Processing strategies and software solutions for data-independent acquisition in mass spectrometry.
Data-independent acquisition (DIA) offers several advantages over data-dependent acquisition (DDA) schemes for characterizing complex protein digests analyzed by LC-MS/MS. In contrast to the sequential detection, selection, and analysis of individual ions during DDA, DIA systematically parallelizes the fragmentation of all detectable ions within a wide m/z range regardless of intensity, thereby providing broader dynamic range of detected signals, improved reproducibility for identification, better sensitivity, and accuracy for quantification, and, potentially, enhanced proteome coverage. To fully exploit these advantages, composite or multiplexed fragment ion spectra generated by DIA require more elaborate processing algorithms compared to DDA. This review examines different DIA schemes and, in particular, discusses the concepts applied to and related to data processing. Available software implementations for identification and quantification are presented as comprehensively as possible and examples of software usage are cited. Processing workflows, including complete proprietary frameworks or combinations of modules from different open source data processing packages are described and compared in terms of software availability and usability, programming language, operating system support, input/output data formats, as well as the main principles employed in the algorithms used for identification and quantification. This comparative study concludes with further discussion of current limitations and expectable improvements in the short- and midterm future.


Training in and comfort with diagnosis and management of ophthalmic emergencies among emergency medicine physicians in the United States.
Patients with ophthalmic emergencies often present to emergency rooms. Emergency medicine (EM) physicians should feel comfortable encountering these conditions. We assessed EM physicians' comfort working up, diagnosing, and managing ophthalmic emergencies. 329 EM physicians participated in this cross-sectional multicentre survey. Questions inquired about the amount, type, and self-perceived adequacy of ophthalmic training. Likert scales were used to assess confidence and comfort working up, diagnosing, and managing ophthalmic emergencies. Participants recall receiving a median of 5 and 10 h of ophthalmic training in medical school and residency, respectively. Few feel this prepared them for residency (16.5%) or practice (52.0%). Only 50.6% feel confident with their ophthalmic exam. Most (75.0%) feel confident in their ability to identify an ophthalmic emergency, but 58.8% feel well prepared to work them up. Responders feel more comfortable diagnosing acute retrobulbar hematoma (72.5%), retinal detachment (69.8%), and acute angle closure glaucoma (78.0%) than central retinal artery occlusion (28.9%) or giant cell arteritis (53.2%). Only 60.2% feel comfortable determining if canthotomy and cantholysis is necessary in the setting of acute retrobulbar hematoma, and 40.3% feel comfortable performing the procedure. There was a trend towards attending physicians and providers in urban and academic settings feeling more comfortable diagnosing and managing ophthalmic emergencies compared to trainees, non-urban, and non-academic physicians. Many participants do not feel comfortable using ophthalmic equipment, performing an eye exam, making vision or potentially life-saving diagnoses, or performing vision-saving procedures, suggesting the need to increase ophthalmic training in EM curricula.


Effects of female sex hormones on expression of the Ang-(1-7)/Mas-R/nNOS pathways in rat brain.
Female sex hormones are considered to reduce the risk of ischemic stroke. As a part of the renin-angiotensin system, angiotensin-(1-7) [Ang-(1-7)] has recently been reported to play a role in protecting neuronal tissues from ischemic stroke. Thus, we examined the effects of female sex hormones on the levels of Ang-(1-7) and its downstream pathways in the brain. Female rats were ovariectomized and 17β-estradiol (17β-EST), progesterone (PGR), or a combination of 17β-EST plus PGR were administered. Our data demonstrated that lack of female sex hormones significantly decreased the levels of Ang-(1-7) in the cerebral cortex and hippocampal CA1 area. Also, we observed a linear relationship between cortex levels of Ang-(1-7) and plasma brain natriuretic peptide levels (as an indicator for risk of ischemic stroke). We further showed that lack of female sex hormones decreased the expression of Ang-(1-7), Mas-receptor (Mas-R), and neuronal nitric oxide synthase (nNOS). Overall, our findings show for the first time that Ang-(1-7) and Mas-R/nNOS in the cortex are influenced by circulating 17β-EST and (or) PGR, whereas Ang-(1-7) and its pathways in the hippocampal CA1 area are primarily altered by 17β-EST. This suggests that female sex hormones play a role in regulating the expression of Ang-(1-7) and its pathways during ischemic brain injuries.


[The relationship among the adaptation modes of Roy and NANDA taxonomy of nursing diagnoses].
The present study is theoretical-reflexive with the purpose to establish a correlation between NANDA's taxonomy diagnoses and the adaptation modes proposed by Roy. Authors defined the relationships among the indicators of positive adaptation, the common problems of adaptation proposed by Roy and NANDA's nursing diagnoses. Results showed a strong correspondence between the existent concepts in the studied theoretical model and NANDA's taxonomy of nursing diagnoses. Authors concluded that there is a possibility of using NANDA's nursing diagnoses and the nursing process based on Roy's Adaptation Theory.


Development of thyroid-stimulating hormone beta subunit-producing cells in the chicken embryonic pituitary gland.
In previous studies, the distribution of thyrotropes in the chicken pituitary gland has been analyzed by immunohistochemistry using heterologous antibodies. In this study, we examined the distribution of thyroid-stimulating hormone beta subunit-immunopositive (TSHbeta-ip) cells and the expression of TSHbeta mRNA in the pituitary glands of chicken embryos by immunohistochemistry using a specific antiserum to the chicken TSHbeta, in situ hybridization and RT-PCR. Immunohistochemical and morphometric analyses revealed that the TSHbeta-ip cells first appeared on embryonic day 10 (E10) in the pituitary gland and were mainly distributed in the cephalic lobe and that the cell density on E20 was almost 4 times greater than that on E10. The chicken TSHbeta-ip cells could be classified into two types based on morphological characteristics: round-shaped cells and club-shaped cells, which have long cytoplasmic processes. In situ hybridization analysis revealed that TSHbeta mRNA-expressing cells were expressed from E9 in the cephalic lobe and that the extent of TSHbeta mRNA-expressing cells coincided with that of TSHbeta-ip cells. RT-PCR also showed that TSHbeta mRNA was expressed from E9 and that Pit-1 mRNA was expressed from E5. These results clearly demonstrated that the expression of chicken TSHbeta mRNA starts on E9, that TSHbeta-ip cells appear on E10, mainly in the cephalic lobe, and that TSHbeta-ip cells can be classified into two cell types (round- and club-shaped cells).


Infrared spectroscopy and elastic properties of nanocrystalline Mg-Mn ferrites prepared by co-precipitation technique.
Nanoparticles having particle size in the range 25-40 nm for compositions x = 0.0, 0.2, 0.4 and 0.5 of Mg(x)Mn(1-x)Fe2O4 spinel ferrite system have been prepared by chemical co-precipitation route. The microstructure, infrared spectral and elastic properties have been studied by means of energy dispersive analysis of X-rays (EDAX), transmission electron microscopy (TEM), X-ray diffraction (XRD) and infrared spectroscopic (IR) measurements, before (W) and after high temperature annealing A(w). The force constants for tetrahedral and octahedral sites determined by infrared spectral analysis, lattice constant and X-ray density values by X-ray diffraction pattern analysis; have been used to calculate elastic constants. The magnitude of force constant and elastic moduli for nanocrystalline W-samples are found to be larger as compared to coarse grained A(w)-samples. The results have been explained in the light of redistribution of cations and as a result change in mean ionic charge for such cationic sites, elastic energy and grain size reduction effect of Nanoparticles.


United States feedlot operator willingness to pay for disposal capacity to address foreign animal disease risk.
Foreign animal diseases can cause severe and lasting economic impacts to producers, directly and indirectly. Understanding producer investment cost structures can provide industry and policy makers better tools to encourage biosecurity adoption. Consistent with the literature, many factors can contribute to an individual operator's decision to invest in biosecurity based on individual characteristics, perception of disease likelihood, or expected losses associated with a disease event. We used a producer survey and a one-and-one-half bound econometric model to estimate feedlot operator willingness to pay to invest in disposal capacity within the next 3 years. Results indicate an average willingness to pay of $14,310 for a one-time investment in on-farm disposal capacity to address carcass movement restrictions during a disease outbreak. We found several factors that contribute to and explain the heterogeneity between feedlots and their adoption decisions. Primarily, size of the feedlot and death loss rate significantly impact adoption, which both potentially speak to the financial liquidity and investment potential of a feedlot enterprise. While there is no failsafe in disease prevention, these results provide a better understanding for how to study and structure policy and cost structures to incentivize adoption of biosecurity.


Discovery of novel focal adhesion kinase inhibitors using a hybrid protocol of virtual screening approach based on multicomplex-based pharmacophore and molecular docking.
Focal adhesion kinase (FAK) is a tyrosine kinase that functions as a key orchestrator of signals leading to invasion and metastasis. In the current study, the multicomplex-based pharmacophore (MCBP)-guided method has been suggested to generate a comprehensive pharmacophore of FAK kinase based on seven crystal structures of FAK-inhibitor complexes. In this investigation, a hybrid protocol of virtual screening methods, comprising of pharmacophore model-based virtual screening (PB-VS) and docking-based virtual screening (DB-VS), is used for retrieving new FAK inhibitors from commercially available chemical databases. This hybrid virtual screening approach was then applied to screen several chemical databases, including the Specs (202,408 compounds) database. Thirty-five compounds were selected from the final hits and should be shifted to experimental studies. These results may provide important information for further research of novel FAK inhibitors.


Phase variable DNA repeats in Neisseria gonorrhoeae influence transcription, translation, and protein sequence variation.
There are many types of repeated DNA sequences in the genomes of the species of the genus Neisseria, from homopolymeric tracts to tandem repeats of hundreds of bases. Some of these have roles in the phase-variable expression of genes. When a repeat mediates phase variation, reversible switching between tract lengths occurs, which in the species of the genus Neisseria most often causes the gene to switch between on and off states through frame shifting of the open reading frame. Changes in repeat tract lengths may also influence the strength of transcription from a promoter. For phenotypes that can be readily observed, such as expression of the surface-expressed Opa proteins or pili, verification that repeats are mediating phase variation is relatively straightforward. For other genes, particularly those where the function has not been identified, gathering evidence of repeat tract changes can be more difficult. Here we present analysis of the repetitive sequences that could mediate phase variation in the Neisseria gonorrhoeae strain NCCP11945 genome sequence and compare these results with other gonococcal genome sequences. Evidence is presented for an updated phase-variable gene repertoire in this species, including a class of phase variation that causes amino acid changes at the C-terminus of the protein, not previously described in N. gonorrhoeae.


Intracranial haemorrhage in children and adolescents with severe haemophilia A or B - the impact of prophylactic treatment.
The discussion of prophylactic therapy in haemophilia is largely focused on joint outcomes. The impact of prophylactic therapy on intracranial haemorrhage (ICH) is less known. This study aimed to analyse ICH in children with haemophilia, with a focus on different prophylaxis regimens and sequelae of ICH. We conducted a multicentre retrospective and prospective study that included 33 haemophilia centres from 20 countries. Inclusion criteria were children and adolescents born between 1993 and 2014, with severe haemophilia A or B without inhibitors. Participants were categorized by prophylaxis regimen: full, partial or none, based on dose and dose frequency of regular infusions. The cohort study included 1515 children: 29 cases of ICH over 8038 patient years were reported. The incidence of ICH in the prophylaxis group, 0·00033 cases of ICH/patient year, was significantly lower compared to the no prophylaxis group, 0·017 cases of ICH/patient year (RR 50·06; P < 0·001) and the partial prophylaxis group, 0·0050 cases of ICH/patient year (RR 14·92; P = 0·007). In the on-demand-group, 8% (2/24) children with ICH died and 33% had long-term sequelae, including intellectual and behavioural problems, paresis and epilepsy. Children on regular, frequent prophylaxis have a low risk of ICH compared to those using non-frequent or no prophylaxis.


[Immediate complications of fulguration of ventricular tachycardia and accessory pathways. Analysis of 318 endocavitary shocks].
Abnormal events occurring immediately following electric stimulation were studied in 85 patients--mean age 38.5 years (14-78)--during the performance of 318 intracardiac shocks applied in 110 sessions. This electric stimulation was done for treatment of tachycardias related to an accessory pathway (series AP: 64 patients), or ventricular tachycardias (series VT: 21 patients). The number of shocks per session was 2.4 +/- 1.4 and 4.6 +/- 3, for the series AP and VT respectively, and the cumulative energy per session, was 405 +/- 221 J and 1,007 +/- 735 J. Only events occurring within the first 30 minutes following the shocks, were evaluated. In the series AP, the 64 patients received a total of 208 shocks in 86 sessions, and 68 abnormal events were observed (33%): 35 complete atrio-ventricular blocks, of more than 10 seconds (17%), 29 sinus pauses exceeding 3 seconds (14%) and able to stretch to 30 seconds, 3 ventricular fibrillations (1.4%) and 1 atrial fibrillation. In the series TV, 21 patients received 110 shocks in 24 sessions, and only 10 abnormal events occurred (9%): 2 transient episodes of electromechanical dissociation (1.8%), 3 uniform VT (2.7%), 1 complete atrio-ventricular block (10 min.), 1 cardiac pause (4 sec), 1 ventricular fibrillation, 1 isolated haemodynamic depression and 1 Prinzmetal syndrome. All these events were temporary, 5 ventricular arrhythmias in 6 were treated with a new intracardiac shock, and there were no deaths related to electric stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Metabolic disposition of enciprazine, a non-benzodiazepine anxiolytic drug, in rat, dog and man.
1. The excretion and metabolism of enciprazine, an anxiolytic drug, was examined in rat, dog and man. 2. In rats and dogs that received 14C-enciprazine dihydrochloride orally and by i.v. injection, the drug was well absorbed. Radioactivity was excreted predominantly in the faeces of rats, equally in urine and faeces of dogs, and to a major extent in human urine. 3. Metabolic profiles, which were evaluated in urine and in rat bile, were similar following oral and i.v. dosing to rats and dogs. 4. Unchanged drug was not detected in rat, dog or human excreta. Glucuronide conjugates of 4-hydroxyenciprazine, m-desmethylenciprazine, p-desmethylenciprazine and enciprazine were detected in the excreta of all three species. A glycol metabolite was present only in rat bile and human urine. A metabolite desmethylated in the phenyl ring of the phenylpiperazine moiety also appeared to be present only in human urine. 5. Structural confirmation of the major metabolites in human urine and rat bile was accomplished by h.p.l.c.-mass spectrometry.


Quality of Life of Myasthenia Gravis Patients in Regard to Epidemiological and Clinical Characteristics of the Disease.
Myasthenia gravis (MG) affects overall quality of life (QoL). The aim of the research was to evaluate QoL in patients suffering from MG in regard to epidemiological and clinical factors of the disease. The study included 70 patients. The severity of clinical manifestation was estimated using quantitative MG score and MG composite score. Patients were classified by using Myasthenia Gravis Foundation of America Classification. The Questionnaire of Life Quality Specific for Myasthenia Gravis-15 items (MGQOL15) is developed for QoL assessment in patients suffering from MG. In addition to the MGQOL15 revised version (MGQOL15r), a 36-item health survey of the Medical Outcomes Study Short Form (SF36) questionnaire, the Hamilton scales for the assessment of anxiety (HAM-A), and depression (HAM-D) were also used. MGQOL15r scores are negatively correlated with SF36 scores and positively correlated with scores on HAM-A and HAM-D scales (P<0.001). Patients with longer disease duration and severe clinical manifestation often manifest anxiety, depression, and have poorer QoL (P<0.05). In relation to the presence of the anti-nAchR antibody, statistically significant differences were found in relation to the summed scores on scales for assessing QoL, as well as on a HAM-A scale (P<0.05). Physical workers and unemployed patients had worse scores in relation to retired and administrators/intellectual workers on all scales (P<0.001). MGQOL15r is a life quality assessment questionnaire that could be used in routine practice in patients with MG. It is much simpler for use in these patients than SF36 and provides relevant data.


Enhancement in the magnetic moment with Cr3+ doping and its effect on the magneto-structural properties of Ce(0.1)Y(2.9)Fe5O12.
A change in the overall magnetic moment of Cr(3+) doped cubic garnet ferrites prepared by the modified sol-gel auto combustion method has been investigated. A systematic Crystal Field Theory (CFT) approach is utilized towards understanding this variation in the overall magnetic moment. The malate glycolate precursor obtained in the sol-gel autocombustion method proves to be efficient in the monophasic preparation of the garnet system. X-Ray Diffraction (XRD) confirms the phase formation and purity. X-ray Photoelectron Spectroscopy (XPS) and Raman spectroscopy have been utilized to confirm the valence states of the elements and monophasic formation of the compounds. A change in the magnetic hyperfine field with doping is revealed by Mossbauer Spectroscopy. A Vibrating Sample Magnetometer (VSM) has been employed to probe the change in the magnetic properties with the change in the composition and temperature. The decrease in the magnitude of the antiferromagnetic interaction at a and d sites, with the inclusion of Cr(3+) at the a site and a contribution of L-S coupling from the Cr(3+) ions towards an increase in the resultant magnetic moment, is the significant finding of this investigation.


Ectopic fat: the true culprit linking obesity and cardiovascular disease?
Obesity is a major risk factor for cardiovascular disease and its complications. However, not all fat depots share the same characteristics. Recent studies have found that ectopic rather than subcutaneous fat accumulation is associated with increased cardiometabolic risk. However, ectopic fat accumulation can be seen initially as a protective mechanism against lipotoxicity. Subsequently the adipose tissue becomes dysfunctional, thus inducing systemic metabolic alterations (through release of cytokines) or specific organ dysfunctions. The purpose of this review is to summarise the current available data on the impact of excess adiposity vs ectopic fat in the development of cardio-metabolic diseases.


[Changes of intraocular cytokine level in patients with vascular and neovascular retinal pathology depending on pathologic process activity].
Cytokine and growth factors levels were estimated in anterior chamber humor of patients with different diseases manifesting with vascular and neovascular retinal changes and various pathologic process activity. 40 patients with macula edema, retinal and choroid neovascularization were examined. Process activity was determined based on data obtained using high-resolution optical coherence tomography and fluorescent angiography. Quantitative concentration of interleukine 6, 8, vascular endothelium growth factor and monocyte chemoattractive protein-1 in anterior chamber aqueous humor was measured using enzyme immunoassay. Increased level of cytokines studied was found in all forms of the diseases.


Rate of oxidation of P680 in isolated photosystem 2 reaction centers monitored by loss of chlorophyll stimulated emission.
We have continued our studies of the primary photochemistry of isolated photosystem 2 reaction centers using femtosecond transient absorption spectroscopy. Experiments were performed over a wide range of excitation and probe wavelengths, using several data collection time scales. This has enabled us to resolve five different lifetimes ranging between 100 fs and 200 ps plus a nanosecond component. We demonstrate here and elsewhere [e.g., Durrant, J.R., Hastings, G., Joseph, D. M., Barber, J., Porter, G., & Klug, D. R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11632-11636] that the kinetic spectra associated with all but two of these lifetimes are clearly distinguishable. We have previously reported that a 21-ps lifetime is associated with pheophytin reduction [Hastings, G., Durrant, J. R., Hong, Q., Barber, J., Porter, G., & Klug, D. R. (1992) Biochemistry 31, 7638-7647]. In this paper, we show that it is possible to spectrally and temporally resolve stimulated emission from PS2 reaction centers with great accuracy and that this stimulated emission is largely unaffected by those kinetic components which are faster than 21 ps. The observation of a distinct stimulated emission band allows us to distinguish charge-separated states from chlorin singlet states. In this way, we are able to show that the proportion of charge-separated states prior to the 21-ps component is between 0% and 25%. We also show that the shape of the spectrum which we obtain for the state P680+Ph- is essentially invariant between 100 ps and 9 ns, and is the same as that previously reported for P680+Ph- by other researchers.(ABSTRACT TRUNCATED AT 250 WORDS)


Fast Detector/First Responder: Interactions between the Superior Colliculus-Pulvinar Pathway and Stimuli Relevant to Primates.
Primates are distinguished from other mammals by their heavy reliance on the visual sense, which occurred as a result of natural selection continually favoring those individuals whose visual systems were more responsive to challenges in the natural world. Here we describe two independent but also interrelated visual systems, one cortical and the other subcortical, both of which have been modified and expanded in primates for different functions. Available evidence suggests that while the cortical visual system mainly functions to give primates the ability to assess and adjust to fluid social and ecological environments, the subcortical visual system appears to function as a rapid detector and first responder when time is of the essence, i.e., when survival requires very quick action. We focus here on the subcortical visual system with a review of behavioral and neurophysiological evidence that demonstrates its sensitivity to particular, often emotionally charged, ecological and social stimuli, i.e., snakes and fearful and aggressive facial expressions in conspecifics. We also review the literature on subcortical involvement during another, less emotional, situation that requires rapid detection and response-visually guided reaching and grasping during locomotion-to further emphasize our argument that the subcortical visual system evolved as a rapid detector/first responder, a function that remains in place today. Finally, we argue that investigating deficits in this subcortical system may provide greater understanding of Parkinson's disease and Autism Spectrum disorders (ASD).


Eosinophilic globules in pigmented spindle cell nevus.
Reed's pigmented spindle cell nevus is often misdiagnosed as malignant melanoma despite reliable clinical and histopathologic diagnostic features. In the present report, 10 cases of pigmented spindle cell nevus were studied with step sections to identify Kamino's eosinophilic globules. Eighty percent of the cases disclosed numerous eosinophilic globules, supporting the hypothesis that this nevus is a variant of Spitz's nevus. Kamino's eosinophilic globules could be considered another important sign for the differential diagnosis between pigmented spindle cell nevus and malignant melanoma.


[Clinical effect of recombinant human granulocyte colony-stimulating factor on aplastic anemia].
The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutropenia was studied in 30 patients with aplastic anemia (AA). RhG-CSF was administered intravenously daily at a dose of 2, 5, 10, or 20 micrograms/kg/day for more than 7 days. In the patients whose absolute neutrophil counts (ANC) were more than 0.1 X 10(9)/l, the rhG-CSF injections at greater than or equal to 5 micrograms/kg/day caused rapid and selective elevation of ANC which maintained during the injection period. Most of the patients were well tolerated, and minor side effects were observed in only 3 patients. These findings suggest that daily injections of rhG-CSF at a dose of greater than or equal to 5 micrograms/kg/day may be an effective strategy for the treatment of bacterial and/or fungal infections in AA patients.


Body Praxis and Networks of Power.
Departing from what has in medical anthropology been termed the individual body, the social body and body politics, actor-networks in medical pluralism are investigated on the basis of a study of complementary and alternative forms of medicine (CAM) in Denmark, including participant-observation in 12 clinics of reflexology, biopathy and kinesiology, as well as interviews and informal conversations with more than 40 alternative practitioners and 300 patients of CAM clinics. In this study, several actor-networks that connect metaphorical models of the body, clinical technology, social relations and political structures of the Danish society are revealed: a technocrat network, a social-democratic consultancy network and a neo-liberal network. The co-existence of several actor-networks has phenomenological as well as structural implications. The implications for patients using several forms of therapy is important insofar as the patients' move between different actor-networks of healing implies switches between different experiences of body and self. Each of the actor-networks at the same time implies different positions in relation to the public healthcare system, and some actor-networks appear to be more compatible than others with the generalized and technical properties of public healthcare.


Fundamental differences between perception and cognition aside from cognitive penetrability.
Fundamental differences between perception and cognition argue that the distinction can be maintained independently of cognitive penetrability. The core processes of cognition can be integrated under the theory of relational knowledge. The distinguishing properties include symbols and an operating system, structure-consistent mapping between representations, construction of representations in working memory that enable generation of inferences, and different developmental time courses.


Evidence for the formation of symmetric and asymmetric DLPC-DAPC lipid bilayer domains.
We investigated if mixtures of the phosphatidylcholine (PC) lipids 1,2-dilauroyl-sn-glycero-3-phosphocholine (C12:0 PC; DLPC) and 1,2-diarachidoyl-sn-glycero-3-phosphocholine (C20:0 PC; DAPC), which differ by eight methylene groups in acyl chain length, lead to the spontaneous formation of distinct lipid rafts and asymmetric bilayers. The experiments were performed using Atomic Force Microscopy (AFM). We show that DLPC and DAPC mixed at a molar ratio of 1:1 lead to the formation of single, double and triple bilayers with peaks at 6.14 ± 0.11, 13.27 ± 0.17 and 20.54 ± 0.46 nm, respectively (n=750). Within these formations discrete height steps of 0.92 nm can be resolved (n=422). The most frequently observed height steps value of 0.92 nm matches best with the calculated mean lipid hydrophobic thickness difference for asymmetric C12:0 PC and C20:0 PC lipid bilayers of 0.88 nm. This indicates the ability of DLPC and DAPC to form asymmetric lipid bilayers.


Predictive value of the thymofatty specimen weight index in outcomes of extended thymectomy due to non-thymomatous myasthenia gravis.
To evaluate the predictive value of the intraoperative thymofatty specimen weight (TFSW) index on predicting the prognosis of extended thymectomy (ET) for non-thymomatous myasthenia gravis. This is a prospective non-interventional study in which patients who underwent ET between January 2012 and June 2015 were enrolled. Resected thymus and surrounding adipose tissues were weighed using an electronic scale intraoperatively and adjusted to the body surface area (BSA) to calculate the TFSW index. The primary end point was defined as complete stable remission (CSR) according to the Myasthenia Gravis Foundation of America (MGFA) guidelines. One hundred and eighteen patients who completed postoperative follow-up were included in this study. After a mean follow-up period of 44 months, 68 (57.6%) patients reached clinical CSR. The MGFA class, histopathology and TFSW index were associated with a postoperative CSR in univariate analysis. When the Cox hazard multiple regression model was used, the TFSW index was found to be an independent predictor for CSR (hazard ratio 2.056; 95% confidence interval 1.182-3.576). Based on ROC analysis, an optimal TFSW index cut-off value (35.9 g/m2) with the highest sensitivity and specificity was determined. The TFSW index is an important independent predictor for mid-term CSR after ET in non-thymomatous myasthenia gravis patients. During the ET surgery, every effort should be made to take a tissue specimen with a TFSW index more than 35.9 g/m2.


Association between reversal of multidrug resistance by methyl jasmonate and P-glycoprotein ATPase activity in hepatocellular carcinoma.
To study the effects of methyl jasmonate on multidrug resistance in a mouse model of hepatocellular carcinoma. Multidrug resistant H22 (H22/FAP) hepatocellular carcinoma cells were produced in vitro by continuous exposure to increasing doses of doxorubicin, cisplatin and 5-fluorouracil (FAP regimen). Cell toxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolum bromide (MTT) assay. Survival time was calculated for BALB/c mice that received intraperitoneal injections of H22/FAP cells followed by treatment with methyl jasmonate or verapamil in combination with FAP for 7 days. Adenosine triphosphate (ATP) hydrolysis was used to measure the activity of permeability-glycoprotein (P-gp) ATPase activity in plasma membranes. The MTT assay showed that methyl jasmonate significantly enhanced the cytotoxicity of the FAP regimen in multidrug resistant H22/FAP cells. Methyl jasmonate (10 mg/kg and 5 mg/kg) combined with FAP significantly increased survival time in BALB/c mice by 44.25% and 48.01%, respectively, compared with FAP. Methyl jasmonate increased P-gp ATPase activity. The combined use of methyl jasmonate and the FAP regimen might be a novel strategy for overcoming the multidrug resistance often observed in hepatocellular carcinoma.


EST-SSR Marker Development and Full-Length Transcriptome Sequence Analysis of Tiger Lily (Lilium lancifolium Thunb).
The fast advancement and deployment of sequencing technologies after the Human Genome Project have greatly increased our knowledge of the eukaryotic genome sequences. However, due to technological concerns, high-quality genomic data has been confined to a few key organisms. Moreover, our understanding of which portions of genomes make up genes and which transcript isoforms synthesize these genes is scarce. Therefore, the current study has been designed to explore the reliability of the tiger lily (Lilium lancifolium Thunb) transcriptome. The PacBio-SMRT was used for attaining the complete transcriptomic profile. We obtained a total of 815,624 CCS (Circular Consensus Sequence) reads with an average length of 1295 bp. The tiger lily transcriptome has been sequenced for the first time using third-generation long-read technology. Furthermore, unigenes (38,707), lncRNAs (6852), and TF members (768) were determined based on the transcriptome data, followed by evaluating SSRs (3319). It has also been revealed that 105 out of 128 primer pairs effectively amplified PCR products. Around 15,608 transcripts were allocated to 25 distinct KOG Clusters, and 10,706 unigenes were grouped into 52 functional categories in the annotated transcripts. Until now, no tiger lily lncRNAs have been discovered. Results of this study may serve as an extensive set of reference transcripts and help us learn more about the transcriptomes of tiger lilies and pave the path for further research.


Homology-dependent underwinding of duplex DNA in recA protein generated paranemic complexes.
RecA protein promoted formation of paranemic joints, in which a recA-ssDNA complex and a nicked circular dsDNA molecule are homologously aligned without net cross-strand interwinding, is accompanied by extensive underwinding of the dsDNA molecule. When the nick is sealed by DNA ligase, a highly negatively superhelical DNA molecule is formed. This underwinding has the following properties: (a) it occurs within 2 min; (b) it is completely homology dependent; (c) it does not require a homologous free DNA end. The resulting underwound DNA species is comprised of a heterogeneous population of topoisomers. The degree of unwinding exhibits a strong dependence on the fractional length of homology in the dsDNA molecule and indicates that paranemic joints can extend for at least 2900 base pairs. The rapid underwinding associated with paranemic joint formation is followed by a longer phase in which the dsDNA molecule is more extensively underwound.


[Hermeneutic Phenomenological Study on Caring Experience of Spouses of Elderly People with Dementia at Home].
This study aimed to understand and describe the caring experiences of spouses of elderly people with dementia. The hermeneutic phenomenological method was used and participants were 12 spouses aged 65 and over who were taking care of their husbands or wives with dementia at home. Data were collected from individual in-depth interviews on participants' actual caring experiences. Additionally, novels, movies, and memoirs on elderly couples with partner who had dementia were included as data for the analysis. The qualitative data analysis software program was used to manage and process the collected qualitative data. Data were analyzed using hermeneutic phenomenological analysis based on four fundamental existentials including lived body, lived space, lived time, and lived others. Five essential themes emerged from the analysis: 1) body moving like an old machine, 2) swamp of despair filling with hope, 3) sweet time after bitterness, 4) disappointed elderly couple in the empty nest, and 5) unappreciation vs. empathetic feelings. These essential themes were comprehensively summarized as "the road leading to the maturation of life with dedication and hope while bearing the weight of caring based on the couple's relationship." The findings indicate that the nature of the caring experience of spouses of elderly individuals with dementia is filled with many dynamic and paradoxical dimensions. Thus, results of the study would help with developing interventions tailored specifically for elderly spouse caregivers to support their role adaptation and ultimately improving their quality of life.


Climate change policies: The role of democracy and social cognitive capital.
The impact of democracy on governments' choice of environmental policies has attracted significant academic attention in recent years. However, less attention has been devoted to the role of the social cognitive capital of the national population. Does society's cognitive capital matter in governmental choice regarding environmental policies, if at all? This study addresses this question through a large-N analysis of 94 countries accounting for the role of both political regimes and social capital in governmental choice of climate change policies. We find that higher social cognitive capital within a democratic state radically increases that state's commitment to adopt environmental policies. More specifically, a 1-point increase in the democracy index is associated with nearly 5 points increase in the adoption of the Climate Laws, Institutions and Measures Index (CLIMI). In a similar vein, a 10 points increase in social cognitive capital is associated with a nearly 16 points increase in CLIMI. The findings presented in this study aim to contribute to the ongoing debate on the impact of democracy and the cognitive capital of society on international environmentalism. The findings will also be interesting for scholars working on the impact of political institutional factors and the role of society in environmental policy choices made at the international level.


Jaw fixation as the key to diagnosis of fibrodysplasia ossificans progressiva.
Fibrodysplasia ossificans progressiva is a very rare and disabling hereditary disorder of connective tissue characterised by symmetric congenital anomalies of the great toes and thumbs and by progressive heterotopic ossification of tendons, ligaments, fasciae and striated muscles. In this case we report a 17-year-old boy who presented with a painful swelling of the right mandibula with trismus. Multiple heterotopic soft tissue calcifications, severe scoliosis and typical anomalies of toes and thumbs on the radiographs were pathognomonic for fibrodysplasia ossificans progressiva.


[Problems in the treatment of early carcinoma of the uterine cervix].
Limited operation is in side spread use recently in surgical treatment of in situ (Stage 0) and microinvasive (Stage Ia) carcinomas of the uterine cervix. Which purpose is to avoid such postoperative complications as vesical paralysis, therefore the simple total or modified radical hysterectomy is performed. However, the conization of the cervix may be received among the young women with strong desire to preserve their child-bearing potential. It is utmost importance to make a correct histological diagnosis prior to the performance of these procedures. In addition it is of importance to examine the histological rest of cancer, postoperatively. On the radiation therapy for Stage 0 and Stage Ia cancers, it is a general agreement that be treated only by intracavitary irradiation.


Cancer nanomedicine: a review of nano-therapeutics and challenges ahead.
Cancer is known as the most dangerous disease in the world in terms of mortality and lack of effective treatment. Research on cancer treatment is still active and of great social importance. Since 1930, chemotherapeutics have been used to treat cancer. However, such conventional treatments are associated with pain, side effects, and a lack of targeting. Nanomedicines are an emerging alternative due to their targeting, bioavailability, and low toxicity. Nanoparticles target cancer cells via active and passive mechanisms. Since FDA approval for Doxil®, several nano-therapeutics have been developed, and a few have received approval for use in cancer treatment. Along with liposomes, solid lipid nanoparticles, polymeric nanoparticles, and nanoemulsions, even newer techniques involving extracellular vesicles (EVs) and thermal nanomaterials are now being researched and implemented in practice. This review highlights the evolution and current status of cancer therapy, with a focus on clinical/pre-clinical nanomedicine cancer studies. Insight is also provided into the prospects in this regard.


[Genes and chromosomes: imaging in genetics].
FISH methodologies have made spectacular progress and found wide applications in several areas of clinical studies and research. These techniques are successfully used for visualisation of specific DNA sequences in metaphase chromosomes and interphase cells making this approach, with appropriately chosen probes, a useful adjuvant to conventional cytogenetics in the study of chromosome abnormalities. Improvements have been made in probe generation, developments of new fluorochromes, combinatorial and ratio labelling for multicolor signals and novel hybridization targets as extended DNA. By varying the probe and the target in fluorescence hybridization, numerous applications are being implemented in many fields of human genetics, from clinical cytogenetics to the identification and study of genes involved in monogenic disorders and oncogenic rearrangements.


Supplying the energy and fiber needs of dairy cows from alternate feed sources.
Alternate feeds are a major resource of the dairy industry. The major issue involving them is a method to predict accurately nutritive value from laboratory analyses. Variation in nutrient content of most alternate feeds is greater than in feed grains. Another issue is which depression factors to use in adjusting values for TDN from maintenance to production intakes. The NRC uses an average depression of 8% for all feeds; others think each feedstuff should be depressed individually, and discount factors have been proposed. For some alternate feeds, large differences in net energy estimates occur. Neutral detergent fiber has been proposed as an indicator of productive energy, but it has several deficiencies with alternate feeds high in fat, molasses, or ash. A summative equation based on fat, ash, protein, NDF, and lignin has wider application for predicting NE1 for all feeds. A roughage value index reflects a feed's property to stimulate chewing and rumination. Its use has special relevance for alternate feeds with small particle sizes, which may induce little chewing. Supplemental fat may increase the metabolizable energy converted to milk, but respiration experiments are needed.


Multiple minute digitate hyperkeratosis affecting the face and folds: clinical, dermoscopic, and histological report of a familial case.
A case of a generalized non-follicular digitate keratosis classified as multiple minute digitate hyperkeratosis is described with suggestive clinical, dermoscopic, and histopathogical data. The patient was a 52-year-old Caucasian woman presenting a 6-year history of multiple asymptomatic skin-colored digitate lesions, 3 to 5 mm long and 1 to 2 mm wide, distributed on the forehead, neck, and extensor surface of the arms as well as in the inframammary folds, axillae, and lower limbs, especially on the popliteal fold. She reported having a 67-year-old sister and a 39-year-old niece with an identical eruption. Treatment with 15% glycolic acid (AHA) lotion and heliotherapy improved this disturbing eruption.


Endoscopic treatment for gastric antral vascular ectasia.
Gastric antral vascular ectasia (GAVE) is one of the uncommon causes of upper gastrointestinal bleeding. Major treatment of GAVE includes pharmacotherapy, endoscopy, and surgery. The efficacy and safety of pharmacotherapy have not been sufficiently confirmed; and surgery is just considered when conservative treatment is ineffective. By comparison, endoscopy is a common treatment option for GAVE. This paper reviews the currently used endoscopic approaches for GAVE, mainly including argon plasma coagulation (APC), radiofrequency ablation (RFA), and endoscopic band ligation (EBL). It also summarizes their efficacy and procedure-related adverse events. The endoscopic success rate of APC is 40-100%; however, APC needs several treatment sessions, with a high recurrence rate of 10-78.9%. The endoscopic success rates of RFA and EBL are 90-100% and 77.8-100%, respectively; and their recurrence rates are 21.4-33.3% and 8.3-48.1%, respectively. Hyperplastic gastric polyps and sepsis are major adverse events of APC and RFA; and Mallory-Weiss syndrome is occasionally observed after APC. Adverse events of EBL are rare and mild, such as nausea, vomiting, esophageal or abdominal pain, and hyperplastic polyps. APC is often considered as the first-line choice of endoscopic treatment for GAVE. RFA and EBL have been increasingly used as alternatives in patients with refractory GAVE. A high recurrence of GAVE after endoscopic treatment should be fully recognized and cautiously managed by follow-up endoscopy. In future, a head-to-head comparison of different endoscopic approaches for GAVE is warranted.


CSF biomarkers in delirium: a systematic review.
In recent years, there has been a blossoming of studies examining cerebrospinal fluid (CSF) as a method of studying the pathophysiology of delirium. We systematically reviewed the literature for CSF studies in delirium and provide here a summary of the implications for our understanding of delirium pathophysiology. We also summarise the methods used for CSF analysis and discuss challenges and implications for future studies. In this systematic review, we screened MEDLINE, EMBASE, PsycINFO, Web of Science, PubMed and the Cochrane Library for articles on CSF biomarkers in delirium, published on 3 September 2016. Studies were required to use Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria for delirium or a validated tool. We excluded case reports. There were no other restrictions on study type. We identified 3280 articles from our initial search, and 22 articles were included in this review. All studies were prospective, including over 400 patients with delirium and 700 controls. More than 70 different biomarkers were studied. Studies could not be compared with each other for meta-analysis because of their heterogeneity and varied widely in their risk of bias and quality assessments. The 22 studies identified in this review reveal a small but growing literature, in which many of the important hypotheses in delirium pathogenesis have been examined, but from which few firm conclusions can currently be drawn. Nevertheless, the overall interpretation of the literature supports the vulnerable brain concept, that is, that biomarker evidence of, for example, Alzheimer's disease pathology and/or neuroinflammation, is associated with delirium.


Development of a Two-Stage Hydrometallurgical Process for Gold-Antimony Concentrate Treatment from the Olimpiadinskoe Deposit.
An integrated two-stage metallurgical process has been developed to process concentrates from the Olimpiadinskoe deposit, which contain high levels of antimony and arsenic. The optimal parameters for the alkaline sulfide leaching process of the initial concentrate from the Olimpiadinskoe deposit were determined to achieve the maximum extraction of antimony at a 99% level. The recommended parameters include an L:S ratio of 4.5:1, a sodium sulfide concentration of 61 g/L, a sodium hydroxide concentration of 16.5 g/L, a duration of 3 h, and a temperature of 50 °C. A synergistic effect of co-processing alkaline sulfide leach cakes with sulfuric and nitric acids was observed. The pre-treatment step reduced the nitric acid composition by converting carbonates into gypsum and increased the arsenic extraction by 15% during subsequent nitric acid leaching. The laboratory research on the nitric acid leaching of decarbonized cake established the key parameters for the maximum iron and arsenic extraction in solution (92% and 98%, respectively), including an L:S ratio of 9:1, a nitric acid concentration of 6 mol/L, and a time of 90 min. Full polynomial equations for the iron and arsenic extraction from the decarbonized cake were derived. The model demonstrated a high relevance, as evidenced by the determination coefficients (R2) of 96.7% for iron and 93.2% for arsenic. The technology also achieved a high gold recovery rate of 95% from the two-stage alkaline sulfide and nitric acid leach cake. Furthermore, the maximum deposition of arsenic from the nitrate leach solution in the form of insoluble As2S3 was determined to be 99.9%. A basic technological flow sheet diagram for processing the flotation gold-antimony concentrate from the Olimpiadinskoe deposit was developed, including two stages: the production of metallic antimony and the gold extraction from the nitric leach cake.


Process and meaning: nonlinear dynamics and psychology in visual art.
Creating and viewing visual art are both nonlinear experiences. Creating a work of art is an irreversible process involving increasing levels of complexity and unpredictable events. Viewing art is also creative with collective responses forming autopoietic structures that shape cultural history. Artists work largely from the chaos of the unconscious and visual art contains elements of chaos. Works of art by the author are discussed in reference to nonlinear dynamics. "Travelogues" demonstrates continued emerging interpretations and a deterministic chaos. "Advice to the Imperfect" signifies the resolution of paradox in the nonlinear tension of opposites. "Quanah" shows the nonlinear tension of opposites as an ongoing personal evolution. "The Mother of All Things" depicts seemingly separate phenomena arising from undifferentiated chaos. "Memories" refers to emotional fixations as limit cycles. "Compassionate Heart," "Wind on the Lake," and "Le Mal du Pays" are a series of works in fractal format focusing on the archetype of the mother and child. "Sameness, Depth of Mystery" addresses the illusion of hierarchy and the dynamics of symbols. In "Chasadim" the origin of worlds and the regeneration of individuals emerge through chaos. References to chaos in visual art mirror the nonlinear complexity of life.


Expression analysis of mortalin, a unique member of the Hsp70 family of proteins, in rat tissues.
We have investigated the expression of mortalin in rat tissues by Northern analysis, RNA in situ hybridization, and immunohistochemical studies. By Northern assay, the highest level of expression was detected in brain, heart, and skeletal muscle followed by lung, liver, and kidney, and the least level of expression was detected in testis and spleen. RNA in situ and immunohistochemical studies showed that mortalin expression is significantly higher in upper nondividing layers than in the lower basal layers of skin, in neurons and nerve fibers than in surrounding glial cells in brain, in cardiomyocytes than in nonmyocytes in heart, and in interstitial secretory tissue than in germinating follicles in ovary. Such tissue- and cell-specific expression patterns of mortalin coordinates with its earlier reported antiproliferative function in normal cells. However, a deregulation of the expression is observed in rat brain tumor along with the detection of nonpancytosolic mortalin in rat glioma cell line C6. The study suggests that mortalin is involved in pathways that regulate division capacities of cells in vivo.


Evaluation of risk scores derived from the health family tree program.
Family health history is an independent risk factor for certain diseases. The Health Family Tree (HFT) was developed and used to document and assess family health history from the families of high school students since 1980. While the risk algorithm of the HFT was initially validated, 20 years of use as a public health tool in the community provides an extremely large dataset for more rigorous validation. A retrospective cohort study was used with the events before the "cut-off" year as the baseline and the events after the "cut-off" year as the follow-up. Baseline data were used in the algorithm to calculate the Family History Score (FHS). Cox proportional hazards model was used to test the dose-response nature of the FHS for predicting incident events. An FHS >/=1 was determined to be a significant predictor for future development of diabetes, myocardial infarction, and early onset of myocardial infarction.


Canonical transient receptor potential channel subtype 3-mediated hair cell Ca(2+) entry regulates sound transduction and auditory neurotransmission.
The physiological significance of canonical transient receptor potential (TRPC) ion channels in sensory systems is rapidly emerging. Heterologous expression studies show that TRPC3 is a significant Ca(2+) entry pathway, with dual activation via G protein-coupled receptor (GPCR)-phospholipase C-diacylglycerol second messenger signaling, and through negative feedback, whereby a fall in cytosolic Ca(2+) releases Ca(2+) -calmodulin channel block. We hypothesised that the latter process contributes to cochlear hair cell cytosolic Ca(2+) homeostasis. Confocal microfluorimetry with the Ca(2+) indicator Fluo-4 acetoxymethylester showed that, when cytosolic Ca(2+) was depleted, Ca(2+) re-entry was significantly impaired in mature TRPC3(-/-) inner and outer hair cells. The impact of this disrupted Ca(2+) homeostasis on sound transduction was assessed with the use of distortion product otoacoustic emissions (DPOAEs), which constitute a direct measure of the outer hair cell transduction that underlies hearing sensitivity and frequency selectivity. TRPC3(-/-) mice showed significantly stronger DPOAE (2f1 - f2 ) growth functions than wild-type (WT) littermates within the frequency range of best hearing acuity. This translated to hyperacusis (decreased threshold) measured by the auditory brainstem response (ABR). TRPC3(-/-) and WT mice did not differ in the levels of temporary and permanent threshold shift arising from noise exposure, indicating that potential GPCR signaling via TRPC3 is not pronounced. Overall, these data suggest that the Ca(2+) set-point in the hair cell, and hence membrane conductance, is modulated by TRPC3s through their function as a negative feedback-regulated Ca(2+) entry pathway. This TPRC3-regulated Ca(2+) homeostasis shapes the sound transduction input-output function and auditory neurotransmission.


Achieving Stable Radiation Pressure Acceleration of Heavy Ions via Successive Electron Replenishment from Ionization of a High-Z Material Coating.
A method to achieve stable radiation pressure acceleration (RPA) of heavy ions from laser-irradiated ultrathin foils is proposed, where a high-Z material coating in front is used. The coated high-Z material, acting as a moving electron repository, continuously replenishes the accelerating heavy ion foil with comoving electrons in the light-sail acceleration stage due to its successive ionization under laser fields with Gaussian temporal profile. As a result, the detrimental effects such as foil deformation and electron loss induced by the Rayleigh-Taylor-like and other instabilities in RPA are significantly offset and suppressed so that stable acceleration of heavy ions are maintained. Particle-in-cell simulations show that a monoenergetic Al^{13+} beam with peak energy 3.8 GeV and particle number 10^{10} (charge >20 nC) can be obtained at intensity 10^{22} W/cm^{2}.


Understanding Obesity-Related High Output Heart Failure and Its Implications.
Morbid obesity remains most common cause of high output failure. The prevalence of the obesity is growing when two-thirds of American adults already are overweight or obese. Obesity is the risk factor for heart disease and eventually leads to heart failure. High output heart failure is common in obese patients and is characterized by high cardiac output, decreased systemic vascular resistance, and increased oxygen consumption. It often occurs in patients with chronic severe anemia, hyperthyroidism, pregnancy, arterial-venous fistulas, and liver disease. However, the pathogenesis of obesity-related high output heart failure is not fully understood. The clinical management of obesity-related high output heart failure follows conventional heart failure regimens due to lack of specific clinical recommendations. This article reviews the possible pathophysiological mechanisms and causes that contribute to obesity-related high output heart failure. This review also focuses on the implications for clinical practice and future research involved with omics technologies to explore possible molecular pathways associated with obesity-related high output heart failure.


Lipopolysacharides from anaerobic gram-negative rods.
The chemical composition and antigenic specificity of the cell wall lipopolysaccharides of the two main groups of Bacteroidaceae, Fusobacterium and Bacteroides species, are reviewed. Cell wall lipopolysaccharides from Fusobacterium species contain 2-keto-3-deoxy-octonate and heptose, but lipopolysaccharides isolated from Bacteroides species do not.


[Characteristics of nitrogen and phosphorus retention in two different channel forms in a typical headwater stream in the suburb of Hefei City, China ].
To investigate the characteristics of ammonium and phosphorus retention in two typical channel forms, deep pool and winding ditch in headwater stream, four field tracer experiments were conducted in a first-order stream of Ershibu River in Hefei suburban, in which a solution of biologically active (NH4Cl and KH2PO4) and conservative (NaCl) tracers was released to the head of each reach at a constant rate. According to the data sets of tracer experiments, mechanisms of ammonium and phosphorus retention were interpreted by using OTIS model code, transient storage metrics and nutrient spiraling theory. Study results showed that: (1) The value of As in deep pool was larger than that in winding ditch, whereas its value of hydrological parameter α was lower by an order of magnitude than that of winding ditch; (2) The value of NH(4)+ -λ in main channel was higher by two to three orders of magnitude than that of NH(4)+ -λs,in transient storage zone in deep pool, but in winding ditch the two parameters were closer in terms of numerical size; (3) In deep pool, the value of NH+(4) -Vf was higher by an order of magnitude than that of SRP-Vf, in winding ditch, however, not only the two values of NH(4)+ -Vf and SRP-Vf were close to each other, but NH(4)+ -Sw was nearly equal to SRP-Sw in numerical size as well; (4) The value of NH(4)+ -U was larger by two to three orders of magnitude than that of SRP-U in deep pool, whereas in winding ditch NH(4)+ -U was just larger by one to two orders of magnitude than SRP-U in size; (5) In general, significant difference existed between deep pool and winding ditch in the effect on ammonium and phosphorus retention, and marked retention efficiency was observed for ammonium rather than SRP in deep pool.


Ectopic pregnancy treatment by combination therapy.
Detectability of early stages of ectopic pregnancies has increased due to improvements in ultrasonographic and biochemical techniques. Since the patients' future procreative plans must be taken into consideration when commencing treatment, the goal of this work was to compare the effects of treatment methods and their impact on fertility. The study included 91 patients treated surgically for ectopic pregnancy. The choice of treatment depended on patients' general condition, ultrasonographic evaluation and serum level of beta-hCG. A combination of laparoscopic and conservative systemic treatment was applied in 70% of cases. More rapid beta-hCG reduction was noted when laparoscopy and intra-oviductal injection of hyperosmolar glucose or methotrexate (MTX) were combined with intramuscular administration of MTX at a dose of 50 mg/m2. Follow-up examination of 66 patients revealed that the greatest number of spontaneous pregnancies (48%) resulted after this combination therapy. We conclude that this combination treatment is safe and provides satisfactory results in terms of future fertility.


Imparting Outstanding Dispersibility to Nanoscaled 2D COFs for Constructing Organic Solvent Forward Osmosis Membranes.
In the context of thin-film nanocomposite membranes with interlayer (TFNi), nanoparticles are deposited uniformly onto the support prior to the formation of the polyamide (PA) layer. The successful implementation of this approach relies on the ability of nanoparticles to meet strict requirements regarding their sizes, dispersibility, and compatibility. Nevertheless, the synthesis of covalent organic frameworks (COFs) that are well-dispersed, uniformly morphological, and exhibit improved affinity to the PA network, while preventing agglomeration, remains a significant challenge. In this work, a simple and efficient method is presented for the synthesis of well-dispersed, uniformly morphological, and amine-functionalized 2D imine-linked COFs regardless of the ligand composition, group type, or framework pore size, by utilizing a polyethyleneimine (PEI) shielded covalent self-assembly strategy. Subsequently, the as-prepared COFs are incorporated into TFNi for the recycling of pharmaceutical synthetic organic solvents. After optimization, the membrane exhibits a high rejection rate and a favorable solvent flux, making it a reliable method for efficient organic recovery and the concentration of active pharmaceutical ingredient (API) from the mother liquor through an organic solvent forward osmosis (OSFO) process. Notably, this study represents the first investigation of the impact of COF nanoparticles in TFNi on OSFO performance.


Untangling the Rhizosphere Bacterial Community Composition and Response of Soil Physiochemical Properties to Different Nitrogen Applications in Sugarcane Field.
Minimizing the use of chemical fertilizers and investigating an appropriate ecofriendly level of nitrogen fertilizer is the key to sustainable agriculture. Sugarcane is the main cash crop of China, especially in the Guangxi region. Information regarding the effect of different nitrogen levels on sugarcane rhizosphere microbiota is still limited. In this study, we evaluated the effect of four different levels of nitrogen fertilizers on rhizosphere bacterial composition using high throughput sequencing, along with soil physiochemical properties, sugarcane agronomic and yield performance. The four treatment combinations were CK (no fertilizers), L (Low, 100 kg ha-1), M (Medium, 150 kg ha-1), and H (High, 200 kg ha-1). The results showed that M nitrogen application significantly altered the rhizosphere bacterial community, soil properties, and sugarcane yield. The richness and evenness of the bacterial community were higher in M treatment than CK. In M treatment important bacterial phyla Acidobacteria and Proteobacteria increased by 47 and 71%, respectively; and at genus level, Acidothermus and Bradyrhizobium increased by 77.2 and 30.3%, respectively, compared to CK. Principal component analysis (PCA) and cluster analysis further confirmed the level of differences among the treatments. The PCA analysis explained 80% of the total variation among the treatments. Spearmen correlation heatmap showed that environmental factors such as pH, AP (available phosphorous), AK (available potassium), and SCAT (soil catalase) were the key factors impacting sugarcane rhizosphere microbiome composition. The H and L nitrogen application alter the bacterial community and sugarcane performance but the M nitrogen application appears to be ecofriendly, productive, and an appropriate nitrogen application rate that could be further used in the Guangxi region.


A simple method to improve the quality of diffusion-weighted magnetic resonance imaging with rapid histologic correlation in a murine model.
Diffusion-weighted magnetic resonance imaging (DW-MRI) has been used extensively in biomedical research. However, this technique has often suffered from distortion artifacts because of the magnetic field inhomogeneity surrounding the tissues. Histology is important for validating MRI interpretations, but correlating MRIs with tissue samples is challenging. Here we propose a method to improve DW-MRI and facilitate the matching between MRIs and tissue samples. A cryostat embedding medium, optimal cutting temperature (OCT) compound, was used to cover the examined target during the MRI studies. Frozen OCT compound could aid the examined target to be sectioned in parallel with the imaging plane. Phantom experiments demonstrated that embedding in OCT compound improved the magnetic field inhomogeneity while maintaining the apparent diffusion coefficient. Animal experiments revealed significantly reduced distortions in DW images in both the axial and coronal planes. The in vivo MRIs were easily matched with histologic specimens in a slice-to-slice fashion to examine the corresponding tissue microenvironment. This simple method might improve the quality of DW-MRI and provide histologic information for MRI to serve as an image biomarker.


Early endovascular management of oculomotor nerve palsy associated with posterior communicating artery aneurysms.
Palsy of the third cranial nerve (oculomotor nerve, CNIII) is a well-known clinical presentation of posterior communicating artery (P-com) aneurysm. We report a series of 11 patients with partial or complete third nerve palsy secondary to P-com aneurysm. All were treated with endovascular embolization within seven days of symptom onset. Third nerve palsy symptoms resolved in 7/11 (64%), improved in 2/11 (18%) and did not change in 2/11 (18%) patients.


Co-occurence of filamentation defects and impaired biofilms in Candida albicans protein kinase mutants.
Pathogenicity of Candida albicans is linked with its developmental stages, notably the capacity switch from yeast-like to hyphal growth, and to form biofilms on surfaces. To better understand the cellular processes involved in C. albicans development, a collection of 63 C. albicans protein kinase mutants was screened for biofilm formation in a microtitre plate assay. Thirty-eight mutants displayed some degree of biofilm impairment, with 20 categorised as poor biofilm formers. All the poor biofilm formers were also defective in the switch from yeast to hyphae, establishing it as a primary defect. Five genes, VPS15, IME2, PKH3, PGA43 and CEX1, encode proteins not previously reported to influence hyphal development or biofilm formation. Network analysis established that individual components of some processes, most interestingly MAP kinase pathways, are not required for biofilm formation, most likely indicating functional redundancy. Mutants were also screened for their response to bacterial supernatants and it was found that Pseudomonas aeruginosa supernatants inhibited biofilm formation in all mutants, regardless of the presence of homoserine lactones (HSLs). In contrast, Candida morphology was only affected by supernatant containing HSLs. This confirms the distinct HSL-dependent inhibition of filamentation and the HSL-independent impairment of biofilm development by P. aeruginosa.


Intensive insulin therapy in insulin dependent diabetes and combination therapy.
Intensive insulin therapy (IIT) and combination therapy using sulfonylurea and insulin are two insulin regimens being used more frequently to improve glycemic control. For those patients with insulin-dependent diabetes, IIT or multiple daily injection therapy mimics normal pancreatic function by its timing of insulin delivery. The improvement in glycemic control carries with it the risk of a two- to threefold increase in episodes of hypoglycemia. For those with non-insulin-dependent diabetes, combination therapy attempts to provide a bridge between maximal dose oral hypoglycemic agents and aggressive insulin therapy. Although this therapy remains controversial, it has proved useful in select patient groups. This article discusses the rationale for IIT, and its implementation. Variables that affect IIT are discussed. The combination therapy section provides guidelines for patient selection and insulin protocols for evening insulin administration. The health care provider is familiarized with these alternative therapies and their successful applications.


[Outcomes of preoperative chemoradiotherapy for rectal cancer with invasion to the adjacent organs].
We reviewed the clinical records of 13 patients who received preoperative chemoradiotherapy(CRT)to evaluate the clinical effectiveness of CRT for T4b rectal cancer. Preoperative radiotherapy consisted of 40-50 Gy delivered in fractions of 1.8-2.0 Gy per day, 5 days per week. Treatment with intravenous 5-fluorouracil, oral tegafur-uracil(UFT-E)with l-leucovorin, oral S-1, or intravenous irinotecan(CPT-11)with oral S-1 was administered during radiotherapy. At 63 days after CRT, 1 patient died because of pelvic abscess. Complete response(CR)or partial response(PR)was observed in 7 patients, 1 month after CRT. Curative surgery was performed in 9 patients. Among 10 patients who underwent surgery 70 days after CRT, 5 who showed PR 1 month after CRT underwent curative surgery; both urinary and anal function were preserved in 4 of these patients. Histological invasion to the adjacent organs was not observed in 6 patients, and 1 patient achieved histological CR. Of the 9 patients who underwent curative surgery, recurrence was observed in 2; however, the other patients survived without recurrence. Preoperative CRT was considered to be effective in improving the resection rate and prognosis in patients with T4b rectal cancer. However, careful attention should be paid to the severe toxicities associated with CRT, such as pelvic abscess.


Full protein flexibility is essential for proper hot-spot mapping.
A traditional technique for structure-based drug design (SBDD) is mapping of protein surfaces with probe molecules to identify "hot spots" where key functional groups can best complement the receptor. Common methods, such as minimization of probes or calculation of grids, use a fixed protein structure in the gas phase, ignoring both protein flexibility and proper competition between the probes and water. As a result, the potential surface is quite rugged, and many spurious local minima are identified. In this work, we compared rigid and fully flexible proteins in mixed-solvent molecular dynamics, which allows for flexibility and full solvent effects. We were surprised to find that the large number of local minima are still found when a protein's conformational sampling is restricted; the dynamic averaging of probes and competition with water do not smooth the potential surface as one might expect. Only when a protein is allowed to be fully flexible in the simulation are the proper minima located and the spurious ones eliminated. Our results indicate that inclusion of full protein flexibility is critical to accurate hot-spot mapping for SBDD.


A Method for Evaluating Insecticide Efficacy against Bed Bug, Cimex lectularius, Eggs and First Instars.
Standard toxicity evaluations of insecticides against insect pests are primarily conducted on adult insects. Evaluations are based on a dose-response or concentration-response curve, where mortality increases as the dose or concentration of an insecticide is increased. Standard lethal concentration (LC50) and lethal dose (LD50) tests that result in 50% mortality of a test population can be challenging for evaluating toxicity of insecticides against non-adult insect life stages, such as eggs and early instar or nymphal stages. However, this information is essential for understanding insecticide efficacy in all bed bug life stages, which affects control and treatment efforts. This protocol uses a standard dipping bioassay modified for bed bug eggs and a contact insecticidal assay for treating nymphal first instars. These assays produce a concentration-response curve to further quantify LC50 values for insecticide evaluations.


[Clinical significance of cytogenetic monitoring in chronic myeloid leukemia].
Objective: To analyze the association of cytogenetic abnormalities with the prognosis of chronic myeloid leukemia (CML) patients in tyrosine kinase inhibitors (TKI) era. Methods: Karyotype analysis of chromosome G-banding was carried out in 387 newly diagnosed CML patients by short-term culture of bone marrow cells. The correlation of cytogenetic abnormalities and CML progression was explored in combination with ABL tyrosine point mutations. Result: Of 387 patients with positive BCR-ABL fusion gene assayed by fluorescence in situ hybridization (FISH) technique, 94.1% (364/387) patients were Ph positive and 5.9% (23/387) Ph negative; 320 patients (87.9%) had a translocation t (9;22) (q34;q11) and 5 (1.4%) a variant translocation t (v;22) . Additional cytogenetic aberrations (ACA) at diagnosis were found in 10.7% (39/387) Ph(+) patients, major route ACA in 22 (56.4%) cases and minor route ACA in 15 (38.5%) cases and 2 patients (5.1%) lacked the Y chromosome (-Y) ; 23.4% (71/303) patients occurred ACA during TKI treatment and the most frequent abnormalities were abnormal chromosome numbersd, which were likely associated with high proportion of disease progression (χ(2)=168.21, P<0.001) and ABL tyrosine point mutations (χ(2)=29.04, P<0.001) . Newly diagnosed CML-CP patients with t (9;22) (q34;q11) had a longer event-free survival (EFS) and disease-free survival (DFS) rates than that of patients with ACA (P=0.037; P=0.003) , while the overall survival (OS) had no significant differences (P=0.209) . As for CML-CP patients that occurred ACA during TKI therapy would have a marked low OS, EFS and DFS (all P<0.001) compared with no ACA occurred patients. Survival of advanced patients that occurred ACA were dramatically reduced. Conclusion: ACA often emerged during the disease progress in CML patients, regular and timely detection of chromosomes karyotype and ABL tyrosine point mutations during TKI treatment was important for therapeutic evaluation, progress and prognosis of CML.


Value-Based Payment Reform and the Medicare Access and Children's Health Insurance Program Reauthorization Act of 2015: A Primer for Plastic Surgeons.
In 2015, the U.S. Congress passed the Medicare Access and Children's Health Insurance Program Reauthorization Act, which effectively repealed the Centers for Medicare and Medicaid Services sustainable growth rate formula and established the Centers for Medicare and Medicaid Services Quality Payment Program. The Medicare Access and Children's Health Insurance Program Reauthorization Act represents an unparalleled acceleration toward value-based payment models and a departure from traditional volume-driven fee-for-service reimbursement. The Quality Payment Program includes two paths for provider participation: the Merit-Based Incentive Payment System and Advanced Alternative Payment Models. The Merit-Based Incentive Payment System pathway replaces existing quality reporting programs and adds several new measures to create a composite performance score for each provider (or provider group) that will be used to adjust reimbursed payment. The advanced alternative payment model pathway is available to providers who participate in qualifying Advanced Alternative Payment Models and is associated with an initial 5 percent payment incentive. The first performance period for the Merit-Based Incentive Payment System opens January 1, 2017, and closes on December 31, 2017, and is associated with payment adjustments in January of 2019. The Centers for Medicare and Medicaid Services estimates that the majority of providers will begin participation in 2017 through the Merit-Based Incentive Payment System pathway, but aims to have 50 percent of payments tied to quality or value through Advanced Alternative Payment Models by 2018. In this article, the authors describe key components of the Medicare Access and Children's Health Insurance Program Reauthorization Act to providers navigating through the Quality Payment Program and discuss how plastic surgeons may optimize their performance in this new value-based payment program.


Multiplex Genome Editing in Yeast by CRISPR/Cas9 - A Potent and Agile Tool to Reconstruct Complex Metabolic Pathways.
Numerous important pharmaceuticals and nutraceuticals originate from plant specialized metabolites, most of which are synthesized via complex biosynthetic pathways. The elucidation of these pathways is critical for the applicable uses of these compounds. Although the rapid progress of the omics technology has revolutionized the identification of candidate genes involved in these pathways, the functional characterization of these genes remains a major bottleneck. Baker's yeast (Saccharomyces cerevisiae) has been used as a microbial platform for characterizing newly discovered metabolic genes in plant specialized metabolism. Using yeast for the investigation of numerous plant enzymes is a streamlined process because of yeast's efficient transformation, limited endogenous specialized metabolism, partially sharing its primary metabolism with plants, and its capability of post-translational modification. Despite these advantages, reconstructing complex plant biosynthetic pathways in yeast can be time intensive. Since its discovery, CRISPR/Cas9 has greatly stimulated metabolic engineering in yeast. Yeast is a popular system for genome editing due to its efficient homology-directed repair mechanism, which allows precise integration of heterologous genes into its genome. One practical use of CRISPR/Cas9 in yeast is multiplex genome editing aimed at reconstructing complex metabolic pathways. This system has the capability of integrating multiple genes of interest in a single transformation, simplifying the reconstruction of complex pathways. As plant specialized metabolites usually have complex multigene biosynthetic pathways, the multiplex CRISPR/Cas9 system in yeast is suited well for functional genomics research in plant specialized metabolism. Here, we review the most advanced methods to achieve efficient multiplex CRISPR/Cas9 editing in yeast. We will also discuss how this powerful tool has been applied to benefit the study of plant specialized metabolism.


Mutations in CCDC11, which encodes a coiled-coil containing ciliary protein, causes situs inversus due to dysmotility of monocilia in the left-right organizer.
In vertebrates, establishment of left-right (LR) asymmetry is dependent on cilia-driven fluid flow within the LR organizer. Mutations in CCDC11 disrupt LR asymmetry in humans, but how the gene functions in LR patterning is presently unknown. We describe a patient with situs inversus totalis carrying homozygous loss-of-function mutations in CCDC11. We show that CCDC11 is an axonemal protein in respiratory cilia, but is largely dispensable for their structure and motility. To investigate the role of CCDC11 in LR development, we studied the zebrafish homolog of the gene. Like in human respiratory cilia, loss of Ccdc11 causes minor defects in the motility of zebrafish kidney cilia, although the protein localizes to their axonemes and base. By contrast, Ccdc11 localizes exclusively to the basal bodies of cilia within Kupffer's vesicle, the organ of laterality of teleost fishes, and within the spinal canal. Moreover, the rotational motion of the cilia in these tissues of ccdc11-deficient embryos was strongly impaired. Our findings demonstrate that CCDC11 has a conserved essential function in cilia of the vertebrate LR organizer. To the best of our knowledge, this is the first ciliary component, which has a differential localization and function in different kinds of motile cilia.


Colloidal synthesis of lead oxide nanocrystals for photovoltaics.
Lead oxide nanocrystals are synthesised by injecting oxygen gas into an air and moisture free complex of Pb oleylamine and oleic acid in octadecene. Using various characterization methods including fabrication and testing of photovoltaic devices we explore the material properties and photovoltaic application of lead oxide nanocrystal films.


Spin-Orbital Correlated Dynamics in the Spinel-Type Vanadium Oxide MnV_{2}O_{4}.
We investigate the magnetic dynamics in the spinel-type vanadium oxide MnV_{2}O_{4}. Inelastic neutron scattering around 10 meV and a Heisenberg model analysis have revealed that V^{3+} spin-wave modes exist at a lower-energy region than previously reported. The scattering around 20 meV cannot be reproduced with the spin-wave analysis. We propose that this scattering could originate from the spin-orbital coupled excitation. This scattering is most likely attributable to V^{3+} spin-wave modes, entangled with the orbital hybridization between t_{2g} orbitals.


Reproducibility of the analytab (API 20E) system.
The reproducibility of the Analytab (API 20E) system for identification of Enterobacteriaceae was evaluated with 110 clinical isolates. Each isolate was identified by two technologists at different times. Genus-species identification was 97.3% reproducible; however, only 55.5% of the strains gave identical reactions in all 20 of the API 20E biochemical tests on repeat testing. Of those strains which varied, 56% possessed only one variable biochemical test. The reproducibility for each biochemical test was calculated and ranged from 89 to 100%. A subset of 20 of the most variable strains was tested further under conditions of varying incubation time (15 and 22 h) and inoculum concentration (10(7), 10(5), and 10(3) colony-forming units per ml), and by having four technologists interpret the test results. The reproducibility for each biochemical test for these 20 variable strains ranged from 86 to 99%. Less variation in interpretation by technologists was seen at an incubation time of 22 h and an inoculum concentration of 10(7) colony-forming units per ml. Consideration of the reproducibility for each biochemical test can aid in determining the probability that two isolates suspected of being the same strain, but with API profiles which differ by one or more biochemical test results, are in fact the same strain. Variables such as inoculum size, incubation time, technologist interpretation, and strip variability affect the API test results and should be standardized to minimize their effects.


Nitrous oxide emission factors for urine and dung from sheep fed either fresh forage rape (Brassica napus L.) or fresh perennial ryegrass (Lolium perenne L.).
In New Zealand, agriculture is predominantly based on pastoral grazing systems and animal excreta deposited on soil during grazing have been identified as a major source of nitrous oxide (N2O) emissions. Forage brassicas (Brassica spp.) have been increasingly used to improve lamb performance. Compared with conventional forage perennial ryegrass (Lolium perenne L.), a common forage in New Zealand, forage brassicas have faster growth rates, higher dry matter production and higher nutritive value. The aim of this study was to determine the partitioning of dietary nitrogen (N) between urine and dung in the excreta from sheep fed forage brassica rape (B. napus subsp. oleifera L.) or ryegrass, and then to measure N2O emissions when the excreta from the two different feed sources were applied to a pasture soil. A sheep metabolism study was conducted to determine urine and dung-N outputs from sheep fed forage rape or ryegrass, and N partitioning between urine and dung. Urine and dung were collected and then used in a field plot experiment for measuring N2O emissions. The experimental site contained a perennial ryegrass/white clover pasture on a poorly drained silt-loam soil. The treatments included urine from sheep fed forage rape or ryegrass, dung from sheep fed forage rape or ryegrass, and a control without dung or urine applied. N2O emission measurements were carried out using a static chamber technique. For each excreta type, the total N2O emissions and emission factor (EF3; N2O-N emitted during the 3- or 8-month measurement period as a per cent of animal urine or dung-N applied, respectively) were calculated. Our results indicate that, in terms of per unit of N intake, a similar amount of N was excreted in urine from sheep fed either forage rape or ryegrass, but less dung N was excreted from sheep fed forage rape than ryegrass. The EF3 for urine from sheep fed forage rape was lower compared with urine from sheep fed ryegrass. This may have been because of plant secondary metabolites, such as glucosinolates in forage rape and their degradation products, are transferred to urine and affect soil N transformation processes. However, the difference in the EF3 for dung from sheep fed ryegrass and forage rape was not significant.


The Role of miR-126 in Critical Limb Ischemia Treatment Using Adipose-Derived Stem Cell Therapeutic Factor Concentrate and Extracellular Matrix Microparticles.
BACKGROUND Paracrine factors secreted by adipose-derived stem cells can be captured, fractionated, and concentrated to produce therapeutic factor concentrate (TFC). The present study examined whether TFC effects could be enhanced by combining TFC with a biological matrix to provide sustained release of factors in the target region. MATERIAL AND METHODS Unilateral hind limb ischemia was induced in rabbits. Ischemic limbs were injected with either placebo control, TFC, micronized small intestinal submucosa tissue (SIS), or TFC absorbed to SIS. Blood flow in both limbs was assessed with laser Doppler perfusion imaging. Tissues harvested at Day 48 were assessed immunohistochemically for vessel density; in situ hybridization and quantitative real-time PCR were employed to determine miR-126 expression. RESULTS LDP ratios were significantly elevated, compared to placebo control, on day 28 in all treatment groups (p=0.0816, p=0.0543, p=0.0639, for groups 2-4, respectively) and on day 36 in the TFC group (p=0.0866). This effect correlated with capillary density in the SIS and TFC+SIS groups (p=0.0093 and p=0.0054, respectively, compared to placebo). A correlation was observed between miR-126 levels and LDP levels at 48 days in SIS and TFC+SIS groups. CONCLUSIONS A single bolus administration of TFC and SIS had early, transient effects on reperfusion and promotion of ischemia repair. The effects were not additive. We also discovered that TFC modulated miR-126 levels that were expressed in cell types other than endothelial cells. These data suggested that TFC, alone or in combination with SIS, may be a potent therapy for patients with CLI that are at risk of amputation.


Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors.
The forkhead transcription factor FoxM1 has been reported to regulate, variously, proliferation and/or spindle formation during the G2/M transition of the cell cycle. Here we define specific functions of FoxM1 during brain development by the investigation of FoxM1 loss-of-function mutations in the context of Sonic hedgehog (Shh)-induced neuroproliferation in cerebellar granule neuron precursors (CGNP). We show that FoxM1 is expressed in the cerebellar anlagen as well as in postnatal proliferating CGNP and that it is upregulated in response to activated Shh signaling. To determine the requirements for FoxM1 function, we used transgenic mice carrying conventional null alleles or conditionally targeted alleles in conjunction with specific Cre recombinase expression in CGNP or early neural precursors driven by Math1 or Nestin enhancers. Although the overall cerebellar morphology was grossly normal, we observed that the entry into mitosis was postponed both in vivo and in Shh-treated CGNP cultures. Cell cycle analysis and immunohistochemistry with antibodies against phosphorylated histone H3 indicated a significant delay in the G2/M transition. Consistent with this, FoxM1-deficient CGNP showed decreased levels of the cyclin B1 and Cdc25b proteins. Furthermore, the loss of FoxM1 resulted in spindle defects and centrosome amplification. These findings indicate that the functions of FoxM1 in Shh-induced neuroproliferation are restricted to the regulation of the G2/M transition in CGNP, most probably through transcriptional effects on target genes such as those coding for B-type cyclins.


Applications of artificial intelligence in COVID-19 pandemic: A comprehensive review.
During the current global public health emergency caused by novel coronavirus disease 19 (COVID-19), researchers and medical experts started working day and night to search for new technologies to mitigate the COVID-19 pandemic. Recent studies have shown that artificial intelligence (AI) has been successfully employed in the health sector for various healthcare procedures. This study comprehensively reviewed the research and development on state-of-the-art applications of artificial intelligence for combating the COVID-19 pandemic. In the process of literature retrieval, the relevant literature from citation databases including ScienceDirect, Google Scholar, and Preprints from arXiv, medRxiv, and bioRxiv was selected. Recent advances in the field of AI-based technologies are critically reviewed and summarized. Various challenges associated with the use of these technologies are highlighted and based on updated studies and critical analysis, research gaps and future recommendations are identified and discussed. The comparison between various machine learning (ML) and deep learning (DL) methods, the dominant AI-based technique, mostly used ML and DL methods for COVID-19 detection, diagnosis, screening, classification, drug repurposing, prediction, and forecasting, and insights about where the current research is heading are highlighted. Recent research and development in the field of artificial intelligence has greatly improved the COVID-19 screening, diagnostics, and prediction and results in better scale-up, timely response, most reliable, and efficient outcomes, and sometimes outperforms humans in certain healthcare tasks. This review article will help researchers, healthcare institutes and organizations, government officials, and policymakers with new insights into how AI can control the COVID-19 pandemic and drive more research and studies for mitigating the COVID-19 outbreak.


Anterior Chamber Depth Change Following Cataract Surgery in Pseudoexfoliation Syndrome; a Preliminary Study.
To assess the pseudophakic anterior chamber depth (PP-ACD) or effective lens position (ELP) change after cataract surgery in patients with pseudoexfoliation syndrome (PEX). Consecutive eyes with PEX and cataract underwent standard phacoemulsification and were implanted with single-piece acrylic posterior chamber intraocular lenses (IOLs). Eyes with severe PEX and with axial length (AL) greater than 24 mm or less than 22 mm were not included. Eyes with capsular complication or unstable bags that needed capsular tension ring insertion were excluded. The SRK-II formula was applied to calculate IOL power for postoperative emmetropia. PP-ACD or ELP was measured using anterior segment optical coherence tomography. Data obtained at one and six months post operation were evaluated during analysis. Twenty-six eyes of 26 subjects (mean age: 72 years; range: 60-84 years) were studied. PP-ACD was deepened (mean change: 0.08 mm) and a concurrent hyperopic shift (0.3 D) was observed postoperatively between month 1 and month 6 (P values ≤0.002). PP-ACD and postoperative refraction changes were correlated with age and AL (P values < 0.025), respectively. Increased hyperopic shift and PP-ACD deepening in eyes with posterior capsule opacification (PCO) was noted postoperatively at six months, but the difference was not statistically significant (P values = 0.15 and 0.2, respectively). After cataract surgery in eyes with PEX syndrome, a significant backward movement of the IOL occurs postoperatively in the first six months, which is associated with a concurrent small hyperopic shift.


Ocular torsion and vertical misalignment.
This article considers vertical misalignment and torsion of the eyes that arise from disorders of vestibulo-ocular reflex (VOR) pathways. Infarction of the nodulus is one of the causes of skew deviation, a vertical strabismus accompanied by torsion of the eyes and tilt of the subjective visual vertical. Vertical components of childhood strabismus may arise from dysgenesis of vestibular projections in the brainstem. If vertical misalignment decreases greatly in the supine position compared to the erect poison one may conclude that skew deviation rather than a fourth nerve palsy is responsible for the strabismus. Impairment of the horizontal translational VOR in patients with skew has provided further evidence that imbalance in the otolith-ocular pathway, caused by disruption of projections from the utricle to motor neurons, is the mechanism of skew deviation. Bedside examination showing a normal horizontal head impulse test, direction-changing nystagmus in eccentric gaze, or skew deviation is sensitive and specific for stroke. Skew deviation can identify stroke when an abnormal head impulse test falsely suggests a peripheral vestiblular lesion. Reduction in gain and failure of adaptation to vision of the torsional angular VOR in head positions away from the erect signify fundamental differences in the central organization of convergence of semicircular canal and otolith signals, when compared to the horizontal and vertical angular VORs. The effects of head position and of lesions of the nodulus are assuming increasing importance in analysis and differential diagnosis of vertical misalignment and torsion of the eyes.


History of child maltreatment and excessive dietary and screen time behaviors in young adults: Results from a nationally representative study.
Child maltreatment is common and has been associated with substance use addictions, yet few studies have examined associations with potentially addictive dietary and screen time behaviors. The goal of this study was to assess associations between retrospectively self-reported child maltreatment (sexual abuse, physical abuse, emotional abuse, and neglect) and excessive self-reported dietary (sugar sweetened beverage and fast food consumption) and screen time behaviors (television/video watching and leisure time computer use) in early adulthood, overall and by sex and race/ethnicity. Associations were examined using data from 10,813 participants 24-32 years old from the National Longitudinal Study of Adolescent to Adult Health. We used predicted marginal proportions accounting for the complex sample design to obtain prevalence ratios (PRs) and adjusted for demographic characteristics and physical activity. In females, exposure to poly-maltreatment (2+ types of child maltreatment) was associated with excessive sugar sweetened beverage consumption, television/video watching, and leisure time computer use; in males, exposure to poly-maltreatment was associated with excessive sugar sweetened beverage consumption, television/video watching, and fast food consumption. Some associations were particularly strong in racial/ethnic minorities, especially Latina females (poly-maltreatment-sugar sweetened beverage association: aPR = 6.14, 95% CI:2.12, 17.75; poly-maltreatment-computer use association: aPR = 3.08, 95% CI:1.44, 6.58). These findings show that child maltreatment is associated with excessive dietary and screen time behaviors into adulthood, and these associations are present in racial/ethnic groups at high risk of cardiometabolic disease. Extension of an addiction paradigm to include dietary and screen time behaviors may inform health risks and disease prevention efforts in child maltreatment survivors.


Short night-time sleep duration is associated with thyroid nodules: A community-based survey from Guangzhou, China.
Sleep plays a critical role in maintaining human health. This study aimed to explore the association between sleep status and thyroid nodules. A total of 2414 individuals aged 18 or older with euthyroidism were enrolled in this community-based survey. Sleep status was self-reported. Thyroid ultrasonography was performed to measure nodules. Multiple logistic analyses were applied to adjust for confounding factors. The percentages of thyroid nodules among individuals who slept <5 hours, 5-8 hours, and >8 hours per night were 57.79% (115/199), 44.19% (833/1885) and 42.73% (141/330), respectively (p = 0.001). Individuals who slept <5 hours per night had a significantly higher percentage of thyroid nodules than those who slept 5-8 hours per night (57.79% vs. 44.19%, p = 0.001) or >8 hours per night (57.79% vs. 42.73%, P < 0.001). However, no similar result was shown between individuals who slept >8 hours and 5-8 hours per night (42.73% vs. 44.19%, p = 0.621). Multiple logistic analysis showed that a sleep duration of <5 hours per night was significantly associated with thyroid nodules (odds ratio (OR) 1.643, 95% confidence interval (CI) 1.084-2.490, p = 0.019) when compared to a sleep duration of >8 hours per night. However, a sleep duration of <5 hours per night was not associated with thyroid nodules compared to a sleep duration of 5-8 hours (OR 1.294, 95% CI 0.918-1.824, p = 0.141). Similarly, no significant differences were seen among sleep duration per day, time of falling asleep, habit of daytime napping or thyroid nodules in multiple logistic analyses (all p > 0.05). Short nighttime sleep duration was associated with thyroid nodules in our community-based population. Screening for thyroid nodules among these individuals is recommended.