Psychotherapies for Generalized Anxiety Disorder in Adults: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials.
Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatments for GAD, but which should be considered as first-line treatment needs to be clarified. To use a network meta-analysis to examine the short- and long-term associations of different psychotherapies with outcomes of effectiveness and acceptability in adults with GAD. MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials were searched from database inception to January 1, 2023, to identify randomized clinical trials (RCTs) of psychotherapies for adults with GAD. RCTs comparing any type of psychotherapy against another or with a control condition for the treatment of adults (≥18 years, both sexes) with a primary diagnosis of GAD were eligible for inclusion. This study followed Cochrane standards for extracting data and assessing data quality and used the PRISMA guideline for reporting. Risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis was used to rate the certainty of evidence for meta-analytical results. Eight psychotherapies were compared against one another and with 2 control conditions. Primary outcomes were severity of GAD symptoms and acceptability of the psychotherapies. Random-effects model pairwise and network meta-analyses were conducted. For effectiveness, standardized mean differences (SMDs) were pooled, and for acceptability, relative risks with 95% CIs were calculated. Data from 66 RCTs were included. Effect size estimates on data from 5597 participants (mean [SD], 70.9% [11.9%] women; mean [SD] age, 42.2 [12.5] years) suggested that third-wave cognitive behavior therapies (CBTs) (SMD, -0.78 [95% CI, -1.19 to -0.37]; certainty, moderate), CBT (SMD, -0.68 [95% CI, -1.05 to -0.32]; certainty, moderate), and relaxation therapy (SMD, -0.54 [95% CI, -1.04 to -0.05]; certainty, low) were associated with reduced GAD symptoms vs treatment as usual. Relative risks for all-cause discontinuation (indication of acceptability) signaled no differences compared with treatment as usual for all psychotherapies (eg, relative risk, 1.07 [95% CI, 0.73-1.57] for CBT vs treatment as usual). When excluding studies at high risk of bias, relaxation therapy lost its superiority over treatment as usual (SMD, -0.40; 95% CI, -1.15 to 0.34). When considering anxiety severity at 3 to 12 months after completion of the intervention, only CBT remained significantly associated with greater effectiveness than treatment as usual (SMD, -0.58; 95% CI, -0.93 to -0.23). Given the evidence in this systematic review and network meta-analysis for its associations with both acute and long-term effectiveness, CBT may represent the first-line therapy of GAD. Third-wave CBTs and relaxation therapy were associated with short-term effectiveness and may also be offered.


Linkage exclusion between the autosomal dominant polycystic kidney disease locus and chromosome 16 markers in a new family.
A family segregating for autosomal dominant polycystic kidney disease (ADPKD) is reported. The clinical picture was typical for ADPKD in some family members, although others showed mild involvement. DNA from family members was probed with seven chromosome 16 single-copy DNA sequences that mapped to the telomere of the short arm of the chromosome. The most likely order of six of the probes from the telomere is palpha3'HVR.64 at the designated locus D16S85, CRI-0327 at D16S63, CRI-090 at D16S45, CRI-0129 at D16S56, CRI-0133 at D16S58, and CRI-0136 at D16S60, with the PKD1 locus for ADPKD between D16S85 and D16S63. The seventh probe 24-1 at D16S80 had not been ordered in relation to the other sequences, but PKD1 had been mapped between it and D16S85. The three probes that were informative in our family, palpha3'HVR.64, CRI-090, and CRI-0136 had been linked to the disease locus at recombination frequencies of 4% and approximately 6 and 12%, respectively. Linkage was excluded between the ADPKD locus in our family and palpha3'HVR.64 at a recombination value of up to 6%. Linkage was also excluded between CRI-090 and the disease locus at a recombination value of up to 5%. The data for linkage between CRI-0136 and the ADPKD locus in our family were inconclusive. Multipoint analysis excluded the possibility that the disease in this family lies between the flanking genetic markers that have previously been used to define the genetic interval in which the most common form of polycystic kidney disease, PKD1, lies. We have not made a positive assignment of the ADPKD mutation in this family.(ABSTRACT TRUNCATED AT 250 WORDS)


Striving for the best of both worlds: Samoan parenting in New Zealand.
This qualitative, exploratory study based on the principles of the Strauss and Corbin grounded theory method, considered the parenting patterns of fourteen parents bringing up their children in New Zealand. This paper presents findings, which suggest that being a Samoan parent in New Zealand is influenced by cultural pride that is shaped by a context described as the rat-race and intervening conditions which encompass the nineties trend. Samoan parents manage their parental roles by making a conscious effort. As a result, they experience a parenting style that involves striving for the best of both worlds.


Low-affinity signature of the rat beta-parvalbumin CD site. Evidence for remote determinants.
Although rat beta-parvalbumin and chicken parvalbumin 3 (CPV3) are identical at 74 of 108 residues, rat beta exhibits perceptibly lower Ca2+ and Mg2+ affinities. At 25 degrees C, in Hepes-buffered saline, at pH 7.4, the overall deltadeltaG degrees ' values are 2.0 and 3.9 kcal/mol, respectively. These differences primarily reflect the disparate behavior of the CD sites in the two proteins. Their respective binding constants for Ca2+, for example, are 1.5 x 10(6) and 2.4 x 10(7) M-1. The extent to which this differential behavior is dictated by local and remote sequence differences is unknown. To explore this question, we performed mutagenesis on rat beta, substituting the corresponding CPV3 codon for residues 49, 50, 57, 58, 59, and 60. The resulting CD site is identical to CPV3 at 27 of 30 positions. The mutations were introduced in four stages, replacing residues 49 and 50 (yielding beta 49/50), then 57 and 58 (beta 49/50/57/58), then 59 (beta 49/50/57/58/59), and finally 60 (beta 49/50/57/58/59/60). Apoprotein stability was examined by scanning calorimetry and chemical denaturation and divalent ion affinity by titration calorimetry. All four variants exhibit elevated Tm values and are between 0.13 and 0.39 kcal/mol more stable at 25 degrees C. Although all four proteins display heightened divalent ion affinity, the increases are small. The maximal deltadeltaG degrees ' values, observed for 49/50/57/58/59/60, are just -0.56 and -0.96 kcal/mol for Ca2+ and Mg2+, respectively. Evidently, structural features beyond the metal ion-binding motif contribute to the unusual divalent ion-binding behavior associated with the rat beta CD site.


Significant reduction in blood loss in patients undergoing minimal extracorporeal circulation.
Several recent studies have shown differences in blood loss and allogeneic transfusion requirements between on-pump and off-pump coronary artery bypass grafting (CABG). Recently a new concept, the mini-extracorporeal circulation, was introduced to minimize the side effects of extracorporeal circulation. Therefore, there are no data comparing the three techniques with special emphasis to blood loss and transfusion requirements. Two hundred and eighty-five patients undergoing first-time coronary artery bypass grafting were retrospectively matched for number of grafts, age and sex. Ninety-five patients underwent surgery with the off-pump CABG (OPCAB) technique, 97 patients using conventional CABG with cold cardioplegia (CCABG) and 93 patients with the mini-extracorporeal circuit with warm blood cardioplegia (MCABG). Blood loss for the CCABG group with a mean loss of 819 +/- 557 mL and the OPCAB group with a mean loss of 870 +/- 768 mL was significant different compared to the MCABG group with a mean loss of 679 +/- 290 mL. The use of units red blood cell units was significantly higher for CCABG group and OPCAB group compared to the MCABG group. On the day of operation the use of platelet concentrate was significantly higher for the CCABG group compared to MCABG group. As a consequence of improvements of several components of the mini heart lung machine, significantly less blood products are needed in MCABG patients. The expected reduced need for transfusion when the pump was completely avoided could not be confirmed in this single retrospective cohort study.


In vivo evaluation of the safety of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator cDNA to the lung.
Cystic fibrosis (CF) is a common, fatal hereditary disease resulting from mutations of the human cystic fibrosis transmembrane conductance regulator (CFTR) gene in which epithelial cells throughout the body manifest altered regulation of apical membrane chloride secretion. Although the disease affects multiple organs throughout the body, over 90% of patients die of complications of the lung involvement. The feasibility of adenovirus-derived vectors for in vivo delivery of the human CFTR cDNA to treat the pulmonary component of CF is currently being evaluated using in vitro and in vivo approaches. Defining the therapeutic window between biological efficacy and toxicity is an important part of this work. Here we present data regarding the preclinical evaluation of the safety of in vivo delivery of the human CFTR cDNA to the cotton rat airway epithelium using the replication-deficient adenoviral vector Av1Cf2 or a similar vector, Av1LacZ4, expressing the Escherichia coli LacZ gene as a histologic marker. Gene transfer to the respiratory epithelium was efficient, as demonstrated by in situ hybridization and histochemical staining. Administration of these vectors resulted in a mild, transient, dose-dependent cellular inflammatory response similar in character to that seen with adenovirus 5 (Ad5), but far less in intensity, which was not associated with structural lung damage or mortality. Av1Cf2 DNA sequences were easily detected in the lung after pulmonary administration, but could not be demonstrated in organs other than the lung. These preclinical observations suggest that adenovirus-mediated gene transfer to the airway epithelium can be achieved efficiently, but is accompanied by a dose- and time-dependent inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension.
To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment.


Prospective Assessment of Ultrasound Shear Wave Elastography for Discriminating Biliary Atresia from other Causes of Neonatal Cholestasis.
To prospectively assess the diagnostic performance of ultrasound shear wave elastography (SWE) and hepatobiliary laboratory biomarkers for discriminating biliary atresia from other causes of neonatal cholestasis. Forty-one patients <3 months of age with neonatal cholestasis (direct bilirubin >2 mg/dL) and possible biliary atresia were prospectively enrolled. Both 2-dimensional (2D) and point ultrasound SWE were performed prior to knowing the final diagnosis. Median 2D (8) and point (10) shear wave speed measurements were calculated for each subject and used for analyses. The Mann-Whitney U test was used to compare shear wave speed and laboratory measurements between patients with and without biliary atresia. Receiver operating characteristic curve analyses and multivariable logistic regression were used to evaluate diagnostic performance. Thirteen subjects (31.7%) were diagnosed with biliary atresia, and 28 subjects (68.3%) were diagnosed with other causes of neonatal cholestasis. Median age at the time of ultrasound SWE was 37 days. Median 2D (2.08 vs 1.49 m/s, P = .0001) and point (1.95 vs 1.21 m/s, P = .0014) ultrasound SWE measurements were significantly different between subjects with and without biliary atresia. Using a cut-off value of >1.84 m/s, 2D ultrasound SWE had a sensitivity = 92.3%, specificity = 78.6%, and area under the receiver operating characteristic curve (AuROC) of 0.89 (P < .0001). Using a cut-off value of >320 (U/L), gamma-glutamyl transferase (GGT) had a sensitivity = 100.0%, specificity = 77.8%, and AuROC of 0.85 (P < .0001). Multivariable logistic regression demonstrated an AuROC of 0.93 (P < .0001), with 2 significant covariates (2D ultrasound SWE [OR = 23.06, P = .01]; GGT [OR = 1.003, P = .036]). Ultrasound SWE and GGT can help discriminate biliary atresia from other causes of neonatal cholestasis.


Online and Offline Friendship Among Italian Adolescent Girls Following a Non-Traditional School Track.
There is still a question of whether online friendship predicts changes in face-to-face friendship (Reduction Hypothesis) or face-to-face friendship predicts changes in online friendship (Compensation Hypothesis) during adolescence. The purpose of this study was to compare these two hypotheses to determine which comes first: online friendship or offline friendship. Eighty adolescent girls between the ages of 14 and 19 years (mean, 16.07 years; standard deviation, 1.28 years) on a non-traditional school track completed self-report questionnaires. Two wave longitudinal models were tested with the use of cross-lagged analysis to compare the hypotheses. Analysis showed that negative face-to-face friendship quality predicted online friendship but that the opposite was not true. The study's findings underlined the compensation role of online friendship for girls with poor or unsatisfactory offline social worlds. The implications of this information and suggestions for clinicians and professionals to use to enhance adolescent social skills and to promote appropriate use of the Internet will be discussed.


[Treatment of non hodgkinian malignant lymphomas in children].
Non Hodgkin Lymphomas are in children nostly diffuse and non or poorly differentiated. The exact frontiers with ALL are difficult to assess. With old classical treatments, the chances of cure were limited to localized tumors (stage I). The present indications of combined intensive chemotherapies, of neuromeningeal prophylaxis, and radiotherpy are analyzed. Preliminary results in 51 children treated first in 1973-1974 are presented. The rate of complete remission is 82%. Actuarial survival rate is 57% at 30 months. The aim and the limitations of treatment protocol are discussed.


Aquafoldmer-Based Aquaporin-like Synthetic Water Channel.
Synthetic water channels were developed with an aim to replace aquaporins for possible uses in water purification, while concurrently retaining aquaporins' ability to conduct highly selective superfast water transport. Among the currently available synthetic water channel systems, none possesses water transport properties that parallel those of aquaporins. In this report, we present the first synthetic water channel system with intriguing aquaproin-like features. Employing a "sticky end"-mediated molecular strategy for constructing abiotic water channels, we demonstrate that a 20% enlargement in angstrom-scale pore volume could effect a remarkable enhancement in macroscopic water transport profile by 15 folds. This gives rise to a powerful synthetic water channel able to transport water at a speed of ∼3 × 109 H2O s-1 channel-1 with a high rejection of NaCl and KCl. This high water permeability, which is about 50% of aquaporin Z's capacity, makes channel 1 the fastest among the existing synthetic water channels with high selectivity.


Frequent emergence and functional resurrection of processed pseudogenes in the human and mouse genomes.
Despite the wide distribution of processed pseudogenes in mammalian genomes, such as those of human and mouse, relatively little is known about their roles in genomic evolution. While gene duplications are recognized as one of the major driving forces in genome evolution, processed pseudogenes, which are retrotransposed copies of mRNAs, have been regarded as junk or selfish DNA for a long time. In order to elucidate the quantitative and qualitative contribution of processed pseudogenes to the mammalian genome evolution, we attempted to detect processed pseudogenes by extensively mapping the mRNAs to both the human and mouse genomes, and then we estimated the rate of their emergence. As a result, we revealed that the rate of pseudogene emergence was about 1-2% per gene per million years, which was as high as the rate (0.9%) of gene duplication in the human genome, although the rate of pseudogene emergence was found to drastically decrease in the hominid lineage. Furthermore, 1% of the processed pseudogenes seemed to be reinvigorated by post-retrotransposition transcription, many of them preserving the intact coding regions. Since the expression patterns of transcribed pseudogenes in various tissues were quite different between human and mouse, their emergence might have led to species-specific evolution. Our results indicate that the generation of processed pseudogenes was not wholly futile but instead has been an indispensable resource, driving dynamic evolution of the mammalian genomes.


Smoking, hormonal factors and molecular markers in female lung cancer.
There has been substantial argumentation about differences in lung cancer occurrence and characteristics between men and women. Lung cancer incidence suggests that gender-related factors may influence lung cancer risk. The carcinogenic effect of tobacco smoke and the use of hormone replacement therapy could result in susceptibility to lung cancer among women. Mutations in EGFR and HER-2/neu genes, and ROS1 gene fusions may also play a role in gender-based survival rate differences. This review summarizes the latest data of disease markers and its usefulness in female lung cancer.


Reasons behind the relative abundances of heptacoordinate complexes along the late first-row transition metal series.
A series of transition metal complexes [ML(1)] (H2L(1) = 1,4,10-trioxa-7,13-diazacyclopentadecane-N,N'-diacetic acid, M = Co, Ni, Cu, or Zn) have been prepared and characterized. The X-ray structures of the [CoL(1)] and [CuL(1)] complexes reveal that the metal ions are seven-coordinated with a distorted pentagonal bipyramidal coordination. The five donor atoms of the macrocycle define the pentagonal plane of the bipyramid, while two oxygen atoms of the carboxylate groups coordinate apically. The [NiL(1)] complex presents a very distorted structure with long Ni-O distances involving two oxygen atoms of the crown moiety [2.544(3) Å]. This distortion is related to the Jahn-Teller effect that is expected to operate in d(8) pentagonal bipyramidal complexes. The spectroscopic characterization of the [ZnL(1)] and [CuL(1)] complexes using NMR and EPR and the theoretical calculation of the (13)C NMR shifts and g- and A-tensors using DFT confirm that these complexes retain the pentagonal bipyramidal coordination in aqueous solution. The stability trend of the [ML(1)] complexes (Co(2+) > Ni(2+) < Cu(2+) > Zn(2+)), which is in contradiction with the Irving-Williams order, has been analyzed using DFT calculations (TPSSh functional). The free energy values calculated in the gas phase for [CoL(1)](g) + [M(H2O)6](2+)(g) → [ML(1)](g) + [Co(H2O)6](2+)(g) (M = Ni, Cu, Zn) reproduce fairly well the stability trend observed experimentally, the agreement being improved significantly upon inclusion of solvent effects. Our results indicate that the pentagonal bipyramidal coordination is particularly unfavorable for Ni(2+), and thus preorganized ligands that favor this geometry such as L(1) are selective for Co(2+) over Ni(2+) cations.


Postpartum depression and health-related quality of life: a Saudi Arabian perspective.
The mental and physical functioning of an individual is partly determined by their health-related quality of life (HRQOL), which is a multifaceted component. Women who have recently given birth must have a good quality of life to provide proper care and development for their infant. The purpose of this study was to assess the relationship between postpartum depression (PPD) and HRQOL in Saudi Arabian women and to identify potential risk factors that could influence them. This study comprised 253 mothers aged 1-24 weeks postpartum from several health centers in Saudi Arabia, recruited by random purposive sampling. The study's questionnaire featured three sections: the first section had demographic information; the second and third sections contained the Edinburgh Postnatal Depression Scale (EPDS) scale and the HRQOL scale (SF-12), respectively. Data were analyzed using descriptive statistics, chi square analyses, independent samples t-tests and binary logistic regression analysis using IBM SPSS 25. Results of current study indicate that 59.68% of the patients exhibited probable post-partum depression symptoms. Participants who were depressed had significantly lower mental component (MCS) and physical component scores than participants who were in good health. When compared to non-smokers, smokers have a 21-fold higher risk of developing depression. Similar to this, mothers who worked had a 3.98 times higher risk of depression, and patients with a history of depression had a 3.6 times higher chance of getting PPD. The probability of developing PPD was also significantly higher in those who lived outside the Riyadh region, had given birth more than twice before this time, and had experienced undesired pregnancies. Our study demonstrated an inverse correlation between postpartum depression and health-related quality of life scores. Treatment for depression, particularly among mothers, is crucial for improving their quality of life and, as a result, creating a favorable environment for the development of newborn babies.


Hepatic arterial infusion chemotherapy with continuous low dose administration of cisplatin and 5-fluorouracil for multiple recurrence of hepatocellular carcinoma after surgical treatment.
To date, conventional treatments for multiple intrahepatic recurrence of hepatocellular carcinoma (HCC) after surgery are unsuccessful. The aim of this retrospective study was to evaluate the prognostic effectiveness of a new infusion chemotherapy of cisplatin (CDDP) and 5-fluorouracil (5-FU) via hepatic artery for HCC with multiple intrahepatic recurrence. Fifty-two patients, who had postoperative multiple recurrence of HCC (more than 3 tumors), were enrolled in this study. Thirty-one patients were treated by hepatic arterial infusion chemotherapy via a subcutaneously implanted injection port. A one-week course of this treatment consisted of daily administration of cisplatin (10 mg for 1 h on days 1-5) and subsequent daily administration of 5-fluorouracil (250 mg for 5 h on days 1-5). Three to six sequential one-week courses were performed (the CDDP,5-FU group). Twenty-one patients underwent conventional interventional therapies including transcatheter arterial chemoembolization, lipiodolization (the conventional group). The complete response rate and the effective response rate in the CDDP,5-FU group were 29.0% and 71.0%, respectively. The 5-year survival rate in this group was 45.7%, which was significantly better than that in the conventional group. Based on multivariate analysis, CDDP,5-FU hepatic arterial infusion chemotherapy was found to be significant in prolonging survival, and this treatment achieved favorable therapeutic results for multiple recurrence of HCC. As part of a multidisciplinary approach this treatment is expected to improve the prognosis of patients with advanced HCC.


A MULTI-CENTER SHIELDING VERIFICATION STUDY FOR RADIOTHERAPY LINAC BUNKERS IN KARACHI, PAKISTAN.
The high energy radiotherapy linear accelerators (LINAC) offer considerable risk of radiation hazards to patient, worker and public if adequate safety measures are not taken into the account. Proper bunker designing with appropriate shielding is an important safety measure, which protects workers and member of general public. The present study describes the details of shielding of LINAC bunker in four radiotherapy centers of Karachi city. In order to conduct the study, shielding of five LINAC installed in four radiotherapy centers was assessed by considering real occupancy factor, dose limits for worker and public, etc. to verify that shielding of the bunkers conforms to the national and international standards like International Atomic Energy Agency and National Council on Radiation Protection and Measurement. After the assessment, it was concluded that all bunkers conform to the radiation protection requirements and present adequate shielded. This is an important step to achieve as low as reasonably achievable principle and protect workers and member of general public.


Autism spectrum disorder phenotypes and prenatal exposure to methylmercury.
There continues to be public concern that mercury exposure and autism spectrum disorder (ASD) may be associated. The primary source of exposure to organic mercury in humans is to methylmercury from fish consumption. We evaluated the association between prenatal methylmercury exposure and ASD phenotype in children and adolescents in the Republic of Seychelles, where fish consumption is high. We administered the Social Communication Questionnaire to parents of a cohort of 1784 children, adolescents, and young adults. The Social Responsiveness Scale was administered to teachers of 537 cohort subjects at about 10 years of age. Prenatal exposure to methylmercury was measured in maternal hair samples collected at or near the time of birth. Multivariable regression models evaluated the relationship between prenatal methylmercury exposure and ASD phenotypic scores, adjusting for relevant covariates. The mean prenatal methylmercury exposure for subjects in the analysis was 8.4 ppm (standard deviation [SD] = 5.7). The mean Social Communication Questionnaire score was 8.0 (SD = 4.4). The mean prenatal methylmercury exposure for subjects with Social Responsiveness Scale scores was 6.7 ppm (SD = 4.4) and the mean Social Responsiveness Scale score was 57.6 (SD = 26.8). No consistent association between prenatal methylmercury exposure and ASD screening instrument was found, using linear and nonlinear regression analyses. Prenatal exposure to methylmercury was not associated with ASD phenotypic behaviors in our cohort of high fish consumers. Our findings contribute to the growing literature suggesting that exposure to methylmercury does not play an important role in the development of ASD phenotypic behavior.


Refinements to the diastereoisomer-specific method for the analysis of hexabromocyclododecane.
The emergence of hexabromocyclododecane (HBCD) as a bromine-based flame retardant of concern is partly attributable to recent measurements on the environmental occurrence of the individual diastereoisomers (alpha, beta and gamma). These measurements were fuelled by a newly developed liquid chromatography/tandem mass spectrometric (LC/MS/MS)-based analytical method. However, in the course of our recent studies on the environmental fate and behaviour of the diastereoisomers of HBCD, some interesting features of the LC/MS/MS method became apparent. For example, the ion signal of the native ions was found to be dependent on the final extract volume. This was true for both biotic and sediment samples and was found to arise from the suppression of the ion signal due to endogenous material in the extracts that escape clean-up. We have also found differences in the stability of the diastereoisomers in different solvents. If left unaccounted for, both factors can compromise analytical measurement data. By way of a series of controlled experiments conducted at our two laboratories [Department of Fisheries & Oceans Canada (DFO) and Environment Canada (EC)], we illustrate these features and demonstrate that use of newly synthesized labelled HBCD isomers [(13-carbon (13C) and deuterium (d18)] can minimize and often circumvent matrix-related effects.


Regiochemical effects on molecular stability: a mechanochemical evaluation of 1,4- and 1,5-disubstituted triazoles.
Poly(methyl acrylate) chains of varying molecular weight were grown from 1,4- as well as 1,5-disubstituted 1,2,3-triazoles. Irradiating acetonitrile solutions of these polymers with ultrasound resulted in the formal cycloreversion of the triazole units, as determined by a variety of spectroscopic and chemical labeling techniques. The aforementioned reactions were monitored over time, and the rate constant for the cycloreversion of the 1,5-disubstituted triazole was measured to be 1.2 times larger than that of the 1,4-disubstituted congener. The difference was attributed to the increased mechanical deformability of the 1,5-regioisomer as compared to the 1,4-isomer. This interpretation was further supported by computational studies, which employed extended Bell theory to predict the force dependence of the activation barriers for the cycloreversions of both isomers.


Measuring the outputs of Australian nursing research published 1995-2000.
To analyse the research published in refereed nursing journals by Australian authors from 1995 to 2000. Analysis of the research topics and types of methodologies used by Australian nurse researchers has not been recently undertaken. The study was similar to an analysis of United Kingdom (UK) nursing research between 1988 and 1995 to allow comparison between the two countries. A quantitative approach analysed the research abstracts for the topic researched, source of data, location of data collection, paradigm and methodology used and funding source. A total of 509 articles from 11 generalist Australian and UK nursing journals were analysed. The highest numbers of articles were published in Australian Journal of Advanced Nursing and Journal of Advanced Nursing. The most popular topics were education of nurses (18.7%, n=95) and practice issues relating to patient care (15.3%, n=78). However, scant attention was paid to major Australian health issues. Most research was undertaken in the hospital setting (55.8%, n=247). Data were most often drawn from nurses themselves (40.7%, n=206), followed by patients (25.5%, n=129). Both quantitative (41%, n=203) and qualitative approaches (47%, n=230) were employed. A minority of studies acknowledged any funding (14.9%, n=76). Research findings need to be applied in practice to improve patient care. Nurse researchers need to publish their findings and align their research interests to meet national health priorities. They need to be involved in setting these health priorities to ensure that nursing has a place in health research.


Morphometric characteristics of epitheliocytes in the choroid plexus of the cerebral ventricles in humans during aging.
Morphometric studies of villous epitheliocytes of the choroid plexus of the lateral (glomus) and third and fourth (lateral zone) ventricles of the brain were undertaken in humans aged from 22 to 89 years. Cell height, width, and cross-sectional area were measured, along with the cross-sectional areas of nuclei and cytoplasm for calculation of the nucleus:cytoplasm ratio. These studies showed that epitheliocytes were of variable shape depending on their locations on the surfaces of villi. Epitheliocyte height and the cross-sectional areas of the cytoplasm and cells were greatest in the choroid plexus of the lateral ventricle, while the cross-sectional area of the nucleus and the nucleus:cytoplasm ratio were greatest in the choroid plexus of the fourth ventricle; these features correlate with their functional characteristics. Aging is associated with decreases in the sizes of epitheliocytes and their nuclei and a reduction in the nucleus:cytoplasm ratio, with the development of adaptive rearrangements.


Significant Upregulation of HERV-K (HML-2) Transcription Levels in Human Lung Cancer and Cancer Cells.
Lung cancer is the second most common cancer worldwide and the leading cause of cancer death in the world. Therefore, there is an urgent need to develop new and effective biomarkers for diagnosis and treatment. Under this circumstance, human endogenous retroviruses (HERVs) were recently introduced as novel biomarkers for cancer diagnosis. This study focused on the correlation between lung cancer and HERV-K (HML-2) transcription levels. At the cellular level, different types of lung cancer cells and human normal lung epithelial cells were used to analyze the transcription levels of the HERV-K (HML-2) gag, pol, and env genes by RT-qPCR. At the level of lung cancer patients, blood samples with background information from 734 lung cancer patients and 96 healthy persons were collected to analyze the transcription levels of HERV-K (HML-2) gag, pol, and env genes. The results showed that the transcriptional levels of the HERV-K (HML-2) gag, pol, and env genes in lung cancer cells and lung cancer patient blood samples were significantly higher than those in the healthy controls, which was also verified by RNAScope ISH technology. In addition, we also found that there was a correlation between the abnormal transcription levels of HERV-K (HML-2) genes in lung cancer patients and the clinicopathological parameters of lung cancer. We also identified the distribution locations of the gag, pol, and env primer sequences on each chromosome and analyzed the function of these loci. In conclusion, HERV-K (HML-2) genes may be a potential biomarker for the diagnosis of lung cancer.


An in vitro Assessment of the Haemodynamic Features Occurring Within the True and False Lumens Separated by a Dissection Flap for a Patient-Specific Type B Aortic Dissection.
One of the highest mortality rates of cardiovascular diseases is aortic dissections with challenging treatment options. Currently, less study has been conducted in developing in vitro patient-specific Type B aortic dissection models, which mimic physiological flow conditions along the true and false lumens separated by a dissection flap with multiple entry and exit tears. A patient-specific Stanford Type B aortic dissection scan was replicated by an in-house manufactured automatic injection moulding system and a novel modelling technique for creating the ascending aorta, aortic arch, and descending aorta incorporating arterial branching, the true/false lumens, and dissection flap with entry and exit intimal tears. The physiological flowrates and pressure values were monitored, which identified jet stream fluid flows entering and exiting the dissection tears. Pressure in the aorta's true lumen region was controlled at 125/85 mmHg for systolic and diastolic values. Pressure values were obtained in eight sections along the false lumen using a pressure transducer. The true lumen systolic pressure varied from 122 to 128 mmHg along the length. Flow patterns were monitored by ultrasound along 12 sections. Detailed images obtained from the ultrasound transducer probe showed varied flow patterns with one or multiple jet steam vortices along the aorta model. The dissection flap movement was assessed at four sections of the patient-specific aorta model. The displacement values of the flap varied from 0.5 to 3 mm along the model. This model provides a unique insight into aortic dissection flow patterns and pressure distributions. This dissection phantom model can be used to assess various treatment options based on the surgical, endovascular, or hybrid techniques.


Hydrodynamics, wall-slip, and normal-stress differences in rarefied granular Poiseuille flow.
Hydrodynamic fields, macroscopic boundary conditions, and non-Newtonian rheology of the acceleration-driven Poiseuille flow of a dilute granular gas are probed using "direct simulation Monte Carlo" method for a range of Knudsen numbers (Kn, the ratio between the mean free path and the macroscopic length), spanning the rarefied regime of slip and transitional flows. It is shown that the "dissipation-induced clustering" (for 1-e_{n}>0, where e_{n} is the restitution coefficient), leading to inhomogeneous density profiles along the transverse direction, competes with "rarefaction-induced declustering" (for Kn>0) phenomenon, leaving seemingly "anomalous" footprints on several hydrodynamic and rheological quantities; one example is the well-known rarefaction-induced temperature bimodality, which could also result from inelastic dissipation that dominates in the continuum limit (Kn→0) as found recently [Alam et al., J. Fluid Mech. 782, 99 (2015)JFLSA70022-112010.1017/jfm.2015.523]. The simulation data on the slip velocity and the temperature slip are contrasted with well-established boundary conditions for molecular gases. A modified Maxwell-Navier-type boundary condition is found to hold in granular Poiseuille flow, with the velocity slip length following a power-law relation with Knudsen number Kn^{δ}, with δ≈0.95, for Kn≤0.1. Transverse profiles of both first [N_{1}(y)] and second [N_{2}(y)] normal stress differences seem to correlate well with respective density profiles at small Kn; their centerline values [N_{1}(0) and N_{2}(0)] can be of "odd" sign with respect to their counterparts in molecular gases. The phase diagrams are constructed in the (Kn,1-e_{n}) plane that demarcates the regions of influence of inelasticity and rarefaction, which compete with each other resulting in the sign change of both N_{1}(0) and N_{2}(0). The results on normal stress differences are rationalized via a comparison with a Burnett-order theory [Sela and Goldhirsch, J. Fluid Mech. 361, 41 (1998)JFLSA70022-112010.1017/S0022112098008660], which is able to predict their correct behavior at small values of the Knudsen number. Lastly, the Knudsen paradox and its dependence on inelasticity are analyzed and contrasted with related recent works.


Molecular dynamics simulations of p53 DNA-binding domain.
We have studied room-temperature structural and dynamic properties of the p53 DNA-binding domain in both DNA-bound and DNA-free states. A cumulative 55 ns of explicit solvent molecular dynamics simulations with the particle mesh Ewald treatment of electrostatics was performed. It was found that the mean structures in the production portions of the trajectories agree well with the crystal structure: backbone root-mean-square deviations are in the range of 1.6 and 2.0 A. In both simulations, noticeable backbone deviations from the crystal structure are observed only in loop L6, due to the lack of crystal packing in the simulations. More deviations are observed in the DNA-free simulation, apparently due to the absence of DNA. Computed backbone B-factor is also in qualitative agreement with the crystal structure. Interestingly, little backbone structural change is observed between the mean simulated DNA-bound and DNA-free structures. A notable difference is observed only at the DNA-binding interface. The correlation between native contacts and inactivation mechanisms of tumor mutations is also discussed. In the H2 region, tumor mutations at sites D281, R282, E285, and E286 may weaken five key interactions that stabilize H2, indicating that their inactivation mechanisms may be related to the loss of local structure around H2, which in turn may reduce the overall stability to a measurable amount. In the L2 region, tumor mutations at sites Y163, K164, E171, V173, L194, R249, I251, and E271 are likely to be responsible for the loss of stability in the protein. In addition to apparent DNA contacts that are related to DNA binding, interactions R175/S183, S183/R196, and E198/N235 are highly occupied only in the DNA-bound form, indicating that they are more likely to be responsible for DNA binding.


Rotating Ring-Disk Electrode and Quantum-Chemical Study of the Electrochemical Reduction of Monoiodoacetic Acid and Iodoform.
This study examined the electrochemical (EC) reduction of monoiodoacetic acid (MIAA) and iodoform (CHI3), which are typical iodine-containing disinfection byproducts (I-DBPs). Experiments carried out using the method of a rotating ring-disk electrode (RRDE) with a gold working electrode showed that the reduction of CHI3 and MIAA is diffusion-controlled. The MIAA diffusion coefficient was determined to be (1.86 ± 0.24)·10(-5) cm(2) s(-1). The yield of the iodide ion formed as a result of MIAA or CHI3 reduction was affected by the presence of dissolved organic matter (DOM) and resorcinol. Increasing concentrations of DOM or resorcinol did not affect the EC reduction of the examined I-DBPs, but the formation of iodide was suppressed. This indicated that free iodine, ·I, was formed as a result of the first step in the EC reduction of MIAA and CHI3. This also indicated that the pathway of the EC reduction of MIAA and CHI3 was different from that typical for the reduction of Br- and Cl-containing DBPs, in which case Br(-) or Cl(-) tend to be formed as a result of the electron transfer. Quantum-chemical (QC) calculations confirmed the thermodynamic likelihood of and possible preference to the formation of free iodine species as a result of the EC reduction of MIAA, CHI3, and other I-DBPs.


Severe case of Lemierre syndrome with multiple neurological and ophthalmological sequelae.
A 56-year-old man was admitted to intensive care with septic shock, multiple facial abscesses and thrombophlebitis of the right internal jugular vein with extensive intracranial extension. A diagnosis of Lemierre syndrome due to Streptococcus anginosus was made and treatment initiated with high-dose ceftriaxone and metronidazole, along with surgical debridement. His admission was complicated by raised intraocular pressures and visual loss requiring bilateral canthotomies. Despite therapeutic anticoagulation with enoxaparin, he also developed an ischaemic basal ganglia infarct. After a prolonged and complex hospital stay, the patient was later readmitted with an intracerebral abscess requiring surgical excision and a second course of antibiotics. This case highlights the value of early recognition of this rare but potentially life-threatening condition, considerations around anticoagulation and antibiotic decisions, and the importance of close multidisciplinary follow-up even after discharge from hospital.


Optimization of Patient Selection for Neoadjuvant Chemotherapy in Muscle-invasive Urothelial Carcinoma of the Bladder.
Radical cystectomy (RC) is delayed in a subset of patients who respond poorly to neoadjuvant chemotherapy (NAC). The present study investigated the clinicopathologic characteristics predicting extravesical disease at RC and the factors associated with NAC tolerability to improve patient selection and the sequence of definitive therapy. Patients with cT2 urothelial carcinoma of the bladder who underwent NAC were stratified by the final pathologic stage: complete (ypT0N0), partial (≤ pT2), and nonresponse (> pT2 and/or N+). Patients treated with upfront cystectomy were divided into those with organ-confined (≤ pT2) and those with extravesical disease (> pT2 and/or N+). Of 145 patients, 89 received NAC and 56 underwent upfront RC. The univariate predictors of extravesical disease in the patients treated with upfront RC included increased age (P = .021), higher Eastern Cooperative Oncology Group performance status (P < .001), hydronephrosis (P = .021), and cardiovascular risk factors. The complete, partial, and nonresponse rates to NAC were 25.8%, 39.3%, and 34.8%, respectively. The multivariate predictors of pathologic progression on NAC included low serum albumin (P = .005), hydronephrosis (P = .040), incomplete NAC (P = .014), and alternative NAC (non-gemcitabine/cisplatin or MVAC, P = .022). Significant multivariate predictors of incomplete NAC included increased age, coronary artery disease (P = .027), and Eastern Cooperative Oncology Group performance status. Redundant clinicopathologic features predicted adverse cystectomy pathology in patients treated with both NAC and upfront RC. The results of the present study demonstrated an inferior pathologic response to alternative NAC regimens in clinically organ-confined disease and implicated cardiovascular comorbidities and nutritional status in the tolerability and response to NAC. Our findings predicate the importance of using patient-specific factors to guide the sequence of definitive treatment toward timely, centralized care to improve clinical outcomes.


Benzoxazoles, Phthalazinones, and Arylurea-Based Compounds with IMP Dehydrogenase-Independent Antibacterial Activity against Francisella tularensis.
Francisella tularensis is the causative agent of tularemia and a potential biowarfare agent. The virulence of F. tularensis is decreased by deletion of guaB, the gene encoding IMP dehydrogenase (IMPDH), suggesting that this enzyme is a target for antibacterial design. Here we report that F. tularensis growth is blocked by inhibitors of bacterial IMPDHs. Seventeen compounds from two different frameworks, designated the D and Q series, display antibacterial activities with MICs of <1 μM. These compounds are also active against intracellular infections. Surprisingly, antibacterial activity does not correlate with IMPDH inhibition. In addition, the presence of guanine does not affect the antibacterial activity of most compounds, nor does the deletion of guaB These observations suggest that antibacterial activity derives from inhibition of another target(s). Moreover, D compounds display antibacterial activity only against F. tularensis, suggesting the presence of a unique target or uptake mechanism. A ΔguaB mutant resistant to compound D73 contained a missense mutation (Gly45Cys) in nuoB, which encodes a subunit of bacterial complex I. Overexpression of the nuoB mutant conferred resistance to D73 in both wild-type and ΔguaB strains. This strain was not resistant to Q compounds, suggesting that a different off-target mechanism operates for these compounds. Several Q compounds are also effective against Mycobacterium tuberculosis, in which a second target has also been implicated, in addition to IMPDH. The fortuitous presence of multiple targets with overlapping structure-activity relationships presents an intriguing opportunity for the development of robust antibiotics that may avoid the emergence of resistance.


A novel transthyretin variant p.H110D (H90D) as a cause of familial amyloid polyneuropathy in a large Irish kindred.
Hereditary transthyretin (ATTR) amyloidosis is caused by inheritance of an abnormal TTR gene in an autosomal dominant fashion. In its native state, TTR is a homotetramer consisting of four identical polypeptides. Mutations in the TTR gene contribute to destabilization and dissociation of the TTR tetramer, enabling abnormally folded monomers to self-assemble as amyloid fibrils. Currently, over 120 TTR variants have been described, with varying geographic distributions, degrees of amyloidogenicity and organ involvement. We report here a large Irish family with familial amyloid polyneuropathy (FAP), consisting of multiple affected generations, caused by a novel TTR mutation; p.H110D (H90D). The demonstration, by immunohistochemistry and laser micro dissection-mass spectrometry (LMD/MS) that the amyloid fibrils were composed of TTR, in conjunction with a typical FAP phenotype, indicates that the novel TTR mutation was the cause of amyloidosis. We used a molecular visualization tool PyMOL to analyze the effect of the p.H110D (H90D) replacement on the stability of the TTR molecule. Our data suggest that the loss of two hydrogen bonds and the presence of an additional negative charge in the core of a cluster of acidic residues significantly perturb the tetramer stability and likely contribute to the pathogenic role of this variant.


Effects of Chronic, Low-Dose Cannabinoids, Cannabidiol, Delta-9-Tetrahydrocannabinol and a Combination of Both, on Amyloid Pathology in the 5xFAD Mouse Model of Alzheimer's Disease.
Background: There is an urgent need for novel therapies to treat Alzheimer's disease. Among others, the use of cannabinoids such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been proposed as a putative approach based on their anti-inflammatory effects. Methods: The present work was designed to explore the effects of chronic (28 days) treatment with low doses of cannabinoids: CBD (0.273 mg/kg), THC (0.205 mg/kg) or a combination of both (CBD:THC; 0.273 mg/kg:0.205 mg/kg) in the 5xFAD mouse model of AD. Results: Our data revealed that THC-treated 5xFAD mice (but not other treatment groups) exhibited anxiogenic and depressant-like behavior. A significant improvement in spatial memory was observed only in the CBD:THC-treated group. Interestingly, all cannabinoid-treated groups showed significantly increased cortical levels of the insoluble form of beta amyloid 1-42. These effects were not accompanied by changes in molecular parameters of inflammation at the mRNA or protein level. Conclusions: These data reveal differential effects of chronic, low-dose cannabinoids and point to a role of these cannabinoids in the processing of amyloid peptides in the brains of 5xFAD mice.


Correlation between induction of duodenal tumor by hydrogen peroxide and catalase activity in mice.
Incidences of duodenal tumor induced by oral administration of hydrogen peroxide (HPO) and catalase activities in the duodenal mucosa, blood and liver were correlated in C3H/HeN, C57BL/6N, (C57BL X C3H)F1 (B6C3F1) and hypocatalasemic C3H/Cbs mice. A solution of 0.4% HPO was given to the mice as drinking water for about 6 months. Incidences of duodenal tumor were 11.1% in C3H, 31.8% in B6C3F1, 100% in C57BL and 91.7% in C3H/Cbs mice. Catalase activities (10(-4) k/mg protein) in the duodenal mucosa, blood and liver were 5.3, 7.8 and 75.3 in C3H, 1.7, 7.7 and 62.8 in B6C3F1, 0.7, 5.1 and 40.7 in C57BL, and 0.4, 0.4 and 33.3 in C3H/Cbs mice, respectively. The coefficients of correlation (r) of catalase activities with the incidences of duodenal tumor in C3H, B6C3F1 and C57BL mice are -0.83 in duodenal mucosa, -0.98 in blood and -0.99 in liver. The results indicate that the incidence of duodenal tumor induction by HPO is dependent on the individual mouse strain and may be determined by the genes controlling the catalase activities.


Histopathology of the Inner Ear in Charcot-Marie-Tooth Syndrome Caused by a Missense Variant (p.Thr65Ala) in the MPZ Gene.
Charcot-Marie-Tooth (CMT) syndrome is a clinically and genetically heterogeneous group of neuropathies affecting both peripheral motor and sensory nerves. Progressive sensorineural hearing loss, vestibular abnormalities, and dysfunction of other cranial nerves have been described. This is the second case report of otopathology in a patient with CMT syndrome. Molecular genetic testing of DNA obtained at autopsy revealed a missense variant in the MPZ gene (p.Thr65Ala), pathogenic for an autosomal-dominant form of CMT1B. The temporal bones were also prepared for light microscopy by hematoxylin and eosin and Gömöri trichome stains, and immunostaining for anti-myelin protein zero. Pathology was consistent with a myelinopathy of the auditory, vestibular, and facial nerves bilaterally. The pathophysiology of cranial nerve dysfunction in CMT is unknown. Findings in the current case suggested, at least in cranial nerves 7 and 8, that a myelinopathy may be causative.


A relationship between estrogen sulfurylation and estrogen and progesterone receptor status in human mammary carcinoma.
It was previously demonstrated that a correlation existed between estrogen receptor (ER) status and levels of estrogen sulfotransferase in human mammary cancer, high levels being associated with ER-positive and low levels with ER-negative tumors. We have now examined these same parameters, along with progesterone receptor (PGR) status, in 44 primary human mammary tumors. Tumors which were both ER-positive and PGR-positive (n = 21), showed significantly higher levels of estrogen sulfotransferase compared to ER-positive PGR-negative (n = 12) and ER-negative PGR-negative (n = 11) tumors. These values (pmol estradiol sulfate per mg protein per 2 hr) were 72 +/- 12 (S.E.), 25 +/- 5, and 11 +/- 4 (p less than 0.01 and less than 0.005, respectively). There was no significant difference between ER-positive PGR-negative and ER-negative PGR-negative tumors. The possible involvement of PGR in the regulation of estrogen sulfotransferase is discussed.


Secondary erythrocytosis.
Erythrocytosis is associated with an elevation of the hemoglobin level above 16.5 g/dL in men and above 16 g/dL in women and an elevation of the hematocrit level above 49% in men and > 48% in women. In primary erythrocytosis, the defect is a clonal disorder in the myeloid compartment of the bone marrow, leading to an increased red cell production. Secondary erythrocytosis is the result of external stimuli to the bone marrow, leading to the production of red cells in excess. Secondary erythrocytosis is more common than primary erythrocytosis and has a broad differential diagnosis. This review will discuss secondary erythrocytosis, its causes, clinical presentation, and both diagnostic and therapeutic approaches. Although secondary erythrocytosis is more common than PV, there are still challenges and difficulties associated with the distinction between these two conditions. Moreover, there is a paucity of data and guidance when it comes to the management of certain congenital and acquired conditions. A pragmatic approach is recommended in order to identify the cause for this condition. Treatment should be directed at the management of the underlying cause.


The significance of intraocular hemorrhages due to subarachnoid hemorrhage.
A retrospective study of 320 patients with spontaneous subarachnoid hemorrhage revealed a 20.8% incidence of intraocular hemorrhages. While diagnostically helpful, intraocular hemorrhages also were prognostically significant. The overall patient mortality was 31.6%. In those with intraocular hemorrhages the mortality was 53.6% compared to 19.7% in those without intraocular hemorrhages. Fifty-eight percent with bilateral intraocular hemorrhages died versus 48% with unilateral hemorrhages. Vitreous hemorrhage, though infrequent, may be a major complication in survivors of subarachnoid hemorrhage.


The future of vaccines in the management of addictive disorders.
Conventional substance abuse treatments have had only limited success. As a result, new approaches, including vaccination to block the effects of drugs such as cocaine, nicotine, methamphetamine, and phencyclidine, are in development. Although a number of possible rationales for the effects of antidrug vaccines have been suggested, the most straightforward and intuitive mechanism would involve binding of the drug by antibodies in the bloodstream, thereby blocking entry or reducing the rate of entry of the drug into the central nervous system. The theoretical parameters that would influence vaccine-induced drug pharmacodynamics are presented in this review, along with the current status on vaccine development for nicotine, cocaine, methamphetamine, and phencyclidine.


EMP2 re-expression inhibits growth and enhances radiosensitivity in nasopharyngeal carcinoma.
Although radiation therapy is the primary treatment for nasopharyngeal carcinoma, radioresistance remains a major obstacle to successful treatment in many cases, and the exact underlying molecular mechanisms are still ill-defined. EMP2, epithelial membrane protein-2, was a recently identified potential oncogene involved in multiple biological processes including cell migration and cell proliferation. This study was to explore the potential relationship between EMP2 expression, nasopharyngeal carcinoma genesis, and radioresistance. EMP2 expression status in 98 nasopharyngeal carcinoma clinical samples was examined by immunohistochemical staining. As a result, most of the nasopharyngeal carcinoma tumor samples were weakly or negatively stained, while paired adjacent normal tissues were moderately or strongly stained. Moreover, patients with higher expression of EMP2 had significant longer survival times. EMP2 re-expression suppresses cell growth, induces S-phase cell cycle arrest, and promotes radiosensitivity and apoptosis in nasopharyngeal carcinoma cells. These results support that loss of EMP2 is common, and its re-expression may serve as an approach to enhance radiation sensitivity in nasopharyngeal carcinoma.


Hierarchical partitions of social networks between rivaling leaders.
A model algorithm is proposed to imitate a series of of consecutive conflicts between leaders in social groups. The leaders are represented by local hubs, i.e., nodes with highest node degrees. We simulate subsequent hierarchical partitions of a complex connected network which represents a social structure. The partitions are supposed to appear as actions of members of two conflicted groups surrounding two strongest leaders. According to the model, links at the shortest path between the rival leaders are successively removed. When the group is split into two disjoint parts then each part is further divided as the initial network. The algorithm is stopped, if in all parts a distance from a local leader to any node in his group is shorter than three links. The numerically calculated size distribution of resulting fragments of scale-free Barabási-Albert networks reveals one largest fragment which contains the original leader (hub of the network) and a number of small fragments with opponents that are described by two Weibull distributions. A mean field calculation of the size of the largest fragment is in a good agreement with numerical results. The model assumptions are validated by an application of the algorithm to the data on political blogs in U.S. (L. Adamic and N. Glance, Proc. WWW-2005). The obtained fragments are clearly polarized; either they belong to Democrats, or to Republicans. This result confirms that during conflicts, hubs are centers of polarization.


[Epidemiology of the mild and moderate brain injuries].
Unlike severe head injuries upon which much attention is focused, mild or moderate brain injuries are not or not well known and often neglected in maxillofacial surgery. Nevertheless, they are frequent in our routine facial traumatology activity. Studying the epidemiological data shows that mild brain injuries account for 64 to 94% of all head injured patients whereas moderate injuries occur in 3 to 23%. Furthermore, owing to their frequent occurrence, their high potential for sequelae and because they especially affect young people, they are a real public-health problem.


Factors associated with influenza vaccination coverage and willingness in the elderly with chronic diseases in Shenzhen, China.
Elderly individuals with chronic illnesses are more prone to get influenza. We aimed to investigate the factors associated with influenza coverage and willingness in chronic disease patients aged ≥60 years in Longhua district, Shenzhen City of southern China. Data collected in October 2020 were used in this work. The immunization status of older persons with chronic conditions and their willingness to receive the vaccine were assessed. Multivariable logistic regression was employed to determine the respective independent factors related to vaccination coverage and willingness for influenza. Only 4.8% of 5045 people were immunized against influenza, whereas 92.7% of the individuals agreed to receive the vaccine. Individuals between the ages of 70 and 79 (adjusted OR [aOR] 1.47, P = .012), those with higher education levels (aOR 1.53, P = .005 for high school; aOR 2.44, P < .001 for college or above), those who use of a family doctor (aOR 2.91, P < .001), those who frequently have physical examinations once a year (aOR 2.52, P < .001), and those who have never smoked (aOR 1.62, P = .018) were positively associated with the influenza vaccination. Meanwhile, older age was adversely linked with influenza vaccination willingness (aOR 0.68 for 70-79 years, P = .003; aOR 0.55 for≥80 years, P = .025) in contrast to those aged 60-69. High willingness to get vaccinated was more frequent in people with a high school diploma (aOR 1.33, P = .037). In this work, we observed that the coverage is poor but the immunization desire is high regarding influenza vaccination. Interestingly, older age was associated with higher coverage and lower willingness. These suggest that raising immunization rates among older people with chronic conditions and strengthening health education for caregivers should be the primary concerns.


Persistence of protective pneumococcal antibody following vaccination in patients with the nephrotic syndrome.
We have determined the level of persisting pneumococcal antibody in a group of nephrotic children vaccinated by us 5 years ago. Of the 19 vaccinated children, 2 have died and 1 has moved away. Sera from the remaining 16 patients were examined by radioimmunoassay to determine the antibody response to 11 of the 14 types contained in the polyvalent pneumococcal vaccine. The lowest protective level of geometric mean titre (GMT) of antibody in our laboratory is 300 ng antibody nitrogen per millilitre. 56% (9/16) of the patients showed adequate GMT 5 years after vaccination. All 9 patients had minimal change nephrotic syndrome. 44% (7/16) of the children had a GMT less than 300 ng antibody nitrogen per millilitre. 3 of these patients had focal sclerosis, 3 had membranoproliferative glomerulonephritis, and 1 patient had IgM nephropathy. Of these 7 patients, 1 with the lowest GMT (23 ng antibody nitrogen per millilitre) developed pneumococcal peritonitis. During this same period, in 20 other unvaccinated nephrotic patients followed continuously from 1976 to 1981, 7 cases of pneumococcal peritonitis occurred (p less than 0.05). Additionally, 1 unvaccinated child died of pneumococcal sepsis. Our study indicates that patients with minimal change nephrotic syndrome continue to maintain adequate amounts of antibody, but those with disease other than minimal change nephrotic syndrome are unable to maintain an adequate level of antibody.


Comparison of effectiveness of epidural analgesia and monitored anesthesia care for high-intensity focused ultrasound treatment of adenomyosis.
High-intensity focused ultrasound (HIFU) is a noninvasive thermodestructive procedure targeting internal organs with concentrated sonification energy that may cause pain. We aimed to compare the effectiveness of epidural analgesia (EA) and monitored anesthesia care (MAC) in HIFU treatment of uterine adenomyosis. Sixty-eight patients were included in this case-control study. Thirty-seven patients underwent MAC; 31 patients underwent fluoroscope-guided epidural analgesia. The primary outcome was a frequency of patients reporting severe or very severe intraoperative pain. Secondary outcomes were differences in dosages of analgesics, ablation ratio, and other clinical factors. The EA group reported a significantly lower frequency of severe or very severe intraoperative pain than did the MAC group (41.9% vs. 75.7%; p = .006). Consumption of remifentanil during treatment was significantly lower in the EA group (173 ± 189 µg vs. 426 ± 380 µg; p = .001), as was the use of fentanyl in the recovery room (52 ± 38 µg vs. 75 ± 44 µg; p = .030). Multivariable analysis revealed EA to be the largest contributing factor to increased nonperfused volume ratio (B = 0.41; 95% confidence interval = 0.29 to 0.53; p < .001). The frequency of thermal injury after HIFU was significantly lower in the EA group (22.6% vs. 54.1%; p = .008). EA during HIFU treatment of uterine adenomyosis improved quality of pain control and ablation ratio over MAC without increasing risk of treatment-related complications. EA also reduced consumption of opioid analgesics during and after HIFU treatment.


Health profile of middle-aged women: The Women's Health in the Lund Area (WHILA) study.
Middle-aged women experience various health-related problems. The aim of this study was to evaluate the impacts of menopause status and hormone intervention on women's health. In an ongoing, population-based study, 4943 women, born 1935 to 1945 and living in the Lund area of Southern Sweden, were included in this analysis. They completed a generic questionnaire pertaining to socio-demographic background and current health-related symptoms. Among the cohort, 9% of women were pre-menopausal (PM), 52% were post-menopausal without hormone replacement therapy (PMO) and 39% were current hormone replacement therapy users (PMT). Hot flushes and vaginal dryness were strongly related to menopausal status. The prevalence of somatic symptoms worsened progressively from the groups of PM to PMO to PMT. The most abundant complaints were headache and muscle-skeletal-joint problems. A total of 85% of women experienced psychological problems. Contrary to our expectation, a poorer profile of psychological health was found in the PMT group when compared with the PMO group. The high prevalence of symptoms in middle-aged women could be attributed to age, hormonal influence as well as personality.


Total synthesis of batzelladine D.
[structure: see text] Stereoselective total synthesis of batzelladine D was accomplished in 15 steps. This synthesis features (i) successive 1,3-dipolar cycloaddition reactions to form the 2,5-disubstituted pyrrolidine ring system, (ii) esterification of the side chain to the bicyclic guanidine carboxylate, a common synthetic intermediate of batzelladine alkaloids, and (iii) tricyclic guanidine formation under the Mitsunobu reaction conditions.


Metronidazole in Scabies.
Twenty-five patients with scabies were studied for the evaluation of metronidazole as an oral therapeutic agent. These patients were given 400 mg of metronidazole three times daily for 8 days. Good to excellent results were observed in 6 (27.27%) patients, 8 (36.36%) patients showed a fair response and no response was observed in 8 patients (36.36%). The significance of these results are discussed.


Description of Antihypertensive Medication Use in a Pediatric Practice: Single and Multiple Antihypertensive Medication Therapy.
Prescription of multiple antihypertensive medications for the treatment of essential hypertension (HTN) has been well described in adults but not in children and adolescents. The authors describe the frequency with which children with essential HTN are prescribed a single vs two or more concomitantly administered antihypertensive medications. They also describe demographic features and comorbidities associated with the prescription of a single vs multiple antihypertensive medications. Multiple antihypertensive medication use in the management of pediatric HTN, as in the management of adult HTN, is not uncommon. In this single-center, retrospective study of 113 children with essential HTN, 28% of children were concomitantly prescribed two or more antihypertensive medications for poorly controlled blood pressure following prescription of a single medication. Demographic and comorbid conditions associated with the prescription of more than one antihypertensive medication include advanced hypertensive stage, race, and a family history of HTN.


Issues of using tactile mice by individuals who are blind and visually impaired.
Tactile mice, computer mice modified to have tactile pin displays on their upper surface, have been developed to enable access to 2-D graphical information for individuals who are blind or visually impaired; however, they have yet to really be adopted by the community. We suggest that this is due to the significant lack of accuracy in the haptic position information, which is critical for individuals to haptically piece together a 2-D graphic. We have identified two main design issues that affect this accuracy. Making simple modifications to correct these problems, we show a significant improvement in performance.


Regional and temporal trends in migration among people living with HIV/AIDS in British Columbia, 1993-2005.
To examine regional and temporal trends in migration among patients receiving HIV treatment in British Columbia (BC). Patients initiating antiretroviral therapy in BC between January 1993 and November 2004 were followed until November 2005. Migration was calculated as the cumulative number of times a patient's residential address changed during their course of treatment. Analyses were performed at the provincial and at the regional health authority (HA) and local health area levels. Demographic methods were used to estimate the in- and out-migration rates, indices of dissimilarity and concentration across regions over time. A total of 3,588 participants were followed during the study period. Individuals who migrated most often migrated to the Vancouver Coastal HA (from the Interior: 30%, Fraser: 41%, Vancouver Island: 28%, and Northern: 19%), specifically the city of Vancouver, which has been treating the most patients with HIV since the early stages of the epidemic. We also showed that this movement intensified as more contemporary HAART regimens became available (p-value for trend < 0.01). Our results demonstrate that migration among people with HIV in BC is not homogeneous, with areas around large urban centres having the highest influx of patients. It is thus important that health authorities in BC work in partnership to monitor and evaluate accessibility of HIV-related health care services to ensure universal access for all patients. Furthermore, enhanced HIV care and support services need to be developed, on a province-wide basis, and funding allocation needs to be adjusted to reflect patient migration in BC.


Minimally invasive valve surgery in high-risk patients.
The use of minimally, or less invasive, approaches to cardiac valve surgery has increased over the past decade. Because of its less traumatic nature, early studies in lower risk patients demonstrated the approach to be associated with an enhanced recovery, increased patient satisfaction, and good operative outcomes. With time, despite a steep learning curve, surgeons expanded this approach to perform more complex procedures, and include patients with more co-morbidity. The aim of this publication is to review the current literature involving the use of minimally invasive valve surgery (MIVS) in higher-risk patients.


[Distribution characteristics of basic syndromes of chronic functional constipation and its related factors analysis].
To explore the distribution characteristics of basic syndromes and its related factors in patients with chronic functional constipation (CFC). The complete data of 538 patients with CFC were collected and initial database was established with Epidata 3. 0. TCM syndrome typing was performed. The distribution characteristics of basic syndromes were analyzed using SPSS 17. 0 Software. The univariate and multivariate Logistic regression analyses were performed with SPSS 17. 0 Software to determine basic syndrome related factors such as age, engaged professionals, sleep quality, depression, mental stress, interpersonal relations, work fatigue, stimulating beverage, exercise conditions, Western medicine type of constipation, and so on. The TCM syndrome frequency of CFC patients was sequenced from high to low as qi deficiency syndrome (380 cases, 70.6%), qi stagnation syndrome (337 cases, 62.6%), blood deficiency syndrome (234 cases, 43.5%), yin deficiency syndrome (220 cases, 40.9%), yang deficiency syndrome (197 cases, 36.6%), and others(58 cases, 10. 8%) . Most patients were complicated with complex syndromes, and the most common complex syndromes were qi deficiency complicated qi stagnation syndrome (275 cases, 51.1%) and qi deficiency complicated blood deficiency syndrome (222 cases, 41.3%). Aging, work fatigue, and exercise conditions were main related factors for qi deficiency syndrome (P <0. 01, P <0. 05). Poor emotional (depression and anxiety tendencies), mental stress, interpersonal relations, defecation barriers constipation were main related factors for qi stagnation syndrome (P <0.01). Sleep quality and poor emotional (depression and anxiety tendencies) were main related factors for blood deficiency syndrome (P <0. 01, P < 0.05). Stimulating beverages were main related factor for yin deficiency syndrome (P <0.05). Engaged in mental work and slow transit constipation were main related factors for yang deficiency syndrome (P < 0. 01, P <0. 05). CFC is featured as complex syndromes. The most common complex syndromes were qi deficiency complicated qi stagnation syndrome and qi deficiency complicated blood deficiency syndrome. Basic syndrome related factors such as age, engaged professionals, sleep quality, poor emotional (depression and anxiety tendencies), mental stress, interpersonal relations, work fatigue, stimulating beverage, exercise conditions, Western medicine type of constipation were associated with the distribution of CFC syndromes.


Survival and Predictors of Mortality in Acute Kidney Injury Patients Treated with Sustained Low Efficiency Dialysis.
Sustained low efficiency dialysis (SLED) is an increasingly common treatment option for acute kidney injury (AKI) patients, but there are few studies examining the survival and predictive outcome of this therapy. The study aims to evaluate survival, pre-SLED predictors and complications associated with SLED. This was a retrospective cohort study of 91 patients with AKI treated with SLED in a tertiary hospital from January 2014 to August 2018. The primary outcomes were in-hospital and 30-day mortality. The secondary outcomes were the clinical and laboratory pre-SLED characteristics that were associated with survival and complication of SLED. Median survival of AKI patients treated with SLED was 17 days and the 30-day mortality rate was 58%. Pre-SLED serum levels of creatinine (adjusted HR 0.82, 95% CI 0.71-0.94), albumin (adjusted HR 0.57, 95% CI 0.4-0.81), potassium (adjusted HR 1.38, 95% CI 1.1-1.73) and number of SLED (adjusted HR 0.95, 95% CI 0.91-1) served as predictors of survival. Arrhythmia was found 3.3% and intradialytic hypotension in 13.2% of patients. No patient had bleeding complications. Our study found similar in-hospital and 30-day mortality for AKI patients treated with SLED. High pre-SLED levels of serum albumin, creatinine and number of SLED were significantly associated with reduced risk of death and high pre-SLED serum potassium was associated with increased risk of death. These results indicate that SLED is safe treatment, with few haemorrhage and haemodynamic complications.


Serum tissue factor as a biomarker for renal clear cell carcinoma.
to determine the usefulness of serum TF as a potential marker for patients with clear cell RCC. prospective study of 30 patients with clear cell RCC submitted to nephrectomy and 16 controls without clear cell RCC treated surgically for other conditions. TF is a endothelium marker that was correlated with worse prognosis in a variety of solid tumors including RCC. Serum TF was collected before surgery at the operating room and in the postoperative setting after at least four weeks. Serum samples were analyzed with a commercial ELISA kit for human TF (R&D Systems®). Mean preoperative serum TF levels in clear cell RCC patients and in controls were 66.8 pg/dL and 28.4 pg/dL, respectively (p<0.001). Mean postoperative serum TF levels in clear cell RCC patients were 26.3 pg/dL. In all patients with clear cell RCC postoperative serum levels of TF were lower, with a mean reduction of 41.6 pg/dL in the postoperative setting (p<0.001). Linear regression revealed that tumor size was correlated with the postoperative reduction of serum TF levels (p=0.037). We have shown a 3-fold reduction in the median preoperative serum levels of TF in patients with clear cell RCC after surgery. We have also shown a difference of the same magnitude in the serum levels of TF compared with those of a control group of patients with benign diseases. TF appears to be a useful serum marker for the presence of clear cell RCC. Further studies are needed to validate these findings.


The oxidation of 3-hydroxybutyrate in developing rat jejunum.
Ketone bodies and glutamine are the primary oxidative substrates in the intestine of fasting adult rats. Because suckling rats consume the majority of their calories in the form of lipid and as a result have elevated blood ketone concentrations similar to fasting adult rats, we examined the role of ketone oxidation as a source of energy in the intestine of suckling rats. In suckling rats the rate of [3-14C]DL-3-hydroxybutyrate oxidation in intestinal tissue slices, enterocytes, and intestinal mitochondria was 0.15 +/- 0.01 nmol/h/mg wet wt, 8.6 +/- 1.1 nmol/h/mg protein and 8.3 +/- 1.3 nmol/h/mg protein, respectively. In suckling rats the rate of intestinal oxidation of [3-14C]DL-3-hydroxybutyrate was 75% lower than the rate in weaned rats in intestinal tissue slices, 55% lower in enterocytes, and 50% lower in intestinal mitochondria. The activity of two enzymes involved in ketone oxidation, 3-hydroxybutyrate dehydrogenase, and acetoacetyl-CoA thiolase was 38% and 55% higher in intestinal homogenates of suckling rats compared with adult rats. In contrast, 3-oxoacid CoA-transferase activity, an enzyme also involved in 3-hydroxybutyrate oxidation, was one third that of adults. These studies indicate that intestinal oxidation of 3-HB occurs in suckling rat pups, but is lower than the rate of oxidation in the intestine of weaned rats.


[Studies on paclitaxel-loaded methoxy poly (ethylene glycol)/poly (L-lactic acid) diblock copolymer nanoparticles].
Paclitaxel-loaded methoxy poly (ethylene glycol )-b-poly (L-lactic acid) diblock copolymer nanoparticles (PMT) were prepared by a self-emulsification/solvent evaporation method. The PMT morphology, size and its distribution, and drug release in vitro were investigated by DLS, UV, TEM and HPLC. The results indicate that PMT show a spherical morphology with inner core and outer shell. The diameter (nm) of PMT increases with the increase of the drug-loaded amount. The initial burst release is not observed, the drug releasing rate in vitro is lower, and the accumulated release increases with the increase of replacement amout of the pH7. 4 medium. This study develops a new formulation for paclitaxel and provides an experimental basis for the intravenous administration of paclitaxel.


Specificity in Arabidopsis thaliana recruitment of root fungal communities from soil and rhizosphere.
Biotic and abiotic conditions in soil pose major constraints on growth and reproductive success of plants. Fungi are important agents in plant soil interactions but the belowground mycobiota associated with plants remains poorly understood. We grew one genotype each from Sweden and Italy of the widely-studied plant model Arabidopsis thaliana. Plants were grown under controlled conditions in organic topsoil local to the Swedish genotype, and harvested after ten weeks. Total DNA was extracted from three belowground compartments: endosphere (sonicated roots), rhizosphere and bulk soil, and fungal communities were characterized from each by amplification and sequencing of the fungal barcode region ITS2. Fungal species diversity was found to decrease from bulk soil to rhizosphere to endosphere. A significant effect of plant genotype on fungal community composition was detected only in the endosphere compartment. Despite A. thaliana being a non-mycorrhizal plant, it hosts a number of known mycorrhiza fungi in its endosphere compartment, which is also colonized by endophytic, pathogenic and saprotrophic fungi. Species in the Archaeorhizomycetes were most abundant in rhizosphere samples suggesting an adaptation to environments with high nutrient turnover for some of these species. We conclude that A. thaliana endosphere fungal communities represent a selected subset of fungi recruited from soil and that plant genotype has small but significant quantitative and qualitative effects on these communities.


Reshaping of Gait Coordination by Robotic Intervention in Myelopathy Patients After Surgery.
The Ossification of the Posterior Longitudinal Ligament (OPLL) is an idiopathic degenerative spinal disease which may cause motor deficit. For patients presenting myelopathy or severe stenosis, surgical decompression is the treatment of choice; however, despite adequate decompression residual motor impairment is found in some cases. After surgery, there is no therapeutic approach available for this population. The Hybrid Assistive Limb® (HAL) robot suit is a unique powered exoskeleton designed to predict, support, and enhance the lower extremities performance of patients using their own bioelectric signals. This approach has been used for spinal cord injury and stroke patients where the walking performance improved. However, there is no available data about gait kinematics evaluation after HAL therapy. Here we analyze the effect of HAL therapy in OPLL patients in acute and chronic stages after decompression surgery. We found that HAL therapy improved the walking performance for both groups. Interestingly, kinematics evaluation by the analysis of the elevation angles of the thigh, shank, and foot by using a principal component analysis showed that planar covariation, plane orientation, and movement range evaluation improved for acute patients suggesting an improvement in gait coordination. Being the first study performing kinematics analysis after HAL therapy, our results suggest that HAL improved the gait coordination of acute patients by supporting the relearning process and therefore reshaping their gait pattern.


The Paradox of Sexual Dysfunction Observed during Pregnancy.
The aim of this study is to analyze the evolution of sexual function throughout pregnancy and highlight the predicting factors of sexual dysfunction in pregnant women. Our study included 144 participants, aged 16 to 45. Patients were evaluated three times during pregnancy by filling out the Female Sexual Function Index (FSFI) and the Body Exposure in Sexual Activities Questionnaire (BESAQ). At the time of the last evaluation, we asked patients to also fill out Beck's Depression Inventory (BDI-II) and a questionnaire regarding their psychological status and relationship satisfaction. We observed that the FSFI lubrication, satisfaction, and pain domains and the FSFI total score significantly decreased from the 1st to the 3rd evaluation. We observed that an increase in BDI score and the presence of abortion in the patient's history increase the risk of developing female sexual dysfunction (FSD). Higher BMIs were found to be a protective factor against FSD, as was being unmarried. The relationship satisfaction score was found to be an independent predictor of FSD. These findings support previous studies that indicate that pregnancy and postpartum sexuality are multifaceted phenomena and that psycho-social factors have a greater impact on sexuality than biological factors.


Analysis of Behavioural Characteristics Related to Unintentional Injury in Southeast Chinese Adolescents: Evidence from a School-Based Survey.
The purpose of this study was to explore the epidemiological features of common unintentional injury-related behaviours and to identify possible factors that lead to these unsafe behaviours among adolescents. A representative sample of 10,806 students was recruited from 77 schools by using the two-stage stratified random sampling method. All participants took a self-administered questionnaires and data were analysed to estimate the prevalence of unintentional injury-related behaviours and to identify the influential factors for these behaviours. The prevalence of unsafe swimming, jaywalking, illegal bicycling and not wearing a seat belt was 6.35%, 33.08%, 18.10% and 15.73%, respectively. The proportion of students who had two, three or four unintentional injury-related behaviours was 14.59%, 4.27% and 0.57%, respectively. Multiple regression analysis showed that male adolescents, living in an urban area and attending a vocational-technical school might contribute to the occurrence of four unintentional injury-related behaviours. In addition, the marital status of parents and father with a college degree or above were negatively associated with the adolescent's behaviour of not wearing a seat belt. Considering diverse epidemiological characteristics of unintentional injury-related behaviours among adolescents, targeted interventions such as enhancing self-protection capabilities and strengthening safety consciousness by family, school and related departments should be implemented to lower the occurrence of unintentional injury-related behaviours.


EXTRADIGESTIVE MANIFESTATIONS OF GASTROESOPHAGEAL REFLUX DISEASE: DEMOGRAPHIC, CLINICAL, BIOLOGICAL AND ENDOSCOPIC FEATURES.
Gastroesophageal reflux disease (GERD) with extradigestive manifestations is a disorder increasingly recognized both by gastroenterologists, pneumologists, otolaryngologists and cardiologists. To evaluate the demographical, clinical, biological and endoscopic features of the patients with gastroesophageal reflux disease and extradigestive manifestations (chronic laryngitis, asthma, pseudoangina). Prospective case-control study, including 137 patients selected from patients referred to the Iasi Institute of Gastroenterology and Hepatology between July 2014-September 2015. In the presence of typical GERD symptoms (heartburn or regurgitation), the patients were assessed by upper digestive endoscopy for the detection or exclusion of esophagitis. Despite the absence of esophageal lesions, the patients were further assessed by impedance-pHmetry. Depending on the dominant extradigestive manifestation, the patients were assigned into 3 groups: 94 chronic laryngitis patients, 24 asthma patients and 19 pseudoangina patients. Females were more frequent among pseudoangina patients (68.4%). Mean age of the male patients with dysphonia or asthma was lower (p=0.002), the majority (78.1%) living in urban areas. Obesity was predominant in pseudoangina group (52.6%), as compared to dysphonia group (16%) the differences being statistically significant (p=0.002). A share of 57.9% of pseudoangina patients were dyslipidemic, in contrast to dysphonia (24.5%) or asthma group (37.5%) (p=0.013). Esophagitis was also more frequent at pseudoangina group (84.2%), but with no significant statistical difference between the study groups (79.8% and 75%, respectively) (p=0.115). It seems that Helicobacterpylori infection tends to be protective in patients with GERD and pseudoangina (RR=0.61), but it can not be extrapolated to the general population (p=0.459). GERD with extradigestive manifestations is a prevalent and heterogeneous disease. There are demographic, clinical, biological and endoscopic differences between patiens with extradigestive GERD.


Automatic recognition of harmonic bird sounds using a frequency track extraction algorithm.
This paper demonstrates automatic recognition of vocalizations of four common bird species (herring gull [Larus argentatus], blue jay [Cyanocitta cristata], Canada goose [Branta canadensis], and American crow [Corvus brachyrhynchos]) using an algorithm that extracts frequency track sets using track properties of importance and harmonic correlation. The main result is that a complex harmonic vocalization is rendered into a set of related tracks that is easily applied to statistical models of the actual bird vocalizations. For each vocalization type, a statistical model of the vocalization was created by transforming the training set frequency tracks into feature vectors. The extraction algorithm extracts sets of frequency tracks from test recordings that closely approximate harmonic sounds in the file being processed. Each extracted set in its final form is then compared with the statistical models generated during the training phase using Mahalanobis distance functions. If it matches one of the models closely, the recognizer declares the set an occurrence of the corresponding vocalization. The method was evaluated against a test set containing vocalizations of both the 4 target species and 16 additional species as well as background noise containing planes, cars, and various natural sounds.


Perfluorochemicals and cell biotechnology.
Perfluorochemical (PFC) liquids have properties, especially high gas solubility, which make these compounds useful in medicine and biotechnology. PFCs are being employed to facilitate respiratory gas supply to both prokaryotic and eukaryotic cells and, in some systems, to improve biomass production and yields of commercially-important cellular products. Animal (including human) and plant cells have also been cultured at the interface between PFC liquids and aqueous culture medium, while fluorocarbon polymers have been employed as gaspermeable membranes in eukaryotic cell cultures. This paper presents an overview of the applications and beneficial effects of PFCs in microbial, animal and plant culture systems. PFCs have been compared with other physical and chemical options for manipulating respiratory gas supply to cultured cells. PFC-facilitated improvements in cell culture technology will have increasingly important biotechnological implications.


Future Perspectives for the Identification and Sequencing of Nicotinamide Adenine Dinucleotide-Capped RNAs.
Ribonucleic acid (RNA) is composed primarily of four canonical building blocks. In addition, more than 170 modifications contribute to its stability and function. Metabolites like nicotinamide adenine dinucleotide (NAD) were found to function as 5'-cap structures of RNA, just like 7-methylguanosine (m7G). The identification of NAD-capped RNA sequences was first made possible by NAD captureSeq, a multistep protocol for the specific targeting, purification, and sequencing of NAD-capped RNAs, developed in the authors' laboratory in the year 2015. In recent years, a number of NAD-RNA identification protocols have been developed by researchers around the world. They have enabled the discovery and identification of NAD-RNAs in bacteria, archaea, yeast, plants, mice, and human cells, and they play a key role in studying the biological functions of NAD capping. We introduce the four parameters of yield, specificity, evaluability, and throughput and describe to the reader how an ideal NAD-RNA identification protocol would perform in each of these disciplines. These parameters are further used to describe and analyze existing protocols that follow two general methodologies: the capture approach and the decapping approach. Capture protocols introduce an exogenous moiety into the NAD-cap structure in order to either specifically purify or sequence NAD-capped RNAs. In decapping protocols, the NAD cap is digested to 5'-monophosphate RNA, which is then specifically targeted and sequenced. Both approaches, as well as the different protocols within them, have advantages and challenges that we evaluate based on the aforementioned parameters. In addition, we suggest improvements in order to meet the future needs of research on NAD-modified RNAs, which is beginning to emerge in the area of cell-type specific samples. A limiting factor of the capture approach is the need for large amounts of input RNA. Here we see a high potential for innovation within the key targeting step: The enzymatic modification reaction of the NAD-cap structure catalyzed by ADP-ribosyl cyclase (ADPRC) is a major contributor to the parameters of yield and specificity but has mostly seen minor changes since the pioneering protocol of NAD captureSeq and needs to be more stringently analyzed. The major challenge of the decapping approach remains the specificity of the decapping enzymes, many of which act on a variety of 5'-cap structures. Exploration of new decapping enzymes or engineering of already known enzymes could lead to improvements in NAD-specific protocols. The use of a curated set of decapping enzymes in a combinatorial approach could allow for the simultaneous detection of multiple 5'-caps. The throughput of both approaches could be greatly improved by early sample pooling. We propose that this could be achieved by introducing a barcode RNA sequence before or immediately after the NAD-RNA targeting steps. With increased processing capacity and a potential decrease in the cost per sample, protocols will gain the potential to analyze large numbers of samples from different growth conditions and treatments. This will support the search for biological roles of NAD-capped RNAs in all types of organisms.


Can G-CSF cause leukemia in hematopoietic stem cell donors?
A large majority of allogeneic hematopoietic stem cell donations are achieved using granulocyte-colony stimulating factor (G-CSF). G-CSF use has been associated with later development of myelodysplastic syndromes/acute myelogenous leukemia (MDS/AML) in several clinical circumstances. Although clinical data to date have failed to identify any increased incidence of MDS/AML in G-CSF mobilized donors, the quality of these data are insufficient to exclude a long-term risk. Physicians should explain the potential risk to donors, and where appropriate, offer donors the option of marrow donation.


Silica nanoparticles inhibit brown adipocyte differentiation via regulation of p38 phosphorylation.
Nanoparticles are of great interest due to their wide variety of biomedical and bioengineering applications. However, they affect cellular differentiation and/or intracellular signaling when applied and exposed to target organisms or cells. The brown adipocyte is a cell type important in energy homeostasis and thus closely related to obesity. In this study, we assessed the effects of silica nanoparticles (SNPs) on brown adipocyte differentiation. The results clearly showed that brown adipocyte differentiation was significantly repressed by exposure to SNPs. The brown adipocyte-specific genes as well as mitochondrial content were also markedly reduced. Additionally, SNPs led to suppressed p38 phosphorylation during brown adipocyte differentiation. These effects depend on the size of SNPs. Taken together, these results lead us to suggest that SNP has anti-brown adipogenic effect in a size-dependent manner via regulation of p38 phosphorylation.


Limitations of Sulforhodamine 101 for Brain Imaging.
Since 2004, the red fluorescent dye Sulforhodamine 101 (SR101) has been boosting the functional analysis of astrocytes in a functional environment in an unprecedented way. However, two major limitations have been challenging the usefulness of this tool for cellular imaging: (i) SR101 is not as specific for astrocytes as previously reported; and (ii) discoveries of severe excitatory side effects of SR101 are bearing the risk of unwanted alteration of the system of interest. In this article, we summarize the current knowledge about SR101-labeling protocols and discuss the problems that arise from varying of the staining protocols. Furthermore, we provide a testable hypothesis for the observed hyper-excitability that can be observed when using SR101.


Removal of hepatocellular carcinoma extending into the right atrium with extracorporeal circulation.
Hepatocellular carcinoma with tumor thrombus extending into the right atrium is rare and has an extremely poor prognosis. Surgery was once regarded as a contraindication, then as a palliative method to prevent emergencies such as pulmonary embolism or heart failure. With advances of imaging techniques, hepatectomy and widespread use of extracorporeal circulation, conventional viewpoint has gradually changed. For patients with adequate hepatic function reserve and no distant metastases, surgery is recommended. During the past four years, we experienced two such patients, for both of whom we simultaneously resected the hepatic tumor and tumor thrombus in the right atrium under cardiopulmonary circulation and total hepatic blood exclusion. Both of the patients survived the surgery. During the follow-up, one patient died 6 months later due to multiple lung metastases and tumor progression. The other patient experienced recurrence 4 months after surgery and underwent adjuvant treatment modalities including chemotherapy, radiofrequency ablation and transcatheter arterial chemoembolization. Thirty-eight months later, the patient died of multiple metastasis and hepatic failure.


Evidence-based practice and clinical work assessment.
Despite the growing emphasis for evidence-based practice, there are barriers to adopting this paradigm. These include (1) the lack of consistent method to measure clinical work, (2) task orientation in current measurement methods, and (3) a lack of awareness among staff nurses about evidence-based practice. In addition, clinical unit cultures are perceived as barriers and often described as cultures of "habit and opinion." Three conceptual models are discussed as a method to assist clinicians in conducting an evidenced-based clinical work assessment to advance evidence-based practice.