluent, while FS2 had 4.51 mg/L. For soluble phosphorus removal, FS1 achieved 95.2%, while FS2 reached only 68.5%. Both feeding schemes achieved ≥ 95% removal of COD. A good power regression was observed between total nitrogen (sum of all three nitrogen species) and the carbon to nitrogen (C/N) ratio, with the correlation coefficients of 0.9729 and 0.9542 for FS1 and FS2, respectively, based on which it was concluded that higher C/N ratios were required to achieve higher nitrogen removal efficiencies.


Sweeteners' Influence on In Vitro α-Glucosidase Inhibitory Activity, Cytotoxicity, Stability and In Vivo Bioavailability of the Anthocyanins from Lingonberry Jams.
Several lines of evidence demonstrate the multiple health-promoting properties of anthocyanins, but little is known regarding the bioavailability of these phytochemicals. Therefore, the stability during storage and bioavailability of anthocyanins from lingonberries jams were determined by HPLC, together with the impact of used sweeteners on their adsorption. Further, the in vitro α-glucosidase inhibition using spectrophotometric methods and cytotoxicity determined on normal and colon cancer cells were communicated. The content of anthocyanins was significantly decreased during storage in coconut sugar-based jam, but was best preserved in jam with fructose and stevia. Fructose and stevia-based jams showed the highest inhibition activity upon α-glucosidase. Lingonberry jams showed no cytotoxic effects on normal cells, but at low concentration reduced the tumor cells viability. Anthocyanins were still detectable in rats' blood streams after 24 h, showing a prolonged bioavailability in rats. This study brings important results that will enable the development of functional food products.


Microbiota and growth among infants and children in low-income and middle-income settings.
Adequate nutrition is essential but insufficient for optimal childhood growth and development. Increasingly, it is clear that the gut microbiota modulates childhood growth and may be particularly important in low-income and middle-income countries (LMIC), where growth faltering, undernutrition, environmental contamination and enteric pathogens are more common. We summarize recent evidence demonstrating the role of the gut microbiota in impacting childhood growth and interventions targeting the gut microbiota to impact growth in children in LMIC settings. Recent studies show that maturation of the infant microbiota is linked with the development of the immune system, which is key to host-microbe symbiosis. Infants lacking Bifidobacterium longum subsp. Infantis , which predominates breastfed microbiome, display immune activation while supplementation is linked to increased immune tolerance and among undernourished children, promotes growth. Microbiome-directed complimentary foods (MDCF) containing local ingredients is a novel strategy to promote gut microbiota development, especially among undernourished children and improve growth. Dietary patterns during pregnancy may drive selection of gut microbial species that impact infant health and growth. Growth patterns among children in LMIC settings are closely associated with the diversity and maturity of the infant microbiome. Prebiotics, probiotics, and synbiotics targeting microbiota dysbiosis may impact birth outcomes, infant immune development and infections, and childhood growth in LMIC settings.


A design of irregular grid map for large-scale Wi-Fi LAN fingerprint positioning systems.
The rapid growth of mobile communication and the proliferation of smartphones have drawn significant attention to location-based services (LBSs). One of the most important factors in the vitalization of LBSs is the accurate position estimation of a mobile device. The Wi-Fi positioning system (WPS) is a new positioning method that measures received signal strength indication (RSSI) data from all Wi-Fi access points (APs) and stores them in a large database as a form of radio fingerprint map. Because of the millions of APs in urban areas, radio fingerprints are seriously contaminated and confused. Moreover, the algorithmic advances for positioning face computational limitation. Therefore, we present a novel irregular grid structure and data analytics for efficient fingerprint map management. The usefulness of the proposed methodology is presented using the actual radio fingerprint measurements taken throughout Seoul, Korea.


Differentiation-arrested rat fetal lung in primary monolayer cell culture. III. Antioxidant enzyme activity.
Differentiation-arrested monolayer lung cell cultures were developed from day 18, 20, and 22 rat fetuses and 3-day-old neonatal rats. These cultures were examined for antioxidant enzyme activity, and the values obtained were compared with previously reported in vivo activity. All cultures were catalase deficient, and activity could be restored by the addition of 0.25 microM Fe(NO3)3 X 9H2O to the culture medium. The other measured antioxidant enzymes--copper-zinc and manganese superoxide dismutase, glutathione peroxidase, and glucose 6-phosphate dehydrogenase-demonstrate gestation-dependent increases of activity in vivo that were not evident in vitro, supporting the concept of a circulating "maturation factor" during fetal life. When cultures from fetal days 20 and 22 and from neonatal day 3 lungs were challenged with 50% oxygen in the presence of serum, antioxidant enzyme activities were unchanged, and there was no evidence of cell damage as assessed by release of lactate dehydrogenase. In the absence of serum, however, fetal day 20 (but not fetal day 22 or neonatal day 3) lung cells showed evidence of cell damage and increased antioxidant enzyme activities. It is concluded that cultured immature fetal cells are more susceptible to oxygen toxicity than those derived from mature fetal or neonatal animals. This increased susceptibility cannot be explained on the basis of the reduced antioxidant enzyme activity observed in vivo.


Preoperative autologous blood donation and plateletpheresis in patients undergoing elective cardiac operations--factors that influence the need for homologous blood transfusion.
An increased awareness of the adverse effects of homologous blood transfusion prompted us to initiate a blood conservation program consisting of preoperative autologous blood donation and platelet-rich plasma-pheresis. We studied 120 patients who underwent elective cardiac surgery at Aomori General Hospital between January 1991 and September 1994. If their hemoglobin values exceeded 12 g/ml, 400 g of whole blood was drawn 3 times before the operation. Platelet-poor plasma was collected 10 days before the operation and platelet-rich plasma was collected the day before the operation. However, despite participation in this program, 42 of 120 patients (35%) required homologous blood transfusion perioperatively. Factors that influenced the need for homologous blood transfusion were identified retrospectively, with the following found to be significant by univariate analysis: operative procedures performed, cardiopulmonary bypass time, and the amount of autologous blood and autologous plasma donated. Although the effectiveness of our blood conservation procedure remains to be verified, it reduced the need for the transfusion of homologous blood. Thus, additional units of autologous blood are required to obviate the need for homologous transfusion in patients undergoing long cardiopulmonary bypass procedures.


Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite.
Apicomplexan pathogens are obligate intracellular parasites. To enter cells, they must bind with high affinity to host cell receptors and then uncouple these interactions to complete invasion. Merozoites of Plasmodium falciparum, the parasite responsible for the most dangerous form of malaria, invade erythrocytes using a family of adhesins called Duffy binding ligand-erythrocyte binding proteins (DBL-EBPs). The best-characterized P. falciparum DBL-EBP is erythrocyte binding antigen 175 (EBA-175), which binds erythrocyte surface glycophorin A. We report that EBA-175 is shed from the merozoite at around the point of invasion. Shedding occurs by proteolytic cleavage within the transmembrane domain (TMD) at a site that is conserved across the DBL-EBP family. We show that EBA-175 is cleaved by PfROM4, a rhomboid protease that localizes to the merozoite plasma membrane, but not by other rhomboids tested. Mutations within the EBA-175 TMD that abolish cleavage by PfROM4 prevent parasite growth. Our results identify a crucial role for intramembrane proteolysis in the life cycle of this pathogen.


Supramolecular Chirality Suppresses Molecular Chirality: Selective Chiral Recognition in Hierarchically Coassembled Pyridine-Benzimidazole Conjugates with Precise ee% Detection.
Incorporation of aromatic chiral species with axial, helical, or propeller chirality in surapmolecular chiral motifs would potentially facilitate the chiroptical applications such as enantiomeric excess detection, chiral sensing, and displays, which however suffer from inevitable competition between supramolecular chirality and molecular chirality and remain major challenges. Here, we show the programmable coassembly of pyridine-cored benzimidazole derivatives with intrinsic propeller chirality, which shall form binary and ternary aggregates with chiral acids as well as metal ions though H-bonds and metal-ligand coordination interactions in an orthogonal manner, to enhance and flexibly control the chiroptical properties. Solid-state X-ray structures of pyridine-benzimidazole derivatives suggested they adopted the propeller molecular chirality. Competition between molecular and supramolecular chirality and dynamic binding toward enantiomers of pyridine-benzimidazole derivatives was observed in the coassembly systems based on the chiroptical responses and molecular dynamic simulation. Compared to the intrinsic racemic assembly, coassembly systems produced chiroptical responses including the Cotton effect and circularly polarized luminescence (CPL) with relatively high dissymmetry factor (gabs up to 4.9 × 10-2, glum up to 9.6 × 10-3). Furthermore, chiroptical responses were further controlled by introducing metal ions, achieving inverted handedness and tunable dissymmetry factors. This work provides feasible strategies to efficiently regulate and enhance the chiroptical properties of intrinsic aromatics via multiple interactions, which also expressed great potential in quantitative ee% sensing for chiral acids.


Direct Nucleophilic Difluoromethylation of Carbonyl Compounds.
Phosphonium salt ([Ph3P(+)CF2H] Br(-), DFPB) was found to be an efficient nucleophilic difluoromethylation reagent. Although DFPB is known as a phosphonium ylide precursor, its reaction with carbonyl compounds under traditional "Wittig reaction conditions" did not give the expected Wittig difluoroolefinated products, but afforded the nucleophilic difluoromethylation products, α-CF2H alcohols. Mechanistic investigation reveals that the unexpected transformation proceeded via the direct transfer of the CF2H group, which resulted from the high P-O affinity.


Immunoregulatory properties of the cytokine IL-34.
Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more complex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Until now, studies have demonstrated that this cytokine is released by some tissues that differ to those where CSF-1 is expressed and is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation. The involvement of IL-34 has been shown in areas as diverse as neuronal protection, autoimmune diseases, infection, cancer, and transplantation. Our recent work has demonstrated a new and possible therapeutic role for IL-34 as a Foxp3+ Treg-secreted cytokine mediator of transplant tolerance. In this review, we recapitulate most recent findings on IL-34 and its controversial effects on immune responses and address its immunoregulatory properties and the potential of targeting this cytokine in human.


Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection.
Maternally-derived antibodies (MDAs) can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP) or intranasal (IN) route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN) was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition.


New insights into function of the growth plate: clinical observations, chondrocyte enlargement and a possible role for membrane transporters.
The mammalian growth plate is a complex structure which is essential for the elongation of long bones. However, an understanding of how the growth plate functions at the cellular level is lacking. This review, summarises the factors involved in growth-plate regulation, its failure and the consequence of injury. We also describe some of the cellular mechanisms which underpin the increase in volume of the growth-plate chondrocyte which is the major determinant of the rate and extent of bone lengthening. We show how living in situ chondrocytes can be imaged using 2-photon laser scanning microscopy to provide a quantitative analysis of their volume. This approach should give better understanding of the cellular control of bone growth in both healthy and failed growth plates.


Differences in Larval Arm Movements Correlate with the Complexity of Musculature in Two Phylogenetically Distant Echinoids, Eucidaris tribuloides (Cidaroidea) and Lytechinus variegatus (Euechinoidea).
Within a common body plan, echinoid planktotrophic larvae are morphologically diverse, with variations in overall size, the length, and number of arms and the presence or absence of epidermal structures. In this report, we are interested in variation in larval arm-flexing behavior and correlated differences in larval musculature. Larvae of the cidaroid Eucidaris tribuloides exhibit conspicuous and regular arm-flexing behavior. In contrast, Lytechinus variegatus, a representative of the euechinoid clade, does not exhibit this behavior. We hypothesized that there were differences in musculature that correlated with this behavioral contrast and compared the development and structure of larval muscles between these species. We report substantial differences in some aspects of larval musculature. In addition to previously described oral musculature, both larvae possessed polygon-shaped musculature at the basal end of the larva. However, larval musculature in E. tribuloides was larger and contained additional muscles not observed in larvae of L. variegatus. Therefore, a conspicuous larval behavior consisting of repeated flexing of the postoral and posterodorsal larval arms was correlated with a larger, more complex musculature. This simple contrast indicates that larval musculature not associated with endoderm evolves in a manner that relates to differences in larval behavior and that additional comparisons are warranted.


The new American diet and the changing face of foodborne illness.
Pathogens responsible for foodborne illness are changing, owing to changes in the American diet as well as in food production and distribution. Microbial adaptations to heat, acid, cold, and antibiotics have made food safety a challenging task. This article reviews the common pathogens, their sources, and treatment.


Registration online.
The Nursing and Midwifery Council has launched a secure service that allows nurses to register and manage their registration online. Users can view their registration status, update contact details, view and print a statement of entry, submit notification of practice, pay the annual retention or renewal fees, set up a direct debit for annual fee payments, provide equality and diversity information, and give the geographical location of employment. Go to tinyurl.com/mj2ahxk to set up an account.


Personalized Network Modeling of the Pan-Cancer Patient and Cell Line Interactome.
Personalized network inference on diverse clinical and in vitro model systems across cancer types can be used to delineate specific regulatory mechanisms, uncover drug targets and pathways, and develop individualized predictive models in cancer. We developed TransPRECISE (personalized cancer-specific integrated network estimation model), a multiscale Bayesian network modeling framework, to analyze the pan-cancer patient and cell line interactome to identify differential and conserved intrapathway activities, to globally assess cell lines as representative models for patients, and to develop drug sensitivity prediction models. We assessed pan-cancer pathway activities for a large cohort of patient samples (> 7,700) from the Cancer Proteome Atlas across ≥ 30 tumor types, a set of 640 cancer cell lines from the MD Anderson Cell Lines Project spanning 16 lineages, and ≥ 250 cell lines' response to > 400 drugs. TransPRECISE captured differential and conserved proteomic network topologies and pathway circuitry between multiple patient and cell line lineages: ovarian and kidney cancers shared high levels of connectivity in the hormone receptor and receptor tyrosine kinase pathways, respectively, between the two model systems. Our tumor stratification approach found distinct clinical subtypes of the patients represented by different sets of cell lines: patients with head and neck tumors were classified into two different subtypes that are represented by head and neck and esophagus cell lines and had different prognostic patterns (456 v 654 days of median overall survival; P = .02). High predictive accuracy was observed for drug sensitivities in cell lines across multiple drugs (median area under the receiver operating characteristic curve > 0.8) using Bayesian additive regression tree models with TransPRECISE pathway scores. Our study provides a generalizable analytic framework to assess the translational potential of preclinical model systems and to guide pathway-based personalized medical decision making, integrating genomic and molecular data across model systems.


Laryngeal Granuloma - Benefit in Treatment with Zinc Supplementation?
Laryngeal granulomas present as contact and postintubation ulcers and granulomas. Essentially, a contact granuloma is a pseudotumor of the lateral wall of the posterior glottis. The most common etiological factor is voice abuse, with predisponing factors such as reflux disease. Postintubation ulcers and granulomas, although of different etiology, according to all the other traits belong to this clinical entity. The therapy of choice is conservative treatment. Surgical laser excision is indicated for resistant cases and those whose size is causing respiratory distress. Treatment of laryngeal granulomas with zinc supplementation is reported in the literature as one of the forms of conservative treatment, and we wanted to consider it in this review. Zinc is an essential mineral that plays a vital role in many biochemical reactions and is considered very important for wound healing.