Analysis of the Relationship between the Location of the Anterior Ethmoid Artery and Keros Classification.
Objective We sought to identify a relationship between skull base height and anterior ethmoid artery (AEA) anatomy. Study Design Retrospective radiologic chart review. Setting University of Arkansas for Medical Sciences. Subjects Patients seen in a tertiary rhinology clinic between September 2014 and October 2015. Methods Review of 101 maxillofacial computed tomography scans with institutional review board approval. Skull base height and AEA locations were measured on each side. Prevalence of the AEA outside of the skull base and distance of the AEA from skull base were calculated and compared with Keros classification using χ2 testing. Comparisons of skull base height between sexes and age and distance between skull base and the AEA among Keros 2 and Keros 3 patients were made using an unpaired, 2-tailed t test. Results The AEA was located below the skull base in 25.7% of cases and more often in Keros type 3 (55%) than in Keros type 2 (29.5%) or Keros type 1 (0%) ( P < .05). Male patients were significantly more likely to have a greater average skull base height (5.25 vs 4.28 mm) and to have AEAs below the skull base (38.4% vs 14.8%). In addition, the distance of the AEA from the skull base was significantly higher in Keros type 3 patients compared with Keros type 2 patients (4.55 vs 3.42 mm, P = .001). Conclusions Variations in the AEA pathway occur more in male patients and those with higher Keros classifications. The distance between the variant AEA and the skull base increases with higher Keros classification. Keros classification can yield insight to the location of the AEA.


Totally extraperitoneal repair of obturator hernia.
One distinct advantage of the 1aparoscopic inguinal hernia repair is the opportunity for clear visualization of the direct, indirect, femoral, and obturator spaces. The surgeon should routinely inspect all of them. Obturator hernia accounts for as few as 0.073% of all hernias, but the mortality rate when it is acutely incarcerated can be as high as 70%. There is only one previous report of a totally extraperitoneal repair for obturator hernia. Five such procedures are described. A retrospective review was undertaken to evaluate one surgeon's experience with the totally extraperitoneal repair of obturator hernia over a 4-year period. Four of five cases were completed, and the remaining case was converted to an open procedure. Three hernias were on the right side, and two on the left. One patient presented with an acutely incarcerated obturator hernia and underwent a small bowel resection for strangulated bowel within the obturator space. The other four hernias were found during totally extraperitoneal repair, and the patients were discharged home several hours later. There was one complication, a midline wound infection in the patient with strangulated bowel. It was treated with dressing changes. There were no other complications, and during a follow-up period of 3 to 48 months, there was no recurrence. The laparoscopic totally extraperitoneal approach allows inspection and repair of direct, indirect, femoral, and obturator hernias. This study found this procedure to be feasible, safe, and highly effective for the diagnosis and repair of obturator hernias.


Hormonal stimulation of eucaryotic cell ADP-ribosylation.
The effect of thyrotropin (TSH) on the ADP-ribosylation of endogenous thyroid cell acceptor proteins was examined. Cells were "permeabilized" at 4 degrees C in hypotonic medium and then exposed to [(32)P]- or [(3)H-adenine]NAD(+). The net incorporation of labeled ADP-ribose was measured by trichloroacetic acid precipitation. TSH (100 mU/ml) enhanced ADP-ribosylation with a maximum effect after 30-60 min in the majority of experiments. TSH stimulation was observed even when the incubation contained 1,000-fold more exogenous NAD(+) than the amount of NAD(+) contributed by the permeabilized cells, indicating an effect on enzymatic activity rather than an alteration in NAD(+) pool size or specific activity. No incorporation of radioactivity from labeled NAD(+) was observed in cells not rendered permeable to NAD(+) by hypotonic shock. TSH did not increase the rate of disappearance of trichloroacetic-precipitable radioactivity and did not contain intrinsic NAD(+) glycohydrolase activity. Alkali and snake venom phosphodiesterase, but not ribonuclease or deoxyribonuclease digestion of trichloroacetic acid precipitable thyroid cell radioactivity, revealed primarily 5'-AMP, consistent with an effect of TSH on mono-ADP ribosylation. Nicotinamide and thymidine (50 mM) inhibited both basal and TSH-stimulated ADP-ribosylation of thyroid cell protein. Dibutyryl cyclic (c)AMP (0.1 mM) inhibited endogenous ADP-ribosylation by approximately 35% but had no effect at lower concentrations. 0.5 mM isobutylmethylxanthine inhibited this reaction by approximately 60%. We suggest that TSH enhances thyroid cell ADP-ribosylation by a mechanism independent of cAMP as a second messenger, and that ADP-ribosylation plays a role in the expression of TSH.


Eukaryotic aldehyde dehydrogenase (ALDH) genes: human polymorphisms, and recommended nomenclature based on divergent evolution and chromosomal mapping.
As currently being performed with an increasing number of superfamilies, a standardized gene nomenclature system is proposed here, based on divergent evolution, using multiple alignment analysis of all 86 eukaryotic aldehyde dehydrogenase (ALDH) amino-acid sequences known at this time. The ALDHs represent a superfamily of NAD(P)(+)-dependent enzymes having similar primary structures that oxidize a wide spectrum of endogenous and exogenous aliphatic and aromatic aldehydes. To date, a total of 54 animal, 15 plant, 14 yeast, and three fungal ALDH genes or cDNAs have been sequenced. These ALDHs can be divided into a total of 18 families (comprising 37 subfamilies), and all nonhuman ALDH genes are named here after the established human ALDH genes, when possible. An ALDH protein from one gene family is defined as having approximately < or = 40% amino-acid identity to that from another family. Two members of the same subfamily exhibit approximately > or = 60% amino-acid identity and are expected to be located at the same subchromosomal site. For naming each gene, it is proposed that the root symbol 'ALDH' denoting 'aldehyde dehydrogenase' be followed by an Arabic number representing the family and, when needed, a letter designating the subfamily and an Arabic number denoting the individual gene within the subfamily; all letters are capitalized in all mammals except mouse and fruit fly, e.g. 'human ALDH3A1 (mouse, Drosophila Aldh3a1).' It is suggested that the Human Gene Nomenclature Guidelines (http://++www.gene.ucl.ac.uk/nomenclature/guidelines.h tml) be used for all species other than mouse and Drosophila. Following these guidelines, the gene is italicized, whereas the corresponding cDNA, mRNA, protein or enzyme activity is written with upper-case letters and without italics, e.g. 'human, mouse or Drosophila ALDH3A1 cDNA, mRNA, or activity'. If an orthologous gene between species cannot be identified with certainty, sequential naming of these genes will be carried out in chronological order as they are reported to us. In addition, 20 human ALDH variant alleles that have been reported to date are listed herein and are recommended to be given numbers (or a number plus a capital letter) following an asterisk (e.g. 'ALDH3A2*2, ALDH2*4C'). It is anticipated that this eukaryotic ALDH gene nomenclature system will be extended to include bacterial genes within the next 2 years and that this nomenclature system will require updating on a regular basis; an ALDH Web site has been established for this purpose (http://++www.uchsc.edu/sp./sp./alcdbase/a ldhcov.html) and will serve as a medium for interaction amongst colleagues in this field.


The training value of a low-fidelity cervical biopsy workshop.
Cervical biopsy increases diagnostic yield compared with cytology and reduces time between presentation with and diagnosis of cervical cancer. Procedural training however needs to evolve in line with legislated working time restrictions and patient safety concerns. This makes gynecologic procedures ideal for simulation training. To date, no studies have looked at the use of low-fidelity simulation models to teach cervical punch biopsy. A cervical punch biopsy model was created using home and departmental waste products. The simulation model was tested by expert colposcopists and used during a gynecology trainee cervical study day. Twenty-one trainees attended a lecture that showed photographs of normal and abnormal cervices and a workshop where colposcopists demonstrated the technique before direct hands-on training with the simulator. Participants were asked to complete a survey, using a 5-point Likert scale, outlining the educational value of the workshop. Five low-fidelity cervical biopsy simulation models were created, these cost nothing, took an hour to make, and were easily transported. Of the different "cervix" materials tested, sponge provided the most realistic traction and the least fragmented biopsies (3-5 mm). Eighteen trainees completed the survey of whom all strongly agreed that learning was enhanced compared with didactics alone. The mean score for the value of the simulation in preparing trainees to perform future cervical biopsies was 4.7 (SD = 0.42) (95% confidence interval, 4.49-4.90). Our low-fidelity cervical biopsy models are easy to make, portable, and low cost. Trainees have reported the significant educational value of this simulation model in teaching an outpatient gynecologic/colposcopy procedure in a nonclinical environment.


Amphotericin B alters the affinity and functional activity of the oligopeptide chemotactic factor receptor on human polymorphonuclear leukocytes.
Leukocyte chemotaxis is initiated by the binding of chemotactic factors to specific, high-affinity receptors. Amphotericin B, a polyene antibiotic that binds to membrane cholesterol, inhibits human neutrophil (PMN) chemotaxis. We examined the effects of this drug on PMN functions mediated by the oligopeptide chemotactic factor receptor. The antibiotic irreversibly inhibited chemotaxis and depressed the binding of the radiolabeled chemoattractant, fMet-Leu-[3H]Phe, to its receptor without affecting the receptor's specificity. The drug lowered the binding affinity of the receptor by up to fivefold and slightly increased its number. Doses of amphotericin B that depressed receptor affinity and inhibited chemotaxis did not diminish lysosomal enzyme secretion or superoxide anion production. Nystatin, a less potent polyene antibiotic, also diminished chemotactic factor binding, but to a lesser degree than amphotericin B did. A chemically unrelated antifungal agent had no effect on either binding or chemotaxis. Thus, pharmacologic manipulation can alter the affinity of the chemotactic factor receptor on human PMN; this alteration is associated with a change in receptor function. The data suggest that receptor affinity regulates or at least reflects its functional state, and that the transduction mechanisms for various biologic responses mediated by the chemoattractant receptor are heterogeneous. By pharmacologic alterations of receptor affinity, one may be able to modulate specific biologic responses elicited by chemoattractant receptor-ligand interactions.


Mucocutaneous manifestations and nail changes in patients with end-stage renal disease on hemodialysis.
Mucocutaneous manifestations are common among patients on hemodialysis (HD). This study was undertaken to determine the prevalence of mucocutaneous manifestations in patients with end-stage renal disease (ESRD) who are on HD. In this cross-sectional, descriptive and analytic study conducted in 2009, 100 patients on HD at the Five Azar Hospital in Gorgan city were randomly selected. All the patients underwent detailed examination by a dermatologist to look for lesions in the skin, hair, nail and mucous membranes; if felt necessary, biopsy was obtained from the lesions. The findings were statistically analyzed using SPSS-13 software. For evaluation of normality of distribution, Kolmogorov-Smirnov was used, for quantitative variables Mann-Whitney and T-test (abnormal distribution) were used and for qualitative variables, Chi-2 and Fisher were used. In this study, P-value less than 0.05 was considered significant. Fifty-one males and 49 females were enrolled. The mean age was 49 ± 12 years. Diabetes was the most common cause of ESRD. In 95% of the patients, at least one mucocutaneous manifestation was present. Xerosis (78.3%) was the most common lesion, followed by pruritus (39.1%), lentigo (34.8%), skin discoloration (32.6%), leukonychia (32%) and thinning of the nail bed (24%). Xerosis, scaling, lentigo, folliculitis, idiopathic guttate hypopigmentation, leukonychia and half and half nail were associated with age. A significant relationship was seen between duration on dialysis and skin discoloration and leukonychia. Clubbing had a significant association with calcium-phosphorus product (Ca × P). There was a significant association between serum ferritin level and pruritus and tinea versicolor lesions. Our study shows that mucocutaneous manifestations are common among patients with ESRD. Identification of these manifestations and their association with causative factors are useful for preventing the lesions.


[Peculiarities of the development and clinical course of myocardial infarction depending on solar activity].
Analysis of 214,908 calls for ambulance demonstrated a significant (p = 0.95) rise in the frequency of acute myocardial infanction (AMI) in men in a year of low solar activity (LSA) and in women during a year with high solar activity (HSA). The increased incidence of sudden death, clinical death, cardiogenic shock, and pulmonary oedema was associated with HSA. The largest number of calls for AMI patients was recorded between 9.00 and 12.00, the lowest from 3.00 to 6.00. The frequency of AMI in the daytime was higher than at night. This difference was also apparent in "astronomic" seasons and half years with low and high solar activity. The incidence of AMI was highest during "astronomic" autumn and lowered in winter time. It was elevated in December of the LSA year and in May of the HSA year, in Mondays of HSA and Thursdays of LSA years. The minimal number of AMI episodes was recorded in weekends. Short daylight period and low air temperature combined with changes of atmospheric pressure and relative humidity during the cold period of the LSA year associated with a significant rise in the incidence of AIM. The overall frequency of AMI significantly increased during magnetic storms compared with the preceding days or immediately after them at both HSA and LSA. Mean daily frequency of AMI significantly increased within 24 hours before a magnetic storm only in the HAS year.


Comparison of TG-43 dosimetric parameters of brachytherapy sources obtained by three different versions of MCNP codes.
Monte Carlo simulations are widely used for calculation of the dosimetric parameters of brachytherapy sources. MCNP4C2, MCNP5, MCNPX, EGS4, EGSnrc, PTRAN, and GEANT4 are among the most commonly used codes in this field. Each of these codes utilizes a cross-sectional library for the purpose of simulating different elements and materials with complex chemical compositions. The accuracies of the final outcomes of these simulations are very sensitive to the accuracies of the cross-sectional libraries. Several investigators have shown that inaccuracies of some of the cross section files have led to errors in 125I and 103Pd parameters. The purpose of this study is to compare the dosimetric parameters of sample brachytherapy sources, calculated with three different versions of the MCNP code - MCNP4C, MCNP5, and MCNPX. In these simulations for each source type, the source and phantom geometries, as well as the number of the photons, were kept identical, thus eliminating the possible uncertainties. The results of these investigations indicate that for low-energy sources such as 125I and 103Pd there are discrepancies in gL(r) values. Discrepancies up to 21.7% and 28% are observed between MCNP4C and other codes at a distance of 6 cm for 103Pd and 10 cm for 125I from the source, respectively. However, for higher energy sources, the discrepancies in gL(r) values are less than 1.1% for 192Ir and less than 1.2% for 137Cs between the three codes.


Yin Yang 1 promotes hepatic steatosis through repression of farnesoid X receptor in obese mice.
Non-alcoholic fatty liver disease (NAFLD) is characterised by accumulation of excessive triglycerides in the liver. Obesity is usually associated with NAFLD through an unknown mechanism. To investigate the roles of Yin Yang 1 (YY1) in the progression of obesity-associated hepatosteatosis. Expression levels of hepatic YY1 were identified by microarray analysis in high-fat-diet (HFD)-induced obese mice. Liver triglyceride metabolism was analysed in mice with YY1 overexpression and suppression. YY1 expression was markedly upregulated in HFD-induced obese mice and NAFLD patients. Overexpression of YY1 in healthy mice promoted hepatosteatosis under high-fat dietary conditions, whereas liver-specific ablation of YY1 using adenoviral shRNA ameliorated triglyceride accumulation in obese mice. At the molecular level, YY1 suppressed farnesoid X receptor (FXR) expression through binding to the YY1 responsive element at intron 1 of the FXR gene. These findings indicate that YY1 plays a crucial role in obesity-associated hepatosteatosis, through repression of FXR expression.


Operationalizing blue carbon principles in France: Methodological developments for Posidonia oceanica seagrass meadows and institutionalization.
Conservation of ecosystems is an important tool for climate change mitigation. Seagrasses, mangroves, saltmarshes and other marine ecosystems have particularly high capacities to sequester and store organic carbon (blue carbon), and are being impacted by human activities. Calls have been made to mainstream blue carbon into policies, including carbon markets. Building on the scientific literature and the French voluntary carbon standard, the 'Label Bas-Carbone', we develop the first method for the conservation of Posidonia oceanica seagrasses using carbon finance. This methodology assesses the emission reduction potential of projects that reduce physical impacts from boating and anchoring. We show how this methodology was institutionalized thanks to a tiered approach on key parameters including carbon stocks, degradation rates, and decomposition rates. We discuss future needs regarding (i) how to strengthen the robustness of the method, and (ii) the expansion of the method to restoration of seagrasses and to other blue carbon ecosystems.


Castleman's disease imitating adrenal mass in the retroperitoneal area.
Castleman's disease (CD) is a non-clonal lymph node hyperplasia, mostly seen in the mediastinum. It has various clinical and pathological outcomes. There are different treatments because of its rare occurance and heterogenity. We present 2 cases which were referred to our clinic as retroperitoneal mass and diagnosed as CD after surgical resection.


Crystal structures of the all-cysteinyl-coordinated D14C variant of Pyrococcus furiosus ferredoxin: [4Fe-4S] ↔ [3Fe-4S] cluster conversion.
The structure of the all-cysteinyl-coordinated D14C variant of [4Fe-4S] ferredoxin from the hyperthermophilic archaeon Pyrococcus furiosus has been determined to 1.7 Å resolution from a crystal belonging to space group C222(1) with two types of molecules, A and B, in the asymmetric unit. A and B molecules have different crystal packing and intramolecular disulfide bond conformation. The crystal packing reveals a β-sheet interaction between A molecules in adjacent asymmetric units, whereas B molecules are packed as monomers in a less rigid position next to the A-A extended β-sheet dimers. The A molecules contain an intramolecular disulfide bond in a double conformation with 60% occupancy left-handed and 40% occupancy right-handed spiral conformation, whereas B molecules have an intramolecular disulfide bond in a right-handed spiral conformation. The cluster in D14C [4Fe-4S] P. furiosus ferredoxin was chemically oxidized at pH 5.8 to [3Fe-4S]. For purification at pH 8.0, two forms of the protein are obtained. Mass spectrometric analysis shows that the two forms are the D14C [3Fe-4S] P. furiosus ferredoxin monomer and a disulfide-bonded dimer of D14C [3Fe-4S] P. furiosus ferredoxin. When oxidization and purification are carried out at pH 5.8, only the monomer is obtained. The crystal structure of D14C [3Fe-4S] P. furiosus ferredoxin monomer was determined to 2.8 Å resolution from a crystal belonging to space group P2(1)2(1)2(1) with two molecules in the asymmetric unit. The molecules resemble molecule A of D14C [4Fe-4S] P. furiosus ferredoxin and electron density clearly shows the presence of a [3Fe-4S] cluster.


Activation of the replicative DNA helicase: breaking up is hard to do.
The precise duplication of the eukaryotic genome is accomplished by carefully coordinating the loading and activation of the replicative DNA helicase so that each replication origin is unwound and assembles functional bi-directional replisomes just once in each cell cycle. The essential Minichromosome Maintenance 2-7 (Mcm2-7) proteins, comprising the core of the replicative DNA helicase, are first loaded at replication origins in an inactive form. The helicase is then activated by recruitment of the Cdc45 and GINS proteins into a holo-helicase known as CMG (Cdc45, Mcm2-7, GINS). These steps are regulated by multiple mechanisms to ensure that Mcm2-7 loading can only occur during G1 phase, whilst activation of Mcm2-7 cannot occur during G1 phase. Here we review recent progress in understanding these critical reactions focusing on the mechanism of helicase loading and activation.


[Clinical aspects of salivary gland tumors].
This paper reports on epithelial tumours arising primarily in the major and minor salivary glands. The purpose of this presentation is to summarize our experience of salivary gland tumours on the basis of a material comprising of approximately 3000 salivary gland tumours as well as a review of the literature to date. The tumours are classified according to the classification recommended by WHO 1972. The incidence, location, symptomatology, grade of malignancy and treatment of the different tumour types in this classification are reviewed. Diagnostic procedures are discussed and a scheme for surgical treatment and radiotherapy of the different types of salivary gland tumours is proposed.


Extracorporeal fertilization in the world and in Croatia.
To point out the dangers, side effects and risks of medical assisted fertilization, in vitro fertilization, embryo transfer and injection on sperm in ovum for mother and the child. On the one hand the negative side effects for women of an abrupt rising risk for the development of neoplasm under pharmaceutical therapy are mentioned. Especially under a therapy which has the purpose to stimulate the ovulation of the ovary it lies around 100%. An increased level of certain hormones, as for example HCG, which influences the ovulation, is closely related with the risk of developing ovarian cancer. Clinical studies at more than 12000 infertile women (primary and secondary acyesis), with an average age of 30 years, show an elevated risk for the development of a malignant tumor of 98%. Also the application of Gonadotrophin is connected with a risk of 146% for the occurrence of cancer after a period of 15 years. FDT involves a risk of about 12% for the occurrence of breast cancer and shows also an aggravation for the risk of cancer of the endometrium from 79% up to 1152%. On the other hand the risk of spontaneous miscarriages under MAF, which is near 20%, and serious illness of the children, including 47% with need of intensive care unit support after birth, need to be realized. Furthermore the investigation of naturally obtained twins and through ART obtained twins shows in the arrangement a slower and poorer development of the children in the ART group with also great differences in physical development. In total the number of inherent malformation of newborns under the use of ART rises from 47 to 177%. With an installment of 9% we notice that children who came into being by IVF and ICS also fall more frequently ill. (Teething troubles, more hospitalizations and operations, higher frequency of major inherent malformations). All women who want to undergo a medical assisted fertilization should be informed about the side effects and risks for mother and child.


Sensing the Local Magnetic Environment through Optically Active Defects in a Layered Magnetic Semiconductor.
Atomic-level defects in van der Waals (vdW) materials are essential building blocks for quantum technologies and quantum sensing applications. The layered magnetic semiconductor CrSBr is an outstanding candidate for exploring optically active defects because of a direct gap, in addition to a rich magnetic phase diagram, including a recently hypothesized defect-induced magnetic order at low temperature. Here, we show optically active defects in CrSBr that are probes of the local magnetic environment. We observe a spectrally narrow (1 meV) defect emission in CrSBr that is correlated with both the bulk magnetic order and an additional low-temperature, defect-induced magnetic order. We elucidate the origin of this magnetic order in the context of local and nonlocal exchange coupling effects. Our work establishes vdW magnets like CrSBr as an exceptional platform to optically study defects that are correlated with the magnetic lattice. We anticipate that controlled defect creation allows for tailor-made complex magnetic textures and phases with direct optical access.


How social opinion influences syntactic processing-An investigation using virtual reality.
The extent to which you adapt your grammatical choices to match that of your interlocutor's (structural priming) can be influenced by the social opinion you have of your interlocutor. However, the direction and reliability of this effect is unclear as different studies have reported seemingly contradictory results. We have operationalized social perception as the ratings of strangeness for different avatars in a virtual reality study. The use of avatars ensured maximal control over the interlocutor's behaviour and a clear dimension along which to manipulate social perceptions toward this interlocutor. Our results suggest an inverted U-shaped curve in structural priming magnitude for passives as a function of strangeness: the participants showed the largest priming effects for the intermediately strange, with a decrease when interacting with the least- or most-strange avatars. The relationship between social perception and priming magnitude may thus be non-linear. There seems to be a 'happy medium' in strangeness, evoking the largest priming effect. We did not find a significant interaction of priming magnitude with any social perception.


Mutations in Fibronectin Cause a Subtype of Spondylometaphyseal Dysplasia with "Corner Fractures".
Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of collagens, fibrillin-1, and other proteins. It is also known to play roles in skeletal tissues through its secretion by osteoblasts, chondrocytes, and mesenchymal cells. Spondylometaphyseal dysplasias (SMDs) comprise a diverse group of skeletal dysplasias and often manifest as short stature, growth-plate irregularities, and vertebral anomalies, such as scoliosis. By comparing the exomes of individuals with SMD with the radiographic appearance of "corner fractures" at metaphyses, we identified three individuals with fibronectin (FN1) variants affecting highly conserved residues. Furthermore, using matching tools and the SkelDys emailing list, we identified other individuals with de novo FN1 variants and a similar phenotype. The severe scoliosis in most individuals and rare developmental coxa vara distinguish individuals with FN1 mutations from those with classical Sutcliffe-type SMD. To study functional consequences of these FN1 mutations on the protein level, we introduced three disease-associated missense variants (p.Cys87Phe [c.260G>T], p.Tyr240Asp [c.718T>G], and p.Cys260Gly [c.778T>G]) into a recombinant secreted N-terminal 70 kDa fragment (rF70K) and the full-length fibronectin (rFN). The wild-type rF70K and rFN were secreted into the culture medium, whereas all mutant proteins were either not secreted or secreted at significantly lower amounts. Immunofluorescence analysis demonstrated increased intracellular retention of the mutant proteins. In summary, FN1 mutations that cause defective fibronectin secretion are found in SMD, and we thus provide additional evidence for a critical function of fibronectin in cartilage and bone.


TMEM Proteins in Cancer: A Review.
A transmembrane protein (TMEM) is a type of protein that spans biological membranes. Many of them extend through the lipid bilayer of the plasma membrane but others are located to the membrane of organelles. The TMEM family gathers proteins of mostly unknown functions. Many studies showed that TMEM expression can be down- or up-regulated in tumor tissues compared to adjacent healthy tissues. Indeed, some TMEMs such as TMEM48 or TMEM97 are defined as potential prognostic biomarkers for lung cancer. Furthermore, experimental evidence suggests that TMEM proteins can be described as tumor suppressors or oncogenes. TMEMs, such as TMEM45A and TMEM205, have also been implicated in tumor progression and invasion but also in chemoresistance. Thus, a better characterization of these proteins could help to better understand their implication in cancer and to allow the development of improved therapy strategies in the future. This review gives an overview of the implication of TMEM proteins in cancer.


Changes in mitochondrial electron partitioning in response to herbicides inhibiting branched-chain amino acid biosynthesis in soybean.
The adaptation of the respiratory metabolism in roots of soybean (Glycine max L. Merr. cv Ransom) treated with herbicides that inhibit the enzyme acetolactate synthase (ALS) was analyzed. A new gas phase dual-inlet mass spectrometry system for simultaneous measurement of 34O2 to 32O2 and O2 to N2 ratios has been developed. This system is more accurate than previously described systems, allows measurements of much smaller oxygen gradients, and, as a consequence, works with tissues that have lower respiration rates. ALS inhibition caused an increase of the alternative oxidase (AOX) protein and an accumulation of pyruvate. The combination of these two effects is likely to induce the activation of the alternative pathway and its participation in the total respiration. Moreover, the start of the alternative pathway activation and the increase of AOX protein were before the decline in the activity of cytochrome pathway. The possible role of AOX under ALS inhibition is discussed.


Attitudes of Physicians, Midwives, and Nurses About Doulas: A Scoping Review.
Evidence supports numerous positive clinical benefits of doula care. There are varying attitudes among physicians, midwives, and nurses toward support of doulas in a collaborative approach with women in labor. Tension and conflict with use of doulas may occur in some intrapartum settings in the United States. A scoping review of the literature between January 2008 and January 2018 was conducted using PubMed, CINAHL, Google Scholar, and Scopus database to identify specific attitudes of physicians, midwives, and nurses toward doulas; 1,810 records were identified and initially reviewed. Inclusion criteria included original research published in the last 10 years and in the English language. Articles were excluded if the research was not original and if obstetrical providers' or nurses' attitudes toward doulas were not included. Three records met criteria for inclusion. All used a cross-sectional survey design. Two were set in Canada exclusively and one was inclusive of nurses and doulas in both Canada and the United States. Themes emerged that may explain the influence and variances in attitudes toward doulas and the support they provide to laboring women. More research is needed to identify attitudes of members of the maternity care team toward doulas and to better understand implications of their attitudes on working together collaboratively and on patient outcomes.


Aggregation of complement receptors on human neutrophils in the absence of ligand.
C3bi receptors (CR3) on human polymorphonuclear leukocytes (PMN) bind ligand-coated particles and promote their ingestion. The binding activity of CR3 is not constitutive but is transiently enabled by phorbol esters (Wright, S. D., and B. D. Meyer, 1986, J. Immunol. 136:1759-1764). Our observations indicate that the capacity of CR3 to bind ligand is tightly correlated with the degree of ligand-independent aggregation of the receptor in the plane of the membrane. Fixed PMN were labeled with anti-CR3 monoclonal antibodies and streptavidin colloidal gold before viewing in the electron microscope either en face or in thin section. On unstimulated PMN, gold particles marking CR3 were dispersed randomly. Stimulation of PMN for 25 min with phorbol myristate acetate (PMA) dramatically enhances binding of C3bi-coated particles, and the CR3 on such stimulated cells was observed in clusters containing more than six gold particles. CR3 was not aggregated over coated pits. After 50 min in PMA, the binding activity of CR3 falls, and the distribution of CR3 was again observed to be disperse. If a hydrophilic phorbol ester was washed away after a 20-min stimulation, binding activity remains elevated for at least 50 min, and CR3 remained aggregated. Thus, clustering of CR3 was temporally correlated with its ability to bind ligand and initiate phagocytosis. Unlike CR3, Fc receptors and HLA did not exhibit changes in their aggregation state in response to PMA. Treating PMN with formyl-methionyl-leucyl-phenylalanine, which enhances expression of CR3 but not its function, did not lead to aggregation of CR3. These observations suggest that a clustered configuration is a precondition necessary for binding ligand and signaling phagocytosis.


Food Insecurity, Food Deserts, and Waist-to-Height Ratio: Variation by Sex and Race/Ethnicity.
The purpose of this study is to investigate the association between two food-related hardships-food insecurity and living in a food desert-on waist-to-height ratio (WHtR). Data on participants from waves I and IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) were analyzed. The association between food-related hardships and waist-to-height ratio were examined using logistic regression. Models were stratified by sex and race/ethnicity to examine potential moderating effects. Study results suggest food insecurity has a positive association with WHtR among female respondents (OR = 1.360, p = .017). Living in a food desert has a positive association with WHtR among both females (OR = 1.247, p = .026) and males (OR = 1.245, p = .024). In models stratified by race/ethnicity living in a food desert is positively associated with WHtR among White respondents (OR = 1.279, p = .003). Given the link between food-related hardships and obesity, targeted interventions that alleviate food insecurity and inadequate access to healthy food retailers could be effective in reducing obesity.


Physical, chemical and pedogenetical properties of soil in relation with altitude at Kazdagi upland black pine forest.
In this study an attempt was made to investigate the physical, chemical and pedogenetical soil properties of black pine forests at over 1400 metre (m) altitude of Kazdagi mountainous uplands. Soil profiles (37 numbers) were dug, examined and sampled considering the horizons and soil volume weight, fine soil weight, stoniness, pH, total nitrogen, soil organic carbon and pedogenesis alterations were tried to be explored in relation with elevating altitude. While the altitude increased, soil organic carbon and total nitrogen values decreased at A horizon, and pH decreased at Bw horizons. Soil volume weight, fine soil weight, stoniness values of A horizon has positively and strong correlation with elevation with the coefficient values 0.699, 0.518 and 0.573 respectively at 0.01 significance. The highest regression values between altitude and volume weight, soil organic carbon contents (%) and soil total nitrogen contents (%) were detected with R2 coefficients 0.489, 0.295 and 0.247 for A and 0.556, 0.311 and 0.286 for Bw horizons respectively. The achieved results reveal that the elevation effect is remarkable in particular for the uppermost soil horizons. Furthermore the soil generation in fact functions well up to 1550 m altitude at Kazdagi mountainous land where we determined that at upper elevations Inceptisols replace with Alfisols in comparison with each other.


Optimizing the intervention in research studies.
One of the many challenges of nursing intervention studies is to assure that significant effects of the intervention are detected in the research. Optimizing the intervention in the design of the study can increase the potential for finding positive outcomes, if they are, in fact, present. Attending to the operationalization, strength, integrity, and timing of the intervention, as well as to the contrast between the treatment and control groups, can optimize the intervention in intervention research.


Purification and characterization of the soluble methane monooxygenase of the type II methanotrophic bacterium Methylocystis sp. strain WI 14.
Methane monooxygenase (MMO) catalyzes the oxidation of methane to methanol as the first step of methane degradation. A soluble NAD(P)H-dependent methane monooxygenase (sMMO) from the type II methanotrophic bacterium WI 14 was purified to homogeneity. Sequencing of the 16S rDNA and comparison with that of other known methanotrophic bacteria confirmed that strain WI 14 is very close to the genus Methylocystis. The sMMO is expressed only during growth under copper limitation (<0.1 microM) and with ammonium or nitrate ions as the nitrogen source. The enzyme exhibits a low substrate specificity and is able to oxidize several alkanes and alkenes, cyclic hydrocarbons, aromatics, and halogenic aromatics. It has three components, hydroxylase, reductase and protein B, which is involved in enzyme regulation and increases sMMO activity about 10-fold. The relative molecular masses of the native components were estimated to be 229, 41, and 18 kDa, respectively. The hydroxylase contains three subunits with relative molecular masses of 57, 43, and 23 kDa, which are present in stoichiometric amounts, suggesting that the native protein has an alpha(2)beta(2)gamma(2) structure. We detected 3.6 mol of iron per mol of hydroxylase by atomic absorption spectrometry. sMMO is strongly inhibited by Hg(2+) ions (with a total loss of enzyme activity at 0.01 mM Hg(2+)) and Cu(2+), Zn(2+), and Ni(2+) ions (95, 80, and 40% loss of activity at 1 mM ions). The complete sMMO gene sequence has been determined. sMMO genes from strain WI 14 are clustered on the chromosome and show a high degree of homology (at both the nucleotide and amino acid levels) to the corresponding genes from Methylosinus trichosporium OB3b, Methylocystis sp. strain M, and Methylococcus capsulatus (Bath).


Magnetic resonance imaging of the supra-cervical fetal membrane detects an increased risk of prelabor rupture of membranes.
In 10% of term deliveries and 40% of preterm deliveries, the fetal membrane (FM) ruptures before labor. However, the ability to predict these cases of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) is very limited. In this paper, our objective was to determine whether a prediction method based on T2 weighted magnetic resonance imaging (MRI) of the supra-cervical FM could predict PROM and PPROM. This prospective cohort study enrolled 77 women between the 28th and 37th weeks of gestation. Two indicators of fetal membrane defects, including prolapsed depth >5 mm and signal abnormalities, are investigated for our prediction. Fisher's exact test was used to determine whether prolapsed depth >5 mm and/or signal abnormalities were associated with PROM and PPROM. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for prolapsed depth >5 mm, signal abnormalities, and the combination of prolapsed depth >5 mm and signal abnormalities. Among 12 women with PROM (5 preterm and 7 term, prior to labor onset), 9 had membrane prolapse >5 mm and 5 had FM signal abnormalities. Among 65 women with rupture of membranes at term, 2 had membrane prolapse >5 mm and 1 had signal abnormalities. By Fisher's exact test both indicators, membrane prolapse >5 mm and signal abnormalities, were associated with PROM (P<0.001, P<0.001) and PPROM (P=0.001, P<0.001). Additionally, membrane prolapse >5 mm, signal abnormalities, and the combination of the two indicators all demonstrated high specificity for predicting PROM (96.9%, 98.5%, and 100%, respectively) and PPROM (90.3%, 97.2%, and 100%, respectively). MRI can distinguish the supra-cervical fetal membrane in vivo and may be able to identify women at high risk of PPROM.


Sequence determination and analysis of the full-length genome of colorado tick fever virus, the type species of genus Coltivirus (Family Reoviridae).
The Colorado tick fever virus (CTFV) is the type species of genus Coltivirus, family Reoviridae. Its genome consisting of 12 segments of dsRNA was completely sequenced. It was found to be 29,174 nucleotides long (the longest of all Reoviridae genomes characterized to date). Conserved sequences at the 5' end (SACUUUUGY) and at the 3' end (WUGCAGUS) of the 12 segments were identified. The analysis of the putative proteins deduced from the nucleotide sequences permitted to identify functional motifs. In particular, the VP1 was identified unambiguously as the viral RNA dependent RNA pylmerase (RDRP) (VP1pol), with a GDD located at a similar position to Reoviridae RDRPs. In other genes, RGD cell-binding, NTPAse, single strand binding protein and kinase motifs were identified. Comparison with Reoviridae proteins showed significant similarities to RDRPs (CTFV-VP1) and sigma C protein of orthoreovirus (CTFV-VP6). Similarities to nonviral enzymatic proteins, such as methyltransferases, NTPAses, RNA replication factors, were also identified.


A Case of Late Diagnosis of Acute Aortic Dissection Involving the Carotid Arteries in a Patient Presenting with Signs of Acute Ischemic Stroke.
BACKGROUND Acute aortic dissection (AAD) is a rare but life-threatening condition with high mortality. The Stanford classification of aortic dissection includes type A, which originates in the ascending aorta, and type B, which originates in the descending aorta. The diagnosis may be missed due to its ability to mimic other more common cardiovascular conditions. A case is presented of late diagnosis of AAD involving the right carotid arteries in a 55-year-old man who presented with acute ischemic stroke. CASE REPORT A 55-year-old man presented with sudden onset of left-sided facial weakness and aphasia. He was diagnosed with acute ischemic stroke and treated with tissue plasminogen activator. Further imaging showed an AAD involving the entire length of the aorta. Treatment with tissue plasminogen activator was discontinued, and the patient underwent surgical repair of the aorta. His hospital stay was complicated by acute kidney injury (AKI), pneumonia, and sepsis, and he died three weeks later from renal failure. CONCLUSIONS This case demonstrated that AAD can be challenging to diagnose, and may present atypically with ischemic stroke when it involves the carotid arteries. In such cases, imaging studies of the chest, abdomen, and head and neck may identify AAD and prevent inappropriate treatment with anticoagulants.


Tanshinone IIA reduces the risk of Alzheimer's disease by inhibiting iNOS, MMP‑2 and NF‑κBp65 transcription and translation in the temporal lobes of rat models of Alzheimer's disease.
Tanshinone IIA (Tan IIA), one of the major active constituents of the medicinal herb Salvia miltiorrhiza, has been reported to possess neuroprotective effects against the pathological features of Alzheimer's disease (AD), but the molecular mechanism underlying this effect remains unclear. To examine the effect of Tan IIA on AD, as well as the underlying molecular mechanisms, in vivo animal experiments and in vitro molecular biology investigations were employed in the present study. Firstly, a rat model of AD was successfully established by direct injection of the amyloid beta protein (Aβ) and then these rats were administered an interventional treatment of Tan IIA. The learning and memory ability of rats was evaluated in four groups (Control, Sham, AD and Tan IIA) utilizing a Morris water maze test. Quantitative (q)PCR was employed to detect the mRNA expression of inducible nitric oxide synthase (iNOS), matrix metalloproteinase‑2 (MMP‑2) and nuclear transcription factor kappa (NF‑κBp65) in temporal lobe tissues and protein expression was determined with western blot analysis. In addition, association analyses between iNOS, MMP‑2 and NF‑κBp65 at a transcriptional and translational level were performed utilizing Spearman's correlation analysis. In the present study, the results revealed that rats in the AD group demonstrated significant disruptions in learning and memory ability, and the symptoms were evidently reduced by Tan IIA. Furthermore, the upregulation of iNOS, MMP‑2 and NF‑κBp65 at a transcriptional and translational level in AD rats was distinctly inhibited by Tan IIA. Therefore, it was concluded that iNOS, MMP‑2 and NF‑κBp65 are involved in AD development, and Tan IIA may reduce AD risk by inhibiting transcription and translation of these genes. Furthermore, the positive correlation of iNOS and MMP‑2 with NF‑κBp65, respectively, provides evidence supporting the hypothesis that Tan IIA reduces AD risk by inhibiting iNOS and MMP‑2 at a transcriptional and translational level through the NF‑κB pathway. In summary, Tan IIA is an effective neuroprotective agent for AD therapy, and iNOS, MMP‑2 and NF‑κBp65 may be the potential molecular targets for manipulating this effect therapeutically.


Pharmacology of the central control of micturition.
Micturition is the process whereby urine is collected in the bladder until such time as it is convenient to void. The two phases of the cycle are controlled by several reflexes but the act of voiding is usually initiated voluntarily. To date, pharmacological research on the central control of micturition has concentrated on influences of the brain stem and spinal cord, and in particular of the locus coeruleus, the "pontine micturition reflex centre". Studies have shown that spontaneous bladder motility is affected by agents acting upon receptors for acetylcholine, noradrenaline, dopamine, opioids, GABA and glutamate. It is now necessary to extend these studies to conscious animals so that reflex activity is not affected by anaesthesia and the effects of drugs on the collecting and emptying phases can be examined.


Attitude of transplant centers in the Middle East towards the follow-up of renal allograft live donors.
In an attempt to survey the attitude of the heads of some distinguished transplant programs in the Middle East countries towards the follow-up and complications that may ensue in the live renal allograft donors, we sent a questionnaire to 29 active renal transplant centers in the Kingdom of Saud Arabia (KSA) and some other Middle East countries, which together perform about 1500 living renal transplantations annually. The study was performed during November-December, 2005. Th questionnaire was intended to evaluate the presence of a protocol that guides the physicians in their selection, work-up and follow-up of the live renal allograft donors, the presence of regular time schedule for follow-up of the donors during the first year and thereafter, and the tests performed during these clinic visits, the physicians' perception towards the life-long health insurance of the live donors as well as the physicians' estimates of the major complications that may occur in the live donors such a hypertension, proteinuria, chronic renal failure, early surgical complications and depression. There were 20 responses (69%) from transplant centers that together perform about 1200 (80%) living rena transplantations annually. There were 18 (90%) respondents who had a protocol to guide the selection o the live renal allograft donors, 10 (52.6%) had a written policy for post-donation follow-up of live renal allograft donors, 15 (83.3%) would see the donors for the first time within three months post-discharge, 10 (66.7%) would see the donors every three months thereafter during the first year and 11 (68.8%) would see them once a year after the first year. There was a consensus among the respondents to monitor the renal function tests that include plasma urea creatinine and urinalysis. The post donation incidence of hypertension, proteinuria, chronic renal failure, early surgical complications and psychological problems such as depression was estimated by more than 80% of the respondents as 1-5%. We conclud that the current practices concerning the follow-up of renal allograft live donors by the dialysis centers i the Middle East seem promising. However, this being a questionnaire survey, results may not be totall accurate. Prospective studies are required to ensure that protocols for follow-up are abided by.


A linker strategy for trans-FRET assay to determine activation intermediate of NEDDylation cascade.
Förster resonance energy transfer (FRET) technology has been widely used in biological and biomedical research and is a valuable tool for elucidating molecular interactions in vitro and in vivo. Quantitative FRET analysis is a powerful method for determining biochemical parameters and molecular distances at nanometer levels. Recently, we reported theoretical developments and experimental procedures for determining the dissociation constant, Kd and enzymatic kinetics parameters, Kcat and KM, of protein interactions with the engineered FRET pair, CyPet and YPet. The strong FRET signal from this pair made these developments possible. However, the direct link of fluorescent proteins with proteins of interests may interfere with the folding of some fusion proteins. Here, we report a new protein engineering strategy for improving FRET signals by adding a linker between the fluorescent protein and the targeted protein. This improvement allowed us to follow the covalent conjugation of NEDD8 to its E2 ligase in the presence of E1 and ATP, which was difficult to determine without linker. Three linkers, LAEAAAKEAA, TSGSPGLQEFGT, and LAAALAAA, which are alpha helix or random coil, all significantly improved the FRET signals. Our results show a general methodology for improving trans-FRET signals to effectively determine biochemical reaction intermediates.


Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet.
The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes.


Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study.
Exposure to cardiovascular risk factors during childhood and adolescence may be associated with the development of atherosclerosis later in life. To study the relationship between cardiovascular risk factors measured in childhood and adolescence and common carotid artery intima-media thickness (IMT), a marker of preclinical atherosclerosis, measured in adulthood. Population-based, prospective cohort study conducted at 5 centers in Finland among 2229 white adults aged 24 to 39 years who were examined in childhood and adolescence at ages 3 to 18 years in 1980 and reexamined 21 years later, between September 2001 and January 2002. Association between cardiovascular risk variables (levels of low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides; LDL-C/HDL-C ratio; systolic and diastolic blood pressure; body mass index; smoking) measured in childhood and adulthood and common carotid artery IMT measured in adulthood. In multivariable models adjusted for age and sex, IMT in adulthood was significantly associated with childhood LDL-C levels (P =.001), systolic blood pressure (P<.001), body mass index (P =.007), and smoking (P =.02), and with adult systolic blood pressure (P<.001), body mass index (P<.001), and smoking (P =.004). The number of risk factors measured in 12- to 18-year-old adolescents, including high levels (ie, extreme age- and sex-specific 80th percentile) of LDL-C, systolic blood pressure, body mass index, and cigarette smoking, were directly related to carotid IMT measured in young adults at ages 33 through 39 years (P<.001 for both men and women), and remained significant after adjustment for contemporaneous risk variables. The number of risk factors measured at ages 3 to 9 years demonstrated a weak direct relationship with carotid IMT at ages 24 to 30 years in men (P =.02) but not in women (P =.63). Risk factor profile assessed in 12- to 18-year-old adolescents predicts adult common carotid artery IMT independently of contemporaneous risk factors. These findings suggest that exposure to cardiovascular risk factors early in life may induce changes in arteries that contribute to the development of atherosclerosis.


Surface Tensions of Ionic Liquids: Non-Regular Trend Along the Number of Cyano Groups.
Ionic liquids (ILs) with cyano-functionalized anions are a set of fluids that are still poorly characterized despite their remarkably low viscosities and potential applications. Aiming at providing a comprehensive study on the influence of the number of -CN groups through the surface tension and surface organization of ILs, the surface tensions of imidazolium-based ILs with cyano-functionalized anions were determined at atmospheric pressure and in the (298.15 to 343.15) K temperature range. The ILs investigated are based on 1-alkyl-3-methylimidazolium cations (alkyl = ethyl, butyl and hexyl) combined with the [SCN]-, [N(CN)2]-, [C(CN)3]- and [B(CN)4]-anions. Although the well-known trend regarding the surface tension decrease with the increase of the size of the aliphatic moiety at the cation was observed, the order obtained for the anions is more intricate. For a common cation and at a given temperature, the surface tension decreases according to: [N(CN)2]- > [SCN]- > [C(CN)3]- > [B(CN)4]-. Therefore, the surface tension of this homologous series does not decrease with the increase of the number of -CN groups at the anion as has been previously shown by studies performed with a more limited matrix of ILs. A maximum in the surface tension and critical temperature was observed for [N(CN)2]-based ILs. Furthermore, a minimum in the surface entropy, indicative of a highly structured surface, was found for the same class of ILs. All these evidences seem to be a result of stronger hydrogen-bonding interactions occurring in [N(CN)2]-based ILs, when compared with the remaining CN-based counterparts, and as sustained by cation-anion interaction energies derived from the Conductor Like Screening Model for Real Solvents (COSMO-RS).


Excavation Equipment Recognition Based on Novel Acoustic Statistical Features.
Excavation equipment recognition attracts increasing attentions in recent years due to its significance in underground pipeline network protection and civil construction management. In this paper, a novel classification algorithm based on acoustics processing is proposed for four representative excavation equipments. New acoustic statistical features, namely, the short frame energy ratio, concentration of spectrum amplitude ratio, truncated energy range, and interval of pulse are first developed to characterize acoustic signals. Then, probability density distributions of these acoustic features are analyzed and a novel classifier is presented. Experiments on real recorded acoustics of the four excavation devices are conducted to demonstrate the effectiveness of the proposed algorithm. Comparisons with two popular machine learning methods, support vector machine and extreme learning machine, combined with the popular linear prediction cepstral coefficients are provided to show the generalization capability of our method. A real surveillance system using our algorithm is developed and installed in a metro construction site for real-time recognition performance validation.


Comprehensive multiparameter genetic analysis improves circulating tumor DNA detection in head and neck cancer patients.
Tumor-specific genetic aberrations in cell-free DNA (cfDNA) from plasma are promising biomarkers for diagnosis of recurrent head and neck squamous cell carcinoma (HNSCC). However, the sensitivity when using somatic mutations only in cfDNA is suboptimal. Here, we combined detection of copy number aberrations (CNAs), human papillomavirus (HPV) DNA and somatic mutations in a single sequencing workflow. Pretreatment plasmas of 40 patients and 20 non-cancer controls were used for analysis. Plasma DNA underwent low-coverage whole genome sequencing (lcWGS) to detect both CNAs and HPV-DNA, and deep sequencing to detect mutations in 12 frequently altered cancer driver genes in HNSCC using the same sequencing library. A specific analysis pipeline line was developed for data mining. The corresponding tumors were analyzed using slightly adapted protocols. Using the developed method, somatic mutations and CNAs were detected in plasma DNA of HNSCC patients in 67% and 52%, respectively. HPV-DNA in plasma was detected in 100% of patients with HPV-positive tumors, and not in plasma of patients with HPV-negative tumors or non-cancer controls. Combined analysis increased the detection rate of tumor DNA in plasma to 78%. The detection rate was significantly associated with the stage of disease of the tumor. Neither HPV status nor location of the primary tumor influenced detection of CNAs or somatic mutations in plasma. This study demonstrates that the combined analysis of CNAs, HPV and somatic mutations in plasma of HNSCC patients is feasible and contributes to a higher sensitivity of the assay compared to single modality analyses.


Educational needs assessment for psychiatry residents to prevent suicide: a qualitative approach.
Suicide is a commonly encountered and stressful event in professional life of any psychiatrist. Suicide risk assessment is a major gateway to patient treatment and management. It is a core competency requirement in training of psychiatry. The present study designed to assesseducational needsfor suicide prevention in residents of psychiatry in two medical schools in Iran, Isfahan University of Medical Sciences (IUMS) and Shahid Beheshti Medical University (SBUMS) inTehran. This was a qualitative triangulation study, conducted in two steps. The first step was based on a phenomenological approach and the second was based on focus groups. The studied population was the psychiatric residents of IUMS and SBUMS. Purposive sampling was implemented until saturation. Interviews were performed. Colaizzi method was used to analyze the data. In the second step, participants attended a session, in which all final codes of the first step were discussed, and regarding the views, educational priorities and needs were listed. A total of 2047 codes, extracted from 31 interviews, analyzed through Colaizzi method, were categorized in three groups: Educational, facilities and processes, human resources. According to defects of current educational program, we suggest regular reevaluations and revisions of clinical training programs according to current needs.


Perspectives on Dye Sensitization of Nanocrystalline Mesoporous Thin Films.
Recent advances in our mechanistic understanding of dye-sensitized electron transfer reactions occurring at metal oxide interfaces are described. These advances were enabled by the advent of mesoporous thin films, comprised of anatase TiO2 nanocrystallites, that are amenable to spectroscopic and electrochemical characterization in unprecedented molecular-level detail. The metal-to-ligand charge transfer (MLCT) excited states of Ru polypyridyl compounds serve as the dye sensitizers. Excited-state injection often occurs on ultrafast time scales with yields that can be tuned from unity to near zero through modification of the sensitizer or the electrolyte composition. Transport of the injected electron and the oxidized sensitizer (hole hopping) are both operative in the composite mechanism for charge recombination between the injected electron and the oxidized sensitizer. Sensitizers that contain a pendant electron donor, as well as core/shell SnO2/TiO2 nanostructures, often prolong the lifetime of the injected electron and provide fundamental insights into adiabatic and nonadiabatic electron transfer mechanisms. Regeneration of the oxidized sensitizer by iodide is enhanced through halogen bonding, orbital pathways, and ion pairing. A substantial ∼10 MV cm-1 electric field is created by electron injection into TiO2 nanocrystallites that induces ion migration, reports on the sensitizer dipole orientation, and (in some cases) reorients or flips the sensitizer. Dye-sensitized conductive oxides also promote long-lived charge separation with bias dependent kinetics that provide insights into the reorganization energies associated with electron and proton-coupled electron transfer in the electric double layer.


Binary regression in truncated samples, with application to comparing dietary instruments in a large prospective study.
We examine two issues of importance in nutritional epidemiology: the relationship between dietary fat intake and breast cancer, and the comparison of different dietary assessment instruments, in our case the food frequency questionnaire (FFQ) and the multiple-day food record (FR). The data we use come from women participants in the control group of the Dietary Modification component of the Women's Health Initiative (WHI) Clinical Trial. The difficulty with the analysis of this important data set is that it comes from a truncated sample, namely those women for whom fat intake as measured by the FFQ amounted to 32% or more of total calories. We describe methods that allow estimation of logistic regression parameters in such samples, and also allow comparison of different dietary instruments. Because likelihood approaches that specify the full multivariate distribution can be difficult to implement, we develop approximate methods for both our main problems that are simple to compute and have high efficiency. Application of these approximate methods to the WHI study reveals statistically significant fat and breast cancer relationships when a FR is the instrument used, and demonstrate a marginally significant advantage of the FR over the FFQ in the local power to detect such relationships.


Improving the Degree of Pubic Arch Post-Yoga Exercise During Pregnancy.
Yoga exercises undertaken during the maternity period may reduce unpleasant symptoms during pregnancy and reduce delivery pain. Flexibility of the hip joint improves the degree of pubic arch created in an open-leg posture and widens the pelvic outlet region, shortening the time required for delivery and facilitating easy delivery. The degree of pubic arch is related to the flexibility of the hip joint. Although many studies have shown the effect of yoga exercise during pregnancy, the effect on the degree of the pubic arch has not been elucidated. To elucidate whether the degree of the pubic arch is improved by yoga exercise during pregnancy, this study enrolled 177 pregnant subjects. The degree of pubic arch pre- and post-yoga exercise was measured using instruments in an open-leg posture (seated with femurs abducted). The mean pubic arch pre- and post-yoga was 122.61 and 127.93 degrees, respectively. The degree of pubic arch post-yoga sessions was significantly increased compared with pre-yoga sessions (p < 0.01). This study showed that yoga exercises during the pregnancy period appear to improve the degree of pubic arch.


Time to recovery of the hypothalamic-pituitary-adrenal axis after curative resection of adrenal tumors in patients with Cushing's syndrome.
The recovery time of the hypothalamic-pituitary-adrenal (HPA) axis after curative resection of adrenal tumors in patients with Cushing's syndrome is poorly documented. Eight consecutive patients were treated with a standardized hydrocortisone replacement strategy after curative resection of a cortisol-secreting tumor and the time to recovery of the HPA axis was determined. Hypercortisolism was documented by elevated 24-hour urinary free cortisol levels. Cure was documented by undetectable postoperative morning serum cortisol levels. Each patient received replacement hydrocortisone after surgery and was reevaluated every 3 to 6 months with an adrenocorticotrophic hormone (ACTH) stimulation test. Each patient was also monitored carefully for symptoms and signs of adrenal insufficiency, which was defined as symptoms consistent with this diagnosis that responded to increases in hydrocortisone levels. After surgical resection, each patient was cured of hypercortisolism. Subsequently, despite replacement hydrocortisone, each patient had symptoms of hypocortisolism, and in four of eight patients the dose of hydrocortisone was increased to relieve the symptoms. Patients required a median time of 15 months (range, 9 to 22 months) to recover a normal ACTH stimulation test and 19 months (range, 12 to 24 months) to allow discontinuation of replacement doses of hydrocortisone. The results suggest that surgical resection of a cortisol-secreting adrenal tumor will result in rapid cure of hypercortisolism, but complete recovery of the HPA axis and discontinuation of replacement steroids will require between 1 and 2 years. Normal adrenal function, as assessed by the cortisol response to ACTH, returns despite replacement doses of hydrocortisone, and replacement doses of hydrocortisone can be tapered rapidly or discontinued after a normal ACTH stimulation test.


An atomistic mechanism for the degradation of perovskite solar cells by trapped charge.
It is unmistakably paradoxical that the most vulnerable aspect of the photoactive organic-inorganic hybrid perovskite is its instability against light. Why and how perovskites break down under light irradiation and what happens at the atomistic level of these materials during the degradation process still remain unanswered. In this paper, we found the culprit and verified the mechanism for the irreversible degradation of hybrid perovskite materials from our experimental investigation and ab initio molecular dynamics (AIMD) simulation. We initially found that the electrostatic charges generated by light irradiation and trapped along the grain boundaries of the perovskite crystal result in oxygen-induced irreversible degradation in dry air. This result, together with our previous experimental finding on the same critical role of trapped charges in the perovskite degradation under moisture, suggests that the trapped charges are the main culprit in both the oxygen- and moisture-induced degradation of perovskite materials. Detailed roles of oxygen and water molecules were investigated using AIMD simulation by tracking the atomic motions in the outermost layers of the oxygen- or water-covered methylammonium lead triiodide (denoted MAPbI3 for CH3NH3PbI3) perovskite crystal with trapped charges. In the first few picoseconds of our simulation, trapped charges start disrupting the crystal structure, leading to a short-range interaction between oxygen or water molecules and the compositional ions of MAPbI3. We found that there exist different degradation pathways depending on both the polarity of the trapped charge and the kind of gas molecule. We also verified that a more structurally stable, multi-component perovskite material (with the composition of MA0.6FA0.4PbI2.9Br0.1) showed much stronger resistance against light-induced degradation than MAPbI3 even in 100%-oxygen ambience or humid air.


Catheter-related infection in infants due to an unusual lipophilic yeast--Malassezia furfur.
Malassezia furfur (Pityrosporum orbiculare, P ovale), a lipophilic yeast that is part of the normal skin flora, causes tinea versicolor but has only rarely been associated with more serious infections. We report five episodes in four infants of catheter-related infection caused by this organism. All episodes occurred in infants who had survived serious neonatal disorders and were receiving prolonged therapy with intravenous fat emulsion. Sudden onset of fever without focal findings was the usual presentation; however, one afebrile patient had recurrent episodes of apnea, bradycardia, and cyanosis. Thrombocytopenia was a prominent finding. Patients were generally treated with amphotericin B. All patients recovered when the colonized catheter was removed or fat emulsion therapy was stopped. The yeast usually grew slowly in blood culture media but grew readily when subcultured onto Sabouraud's medium coated with sterile olive oil. Yeasts were readily identified in all four patients in whom a buffy coat Gram stain was obtained of blood from the central intravenous catheter. M furfur may be a fairly common but unrecognized cause of catheter-related sepsis in infants receiving long-term fat emulsion therapy. This organism should be sought whenever routine blood cultures are negative for bacteria and yeasts are observed in a buffy coat Gram stain.


The ketogenic diet: 1997.
There has been a dramatic resurgence of interest in the ketogenic diet during the past several years. For many children with difficult-to-control epilepsy, the diet presents an alternative approach to trying multiple medications. The ketogenic diet's current success rate, when properly executed, greatly exceeds that of the medications which have recently become available. Its side effects, both cognitive and allergic, appear fewer than most available medications. The ketogenic diet is also cheaper than most new anticonvulsants. Even though we now know that the diet works, we still do not know how it works. Nor do we know how most anticonvulsants work. The mechanism of action of the ketogenic diet appears to rely on a fundamental change in the brain's metabolism from that of a glucose-based energy substrate to a ketone-based substrate. This change is, in some fashion, critical to the maintenance of seizure threshold. Why should the source of the energy make a difference in seizure threshold? The change in seizure threshold appears to occur without affecting the brain's ability to carry out its normal complex functions. Could the brain's utilization of an energy substrate for seizure control be different from its utilization of energy for normal brain function? If so it should it be possible to study the metabolic differences between the two and develop a biochemistry of epilepsy, which is differentiated from the biochemistry of normal cognition and function. The ketogenic diet is successful in controlling or ameliorating a broad spectrum of seizure types and etiologies. Perhaps then, common metabolic pathways, independent of seizure type, are used in the initiation and spread of electrical seizures. Based on clinical experience and limited research data, it would appear that different seizures and different epilepsies must have metabolic pathways in common that make them susceptible to treatment with a common metabolic therapy. If we could understand how the ketogenic diet "works," how changing from a glucose substrate' to a ketone body substrate is anticonvulsant, then perhaps a medication could be developed that would simulate the biochemical effects of the ketogenic diet. Such an approach would be a major departure in the study of the neuroscience of epilepsy. The ketogenic diet offers a new paradigm to think about epilepsy and its treatment, and perhaps will stimulate new approaches to this still often devastating condition.


Secondary malignancies in pediatric cancer survivors: perspectives and review of the literature.
With continuing improvements in the successful treatment of pediatric malignancies, long term survivors of pediatric cancers and their providers are faced with new oncologic issues regarding long-term morbidities. As pediatric cancer survivors have matured into adulthood, the development of secondary malignancies has become a significant issue for these patients. Whether a consequence of treatment for the patient's original cancer, such as chemotherapy, ionizing radiation, or hematopoietic stem cell transplantation, secondary malignancies now present patients and providers with new challenges regarding treatment, surveillance and counseling. We review the major risk factors for secondary malignancies in pediatric cancer survivors, with particular emphasis on important molecular and cytogenetic risk factors, both inherited and acquired. We conclude with a discussion of recommendations for surveillance and counseling of these patients.


Glycosylated amyloid-like proteins in the structural extracellular polymers of aerobic granular sludge enriched with ammonium-oxidizing bacteria.
A new type of structural extracellular polymers (EPS) was extracted from aerobic granular sludge dominated by ammonium-oxidizing bacteria. It was analyzed by Raman and FTIR spectroscopy to characterize specific amino acids and protein secondary structure, and by SDS-PAGE with different stains to identify different glycoconjugates. Its intrinsic fluorescence was captured to visualize the location of the extracted EPS in the nitrifying granules, and its hydrogel-forming property was studied by rheometry. The extracted EPS is abundant with cross ß-sheet secondary structure, contains glycosylated proteins/polypeptides, and rich in tryptophan. It forms hydrogel with high mechanical strength. The extraction and discovery of glycosylated proteins and/or amyloids further shows that conventionally used extraction and characterization techniques are not adequate for the study of structural extracellular polymers in biofilms and/or granular sludge. Confirming amyloids secondary structure in such a complex sample is challengeable due to the possibility of amyloids glycosylation and self-assembly. A new definition of extracellular polymers components which includes glycosylated proteins and a better approach to studying them is required to stimulate biofilm research.


Results of 100 consecutive laparoscopic distal pancreatectomies: postoperative outcome, cost-benefit analysis, and quality of life assessment.
Laparoscopic distal pancreatectomy (LDP) has been recently proposed as the procedure of choice for lesions of the pancreatic body and tail in experienced centres. The purpose of this study is to assess the potential advantages of LDP in a consecutive series of 100 patients. Propensity score matching was used to identify patients for comparison between LDP and control open group. Match criteria were: age, gender, ASA score, BMI, lesion site and size, and malignancy. All patients were treated according to an early feeding recovery policy. Primary endpoint was postoperative morbidity rate. Secondary endpoints were operative time, blood transfusion, length of hospital stay (LOS), hospital costs, and quality of life. Thirty patients of the LDP group had pancreatic adenocarcinoma. Conversion to open surgery was necessary in 23 patients. Mean operative time was 29 min shorter in the open group (p = 0.002). No significant difference between groups was found in blood transfusion rate and postoperative morbidity rate. LDP was associated with an early postoperative rehabilitation and a shorter LOS in uneventful patients. Economic analysis showed <euro> 775 extra cost per patient of the LDP group. General health perception and vitality were better in the LDP group one month after surgery. Laparoscopic distal pancreatectomy improved short-term postoperative recovery and quality of life in a consecutive series of both cancer and non-cancer patients. Despite the extra cost, the laparoscopic approach should be considered the first option in patients undergoing distal pancreatectomy.


Fast inhibition underlies the transmission of auditory information between cochlear nuclei.
A direct commissural connection between cochlear nuclei provides a pathway by which binaural input can influence the processing of acoustic information through the ventral cochlear nucleus. Despite anatomical evidence to suggest the existence of such a pathway, its nature and behavior have not been investigated previously. This in vivo intracellular electrophysiological study provides direct evidence of monosynaptic (mean latency, 1.43 msec), inhibitory commissural input to T stellate cells. This inhibition is fast acting (duration, <10 msec), occurring with little synaptic delay ( approximately 0.3 msec). Electrical stimulation also revealed the initiation of antidromic responses in the onset chopper population, signifying D stellate neurons as a source of commissural inputs. Activation of the commissural connection was most evident in response to broadband stimuli. These results provide the first compelling evidence of a fast, monosynaptic commissural pathway arising from contralateral D stellate neurons providing broadband inhibitory input to T stellate cells.


[The effect of noradrenaline on the neuronal reactions of the motor cortex evoked by conditional stimulation].
In chronic experiments on cats the influence of iontophoretic application of adrenomimetic ephedrin and beta-adrenoblocker obsidan (propranolol) on motor cortex neuron reactions following conditional stimuli was investigated under instrumental placing reaction. It was shown for a majority of neurons that the background impulse activity and reactions following conditional stimulation were suppressed by the influence of ephedrin and on the contrary were increased by obsidan application. It is concluded that there exists a consistent tonic suppressing influence of the noradrenergic system on background and evoked cortical neurons impulse activity in the natural state. It is supposed that noradrenergic influence temporal increase may serve as an important link in mechanisms of external inhibition during stress situations, aversive effects, and distractive external excitations.


Targeted transferrin-modified polymeric micelles: enhanced efficacy in vitro and in vivo in ovarian carcinoma.
In this study, transferrin (Tf)-modified poly(ethylene glycol)-phosphatidylethanolamine (mPEG-PE) micelles loaded with the poorly water-soluble drug, R547 (a potent and selective ATP-competitive cyclin-dependent kinase (CDK) inhibitor), were prepared and evaluated for their targeting efficiency and cytotoxicity in vitro and in vivo to A2780 ovarian carcinoma cells, which overexpress transferrin receptors (TfR). At 10 mM lipid concentration, both Tf-modified and plain micelles solubilized 800 μg of R547. Tf-modified micelles showed enhanced interaction with A2780 ovarian carcinoma cells in vitro. The involvement of TfR in endocytosis of Tf-modified micelles was confirmed by colocalization studies of micelle-treated cells with the endosomal marker Tf-Alexa488. We confirmed endocytosis of micelles in an intact form with micelles loaded with a fluorescent dye and additionally labeled with fluorescent lipid. The in vitro cytotoxicity and in vivo tumor growth inhibition studies in A2780-tumor bearing mice confirmed the enhanced efficacy of Tf-modified R547-loaded micelles compared to free drug solution and to nonmodified micelles. The results of this study demonstrate the potential application of Tf-conjugated polymeric micelles in the treatment of tumors overexpressing TfR.


Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor Iressa (ZD1839, Gefitinib).
Iressa (ZD1839, Gefitinib), used in clinics to treat non-small cell lung cancer patients, is a tyrosine kinase receptor inhibitor that leads to specific decoupling of epidermal growth factor receptor (EGFR) signaling. Recent data indicate that Iressa is especially effective in tumors with certain EGFR mutations; however, a subset of these tumors does not respond to Iressa. In addition, certain populations have an elevated risk of side effects during Iressa treatment. The human ABCG2 (BCRP/MXR/ABCP) transporter causes cancer drug resistance by actively extruding a variety of cytotoxic drugs, and it functions physiologically to protect our tissues from xenobiotics. Importantly, ABCG2 modifies absorption, distribution, and toxicity of several pharmacologic agents. Previously, we showed that ABCG2 displays a high-affinity interaction with several tyrosine kinase receptor inhibitors, including Iressa. Here, we show that the expression of ABCG2, but not its nonfunctional mutant, protects the EGFR signaling-dependent A431 tumor cells from death on exposure to Iressa. This protection is reversed by the ABCG2-specific inhibitor, Ko143. These data, reinforced with cell biology and biochemical experiments, strongly suggest that ABCG2 can actively pump Iressa. Therefore, variable expression and polymorphisms of ABCG2 may significantly modify the antitumor effect as well as the absorption and tissue distribution of Iressa.


Impact of changes in the methodology of external price referencing on medicine prices: discrete-event simulation.
Several governments apply the policy of external price referencing (EPR), which considers the prices of a medicine in one or more other countries for the purpose of setting the price in the own country. Different methodological choices can be taken to design EPR. The study aimed to analyse whether, or not, and how changes in the methodology of EPR can impact medicine prices. The real-life EPR methodology as of Q1/2015 was surveyed in all European Union Member States (where applicable), Iceland, Norway and Switzerland through a questionnaire responded by national pricing authorities. Different scenarios were developed related to the parameters of the EPR methodology. Discrete-event simulations of fictitious prices in the 28 countries of the study that had EPR were run over 10 years. The continuation of the real-life EPR methodology in the countries as surveyed in 2015, without any change, served as base case. In most scenarios, after 10 years, medicine prices in all or most surveyed countries were-sometimes considerably-lower than in the base case scenario. But in a few scenarios medicine prices increased in some countries. Consideration of discounts (an assumed 20% discount in five large economies and the mandatory discount in Germany, Greece and Ireland) and determining the reference price based on the lowest price in the country basket would result in higher price reductions (on average - 47.2% and - 34.2% compared to the base case). An adjustment of medicine price data of the reference countries by purchasing power parities would lead to higher prices in some more affluent countries (e.g. Switzerland, Norway) and lower prices in lower-income economies (Bulgaria, Romania, Hungary, Poland). Regular price revisions and changes in the basket of reference countries would also impact medicine prices, however to a lesser extent. EPR has some potential for cost-containment. Medicine prices could be decreased if certain parameters of the EPR methodology were changed. If public payers aim to apply EPR to keep medicine prices at more affordable levels, they are encouraged to explore the cost-containment potential of this policy by taking appropriate methodological choices in the EPR design.


Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses.
To elucidate the nature of signals that control the level and spatial distribution of mRNAs encoding acetylcholine receptor (AChR), alpha-, beta-, gamma-, delta- and epsilon-subunits in muscle fibers chronic paralysis was induced in rat leg muscles either by surgical denervation or by different neurotoxins that cause disuse of the muscle or selectively block neuromuscular transmission pre- or postsynaptically and cause an increase of AChRs in muscle membrane. After paralysis, the levels and the spatial distributions of the different subunit-specific mRNAs change discoordinately and seem to follow one of three different patterns depending on the subunit mRNA examined. The level of epsilon-subunit mRNA and its accumulation at the end-plate are largely independent on the presence of the nerve or electrical muscle activity. In contrast, the gamma-subunit mRNA level is tightly coupled to innervation. It is undetectable or low in innervated normally active muscle and in innervated but disused muscle, whereas it is abundant along the whole fiber length in denervated muscle or in muscle in which the neuromuscular contact is intact but the release of transmitter is blocked. The alpha-, beta-, and delta-subunit mRNA levels show a different pattern. Highest amounts are always found at end-plate nuclei irrespective of whether the muscle is innervated, denervated, active, or inactive, whereas in extrasynaptic regions they are tightly controlled by innervation partially through electrical muscle activity. The changes in the levels and distribution of gamma- and epsilon-subunit-specific mRNAs in toxin-paralyzed muscle correlate well with the spatial appearance of functional fetal and adult AChR channel subtypes along the muscle fiber. The results suggest that the focal accumulation at the synaptic region of mRNAs encoding the alpha-, beta-, delta-, and epsilon-subunits, which constitute the adult type end-plate channel, is largely determined by at least two different neural factors that act on AChR subunit gene expression of subsynaptic nuclei.


Regional and cellular expression of the parkin gene in the rat cerebral cortex.
A mutation in the parkin gene has been identified as the cause for an autosomal recessively inherited form of early onset Parkinson's disease. We have recently isolated the mRNA coding for the rat homologue of parkin and showed its widespread expression in the central nervous system (CNS) by in situ hybridization. In the present study we investigated the distribution of parkin in the rat cerebral cortex with a polyclonal antibody that reacts with a single approximately 52-kDa protein, corresponding to the predicted molecular mass of parkin. Conventional light microscopic studies revealed intense parkin immunoreactivity (IR) throughout the cortex. Examination of mixed cortical neuro-glial cultures by indirect immunofluorescence technique coupled to traditional epifluorescence and confocal microscopy analysis demonstrated the expression of parkin in the cytoplasm and neurites of neurons, and its absence in glial fibrillary acidic protein (GFAP)-positive astrocytes. The predominant neuronal parkin-IR and -mRNA expression was confirmed by Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR), respectively, performed on highly enriched neuronal and type I astrocytes cultures. The information gathered in our study about the cellular and subcellular distribution of parkin should facilitate further research on its physiological role in the nervous system.


Δ(9)-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells.
We recently reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ(9)-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ(9)-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ(9)-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ(9)-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ(9)-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ(9)-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ(9)-THC up-regulation of FA2H in MDA-MB-231 cells.


Prevalence, Bacterial Load, and Antimicrobial Resistance of Salmonella Serovars Isolated From Retail Meat and Meat Products in China.
Salmonella remains the leading cause of reported bacterial foodborne disease in China. Meat products are recognized as one of the major sources of human salmonellosis; however, there is a lack of comprehensive, quantitative data concerning Salmonella contamination of these foods. Therefore, the objectives of this study were to investigate the prevalence, bacterial load, and antimicrobial resistance profiles of various Salmonella serovars in retail meat across the whole of China. Between July 2011 and June 2016, a total of 807 retail meat samples were collected, covering most provincial capitals in China. Overall, 159 (19.7%) samples tested positive for Salmonella. The highest contamination rate occurred in pork (37.3%, n = 287), followed by beef (16.1%, n = 161), mutton (10.9%, n = 92), dumplings (6.6%, n = 212), and smoked pork (3.6%, n = 55). Most probable number (MPN) analysis revealed that contamination was mainly in the range of 0.3-10 MPN/g among those samples testing positive using this method (n = 83), with eight samples exceeding 110 MPN/g. Among the 456 Salmonella enterica subsp. enterica isolates obtained in this study, 29 serovars and 33 multilocus sequence typing patterns were identified, with S. Derby, S. Typhimurium, S. London, S. Rissen, S. 1,4,[5],12:i:-, S. Weltevreden, and S. Enteritidis being the most prevalent. Among the 218 non-duplicate isolates, 181 (83.0%) were resistant to at least one class of antimicrobials and 128 (58.7%) were resistant to at least three classes. High rates of resistance were observed for tetracycline (65.6%), ampicillin (45.4%), trimethoprim-sulfamethoxazole (40.8%), streptomycin (40.4%), and nalidixic acid (35.8%), with the seven most prevalent serovars, except S. Weltevreden, showing higher rates of resistance and multidrug resistance compared with the less dominant serovars. Of note, all S. Indiana isolates exhibited resistance to extended-spectrum cephalosporins (including ceftriaxone and cefepime), ciprofloxacin, and multiple other classes of antibiotics. Further, two S. 1,4,[5],12:i:- isolates showed resistance to imipenem. This study provides systematic and comprehensive data on the prevalence and antimicrobial resistance profiles of various Salmonella serovars isolated from meat products in China, indicating their potential risk to public health.


Capsids are formed in a mutant virus blocked at the maturation site of the UL26 and UL26.5 open reading frames of herpes simplex virus type 1 but are not formed in a null mutant of UL38 (VP19C).
Previously we reported that null mutant viruses of UL19 (VP5) or of UL18 (VP23), essential components of herpes simplex virus type 1 (HSV-1) capsid shells, do not form precursor capsid structures as judged by sedimentation and electron microscope analysis. A goal of the present experiments was to isolate a null mutant virus for the remaining essential component of capsid shells, VP19C, encoded by the UL38 open reading frame (ORF). Furthermore, we wished to determine if a virus altered in the UL26 maturation cleavage site at residues 610 and 611 produced a lethal phenotype. Therefore, we decided to isolate cell lines that encode and express multiple capsid genes. Several cell lines were isolated by transformation of Vero cells and one designated C32 expressed all of the essential capsid proteins. Using this cell line we isolated a null mutant virus in the UL38 ORF and a mutant virus that was altered at residues 610 and 611 of the UL26 and UL26.5 gene products. We found that the null mutant in VP19C did not form a detectable product as judged by sedimentation and electron microscope analyses following infection of nonpermissive cells. The mutant virus altered at the UL26 maturation site resulted in the accumulation of B capsids. Therefore, cleavage at this site was essential for the maturation of B capsids into C capsids. Interestingly, the absence of cleavage at the maturation site was required for the retention of VP24 in the capsid.


Incidental cholecystectomy in the over-70 age group. A 19-year retrospective, comparative study.
To analyse the outcome of incidental cholecystectomy in the over 70 age-group during surgery for gastrointestinal malignancies. Nineteen-year retrospective, comparative study. Department of Surgery B, Belinson Campus, Rabin Medical Center. The hospitalization records of 4,072 patients who underwent cholecystectomy between 1975 and 1994 were reviewed. The incidental cholecystectomy cases for this period were identified and those performed during surgery for gastrointestinal malignancy were analysed separately. A sex- and age-matched control group was identified for comparison. Postoperative complications, overall morbidity and mortality, postoperative hospitalization days. Statistical differences in gallbladder-related complications and mortality among groups. Mortality and overall morbidity were significantly increased in the no-cholecystectomy group. Hospitalization days were increased significantly in the group not under-going cholecystectomy and although it didn't reach statistical significance, there was a clear trend for increased number of pulmonary complication in this same group. Sepsis and multiorgan failure, as an expression of acutely, postoperative symptomatic gallbladder were the major cause of death in the no-incidental-cholecystectomy group. Incidental cholecystectomy is safe and should be considered in every case of abdominal surgery, regardless of the age of the patient. In the over 70 age group, complication and mortality rates increase significantly and dreadfully when the gallbladder is left in situ after surgery for gastrointestinal tumors. Incidental cholecystectomy is not warranted in patients undergoing palliative procedures or in whom life expectancy is less than 6 months.


The representation of sound localization cues in the barn owl's inferior colliculus.
The barn owl is a well-known model system for studying auditory processing and sound localization. This article reviews the morphological and functional organization, as well as the role of the underlying microcircuits, of the barn owl's inferior colliculus (IC). We focus on the processing of frequency and interaural time (ITD) and level differences (ILD). We first summarize the morphology of the sub-nuclei belonging to the IC and their differentiation by antero- and retrograde labeling and by staining with various antibodies. We then focus on the response properties of neurons in the three major sub-nuclei of IC [core of the central nucleus of the IC (ICCc), lateral shell of the central nucleus of the IC (ICCls), and the external nucleus of the IC (ICX)]. ICCc projects to ICCls, which in turn sends its information to ICX. The responses of neurons in ICCc are sensitive to changes in ITD but not to changes in ILD. The distribution of ITD sensitivity with frequency in ICCc can only partly be explained by optimal coding. We continue with the tuning properties of ICCls neurons, the first station in the midbrain where the ITD and ILD pathways merge after they have split at the level of the cochlear nucleus. The ICCc and ICCls share similar ITD and frequency tuning. By contrast, ICCls shows sigmoidal ILD tuning which is absent in ICCc. Both ICCc and ICCls project to the forebrain, and ICCls also projects to ICX, where space-specific neurons are found. Space-specific neurons exhibit side peak suppression in ITD tuning, bell-shaped ILD tuning, and are broadly tuned to frequency. These neurons respond only to restricted positions of auditory space and form a map of two-dimensional auditory space. Finally, we briefly review major IC features, including multiplication-like computations, correlates of echo suppression, plasticity, and adaptation.