The craniofacial dysostosis syndromes: current surgical thinking and future directions.
Craniofacial dysostosis is the term applied to familial forms of craniosynostosis in which the sutural involvement generally includes the cranial vault, cranial base, and midfacial skeletal structures. The syndromic forms of craniofacial dysostosis were initially described by Carpenter, Apert, Crouzon, Saethre and Chotzen, Pfeiffer, and others. In addition to the dysmorphic cranial features, affected individuals may have profound alterations in facial skeletal development. Surgical reconstruction requires thoughtfully sequenced and staged procedures with consideration for the individual's specific malformations, craniofacial growth patterns, and psychosocial needs. Management of the craniofacial dysostosis syndromes is surgical, but the indications and the timing, type, and effectiveness of each stage of reconstruction have not been well evaluated and remains as much an art as a science. This article reviews the specific characteristic clinical features of the craniofacial dysostosis syndromes and presents current philosophy and rationale for the staging of reconstruction.


Cardiovascular Fat, Menopause, and Sex Hormones in Women: The SWAN Cardiovascular Fat Ancillary Study.
Cardiovascular risk increases in women after menopause. Mounting evidence demonstrates a role of cardiovascular fat (CF) in the pathogenesis of coronary heart disease, but no research has examined CF in relation to sex hormones or menopausal status in women. The objective was to determine the relationship between CF depots, menopausal status, and endogenous sex hormones. Cross-sectional and longitudinal study designs were used. The setting included the Study of Women's Health Across the Nation (SWAN) Heart and Cardiovascular Fat Ancillary Study. A total of 456 women (mean age, 50.75 y); 62% premenopausal/early perimenopausal, and 38% late peri-/postmenopausal. Menopausal status, endogenous sex hormones measured simultaneously with CF volumes, and circulating estradiol available 4.80 years (median) before CF measures. Volumes of CF (epicardial adipose tissue [EAT], paracardial adipose tissue [PAT], total heart adipose tissue [TAT = EAT + PAT], and aortic perivascular adipose tissue [PVAT]). In final models, late peri-/postmenopausal women had 9.88% more EAT, 20.72% more PAT, and 11.69% more TAT volumes than pre-/early perimenopausal women (P < .05). PVAT was not associated with menopausal status. In final models, lower estradiol concentrations were associated with greater volumes of PAT and TAT (P < .05). Women with the greatest reduction in estradiol since baseline had greater volumes of PAT compared to women with the least reduction (P = .02). Late peri-/postmenopausal women have greater volumes of heart fat compared with pre-/early perimenopausal women independent of age, obesity, and other covariates. Endogenous sex hormones are associated with CF. Perhaps CF plays a role in the higher risk of coronary heart disease reported in women after menopause.


Outcomes of 556 consecutive patients with stage I-III colon cancer managed in a single center over 10 years.
The Bank of Cyprus Oncology Center is the largest cancer center in Cyprus, providing standalone oncology services to a population of just under a million. The aim of the study was to calculate disease-free survival (DFS) and overall survival (OS) for consecutive patients with stage I-III colon cancer over a 10-year period, by collecting retrospective data from patients' medical charts. We identified 556 patients with a median age at diagnosis of 67 (range 18-88). The majority of them were male (60%). Just over half of stage II patients received chemotherapy: capecitabine (44%) and FOLFOX/CapeOx (7%). Treatment administered in stage III was as follows: CapeOx (48%); FOLFOX (28%); capecitabine (12%); 5-fluorouracil (4%); and 8% received no treatment. DFS at 5 years was: stage I 90%; stage II 85%; and stage III 69%. Cancer-specific OS at 5 years was: stage I 94%; stage II 93%; and stage III 81%. Favorable outcomes were also maintained at 10 years (stage I 94%; stage II 84%; and stage III 70%). On multivariate analysis, only stage was statistically significant as a prognostic factor, whereas high-risk features (pT4±pN2), disease location (right vs. left), and age >70 years old did not reach statistical significance. Despite our country's fragmented healthcare system, with multiple referring surgeons from the private and public sectors, the outcomes achieved were highly consistent with those published in the international literature. This can be attributed to optimal multidisciplinary management and follow-up care.


[Latent form of glutathione reductase in the rat liver].
The existence of membrane-bound forms of glutathione reductase in rat liver and transplantable hepatoma G-27 was demonstrated, using differential centrifugation techniques. The activity of the sedimentable form of the liver enzyme was detected only in the presence of detergents. Conditions for the manifestation of the latent glutathione reductase activity in whole liver homogenates and in the 105000 g pellet were determined. Solubilization of the latent form of the enzyme in the presence of sodium deoxycholate increases 2-fold the glutathione reductase activity in liver homogenates (but not in hepatoma). Simultaneous determination of the disulfidereductase, nonspecific NADPH-oxidase and gamma-glutamyltransferase (membrane-bound enzyme of glutathione metabolism) activities was performed.


Postprandial interleukin-6 release from skeletal muscle in men with impaired glucose tolerance can be reduced by weight loss.
Obesity and type 2 diabetes mellitus are associated with increased levels of IL-6, a marker of inflammation. This study addressed the question of whether IL-6 was released from skeletal muscle after a high-fat meal in men with impaired glucose tolerance (IGT), a prediabetic state, and whether IL-6 release could be reduced by weight loss. Skeletal muscle metabolism was studied in men with IGT (n = 11) and compared with men with normal glucose tolerance (NGT, n = 9), matched for body mass index and age. IL-6 flux over skeletal muscle was measured with the forearm model. Eight IGT men were willing to participate in a 12-wk weight loss program and were tested again. IL-6, but not C-reactive protein or TNF-alpha receptor 1 and 2, was released by skeletal muscle. Muscle IL-6 release was higher in IGT than in NGT during fasting (IGT = 2.26 +/- 1.89 vs. NGT = 0.87 +/- 0.48 fmol x 100 ml tissue(-1) x min(-1), P = 0.04) and after a meal (mean area under the curve per minute: IGT = 3.48 +/- 2.63 vs. NGT = 1.37 +/- 0.75 fmol x 100 ml tissue(-1) x min(-1); P = 0.03). In the IGT men, body weight loss resulted in a decrease of postprandial IL-6 release from skeletal muscle (-52%; P = 0.04), reaching levels of the obese, NGT controls. The present data suggest that a high-fat meal can evoke IL-6 release from muscle and that the IL-6 release is a consequence rather than a cause of the obese, insulin-resistant, and/or IGT state.


Protonmotive functions of cytochrome c oxidase in reconstituted vesicles. Influence of turnover rate on 'proton translocation'.
1. Oxidation of ferrocytochrome c by cytochrome c oxidase incorporated into proteoliposomes induces a transient acidification of the external medium. This change is dependent on the presence of valinomycin and can be abolished by carbonyl cyanide p-trifluoromethoxyphenylhydrazone or by nigericin. The H+/e- ratio for the initial acidification varies with the internal buffering capacity of the vesicles, and under suitable conditions approaches + 1, the pulse slowly decaying to give a net alkalinity change with H+/e- value approaching -1. 2. Inhibition of cytochrome c oxidase turnover by ferricytochrome c or by azide addition results in ferrocytochrome c-dependent H+ pulses with decreasing H+/e- ratios. The rate of the initial H+ production remains higher than the rate of equilibration of the pH gradient, indicating an intrinsic dependence of the H+/e- ratio on enzyme turnover. The final net alkalinity changes are relatively unaffected by turnover inhibition.


The Metastasis Potential Promoting Capacity of Cancer-Associated Fibroblasts Was Attenuated by Cisplatin via Modulating KRT8.
Cancer-associated fibroblasts (CAFs) are an essential component of tumor microenvironment. They are attracting increasing attentions due to their crucial role in tumor growth, drug-resistance and metastasis. Cisplatin is a first-line chemotherapy drug applying in various types of cancer. There are intensive studies on cisplatin's effect on tumor cells, however, its effect on CAFs remains poorly understood. In the present study, we investigated the effect of cisplatin on CAFs. Cell migration was detected by wound healing assay. Cell invasion was performed by the transwell assay. mRNA expression was detected by quantitative PCR, and protein expression was detected by Western blotting. Tumor growth was measured using BALB/c nude mice tumor models. Cisplatin attenuated the promoting capacity of CAFs on lung cancer cell migration and invasion, via suppressing CAFs' effect on metastasis-related genes including Twist1, vascular endothelial growth factor receptor (VEGFR), MMP2, and AKT signaling pathway. Keratin 8 (KRT8) was identified as a target of cisplatin. KRT8 upregulation in CAFs is responsible for the inhibitory effect of cisplatin on lung cancer cells metastasis potential through AKT pathway suppression. The stimulation of AKT by AKT activator SC79 reversed KRT8's effect on cell migration. Importantly, in vivo study also showed that CAFs enhanced tumor growth significantly, and cisplatin effectively abrogated the promoting effect of CAFs on tumor growth. Our results revealed a novel mechanism that cisplatin attenuated the metastasis promoting effect of CAFs via KRT8/AKT signaling pathway. This finding highlights KRT8 in CAFs as a potential therapeutic candidate for metastasis treatment.


Prenatal diagnosis and postnatal outcome of fetal intracranial hemorrhage.
The aim of this study was to present our experience with six cases of fetal intracranial hemorrhage (ICH) in terms of prenatal diagnostic features, and postnatal outcome. The database of prenatal diagnosis unit was searched for antenatally diagnosed ICH cases. Maternal characteristics, ultrasound (US), and magnetic resonance imaging (MRI) findings, clinical course, and postnatal outcome were noted. We evaluated six consecutive cases of fetal ICH. One case was terminated at 24 weeks, and remaining five cases were delivered between 34 and 38 weeks. Five cases (5/6) had intraventricular, and one (1/6) had intraparenchymal hemorrhage. Hemorrhages were right sided in five cases (5/6), left sided in one case (1/6). Dilated and echogenic ventricular wall were the common US findings. No predisposing factor was detected in four of the cases, and intrauterine growth restriction was an underlying factor in two fetuses. Intrauterine progression of the hydrocephaly, and parenchymal thinning was seen in four cases (4/6). In three of four cases (3/4) with progressive grade 3-4 hemorrhage and hydrocephaly, postnatal outcome were dismal, and one case had mild neurological impairment at three months. In one case which had non-progressive mild ventriculomegaly, the lesion regressed after 4 weeks, and had normal short-term outcome Fetal ICH can be accurately identified and categorized by antenatal sonography, and fetal MRI. Although intrauterine regression or normal short-term postnatal outcome is possible, the outcome is usually poor for fetuses with high grade and/or progressive lesions. Therefore, further studies assessing long-term postnatal outcome are needed.


A finite element analysis of a T12 vertebra in two consecutive examinations to evaluate the progress of osteoporosis.
Osteoporosis is a metabolic disease that causes bones to become fragile and be more likely to break. As basic clinical examinations to detect osteoporosis, dual energy X-ray absorptiometry (DXA) and quantitative computer tomography (QCT) are used. In the framework of a typical clinical examination, QCT scans were obtained from the T12 vertebra of an elderly woman and osteoporosis was diagnosed. One year later, new QCT scans were obtained in order to evaluate her clinical condition. Using both sets as primary information, two patient-specific finite element (FE) models were created and analyzed under compressive load. Vertebral bone was treated as orthotropic material and its elastic modulus was set as an indirect function of Hounsfield Units (HU). Commercial software for medical image processing and FE analysis, along with in house codes, were used for the mechanical analysis of the FE models. Alterations in the geometry/shape of the vertebra as well as in the distributions of several mechanical quantities were detected between the two FE models. As far as the volume of the vertebra is concerned, it augmented by a percentage of 9.7% while the volume of the vertebral body alone increased by 5.6%. In all the maximum values of the mechanical quantities a measurable reduction was observed (axial compressive displacement: 37.9%, von Mises stress: 23.8%, von Mises strains: 15.1%) and all the investigated distributions in the second FE model became smoother. Finally, the percentage of volume with von Mises strains greater than 4500 microstrain dropped from 8.9%, in the first examination, to 4.9% in the second one. Clinically, the prescribed medication seems to have reinforced the structural stability of the vertebra as a whole and through external remodeling the shape of the vertebra changed in a way that the majority of its volume was relieved from stresses and strains of high magnitude.


Metabolic syndrome and risk of acute myocardial infarction a case-control study of 26,903 subjects from 52 countries.
This study examines the risk of acute myocardial infarction (MI) conferred by the metabolic syndrome (MS) and its individual factors in multiple ethnic populations. The risk of the MS on MI has not been well characterized, especially in multiple ethnic groups. Participants in the INTERHEART study (n = 26,903) involving 52 countries were classified using the World Health Organization (WHO) and International Diabetes Federation (IDF) criteria for MS, and their odds ratios (ORs) for MI were compared with the individual MS component factors. The MS is associated with an increased risk of MI, both using the WHO (OR: 2.69; 95% confidence interval [CI]: 2.45 to 2.95) and IDF (OR: 2.20; 95% CI: 2.03 to 2.38) definitions, with corresponding population attributable risks of 14.5% (95% CI: 12.7% to 16.3%) and 16.8% (95% CI: 14.8% to 18.8%), respectively. The associations are directionally similar across all regions and ethnic groups. Using the WHO definition, the association with MI by the MS is similar to that of diabetes mellitus (OR: 2.72; 95% CI: 2.53 to 2.92) and hypertension (OR: 2.60; 95% CI: 2.46 to 2.76), and significantly stronger than that of the other component risk factors. The clustering of > or =3 risk factors with subthreshold values is associated with an increased risk of MI (OR: 1.50; 95% CI: 1.24 to 1.81) compared with having component factors with "normal" values. The IDF definition showed similar results. In this large-scale, multi-ethnic, international investigation, the risk of MS on MI is generally comparable to that conferred by some, but not all, of its component risk factors. The characterization of risk factors, especially continuous variables, as dichotomous will underestimate risk and decrease the magnitude of association between MS and MI.


Impact of the Agency for Healthcare Research and Quality's Safety Program for Perinatal Care.
The Safety Program for Perinatal Care (SPPC) seeks to improve safety on labor and delivery (L&D) units through three mutually reinforcing components: (1) fostering a culture of teamwork and communication, (2) applying safety science principles to care processes; and (3) in situ simulation. The objective of this study was to describe the SPPC implementation experience and evaluate the short-term impact on unit patient safety culture, processes, and adverse events. We supported SPPC implementation by L&D units with a program toolkit, trainings, and technical assistance. We evaluated the program using a pre-post, mixed-methods design. Implementing units reported uptake of program components, submitted hospital discharge data on maternal and neonatal adverse events, and participated in semi-structured interviews. We measured changes in safety and quality using the Modified Adverse Outcome Index (MAOI) and other perinatal care indicators. Forty-three L&D units submitted data representing 97,740 deliveries over 10 months of follow-up. Twenty-six units implemented all three program components. L&D staff reported improvements in teamwork, communication, and unit safety culture that facilitated applying safety science principles to clinical care. The MAOI decreased from 5.03% to 4.65% (absolute change -0.38% [95% CI, -0.88% to 0.12%]). Statistically significant decreases in indicators for obstetric trauma without instruments and primary cesarean delivery were observed. A statistically significant increase in neonatal birth trauma was observed, but the overall rate of unexpected newborn complications was unchanged. The SPPC had a favorable impact on unit patient safety culture and processes, but short-term impact on maternal and neonatal adverse events was mixed.


[Acute renal insufficiency in exogenous poisoning (problems of classification and pathogenesis)].
Acute renal insufficiency (ARI) -- one of the most frequent manifestations of many exogenous intoxications. On the ground of a morphological investigation of 625 kidneys in poisoning with various poisons, the authors have come to the conclusion that the acute nephrotic syndrome is the basis of ARI in a "toxic" kidney". A morphological classification of the nephrotic syndrome is given: necrotic nephrosis hydropic nephrosis (glycolic nephrosis), cortical necrosis of the kidney, excretory nephrosis, acute lipid nephrosis. Morphological characteristics of the nephrotic syndrome forms referred to above are presented. Lesions of the kidney in exogenous intoxications are caused first of all by the direct toxic action of a poison. Toxic shock is an important factor in the development of ARI.


Effects of thyroid hormones on adipose tissue development in Sherman and Zucker rats.
It has been reported that mild hyperthyroidism in the young Sherman rat induces adipose tissue hyperplasia, concomitant with cell size reduction, and that hypothyroidism induces opposite effects. The present experiments were designed to study the evolution of cellularity in retroperitoneal and epididymal adipose tissue during a long term thyroxine (T4) treatment or in T4-treated rats, after the treatment had been stopped. In both cases, hyperplasia was transient with the observation that the adipocyte number observed in 3-mo-old control rats was reached earlier in T4-treated rats. In hypothyroid rats, hypoplasia was also transient, because once the treatment was stopped, the cell number overtook that of controls. Zucker rats were also treated with T4, because hypoplasia has been observed in young obese (fa/fa) rats and these rats are reported to be hypothyroid. T4 treatment increased their adipocyte number up to the level of nonobese (Fa/fa) untreated rats, while hypertrophy, although reduced, was persistent. In Sherman and Zucker rats, adipose tissue lipoprotein lipase activity was decreased by T4 treatment in parallel with and perhaps because of adipocyte size reduction. We suggest that hyperplasia induced by thyroid hormones results from a precocious differentiation of preadipocytes and does not necessarily imply an increased preadipocytes multiplication.


In Vitro Synergistic Effects of Antimicrobial Combinations on Extensively Drug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Isolates.
Extensively drug-resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii are a threat to hospitalized patients. We evaluated the effects of antimicrobial combinations on XDR P. aeruginosa and A. baumannii isolates. P. aeruginosa and A. baumannii isolates, which were resistant to all antibiotics except colistin (CL), were collected from eight hospitals in Korea. Genes encoding metallo-β-lactamases (MBLs) and OXA carbapenemases were detected by PCR in eight P. aeruginosa and 30 A. baumannii isolates. In vitro synergy of antimicrobial combinations was tested by using the checkerboard method. Minimum inhibitory concentrations of β-lactams, aminoglycosides, and fluoroquinolones were very high, while that of CL was low for majority of XDR P. aeruginosa and A. baumannii isolates. Antimicrobial combinations including Imipenem (IPM)-CL, ceftazidime (CAZ)-CL, and rifampin (RIF)-CL exerted only additive/indifferent effects on majority of XDR P. aeruginosa isolates. Proportions of XDR A. baumannii isolates that showed synergistic and additive/indifferent inhibition after treatment with antimicrobial combinations used are as follows: IPM-ampicillin-sulbactam (AMS), 17% and 80% isolates, respectively; IPM-rifampin (RIF), 13% and 81% isolates, respectively; IPM-CL, 13% and 87% isolates, respectively; and RIF-COL, 20% and 73% isolates, respectively. Significant proportion (19%) of XDR P. aeruginosa isolates produced MBLs, and majority (82%) of A. baumannii isolates produced either MBLs or OXA-23. Our results suggest that combinations of IPM-AMS, IPM-RIF, IPM-CL, and RIF-CL are more useful than individual drugs for treating 13-20% of XDR A. baumannii infections.


[The characteristics of the sympathico-adrenal and kinin systems in engineers in the early stages of arterial hypertension].
Overall seventy-two engine-drivers with borderline arterial hypertension (BAH) and stage I arterial hypertension (AH) were studied for the condition of the sympathoadrenal and kinin systems before and after trip. Both groups exhibited a rise in the activity of the sympathoadrenal system before trip, with still greater rise being recordable after trip. BAH and stage I AH subjects demonstrated an increased activity of the kinin system of the kidneys before trip and decreased one after trip. Suppression of the kinin system of the kidneys with simultaneous progression of pressor effects leads to decline in adaptation to physical and psychoemotional overloads in those engine-drivers presenting with early stages of AH.


Significance of new Q waves after aortocoronary bypass surgery. Correlation with changes in ventricular wall motion.
From June 1969 to December 1974, 142 patients underwent aortocoronary bypass surgery at the Veterans Administration Hospital, San Francisco. Seventeen patients developed new Q waves; two of four deaths in the hospital occurred among these 17 patients. Preoperative and postoperative catheterization data were available for analysis in 12 of the 15 surviving patients. Longitudinal, transverse, and hemiaxial segmental analysis of preoperative and postoperative single plane, 30 degrees right anterior oblique left ventriculograms revealed deterioration in wall motion in all 12 patients. The deterioration corresponded to the area on the electrocardiogram where the new Q waves appeared. In ten of 12 patients, ejection fraction also deteriorated. Twenty-six of 29 grafts were patent. New Q waves after aortocoronary bypass surgery correlate well with the appearance of localized abnormalities in wall motion. We found no evidence that perioperative appearance of Q waves was not due to new perioperative myocardial infarction.


Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future.
It has been more than two decades since the formulation of the so-called 'trade-off' hypothesis as an alternative to the then commonly accepted idea that parasites should always evolve towards avirulence (the 'avirulence hypothesis'). The trade-off hypothesis states that virulence is an unavoidable consequence of parasite transmission; however, since the 1990s, this hypothesis has been increasingly challenged. We discuss the history of the study of virulence evolution and the development of theories towards the trade-off hypothesis in order to illustrate the context of the debate. We investigate the arguments raised against the trade-off hypothesis and argue that trade-offs exist, but may not be of the simple form that is usually assumed, involving other mechanisms (and life-history traits) than those originally considered. Many processes such as pathogen adaptation to within-host competition, interactions with the immune system and shifting transmission routes, will all be interrelated making sweeping evolutionary predictions harder to obtain. We argue that this is the heart of the current debate in the field and while species-specific models may be better predictive tools, the trade-off hypothesis and its basic extensions are necessary to assess the qualitative impacts of virulence management strategies.


The New Quadrivalent Adjuvanted Influenza Vaccine for the Italian Elderly: A Health Technology Assessment.
The elderly, commonly defined as subjects aged ≥65 years, are among the at-risk subjects recommended for annual influenza vaccination in European countries. Currently, two new vaccines are available for this population: the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (hdQIV). Their multidimensional assessment might maximize the results in terms of achievable health benefits. Therefore, we carried out a Health Technology Assessment (HTA) of the aQIV by adopting a multidisciplinary policy-oriented approach to evaluate clinical, economic, organizational, and ethical implications for the Italian elderly. A HTA was conducted in 2020 to analyze influenza burden; characteristics, efficacy, and safety of aQIV and other available vaccines for the elderly; cost-effectiveness of aQIV; and related organizational and ethical implications. Comprehensive literature reviews/analyses were performed, and a transmission model was developed in order to address the above issues. In Italy, the influenza burden on the elderly is high and from 77.7% to 96.1% of influenza-related deaths occur in the elderly. All available vaccines are effective and safe; however, aQIV, such as the adjuvanted trivalent influenza vaccine (aTIV), has proved more immunogenic and effective in the elderly. From the third payer's perspective, but also from the societal one, the use of aQIV in comparison with egg-based standard QIV (eQIV) in the elderly population is cost-effective. The appropriateness of the use of available vaccines as well as citizens' knowledge and attitudes remain a challenge for a successful vaccination campaign. The results of this project provide decision-makers with important evidence on the aQIV and support with scientific evidence on the appropriate use of vaccines in the elderly.


Sex redefined: the reclassification of oral-genital contact.
Although partially anecdotal, some evidence suggests that oral-genital contact is increasingly excluded from young people's notions of what behaviors constitute sex. Such a shift may have implications for STD prevention. In 2007, a convenience sample of 477 university students participated in a survey that included the question "Would you say you 'had sex' with someone if the most intimate behavior you engaged in was" each of 11 behaviors. Chi-square tests and independent samples t tests were used to assess gender differences, and chi-square analyses were used to compare the data with similar data collected in 1991. Predictors of beliefs concerning the classification of oral-genital contact were assessed using logistic regression analysis. The majority of respondents indicated that penile-vaginal intercourse and penile-anal intercourse constitute sex (98% and 78%, respectively), but only about 20% believed the same was true of oral-genital contact. The proportion classifying oral-genital contact as sex in 2007 was about half that in 1991. This difference was consistent for both sexes and for both giving and receiving oral-genital stimulation. Responses did not vary by respondents' sexual experience or demographic characteristics. Sociocultural conceptualizations of oral-genital contact have shifted in a way that may leave people who engage in this activity unmindful of its potential health risks. Sex education programs, which generally focus on penile-vaginal contact, could help STD prevention efforts by explaining the risks associated with oral-genital stimulation and the measures that can be taken to minimize those risks.


[Clinical laboratory diagnosis of trichomoniasis in patients with internal diseases].
Urogenital trichomoniasis is an infectious inflammatory disease of the urogenital system caused by protozoan Trichomonas vaginalis and characterized by rapid dissemination and development of complications. Because laboratory diagnosis by microscopic methods encounters difficulty, we undertook detection of T. vaginalis by microscopic study of native and stained (methylene blue, acridine orange, Gram, Romanovsky-Giemsa) uretheral scrapings. 69 patients having no clinical signs of the disease were examined after sexual contacts with women suffering infection of the urogenital tract. Staining with acridine orange and by Romanovsky-Giemsa method proved the most informative methods for diagnosis of torpid trichomoniasis (85.5 and 75.4% respectively). The study of native samples is of little informative value (5.8%). The data obtained were used to develop an algorithm of microscopic investigation for the examination of patients with urogenital acute, subacute or chronic trichomoniasis and carriers of T. vaginalis.


Appraising the nature of luteinizing hormone secretory events in men.
We have appraised the nature of spontaneous luteinizing hormone (LH) secretory events in normal men by analyzing immunoactive LH concentrations in blood samples withdrawn at 5-min intervals for 24 h in eight healthy individuals. A novel discrete deconvolution algorithm was applied to determine apparent instantaneous LH secretory rates from these LH concentration series. These analyses unmasked unique attributes of spontaneous LH secretory events, which were represented as delimited momentary augmentations in endogenous LH secretory rates interspersed among intervals of relative secretory quiescence. For three different peak-detection thresholds (P = 0.02, = 0.01, and = 0.005), the frequency of LH secretory episodes was significantly greater than that of LH "pulses" judged from concentration data alone. Moreover, the total mass of LH released within discrete secretory episodes could account for approximately 90% of LH secreted during the day. This model of distinct, short-lived, burst-like secretion of LH has important implications for further investigations of the neuroendocrine regulation of gonadotropin secretion in humans.


Prediction of digestible energy of feed ingredients for growing pigs using a computer-controlled simulated digestion system.
The objectives of this experiment were to evaluate in vitro DE (IVDE) of selected feed ingredients using a computer-controlled simulated digestion system (CCSDS) and predict DE of ingredients for growing pigs. Samples of 6 ingredients with a wide range in energy and nutrient profile were collected. The CP and GE contents ranged from 9.9 to 50.9% and 4,493 to 4,841 kcal/kg (DM basis), respectively. Two control diets were formulated to achieve different CP contents (12.5 and 20.0%). Three experimental diets were formulated by replacing 20% of the high-CP control diet with corn, wheat, or wheat bran, whereas 3 additional diets were formulated by replacing 20% of the low-CP control diet with soybean meal, rapeseed meal, or cottonseed meal. The DE was determined using barrows (n = 24; initial BW = 35.9 ± 1.9 kg) in 2 periods with 6 observations per diet treatment and ranged from 2,769 to 4,368 kcal/kg. The equation for the DE content (kcal/kg of DM) using chemical components as independent variables was DE = 4,186 + 0.06 × CP + 79.33 × ether extract - 14.57 × NDF - 47.99 × ADF, with R(2) = 0.995, residual SD (RSD) = 89.5 kcal/kg, CV = 2.4%, and P = 0.10 (chemical component values; %). The IVDE ranged from 2,289 to 3,724 kcal/kg and was highly related to the determined DE content of the ingredients (R(2) = 0.91, RSD = 193 kcal/kg, and CV = 5.2%). The relationship between IVDE:GE and DE:GE was very high (R(2) = 0.93, RSD = 3.8%, and CV = 4.7%). The average values of CV for IVDE (0.75%) and IVDE:GE (0.73%) were less than that for determined DE (2.58%) and DE:GE (2.54%), respectively. In conclusion, the IVDE content determined, using a CCSDS with relatively high accuracy and acceptable repeatability, might be used to predict DE of feed ingredients for growing pigs.


Reversal reaction in lepromatous patients induced by a vaccine containing killed ICRC bacilli--a report of five cases.
Clinico-pathological features of five cases of lepromatous leprosy exhibiting "reversal" reaction with upgrading of lesions following vaccination with ICRC vaccine have been described. Two patients also developed ENL. Associated with the "reversal" reaction, the patients exhibited lepromin conversion. No evidence of fresh nerve lesions was observed in any patient. Besides lepromin conversion, occurrence of "reversal" reaction is yet another evidence of immunogenicity of the ICRC vaccine.


Genome evolution of a tertiary dinoflagellate plastid.
The dinoflagellates have repeatedly replaced their ancestral peridinin-plastid by plastids derived from a variety of algal lineages ranging from green algae to diatoms. Here, we have characterized the genome of a dinoflagellate plastid of tertiary origin in order to understand the evolutionary processes that have shaped the organelle since it was acquired as a symbiont cell. To address this, the genome of the haptophyte-derived plastid in Karlodinium veneficum was analyzed by Sanger sequencing of library clones and 454 pyrosequencing of plastid enriched DNA fractions. The sequences were assembled into a single contig of 143 kb, encoding 70 proteins, 3 rRNAs and a nearly full set of tRNAs. Comparative genomics revealed massive rearrangements and gene losses compared to the haptophyte plastid; only a small fraction of the gene clusters usually found in haptophytes as well as other types of plastids are present in K. veneficum. Despite the reduced number of genes, the K. veneficum plastid genome has retained a large size due to expanded intergenic regions. Some of the plastid genes are highly diverged and may be pseudogenes or subject to RNA editing. Gene losses and rearrangements are also features of the genomes of the peridinin-containing plastids, apicomplexa and Chromera, suggesting that the evolutionary processes that once shaped these plastids have occurred at multiple independent occasions over the history of the Alveolata.


The MTDH (-470G>A) polymorphism is associated with ovarian cancer susceptibility.
MTDH (metadherin), an important oncogene that is widely overexpressed in various cancers, is a potential biomarker of tumor malignancy. Variants in MTDH have been associated with susceptibility to breast cancer. However, no studies assessing MTDH gene polymorphisms and their potential relationship to ovarian cancer susceptibility have been reported. Thus, we investigated the association of MTDH (-470G>A) polymorphism with ovarian cancer development in 145 ovarian cancer patients and 254 matched control subjects, using sequence analysis. We found that the MTDH (-470G>A) polymorphism was statistically correlated with ovarian cancer risk (under the additive genetic model, GG vs. GA vs AA, P = 0.042). Compared with genotypes containing the G allele (GG and GA), the AA genotype may decrease the risk of ovarian cancer (P = 0.0198, OR = 0.33, 95% CI [0.12∼0.78]). Compared with the G allele, the A allele is protective against ovarian cancer risk (P = 0.01756, OR = 0.66, 95% CI [0.46∼0.93]). Furthermore, a statistically significant association between the GG and GA+AA genotypes and the clinical stage was observed (P = 0.038). These data suggest that MTDH (-470G>A) could be a useful molecular marker for assessing ovarian cancer risk and for predicting ovarian cancer patient prognosis.


Grid heterogeneity in in-silico experiments: an exploration of drug screening using DOCK on cloud environments.
Large-scale in-silico screening is a necessary part of drug discovery and Grid computing is one answer to this demand. A disadvantage of using Grid computing is the heterogeneous computational environments characteristic of a Grid. In our study, we have found that for the molecular docking simulation program DOCK, different clusters within a Grid organization can yield inconsistent results. Because DOCK in-silico virtual screening (VS) is currently used to help select chemical compounds to test with in-vitro experiments, such differences have little effect on the validity of using virtual screening before subsequent steps in the drug discovery process. However, it is difficult to predict whether the accumulation of these discrepancies over sequentially repeated VS experiments will significantly alter the results if VS is used as the primary means for identifying potential drugs. Moreover, such discrepancies may be unacceptable for other applications requiring more stringent thresholds. This highlights the need for establishing a more complete solution to provide the best scientific accuracy when executing an application across Grids. One possible solution to platform heterogeneity in DOCK performance explored in our study involved the use of virtual machines as a layer of abstraction. This study investigated the feasibility and practicality of using virtual machine and recent cloud computing technologies in a biological research application. We examined the differences and variations of DOCK VS variables, across a Grid environment composed of different clusters, with and without virtualization. The uniform computer environment provided by virtual machines eliminated inconsistent DOCK VS results caused by heterogeneous clusters, however, the execution time for the DOCK VS increased. In our particular experiments, overhead costs were found to be an average of 41% and 2% in execution time for two different clusters, while the actual magnitudes of the execution time costs were minimal. Despite the increase in overhead, virtual clusters are an ideal solution for Grid heterogeneity. With greater development of virtual cluster technology in Grid environments, the problem of platform heterogeneity may be eliminated through virtualization, allowing greater usage of VS, and will benefit all Grid applications in general.


A case-based, problem-based learning approach to prepare master of public health candidates for the complexities of global health.
Global health is a dynamic, emerging, and interdisciplinary field. To address current and emerging global health challenges, we need a public health workforce with adaptable and collaborative problem-solving skills. In the 2013-2014 academic year, the Hubert Department of Global Health at the Rollins School of Public Health-Emory University launched an innovative required core course for its first-year Master of Public Health students in the global health track. The course uses a case-based, problem-based learning approach to develop global health competencies. Small teams of students propose solutions to these problems by identifying learning issues and critically analyzing and synthesizing new information. We describe the course structure and logistics used to apply this approach in the context of a large class and share lessons learned.


Iatrogenic arterial injuries resulting from invasive procedures.
The many invasive arterial procedures that require cannulation of an artery with a large or traumatic catheter can be expected to produce iatrogenic injuries in a certain number of patients. While almost all arterial cannulation procedures are performed by physicians, nurses play a major role in performing baseline assessment of arterial blood flow, monitoring indwelling catheters, and detecting evidence of arterial injury. Clinical manifestations may appear during a procedure, while an indwelling arterial catheter is in place or after the catheter has been removed. Vigilant attention is essential to prevent serious injury or death due to a complication of an iatrogenic arterial injury.


[Role of antibodies in protection from pseudotuberculous infection and intoxication].
Lethal doses of virulent pseudotuberculosis bacilli and antipseudotuberculosis sera of different specificity were injected to albino mice simultaneously. A high neutralizing activity of antibodies against pseudotuberculosis intoxication was demonstrated. The type-specific antibodies proved to protect the mice from the toxins of the homologous types of the microbe only. Group antibodies of plaque antiserum and serum procured from the pseudoteburculosis convalescent produced a cross antitoxic action. The antiinfectious effect from the antibody administration was weak. Apparently in pseudotuberculosis the antibodies were the principal factor of the toxin neutralization and were of auxiliary significance in the protection from the developing infection. Neutralization of pseudotuberculosis toxins with plague antiserum served as an additional confirmation of cross immunity between plague and pseudotuberculosis.


Immunosuppressive therapy in lung injury due to paraquat poisoning: a meta-analysis.
Immunosuppressive therapy has been shown to improve outcomes in patients with paraquat poisoning. The objective of this study was to evaluate the efficacy of immunosuppressive therapy in the management of lung injury due to paraquat poisoning. We searched the MEDLINE, OVID, and CINAHL databases for relevant studies published from 1980 to 2006. We included studies if (a) the study design was a randomised controlled trial, observational study with historical controls or observational study; (b) the study population included patients with paraquat poisoning, and received immunosuppressive therapy; and (c) the study provided data on mortality. We calculated the survival rate with 95 percent confidence intervals (CI) for observational studies, and relative risk and 95 percent CI for dichotomous outcomes. 12 studies--four non-randomised, six non-randomised comparing historical controls, and two randomised controlled trials--had employed immunosuppressive therapy in the management of paraquat poisoning. The survival rate in the four non-randomised studies (39 patients) was 74.4 percent (95 percent CI 58.9-85.4). The relative risk of immunosuppressive therapy in decreasing mortality with paraquat poisoning was 0.55 (95 percent CI 0.39-0.77) and 0.6 (95 percent CI 0.27-1.34) for the non-randomised studies (comparing historical controls) and randomised controlled studies, respectively. There was significant heterogeneity and evidence of publication bias. One out of four patients (95 percent CI 3-5) were successfully treated with immunosuppressive therapy for paraquat poisoning. However, due to significant heterogeneity and publication bias, a large randomised controlled trial will be required to affirm the role of immunosuppression in paraquat poisoning.


[Antiepileptic monotherapy and combination therapy of simple focal seizures].
According to present state of literature complete seizure control can be obtained in about 50% of patients with simple partial seizures. In several studies on previously untreated patients with simple partial seizures most patients became seizure-free with carbamazepine or phenobarbital or phenytoin or primidone or valproic acid used as monotherapy. Previous experience has shown that in patients whose seizures are not completely controlled by monotherapy drug combinations like carbamazepine with phenobarbital or primidone or valproic acid and phenytoin with phenobarbital or primidone or valproic acid should be initiated. Several animal experiments are suggestive for a synergistic effect of different antiepileptic drugs. In a previously published study on carbamazepine monotherapy, 6 out of 9 patients with simple partial seizures became seizure-free or improved markedly by this treatment.


Selective Single-Molecule Nanopore Detection of mpox A29 Protein Directly in Biofluids.
Single-molecule antigen detection using nanopores offers a promising alternative for accurate virus testing to contain their transmission. However, the selective and efficient identification of small viral proteins directly in human biofluids remains a challenge. Here, we report a nanopore sensing strategy based on a customized DNA molecular probe that combines an aptamer and an antibody to enhance the single-molecule detection of mpox virus (MPXV) A29 protein, a small protein with an M.W. of ca. 14 kDa. The formation of the aptamer-target-antibody sandwich structures enables efficient identification of targets when translocating through the nanopore. This technique can accurately detect A29 protein with a limit of detection of ∼11 fM and can distinguish the MPXV A29 from vaccinia virus A27 protein (a difference of only four amino acids) and Varicella Zoster Virus (VZV) protein directly in biofluids. The simplicity, high selectivity, and sensitivity of this approach have the potential to contribute to the diagnosis of viruses in point-of-care settings.


[Phenotypic features of a strain of Yersinia pseudotuberculosis with the pVM82 plasmid, detected at pseudotuberculosis outbreak foci].
The phenotypic properties conferred to Yersinia pseudotuberculosis cells by the genetical determinants of a 25Md fragment of the plasmid pVM82 coding for the modified cellular immune response in the infected organism. The fragment was shown to determine the conjugative properties of the plasmid, the resistance of bacterial cells to a number of hydrophobic agents and cellular ability to absorb the Congo red dye. The latter confirms the presence of additional structural components in the cell wall of the strain harbouring the plasmid pVM82. The increased resistance of the plasmid-containing strain to bactericidal effect of the blood plasma was demonstrated as compared with the resistance of the strains harbouring the p57 plasmid lacking the 25Md fragment or no plasmid at all.


Aged mice have enhanced endocortical response and normal periosteal response compared with young-adult mice following 1 week of axial tibial compression.
With aging, the skeleton may lose its ability to respond to positive mechanical stimuli. We hypothesized that aged mice are less responsive to loading than young-adult mice. We subjected aged (22 months) and young-adult (7 months) BALB/c male mice to daily bouts of axial tibial compression for 1 week and evaluated cortical and trabecular responses using micro-computed tomography (µCT) and dynamic histomorphometry. The right legs of 95 mice were loaded for 60 rest-inserted cycles per day to 8, 10, or 12 N peak force (generating mid-diaphyseal strains of 900 to 1900 µε endocortically and 1400 to 3100 µε periosteally). At the mid-diaphysis, mice from both age groups showed a strong anabolic response on the endocortex (Ec) and periosteum (Ps) [Ec.MS/BS and Ps.MS/BS: loaded (right) versus control (left), p < .05]. Generally, bone formation increased with increasing peak force. At the endocortical surface, contrary to our hypothesis, aged mice had a significantly greater response to loading than young-adult mice (Ec.MS/BS and Ec.BFR/BS: 22 months versus 7 months, p < .001). Responses at the periosteal surface did not differ between age groups (p > .05). The loading-induced increase in bone formation resulted in increased cortical area in both age groups (loaded versus control, p < .05). In contrast to the strong cortical response, loading only weakly stimulated trabecular bone formation. Serial (in vivo) µCT examinations at the proximal metaphysis revealed that loading caused a loss of trabecular bone in 7-month-old mice, whereas it appeared to prevent bone loss in 22-month-old mice. In summary, 1 week of daily tibial compression stimulated a robust endocortical and periosteal bone-formation response at the mid-diaphysis in both young-adult and aged male BALB/c mice. We conclude that aging does not limit the short-term anabolic response of cortical bone to mechanical stimulation in our animal model.


Exercise training in transgenic mice is associated with attenuation of early breast cancer growth in a dose-dependent manner.
Epidemiological research suggests that regular physical activity confers beneficial effects that mediate an anti-tumor response and may reduce cancer recurrence. It is unclear what amount of physical activity is necessary to exert such a protective effect and what mechanisms are involved. We investigated the effects of voluntary wheel running on tumor progression and cytokine gene expression in the transgenic polyoma middle T oncoprotein (PyMT) mouse model of invasive breast cancer. Runners showed significantly reduced tumor sizes compared with non-runners after 3 weeks of running (p ≤ 0.01), and the greater the running distance the smaller the tumor size (Pearson's r = -0.61, p ≤ 0.04, R(2) = 0.38). Mice running greater than 150 km per week had a significantly attenuated tumor size compared with non-runners (p ≤ 0.05). Adipose tissue mass was inversely correlated with tumor size in runners (Pearson's r = -0.77, p = 0.014) but not non-runners. Gene expression of CCL22, a cytokine associated with recruitment of immunosuppressive T regulatory cells, was decreased in tumors of runners compared to non-runners (p ≤ 0.005). No differences in tumor burden or metastatic burden were observed between runners and non-runners after ten weeks of running when the study was completed. We conclude that voluntary wheel running in PyMT mice correlates with an attenuation in tumor progression early during the course of invasive breast cancer. This effect is absent in the later stages of overwhelming tumor burden even though cytokine signaling for immunosuppressive regulatory T cells was down regulated. These observations suggest that the initiation of moderate exercise training for adjunctive therapeutic benefit early in the course of invasive breast cancer should be considered for further investigation.


Conundrum, an ARHGAP18 orthologue, regulates RhoA and proliferation through interactions with Moesin.
RhoA, a small GTPase, regulates epithelial integrity and morphogenesis by controlling filamentous actin assembly and actomyosin contractility. Another important cytoskeletal regulator, Moesin (Moe), an ezrin, radixin, and moesin (ERM) protein, has the ability to bind to and organize cortical F-actin, as well as the ability to regulate RhoA activity. ERM proteins have previously been shown to interact with both RhoGEF (guanine nucleotide exchange factors) and RhoGAP (GTPase activating proteins), proteins that control the activation state of RhoA, but the functions of these interactions remain unclear. We demonstrate that Moe interacts with an unusual RhoGAP, Conundrum (Conu), and recruits it to the cell cortex to negatively regulate RhoA activity. In addition, we show that cortically localized Conu can promote cell proliferation and that this function requires RhoGAP activity. Surprisingly, Conu's ability to promote growth also appears dependent on increased Rac activity. Our results reveal a molecular mechanism by which ERM proteins control RhoA activity and suggest a novel linkage between the small GTPases RhoA and Rac in growth control.


Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial.
Genetic variation in the endogenous opioid system has been identified as 1 potential source of individual variability in naltrexone treatment outcomes. The majority of naltrexone pharmacogenetic studies have focused on a particular single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1; rs1799971; commonly known as the Asn40Asp SNP) in Caucasian samples with decidedly mixed results. The goal of this study was to test the pharmacogenetic effects of naltrexone on subjective response to alcohol and self-administration of alcohol in individuals of East Asian descent. We hypothesized that naltrexone, compared with placebo, would potentiate the aversive and sedative effects of alcohol and reduce alcohol self-administration to a greater extent in Asp40 carriers. Participants (N = 77; Asn40Asn, n = 29; Asn40Asp, n = 34, and Asp40Asp, n = 14) completed 2 double-blinded and counterbalanced experimental sessions: one after taking naltrexone (50 mg/d) for 5 days and one after taking matched placebo for 5 days. In each experimental session, participants received a priming dose of intravenous alcohol up to the breath alcohol concentration target of 0.06 g/dl which was immediately followed by an alcohol self-administration period (1 hour). There were no pharmacogenetic effects observed for alcohol-induced stimulation, sedation, craving for alcohol, or alcohol self-administration in the laboratory. During the self-administration period, Asp40 carriers consumed fewer drinks and had a longer latency to first drink as compared to Asn40 homozygotes. These findings in East Asians add to the mixed literature on naltrexone pharmacogenetics from predominantly Caucasian samples and highlight the complexity of these effects and their overall limited replicability. It is plausible that a consistent pharmacogenetic effect in tightly controlled preclinical and experimental medicine models "fades" in more complex and heterogeneous settings and samples.


Lung cancer screening-don't forget the chest radiograph.
Lung cancer is a major health burden and early detection only bears the possibility of curative treatment. Screening with computed tomography (CT) recently demonstrated a mortality reduction in selected patients and has been incorporated in clinical guidelines. Problems of screening with CT are the excessive number of false positive findings, costs, radiation burden and from a global point of view shortage of CT capacity. In contrast, chest radiography could be an ideal screening tool in the early detection of lung cancer. It is widely available, easy to perform, cheap, the radiation burden is negligible and there is only a low rate of false positive findings. Large randomized controlled trials could not show a mortality reduction, but different large population-based cohort studies have shown a lung cancer mortality reduction. It has been argued that community-based cohort studies are more closely reflecting the "real world" of everyday medicine. Radiologists should be aware of the found mortality reduction and realize that early detection of lung cancer is possible when reading their daily chest radiographs. Offering a chest radiograph in selected scenarios for the early detection of lung cancer is therefore still justified.


Negative emotionality and disconstraint influence PTSD symptom course via exposure to new major adverse life events.
Identifying the factors that influence stability and change in chronic posttraumatic stress disorder (PTSD) is important for improving clinical outcomes. Using a cross-lagged design, we analyzed the reciprocal effects of personality and PTSD symptoms over time and their effects on stress exposure in a sample of 222 trauma-exposed veterans (ages 23-68; 90.5% male). Personality functioning and PTSD were measured approximately 4 years apart, and self-reported exposure to major adverse life events during the interim was also assessed. Negative emotionality positively predicted future PTSD symptoms, and this effect was partially mediated by exposure to new events. Constraint (negatively) indirectly affected PTSD via its association with exposure to new events. There were no significant effects of positive emotionality nor did PTSD symptom severity exert influences on personality over time. Results indicate that high negative affect and disconstraint influence the course of PTSD symptoms by increasing exposure to stressful life events.


Brain lactate synthesis in thiamine deficiency: a re-evaluation using 1H-13C nuclear magnetic resonance spectroscopy.
Region-selective accumulation of brain lactate occurs in TD; however, the mechanisms responsible have not been elucidated fully. (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy were therefore used to investigate de novo lactate synthesis from [1-(13)C]glucose in vulnerable (medial thalamus) and nonvulnerable (frontal cortex) brain regions of rats made thiamine deficient by administration of the central thiamine antagonist pyrithiamine. De novo synthesis of lactate was increased in the medial thalamus to 148% and 226% of pair-fed control values at presymptomatic and symptomatic stages of thiamine deficiency, respectively, whereas no such changes were observed in the frontal cortex. Administration of a glucose load selectively worsened the changes in medial thalamus. Pyruvate recycling and peripherally derived lactate did not contribute significantly to the lactate increase within the thiamine-deficient brain. Increases in immunolabeling of the lactate dehydrogenase isoenzymes (LDH1 and LDH5) were observed in the medial thalamus of thiamine-deficient animals. Metabolic impairment due to thiamine deficiency thus results in increased glycolysis, increased LDH immunolabeling of neurons and astrocytes and increased de novo synthesis of lactate in brain regions vulnerable to thiamine deficiency. These results are consistent with the notion that focal lactate accumulation participates in the worsening of neurologic symptoms in thiamine-deficient patients.


Preoperative anthropomorphic radiographic measurements can predict postoperative pancreatic fistula formation following pancreatoduodenectomy.
Postoperative pancreatic fistulae (POPF) are a major contributing factor to pancreatoduodenectomy-associated morbidity. Established risk calculators mostly rely on subjective or intraoperative assessments. We hypothesized that various objective preoperatively determined computed tomography (CT) measurements could predict POPF as well as validated models and allow for more informed operative consent in high-risk patients. Patients undergoing elective pancreatoduodenectomies between January 2013 and April 2018 were identified in a prospective database. Comparative statistical analyses and multivariable logistic regression models were generated to predict POPF development. Model performance was tested with receiver operating characteristics (ROC) curves. Pancreatic neck attenuation (Hounsfield units) was measured in triplicate by pancreatic protocol CT (venous phase, coronal plane) anterior to the portal vein. A pancreatic density index (PDI) was created to adjust for differences in contrast timing by dividing the mean of these measurements by the portal vein attenuation. Total areas of subcutaneous fat and skeletal muscle were calculated at the L3 vertebral level on axial CT. Pancreatic duct (PD) diameter was determined by CT. In the study period 220 patients had elective pancreatoduodenectomies with 35 (16%) developing a POPF of any grade. Multivariable regression analysis revealed that demographics (age, sex, and race) were not associated with POPF, yet patients resected for pancreatic adenocarcinoma or chronic pancreatitis were less likely to develop a POPF (10 vs. 24%; p = 0.004). ROC curves were created using various combinations of gland texture, body mass index, skeletal muscle index, sarcopenia, PDI, PD diameter, and subcutaneous fat area indexed for height (SFI). A model replacing gland texture with SFI and PDI (AUC 0.844) had similar predictive performance as the established model (p = 0.169). A combination of preoperative objective CT measurements can adequately predict POPF and is comparable to established models relying on subjective intraoperative variables. Validation in a larger dataset would allow for better preoperative stratification of high-risk patients and improve informed consent among this patient population.


Aspergillus species from Brazilian dry beans and their toxigenic potential.
Aspergilli are common contaminants of food and feed and a major source of mycotoxins. In this study, 87 Aspergillus strains were isolated from beans from 14 different cities in Brazil and identified to the species level based on partial calmodulin and β-tubulin sequence data. All green spored isolates belonged to section Flavi and were identified as A. flavus (n = 39) or A. pseudocaelatus (n = 1). All black spored isolates belonged to section Nigri and were identified as A. niger (n = 24) or A. luchuensis (n = 10), while the yellow spored strains were identified as A. westerdijkiae (n = 7), A. ostianus (n = 3), A. ochraceus (n = 1) or A. wentii (n = 2). The toxigenic potential of these Aspergillus strains from beans was studied by the prospection of genes in three of the major mycotoxin clusters: aflatoxin (seven genes checked), ochratoxin A (four genes) and fumonisin (ten genes and two intergenic regions). Genes involved in the biosynthesis of aflatoxin were only detected in A. flavus isolates: 17/39 A. flavus isolates proved to contain all the aflatoxin genes tested, the others missed one or more genes. The full complement of fumonisin biosynthesis genes was identified in all A. niger isolates. Finally, no genes for ochratoxin A were detected in any of the isolates. Our work suggests that aflatoxin production by some A. flavus strains and fumonisin production by A. niger isolates form the largest mycotoxin risks in Brazilian beans.


Recent innovation in benchmark rates (BMR): evidence from influential factors on Turkish Lira Overnight Reference Interest Rate with machine learning algorithms.
Some countries have announced national benchmark rates, while others have been working on the recent trend in which the London Interbank Offered Rate will be retired at the end of 2021. Considering that Turkey announced the Turkish Lira Overnight Reference Interest Rate (TLREF), this study examines the determinants of TLREF. In this context, three global determinants, five country-level macroeconomic determinants, and the COVID-19 pandemic are considered by using daily data between December 28, 2018, and December 31, 2020, by performing machine learning algorithms and Ordinary Least Square. The empirical results show that (1) the most significant determinant is the amount of securities bought by Central Banks; (2) country-level macroeconomic factors have a higher impact whereas global factors are less important, and the pandemic does not have a significant effect; (3) Random Forest is the most accurate prediction model. Taking action by considering the study's findings can help support economic growth by achieving low-level benchmark rates.


Magnetic resonance arthrography versus arthroscopy in the evaluation of articular hip pathology.
In this study, we compared magnetic resonance arthrography results with hip arthroscopy findings to assess the diagnostic value of this imaging technique in evaluating acetabular labral tears and concurrent articular hip pathology. One hundred one consecutive patients (102 hips) with a clinical diagnosis of acetabular labral tear were assessed using magnetic resonance arthrography and had hip arthroscopy after failing to improve with nonoperative treatment. Magnetic resonance arthrography detected 71 of 93 (76%) acetabular labral tears (92 patients) with five false positive studies in five patients (4.9%). Articular cartilage findings diagnosed by magnetic resonance arthrography were confirmed by arthroscopy in 64 hips in 64 patients (62.7%). With respect to labral pathology, magnetic resonance arthrography showed a sensitivity of 71%, specificity of 44% positive predictive value of 93%, negative predictive value of 13%, and accuracy of 69%. With respect to articular cartilage pathology, magnetic resonance arthrography had a sensitivity of 47%, specificity of 89%, positive predictive value of 84%, negative predictive value of 59%, and accuracy of 67%. Although magnetic resonance arthrography is an excellent positive predictor in diagnosing acetabular labral tears and articular cartilage abnormalities, it has limited sensitivity. A negative imaging study does not exclude important intra-articular pathology that can be identified and treated arthroscopically.


Moving the insulin-regulated glucose transporter GLUT4 into and out of storage.
The glucose transporter isoform GLUT4 is unique among the glucose transporter family of proteins in that, in resting cells, it is sequestered very efficiently in a storage compartment. In insulin-sensitive cells, such as fat and muscle, insulin stimulation leads to release of GLUT4 from this reservoir and its translocation to the plasma membrane. This process is crucial for the control of blood and tissue glucose levels. Investigations of the composition and structure of the GLUT4 storage compartment, together with the targeting motifs that direct GLUT4 to this compartment, have been extensive but have been controversial. Recent findings have now provided a clearer consensus of opinion on the mechanisms involved in the formation of this storage compartment. However, another controversy has now emerged, which is unresolved. This concerns the issue of whether the insulin-regulated step occurs at the level of release of GLUT4 from the storage compartment or at the level at which released vesicles fuse with the plasma membrane.


Structural insight into the recognition of pathogen-derived phosphoglycolipids by C-type lectin receptor DCAR.
The C-type lectin receptors (CLRs) form a family of pattern recognition receptors that recognize numerous pathogens, such as bacteria and fungi, and trigger innate immune responses. The extracellular carbohydrate-recognition domain (CRD) of CLRs forms a globular structure that can coordinate a Ca2+ ion, allowing receptor interactions with sugar-containing ligands. Although well-conserved, the CRD fold can also display differences that directly affect the specificity of the receptors for their ligands. Here, we report crystal structures at 1.8-2.3 Å resolutions of the CRD of murine dendritic cell-immunoactivating receptor (DCAR, or Clec4b1), the CLR that binds phosphoglycolipids such as acylated phosphatidyl-myo-inositol mannosides (AcPIMs) of mycobacteria. Using mutagenesis analysis, we identified critical residues, Ala136 and Gln198, on the surface surrounding the ligand-binding site of DCAR, as well as an atypical Ca2+-binding motif (Glu-Pro-Ser/EPS168-170). By chemically synthesizing a water-soluble ligand analog, inositol-monophosphate dimannose (IPM2), we confirmed the direct interaction of DCAR with the polar moiety of AcPIMs by biolayer interferometry and co-crystallization approaches. We also observed a hydrophobic groove extending from the ligand-binding site that is in a suitable position to interact with the lipid portion of whole AcPIMs. These results suggest that the hydroxyl group-binding ability and hydrophobic groove of DCAR mediate its specific binding to pathogen-derived phosphoglycolipids such as mycobacterial AcPIMs.


High-efficiency antibody discovery achieved with multiplexed microscopy.
The analysis of secreted antibody from large and diverse populations of B cells in parallel at the clonal level can reveal desirable antibodies for diagnostic or therapeutic applications. By immobilizing B cells in microdroplets with particulate reporters, decoding and isolating them in a microscopy environment, we have recovered panels of antibodies with rare attributes to therapeutically relevant targets. The ability to screen up to 100 million cells in a single experiment can be fully leveraged by accessing primary B-cell populations from evolutionarily divergent species such as chickens.


Bilateral stenting of symptomatic and asymptomatic internal carotid artery stenosis due to fibromuscular dysplasia.
Stent grafting of internal carotid artery (ICA) stenoses due to fibromuscular dysplasia has been rarely and only unilaterally carried so far. Bilateral carotid stent grafting of ICA stenoses due to fibromuscular dysplasia has not been reported previously. In a 37 year old woman with recurrent right hemispheric transitory ischaemic attacks, a non-disabling minor stroke, and recurrent right amaurosis fugax despite antithrombotic therapy, cerebral angiography disclosed a long segment narrowing, distal, high grade (95%) stenosis of the right ICA and a long narrowing, distal high grade (70%) stenosis of the left ICA. Morphological features of both stenoses were indicative of fibromuscular dysplasia. The right sided stenosis was stented with a PTFE-HEMOBAHN endoprosthesis; this was followed by a brief, postprocedural left sided hemiparesis. The left sided ICA stenosis was successfully stented by the same procedure. Nine months later, both stents were still patent and the patient was symptom free. Bilateral carotid stenting may remain an alternative to endarterectomy in bilateral ICA stenosis due to fibromuscular dysplasia when ischaemic events persist despite full antithrombotic therapy.


Report from the 37th san antonio breast cancer symposium, 9-13th december 2014, Texas, USA.
The 37th San Antonio Breast Cancer Symposium (SABCS) was held at the Henry B. Gonzalez Conference Centre in San Antonio, Texas, USA between the 9 and 13th of December 2014. It brought together an interaction between basic scientists and clinicians involved in the management of breast cancer. The symposium included six general sessions, poster discussion, and poster sessions. The most important highlights in the fields of advancing endocrine therapy; hormone receptor positive advanced breast cancer and hormonal resistant therapy; targeted therapies; genetics and genomics; supportive (adjunct) care; chemotherapy treatments; breast screening and risk stratification; male breast cancer and future potential directions were included here.


Phenomenological Inferences on the Kinetics of a Mechanically Activated Knoevenagel Condensation: Understanding the "Snowball" Kinetic Effect in Ball Milling.
We focus on understanding the kinetics of a mechanically activated Knoevenagel condensation conducted in a ball mill, that is characterized by sigmoidal kinetics and the formation of a rubber-like cohesive intermediate state coating the milling ball. The previously described experimental findings are explained using a phenomenological kinetic model. It is assumed that reactants transform into products already at the very first collision of the ball with the wall of the jar. The portion of reactants that are transformed into products during each oscillation is taken to be a fraction of the amount of material that is trapped between the ball and the wall of the jar. This quantity is greater when the reaction mixture transforms from its initial powder form to the rubber-like cohesive coating on the ball. Further, the amount of reactants processed in each collision varies proportionally with the total area of the layer coating the ball. The total area of this coating layer is predicted to vary with the third power of time, thus accounting for the observed dramatic increase of the reaction rate. Supporting experiments, performed using a polyvinyl acetate adhesive as a nonreactive but cohesive material, confirm that the coating around the ball grows with the third power of time.


Increases in cardiac output can reverse flow deficits from vasospasm independent of blood pressure: a study using xenon computed tomographic measurement of cerebral blood flow.
Vasospasm after subarachnoid hemorrhage remains a management challenge. The accepted treatment involves hypertensive, hypervolemic, hemodilution therapy. However, there is variation in the application of this treatment. Most authors increase mean arterial pressure (MAP), which can be associated with significant morbidity. Others increase cardiac output (CO). In this study, we examined the relationship between volume status, CO, and MAP and cerebral blood flow (CBF) in the setting of vasospasm. A xenon blood flow tomography-based system was used to quantitate CBF. Sixteen patients with vasospasm after subarachnoid hemorrhage were treated with hypervolemia, phenylephrine to increase MAP, or dobutamine to increase CO. Direct CBF measurements were obtained before and after treatment. A strength of this study is that only one variable (central venous pressure, MAP, or CO) was manipulated in each patient, and the effect of this change was measured immediately. With phenylephrine, mean MAP increased from 102.4 to 132.1 mm Hg. In regions of diminished CBF due to vasospasm, mean CBF increased from 19.2 to 33.7 ml/100 g/min. Similarly, dobutamine increased the cardiac index from a mean of 4.1 to 6.0 L/min/m(2) and slightly decreased MAP. CBF increased from a mean of 24.8 to 35.4 ml/100 g/min. Both were statistically significant changes. With hypervolemia, the average central venous pressure increased from a mean of 5.4 to 7.3 cm H(2)O; no changes in mean CBF were noted. This article reports the first human study that shows with direct measurements the independent influence of CO in the setting of vasospasm. Increases in CO without changes in MAP can elevate CBF. This finding has immediate clinical application because CO manipulation is much safer than increasing MAP. Because both interventions were equally efficacious, our protocol has been changed to augment CO as a first measure. Induced hypertension is reserved for patients in whom this initial treatment fails.


Arocalciferols: synthesis and biological evaluation of aromatic side-chain analogues of 1 alpha,25-dihydroxyvitamin D3(1a).
Aromatic side-chain analogues (arocalciferols 6-9) of the steroid hormone 1 alpha,25-dihydroxyvitamin D3 (1) were synthesized and biologically evaluated. The analogues were prepared by coupling the vitamin D A-ring enyne 14 with the appropriate enol triflate of a modified CD steroid fragment of the type 22. The resulting dienyne 23 was then transformed in three steps to the vitamin D analogues 6-9. Biological evaluation of these analogues have provided information concerning side-chain topographical effects on in vivo and in vitro activity.


Collectively achieving primary health care and educational goals through school-based platforms: financing solutions for intersectoral collaboration.
Despite abundant evidence demonstrating that improvements to health and education are positively correlated, and the importance of school-based platforms to achieve shared impacts, collaboration between ministries of health and education remains limited across low- and middle-income countries. Enhancing this collaboration is essential to realize mutually beneficial results, especially following the COVID-19 pandemic, which severely impacted health and education outcomes globally and highlighted the importance of resilient, domestically funded systems for delivering key social services including primary health care and education. We argue that the lack of an effective joint financing mechanism has hindered adoption of collaborative multisectoral approaches such as the WHO/UNESCO's Health Promoting Schools (HPS) model. HPS is well-positioned to organize, finance, and deliver primary health care and education services through a school-based platform and strategy. Case studies from several low- and middle-income countries highlight the need to expand limited inter-ministerial collaborations to achieve cross-sectoral benefits and ensure sustainability of HPS beyond the lifecycle of external partners' support. It is important to identify ways to widen the resource envelope for sector-specific activities and create efficiencies through mutually beneficial outcomes. This paper offers two pragmatic solutions: an inter-ministerial joint financing mechanism that starts with alignment of budgets but matures into a formal system for pooling funds, or a fixed-term co-financing mechanism that uses donor contributions to catalyze inter-ministerial collaborations. Achieving sustainability in these initiatives would require engaging the ministries of health, education, and finance; developing a common administrative, financial, and monitoring mechanism; and securing long-term commitment from all concerned stakeholders.


Contour Transformer Network for One-Shot Segmentation of Anatomical Structures.
Accurate segmentation of anatomical structures is vital for medical image analysis. The state-of-the-art accuracy is typically achieved by supervised learning methods, where gathering the requisite expert-labeled image annotations in a scalable manner remains a main obstacle. Therefore, annotation-efficient methods that permit to produce accurate anatomical structure segmentation are highly desirable. In this work, we present Contour Transformer Network (CTN), a one-shot anatomy segmentation method with a naturally built-in human-in-the-loop mechanism. We formulate anatomy segmentation as a contour evolution process and model the evolution behavior by graph convolutional networks (GCNs). Training the CTN model requires only one labeled image exemplar and leverages additional unlabeled data through newly introduced loss functions that measure the global shape and appearance consistency of contours. On segmentation tasks of four different anatomies, we demonstrate that our one-shot learning method significantly outperforms non-learning-based methods and performs competitively to the state-of-the-art fully supervised deep learning methods. With minimal human-in-the-loop editing feedback, the segmentation performance can be further improved to surpass the fully supervised methods.


Identification of the invariant chain (CD74) as an angiotensin AGTR1-interacting protein.
Little is known about the protein-protein interactions that regulate the trafficking of the angiotensin II type I receptor (AGTR1) through the biosynthetic pathway. The membrane-proximal region of the cytoplasmic tail of the AGTR1 has been identified by site-directed mutagenesis studies as an essential site for normal AGTR1 folding and surface expression. Based on yeast two-hybrid screening of a human kidney cDNA library with the AGTR1 carboxyl-terminal tail as a bait, we identified the invariant chain (CD74) as a novel interacting protein. This association was confirmed by co-immunoprecipitation and co-localization studies. The binding site for CD74 on the AGTR1 carboxyl-terminal tail was localized to a site previously identified as important for the exit of the AGTR1 from the endoplasmic reticulum (ER), and conserved in many G protein-coupled receptors. Transient co-expression of CD74 with the AGTR1 in CHO-K1 cells consistently reduced the AGTR1 density at the cell surface. Furthermore, the interaction of CD74 with the carboxyl-terminal tail of the AGTR1 caused its retention in the ER and promoted its proteasomal degradation. These observations indicate that CD74 and the AGTR1 become associated in the early biosynthetic pathway, and that CD74 is a negative regulator of AGTR1 expression.


Cost-effectiveness of human papillomavirus DNA testing in the United Kingdom, The Netherlands, France, and Italy.
European countries with established cytology-based screening programs for cervical cancer will soon face decisions about whether to incorporate human papillomavirus (HPV) DNA testing and what strategies will be most cost-effective. We assessed the cost-effectiveness of incorporating HPV DNA testing into existing cervical cancer screening programs in the United Kingdom, The Netherlands, France, and Italy. We created a computer-based model of the natural history of cervical carcinogenesis for each using country-specific data on cervical cancer risk and compared each country's current screening policy with two new strategies: 1) cytology throughout a woman's lifetime, using HPV DNA testing as a triage strategy for equivocal cytology results ("HPV triage"), as well as 2) cytology until age 30 years and HPV DNA testing in combination with cytology in women more than 30 years of age ("combination testing"). Outcomes included reduction in lifetime cervical cancer risk, increase in life expectancy, lifetime costs, and incremental cost-effectiveness ratios, expressed as cost per year of life saved. We explored alternative protocols and conducted sensitivity analysis on key parameters of the model over a relevant range of values to identify the most cost-effective options for each country. Both HPV DNA testing strategies, HPV triage and combination testing, were more effective than each country's status quo screening policy. Incremental cost-effectiveness ratios for HPV triage were less than $13,000 per year of life saved, whereas those for combination testing ranged from $9800 to $75,900 per year of life saved, depending on screening interval. We identified options that would be very cost-effective (i.e., cost-effectiveness ratio less than the gross domestic product per capita) in each of the four countries. HPV DNA testing has the potential to improve health benefits at a reasonable cost compared with current screening policies in four European countries.


Fetal electrocardiogram extraction by sequential source separation in the wavelet domain.
This paper addresses the problem of fetal electrocardiogram extraction using blind source separation (BSS) in the wavelet domain. A new approach is proposed, which is particularly advantageous when the mixing environment is noisy and time-varying, and that is shown, analytically and in simulation, to improve the convergence rate of the natural gradient algorithm. The distribution of the wavelet coefficients of the source signals is then modeled by a generalized Gaussian probability density, whereby in the time-scale domain the problem of selecting appropriate nonlinearities when separating mixtures of both sub- and super-Gaussian signals is mitigated, as shown by experimental results.


An efficient method for the creation of tunable optical line traps via control of gradient and scattering forces.
Interparticle interaction energies and other useful physical characteristics can be extracted from the statistical properties of the motion of particles confined by an optical line trap. In practice, however, the potential energy landscape, U(x), imposed by the line provides an extra, and in general unknown, influence on particle dynamics. We describe a new class of line traps in which both the optical gradient and scattering forces acting on a trapped particle are designed to be linear functions of the line coordinate and in which their magnitude can be counterbalanced to yield a flat U(x). These traps are formed using approximate solutions to general relations concerning non-conservative optical forces that have been the subject of recent investigations [Y. Roichman, B. Sun, Y. Roichman, J. Amato-Grill, and D. G. Grier, Phys. Rev. Lett. 100, 013602-4 (2008).]. We implement the lines using holographic optical trapping and measure the forces acting on silica microspheres, demonstrating the tunability of the confining potential energy landscape. Furthermore, we show that our approach efficiently directs available laser power to the trap, in contrast to other methods.


General method for exact evaluation of parameters of the elementary steps of coupled reactions. Invariant analysis.
A general method has been devised for the exact evaluation of the rate constants of the elementary steps of a system consisting of any number of coupled reactions. The method is independent of the structure of the network of coupled steps. The precision of the data evaluation is solely dependent on the quality of the detection unit. The application of the method is illustrated with data collected for the binding of the competitive inhibitor proflavine to chymotrypsin under such conditions that five states of the enzyme are required to interpret the results. In the absence of a substance possessing the binding specificity, the enzyme is present as an equilibrium between an active and an inactive conformer. The latter prevails. The binding of the specific inhibitor releases a slow proton transfer from the medium to the alpha-amino group of Ile-16. Subsequently, the enzyme-inhibitor (or enzyme-substrate) complex re-arranges to the catalytically active form, which is retained until the supply of specific substrate is exhausted. The control features described are general, but are particularly conspicuous under the special environmental conditions used here. A comparison between data for alpha- and delta-forms of chymotrypsin showed that the chain ends of the former impeded the substrate binding and that the activity controlling conformational change occurred in the interior of the enzyme molecule.


Vitamin D supplementation.
Vitamin D testing and supplementation is of great interest to neurologists and their patients. Recommended nutritional intakes of vitamin D in the UK remain focused on bone health, despite increasing evidence for a role outside this area. Here we discuss how neurologists might approach vitamin D testing and supplementation, focusing on two conditions associated with vitamin D deficiency that have an increased risk of downstream complications resulting from these: multiple sclerosis and epilepsy. We set out a rationale for testing serum 25-hydroxyvitamin D concentrations and discuss our personal practice in terms of supplementation, with evidence where available.


Analysing the effects of working period on psychophysiological states of seafarers.
Human factor has become a critical issue due to the fact that all operational processes in maritime transportation have been accelerated with technological innovations. Irregular and long working hours, rapid change of working environments and other organisational and/or individual factors have negative impact on the performance of the seafarers as well as other transportation workers and/or shift workers. Seafarers working under the influence of these stressor factors, naturally, are affected from psychophysiological and cognitive aspects, which in return decrease their overall performances. The study mainly aimed to investigate which of the above mentioned affecting factors had greater impact on seafarers' performances. For this purpose, data for 14 healthy male seafarers on board different vessels was collected. The collected data included the number of port visits, frequency of change of circadian rhythm, total working hours and watchkeeping periods in the recent month. In order to analyse the psychophysiological effect of working period, electrodermal activity and heart rate variability measurements for arousal mood and data from 2-choice reaction time tests for cognitive performance were collected from the seafarers. Obtained data was analysed in SPSS software programme applying multiple regression with factor analysis to model the dependence between psychophysiological states of seafarers and working periods. According to the results, it was determined that the change of circadian rhythm is the main determinant factor for seafarers. The results showed that when seafarer's circadian rhythm is changed more frequently, they experience more drowsiness.


Neural network for graphs: a contextual constructive approach.
This paper presents a new approach for learning in structured domains (SDs) using a constructive neural network for graphs (NN4G). The new model allows the extension of the input domain for supervised neural networks to a general class of graphs including both acyclic/cyclic, directed/undirected labeled graphs. In particular, the model can realize adaptive contextual transductions, learning the mapping from graphs for both classification and regression tasks. In contrast to previous neural networks for structures that had a recursive dynamics, NN4G is based on a constructive feedforward architecture with state variables that uses neurons with no feedback connections. The neurons are applied to the input graphs by a general traversal process that relaxes the constraints of previous approaches derived by the causality assumption over hierarchical input data. Moreover, the incremental approach eliminates the need to introduce cyclic dependencies in the definition of the system state variables. In the traversal process, the NN4G units exploit (local) contextual information of the graphs vertices. In spite of the simplicity of the approach, we show that, through the compositionality of the contextual information developed by the learning, the model can deal with contextual information that is incrementally extended according to the graphs topology. The effectiveness and the generality of the new approach are investigated by analyzing its theoretical properties and providing experimental results.


Evolutionarily conserved anterior expansion of the central nervous system promoted by a common PcG-Hox program.
A conserved feature of the central nervous system (CNS) is the prominent expansion of anterior regions (brain) compared with posterior (nerve cord). The cellular and regulatory processes driving anterior CNS expansion are not well understood in any bilaterian species. Here, we address this expansion in Drosophila and mouse. We find that, compared with the nerve cord, the brain displays extended progenitor proliferation, more elaborate daughter cell proliferation and more rapid cell cycle speed in both Drosophila and mouse. These features contribute to anterior CNS expansion in both species. With respect to genetic control, enhanced brain proliferation is severely reduced by ectopic Hox gene expression, by either Hox misexpression or by loss of Polycomb group (PcG) function. Strikingly, in PcG mutants, early CNS proliferation appears to be unaffected, whereas subsequent brain proliferation is severely reduced. Hence, a conserved PcG-Hox program promotes the anterior expansion of the CNS. The profound differences in proliferation and in the underlying genetic mechanisms between brain and nerve cord lend support to the emerging concept of separate evolutionary origins of these two CNS regions.


Confinement effects on lyotropic nematic liquid crystal phases of graphene oxide dispersions.
Graphene oxide (GO) forms well ordered liquid crystal (LC) phases in polar solvents. Here, we map the lyotropic phase diagram of GO as a function of the lateral dimensions of the GO flakes, their concentration, geometrical confinement configuration and solvent polarity. GO flakes were prepared in water and transferred into other polar solvents. Polarising optical microscopy (POM) was used to determine the phase evolution through the isotropic-biphasic-nematic transitions of the GO LC. We report that the confinement volume and geometry relative to the particle size is critical for the observation of the lyotropic phase, specifically, this determines the low-end concentration limit for the detection of the GO LC. Additionally, a solvent with higher polarisability stabilises the LC phases at lower concentrations and smaller flake sizes. GO LCs have been proposed for a range of applications from display technologies to conductive fibres, and the behaviour of LC phase formation under confinement imposes a limit on miniaturisation of the dimensions of such GO LC systems which could significantly impact on their potential applications.


Solid lipid nanoparticles (SLN) of tretinoin: potential in topical delivery.
The objective of this investigation was to develop solid lipid nanoparticles (SLN) of tretinoin (TRE) with the help of facile and simple emulsification-solvent diffusion (ESD) technique and to evaluate the viability of an SLN based gel in improving topical delivery of TRE. The feasibility of fabricating SLN of TRE by the ESD method was successfully demonstrated in this investigation. The developed SLN were characterized for particle size, polydispersity index, entrapment efficiency of TRE and morphology. Studies were carried out to evaluate the ability of SLN in improving the photostability of TRE as compared to TRE in methanol. Encapsulation of TRE in SLN resulted in a significant improvement in its photostability in comparison to methanolic TRE solution and also prevented its isomerization. Furthermore, the skin irritation studies carried out on rabbits showed that SLN based TRE gel is significantly less irritating to skin as compared to marketed TRE cream and clearly indicated its potential in improving the skin tolerability of TRE. In vitro permeation studies through rat skin indicated that an SLN based TRE gel has permeation profile comparable to that of the marketed TRE cream.


Incidence of stress-related disorders among American and Brazilian men and women.
Cross-cultural differences in physical and emotional responses to stressors are reported in this study. Among professionals (e.g., managers, supervisors), the incidence of stress-related disorders can have remarkable impact upon organizational performance as well as personal well-being. In order to study the relationship of nationality and gender to stress-related disorders, 148 American and 180 Brazilian professionals completed a questionnaire asking them to identify their unique responses to occupational stressors. Statistical analysis indicated that significant differences exist between the responses based upon both nationality and gender. Specifically, Americans reported a significantly higher incidence of allergies and irritable bowel syndrome, while Brazilians reported a higher incidence of Raynaud's syndrome (major manifestations are cold hands/feet). The males reported a higher incidence of high blood pressure and TMJ dysfunction/bruxism (a major manifestation is teeth grinding), while the females reported a higher incidence of tension headaches. The results are discussed in comparison to other cross-cultural and cross-gender studies with similar outcomes.


The role of prolactin in fish reproduction.
Prolactin (PRL) has one of the broadest ranges of functions of any vertebrate hormone, and plays a critical role in regulating aspects of reproduction in widely divergent lineages. However, while PRL structure, mode of action and functions have been well-characterised in mammals, studies of other vertebrate lineages remain incomplete. As the most diverse group of vertebrates, fish offer a particularly valuable model system for the study of the evolution of reproductive endocrine function. Here, we review the current state of knowledge on the role of prolactin in fish reproduction, which extends to migration, reproductive development and cycling, brood care behaviour, pregnancy, and nutrient provisioning to young. We also highlight significant gaps in knowledge and advocate a specific bidirectional research methodology including both observational and manipulative experiments. Focusing research efforts towards the thorough characterisation of a restricted number of reproductively diverse fish models will help to provide the foundation necessary for a more explicitly evolutionary analysis of PRL function.


Chemotherapy or targeted therapy as second-line treatment of advanced gastric cancer. A systematic review and meta-analysis of published studies.
Chemotherapy is a cornerstone in treatments of gastric cancer, but despite its benefit, less than 60% of patients receive salvage therapy in clinical practice. We performed a systematic review and meta-analysis based on trial data on the role of second-line treatment of advanced gastric cancer. MEDLINE/PubMed and Cochrane Library were searched for randomized phase III trials that compared active therapy to best supportive care in advanced gastric cancer. Data extraction was conducted according to the PRISMA statement. Summary HR for OS was calculated using a hierarchical Bayesian model and subgroup analysis was performed based on baseline Eastern Cooperative Oncology Group Performance Status (ECOG) performance status (0 vs. 1 or more). A total of 1,407 patients were evaluable for efficacy, 908 were treated in the experimental arms, with chemotherapy (231 pts) or with targeted therapies (677 pts). The risk of death was decreased by 18% (HR = 0.82; 95% CI, 0.79-0.85; posterior probability HR≥1: <0.00001) with active therapies. Chemotherapy and ramucirumab were able to decrease this risk by 27% and 22%, respectively. No differences were found between chemotherapy and ramucirumab. In patients with ECOG = 0 a greater benefit was found for chemotherapy with a reduction of the risk of death by 43% and no benefits were found for ramucirumab or everolimus. In patients with ECOG = 1 or more a significant reduction of the risk of death by 32% was reported in patients treated with ramucirumab, even if no significant difference was reported between chemotherapy and ramucirumab. This analysis reports that active and available therapies are able to prolong survival in patients with advanced gastric cancer with a different outcome based on initial patient's performance status. New trials based on a better patient stratification are awaited.


Shape from shading from images rendered with various surface types and light fields.
Shape constancy is referred to as the tendency for the perceived shape of an object to remain unchanged even under changed viewing and illumination conditions. We investigated, in two experiments, whether shape constancy would hold for images of 3-D solid objects defined by shading only, whose renderings differed in terms of surface material type (bi-directional reflectance distribution functions), light field, light direction, shape, and specularity. Observers were presented with the image of a sphere or an ellipsoid and required to set perceived orientation and cross-section profile on designated points of the image. Results showed that shape judgments varied with all the aforementioned variables except specularity. Shape estimates were more precise with specular than asperity scattering surfaces, collimated than hemispherical diffuse lighting conditions, lower than higher elevations, spherical than ellipsoidal shapes, but not different between surfaces having differing specularity. These results suggest that shape judgments are made largely on the basis of the overall intensity distribution of shading, and that the portions of intensity distribution that are due to nonstructural variables such as surface material type or light field are not excluded in the process of shape estimation, as if being due to structural components. It is concluded that little constancy is expected in the perception of shape from shading.