Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal bioassays.
Spondias mombin (Linn), Nymphaea lotus (Linn) and Luffa cylindrica (Linn) (syn Luffa aegyptiaca Mill) are plants traditionally used as food ingredients and in the management of diseases, including cancer, in Nigeria. Despite the therapeutic potentials attributed to these plants, reports on their genotoxicity are scanty. In this study, the genotoxicity of the aqueous and hydro-methanol extract of these plants was evaluated using mouse bone marrow micronucleus and sperm morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was first used to assess acute toxicity of the aqueous and hydro-methanol extracts in Swiss albino mice. For each extract, there were five groups of mice (n=4/group) treated with different concentrations of the extract as against the negative and positive control group for the genotoxicity study. In the antigenotoxicity study, five groups of mice were exposed to five different concentrations of the extracts along with 60 mg/kg of methyl methane sulfonate (MMS), which was used to induce genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in the genotoxicity and antigenotoxicity groups. Administration of each of the extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in mice. At the concentrations tested, all the extracts, except aqueous S. mombin, increased micronucleated polychromatic erythrocytes. The aqueous and hydro-methanol extracts of N. lotus increased the frequency of aberrant sperm cells. All the extracts were also able to ameliorate MMS induced genotoxicity in bone marrow cells of the exposed mice. The results showed the potential of the extracts to induce somatic and germ cell mutation in male mice. The extracts also ameliorated the genotoxic effect of MMS.


Thickness fluctuations in turbulent soap films.
Rapidly flowing soap films provide a simple and attractive system to study two-dimensional hydrodynamics and turbulence. By measuring the rapid fluctuations of the thickness of the film in the turbulent regime, we find that the statistics of these fluctuations closely resemble those of a passive scalar field in a turbulent flow. The scalar spectra are well described by Kolmogorov-like scaling while the high-order moments show clear deviations from regular scaling just like dye or temperature fluctuations in 3D turbulent flows.


Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer.
Objective: Lynch syndrome (LS) predisposes patients to early onset endometrioid endometrial cancer (EEC). However, little is known about LS-related EEC in the Chinese population. The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese patients with EEC. Methods: We applied universal immunohistochemistry screening to detect the expression of mismatch repair (MMR) proteins, which was followed by MLH1 methylation analysis to identify suspected LS cases, next-generation sequencing (NGS) to confirm LS, and microsatellite instability (MSI) analysis to verify LS. Results: We collected 211 samples with EEC. Twenty-seven (27/211, 12.8%) EEC cases had a loss of MMR protein expression. After MLH1 methylation analysis, 16 EEC cases were suggested to be associated with LS. Finally, through NGS and MSI analysis, we determined that 10 EEC (10/209, 4.78%) cases were associated with LS. Among those cases, 3 unreported mutations (1 frameshift and 2 nonsense) were identified. MSH6 c.597_597delC, found in 4 patients, is likely to be a founder mutation in China. Conclusions: We demonstrated the feasibility of a process for LS screening in Chinese patients with EEC, by using universal immunohistochemistry screening followed by MLH1 methylation analysis and confirmation through NGS and MSI analysis. The novel mutations identified in this study expand knowledge of LS.


A novel pathway for adrenergic stimulation of cAMP-response-element-binding protein (CREB) phosphorylation: mediation via alpha1-adrenoceptors and protein kinase C activation.
Because of the central role of adrenergic mechanisms in the expression of crucial genes during brown adipocyte differentiation, we examined the activation (phosphorylation) of CREB (cAMP-response-element-binding protein) in mouse brown adipocytes in primary culture. We found that noradrenaline ('norepinephrine') stimulated CREB phosphorylation rapidly (maximum effect in < or =5 min with slow decay) and efficiently (EC(50), 6 nM). The increase in CREB phosphorylation coincided with increased expression of an artificial cAMP-response-element-containing reporter construct. CREB phosphorylation was partly inhibitable, both by the beta-adrenergic antagonist propranolol and by the alpha(1)-adrenergic antagonist prazosin. Adenylate cyclase hyperactivation (by forskolin) could stimulate CREB phosphorylation to the same extent as noradrenaline. The alpha(1)-adrenergic agonist cirazoline also increased CREB phosphorylation. An increase in intracellular [Ca(2+)] had, however, no effect, but protein kinase C activation by PMA was a potent stimulator. The cirazoline-stimulated (alpha(1)-adrenergic) CREB phosphorylation was inhibited by a desensitizing pretreatment with PMA, demonstrating that the alpha(1)-stimulation was mediated via protein kinase C activation; neither Src nor extracellular-signal-regulated kinases 1 and 2 activation was involved in the signalling process. We conclude that CREB phosphorylation in brown adipocytes is mediated not only through the classical beta-adrenergic/cAMP pathway but also through a novel alpha(1)-adrenergic/protein kinase C/CREB pathway, which has not been described previously in any tissue.


Three resonant ultracold bosons: off-resonance effects.
We solve a finite range two-channel model for three resonant identical bosons. The model provides a minimal description of the various magnetic Feshbach resonances in single species ultracold bosonic systems, including off-resonant scattering. We obtain important insights into the interpretation of seminal experiments: the three-body recombination rate measured in sodium and the Efimov resonances observed in cesium. This approach quantifies nonuniversal effects appearing for a finite magnetic field detuning.


Increased Causal Connectivity Related to Anatomical Alterations as Potential Endophenotypes for Schizophrenia.
Anatomical and functional abnormalities in the cortico-cerebellar-thalamo-cortical circuit have been observed in schizophrenia patients and their unaffected siblings. However, it remains unclear to the relationship between anatomical and functional abnormalities within this circuit in schizophrenia patients and their unaffected siblings, which may serve as potential endophenotypes for schizophrenia.Anatomical and resting-state functional magnetic resonance imaging data were acquired from 49 first-episode, drug-naive schizophrenia patients, 46 unaffected siblings, and 46 healthy controls. Data were analyzed by using voxel-based morphometry and Granger causality analysis.The patients and the siblings shared anatomical deficits in the left middle temporal gyrus (MTG) and increased left MTG-left angular gyrus (AG) connectivity. Moreover, the left MTG-left AG connectivity negatively correlates to the duration of untreated psychosis in the patients.The findings indicate that anatomical deficits in the left MTG and its increased causal connectivity with the left AG may serve as potential endophenotypes for schizophrenia with clinical implications.


The use of the maharanobis and modified distances for the improvement of simulation of glutamic acid production.
A modified simulation procedure based on a statistical approach was investigated. The procedure predicts the time course of fed-batch culture for glutamic acid production by a temperature-sensitive strain of Brevibacterium flavum. The statistical approach requires only a data base of state points obtained in experiments, and not perfect identification of fermentation models. The simulation procedure is based on regression analysis to estimate specific rate parameters of system equations using the data points selected with reference to the Euclid distance. It was modified in that the data selection procedure included the use of the Maharanobis distance as well as a modified distance defined in this study. Simulation results using the modified procedure allow reasonable prediction of the time course of fed-batch culture for glutamic acid compared to that involving the Euclid distance alone.


[Calculation of orbital fat volumes for determining treatment timing for thyroid- associated ophthalmopathy].
To analyze the relationship between orbital fat volume and the progression and prognosis of thyroid- associated ophthalmopathy (TAO) and determine the optimal treatment timing for TAO. The clinical data were collected from 35 patients (70 orbits) with a definite diagnosis of TAO between January, 2016 and December, 2016. The correlation between orbital fat volume and the clinical parameters was evaluated. We also analyzed the correlation of the signal intensity ratio (SIR) of the extraocular muscles with the clinical parameters. The orbital fat volume was compared between patients with TAO and 12 control subjects. The orbital fat volume was significantly correlated with the duration of TAO (r=0.480, P<0.01), but showed no significant difference between patients with a disease course within 6 months and those with a disease course of 6 to 12 months (P=0.084). The patients with a disease course beyond 12 months had a significantly greater orbital fat volume than those with a disease course of 6 months (P<0.01) or 6 to 12 months (P<0.05). The orbital fat volume was correlated with the degree of proptosis (r=0.622, P<0.01), and an increase of exophthalmos by 1 mm was associated with a total orbital volume increment of 0.88 mL. The clinical activity score was correlated with the SIR of the extraorbital muscles (r=0.536, P<0.01) and levels of anti-thyroid-stimulating hormone receptor antibody (r=0.416,P<0.01). The orbital fat volume was significantly greater in TAO patients than in the healthy individuals (P<0.01). In patients with TAO, the peak increase of orbital fat volume occurs one year after the disease onset. Measurement of the orbital fat volume combined with SIR of the extraorbital muscles can serve as an indicator for determining the optimal timing for intervention of TAO and helps in the evaluation of prognosis of the patients.


Characterization of bovine seminal plasma by proteomics.
Previous investigations of bovine seminal plasma (BSP) have revealed the identities of the three major proteins, BSP-PDC109, BSP-A3 and BSP-30 kDa, which together constitute about half of the total protein, as well as about 30 of the minor proteins. Analyses of BSP by 2-DE have revealed about 250 protein spots, suggesting that much of the BSP proteome remains undescribed. In this study, BSP has been analyzed by 2-D LC-based and SDS-PAGE-based proteomic methods. Ninety-nine proteins were identified, including 49 minor proteins that have not previously been described in seminal plasma of any species.


Comparison of induced corpora lutea from prepuberal gilts and spontaneous corpora lutea from mature gilts: in vitro progesterone production.
Prepuberal (P) gilts were induced to ovulate with pregnant mare serum gonadotropin followed 72 h later by human chorionic gonadotropin (hCG). Three P gilts and three mature (M) gilts each were ovariectomized on d 10, 14, 18, 22 and 26 (d 0 = day of hCG for P gilts and onset of estrus for M gilts). Gilts ovariectomized on d 14, 18, 22 and 26 were hysterectomized on d 6 to ensure maintenance of the corpora lutea (CL). Two to five grams of minced luteal tissue were dispersed using collagenase and hyaluronidase in HEPES buffered salt solution supplemented with glucose and bovine serum albumin. Dispersed cells were rinsed in Dulbecco's Modified Eagle Medium (DMEM), counted (ratio of large to total number of luteal cells determined) and then incubated for 1 h in DMEM. With aliquots standardized to 2.5 X 10(4) viable, large cells (greater than 25 micron diameter) were incubated in 1 ml DMEM for 2 h in the presence of either 10, 50, 100 or 1,000 ng luteinizing hormone (LH); .1, 1, 10 or 100 ng hCG; 10, 100 or 1,000 ng norepinephrine (NE) or either .75, or 1.5 mM dibutyrl cyclic adenosine monophosphate (dbcAMP). Progesterone (P4) in the medium was quantified by radioimmunoassay. Basal P4 production (no P4 stimulator added to the medium) on d 10, 14, 18, 22 and 26 for P gilts was 246 +/- 9, 66 +/- 4, 64 +/- 6, 41 +/- 3 and 69 +/- 6 ng/ml medium, respectively, and for M gilts was 281 +/- 12, 128 +/- 8, 53 +/- 4, 82 +/- 6, 101 +/- 5 ng/ml medium, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Trait profiles in difficult-to-treat asthma: Clinical impact and response to systematic assessment.
Multidisciplinary systematic assessment improves outcomes in difficult-to-treat asthma, but without clear response predictors. Using a treatable-traits framework, we stratified patients by trait profile, examining clinical impact and treatment responsiveness to systematic assessment. We performed latent class analysis using 12 traits on difficult-to-treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV1 , exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment. Among 241 patients, two airway-centric profiles were characterized by early-onset with allergic rhinitis (n = 46) and adult onset with eosinophilia/chronic rhinosinusitis (n = 60), respectively, with minimal comorbid or psychosocial traits; three non-airway-centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance (n = 51), psychosocial (anxiety, depression, smoking, unemployment) dominance (n = 72), or multi-domain impairment (n = 12). Compared to airway-centric profiles, non-airway-centric profiles had worse baseline ACQ-6 (2.7 vs. 2.2, p < .001) and AQLQ (3.8 vs. 4.5, p < .001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway-centric profiles had more FEV1 improvement (5.6% vs. 2.2% predicted, p < .05) while non-airway-centric profiles trended to greater exacerbation reduction (1.7 vs. 1.0, p = .07); mOCS dose reduction was similar (3.1 mg vs. 3.5 mg, p = .782). Distinct trait profiles in difficult-to-treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult-to-treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention.


Alteration of organic acid metabolism in Arabidopsis overexpressing the maize C4 NADP-malic enzyme causes accelerated senescence during extended darkness.
The full-length cDNA encoding the maize (Zea mays) C(4) NADP-malic enzyme was expressed in Arabidopsis (Arabidopsis thaliana) under the control of the cauliflower mosaic virus 35S promoter. Homozygous transgenic plants (MEm) were isolated with activities ranging from 6- to 33-fold of those found in the wild type. The transformants did not show any differences in morphology and development when grown in long days; however, dark-induced senescence progressed more rapidly in MEm plants compared to the wild type. Interestingly, senescence could be retarded in the transgenic lines by exogenously supplying glucose, sucrose, or malate, suggesting that the lack of a readily mobilized carbon source is likely to be the initial factor leading to the premature induction of senescence in MEm plants. A comprehensive metabolic profiling on whole rosettes allowed determination of approximately 80 metabolites during a diurnal cycle as well as following dark-induced senescence and during metabolic complementation assays. MEm plants showed no differences in the accumulation and degradation of carbohydrates with respect to the wild type in all conditions tested, but accumulated lower levels of intermediates used as respiratory substrates, prominently malate and fumarate. The data indicated that extremely low levels of malate and fumarate are responsible for the accelerated dark-induced senescence encountered in MEm plants. Thus, in prolonged darkness these metabolites are consumed faster than in the wild type and, as a consequence, MEm plants enter irreversible senescence more rapidly. In addition, the data revealed that both malate and fumarate are important forms of fixed carbon that can be rapidly metabolized under stress conditions in Arabidopsis.


Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node.
Lymph nodes (LNs) contain innate-like lymphocytes that survey the subcapsular sinus (SCS) and associated macrophages for pathogen entry. The factors promoting this surveillance behavior have not been defined. Here, we report that IL7R(hi)Ccr6(+) lymphocytes in mouse LNs rapidly produce IL17 upon bacterial and fungal challenge. We show that these innate-like lymphocytes are mostly LN resident. Ccr6 is required for their accumulation near the SCS and for efficient IL17 induction. Migration into the SCS intrinsically requires S1pr1, whereas movement from the sinus into the parenchyma involves the integrin LFA1 and its ligand ICAM1. CD169, a sialic acid-binding lectin, helps retain the cells within the sinus, preventing their loss in lymph flow. These findings establish a role for Ccr6 in augmenting innate-like lymphocyte responses to lymph-borne pathogens, and they define requirements for cell movement between parenchyma and SCS in what we speculate is a program of immune surveillance that helps achieve LN barrier immunity.


Studies on the polyoma tumor-specific transplantation antigen (TSTA): selection and characterization of TSTA-negative segregants from somatic hybrids.
Two polyoma-TSTA-negative variants were selected independently from a polyoma fibrosarcoma/Moloney lymphoma somatic hybrid, by repeated passages in polyoma-virus-preimmunized mice. One of the variants had lost all its polyoma DNA, while the other only retained a deleted piece of its integrated polyoma DNA. In contrast to the parental hybrid clone, none of the variants produced detectable amounts of T-antigens. This finding indicates that a detectable expression of the products of the polyoma virus early genome, the T-antigens, is important either directly or indirectly for the expression of TSTA.


Crystallographic studies of Savinase, a subtilisin-like proteinase, at pH 10.5.
The effect of high pH (pH 10.5) on Savinase, a subtilisin-like serine proteinase, has been investigated using X-ray crystallography. The structures of two Savinase mutants were determined at two different pH values, namely pH 6.0, where the enzyme is inactive (this is the pH at which most of the structural work has been carried out on other serine proteinases), and pH 10.5, where Savinase is active. Comparison of these high resolution (0.16 nm) structures showed four related sets of changes between the two pH values. First, the difference in protonation state of the active-site histidine leads to a change in conformation of the active-site triad. Secondly, there are resulting changes in the water structure around this histidine residue with much increased mobility of the water in the active-site at pH 10.5. Thirdly, the two substrate-binding loops on either side of the binding site are less well linked by ordered water molecules at pH 10.5 and show substantially increased flexibility. Finally, the first substrate-binding loop, residues at positions 99-104, moves slightly so as to widen the substrate channel.


Diastereoselective Synthesis of Phosphinic Dipeptide Isosteres: Domino Chirality Transfer during a Stereocontrolled P-Michael Reaction.
A highly diastereoselective P-Michael addition of chiral aminophosphinic acids to achiral acrylates has been developed, leading to phosphinic dipeptide isosteres in high yields and dr of up to >50:1. The method allows for the diastereoselective preparation of target compounds without the need for chiral auxiliaries or P-chiral substrates. A possible mechanistic explanation involves a domino chirality transfer from the aminophosphinic acid to the P center, amplified by a crucial benzhydryl ester group, and then to the α-carbon.


Transrectal ultrasonography and cervical neoplasia. A preliminary report.
Transrectal ultrasonography is a new diagnostic method recently introduced in the study of normal and pathologic pelvis. The Authors describe their preliminary experience with the use of a rectal linear probe in the evaluation of the carcinoma of the cervix. This ultrasonographic method has resulted very useful in providing an imaging of cervical cancer in evaluating its effective diffusion and in precising demeasurements of the neoplastic mass. The results are particularly encouraging and justify continued experimentation.


Autosomal dominant striatonigral degeneration. A clinical, pathologic, and biochemical study of a new genetic disorder.
An autosomal dominant striatonigral degeneration is present in a family of Portuguese ancestry numbering in excess of 329 persons in eight generations. The illness begins in the second, third, or fourth decade, and progresses for about 15 years with parkinsonian rigidity, spasticity, spastic dysarthria, and abnormalities of eye movement. Neuropathologic findings are severe neuronal loss and astrocytic gliosis in the corpus striatum and substantia nigra, with a moderate neuronal loss in the dentate nucleus of the cerebellum and nucleus ruber of the midbrain. This is a new genetic entity, distinct from other autosomal dominant neurologic disorders such as nigrospinodentatal degeneration, olivopontocerebellar degeneration, dystonia musculorum deformans, Machado's disease, and Huntington's disease.


A cross-sectional survey on mother-to-child transmission of HIV among the migrant population in Dongguan, China.
The migrant population, consisting of individuals who relocate from rural to urban areas, faces unique challenges that heighten their vulnerability to HIV infection. These challenges stem from a combination of sociodemographic factors and limited access to healthcare services. Understanding the dynamics of HIV transmission within this population is crucial for the development of effective prevention strategies. To investigate the factors contributing to HIV vulnerability among migrants, we conducted a cross-sectional study at Dongguan People's Hospital from January 1, 2018, to December 31, 2021. Our study focused on pregnant women living with HIV and their infants, with a particular emphasis on sociodemographic characteristics, HIV testing and treatment profiles, and neonatal clinical data. Data were systematically collected using standardized forms. Analysis of data from 98 participants revealed noteworthy findings. No significant associations were observed between age, marital status, and educational background regarding HIV vulnerability. Similarly, factors such as the status of sexual partners, spousal therapy, and the number of children had no significant impact. However, our analysis highlighted the critical role of treatment strategies for HIV-positive women and the timing of antiretroviral therapy initiation for women with HIV, both of which were associated with HIV transmission (P < 0.05). Additionally, factors such as feeding type, neonatal antiretroviral prophylaxis, and preventive treatment strategies showed significant associations, while the preventive treatment program for neonates demonstrated no significant impact. These findings provide valuable insights into the specific risk factors and barriers to HIV prevention faced by the migrant population in Dongguan. They underscore the importance of targeted interventions and policies aimed at curtailing mother-to-child HIV transmission. By addressing the unique challenges experienced by migrant mothers and their infants, this study contributes significantly to broader efforts in controlling the spread of HIV, ultimately enhancing the health outcomes and well-being of Dongguan's migrant population. Furthermore, our research introduces a distinctive perspective within the extensively examined domain of Prevention of Mother-to-Child Transmission (PMTCT) programs, focusing on the internally migrant Chinese population, an understudied demographic group in this context. This study, conducted in Dongguan, China, represents one of the pioneering investigations into pregnant women with HIV and their infants within this migrant community.


Peripheral postsynaptic alpha-adrenoceptor blocking properties of some new dihydrobenzofurane and imidazoline derivatives in pithed rats.
Peripheral postsynaptic alpha-adrenoceptor blocking properties of six new dihydrobenzofurane and imidazoline derivatives have been investigated in pithed rat against the pressor effects of phenylephrine and cirazoline (alpha 1-agonists) and clonidine and azepexole (alpha 2-agonists). Except for (N-methylimidazolinyl-2)-2 dihydro-2,3 benzofurane (II) that acted neither on alpha 1- nor alpha 2-adrenoceptors, all the compounds revealed blocking effects - plus or minor - on both alpha 1- and alpha 2-adrenoceptors. (Imidazolinyl-2)-2-chloro-7 dihydro-2,3-benzofurane (IV) is equipotent in blocking both alpha 1- and alpha 2-adrenoceptors. 7-Methoxy-(imidazolinyl-2)-2 dihydro-2,3-benzofurane (III) and (imidazolinyl-2)-2-fluoro-7-dihydro-2,3-benzofurane (V) block more effectively alpha 1- than alpha 2-adrenoceptors whereas (imidazolinyl-2)-2-benzocyclobutane (VI) is more potent in blocking alpha 2- than alpha 1-adrenoceptors. (Imidazolinyl-2)-2-dihydro-2,3-benzofurane (I) is a preferential alpha 2-adrenoceptor blocking agent. The most effective agents on alpha 2-adrenoceptors are under further pharmacological investigations.


Stability and activity of lysozyme in stoichiometric and non-stoichiometric protic ionic liquid (PIL)-water systems.
There has been a substantial increase in enzyme applications within the biochemical and pharmaceutical industries, for example, as industrial biocatalysts. However, enzymes have narrow marginal stability which makes them prone to become inactive and/or denature with a slight change in the solvent environment. Typically industrial applications require harsher solvent environments than enzyme native environments, and hence there is a need to understand solvent-protein interactions in order to develop strategies to maintain, or enhance, the enzymatic activity under industrially relevant solvent conditions. Previously we have shown that protic ionic liquids (PILs) with water can have a stabilising effect on lysozyme, with a large variation dependent on which PIL ions are present, and the water concentration [E. C. Wijaya et al., Phys. Chem. Chem. Phys. 18(37), 25926-25936 (2016)]. Here we extend on this work using non-stoichiometric aqueous PIL solvents to investigate, and isolate, the role of pH and ionicity on enzymes. We have used the PILs ethylammonium nitrate (EAN) and ethanolammonium formate (EOAF) since our previous work has identified these as good solvents for lysozyme. Solvent libraries were made from these two PILs with an additional precursor acid or base to modify the acidity/basicity of the neutral stoichiometric PIL, and with water added, to have solutions with 4-17 mol. % of the PIL ions in water. Molar ratios of base:acid were varied between 1:1.05 and 2:1 for EAN and 1:1.25 and 2:1 for EOAF, which enabled from highly basic to highly acidic solutions to be obtained. This was to modify the acidity/basicity of the neutral stoichiometric PILs, without the addition of buffers. The structure and stability of hen egg white lysozyme (HEWL) were explored under these solvent conditions using synchrotron small angle X-ray scattering (SAXS), Fourier transform infrared (FTIR), and activity assays. The radius of gyration and Kratky plots obtained from the SAXS data showed little change with varying ionicity or acid:base ratio. FTIR showed that α-helix was maintained in all, except for the most acidic solvent conditions. The activity data show that HEWL was active between pH 0 and 11 for the EA:N-water system and pH 4.4 and 11 for the EOA:F-water system. This work indicates that ionic liquids have the potential to enable enzymes to maintain activity across a broader range of solvent conditions.


Robust, Durable Gene Activation In Vivo via mRNA-Encoded Activators.
Programmable control of gene expression via nuclease-null Cas9 fusion proteins has enabled the engineering of cellular behaviors. Here, both transcriptional and epigenetic gene activation via synthetic mRNA and lipid nanoparticle delivery was demonstrated in vivo. These highly efficient delivery strategies resulted in high levels of activation in multiple tissues. Finally, we demonstrate durable gene activation in vivo via transient delivery of a single dose of a gene activator that combines VP64, p65, and HSF1 with a SWI/SNF chromatin remodeling complex component SS18, representing an important step toward gene-activation-based therapeutics. This induced sustained gene activation could be inhibited via mRNA-encoded AcrIIA4, further improving the safety profile of this approach.


The prevalence of human papilloma virus DNA in women with mucopurulent endocervicitis.
The aim of the study was to determine the prevalence of human papillomavirus (HPV) infection in a group of patients with mucopurulent endocervicitis. One hundred and forty-eight patients who came for their routine medical screening and were diagnosed with mucopurulent endocervicitis were enrolled in the study. HPV DNA was sought in cervical swab specimens placed in digene transport medium by use of the Digene Hybrid Capture assay. HPV infection was detected in 5.4% (8/148) of the patients with mucopurulent endocervicitis. The mean age of the patients was 36.4+/-8.2 (18-54) years. Approximately 40% (59/148) of the patients used intrauterine devices currently or in the past, while 16.2% (24/148) used combined oral contraceptives as the contraceptive method. HPV DNA was detected in eight patients: five had infections with low-risk subtypes, one with high/intermediate risk subtypes and one with the combination of high- and low-risk subtypes. The mean age of the HPV infected patients was significantly lower than the HPV negative patients (28.2+/-6.3 versus 36.9+/-8.1 years, p = 0.003). Risk factors for HPV infection did not differ between the infected and uninfected groups. HPV infection should be sought in patients with clinical evidence of mucopurulent endocervicitis even without risk factors for cervical neoplasia.


[Genomic variation of laboratory strains and natural populations of Drosophila melanogaster exposed to X-irradiation].
The spontaneous and X-ray-induced mutation rates and spectrums were estimated in laboratory strains and natural populations of Drosophila melanogaster from the Chernobyl meltdown area. Laboratory strains Oregon R and y2w alpha 4 were stable. In all natural populations, the spontaneous mutation rate was an order of magnitude higher (10(-3)) than in laboratory strains. Irradiation at a total dose of 3000 R was shown to induce genetic instability in the stable laboratory strain y2w alpha 4 and to increase the mutation rate and spectrum range in the unstable natural population P1. A high level of genetic instability was observed both in the first and second generations. Genetic analysis by means of classical genetic and molecular methods was performed; in crosses, a collection of spontaneous and induced mutants was used. The molecular genetic nature of mutations at the white and cut loci was analyzed by Southern blot-hybridization. Mutations at the white locus were shown to result both from transposition and recombination events; cut mutations were caused by deletions.


The effect of inhaled ipratropium bromide alone and in combination with oral terfenadine on bronchoconstriction provoked by adenosine 5'-monophosphate and histamine in asthma.
The aim of this study was to investigate the effect of terfenadine, an antihistamine, 180 mg orally, the anticholinergic drug, ipratropium bromide (IB), 0.5 mg nebulized aerosol, the combination of these two drugs, and placebo tablets and aerosol on histamine- and adenosine 5'-monophosphate (AMP)-induced bronchoconstriction in a randomized, double-blind fashion. Airway response was evaluated as FEV1. After placebo, the geometric mean (GM) provocative concentration causing a 20% in FEV1 from the postsaline baseline value (PC20) for histamine and AMP was 0.63 and 5 mg/ml, respectively. Terfenadine displaced the FEV1 concentration-response curves obtained with both histamine (GM PC20 values increasing to 26.92 mg/ml) and AMP (GM PC20 values increasing to 26.7 mg/ml) to the right. IB had a small, but significant, protective effect against the fall in FEV1 produced by histamine and AMP, the GM PC20 values increasing to 1.69 and to 12.6 mg/ml, respectively. Terfenadine and IB in combination produced protection against histamine and AMP that was more than the production produced by either drug alone, the GM PC20 values increasing to 54.76 and 47.7 mg/ml, respectively. There was no correlation between degree of bronchodilatation induced by active treatments and concentration ratios for AMP or histamine. These data suggest that histamine release and vagal reflexes both contribute to AMP-induced bronchoconstriction in clinical asthma in man.


Host soluble factors with blocking and stimulating activity on the expression of the bovine leukemia virus.
The bovine leukemia virus (BLV), like the human T cell leukemia viruses (HTLV-I and -II), is usually present in its host in a transcriptionally repressed state. However, the viral genome becomes derepressed a few hours after the infected lymphocytes are cultured in vitro. Depending upon the concentrations tested, plasma and lymphatic fluid of BLV-infected cattle have either stimulatory (BSF) or inhibitory (PBB) activity on viral expression in these cultures. These activities can be separated by chromatographic procedures. BSF is either an antiviral antibody or a BLV-induced molecule that binds to IgG. After complete removal of BSF, the PBB activity can be more consistently detected in bovine plasma and lymphatic fluid. PBB activity can also be demonstrated in human plasma. It seems likely that this activity is responsible for the latent state in which BLV, HTLV-I and -II, and human immunodeficiency virus are usually present in their hosts.


The response of Nannochloropsis gaditana to nitrogen starvation includes de novo biosynthesis of triacylglycerols, a decrease of chloroplast galactolipids, and reorganization of the photosynthetic apparatus.
Microalgae of the genus Nannochloropsis are capable of accumulating triacylglycerols (TAGs) when exposed to nutrient limitation (in particular, nitrogen [N]) and are therefore considered promising organisms for biodiesel production. Here, after nitrogen removal from the medium, Nannochloropsis gaditana cells showed extensive triacylglycerol accumulation (38% TAG on a dry weight basis). Triacylglycerols accumulated during N deprivation harbored signatures, indicating that they mainly stemmed from freshly synthesized fatty acids, with a small proportion originating from a recycling of membrane glycerolipids. The amount of chloroplast galactoglycerolipids, which are essential for the integrity of thylakoids, decreased, while their fatty acid composition appeared to be unaltered. In starved cells, galactolipids were kept at a level sufficient to maintain chloroplast integrity, as confirmed by electron microscopy. Consistently, N-starved Nannochloropsis cells contained less photosynthetic membranes but were still efficiently performing photosynthesis. N starvation led to a modification of the photosynthetic apparatus with a change in pigment composition and a decrease in the content of all the major electron flow complexes, including photosystem II, photosystem I, and the cytochrome b(6)f complex. The photosystem II content was particularly affected, leading to the inhibition of linear electron flow from water to CO(2). Such a reduction, however, was partially compensated for by activation of alternative electron pathways, such as cyclic electron transport. Overall, these changes allowed cells to modify their energetic metabolism in order to maintain photosynthetic growth.


Malignant syphilis with ocular involvement and organism-depleted lesions.
Diagnosis and treatment of syphilis are challenging because of the condition's diverse clinical symptoms, histopathological variance, and the lack of definite tests for treatment follow-up. We report a case of secondary pustular-ulcerative malignant syphilis with ocular involvement in a human immunodeficiency virus-infected patient. It was striking to find that ulcerative lesions can be highly organism depleted.


Associations between changes in abdominal and thigh muscle quantity and quality.
Computed tomography (CT) images at L4-L5, T12-L1 and the midthigh are commonly used to assess abdominal adiposity, liver fat, and muscle quantity (mass) and quality (lipid), respectively. Unknown is whether abdominal skeletal muscle (SM) at L4-L5 or T12-L1 can also be used to reflect thigh SM quantity and quality, which is often considered the criterion measure. Also unclear is whether changes in thigh SM quantity and quality are reflected by corresponding changes in abdominal SM quantity and quality. We examined the associations between abdominal SM and thigh SM quantity and quality in overweight/obese postmenopausal women before (n = 125) and after (n = 86) a 6-month exercise intervention trial. CT was used to assess muscle quantity and quality at the midthigh, L4-L5, and T12-L1. At baseline, abdominal SM quality was significantly associated with thigh SM quality at L4-L5 and T12-L1 (R2 = 0.22 and R2 = 0.37, respectively; P < 0.01). Similarly, at baseline, abdominal SM quantity and quality was significantly associated with thigh SM quantity at L4-L5 and T12-L1 (R2 = 0.37 and R2 = 0.48, respectively; P < 0.01). Changes in thigh SM mass were marginally associated with changes in abdominal SM at T12-L1 (R2 = 0.08, P = 0.01) but not at L4-L5 (P > 0.10). Changes in thigh SM quality were associated with corresponding changes in abdominal SM quality at both L4-L5 and T12-L1 (R2 = 0.43 and R2 = 0.73, respectively). Measurements obtained from a single CT image taken within the abdomen are moderately correlated with measures of thigh SM quantity and quality at baseline. Changes in thigh SM mass are poorly tracked by changes in abdominal SM. However, abdominal SM does provide comparable measures of muscle quality change.


Structural proteins of Chikungunya virus.
Polyacrylamide gel analysis of the structural proteins of African and Asian strains of Chikungunya virus, an alphavirus, showed that both strains contain three structural proteins: glycosylated E1 and E2, embedded in the viral envelope, and a nonglycosylated nucleocapsid protein. In pulse-chase experiments the precursor protein PE2 was chased into glycoprotein E2, which migrated slightly faster than did glycoprotein E1. The third Chikungunya glycoprotein, E3, was not associated with mature virions but was released into culture fluids. With glycoproteins E1 and E2, separated by glass wool column chromatography, it was shown that hemagglutinating activity is associated with glycoprotein E1.


[Voice rehabilitation after laryngectomy].
Laryngeal and hypopharyngeal carcinomas are among the most common malignant tumours of the head and neck region, accounting for about 3,000 new cases per year. Despite enormous advances in organ preservation surgery and chemoradiotherapy, total laryngectomy is still necessary in approximately one quarter of affected patients. The removal of the larynx results in the loss of 3 important functions, i. e., voice production, the air conditioning mechanism of the nose, and the ability to smell. Whereas voice rehabilitation has been a mainstay of treatment from the very beginning of laryngeal surgery, pulmonary and olfactory rehabilitation has received increasing attention only in the past 2 decades. Today every head and neck surgical oncologist should be familiar with the various methods of voice rehabilitation and the use of heat and moisture exchangers for air conditioning. The objective of this article is to provide an overview of current methods of rehabilitation after total laryngectomy and to introduce young surgeons with an interest in voice rehabilitation to available techniques.


An Analysis of Five TrkB Gene Polymorphisms in Schizophrenia and the Interaction of Its Haplotype with rs6265 BDNF Gene Polymorphism.
The BDNF dysfunction in the schizophrenia has been soundly documented. The TrkB gene is a high-affinity receptor of the BDNF that is changed in schizophrenia and mood disorders. The study had two aims: first, to identify whether the five nucleotide polymorphisms (SNPs) in TrkB gene are associated with a diagnosis of schizophrenia; and the latter, if any association exists between the TrkB SNPs and psychopathology, suicide attempts, and family history of schizophrenia in a Caucasian population. Case-control study (401 patients and 657 healthy controls) was used to examine a predisposition for schizophrenia. The tests for psychopathology, suicide attempts, and family history of schizophrenia were conducted only in patient group. The severity of the schizophrenia was measured using the five-factor model of the PANSS. In addition, the haplotype analysis for both the separate for SNPs of TrkB gene and in combination with the rs6265 SNP BDNF gene was conducted. Our case-control study revealed that the genetic variants of rs10868235 (T/T polymorphic genotype) and rs1387923 (G/G polymorphic genotype) of the TrkB gene were associated with a higher risk of developing schizophrenia in men. However, the A/A wild genotype of rs1387923 was connected with a lower risk for both the development of and the family manifestation of schizophrenia in men. The G polymorphic allele of rs1565445 was associated with an increased risk of suicide in schizophrenia. The tested SNPs of the TrkB gene did not modulate the psychopathology of schizophrenia. The haplotype that was built with five SNPs in the TrkB gene was protective for men, but after joining the rs6265 SNP of the BDNF gene, a haplotype that was protective for women was created.


Entangled photon absorption in an organic porphyrin dendrimer.
Two-photon absorption spectroscopy is an intensity dependent nonlinear effect related to the excitation of virtual intermediate states. The classical two-photon absorption has an extremely low efficiency which is quantified by its cross-section (delta approximately 10(-48) cm4 s at 800 nm). To overcome this limitation, we demonstrate a novel effect of the two-photon absorption method utilizing the high degree of quantum optical correlation between photon pairs created by the process of spontaneous parametric downconversion. A large entangled two-photon absorption cross-section (delta(e) approximately 10(-17) cm2 at 800 nm) was measured in an organic porphyrin dendrimer. We also discuss the nonmonotonic behavior of variation of the entangled two-photon absorption cross-section by controlling the entanglement time. This novel effect may open new avenues for ultrasensitive detection in chemical and biological systems. TPA spectroscopy has been considered as a powerful tool in physics, chemistry, and biology. The inherent nonlinear process of the classical TPA is distinguishable from the single photon absorption (SPA) linear process. Although the benefits of greater penetration depth and better control and reduction of scattering, the TPA spectroscopy has been restricted by the necessity of a high power optical source due to the low efficiency of the TPA effect. The use of entangled photons from a correlated source for the purpose of the two-photon effect is promising in this regard as one may obtain two-photon effects with very small numbers of photons.


High Rates of Diabetes Mellitus, Pre-diabetes and Obesity Among Somali Immigrants and Refugees in Minnesota: A Retrospective Chart Review.
We examined the prevalence of cardiovascular risk factors among Somali refugees at a midwestern hospital in the U.S. This was a retrospective cohort study of 1007 adult Somali patients and an age and frequency-matched cohort of non-Somali patients actively empanelled to a large, academic primary care practice network in the Midwest United States between January 1, 2011 and December 31, 2012. Cardiovascular risk factors were obtained by chart review and compared between the two cohorts using a Chi squared test. Median age was 35 years (Q1, Q3; 27, 50). The prevalence of diabetes was significantly higher among Somali versus non-Somali patients (12.1 vs 5.3 %; p = 0.0001), as was prediabetes (21.3 vs 17.2 %; p < 0.02) and obesity (34.6 vs 32.1 %; p = 0.047). After adjusting for age, sex, body mass index, education and employment, among the Somali patients, the odds ratio (95 % confidence interval) for diabetes was 2.78 (1.76-4.40) and 1.57 (1.16-2.13) for pre-diabetes. There was a significantly higher prevalence of diabetes, pre-diabetes and obesity among Somali patients compared with non-Somali patients. Further research into the specific causes of these disparities and development of targeted effective and sustainable interventions to address them is needed.


[Helicobacter pylori and gastric ulcer].
In connection with longitudinal ulcer studies and the demonstration of Helicobacter pylori as the main cause of chronic gastritis, new aspects of gastric ulcer recurrences and healing become evident. This extends the possibilities to prognosticate the course of gastric ulcer and to use more effective treatment.


Coping with domestic violence in pregnancy.
This article defines the term domestic violence, outlines its prevalence, and indicates a link between domestic violence and pregnancy outcomes. A need for the identification and development of intervention strategies by UK midwives is proposed and some consideration and concerns regarding their implementation are expressed.


This is me: A qualitative investigation of young people's experience of growing up with visual impairment.
Childhood visual impairment (VI) has a profound impact on many aspects of childhood and adolescence. This is well-documented in cross-sectional and/or quantitative studies utilizing self-report instruments which compare children with and without VI. Young people's views on the experience of growing up with VI as a developmental, change-driven process remain largely unexplored. As part of our broader research programme on quality of life of visually impaired children and young people in the United Kingdom, in-depth, semi-structured interviews were conducted between March and June 2015, with a stratified sample of 17 young people with VI, aged 16-19 years. An age-sensitive, empirically-based topic guide encouraged retrospective reflections on participants' experiences of growing up with VI, including age-normative and vision-specific challenges. Descriptions of growing up with VI largely centered on an overarching higher-order theme labelled becoming me. Four themes representing everyday activities, attitudes, preferences and perceptions in relation to i) social relationships, ii) independence and responsibilities, iii) the future, and iv) rising to challenges emerged and were used by participants in their description of three stages in which they developed a sense of self: i) laying the foundations, ii) testing the waters, and iii) this is me. Differences in manifestation of VI influenced how young people made sense of their experiences and their sense of self. Findings are discussed in relation to normative and vision-specific changes in psychosocial development during adolescence, including the development of identity. They highlight the need for ongoing monitoring of subjective well-being in a clinical population with a unique early life course trajectory.


Developing tools for evaluating inoculation methods of biocontrol Streptomyces sp. strains into grapevine plants.
The endophytic Streptomyces sp. VV/E1, and rhizosphere Streptomyces sp. VV/R4 strains, isolated from grapevine plants were shown in a previous work to reduce the infection rate of fungal pathogens involved in young grapevine decline. In this study we cloned fragments from randomly amplified polymorphic DNA (RAPD), and developed two stably diagnostic sequence-characterized amplified region (SCAR) markers of 182 and 160 bp for the VV/E1 and VV/R4 strains, respectively. The SCAR markers were not found in another 50 actinobacterial strains isolated from grapevine plants. Quantitative real-time PCR protocols based on the amplification of these SCAR markers were used for the detection and quantification of both strains in plant material. These strains were applied on young potted plants using two methods: perforation of the rootstock followed by injection of the microorganisms or soaking the root system in a bacterial suspension. Both methods were combined with a booster treatment by direct addition of a bacterial suspension to the soil near the root system. Analysis of uprooted plants showed that those inoculated by injection exhibited the highest rate of colonization. In contrast, direct addition of either strain to the soil did not lead to reliable colonization. This study has developed molecular tools for analyzing different methods for inoculating grapevine plants with selected Streptomyces sp. strains which protect them from fungal infections that enter through their root system. These tools are of great applied interest since they could easily be established in nurseries to produce grafted grapevine plants that are protected against fungal pathogens. Finally, this methodology might also be applied to other vascular plants for their colonization with beneficial biological control agents.


Successful treatment of active haemorrhage from a duodenal diverticulum using surgicel (absorbable haemostat): a case report.
Haemorrhage is one of the rare but serious complications of duodenal diverticula. Current methods of treatment include: endoscopy with injection therapy or hemoclip application and diverticulectomy. In this paper we present the case of a 61 year old man with life threatening haemorrhage who was managed successfully with gentle packing of a bleeding duodenal diverticulum using SURGICEL (Absorbable Haemostat). This appears to be a simple and effective way of dealing with the problem especially in situations where other methods are ineffective or inapplicable. Early surgical intervention before the development of any coagulopathy increases the chances of a successful outcome. It has not been possible to find a similar report from a thorough literature search.


Acute Effect of Heavy Load Back Squat and Foam Rolling on Vertical Jump Performance.
Purpose: In a rested state, foam rolling has been shown to improve blood flow to the working tissues. When inducing post-activation performance enhancement (PAPE), previous research suggests a longer recovery period between the conditioning activity and performance assessment in weaker participants (back squat <2.0 × body mass). It is possible that a cool-down effect may take place between the conditioning activity and performance assessment for these participants. Therefore, the purpose of this investigation was to determine if foam rolling could help mitigate any cool-down effect to help participants capitalize on PAPE. Methods: Seventeen physically active participants completed baseline jumps followed by rest (control), back squat exercise (heavy squats), rest and foam rolling (FR), and heavy squats followed by foam rolling (combo). VJ performance was assessed three times post-treatment with 2 min between each assessment. Results: VJ height and impulse were greater at baseline than at any other time point across all sessions (p < .001). Impulse for the control and FR sessions were greater than the squats session (p < .015). Impulse for the combo session was less than the FR session (p = .04). Conclusions: Foam rolling did not have a significant impact on attenuating any cool-down effect. In addition, our heavy squats protocol appears to induce too much fatigue that possibly masked the effects of PAPE.


Carnitine and Depression.
Depression has become one of the most common mental diseases in the world, but the understanding of its pathogenesis, diagnosis and treatments remains insufficient. Carnitine is a natural substance that exists in organisms, which can be synthesized in vivo or supplemented by intake. Relationships of carnitine with depression, bipolar disorder and other mental diseases have been reported in different studies. Several studies show that the level of acylcarnitines (ACs) changes significantly in patients with depression compared with healthy controls while the supplementation of acetyl-L-carnitine is beneficial to the treatment of depression. In this review, we aimed to clarify the effects of ACs in depressive patients and to explore whether ACs might be the biomarkers for the diagnosis of depression and provide new ideas to treat depression.


Interactions of human platelets with insoluble anticoagulant modified polystyrene resins.
The interactions of two insoluble anticoagulant polystyrene derivatives with human platelets were studied in an in vitro system similar to a chromatography column. Blood was pumped through the column and platelets were counted before and after passage through the column. Interaction of platelets with the beads led to retention of platelets in the column. The same experiment was performed with several donors. Different pretreatments were assayed and compared for both materials: platelet poor plasma, antithrombin III-depleted platelet poor plasma and an antithrombin III solution. Platelet retention depends on the polymer composition: the material containing glutamic acid sulphamide groups, which has a larger anticoagulant activity in plasma than the materials only substituted by sulphonate groups, is always less reactive towards platelets. The differences in the effects of pretreatment on both materials can be correlated with the variations of antithrombin adsorption on the synthetic surfaces.


Infected Retained Catheter-Related Sheath, an Underrecognized Complication of Central Venous Catheter Insertion: A Case Report.
BACKGROUND Central venous catheters are indicated for a variety of conditions, including hemodynamic monitoring, hemodialysis, and long-term antibiotic and chemotherapy delivery. Several million are placed each year. Development of a fibrin sheath around the catheter is a common occurrence, with a reported incidence of 42-100% within 7 days of catheter placement. It is uncommon for these sheaths to be left in the patient upon removal of the catheter and even far more uncommon for these retained sheaths to lead to complications. CASE REPORT We present the case of a 45-year-old woman with a previous history of superior mesenteric artery syndrome and chronic protein calorie malnutrition on total parenteral nutrition through a long-term indwelling central venous catheter. She presented with concerns of persistent bacteremia despite outpatient intravenous antibiotic therapy, requiring removal of her central venous catheter. A transesophageal echocardiogram was performed to rule out infective endocarditis. Findings showed a highly mobile mass extending from the superior vena cava into the right atrium, most consistent with a retained catheter-related sheath. Due to concern for this being a nidus of her persistent bacteremia, she underwent mechanical thrombectomy, with excellent results and subsequent clearing of her bacteremia. CONCLUSIONS Placement of central venous catheters is becoming a commonplace occurrence, with millions placed each year. Retained catheter-related sleeves are a potential complication, with further research needed to help determine the clinical significance and best treatment approach.


[Research of ultrasonic emulsifying and drawing away technique on biological tissue].
Technique of ultrasonic emulsifying and drawing away on biological tissue can achieve the purpose of operating treatment. Having the aid of ultrasonic wave technique, it transforms electronic energy into kinetic energy of high frequency mechanical vibration. Making use of the function of stronger instantaneous shock acceleration more than the minium cutting threshold of biological tissue, it cuts biological tissue pathologically changed and not needed, then smashes and emulsifies it, draws away the emulsified tissue by pump system.


Mitochondrial disorders and the eye.
The clinical significance of disturbed mitochondrial function in the eye has emerged since mitochondrial DNA (mtDNA) mutation was described in Leber's hereditary optic neuropathy. The spectrum of mitochondrial dysfunction has become apparent through increased understanding of the contribution of nuclear and somatic mtDNA mutations to mitochondrial dynamics and function. Common ophthalmic manifestations of mitochondrial dysfunction include optic atrophy, pigmentary retinopathy, and ophthalmoplegia. The majority of patients with ocular manifestations of mitochondrial disease also have variable central and peripheral nervous system involvement. Mitochondrial dysfunction has recently been associated with age-related retinal disease including macular degeneration and glaucoma. Therefore, therapeutic targets directed at promoting mitochondrial biogenesis and function offer a potential to both preserve retinal function and attenuate neurodegenerative processes.


[A clinical study of recombinant human G-CSF in gynecological tumor patients with neutropenia due to chemotherapy (rG.CSF Clinical Study Group)].
We evaluated clinical efficacy of recombinant human granulocyte colony stimulating factor (rG-CSF), successfully expressed in Chinese hamster ovarian cell, in gynecological tumor patients (pts) with neutropenia due to chemotherapy (CT). Fifty-eight pts with advance or relapsed gynecological malignancy were entered into this study. These pts had neutropenia below 1,000/cmm by CT and in the next cycle of CT they were treated with daily rG-CSF (2 micrograms/kg/day, subcutaneously) starting from the next day of CT for 14 days. The activities of rG-CSF were evaluated using following indices calculated for each cycle: a) the absolute neutrophil count (ANC) at nadir, b) the period for restoration in ANC above 1,500/cmm, and c) the total area below the 1,000/cmm level in ANC calculated by a computer. Forty-seven out of 52 evaluable pts (90.4%) showed good response to rG-CSF. Only adverse events considered possibly due to rG-CSF were transient fever and anorexia, one case each. In conclusion, rG-CSF appears to be well tolerated by gynecological tumor patients and to considerably rescue them from neutropenia caused by intensive chemotherapy.


Control of human sperm intracellular pH by cholesterol and its relationship to the response of the acrosome to progesterone.
When incubated in vitro, human sperm gradually become capable of acrosome-reacting in response to the agonist progesterone. Loss of unesterified cholesterol is required for sperm to become responsive to progesterone, but how cholesterol regulates acrosomal responsiveness is unknown. These experiments tested the hypothesis that loss of sperm cholesterol leads to a rise in the intracellular pH (pH(i)) that makes the sperm responsive to progesterone. pH(i) was measured using BCECF (2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein) in freshly ejaculated sperm (T0 sperm) and in sperm incubated in vitro overnight (T24 sperm). During incubation, pH(i) increased from 6.94 +/- 0.03 to 7.08 +/- 0.01 (mean +/- SEM, n = 4, p < 0.01). Incubating sperm 24 h in medium supplemented with 1 microM cholesterol to prevent loss of sperm cholesterol suppressed the rise of pH(i) (T24C sperm, pH(i) = 6.96 +/- 0.03, n = 4, p = 0.64 compared to T0 sperm). To test whether their lower pH(i) prevents T24C sperm from reacting, we treated T24C sperm with the alkalinizing agents trimethylamine chloride (TMA) or NH4Cl. These agents did cause T24C sperm to respond to progesterone in a dose-dependent fashion, but they also caused a similar increase in the number of reacting T24 sperm. These agents probably do not reverse the inhibiting effects of high cholesterol but rather make responsive a subpopulation of sperm that is present regardless of the cholesterol content. NH4Cl and TMA did not make T0 sperm responsive to progesterone. The acidifying agent sodium propionate did not diminish the response of T24 sperm to progesterone. In summary, pH(i) increases during incubation in vitro in a cholesterol-dependent fashion. Elevated pH(i) alone is probably not sufficient to make sperm acrosomally responsive.


Immunoaffinity column clean-up and thin layer chromatography for determination of ochratoxin A in green coffee.
An immunoaffinity clean-up-based method for determining ochratoxin A (OTA) in green coffee aiming at one-dimensional thin layer chromatography (TLC) analysis was established. OTA was extracted with a mixture of methanol and aqueous sodium hydrogen carbonate solution, purified through an immunoaffinity column, separated on normal or reversed-phase (RP) TLC plates and detected and quantified by visual and densitometric analysis. The linear equation of the standard calibration curve by densitometric analysis gave R(2) > 0.999 (0.04-84 ng). The mean recovery (R) of OTA from spiked samples (1.8-109 microg kg(-1)) by densitometric and visual analyses were 98.4 and 103.8%, respectively. The relative standard deviations (RSD) for densitometric and visual analysis varied from 1.1 to 24.9% and from 0.0 to 18.8%, respectively. The RSD for naturally contaminated samples by densitometry (three levels of contamination, n = 3) varied from 11.1 to 18.1%. The correlation (R(2)) between high-performance liquid chromatography (HPLC) and densitometry, and between visual and densitometric analysis for spiked samples were > 0.99. The limit of detection (LOD) of the method was 0.5 microg kg(-1) for normal TLC. Toluene-ethyl acetate-88% formic acid (6:3:1 v/v/v) and acetonitrile-methanol-water-glacial acetic acid (35:35:29:10 v/v/v/v) were regarded as the suitable TLC solvents for eluting both standards and samples on normal and RP TLC plates, respectively. Toluene-acetic acid (99:1 v/v) was chosen as the spotting solvent among several others for giving the best sensitivity and resolution of OTA on TLC plates as well as the best recovery of OTA from standard and sample extract residues. Preliminary studies were carried out to investigate the reuse of the immunoaffinity column and the interference of caffeine in the OTA recovery.


Secukinumab improves hand, foot and nail lesions in moderate-to-severe plaque psoriasis: subanalysis of a randomized, double-blind, placebo-controlled, regimen-finding phase 2 trial.
Psoriasis affecting sites such as the hands, feet and nails can be particularly difficult to treat. There are limited data on the efficacy of biological agents to treat these specific localizations. This analysis of a phase 2 regimen-finding study evaluated the efficacy of secukinumab in subjects with moderate-to-severe psoriasis and non-pustular involvement of the hands, feet and/or nails. Subjects were randomized (1 : 2 : 2 : 1) to one of three subcutaneous secukinumab 150-mg induction regimens [Single (Week 0), Monthly (Weeks 0, 4, 8), Early (Weeks 0, 1, 2, 4)] or placebo. In the subgroup (n = 131) with hand and/or foot psoriasis [baseline 5-point hand/foot Investigator's Global Assessment (IGA) score ≥2], efficacy was assessed as percentage of subjects achieving an IGA response [a score of 0 (clear) or 1 (minimal) and an improvement of ≥2 points on the 5-point hand/foot scale vs. baseline] at Week 12. In the subgroup (n = 304) with fingernail psoriasis (baseline composite score ≥1), efficacy was assessed as mean percentage change from baseline to Week 12 in a composite score. At Week 12, a markedly higher percentage of subjects with hand and/or foot psoriasis achieved an IGA response with the Early regimen vs. placebo (54.3% vs. 19.2%, P = 0.005). The composite fingernail score improved with the Early and Monthly regimens, but worsened with placebo [percentage mean change from baseline (SE): -19.1% (6.12) and -10.6% (7.06) vs. 14.4% (11.92); P = 0.010 vs. placebo for Early, P = 0.027 for Monthly). Secukinumab was well tolerated. Secukinumab demonstrated a beneficial effect on psoriasis of the hands/feet/nails in this short-term assessment.


Benefits of whole-body vibration with an oscillating platform for people with multiple sclerosis: a systematic review.
The objective of this work was to investigate the effects of whole-body vibration on people with multiple sclerosis (MS). PubMed, CINAHL and Scopus databases were systematically searched for studies on the use of whole-body vibration (WBV) exercise in people with MS. These searches were supplemented with material identified in the references and in the authors' personal files. A qualitative analysis was performed to summarize the findings. Five studies with a total of seventy-one subjects were identified. All of these studies had small numbers of subjects (3-25), and two of the studies had no control groups. Some investigations have shown significant improvements of the muscle strength, of the functional mobility, and of the timed get up and go test in patients with MS. The number of publications found in the databanks searched is small, and in general, they have limitations in the design of protocols with a weakness to the interpretation of the findings. However, the analysis of the findings in these studies permits to conclude that some papers indicate that WBV exercises could benefit patients with MS. In addition, we suggest further larger scale investigations with controlled parameters and well-designed protocols into the effects of WBV exercises in people with MS.


Drosophila alpha-actinin in ovarian follicle cells is regulated by EGFR and Dpp signalling and required for cytoskeletal remodelling.
alpha-Actinin is an evolutionarily conserved actin filament crosslinking protein with functions in both muscle and non-muscle cells. In non-muscle cells, interactions between alpha-actinin and its many binding partners regulate cell adhesion and motility. In Drosophila, one non-muscle and two muscle-specific alpha-actinin isoforms are produced by alternative splicing of a single gene. In wild-type ovaries, alpha-actinin is ubiquitously expressed. The non-muscle alpha-actinin mutant Actn(Delta233), which is viable and fertile, lacks alpha-actinin expression in ovarian germline cells, while somatic follicle cells express alpha-actinin at late oogenesis. Here we show that this latter population of alpha-actinin, termed FC-alpha-actinin, is absent from the dorsoanterior follicle cells, and we present evidence that this is the result of a negative regulation by combined Epidermal growth factor receptor (EGFR) and Decapentaplegic signalling. Furthermore, EGFR signalling increased the F-actin bundling activity of ectopically expressed muscle-specific alpha-actinin. We also describe a novel morphogenetic event in the follicle cells that occurs during egg elongation. This event involves a transient repolarisation of the basal actin fibres and the assembly of a posterior beta-integrin-dependent adhesion site accumulating alpha-actinin and Enabled. Clonal analysis using Actn null alleles demonstrated that although alpha-actinin was not necessary for actin fibre formation or maintenance, the cytoskeletal remodelling was perturbed, and Enabled did not localise in the posterior adhesion site. Nevertheless, epithelial morphogenesis proceeded normally. This work provides the first evidence that alpha-actinin is involved in the organisation of the cytoskeleton in a non-muscle tissue in Drosophila.


Fifteen-minute consultation: Intubation of the critically ill child presenting to the emergency department.
Intubation of critically ill children presenting to the emergency department is a high-risk procedure. Our article aims to offer a step-by-step guide as to how to plan and execute a rapid, successful intubation in a way that minimises risk of adverse events and patient harm. We address considerations such as the need for adequate resuscitation before intubation and selection of equipment and personnel. We also discuss drug choice for induction and peri-intubation instability, difficult airway considerations as well as postintubation care. Focus is also given on the value of preintubation checklists, both in terms of equipment selection and in the context of staff role designation and intubation plan clarity. Finally, in cases of failed intubation, we recommend the application of the Vortex approach, highlighting, thus, the importance of avoiding task fixation and maintaining our focus on what matters most: adequate oxygenation.


Single Incision, Dual Window Approach for a Comminuted Distal Radius Fracture.
Introduction Complex distal radius fractures often involve a fragment of the volar-ulnar articular surface and the radial styloid. The volar ulnar corner of the distal radius is an important constraint to volar translation of the carpus and thus requires stable fixation to prevent wrist displacement. The traditional volar Henry approach often requires undue tension on the median nerve while retracting for access to the ulnar aspect of the radius. To protect the median nerve from iatrogenic injury and to improve exposure of the surgical site, we propose a single incision, dual window approach to the distal radius for complex bi-columnar fractures. Methods This technique combines the trans-Flexor Carpi Radialis (FCR) approach with a subcutaneous dissection to the ulnar aspect of the wrist. This window utilizes the interval between the ulnar neurovascular bundle and the carpal tunnel contents. Results This technique allows the surgeon to work through either window and thus visualize and directly fixate the various fracture fragments. We have treated complex articular distal radius fractures associated with ulnar communition with this novel technique and it has provided direct reduction with improved fragment access. The surgical technique, a case presentation and results are detailed in this report. Conclusion This case report has demonstrated that complex bi-columnar fractures of the distal radius can be effectively approached and fixated with a single incision dual window approach.


Comparative Study: Impacts of Ca and Mg Salts on Iron Oxygen Carriers in Chemical Looping Combustion of Biomass.
Chemical looping combustion (CLC) is one of the most promising methods for carbon capture and storage (CCS). An oxygen carrier, i.e., a mineral that can be oxidized and reduced, is used to convert the fuel in the process. The produced CO2 is inherently separated from the air components that enables easier CCS. The use of biomass-based fuels is desirable since it can lead to negative CO2 emissions. On the other hand, alkali compounds from the biomass may interact with the oxygen carrier causing problems, such as deactivation of the oxygen carrier. The most common oxygen carriers contain iron, since iron-based ores and industrial waste materials are readily available and cost-efficient. Therefore, the interaction between the iron oxygen carriers and the biomass ash-forming compounds needs to be investigated. Since Ca/Mg are abundant in biomass, it is important to clarify how their compounds interact with the oxygen carrier. In this study, the effect of Ca/Mg carbonates, chlorides, nitrates, sulfates, and phosphates along with synthetic biomass-derived ash on iron oxides was investigated. Redox reactions were investigated at 950 °C during 5 h under both oxidizing and reducing atmospheres. The results showed that the effect of Ca/Mg salts on the oxygen carrier varied depending on the anion of the salt. Generally, the nitrate- and phosphate-based salts of both Ca and Mg showed the harshest effect regarding agglomeration of the oxygen carriers. It was shown that the Ca/Mg-based compounds interacted differently with iron oxides, which was an unexpected result.


The Household Health Spending and Impoverishment: Findings from the Households Survey in Shiraz, Iran.
The present study aimed to investigate the households' impoverishment due to the healthcare costs in Shiraz in 2012. In this household's survey, 800 households were studied in Shiraz. The study sample was selected using stratified and cluster sampling in the urban and rural areas, respectively. The information was collected using the household section of the World Health Survey questionnaire. In order to determine impoverishment due to health spending, at first, the households' food-based poverty line (subsistence expenditure) was measured. Then, households' health expenditure was subtracted from their total expenditure and if the obtained value was lower than the households' food-based poverty line, the households was considered to be impoverished due to health expenditures. The collected data were entered into the SPSS (version 16) statistical software and analyzed using descriptive statistic, Chi-square test, and logistic regression in backward method. The study results showed that 7.1% of the households (CI: 0.071 ± 0.018) were impoverished because of healthcare expenditures. Besides, the households in the first quintile were more likely to be faced with poverty compared to those in the other quintiles (p < 0.05). Being covered by health insurance did not affect the protection from poverty due to health costs. Moreover, the participants living in rural areas were faced with poverty more than those living in urban areas (p < 0.05). It seems that health expenditure can be an economic shock for household in Shiraz and through spending on health a household may fall into poverty. As insurance had no effect on impoverishment, it implies that change in health insurance plans and ways of health financing is necessary.


Investigation of Various Organic Radicals Dispersed in Polymethylmethacrylate Matrices Using the Electron Spin Resonance Spectroscopy Technique.
The electron spin resonance (ESR) spectroscopy technique was used to study various organic radicals, such as 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO), 4-hydroxy-TEMPO (TEMPOL), 2-X-nitronylnitroxide (2-X-NN, X = Ph, NO2Ph, or cyclohexyl), 4-Y-benzonitronylnitroxide (4-Y-PhBzNN, Y = Ph or NO2Ph), and 2-Z-iminonitroxide (2-Z-IN, Z = Ph or NO2Ph) dispersed in a polymethylmethacrylate (PMMA) matrix. The experiments were conducted at room temperature. The complex nature of the recorded ESR spectra could be attributed to the superposition of the rotational diffusion component of TEMPO (or TEMPOL) in the nanospace of the PMMA matrix with the rigid-limit component. A single component of the rigid-limit was observed for 2-X-NN and 4-Y-PhBzNN radicals dispersed in the PMMA matrix. The isotropic components of g and hyperfine ( A ) tensor, estimated by analyzing the solution spectra, were used to determine the g and A components of 4-Y-PhBzNN. Only the rotational diffusion component was observed for the 2-Z-IN radical. These results demonstrated that the PMMA matrix contains cylindrical nanospaces. Various radicals other than TEMPO derivatives could be used in the ESR spin probe technique as probe molecules for determining the structures, sizes, and shapes of the nanospaces.


Changes in Inflammatory Biomarkers in Patients with Schizophrenia: A 3-Year Retrospective Study.
Accumulating evidence suggested that immune system activation might be involved in the pathophysiology of schizophrenia. The neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) can measure inflammation. This study aimed to investigate the inflammatory state in patients with schizophrenia by using these indicators. In this study, the complete blood count data for 187 continuing hospitalized patients with schizophrenia and 187 age- and sex-matched healthy participants was collected annually from 2017 to 2019. Platelet (PLT), lymphocyte (LYM), monocyte (MON) and neutrophil (NEU) counts were aggregated and NLR, MLR, PLR, and SII were calculated. Using a generalized linear mixed model, we assessed the impact of age, sex, diagnosis, and sampling year on the above indicators and evaluated the interaction between the factors. According to the estimation results of the generalized linear mixed model, the NLR increased by 0.319 (p = 0.004), the MLR increased by 0.037 (p < 0.001), and the SII increased by 57.858 (p = 0.018) in patients with schizophrenia. Data after two years of continuous antipsychotic treatment showed that the NLR and MLR were higher in patients with schizophrenia than those in healthy controls, while the PLT and LYM counts were decreased in patients with schizophrenia. The schizophrenia diagnosis was correlated to the MON and LYM count, NLR, MLR, and SII (p < 0.05). The differences in these markers were stable and cannot be eliminated by a full course of treatment. This study provides impetus for the inflammatory hypothesis of schizophrenia.


Distance to Cannabis Shops and Age of Onset of Cannabis Use.
In the Netherlands, cannabis use is quasi-legalized. Small quantities of cannabis can be bought in cannabis shops. We investigate how the distance to the nearest cannabis shop affects the age of onset of cannabis use. We use a mixed proportional hazard rate framework to take account of observable as well as unobservable characteristics that influence the uptake of cannabis. We find that distance matters. Individuals who grow up within 20 km of a cannabis shop have a lower age of onset.


9,10-Anthracene dicarboxylate bridged complexes with M2 quadruply bonded dimetal units: [[M2(O2CtBu)3]2(mu-9,10-An(CO2)2)], where M = Mo or W.
From the reactions between [M2(O2CtBu)4] and 9,10-anthracenedicarboxylic acid in toluene, the dicarboxylate bridged complexes [[M2(O2CtBu)3]2(mu-9,10An(CO2)2)], have been obtained as microcrystalline yellow (M = Mo) and red (M = W) powders. The powders are soluble in THF forming intense red (M = Mo) and green (M = W) solutions. The electronic absorption spectra in 2-MeTHF have been recorded as a function of temperature (2-298 K) and show a small bathochromic shift on cooling. The electronic structures have been investigated by molecular orbital calculations employing density functional theory on the model compounds [(HCO2)3M2]2(mu-9,10-An(CO2)2) where the M4 unit is constrained to lie in a plane. These reveal a minimum energy, gas-phase structure wherein the plane of the anthracene is twisted by ca. 54 degrees with respect to its 9,10-carboxylate units for both Mo and W. The results of these calculations are correlated with the electronic absorption spectral data and the electrochemical measurements (CV and DPV) of the first and second oxidation waves. The EPR spectra of the radical cations formed by single-electron oxidation with [Cp2Fe](+)[PF6]- in a THF-CH2Cl2 solvent mixture show that the complexes are valence trapped at ambient temperature on the EPR timescale. These results are discussed in the light of recent studies of dicarboxylate-linked MM quadruple bonds.


Ticks and Tick Bites Presenting as "Funny Moles": A Review of Different Presentations and a Focus on Tick-borne Diseases.
Purpose: To describe a man with an adherent tick mimicking a melanoma, summarize the salient features of this condition, and review other cases of ticks mistaken for dermatoses. Background: Ticks are obligatory ectoparasites. Disease-causing ticks belong to two families: Ixodidae (hard ticks) and Argasidae (soft ticks). Ticks thrive by consuming blood from animal hosts, and the transfer of infected blood from one host to the next is the method by which ticks spread disease. Materials and methods: The authors describe a man who presented to their dermatology clinic in New York with an unusual black pigmented lesion on the right zygomatic region of his face. He was worried about how rapidly the lesion had developed and the tingling of the skin surrounding it. Since the patient had a history of nonmelanoma skin cancer, he was concerned that the lesion was a melanoma. An excisional biopsy of the lesion revealed a non-Ixodes tick with a surrounding tick-bite reaction. Results: Ticks cause cutaneous manifestations through physical trauma and their salivary contents. A number of reports describe a similar phenomenon of a persistent tick being mistaken for a nodule or tumor. Management includes complete removal of a tick, either mechanically or surgically, along with the appropriate work-up for tick-borne diseases in the relevant geographic location. The decision to test for systemic disease depends on the clinical presentation of the patient and geographic location of the tick bite. Conclusion: A patient presented to the authors' dermatology clinic with a pigmented lesion suspicious for a melanoma, but the lesion was actually an adherent non-Ixodes tick. This case illustrates the importance of keeping insects and arthropods in the differential diagnosis of a sudden- and recent-onset pigmented skin lesion.


Major problems and key issues in Maternal Health in Nepal.
This paper highlights some of the challenges facing maternal health in Nepal and to suggest possible solutions for improvements. Key literature from across the globe is reviewed and discussed in a Nepalese context. Maternal mortality remains one of the biggest public health problems in Nepal. Lack of access to basic maternal healthcare, difficult geographical terrain, poorly developed transportation and communication systems, poverty, illiteracy, women's low status in the society, political conflict, shortage of health care professional and under utilization of currently available services are major challenges to improving maternal health in Nepal. In order to effect real improvements in maternal health, attention needs to be focused both on biomedical and social interventions. Improving health facilities, mother's nutrition, women's position in the society such as freedom of movement, providing education to female children, integrating Traditional Birth Attendants into local health services can play a vital role in the improvement of mothers' health.


Microfluidic fluorescence in situ hybridization and flow cytometry (μFlowFISH).
We describe an integrated microfluidic device (μFlowFISH) capable of performing 16S rRNA fluorescence in situ hybridization (FISH) followed by flow cytometric detection for identifying bacteria in natural microbial communities. The device was used for detection of species involved in bioremediation of Cr(vi) and other metals in groundwater samples from a highly-contaminated environmental site (Hanford, WA, USA). The μFlowFISH seamlessly integrates two components: a hybridization chamber formed between two photopolymerized membranes, where cells and probes are electrophoretically loaded, incubated and washed, and a downstream cross structure for electrokinetically focusing cells into a single-file flow for flow cytometry analysis. The device is capable of analyzing a wide variety of bacteria including aerobic, facultative and anaerobic bacteria and was initially tested and validated using cultured microbes, including Escherichia coli, as well as two strains isolated from Hanford site: Desulfovibrio vulgaris strain RCH1, and Pseudomonas sp.strain RCH2 that are involved in Cr(vi) reduction and immobilization. Combined labeling and detection efficiencies of 74-97% were observed in experiments with simple mixtures of cultured cells, confirming specific labeling. Results obtained were in excellent agreement with those obtained by conventional flow cytometry confirming the accuracy of μFlowFISH. Finally, the device was used for analyzing water samples collected on different dates from the Hanford site. We were able to monitor the numbers of Pseudomonas sp. with only 100-200 cells loaded into the microchip. The μFlowFISH approach provides an automated platform for quantitative detection of microbial cells from complex samples, and is ideally suited for analysis of precious samples with low cell numbers such as those found at extreme environmental niches, bioremediation sites, and the human microbiome.


Surface States in Holographic Weyl Semimetals.
We study the surface states of a strongly coupled Weyl semimetal within holography. By explicit numerical computation of an inhomogeneous holographic Weyl semimetal, we observe the appearance of an electric current restricted to the surface in the presence of an electric chemical potential. The integrated current is universal in the sense that it only depends on the topology of the phases showing that the bulk-boundary correspondence holds even at strong coupling. The implications of this result are subtle and may shed some light on anomalous transport at weak coupling.


Vibrotactile perception sensitivity and its relation to hand-arm vibration exposure.
Vibrotactile perception thresholds (VPT) at seven test frequencies (8-500 Hz) have been measured and evaluated among 170 male employees at a heavy engineering production workshop, 125 of them were at present, or in the past, exposed to hand-arm vibration. All participants were examined by a physician and none had symptoms of diseases or were exposed to other factors known to cause sensory neuropathies. VPTs [for the three lowest (8-32 Hz; non-Pacinian), for the four highest (63-500 Hz; Pacinian) and for all test frequencies together] and a sensitivity index (SI) has been individually graded in four (normal, slightly deteriorated, deteriorated and seriously deteriorated) and two (normal, abnormal) stages, respectively, and put in relation to individual exposure of vibration. The results do not show any clear relationship on an individual basis between vibration exposure and degraded vibrotactile perception. On a group basis, however, there is a clear tendency towards detoriorated VPTs when the study group is divided in exposure categories. The detorioration is most pronounced in the frequency range mediated by Pacinian corpuscles. In this range an approximately four-fold increase of relative risk for elevated VPT for those in the highest exposure category was observed compared to the non-exposed group. Corresponding relative risk estimate for SI is about 6. Therefore, the results suggest an existence of an exposure-response relationship.


Sultamicillin in the treatment of superficial skin and soft tissue infections in children.
Fifty-two children with superficial skin and soft tissue infections were randomized to receive sultamicillin or cloxacillin for 7 days. Twenty-one children in each group finished the study. A total of 16 of 21 in the sultamicillin group and 13 of 21 in the cloxacillin group were cured. One child in the sultamicillin group and two in the cloxacillin group failed therapy. Four children who received sultamicillin and six who received cloxacillin had recurrences of lesions. Differences were not statistically significant.


Modern Rutherford experiment: tunneling of the most neutron-rich nucleus.
A modern variation of the Rutherford experiment to probe the tunneling of exotic nuclear matter from the measurement of the residues formed in the bombardment of (197)Au by extremely neutron-rich (8)He nuclei is presented. Using a novel off-beam technique the most precise and accurate measurements of fusion and neutron transfer involving reaccelerated unstable beams are reported. The results show unusual behavior of the tunneling of (8)He compared to that for lighter helium isotopes, highlighting the role of the intrinsic structure of composite many-body quantum systems and pairing correlations.


Perinatal group B streptococcal infections in Israel.
Among 12,500 babies born in our hospital from 1977 to 1982, there was one case of neonatal sepsis due to Group B beta-hemolytic Streptococcus (GBS), an incidence which is significantly lower than that reported in Western countries (3 to 6 per 1,000 live births). Among 385 pregnant women from Jerusalem and Haifa, the vaginal colonization rate with GBS was 2.8%, in contrast with 4.6 to 36% reported in Western countries. Umbilical and ear cultures were obtained from the infants of the 85 mothers who were examined in Haifa. These cultures were repeated at 3 to 5 days of age in 60 of the 85 babies. From the above data, mother-to-infant transmission rates and neonatal nosocomial infection rates with GBS were found to be 66 and 6.6%, respectively, which correlates well with 60 to 75% and 12 to 27% reported in the literature. The low incidence of GBS neonatal sepsis in our survey may be related to the low maternal colonization rate with GBS. The low maternal colonization rate could be related to still unidentified epidemiological and environmental factors.


Ectopic expression of CITED2 prior to reprogramming, promotes and homogenises the conversion of somatic cells into induced pluripotent stem cells.
Cited2 plays crucial roles in mouse embryonic stem cells self-renewal, the initiation of the somatic reprogramming process into induced pluripotent stem cells (iPSC) and the suppression of cell senescence. Here, we investigated the potential of CITED2 expression in combination with the Oct4, Sox2, Klf4 and c-Myc factors for reprogramming of primary mouse embryonic fibroblasts (MEF) at passage 2 and 4. The ectopic CITED2 expression in primary MEF prior to the onset of the reprogramming process, generated iPSC with less variability in the expression of endogenous pluripotency-related genes. In contrast, part of the MEF reprogrammed without ectopic expression of CITED2 at passage 4 originated partially reprogrammed iPSC or pre-iPSC. However, the overexpression of CITED2 in the pre-iPSC was insufficient to complete the reprogramming process into iPSC. These results indicated that ectopic CITED2 expression at the onset of the reprogramming process in combination with the reprogramming factors promotes a complete and homogeneous conversion of somatic cells into iPSC.


Post-operative Complications Following Emergency Operations Performed by Trainee Surgeons: A Retrospective Analysis of Surgical Deaths.
Adequate surgical care of patients and concurrent training of residents is achieved in elective procedures through careful case selection and adequate supervision. Whether this applies when trainees are involved in emergency operations remains equivocal. The aim of this study was therefore to compare the risk of post-operative complications following emergency procedures performed by senior operators compared with supervised trainees. This is a retrospective cohort study examining in-hospital deaths of patients across all surgical specialties who underwent emergency surgery in Australian public hospitals reported to the national surgical mortality audit between 2009 and 2015. Multivariable logistic regression was used to explore whether there was an association between the level of operator experience (senior operator vs trainee) and the occurrence of post-operative surgical complications following an emergency procedure. Our population consisted of 6920 patients. There were notable differences between the trainees and senior operator groups; trainees more often operated on patients aged over 80 years, with cardiovascular and neurological risk factors. Senior operators more often operated on very young and obese patients with advanced malignancy and hepatic disease. Supervised trainees had a lower rate of post-operative complications compared with senior operators; 18% (n = 396) and 25% (n = 1210), respectively (p < 0.05). Operations performed by trainees were associated with an 18% decrease (95% CI 5-29%; p < 0.05) in odds of post-operative complications compared with senior operators, adjusting for potential confounders. Contrary to popular belief, our results suggest that supervised trainees safely perform emergency operations, provided that cases are judiciously selected.


Establishment of a functional ovine fetoplacental artery endothelial cell line with a prolonged life span.
To study mechanisms governing fetoplacental vascular function, we have established a primary ovine fetoplacental artery endothelial (OFPAE) cell line. These OFPAE cells produce nitric oxide (NO), proliferate, and migrate in response to fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF). To overcome the senescence crisis that this primary OFPAE cell line will eventually enter, we attempted to establish a functional OFPAE cell line with a prolonged life span by transfecting cells with plasmids containing a neomycin resistance gene and a simian virus 40 gene (SV40) expressing large T (T) and small t (t) antigens. The OFPAE cells at passage 8 were transfected. After neomycin selection, the surviving OFPAE (designated SV40 OFPAE) cells were expanded up to passage 80. Up to passage 30, these SV40 OFPAE cells maintained a morphology similar to untransfected OFPAE cells. Expression of T and t antigens in SV40 OFPAE cells was confirmed by immunocytochemistry. These SV40 OFPAE cells exhibited positive uptake of acetylated low-density lipoprotein (Ac-LDL) and positive staining for NO synthase 3 (NOS3) and formed capillary-like tube structures on Matrigel. Up to passages 20-23, these SV40 OFPAE cells proliferated (P < 0.05) and produced (P < 0.05) NO in response to both FGF2 and VEGF. Moreover, this cell proliferation stimulated by FGF2 and VEGF was dose-dependently inhibited (P < 0.05) by PD98059 (a selective mitogen-activated protein kinase 1 and 2 [MAP2K1/2, also termed MEK1/2] inhibitor) or by LY294002 (a selective phosphoinositide 3-kinase [PI3K] inhibitor). These data indicate that SV40 OFPAE cells, at least at passage 23, retain endothelial phenotypes and functions similar to their parental, untransfected OFPAE cells. Thus, a functional OFPAE cell line with an extended life span has been successfully established, potentially providing a valuable cell model for studying fetoplacental endothelial function.


Perception of patients, physiotherapists and traditional Chinese medicine practitioners towards manual physiotherapy and Tuina (Chinese manipulative therapy) in Australia: a qualitative research.
The aim of this study is to gain insight and understanding of the perception of Australian patients toward manual therapies. The study also tries to increase our understanding of manual techniques used by manual therapists. This is qualitative field research emphasising the sociological perspective, to interpret health services recipients' meanings in specific social settings. An unstructured interview is the major study design. The interview study method was conducted jointly with clinical observational techniques. A total of 30 subjects who met the selection criteria were selected. Finally 19 patient participants and 5 practitioner participants entered the study. Most participants in the research got to know physiotherapy through media and referral from general practitioners. After having gained some experience of manual physiotherapy, patients were expecting a fresh approach from Tuina (Chinese manipulative therapy). Although 94% of patient participants were satisfied with Tuina treatment, most of them could not distinguish differences in technique between Tuina and manual physiotherapy. Some patients consider Tuina as a more costly choice. Most practitioners preferred to use stronger pressure-based methods on trigger points while those who had received formal training in Tuina were in favour of much gentler techniques. Manual physiotherapy is the first-line choice for many Australian patients. Tuina, as a relatively new method, is often considered as the last-resort treatment due to lack of proper private health insurance coverage. However, most patient participants preferred gentler manual methods, such as Tuina, compared with strong force-based approaches. This study stressed patients' feelings and needs, which may have an impact on clinical outcomes. This study asserts some possible ways to enhance patient care that would include providing relevant education as part of manual therapy courses, encouraging continual development of the therapists and encouraging patient participation in the treatment process.


New data clarifying the taxonomy of European members of the Lepidocyrtus pallidus-serbicus group (Collembola, Entomobryidae).
The genus Lepidocyrtus is fairly well explored in Hungary and was up to now represented by 18 species. Systematic mesofauna survey of a swamp woodland gave us the opportunity to describe the new species, L. florae sp. nov., characterized by the dark blue color, the dorsal macrochaetae formula A0A2aA2A3S3Pa5/00/0101+2 and the absence of scales on the antennae. Related species L. arrabonicus, L. pallidus, L. pseudosinelloides and L. weidneri were also revised with particular attention to clarify the interpretation of the dorsal chaetotaxy of the head. The observed variability in abdominal chaetotaxy of L. pallidus suggests that the only character differentiating between this species and L. weidneri is the labial chaetotaxy, with chaeta r (in L. pallidus) and chaeta R (in L. weidneri). An identification key to European Lepidocyrtus species with dorsal trunk macrochaetae formula 00/0101+2 is also provided.