Middle cerebral artery blood flow velocity, end-tidal pC02 and blood pressure in patients with obstructive sleep apnea and in healthy subjects during continuous positive airway pressure breathing.
There is conflicting evidence in the literature as to the potential effect of continuous positive airway pressure (CPAP) on cerebral perfusion. Compromising cerebral perfusion could possibly outweigh the benefit of improved oxygenation. Patients with the obstructive sleep apnea syndrome (OSAS) have been claimed to have a higher cerebrovascular reactivity to changes in end-tidal pC02. In this study, we investigated 23 patients with OSAS and 7 6 healthy young adults in the waking state. Both groups performed a series of lOmin of normal breathing, 20min with 9 cmH20 nasal CPAP, and then TOmin of normal breathing while wearing a nasal CPAP mask. The following parameters were assessed: bilateral transcranial Doppler signal of the middle cerebral artery, systolic and diastolic blood pressure assessed manually, and cerebrovascular reactivity to changes in pC02 during hyperventilation and rebreathing into an airbag. Continuous end-tidal pC02 measurements were performed in 74 subjects. As compared with normal breathing middle cerebral artery blood flow velocity and pC02 remained unchanged during CPAP. Systolic and diastolic blood pressure increased slightly by 1.2mmHg (p = 0.015) and 1.1 mmHg (p = 0.007), respectively. Cerebrovascular reactivity did not differ in the two groups. Nasal CPAP of 9 cmH20 is a safe treatment with respect to the maintenance of cerebral blood flow. Our study gives further evidence for the autoregulation's capacity to maintain cerebral blood flow velocity constant during different levels of intrathoracic pressure and different cerebral perfusion pressures. We could not demonstrate any difference in cerebrovascular reactivity between patients with OSAS and healthy persons. [Neurol Res 1999; 21: 737-741].


Correlated disordered interactions on Potts models.
Using a weak-disorder scheme and real-space renormalization-group techniques, we obtain analytical results for the critical behavior of various q-state Potts models with correlated disordered exchange interactions along d(1) of d spatial dimensions on hierarchical (Migdal-Kadanoff) lattices. Our results indicate qualitative differences between the cases d-d(1)=1 (for which we find non-physical random fixed points, suggesting the existence of non-perturbative fixed distributions) and d-d(1)>1 (for which we do find acceptable perturbative random fixed points), in agreement with previous numerical calculations by Andelman and Aharony [Phys. Rev. B 31, 4305 (1985)]. We also rederive a criterion for relevance of correlated disorder, which generalizes the usual Harris criterion.


A Rare Case of Eosinophilic Granulomatosis with Polyangiitis Associated with Cryoglobulinemia Presenting with a Bullous Skin Eruption of the Lower Limbs.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody- (ANCA-) associated small vessel vasculitis with multisystem involvement. It is characterized with asthma, eosinophilia, and renal and peripheral nervous system involvement. However, EGPA presenting with bullous skin eruption is an uncommon dermatological manifestation. We report a rare case of EGPA overlapped with mixed essential cryoglobulinemia presenting with a bullous skin eruption. A 49-year-old female presented with bilateral lower limb erythematous bullous rash with bilateral lower limb numbness. She had bilateral ankle edema with frothyuria and a recent onset wheeze. Blood investigations revealed a marked peripheral eosinophilia with positive P-ANCA. Skin biopsy was suggestive of leukocytoclastic vasculitis. She also had positive cryoglobulins with a high rheumatoid factor titre. The patient was diagnosed of having EGPA with overlapping mixed essential cryoglobulinemia. Her skin eruptions and systemic manifestations improved with prednisolone and cyclophosphamide therapy. EGPA can rarely present with a bullous skin eruption and may rarely associate with secondary cryoglobulinemia. Early recognition of these rare manifestations and prompt treatment would prevent further complications and death.


Ferrocyanide - a novel catalyst for oxymyoglobin oxidation by molecular oxygen.
A comparative study of the rates of ferrocyanide-catalyzed oxidation of several oxymyoglobins by molecular oxygen is reported. Oxidation of the native oxymyoglobins from sperm whale, horse and pig, as well as the chemically modified (MbO(2)) sperm whale oxymyoglobin, with all accessible His residues alkylated by sodium bromoacetate (CM-MbO(2)), and the mutant sperm whale oxymyoglobin [MbO(2)(His119-->Asp)], was studied. The effect of pH, ionic strength and the concentration of anionic catalyst ferrocyanide, [Fe(CN)(6)](4-), on the oxidation rate is investigated, as well as the effect of MbO(2) complexing with redox-inactive Zn(2+), which forms the stable chelate complex with functional groups of His119, Lys16 and Asp122, all located nearby. The catalytic mechanism was demonstrated to involve specific [Fe(CN)(6)](4-) binding to the protein in the His119 region, which agrees with a high local positive electrostatic potential and the presence of a cavity large enough to accommodate [Fe(CN)(6)](4-) in that region. The protonation of the nearby His113 and especially His116 plays a very important role in the catalysis, accelerating the oxidation rate of bound [Fe(CN)(6)](4-) by dissolved oxygen. The simultaneous occurrence of both these factors (i.e. specific binding of [Fe(CN)(6)](4-) to the protein and its fast reoxidation by oxygen) is necessary for the efficient ferrocyanide-catalyzed oxidation of oxymyoglobin.


Breaking bad news.
Breaking bad news has been ignored in the past and still depends largely on culture and social state. We experience now a strong trend towards full information in modern societies. The article describes the typical stages patients go through when dealing with bad news. Recommendations how to break bad news stress the importance of privacy and enough time, the necessity to learn how much knowledge is pre-existing, to wait until the patient signalizes readiness, to give the information in small, understandable portions, to recognize and encourage emotions and to sum up and schedule further meetings. A special appraisal of the situation in gastrointestinal endoscopy is given.


Mixed quantum-classical molecular dynamics simulation of vibrational relaxation of ions in an electrostatic field.
The vibrational relaxation of ions in low-density gases under the action of an electrostatic field is reproduced through a molecular dynamics simulation method. The vibration is treated though quantum mechanics and the remaining degrees of freedom are considered classical. The procedure is tested through comparison against analytic results for a two-dimensional quantum model and by studying energy exchange during binary ion-atom collisions. Finally, the method has been applied successfully to the calculation of the mobility and the vibrational relaxation rate of O2+ in Kr as a function of the mean collision energy using a model interaction potential that reproduces the potential minimum of a previously known ab initio potential surface. The calculation of the steady mean vibrational motion of the ions in (flow) drift tubes seems straightforward, though at the expense of large amounts of computer time.


New perspectives on the storage and organization of muscle glycogen.
Due to its large mass, skeletal muscle contains the largest depot of stored carbohydrate in the body in the form of muscle glycogen. Readily visualized by the electron microscope, glycogen granules appear as bead-like structures localized to specific subcellular locales. Each glycogen granule is a functional unit, not only containing carbohydrate, but also enzymes and other proteins needed for its metabolism. These proteins are not static, but rather associate and dissociate depending on the carbohydrate balance in the muscle. This review examines glycogen-associated proteins, their interactions, and roles in regulating glycogen metabolism. While certain enzymes such as glycogen synthase and glycogen phosphorylase have been extensively studied, other proteins such as the glycogen initiating and targeting proteins are just beginning to be understood. Two metabolically distinct forms of glycogen, pro- and marcoglycogen have been identified that vary in their carbohydrate complement per molecule and have different sensitivities to glycogen synthesis and degradation. Glycogen regulation takes place not only by allosteric regulation of enzymes, but also due to other factors such as subcellular location, granule size, and association with various glycogen-related proteins.


Molecular characterization of cryptosporidium in children aged 0- 5 years with diarrhea in Jos, Nigeria.
Cryptosporidium is an important cause of diarrhea in children and immune-compromised individuals. Recent advances in molecular diagnostics have led to the discovery of subtype families that are thought to be more commonly associated with diarrhea. We aimed to isolate and characterize Cryptosporidium spp among children with diarrhea in Jos, Nigeria. Stool samples were collected from165 children aged 0-5 years with diarrhea. Cryptosporidium oocysts were examined by wet mount preparation, using formalin ether and a modified acid fast staining method. DNA was extracted from positive samples using QIAamp DNA stool mini kit and PCR-RFLP assay was carried out after quantification. Genotyping and phylogenetic analysis were done to determine the subtype families and their relatedness. From the 165 children studied, 8 (4.8%) were infected with Cryptosporidium. PCR-RFLP assay and genotype characterization found the following Cryptosporidium species: C. hominis 6 (75%) and C. parvum 2 (25.0%), with family subtypes Id-5, Ie-1 and IIa-1, IId-1 respectively.The most common species was C. hominis and the frequent subtype was C. hominis-Id 5 (62.5%). Cryptosporidium is not an uncommon cause of diarrhea in children, with C. hominis being the dominant species. Also C. hominis Id is the commonest sub-family subtype. Put together, zoonotic species may be an important cause of diarrhea in children aged 0-5 years in Jos, Nigeria.


Luminescent thermometer based on Eu3+ /Tb3+ -organic-functionalized mesoporous silica.
In this work we investigate a mesoporous silica (MS) decorated with dipyridyl-pyridazine (dppz) ligands and further grafted with a mixture of Eu3+ /Tb3+ ions (28.45%:71.55%), which was investigated as a potential thermometer in the 10-360 K temperature range. The MS material was prepared employing a hetero Diels-Alder reaction: 3,6-di(2-pyridyl)-1,2,4,5-tetrazine was reacted with the double bonds of vinyl-silica (vSilica) followed by an oxidation procedure. We explore using the dppz-vSilica material to obtain visible emitting luminescent materials and for obtaining a luminescent thermometer when grafted with Eu3+ /Tb3+ ions. For the dppz-vSilica@Eu,Tb material absolute sensitivity Sa of 0.011 K-1 (210 K) and relative sensitivity Sr of 1.32 %K-1 (260 K) were calculated showing good sensing capability of the material. Upon temperature change from 10 K to 360 K the emission color of the material changed gradually from yellow to red.


Oncogenes are to lose control on signaling following mutation: should we aim off target?
Rationalized cancer therapy aims at blocking overactive signaling pathways in cancer cells using kinase inhibitors. Essential for its success is the identification of suitable drug targets. Several recent reports have shown that by using control analysis, one can determine which component of a pathway is in control of its output. However, it has not been analyzed how a mutation in an oncogene affects the extent to which the various components are important. Are the same proteins still important after an oncogene has been activated? In the present study, we show that, upon mutation, oncogenes such as mutant kinases tend to lose part of their control on signaling. On the other hand, some of the nonmutated genes may become more important, when compared to the situation before the mutation. This may imply that, perhaps paradoxically, signaling proteins encoded by nonmutated genes should make better drug targets against cancer.


Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice.
Fragile X syndrome (FXS) is caused by silencing of the FMR1 gene leading to loss of the protein product fragile X mental retardation protein (FMRP). FXS is the most common monogenic cause of intellectual disability. There are two known mammalian paralogs of FMRP, FXR1P, and FXR2P. The functions of FXR1P and FXR2P and their possible roles in producing or modulating the phenotype observed in FXS are yet to be identified. Previous studies have revealed that mice lacking Fxr2 display similar behavioral abnormalities as Fmr1 knockout (KO) mice. In this study, we expand upon the behavioral phenotypes of Fmr1 KO and Fxr2+/- (Het) mice and compare them with Fmr1 KO/Fxr2 Het mice. We find that Fmr1 KO and Fmr1 KO/Fxr2 Het mice are similarly hyperactive compared to WT and Fxr2 Het mice. Fmr1 KO/Fxr2 Het mice have more severe learning and memory impairments than Fmr1 KO mice. Fmr1 KO mice display significantly impaired social behaviors compared to WT mice, which are paradoxically reversed in Fmr1 KO/Fxr2 Het mice. These results highlight the important functional consequences of loss or reduction of FMRP and FXR2P.


Gelsolin restores A beta-induced alterations in choroid plexus epithelium.
Histologically, Alzheimer's disease (AD) is characterized by senile plaques and cerebrovascular amyloid deposits. In previous studies we demonstrated that in AD patients, amyloid-beta (A beta) peptide also accumulates in choroid plexus, and that this process is associated with mitochondrial dysfunction and epithelial cell death. However, the molecular mechanisms underlying A beta accumulation at the choroid plexus epithelium remain unclear. A beta clearance, from the brain to the blood, involves A beta carrier proteins that bind to megalin, including gelsolin, a protein produced specifically by the choroid plexus epithelial cells. In this study, we show that treatment with gelsolin reduces A beta-induced cytoskeletal disruption of blood-cerebrospinal fluid (CSF) barrier at the choroid plexus. Additionally, our results demonstrate that gelsolin plays an important role in decreasing A beta-induced cytotoxicity by inhibiting nitric oxide production and apoptotic mitochondrial changes. Taken together, these findings make gelsolin an appealing tool for the prophylactic treatment of AD.


Strain Modulation by van der Waals Coupling in Bilayer Transition Metal Dichalcogenide.
Manipulation of lattice strain is emerging as a powerful means to modify the properties of low-dimensional materials. Most approaches rely on external forces to induce strain, and the role of interlayer van der Waals (vdW) coupling in generating strain profiles in homobilayer transition metal dichalcogenide (TMDC) films is rarely considered. Here, by applying atomic-resolution electron microscopy and density functional theory calculations, we observed that a mirror twin boundary (MTB) modifies the interlayer vdW coupling in bilayer TMDC films, leading to the development of local strain for a few nanometers in the vicinity of the MTB. Interestingly, when a single MTB in one layer is "paired" with another MTB in an adjacent layer, interlayer-induced strain is reduced when the MTBs approach each other. Therefore, MTBs are not just 1D discontinuities; they can exert localized 2D strain on the adjacent lattices.


Self-reported defence mechanisms as an outcome measure in psychotherapy: a study on the German version of the Defence Style Questionnaire DSQ 40.
The psychoanalytically informed construct of 'defence mechanisms' is of central importance for the understanding of the dynamics of inner conflicts and the onset of neurotic symptoms. Objective and valid assessment of 'defence' is difficult. There are a number of observer rating instruments but only few self-report questionnaires. The German version of the 'Defence Style Questionnaire - DSQ 40' (Andrews, Singh, & Bond, 1993) was examined with regard to its factorial and content validity, and its sensitivity to change during inpatient psychotherapy. One hundred and fifty-five patients with mixed diagnoses were administered the DSQ 40 and the SCL-90-R before and after 3 months of inpatient psychotherapy. Diagnoses were mostly affective and anxiety disorders as well as eating disorders, and there was a high comorbidity of personality disorders. After deletion of some items due to insufficient pairwise item-intercorrelation or false classification to a defence mechanism by experienced clinicians, we found three stable factors of defence (maladaptive, intermediate-neurotic and adaptive) consistent with the previous research. After 3 months of therapy, a decrease in maladaptive mechanisms and an increase in adaptive patterns were found, while neurotic mechanisms did not change on average. Our shortened version of the DSQ 40 was shown to be a valid instrument for the assessment of defence mechanisms and change in these mechanisms after psychotherapy. Our design did not permit an assessment of whether or not the change in defence mechanisms was due to the therapeutic treatment.


Circulating neuroactive C21- and C19-steroids in young men before and after ejaculation.
Twelve neuroactive and neuroprotective steroids, androgens and androgen precursors i.e. 3alpha,17beta-dihydroxy-5alpha-androstane, 3alpha-hydroxy-5alpha-androstan-17-one, 3alpha-hydroxy-5beta-androstan-17-one, androst-5-ene-3beta,17beta-diol, 3beta,17alpha-dihydroxy-pregn-5-en-20-one (17alpha-hydroxy-pregnenolone), 3beta-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, androst-4-ene-3,17-dione (androstenedione), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), 3beta-hydroxy-pregn-5-en-20-one (pregnenolone), 7alpha-hydroxy-DHEA, and 7beta-hydroxy-DHEA were measured using the GC-MS system in young men before and after ejaculation provoked by masturbation. The circulating level of 17alpha-hydroxypregnenolone increased significantly, whereas the other circulating steroids were not changed at all. This fact speaks against the hypothesis that a drop in the level of neuroactive steroids, e.g. allopregnanolone may trigger the orgasm-related increase of oxytocin, reported by other authors.


Nonequilibrium pattern formation in the crystallization of polymer blend films.
We show that the morphology of polyethylene oxide crystallization in thin films can be tuned to obtain circular spherulites, seaweed and symmetric dendrites, and fractal aggregation forms through the addition of clay particles and the amorphous polymer, polymethyl methacrylate. The thin-film polymer crystallization patterns are compared to a two-dimensional phase field model of dendritic growth in Ni/Cu alloys with a variable surface tension anisotropy epsilon. Some aspects of polymer crystallization patterns can be understood from the phase field calculations, but a more general model is required to describe the full range of observed patterns.


Public attitudes toward psychiatric treatment. An international comparison.
In order to examine whether there is a relationship between the state of mental health care and the acceptance of psychiatry, public attitudes toward psychiatric treatment in three countries where the reform of mental health care has progressed to a different degree will be compared. Population surveys on public beliefs about mental illness and attitudes toward psychiatric treatment were conducted in Bratislava, Slovak Republic, and Novosibirsk, Russia. The data were compared with those from a population survey that had recently been carried out in Germany. In all three surveys, the same sampling procedure and fully structured interview were applied. Although respondents from all three countries were equally inclined to seek help from mental health professionals, those from Bratislava and Novosibirsk tended to recommend more frequently to address other medical or nonmedical professionals or members of the lay support system. In all three countries, psychotherapy was the most favored treatment modality, followed by psychotropic medication. Although natural remedies were more frequently recommended in Bratislava and Novosibirsk, meditation/yoga was more popular among the German public. Across all three countries, the endorsement of a brain disease as cause was associated with a greater willingness to seek help from medical professionals (psychiatrist, GP). Respondents who adopted biological causes tended to recommend psychotropic medication more frequently. In countries with less developed mental health care systems, there appears to be a tendency of the public toward more frequently relying on helping sources outside the mental health sector and on traditional "alternative" treatment methods. However, it is our prognosis that with the progress of reforms observed, differences may further decrease.


Highlights from the Biennial International Congress on Schizophrenia Research (ICOSR), March 24-March 28, 2017.
The 2017 International Congress on Schizophrenia Research, held in San Diego, California (March 24-28, 2017), attracted over 900 attendees from 34 countries. With the gracious assistance of Congress president James Meador-Woodruff, we bring you the following reports on the prospects for new drugs to treat schizophrenia.


[Agonists of beta2 adrenergic receptor in the therapy of obstructive diseases].
Inhaled bronchodilators are a basic element of the pharmacologic management of asthma and COPD. Long-acting beta2-agonists (LABAs) are recommended for use by a majority of recent guidelines as a maintenance treatment in asthma and COPD. It was documented that these medications improve objective measures of lung function and reduce main symptoms of diseases. However inhaled LABAs have been reported to increase some cardiovascular diseases and contribute to the occurrence of arrhythmias. Few studies have documented the sufficient observations to show that LABAs are safe in clinical practice and are still an essential in therapy in patients with obstructive diseases.


A phenylalanine-55 to serine amino-acid substitution in the human glycoprotein IX leucine-rich repeat is associated with Bernard-Soulier syndrome.
The platelet membrane glycoprotein (GP) Ib-IX-V complex, the major von Willebrand factor receptor on platelets, is absent or dysfunctional in patients with the Bernard-Soulier syndrome (BSS). The four single subunits of the GPIb-IX-V complex (GPIb alpha, Ib beta, IX and V) are molecular products of different genes. Several point mutations and deletions affecting the GPIb alpha gene have been identified as the cause of BSS, whilst in four BSS families a GPIX gene defect has been reported. Moreover, a single case of BSS has been associated with a genetic defect of GPIb beta. We investigated the molecular basis of another case of BSS with a deficient expression of GPIX, as detected by immunofluorescence studies. After amplification of the entire GPIX coding region, nucleotide sequence analysis showed a homozygous single point mutation predicting a phenylalanine to serine substitution at position 55 of the mature GPIX within its unique leucine-rich repeat. By allele-specific oligonucleotide hybridization we confirmed the homozygosity of the patient as well as the carrier state of two out of three of his children studied. Although the parents of the patient, who were first cousins, were no longer alive and thus not available for study, we speculate that the molecular defect observed in the proband was inherited from both parents, who probably were heterozygous for this GPIX gene defect. This study confirms that BSS may be caused by many different subtle molecular defects that often prevent the assembly and expression of a functional GPIb-IX-V complex.


Immunization with PhtD truncated fragments reduces nasopharyngeal colonization by Streptococcus pneumoniae.
Despite the undeniable success of polysaccharide vaccines against Streptococcus pneumoniae infections, there is a consensus on the scientific field that this approach should be revised in order to overpass the problems related with these formulations, such as serotype replacement and high production costs. The study of conserved pneumococcal proteins or its truncated fragments has emerged as a serotype independent alternative. In this work, we have characterized the immune response elicited by systemic immunization of mice with the Histidine triad protein D (PhtD) and its' amino and carboxyl terminal fragments. The proteins were shown to be immunogenic and protective against pneumococcal colonization, with increased IL-17 production, and induction of antibodies able to limit pneumococcal adhesion to human respiratory cells. Antiserum against PhtD_Nter, but not C_ter or PhtD, promoted an increase in bacterial phagocytosis in vitro. Interestingly, antibodies against the PhtD_Nter displayed cross-reactivity with two other pneumococcal proteins, PspA and PspC, due to sequence similarities in the proline rich region of the molecules. On a whole, our results support the inclusion of PhtD, and more specifically, its N-terminal fragment, in a multicomponent serotype independent vaccine.


Increased tube formation and up-regulation of FGFR3 mRNA expression in microvascular endothelial cell by exosomes derived from SW480-7.
Extracellular vesicles (exosome-like vesicles) are small membrane vesicles ranging from 20-200nm in size that are released by various cells into the extracellular space. These extracellular vesicles play a major role in cell-to-cell communication and contain materials, such as proteins, mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The effect of exosomes derived from an invasive colon cancer cell line on angiogenesis is unclear. Hence, the aim of this study is to investigate the effect of exosomes derived from an invasive colon cancer cell line on angiogenesis of endothelial cells. In the present study, the exosomes from the cell culture supernatants of an invasive colon cancer cell line SW480-7 were characterised. The effect on tube formation and expression of angiogenic genes in a microvascular endothelial cell, telomerase-immortalised microvascular endothelial cell (TIME) was examined after co-cultured with exosomes secreted from SW480-7. Zetasizer result showed average diameter of exosomes derived from SW480-7 was 246.2 nm and morphological analysis showed the size of majority of exosomes were less than 200 nm. Results showed that exosomes derived from SW480-7 increased tube formation and up-regulated FGFR3 mRNA expression in TIME. Our findings suggest that exosomes derived from SW480-7 increased tube formation and up-regulated expression of FGFR3 mRNA in TIME.


Dnd1-mediated epigenetic control of teratoma formation in mouse.
Spontaneous testicular teratoma develops from primordial germ cells (PGCs) in embryos; however, the molecular mechanisms underlying teratoma formation are not fully understood. Mutation of the dead-end 1 (Dnd1) gene, which encodes an RNA-binding protein, drastically enhances teratoma formation in the 129/Sv mouse strain. To elucidate the mechanism of Dnd1 mutation-induced teratoma formation, we focused on histone H3 lysine 27 (H3K27) trimethylation (me3), and found that the levels of H3K27me3 and its responsible methyltransferase, enhancer of zeste homolog 2 (Ezh2), were decreased in the teratoma-forming cells of Dnd1 mutant embryos. We also showed that Dnd1 suppressed miR-26a-mediated inhibition of Ezh2 expression, and that Dnd1 deficiency resulted in decreased H3K27me3 of a cell-cycle regulator gene, Ccnd1 In addition, Ezh2 expression or Ccnd1 deficiency repressed the reprogramming of PGCs into pluripotent stem cells, which mimicked the conversion of embryonic germ cells into teratoma-forming cells. These results revealed an epigenetic molecular linkage between Dnd1 and the suppression of testicular teratoma formation.


An Infrequent Cause of Apical Ventricular Aneurysm in the United States.
Chronic Chagas cardiomyopathy (CCC) is a late complication of Chagas disease with various manifestations including arrhythmia, heart failure, thromboembolism, and stroke. In a patient with symptoms of heart failure and left ventricular apical aneurysm unexplained by structural heart or coronary vascular abnormalities, CCC should be strongly considered and inquiry made about exposure status. Typical electrocardiographic findings of bundle branch block, complete heart blocks, and ventricular arrhythmia are helpful clues. A positive trypanosomal immunoglobulin G antibody is supportive. Initiation of stage appropriate guideline-recommended heart failure regimen is the goal with careful attention paid to prevention of sudden cardiac death from ventricular arrhythmias.


Genomic Profiling of Chronic Myelogenous Leukemia: Basic and Clinical Approach.
Chronic myeloid leukemia (CML) is a hematological stem cell cancer driven by BCR-ABL1 fusion protein. We review the previous and recent evidence on the significance of CML in diagnostic and clinic management. The technical monitoring of BCR-ABL1 with quantitative real time-PCR has been used in assessing patient outcome. The cytogenetic mark of CML is Philadelphia chromosome, that is formed by reciprocal chromosomal translocations between human chromosome 9 and 22, t(9:22) (q34:q11). It makes a BCR-ABL1 fusion protein with an anomaly tyrosine kinase activity that promotes the characteristic proliferation of progenitor cells in CML and acute lymphoblastic lymphoma. The targeting of BCR-ABL1 fusion kinase is the first novel paradigm of molecularly targeted curing.


[Experimental study on the viscoelastic properties of cancellous bone of the os calcaneus, os lunatum and os capitalum].
We have researched the viscoelastic properties of the cancellous bones of the os calcaneus, os lunatum and os capitalum. The compressing stress relaxation experiment and the creep experiment in the vertical, horizontal and 45 degree directions on the os calcaneus were performed. The data and curve of the compressing stress relaxation and creep were obtained. By masing regression analysis we worked out the compressing reduced stress relaxation and creep functions and curves. The results show that the quantities of compressing stress relaxation and creep of the calcaneus in the vertical direction are larger than those in the other two directions. The initial quantities of creep of the os capitalum are larger than those of the os lunatum, and there are no significant different between the quantities of stress relaxation of the cancellous bones of the os lunatum and os capitalum.


[Prevalence of caries and dental erosion among school children in The Hague from 1996-2005].
In 2005 a dental survey of the prevalence of caries among 6- and 12-year-old schoolchildren in The Hague was carried out. In the case of the 12-year-olds, the prevalence of dental erosion was also studied. The sample consisted of 814 students in twelve primary schools in The Hague. The results reveal that since the previous study, in 2002, the trend in the direction of an increasing percentage of children with deciduous caries-free teeth and permanent caries-free teeth had continued. In the case of the children who were not caries-free, it was noticeable that, in general, the number of new dental caries (dmfs- and DMFS-score) had not changed in the period 1996-2005, while the number of restorations among the 6- and 12-year olds had decreased. The mean restorative index in the deciduous dentition of 6-year-olds decreased from approximately 40% in 1996 to approximately 20% in 2005; with respect to permanant dentition among 12-year-olds, the percentage decreased from more than 90% to 60%. The percentage of 12-year-olds with dental erosion in 2005 remained unchanged as compared with 2002: 24%. The research revealed that there was no increase in dental caries or dental erosion among the 6- and 12-year-old school children in The Hague.


Perception of COVID-19 infection risk among students in healthcare professions: a qualitative study.
The aim of this study was to describe how students in healthcare professions perceived the risk of COVID-19 infection during their curricular internships in the post-lockdown period, in order to evaluate possible corrective and/or improvement actions to ensure future safe learning experiences. Is a descriptive qualitative study conducted in March 2021 using Focus Groups, with the participation of students from all the involved study programs, based on a voluntary proactive sampling approach. The study was conducted among students in healthcare professions at the University of Bologna, in collaboration with the Local Health Authority of Imola, who were undertaking curricular internships in various public or private healthcare, social, and non-healthcare settings, as specified in the educational plan. The results showed that the students reported having knowledge about preventive measures to avoid infection, being attentive observers of the organizational aspects within their internship contexts, and considering the internship tutor as a significant guiding figure in their perception of risk and the related measures to be adopted. Despite the challenges, the students evaluated their internship experience as an opportunity to acquire distinctive skills. Students who embarked on their internships without prior experience expressed additional and diverse aspects that warrant further investigation. Therefore, it was deemed necessary to conduct further qualitative research to broaden the perception of SARS-CoV-2 infection risk in this group of students.


Sequence, mapping and disruption of CCC1, a gene that cross-complements the Ca(2+)-sensitive phenotype of csg1 mutants.
We have isolated, sequenced, mapped and disrupted a novel gene, CCC1, from Saccharomyces cerevisiae. This gene displays non-allelic complementation of the Ca(2+)-sensitive phenotype conferred by the csg1 mutation. The ability of this gene, in two copies per cell, to reverse the csg1 defect suggests it may have a role in regulating Ca2+ homeostasis. The sequence of CCC1 indicates that it encodes a 322 amino acid, membrane-associated protein. The CCC1 gene is located on the right arm of chromosome XII.


Photocatalytic Abatement of Volatile Organic Compounds by TiO2 Nanoparticles Doped with Either Phosphorous or Zirconium.
The aim of this work is to study the activity of novel TiO2-based photocatalysts doped with either phosphorus or zirconium under a UV-Vis source. A set of mesoporous catalysts was prepared by the direct synthesis: TiO2_A and TiO2_B (titanium oxide synthesized by two different procedures), P-TiO2 and Zr-TiO2 (binary oxides with either nonmetal or metal into the TiO2 framework). Complementary characterizations (N2 physisorption at 77 K, X-ray powder diffraction (XRD), field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX) analysis, X-ray Photoelectron Spectroscopy (XPS), and (DR)UV-Vis spectroscopy) were used to investigate the physicochemical properties of the prepared catalysts. Then, the photocatalysts were tested for the oxidation of propylene and ethylene under UV-Vis light. As a result, the most promising catalyst for both the propylene and ethylene oxidation reactions was the P-TiO2 (propylene conversion = 27.8% and ethylene conversion = 13%, TOS = 3 h), thus confirming the beneficial effect of P-doping into the TiO2 framework on the photocatalytic activity.


Differential effects of 5-hydroxytryptaminergic antagonists upon apomorphine- and lergotrile-induced hypothermia and stereotyped behaviour in rats.
The dopaminergic stimulants apomorphine and lergotrile both evoked hypothermia and stereotyped behaviour in rats. These drug effects were sensitive to antagonism by haloperidol, a dopaminergic receptor blocker. In rats pretreated with 5-hydroxytryptaminergic receptor blockers, cinanserin reduced apomorphine-induced hypothermia but cyproheptadine did not. Both cinanserin and cyproheptadine significantly potentiated lergotrile-induced hypothermia. Similarly, the stereotypic effects of apomorphine were partly reduced by cyproheptadine, although higher doses of cyproheptadine did potentiate lergotrile-induced stereotyped behaviour. These findings of different influences of 5-HT antagonists upon the effects of apomorphine and lergotrile indicate that these two dopaminergic stimulants may not work in identical manner to produce outwardly similar drug effects.


[Overview of the HIV epidemics in France and worldwide ].
In 2012, an estimated 35.3 million people were living with HIV worldwide and new HIV infections (2.3 million) were down 20% compared to 2001. Over the past year, tremendous progress has been achieved in the fight against HIV, including expanded access to antiretroviral therapy (ART) and services to prevent mother-to-child transmission of HIV. However, progress is uneven. The regions most affected by HIV, Sub-Saharan Africa and the Caribbean, have seen a significant increase in ART coverage and drop in new HIV infections, while for other regions, such as the Middle East, North Africa, Eastern Europe and Central Asia, HIV trends have become worrisome. In many high-income countries, such as France, HIV epidemics are far from over, especially among men who have sex with men, where the HIV epidemic remains uncontrolled. Global, rapid scale-up of ART programs significantly decreased HIV/AIDS-related morbidity and mortality but has not been successful in preventing late HIV diagnosis. Reducing the time interval between HIV infection and diagnosis remains one of the biggest challenges that all HIV-affected countries have to face to further reduce HIV/AIDS-related mortality and control the HIV epidemic.


Novel Cellularly Active Inhibitor Regresses DDAH1 Induced Prostate Tumor Growth by Restraining Tumor Angiogenesis through Targeting DDAH1/ADMA/NOS Pathway.
Dimethylarginine dimethylaminohydrolase1 (DDAH1) inhibitors are important therapeutics by virtue of their ability to control nitric oxide (NO) production by elevating asymmetric dimethylarginine (ADMA) levels. In a screening campaign, we identified that DD1E5 (3-amino-6- tert-butyl-N-(1,3-thiazol-2-yl)-4-(trifluoromethyl)thieno[2,3- b]pyridine-2- carboxamide) inhibits the DDAH1 activity both in vitro and in cultured cells. Mechanistic studies found that DD1E5 is a competitive inhibitor (dissociation constant ( Ki) of 2.05 ± 0.15 μM). Enzyme kinetic assays showed time and concentration dependent inhibition of DDAH1 with DD1E5, which shows tight binding with an inactivation rate constant of 0.2756 ± 0.015 M-1 S-1. Treatment of cancer cells with DDAH1 inhibitors shows inhibition of cell proliferation and a subsequent decrease in NO production with ADMA accumulation. DD1E5 reversed the elevated VEGF, c-Myc, HIF-1α, and iNOS levels induced by exogenous DDAH1 overexpression in PCa cells. Moreover, DD1E5 significantly increased intracellular levels of ADMA and reduced NO production, suggesting its therapeutic potential for cancers in which DDAH1 is upregulated. In in vitro assays, DD1E5 abrogated the secretion of angiogenic factors (bFGF and IL-8) into conditional media, indicating its antiangiogenic potential. DD1E5 inhibited in vivo growth of xenograft tumors derived from PCa cells with DDAH1 overexpression, by reducing tumor endothelial content represented with low CD31 expression. VEGF, HIF-1α, and iNOS expression were reversed in DD1E5 treated tumors compared to respective control tumors. In this work, integrating multiple approaches shows DD1E5 is a promising tool for the study of methylarginine-mediated NO control and a potential therapeutic lead compound against pathological conditions with elevated NO production such as cancers and other diseases.


Sub-23 nm Particles Dominate Non-Volatile Particle Number Emissions of Road Traffic.
Ultrafine particles (<100 nm) in urban air are a serious health hazard not yet fully understood. Therefore, particle number concentration monitoring was recently included in the WHO air quality guidelines. At present, e.g., the EU regulates particle number only regarding the emissions of solid particles larger than 23 nm emitted by vehicles. The aim of this study was to examine the non-volatile fraction of sub-23 nm particles in a traffic-influenced urban environment. We measured the number concentration of particles larger than 1.4, 3, 10, and 23 nm in May 2018. Volatile compounds were thermally removed in the sampling line and the line losses were carefully determined. According to our results, the sub-23 nm particles dominated the non-volatile number concentrations. Additionally, based on the determined particle number emission factors, the traffic emissions of non-volatile sub-10 nm particles can be even 3 times higher than those of particles larger than 10 nm. Yet, only a fraction of urban sub-10 nm particles consisted of non-volatiles. Thus, while the results highlight the role of ultrafine particles in the traffic-influenced urban air, a careful consideration is needed in terms of future particle number standards to cover the varying factors affecting measured concentrations.


[Radiodiagnosis in the planning of surgical treatment for extensive jaw cysts].
To make an algorithm for the optimal planning of a surgical procedure in patients with jaw cysts. Sixty-six patients were operated on using cystotomy. The planning stage used radiation examination, including 7 survey radiographies, 62 orthopantomographies, and 33 computed tomographies (CT). The informative indicators of the most commonly used radiation techniques for this abnormality were compared. High technology radiation techniques (CT) showed the highest informative and diagnostic values. The investigation indicated the relationship of a surgical technique and the anatomic and topographic relations of a pathological process. The findings make it possible to prevent complications and recurrences during this treatment modality and to create favorable conditions for bone regeneration.


ADHD Is Comorbid to Migraine in Childhood: A Population-Based Study.
Objective: Recurrent headaches and ADHD are prevalent in the pediatric population. Herein, we assess if ADHD is comorbid to headaches overall, to headache subtypes (e.g., migraine), and to headache frequency. Method: Informed consent and analyzable data were obtained for 5,671 children aged 5 to 12 years (65.9% of the target sample). Parents and teachers were interviewed using validated questionnaires based on the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5). Relative risks were modeled using univariate and multivariate analyses. Results: As contrasted to nonheadache controls, the prevalence of ADHD was significantly higher in children with migraine (p < .001) but not in those with tension-type headaches. In children with migraine, risk of ADHD increased as a function of headache frequency (p < .05). Conclusion: Migraine and frequent migraine are comorbid to ADHD. Future studies should focus on the impact of the association on the burden to the children and their families.


[Standardisation proposal for monitoring rheumatoid arthritis patients in Croatia].
Monitoring of outcome measures is carried out because of the assessment of medical care quality, also in scientific researches i.e. clinical trials. However, it is rarely carried out in daily clinical practice due to lack of time. Our goal was to choose the outcome measures set for monitoring disease activity in rheumatoid arthritis (RA) which encompasses validity, reliability and sensitivity and also primarily satisfies feasybility criteria in daily clinical practice. We have analyzed the following parametres in 83 unselected patients with RA diagnosis in our department: the mutual relation of single measures of the disease activity (Ritchie index, number of swollen joints, general health status assessment with VAS and SE), their relation to the DAS and HAQ and the relation between the DAS and HAQ. We have recently replaced the Ritchie index by 28DAS, and HAQ by mHAQ. The values of correlation between the single measures of the disease activity which we had found out by statistical processing justify their usage in assessment of the clinical status, however the non-existence of the correlations compared to HAQ points to unreliability when used in evaluation of the disease activity. Unlike the single measures, DAS has positive correlation compared to HAQ. Based on our experience in past two years and recommendations found in literature, we suggest introducing the outcome measures set for monitoring disease activity in rheumatoid arthritis in clinical care. That would be mHAQ as the long-term outcome in measuring the disease activity and parametres by which DAS28 (number of tender joints, number of swollen joints, general health status assessment by VAS, SE) can be calculated as short-term outcome.


Characteristics and risks of drivers with low annual distance driven.
It has been noted by several authors that risk (defined only in terms of total expected numbers of crash involvements per total distance driven) paints a misleading picture of crash liability, particularly for the young and the old, as their high risk is associated with risky driving patterns typical of people who drive low annual kms. This article sets out to analyze these driving patterns of low-km drivers and to evaluate the risk of these patterns. As licensing programs tend to focus on young and old drivers, who tend to drive lower annual distances, income and employment data are also analyzed for low-km drivers. This is to provide a better picture for policy makers of the sort of people and the sorts of transportation requirements that their policies may affect. Crash data and travel data were disaggregated by driver characteristics and by driving conditions (road type, day and night, weekend and weekday) and combined to form estimates of risk for typical driving patterns of driver groups. Characteristics of driving patterns and of the drivers themselves were derived for groups defined by age and by the amount of annual driving undertaken. Older drivers who drive less tend to have higher risk per km mainly due to their predominantly urban trips. Nevertheless, because older drivers on average manage to reduce their risk per distance driven by choosing driving patterns that are safer than the driving patterns of other age groups, the risk of older drivers as a group is not overestimated. Despite being quite different from one another, the low- and high-km driving patterns of younger drivers were found to impose identical risks.


Altered brain language network in idiopathic peripheral facial paralysis patients with dysarthria.
Dysarthria is one of the common symptoms of facial paralysis (FP). This study aimed to investigate functional alterations in the brain language network in early idiopathic peripheral FP patients with dysarthria using resting-state functional magnetic resonance imaging (fMRI). A total of 45 cases of FP (left 22, right 23) and 34 cases of healthy control (HC) were recruited into this study. The data of patients with left-side FP and matched controls (17 cases) were flipped from left to right, and the brain regions were defined as ipsilateral and contralateral regions. The FC of 16 ROIs in classical language centers and regions that may be involved in language function were calculated. After identifying the differences of FC between the two groups, the correlation analysis between altered FC and TFGS score of oral muscle movement in FP group were analyzed. The FC between bilateral language regions has a significantly decreased trend in FP group compared with HC group (P<0.05). The ipsilateral inferior frontal gyrus, superior temporal gyrus, and middle temporal gyrus exhibited significantly decreased FC with multiple brain regions. In addition, we found that thalamus and cerebellum also with a significant alteration in FC in FP patients indicating that these two regions may also be involved in the mechanism of dysarthria in FP. The correlation analysis results indicated that the decrease of FC was positively correlated with the severity of oral paralysis. Idiopathic peripheral FP with dysarthria induces several FC alterations in the brain language network. The severity of oral paralysis is associated with these functional alterations.


Gastrointestinal tract perforation due to blunt abdominal trauma.
A retrospective clinical study was performed to evaluate the etiology, diagnosis, and management of gastrointestinal tract perforation (GITP) due to blunt abdominal trauma (BAT) in order to find a predictor to avoid delay in diagnosis. Thirty-five children with GITP out of 805 BAT victims (4.3%) over a 21-year period formed the study group. Different parameters including preoperative (mechanism of injury, abdominal and X- ray findings at presentation, diagnostic modalities), operative (type and site of GITP, intra-abdominal associated injuries, surgical method), and postoperative (complications, mortality) status were analyzed. The patients were subdivided according to their initial clinical presentation as group I: evidence of peritonitis (n = 19, 54%); group II: abdominal findings such as distension, minimal tenderness, and guarding (n = 10, 29%); and group III: normal abdominal findings (n = 6, 26%). These groups were also statistically compared to each other with regard to the parameters mentioned above. The Mann-Whitney U, Wilcoxon rank-sum, and Kruskal-Wallis tests were used for statistical analysis. P < 0.05 was considered to be statistically significant. There were 28 boys and 7 girls; the mean age was 8.2 +/- 2.4 years. Mechanisms of injury were motor vehicle accidents (MVA) (60%), falls (26%), and bicycle accidents (BA) (14%). Group I patients presented with significantly higher transaminase levels and white blood cell counts than groups II and III. Group I patients and MVA victims were operated upon significantly earlier than group III patients and BA victims because of significantly earlier development of clinical signs of peritonitis. A significantly higher number of multiple perforations was encountered in Group I and MVA victims than in groups II and III and BA victims. The presence of multiple perforations correlated significantly with the earlier development of clinical signs of peritonitis. The analysis of site of perforation with regard to the other parameters did not differ significantly. Fifty-four percent (n = 19) of the patients presented with peritonitis; a pneumoperitoneum was detected in 46% (n = 16). Diagnosis was accomplished by plain radiographs, ultrasound, computed tomography, and, most importantly, frequent abdominal examination of the patient. The sites of perforation were the stomach (4), duodenum (2), jejunum (11), ileum (12), jejunum and ileum (3), colon (2), and ileum and colon (1). Simple closure was the most common surgical procedure (n = 21), followed by resection and anastomosis (n = 12) and simple closure plus creation of a proximal ostomy (n = 2). Two deaths (5.7%) were directly due to head injuries. Our experience revealed that in spite of advanced imaging and laboratory modalities, frequent evaluation of the patient by an experienced surgeon is still the most important tool for early diagnosis and appropriate treatment. A child with BAT should be an inpatient and a high index of suspicion is always required, even in the presence of normal abdominal findings.


An exploration of the relationship between postnatal distress and maternal role attainment, breast feeding problems and breast feeding cessation in Australia.
To explore the relationships between maternal distress, breast feeding cessation, breast feeding problems and breast feeding maternal role attainment. Longitudinal cohort study. Three urban hospitals within Sydney, Australia. 449 women were invited to participate in the study, with an 81% response rate. Self-report questionnaires were used to collect the data in pregnancy (28-36 weeks) and 2 weeks and 3 months after birth. The Edinburgh Postnatal Depression Scale (EPDS) was used to measure postnatal distress, and the Maternal Role Attainment subscale (MRA) of the Maternal Breast Feeding Evaluation Scale (MBFES) was used to measure breast feeding maternal role attainment. Women with high MRA were less likely to stop breast feeding (even when they had breast feeding problems) than women with low MRA. Antenatal EPDS and anxiety scores were not related to breast feeding cessation or breast feeding problems when analysed alone. As hypothesised, the relationship between breast feeding cessation and postnatal distress (EPDS scores) varied according to MRA level. Women who were categorised as high MRA and no longer breast feeding had higher EPDS scores and were more likely to be categorised as distressed (36%) than women who had low MRA (<12%) or women who had high MRA and continued to breast feed (7%). There is a complex relationship between maternal identity, stopping breast feeding earlier than desired, and psychological distress. Women with strong beliefs about the importance of breast feeding to their maternal role may benefit from psychological assessment and support should they decide to stop breast feeding earlier.


High-intensity interval training for chronic pain conditions: a narrative review.
Chronic pain is defined as pain that persists past the normal healing time. Physical activity and exercise programs are increasingly being promoted and used for a variety of chronic pain conditions. Evidence suggests that physical exercise is an intervention with few adverse events that may improve pain severity and physical function, thus improving the quality of life. High-intensity interval training (HIIT) has been shown to improve physical outcome measures and to decrease disorder-related disability in people with chronic disorders. Since an overview of the benefits of HIIT on chronic pain conditions has not been published yet, this review aims to report the effects of HIIT alone or in combination with other forms of training on different kind of chronic pain conditions. A search in the main scientific electronic databases was performed. The results of the studies included in this review showed that HIIT is beneficial for several chronic pain conditions, improving pain and physical function. Since HIIT could represent a valid help to conventional drug therapies, it could improve the quality of life of these subjects. The actual quality of evidence remains very low, and further high evidence studies are needed to confirm the promising outcomes reported in this review.


Development of an in vitro model system for studying the interaction of Equus caballus IgE with its high-affinity receptor FcεRI.
The interaction of IgE with its high-affinity Fc receptor (FcεRI) followed by an antigenic challenge is the principal pathway in IgE mediated allergic reactions. As a consequence of the high affinity binding between IgE and FcεRI, along with the continuous production of IgE by B cells, allergies usually persist throughout life, with currently no permanent cure available. Horses, especially race horses, which are commonly inbred, are a species of mammals that are very prone to the development of hypersensitivity responses, which can seriously affect their performance. Physiological responses to allergic sensitization in horses mirror that observed in humans and dogs. In this paper we describe the development of an in situ assay system for the quantitative assessment of the release of mediators of the allergic response pertaining to the equine system. To this end, the gene encoding equine FcεRIα was transfected into and expressed onto the surface of parental Rat Basophil Leukemia (RBL-2H3.1) cells. The gene product of the transfected equine α-chain formed a functional receptor complex with the endogenous rat β- and γ-chains. The resultant assay system facilitated an assessment of the quantity of mediator secreted from equine FcεRIα transfected RBL-2H3.1 cells following sensitization with equine IgE and antigenic challenge using β-hexosaminidase release as a readout. Mediator release peaked at 36.68% ± 4.88% at 100 ng ml(-1) of antigen. This assay was modified from previous assays used to study human and canine allergic responses. We have also shown that this type of assay system has multiple applications for the development of diagnostic tools and the safety assessment of potential therapeutic intervention strategies in allergic disease.


[New organ-preserving technics for third-grade splenic trauma. An experimental study].
We studied two new techniques for orthotopic preservation of the spleen in an animal model with respect to their technical feasibility and their hemostatic efficacy. This study was performed in two stages. In the first, the treatment of central bursting ruptures by splenorrhaphy using a resorbable compressive mesh was tested. 20 sheep have been used for this part of the study. They were divided into four groups (A: control, B: sham operation, C: splenectomy, D: mesh splenorrhaphy). Following completion of this stage, two animals from group A and two from group B were used to test a second experimental setting. Experimental trauma corresponding to isolated third degree polar rupture of the spleen was induced. This was then treated by a polar resection using stapling instruments. All animals from each stage were subjected to spleen scanning three months postoperatively, followed by splenectomy. The spleens were then examined histologically. Both macroscopically and microscopically normal splenic tissue was found. No difference between the different groups could be detected by laboratory investigations. Gamma-globulins and total serum proteins were within normal ranges after five weeks. Splenic scan revealed an excellent function of the pulp. Both techniques are distinguished by their facility and rapidity, as well as reliable hemostasis and minimal technical prerequisites.


Accelerated partial-breast irradiation using proton beams: initial clinical experience.
We present our initial clinical experience with proton, three-dimensional, conformal, external beam, partial-breast irradiation (3D-CPBI). Twenty patients with Stage I breast cancer were treated with proton 3D-CPBI in a Phase I/II clinical trial. Patients were followed at 3 to 4 weeks, 6 to 8 weeks, 6 months, and every 6 months thereafter for recurrent disease, cosmetic outcome, toxicity, and patient satisfaction. With a median follow-up of 12 months (range, 8-22 months), no recurrent disease has been detected. Global breast cosmesis was judged by physicians to be good or excellent in 89% and 100% of cases at 6 months and 12 months, respectively. Patients rated global breast cosmesis as good or excellent in 100% of cases at both 6 and 12 months. Proton 3D-CPBI produced significant acute skin toxicity with moderate to severe skin color changes in 79% of patients at 3 to 4 weeks and moderate to severe moist desquamation in 22% of patients at 6 to 8 weeks. Telangiectasia was noted in 3 patients. Three patients reported rib tenderness in the treated area, and one rib fracture was documented. At last follow-up, 95% of patients reported total satisfaction with proton 3D-CPBI. Based on our study results, proton 3D-CPBI offers good-to-excellent cosmetic outcomes in 89% to 100% of patients at 6-month and 12-month follow-up and nearly universal patient satisfaction. However, proton 3D-CPBI, as used in this study, does result in significant acute skin toxicity and may potentially be associated with late skin (telangiectasia) and rib toxicity. Because of the dosimetric advantages of proton 3D-CPBI, technique modifications are being explored to improve acute skin tolerance.


Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine in anaplastic large cell lymphoma.
DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16(INK4A) after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use.


Obstetric outcome of 904 pregnancies after intracytoplasmic sperm injection.
The obstetric data of 904 consecutive pregnancies obtained after intracytoplasmic sperm injection (ICSI) using ejaculated spermatozoa (group I), epididymal spermatozoa (group II), testicular spermatozoa (group III) and after the replacement of frozen-thawed embryos (group IV) are described. In all, there were 785 pregnancies in group I, 37 pregnancies in group II, 30 pregnancies in group III and 52 pregnancies in group IV. A total of 24 pregnancies (2.5%) have so far been lost to follow-up. The incidence of pregnancy loss, i.e. subclinical pregnancies, clinical abortions and ectopic pregnancies were highest in group IV (61.4%). Early pregnancy loss in groups I, II and III were 21.9, 37.8 and 33.3% respectively. Prenatal diagnosis was performed in 64.4% of the clinical pregnancies: amniocentesis in 48.2% and chorionic villus sampling in 16.2%. The karyotypes were normal in 97.6% of the prenatal diagnoses and there were 1.2% de novo and 1.2% inherited chromosome aberrations. Pregnancy complications such as prematurity and low birthweight were related to pregnancy multiplicity. Perinatal mortality occurred in 15 babies (17.1 per thousand), including nine intrauterine fetal deaths after 25 weeks of gestation and six cases of mortality during the first 7 days after birth. There is no evidence that the technique of ICSI using sperm cells of different origins yielded a higher obstetric risk.


Pharmacokinetics and safety of dexlansoprazole MR in pediatric patients with symptomatic gastroesophageal reflux disease.
To evaluate the safety and pharmacokinetic profile of dexlansoprazole modified-release (MR) capsules in pediatric patients with symptomatic gastroesophageal reflux disease (GERD). This Phase I, open-label study enrolled male and female patients (1 to 11 years of age) with GERD. Patients received dexlansoprazole MR 15 mg, 30 mg, or 60 mg (according to weight) once daily for 7 days. Blood samples for the measurement of plasma dexlansoprazole concentrations were collected for 24 hours after the day 7 dose. Dexlansoprazole plasma concentrations and pharmacokinetic parameters were summarized by dose group. Safety assessments included adverse events (AEs), clinical laboratory evaluations, fasting gastrin concentrations, physical examinations, electrocardiograms, and vital signs. Thirty-six patients received study drug (12 per dose group), and 31 had evaluable pharmacokinetic data. There was a significant effect of weight on dose-normalized area under the curve (AUC, P=0.003) and dose-normalized maximum plasma concentration (Cmax) (P=0.013), indicating that for a given dose, dexlansoprazole exposure decreases as body weight increases. After adjusting for body weight, both dexlansoprazole Cmax and AUC increased in an approximately dose-proportional manner with increasing dexlansoprazole dose. A total of ten of 36 patients reported at least one treatment-emergent AE, with most events considered mild in intensity. The most common AEs were vomiting, abdominal pain, diarrhea, and nausea. In 1- to 11-year-old patients with symptomatic GERD, weight-adjusted dexlansoprazole AUC and Cmax increased approximately dose-proportionally. However, for a given dose, dexlansoprazole exposure decreased with increasing body weight. Dexlansoprazole MR was well tolerated, and the incidence of AEs did not increase with increasing dose.


Geometric transition and electronic properties of titanium-doped aluminum clusters: Al(n)Ti (n = 2-24).
Equilibrium geometries of AlnTi (n = 2-24) clusters were studied using density-functional theory with generalized gradient approximation. The resulting geometries showed that the titanium atom remains on the surface of clusters for n < 20 but is endohedrally doped from n = 20. This structural transition confirms the previous experiment results obtained by studying their abilities for argon physisorption (Lang, S. M.; Claes, P.; Neukermans, S.; Janssens, E. J. Am. Soc. Mass Spectrom.2011, 22, 1508). The average bond lengths, coordination numbers, relative stabilities, electronic properties, and other relevant properties were discussed. It was found that the doped titanium atoms strengthen the stabilities of the pure aluminum clusters. The coordination numbers of titanium atoms along with the average Al-Ti bond lengths undergo dramatic increases during the structural transition. The intra-atomic hybridization exists in both Ti and Al atoms, and charge transfer from Al atoms to Ti atom were found in these complexes, which should reflect the strength of Al-Ti interactions. Electronic structure analysis based on the partial density of states reveals stronger Al-Ti interactions for the endohedrally doped structures.


Rhodium-catalyzed asymmetric formal cycloadditions of racemic butadiene monoxide with imines.
A simple chiral sulfur-alkene hybrid ligand has proven to be highly effective for rhodium-catalyzed formal cycloaddition reactions of racemic butadiene monoxide and imines to furnish spirooxindole oxazolidines or 1,3-oxazolidines with high yields and stereoselectivities. A possible dynamic kinetic resolution as well as a kinetic resolution is considered to be involved in this catalytic process.


A one year review of eclampsia in an Ethiopian Tertiary Care Center (Saint Paul's Hospital Millennium Medical College, SPHMMC).
Eclampsia remains one of the five major causes of maternal mortality in developing countries. Advances in diagnosis and management have led to a significant reduction in maternal mortality and morbidity from this disease in developed countries. In developing countries the incidence of maternal death attributed to eclampsia remains high and, in Ethiopia, maternal mortality from this complication has instead risen over the last decade. The purpose of this study was to review the incidence of eclampsia at the largest feto-maternal center in the country over 1 year in an attempt to determine what quality improvement measures are needed and could realistically be implemented within the system to decrease this complication. There were a total of 104 eclamptic patients during the study period. The hospital incidence of eclampsia was 82/10,000 deliveries excluding those arriving to the hospital in the postpartum period (28 cases). There were eight maternal deaths making the case fatality rate one in 13 cases. The median convulsion to arrival time, referral to arrival time and magnesium sulphate administration time were found to be 3, 2 and 3 h, respectively. The probability of multiple seizures (≥3 episodes) was increased significantly with the prolongation of these time variables. Occurrence of multiple seizures was in turn significantly associated with adverse maternal outcomes (ICU admission, morbidities and mortalities). As expected, there was a high incidence of eclampsia and eclampsia related maternal death in the hospital. We recommend a thorough assessment of the referral system, upgrading and capacity building of more health facilities, organizing trainings and drills in health facilities; and availing magnesium sulphate in all health centers among others.


Baseline toxic mixtures of non-toxic chemicals: "solubility addition" increases exposure for solid hydrophobic chemicals.
This study addresses the question whether hydrophobic organic chemicals exerting no toxicity at their solubility limit (saturation) can form a toxic mixture. Spiking methods generally do not allow testing exactly at saturation without introducing microcrystals. Passive dosing was thus applied to test the acute toxicity of several high melting point PAHs and their mixtures at the respective saturation levels to aquatic and terrestrial invertebrates. With the aquatic Daphnia magna, anthracene, chrysene, and benzo(a)pyrene resulted in no or limited acute toxicity (0-20%), whereas binary and tertiary mixtures of these resulted in significant acute toxicity (70-88%). Toxicity of PAHs and their mixtures could be fitted with one (sum) chemical activity-response curve in accordance with a similar mode of toxic action (i.e., concentration addition). The effective chemical activity (Ea-50) of 0.029 and the effective concentration on a lipid basis (EC(lipid, eq.)-50) of 95.7 mM were well within the range for baseline toxicity. Similar mixtures showed less toxicity to the terrestrial Folsomia candida due to steady-state body-burdens being below equilibrium partitioning levels. The results of the present study raise questions about the focus of risk assessment schemes and toxicity testing guidelines on individual substances, since apparently non-toxic chemicals might become toxic in a mixture.


[Sleep in intensive care: a crucial but little-known issue].
A CRUCIAL BUT LITTLE-KNOWN ISSUE. Polysomnography is the best tool to study sleep in intensive care unit (ICU), but this recording is complex to perform in such environment. Sleep alterations in ICU patients are specific and include electroencephalographic abnormalities during sleep and wake, rendering sleep scoring more complicated. Severe deficit in deep sleep, rapid eye movement sleep and an important sleep fragmentation are reported by most studies. Sleep cycles are disorganized with many sleep episodes during daytime. Sleep disruptions result from light levels, noisy environment, and 24-hours nurses care. Assisted ventilation, sedation, loss of circadian rhythms also contribute to these disruptions. Biological and neurobehavioral consequences of sleep alterations lengthen weaning from mechanical ventilation and have some deleterious impacts on morbidity and mortality. Procedures to promote sleep have been attempted, with limited results to date. However, recent innovation might help to monitor sleep and help patients to achieve some restorative sleep.


Attitudes, Norms, and the Effect of Social Connectedness on Adolescent Sexual Risk Intention.
Risky sexual behaviors put adolescents at increased risk of adverse outcomes. Parents, school-based adults, and peers play important roles in influencing these sex intentions. This work explored the influence of parent-child sex communication on adolescent attitudes, perceived norms, and intentions to have sex, including the moderating role of social support from school-based adults, in a sample of 21,731 adolescents in California. Although increased parent-child sex communication was associated with intentions to have sex, it also exhibited protective effects, increasing abstinence attitudes among youth that led to decreased intention directly and via support from school-based adults. Although many factors influencing sexual behaviors are largely intrapersonal, these findings indicate the importance of an ecological approach to reducing adolescent sexual risk behaviors through engagement of parents and increased school connectedness.


[Effect of a low concentration of hydrogen peroxide on metabolism of blood cells].
Hydrogen peroxide is known to posses a wide range of physiological effects towards functional activity of cells. We have investigated the influence of H2O2 on the activity of glycolys in the native blood cells. Adding of hydrogen peroxide up to final concentration 50 microM led to decrease of activity some glycolytic enzymes. H2O2 inhibited consumption of glucose by blood cells. Despite the fact that H2O2 is well known as prooxidant, we observed decrease of the level of thiobarbituric acid reactive species in the blood cells after their incubation in the presence of hydrogen peroxide for 2 hours. Based on these data we supposed that effects of hydrogene peroxide occur via signal transduction pathways.


Factors associated with seeking readmission among clients admitted to medical withdrawal management.

The objectives of the present paper were to determine the rate and factors associated with seeking readmission among the clients admitted to an inpatient medical withdrawal management program, Vancouver Detox (VD). All clients who were admitted to VD between July 1, 2003, and June 30, 2004, were included in the study, and were followed up for 1 year. Multinomial logistic regression was performed to investigate the potential risk factors associated with short-term (1 month) and long-term (2 to 12 months) requests for readmission simultaneously. The risk factor associated with short-term request for readmission was leaving VD against medical advice (AMA) during the index admission. Clients who reported to have hepatitis C virus (HCV) infection, whose primary preferred substance was alcohol, and those who were poly-drug users were more likely to request readmission in long-term. Clients with no fixed address were less likely to seek readmission between months 2 and 12.


Fusion of a superfamily 1 helicase and an inactivated DNA polymerase is a signature of common evolutionary history of Polintons, polinton-like viruses, Tlr1 transposons and transpovirons.
Polintons (polintoviruses), polinton-like viruses (PLVs) and virophages belong to a recently described major class of eukaryotic viruses that is characterized by a distinct virion morphogenetic protein module and, in many members, a protein-primed family B DNA polymerase (pDNAP). All Polintons, by definition, encode a pDNAP and a retrovirus-like integrase. Most of the PLV lack these genes and instead encode a large protein containing a superfamily 1 (SF1) helicase domain. We show here that the SF1 helicase domain-containing proteins of the PLV also contain an inactivated pDNAP domain. This unique helicase-pDNAP fusion is also encoded by transpovirons, enigmatic plasmid-like genetic elements that are associated with giant viruses of the family Mimiviridae. These findings indicate the directionality of evolution of different groups of viruses and mobile elements in the Polinton-centered class. We propose that the PLV evolved from a polinton via fusion of the pDNAP gene with a helicase gene that was accompanied by mutations in the pDNAP active site, likely resulting in inactivation of the polymerase activity. The transpovirons could have evolved from PLV via the loss of several genes including those encoding the morphogenetic module proteins. These findings reaffirm the central evolutionary position of the Polintons in the evolution of eukaryotic viruses and other mobile genetic elements.


Cucurbit chlorotic yellows virus: Insights Into Its Natural Host Range, Genetic Variability, and Transmission Parameters.
Cucurbit chlorotic yellows virus (CCYV) (genus Crinivirus, family Closteroviridae) is implicated in cucurbit yellows disease (CYV), causing typical interveinal yellowing symptoms in leaves, and is transmitted by Bemisia tabaci Mediterranean (MED) and Middle East-Asia Minor 1 (MEAM1). Due to its recent report in cucurbit crops in Greece, field surveys were conducted during 2011-2016 to determine the presence of the virus in symptomatic cucurbits and alternative hosts among arable weed species. Results indicated the restricted spread of the virus and identified 13 weed species as CCYV hosts for the first time. Sequence analysis of the RNA-dependent RNA polymerase (RNA1) coat and minor coat proteins (RNA2) revealed very low genetic diversity (<0.1%) among the Greek isolates. Transmission experiments were also conducted using B. tabaci MED with retention determined at four days, whereas transmission efficiency was positively correlated with the number of adults used, features linked to the virus semipersistent mode of transmission.


One-Step Microwave-Assisted Hydrothermal Preparation of Zn-ZnO(Nw)-rGO Electrodes for Supercapacitor Applications.
Zn-ZnO(Nw)-rGO hybrid electrodes for supercapacitor applications were successfully prepared in situ by a one-step microwave-assisted hydrothermal method by deposition of reduced graphene oxide (rGO) on the structure of ZnO nanowires grown on the Zn foil. During the hydrothermal treatment, two processes occur the reduction of graphene oxide (GO) and the deposition of rGO on the Zn-ZnO(Nw) support. The growth of ZnO nanowires was achieved by thermal oxidation below the melting point of the Zn foil in a controlled atmosphere. The as-obtained electrodes were assessed for structural, optical, and morphological properties by X-ray diffraction, Raman spectroscopy, ultraviolet-visible spectroscopy, SEM microscopy, and EDX analysis. The supercapacitor properties of the Zn-ZnO(Nw)-rGO hybrid electrodes were investigated by cyclic voltammetry, electrochemical impedance spectroscopy, and galvanostatic charge-discharge analysis. The CV curve reveals that the Zn-ZnO(Nw)-rGO hybrid structures work as negative electrodes and exhibit a non-ideal rectangle-like shape, suggesting that the as-synthesized structure behaves as a pseudo-capacitor. A maximum capacitance was determined to be 395.79 mF cm-2 at a scan rate of 5 mV s-1. Based on GCD analysis, the maximum specific capacitance of 145.59 mF cm-2 was achieved at a low power density of 2 mA cm-2. The cycle life assessment of the Zn-ZnO(Nw)-rGO hybrid electrode over a 250-cycle number was performed by CV and GCD analysis. The maximum retention rate of 120.86% was achieved from GCD analysis over 250 cycles for the Zn-ZnO(Nw)-rGO hybrid electrode.


[Levels of interleukin-4 (IL-4) in lymphocyte cultures of subjects with HIV-1 infection].
The authors report IL-4 levels in peripheral blood mononuclear cells (PBMC), stimulated with MoAb anti-CD3, in subjects with HIV-1 infection, classified according to the criteria of Centers for Disease Control (CDC) in various stages. The results "in vitro" have indicate that PBMC IL-4 levels were in normal range also in advanced stages of retroviral infection, and were correlated to low levels of CD4+ lymphocytes and, sometimes, to high levels of IgE immunoglobulins. The normality of IL-4 levels in advanced stages or in presence of decreased CD4+ cells, suggests that the production of this cytokine is also present in other subsets of mononuclear cells not involved in this infection. Moreover the presence of significant correlation between high levels of Ig E and IL-4 suggests a possible pathogenetic role of IL-4 in the determination of isotypic switch of this immunoglobulin.


Loss of imprinting of insulin-like growth factor 2 is associated with increased risk of primary lung cancer in the central China region.
To determine the imprinting status of the IGF2 in Chinese patients with primary lung cancer and to analyze the clinical significance of the loss of imprinting (LOI) of IGF2. PCR- RFLP and RT-PCR-RFLP were carried out to select heterozygous cases for the ApaI polymorphism within exon 9 of the IGF2 gene and further analyze IGF2 LOI in 64 lung cancer patients, respectively. Of 64 lung cancer patients, 31 were heterozygous for IGF2. The positive rates of IGF2 LOI of lung cancer foci, matched paracancer tissues, and normal lung tissues were 77.4% (24/31), 61.3% (19/31), and 29.0% (9/31), respectively. The LOI differences for IGF2 among the three groups were statistically significant (χ2=15.267, p=0.000), and the LOI frequency of IGF2 in normal lung tissue was significantly lower than that in lung cancer foci and paracancer tissues (χ2=14.577, p=0.000; χ2=6.513, p=0.011). No statistical difference was observed between the lung tumor group and the matched paracancer group (χ2=1.897, p=0.168). The prevalence of advanced clinical stages (χ2=2.379; p=0.017) and lymph node metastasis (χ2=5.552; p=0.018) was significantly higher for LOI- positive paracancer tissues than for LOI-negative paracancer tissues. IGF2 LOI is highly frequent in Chinese primary lung cancer patients, especially those with increased risk of lymph node metastasis and advanced clinical stages. IGF2 LOI may be an early epigenetic event in human lung carcinogenesis.


Robotic Rehabilitator of the Rodent Upper Extremity: A System and Method for Assessing and Training Forelimb Force Production after Neurological Injury.
Rodent models of spinal cord injury are critical for the development of treatments for upper limb motor impairment in humans, but there are few methods for measuring forelimb strength of rodents, an important outcome measure. We developed a novel robotic device--the Robotic Rehabilitator of the Rodent Upper Extremity (RUE)--that requires rats to voluntarily reach for and pull a bar to retrieve a food reward; the resistance of the bar can be programmed. We used RUE to train forelimb strength of 16 rats three times per week for 23 weeks before and 38 weeks after a mild (100 kdyne) unilateral contusion at the cervical level 5 (C5). We measured maximum force produced when RUE movement was unexpectedly blocked. We compared this blocked pulling force (BPF) to weekly measures of forelimb strength obtained with a previous, well-established method: the grip strength meter (GSM). Before injury, BPF was 2.6 times higher (BPF, 444.6 ± 19.1 g; GSM, 168.4 ± 3.1 g) and 4.9 times more variable (p < 0.001) than pulling force measured with the GSM; the two measurement methods were uncorrelated (R(2) = 0.03; p = 0.84). After injury, there was a significant decrease in BPF of 134.35 g ± 14.71 g (p < 0.001). Together, our findings document BPF as a repeatable measure of forelimb force production, sensitive to a mild spinal cord injury, which comes closer to measuring maximum force than the GSM and thus may provide a useful measure for quantifying the effects of treatment in rodent models of SCI.


A novel language-neutral Visual Cognitive Assessment Test (VCAT): validation in four Southeast Asian countries.
Cognitive screeners are imperative for early diagnosis of dementia. The Visual Cognitive Assessment Test (VCAT) is a language-neutral, visual-based test which has proven useful for a multilingual population in a single-center study. However, its performance utility is unknown in a wider and more diverse Southeast Asian cohort. We recruited 164 healthy controls (HC) and 120 cognitively impaired (CI) subjects- 47 mild cognitive impairment (MCI) and 73 mild Alzheimer's disease (AD) dementia participants, from four countries between January 2015 and August 2016 to determine the usefulness of a single version of the VCAT, without translation or adaptation, in a multinational, multilingual population. The VCAT was administered along with established cognitive evaluation. The VCAT, without local translation or adaptation, was effective in discriminating between HC and CI subjects (MCI and mild AD dementia). Mean (SD) VCAT scores for HC and CI subjects were 22.48 (3.50) and 14.17 (5.05) respectively. Areas under the curve for Montreal Cognitive Assessment (0.916, 95% CI 0.884-0.948) and the VCAT (0.905, 95% CI 0.870-0.940) in discriminating between HCs and CIs were comparable. The multiple languages used to administer VCAT in four countries did not significantly influence test scores. The VCAT without the need for language translation or cultural adaptation showed satisfactory discriminative ability and was effective in a multinational, multilingual Southeast Asian population.


Interaction of atenolol with the systemic and regional hemodynamic effects of hydralazine in conscious renal hypertensive rabbits.
Using the radioactive microsphere technique, we investigated the interaction between atenolol and hydralazine after acute administration in conscious hypertensive rabbits. Hydralazine, 0.3 mg/kg i.v., increased heart rate, stroke volume and cardiac output and decreased total peripheral resistance. Only at higher doses (1.0 and 3.0 mg/kg i.v.) was a fall in arterial blood pressure observed due to a further reduction in total peripheral resistance. The drug caused vasodilatation in the heart, brain, kidneys, skeletal muscles, diaphragm, chest wall and large intestine and a, probably reflex-mediated, vasoconstriction in the skin, stomach and small intestine. In the heart hydralazine preferentially increased blood flow to the outer layers of the left ventricular wall, which resulted in a significant decrease in the endocardial/epicardial blood flow ratio. Hydralazine also greatly enhanced the percentage of 15-micron microspheres distributed to the lungs, indicating an increased arteriovenous anastomotic flow. Atenolol (1 mg/kg i.v.) elicited bradycardia and moderately reduced blood pressure due to a decrease in cardiac output. Pretreatment with atenolol attenuated the cardiac stimulation and thereby accentuated the hypotensive effect of hydralazine, 0.3 mg/kg. With the high hydralazine dose (3.0 mg/kg) the synergistic effect on blood pressure disappeared due to an increase in cardiac output, despite effective beta adrenoceptor blockade. Moreover, atenolol interfered with the vasodilator response of hydralazine in the heart, skeletal muscles and the arteriovenous anastomoses. The beta adrenoceptor antagonist increased the endocardial/epicardial blood flow ratio and thereby abolished the negative effect of hydralazine on this parameter. In conclusion, the antihypertensive drugs acted synergistically only at a low hydralazine dose.(ABSTRACT TRUNCATED AT 250 WORDS)


Lack of efficacy of thermography as a screening tool for minimal and stage I breast cancer.
In a study of thermograms of 42 patients with Stage 1 or smaller carcinomas of the breast, 44 confounding cases and 64 randomly selected subjects being screened, we found that the ability of expert thermographers to identify the patients with carcinoma correctly (true positive = 0.238) varied little from the ability of untrained readers (true positive = 0.301). Furthermore, in the expert group, the indexes of suspicion were so high (0.436) and the true-positive levels were so relatively low (0.238, P = 0.0005) that thermography may well have a very limited role as a screening or pre-screening modality for the detection of minimal or Stage 1 breast cancers.


A Small-Molecule Cocktails-Based Strategy in Culture of Mesenchymal Stem Cells.
Mesenchymal stem cells (MSCs) have a variety of unique properties, such as stem cell multipotency and immune regulation, making them attractive for use in cell therapy. Before infusion therapy, MSCs are required to undergo tissue separation, purification, and expansion in vitro for a certain duration. During the process of in vitro expansion of MSCs, the influence of culture time and environment can lead to cell senescence, increased heterogeneity, and function attenuation, which limits their clinical applications. We used a cocktail of three small-molecule compounds, ACY (A-83-01, CHIR99021, and Y-27632), to increase the proliferation activity of MSCs in vitro and reduce cell senescence. ACY inhibited the increase in heterogeneity of MSCs and conserved their differentiation potential. Additionally, ACY maintained the phenotype of MSCs and upregulated the expression of immunomodulatory factors. These results suggest that ACY can effectively improve the quantity and quality of MSCs.


Lifestyle of Patients with Atrial Fibrillation Following Self-Management Interventions: a Randomized Clinical Trial.
Introduction: Cardiovascular diseases are the most common cause of death in most countries, such as Iran. Cardiac arrhythmias, including Atrial Fibrillation (AF) comprise an important category of these diseases. During recent years, AF has become a serious medical condition. This study aimed to investigate the effect of self-management interventions on the lifestyle of patients with AF. Methods: In this Randomized Clinical Trial study, 88 patients were selected and randomly assigned to intervention and control groups. The intervention group received self-management interventions, including education and telephone follow-ups. The data were collected using a demographic questionnaire and Walker's health-promoting lifestyle profile II, before the intervention and four and twelve weeks after the intervention. The significance level was considered to be 0.05. Results: The results showed a significant increase in the intervention group's lifestyle mean score, four and twelve weeks after the intervention as compared with control group However, this increase was not similar in all the lifestyle dimensions. Conclusion: In conclusion, implementation of self-management interventions could improve the lifestyle of the patients with Atrial Fibrillation. The results can help nurses to conduct self-management interventions into such patients' care plan and prevent many physical, psychological, and social problems that negatively affect patients and their lifestyle.


Women are more susceptible to caries but individuals born with clefts are not.
The identification of individuals at a higher risk of developing caries is of great interest. Isolated forms of cleft lip and palate are among the most common craniofacial congenital anomalies in humans. Historically, several reports suggest that individuals born with clefts have a higher risk for caries. Caries continues to be the most common infectious noncontagious disease worldwide and a great burden to any health system. The identification of individuals of higher susceptibility to caries is of great interest. In this paper, we assessed caries experience of 1,593 individuals from three distinct populations. The study included individuals born with clefts, their unaffected relatives, and unrelated unaffected controls that were recruited from areas with similar cultural pressures and limited access to dental care. DMFT/dmft scores were obtained, and caries experience rates were compared among the three groups in each geographic area. Individuals born with clefts did not present higher caries experience in comparison to their unaffected relatives or unrelated unaffected controls. Women tend to present higher caries rates in comparison to men. Our work provides strong evidence that individuals born with clefts are not at higher risk to caries; however, women tend to have more severe caries experience.


Identification of hormonally responsive proteins in primary Sertoli cell culture medium by anion-exchange high performance liquid chromatography.
Twenty day-old rats were used to prepare Sertoli cell-enriched cultures which were grown for 4 days in serum-free medium supplemented with human transferrin, epidermal growth factor, and insulin. Proteins in the medium were first fractionated by anion-exchange HPLC. Forty-five to 50 fractions were collected, and each was examined by electrophoresis in sodium dodecyl sulfate-containing polyacrylamide gels. Using silver nitrate as a stain, more than 30 proteins were routinely identified. Rat androgen binding protein and rat transferrin were measured by immunoassays. When the cultures were supplemented with either testosterone, FSH, or both hormones and the media fractionated by HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, these proteins could be tentatively categorized as follows: unresponsive to added hormones; responsive primarily to testosterone; responsive primarily to FSH; or responsive to testosterone or FSH but maximally responsive to both hormones. This report provides a method for identifying proteins in Sertoli cell-enriched cultures and has allowed us to show for the first time that many are responsive to hormones. The procedure takes advantage of the large loading capacity of the HPLC column to allow fractionation of liter quantities of medium. The high resolving power of the column permits preparation of fractions which are highly enriched with one or a limited number of proteins. The purification of many of these proteins is now feasible. The approach described is generally applicable for isolation of proteins from media from a variety of cells.


Effects of cyanoacrylate tissue adhesives on cartilage graft viability.
Cartilage graft fixation using cyanoacrylate tissue adhesives has aided in the accuracy and stability of these grafts in facial reconstructive procedures. To objectively determine how these adhesives affect cartilage viability, freshly harvested cartilage from septoplasty procedures was bonded in vitro with one of four cyanoacrylate adhesives: Histoacryl, Bucrylate, Krazy Glue, or Eastman 910 monomer. Viable chondrocytes will incorporate the sulfur-35 (35S) isotope in the synthesis of chondroitin sulfate, and is therefore a reliable test of cartilage viability. The bonded cartilage specimens were stored from 3 days to 4 weeks at 4 degrees C and then were incubated with the 35S isotope. Autoradiographs were made and the sections were counterstained. Throughout the study period, there was no statistical difference in the viability of Histoacryl-bonded specimens as compared to the controls. Specimens bonded with Bucrylate, Krazy Glue, and Eastman 910 monomer statistically demonstrated markedly less viability compared to those bonded with Histoacryl at the P = .01 level of significance. Further, the cartilage separated from these latter adhesives at the longer study times, most likely secondary to cartilage devitalization. Histoacryl optimizes graft viability as compared to these other available cyanoacrylate tissue adhesives in vitro.


Effect of ant attendance by Monomorium minimum (Buckley) (Hymenoptera: Formicidae) on predation and parasitism of the soybean aphid Aphis glycines Matsumura (Hemiptera: Aphididae).
Ant attendance is known to affect the population dynamics of aphids and may increase or decrease aphid populations through stimulation, predation, or protection. In this study, we performed a series of laboratory experiments to examine the effects of ant attendance on populations of the soybean aphid Aphis glycines. Aphid colonies were exposed to the predators Harmonia axyridis (Coccinellidae) and Orius insidiosus (Anthocoridae) and a parasitoid Aphidius colemani (Aphidiidae) in the presence and absence of attending Monomorium minimum (Formicidae). We also tested for direct effects of ant attendance in the absence of natural enemies. Ants attending soybean aphid populations were observed harassing or killing O. insidiosus and H. axyridis. Attendance interfered with both predator species, resulting in reduced predation and an increase in aphid numbers up to 10-fold in the presence of ants. Ants were not observed directly interfering with the parasitoid A. colemani, but the number of parasitized aphids was higher in aphid colonies that were left unattended by ants.


Endoscopic management of a primary duodenal carcinoid tumor.
Carcinoids are rare, slow-growing tumors originating from a variety of different neuroendocrine cell types. They are identified histologically by their affinity for silver salts and by positive reactions to neuroendocrine markers such as neuron-specific enolase, synaptophysin and chromogranin. They can present with various clinical symptoms and are difficult to diagnose. We present the case of a 43-year-old woman who was referred for evaluation of anemia. Upper endoscopy showed a duodenal bulb mass around 1 cm in size. Histopathological and immunohistochemistry staining were consistent with the diagnosis of a carcinoid tumor. Further imaging and endoscopic studies showed no other synchronous carcinoid lesions. Endoscopic ultrasound (EUS) revealed a 1 cm lesion confined to the mucosa and no local lymphadenopathy. Successful endoscopic mucosal resection of the mass was performed. Follow-up surveillance 6 months later with EUS and Octreoscan revealed no new lesions suggestive of recurrence. No consensus guidelines exist for the endoscopic management of duodenal carcinoid tumors. However, endoscopic resection is safe and preferred for tumors measuring 1 cm or less with no evidence of invasion of the muscularis layer.


Clinical outcome of patients treated with re-irradiation for spine or pelvic bone metastasis: A multi-institutional analysis of 98 patients.
The present study aimed to describe the clinical results of re-irradiation (Re-RT) for spine or pelvic bone metastasis at the same initial irradiated area. Between April 2010 and March 2014, cases involving 98 patients with spine or pelvic bone metastasis who had undergone Re-RT at five institutions were reviewed. The clinical outcomes following Re-RT were evaluated, including overall survival (OS) and severe adverse events. The median time interval from initial radiation therapy (RT) to Re-RT was 439 days (range, 23-4,993 days), and the median duration of patient follow-up was 256 days (range, 11-2,284 days). The median biological effective dose for the Re-RT was 150 Gy2 (range, 17-240 Gy2; α/β = 2). Severe late adverse events occurred in two patients who underwent three-dimensional conformal radiotherapy for lumbar spine or pelvic bone metastases, which may be associated with tumor progression. The median survival time following Re-RT was 255 days, and the actuarial OS rate at 1 year was 36%. The interval between initial RT and Re-RT, and their performance statuses (PS) were significant independent prognostic factors for OS rates in multivariate analysis. Re-RT for spine or pelvic bone metastases is a relatively acceptable option with low risk of anticipated severe adverse events, particularly for patients with good PS following a long disease-free interval.